Genetic polymorphism and effect of natural selection at domain I of apical membrane antigen-1 (AMA-1) in Plasmodium vivax isolates from Myanmar

Malaria is endemic or hypoendemic in Myanmar and the country still contributes to the high level of malaria deaths in South-East Asia. Although information on the nature and extent of population diversity within malaria parasites in the country is essential not only for understanding the epidemic situation but also to establish a proper control strategy, very little data is currently available on the extent of genetic polymorphisms of the malaria parasites in Myanmar. In this study, we analyzed the genetic polymorphism and natural selection at domain I of the apical membrane antigen-1 (AMA-1) among Plasmodium vivax Myanmar isolates. A total of 34 distinguishable haplotypes were identified among the 76 isolates sequenced. Comparison with the previously available PvAMA-1 sequences in the GenBank database revealed that 21 of them were new haplotypes that have never been reported till date. The difference between the rate of nonsynonymous (dN) and synonymous (dS) mutations was positive (dN − dS, 0.013 ± 0.005), suggesting the domain I is under positive natural selection. The Tajima's D statistics was found to be −0.74652, suggesting that the gene has evolved under population size expansion and/or positive selection. The minimum recombination events were also high, indicating that recombination may occur within the domain I resulting in allelic diversity of PvAMA-1. Our results collectively suggest that PvAMA-1 displays high genetic polymorphism among Myanmar P. vivax isolates with highly diversifying selection at domain I. These results have significant implications in understanding the nature of P. vivax population circulating in Myanmar as well as providing useful information for malaria vaccine development based on this antigen.     

High frequency of genetic diversity of Plasmodium vivax field isolates in Myanmar

Malaria is one of the most serious problems threatening human health in Myanmar. Although the morbidity and mortality rates due to malaria have been gradually declining, Myanmar still contributes to a large proportion of malarial death in the South-East Asia region. However, little is known about the nature and extent of genetic diversity of the malarial parasites circulating in Myanmar. In this study, we investigated the overall infection status of Plasmodium and the population diversity of Plasmodium vivax by analyzing three genetic markers, circumsporozoite protein (CSP), merozoite surface protein-1 (MSP-1), and merozoite surface protein-3 (MSP-3α), of P. vivax field isolates collected from infected individuals. In 349 blood samples collected from the individuals who exhibited clinical symptoms associated with malaria, 63.0% showed a positive result for malaria (220/349). P. vivax was detected in 58.2% (128/220) and Plasmodium falciparum was detected in 29.1% (64/220). Mixed infections with both parasites were detected in 12.7% (28/220). The 116 blood samples in which single infection of P. vivax was confirmed were selected and subjected to further genetic analysis. Genotyping of the CSP gene of P. vivax showed that VK210 type (98.3%, 114/116) is predominant in Myanmar, but a significant level of mixed infections of VK210 and VK247 types (24.1%, 28/116) was also identified. Sequence analyses of MSP-1 and MSP-3α genes revealed a large number of distinguishable alleles: 12 for MSP-1 and 25 for MSP-3α. These results collectively suggest that the P. vivax population in Myanmar is highly diverse and multiple clonal infections are prevalent in the country.     

Genetic diversity and natural selection of Duffy binding protein of Plasmodium vivax Korean isolates

Plasmodium vivax Duffy binding protein (PvDBP) is a micronemal type I membrane protein that plays an essential role in erythrocyte invasion of merozoites. PvDBP is a prime blood stage vaccine candidate antigen against P. vivax, but its polymorphic nature represents a major obstacle to the successful design of a protective vaccine against vivax malaria. In this study, we analyzed the genetic polymorphism and natural selection at the N-terminal cysteine-rich region of PvDBP (PvDBPII) among 70 P. vivax isolates collected from Korean patients during 2005–2010. Seventeen single nucleotide polymorphisms (SNP), which resulted in 14 non-synonymous and 3 synonymous mutations, were found in PvDBPII among the Korean P. vivax isolates. Sequence analyses revealed that 13 different PvDBPII haplotypes, which were clustered into 3 distinct clades, were identified in Korean P. vivax isolates. The difference between the rates of nonsynomyous and synonymous mutations suggested that the region has evolved under natural selection. High selective pressure preferentially acted on regions identified or predicted to be B- and T-cell epitopes and MHC binding regions of PvDBPII. Recombination may also contribute to genetic diversity of PvDBPII. Our results suggest that PvDBPII of Korean P. vivax isolates display a limited genetic polymorphism and are under selective pressure. These results have significant implications for understanding the nature of the P. vivax population circulating in Korea and provide useful information for development of malaria vaccines based on this antigen.     

