Suchergebnisse

India has the greatest number of HIV infections in Asia and the third highest total number of infected persons globally. Men who have sex with men (MSM) are considered by the Government of India's National AIDS Control Organization (NACO) a "core risk group" for HIV in need of HIV prevention efforts. However there is a dearth of information on the frequency of participation in HIV prevention interventions and subsequent HIV risk and other correlates among MSM in India. Recruited through peer outreach workers, word of mouth and snowball sampling techniques, 210 MSM in Chennai completed an interviewer-administered assessment, including questions about participating in any HIV prevention interventions in the past year, sexual risk taking, demographics, MSM identities, and other psychosocial variables. Bivariate and multivariable logistic regression procedures were used to examine behavioral and demographic correlates with HIV prevention intervention participation. More than a quarter (26%) of the sample reported participating in an HIV prevention intervention in the year prior to study participation. Participants who reported engaging in unprotected anal sex (UAS; odds ratio [OR] = 0.28; p = 0.01) in the 3 months prior to study enrollment were less likely to have participated in an HIV prevention program in the past year. MSM who were older (OR = 1.04; p = 0.05), kothis (feminine acting/appearing and predominantly receptive partners in anal sex) compared to panthis (masculine appearing, predominantly insertive partners; OR = 5.52, p = 0.0004), those with higher educational attainment (OR = 1.48, p = 0.01), being "out" about having sex with other men (OR = 4.03, p = 0.0001), and MSM who reported ever having been paid in exchange for sex (OR = 2.92, p = 0.001) were more likely to have reported participation in an HIV prevention intervention in the preceding year. In a multivariable model, MSM reporting UAS in the prior 3 months were less likely to have participated in an HIV prevention intervention (AOR = 0.34, p = ...

BACKGROUND & OBJECTIVES: To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR. METHODS: A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination. RESULTS: Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region. INTERPRETATION & CONCLUSIONS: While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding ...

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in noncommunicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response occurring in a subset of TB-HIV co-infected patients initiating anti-retroviral therapy (ART). Here, we examined monocyte activation by prospectively quantitating pro-inflammatory plasma markers and monocyte subsets in TB-HIV coinfected patients from a South Indian cohort at baseline and following ART initiation at the time of IRIS, or at equivalent time points in non-IRIS controls. Pro-inflammatory biomarkers of innate and myeloid cell activation were increased in plasma of IRIS patients pre-ART and at the time of IRIS; this association was confirmed in a second cohort in South Africa. Increased expression of these markers correlated with elevated antigen load as measured by higher sputum culture grade and shorter duration of anti-TB therapy. Phenotypic analysis revealed the frequency of CD14++CD162 monocytes was an independent predictor of TB-IRIS, and was closely associated with plasma levels of CRP, TNF, IL-6 and tissue factor during IRIS. In addition, production of inflammatory cytokines by monocytes was higher in IRIS patients compared to controls pre- ART. These data point to a major role of mycobacterial antigen load and myeloid cell hyperactivation in the pathogenesis of TB-IRIS, and implicate monocytes and monocyte-derived cytokines as potential targets for TB-IRIS prevention or treatment. ; European Union (PIRSES-GA-2011-295214) ; Medical Research Council (U1175.02.002.00014.01) ; Wellcome Trust (084323, 088316) ; National Research Foundation (NRF) of South Africa (UID: 85858). ; Wellcome Trust fellowship (098316) ; South African Department of Science and Technology co-funding (DST/CON 0257/2012) ; EDCTP Strategic Primer Grant (SP.2011.41304.074) ; National Institute of Allergy and Infectious Diseases grant (U01AI089244)

In India, research prioritization in Maternal, Newborn, and Child Health and Nutrition (MNCHN) themes has traditionally involved only a handful of experts mostly from major cities. The Indian Council of Medical Research (ICMR)-INCLEN collaboration undertook a nationwide exercise engaging faculty from 256 institutions to identify top research priorities in the MNCHN themes for 2016-2025. The Child Health and Nutrition Research Initiative method of priority setting was adapted. The context of the exercise was defined by a National Steering Group (NSG) and guided by four Thematic Research Subcommittees. Research ideas were pooled from 498 experts located in different parts of India, iteratively consolidated into research options, scored by 893 experts against five pre-defined criteria (answerability, relevance, equity, investment and innovation) and weighed by a larger reference group. Ranked lists of priorities were generated for each of the four themes at national and three subnational (regional) levels [Empowered Action Group & North-Eastern States, Southern and Western States, & Northern States (including West Bengal)]. Research priorities differed between regions and from overall national priorities. Delivery domain of research which included implementation research constituted about 70 per cent of the top ten research options under all four themes. The results were endorsed in the NSG meeting. There was unanimity that the research priorities should be considered by different governmental and non-governmental agencies for investment with prioritization on implementation research and issues cutting across themes.

A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine. ; Funding Agencies|University of Otago; Health Research Council; Maurice Wilkins Centre; European Union [FP7-278864-2]; German Center for Infection Research (DZIF); Fundacao para a Ciencia e a Tecnologia, Portugal [UID/Multi/04413/2013, SFRH/BPD/100688/2014, SFRH/BPD/95406/2013]; Wellcome Trust [201344/Z/16/Z]; Medical Research Council UK [MR/K000551/1, MR/M01360X/1, MR/N010469/1]; Indian Council of Medical Research, New Delhi; L2 Diagnostics LLC, New Haven; Pacific Biosciences, Inc.; Illumina, Inc.; European Society of Mycobacteriology; Hain Lifescience; UK Department of Health [HICF-T5-342, WT098600]; Wellcome Trust