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 +: Rate All:

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

NOTIFICATIONS ASIAM ALL FORMS SMEAR POSITIVE (N+R)

NOTIFICATIONS/100,000 ASIAM ALL FORMS SMEAR POSITIVE (N+R) NOTIFICATIONS/100,000 ASIAM ALL FORMS SMEAR POSITIVE (N+R)

Average Prevalence 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 = 520/100,000 Prevalence rate of SM = 270/100,000 HIV + TB: 2.5% in 95 > 8.9% in 2000 > 10.3 in 2001

Observations Trend of notifications is inconclusive New SM+ notification rate in 1991< 20% of SM + prevalence rate ( ) 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 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) 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

suspects sputum positivity rate smear positive cases % population examined

sputum positivity rate proportion of population examined by direct microscopy

RESULTS OF DIRECT MICROSCOPY IN DISTRICT X FROM 1997 TILL 2001

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

Indicators to evaluate microscopy using 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 microscopy using 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 microscopy using 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 microscopy using the laboratory register % of suspects with three smear results N suspects with 3 smear result(s) during a quarter or year x 100 N 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?