Rapid Dissemination of Newly Introduced Plasmodium vivax Genotypes in South Korea

Reemerged Plasmodium vivax malaria in South Korea has not yet been eradicated despite continuous governmental efforts. It has rather become an endemic disease. Our study aimed to determine the genetic diversity in P. vivax merozoite surface protein-1 (PvMSP-1) and circumsporozoite protein (PvCSP) genes over an extended period after its reemergence to its current status. Sequence analysis of PvMSP-1 gene sequences from the 632 P. vivax isolates during 1996–2007 indicates that most isolates recently obtained were different from isolates obtained in the initial reemergence period. There was initially only one subtype (recombinant) present but its subtypes have varied since 2000; six MSP-1 subtypes were recently found. A similar variation was observed by CSP gene analysis; a new CSP subtype was found. Understanding genetic variation patterns of the parasite may help to analyze trends and assess extent of endemic malaria in South Korea.     

Genetic diversity in the C-terminal 42 kDa region of merozoite surface protein-1 of Plasmodium vivax (PvMSP-1(42)) among Indian isolates

Plasmodium vivax merozoite surface protein 1 (PvMSP-1) is a leading malaria vaccine candidate. This protein is processed to give rise to various sized fragments during merozoite maturation. Here, we describe the analysis of genetic diversity in the 42 kDa C-terminal part of this protein among 33 Indian P. vivax isolates. A total of 27 haplotypes with 72 mutations and 0.0212 ± 0.0005S.D. over all π nucleotide diversity were observed among the isolates. Twenty-six of 27 haplotypes reported here were new as they have not been reported so far from any other country. The difference between non-synonymous (dN) and synonymous (dS) mutations was found to be positive (0.0081 ± 0.0051) for the entire 42 kDa region. Further analysis revealed that 33 kDa (MSP-1₃₃) fragment of the MSP-1₄₂ was highly polymorphic with π nucleotide diversity 0.0290 ± 0.0007S.D. The dN-dS for this region of MSP-1 was also positive (0.0114 ± 0.0071S.E.). On the other hand, there was no non-synonymous mutation in the 19 kDa (MSP-1₁₉) fragment of the MSP-1₄₂ and thus it was highly conserved. In conclusion, MSP-1₃₃ fragment was highly polymorphic and appeared to be under diversifying selection whereas there was no selection at MSP-1₁₉ region among the isolates. Present study will be helpful for the development of PvMSP-1 based vaccine against P. vivax malaria.     

Interaction of malaria with a common form of severe thalassemia in an Asian population

