Project description:DESIGN:We sought to investigate the evolutionary and historical reasons for the different epidemiological patterns of HIV-1 in the early epidemic. In order to characterize the demographic history of HIV-1 subtypes A and D in east Africa, we examined molecular epidemiology, geographical and historical data. METHODOLOGY:We employed high-resolution phylodynamics to investigate the introduction of HIV-1A and D into east Africa, the geographic trends of viral spread, and the demographic growth of each subtype. We also used geographic information system data to investigate human migration trends, population growth, and human mobility. RESULTS:HIV-1A and D were introduced into east Africa after 1950 and spread exponentially during the 1970s, concurrent with eastward expansion. Spatiotemporal data failed to explain the establishment and spread of HIV based on urban population growth and migration. The low prevalence of the virus in the Democratic Republic of Congo before and after the emergence of the pandemic was, however, consistent with regional accessibility data, highlighting the difficulty in travel between major population centers in central Africa. In contrast, the strong interconnectivity between population centers across the east African region since colonial times has likely fostered the rapid growth of the epidemic in this locale. CONCLUSION:This study illustrates how phylodynamic analysis of pathogens informed by geospatial data can provide a more holistic and evidence-based interpretation of past epidemics. We advocate that this 'landscape phylodynamics' approach has the potential to provide a framework both to understand epidemics' spread and to design optimal intervention strategies.
Project description:The HIV-1 subtype C accounts for an important fraction of HIV infections in east Africa, but little is known about the genetic characteristics and evolutionary history of this epidemic. Here we reconstruct the origin and spatiotemporal dynamics of the major HIV-1 subtype C clades circulating in east Africa. A large number (n = 1,981) of subtype C pol sequences were retrieved from public databases to explore relationships between strains from the east, southern and central African regions. Maximum-likelihood phylogenetic analysis of those sequences revealed that most (>70%) strains from east Africa segregated in a single regional-specific monophyletic group, here called C(EA). A second major Ethiopian subtype C lineage and a large collection of minor Kenyan and Tanzanian subtype C clades of southern African origin were also detected. A bayesian coalescent-based method was then used to reconstruct evolutionary parameters and migration pathways of the C(EA) African lineage. This analysis indicates that the C(EA) clade most probably originated in Burundi around the early 1960s, and later spread to Ethiopia, Kenya, Tanzania and Uganda, giving rise to major country-specific monophyletic sub-clusters between the early 1970s and early 1980s. The results presented here demonstrate that a substantial proportion of subtype C infections in east Africa resulted from dissemination of a single HIV local variant, probably originated in Burundi during the 1960s. Burundi was the most important hub of dissemination of that subtype C clade in east Africa, fueling the origin of new local epidemics in Ethiopia, Kenya, Tanzania and Uganda. Subtype C lineages of southern African origin have also been introduced in east Africa, but seem to have had a much more restricted spread.
Project description:India achieved the title of a polio-free country in March 2014 after a prolonged battle with the poliovirus that threatened millions of children and paralyzed scores of them. Although there has been considerable documentation of the technical strategies applied over the years, not enough has been written on the other warfront that had opened, namely, the battle between the people and the polio eradication program. This article describes the immense people-driven challenges to the polio program and the need for tailor-made and novel responses. This is when the U.S. Agency for International Development-funded CORE Group Polio Project (CGPP)/India stepped in and started work in 1999. The project, a consortium of CORE Group member international non-governmental organizations (NGOs) and local NGOs, formed a bridge between communities and the government program. This article describes how CGPP/India listened to the families and communities who refused to participate in the polio eradication program and then strategically addressed their concerns. These lessons from India can benefit other public health priorities that require civil society involvement, as most public health efforts do.
Project description:BackgroundMulti-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment.Methods and findingsWe developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation. We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission--by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality.ConclusionsAs transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements.
Project description:BackgroundEpidemic HIV-2 (groups A and B) emerged in humans circa 1930-40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985-91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread. Male circumcision (MC) is known to correlate negatively with HIV-1 prevalence in Africa, but studies examining this issue for HIV-2 are lacking.MethodsWe reviewed published HIV-2 serosurveys for 30 cities of all West African countries and obtained credible estimates of real prevalence through Bayesian estimation. We estimated past MC rates of 218 West African ethnic groups, based on ethnographic literature and fieldwork. We collected demographic tables specifying the ethnic partition in cities. Uncertainty was incorporated by defining plausible ranges of parameters (e.g. timing of introduction, proportion circumcised). We generated 1,000 sets of past MC rates per city using Latin Hypercube Sampling with different parameter combinations, and explored the correlation between HIV-2 prevalence and estimated MC rate (both logit-transformed) in the 1,000 replicates.Results and conclusionsOur survey reveals that, in the early 20th century, MC was far less common and geographically more variable than nowadays. HIV-2 prevalence in 1985-91 and MC rates in 1950 were negatively correlated (Spearman rho = -0.546, IQR: -0.553--0.546, p≤0.0021). Guinea-Bissau and Côte d'Ivoire cities had markedly lower MC rates. In addition, MC was uncommon in rural southwestern Côte d'Ivoire in 1930.The differential HIV-2 spread in West Africa correlates with different historical MC rates. We suggest HIV-2 only formed early substantial foci in cities with substantial uncircumcised populations. Lack of MC in rural areas exposed to bushmeat may have had a role in successful HIV-2 emergence.
