Abstract
Setting
Harare’s high density suburbs.
Objectives
To investigate the burden, duration and risk factors for prevalent TB and explore potential control strategies.
Methods
Randomly selected adults had TB culture, symptom screen and HIV serology. Prevalent TB was defined as undiagnosed or still culture-positive. Notification data and HIV prevalence in TB outpatients were used to estimate duration of infectiousness (prevalence/estimated incidence).
Results
Among 10,092 participants, 40 (0.40%; 95%CI 0.28 to 0.54%) had prevalent smear-positive TB. HIV (adjusted odds ratio [aOR] 3.1; 95%CI 1.6 to 6.3); population attributable fraction [PAF] 33%), male sex (aOR 3.1; 95%CI 1.5 to 6.4; PAF 40%), and overcrowding (PAF 34%) were significant risk factors, with past TB treatment significant for HIV-negative participants only (PAF 7%). Recent household TB contact was not significant (PAF 10%). HIV prevalence was 21.1%. 76.9% HIV-positive participants were previously untested. Durations of infectiousness were at least 18 weeks in HIV-positive and approximately 1 year in HIV-negative patients.
Conclusions
Overcrowding, male sex and HIV infection were major risk factors for prevalent smear-positive TB. Reducing diagnostic delay may have higher potential to improve control of prevalent TB than interventions targeted to household contacts, TB treatment outcomes, or TB/HIV interventions under current levels of awareness of HIV status.
Keywords: Tuberculosis, HIV, prevalence study, Africa, Risk factors
Introduction
Community-based surveys for undiagnosed or still infectious (defined here as “prevalent”) TB provide a rigorous assessment of TB control, and can provide estimates of mean duration of infectiousness before diagnosis.1 There is considerable uncertainty around the global burden of prevalent TB, especially in African countries with generalised HIV epidemics.2
The impact of HIV on prevalent TB is not fully understood.1;3-5 The high incidence of HIV-related TB does not necessarily imply that HIV increases the prevalence of infectious TB, because the duration of smear-positivity before diagnosis appears to be much shorter for HIV-related TB, at least in studies carried out under access to good diagnostic services including TB culture.3;4 This may not apply to more typical African settings, however.5;6 The epidemiology of undiagnosed smear-positive TB is of major relevance to TB control, since such individuals are the main source of secondary infections in their communities. For example, observations in the 1970s that incomplete TB treatment could lead to prolonged smear-positivity led to the emphasis on treatment completion that characterises the DOTS strategy.7
As part of a cluster-randomised trial of intensified case-finding for TB (DETECTB),8 we carried out a prevalence survey for HIV infection and active TB disease in Harare, and simultaneously estimated HIV-specific TB case-notification rates. The aims were to estimate the prevalence of infectious TB at the community level, identify risk factors, and estimate duration of smear-positivity before diagnosis of HIV infected and uninfected TB patients. Zimbabwe has been severely affected by HIV with adult prevalence in decline from a peak prevalence of 29% in 1997. TB case-notifications have increased 10-fold since 1980.
Study population and methods
Community-based survey
46 study neighbourhoods were enumerated, and consenting adults (≥16 years) from a 12% random sample of households were interviewed and asked for blood for HIV serology and two sputum specimens (“spot-morning”) for TB culture (irrespective of reported symptoms). Households were visited up to three times, including one weekend visit, before non-participants were classified as unreachable.
The sampling strategy and survey size were in accord with the broader study aims: to ascertain pre-intervention prevalence in defined study communities with sufficient precision to give 80% power to detect a 30% decline and allow for covariate adjustment, assuming pre-intervention prevalence of culture positivity of 1%.
TB suspects, pre-defined as having ≥1 TB symptom (cough, haemoptysis, feeling feverish, night sweats, weight loss) or a positive screening culture, had further investigation with repeat smears, cultures, radiography, and response to antibiotics.
Case definitions for prevalent TB
Pre-set case-definitions of prevalent TB required confirmation of disease at follow-up (positive culture, or radiological or progressive clinical disease with response to TB treatment), unless they had died in the interim (considered TB if screening culture-positive) 8. Patients on TB treatment when recruited were only considered to have prevalent disease if still infectious (culture-positive). Point prevalence estimates for prevalence of smear and culture positivity, respectively, included only results from the initial two screening specimens (not follow-up specimens), and only patients meeting the above definitions for confirmed TB disease.
