Community-level variation in TB testing history in Blantyre, Malawi.

SETTING: Equitable access to TB testing is vital for achieving global diagnosis and treatment targets, but access to diagnostic services is often worse in poorer communities. The SCALE (Sustainable Community-wide Active case-finding for Lung hEalth) survey estimated TB prevalence in Blantyre City, Malawi, and recorded previous engagement with TB services.OBJECTIVE: To explore local variation in the prevalence of ever-testing for TB in Blantyre and investigate potential socio-economic drivers.DESIGN: We fit a mixed-effects model to self-reported prior TB testing from survey participants across 72 neighbourhood clusters, adjusted for sex, age and HIV status and with cluster-level random intercepts. We then evaluated to what extent cluster-level variation was explained by two alternate poverty indicators.RESULTS: We observed substantial variation between clusters in previous TB testing, with little correlation between neighbouring clusters. Individuals residing in less affluent households, on average, had lower odds of having undergone prior testing. However, adjusting for poverty did not explain the cluster-level variations observed.CONCLUSION: Despite a decade of increased active case-finding efforts, access to TB testing is inconsistent across the population of Blantyre. This likely reflects health inequities that also apply to TB testing in many other settings, and motivates collection and analysis of TB testing data to identify the drivers behind these inequities.

Missed opportunities for diagnosis and treatment in patients with TB symptoms: a systematic review.

BACKGROUND: The identification of patients with symptoms is the foundation of facility-based TB screening and diagnosis, but underdiagnosis is common. We conducted this systematic review with the hypothesis that underdiagnosis is largely secondary to patient drop out along the diagnostic and care pathway. METHODS: We searched (up to 22 January 2019) MEDLINE, Embase, and Cinahl for studies investigating patient pathway to TB diagnosis and care at health facilities. We used Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. We reported proportions of patients with symptoms at each stage of the pathway from symptom screening to treatment initiation. RESULTS: After screening 3,558 abstracts, we identified 16 eligible studies. None provided data addressing the full cascade of care from clinical presentation to treatment initiation in the same patient population. Symptom screening, the critical entry point for diagnosis of TB, was not done for 33-96% of participants with symptoms in the three studies that reported this outcome. The proportion of attendees with symptoms offered a diagnostic investigation (data available for 15 studies) was very low with a study level median of 38% (IQR 14-44, range 4-84). CONCLUSIONS: Inefficiencies of the TB symptom screen-based patient pathway are a major contributor to underdiagnosis of TB, reflecting inconsistent implementation of guidelines to ask all patients attending health facilities about respiratory symptoms and to offer diagnostic tests to all patients promptly once TB symptoms are identified. Better screening tools and interventions to improve the efficiency of TB screening and diagnosis pathways in health facilities are urgently needed.

CONTEXTE: L'identification des patients symptomatiques est à la base du dépistage et du diagnostic de la TB en centres de soins, mais les sous-diagnostics sont fréquents. Nous avons réalisé cette revue systématique en émettant l'hypothèse que le sous-diagnostic était bien moins important que la perte de vue des patients tout au long du parcours diagnostique et thérapeutique. MÉTHODES: Nous avons interrogé les bases de données MEDLINE, Embase et Cinahl (jusqu'au 22 janvier 2019) pour identifier les études ayant évalué le parcours diagnostique et thérapeutique des patients atteints de TB en centres de soins. Nous avons utilisé le QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) afin d'évaluer le risque de biais. Nous avons rapporté les proportions de patients présentant des symptômes à chaque stade du parcours, du dépistage symptomatique à l'instauration du traitement. RÉSULTATS: Après avoir passé en revue 3 558 résumés, nous avons identifié 16 études éligibles. Aucune ne fournissait, dans une même population de patients, de données sur l'ensemble de la cascade de soins, de la présentation clinique à l'instauration du traitement. Le dépistage symptomatique (point de départ essentiel du diagnostic de la TB) n'avait pas été réalisé pour 33­96% des participants symptomatiques dans les trois études ayant rapporté ce résultat. La proportion de personnes symptomatiques consultant à qui un examen diagnostique a été proposé (données disponibles pour 15 études) était très faible, avec une médiane de 38% (IQR 14­44 ; écart 4­84). CONCLUSIONS: Le manque d'efficacité du parcours patient fondé sur le dépistage symptomatique de la TB est un facteur contributif majeur du sous-diagnostic de la maladie. Cette inefficacité reflète une mise en œuvre incohérente des recommandations qui stipulent de demander à tous les patients consultant en centres de soins s'ils présentent des symptômes respiratoires et de proposer rapidement des tests diagnostiques à tous les patients une fois les symptômes de TB identifiés. De meilleurs outils et interventions de dépistage permettant d'améliorer l'efficacité du parcours de dépistage et de diagnostic de la TB en centres de soins sont urgemment nécessaires.

