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  1. Cattani JA, Gibson FD, Alpers MP, Crane GG
    Trans R Soc Trop Med Hyg, 1987;81(5):705-9.
    PMID: 3329776
    Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with greater than or equal to 50% oval red cells matched by age, sex and village of residence with controls having less than or equal to 30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0.009), for P. falciparum (P = 0.044), and for all species of malaria parasites (P = 0.013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0.01 less than P less than 0.025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.
    Matched MeSH terms: Plasmodium vivax/immunology
  2. Thomas V, Hock SK, Leng YP
    Trop Doct, 1981 Oct;11(4):149-54.
    PMID: 7027557
    A seroepidemiological study was carried out on Orang Asli (Aborigines) children who lead a semi-nomadic life in the deep jungles of Ulu Kelantan, Malaysia. Out of a total of about 190 children below 14 years, 143 were studied. Blood was collected from finger pricks on standard "strip type" filter papers for indirect fluorescent antibody (IFA) tests with Plasmodium falciparum antigen. A positive reaction at 1:10 dilution in infants and young children was considered positive and the reasons are given. The P. falciparum antibody prevalence rate was 84.6% compared to 81.8% spleen and 43.4% parasite rates. Both P. Falciparum and P. vivax were present in children. The age-specific patterns of antibody, spleen and parasite rates were those of a hyperendemic community. There was a positive correlation between antibody and spleen rates up to the age of 9 years. In older children, the antibody rates increased while the spleen and the parasite rates dropped.
    Matched MeSH terms: Plasmodium vivax/immunology
  3. Wirtz RA, Rosenberg R, Sattabongkot J, Webster HK
    Lancet, 1990 Sep 8;336(8715):593-5.
    PMID: 1975379
    The distribution in Thailand of antibody to a recently discovered variant of circumsporozoite proteins of Plasmodium vivax was determined by enzyme-linked immunosorbent assay (ELISA). The ELISA capture antigens were a synthetic peptide of the principal variant sequence ANGAGNQPG and a candidate P vivax vaccine that contained the predominant repeat sequence GDRAA/DGQPA. Serological evidence of recent inoculation with the variant was found throughout Thailand and in migrants from Cambodia, Malaysia, and Burma. IgG antibody to the two P vivax circumsporozoite proteins was detected in 217 of 804 test sera (27%). Within the regions studied the proportion of positive sera specific for the variant epitope ranged from 28% to 66%. A vaccine against the predominant repeat domain may rapidly select for the variant, which already appears to be widespread within Thailand.
    Matched MeSH terms: Plasmodium vivax/immunology*
  4. Mathews HM, Dondero TJ
    Am J Trop Med Hyg, 1982 Jan;31(1):14-8.
    PMID: 7036766
    The indirect hemagglutination test was used to measure malaria antibody levels in residents of an endemic area of Malaysia. Blood specimens were collected at 4-week intervals for a year. Seropositivity rates increased with age and number of episodes of malaria in young children. Although antibody levels were variable, titers tended to rise with parasitemia and fall in the absence of detected parasites. In general, the serologic indices tended to reflect the parasitologic findings.
    Matched MeSH terms: Plasmodium vivax/immunology*
  5. Kumar GS, Mak JW, Lam PL, Tan MA, Lim PK
    PMID: 3129797
    Malarial antibodies in 80 patients were measured using the diffusion-in-gel enzyme linked immunosorbent assay (DIG-ELISA), enzyme-linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) test. Good correlations were obtained between all three tests in terms of sensitivity and reliability. DIG-ELISA has the advantage of being a rapid diagnostic tool for the detection of malarial antibodies.
    Matched MeSH terms: Plasmodium vivax/immunology
  6. Muh F, Kim N, Nyunt MH, Firdaus ER, Han JH, Hoque MR, et al.
    PLoS Negl Trop Dis, 2020 06;14(6):e0008323.
    PMID: 32559186 DOI: 10.1371/journal.pntd.0008323
    Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P. vivax and P. knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P. vivax cases are in decline, zoonotic P. knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P. vivax blood-stage antigen-specific antibodies against P. knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P. vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P. knowlesi merozoites. Recombinant P. vivax and P. knowlesi proteins were also recognized by P. knowlesi- and P. vivax-infected patient antibodies, respectively. Immunoglobulin G against P. vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P. knowlesi. This study demonstrates that there is extensive cross-reactivity between antibodies against P. vivax to P. knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.
    Matched MeSH terms: Plasmodium vivax/immunology*
  7. Chen Y, Chan CK, Kerishnan JP, Lau YL, Wong YL, Gopinath SC
    BMC Infect Dis, 2015;15:49.
    PMID: 25656928 DOI: 10.1186/s12879-015-0786-2
    Plasmodium knowlesi was identified as the fifth major malaria parasite in humans. It presents severe clinical symptoms and leads to mortality as a result of hyperparasitemia in a short period of time. This study aimed to improve the current understanding of P. knowlesi and identify potential biomarkers for knowlesi malaria.
