Background: All jawed-vertebrates have four T cell receptor (TCR) chains: alpha (TRA), beta (TRB), gamma (TRG) and delta (TRD). Marsupials appear unique by having an additional TCR: mu (TRM). The evolutionary origin of TRM and its relationship to other TCR remain obscure, and is confounded by previous results that support TRM being a hybrid between a TCR and immunoglobulin locus. The availability of the first marsupial genome sequence allows investigation of these evolutionary relationships.

The Medicaid expansion enrolled a population no more likely to be prescribed opioids than the base Medicaid population while significantly increasing uptake of 2 drugs used in medication-assisted treatment.

IntroductionAs access to antiretroviral therapy (ART) increases, the success of treatment programmes depends on ensuring high patient retention in HIV care. We examined retention and attrition among adolescents in ART programmes across clinics operated by The AIDS Support Organization (TASO) in Uganda, which has operated both facility- and community-based distribution models of ART delivery since 2004.MethodsUsing a retrospective cohort analysis of patient-level clinical data, we examined attrition and retention in HIV care and factors associated with attrition among HIV-positive adolescents aged 10–19 years who initiated ART at 10 TASO clinics between January 2006 and December 2011. Retention in care was defined as the proportion of adolescents who had had at least one facility visit within the six months prior to 1 June 2013, and attrition was defined as the proportion of adolescents who died, were lost to follow-up, or stopped treatment. Descriptive statistics and Cox proportional hazards regression models were used to determine the levels of retention in HIV care and the factors associated with attrition following ART initiation.ResultsA total of 1228 adolescents began ART between 2006 and 2011, of whom 57% were female. The median duration in HIV care was four years (IQR=3–6 years). A total of 792 (65%) adolescents were retained in care over the five-year period; 36 (3%) had died or transferred out and 400 (32%) were classified as loss to follow-up. Factors associated with attrition included being older (adjusted hazard ratio (AHR)=1.38, 95% confidence interval (CI) 1.02–1.86), having a higher CD4 count (250+ cells/mm3) at treatment initiation (AHR=0.49, 95% CI 0.34–0.69) and HIV care site with a higher risk of attrition among adolescents in Gulu (AHR=2.26; 95% CI 1.27–4.02) and Masindi (AHR=3.30, 95% CI 1.87–5.84) and a lower risk of attrition in Jinja (AHR=0.24, 95% CI 0.08–0.70). Having an advanced WHO clinical stage at initiation was not associated with attrition.ConclusionsWe found an overall retention rate of 65%, which is comparable to rates achieved by TASO's adult patients and adolescents in other studies in Africa. Variations in the risk of attrition by TASO treatment site and by clinical and demographic characteristics suggest the need for early diagnosis of HIV infection, use of innovative approaches to reach and retain adolescents living with HIV in treatment and identifying specific groups, such as older adolescents, that are at high risk of dropping out of treatment for targeted care and support.

BackgroundTuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only “supportive treatment supervision by treatment partners”, many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure.DiscussionDOT is designed to promote proper adherence to the full course of drug therapy in order to improve patient outcomes and prevent the development of drug resistance. Yet over 8 billion dollars is spent on TB treatment each year and thousands undergo DOT for all or part of their course of treatment, despite the absence of rigorous evidence supporting the superior effectiveness of DOT over self-administration for achieving drug susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with financial and opportunity costs, and the potential for intensified stigma.To rigorously evaluate the effectiveness of DOT and identify the essential contributors to both successful treatment and minimized patient burden, we call for a pragmatic experimental trial conducted in real-world program settings, the gold standard for evidence-based health policy decisions. It is time to invest in the rigorous evaluation of DOT and reevaluate the DOT requirement for TB treatment worldwide.SummaryRigorously evaluating the choice of treatment supporter, the frequency of health care worker contact and the development of new educational materials in a real-world setting would build the evidence base to inform the optimal design of TB treatment protocol. Implementing a more patient-centered approach may be a wise reallocation of resources to raise TB cure rates, prevent relapse, and minimize the emergence of drug resistance. Maintaining the status quo in the absence of rigorous supportive evidence may diminish the effectiveness of TB control policies in the long run.

