Felix Lankester

Great ape genetic diversity and population history

Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria–Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Evidence from Cameroon reveals differences in the genetic structure and histories of chimpanzee populations

The history of the genus Pan is a topic of enduring interest. Chimpanzees (Pan troglodytes) are often divided into subspecies, but the population structure and genetic history of chimpanzees across Africa remain unclear. Some population genetics studies have led to speculation that, until recently, this species constituted a single population with ongoing gene flow across its range, which resulted in a continuous gradient of allele frequencies. Chimpanzees, designated here as P. t. ellioti, occupy the Gulf of Guinea region that spans southern Nigeria and western Cameroon at the center of the distribution of this species. Remarkably, few studies have included individuals from this region, hindering the examination of chimpanzee population structure across Africa. Here, we analyzed microsatellite genotypes of 94 chimpanzees, including 32 designated as P. t. ellioti. We find that chimpanzees fall into three major populations: (i) Upper Guinea in western Africa (P. t. verus); (ii) the Gulf of Guinea region (P. t. ellioti); and (iii) equatorial Africa (P. t. troglodytes and P. t. schweinfurthii). Importantly, the Gulf of Guinea population is significantly different genetically from the others, sharing a last common ancestor with the populations in Upper Guinea ~0.46 million years ago (mya) and equatorial Africa ~0.32 mya. Equatorial chimpanzees are subdivided into up to three populations occupying southern Cameroon, central Africa, and eastern Africa, which may have constituted a single population until ~0.10–0.11 mya. Finally, occasional hybridization may be occurring between the Gulf of Guinea and southern Cameroon populations.

Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions

ABSTRACT Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene. A plethora of novel AdV sequences were identified, representing at least 45 distinct AdVs. From the AdV-positive individuals, 29 nearly complete hexon genes were amplified and, based on phylogenetic analysis, tentatively allocated to all known human AdV species (Human adenovirus A to Human adenovirus G [HAdV-A to -G]) as well as to the only simian AdV species (Simian adenovirus A [SAdV-A]). Interestingly, five of the AdVs detected in great apes grouped into the HAdV-A, HAdV-D, HAdV-F, or SAdV-A clade. Furthermore, we report the first detection of AdVs in New World monkeys, clustering at the base of the primate AdV evolutionary tree. Most notably, six chimpanzee AdVs of species HAdV-A to HAdV-F revealed a remarkably close relationship to human AdVs, possibly indicating recent interspecies transmission events.

Dynamics of a morbillivirus at the domestic–wildlife interface: Canine distemper virus in domestic dogs and lions

Significance Morbilliviruses are a growing concern because of their ability to infect multiple species. The spill-over of canine distemper virus (CDV) from domestic dogs has been associated with severe declines in wild carnivores worldwide, and therefore mass dog vaccination has been suggested as a potential control strategy. Focusing on three decades of CDV exposure data in dogs and lions of the Serengeti, we show that cyclic infection dynamics in lions initially driven by dogs became more frequent and asynchronous, suggesting that the wider dog population and other wildlife species drive CDV dynamics. Hence, although widespread dog vaccination reduced the infection in dogs, transmission to lion populations still occurred, warranting further investigation into effective management options of CDV in this species-rich ecosystem. Morbilliviruses cause many diseases of medical and veterinary importance, and although some (e.g., measles and rinderpest) have been controlled successfully, others, such as canine distemper virus (CDV), are a growing concern. A propensity for host-switching has resulted in CDV emergence in new species, including endangered wildlife, posing challenges for controlling disease in multispecies communities. CDV is typically associated with domestic dogs, but little is known about its maintenance and transmission in species-rich areas or about the potential role of domestic dog vaccination as a means of reducing disease threats to wildlife. We address these questions by analyzing a long-term serological dataset of CDV in lions and domestic dogs from Tanzania’s Serengeti ecosystem. Using a Bayesian state–space model, we show that dynamics of CDV have changed considerably over the past three decades. Initially, peaks of CDV infection in dogs preceded those in lions, suggesting that spill-over from dogs was the main driver of infection in wildlife. However, despite dog-to-lion transmission dominating cross-species transmission models, infection peaks in lions became more frequent and asynchronous from those in dogs, suggesting that other wildlife species may play a role in a potentially complex maintenance community. Widespread mass vaccination of domestic dogs reduced the probability of infection in dogs and the size of outbreaks but did not prevent transmission to or peaks of infection in lions. This study demonstrates the complexity of CDV dynamics in natural ecosystems and the value of long-term, large-scale datasets for investigating transmission patterns and evaluating disease control strategies.

