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PN-AAJ-<36 BOlmLJOGR.AJMIC DATA SHETL cWMTUer wJNU It Ir €1wi ( " APl0-0000-0000 1 TIT.E AM) SIuRTTLE i,) Possible disinfection cf oral rehydration solutions -L fI.tAL AtmrmS (JG) Cash, Richard; Chan, Lincoln s. "3OIATE AW'iM)S (1SI) Camp Dresser and McKee, Inc. Coordination and Information 7 nter, operated by CDM FIVE) 6. DOCUM.NT DATE (1 0) 1980 17. 1UJanr OF 1 6p. A:--!. 120) L ARC NUMN (173 628. 662.c'38 9. REFERE1-E ORGAI2ATION (13 ) 10. SUPLEMENT^ay ;NOMS (sooJ (Report prepared by the Water and Sanitation for Health (WASH) Project 1I. ANSTRACT (90) 12. DESCRI7TORS (420) 1S. IRJECT NUMBER (IBO) Disinfectants Water supply and health 931117600 Potable water Water treatment -- Contamination Dehydratioa II- ROTJLACrNO1.(I ) I&CONTRACt TD/DSPP.-C-0080 TYN (14t9 16. TYPE OF DOCL EN (16d A ) 59U-7 (10-79)
Transcript

PN-AAJ-lt36BOlmLJOGRAJMIC DATA SHETL cWMTUerwJNU It Ir euro1wi ( APl0-0000-0000 1 TITE AM) SIuRTTLE i)Possible disinfection cf oral rehydration solutions

-LfItAL AtmrmS (JG)

Cash Richard Chan Lincoln

s3OIATE AWiM)S (1SI)

Camp Dresser and McKee Inc

Coordination and Information 7 nter operated by CDM FIVE)

6DOCUMNT DATE (1 0) 1980

17 1UJanrOF 1 6p

A-- 120) L ARC NUMN (173 628 662c38

9 REFERE1-E ORGAI2ATION (13 )

10 SUPLEMENT^ay NOMS (sooJ

(Report prepared by the Water and Sanitation for Health (WASH) Project

1I ANSTRACT (90)

12 DESCRI7TORS (420) 1S IRJECT NUMBER (IBO) Disinfectants Water supply and health 931117600 Potable water Water treatment --Contamination Dehydratioa II- ROTJLACrNO1(I ) IampCONTRACt

TDDSPP-C-0080 TYN (14t9

16 TYPE OF DOCL EN (16d

A ) 59U-7 (10-79)

f21 - I - S i

COORDINATION AND INFORMATION CENTER

Opefated b CDM FIVE fur the ULS Agenc

for Inlter naiional Deeloprnent

1611 N Kent Street Room 1002

Arlington Virginia 22209 USA Telephone (703) 2434-20

Telex No WUI 64552

Cabe Address WASHAID

POSSIBLE DISINFECTION OF

ORAL REHYDRATION SOLUTIONS

Notes from November 18 198U Meeting

w ith

Drs Richard Cath and Lincoln Chen

ADDSPE-C70080 931117600

REASON FOR THIS REPORT

Recently the question of whether or not to consider the

introduction of a disinfectant into oral rehydration packages

was raised Disinfection should at least be considered it is

contended since most households in Third World countries do not

have access to safe uater Several problems are however attendant

upon the use of a disinfectant in this capacity among them

-)ssiL- chemical interactions with other components of the

packa1 biologic reactions with the inflamed gut and problems

Qf ) taste and acceptability Because of these problems it

was thought useful to hold a serious discussion of the issues

before deciding to routinely include a disinfectant in OR

packages Dro Richard Cash and Lincoln Chen of the Harvard

School of Public Health were invited as gu2st consultants and a

group of AID technical personnel was gathered

1For a list of attendees see Attachment IV

POSSIBLE DISINFECTION OF ORAL REHYDRATION SOLUTIONS

Notes from November 13 1980 Meeting with

Drs Richard Cash and Lincoln Chen

Drs Cash and Chen began their discussion with DSHEA and WASH

staff by posing two questions The first question was

As drinking water in LDCs is often contamishynated should an effort be made to insure the potability of oral rehydration solutions

Dr Cnen presented data from the following studies which illusshy

trate that the growth of micro-organisms is supported in OR

solutions

1) Richard Guerrant in Brazil (now Department of Geograpk~ic

Medicine University of Virginia Charlottesville) foundJ

E Coli after 24 hours in concentrations of 105 per

100 ml in OR solutions made up by villagers regardless

of the initial purity of the water to which the salts

were added

2) Gerry Keusch actHarvard found the follcwing rumbers of

E Coli in various OR solutions Note These solutions

consisted of river water added E Coli and oral therapy

salts

Time (hrs) 1 4 8 16

E Ccli 1O1 10 1-10 106

The discussion then dealt with many questions about ORS and ORT

with potential for field research These questions are sununashy

rized in Attachment I

The first question raised was Are there negative effects (egreinf tion o prolongation of the diarrheal episode) of drinkingcontaminated ORS given that tne gut is already inflamed the answer to this question Js unknown but the suggestion was made that Mike Levine at the University of Maryland might be able toinclude an approach to this question in his volunteer diarrheal studies It should be noted however that the results of either animal or human adult studies of chis question might not be directly applicable to children under five thus one might argue Cfor using a natural experiment in an on-going oral rehydrationtherapy field project

