Cases and Rates in 1991

Table 6

Population: ?• New SM +: N = 8,507• All Cases: N = 10,903

Table 8

Population: ?• New SM +: N = 8,835• All cases: N = 10,872

Table 7

Population: 8,904,395• New SM +: N = 8,103• Rate = 91/100,000• All Cases: N =11,036• Rate = 123/100,000

Rate SM + : 220 - 20

Rate All : 276 - 26

Cases and Rates in 2009

• N SM +: N = 17,863

• Rate N SM + = 133/100,000

• All forms: N = 38,770

• Rate All forms: 289/100,000

• Source cases: Page 9 R10 proposal

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

1 3 5 7 9 11 13 15 17 19 21 23 25 27

NOTIFICATIONS ASIAM 1982-2008

ALL FORMS

SMEAR POSITIVE (N+R)

NOTIFICATIONS/100,000 ASIAM 1982-2006

ALL FORMS

SMEAR POSITIVE (N+R)

0

50

100

150

200

250

300

1 3 5 7 9 11 13 15 17 19 21 23 25 27

NOTIFICATIONS/100,000 ASIAM 1982-2008

ALL FORMS

SMEAR POSITIVE (N+R)

Average Prevalence 1981-1989

Table 5:

• Survey population: N = 71,398

• Smear-positive cases: N = 374

• Prevalence smear-positive cases

= 520/ 100,000 population

Note:

Table 4: ARI in 1970 between 4.7 and 2.7 !!

Prevalence in 2001

• SM+: 270/100,000

• Cult+: 902/100,000

• CDR SM +: 124/270 = 46%

• Trend of prevalence:

520 (81-89) > 270 (01)

True decline or unreliable survey data?

Conclusions

The TB problem is still serious as:• Notification rate SM+ = 91/100,000 in 1991

(74% of all cases are new smear-positive)• Notification rate SM+ = 141/100,000 in 2000• Prevalence rate of SM+ 81-89 = 520/100,000• Prevalence rate of SM+ 2001 = 270/100,000 • HIV + TB: 2.5% in 95 > 8.9% in 2000 > 10.3 in

2001

Observations

• Trend of notifications 82-91 is inconclusive

• New SM+ notification rate in 1991< 20% of SM + prevalence rate (1981-1989)

• Rate SM+ ranges from 220/100,000 in province 1 to 17/100,000 in province 17

• 20% of cases are registered in the capital

• 36% of cases in the capital are > 54

Observations

• Trend of notifications 92-2004 steady increase

• DOTS introduced in 1994

• In 2004 ~ 50% of prevalent cases detected

• Still considerable differences between provinces

• TB problem increasing due to HIV

Final Conclusions

• The TB problem in Asiam is serious

• The NTP in Asiam detects only 50% of the prevalent cases

• Case-detection in a number of provinces is very low

• How to increase coverage and detection?

Problem description and Situational analysis

• TB prevalence survey data

• Tuberculin survey data: prevalence of infection with M.tuberculosis

• Case notifications recent and past years

• Age, Gender, Area differences

• Rates and trend

• Drug resistance survey data

• HIV prevalence, incidence and trend

Conclude:

• Size of TB problem: High, medium, low?

High: > 50 new sm+ cases/100,000 per yr.

Low: < 10 new sm+ cases/100,000 per yr.

• Trend: Increase, decrease, stable?

• Program coverage: % of districts?

Estimate number of expected TB notifications

for each year during plan period! (3 to 5years)

Block 5

1. 8,507/38,868 = 22% (see table 6, set I)3. 93/171 centers = 53% (see table 10, set I)4. 38,868 x 3 = 116,604 : 260 = 448 : 93 = ~ 5

(4.8)5. 9,000,000 : 100,000 = 90 x 520 = 46,800 x 35%

= 16,380 x 30 = 491,400 : 260 = 1,890 : 93 = 20,3

Yes the number is sufficient

Block 5

6. Positive suspects 33.6% (2002 review, 18)

7. 141 microscopy centers (2002 review, 14)

8. 15,640 : 33.6 x 100 = 46,548 x 3 = 139,642 : 260 = 537 : 141 = ~ 4 (3.8)

9. 12,014,000 : 100,000 x 270 = 32,438 x 70% = 22,706 x 30 = 681,194 : 260 = 2,620 : 141 = 18,6

