Malnutrition is a determining factor in diarrhealduration, but not incidence, among youngchildren in a longitudinal study in ruralBangladesh1 -3
Robert E Black, MD, MPH, Kenneth H Brown, MD, and Stan Becker, PhD
ABSTRACT Diarrhea and malnutrition are common in young children in developingcountries and a reciprocal relationship has been postulated with diarrhea leading to malnutritionand malnutrition predisposing to diarrhea. To investigate the importance of malnutrition as adetermining factor in diarrheal illnesses, data were analyzed from a longitudinal community-based study done in rural Bangladesh. Children classified by nutritional status according to avariety of anthropometric indicators were prospectively evaluated for incidence, duration, andetiology of diarrhea. Children with low weight for length had longer durations of diarrhea thanbetter nourished children; however, children of differing nutritional status had similar diarrhealincidences. The duration of diarrhea, including that associated with enterotoxigenic Escherichia
co/i and Shigella, increased progressively as nutritional status indicators worsened. These resultssuggest that nutritional interventions alone are unlikely to reduce the high incidence of diarrhea,but that efforts to improve nutritional status may have a beneficial effect on the duration ofdiarrhea and its unfavorable nutritional consequences. Am J C/in Nuir 1984;39:87-94.
KEY WORDS Infantile diarrhea, Escherichia co/i, malnutrition, nutritional status, Shigella
Introduction
Diarrheal diseases and malnutrition arecommon in children ofdeveloping countriesand an interaction between them has beenpostulated (1 , 2). Diarrhea has been foundto have an adverse effect on growth and tobe an important cause of malnutrition (3-5). At the same time, malnourished childrenhave a greater severity of diarrhea (6) andan increased risk of death from a variety ofinfectious diseases, including diarrhea (7, 8).
Several field studies have suggested thatnutritional status is a determinant of theprevalence of diarrhea (9-1 1). An increasedprevalence of diarrhea could be due eitherto an increased incidence of diarrheal epi-sodes or to a longer average duration ofillness, but few previous studies have exam-med these factors separately. Furthermore,the limited reported results are not consist-ent. One study in Guatemala (12) found anincreased incidence of diarrhea in under-weight (lower weight for age) children 1 to 4
yr old, but three other studies did not find a
I From the Center for Vaccine Development (REB),University of Maryland School of Medicine, Baltimore,MD 21201; the International Centre for DiarrhoealDiseases Research (REB, KHB, SB), Bangladesh,Dhaka, Bangladesh; and the Division of GeographicMedicine (KHB), Department of Medicine and Gastro-enterology and Nutrition Unit, Department of Pediat-rics, School of Medicine and Division of Human Nu-trition, Department of International Health, School ofHygiene and Public Health, Johns Hopkins University,Baltimore, MD 21205
2 The field work of this study was supported bythe International Centre for Diarrhoeal Diseases Re-search, Bangladesh (ICDDR,B), and by NIH Grant5RO7AI10048-17. REB undertook the field work whileassigned to the ICDDR,B from the Bureau of Epide-miology, Centers for Disease Control, Atlanta, GA. Theanalysis was supported by the Center for Vaccine De-velopment and by the Rockefeller Foundation. Thecomputer time for this analysis was supported in partthrough the facilities of the Computer Science Centerofthe University of Maryland.
3 Address reprint requests to: Dr R Black, Center forVaccine Development, University of Maryland SchoolofMedicine, 29 S Greene Street, Baltimore, MD 21201.
Received April 8, 1983.Accepted for publication July 26, 1983.
relationship between young children’s rela-tive weight and their diarrheal incidence (9,13, 14). A study in Nigeria (9), but not onein Bangladesh (14), found an increased diar-rheal incidence in wasted (low weight forlength) children. Although several field stud-ies have suggested that malnourished chil-dren may have diarrheal episodes of longerduration, the use in most of these studies ofa recall period for diarrheal occurrence of 1wk (or more) and the lack of precise criteriafor the beginning and end ofdiarrhea renderthe data on diarrheal duration of question-able value. Several hospital based studiesindicated that cholera had a longer durationin both children and adults with poorer nu-tritional status than in better nourished pa-tients (15-17).
