Adam Akullian

Sexual partnership age pairings and risk of HIV acquisition in rural South Africa.

Objective: To quantify the contribution of specific sexual partner age groups to the risk of HIV acquisition in men and women in a hyperendemic region of South Africa. Design: We conducted a population-based cohort study among women (15–49 years of age) and men (15–55 years of age) between 2004 and 2015 in KwaZulu-Natal, South Africa. Methods: Generalized additive models were used to estimate smoothed HIV incidence rates across partnership age pairings in men and women. Cox proportional hazards regression was used to estimate the relative risk of HIV acquisition by partner age group. Results: A total of 882 HIV seroconversions were observed in 15 935 person-years for women, incidence rate = 5.5 per 100 person-years [95% confidence interval (CI), 5.2–5.9] and 270 HIV seroconversions were observed in 9372 person-years for men, incidence rate = 2.9 per 100 person-years (95% CI, 2.6–3.2). HIV incidence was highest among 15–24-year-old women reporting partnerships with 30–34-year-old men, incidence rate = 9.7 per 100 person-years (95% CI, 7.2–13.1). Risk of HIV acquisition in women was associated with male partners aged 25–29 years (adjusted hazard ratio; aHR = 1.44, 95% CI, 1.02–2.04) and 30–34 years (aHR = 1.50, 95% CI, 1.08–2.09) relative to male partners aged 35 and above. Risk of HIV acquisition in men was associated with 25–29-year-old (aHR = 1.72, 95% CI, 1.02–2.90) and 30–34-year-old women (aHR = 2.12, 95% CI, 1.03–4.39) compared to partnerships with women aged 15–19 years. Conclusion: Age of sexual partner is a major risk factor for HIV acquisition in both men and women, independent of ones own age. Partner age pairings play a critical role in driving the cycle of HIV transmission.

Environmental Transmission of Typhoid Fever in an Urban Slum

Background Enteric fever due to Salmonella Typhi (typhoid fever) occurs in urban areas with poor sanitation. While direct fecal-oral transmission is thought to be the predominant mode of transmission, recent evidence suggests that indirect environmental transmission may also contribute to disease spread. Methods Data from a population-based infectious disease surveillance system (28,000 individuals followed biweekly) were used to map the spatial pattern of typhoid fever in Kibera, an urban informal settlement in Nairobi Kenya, between 2010–2011. Spatial modeling was used to test whether variations in topography and accumulation of surface water explain the geographic patterns of risk. Results Among children less than ten years of age, risk of typhoid fever was geographically heterogeneous across the study area (p = 0.016) and was positively associated with lower elevation, OR = 1.87, 95% CI (1.36–2.57), p <0.001. In contrast, the risk of typhoid fever did not vary geographically or with elevation among individuals less than 6b ten years of age. Conclusions Our results provide evidence of indirect, environmental transmission of typhoid fever among children, a group with high exposure to fecal pathogens in the environment. Spatially targeting sanitation interventions may decrease enteric fever transmission.

Cautioning the use of degree-day models for climate change projections in the presence of parametric uncertainty

Developmental models, such as degree-day models, are commonly used to predict the impact of future climate change on the intensity, distribution, and timing of the transmission of infectious diseases, particularly those caused by pathogens carried by vectors or intermediate hosts. Resulting projections can be useful in policy discussions concerning regional or national responses to future distributions of important infectious diseases. Although the simplicity of degree-day models is appealing, little work has been done to analyze their ability to make reliable projections of the distribution of important pathogens, vectors, or intermediate hosts in the presence of the often considerable parametric uncertainty common to such models. Here, a population model of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, was used to investigate the sensitivity of host range predictions in Sichuan Province, China, to uncertainty in two key degree-day model parameters: delta(min) (minimum temperature threshold for development) and K (total degree-days required for completion of snail development). The intent was to examine the consequences of parametric uncertainty in a plausible biological model, rather than to generate the definitive model. Results indicate that model output, the seasonality of population dynamics, and range predictions, particularly along the edge of the range, are highly sensitive to changes in model parameters, even at levels of parametric uncertainty common to such applications. Caution should be used when interpreting the results of degree-day models used to generate predictions of disease distribution and risk under scenarios of future climate change, and predictions should be considered most reliable when the temperature ranges used in projections resemble those used to estimate model parameters. Given the potential for substantial changes in degree-day model output with modest changes in parameter values, caution is warranted when results will be used to inform policy and management decisions.

