Long-term impact of the adoption of bedaquiline-containing regimens on the burden of drug-resistant tuberculosis in China.

BACKGROUND: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China. METHODS: A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment. RESULTS: In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption. CONCLUSIONS: Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.

Female-Driven Multiple Concurrent Sexual Partnership Systems in a Rural Part of a Southern Tanzanian Province.

BACKGROUND: Multiple concurrent sexual relationships are one of the major challenges to HIV prevention in Tanzania. This study aims to explore sexual behaviour patterns including the practice of multiple concurrent sexual partnerships in a rural Tanzanian setting. METHODS: This qualitative study used focus group discussions and in-depth interviews with men and women from the community as well as ethnographic participant observations. The data was collected during 16 months of fieldwork in 2007, 2008, and 2009. The focus group discussions and in-depth interviews were transcribed verbatim and translated into English. The data was analysed through the process of latent content analysis. An open coding coding process was applied to create categories and assign themes. FINDINGS: Mafiga matatu was an expression used in this society to describe women's multiple concurrent sexual partners, usually three partners, which was described as a way to ensure social and financial security for their families as well as to achieve sexual pleasure. Adolescent initiation ceremonies initiated and conducted by grand mothers taught young women why and how to engage successfully in multiple concurrent sexual relationships. Some men expressed support for their female partners to behave according to mafiga matatu, while other men were hesitant around this behaviour. Our findings indicate that having multiple concurrent sexual partners is common and a normative behaviour in this setting. Economical factors and sexual pleasure were identified as drivers and viewed as legitimate reason for women to have multiple concurrent sexual partnerships. CONCLUSIONS: Structural changes improving women's financial opportunities and increasing gender equality will be important to enable women to not depend on multiple concurrent sexual partnerships for financial security. Future research should explore how normative sexual behaviour changes as these structural changes take place.

Antiretroviral treatment coverage in a rural district in Tanzania--a modeling study using empirical data.

BACKGROUND: The Tanzanian Government started scaling up its antiretroviral treatment (ART) program from referral, regional and district hospitals to primary health care facilities in October 2004. In 2010, most ART clinics were decentralized to primary health facilities. ART coverage, i.e. people living with HIV (PLHIV) on combination treatment as a proportion of those in need of treatment, provides the basis for evaluating the efficiency of ART programs at national and district level. We aimed to evaluate adult ART and pre-ART care coverage by age and sex at CD4 < 200, < 350 and all PLHIV in the Rufiji district of Tanzania from 2006 to 2010. METHODS: The numbers of people on ART and pre-ART care were obtained from routinely aggregated, patient-level, cohort data from care and treatment centers in the district. We used ALPHA model to predict the number in need of pre-ART care and ART by age and sex at CD4 < 200 and < 350. RESULTS: Adult ART coverage among PLHIV increased from 2.9% in 2006 to 17.6% in 2010. In 2010, coverage was 20% for women and 14.8% for men. ART coverage was 30.2% and 38.7% in 2010 with reference to CD4 criteria of 350 and 200 respectively. In 2010, ART coverage was 0 and 3.4% among young people aged 15-19 and 20-24 respectively. ART coverage among females aged 35-39 and 40-44 was 30.6 and 35% respectively in 2010. Adult pre-ART care coverage for PLHIV of CD4 < 350 increased from 5% in 2006 to 37.7% in 2010. The age-sex coverage patterns for pre-ART care were similar to ART coverage for both CD4 of 200 and 350 over the study period. CONCLUSIONS: ART coverage in the Rufiji district is unevenly distributed and far from the universal coverage target of 80%, in particular among young men. The findings in 2010 are close to the most recent estimates of ART coverage in 2013. To strive for universal coverage, both the recruitment of new eligible individuals to pre-ART and ART and the successful retention of those already on ART in the program need to be prioritized.

Antiretroviral treatment knowledge and stigma--implications for programs and HIV treatment interventions in rural Tanzanian populations.

OBJECTIVE: To analyse antiretroviral treatment (ART) knowledge and HIV- and ART-related stigma among the adult population in a rural Tanzanian community. DESIGN: Population-based cross-sectional survey of 694 adults (15-49 years of age). METHODS: Latent class analysis (LCA) categorized respondents' levels of ART knowledge and of ART-related stigma. Multinomial logistic regression assessed the association between the levels of ART knowledge and HIV- and ART-related stigma, while controlling for the effects of age, gender, education, marital status and occupation. RESULTS: More than one-third of men and women in the study reported that they had never heard of ART. Among those who had heard of ART, 24% were east informed about ART, 8% moderately informed, and 68% highly informed. Regarding ART-related stigma, 28% were least stigmatizing, 41% moderately stigmatizing, and 31% highly stigmatizing toward persons taking ART. Respondents that had at least primary education were more likely to have high levels of knowledge about ART (OR 3.09, 95% CI 1.61-5.94). Participants highly informed about ART held less HIV- and ART-related stigma towards ART patients (OR 0.26, 95% CI 0.09-0.74). CONCLUSION: The lack of ART knowledge is broad, and there is a strong association between ART knowledge and individual education level. These are relevant findings for both HIV prevention and HIV treatment program interventions that address ART-related stigma across the entire spectrum of the community.

Challenges to ART scale-up in a rural district in Tanzania: stigma and distrust among Tanzanian health care workers, people living with HIV and community members.

OBJECTIVE: To explore attitudes, perceptions and practices among health care workers, antiretroviral treatment (ART) patients and community members regarding ART care and the social consequences of ART roll-out in rural Tanzania. METHODS: We performed focus group discussions and in-depth interviews with health care workers, community members, ART patients, religious leaders, as well as social workers. Field observations and ethnographic assessments were conducted in parallel. RESULTS: We found widespread negative attitudes and perceptions of ART care HIV testing and the ART programme, a lack of trust in its sustainability, as well as lack of community and health worker involvement in the programme planning and treatment. HIV-positive individuals on ART reported risky behaviours with the aim of revenge and were feared by community members. We also found that the ART availability was seen as an incentive to engage in HIV testing among some community members. CONCLUSION: Our findings underline the importance of involving health workers and the community at a high level and their important role in promoting trust in the ART programme. There is an immense need to adjust interventions focusing on stigma reduction in the direction of ART scale-up and to build awareness among ART patients so they understand how risky behaviours affect their personal well-being and the community at large.

Death receptor ligation or exposure to perforin trigger rapid egress of the intracellular parasite Toxoplasma gondii.

The obligate intracellular parasite Toxoplasma gondii chronically infects up to one-third of the global population, can result in severe disease in immunocompromised individuals, and can be teratogenic. In this study, we demonstrate that death receptor ligation in T. gondii-infected cells leads to rapid egress of infectious parasites and lytic necrosis of the host cell, an active process mediated through the release of intracellular calcium as a consequence of caspase activation early in the apoptotic cascade. Upon acting on infected cells via death receptor- or perforin-dependent pathways, T cells induce rapid egress of infectious parasites able to infect surrounding cells, including the Ag-specific effector cells.