In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and β thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE β thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE β thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE β thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE β thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs.In excess of 300,000 babies have been estimated recently to be born each year with a serious inherited hemoglobin disorder (1). In sub-Saharan Africa, the main diseases of this type result from HbS or α thalassemia. Throughout the Mediterranean region and the Middle East, α and β thalassemia predominate, although the sickle-cell gene occurs in the oasis populations of Saudi Arabia and extends to some of the tribal groups in India, where β thalassemia also occurs at a high frequency (2). In the eastern parts of the Indian subcontinent, Bangladesh, Myanmar, Thailand, and in other parts of Southeast Asia, HbE is by far the most common hemoglobin variant (2), although both α and β thalassemia also occur at variable frequencies. Because HbE is synthesized at a reduced rate, it behaves phenotypically like a mild form of β thalassemia (3). Because of its extremely high frequency, reaching a 70% carrier rate in some populations, it often is found in the compound heterozygous state with β thalassemia, a condition called HbE β thalassemia. This is the most common severe form of thalassemia in many Asian countries; in Thailand, for example, there are estimated to be ≈100,000 patients with this disease, and in Bangladesh, there are estimated to be twice this number (4, 5).One of the extraordinary features of HbE β thalassemia, and one that makes its control and management extremely difficult, is its remarkable clinical diversity (2). This is well exemplified in Sri Lanka, where it accounts for one-third of the cases of severe thalassaemia (6). Despite the fact that the common β thalassemia mutations are all of the severe variety that are associated with very limited or no β chain production (6), this interaction results in a spectrum of patients ranging from those who are transfusion-dependent for life to others who, despite moderately severe anemia, grow and develop normally (7, 8). Detailed analysis of these patients over the last 10 years has made possible the definition of mild and severe phenotypes and the determination of at least some of the genetic and adaptive factors that may be responsible for this wide variation in phenotype (7, 8). However, like similar studies in other populations (9, 10), these findings only account for ≈30% of the phenotypic heterogeneity.There have been no studies reporting the interaction of malaria with severe forms of thalassemia. Because environmental factors of this kind have been neglected in the study of the phenotypic variation of the thalassemias and because until recently both Plasmodium vivax and Plasmodium falciparum malaria have been a serious health burden in Sri Lanka (11, 12), particularly because the increasingly severe spectrum of disease caused by P. vivax malaria only has been appreciated in recent years (13, 14), studying the potential interaction between these forms of malaria and HbE β thalassemia seemed important.     

Sri Lankan National Melioidosis Surveillance Program Uncovers a Nationwide Distribution of Invasive Melioidosis

The epidemiologic status of melioidosis in Sri Lanka was unclear from the few previous case reports. We established laboratory support for a case definition and started a nationwide case-finding study. Suspected Burkholderia pseudomallei isolates were collated, identified by polymerase chain reaction assay, referred for Matrix Assisted Laser Desorption Ionization-Time of Flight analysis and multilocus sequence typing (MLST), and named according to the international MLST database. Between 2006 and early 2014, there were 32 patients with culture-confirmed melioidosis with an increasing annual total and a falling fatality rate. Patients were predominantly from rural communities, diabetic, and male. The major clinical presentations were sepsis, pneumonia, soft tissue and joint infections, and other focal infection. Burkholderia pseudomallei isolates came from all parts of Sri Lanka except the Sabaragamuwa Province, the south central hill country, and parts of northern Sri Lanka. Bacterial isolates belonged to 18 multilocus sequence types, one of which (ST 1137) was associated with septicemia and a single-organ focus (Fisher''s exact, P = 0.004). Melioidosis is an established endemic infection throughout Sri Lanka, and is caused by multiple genotypes of B. pseudomallei, which form a distinct geographic group based upon related sequence types (BURST) cluster at the junction of the southeast Asian and Australasian clades.     

An indigenous case of Plasmodium ovale infection in Sri Lanka

Plasmodium ovale, which is generally prevalent only in the African region, has been emerging in the Asian and southeast Asian regions. It has not been reported in Sri Lanka. We report, to our knowledge, an indigenous case of P. ovale infection in Sri Lanka. This patient, who was diagnosed by a polymerase chain reaction, had no history of travel overseas or receipt of a transfusion of blood or any blood products, which makes this a likely case of indigenous transmission. This incidental finding of a P. ovale infection has implications for malaria control in the country and highlights the need to rigorously monitor malaria incidence, as well as prevalent Plasmodium species, with newer and more reliable diagnostics.     