Routinely diagnosed TB patients
In a parallel study, sequential newly diagnosed TB outpatients resident in the same suburbs were asked for blood for HIV serology and two sputum specimens (“spot-morning”) for microscopy and culture. The target was 500 participants (to provide a precision of 5% for HIV prevalence in smear-positive and culture-positive TB patients around an assumed 75% prevalence). Participants were categorized into residents or non-residents of study neighbourhoods by their addresses.
Participants were cross referenced against the 2006 Harare electronic TB case notification database, which includes hospitalized patients. We used capture-recapture to estimate the total number of treated patients (N) during the study period to be N = [(n1 + 1)(n2 + 1)/(m + 1)]−1, where n1 was the number of survey participants, n2 was the number of patients captured from selected suburbs in the electronic notification database within the survey period, and m was the number captured by both methods.9
Laboratory methods
Both smears and cultures were processed immediately for participants with ≥1 symptom. For asymptomatic participants, a single pooled specimen was cultured, with storage of 2 smears read if the pooled culture was positive. Smears were made from concentrated decontaminated (4% NaOH) sputum and read by fluorescence microscopy (Auramine-O). Culture used Lowenstein-Jensen (LJ) slopes.
HIV serology used Determine (Abbott Diagnostics, Johannesburg, South Africa), with all positives and 10% of negatives confirmed by Unigold (Trinity Biotech, Dublin, Ireland). Oral mucosal transudate from participants not willing to provide serum was tested using Vironostika (Vironostika; BioMérieux, Marcy l’Etoile, France), with no confirmatory testing (used for study purposes only).
Ethical Approval
Written informed consent was provided by all participants. Approval was granted by the Ethics Committees of Biomedical Research and Training Institute, Harare, Medical Research Council of Zimbabwe and London School of Hygiene and Tropical Medicine. VCT was provided to all participants wanting to know their status, with onwards referral for HIV-positive participants.
Statistical Methods
Crowding was calculated as persons per dwelling / number of rooms. Where information on crowding (number of members and rooms) was reported differently by members of the same household a simple algorithm was run to provide consistency and fill in missing data with information provided by other household members. Eight household assets were used to assess socioeconomic status. Smokers were defined by regular smoking for ≥ one year. Problem drinking was as defined by the Alcohol Use Disorders Identification Test (AUDIT).10 As there was no evidence for clustering, exact binomial confidence intervals (CI) were used. Multivariate analysis of risk factors for TB used logistic regression. Population attributable fraction (PAF) was estimated with adjustment for covariates using the aflogit command.11 Duration of infectiousness for smear-positive TB was estimated as prevalence divided by incidence for HIV-positive and HIV-negative participants.3;4
Results
The study neighbourhoods contained 110,432 adults in 41,419 households, including 2,432 (2.2%) temporarily residing elsewhere. As shown in Figure 1, of 12,426 adults in selected households, 10,092 (81.2%) provided sputum and 9,070 (73.0%) also provided HIV specimens (8,304 [91.6%] blood), results of which were unreadable for 10 participants. Participation rates were considerably higher for women than men (Figure 1).
Figure 1. Participation rates in adults from selected households.
Participant characteristics are shown in Table 1. HIV prevalence was 21.1%. Screening cultures from 88 participants grew M. tuberculosis, of whom 66 (75%) had TB confirmed, while 21 did not meet pre-set definitions for confirmed disease (see Methods). Of these, 2 were smear-positive and 1 of 19 tested was HIV-positive. Reasons for not meeting definitions were: - no evidence of disease on follow-up investigations (12), relocated before culture results available (8, including 5 reporting symptoms at screen), treated for TB but no clinical or radiological response and follow-up cultures negative (1). In total, 91 participants (0.90%; 95% CI 0.72 to 1.09%) met definitions for active TB, previously undiagnosed in 82 (90%) and treated but still culture-positive in 9 (median 11 days on treatment, range 1 to 31 day).