Since previous field studies of nutritionalstatus as a risk factor for diarrhea have notdetermined the etiological agents associatedwith the illnesses, it is also possible that theincreased prevalence of diarrhea in mal-nourished children is due to their greaterpropensity to have specific types of diarrhea(eg, shigellosis or giardiasis) that are associ-ated with a longer illness. Alternatively, in-testinal malabsorption, frequently associ-ated with severe malnutrition, may be re-sponsible for noninfectious diarrhea in themore undernourished children. Thus, stud-ies to determine if malnourished childrenhave an increased incidence or duration ofdiarrhea need to consider illnesses due tospecific enteropathogens. We assessed theincidence and duration of diarrhea associ-ated with bacterial, viral and parasitic path-ogens in a longitudinal study in rural Bang-ladesh ( 1 8). Two agents, enterotoxigenicEscherichia co/i (ETEC) and Shigella, ad-counted for more than 40% of diarrhealepisodes in children less than 5 yr old in thestudy communities (19).
Since classification of children’s nutri-tional status based on weight as a percentageof the expected weight for a child ofthat agedoes not permit a differentiation betweenacute and chronic undernutrition, we class-ified children according to a wider variety ofindicators. Relative weight for age, lengthfor age, and weight for length were used, aswas a cross-classification of these indicatorsto establish categories of children who were
normal, wasted, stunted, or concurrentlywasted and stunted as proposed by Waterlowet al (20). Children so classified were pro-spectively evaluated for the etiology, mci-dence, and duration ofdiarrhea occurring insubsequent 60-day periods.
Methods
The study was conducted in two villages in theMatlab field research area of the International Centrefor Diarrhoeal Diseases Research, Bangladesh(ICDDR,B) between March 30, 1978 and March 28,1979. The study was approved by the ethical reviewcommittee of the ICDDR,B and by the BangladeshMedical Research Council. Informed consent was oh-tamed to include 177 (94%) of the 188 available chil-dren between 2 and 48 months of age in the villages.Twenty additional children joined the study group dur-ing the year, for a total of 197 children participating inthe study. One hundred twenty-five children were lessthan 24 months old (18). Descriptions of the villages,study population, surveillance methodology, and labo-ratory procedures have been published (18, 19, 21, 22).An episode of diarrhea was defined when four or moreliquid stools were passed on at least 1 day; the episodewas considered to be resolved on the 1St day with fewerthan three liquid stools. However, if a child had threeor more liquid stools on any day within 3 days after anepisode ofdiarrhea, that day and intervening days wereincluded in the same episode. Enteropathogens wereconsidered to be associated with a diarrheal episode ifthey were identified from a specimen obtained duringor 1 day before or after the episode.
Monthly measurements of each child’s physicalgrowth were obtained by standard techniques (23, 24).Briefly, nude or lightly clothed children were weighedto the nearest 0. 1 kg on a Salter scale, which wasfrequently standardized against known weights. Recum-bent length was measured to the nearest 0. 1 cm on awooden platform with a sliding footboard. Sex-specificdata for weight and length for age and weight for lengthwere compared with the data from the National Centerfor Health Statistics (NCHS) population (25). Statisticsfor recumbent length were available from the NCHSsample only for children up to 36 months ofage, so theStuart and Meredith (26) reference population was usedfor children over 36 months ofage. Measurements wereexpressed as a percentage of the NCHS (or Stuart andMeredith) median or as multiples of the standard de-viation (Z score)4 of the reference population. Finally,measurements for weight and length, expressed simplyas more or less than 2 SD below the NCHS medianweight for length and length for age, were used for across-tabulation. Children with weights more than 2 SDbelow the reference median weight for length wereconsidered wasted and those more than 2 SD below thereference median length for age were defined as stunted.Other children were considered “normal.”
observed weight for length-reference weight for length
Since the children’s nutritional status demonstratedmarked seasonal changes (24), children were classifiedinto nutritional status groups at the beginning of con-secutive, nonoverlapping 60-day periods. Six such pe-riods(l yr) were usually available for each child. Periodsin which the child was less than or at least 24 monthsold at the beginning of the period were analyzed sepa-rately. When episodes of diarrhea began in one 60-dayperiod but continued into the subsequent period, allcontiguous days of illness were used to determine thetotal duration h�t the episode was only counted in thefirst period. The incidence and average duration of alldiarrheas and of diarrheas associated with ETEC andShigella were calculated for specific groups and com-pared using I tests, Z tests for differences in proportionsand analyses of variance (27).
Results
For children less than 24 months old, themean duration of diarrhea in the lowestweight for length group (less than 80% ofthe NCHS standard) was 56% longer thanthe duration for children who were at least90% of the standard (Table 1). Consideringetiology, there was an increase of more than150% in the duration of ETEC and Shigella
diarrheal episodes (both p < 0.05). The in-cidence of all diarrhea or of diarrhea asso-ciated with ETEC or Shigella did not differamong the groups.
With weight for age and length for agegroupings, trends toward longer durations inless well-nourished children were also appar-ent; however, the durations were signifi-cantly different only for ETEC diarrhea (Ta-
TABLE I
ble 1). Again, the groups did not differ indiarrheal incidence.
