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Malaria Journal Jan 2024Though Plasmodium vivax is the second most common malaria species to infect humans, it has not traditionally been considered a major human health concern in central...
BACKGROUND
Though Plasmodium vivax is the second most common malaria species to infect humans, it has not traditionally been considered a major human health concern in central Africa given the high prevalence of the human Duffy-negative phenotype that is believed to prevent infection. Increasing reports of asymptomatic and symptomatic infections in Duffy-negative individuals throughout Africa raise the possibility that P. vivax is evolving to evade host resistance, but there are few parasite samples with genomic data available from this part of the world.
METHODS
Whole genome sequencing of one new P. vivax isolate from the Democratic Republic of the Congo (DRC) was performed and used in population genomics analyses to assess how this central African isolate fits into the global context of this species.
RESULTS
Plasmodium vivax from DRC is similar to other African populations and is not closely related to the non-human primate parasite P. vivax-like. Evidence is found for a duplication of the gene PvDBP and a single copy of PvDBP2.
CONCLUSION
These results suggest an endemic P. vivax population is present in central Africa. Intentional sampling of P. vivax across Africa would further contextualize this sample within African P. vivax diversity and shed light on the mechanisms of infection in Duffy negative individuals. These results are limited by the uncertainty of how representative this single sample is of the larger population of P. vivax in central Africa.
Topics: Animals; Humans; Plasmodium vivax; Malaria, Vivax; Malaria; Africa, Central; Genomics; Duffy Blood-Group System
PubMed: 38238806
DOI: 10.1186/s12936-024-04852-y -
Nature Communications May 2021Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described....
Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax (n = 558) establishes South Asian isolates (n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps, and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b. Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic diversity, and genetic evidence of recent directional selection in this important human pathogen.
Topics: Africa, Eastern; Antimalarials; Asia; Drug Resistance; Duffy Blood-Group System; Genes, Protozoan; Genetic Loci; Humans; Malaria, Vivax; Phylogeny; Phylogeography; Plasmodium vivax; Polymorphism, Single Nucleotide; Protozoan Proteins; Reticulocytes; Selection, Genetic
PubMed: 34039976
DOI: 10.1038/s41467-021-23422-3 -
International Journal of Environmental... May 2019: Malaria is one of the infectious diseases of greatest interest to the scientific community and of greatest concern to international health authorities. Traditionally,...
: Malaria is one of the infectious diseases of greatest interest to the scientific community and of greatest concern to international health authorities. Traditionally, the focus has been on , the parasite that causes the most severe form of the disease in Africa. However, in the last twenty years, the parasite, responsible for a large number of cases in Latin America, the Middle East, South and Southeast Asia, the Horn of Africa, and Oceania, has also generated enormous interest due, among other things, to the published evidence that it can cause severe malaria. : In this paper, the international scientific publication on malaria and has been analyzed using the Scopus database to try to define global trends in this field of study. : It has been shown that events such as the emergence of resistance to certain drugs can break a trend. The important role of non-malaria-endemic countries such as the USA or Switzerland in malaria research is also evident. : International cooperation will be essential for the eradication of the disease. Moreover, in this sense, the general vision given by the bibliometric analysis of malaria caused by is fundamental to paint the picture regarding the current situation and encourage international cooperation and control efforts.
Topics: Bibliometrics; Global Health; Humans; International Cooperation; Malaria, Vivax; Middle Aged; Plasmodium vivax; Research
PubMed: 31159165
DOI: 10.3390/ijerph16111928 -
The Journal of Infectious Diseases Jan 2022Plasmodium falciparum malaria dominates throughout sub-Saharan Africa, but the prevalence of Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax...
BACKGROUND
Plasmodium falciparum malaria dominates throughout sub-Saharan Africa, but the prevalence of Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax increasingly contribute to infection in countries that control malaria using P. falciparum-specific diagnostic and treatment strategies.
METHODS
We performed quantitative polymerase chain reaction (qPCR) on 2987 dried blood spots from the 2015-2016 Malawi Demographic and Health Survey to identify presence and distribution of nonfalciparum infection. Bivariate models were used to determine species-specific associations with demographic and environmental risk factors.