Table 1. Baseline characteristics of participants screened for TB disease.
| Characteristicsa | All participants (n=10092) Number, % |
|
|---|---|---|
| Age | ||
| 16 to 24 | 4,132 | 41.0 |
| 25 to 34 | 3,110 | 30.8 |
| 35 to 44 | 1,362 | 13.5 |
| 45 years or more | 1,488 | 14.7 |
| Female | 6121 | 60.7 |
| HIV positive | 1,916 | 21.1 |
| Past TB treatment | 334 | 3.3 |
| On TB treatment | 74 | 0.7 |
| Household TB contact | ||
| 1 contact in last 2 yrs | 1,102 | 10.9 |
| ≥ 2 contacts in last 2 yrs | 215 | 2.1 |
| Ever drink alcohol | 1,915 | 19.0 |
| AUDIT score (Mean (SD)) | 2.6 (5.9) | |
| Visit a beer hall ≥ monthly | 1,634 | 16.2 |
| Never smoked | 9,028 | 89.5 |
| Current smoker | 867 | 8.6 |
| Former smoker | 196 | 1.9 |
| No. of assets owned (Mean (SD)) | 6.1 (1.4) | |
| Crowding: Mean persons/room(SD) | 2.0 (0.9) | |
| >2 to 4 persons per room | 3,697 | 36.7 |
| >4 persons per room | 200 | 2.0 |
| Church attendance ≥ weekly | 7,268 | 72.0 |
Data missing for sex (1 participants), HIV status (1,032 participants; 457 men and 575 women), past TB (3 participants), on TB treatment (3 participants), household contact (3 participants), ever drink alcohol (5 participants), AUDIT score (11 participants), beerhall attendance (3 participants), smoking (1 participants), asset score (26 participants), crowding (18 participants), church attendance (4 participants)
The prevalence of smear-positivity (overall 0.40%, 95% CI 0.28 to 0.54) and culture-positivity (overall 0.65%, 95% CI 0.51 to 0.83%) by HIV status and gender are shown in Table 2. There was no evidence of community level or household level clustering of TB disease (p = 0.500 and p = 0.101, respectively). Only three households had more than one TB case.
Table 2. Prevalence of TB disease (per 100 participants), overall and according to gender, HIV status, and results of screening smear and cultures.
| Number of cases and point prevalence of TB (per 100 participants), by sex and HIV status* |
||||||
|---|---|---|---|---|---|---|
| All participants | Overall (n=10,092) | HIV−ve (n = 7144) | HIV+ve (n=1916) | |||
| TB | Prevalence | TB | Prevalence | TB | Prevalence | |
| Smr+c ult+ TB | 40 | 0.40 (0.28 to 0.54) | 20 | 0.28 (0.17 to 0.43) | 19 | 0.99 (0.60 to 1.54) |
| All culture +ve TB† | 66 | 0.65 (0.51 to 0.83) | 29 | 0.41 (0.27 to 0.58) | 34 | 1.77 (1.23 to 2.47) |
| Men | Overall (n=3970) | HIV−ve (n=2928) | HIV+ve (n=585) | |||
| TB | Prevalence | TB | Prevalence | TB | Prevalence | |
| Smr+c ult+ TB | 23 | 0.58 (0.37 to 0.87) | 13 | 0.44 (0.24 to 0.76) | 10 | 1.71 (0.82 to 3.12) |
| All culture +ve TB† | 31 | 0.78 (0.53 to 1.11) | 16 | 0.55 (0.31 to 0.89) | 14 | 2.40 (1.31 to 3.99) |
| Women | Overall (n=6121) | HIV−ve (n=4216) | HIV+ve (n=1330) | |||
| TB | Prevalence | TB | Prevalence | TB | Prevalence | |
| Smr+c ult+ TB | 17 | 0.28 (0.16 to 0.44) | 7 | 0.17 (0.07 to 0.34) | 9 | 0.68 (0.31 to 1.28) |
| All culture +ve TB† | 35 | 0.57 (0.40 to 0.79) | 13 | 0.31 (0.16 to 0.53) | 20 | 1.50 (0.92 to 2.31) |
Gender missing for one participant. HIV status missing for 1032 participants
Includes smear-negative and smear-positive cases (all smear-positive cases were culture positive)
Considered risk factors for undiagnosed or still infectious smear-positive TB
On univariate analysis (Table 3), HIV infection was a significant risk factor for smear-positive prevalent TB, but with no extra risk from past TB treatment (compared to HIV-negative participants with no past TB treatment: HIV-positive and no past TB treatment OR 4.12; 95% CI 2.10 to 8.09: HIV-positive plus past TB treatment OR 4.21; 95% CI 0.97 to 18.34). Past TB treatment was, however, a strong risk factor in HIV-negative participants (OR 10.85, 95% CI 3.14 to 37.54). Male sex and overcrowding (more than 2 people per room), were also significant, while greater number of households assets, church attendance and young age were protective.