Children were classified by their Z scoreof weight for length, weight for age, andlength for age to determine more preciselyhow diarrheal duration varied as a functionof nutritional status. As shown in Figure 1,the duration of ETEC diarrhea declined pro-gressively as the Z score increased for eachof the anthropometric measures. Comparedwith the best nourished group, the averageduration of ETEC diarrhea was significantlylonger for weight for length groups of lessthan - 1 Z score, for length for age groupsof less than -2 Z scores, and for weight forage groups ofless than -3 Z scores. Betweenthe highest and the lowest weight for lengthz score groups, the average duration ofETEC diarrhea increased from 4.8 to 17.2days. Similarly, the average duration of alldiarrhea increased from 7. 1 to 10.3 days andof Shigella diarrhea from 6.5 to 2 1.3 days.
When children were grouped by both theirweight for length and length for age, thosewith wasting or concurrent wasting andstunting had the longest durations of diar-rhea (Table 2). Those who were stunted butnot wasted had a slight increase in diarrhealduration compared with normal children.The groups did not differ in their diarrhealincidence.
The diarrheal duration and incidence forchildren more than 24 months of age did
Duration (days) and incidence (episodes per 1000 days) ofall diarrhea and ofdiarrhea associated withenterotoxigenic Escherichia co/i or Shigella in 60-day periods after classification of children <24 mo old bynutritional status
FIG 1. Duration of diarrhea associated with enterotoxigenic E co/i by indicated anthropometric Z scores(NCHS/Center for Disease Control reference) in children less than 24 months old.
TABLE 2Duration of all diarrhea and ofdiarrhea associated with enterotoxigenic E co/i or Shigella in 60-day periods afteranthropometric cross-classification of children <24 mo old by wt for length and length for age Z scores
Anthropometric classification All diarrhea E co/i diarrhea Shigella diarrhea
* Significant differences (p < 0.05) found for duration of E co/i diarrhea in normal vs wasted children and vs
stunted children.
not vary according to their nutritional status.The best nutritional status groups for weightfor length had average durations of all diar-rhea, ETEC diarrhea and Shigella diarrheaof9.7, 9.2, and 12.3 days, respectively. Com-pared with younger children, these durationswere 2 to 4 days longer than the averagedurations of the corresponding best nour-ished groups of children, but similar to themoderately malnourished groups.
Discussion
Anthropometry is often used to evaluatethe nutritional status of children in a com-munity (28, 29). Ofthe wide variety of meas-
urements that can be taken, weight andlength (or height) are the most frequentlyused (20). The child’s weight is often com-pared with an international reference popu-lation and expressed as a percentage of thereference median weight for age as describedby Gomez et al (30) or as a Z score (20).The use of the child’s relative weight for ageis limited because it does not discriminatebetween acute and chronic malnutrition.Thus, the use ofweight for length, a measurethat could reflect a more recent nutritionalinsult, has been recommended (20). A fur-ther refinement is the cross-classification ofchildren based on their relative length forage (to assess stunting) and weight for length
(to assess wasting) (20). It has been assumedthat children with wasting or concurrentwasting and stunting would be at the highestrisk for the adverse consequences of acutemalnutrition. Indeed, it has been demon-strated that wasted children have higherrates ofmortality (7, 8).
Among children in the first 2 yr of life inthis study, the child’s relative weight forlength, ie, degree of wasting, was the strong-est anthropometic predictor of diarrheal du-ration. Even children between - 1 and -2SD below the reference median had a longerduration ofETEC diarrhea than better nour-ished village children. Furthermore, meandurations increased progressively as the Zscore declined. Our study was unable todetermine if there is a threshold level ofwasting below which there is a substantialincrease in diarrheal duration. The deter-mination of such a threshold would be ofuse to establish a cutoff value for anthropo-metric screening programs. At this point, itwould appear that children more than 2 Zscores below the median weight for lengthcan be identified as being at increased riskof prolonged diarrhea after an acute entericillness.
No relationship was found between nutri-tional status and the incidence of diarrheain general or of ETEC or Shigella diarrhea.The incidence of diarrhea is determined bythe number of pathogens ingested (3 1) andby host factors, such as by the level of gastricacidity (32) and the state of intestinal im-munity (3 1). One might expect that mal-nourished children would have greater ex-posure to enteric pathogens because of theunsanitary conditions of poor communitiescompared with the residences ofbetter nour-ished and wealthier children. However, allchildren in this study lived in the same vil-lages and were exposed to the same vehiclesof infection, such as fecally contaminatedfood and water (22). Although hypochlor-hydria has been reported in children withsevere protein-energy malnutrition (33),there is little evidence that moderatelywasted children, such as we studied, havesufficiently reduced gastric acid to increasetheir risk of diarrheal diseases. It is alsounlikely that immunological factors sub-stantially influence the risk of diarrhea in
these young children. There are many dif-ferent bacterial, viral, and parasitic agentsresponsible for diarrhea and the ETEC andShigella identified in this study were of manydifferent serotypes (Black RE, unpublisheddata). Since the natural immunity that doesdevelop is probably pathogen and even ser-otype specific (34, 35), it is unlikely thatyoung children have sufficient immunity toprevent many illnesses from occurring (19,36).