Project description:The implementation of the COVID-19 national lockdown announced suddenly in March 2020 in India provided a unique opportunity to capture real-time changes in business sentiments during episodes of unexpected and sudden disruptions. Using a logit-probability model to analyse data of this natural experiment showed that firms' 6-months ahead sentiments for its financial condition worsened drastically during lockdown compared to firms surveyed immediately prior to the announcement. Further, smaller firms showed a relatively higher impact. We also find that firms perceive this as a relatively higher demand shock in terms of falling domestic sales post-lockdown whereas supply shocks are perceived to be on the downside. Lastly the mitigation strategy of firms involved reducing employment for unskilled workers and wages for skilled workers. This unique study gives insights not only about firms and their strategies but regarding appropriate policy choices during lockdown. The lessons are applicable for governments which imposed local lockdowns during the second wave and potential disruption for the expected third wave.Supplementary informationThe online version contains supplementary material available at 10.1007/s41775-021-00121-w.
Project description:The unprecedented impact and modeling efforts associated with the 2014-2015 Ebola epidemic in West Africa provides a unique opportunity to document the performances and caveats of forecasting approaches used in near-real time for generating evidence and to guide policy. A number of international academic groups have developed and parameterized mathematical models of disease spread to forecast the trajectory of the outbreak. These modeling efforts often relied on limited epidemiological data to derive key transmission and severity parameters, which are needed to calibrate mechanistic models. Here, we provide a perspective on some of the challenges and lessons drawn from these efforts, focusing on (1) data availability and accuracy of early forecasts; (2) the ability of different models to capture the profile of early growth dynamics in local outbreaks and the importance of reactive behavior changes and case clustering; (3) challenges in forecasting the long-term epidemic impact very early in the outbreak; and (4) ways to move forward. We conclude that rapid availability of aggregated population-level data and detailed information on a subset of transmission chains is crucial to characterize transmission patterns, while ensemble-forecasting approaches could limit the uncertainty of any individual model. We believe that coordinated forecasting efforts, combined with rapid dissemination of disease predictions and underlying epidemiological data in shared online platforms, will be critical in optimizing the response to current and future infectious disease emergencies.
Project description:The human immunodeficiency virus type 1 (HIV-1) subtype G is the second most prevalent HIV-1 clade in West Africa, accounting for nearly 30% of infections in the region. There is no information about the spatiotemporal dynamics of dissemination of this HIV-1 clade in Africa. To this end, we analyzed a total of 305 HIV-1 subtype G pol sequences isolated from 11 different countries from West and Central Africa over a period of 20 years (1992 to 2011). Evolutionary, phylogeographic and demographic parameters were jointly estimated from sequence data using a Bayesian coalescent-based method. Our analyses indicate that subtype G most probably emerged in Central Africa in 1968 (1956-1976). From Central Africa, the virus was disseminated to West and West Central Africa at multiple times from the middle 1970s onwards. Two subtype G strains probably introduced into Nigeria and Togo between the middle and the late 1970s were disseminated locally and to neighboring countries, leading to the origin of two major western African clades (G WA-I and G WA-II). Subtype G clades circulating in western and central African regions displayed an initial phase of exponential growth followed by a decline in growth rate since the early/middle 1990 s; but the mean epidemic growth rate of G WA-I (0.75 year-1) and G WA-II (0.95 year-1) clades was about two times higher than that estimated for central African lineages (0.47 year-1). Notably, the overall evolutionary and demographic history of G WA-I and G WA-II clades was very similar to that estimated for the CRF06_cpx clade circulating in the same region. These results support the notion that the spatiotemporal dissemination dynamics of major HIV-1 clades circulating in western Africa have probably been shaped by the same ecological factors.
Project description:To describe patterns of HIV infection among stable sexual partnerships across sub-Saharan Africa (SSA).The authors defined measures of HIV discordancy and conducted a comprehensive quantitative assessment of discordancy among stable partnerships in 20 countries in SSA through an analysis of the Demographic and Health Survey data.HIV prevalence explained at least 50% of the variation in HIV discordancy, with two distinct patterns of discordancy emerging based on HIV prevalence being roughly smaller or larger than 10%. In low-prevalence countries, approximately 75% of partnerships affected by HIV are discordant, while only about half of these are discordant in high-prevalence countries. Out of each 10 HIV infected persons, two to five are engaged in discordant partnerships in low-prevalence countries compared with one to three in high-prevalence countries. Among every 100 partnerships in the population, one to nine are affected by HIV and zero to six are discordant in low-prevalence countries compared with 16-45 and 9-17, respectively, in high-prevalence countries. Finally, zero to four of every 100 sexually active adults are engaged in a discordant partnership in low-prevalence countries compared with six to eight in high-prevalence countries.In high-prevalence countries, a large fraction of stable partnerships were affected by HIV and half were discordant, whereas in low-prevalence countries, fewer stable partnerships were affected by HIV but a higher proportion of them were discordant. The findings provide a global view of HIV infection among stable partnerships in SSA but imply complex considerations for rolling out prevention interventions targeting discordant partnerships.