High Genetic Diversity of Plasmodium vivax on the North Coast of Papua New Guinea

Despite having the highest Plasmodium vivax burden in the world, molecular epidemiological data from Papua New Guinea (PNG) for this parasite remain limited. To investigate the molecular epidemiology of P. vivax in PNG, 574 isolates collected from four catchment sites in East Sepik (N = 1) and Madang (N = 3) Provinces were genotyped using the markers MS16 and msp1F3. Genetic diversity and prevalence of P. vivax was determined for all sites. Despite a P. vivax infection prevalence in the East Sepik (15%) catchments less than one-half the prevalence of the Madang catchments (27–35%), genetic diversity was similarly high in all populations (H_e = 0.77–0.98). High genetic diversity, despite a marked difference in infection prevalence, suggests a large reservoir of diversity in P. vivax populations of PNG. Significant reductions in transmission intensity may, therefore, be required to reduce the diversity of parasite populations in highly endemic countries such as PNG.     

Molecular characterization of Mycobacterium tuberculosis isolates from Kandy,Sri Lanka

ObjectiveTo determine tuberculosis epidemiology in Kandy, Sri Lanka.MethodsIS6110 RFLP and spoligotyping analyses were performed on 100 Mycobacterium tuberculosis (M. tuberculosis) clinical isolates from Kandy district, Sri Lanka. RFLP hybridization patterns (n=73) were analysed by the software GeneDirectory. Spoligotypes (n=110) were compared with the international database SPOTCLUST.ResultsThe majority of the circulating M. tuberculosis strains in Kandy belong to a single family, but the degree of IS6110 DNA polymorphism was high. 71 (80%) of the strains displayed distinct RFLP patterns and 63 (71%) were clustered into one main family. Within the family three isolates were grouped into one cluster while the rest isolates were grouped into one. The copy number varied from 1 to 17 while single copy strains were predominant (12) and 15 lacked the IS6110 element. Spoligotyping revealed a total of 24 families including the 9 major families. Strains were distributed among all the three principle genetic groups PGG1, PGG2, and PGG3. Except for two strains, the rest were not defined in the latest spoligotype database SpolDB4/SITVIT.ConclusionsThe first study of RFLP and spoligotyping of M. tuberculosis strains in Sri Lanka demonstrates the applicability of the genetic marker IS6110 to differentiate strains and the heterogeneity and predominance of several worldwide-distributed spoligotypes.     

Mutations in the Antifolate-Resistance-Associated Genes Dihydrofolate Reductase and Dihydropteroate Synthase in Plasmodium vivax Isolates from Malaria-Endemic Countries

Parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are known target enzymes of antifolate drugs used for the treatment and prophylaxis of persons with malaria. We sequenced the Plasmodium vivax dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps) genes to examine the prevalence and extent of point mutations in isolates from malaria-endemic countries. Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117T) in the pvdhfr gene were found in isolates from Thailand (96.4%) and Myanmar (71.4%), but in only one isolate (1.0%) from Korea, where sulfadoxine-pyrimethamine has never been used. The pvdhfr point mutations correlated strongly with the pvdhps point mutations and ranged from single to triple mutations (S382A, A383G, and A553G), among isolates from Thailand, Myanmar, and Korea. These findings suggests that the prevalence of mutations in pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine.     

Severe thrombocytopenia suggesting immunological mechanisms in two cases of vivax malaria

Case 1: A 27-year-old woman, referred to our hospital because of relapsing fever after travel to Thailand, was given a diagnosis of vivax malaria. Clinical investigation revealed thrombocytopenia, elevated platelet-associated IgG (PAIgG), and negative antibody against Plasmodium vivax antigen. After antimalarial treatment, the levels of both the platelets and PAIgG returned to normal. Case 2: A 28-year-old Sri Lankan man was admitted to our hospital with a complaint of fever. The patient had thrombocytopenia, elevated PAIgG, and positive antibody against Plasmodium vivax antigen. He contracted malaria in Sri Lanka about 6 months prior to this admission. After treatment, the platelet count and PAIgG level returned to normal. In these two cases, high levels of PAIgG may have been involved in the development of the thrombocytopenia. In the first patient, in particular, the thrombocytopenia was thought to be induced by some immunological mechanism prior to the detection of antimaralial antibodies in serum. Am. J. Hematol. 56:183–186, 1997. © 1997 Wiley-Liss, Inc.     

Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries

Treatment failure of chloroquine for Plasmodium vivax infection has increased in endemic countries. However, the molecular mechanisms for resistance and in vitro susceptibility of P. vivax to chloroquine remain elusive. We investigated the prevalence of mutations in the pvmdr1 and pvcrt-o genes, and the copy number of the pvmdr1 gene in isolates from the Republic of Korea (ROK), Thailand, the Union of Myanmar (Myanmar), and Papua New Guinea (PNG). We also measured in vitro susceptibility of Korean isolates to antimalarial drugs. The pvmdr1 analysis showed that mutations at amino acid position Y976F of pvmdr1 were found in isolates from Thailand (17.9%), Myanmar (13.3%), and PNG (100%), but none from the ROK, and mutation at position F1076L was present in isolates from the ROK (100%), Thailand (60.7%), and Myanmar (46.7%). One copy of the pvmdr1 gene was observed in most isolates and double copy numbers of the gene were observed in two Thai isolates. In the exons of the pvcrt-o gene that were sequenced, a K10 insertion was present in isolates from Thailand (56.0%) and Myanmar (46.2%), and the wild type was found in all Korean isolates. The results suggest that gene polymorphisms and copy number variation was observed in isolates of P. vivax from Southeast Asian countries. In Korean isolates polymorphism as limited to the F1076L variant, and no isolates with high level of resistance were found by in vitro susceptibility determinations. Moreover, our results provide a baseline for future prospective drug studies in malaria-endemic areas.     

Genetic structure of Plasmodium vivax isolates from two malaria endemic areas in Afghanistan

In this study, the nature and extent of genetic diversity of Plasmodium vivax populations circulating in Afghanistan have been investigated by analyzing three genetic markers: csp, msp-1, and msp-3α. Blood samples (n = 202) were collected from patients presenting with vivax malaria from south-western (Herat) and south-eastern (Nangarhar) parts of Afghanistan, and analysed using nested-PCR/RFLP and sequencing methods. Genotyping pvmsp-1 revealed type 1, type 2 and recombinant type 3 allelic variants, with type 1 predominant in parasites in both study areas. The sequence analysis of 57 P. vivax isolates identified a total of 26 distinct alleles. Genotyping pvcsp gene showed that VK210 type (86.6%) is predominant in Afghanistan. Moreover, three major types of the pvmsp-3α locus: type A, type B and type C were distinguished among Afghani isolates. The predominant fragments among Nangarhar and Herat parasites were type A (70.8% and 67.9%, respectively). PCR/RFLP products with Hha I and Alu I were detected 52 and 38 distinct variants among Nangarhar and Herat isolates, respectively. These results strongly indicate that the P. vivax populations in Afghanistan are highly diverse.     

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms

Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (H_E = 0.86) but closely related (G_ST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 (pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P < 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P < 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants.     

Plasmodium falciparum populations from northeastern Myanmar display high levels of genetic diversity at multiple antigenic loci

Levels of genetic diversity of the malaria parasites and multiclonal infections are correlated with transmission intensity. In order to monitor the effect of strengthened malaria control efforts in recent years at the China–Myanmar border area, we followed the temporal dynamics of genetic diversity of three polymorphic antigenic markers msp1, msp2, and glurp in the Plasmodium falciparum populations. Despite reduced malaria prevalence in the region, parasite populations exhibited high levels of genetic diversity. Genotyping 258 clinical samples collected in four years detected a total of 22 PCR size alleles. Multiclonal infections were detected in 45.7% of the patient samples, giving a minimum multiplicity of infection of 1.41. The majority of alleles experienced significant temporal fluctuations through the years. Haplotype diversity based on the three-locus genotypes ranged from the lowest in 2009 at 0.33 to the highest in 2010 at 0.80. Sequencing of msp1 fragments from 36 random samples of five allele size groups detected 13 different sequences, revealing an additional layer of genetic complexity. This study suggests that despite reduced prevalence of malaria infections in this region, the parasite population size and transmission intensity remained high enough to allow effective genetic recombination of the parasites and continued maintenance of genetic diversity.     