People living with HIV travel farther to access healthcare: a population-based geographic analysis from rural Uganda

The availability of specialized HIV services is limited in rural areas of sub‐Saharan Africa where the need is the greatest. Where HIV services are available, people living with HIV (PLHIV) must overcome large geographic, economic and social barriers to access healthcare. The objective of this study was to understand the unique barriers PLHIV face when accessing healthcare compared with those not living with HIV in a rural area of sub‐Saharan Africa with limited availability of healthcare infrastructure.

Geographic distribution of HIV stigma among women of childbearing age in rural Kenya.

Objective(s):HIV stigma is considered to be a major driver of the HIV/AIDS pandemic, yet there is a limited understanding of its occurrence. We describe the geographic patterns of two forms of HIV stigma in a cross-sectional sample of women of childbearing age from western Kenya: internalized stigma (associated with shame) and externalized stigma (associated with blame). Design:Geographic studies of HIV stigma provide a first step in generating hypotheses regarding potential community-level causes of stigma and may lead to more effective community-level interventions. Methods:Spatial regression using generalized additive models and point pattern analyses using K-functions were used to assess the spatial scale(s) at which each form of HIV stigma clusters, and to assess whether the spatial clustering of each stigma indicator was present after adjustment for individual-level characteristics. Results:There was evidence that externalized stigma (blame) was geographically heterogeneous across the study area, even after controlling for individual-level factors (P = 0.01). In contrast, there was less evidence (P = 0.70) of spatial trend or clustering of internalized stigma (shame). Conclusion:Our results may point to differences in the underlying social processes motivating each form of HIV stigma. Externalized stigma may be driven more by cultural beliefs disseminated within communities, whereas internalized stigma may be the result of individual-level characteristics outside the domain of community influence. These data may inform community-level interventions to decrease HIV-related stigma, and thus impact the HIV epidemic.

The Missing 27

Though a wide body of observational and model-based evidence underscores the promise of Universal Test and Treat (UTT) to reduce population-level HIV incidence in high-burden areas of Sub-Saharan Africa (SSA) [1,2], the only cluster-randomized trial of UTT completed to date, ANRS 12249, did not show a significant reduction in incidence [3]. More UTT trials are currently underway, and some have already exceeded the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 targets [4,5]. Still, even with high test and treat coverage, it is unknown whether ongoing trials will engage populations with the greatest potential for onward transmission to achieve the ambitious goal of reducing new HIV infections by 90% between 2010 and 2013 [6]. Ultimately, even strategies that successfully meet or exceed the 90–90–90 targets will leave up to 27% of people living with HIV/AIDS virally nonsuppressed. The epidemiological profile of the ‘missing 27%’ – including their risk behavior, mobility, and network connectedness – is not well understood and must be better characterized to fully evaluate the effectiveness of UTT.

Modeling the Combined Influence of Host Dispersal and Waterborne Fate and Transport on Pathogen Spread in Complex Landscapes

Environmental models, often applied to questions on the fate and transport of chemical hazards, have recently become important in tracing certain environmental pathogens to their upstream sources of contamination. These tools, such as first-order decay models applied to contaminants in surface waters, offer promise for quantifying the fate and transport of pathogens with multiple environmental stages and/or multiple hosts, in addition to those pathogens whose environmental stages are entirely waterborne. Here we consider the fate and transport capabilities of the human schistosome Schistosoma japonicum, which exhibits two waterborne stages and is carried by an amphibious intermediate snail host. We present experimentally derived dispersal estimates for the intermediate snail host and fate and transport estimates for the passive downstream diffusion of cercariae, the waterborne, human-infective parasite stage. Using a one-dimensional advective transport model exhibiting first-order decay, we simulate the added spatial reach and relative increase in cercarial concentrations that dispersing snail hosts contribute to downstream sites. Simulation results suggest that snail dispersal can substantially increase the concentrations of cercariae reaching downstream locations, relative to no snail dispersal, effectively putting otherwise isolated downstream sites at increased risk of exposure to cercariae from upstream sources. The models developed here can be applied to other infectious diseases with multiple life-stages and hosts, and have important implications for targeted ecological control of disease spread.

