Intensified TB case-finding: still wide open to questions and answers Dr Liz Corbett Bloomsbury Wellcome Trust Centre & Clinical Research Unit, London.

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

ICF widely used in all continents– 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 settings

Not formally evaluated as an isolated intervention

Kolin

1961 – 1972 Kolin study– 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

passive CFT

More effective to focus on effective treatment of cases

presenting passively

India

Tumkur District prevalence survey 1960s (TST and CXR)– No TB treatment programme

Follow-up investigation for symptoms (?delay)– 70% of smear-positive patients aware of symptoms

– 50% had already sought care

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

Case-finding studies in 1970s and 1980s– 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

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 1970s

0%

5%

10%

15%

20%

25%

30%

1954 1957 1960 1963 1966 1969 1972

500

1,000

1,500

2,000

2,500

3,000ARITB incidence

Passive & intensified CFT &

BCG

INH RCT:

42% pop INH

12mos

INH all residents

Community-wide preventive therapy: Bethel ARI (%) & incidence rates / 100 000 pop p.a.

Other studies

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

High rates of treatment failure and recurrence

Increasing recognition of the importance of adequate

treatment

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

Low case-detection a major factor limiting TB control– Patients with symptoms cannot access investigations– Marginalised populations– Not all TB is highly symptomatic

HIV-associated TB – Driving up global incidence rates – High prevalence of active TB in HIV care settings– High mortality rates

Modeling the impact of better case-finding

Time ripe to reconsider ICF

ICF goals

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

Reduce TB transmission– General community– Institutional settings– Marginalised populations

Increase case-finding– Target high risk groups– Community-wide approach

ICF challenges

Poor treatment outcomes– Patients detected through ICF unwilling to be treated

– ICF in settings of high primary MDR-TB

Diagnostic approach– 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

Cohort study Prevalence studysnap shot in time

Time (person years)

Incidence and prevalence linked by duration of disease

Prevalent TB disease

High ratio of prevalent: incident disease among HIV-ves– See next slide

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

Case notification rate Point prevalence Ratio2000 China 17 72 4.21997 Philippines 118 229 1.91995 Korea 26 60 2.32004 Harare 441 129 0.3

Harare: symptomatic 21 0.05

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

+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

Isoniazid preventive

therapy

HIV status

Incident or

prevalent TB case

Min. duration of positive smear

(days)*

Max. possible duration of

smear positivity (days)†

Previous TB

treatment

What do we need to know?

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?

ICF and treatment outcomes– High and low MDR-TB settings– IDU

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?

Targeted ICF: how to do it better– 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

Institutional TB

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

Can ICF control institutional TB transmission?– Long term preventive therapy?– Role of culture-based ICF

Ongoing research

Shop keepers: Malawi

ZAMSTAR

DETECTB

Cambodia

Kenya

Others?

Institutional TB: ARTI in student nurses– Others?

Recommended priority groups for targeted ICF

VCT clients

HIV care clinics

Patients starting ARVs (IRIS)

Household contacts

IVDU

Institutions– Prisons

– hospitals

General population screening

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 (Bethel0• One passive = one ICF patient?• Respective roles of reactivation and recent TB infection

Effective screening tool: digital MMR??

Effective diagnostic test

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

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?• 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