Cost-effectiveness of canine vaccination to prevent human rabies in rural tanzania

Context Human rabies causes many deaths in resource-limited countries, and most are due to dog bites. Administration of postexposure prophylaxis is uncommon because of cost and limited access. Contribution Using a model of rabies transmission in 2 rural districts of Tanzania, the authors demonstrated that a campaign of annual rabies vaccination of dogs would be very cost- effective. Implication Annual canine rabies vaccination in sub-Saharan Africa could dramatically decrease the occurrence of this disease in humans. The Editors Rabies is a viral encephalitic disease of mammals that is responsible for an estimated 61000 human deaths each year (1), nearly one third of which occur in rural Africa (2). Once symptoms appear, rabies is almost universally fatal (3). Control of the disease in canines is a potential approach to reducing human rabies incidence because more than 99% of all human cases worldwide result from the bite of a domestic dog (4). Postexposure prophylaxis (PEP), including a series of vaccinations and administration of immunoglobulin, can prevent rabies after a dog bite. Worldwide, more than 7.5 million rabies PEP regimens are delivered annually (5) at an estimated cost of more than

Implementing Pasteur's vision for rabies elimination

1.5 billion (1). Given that a disproportionate rabies burden occurs in sub-Saharan Africa, these costs often fall to the countries that are least able to afford them. In addition, PEP is frequently unavailable in rural areas within the 24-hour period recommended for treatment initiation after exposure to rabies (6). Concerns about program costs and the efficient use of health resources have been identified as major barriers to the implementation of canine vaccination programs (7). One-time canine rabies vaccination campaigns have been evaluated as cost-effective prevention against human rabies in urban Chad (8). However, more than 75% of rabies deaths in Africa occur in rural areas (2), and disease dynamics vary between these 2 settings because of different densities and contact patterns among humans, dogs, and other wildlife (9). Additionally, high birth and death rates in domestic dogs as well as reintroduction of rabies from dogs or wildlife in neighboring, unvaccinated regions make it unlikely that a 1-time vaccination campaign will control canine rabies in rural Africa indefinitely (10). Therefore, we evaluated the cost-effectiveness of rabies control in rural Africa through a strategy of annual canine vaccination campaigns. Methods We developed a mathematical model of rabies transmission to estimate the epidemiologic effects, clinical benefits, economic costs, and cost-effectiveness of canine vaccination coverage strategies ranging from 0% to 95% in rural Tanzania. No vaccination, which is the status quo in most parts of Tanzania, was considered the baseline for our analysis. Outcome measures included numbers of dogs vaccinated, incidence of human rabies, and economic costs (in 2010 U.S. dollars). The analysis was conducted from the perspective of a health policymaker, and we therefore considered health burden in terms of life-years, which in this context were equal to disability-adjusted life-years given that rabies is inevitably fatal. Thus, the entire health burden accrues from deaths rather than illnesses. We assessed economic costs associated with both a canine vaccination campaign and PEP to prevent rabies in exposed persons. In conformity with World Health Organization guidelines (11) and other recommendations for best practices (12), cost-effectiveness outcomes were reported across both 1- and 10-year time horizons on a present-value basis with a 3% annual discount rate. We evaluated the robustness of the results to model inputs, using both probabilistic uncertainty analysis and 1-way sensitivity analysis. We applied World Health Organization recommendations (13, 14) to denote strategies with incremental cost-effectiveness ratios less than the per-capita gross domestic product (GDP) for a life-year saved (GDP,

Implementing Pasteur's vision for rabies elimination: the evidence base and the needed policy actions

1430 for Tanzania [15]) as very cost-effective and ratios less than 3 times the per-capita GDP (

Novel cytomegaloviruses in free-ranging and captive great apes: phylogenetic evidence for bidirectional horizontal transmission

