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Background: Determining patterns of HIV transmission is increasingly important for the most efficient use of modern prevention interventions. HIV phylogeny can provide a better understanding of the mechanisms underlying HIV transmission networks in communities., Methods: To reconstruct the structure and dynamics of a local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env sequences obtained from 785 HIV-infected community residents in the northeastern sector of Mochudi, Botswana, during 2010-2013 was estimated. The genotyping coverage was estimated at 44%. Clusters were defined based on relatedness of HIV-1C env sequences and bootstrap support of splits., Results: The overall proportion of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The proportion of clustered sequences from Mochudi was significantly higher than the proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12; Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI 85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were enumerated, and their sequence signatures were reconstructed. Seven of 20 genotyped seroconverters were found in 7 distinct clusters., Conclusions: The study provides essential characteristics of the HIV transmission network in a community in Botswana, suggests the importance of high sampling coverage, and highlights the need for broad HIV genotyping to determine the spread of community-unique and community-mixed viral variants circulating in local epidemics. The proposed methodology of cluster analysis enumerates circulating HIV variants and can work well for surveillance of HIV transmission networks. HIV genotyping at the community level can help to optimize and balance HIV prevention strategies in trials and combined intervention packages.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number. Author summary: Epidemic control and forecasting relies on accurate quantification of transmission and recovery dynamics. This quantification is achievable through the analysis of phylogenetic relationships among pathogen strains obtained from infected individuals. As a key analytical tool for such inference, we concentrate on the study of the episodic birth-death-sampling (EBDS) models. These models define a probability distribution on time-calibrated phylogenies that enable estimation of time-varying rates of pathogens' transmission, recovery, and sampling. Advances in sequencing technology, however, have led to an increasing amount of genetic data collected from these pathogens. Consequently, the traditional computational methods for analyzing these large-scale data under EBDS models have become inadequate due to their high computational load. We aimed to break this computational bottleneck by developing a new approach, based on the Hamiltonian Monte Carlo sampling, that considerably accelerates inference of all rate parameters compared to the traditional random-walk Metropolis-Hasting method. Our method greatly improves the ability to explore the complex distributions that arise when we want to understand disease dynamics at a more granular temporal resolution. This advancement delivers value to public health as it helps rapid data-driven decision-making during outbreaks and enhances our understanding of the spread of infectious diseases. [ABSTRACT FROM AUTHOR]

Background: The majority of childhood blindness causes in low-income countries are treatable or avoidable. Parents or guardians are responsible for making decisions regarding a child's eye care. Understanding parents' awareness and perception of eye problems in crucial in helping to know parents' eye care-seeking behavior. Objective: To determine parental knowledge, attitudes and practice regarding child eye health. Methods: Seven focus groups were carried out in Northwest Ethiopia on knowledge, attitude and practice of parents towards child eye health. Their responses were tape-recorded and later transcribed. A thematic phenomenological approach was used for the analysis. Result: Seventy-one parents participated in the focus groups. Participants were aware of common eye problems like trachoma, trauma, and glaucoma. However, they were unaware of the causes and etiologies of childhood blindness. Participants perceived that eye problems could be treated with hygiene and food, and often held misconceptions about the cause of strabismus and utilization of wearing spectacles. Conclusion: The study revealed that parents are often unaware of the causes and etiologies of common childhood eye diseases, which has downstream effects on health-seeking behavior. Health promotion efforts, potentially through mass and social media, could be helpful to raise awareness, coupled with training of health professionals at primary and secondary health facility levels. [ABSTRACT FROM AUTHOR]

Introduction: Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues. Design: BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities. Methods: During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16–49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake. Results: Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16–24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised. Conclusion: Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services. [ABSTRACT FROM AUTHOR]

The shape of phylogenetic trees can be used to gain evolutionary insights. A tree's shape specifies the connectivity of a tree, while its branch lengths reflect either the time or genetic distance between branching events; well-known measures of tree shape include the Colless and Sackin imbalance, which describe the asymmetry of a tree. In other contexts, network science has become an important paradigm for describing structural features of networks and using them to understand complex systems, ranging from protein interactions to social systems. Network science is thus a potential source of many novel ways to characterize tree shape, as trees are also networks. Here, we tailor tools from network science, including diameter, average path length, and betweenness, closeness, and eigenvector centrality, to summarize phylogenetic tree shapes. We thereby propose tree shape summaries that are complementary to both asymmetry and the frequencies of small configurations. These new statistics can be computed in linear time and scale well to describe the shapes of large trees. We apply these statistics, alongside some conventional tree statistics, to phylogenetic trees from three very different viruses (HIV, dengue fever and measles), from the same virus in different epidemiological scenarios (influenza A and HIV) and from simulation models known to produce trees with different shapes. Using mutual information and supervised learning algorithms, we find that the statistics adapted from network science perform as well as or better than conventional statistics. We describe their distributions and prove some basic results about their extreme values in a tree. We conclude that network science-based tree shape summaries are a promising addition to the toolkit of tree shape features. All our shape summaries, as well as functions to select the most discriminating ones for two sets of trees, are freely available as an R package at http://github.com/Leonardini/treeCentrality. [ABSTRACT FROM AUTHOR]