Does tuberculosis screening improve individual outcomes? A systematic review.

BACKGROUND: To determine if tuberculosis (TB) screening improves patient outcomes, we conducted two systematic reviews to investigate the effect of TB screening on diagnosis, treatment outcomes, deaths (clinical review assessing 23 outcome indicators); and patient costs (economic review). METHODS: Pubmed, EMBASE, Scopus and the Cochrane Library were searched between 1/1/1980-13/4/2020 (clinical review) and 1/1/2010-14/8/2020 (economic review). As studies were heterogeneous, data synthesis was narrative. FINDINGS: Clinical review: of 27,270 articles, 18 (n=3 trials) were eligible. Nine involved general populations. Compared to passive case finding (PCF), studies showed lower smear grade (n=2/3) and time to diagnosis (n=2/3); higher pre-treatment losses to follow-up (screened 23% and 29% vs PCF 15% and 14%; n=2/2); and similar treatment success (range 68-81%; n=4) and case fatality (range 3-11%; n=5) in the screened group. Nine reported on risk groups. Compared to PCF, studies showed lower smear positivity among those culture-confirmed (n=3/4) and time to diagnosis (n=2/2); and similar (range 80-90%; n=2/2) treatment success in the screened group. Case fatality was lower in n=2/3 observational studies; both reported on established screening programmes. A neonatal trial and post-hoc analysis of a household contacts trial found screening was associated with lower all-cause mortality. Economic review: From 2841 articles, six observational studies were eligible. Total costs (n=6) and catastrophic cost prevalence (n=4; range screened 9-45% vs PCF 12-61%) was lower among those screened. INTERPRETATION: We found very limited patient outcome data. Collecting and reporting this data must be prioritised to inform policy and practice. FUNDING: WHO and EDCTP.

Health-related quality of life of inpatients and outpatients with TB in rural Malawi.

INTRODUCTION: Patients being treated for TB may suffer reductions in health-related quality of life (HRQoL). This study aims to assess the extent of such reductions and the trajectory of HRQoL over the course of treatment in rural Malawi.METHODS: We collected patient demographic and socioeconomic status, TB-related characteristics, and HRQoL data (i.e., EQ-5D and a visual analogue scale VAS) from adults (age ≥18 years) being treated for TB in 12 primary health centers and one hospital in rural Thyolo District, Malawi, from 2014 to 2016. Associations between HRQoL and patient characteristics were estimated using multivariable linear regression.RESULTS: Inpatients (n = 197) consistently showed lower median HRQoL scores and suffered more severe health impairments during hospitalization than outpatients (n = 156) (EQ5D and VAS: 0.79, 55 vs. 0.84, 70). Longer treatment duration was associated with higher HRQoL among outpatients (EQ5D: 0.034 increase per 2 months, 95%CI 0.012-0.057). We found no substantial associations between patients´ demographic and socioeconomic characteristics and HRQoL in this setting.CONCLUSION: HRQoL scores among patients receiving treatment for TB in rural Malawi differ by clinical setting and duration of treatment, with greater impairment among inpatients and those early in their treatment course.

Factors affecting tuberculosis health message recall 2 years after active case finding in Blantyre, Malawi.