4290) as cost-effective. We compared pastoral (Ngorongoro) and agro-pastoral (Serengeti) districts in rural Tanzania as representative of 2 major settlement patterns and canine densities in rural Africa. Although both are sparsely populated compared with cities, agro-pastoral areas generally consist of larger, more closely located villages than found in pastoral areas. Canine density, measured as dogs per square kilometer, was nearly 7 times higher in Serengeti than Ngorongoro. Rabies in Serengeti was endemic, with cases continuously observed, whereas rabies in Ngorongoro was epidemic, with no observed cases between outbreaks (16, 17). Additionally, pilot rabies vaccination campaigns in the 2 districts have required different strategies to achieve high coverage (18). Both districts border Serengeti National Park and are home to abundant and diverse wildlife populations. Although rabies cannot persist solely in wildlife in either district (16), we addressed concerns that vaccination coverage that had been sufficient for control in some regions may be insufficient in these wildlife-rich areas (7) by explicitly including wildlife hosts and their contribution to transmission in our dynamic model. Additional details and a map of these districts are included in the Appendix and Figure 1 of Supplement 1. Supplement 1. Figures We compared our model output with the incidence of canine and human rabies in these 2 districts before large-scale annual vaccination campaigns began. Because of past sporadic vaccination efforts, 5% to 10% of dogs in these districts had been previously vaccinated when the annual canine incidence was 1% to 2%. For human rabies, we had previously estimated an incidence of 1.48 to 4.28 deaths per 100000 people in Ngorongoro before large-scale implementation of canine vaccination, resulting in 2 to 6 rabies deaths per year for the district (22). From animal-bite injury data and availability of PEP, we had estimated that the incidence of human rabies in unvaccinated areas near Serengeti was 4.9 annual deaths (95% CI, 2.9 to 7.2) per 100000 persons in the late 1990s (23), leading to 5 to 13 human cases of rabies annually. Costs of Vaccination We parameterized the costs in our analysis using field data that we collected during annual vaccination campaigns in Serengeti and Ngorongoro and from published literature (18). We considered only the direct costs of vaccination because dogs are often brought to vaccination stations by children and the average income loss from bringing a dog to the central point was therefore considered to be minimal. We generated functions of cost with increasing vaccination coverage. The costs varied between the 2 districts. In the agro-pastoralist district of Serengeti, central-point vaccination campaigns were sufficient to achieve high coverage, whereas in the more sparsely populated pastoral district of Ngorongoro, central-point vaccination campaigns must be supplemented with door-to-door vaccinators to achieve high coverage, increasing the costs per dog vaccinated in Ngorongoro compared with those in Serengeti. We estimated costs as a function of coverage level, taking into account both the fixed costs of program start-up and the decreasing efficiency associated with searching for additional dogs to vaccinate as coverage levels increase (Appendix). Costs of Disease An untreated rabies bite to a human was estimated to result in the loss of 31.4 life-years on average (2), taking into account the typical age-distribution of persons with rabies. Monetary losses accrue through the cost of PEP, estimated to be

Species Association of Hepatitis B Virus (HBV) in Non-Human Apes; Evidence for Recombination between Gorilla and Chimpanzee Variants

111.29 per regimen (24), which includes both direct costs of treatment and indirect costs of transportation and lost income for the days on which treatment is administered. We assumed that a full course of PEP was 100% effective, which was both consistent with clinical data (6) and conservative given that this assumption would bias against canine vaccination. When persons who did not receive PEP progressed to rabies, we considered only the health burden because medical care is not effective and usually not provided in rural African settings. We constructed a probability tree to model the chain of events leading from a rabid dog to PEP, a case of rabies, or neither (Table 2 of Supplement 2 and Figure 1). We did not consider transmission from wildlife to humans because this represented fewer than 1% of human cases (4). However, our previous findings did show that mass vaccination of domestic dogs could concomitantly eliminate disease from wildlife (16), and this would potentially be an additional benefit for conservation (25, 26) as well as human health. Figure 1. Rabies transmission model. Our dynamic compartmental model is stratified by host type. Rabid dogs are linked to human deaths through a probability tree of human health outcomes. The equations governing the movement between classes are given in Table 1 of Supplement 2. PEP = postexposure prophylaxis. Supplement 2. Tables Data collected through contact tracing of all rabies cases detected from January 2002 through December 2006 (16, 17) were used to estimate that each rabid dog bites 0.51 humans (Appendix). We estimated that each rabid dog led to an average of

Bacillus cereus Biovar Anthracis Causing Anthrax in Sub-Saharan Africa-Chromosomal Monophyly and Broad Geographic Distribution.

36.89 in costs from PEP administration and a loss of 1.07 human life-years (Table 2 of Supplement 2). To estimate the cost of disease for each strategy that we considered, we multiplied each of these measures by the canine rabies incidence predicted through simulation. We calculated the cumulative economic cost of disease and vaccination on 2 time scales, annually and over a decade. Cost-Effectiveness Within each district, any strategy that had both greater monetary cost and more lives lost than some other strategy or combination of strategies was considered to be dominated by the latter strategy. For each nondominated scenario, we calculated the inc