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Malaria Journal Oct 2010Singapore has been certified malaria free since November 1982 by the World Health Organization and despite occasional local transmission, the country has maintained the...
BACKGROUND
Singapore has been certified malaria free since November 1982 by the World Health Organization and despite occasional local transmission, the country has maintained the standing. In 2009, three clusters of malaria cases were reported in Singapore.
METHODS
Epidemiological, entomological and molecular studies were carried out to investigate the three clusters, namely Mandai-Sungei Kadut, Jurong Island and Sembawang.
RESULTS
A total of 29 malaria patients, with no recent travel history, were reported in the three clusters. Molecular analysis based on the msp3α and msp1 genes showed two independent local transmissions: one in Mandai-Sungei Kadut and another in Sembawang. Almost all cases within each cluster were epidemiologically linked. In Jurong Island cluster, epidemiological link remains uncertain, as almost all cases had a unique genetic profile. Only two cases shared a common profile and were found to be linked to the Mandai-Sungei Kadut cluster. Entomological investigation found Anopheles sinensis to be the predominant Anopheline in the two areas where local transmission of P. vivax was confirmed. Anopheles sinensis was found to be attracted to human bait and bites as early as 19:45 hrs. However, all Anopheles mosquitoes caught were negative for sporozoites and oocysts by dissection.
CONCLUSION
Investigation of P. vivax cases from the three cluster areas confirmed the occurrence of local transmission in two areas. Although An. sinensis was the predominant Anopheline found in areas with confirmed transmission, the vector/s responsible for the outbreaks still remains cryptic.
Topics: Adult; Animals; Anopheles; Antigens, Protozoan; Humans; Malaria, Vivax; Male; Merozoite Surface Protein 1; Middle Aged; Molecular Epidemiology; Plasmodium vivax; Protozoan Proteins; Singapore
PubMed: 21029478
DOI: 10.1186/1475-2875-9-305 -
Malaria Journal Feb 2008Four of five Plasmodium species infecting humans are present in Madagascar. Plasmodium vivax remains the second most prevalent species, but is understudied. No data is...
BACKGROUND
Four of five Plasmodium species infecting humans are present in Madagascar. Plasmodium vivax remains the second most prevalent species, but is understudied. No data is available on its susceptibility to sulphadoxine-pyrimethamine, the drug recommended for intermittent preventive treatment during pregnancy. In this study, the prevalence of P. vivax infection and the polymorphisms in the pvdhfr and pvdhps genes were investigated. The correlation between these polymorphisms and clinical and parasitological responses was also investigated in P. vivax-infected patients.
METHODS
Plasmodium vivax clinical isolates were collected in eight sentinel sites from the four major epidemiological areas for malaria across Madagascar in 2006/2007. Pvdhfr and pvdhps genes were sequenced for polymorphism analysis. The therapeutic efficacy of SP in P. vivax infections was assessed in Tsiroanomandidy, in the foothill of the central highlands. An intention-to-treat analysis of treatment outcome was carried out.
RESULTS
A total of 159 P. vivax samples were sequenced in the pvdhfr/pvdhps genes. Mutant-types in pvdhfr gene were found in 71% of samples, and in pvdhps gene in 16% of samples. Six non-synonymous mutations were identified in pvdhfr, including two novel mutations at codons 21 and 130. For pvdhps, beside the known mutation at codon 383, a new one was found at codon 422. For the two genes, different combinations were ranged from wild-type to quadruple mutant-type. Among the 16 patients enrolled in the sulphadoxine-pyrimethamine clinical trial (28 days of follow-up) and after adjustment by genotyping, 3 (19%, 95% CI: 5%-43%) of them were classified as treatment failure and were pvdhfr 58R/117N double mutant carriers with or without the pvdhps 383G mutation.
CONCLUSION
This study highlights (i) that genotyping in the pvdhfr and pvdhps genes remains a useful tool to monitor the emergence and the spread of P. vivax sulphadoxine-pyrimethamine resistant in order to improve the national antimalarial drug policy, (ii) the issue of using sulphadoxine-pyrimethamine as a monotherapy for intermittent preventive treatment of pregnant women or children.