SETTING: Urban slums, Blantyre, Malawi. OBJECTIVE: To explore tuberculosis (TB) community-wide active case finding (cwACF) recall and accompanying messaging 2 years after the intervention. DESIGN: This mixed-methods study used population-weighted random cluster sampling to select three cwACF-receiving and three non-cwACF-receiving neighbourhoods in Blantyre. Qualitative data were collected using 12 focus group discussions (community peer-group members) and five in-depth interviews (TB officers) with script guides based on the concepts of the Health Belief Model (HBM). Thematic analysis was used to explore transcripts employing deductive coding. Questionnaires completed by focus group participants were used to collect quantitative data, providing a 'knowledge score' evaluated through univariate/multivariate analysis, analysis of variance and multiple linear regression. RESULTS: Community peer-group participants (n = 118) retained high awareness and positive opinions of cwACF and recognised the relationship between early diagnosis and reduced transmission, considering cwACF to have prompted subsequent health-seeking behaviour. TB-affected individuals (personal/family: 47.5%) had significantly higher knowledge scores than unaffected individuals (P = 0.039), but only if resident in cwACF-receiving neighbourhoods (P = 0.005 vs. P = 0.582), implying effect modification between exposures, albeit statistically under-powered (P = 0.229). CONCLUSION: Consistent with epidemiological evidence and HBM theory, cwACF may have a permanent impact on knowledge and behaviour, particularly in communities with a high prevalence of TB-affected individuals. Behaviour change strategies should be explicitly included in cwACF planning and evaluation.

Predictors of isoniazid preventive therapy completion among adults newly diagnosed with HIV in rural Malawi.

SETTING: To reduce the risk of tuberculosis (TB) among individuals with human immunodeficiency virus (HIV) infection, the World Health Organization recommends at least 6 months of isoniazid preventive therapy (IPT). Completion of IPT remains a major challenge in resource-limited settings. OBJECTIVE: To evaluate predictors of IPT completion in individuals newly diagnosed with HIV. DESIGN: Predictors of IPT completion among adults newly diagnosed with HIV in rural Malawi were evaluated using a multilevel logistic regression model. RESULTS: Of 974 participants who screened negative for active TB and were started on IPT, 732 (75%) completed treatment. Only one IPT-eligible individual refused treatment. Participants who were aged <25 years (compared with those aged 45 years, adjusted OR [aOR] 0.33, 95%CI 0.18-0.60) and male (compared to non-pregnant females, aOR 0.57, 95%CI 0.37-0.88) had lower odds of IPT completion. CONCLUSION: IPT provision at the time of initial HIV diagnosis was highly acceptable in rural Malawi; three quarters of those who initiated IPT successfully completed therapy. We observed lower odds of completion among males and among female participants aged <25 years. Additional efforts may be needed to ensure IPT completion among males and young females who have recently been diagnosed with HIV.

Completion of isoniazid preventive therapy among human immunodeficiency virus positive adults in urban Malawi.

SETTING: Despite worldwide scale-up of human immunodeficiency virus (HIV) care services, relatively few countries have implemented isoniazid preventive therapy (IPT). Among other programmatic concerns, IPT completion tends to be low, especially when not fully integrated into HIV care clinics. OBJECTIVE: To estimate non-completion of 6-month IPT and its predictors among HIV-positive adults aged 16 years. DESIGN: A prospective cohort study nested within a cluster-randomised trial of TB prevention was conducted between February 2012 and June 2014. IPT for 6 months was provided with pyridoxine at study clinics. Non-completion was defined as loss to follow-up (LTFU), death, active/presumptive TB or stopping IPT for any other reason. Random-effects logistic regression was used to determine predictors of non-completion. RESULTS: Of 1284 HIV-positive adults initiated on IPT, 885/1280 (69.1%) were female; the median CD4 count was 337 cells/µl (IQR 199-511); 320 (24.9%) did not complete IPT. After controlling for antiretroviral treatment status, IPT initiation year, age and sex, non-completion of IPT was associated with World Health Organization stage 3/4 (aOR 1.76, 95%CI 1.22-2.55), CD4 count 100-349 cells/µl (aOR 1.93, 95%CI 1.10-3.38) and any reported side effects (aOR 22.00, 95%CI 9.45-46.71). CONCLUSION: Completion of IPT was suboptimal. Interventions to further improve retention should target immunosuppressed HIV-positive adults and address side effects.

