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

XPHACTOR Clinical Score dataset

The World Health Organization (WHO) recommendation for regular tuberculosis (TB) screening of HIV-positive individuals with Xpert MTB/RIF as the first diagnostic test has major resource implications. The aim of our study was to develop a score, comprising elements readily available in primary care, to predict probability of TB in adults attending for routine HIV care screened for TB and found WHO tool positive. We used data collected for “Xpert for people attending HIV/AIDS care: test or review?” (XPHACTOR), a prospective cohort study evaluating a risk-based algorithm to prioritise Xpert MTB/RIF testing amongst adults attending for routine HIV care in South Africa, to develop and validate our clinical score. This dataset contains data for 1,048 HIV-positive adults attending for routine HIV care and reporting ≥1 symptom on the WHO screening tool. The dataset is split 50:50 to derive, and internally validate the prediction model. It includes basic demographics, TB diagnoses, and candidate predictors considered for the score. 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

Linkage to care among adults being investigated for tuberculosis in South Africa: pilot study of a case manager intervention.

OBJECTIVES: We piloted an intervention to determine if support from a case manager would assist adults being investigated for tuberculosis (TB) to link into TB and HIV care. DESIGN: Pilot interventional cohort study. PARTICIPANTS AND SETTING: Patients identified by primary healthcare clinic staff in South Africa as needing TB investigations were enrolled. INTERVENTION: Participants were supported for 3 months by case managers who facilitated the care pathway by promoting HIV testing, getting laboratory results, calling patients to return for results and facilitating treatment initiation. OUTCOMES MEASURED: Linkage to TB care was defined as starting TB treatment within 28 days in those with a positive test result; linkage to HIV care, for HIV-positive people, was defined as having blood taken for CD4 count and, for those eligible, starting antiretroviral therapy within 3 months. Intervention implementation was measured by number of attempts to contact participants. RESULTS: Among 562 participants (307 (54.6%) female, median age: 36 years (IQR 29-44)), most 477 (84.8%) had previously tested for HIV; of these, 328/475 (69.1%) self-reported being HIV-positive. Overall, 189/562 (33.6%) participants needed linkage to care (132 HIV care linkage only; 35 TB treatment linkage only; 22 both). Of 555 attempts to contact these 189 participants, 407 were to facilitate HIV care linkage, 78 for TB treatment linkage and 70 for both. At the end of 3-month follow-up, 40 participants had not linked to care (29 of the 132 (22.0%) participants needing linkage to HIV care only, 4 of the 35 (11.4%) needing to start on TB treatment only and 7 of the 22 (31.8%) needing both). CONCLUSION: Many people testing for TB need linkage to care. Despite case manager support, non-linkage into HIV care remained higher than desirable, suggesting a need to modify this intervention before implementation. Innovative strategies to enable linkage to care are needed

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