The fact that wasted children have longerdurations of diarrhea has several possibleexplanations. The duration of diarrhea maybe a function of the number of bacteria thatenter the small intestine (which probably didnot differ according to nutritional status inthese study children) and certain host fac-tors, such as the rates of immune responseand intestinal repair. Severely malnourishedchildren have been shown to have defects incell-mediated immune function (37-40), areduced secretory IgA response of the respi-ratory tract (41, 42), and a decrease in IgA-containing cells in the jejunal mucosa (43).Since even the best nourished groups ofolder children have diarrheal durations sim-ilar to moderately wasted younger children,immunity, which should be better developedin older children, is not a likely explanationfor the nutrition-related differences in diar-rheal duration.
A possible explanation is that malnour-ished children may have delayed recovery ofthe intestinal mucosa after infection. Brun-ser et al (44) noted a decreased mitotic indexof mucosal cells in marasmic children. Aslower turnover rate for intestinal cellswould be expected to cause a delay in re-placement of damaged enterocytes and cor-rection of functional abnormalities that re-suit from tissue invasion during Shigella orviral diarrheas or from the effects of cell-bound toxin during ETEC diarrhea or chol-era. Such a delay in mucosal recovery couldresult in a more prolonged diarrhea.
Another possible explanation for thelonger diarrhea in relatively malnourishedyoung children is persistent lactose malab-sorption (45, 46) which has been identifiedin one study as the most common reasonfor prolonged diarrhea after an acute entericillness (47). In an earlier study from the same
area of rural Bangladesh, it has been ob-served that diarrhea-free young childrenwith a lower weight for length had a higherfrequency oflactose malabsorption than bet-ter nourished children of the same age (48).After 36 months of age, a high proportionof all children regardless of nutritional sta-tus, had lactose malabsorption. Thus, theeffect of diarrhea on lactose absorptionshould be most pronounced in young chil-dren, who usually have normal lactose ab-sorption if they are well nourished, but re-duced absorption if they are wasted. Thepredominant source of dietary lactose wasbreast milk, which was consumed by nearlyall children younger than 24 months old,both when they were free from illness (49),as well as during diarrhea (Brown KH, un-published data). Since breast-feeding wasuniversal in young study children, the pos-sible roles ofbreast milk either in prolongingdiarrhea (because of lactose malabsorption)or in shortening diarrhea (due to transfer ofpassive immunity to the infant) could notbe investigated.
It is said that a reciprocal relationshipexists in which diarrhea leads to malnutri-tion and malnutrition predisposes to diar-rhea (2). It is clear that diarrhea has adverseeffects on growth (3-5). ETEC diarrhea hadthe most pronounced effect on short-termweight gain and Shigella diarrhea had thelargest effect on annual linear growth inthese study children (5). The previous evi-dence that malnutrition increased the mci-dence ofdiarrhea was mixed and we did notobserve such an effect vis-#{227}-visall diarrheaor the two most frequent types of diarrheaaffecting the study children. Malnourishedchildren did, however, have diarrhea oflonger duration. This longer duration couldalso explain the increased prevalence of diar-rhea that has been noted previously in mal-nourished children. More prevalent diar-rhea, especially ifassociated with malabsorp-tion of lactose and possibly other nutrientswould in turn be expected to exacerbatemalnutrition.
These findings have implications for pub-lic health programs seeking to control mor-bidity and mortality of children in develop-ing countries. Nutritional interventionsalone are not likely to reduce the high mci-
dence of diarrhea. However, efforts to im-prove nutritional status may be successful inlimiting the duration of diarrhea and itsnegative nutritional consequences. Further-more, these results suggest that more mdi-vidualized nutritional and fluid and electro-lyte management of diarrhea may be mdi-cated for malnourished children. fl
The authors are grateful for assistance from theworkers of the Matlab Field Station and from thelaboratory personnel of ICDDR,B. We would also liketo thank Mr E Chan for computer programming andDrs WB Greenough, MM Levine, RB Sack, and GGraham for support and advice during the analysis ofthese studies.
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