Introduction: The Malawi Ministry of Health (MoH) has been in collaboration with Médecins sans Frontières (MSF) to increase access to quality HIV care through decentralization of antiretroviral therapy (ART) diagnosis and treatment from hospital to clinics in Nsanje District since 2011. A population-based household survey was implemented to provide information on HIV prevalence and cascade of care to inform and prioritize community-based HIV interventions in the district. Methods: A cross-sectional survey was conducted between September 2016 and January 2017. Using two-stage cluster sampling, eligible adult individuals aged ≥15 years living in the selected households were asked to participate. Participants were interviewed and tested for HIV at home. Those tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their ART status. All participants tested HIV-positive at the time of the survey were advised to report their HIV test result to the health facility of their choice that MSF was supported in the district. HIV-RNA VL results were made available in this health facility. Results: Among 5,315 eligible individuals, 91.1% were included in the survey and accepted an HIV test. The overall prevalence was 12.1% (95% Confidence Interval (CI): 11.2–13.0) and was higher in women than in men: 14.0% versus 9.5%, P<0.001. Overall HIV-positive status awareness was 80.0% (95%CI: 76.4–83.1) and was associated with sex (P<0.05). Linkage to care was 78.0% (95%CI: 74.3–81.2) and participants in care 76.2% (95%CI: 72.4–79.5). ART coverage among participants aware of their HIV-positive status was 95.3% (95%CI: 92.9–96.9) and was not associated with sex (P = 0.55). Viral load suppression among participants on ART was 89.9% (95%CI: 86.6–92.4) and was not statistically different by sex (p = 0.40). Conclusions: Despite encouraging results in HIV testing coverage, cascade of care, and UNAIDS targets in Nsanje District, some gap remains in the first 90, specifically among men and young adults. Enhanced community engagement and new strategies of testing, such as index testing, could be implemented to identify those who are still undiagnosed, particularly men and young adults. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence in Mozambique (12.6%) is one of the highest in the world, yet ~40% of people living with HIV (PLHIV) do not know their HIV status. Strategies to increase HIV testing uptake and diagnosis among PLHIV are urgently needed. Home-based HIV testing services (HBHTS) have been evaluated primarily as a 1-time campaign strategy. Little is known about the potential of repeating HBHTS to diagnose HIV infection among persons who have never been tested (NTs), nor about factors/reasons associated with never testing in a generalized epidemic setting. Methods: During 2014–2017, counselors visited all households annually in the Chókwè Health and Demographic Surveillance System (CHDSS) and offered HBHTS. Cross-sectional surveys were administered to randomly selected 10% or 20% samples of CHDSS households with participants aged 15–59 years before HBHTS were conducted during the visit. Descriptive statistics and logistic regression were used to assess the proportion of NTs, factors/reasons associated with never having been tested, HBHTS acceptance, and HIV-positive diagnosis among NTs. Results: The proportion of NTs decreased from 25% (95% confidence interval [CI]:23%–26%) during 2014 to 12% (95% CI:11% –13%), 7% (95% CI:6%–8%), and 7% (95% CI:6%–8%) during 2015, 2016, and 2017, respectively. Adolescent boys and girls and adult men were more likely than adult women to be NTs. In each of the four years, the majority of NTs (87%–90%) accepted HBHTS. HIV-positive yield among NTs subsequently accepting HBHTS was highest (13%, 95% CI:10%–15%) during 2014 and gradually reduced to 11% (95% CI:8%–15%), 9% (95% CI:6%–12%), and 2% (95% CI:0%–4%) during 2015, 2016, and 2017, respectively. Conclusions: Repeated HBHTS was helpful in increasing HIV testing coverage and identifying PLHIV in Chókwè. In high HIV-prevalence settings with low testing coverage, repeated HBHTS can be considered to increase HIV testing uptake and diagnosis among NTs. [ABSTRACT FROM AUTHOR]

Introduction: Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. Methods: BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. Results: Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16–24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. Conclusions: Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely. [ABSTRACT FROM AUTHOR]

Background: South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa. Methods: Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13–20 years (Mpumalanga province, 2011–2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software. Results: The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6–7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2–6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931–1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3–2.81x10-3) per site per year. Conclusions: Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial. [ABSTRACT FROM AUTHOR]

Monica Sharma and colleagues discuss evidence-based approaches to improving HIV services for men in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Voluntary medical male circumcision (VMMC) is a critical HIV prevention tool. Since 2007, sub-Saharan African countries with the highest prevalence of HIV have been mobilizing resources to make VMMC available. While implementers initially targeted adult men, demand has been highest for boys under age 18. It is important to understand how male adolescents can best be served by quality VMMC services. Methods and Findings: A systematic literature review was performed to synthesize the evidence on best practices in adolescent health service delivery specific to males in sub-Saharan Africa. PubMed, Scopus, and JSTOR databases were searched for literature published between January 1990 and March 2014. The review revealed a general absence of health services addressing the specific needs of male adolescents, resulting in knowledge gaps that could diminish the benefits of VMMC programming for this population. Articles focused specifically on VMMC contained little information on the adolescent subgroup. The review revealed barriers to and gaps in sexual and reproductive health and VMMC service provision to adolescents, including structural factors, imposed feelings of shame, endorsement of traditional gender roles, negative interactions with providers, violations of privacy, fear of pain associated with the VMMC procedure, and a desire for elements of traditional non-medical circumcision methods to be integrated into medical procedures. Factors linked to effective adolescent-focused services included the engagement of parents and the community, an adolescent-friendly service environment, and VMMC counseling messages sufficiently understood by young males. Conclusions: VMMC presents an opportune time for early involvement of male adolescents in HIV prevention and sexual and reproductive health programming. However, more research is needed to determine how to align VMMC services with the unique needs of this population. [ABSTRACT FROM AUTHOR]

Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent) viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations. [ABSTRACT FROM AUTHOR]