RESULTS
Nonfalciparum infections had broad spatial distributions. Weighted prevalence was 0.025 (SE, 0.004) for P. malariae, 0.097 (SE, 0.008) for P. ovale spp., and 0.001 (SE, 0.0005) for P. vivax. Most infections (85.6%) had low-density parasitemias ≤ 10 parasites/µL, and 66.7% of P. malariae, 34.6% of P. ovale spp., and 40.0% of P. vivax infections were coinfected with P. falciparum. Risk factors for P. malariae were like those known for P. falciparum; however, there were few risk factors recognized for P. ovale spp. and P. vivax, perhaps due to the potential for relapsing episodes.
CONCLUSIONS
The prevalence of any nonfalciparum infection was 11.7%, with infections distributed across Malawi. Continued monitoring of Plasmodium spp. becomes critical as nonfalciparum infections become important sources of ongoing transmission.
Topics: Adolescent; Adult; Female; Humans; Malaria; Malaria, Vivax; Malawi; Male; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Real-Time Polymerase Chain Reaction; Young Adult
PubMed: 34244739
DOI: 10.1093/infdis/jiab353 -
Malaria Journal Nov 2016The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has...
BACKGROUND
The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region. This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity.
METHODS
Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border. Cross-sectional surveys were conducted in villages and camps for internally displaced persons to determine the prevalence of malaria infections. Malaria infections were diagnosed initially by microscopy and later in the laboratory using nested PCR for the SSU rRNA genes. Plasmodium malariae and P. ovale infections were confirmed by sequencing the PCR products. The P. ovale subtypes were determined by sequencing the Pocytb, Pocox1 and Pog3p genes. Parasite populations were evaluated by PCR amplification and sequencing of the MSP-1 genes. Antifolate sensitivity was assessed by sequencing the dhfr-ts and dhps genes from the P. malariae and P. ovale isolates.
RESULTS
Analysis of 2701 blood samples collected from the China-Myanmar border by nested PCR targeting the parasite SSU rRNA genes identified 561 malaria cases, including 161 Plasmodium falciparum, 327 P. vivax, 66 P. falciparum/P. vivax mixed infections, 4 P. malariae and 3 P. ovale spp. P. vivax and P. falciparum accounted for >60 and ~30% of all malaria cases, respectively. In comparison, the prevalence of P. malariae and P. ovale spp. was very low and only made up ~1% of all PCR-positive cases. Nevertheless, these two species were often misidentified as P. vivax infections or completely missed by microscopy even among symptomatic patients. Phylogenetic analysis of the SSU rRNA, Pocytb, Pocox1 and Pog3p genes confirmed that the three P. ovale spp. isolates belonged to the subtype P. ovale curtisi. Low-level genetic diversity was detected in the MSP-1, dhfr and dhps genes of these minor parasite species, potentially stemming from the low prevalence of these parasites preventing their mixing. Whereas most of the dhfr and dhps positions equivalent to those conferring antifolate resistance in P. falciparum and P. vivax were wild type, a new mutation S113C corresponding to the S108 position in pfdhfr was identified in two P. ovale curtisi isolates.
CONCLUSIONS
The four human malaria parasite species all occurred sympatrically at the China-Myanmar border. While P. vivax has become the predominant species, the two minor parasite species also occurred at very low prevalence but were often misidentified or missed by conventional microscopy. These minor parasite species displayed low levels of polymorphisms in the msp-1, dhfr and dhps genes.
Topics: Adult; Child; China; Cluster Analysis; Cross-Sectional Studies; DNA, Protozoan; DNA, Ribosomal; Drug Resistance; Female; Genetic Variation; Humans; Malaria; Male; Microscopy; Myanmar; Phylogeny; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Polymerase Chain Reaction; Prevalence; Protozoan Proteins; RNA, Ribosomal, 18S; Sequence Analysis, DNA; Young Adult
PubMed: 27846879
DOI: 10.1186/s12936-016-1605-y -
Frontiers in Cellular and Infection... 2021In a infection, it was shown a proportionally increased on gametocyte distribution within the bone marrow aspirant, suggesting a role of this organ as a reservoir for...