Dr Cash pointed out that it is important to know at what pointthe water in the OR solution is contamirated at the water source in vessels used for transport from the source to the home during storage in the home by the person who mixes upthe solution (fingers spoon) or from the ORS salts themselves (especially since the ingredients sugar and salt are supportive of bacterial growth

If it can be assumed that the contamination of the solution during the mixing or from the salts is negligible what options could be considered for water purification eg adding a )actericidal agent to the water storage vessels in the home boiling the water to be used (this method was criticized because of its high fuel and time costs) addition of a disinfectant to the ORS packet Finally a paper has been recently received bythe Near East Bureau which suggests that exposure of the mixed solution to the suns ultraviolet irradiation for one hour has a significant bactericidal effect (see Attachment II) Does this approach appear to be feasible

Not much work has been done with regard to what substances mightbe used as a disinfectant in the ORS Vic Wehman mentioned potassium permanganate as a possibility Halogeas such aL

-2shy

r brominehave the t athyoidzchlori qe isahdvanag h

LI Queistions remain to beansered aotdsnetnstesle -4744 4 4 tO I11

hatsha dsnfectant(s would have ahigh i ishy

cidalviricidal- ac tivity be rr wth77e egrd to MIS compnerts not ne7gatielygt Th se its r 2774-gt 144)7th shef-lfe be- i ofthe OR acketedeffepycitoicvenes ofd-atne -lhug gt--

bullpaihtable beof low cpst bechemiclyi~rin i Arelation to n al ions frequently found in i cent

gt] untreated watex such as Fe i Mrn -i --

furhe imotnustoi Wa old be the effec ofthe 7 o ono the hetdisinfecsanteid inf gut

cidinraand reltd stiest evaluat the relative efetveness of vious

i-i7 disinfe ta ts undera variety ofsonditions -

Tes questionsviicidl researchable eare ativiy One might undertakelaboratiory-S

A laterfieldi study

aspart of an on-going OR program could help toansweri questions )abou the tastea ox it and the effects on analready

gut A summa7ry oftheresearchgtlteraturerdcompromised alread

on this question II cent available appears as-AttachmentlltIgt

A danger orei the dbsinfectant iionddt straegyaisthateItsmay

starti- an=uncontrolled series of sugge t o s c n e i g vi a i l miner protein supplementation Theargument( mightb~ae

-) gtthat a childaswellwith diarrheafluid needsC theadto cetan L7Pnutrients as and4electrolytes

e was 4

Rwaeir i o bwtht e L r

Anothe caution raised whether the be74r4d

Ruca w s

i

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

f21 - I - S i

COORDINATION AND INFORMATION CENTER

Opefated b CDM FIVE fur the ULS Agenc

for Inlter naiional Deeloprnent

1611 N Kent Street Room 1002

Arlington Virginia 22209 USA Telephone (703) 2434-20

Telex No WUI 64552

Cabe Address WASHAID

POSSIBLE DISINFECTION OF

ORAL REHYDRATION SOLUTIONS

Notes from November 18 198U Meeting

w ith

Drs Richard Cath and Lincoln Chen

ADDSPE-C70080 931117600

REASON FOR THIS REPORT

Recently the question of whether or not to consider the

introduction of a disinfectant into oral rehydration packages

was raised Disinfection should at least be considered it is

contended since most households in Third World countries do not

have access to safe uater Several problems are however attendant

upon the use of a disinfectant in this capacity among them

-)ssiL- chemical interactions with other components of the

packa1 biologic reactions with the inflamed gut and problems

Qf ) taste and acceptability Because of these problems it

was thought useful to hold a serious discussion of the issues

before deciding to routinely include a disinfectant in OR

packages Dro Richard Cash and Lincoln Chen of the Harvard

School of Public Health were invited as gu2st consultants and a

group of AID technical personnel was gathered

1For a list of attendees see Attachment IV

POSSIBLE DISINFECTION OF ORAL REHYDRATION SOLUTIONS

Notes from November 13 1980 Meeting with

Drs Richard Cash and Lincoln Chen

Drs Cash and Chen began their discussion with DSHEA and WASH

staff by posing two questions The first question was

As drinking water in LDCs is often contamishynated should an effort be made to insure the potability of oral rehydration solutions

Dr Cnen presented data from the following studies which illusshy

trate that the growth of micro-organisms is supported in OR

solutions

1) Richard Guerrant in Brazil (now Department of Geograpk~ic

Medicine University of Virginia Charlottesville) foundJ

E Coli after 24 hours in concentrations of 105 per

100 ml in OR solutions made up by villagers regardless

of the initial purity of the water to which the salts

were added

2) Gerry Keusch actHarvard found the follcwing rumbers of

E Coli in various OR solutions Note These solutions

consisted of river water added E Coli and oral therapy

salts

Time (hrs) 1 4 8 16

E Ccli 1O1 10 1-10 106

The discussion then dealt with many questions about ORS and ORT

with potential for field research These questions are sununashy

rized in Attachment I

The first question raised was Are there negative effects (egreinf tion o prolongation of the diarrheal episode) of drinkingcontaminated ORS given that tne gut is already inflamed the answer to this question Js unknown but the suggestion was made that Mike Levine at the University of Maryland might be able toinclude an approach to this question in his volunteer diarrheal studies It should be noted however that the results of either animal or human adult studies of chis question might not be directly applicable to children under five thus one might argue Cfor using a natural experiment in an on-going oral rehydrationtherapy field project