Population mobility associated with higher risk sexual behaviour in eastern African communities participating in a Universal Testing and Treatment trial.

There are significant knowledge gaps concerning complex forms of mobility emergent in sub‐Saharan Africa, their relationship to sexual behaviours, HIV transmission, and how sex modifies these associations. This study, within an ongoing test‐and‐treat trial (SEARCH, NCT01864603), sought to measure effects of diverse metrics of mobility on behaviours, with attention to gender.

Geographic coverage of male circumcision in western Kenya.

Abstract Voluntary Medical Male Circumcision (VMMC) for human immunodeficiency virus (HIV) prevention has scaled up rapidly among young men in western Kenya since 2008. Whether the program has successfully reached uncircumcised men evenly across the region is largely unknown. Using data from two cluster randomized surveys from the 2008 and 2014 Kenyan Demographic Health Survey (KDHS), we mapped the continuous spatial distribution of circumcised men by age group across former Nyanza Province to identify geographic areas where local circumcision prevalence is lower than the overall, regional prevalence. The prevalence of self-reported circumcision among men 15 to 49 across six counties in former Nyanza Province increased from 45.6% (95% CI = 33.2–58.0%) in 2008 to 71.4% (95% CI = 67.4–75.0%) in 2014, with the greatest increase in men 15 to 24 years of age, from 40.4% (95% CI = 27.7–55.0%) in 2008 to 81.6% (95% CI = 77.2–85.0%) in 2014. Despite the dramatic scale-up of VMMC in western Kenya, circumcision coverage in parts of Kisumu, Siaya, and Homa Bay counties was lower than expected (P < 0.05), with up to 50% of men aged 15 to 24 still uncircumcised by 2014 in some areas. The VMMC program has proven successful in reaching a large population of uncircumcised men in western Kenya, but as of 2014, pockets of low circumcision coverage still existed. Closing regional gaps in VMMC prevalence to reach 80% coverage may require targeting specific areas where VMMC prevalence is lower than expected.

Prioritizing Countries for Interventions to Reduce Child Mortality: Tools for Maximizing the Impact of Mass Drug Administration of Azithromycin

Background As new interventions to reduce childhood mortality are identified, careful consideration must be given to identifying populations that could benefit most from them. Promising reductions in childhood mortality reported in a large cluster randomized trial of mass drug administration (MDA) of azithromycin (AZM) prompted the development of visually compelling, easy-to-use tools that synthesize country-specific data on factors that would influence both potential AZM benefit and MDA implementation success. Methodology/Principal Findings We assessed the opportunity to reduce mortality and the feasibility of implementing such a program, creating Opportunity and Feasibility Indices, respectively. Countries with high childhood mortality were included. A Country Ranking Index combined key variables from the previous two Indices and applied a scoring system to identify high-priority countries. We compared four scenarios with varying weights given to each variable. Twenty-five countries met inclusion criteria. We created easily visualized tools to display the results of the Opportunity and Feasibility Indices. The Opportunity Index revealed substantial variation in the opportunity for an MDA of AZM program to reduce mortality, even among countries with high overall childhood mortality. The Feasibility Index demonstrated that implementing such a program would be most challenging in the countries that could see greatest benefit. Based on the Country Ranking Index, Equatorial Guinea would benefit the most from the MZA of AZM in three of the four scenarios we tested. Conclusions/Significance These visually accessible tools can be adapted or refined to include other metrics deemed important by stakeholders, and provide a quantitative approach to prioritization for intervention implementation. The need to explicitly state metrics and their weighting encourages thoughtful and transparent decision making. The objective and data-driven approach promoted by the three Indices may foster more efficient use of resources.