Delay in seeking care for tuberculosis symptoms among adults newly diagnosed with HIV in rural Malawi.

SETTING: Ten primary health clinics in rural Thyolo District, Malawi. OBJECTIVE: Tuberculosis (TB) is a common initial presentation of human immunodeficiency virus (HIV) infection. We investigated the time from TB symptom onset to HIV diagnosis to describe TB health-seeking behaviour in adults newly diagnosed with HIV. DESIGN: We asked adults (18 years) about the presence and duration of TB symptoms at the time of receiving a new HIV diagnosis. Associations with delayed health seeking (defined as >30 and >90 days from the onset of TB symptoms) were evaluated using multivariable logistic regression. RESULTS: TB symptoms were reported by 416 of 1265 participants (33%), of whom 36% (150/416) had been symptomatic for >30 days before HIV testing. Most participants (260/416, 63%) were below the poverty line (US$0.41 per household member per day). Patients who first sought care from informal providers had an increased odds of delay of >30 days (adjusted odds ratio [aOR] 1.6, 95%CI 0.9-2.8) or 90 days (aOR 2.0, 95%CI 1.1-3.8). CONCLUSIONS: Delayed health seeking for TB-related symptoms was common. Poverty was ubiquitous, but had no clear relationship to diagnostic delay. HIV-positive individuals who first sought care from informal providers were more likely to experience diagnostic delays for TB symptoms.

TB and HIV stigma compounded by threatened masculinity: implications for TB health-care seeking in Malawi.

SETTING: Urban Blantyre, Malawi. OBJECTIVE: To understand why men with tuberculosis (TB) in the community remain undiagnosed. DESIGN: A multi-method qualitative study applying a modified grounded theory approach. Data were gathered from March 2011 to March 2012 from 134 men and women taking part in 1) focus group discussions with community members (n = 6) and health care workers (n = 2), and 2) in-depth interviews with TB patients (n = 20, females n = 14) and chronic coughers (n = 20, women n = 8). Data were analysed inductively to identify, refine and consolidate, and verify emerging concepts and themes. RESULTS: Two emerging themes highlighting compound stigma in this high human immunodeficiency virus (HIV) prevalence, low-income setting are presented. First, cough or any illness that portended a 'serious' condition were accompanied by portrayals of cough, TB and HIV as being interchangeable. Chronic coughers and TB patients described their illness in ways that foregrounded bodily decimation and rupture of social life and masculine identity. Second, 'resistance strategies' entailed resisting classification as (seriously) ill by evading or ambivalently approaching health care, or acknowledging the 'ill' status then actively pursuing health-appropriate behaviours, including changing lifestyle or adopting non-normative gender roles. CONCLUSIONS: Managing patients requires 1) going beyond syndromic management based on vital signs and clinical indicators to recognising and intervening on health care-seeking related tensions to retain individuals in care, and 2) understanding and addressing TB stigma as it manifests and affects men and women differently in specific settings.

High mortality and prevalence of HIV and tuberculosis in adults with chronic cough in Malawi: a cohort study.

BACKGROUND: Adults with suspected tuberculosis (TB) in health facilities in Africa have a high risk of death. The risk of death for adults with suspected TB at community-level is not known but may also be high. METHODS: Adults reporting cough of ⩾ 2 weeks (coughers) during a household census of 19,936 adults in a poor urban setting in Malawi were randomly sampled and age-frequency matched with adults without cough ⩾ 2 weeks (controls). At 12 months, participants were traced to establish vital status, offered human immunodeficiency virus (HIV) testing and investigated for TB if symptomatic (sputum for Xpert(®) MTB/RIF, smear microscopy and culture). RESULTS: Of 345 individuals with cough, 245 (71%) were traced, as were 243/345 (70.4%) controls. TB was diagnosed in 8.9% (16/178) of the coughers and 3.7% (7/187) of the controls (P = 0.039). HIV prevalence among coughers was 34.6% (56/162) and 18.8% (32/170) in controls (P = 0.005); of those who were HIV-positive, respectively 26.8% and 18.8% were newly diagnosed. The 12-month risk of death was 4.1% (10/245) in coughers and 2.5% (6/243) in controls (P = 0.317). CONCLUSION: Undiagnosed HIV and TB are common among adults with chronic cough, and mortality is high in this urban setting. Interventions that promote timely seeking of HIV and TB care are needed.

Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality.

Twenty years of sky-high tuberculosis (TB) incidence rates and high TB mortality in high human immunodeficiency virus (HIV) prevalence countries have so far not been matched by the same magnitude or breadth of responses as seen in malaria or HIV programmes. Instead, recommendations have been narrowly focused on people presenting to health facilities for investigation of TB symptoms, or for HIV testing and care. However, despite the recent major investment and scale-up of TB and HIV services, undiagnosed TB remains highly prevalent at community level, implying that diagnosis of TB remains slow and incomplete. This maintains high transmission rates and exposes people living with HIV to high rates of morbidity and mortality. More intensive use of TB screening, with broader definitions of target populations, expanded indications for screening both inside and outside of health facilities, and appropriate selection of new diagnostic tools, offers the prospect of rapidly improving population-level control of TB. Diagnostic accuracy of suitable (high throughput) algorithms remains the major barrier to realising this goal. In the present study, we review the evidence available to guide expanded TB screening in HIV-prevalent settings, ideally through combined TB-HIV interventions that provide screening for both TB and HIV, and maximise entry to HIV and TB care and prevention. Ideally, we would systematically test, treat and prevent TB and HIV comprehensively, offering both TB and HIV screening to all health facility attendees, TB households and all adults in the highest risk communities. However, we are still held back by inadequate diagnostics, financing and paucity of population-impact data. Relevant contemporary research showing the high need for potential gains, and pitfalls from expanded and intensified TB screening in high HIV prevalence settings are discussed in this review.

The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review.

BACKGROUND: Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. METHODS: We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology. RESULTS: A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology. CONCLUSION: Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ß-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

Chest radiography patterns in 75 adolescents with vertically-acquired human immunodeficiency virus (HIV) infection.

AIM: To evaluate lung disease on chest radiography (CR), the relative frequency of CR abnormalities, and their clinical correlates in adolescents with vertically-acquired human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: CRs of 75 patients [59 inpatients (33 males; mean age 13.7±2.3 years) and 16 outpatients (eight males; mean age 14.1±2.1 years)] were retrospectively reviewed by three independent observers. The overall extent of disease (to the nearest 5%), its distribution, and the proportional extents (totalling 100%) of different radiographic patterns (including ring/tramline opacities and consolidation) were quantified. CR features and clinical data were compared. RESULTS: CRs were abnormal in 51/75 (68%) with "extensive" disease in 38/51 (74%). Ring/tramline opacities and consolidation predominated (i.e., proportional extent >50%) in 26 and 21 patients, respectively. Consolidation was significantly more common in patients hospitalized primarily for a respiratory illness than patients hospitalized for a non-respiratory illness or in outpatients (p<0.005, χ(2) for trend); by contrast, ring/tramline opacities did not differ in prevalence across the groups. On stepwise logistic regression, predominant consolidation was associated with progressive dyspnoea [odds ratio (OR) 5.60; 95% confidence intervals (CI): 1.60, 20.1; p<0.01] and was associated with a primary respiratory cause for hospital admission (OR: 22.0; CI: 2.7, 181.1; p<0.005). Ring/tramline opacities were equally prevalent in patients with and without chronic symptoms and in those admitted to hospital with respiratory and non-respiratory illness. CONCLUSION: In HIV-infected adolescents, evaluated in secondary practice, CR abnormalities are prevalent. The presence of ring/tramline opacities, believed to reflect chronic airway disease, is not linked chronic respiratory symptoms.

Risk factors for mortality in smear-negative tuberculosis suspects: a cohort study in Harare, Zimbabwe.

