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.

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.

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.

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.

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.

Prevalence of latent tuberculosis infection among gold miners in South Africa.

SETTING: South African gold mines. OBJECTIVE: To determine the prevalence of latent tuberculosis infection (LTBI) and risk factors for a positive tuberculin skin test (TST) among gold miners. DESIGN: Cross-sectional survey. Human immunodeficiency virus (HIV) status was determined by self-report and medical records. TST positivity was defined by the mirror method to estimate the prevalence of LTBI, and by the US Centers for Disease Control and Prevention definitions to explore risk factors at the individual level. RESULTS: Among 429 participants (105/130 subjects aged <30 years, 324/390 > or = 30 years), the estimated prevalence of LTBI was 89%; 45.5% of HIV-positive participants had a zero TST response compared to respectively 13% and 13.5% in the HIV-negative and status unknown participants. In participants with TST > 0, there was no significant difference between size of response by HIV status: the mean (standard deviation) widths for HIV-positive, HIV-negative and HIV status unknown were respectively 11.84 (2.75), 12.03 (2.75) and 12.52 mm (3.04) (analysis of variance P = 0.28). Factors independently associated with a TST < 10 mm were positive HIV status (aOR 0.41, 95%CI 0.17-0.96) and not working underground (aOR 0.25, 95%CI 0.09-0.71). CONCLUSIONS: The prevalence of LTBI is very high in gold miners in South Africa. HIV-infected individuals are more likely to have a negative TST, but HIV infection does not affect the size of TST response.

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.

Chronic knee stiffness and swelling in a Zimbabwean adolescent.

A 12-year-old Zimbabwean girl presented with tuberculous monoarthritis. She was moderately wasted, stunted and sexually immature. These clinical findings lead to the diagnosis of underlying HIV infection, which was thought to have been acquired from mother-to-child transmission.

Cholangiocarcinoma presenting in an adolescent with vertically acquired HIV infection.

An adolescent with long-standing HIV infection who was severely immunosuppressed during HIV diagnosis developed cholangiocarcinoma 1.5 years after starting antiretroviral therapy.

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.

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.

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.

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.

Human immunodeficiency virus, smoking and self-rated health in Harare, Zimbabwe.

SETTING: Twenty-two urban factories in Harare. OBJECTIVE: To determine the relationship between the human immunodeficiency virus (HIV), smoking and self-rated health in a high HIV prevalence urban workforce. DESIGN: Cross-sectional survey. RESULTS: Of 7482 employees, 6111 (82%) consented to interview and anonymous HIV serology; 88% were male; median age was 34 years. HIV prevalence was 19%. Current (median 6 cigarettes per day) and former smoking were reported by 17% and 7%, respectively. Smoking (current or former) was more common among HIV-positive (27%) than -negative participants (17%; P < 0.001). Factors significantly associated with being a smoker on multivariate analysis were being HIV-infected (OR 1.5, 95% CI 1.4-1.7), older age (P < 0.001), non-Christian (OR 1.6, 95% CI 1.2-2.2) and manual job (OR 1.4, 95% CI 1.2-1.6). Women (OR 0.05, 95% CI 0.03-0.11) and the better educated (OR 0.7, 95% CI 0.5-0.9) were significantly less likely to smoke. HIV-positive smokers had the highest risk of reporting poor health (adjusted OR compared to HIV-negative non-smokers 3.4, 95% CI 2.3-5.0). CONCLUSIONS: Smoking was significantly more common among HIV-positive than -negative employees in this predominantly male workforce. There was evidence of a combined effect on self-rated poor health, a variable shown to be a strong independent predictor of mortality in industrialised countries. Interventions to encourage smoking cessation may be an important component of HIV care in Southern Africa.

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.

HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners.