Dr Cash pointed out that it is important to know at what pointthe water in the OR solution is contamirated at the water source in vessels used for transport from the source to the home during storage in the home by the person who mixes upthe solution (fingers spoon) or from the ORS salts themselves (especially since the ingredients sugar and salt are supportive of bacterial growth

If it can be assumed that the contamination of the solution during the mixing or from the salts is negligible what options could be considered for water purification eg adding a )actericidal agent to the water storage vessels in the home boiling the water to be used (this method was criticized because of its high fuel and time costs) addition of a disinfectant to the ORS packet Finally a paper has been recently received bythe Near East Bureau which suggests that exposure of the mixed solution to the suns ultraviolet irradiation for one hour has a significant bactericidal effect (see Attachment II) Does this approach appear to be feasible

Not much work has been done with regard to what substances mightbe used as a disinfectant in the ORS Vic Wehman mentioned potassium permanganate as a possibility Halogeas such aL

-2shy

r brominehave the t athyoidzchlori qe isahdvanag h

LI Queistions remain to beansered aotdsnetnstesle -4744 4 4 tO I11

hatsha dsnfectant(s would have ahigh i ishy

cidalviricidal- ac tivity be rr wth77e egrd to MIS compnerts not ne7gatielygt Th se its r 2774-gt 144)7th shef-lfe be- i ofthe OR acketedeffepycitoicvenes ofd-atne -lhug gt--

bullpaihtable beof low cpst bechemiclyi~rin i Arelation to n al ions frequently found in i cent

gt] untreated watex such as Fe i Mrn -i --

furhe imotnustoi Wa old be the effec ofthe 7 o ono the hetdisinfecsanteid inf gut

cidinraand reltd stiest evaluat the relative efetveness of vious

i-i7 disinfe ta ts undera variety ofsonditions -

Tes questionsviicidl researchable eare ativiy One might undertakelaboratiory-S

A laterfieldi study

aspart of an on-going OR program could help toansweri questions )abou the tastea ox it and the effects on analready

gut A summa7ry oftheresearchgtlteraturerdcompromised alread

on this question II cent available appears as-AttachmentlltIgt

A danger orei the dbsinfectant iionddt straegyaisthateItsmay

starti- an=uncontrolled series of sugge t o s c n e i g vi a i l miner protein supplementation Theargument( mightb~ae

-) gtthat a childaswellwith diarrheafluid needsC theadto cetan L7Pnutrients as and4electrolytes

e was 4

Rwaeir i o bwtht e L r

Anothe caution raised whether the be74r4d

Ruca w s

i

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

REASON FOR THIS REPORT

Recently the question of whether or not to consider the

introduction of a disinfectant into oral rehydration packages

was raised Disinfection should at least be considered it is

contended since most households in Third World countries do not

have access to safe uater Several problems are however attendant

upon the use of a disinfectant in this capacity among them

-)ssiL- chemical interactions with other components of the

packa1 biologic reactions with the inflamed gut and problems

Qf ) taste and acceptability Because of these problems it

was thought useful to hold a serious discussion of the issues

before deciding to routinely include a disinfectant in OR

packages Dro Richard Cash and Lincoln Chen of the Harvard

School of Public Health were invited as gu2st consultants and a

group of AID technical personnel was gathered

1For a list of attendees see Attachment IV

POSSIBLE DISINFECTION OF ORAL REHYDRATION SOLUTIONS

Notes from November 13 1980 Meeting with

Drs Richard Cash and Lincoln Chen

Drs Cash and Chen began their discussion with DSHEA and WASH

staff by posing two questions The first question was

As drinking water in LDCs is often contamishynated should an effort be made to insure the potability of oral rehydration solutions

Dr Cnen presented data from the following studies which illusshy

trate that the growth of micro-organisms is supported in OR

solutions

1) Richard Guerrant in Brazil (now Department of Geograpk~ic

Medicine University of Virginia Charlottesville) foundJ

E Coli after 24 hours in concentrations of 105 per

100 ml in OR solutions made up by villagers regardless

of the initial purity of the water to which the salts

were added

2) Gerry Keusch actHarvard found the follcwing rumbers of

E Coli in various OR solutions Note These solutions

consisted of river water added E Coli and oral therapy

salts

Time (hrs) 1 4 8 16

E Ccli 1O1 10 1-10 106

The discussion then dealt with many questions about ORS and ORT

with potential for field research These questions are sununashy

rized in Attachment I

The first question raised was Are there negative effects (egreinf tion o prolongation of the diarrheal episode) of drinkingcontaminated ORS given that tne gut is already inflamed the answer to this question Js unknown but the suggestion was made that Mike Levine at the University of Maryland might be able toinclude an approach to this question in his volunteer diarrheal studies It should be noted however that the results of either animal or human adult studies of chis question might not be directly applicable to children under five thus one might argue Cfor using a natural experiment in an on-going oral rehydrationtherapy field project