Marsupials are a lineage of mammals noted for giving birth to highly altricial young, which complete much of their “fetal” development externally attached to a teat. Postnatal B cell ontogeny and diversity was investigated in a model marsupial species, the gray short-tailed opossum, Monodelphis domestica. The results support the initiation of B cell development late in gestation and progressing into the first two weeks of postnatal life. Transcription of CD79a and CD79b was detected in embryonic tissue prior to birth, while immunoglobulin heavy chain locus transcription was not detected until the first postnatal 24 hours. Transcription of the Ig light chains was not detected until postnatal day 7 at the earliest. The predicted timing of the earliest appearance of mature B cells and completion of gene rearrangements is consistent with previous analyses on the timing of endogenous antibody responses in newborn marsupials. The diversity of early B cell IgH chains is limited, as has been seen in fetal humans and mice, but lacks bias in the gene segments used to encode the variable domains. Newborn light chain diversity is, from the start, comparable to that of the adult, consistent with an earlier hypothesis that light chains contribute extensively to antibody diversity in this species.

Background Maternal mortality remains a major health challenge facing developing countries, with pre-eclampsia accounting for up to 17 percent of maternal deaths. Diagnosis requires skilled health providers and devices that are appropriate for low-resource settings. This study presents the first cost-effectiveness analysis of multiple medical devices used to diagnose pre-eclampsia in low- and middle-income countries (LMICs). Methods Blood pressure and proteinuria measurement devices, identified from compendia for LMICs, were included. We developed a decision tree framework to assess the cost-effectiveness of each device using parameter values that reflect the general standard of care based on a survey of relevant literature and expert opinion. We examined the sensitivity of our results using one-way and second-order probabilistic multivariate analyses. Results Because the disability-adjusted life years (DALYs) averted for each device were very similar, the results were influenced by the per-use cost ranking. The most cost-effective device combination was a semi-automatic blood pressure measurement device and visually read urine strip test with the lowest combined per-use cost of $0.2004 and an incremental cost effectiveness ratio of $93.6 per DALY gained relative to a baseline with no access to diagnostic devices. When access to treatment is limited, it is more cost-effective to improve access to treatment than to increase testing rates or diagnostic device sensitivity. Conclusions Our findings were not sensitive to changes in device sensitivity, however they were sensitive to changes in the testing rate and treatment rate. Furthermore, our results suggest that simple devices are more cost-effective than complex devices. The results underscore the desirability of two design features for LMICs: ease of use and accuracy without calibration. Our findings have important implications for policy makers, health economists, health care providers and engineers.

National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0–92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women’s access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve an equitable and effective HIV response and align government planning with international priorities for gender equality.

BackgroundThe previously-named Mexico City Policy (MCP) — which prohibited non U.S.-based non-governmental organizations (NGOs) from receiving U.S. family planning (FP) funding if they advocated, provided, counseled, or referred clients for abortions, even with non-U.S. funds — was reinstated and expanded in 2017. For the first time, the expanded MCP (EMCP) applies to HIV funding through the President’s Emergency Plan for AIDS Relief (PEPFAR) in addition to FP funding. Previous, and more limited, iterations of the policy forced clinic closures and decreased contraceptive access, prompting the need to examine where and how the EMCP may impact FP/HIV service integration.MethodsThe likelihood of FP/HIV service de-integration under the EMCP was quantified using a composite risk index for 31 PEPFAR-funded countries. The index combines six standardized indicators from publically available sources organized into three sub-indexes: 1) The importance of PEPFAR for in-country service delivery of HIV and FP services; 2) The susceptibility of implementing partners to the EMCP; and 3) The integration of FP/HIV funds and programming through PEPFAR and USAID.ResultsCountries with the highest overall risk scores included Zambia (3.3) Cambodia (3.2), Uganda (3.1), South Africa (2.9), Haiti (2.8), Lesotho (2.8), Swaziland (2.1), and Burundi (1.5). Zambia’s risk score is driven by sub-index 1, having a high proportion of country HIV expenditures provided by PEPFAR (86.3%). Cambodia and Uganda’s scores are driven sub-index 3, with both countries reporting 100% of PEPFAR supported HIV delivery sites were providing integrated FP services in 2017. South Africa’s risk score is driven by sub-index 2, where roughly 60% of PEPFAR funding is to non U.S.-based NGOs. Of the countries with the highest risk scores, Swaziland, Lesotho, and South Africa, are also in the top quartile of PEPFAR countries for HIV prevalence and unintended pregnancies among young women.ConclusionThis analysis highlights where and why the EMCP may have the greatest impact on FP/HIV service integration. The possible disruption of service integration in countries with generalized HIV epidemics highlights significant risks. Researchers, national governments, and non-U.S. funders can consider these risk factors to help target their responses to the EMCP and mitigate potential harms of the policy.