Topics: Adolescent; Adult; Animals; Antimalarials; Child; Child, Preschool; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Female; Humans; Infant; Madagascar; Malaria, Vivax; Male; Molecular Sequence Data; Mutation; Plasmodium vivax; Polymerase Chain Reaction; Polymorphism, Genetic; Protozoan Proteins; Pyrimethamine; Sequence Analysis, DNA; Sulfadoxine; Tetrahydrofolate Dehydrogenase; Treatment Outcome
PubMed: 18302746
DOI: 10.1186/1475-2875-7-35 -
Malaria Journal Oct 2011Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are... (Review)
Review
Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important implications for the assessment of radical treatment efficacy and for malaria control and elimination.
Topics: Humans; Liver; Malaria, Vivax; Models, Biological; Periodicity; Plasmodium vivax; Recurrence; Time Factors
PubMed: 21989376
DOI: 10.1186/1475-2875-10-297 -
PLoS Neglected Tropical Diseases Mar 2015Significant insights into the biology of Plasmodium vivax have been gained from the ability to successfully adapt human infections to non-human primates. P. vivax... (Comparative Study)
Comparative Study
Significant insights into the biology of Plasmodium vivax have been gained from the ability to successfully adapt human infections to non-human primates. P. vivax strains grown in monkeys serve as a renewable source of parasites for in vitro and ex vivo experimental studies and functional assays, or for studying in vivo the relapse characteristics, mosquito species compatibilities, drug susceptibility profiles or immune responses towards potential vaccine candidates. Despite the importance of these studies, little is known as to how adaptation to a different host species may influence the genome of P. vivax. In addition, it is unclear whether these monkey-adapted strains consist of a single clonal population of parasites or if they retain the multiclonal complexity commonly observed in field isolates. Here we compare the genome sequences of seven P. vivax strains adapted to New World monkeys with those of six human clinical isolates collected directly in the field. We show that the adaptation of P. vivax parasites to monkey hosts, and their subsequent propagation, did not result in significant modifications of their genome sequence and that these monkey-adapted strains recapitulate the genomic diversity of field isolates. Our analyses also reveal that these strains are not always genetically homogeneous and should be analyzed cautiously. Overall, our study provides a framework to better leverage this important research material and fully utilize this resource for improving our understanding of P. vivax biology.
Topics: Adaptation, Physiological; Animals; Base Sequence; Genome, Protozoan; Genomics; Haplorhini; Host-Parasite Interactions; Humans; Malaria, Vivax; Plasmodium vivax; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 25768941
DOI: 10.1371/journal.pntd.0003566 -
Antimicrobial Agents and Chemotherapy Apr 2020relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy...
relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward malaria elimination.
Topics: Adolescent; Adult; Antibodies, Protozoan; Antimalarials; Brazil; Child; Cytochrome P-450 CYP2D6; Female; Humans; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; Primaquine; Recurrence; Treatment Failure; Young Adult
PubMed: 32122891
DOI: 10.1128/AAC.02056-19 -
Nature Genetics Aug 2016The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic...
The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.
Topics: Biological Evolution; Genetic Markers; Genetic Variation; Genomics; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 27348299
DOI: 10.1038/ng.3599 -
Parasites & Vectors May 2011Temperature is a key determinant of environmental suitability for transmission of human malaria, modulating endemicity in some regions and preventing transmission in...
BACKGROUND
Temperature is a key determinant of environmental suitability for transmission of human malaria, modulating endemicity in some regions and preventing transmission in others. The spatial modelling of malaria endemicity has become increasingly sophisticated and is now central to the global scale planning, implementation, and monitoring of disease control and regional efforts towards elimination, but existing efforts to model the constraints of temperature on the malaria landscape at these scales have been simplistic. Here, we define an analytical framework to model these constraints appropriately at fine spatial and temporal resolutions, providing a detailed dynamic description that can enhance large scale malaria cartography as a decision-support tool in public health.