In a infection, it was shown a proportionally increased on gametocyte distribution within the bone marrow aspirant, suggesting a role of this organ as a reservoir for this parasite stage. Here, we evaluated the cytoadhesive capacity of gametocytes to bone marrow endothelial cells (HBMEC) and investigated the involvement of some receptors in the cytoadhesion process by using transfected CHO cells (CHO-ICAM1, CHO-CD36 and CHO-VCAM), wild type (CHO-K1) or deficient in heparan and chondroitin sulfate (CHO-745). cytoadhesion assays were performed using a total of 44 isolates enriched in gametocyte stages by Percoll gradient in the different cell lines. The majority of isolates (88.9%) were able to adhere to HBMEC monolayer. ICAM1 seemed to be the sole receptor significantly involved. CD-36 was the receptor with higher adhesion rate, despite no significance was noticed when compared to CHO-745. We demonstrated that gametocyte adheres to bone marrow endothelial cells. Moreover, gametocytes display the ability to adhere to all CHO cells investigated, especially to CHO-ICAM1. These findings bring insights to the comprehension of the role of the bone marrow as a reservoir and the potential impact on parasite transmission to the vector.
Topics: Animals; Bone Marrow; Cricetinae; Cricetulus; Endothelial Cells; Plasmodium falciparum; Plasmodium vivax
PubMed: 34249772
DOI: 10.3389/fcimb.2021.614985 -
PLoS Neglected Tropical Diseases Jun 2019Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in...
Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions. In the past decades, drug resistant P. vivax parasites have emerged, mainly in Southeast Asia, but while some molecular markers of resistance have been identified, none have so far been confirmed experimentally, which limits interpretation of the markers, and hence our ability to monitor and control the spread of resistance. Some of these potential markers have been identified through P. vivax genome-wide population genetic analyses, which highlighted genes under recent evolutionary selection in Southeast Asia, where chloroquine resistance is most prevalent. These genes could be involved in drug resistance, but no experimental proof currently exists to support this hypothesis. In this study, we used Plasmodium knowlesi, the most closely related species to P. vivax that can be cultured in human erythrocytes, as a model system to express P. vivax genes and test for their role in drug resistance. We adopted a strategy of episomal expression, and were able to express fourteen P. vivax genes, including two allelic variants of several hypothetical resistance genes. Their expression level and localisation were assessed, confirming cellular locations conjectured from orthologous species, and suggesting locations for several previously unlocalised proteins, including an apical location for PVX_101445. These findings establish P. knowlesi as a suitable model for P. vivax protein expression. We performed chloroquine and mefloquine drug assays, finding no significant differences in drug sensitivity: these results could be due to technical issues, or could indicate that these genes are not actually involved in drug resistance, despite being under positive selection pressure in Southeast Asia. These data confirm that in vitro P. knowlesi is a useful tool for studying P. vivax biology. Its close evolutionary relationship to P. vivax, high transfection efficiency, and the availability of markers for colocalisation, all make it a powerful model system. Our study is the first of its kind using P. knowlesi to study unknown P. vivax proteins and investigate drug resistance mechanisms.
Topics: Antimalarials; Cloning, Molecular; Drug Resistance; Gene Expression; Genes, Protozoan; Genetics, Microbial; Molecular Biology; Parasitic Sensitivity Tests; Plasmodium knowlesi; Plasmodium vivax
PubMed: 31158222
DOI: 10.1371/journal.pntd.0007470 -
PLoS Neglected Tropical Diseases 2015Plasmodium vivax is the geographically most widespread human malaria parasite. To analyze patterns of microsatellite diversity and population structure across countries...