Genetic diversity of Plasmodium falciparum field samples from an isolated Colombian village

Colombian field isolates of Plasmodium falciparum were analyzed for genetic diversity. Fifty-three samples were collected as thick smears from patients living in Panguí, an isolated area with low migration. While the samples were being collected, Panguí was experiencing an epidemic outbreak of malaria. The samples were typified using nested polymerase chain reaction (PCR) amplification of block 2 of the merozoite surface protein 1 (MSP1) gene and nested PCR with mutation-specific primers for position 108 of the dihydrofolate reductase enzyme gene. The results for the circulating population of parasites in Panguí show low diversity--four allelic forms--using MSP1 as a marker, a fact that contrasts with data reported for certain Asian and African zones. A high percentage of mixed infections was observed, as was high complexity of the infection. No differential distributions were found for any allelic type.     

Microsatellite loci: determining the genetic variability of Plasmodium vivax

Objective To describe the genetic diversity of Plasmodium vivax isolates from different areas in the Brazilian Amazon using 11 polymorphic microsatellites and to evaluate the correlation between microsatellite variation and repeat array length. Methods Microsatellites with variable repeat units and array lengths were selected using in silico search of the P. vivax genome. We designed primers and amplified the selected loci in DNA obtained from patients with P. vivax acute infections. Results Positive correlation between repeat array length and microsatellite variation was detected independently of the size of repeat unit (di, tri, or tetranucleotide). We used these markers to describe the genetic variability of P. vivax isolates from four geographic regions of the Brazilian Amazon. Substantial variability was observed among P. vivax isolates within populations, concurrent with high levels of multiple‐clone infections and high linkage disequilibrium. Overall, structured populations were observed with moderate to high genetic differentiation. Conclusion The markers studied are useful tools for assessing population structure of P. vivax, as demonstrated for Brazilian populations and for searching for evidence of recent selection events associated with different phenotypes, such as drug resistance.     

Plasmodium vivax Duffy binding protein: baseline antibody responses and parasite polymorphisms in a well‐consolidated settlement of the Amazon Region

Objective  To investigate risk factors associated with the acquisition of antibodies against Plasmodium vivax Duffy binding protein (PvDBP) – a leading malaria vaccine candidate – in a well‐consolidated agricultural settlement of the Brazilian Amazon Region and to determine the sequence diversity of the PvDBP ligand domain (DBP_II) within the local malaria parasite population. Methods  Demographic, epidemiological and clinical data were collected from 541 volunteers using a structured questionnaire. Malaria parasites were detected by conventional microscopy and PCR, and blood collection was used for antibody assays and molecular characterisation of DBP_II. Results  The frequency of malaria infection was 7% (6% for P. vivax and 1% for P. falciparum), with malaria cases clustered near mosquito breeding sites. Nearly 50% of settlers had anti‐PvDBP IgG antibodies, as detected by enzyme‐linked immunosorbent assay (ELISA) with subject’s age being the only strong predictor of seropositivity to PvDBP. Unexpectedly, low levels of DBP_II diversity were found within the local malaria parasites, suggesting the existence of low gene flow between P. vivax populations, probably due to the relative isolation of the studied settlement. Conclusion  The recognition of PvDBP by a significant proportion of the community, associated with low levels of DBP_II diversity among local P. vivax, reinforces the variety of malaria transmission patterns in communities from frontier settlements. Such studies should provide baseline information for antimalarial vaccines now in development.     

Genome-wide patterns of population structure and admixture in West Africans and African Americans

Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th–75th percentiles: 11.6–27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade.