Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally.

BACKGROUND: Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. METHODS: Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. RESULTS: Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. CONCLUSIONS: We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated

Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific

The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination

Plasmodium vivax populations are more genetically diverse and less structured than sympatric Plasmodium falciparum populations

The human malaria parasite, Plasmodium vivax, is proving more difficult to control and eliminate than Plasmodium falciparum in areas of co-transmission. Comparisons of the genetic structure of sympatric parasite populations may provide insight into the mechanisms underlying the resilience of P. vivax and can help guide malaria control programs.; P. vivax isolates representing the parasite populations of four areas on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite markers and compared with previously published microsatellite data from sympatric P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83-0.85) was higher than that of P. falciparum (He = 0.64-0.77) in all four populations. Moderate levels of genetic differentiation were found between P. falciparum populations, even over relatively short distances (less than 50 km), with 21-28% private alleles and clear geospatial genetic clustering. Conversely, very low population differentiation was found between P. vivax catchments, with less than 5% private alleles and no genetic clustering observed. In addition, the effective population size of P. vivax (30353; 13043-69142) was larger than that of P. falciparum (18871; 8109-42986).; Despite comparably high prevalence, P. vivax had higher diversity and a panmictic population structure compared to sympatric P. falciparum populations, which were fragmented into subpopulations. The results suggest that in comparison to P. falciparum, P. vivax has had a long-term large effective population size, consistent with more intense and stable transmission, and limited impact of past control and elimination efforts. This underlines suggestions that more intensive and sustained interventions will be needed to control and eventually eliminate P. vivax. This research clearly demonstrates how population genetic analyses can reveal deeper insight into transmission patterns than traditional surveillance methods

Plasmodium vivax Populations Are More Genetically Diverse and Less Structured than Sympatric Plasmodium falciparum Populations

INTRODUCTION: The human malaria parasite, Plasmodium vivax, is proving more difficult to control and eliminate than Plasmodium falciparum in areas of co-transmission. Comparisons of the genetic structure of sympatric parasite populations may provide insight into the mechanisms underlying the resilience of P. vivax and can help guide malaria control programs. METHODOLOGY/PRINCIPLE FINDINGS: P. vivax isolates representing the parasite populations of four areas on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite markers and compared with previously published microsatellite data from sympatric P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83-0.85) was higher than that of P. falciparum (He = 0.64-0.77) in all four populations. Moderate levels of genetic differentiation were found between P. falciparum populations, even over relatively short distances (less than 50 km), with 21-28% private alleles and clear geospatial genetic clustering. Conversely, very low population differentiation was found between P. vivax catchments, with less than 5% private alleles and no genetic clustering observed. In addition, the effective population size of P. vivax (30353; 13043-69142) was larger than that of P. falciparum (18871; 8109-42986). CONCLUSIONS/SIGNIFICANCE: Despite comparably high prevalence, P. vivax had higher diversity and a panmictic population structure compared to sympatric P. falciparum populations, which were fragmented into subpopulations. The results suggest that in comparison to P. falciparum, P. vivax has had a long-term large effective population size, consistent with more intense and stable transmission, and limited impact of past control and elimination efforts. This underlines suggestions that more intensive and sustained interventions will be needed to control and eventually eliminate P. vivax. This research clearly demonstrates how population genetic analyses can reveal deeper insight into transmission patterns than traditional surveillance methods

Plasmodium GPI-anchored micronemal antigen is essential for parasite transmission through the mosquito host.

Plasmodium parasites, the eukaryotic pathogens that cause malaria, feature three distinct invasive forms tailored to the host environment they must navigate and invade for life cycle progression. One conserved feature of these invasive forms is the micronemes, apically oriented secretory organelles involved in egress, motility, adhesion, and invasion. Here we investigate the role of GPI-anchored micronemal antigen (GAMA), which shows a micronemal localization in all zoite forms of the rodent-infecting species Plasmodium berghei. ∆GAMA parasites are severely defective for invasion of the mosquito midgut. Once formed, oocysts develop normally, however, sporozoites are unable to egress and exhibit defective motility. Epitope-tagging of GAMA revealed tight temporal expression late during sporogony and showed that GAMA is shed during sporozoite gliding motility in a similar manner to circumsporozoite protein. Complementation of P. berghei knockout parasites with full-length P. falciparum GAMA partially restored infectivity to mosquitoes, indicating conservation of function across Plasmodium species. A suite of parasites with GAMA expressed under the promoters of CTRP, CAP380, and TRAP, further confirmed the involvement of GAMA in midgut infection, motility, and vertebrate infection. These data show GAMA\u27s involvement in sporozoite motility, egress, and invasion, implicating GAMA as a regulator of microneme function

Multidimensional scaling analysis of <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> microsatellite haplotypes from Papua New Guinea.

<p>Results of multidimensional scaling analysis (MDS) with cleaned datasets are shown for (A) <i>P</i>. <i>falciparum</i> and (B) <i>P</i>. <i>vivax</i>. Dots indicate individual microsatellite haplotypes and colours indicate the four sample catchment areas.</p

Estimates of genetic diversity of <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> populations on the north coast of Papua New Guinea.

<p>n = number of isolates genotyped after exclusion of outliers; <i>H</i>_<i>e</i> = expected heterozygosity; <i>A</i> = Mean number of alleles, <i>R</i>_<i>s</i> = Allelic richness.</p><p>Estimates of genetic diversity of <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> populations on the north coast of Papua New Guinea.</p

Effective population size estimates for <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> populations on the north coast of Papua New Guinea.

<p>SMM = Stepwise mutation model, IAM = Infinite Alleles Model. The mutation rate of 1.59 X 10⁻⁴ for <i>P</i>. <i>falciparum</i> was used for both species. Numbers in brackets are lower and upper estimates derived from using the 95% confidence upper and lower mutation rates for <i>P</i>. <i>falciparum</i> (Lower = 6.98 X 10⁻⁵, Upper = 3.7 X 10⁻⁴) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003634#pntd.0003634.ref011" target="_blank">11</a>].</p><p>Effective population size estimates for <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> populations on the north coast of Papua New Guinea.</p

Estimates of multilocus linkage disequilibrium for <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> populations on the north coast of Papua New Guinea.

<p><i>I</i>^<i>S</i>_<i>A</i> = Index of Association,</p><p>^<i>a</i> = all infections,</p><p>^<i>b</i> = single infections only</p><p>Estimates of multilocus linkage disequilibrium for <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i> populations on the north coast of Papua New Guinea.</p