Intensified TB case-finding: still wide open to questions and answers

Slide 1: Intensified TB case-finding: still wide open to questions and answers Dr Liz Corbett Bloomsbury Wellcome Trust Centre & Clinical Research Unit, London School Hygiene Tropical Medicine Biomedical Research & Training Institute, Harare

Slide 2: Pre-DOTS era ICF widely used in all continents q – Mass mini-radiographs and household enquiries – Diagnosis and treatment +/- sanatoria – Still used in some settings today Use associated with declining TB incidence rates in many q settings Not formally evaluated as an isolated intervention q

Slide 3: Kolin 1961 – 1972 Kolin study q – 5 rounds of MMR – Point prevalence of s+ TB fell from 233 to 56 per 100k – Incidence of s+ TB fell from 142 to 52 per 100k per year – Effective TB treatment introduced + BCG 72% of all cases detected between MMR rounds through q passive CFT More effective to focus on effective treatment of cases q presenting passively

Slide 4: India Tumkur District prevalence survey 1960s (TST and CXR) q – No TB treatment programme Follow-up investigation for symptoms (?delay) q – 70% of smear-positive patients aware of symptoms – 50% had already sought care Bangalore q – CXR versus CXR plus symptom screen • Symptoms added little to CXR • Symptoms alone identified 70% culture-positive TB patients Banerji D, Anderson S. A sociological study of awareness of symptoms among persons with pulmonary tuberculosis. Bull Wld Hlth Org 1963; 29:665-683. Gothi GD, et al. Estimation of prevalence of bacillary tuberculosis on basis of chest x-ray and-or symptomatic screening. Indian J Med Res 1976; 64(8):1150-1159.

Slide 5: Kenya Case-finding studies in 1970s and 1980s q – House-to-house surveys most effective • 80% of cases had been to clinic with symptoms • Distance to clinic – Interview of village elders ineffective – Mothers asked to refer anyone with symptoms in their household • High yield in those who attended • Low population impact (4% all cases)

Slide 6: Korea Routine use of “school leavers” for door-to-door enquiry q – Each employee covered 10,000 pop – Over 50% of cases picked up this way during 1970s

Slide 7: Community-wide preventive therapy: Bethel ARI (%) & incidence rates / 100 000 pop p.a. Passive & intensified CFT & BCG 30% 3,000 ARI INH RCT: TB incidence 25% 2,500 42% pop INH 12mos 20% 2,000 INH all residents 15% 1,500 10% 1,000 5% 500 0% 1954 1957 1960 1963 1966 1969 1972

Slide 8: Other studies Toman (1976) q – 75% of cases self-presenting in countries covered by MMR programmes – Netherlands – annual CXR (2.5 million adults) • 15% of s+ and 25% of c+ TB detected through MMR – Expensive, not cost-effective – Assumes equal public health impact of ACF & PCF pick-up Toman K. Mass radiography in tuberculosis-control. Who Chronicle 1976; 30(2):51-57

Slide 9: Fate of pulmonary TB treated under routine conditions High rates of treatment failure and recurrence q Increasing recognition of the importance of adequate q treatment First priorities: q – Effective diagnosis in patients presenting passively – Effective treatment of those presenting passively – Don’t waste money and risk overwhelming health systems with ICF until these basics are in place  DOTS

Slide 10: ICF in the DOTS era Low case-detection a major factor limiting TB control q – Patients with symptoms cannot access investigations – Marginalised populations – Not all TB is highly symptomatic HIV-associated TB q – Driving up global incidence rates – High prevalence of active TB in HIV care settings – High mortality rates Modeling the impact of better case-finding q Time ripe to reconsider ICF q

Slide 11: ICF goals Reduce morbidity and mortality q – More intensive case-finding leads to fewer TB deaths and less severe post-TB complications – Focus on those most at risk of severe morbidity Reduce TB transmission q – General community – Institutional settings – Marginalised populations Increase case-finding q – Target high risk groups – Community-wide approach

Slide 12: ICF challenges Poor treatment outcomes q – Patients detected through ICF unwilling to be treated – ICF in settings of high primary MDR-TB Diagnostic approach q – Active versus inactive TB – Relatively low % smear-positive cases • Choice of screening and diagnostic tests – Illnesses other than TB • OIs & HIV itself Overwhelm the health system q

