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Intensified TB case-finding: still wide open to questions and answers Dr Liz Corbett Bloomsbury 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

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

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

India l Tumkur District prevalence survey 1960 s (TST and CXR) – No TB India l Tumkur District prevalence survey 1960 s (TST and CXR) – No TB treatment programme l Follow-up investigation for symptoms (? delay) – 70% of smear-positive patients aware of symptoms – 50% had already sought care l Bangalore – 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.

Kenya l Case-finding studies in 1970 s and 1980 s – House-to-house surveys most Kenya l Case-finding studies in 1970 s and 1980 s – 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)

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

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

Other studies l Toman (1976) – 75% of cases self-presenting in countries covered by Other studies l Toman (1976) – 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

Fate of pulmonary TB treated under routine conditions l High rates of treatment failure Fate of pulmonary TB treated under routine conditions l High rates of treatment failure and recurrence l Increasing recognition of the importance of adequate treatment l First priorities: – 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

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

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

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

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

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

Prevalence: incidence Prevalence: incidence

Can have prolonged HIV/TB with minimal symptoms: duration of smr+ before diagnosis Can have prolonged HIV/TB with minimal symptoms: duration of smr+ before diagnosis

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

What do we need to know? l Targeted ICF: how to do it better What do we need to know? l Targeted ICF: how to do it better – Strategies to reach high risk populations (Tables 1 & 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

Institutional TB l How much TB is institutionally acquired? – TST conversion in student Institutional TB l How much TB is institutionally acquired? – 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 l Can ICF control institutional TB transmission? – Long term preventive therapy? – Role of culture-based ICF

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

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

General population screening l Insufficient evidence on which to base recommendations – Potential HUGE: General population screening l Insufficient evidence on which to base recommendations – 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 (Bethel 0 • One passive = one ICF patient? • Respective roles of reactivation and recent TB infection l Effective screening tool: digital MMR? ? l Effective diagnostic test l Effective case-management – 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

Conclusions l ICF is natural extension of DOTS – Operational research priorities & interim Conclusions l ICF is natural extension of DOTS – 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? • • • l TB screening clinics Shop-keepers ZAMSTAR approach Household screening MMRs TB case-finding is HIV case finding – Chronic cough patients in Harare • HIV prevalence 83% overall: 88% in TB patients