Barthélémy Ngoubangoye

Additional haplogroups of Toxoplasma gondii out of Africa: population structure and mouse-virulence of strains from Gabon.

Background Toxoplasma gondii is found worldwide, but distribution of its genotypes as well as clinical expression of human toxoplasmosis varies across the continents. Several studies in Europe, North America and South America argued for a role of genotypes in the clinical expression of human toxoplasmosis. Genetic data concerning T. gondii isolates from Africa are scarce and not sufficient to investigate the population structure, a fundamental analysis for a better understanding of distribution, circulation, and transmission. Methodology/Principal Findings Seropositive animals originating from urban and rural areas in Gabon were analyzed for T. gondii isolation and genotyping. Sixty-eight isolates, including one mixed infection (69 strains), were obtained by bioassay in mice. Genotyping was performed using length polymorphism of 13 microsatellite markers located on 10 different chromosomes. Results were analyzed in terms of population structure by Bayesian statistical modeling, Neighbor-joining trees reconstruction based on genetic distances, F ST and linkage disequilibrium. A moderate genetic diversity was detected. Three haplogroups and one single genotype clustered 27 genotypes. The majority of strains belonged to one haplogroup corresponding to the worldwide Type III. The remaining strains were distributed into two haplogroups (Africa 1 and 3) and one single genotype. Mouse virulence at isolation was significantly different between haplogroups. Africa 1 haplogroup was the most virulent. Conclusion Africa 1 and 3 haplogroups were proposed as being new major haplogroups of T. gondii circulating in Africa. A possible link with strains circulating in South and Central America is discussed. Analysis of population structure demonstrated a local spread within a rural area and strain circulation between the main cities of the country. This circulation, favored by human activity could lead to genetic exchanges. For the first time, key epidemiological questions were addressed for the West African T. gondii population, using the high discriminatory power of microsatellite markers, thus creating a basis for further epidemiological and clinical investigations.

Diversity, host switching and evolution of Plasmodium vivax infecting African great apes

Plasmodium vivax is considered to be absent from Central and West Africa because of the protective effect of Duffy negativity. However, there are reports of persons returning from these areas infected with this parasite and observations suggesting the existence of transmission. Among the possible explanations for this apparent paradox, the existence of a zoonotic reservoir has been proposed. May great apes be this reservoir? We analyze the mitochondrial and nuclear genetic diversity of P. vivax parasites isolated from great apes in Africa and compare it to parasites isolated from travelers returning from these regions of Africa, as well as to human isolates distributed all over the world. We show that the P. vivax sequences from parasites of great apes form a clade genetically distinct from the parasites circulating in humans. We show that this clade’s parasites can be infectious to humans by describing the case of a traveler returning from the Central African Republic infected with one of them. The relationship between this P. vivax clade in great apes and the human isolates is discussed.

Natural simian immunodeficiency virus transmission in mandrills: a family affair?

Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.

Social Structure of a Semi-Free Ranging Group of Mandrills (Mandrillus sphinx): A Social Network Analysis.

The difficulty involved in following mandrills in the wild means that very little is known about social structure in this species. Most studies initially considered mandrill groups to be an aggregation of one-male/multifemale units, with males occupying central positions in a structure similar to those observed in the majority of baboon species. However, a recent study hypothesized that mandrills form stable groups with only two or three permanent males, and that females occupy more central positions than males within these groups. We used social network analysis methods to examine how a semi-free ranging group of 19 mandrills is structured. We recorded all dyads of individuals that were in contact as a measure of association. The betweenness and the eigenvector centrality for each individual were calculated and correlated to kinship, age and dominance. Finally, we performed a resilience analysis by simulating the removal of individuals displaying the highest betweenness and eigenvector centrality values. We found that related dyads were more frequently associated than unrelated dyads. Moreover, our results showed that the cumulative distribution of individual betweenness and eigenvector centrality followed a power function, which is characteristic of scale-free networks. This property showed that some group members, mostly females, occupied a highly central position. Finally, the resilience analysis showed that the removal of the two most central females split the network into small subgroups and increased the network diameter. Critically, this study confirms that females appear to occupy more central positions than males in mandrill groups. Consequently, these females appear to be crucial for group cohesion and probably play a pivotal role in this species.

Malaria-like symptoms associated with a natural Plasmodium reichenowi infection in a chimpanzee

Although Plasmodium infections have never been clearly associated with symptoms in non-human primates, the question of the pathogenicity of Plasmodium parasites in non-human primates still remains unanswered. A young chimpanzee, followed before and after release to a sanctuary, in a semi-free ranging enclosure located in an equatorial forest, showed fever and strong anaemia associated with a high Plasmodium reichenowi infection, shortly after release. The animal recovered from anaemia after several months despite recurrent infection with other Plasmodium species. This may be the first description of malaria-like symptoms in a chimpanzee infected with Plasmodium.

The host specificity of ape malaria parasites can be broken in confined environments.