Table 3. Risk factors for prevalent smear positive TB.
| Univariate | Multivariate analysis | |||
|---|---|---|---|---|
|
|
||||
| Variable | OR | OR | (95% CI) | Population attributable fraction |
| Age less than 25 | 1 | 1 | PT = 0.004 | |
| Age 25-34 | 4.90 | 3.72 | (1.45 to 9.54) | |
| Age 35-44 | 5.09 | 3.20 | (1.10 to 9.32) | |
| Age ≥ 45 | 0.93 | 0.68 | (0.13 to 3.64) | |
| Male | 2.09 | 3.13 | (1.53 to 6.40) | 40.0% |
| HIV−, no past TB | 1 | 1 | ||
| HIV+, no past TB a | 4.12 | 3.26 a | (1.59 to 6.67) | 30.0%a |
| HIV−, past TB | 10.85 | 7.57 | (2.10 to 27.41) | 6.6% |
| HIV+, past TB a | 4.21 | 2.45 a | (0.54 to 11.08) | 3.0%a |
| Household TB contacts | ||||
| None in last 2 yrs | 1 | 1 | PT = 0.34 | |
| 1 contact in last 2 yrs | 1.87 | 1.60 | (0.69 to 3.70) | 6.6% |
| ≥ 2 contacts in last 2 yrs | 2.76 | 2.54 | (0.59 to 10.98) | 3.1% |
| AUDIT score | 1.02 | 1.03 | (0.96 to 1.11) | |
| Smoking (per pack-year) | 1.04 | 1.03 | (0.97 to 1.10) | |
| Beer hall attendance | 0.91 | 0.19 | (0.04 to 0.82) | |
| Church attendance | 0.47 | 0.58 | (0.29 to 1.16) | |
| Crowding | ||||
| Less than 2 per room | 1 | 1 | PT = 0.038 | |
| 2 to 4 per room | 2.57 | 2.19 | (1.12 to 4.26) | 30.3% |
| ≥ 4 per room | 4.14 | 3.64 | (0.81 to 16.46) | 3.7% |
| No. of assets owned (per asset)b | 0.77 | ND | ||
HIV and past TB treatment were modeled as a combined categorical variable because of the significant effect-modification described in the results (p = 0.021). An otherwise similar multivariate model including 3 categories for HIV/past TB, not distinguishing HIV-infected participants on the basis of their past TB treatment history gave adjusted OR for HIV of 3.15 (95% CI 1.6 – 6.3) PAF 33%, as stated in the abstract.
See Methods for description of socioeconomic status variables. Omitted from multivariate analysis as no longer significant and with high number of missing data points
On multivariate analysis (Table 3), age-group (p = 0.013), male sex (adjusted OR 3.1; 95% CI 1.53 to 6.40), HIV-infection (adjusted OR if no past TB 3.26; 95% CI 1.59 to 6.67; adjusted OR if past TB 2.45, 95% CI 0.54 to 11.08), past TB among HIV-negative participants (adjusted OR 7.57, 95% CI 2.10 to 27.41), and overcrowding (test for trend p = 0.038, adjusted odds ratio for 2 to 4 persons per room 2.19, 95% CI 1.12 to 4.26; adjusted odds ratio for ≥4 persons per room 3.64, 95% CI 0.81 to 16.46) remained significant. The effect of past TB differed significantly by HIV status (effect modification term, p = 0.021). Unexpectedly, visiting beer halls was associated with a significantly lower risk of smear-positive TB (adjusted OR 0.19; 95% CI 0.04 to 0.82), but only on multivariate analysis (univariate OR 0.91 95% CI 0.38 to 2.18).
The equivalent multivariate analysis for culture-positive TB gave similar findings, including a significant difference in the effect of past TB by HIV status (p = 0.014).
Population attributable fractions for prevalent smear-positive TB
Population attributable risk fractions (PAF) were considered for seven risk factors, as shown in Table 3. Crowding had the highest PAF (2 to 4 persons per room: 43.4%, more than 4 persons per room 3.5%), followed by male sex (39.0%), HIV infection (33.6% when HIV-positive persons with and without past TB were considered as one group), and past TB treatment (6.7%, all from HIV-negative participants). Attributable fractions for recent household contact were 7.4% for 1 contact, and 3.0% for 2 or more contacts.