Dr Cash pointed out that it is important to know at what pointthe water in the OR solution is contamirated at the water source in vessels used for transport from the source to the home during storage in the home by the person who mixes upthe solution (fingers spoon) or from the ORS salts themselves (especially since the ingredients sugar and salt are supportive of bacterial growth

If it can be assumed that the contamination of the solution during the mixing or from the salts is negligible what options could be considered for water purification eg adding a )actericidal agent to the water storage vessels in the home boiling the water to be used (this method was criticized because of its high fuel and time costs) addition of a disinfectant to the ORS packet Finally a paper has been recently received bythe Near East Bureau which suggests that exposure of the mixed solution to the suns ultraviolet irradiation for one hour has a significant bactericidal effect (see Attachment II) Does this approach appear to be feasible

Not much work has been done with regard to what substances mightbe used as a disinfectant in the ORS Vic Wehman mentioned potassium permanganate as a possibility Halogeas such aL

-2shy

r brominehave the t athyoidzchlori qe isahdvanag h

LI Queistions remain to beansered aotdsnetnstesle -4744 4 4 tO I11

hatsha dsnfectant(s would have ahigh i ishy

cidalviricidal- ac tivity be rr wth77e egrd to MIS compnerts not ne7gatielygt Th se its r 2774-gt 144)7th shef-lfe be- i ofthe OR acketedeffepycitoicvenes ofd-atne -lhug gt--

bullpaihtable beof low cpst bechemiclyi~rin i Arelation to n al ions frequently found in i cent

gt] untreated watex such as Fe i Mrn -i --

furhe imotnustoi Wa old be the effec ofthe 7 o ono the hetdisinfecsanteid inf gut

cidinraand reltd stiest evaluat the relative efetveness of vious

i-i7 disinfe ta ts undera variety ofsonditions -

Tes questionsviicidl researchable eare ativiy One might undertakelaboratiory-S

A laterfieldi study

aspart of an on-going OR program could help toansweri questions )abou the tastea ox it and the effects on analready

gut A summa7ry oftheresearchgtlteraturerdcompromised alread

on this question II cent available appears as-AttachmentlltIgt

A danger orei the dbsinfectant iionddt straegyaisthateItsmay

starti- an=uncontrolled series of sugge t o s c n e i g vi a i l miner protein supplementation Theargument( mightb~ae

-) gtthat a childaswellwith diarrheafluid needsC theadto cetan L7Pnutrients as and4electrolytes

e was 4

Rwaeir i o bwtht e L r

Anothe caution raised whether the be74r4d

Ruca w s

i

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

POSSIBLE DISINFECTION OF ORAL REHYDRATION SOLUTIONS

Notes from November 13 1980 Meeting with

Drs Richard Cash and Lincoln Chen

Drs Cash and Chen began their discussion with DSHEA and WASH

staff by posing two questions The first question was

As drinking water in LDCs is often contamishynated should an effort be made to insure the potability of oral rehydration solutions

Dr Cnen presented data from the following studies which illusshy

trate that the growth of micro-organisms is supported in OR

solutions

1) Richard Guerrant in Brazil (now Department of Geograpk~ic

Medicine University of Virginia Charlottesville) foundJ

E Coli after 24 hours in concentrations of 105 per

100 ml in OR solutions made up by villagers regardless

of the initial purity of the water to which the salts

were added

2) Gerry Keusch actHarvard found the follcwing rumbers of

E Coli in various OR solutions Note These solutions

consisted of river water added E Coli and oral therapy

salts

Time (hrs) 1 4 8 16

E Ccli 1O1 10 1-10 106

The discussion then dealt with many questions about ORS and ORT

with potential for field research These questions are sununashy

rized in Attachment I

The first question raised was Are there negative effects (egreinf tion o prolongation of the diarrheal episode) of drinkingcontaminated ORS given that tne gut is already inflamed the answer to this question Js unknown but the suggestion was made that Mike Levine at the University of Maryland might be able toinclude an approach to this question in his volunteer diarrheal studies It should be noted however that the results of either animal or human adult studies of chis question might not be directly applicable to children under five thus one might argue Cfor using a natural experiment in an on-going oral rehydrationtherapy field project

Dr Cash pointed out that it is important to know at what pointthe water in the OR solution is contamirated at the water source in vessels used for transport from the source to the home during storage in the home by the person who mixes upthe solution (fingers spoon) or from the ORS salts themselves (especially since the ingredients sugar and salt are supportive of bacterial growth

If it can be assumed that the contamination of the solution during the mixing or from the salts is negligible what options could be considered for water purification eg adding a )actericidal agent to the water storage vessels in the home boiling the water to be used (this method was criticized because of its high fuel and time costs) addition of a disinfectant to the ORS packet Finally a paper has been recently received bythe Near East Bureau which suggests that exposure of the mixed solution to the suns ultraviolet irradiation for one hour has a significant bactericidal effect (see Attachment II) Does this approach appear to be feasible

Not much work has been done with regard to what substances mightbe used as a disinfectant in the ORS Vic Wehman mentioned potassium permanganate as a possibility Halogeas such aL