Recent studies have revealed a large diversity of Plasmodium spp. among African great apes. Some of these species are related to Plasmodium falciparum, the most virulent agent of human malaria (subgenus Laverania), and others to Plasmodium ovale, Plasmodium malariae and Plasmodium vivax (subgenus Plasmodium), three other human malaria agents. Laverania parasites exhibit strict host specificity in their natural environment. Plasmodium reichenowi, Plasmodium billcollinsi, Plasmodium billbrayi and Plasmodium gaboni infect only chimpanzees, while Plasmodium praefalciparum, Plasmodium blacklocki and Plasmodium adleri are restricted to gorillas and Plasmodium falciparum is pandemic in humans. This host specificity may be due to genetic and/or environmental factors. Infrastructures hosting captive primates, such as sanctuaries and health centres, usually concentrate different primate species, thus favouring pathogen exchanges. Using molecular tools, we analysed blood samples from captive non-human primates living in Gabon to evaluate the risk of Plasmodium spp. transfers between host species. We also included blood samples from workers taking care of primates to assess whether primate-human parasite transfers occurred. We detected four transfers of Plasmodium from gorillas towards chimpanzees, one from chimpanzees to gorillas, three from humans towards chimpanzees and one from humans to mandrills. No simian Plasmodium was found in the blood samples from humans working with primates. These findings demonstrate that the genetic barrier that determines the apparent host specificity of Laverania is not completely impermeable and that parasite exchanges between gorillas and chimpanzees are possible in confined environments.

Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite Plasmodium praefalciparum. Little is known about the other gorilla- and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum, but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers, as well as convergent evolution, were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor, shows a host-specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000–60,000 years ago followed by a population bottleneck around 4,000–6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.Sequencing of gorilla- and chimpanzee-infecting Plasmodium species elucidates the evolutionary history of the Laverania subgenus and highlights features of the human-infecting Plasmodium falciparum species that enable parasite transmission in humans.

Genomes of an entire Plasmodium subgenus reveal paths to virulent human malaria

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite P. praefalciparum. Although there are further gorilla and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum, none are known to be able to establish repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have analysed multiple genomes from all known Laverania species. Here we estimate the timings of Laverania speciation events, placing P. falciparum speciation 40,000-60,000 years ago followed by a recent population bottleneck. We show that interspecific gene transfers as well as convergent evolution were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and for the first time, features in P. falciparum are revealed that made it the only member of the Laverania able to infect and spread in humans.

Relations between Spatial Distribution, Social Affiliations and Dominance Hierarchy in a Semi-Free Mandrill Population

Although there exist advantages to group-living in comparison to a solitary lifestyle, costs and gains of group-living may be unequally distributed among group members. Predation risk, vigilance levels and food intake may be unevenly distributed across group spatial geometry and certain within-group spatial positions may be more or less advantageous depending on the spatial distribution of these factors. In species characterized with dominance hierarchy, high-ranking individuals are commonly observed in advantageous spatial position. However, in complex social systems, individuals can develop affiliative relationships that may balance the effect of dominance relationships in individuals spatial distribution. The objective of the present study is to investigate how the group spatial distribution of a semi-free ranging colony of Mandrills relates to its social organization. Using spatial observations in an area surrounding the feeding zone, we tested the three following hypothesis: (1) does dominance hierarchy explain being observed in proximity or far from a food patch? (2) Do affiliative associations also explain being observed in proximity or far from a food patch? (3) Do the differences in rank in the group hierarchy explain being co-observed in proximity of a food patch? Our results showed that high-ranking individuals were more observed in proximity of the feeding zone while low-ranking individuals were more observed at the boundaries of the observation area. Furthermore, we observed that affiliative relationships were also associated with individual spatial distributions and explain more of the total variance of the spatial distribution in comparison with dominance hierarchy. Finally, we found that individuals observed at a same moment in proximity of the feeding zone were more likely to be distant in the hierarchy while controlling for maternal kinship, age and sex similarity. This study brings some elements about how affiliative networks and dominance hierarchy are related to spatial positions in primates.

Quantifying transmission by stage of infection in the field: The example of SIV-1 and STLV-1 infecting mandrills.

The early stage of viral infection is often followed by an important increase of viral load and is generally considered to be the most at risk for pathogen transmission. Most methods quantifying the relative importance of the different stages of infection were developed for studies aimed at measuring HIV transmission in Humans. However, they cannot be transposed to animal populations in which less information is available. Here we propose a general method to quantify the importance of the early and late stages of the infection on micro‐organism transmission from field studies. The method is based on a state space dynamical model parameterized using Bayesian inference. It is illustrated by a 28 years dataset in mandrills infected by Simian Immunodeficiency Virus type‐1 (SIV‐1) and the Simian T‐Cell Lymphotropic Virus type‐1 (STLV‐1). For both viruses we show that transmission is predominant during the early stage of the infection (transmission ratio for SIV‐1: 1.16 [0.0009; 18.15] and 9.92 [0.03; 83.8] for STLV‐1). However, in terms of basic reproductive number (R0), which quantifies the weight of both stages in the spread of the virus, the results suggest that the epidemics of SIV‐1 and STLV‐1 are mainly driven by late transmissions in this population. Am. J. Primatol. 77:309–318, 2015.