Estimation of TB case-notification rates and duration of infectiousness
Four hundred and seventy routinely diagnosed TB outpatients were enrolled in a 78 day survey of HIV prevalence and smear-positivity in the same suburbs (91.8% participation), of whom 30.5% lived in a study neighbourhood (not just suburb) and 208 (44.3%) were smear-positive. HIV prevalence was 64.9%. During the same period 790 patients from the same suburbs were recorded in the electronic TB database, with 435 captured by both surveys, giving a total estimate of 915 newly diagnosed TB patients on adjustment for under-capture (see Methods).
Extrapolating these data (Table 4) provides an estimated annual adult case-notification rate for smear-positive TB of 1.64 and 0.24 per 100 persons for HIV-related and HIV-negative disease. Combining incidence with point prevalence rates (prevalence / incidence),3;4 we estimate of mean durations of infectious smear-positivity of 31 to 18 weeks for HIV-positive TB and 55 to 78 weeks for HIV-negative TB (Table 4). The ranges reflect the impact of adjustments for a) likely under-capture of incident TB due to death without diagnosis (assuming 33% case-fatality for HIV-related smear-positive TB and 10% for HIV-negative smear-positive TB)12 plus b) likely under-estimation of HIV prevalence in incident TB patients due to recruitment of only ambulant TB outpatients (assuming true HIV prevalence in all incident smear-positive TB patients to be at least 75%).4;13
Table 4. Estimated TB incidence rates, duration of smear-positivity before diagnosis/loss of infectiousness, and the impact of HIV infection.
| Estimated case-notification & incidence rates for smear-positive TB | Overall | HIV+ve | HIV−ve |
|---|---|---|---|
| Total number of adults in study neighbourhoodsa | 107,980 | 22,797 | 85,183 |
| Expected num. registered smear+ve patients per yearb | 5576 | 374 | 202 |
| Estimated num. undiagnosed / unregistered smear+ve deaths per yearc | 209 | 187 | 22 |
| Adult smear+ve TB case-notification rates per 100 persons/yeard | 0.53 | 1.64 | 0.24 |
| Adult smear+ve TB incidence adjusted for deaths per 100 persons/yeare | 0.73 | 2.46 | 0.26 |
| Duration of smear-positivity before diagnosis and culture conversion | Overall | HIV+ve | HIV−ve |
| - unadjusted (weeks)f | 39 | 31 | 61 |
| - adjusted for deaths (weeks)g | 29 | 21 | 55 |
| - adjusted for death and HIV prevalence bias due to sampling ambulant TB patientsh |
28 | 18 | 78 |
| Disease duration ratios for smear-positive TB by HIV status | HIV+ve/HIV−ve | ||
| - unadjustedi | 0.51 | ||
| - adjusted for deathsj | 0.38 | ||
| - adjusted for death and failure to include non-ambulant TB patientsk | 0.23 | ||
Assuming HIV prevalence of 21.1% as in community-survey participants
From electronic TB register (See Methods)
Assuming death before diagnosis 33% for HIV-positive smear-positive TB, and 10% for HIV-negative smear-positive TB.12
Capture-recapture estimate from known cases by study and electronic register
Capture-recapture estimate followed by adjustment for death before diagnosis
Prevalence divided by capture-recapture case-notification rates,3 assuming community survey prevalence to be representative
Duration estimate adjusting for undiagnosed/unreported deaths
Duration estimates adjusting for undiagnosed/unreported deaths and under-ascertainment of true HIV prevalence from recruitment of ambulant patients only (assumed to be 75% in smear-positive TB patients).4;13
Ratio of duration of smear-positive TB in HIV-positive persons divided by HIV-negative rate
As i., but further adjusted for undiagnosed/unreported deaths
As j., but further adjusted for under-ascertainment of HIV prevalence in smear-positive TB patients
Discussion
This study shows a substantial burden of infectious TB in urban Harare, with 4 in every 1000 screened individuals having smear-positive culture-positive TB, predominantly due to undiagnosed disease. These are below rates reported for Cape Town, South Africa5;14, and Zambia6 but similar15 to or higher16 other African cities. Men, HIV-infected individuals, and more crowded households were disproportionately affected. Unlike in Asia17, we did not find any increased risk from smoking, perhaps reflecting lower median daily consumption.18
We estimate a major impact on the burden of prevalent TB from prolonged infectiousness (at least 18 weeks for HIV-positive and about 1 year for HIV-negative TB patients) before diagnosis, with a small contribution from suboptimal TB treatment: only 4% of participants reporting past treatment had active disease. Past TB treatment was a strong although uncommon risk factor for prevalent TB in HIV-negative participants, with 4 of the 20 prevalent smear-positive HIV-negative patients reporting past TB treatment (plus default before completion reported by 3 of these), but not HIV-positive participants. The population attributable fraction (PAF) was low (7% for smear-positive prevalent disease) compared to overcrowding (47%), male sex (39%) and HIV-infection (34%). This is despite poor treatment outcomes in Harare (59% successful in 2006).
Low PAFs for past TB treatment have been reported from another population in Harare,4 in sharp contrast to studies from the pre-DOTS era7 and more recently from Cape Town.15 If confirmed, our finding that past TB treatment is not a risk factor for prevalent TB disease is important, suggesting that treatment failure among HIV-positive individuals is too poorly tolerated to result in the very prolonged infectious state that makes treatment failure among HIV-negative TB patients such a major public health concern7 and has led to a very cautious approach to active case-finding.
As low/slow case detection appears to be the main bottleneck in TB control in this high HIV prevalence setting and in a similar study from Zambia,6 interventions to provide more rapid and accessible diagnosis, such as intensified case-finding strategies and/or improved diagnostics, have high potential to rapidly improve overall TB control. In contrast, the low PAF for past TB treatment and recent household TB contact (10%) imply limited potential impact from interventions targeting these groups. At present, targeted HIV/TB interventions would also have limited potential because 77% of HIV-positive participants did not know their status.
TB transmission occurs mainly at community-level in resource-poor settings,19;20 with undiagnosed smear-positive patients the main source of secondary infections. The majority of TB cases in high incidence settings reflect recent transmission, not reactivation,21 making control of ongoing transmission the first priority of TB control strategies in endemic settings.2 Prompt clinic-based investigation and effective treatment of self-reported chronic cough was developed as a cost-effective and sustainable TB control strategy (“DOTS”).2 Although sustainable and highly successful at improving treatment outcomes, economic, health system, and logistical barriers can introduce substantial diagnostic delays.22 In most countries, reductions in TB incidence under DOTS have been realized slowly, and can easily be overwhelmed by rapid urbanization or HIV epidemics.2;23
Control of undiagnosed TB under DOTS has only recently been investigated in the context of HIV. Good control despite high TB incidence rates, with brief duration before diagnosis for HIV-related smear-positive TB (6 and 8 weeks), was achieved in South African gold miners and in Zimbabwean factory workers provided with ready access to diagnosis of symptomatic TB, including culture.3;4 HIV infection was not a significant risk factor for undiagnosed smear-positive TB in these two studies, our hypothesis being that this reflects rapid onset of symptoms and health-seeking in HIV-positive individuals, even if unaware of their HIV status.3;4;21 More pronounced barriers to diagnosis in the routine health system may explain why mean durations of HIV-related smear-positivity are higher in this current study, although still only a fraction of our estimates for HIV-negative TB patients.
Limitations of this study include potential ascertainment bias due to low participation by men, although the higher prevalence of undiagnosed TB in male than female participants is consistent with previous surveys24 and our HIV prevalence rates in men and women are similar to other studies in Harare.25 There is also uncertainty around our estimates of duration of infectiousness, as we used routinely diagnosed patients to estimate TB incidence rates. Both church attendance and beerhall attendance were associated with significantly reduced risk of prevalent TB in this study. Given the cross-sectional nature we are unable to exclude reverse causality, or potential confounding (for example by social networks or other lifestyle factors).
DOTS provides a strong foundation that can support more intensive case-finding. The current Global Plan to Stop TB supports active screening for TB, but only in high risk groups such as prisoners and known HIV-positive persons.26 Interventions to facilitate community-based TB and HIV diagnosis more broadly appear highly acceptable and may be more effective than clinic-based approaches alone21;27-29. Halving the 1990 prevalence of undiagnosed TB by 2015 is one of the Millennium Development Goals (MDG).2 In this study we show low case-detection under DOTS to be the major obstacle to achieving this goal. Community-based case-finding has considerable potential to accelerate TB control in high HIV prevalence settings, especially if successfully combined with HIV case-finding, strengthened health systems and routine diagnostic services.
Acknowledgements
This study was funded by the Wellcome Trust.
Funding source: Wellcome Trust
Footnotes
None of the authors have any conflict of interest to declare.
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