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

1 2 3 4 5 6 7 80

5

10

15

20

25

30

suspects

sputum positivity rate

smear positive cases

% population examined

0.1

1

10

100

1 2 3 4 5 6 7 8

sputum positivity rate

proportion of population examinedby direct microscopy

Population examined and positive suspects 1980-1991 (table 6, data set I)

00.10.20.30.40.50.60.7

1980 1982 1984 1986 1988 1990

0

5

10

15

20

25

% of population examined % of suspects positive

year Suspects examined

Positive suspects

% positive suspects

% of population examined

Positive suspects

per 100,000

population 1997 80 22 27.5 0.12 33.8 1998 172 32 18.6 0.27 50.2 1999 230 24 10.4 0.35 36.4 2000 580 20 3.5 0.82 28.2 2001 393 24 6.1 0.56 34.2

RESULTS OF DIRECT MICROSCOPY IN DISTRICT X FROM 1997 TILL 2001

0.1

1

10

100

1000

suspects examined

positive suspects

positivity rate

% population examined

Relation between positivity rate and %

population examined

PARAMETERS FOR PLANNING THE MICROSCOPY NETWORK

• Expected number of smear-positive cases • As a rule one centre per 100,000 population

if case-notification rate of smear + cases =

50/100,000• 3 smears per suspect• Number of smears per technician per day:

Not more than 20• Minimum requirement one positive case per

week per reader in view of proficiency

PARAMETERS FOR PLANNING THE MICROSCOPY NETWORK

• Workload and smear-positivity rate (SPR):

SPR 20% = 1 positive case per 5 suspects = 15 smears to diagnose one sm+ case

SPR 5% = 1 positive case per 20 suspects = 60 smears to diagnose one sm+ case

• Screening of suspects by X-ray?

• Number of existing microscopy centres

• Available technicians and available time for direct microscopy per centre

Conclude:

• Number of microscopy centres sufficient or not? If not how many more needed?

• Available technicians and time sufficient or not? If not train and employ more or ensure more time of available technicians

• Calculate need for microscopes, slides, cups, reagents, slide boxes, laboratory equipment, immersion oil, etc.

External Factors Influencing Smear-Positivity Rate

• Prevalence of Tuberculosis in community

• Prevalence of other conditions causing a chronic cough

• Patients delay/doctors delay

• Selection of suspects

• Active CF surveys

Duration of cough as criteria

Screening of suspects by X-ray

Laboratory Factors Influencing Smear-Positivity Rate

False Positive Results

Acid Fast Particles other than TB bacilli

Food particles

Precipitated stains (filter, use fresh stains)

Saprophytic acid-fast bacilli (distilled water)

Spores, fibers, pollen

Scratches on slide (always use new slides)

Contamination

Laboratory Factors Influencing Smear-Positivity Rate

False Negative Results

Inadequate sputum collection

Selection of particles from sputum

Inadequate storage of sputum specimens and stained smears

Inadequate preparation of smears or staining of slides

Inadequate examination of the smear

Laboratory Factors Influencing Smear-Positivity Rate

False Negative Results

Administrative errors

Reading errors

Time spend on reading

Work load

Labserialnumber

Diagnosis Follow up 1 2 3

x + +

x Neg Neg Neg

x Neg

x +

x Neg + +

Indicators to evaluate microscopyusing the laboratory register

• % of population in the district examined per year by direct microscopy =

suspects in the register (one year)

-------------------------------------------- x 100

population of the district in that year

• Value: 0.6 to 0.9 (Note:Vietnam data)

Indicators to evaluate microscopyusing the laboratory register

• Distribution of positive smear results

80-85% of positive cases show positive in the first smear

Few (~ 5%) positive cases show positive in the third smear only

This distribution should normally appear in

the laboratory register, if not this should be

investigated

Indicators to evaluate microscopyusing the laboratory register

• Smear-positivity rate:

N suspects with positive smear

result(s) during a quarter or year

--------------------------------------- x 100

N suspects examined during

a quarter or year

• Value usually observed: 5 to 15%

Indicators to evaluate microscopyusing the laboratory register

• % of suspects with three smear results

N suspects with 3 smear result(s) during a quarter or year --------------------------------------- x 100N suspects examined during a quarter or year

• Value: Target 100%. Observed in good programs 85-90%

Further use of laboratory register

• Calculation of proportions of suspects by

Gender

Age-groups

Distance to microscopy centre• Time between first examination and diagnosis• Number of examinations per day/ month• Requirements of slides and materials

Link with TB register

• Serial number of laboratory book in TB register and TB registration number in laboratory register

• Are all diagnosed SM + cases (new and previously treated) put on treatment?

• Average time between diagnosis and start of treatment

• % of negative suspects put on treatment

Case of tuberculosis

• A definite case of TB, or one in which a clinician has diagnosed TB and has decided to treat the patient with a full course of TB treatment

• Note: Any person given treatment for tuberculosis should be recorded

A definite case of tuberculosis

• Patient with positive culture or positive LPA test for the Mycobacterium tuberculosis complex

• In countries where culture is not routinely available a patient with one or more initial sputum smears positive for acid fast bacilli (AFB+) is also considered a definite case

Smear positive pulmonary case

• At least one initial sputum smear examination (direct smear microscopy) with at least one AFB provided that there is a functional EQA system with blind rechecking

STAG 2007

New definition of smear-positive PTB

One smear

with at least

one AFB

in 100 fields

Smear-negative pulmonary case

Sputum smear-negative, but culture positive

At least 2 sputum specimens at the start of treatment with functional EQA, high workload and limited human resources

Sputum culture should be performed in settings where HIV > 1% in pregnant women or > 5% in TB patients

Smear-negative PTB case (B)

Decision by a clinician to treat with a full course of anti-TB therapy

X-ray suggestive for active TB and patient is HIV+ (laboratory or clinical evidence)

X-ray suggestive for active TB and no improvement after antibiotics in HIV-negative patients

STAG 2007

New definition of smear-negative PTB

When two smears are negative follow algorithm

for the diagnosis of

smear-negative tuberculosis

Extra-pulmonary case

• Patient with tuberculosis of organs other than the lungs e.g. pleura, lymph nodes, abdomen, genito-urinary tract, skin, joint and bones, meninges

• Note: a patient diagnosed with both pulmonary and extra-pulmonary tuberculosis should be classified as a case of pulmonary tuberculosis

EPTB

• Diagnosis of EPTB should be based on one culture positive specimen, or histological or strong clinical evidence consistent with active extra-pulmonary disease, followed by a decision by a clinician to treat with a full course of anti-tuberculosis chemotherapy

New Case

• Patient who has never had treatment for tuberculosis, or who has taken anti-tuberculosis drugs for less than one month

Previously treated case

• Received 1 month or more anti-TB drugs

• May be smear-positive or –negative

• May have TB at any site

• Further defined by treatment outcome:

• Relapse, Failure and Default

• Note: classification “Chronic” stopped

Indicators for quality of Diagnosis

• Proportions of New SM +, SM - and EPTB depend on efficiency of CF and diagnostic methods used

• Proportions reported by well organised NTP’s are:

60-70% New smear-positive PTB

20-30% New smear-negative PTB

10-20% New EPTB

Indicators for quality of Diagnosis

• Ratio New SM +/New SM- PTB

N new smear-positive TB cases

---------------------------------------

N new smear-negative TB cases

• Value: normally 2 to 2.5, but often lower in high HIV prevalence countries

• Minimum acceptable level 1 to 1.5

Indicators for quality of Diagnosis

• In high HIV-prevalence countries the proportion of EPTB may be higher due to a higher frequency of Pleural Effusions and miliary TB

• Diagnosis of EPTB depends further on clinical capacity, preferences of clinicians and focus on childhood TB

Indicators for quality of Diagnosis

• A SM+/SM- PTB ratio of <1 may indicate that SM- cases are diagnosed without microscopy (X-ray and clinical diagnosis)

• The proportion of relapses: should be < 5-7% of all cases reported or less than <10% of new smear-positive cases reported

• A high proportion of previously treated cases is an indication of poor program and/or poor private sector performance

Block 8: Strategies for DOT• Population 2000: 12,014,000 (table 3. set II)• Cases detected: 18,892 (table 3. set II)• HC’s: 90% x 632 = 569 (table 7. set II)• Area Asiam: 181,035 sq.km. (table 1. Set II)• Area 5 km radius = 3.14 (π) x 5 km² = 78,5

x 569 = 44,667 : 181,035 x 100 = 25% (30% if 115 hospitals also provide A-Dots)

• Beds: 18,892 x 75% = 14,169 : 6 = 2,362• (19 to 21 beds per hospital: 2,362 : 115)

Advantages of SCC

• Lower case-fatality (high sterilising effect)

• Lower relapse rate (role of pyrazinamide)

• Lower default rate (shorter duration)

• Intermittent (3 x per week or on alternating days) as effective as daily treatment

• Effective in HIV+ TB cases (only daily!)

• DOT is essential to prevent R resistance

Intensive phase

• Sterilizing phase to reduce the bacillary load as quick as possible

• Always treat with combination of at least 3 drugs to prevent development of resistance

• Recommended by WHO: 2EHRZ

• EHRZ FDC tablets have been developed in recent years

Continuation phase

• Maintenance phase to take care of dormant bacilli (persisters)

• Always treat with at least 2 drugs

• Duration defined by relapse rate in sensitive patients

• 2RH > 15% relapse rate

• 4RH < 5% relapse rate

Consider how to ensure DOT

• Hospitalise patients during intensive phase?

Consider costs for health service, patients and availability of beds

• Ambulatory treatment at PHC facilities?

Consider feasibility in view of access

• Community based DOT?

Consider presence of volunteers and costs of training and supervision of volunteers

Decide:

• Using Fixed Dose Combination tablets

(ERHZ) or (RHZ) instead of loose formulations?

• Using blister packs?

• Consider costs, logistics, training of staff and revision of guidelines

What is cohort analysis?• A cohort: A group of patients diagnosed and

registered for treatment during a given time period usually one quarter of a year

• Cohorts are defined by: period, type of TB, type of treatment, age, gender, income, etc

• Cohort analysis: Evaluation of treatment outcome when all patients in the cohort have finished treatment and results are collected

Treatment outcome: Cure rate• Initially smear-positive patient who has a

smear negative result in the last month of treatment, and on at least one previous occasion

• Value: > 85% in low HIV prevalence countries, > 80% in high HIV prevalence countries

• A high cure rate is the result of a combination of low other outcome rates!!

Treatment outcome: Treatment completion rate

• Patient who completed treatment but does not meet the criteria for cure or failure

• Depends essentially on the proportion of patients producing sputum during the last month of treatment and the efficiency of sputum collection.

• Value: Not well established!

• Observed: 5-15% of patients, which finish treatment

Treatment outcome: Treatment success rate

• Total of cure and treatment completion rate

• WHO: “Successfully treated”: Essentially a rate showing the effectiveness of case-holding

• Operational indicator: At least 85-90% of cases, which complete treatment should have a final smear result shown in the register (Indicate no sputum obtained in cases which can not produce sputum!)

Treatment outcome: Death rate• Proportion of patients who die while on

treatment, irrespective of the cause

• Factors: Severity of disease at time of diagnosis (diagnostic delay!), initial resistance, type of regimen, age, immunity, HIV status, adherence to treatment.

• Value: with SCC 1-3% , but in high HIV prevalence countries 5-15%!!

Treatment outcome: Failure rate• Smear-positive patient who remained

smear-positive, or became smear-positive again, at least 5 months after the start of treatment

• Factors: Initial resistance, type of regimen, treatment adherence

• Value: In new patients on SCC < 1-2%. In relapse case on retreatment < 3-5%. Other previously treated cases on retreatment?

Treatment outcome:Default rate

• Interrupted treatment rate: Patient who did not collect drugs for 2 months or more at any time after registration

• Most important case-holding indicator!

• Influenced by multiple factors!

Accessibility and acceptability of DOT services: distance, clinic hours, attitude of staff, waiting time, privacy, support, control

Treatment outcome: Default rate

• Patient perspective: convenience, costs, loss of income, side effects, well being after initial treatment, awareness about treatment, availability of drugs, duration of treatment, support, attitude of community, intercurrent events

• Value: Target 0%!

• Good performance < 5%

Treatment outcome:Transferred out rate

• Patient who was transferred to another reporting unit and from whom treatment results are not know

• Depends essentially on mobility of patients and capacity of NTP to retrieve results of transferred patients

• Value: Not defined! Preferably < 5%

• Future: Electronic register?