OBJECTIVE: To investigate the combined effects of HIV infection and silicosis on mycobacterial disease. DESIGN AND SETTING: A retrospective cohort of 1374 HIV-positive and 2648 HIV-negative miners who attended a South African gold mining hospital and primary health clinics. PARTICIPANTS: Miners who had been tested for HIV, with consent, at primary health clinics during 1991-1996, predominantly because of a symptomatic sexually transmitted disease. RESULTS: Tuberculosis (TB) incidence was 4.9 and 1.1 per 100 person-years in HIV-positive and HIV-negative miners respectively. The incidence of Mycobacterium kansasii disease was also high (0.32 and 0.10 per 100 person-years, respectively). Silicosis was highly prevalent, implying inadequate dust control, and was a significant TB risk factor among both HIV-positive and HIV-negative men (adjusted incidence rate ratios 1.4-2.5 according to radiological severity). The data were consistent with the risks of silicosis and HIV combining multiplicatively, but did not fit an additive model. The incidence of HIV-associated TB increased significantly during the study, with no corresponding change in HIV-negative rates, to reach 16.1 per 100 person-years among HIV-positive silicotics. CONCLUSIONS: The risks of silicosis and HIV infection combine multiplicatively, so that TB remains as much a silica-related occupational disease in HIV-positive as in HIV-negative miners, and HIV-positive silicotics have considerably higher TB incidence rates than those reported from other HIV-positive Africans. The increasing impact of HIV over time may indicate epidemic TB transmission with rapid disease development in HIV-infected miners. Similar but currently unrecognized interactions may be contributing to TB control problems in other industrializing countries affected by the HIV epidemic.

Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis.

SETTING: A gold mining company in the Free State Province, South Africa. AIM AND DESIGN: A retrospective cohort study to investigate factors associated with an increased case-fatality rate (CFR) at 6 months in human immunodeficiency virus (HIV) positive and negative tuberculosis (TB) patients. RESULTS: Between April 1993 and March 1997, there were 2236 men with culture-confirmed pulmonary TB in whom HIV status and treatment outcome were known. The overall CFR within the first 6 months of therapy was low (3.6%). After adjusting for confounding factors, HIV infection (OR 15.0, 95%CI 7.4-30.6), self-presentation compared to detection by the active radiological screening programme (OR 5.6, 95%CI 2.6-12.2) and presence of silicosis (OR 3.0, 95%CI 1.4-6.3) were significantly associated with an increased CFR. Opportunistic infections accounted for 56.2% (36/64) of deaths in HIV-positive men. Cryptococcal disease accounted for 75% (27/36) of deaths from opportunistic infections. CONCLUSION: HIV infection and silicosis are both powerful risk factors for TB and are associated with an increased risk of death. Strategies aimed at reducing these two risk factors within the workforce could reduce TB incidence and mortality. In settings with functional DOTS programmes and sufficient resources, expanding the DOTS programme to include active case detection should be explored as a means of reducing TB prevalence and mortality.

Drug-resistant tuberculosis in South African gold miners: incidence and associated factors.

SETTING: A gold mining company in the Free State Province of South Africa. OBJECTIVE: To document the incidence of and factors associated with drug-resistant tuberculosis (TB) in South African gold miners. DESIGN: Review of Mycobacterium tuberculosis drug susceptibility records for the period from 1 July 1993 to 30 June 1997. RESULTS: Over the study period, 2241 miners had culture-positive M. tuberculosis pulmonary disease where isolates were tested for drug susceptibility to the four primary anti-tuberculosis drugs. The proportions of primary and acquired drug resistance were respectively 7.3% and 14.3% for isoniazid and 1.0% and 2.8% for resistance to at least isoniazid and rifampicin (multidrug resistance). Resistance to streptomycin and ethambutol was uncommon, and rifampicin monoresistance was rare. No significant factors for primary drug resistance were identified. Patients with retreatment pulmonary TB who failed primary TB treatment (versus cure) were significantly more likely to have TB with resistance to any TB drug or MDR (odds ratios respectively 9.82, 95%CI 2.97-33.5, and 18.74, 95%CI 1.76-475). Human immunodeficiency virus (HIV) infection was not significantly associated with primary or acquired drug resistance, and there was no trend of increasing resistance over time. CONCLUSION: Anti-tuberculosis drug resistance has remained stable despite the HIV epidemic and increasing TB rates. Directly observed therapy may have contributed to containing the level of drug resistance. Adherence to and completion of treatment are essential to prevent drug resistance and treatment failure, including in situations with high HIV prevalence.