-2shy

r brominehave the t athyoidzchlori qe isahdvanag h

LI Queistions remain to beansered aotdsnetnstesle -4744 4 4 tO I11

hatsha dsnfectant(s would have ahigh i ishy

cidalviricidal- ac tivity be rr wth77e egrd to MIS compnerts not ne7gatielygt Th se its r 2774-gt 144)7th shef-lfe be- i ofthe OR acketedeffepycitoicvenes ofd-atne -lhug gt--

bullpaihtable beof low cpst bechemiclyi~rin i Arelation to n al ions frequently found in i cent

gt] untreated watex such as Fe i Mrn -i --

furhe imotnustoi Wa old be the effec ofthe 7 o ono the hetdisinfecsanteid inf gut

cidinraand reltd stiest evaluat the relative efetveness of vious

i-i7 disinfe ta ts undera variety ofsonditions -

Tes questionsviicidl researchable eare ativiy One might undertakelaboratiory-S

A laterfieldi study

aspart of an on-going OR program could help toansweri questions )abou the tastea ox it and the effects on analready

gut A summa7ry oftheresearchgtlteraturerdcompromised alread

on this question II cent available appears as-AttachmentlltIgt

A danger orei the dbsinfectant iionddt straegyaisthateItsmay

starti- an=uncontrolled series of sugge t o s c n e i g vi a i l miner protein supplementation Theargument( mightb~ae

-) gtthat a childaswellwith diarrheafluid needsC theadto cetan L7Pnutrients as and4electrolytes

e was 4

Rwaeir i o bwtht e L r

Anothe caution raised whether the be74r4d

Ruca w s

i

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

The first question raised was Are there negative effects (egreinf tion o prolongation of the diarrheal episode) of drinkingcontaminated ORS given that tne gut is already inflamed the answer to this question Js unknown but the suggestion was made that Mike Levine at the University of Maryland might be able toinclude an approach to this question in his volunteer diarrheal studies It should be noted however that the results of either animal or human adult studies of chis question might not be directly applicable to children under five thus one might argue Cfor using a natural experiment in an on-going oral rehydrationtherapy field project

Dr Cash pointed out that it is important to know at what pointthe water in the OR solution is contamirated at the water source in vessels used for transport from the source to the home during storage in the home by the person who mixes upthe solution (fingers spoon) or from the ORS salts themselves (especially since the ingredients sugar and salt are supportive of bacterial growth

If it can be assumed that the contamination of the solution during the mixing or from the salts is negligible what options could be considered for water purification eg adding a )actericidal agent to the water storage vessels in the home boiling the water to be used (this method was criticized because of its high fuel and time costs) addition of a disinfectant to the ORS packet Finally a paper has been recently received bythe Near East Bureau which suggests that exposure of the mixed solution to the suns ultraviolet irradiation for one hour has a significant bactericidal effect (see Attachment II) Does this approach appear to be feasible

Not much work has been done with regard to what substances mightbe used as a disinfectant in the ORS Vic Wehman mentioned potassium permanganate as a possibility Halogeas such aL

-2shy

r brominehave the t athyoidzchlori qe isahdvanag h

LI Queistions remain to beansered aotdsnetnstesle -4744 4 4 tO I11

hatsha dsnfectant(s would have ahigh i ishy

cidalviricidal- ac tivity be rr wth77e egrd to MIS compnerts not ne7gatielygt Th se its r 2774-gt 144)7th shef-lfe be- i ofthe OR acketedeffepycitoicvenes ofd-atne -lhug gt--

bullpaihtable beof low cpst bechemiclyi~rin i Arelation to n al ions frequently found in i cent

gt] untreated watex such as Fe i Mrn -i --

furhe imotnustoi Wa old be the effec ofthe 7 o ono the hetdisinfecsanteid inf gut

cidinraand reltd stiest evaluat the relative efetveness of vious

i-i7 disinfe ta ts undera variety ofsonditions -

Tes questionsviicidl researchable eare ativiy One might undertakelaboratiory-S

A laterfieldi study

aspart of an on-going OR program could help toansweri questions )abou the tastea ox it and the effects on analready

gut A summa7ry oftheresearchgtlteraturerdcompromised alread

on this question II cent available appears as-AttachmentlltIgt

A danger orei the dbsinfectant iionddt straegyaisthateItsmay

starti- an=uncontrolled series of sugge t o s c n e i g vi a i l miner protein supplementation Theargument( mightb~ae

-) gtthat a childaswellwith diarrheafluid needsC theadto cetan L7Pnutrients as and4electrolytes

e was 4

Rwaeir i o bwtht e L r

Anothe caution raised whether the be74r4d

Ruca w s

i

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

r brominehave the t athyoidzchlori qe isahdvanag h

LI Queistions remain to beansered aotdsnetnstesle -4744 4 4 tO I11

hatsha dsnfectant(s would have ahigh i ishy

cidalviricidal- ac tivity be rr wth77e egrd to MIS compnerts not ne7gatielygt Th se its r 2774-gt 144)7th shef-lfe be- i ofthe OR acketedeffepycitoicvenes ofd-atne -lhug gt--

bullpaihtable beof low cpst bechemiclyi~rin i Arelation to n al ions frequently found in i cent

