Controlling Latent TB Tuberculosis Infection in High-Burden Countries: A Neglected Strategy to End TB

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries

Data for: "The utility of repeat Xpert MTB/RIF testing to diagnose tuberculosis in HIV-positive adults with initial negative result"

The World Health Organization recommends regular tuberculosis screening of HIV-positive individuals with Xpert MTB/RIF as the first diagnostic test. Further evaluation of those who are HIV-positive and Xpert-negative comprises clinical reassessment, chest radiograph (if available), sputum for mycobacterial culture, and treatment with antibiotic if clinically indicated. The aim of our study was to describe the diagnostic yield from an immediate repeat sputum tested with Xpert, compared to sequential further investigation guided by South African recommendations , amongst HIV-positive adults in South Africa being investigated for TB whose initial sputum Xpert result is negative. It was a sub-study of “Xpert for people attending HIV/AIDS care: test or review?” (XPHACTOR), a prospective cohort study evaluating a risk-based algorithm to prioritise Xpert testing amongst adults attending for routine HIV care in South Africa. This dataset contains data for 227 adults attending for routine HIV care who have an initial negative sputum Xpert result. It includes basic demographics, TB diagnoses, mycobacteriology and chest radiograph results. Data was collected for the purpose of HIV and TB research and can only be reused for related research, in accordance with the participant consent agreement

Stable incidence rates of tuberculosis (TB) among human immunodeficiency virus (HIV)-negative South African gold miners during a decade of epidemic HIV-associated TB.

During the last decade, annual tuberculosis (TB) case-notification rates increased 4-fold, to >4000 cases/100000 person-years, in the study workforce, among whom prevalence of human immunodeficiency virus (HIV) was 30% in 2000. Three separate cohort studies, totalling 6454 HIV-negative participants, were combined and analyzed for time trends. Observed incidence of TB varied between 962 (1991-1994) and 1589 (1999-2000) cases/100000 person-years (P=.17, test for trend). There was, however, a progressive increase in age, and, for each period, older age was associated with increased incidence rates of TB (P<.001). Having adjusted for age differences, there was no significant association between incidence of TB and calendar period (P=.81, test for trend). Relative to 1991-1994, multivariate-adjusted incidence-rate ratios were 0.94, for 1995-1997, 0.96, for 1998-1999, and 1.05, for 1999-2000. Preventing a secondary epidemic of TB among HIV-negative individuals may be achievable with conventional means, even in settings with a high burden of HIV-associated TB

Tuberculosis active case finding: uptake and diagnostic yield among minibus drivers in urban South Africa.

BACKGROUND: Tuberculosis (TB) active case finding is a part of TB control in areas of higher TB prevalence. Congested public transportation settings may be areas of increased TB transmission. We evaluated the uptake and diagnostic yield of an active TB screening program among minibus drivers in a large public transportation facility in Johannesburg, South Africa. METHODS: Over an eight month period, we intensively recruited minibus drivers for TB screening with a goal of 80% uptake among the estimated 2000 drivers. All participants were screened for TB symptoms, offered HIV testing, and had sputum collected for smear microscopy and liquid culture. RESULTS: 686 drivers were screened for TB, representing an uptake of only 34% of all drivers (43% of the target screening). Ten drivers (1.5%) were culture positive for TB, nine of whom were sputum smear microscopy negative. Factors associated with previously undiagnosed TB included a history of incarceration (odds ratio [OR] 5.5, 95% confidence interval: 1.1, 27.3) and HIV positivity (OR 5.3, 95% confidence interval: 1.1, 26.3). CONCLUSIONS: We identified undiagnosed pulmonary TB cases among drivers but at a level that may be insufficient to justify systematic case finding in this population considering the poor uptake

Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study

BACKGROUND: Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa. METHODS: Cohort of adults starting ART at 27 clinics between February 2005 and June 2006, followed to 31st March 2007. Kaplan-Meier survival estimates were used to describe overall mortality. Shared frailty Cox regression was used to identify baseline risk factors for early mortality. RESULTS: Among 1350 participants (median age 35.5 years, 60% female, median CD4 count 83/microL [interquartile range (27-147)], median follow-up 13.4 months), there were 185 deaths, overall mortality rate 13/100 pyrs; for 0-3, 3-9 and >9 months from ART start mortality rates were 24, 13 and 6/100 pyrs respectively. 43% of the deaths were in the first 3 months of treatment. Risk factors for mortality in univariable analysis were baseline CD4 count, viral load, haemoglobin and body mass index, in multivariable analysis adjusting for age and gender, only CD4 count and haemoglobin remained independently associated with proportional hazards not being satisfied for haemoglobin. Adjusted hazard ratios (aHR) for participants with haemoglobin 11.9(f)/12.9 (m) g/mL were 4.99, 3.05 and 0.12 respectively comparing to 10-11.9 (f)/12.9 (m)g/mL in the first 3 months of ART. aHRs for CD4 counts were 0.40, 0.38 and 0.34 for 50-99, 100-200 and >200/microL comparing to <50/microL. CONCLUSIONS: The high mortality rate in the first 3 months underlines the need for earlier HIV diagnosis so that ART can be initiated earlier. Low haemoglobin and low CD4 count are both strong predictors of mortality, and could be used to identify individuals at high risk who might benefit from intensive case management

"That is why I stopped the ART": Patients' & providers' perspectives on barriers to and enablers of HIV treatment adherence in a South African workplace programme

BACKGROUND: As ART programmes in African settings expand beyond the pilot stages, adherence to treatment may become an increasing challenge. This qualitative study examines potential barriers to, and facilitators of, adherence to ART in a workplace programme in South Africa. METHODS: We conducted key informant interviews with 12 participants: six ART patients, five health service providers (HSPs) and one human resources manager. RESULTS: The main reported barriers were denial of existence of HIV or of one's own positive status, use of traditional medicines, speaking a different language from the HSP, alcohol use, being away from home, perceived severity of side-effects, feeling better on treatment and long waiting times at the clinic. The key facilitators were social support, belief in the value of treatment, belief in the importance of one's own life to the survival of one's family, and the ability to fit ART into daily life schedules. CONCLUSION: Given the reported uncertainty about the existence of HIV disease and the use of traditional medicines while on ART, despite a programme emphasising ART counselling, there is a need to find effective ways to support adherence to ART even if the individual does not accept biomedical concepts of HIV disease or decides to use traditional medicines. Additionally, providers should identify ways to minimize barriers in communication with patients with whom they have no common language. Finally, dissatisfaction with clinical services, due to long waiting times, should be addressed

Provider-initiated symptom screening for tuberculosis in Zimbabwe: diagnostic value and the effect of HIV status.

OBJECTIVE: To assess the diagnostic value of provider-initiated symptom screening for tuberculosis (TB) and how HIV status affects it. METHODS: We performed a secondary analysis of randomly selected participants in a community-based TB-HIV prevalence survey in Harare, Zimbabwe. All completed a five-symptom questionnaire and underwent sputum TB culture and HIV testing. We calculated the sensitivity, specificity, and positive and negative predictive values of various symptoms and used regression analysis to investigate the relationship between symptoms and TB disease. FINDINGS: We found one or more symptoms of TB in 21.2% of 1858 HIV-positive (HIV+) and 9.9% of 7121 HIV-negative (HIV-) participants (P or = 2 weeks' duration, any symptom and a positive sputum culture had sensitivities of 48%, 81% and 65%, respectively; in HIV- participants, the sensitivities were 45%, 71% and 74%, respectively. Symptoms had a similar sensitivity and specificity in HIV+ and HIV- participants, but in HIV+ participants they had a higher positive and a lower negative predictive value. CONCLUSION: Even smear-positive TB may be missed by provider-initiated symptom screening, especially in HIV+ individuals. Symptom screening is useful for ruling out TB, but better TB diagnostics are urgently needed for resource-poor settings

The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study

BackgroundThe durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection.MethodsIn a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT.ResultsAmong 18,520 participants (96% male, mean age 41years, median follow-up 2.1years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95% confidence interval (CI), 1.0–1.6) and afterwards 2.3/100 pyrs (95% CI, 1.9–2.7). TB incidence increased within 6months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95% CI, 1.8–2.7).ConclusionsThe durability of protection by IPT was lost within 6–12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0589-3) contains supplementary material, which is available to authorized users