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BACKGROUND: Tuberculosis (TB) mortality remains high across sub-Saharan Africa despite integration of TB and HIV/ART programmes. To inform programme design and service delivery, we estimated mortality by time from starting TB treatment. METHODS: Routinely collected data on TB treatment, vital status, and the timing and causes of death, were linked to cardio-respiratory autopsy data, from 1995-2008, from a cohort of male platinum miners in South Africa. Records were expanded into person-months at risk (pm). RESULTS: 4162 TB episodes were registered; 3170 men were treated for the first time and 833 men underwent retreatment. Overall, 509 men died, with a case fatality of 12.2% and mortality rate of 2.0/100 pm. Mortality was highest in the first month after starting TB treatment for first (2.3/100 pm) and retreatment episodes (4.8/100 pm). When stratified by HIV status, case fatality was higher in HIV positive men not on ART (first episode 14.0%; retreatment episode 26.2%) and those on ART (12.0%; 22.0%) than men of negative or unknown HIV status (2.6%; 3.6%). Mortality was also highest in the first month for each of these groups. Mortality risk factors included older age, previous TB, HIV, pulmonary TB, and diagnostic uncertainty. The proportion of deaths attributable to TB was consistently overestimated in clinical records versus cardio-respiratory autopsy. CONCLUSIONS: Programme mortality was highest in those with HIV and during the first month of TB treatment in all groups, and many deaths were not caused by TB. Resource allocation should prioritise TB prevention and accurate earlier diagnosis, recognise the role of HIV, and ensure effective clinical care in the early stages of TB treatment.

BACKGROUND: HIV and tuberculosis (TB) are the most common causes of death in South Africa. Antiretroviral therapy (ART) programmes should have had an impact on mortality rates. This study describes the impact of HIV, a Wellness (HIV/ART) programme and TB on population-wide trends in mortality and causes of death among South African platinum miners, from before the HIV epidemic into the ART era. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective analysis was conducted using routinely-collected data from an open cohort. Mortality and causes of death were determined from multiple sources, including cardiorespiratory autopsy records. All-cause and cause-specific mortality rates were calculated by calendar year. 41,665 male miners were observed for 311,938 person years (py) with 3863 deaths. The all-cause age-standardised mortality rate increased from 5.9/1000 py in 1992 to 20.2/1000 py in 2002. Following ART rollout in 2003, annual mortality rates fluctuated between 12.4/1000 py and 19.3/1000 py in the subsequent 7 years. Half of all deaths were HIV-related and 21% were caused by TB. Half (50%) of miners who died of HIV after ART rollout had never been registered on the Wellness programme. TB was the most common cause of death in HIV positive miners, increasing from 28% of deaths in the pre-ART period to 41% in the post-ART period. CONCLUSIONS/SIGNIFICANCE: This population-based cohort experienced a rapid increase in mortality from 1996 to 2003 due to increases in HIV and TB mortality. Following ART rollout there was a decrease in mortality, but a steady decrease has not been sustained. Possible explanations for these trends include the changing composition of the workforce, maturation of the HIV epidemic, insufficient uptake of ART and an increase in the proportion of deaths due to TB. In order to make a significant and sustained reduction in mortality in this population, expanding and integrating HIV and TB care and treatment is essential.

BACKGROUND: The mortality rate from unnatural deaths for South Africa is nearly double the world average. Reliable data are limited by inaccurate and incomplete ascertainment of specific causes of unnatural death. This study describes trends in causes of unnatural death between 1992 and 2008 in a cohort of South African miners. METHODOLOGY/PRINCIPAL FINDINGS: The study used routinely-collected retrospective data with cause of death determined from multiple sources including the mine's human resources database, medical records, death registration, and autopsy. Cause-specific mortality rates and Poisson regression coefficients were calculated by calendar year and age group. The cohort included 40,043 men. One quarter of all 2937 deaths were from unnatural causes (n = 805). Causes of unnatural deaths were road traffic accidents 38% (109/100,000 py), homicides 30% (88/100,000 py), occupational injuries 17% (50/100,000 py), suicides 8% (24/100,000 py), and other accidents 6% (19/100,000 py). Rates of unnatural deaths declined by 2% (95%CI -4%,-1%) per year over the study period, driven by declining rates of road traffic and other accidents. The rate of occupational injury mortality did not change significantly over time (-2% per year, 95%CI -5%,+2%). Unnatural deaths were less frequent in this cohort of workers than in the South African population (IRR 0.89, 95%CI 0.82-0.95), particularly homicides (IRR 0.48, 95%CI 0.42-0.55). CONCLUSIONS/SIGNIFICANCE: Unnatural deaths were a common cause of preventable and premature death in this cohort of miners. While unnatural death rates declined between 1992 and 2008, occupational fatalities remained at a high level. Evidence-based prevention strategies to address these avoidable deaths are urgently needed.

Background: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. Methods: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. Results: Clinician- initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (< 5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by > 20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. Conclusions: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.