gt] untreated watex such as Fe i Mrn -i --

furhe imotnustoi Wa old be the effec ofthe 7 o ono the hetdisinfecsanteid inf gut

cidinraand reltd stiest evaluat the relative efetveness of vious

i-i7 disinfe ta ts undera variety ofsonditions -

Tes questionsviicidl researchable eare ativiy One might undertakelaboratiory-S

A laterfieldi study

aspart of an on-going OR program could help toansweri questions )abou the tastea ox it and the effects on analready

gut A summa7ry oftheresearchgtlteraturerdcompromised alread

on this question II cent available appears as-AttachmentlltIgt

A danger orei the dbsinfectant iionddt straegyaisthateItsmay

starti- an=uncontrolled series of sugge t o s c n e i g vi a i l miner protein supplementation Theargument( mightb~ae

-) gtthat a childaswellwith diarrheafluid needsC theadto cetan L7Pnutrients as and4electrolytes

e was 4

Rwaeir i o bwtht e L r

Anothe caution raised whether the be74r4d

Ruca w s

i

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

UNICEF was quoted as estimating the cost of adding purifiers to be about 12 cent per packet or about a 130 increase in the cost of the UNICEF packet (now 64 cents) The money invested inadding disinfectants to ORS which at this time is not known to have any benefit might be used for example to provide

1) appropriate mixing containers or markers 2) improved [ublic education about ORT S3) greater numbers of packets 4) improved distribution strategies 5) assistance to countries to produce their own ORS packets

and 6) efforts to improve habits related to water supply and

personal hygiene

With these cautions in mind some discussion was then devoted to alternatives to any water purification strategy ie reducing the size of ie packet or instructing the mothers to dispose of the ORS solution after a specific period of time

The second question posed by Drs Cash and Chen as fundamental to the first one was

Does the provision of potable drinking waterimprove health (morbidity mortality nutrition and fertility)

Dr Chen commented that the frequency of diarrhea was nat a goodoutcome variable to use in water quality studies because of the cultural variability in definition of diarrhea and the physiological variability in susceptibility to diarrhea Quite simply there is no one-to-one correlation between the Dumber of micro-organisms in a quantity of water and the incidencz of diarrhea Many other variables having an impact on the overall level of health and nutritional status influence a persons susceptibility to diarrhea

-4shy

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

Dr CW suggested that measures cf nutritional status can be morvt prcsclsly Inasurej and are outcomes which might be used to

-i 1f improkeme-ritci in water supply actually improve healthDr Chn skttched out the schematic which appears below

to iilstrati h1i3 point

i2JrA-nclnt in

-Je ~ Impr-vermnt in food crops livestock availability

Dec -ase in timeF-)Ve Ltests laul Increase in it ------to time fmprovement--- a ailable for food __nutritional

--- preparation status

Declease in l-- Decrease in of calories food wastagethroug diarrhea -

FIg 1 Relationsip of improved water supply to improvednutritional status

T --tl -ended wi th the point being thatmade -lany questions re-u r-j ORT and ORS were not as yet answered not only qu stigt-) about the inclusion of lisinfe-tants Given what is no kvn there Jld not seem to be riuch support for including a Intnt in OilS pacvets although a shift in this opinionmil be Aarranted when further research has been done Drs CasI and Ch~en recom-- nd further study of ways to provide safe domiciliary wattr supplies and for rethinking the whole water supply and healti nodel

-5shy

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

ATCVET I POSSIBLE ORSORT RESEARCHI QUSIOS~

-V1 B-ndia

~1$i~Are there negative effec- (eg reinfection or prolong~tion$I~of the diarrheal episQde$) f4 ikik o t~iaeid 01W igiven thant the gut i-s ar inflamnedJ atiOpe nal-

termined by an iutprov~d quallty Qf0118) to cornbinOinstruct~ion of village hialth wQokers (VF~W) and mothers ~~vinpreparation and use-oV )RS with emphasis on use oi clean carrying andstrrage vessels VIIW training mightitlsp acludeteachiag w4ttr source protection and me thod S for Promoting iipxz ed riater use hibitso

b Is thee a mrovemen~4rn mothers learning about 0118 prepara c uii when teaching is done at the cliniclevelin comparison with teaching at homed Whatdone 7 teaching approaches and aids are most effective in eachsetting

3 io-chemical

a What chemical compounds and in what forms might be used for disinfection of water vessels in homes -

b What chemical1corpounds might 4be added to R-pcematerialslto pren thjrwhof micro organi~sms

Swhen the ~contents are mixed with contaminated - aterThe-se c~jSmpoundsl should be inert with respectio the-ORScomponents and metal ions found in-untreated water palatable and not negativelyr affect the4 -

sheif-life of the packet nor the inflamed gut C Mlight a less expensive and relatively safe chemical ~ W

compound be added which would suddenly change color ~-i0 when theOR solution reached a certain level of contamination

-

5 Product Development

4 Are theresignifi(cant advan~tages which canbe gainedbiy changing the ORS package size 4or shap~e

b What instructions are effective in insuring thtii the - - mother correctly mizes and uses ORS

c Are ther lginificani benefits to0f Ypigo -co-loringjthe ORS totmake it more acceptable as a

med c e~ for oralr r r~~ reh~d atFion

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

7- Hea It h

e te-w ob-- r W 9--- a--oo dreroalthaims fiA r te otla Z~c l nsr t sito promoiOandrfiain ofloralso recedratialn a eaRse~afo wtuld--h o pa d iahol s so control -

b t iOker

1)7 r Ix oraenst ad drt rnhliie of -du

-s ih is aadinroadst control

eofte cne

prrne wirh o pminte etr sbO tans porpared with i- w ton t-sur~ witiof-ngil rterebmmendedf orther-e an tsJIozsosd smal al soiuofprinsa healthhcae n

411l-e fo hom us ~ byi~ WHO

oeposurto ) ndhW halts b vedo sdi

out dzrio ato thf e orae eientsO nliter o s

containna tapwaofsalt-~exp s r o s n i h fR1 34gtsure tixunligrtcofne transparent bRy WOie inin thlrnpareet sunlih de strys b coteriae a pathi c1 ein insn Tese1 oluion wads thsered iontioneac eof5 teialelyfethene

In th-e- cSl~ theseofsime inexpenourse ofrasturrdy- on t-e nnschs o 15s teriife n efofRSo~~ii olythleo UAThesC~out Oxnaerda ofA ngedensegautdpt reparad withd ate Fec -hm r of bulk M Wre p aed is t9 shareou rsequ-stat-bullAnddcorse of arstudyt o tEnvrnetl HelhFau of --

Johris Ita t

preparean ofate Foer this proe1 ieswi coftaia D f-

RSwee yofbuk reard isovig~th rqusie~~nJn

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

Attachment II page 2

liters and have a wall thickness of 013 mm and screw cap closures Spectral transmittance curves of specimens of ti~e polythylene material as well as of polypropylene sheets and pyrex glass have shown that the high transmittance values fall appoximately in the range of 260 to 700 nm with minimum transmittance occuring below about 230 nm Accordingly the near UV light and the visible light components of sunlight would be transmitted equally well by containers made of these

ma tt-rials

Two experiments were run on different occasions according to tne following protocol 3 sets of 3 bags each were exposed to uirect sunlight 2 bags were kept in the dark and 2 others were kept under room conditions (artificial and natural light) Samples of the ORS bulk solution taken at 0 hr and of those contained in the experimental bags were examined bacteriologicallv at set intervals by applying techniques using solid media as described in Standard Methods Howeverin the case of the bags exposed to sunlight one bag from each of the three replicate sets was used for examination at the prescribed intervals to avoid any interruption of exposure to sunlight The results given in Tables I and II indicate that a zero coliform countml of ORS which is considered to be a rather stringent requirement were attained in about one hour Similar results were obtained in some 50 experiments using highly contaminated water contained in an assortment of vessels made of transparent glass or plastic and having different colours and shapes2 The rise in temparature of the test ORS not exceeding 5degC on exposure to sunlight for 2 hours leads to the conclusion that in this case heat is not a factor involved in the destruction of nicro-organisms It appears that the germicidal action is due to solar radiation in the

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

A t atW c Ism n

-4 iF ii 44

near UV range (300 to 460 nm) It was also sh~own b ayirha tht co did not undergo any~change in concent

3 b on -1hh aEItvalue of 833 remained

-t and C 6 -H)4 ar is notSir cantly affectedby this ecy-ne The t biI -oaltheRmf-h croorg ntihsms-- egrow-24shy

hours aftesolar irradiatin o for storage tra spor

supported y ev dgace deripsi ire2t l a4doldv

j4 4v 44 l~ h f - 0

p~c~repa rat lon of potable ORS the use oif 4 raduated 4 Vui-s I ale of transparent colourless_ or biu7 i~ce

Pllas1e oi- -ass presentsian additional advantagke Solar 1radiation of pollused water intended fbr ORS preparation and f drinking isisuggested as a useful alternative approach

4hich provides boLh curative and preventive measures

- ll 4) r 4 4444r~

We thank Kalouste GulbenkianFoundati_n Lisbon and DrPEugene rro a for thir-financiail and mopl Se -ectively

nioral sport r sp

o R4-

L i

i4

4

V - 44+ 44 4 = 44 ) i f a -lt )

[] p 444nm4m lil shy

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

ATTACHMENT III ORAL REHYDRATION FLUIDS TO DISINFECT OR NOT TO DISINFECT A PRELIMINARY REPORT OF A LIMITED LITERATURE SEARCH

Purpose of Search

Some conern has arisen over the question of the quality of water used for mixing oral rehydration fluids While oral rehydration has been proven effective in the prevention and treatment of dehydration from diarrhea authors are unanimous in recommending that the safest water possible be used in these solutions (Parker 1980 WHO 1978) and that a fresh solution be prepared at least every 24 hours (Wells et al 1980 Sack et al 197b Cash 1979) the latter to avoid problems of bacterial growth in fluids kept over prolonged periods That organisms can grow in ORS has been demonstrated by Wells et al (1980) V cholerae appears to grow less well because of inhibition by acid byshyprodcts of metabolism (Feldman 1980)

Te questic to be addressed by the literature search arn subseshyquent activities is therefore how best to assure safe water for use in mixing ORS Several optional approaches exist not all of which are equally advantageous They are discussed below

