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Fulltext Accelerated diversification of nonhuman primate malarias in Southeast Asia: adaptive radiation or geographic speciation?

Muehlenbein MP, Pacheco MA, Taylor JE, Prall SP, Ambu L, Nathan S, et al.

Mol Biol Evol, 2015 Feb;32(2):422-39.
PMID: 25389206 DOI: 10.1093/molbev/msu310

Although parasitic organisms are found worldwide, the relative importance of host specificity and geographic isolation for parasite speciation has been explored in only a few systems. Here, we study Plasmodium parasites known to infect Asian nonhuman primates, a monophyletic group that includes the lineage leading to the human parasite Plasmodium vivax and several species used as laboratory models in malaria research. We analyze the available data together with new samples from three sympatric primate species from Borneo: The Bornean orangutan and the long-tailed and the pig-tailed macaques. We find several species of malaria parasites, including three putatively new species in this biodiversity hotspot. Among those newly discovered lineages, we report two sympatric parasites in orangutans. We find no differences in the sets of malaria species infecting each macaque species indicating that these species show no host specificity. Finally, phylogenetic analysis of these data suggests that the malaria parasites infecting Southeast Asian macaques and their relatives are speciating three to four times more rapidly than those with other mammalian hosts such as lemurs and African apes. We estimate that these events took place in approximately a 3-4-Ma period. Based on the genetic and phenotypic diversity of the macaque malarias, we hypothesize that the diversification of this group of parasites has been facilitated by the diversity, geographic distributions, and demographic histories of their primate hosts.

Matched MeSH terms: Plasmodium vivax/classification
Fulltext Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms

Auburn S, Getachew S, Pearson RD, Amato R, Miotto O, Trimarsanto H, et al.

J Infect Dis, 2019 Oct 22;220(11):1738-1749.
PMID: 30668735 DOI: 10.1093/infdis/jiz016

The Horn of Africa harbors the largest reservoir of Plasmodium vivax in the continent. Most of sub-Saharan Africa has remained relatively vivax-free due to a high prevalence of the human Duffy-negative trait, but the emergence of strains able to invade Duffy-negative reticulocytes poses a major public health threat. We undertook the first population genomic investigation of P. vivax from the region, comparing the genomes of 24 Ethiopian isolates against data from Southeast Asia to identify important local adaptions. The prevalence of the Duffy binding protein amplification in Ethiopia was 79%, potentially reflecting adaptation to Duffy negativity. There was also evidence of selection in a region upstream of the chloroquine resistance transporter, a putative chloroquine-resistance determinant. Strong signals of selection were observed in genes involved in immune evasion and regulation of gene expression, highlighting the need for a multifaceted intervention approach to combat P. vivax in the region.

Matched MeSH terms: Plasmodium vivax/classification
Fulltext Sensitive Detection of Plasmodium vivax Using a High-Throughput, Colourimetric Loop Mediated Isothermal Amplification (HtLAMP) Platform: A Potential Novel Tool for Malaria Elimination

Britton S, Cheng Q, Grigg MJ, Poole CB, Pasay C, William T, et al.

PLoS Negl Trop Dis, 2016 Feb;10(2):e0004443.
PMID: 26870958 DOI: 10.1371/journal.pntd.0004443

INTRODUCTION: Plasmodium vivax malaria has a wide geographic distribution and poses challenges to malaria elimination that are likely to be greater than those of P. falciparum. Diagnostic tools for P. vivax infection in non-reference laboratory settings are limited to microscopy and rapid diagnostic tests but these are unreliable at low parasitemia. The development and validation of a high-throughput and sensitive assay for P. vivax is a priority.
METHODS: A high-throughput LAMP assay targeting a P. vivax mitochondrial gene and deploying colorimetric detection in a 96-well plate format was developed and evaluated in the laboratory. Diagnostic accuracy was compared against microscopy, antigen detection tests and PCR and validated in samples from malaria patients and community controls in a district hospital setting in Sabah, Malaysia.
RESULTS: The high throughput LAMP-P. vivax assay (HtLAMP-Pv) performed with an estimated limit of detection of 1.4 parasites/ μL. Assay primers demonstrated cross-reactivity with P. knowlesi but not with other Plasmodium spp. Field testing of HtLAMP-Pv was conducted using 149 samples from symptomatic malaria patients (64 P. vivax, 17 P. falciparum, 56 P. knowlesi, 7 P. malariae, 1 mixed P. knowlesi/P. vivax, with 4 excluded). When compared against multiplex PCR, HtLAMP-Pv demonstrated a sensitivity for P. vivax of 95% (95% CI 87-99%); 61/64), and specificity of 100% (95% CI 86-100%); 25/25) when P. knowlesi samples were excluded. HtLAMP-Pv testing of 112 samples from asymptomatic community controls, 7 of which had submicroscopic P. vivax infections by PCR, showed a sensitivity of 71% (95% CI 29-96%; 5/7) and specificity of 93% (95% CI87-97%; 98/105).
CONCLUSION: This novel HtLAMP-P. vivax assay has the potential to be a useful field applicable molecular diagnostic test for P. vivax infection in elimination settings.

Matched MeSH terms: Plasmodium vivax/classification
Fulltext Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3α and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M

Oyong DA, Wilson DW, Barber BE, William T, Jiang J, Galinski MR, et al.

J Infect Dis, 2019 11 06;220(12):1950-1961.
PMID: 31419296 DOI: 10.1093/infdis/jiz407

BACKGROUND: Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.
METHODS: Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.
RESULTS: The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.
CONCLUSION: Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.

Matched MeSH terms: Plasmodium vivax/classification