Search bioRxivSearch

bioRxiv · 10.1101/477158

Antiretroviral therapy is the principal cause of tuberculosis decline in southern and eastern Africa

Abstract

The incidence of tuberculosis (TB) in southern and eastern Africa was driven sharply upwards during 1980s and 1990s by coinfection with Mycobacterium tuberculosis and the human immunodeficiency virus (HIV). Although drug treatments for TB infection (isoniazid preventive therapy) and disease (combinations of TB drugs) can reduce TB incidence if implemented effectively, we find that antiretroviral therapy (ART) given to people with HIV infection was strongly and systematically associated with the accelerated decline of TB in 12 of the worst affected African countries between 2003 and 2016. Inferring that ART was a significant cause of TB decline, ART prevented approximately 1.88 {+/-} 0.23 million HIV-positive TB cases, or 15.7 {+/-} 1.9 percent of the total number expected. There is no evidence that drug treatment of TB infection (IPT) or disease (combination chemotherapy) played more than a minor role in accelerating TB decline after 2003. In these 12 countries, over the period 2003-16, ART made a major contribution towards achieving international targets for the reduction of TB incidence.\n\nSignificanceTuberculosis (TB) is still the leading cause of death from a single infectious agent. To cut the TB incidence rate by 80% between 2015 and 2030, in line with the WHO End TB Strategy, demands a five-fold increase in the rate of decline worldwide, from 2% to 10%/year. We find that the reduction in TB incidence rate in 12 African countries, at up to 8%/year, is due mainly to the expanded provision of antiretroviral therapy (ART) to people living with HIV, rather than to improvements in the treatment of TB infection and disease. ART should remain central to TB control where rates of TB-HIV coinfection are high, but new efforts are needed to maximize the direct benefits of treating TB infection and disease.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Dye, C., Williams, B. G.. 2018-11-23. Antiretroviral therapy is the principal cause of tuberculosis decline in southern and eastern Africa. https://doi.org/10.1101/477158

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The first reliable autochthonous case of ticks-borne encephalitis infection and detection of tick-borne encephalitis virus in Ixodes ricinus ticks and their hosts in an urban park of Moscow, Russia

Here, we report the first confirmed autochthonous tick-borne encephalitis case diagnosed in Moscow in 2016 and describe the detection of Tick-borne encephalitis virus (TBEV) in ticks and small mammals in a Moscow park.\n\nThe paper includes data from two patients who were bitten by TBEV-infected ticks within the Moscow city limits; one of these cases led to the development of the meningeal form of TBE. Both TBEV-infected ticks attacked patients in the same area. We collected ticks and trapped small mammals in this area in 2017. All samples were screened for the presence of pathogens causing tick-borne diseases by PCR. The TBEV-positive ticks and small mammals tissue samples were subjected to virus isolation. The sequencing of the complete polyprotein gene of the positive samples was performed.\n\nA total of 227 questing ticks were collected. TBEV was detected in five specimens of Ixodes ricinus. We trapped 44 small mammals, mainly bank voles (Myodes glareolus) and pygmy field mice (Apodemus uralensis). Two samples of brain tissue from bank voles yielded a positive signal in RT-PCR for TBEV. We obtained six virus isolates from the ticks and brain tissue of a bank vole. Complete genome sequencing showed that the obtained isolates belong to the European subtype and have low diversity with sequence identities as high as 99.9%. GPS tracking showed that the maximum distance between the exact locations where the TBEV-positive ticks were collected was 185 m. We assume that the forest park was free of TBEV and that the virus was recently introduced.

epidemiology

Optimizing the use of the Men-ACWY conjugated vaccine to control the developing meningococcal W disease outbreak in the Netherlands, a rapid analysis.

BackgroundThere is a developing outbreak of Neisseria meningitidis serotype W (MenW) in the Netherlands. In response, those aged 14 months and 14 years are vaccinated with the conjugated MenACWY vaccine. In the spring of 2018 we aimed to explore the impact of adding a one-off catch-up campaign targeting those aged 15-18 years on the transmission of MenW and the cost-effectiveness of such a campaign.\n\nMethodsWe estimated the growth rate of the MenW outbreak and quantified the impact of various targeted vaccination strategies on the reproductive number, and subsequently projected the future incidence with and without vaccination. Future cases were expressed in costs and QALYS and the incremental cost-effectiveness ratio was obtained.\n\nResultsWe estimate a reproductive number of around 1.4 (95%CI 1.2-1.7) over the period February 2016-February 2018. Adding the catch-up campaign reduces the reproductive number five years earlier than without a catch-up campaign, to a level around 1.2. The vaccination campaign, including the catch-up, will prevent around 100 cases per year in our base case scenario. Given the projected impact and realistic assumptions on costs and QALYs, adding the catch-up can be considered cost-effective using a threshold of {euro}20,000 per QALY.\n\nConclusionAdding the catch-up campaign targeting those aged 15-18 brings the impact of vaccination on reducing transmission five years forward and directly prevents a high-incidence age group from carriage and disease. Such a campaign can be considered cost-effective. Our study did underpin the decision to introduce a catch-up campaign in spring 2019. Furthermore, our applied method can be of interest for anyone solving vaccine allocation questions in a developing outbreak.

epidemiology

Spatiotemporal Variability in Dengue Transmission Intensity in Jakarta, Indonesia

BackgroundApproximately 70% of the global burden of dengue disease occurs on the Asian continent, where many large urban centres provide optimal environments for sustained endemic transmission and periodic epidemic cycles. Jakarta, the capital of Indonesia, is a densely populated megacity with hyperendemic dengue transmission. Characterization of the spatiotemporal distribution of dengue transmission intensity is of key importance for optimal implementation of novel control and prevention programmes, including vaccination. In this paper we use mathematical models to provide the first detailed description of spatial and temporal variability in dengue transmission in Jakarta.\n\nMethodology/Principal FindingsWe applied catalytic models in a Bayesian framework to age-stratified dengue case notification data to estimate dengue force of infection and reporting probabilities in 42 subdistricts of Jakarta. The model was fit to yearly and average annual data covering a 10- year period between 2008 and 2017. We estimated a long-term average annual transmission intensity of 13.0% (95%CrI: 12.9-13.1%) per year in Jakarta province, ranging from 9.0% (95%CrI: 7.7-10.3%) to 16.4% (95%CrI: 15.3-17.4%) across subdistricts. Annual average transmission intensity in Jakarta province during the 10-year period ranged from 1.2% (95%CrI: 1.1-1.3%) in 2017 to 12.4% (95%CrI: 12.1-12.8%) in 2016.\n\nConclusions/SignificanceWhile the absolute number of dengue case notifications cannot be relied upon as a measure of endemicity, the age-distribution of reported dengue cases provides valuable insights into the underlying nature of transmission. Our estimates from yearly and average annual case notification data represent the first detailed estimates of dengue transmission intensity in Jakartas subdistricts, which will be important to consider when assessing the population-level impact and cost-effectiveness of potential control and prevention programmes in Jakarta province, such as the controlled release of Wolbachia-carrying mosquitoes and vaccination.

epidemiology