The Origin of Malarial Parasites in Orangutans

Background Recent findings of Plasmodium in African apes have changed our perspectives on the evolution of malarial parasites in hominids. However, phylogenetic analyses of primate malarias are still missing information from Southeast Asian apes. In this study, we report molecular data for a malaria parasite lineage found in orangutans. Methodology/Principal Findings We screened twenty-four blood samples from Pongo pygmaeus (Kalimantan, Indonesia) for Plasmodium parasites by PCR. For all the malaria positive orangutan samples, parasite mitochondrial genomes (mtDNA) and two antigens: merozoite surface protein 1 42 kDa (MSP-142) and circumsporozoite protein gene (CSP) were amplified, cloned, and sequenced. Fifteen orangutans tested positive and yielded 5 distinct mitochondrial haplotypes not previously found. The haplotypes detected exhibited low genetic divergence among them, indicating that they belong to one species. We report phylogenetic analyses using mitochondrial genomes, MSP-142 and CSP. We found that the orangutan malaria parasite lineage was part of a monophyletic group that includes all the known non-human primate malaria parasites found in Southeast Asia; specifically, it shares a recent common ancestor with P. inui (a macaque parasite) and P. hylobati (a gibbon parasite) suggesting that this lineage originated as a result of a host switch. The genetic diversity of MSP-142 in orangutans seems to be under negative selection. This result is similar to previous findings in non-human primate malarias closely related to P. vivax. As has been previously observed in the other Plasmodium species found in non-human primates, the CSP shows high polymorphism in the number of repeats. However, it has clearly distinctive motifs from those previously found in other malarial parasites. Conclusion The evidence available from Asian apes indicates that these parasites originated independently from those found in Africa, likely as the result of host switches from other non-human primates

A New Malaria Agent in African Hominids

Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually, mainly among African infants. The origin and evolution of this pathogen within the human lineage is still unresolved. A single species, P. reichenowi, which infects chimpanzees, is known to be a close sister lineage of P. falciparum. Here we report the discovery of a new Plasmodium species infecting Hominids. This new species has been isolated in two chimpanzees (Pan troglodytes) kept as pets by villagers in Gabon (Africa). Analysis of its complete mitochondrial genome (5529 nucleotides including Cyt b, Cox I and Cox III genes) reveals an older divergence of this lineage from the clade that includes P. falciparum and P. reichenowi (∼21±9 Myrs ago using Bayesian methods and considering that the divergence between P. falciparum and P. reichenowi occurred 4 to 7 million years ago as generally considered in the literature). This time frame would be congruent with the radiation of hominoids, suggesting that this Plasmodium lineage might have been present in early hominoids and that they may both have experienced a simultaneous diversification. Investigation of the nuclear genome of this new species will further the understanding of the genetic adaptations of P. falciparum to humans. The risk of transfer and emergence of this new species in humans must be now seriously considered given that it was found in two chimpanzees living in contact with humans and its close relatedness to the most virulent agent of malaria

Multiple host-switching of Haemosporidia parasites in bats

<p>Abstract</p> <p>Background</p> <p>There have been reported cases of host-switching in avian and lizard species of <it>Plasmodium </it>(Apicomplexa, Haemosporidia), as well as in those infecting different primate species. However, no evidence has previously been found for host-swapping between wild birds and mammals.</p> <p>Methods</p> <p>This paper presents the results of the sampling of blood parasites of wild-captured bats from Madagascar and Cambodia. The presence of Haemosporidia infection in these animals is confirmed and cytochrome <it>b </it>gene sequences were used to construct a phylogenetic analysis.</p> <p>Results</p> <p>Results reveal at least three different and independent Haemosporidia evolutionary histories in three different bat lineages from Madagascar and Cambodia.</p> <p>Conclusion</p> <p>Phylogenetic analysis strongly suggests multiple host-switching of Haemosporidia parasites in bats with those from avian and primate hosts.</p

Having a pair: the key to immune evasion for the diploid pathogen Schistosoma japonicum

Schistosomes, unlike malaria parasites, are in their diploid stage when targeted by the human immune system. Diploids can be either homozygous or heterozygous. The difference has profound significance for developing immunity and yet has not previously been addressed. We examined the implications of zygosity on immunity to a diploid pathogen, Schistosoma japonicum and showed that the diploid state, and its associated heterozygous advantage, significantly affects the outcome of attack by the immune system and the accumulation of antigenic diversity in the parasite population. We demonstrate here that diploidy provides a novel means of immune evasion for diploid pathogens

Phylogenomic analyses of malaria parasites and evolution of their exported proteins

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>is the most malignant agent of human malaria. It belongs to the taxon Laverania, which includes other ape-infecting <it>Plasmodium </it>species. The origin of the Laverania is still debated. <it>P. falciparum </it>exports pathogenicity-related proteins into the host cell using the <it>Plasmodium </it>export element (PEXEL). Predictions based on the presence of a PEXEL motif suggest that more than 300 proteins are exported by <it>P. falciparum</it>, while there are many fewer exported proteins in non-Laverania.</p> <p>Results</p> <p>A whole-genome approach was applied to resolve the phylogeny of eight <it>Plasmodium </it>species and four outgroup taxa. By using 218 orthologous proteins we received unanimous support for a sister group position of Laverania and avian malaria parasites. This observation was corroborated by the analyses of 28 exported proteins with orthologs present in all <it>Plasmodium </it>species. Most interestingly, several deviations from the <it>P. falciparum </it>PEXEL motif were found to be present in the orthologous sequences of non-Laverania.</p> <p>Conclusion</p> <p>Our phylogenomic analyses strongly support the hypotheses that the Laverania have been founded by a single <it>Plasmodium </it>species switching from birds to African great apes or <it>vice versa</it>. The deviations from the canonical PEXEL motif in orthologs may explain the comparably low number of exported proteins that have been predicted in non-Laverania.</p

Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil

BACKGROUND: Extra-Amazonian autochthonous Plasmodium vivax infections have been reported in mountainous regions surrounded by the Atlantic Forest in Espírito Santo state, Brazil. METHODS: Sixty-five patients and 1,777 residents were surveyed between April 2001 and March 2004. Laboratory methods included thin and thick smears, multiplex-PCR, immunofluorescent assay (IFA) against P. vivax and Plasmodium malariae crude blood-stage antigens and enzyme-linked immunosorbent assay (ELISA) for antibodies against the P. vivax-complex (P. vivax and variants) and P. malariae/Plasmodium brasilianum circumsporozoite-protein (CSP) antigens. RESULTS: Average patient age was 35.1 years. Most (78.5%) were males; 64.6% lived in rural areas; 35.4% were farmers; and 12.3% students. There was no relevant history of travel. Ninety-five per cent of the patients were experiencing their first episode of malaria. Laboratory data from 51 patients were consistent with P. vivax infection, which was determined by thin smear. Of these samples, 48 were assayed by multiplex-PCR. Forty-five were positive for P. vivax, confirming the parasitological results, while P. malariae was detected in one sample and two gave negative results. Fifty percent of the 50 patients tested had IgG antibodies against the P. vivax-complex or P. malariae CSP as determined by ELISA. The percentages of residents with IgM and IgG antibodies detected by IFA for P. malariae, P. vivax and Plasmodium falciparum who did not complain of malaria symptoms at the time blood was collected were 30.1% and 56.5%, 6.2% and 37.7%, and 13.5% and 13%, respectively. The same sera that reacted to P. vivax also reacted to P. malariae. The following numbers of samples were positive in multiplex-PCR: 23 for P. vivax; 15 for P. malariae; 9 for P. falciparum and only one for P. falciparum and P. malariae. All thin and thick smears were negative. ELISA against CSP antigens was positive in 25.4%, 6.3%, 10.7% and 15.1% of the samples tested for "classical" P. vivax (VK210), VK247, P. vivax-like and P. malariae, respectively. Anopheline captures in the transmission area revealed only zoophilic and exophilic species. CONCLUSION: The low incidence of malaria cases, the finding of asymptomatic inhabitants and the geographic separation of patients allied to serological and molecular results raise the possibility of the existence of a simian reservoir in these areas

Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty

<p>Abstract</p> <p>Background</p> <p>The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty.</p> <p>Methods</p> <p>Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models.</p> <p>Results</p> <p>Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT) for malaria was estimated, and a policy of multiple first-line therapies (MFTs) was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases.</p> <p>Conclusions</p> <p>At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults.</p

Patterns of co-speciation and host switching in primate malaria parasites

<p>Abstract</p> <p>Background</p> <p>The evolutionary history of many parasites is dependent on the evolution of their hosts, leading to an association between host and parasite phylogenies. However, frequent host switches across broad phylogenetic distances may weaken this close evolutionary link, especially when vectors are involved in parasites transmission, as is the case for malaria pathogens. Several studies suggested that the evolution of the primate-infective malaria lineages may be constrained by the phylogenetic relationships of their hosts, and that lateral switches between distantly related hosts may have been occurred. However, no systematic analysis has been quantified the degree of phylogenetic association between primates and their malaria parasites.</p> <p>Methods</p> <p>Here phylogenetic approaches have been used to discriminate statistically between events due to co-divergence, duplication, extinction and host switches that can potentially cause historical association between <it>Plasmodium </it>parasites and their primate hosts. A Bayesian reconstruction of parasite phylogeny based on genetic information for six genes served as basis for the analyses, which could account for uncertainties about the evolutionary hypotheses of malaria parasites.</p> <p>Results</p> <p>Related lineages of primate-infective <it>Plasmodium </it>tend to infect hosts within the same taxonomic family. Different analyses testing for congruence between host and parasite phylogenies unanimously revealed a significant association between the corresponding evolutionary trees. The most important factor that resulted in this association was host switching, but depending on the parasite phylogeny considered, co-speciation and duplication may have also played some additional role. Sorting seemed to be a relatively infrequent event, and can occur only under extreme co-evolutionary scenarios. The concordance between host and parasite phylogenies is heterogeneous: while the evolution of some malaria pathogens is strongly dependent on the phylogenetic history of their primate hosts, the congruent evolution is less emphasized for other parasite lineages (e.g. for human malaria parasites). Estimation of ancestral states of host use along the phylogenetic tree of parasites revealed that lateral transfers across distantly related hosts were likely to occur in several cases. Parasites cannot infect all available hosts, and they should preferentially infect hosts that provide a similar environment for reproduction. Marginally significant evidence suggested that there might be a consistent variation within host ranges in terms of physiology.</p> <p>Conclusion</p> <p>The evolution of primate malarias is constrained by the phylogenetic associations of their hosts. Some parasites can preserve a great flexibility to infect hosts across a large phylogenetic distance, thus host switching can be an important factor in mediating host ranges observed in nature. Due to this inherent flexibility and the potential exposure to various vectors, the emergence of new malaria disease in primates including humans cannot be predicted from the phylogeny of parasites.</p