OBJECTIVE: To investigate mortality rates and risk factors for death among smear-negative tuberculosis (TB) suspects. DESIGN: Cohort study nested within a cluster-randomised trial of community-based active case finding. Smear-negative TB suspects were followed for 12 months, with home tracing where necessary. We calculated mortality rates and used regression analysis to investigate the relationship between clinical characteristics and death. RESULTS: Between February 2006 and June 2007, 1195 smear-negative TB suspects were followed for 1136.8 person-years. Human immunodeficiency virus (HIV) prevalence was 63.3%. During follow-up, 139 participants died (11.6%) and mortality rates remained high throughout; 119 (16.5%) HIV-positive individuals and 13 (3.1%) HIV-negative individuals died (HR = 5.8, 95%CI 3.3-10.4, P < 0.001). Advanced immunosuppression was the main risk factor for death among HIV-positive participants, with CD4 count < 50 cells/µ l associated with a 13-fold increased risk of death. Antiretroviral treatment (ART) was initiated by only 106 (14.7%), with long delays in accessing care. CONCLUSION: HIV-positive smear-negative TB suspects are at high and sustained risk of death. Current guidelines for the management of HIV-infected TB suspects are limited, and this study adds to evidence that specific policies are required to promote earlier HIV and TB diagnosis and reduce delays in ART initiation.

Prevalent infectious tuberculosis in Harare, Zimbabwe: burden, risk factors and implications for control.

SETTING: Harare's high density suburbs. OBJECTIVES: To investigate the burden, duration and risk factors for prevalent tuberculosis (TB) and explore potential control strategies. METHODS: Randomly selected adults had TB culture, symptom screen and human immunodeficiency virus (HIV) serology. Prevalent TB was defined as undiagnosed or still culture-positive. Notification data and HIV prevalence in TB out-patients were used to estimate duration of infectiousness (prevalence/estimated incidence). RESULTS: Among 10 092 participants, 40 (0.40%, 95%CI 0.28-0.54) had prevalent smear-positive TB. HIV (adjusted odds ratio [aOR] 3.1, 95%CI 1.6-6.3, population attributable fraction [PAF] 33%), male sex (aOR 3.1, 95%CI 1.5-6.4, 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% of HIV-positive participants were previously untested. Duration of infectiousness was 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 greater potential to improve the control of prevalent TB than interventions targeted at household contacts, TB treatment outcomes, or TB-HIV interventions under current levels of awareness of HIV status.

Diagnostic accuracy of commercial urinary lipoarabinomannan detection in African tuberculosis suspects and patients.

OBJECTIVE: To evaluate a commercially available antigen capture enzyme-linked immunosorbent assay (ELISA) based on detecting lipoarabinomannan (LAM) in urine for the diagnosis of tuberculosis (TB). DESIGN: Consenting TB suspects and registering TB patients prospectively recruited from three hospitals were asked for two sputum specimens for microscopy and culture, urine for LAM testing and blood for human immunodeficiency virus (HIV) testing, with radiological and clinical follow-up for 2 months. RESULTS: Of 427 participants, complete data were available from 397 (307 adult and 23 adolescent TB suspects, and 67 registering TB patients). HIV prevalence was 77%. TB was diagnosed in 195 (49%), including 161 culture-positive patients, and confidently excluded in 114 (29%) participants. LAM ELISA sensitivity was 44% (95%CI 36-52) for culture-confirmed TB (52% in smear-positive patients). Specificity was 89% (95%CI 81-94). Sensitivity was significantly higher in HIV-related TB (52%, 95%CI 43-62, P < 0.001) compared to HIV-negative TB (21%, 95%CI 9-37). Sensitivity in smear-negative patients was low (28%, 95%CI 13-43) for combined HIV-positive and -negative patients. CONCLUSION: Our findings confirm greater sensitivity of urine LAM detection for HIV-related TB. However, both sensitivity and specificity were suboptimal, suggesting that this version cannot confirm or exclude TB in either HIV-infected or non-infected patients.

Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution.

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.