Slide 13: Prevalence study Cohort study snap shot in time Incidence and prevalence linked by duration of disease Time (person years)

Slide 14: Prevalent TB disease High ratio of prevalent: incident disease among HIV-ves q – See next slide Risk groups for prevalent TB disease q – Household contacts – Homeless – IDU – VCT attenders – Home based care – Congregate settings: prisons and miners – Old age and male sex

Slide 15: Prevalence: incidence Case notification rate Point prevalence Ratio 2000 China 17 72 4.2 1997 Philippines 118 229 1.9 1995 Korea 26 60 2.3 2004 Harare 441 129 0.3 Harare: symptomatic 21 0.05

Slide 16: Can have prolonged HIV/TB with minimal symptoms: duration of smr+ before diagnosis HIV Incident Min. duration of Max. possible Previous Isoniazid status or positive smear duration of TB preventive prevalent (days)* smear positivity treatment therapy TB case (days)† +ve Incident 620 Undetermined ‡ 1994 No +ve Incident 272 Undetermined ‡ No No +ve Prevalent 241 292 No Yes** +ve Incident 148 266 No No +ve Incident 53 97 No No +ve Incident 42 89 No No +ve Incident 39 Undetermined †† No No +ve Incident 31 Undetermined †† No No +ve Incident 29 99 No No -ve Incident 26 Undetermined ‡ No No +ve Incident 23 99 No No +ve Incident 9 50 No No +ve Incident 1 71 No No

Slide 17: What do we need to know? ICF in high HIV prevalence populations q – Screening algorithms • Expect these to vary by HIV status • Expect these to vary by effectiveness of DOTS – Can ICF substantially improve TB control? ICF and treatment outcomes q – High and low MDR-TB settings – IDU Better understanding of prevalent TB disease q – Impact of HIV – Why is prevalent TB so common in HIV-ve pops? – Does IPT increase risk of prolonged TB excretion

Slide 18: What do we need to know? Targeted ICF: how to do it better q – Strategies to reach high risk populations (Tables1 & 2) • High risk of TB morbidity • High risk of prevalent active TB – Strategies accessible by the general population • ZAMSTAR • TB screening clinics akin to VCT clinics • TB screening clinics accessible only on referral – Involving the community • TB clubs / shop keepers / home based care – Linked to better management of smear-negative TB

Slide 19: Institutional TB How much TB is institutionally acquired? q – TST conversion in student nurses • 18% p.a. strict US criteria after negative 2-step in Harare – Will have parallel ELISPOT data • ? 10+% annual risk of TB disease if HIV+ve – HIV care patients • Recurrent TB disease in patients on ARVs • Gold miners: – recurrent TB increased from ~8% p.a to ~25% p.a. in HIV+ – Coincided with introduction of HIV care clinic Can ICF control institutional TB transmission? q – Long term preventive therapy? – Role of culture-based ICF

Slide 20: Ongoing research Shop keepers: Malawi q ZAMSTAR q DETECTB q Cambodia q Kenya q Others? q Institutional TB: ARTI in student nurses q – Others?

Slide 21: Recommended priority groups for targeted ICF VCT clients q HIV care clinics q Patients starting ARVs (IRIS) q Household contacts q IVDU q Institutions q – Prisons – hospitals

Slide 22: General population screening Insufficient evidence on which to base recommendations q – Potential HUGE: true TB prevention – Impact of a single round or brief period of highly effective population-based ICF? • DOTS can be the sustainable element (Bethel0 • One passive = one ICF patient? • Respective roles of reactivation and recent TB infection Effective screening tool: digital MMR?? q Effective diagnostic test q Effective case-management q – Note that in high HIV prevalence settings the ratio of prevalent to incident cases may not be all that high – Would expect a rapid impact on new TB cases if prevalent TB disease control is improved

Slide 23: Conclusions ICF is natural extension of DOTS q – Operational research priorities & interim recommendations – p 7 – Targeted linked to IPT and ARVS • VCT clients • Institutional TB control • Household contact screening • IDUs – General populations: model / demonstration programmes? • TB screening clinics • Shop-keepers • ZAMSTAR approach • Household screening • MMRs TB case-finding is HIV case finding q – Chronic cough patients in Harare • HIV prevalence 83% overall: 88% in TB patients