Plasmodium vivax is the geographically most widespread human malaria parasite. To analyze patterns of microsatellite diversity and population structure across countries of different transmission intensity, genotyping data from 11 microsatellite markers was either generated or compiled from 841 isolates from four continents collected in 1999-2008. Diversity was highest in South-East Asia (mean allelic richness 10.0-12.8), intermediate in the South Pacific (8.1-9.9) Madagascar and Sudan (7.9-8.4), and lowest in South America and Central Asia (5.5-7.2). A reduced panel of only 3 markers was sufficient to identify approx. 90% of all haplotypes in South Pacific, African and SE-Asian populations, but only 60-80% in Latin American populations, suggesting that typing of 2-6 markers, depending on the level of endemicity, is sufficient for epidemiological studies. Clustering analysis showed distinct clusters in Peru and Brazil, but little sub-structuring was observed within Africa, SE-Asia or the South Pacific. Isolates from Uzbekistan were exceptional, as a near-clonal parasite population was observed that was clearly separated from all other populations (FST>0.2). Outside Central Asia FST values were highest (0.11-0.16) between South American and all other populations, and lowest (0.04-0.07) between populations from South-East Asia and the South Pacific. These comparisons between P. vivax populations from four continents indicated that not only transmission intensity, but also geographical isolation affect diversity and population structure. However, the high effective population size results in slow changes of these parameters. This persistency must be taken into account when assessing the impact of control programs on the genetic structure of parasite populations.
Topics: Africa; Alleles; Americas; Asia; Cluster Analysis; Cohort Studies; Genetic Variation; Genetics, Population; Genotype; Geography; Haplotypes; Humans; Linkage Disequilibrium; Madagascar; Malaria, Vivax; Microsatellite Repeats; Plasmodium vivax
PubMed: 26125189
DOI: 10.1371/journal.pntd.0003872 -
Malaria Journal Sep 2020Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria...
BACKGROUND
Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria incorporating Plasmodium vivax CSP (PvCSP) have demonstrated their effectiveness in preventing malaria, at least in part. However, genetic diversity of pvcsp in the natural population remains a major concern.
METHODS
A total of 171 blood samples collected from patients infected with Plasmodium vivax in Myanmar were analysed in this study. The pvcsp was amplified by polymerase chain reaction, followed by cloning and sequencing. Polymorphic characteristics and natural selection of pvcsp population in Myanmar were analysed using DNASTAR, MEGA6 and DnaSP programs. The polymorphic pattern and natural selection of publicly accessible global pvcsp sequences were also comparatively analysed.
RESULTS
Myanmar pvcsp sequences were divided into two subtypes VK210 and VK247 comprising 143 and 28 sequences, respectively. The VK210 subtypes showed higher levels of genetic diversity and polymorphism than the VK247 subtypes. The N-terminal non-repeat region of pvcsp displayed limited genetic variations in the global population. Different patterns of octapeptide insertion (ANKKAEDA in VK210 and ANKKAGDA in VK247) and tetrapeptide repeat motif (GGNA) were identified in the C-terminal region of global pvcsp population. Meanwhile, the central repeat region (CRR) of Myanmar and global pvcsp, both in VK210 and VK247 variants, was highly polymorphic. The high level of genetic diversity in the CRR has been attributed to the different numbers, types and combinations of peptide repeat motifs (PRMs). Interestingly, 27 and 5 novel PRMs were found in Myanmar VK210 and VK247 variants, respectively.
CONCLUSION
Comparative analysis of the global pvcsp population suggests a complex genetic profile of pvcsp in the global population. These results widen understanding of the genetic make-up of pvcsp in the global P. vivax population and provide valuable information for the development of a vaccine based on PvCSP.
Topics: Adolescent; Adult; Humans; Malaria, Vivax; Middle Aged; Myanmar; Plasmodium vivax; Polymorphism, Genetic; Protozoan Proteins; Selection, Genetic; Young Adult
PubMed: 32883283
DOI: 10.1186/s12936-020-03366-7 -
The Journal of Infectious Diseases Apr 2022The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental...
BACKGROUND
The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue.
METHODS
In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis.
RESULTS
We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated.
CONCLUSIONS
This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.
Topics: Anemia; Animals; Bone Marrow; Erythropoiesis; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 32556188
DOI: 10.1093/infdis/jiaa177