RESULTS
We defined a dynamic biological model that incorporated the principal mechanisms of temperature dependency in the malaria transmission cycle and used it with fine spatial and temporal resolution temperature data to evaluate time-series of temperature suitability for transmission of Plasmodium falciparum and P. vivax throughout an average year, quantified using an index proportional to the basic reproductive number. Time-series were calculated for all 1 km resolution land pixels globally and were summarised to create high-resolution maps for each species delineating those regions where temperature precludes transmission throughout the year. Within suitable zones we mapped for each pixel the number of days in which transmission is possible and an integrated measure of the intensity of suitability across the year. The detailed evaluation of temporal suitability dynamics provided by the model is visualised in a series of accompanying animations.
CONCLUSIONS
These modelled products, made available freely in the public domain, can support the refined delineation of populations at risk; enhance endemicity mapping by offering a detailed, dynamic, and biologically driven alternative to the ubiquitous empirical incorporation of raw temperature data in geospatial models; and provide a rich spatial and temporal platform for future biological modelling studies.
Topics: Climate; Environment; Geography; Humans; Malaria, Falciparum; Malaria, Vivax; Models, Statistical; Plasmodium falciparum; Plasmodium vivax; Seasons; Temperature
PubMed: 21615906
DOI: 10.1186/1756-3305-4-92 -
The American Journal of Tropical... Dec 2016This paper summarizes our current understanding of the biology of Plasmodium vivax, how it differs from Plasmodium falciparum, and how these differences explain the need...
This paper summarizes our current understanding of the biology of Plasmodium vivax, how it differs from Plasmodium falciparum, and how these differences explain the need for P. vivax-tailored interventions. The article further pinpoints knowledge gaps where investments in research are needed to help identify and develop such specific interventions. The principal obstacles to reduce and eventually eliminate P. vivax reside in 1) its higher vectorial capacity compared with P. falciparum due to its ability to develop at lower temperature and over a shorter sporogonic cycle in the vector, allowing transmission in temperate zones and making it less sensitive to vector control measures that are otherwise effective on P. falciparum; 2) the presence of dormant liver forms (hypnozoites), sustaining multiple relapsing episodes from a single infectious bite that cannot be diagnosed and are not susceptible to any available antimalarial except primaquine, with routine deployment restricted by toxicity; 3) low parasite densities, which are difficult to detect with current diagnostics leading to missed diagnoses and delayed treatments (and protracted transmission), coupled with 4) transmission stages (gametocytes) occurring early in acute infections, before infection is diagnosed.
Topics: Antimalarials; Genetic Variation; Global Health; Humans; Life Cycle Stages; Malaria, Vivax; Plasmodium vivax; Species Specificity
PubMed: 27799636
DOI: 10.4269/ajtmh.16-0160 -
Malaria Journal Aug 2013Plasmodium vivax infections in pregnancy are associated with low birth weight and anaemia. This parasites species is also characterised by relapses, erythrocytic...
BACKGROUND
Plasmodium vivax infections in pregnancy are associated with low birth weight and anaemia. This parasites species is also characterised by relapses, erythrocytic infections initiated by the activation of the dormant liver stages, the hypnozoites, to mature. Genotyping of P. vivax using microsatellite markers has opened the way to comparative investigations of parasite populations. The aim of the study was to assess whether there were any differences between the parasites found in pregnant and non-pregnant patients, and/or between the admission infections and recurrent episodes during follow-up.
METHODS
Blood samples were collected from 18 pregnant and 18 non-pregnant patients, who had at least two recurrent episodes during follow-up, that were recruited in two previous trials on the efficacy of chloroquine treatment of P. vivax infections on the Thai-Myanmar border. DNA was purified and the P. vivax populations genotyped with respect to eight polymorphic microsatellite markers. Analyses of the genetic diversity, multiplicity of infection (MOI), and a comparison of the genotypes in the samples from each patient were conducted.