2tional Modes of Assuring Safe Water for ORS

Doing nothing

Parker et al (1980) suggests that the overriding importance of p-tting water and electrolytes into a dehydrated child makes relatively unLmportant the question of the quality of the water used so that a recortmendation to use the cleanest availshyable water and to dispose of any unused fluid after 24 hous is made

This approach however begs the question of how clean is clean Some communities with only very polluted water supplies as their option would be hard put to fulfill the cr-iteria

To do nothing implies that the possibility of introducing a new inoculum of potential pathogens to an already inflamed gastrointestinal tract posez no problem Despite the paucity of knowledge on the physiologic alterations attendant upon infection of the intestinal mucosa by various organisms it does appear that so-called secretory diarrhea is less vulnerable to the ill effects of a new dose of organisms than invasive diarrhea where the damage to tissues is more

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

Attachmeiit III page 2

severe Most infant diarrhea in developing counshytries is of the former type (Rowland and McCollum 197S) but one cannot rule out the latter in the individual case Nor can one rule out the possishybility of introducing a sufficient dose of an invasive organ ism

The size of the infective does must also be conshysidered Most investigators contacted felt that a dose of organisms sufficient to cause a renewed infection would be rare even without efforts to protect the water supply What seems to occur is a resurgence of symptoms 2-3 days after diarrhea has once abated with the use of ORS This phenomenon may reflect a lag in the growth rate of the newly introduced organisms (Sack 1980)

n the long run in terms of the ultimate oatcome of a given case of diarrhea the previous nutrishytional status of the infant probably exerts more influence than thte quality of water used in mixing the ORS

Boiling

A WHO working group (1975) recommends boiling and cooling any water of doubtful quality to be used in preparing ORS Because of thle obstacles of scarce and costly fuel time for the process and the urgency of getting fluids into the child however Cash (1979) and others recomend against using this option

What is needed then is more rapid yet effective disinfcttant

Adding a chemical disinfectant to the water

Iodine shows the most promise as a potential disshyinfectant to be included in ORS it holds several distinct advantages over chlorine or bromine

- it is more stable tha either Cl or Br

- It is much less reactive with tie glucose in the GRT package

- It is an excellent cysticidal as well as a bactericidal agent

Globaline (riglycine hydroperiodide) waamp suggested

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

Attachment III page 3

which has glucose

proand

ven ffectiproductive

venof

ss low minimal

reactivity change in

witji odor

and taste It was originally de-veloped for use in the cantqn disinfction program of the US Army

Johnn( iijest adding a sufficient c uantity of Globaline to (ORT packages to hardle waters of variable contamination ie a single amount plat-d in all packapes no matti-r what the quality ot wate-r The mor rol luted the- water the longer the- tanrding timfe necessary bfor us

Soevira1 quost ion ariiSe how ver in considering

th4 use of a disi ifrileetant

Wthat is the r-action of the compound with tht inflamd gut No satisfactory answer could b(- obtained with rfp-ct to either irritation of or increased absorption thrjukIt th inflmrd int(stin(

In view of the standi-V time necessary for more cortari na ted water where there is chance for a larger inoculum of orga n1 sn- aiad a gra t(-r bac terial growth potn tial in the ORS it might be better to arld t liinf-ctant to the water store-d in tho home (assuming such to be

Wider rami fi(cations

What of tli ps-ii iity of doing something of a m ) permanent nature about the quality of water availabe for mixing ORS7 There is a trend in ORT ci lo toward morf community level packaging and ditribution of oTr packets Despite problems of impurities short sholf life and less quality control the involvmeint of local people and the posibility of disp-lling the aura of a magical cure make this approach attractive

A workshop on Integrating Oral Reh ydration Therapy into Community Action Prorams (Washington DC 19-21 Mvarch 19J0) discuss-i the realtive advanshytages and disadvantagfs of various means of mixing and distributing O(T packets No conclusions were r0-ache-d although comnunity-based systems were emphas zed Surprising was the failure to even mention focusing community action on the quality of water used whether at the source in transport or in domestic storage Unless community based proshy

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

Attachment III page 4

grams of preventing and treating diarrhea and dehydration encompass these concerns programs willbi rermanently dependent upon the use of disinfecshytants

Raymond B Isely MD MPH DTM Associate Director Water and Sanitation for Realth Project

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely

ATTACHMENT IV ATTENDEES AT MEETING ON DISINFECTION OF ORAL REHYDRATION SOLUTIONS 13 DECEMBER 1980

AID - OFFICE OF HEALTH

Mr Manoj Batavia Is Dayl Donaldson is Veronica Elliott Mr Donald Ferguson Mr F Eugene McJunkin Dr Clifford Pease Dr Irving Taylor Ms Anne Tinker Mr Victor Wehman Ms Kate Jones-Petron

OFFICE OF POPULATION

Mr Duff Gillespie

BUREAU FOR LATIN AMERICA

Ms Julie Klement

BUREAU FOR ASIA

Dr George Curlin

BUREAU FOR THE NEAR EAST NETECH

Dr William Oldham

HARVARD SCHOOL OF PUBLIC HEALTH

Dr Richard Cash Dr Lincoln Chen

WASH CIC

Dr Raymond Isely


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