RESULTS
The P. vivax parasites present in the samples exhibited high genetic diversity (6 to 15 distinct allelic variants found for the 8 loci). Similar expected heterozygosity (He) values were obtained for isolates from pregnant (0.837) and non-pregnant patients (0.852). There were modest differences between the MOI values calculated for both admission and recurrence samples from the pregnant patients (2.00 and 2.05, respectively) and the equivalent samples from the non-pregnant patients (1.67 and 1.64, respectively). Furthermore, the mean number of distinct alleles enumerated in the admission samples from the pregnant (6.88) and non-pregnant (7.63) patients were significantly lower than that found in the corresponding recurrent episodes samples (9.25 and 9.63, respectively).
CONCLUSIONS
The P. vivax populations circulating in inhabitants along the Thai-Myanmar border, an area of low malaria transmission, displayed high genetic diversity. A subtle increase in the multiplicity of P. vivax infections in pregnant patients suggests a higher susceptibility to infection. The higher allelic diversity in the relapse as compared to the admission samples in both patient groups is consistent with the hypothesis that a febrile episode promotes the activation of hypnozoites.
Topics: Adolescent; Adult; Blood; Child; Child, Preschool; DNA Fingerprinting; DNA, Protozoan; Female; Genotype; Humans; Malaria, Vivax; Microsatellite Repeats; Middle Aged; Molecular Epidemiology; Myanmar; Plasmodium vivax; Polymorphism, Genetic; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Thailand; Young Adult
PubMed: 23915022
DOI: 10.1186/1475-2875-12-275 -
Malaria Journal Jul 2013The origins and dispersal of Plasmodium vivax to its current worldwide distribution remains controversial. Although progress on P. vivax genetics and genomics has been...
BACKGROUND
The origins and dispersal of Plasmodium vivax to its current worldwide distribution remains controversial. Although progress on P. vivax genetics and genomics has been achieved worldwide, information concerning New World parasites remains fragmented and largely incomplete. More information on the genetic diversity in Latin America (LA) is needed to better explain current patterns of parasite dispersion and evolution.
METHODS
Plasmodium vivax circumsporozoite protein gene polymorphism was investigated using polymerase chain reaction amplification and restriction fragment length polymorphism (PCR-RFLP), and Sanger sequencing in isolates from the Pacific Ocean coast of Mexico, Nicaragua, and Peru. In conjunction with worldwide sequences retrieved from the Genbank, mismatch distribution analysis of central repeat region (CRR), frequency estimation of unique repeat types and phylogenetic analysis of the 3' terminal region, were performed to obtain an integrative view of the genetic relationships between regional and worldwide isolates.
RESULTS
Four RFLP subtypes, vk210a, b, c and d were identified in Southern Mexico and three subtypes vk210a, e and f in Nicaragua. The nucleotide sequences showed that Mexican vk210a and all Nicaraguan isolates were similar to other American parasites. In contrast, vk210b, c and d were less frequent, had a domain ANKKAEDA in their carboxyl end and clustered with Asian isolates. All vk247 isolates from Mexico and Peru had identical RFLP pattern. Their nucleotide sequences showed two copies of GGQAAGGNAANKKAGDAGA at the carboxyl end. Differences in mismatch distribution parameters of the CRR separate vk247 from most vk210 isolates. While vk247 isolates display a homogeneous pattern with no geographical clustering, vk210 isolates display a heterogeneous geographically clustered pattern which clearly separates LA from non-American isolates, except vk210b, c and d from Southern Mexico.
CONCLUSIONS
The presence of vk210a in Mexico and vk210e, f and g in Nicaragua are consistent with other previously reported LA isolates and reflect their circulation throughout the continent. The vk210b, c and d are novel genotypes in LA. Their genetic relationships and low variability within these vk210 and/or within the vk247 parasites in Southern Mexico suggest its recent introduction and/or recent expansion to this region. The global analysis of P. vivax csp suggests this parasite introduction to the region and likely LA by different independent events.
Topics: Cluster Analysis; DNA, Protozoan; Genotype; Humans; Malaria, Vivax; Mexico; Molecular Epidemiology; Molecular Sequence Data; Nicaragua; Peru; Plasmodium vivax; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Protozoan Proteins; Sequence Analysis, DNA; Sequence Homology
PubMed: 23855807
DOI: 10.1186/1475-2875-12-243