    Matched MeSH terms: Plasmodium vivax/immunology
  8. Gordon DM, Davis DR, Lee M, Lambros C, Harrison BA, Samuel R, et al.
    Am J Trop Med Hyg, 1991 Jul;45(1):49-56.
    PMID: 1867348
    Two hundred and seventy-five Orang Asli volunteers living in nine villages in the Pos Legap Valley of Perak State, peninsular Malaysia, participated in a prospective study designed to characterize the epidemiological, parasitological, and entomological characteristics of Plasmodium falciparum, P. vivax, and P. malariae malaria transmission. Prevalence rates for the three plasmodial species at initiation of the study ranged from 56% in the 0-4-year-old age group to 0% in individuals over the age of 40. Entomological surveys were conducted, enabling us to determine mosquito salivary gland-positive rates and entomological inoculation rates of 1.2 infectious mosquito bites per person per month for P. falciparum, 2.4 for P. vivax, and 0.3 for P. malariae. Cumulative incidence rates over the 16 weeks of the study, following radical cure of all volunteers, were 22.5% for P. falciparum, 12.7% for P. vivax, and 1.5% for P. malariae. The median baseline antibody titer against the immunodominant repetitive B cell epitope of P. falciparum or P. vivax circumsporozoite protein was significantly higher for volunteers who did not become parasitemic. Volunteers were selected for further study if they had evidence of being challenged with P. falciparum sporozoites during the study, based on a two-fold or greater increase in antibody titer against the immunodominant repetitive B cell epitope of the circumsporozoite protein. Resistance to infection was seen in six of 10 individuals who had high (greater than 25 OD units) baseline ELISA titers, compared with only three of 24 individuals who had low baseline ELISA titers (chi 2 P less than 0.02). A similar analysis for P. vivax did not show a significant correlation.
    Matched MeSH terms: Plasmodium vivax/immunology*
  9. Zhang R, Lee WC, Lau YL, Albrecht L, Lopes SC, Costa FT, et al.
    PLoS Negl Trop Dis, 2016 08;10(8):e0004912.
    PMID: 27509168 DOI: 10.1371/journal.pntd.0004912
    Malaria parasites dramatically alter the rheological properties of infected red blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance. This study highlights correlation between rosette formation and altered membrane deformability of P. vivax-infected erythrocytes, where the rosette-forming infected erythrocytes are significantly more rigid than their non-rosetting counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding force of 440pN) resulting in stable rosette formation even under high physiological shear flow stress. Rosetting may contribute to the sequestration of PvIRBC schizonts in the host microvasculature or spleen.
    Matched MeSH terms: Plasmodium vivax/immunology
  10. Han JH, Cho JS, Ong JJY, Park JH, Nyunt MH, Sutanto E, et al.
    PLoS Negl Trop Dis, 2020 Jul;14(7):e0008202.
    PMID: 32645098 DOI: 10.1371/journal.pntd.0008202
    Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179-479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480-690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate.
    Matched MeSH terms: Plasmodium vivax/immunology
  11. Lim PK, Mak JW, Yong HS
    PMID: 1298082
    Two monoclonal antibodies (MAbs), one produced against Plasmodium falciparum (PF-IG8) and the other against P. cynomolgi (PC-IE12) schizont antigens were used in a sandwich ELISA for the detection of circulating plasmodial antigens in sera of patients infected with either P. falciparum, P. vivax or P. malariae. The mean +/- SD optical density (OD) values for the normal control group using PF-108 and PC-1E12 were 0.351 +/- 0.036 and 0.205 +/- 0.044, respectively. Mean OD values for the three infected groups were found to be significantly higher than those of the normal control group for both MAbs. However, ELISA values for individual serum specimens did not correlate with the level of parasitemia in the infected blood. Using a cut-off point of mean OD +/- 3 SD of the normal control group as indicating a positive reading, the specificity of this assay with both MAbs was 100%. The sensitivity of the assay using PF-1G8 was 95% while that obtained with PC-1E12 was 98%.
    Matched MeSH terms: Plasmodium vivax/immunology
  12. Lee M, Davis DR, Ballou WR, Folena-Wasserman G, Lewis GE
    Am J Trop Med Hyg, 1988 Dec;39(6):535-9.
    PMID: 3061309
    A seroepidemiologic survey of Plasmodium vivax and Plasmodium falciparum transmission was conducted in 94 Orang Asli children and adults. The prevalence of malaria was 46% in this population, and infections due to P. vivax and P. falciparum occurred with equal frequency. Multi-species infection was common, particularly in children less than 10 years of age. Circumsporozoite (CS) antibodies to P. vivax were detected by ELISA, using the recombinant protein NS181V20, in sera from 53-95% of all subjects in this study. The specificity of reactivity to NS181V20 was confirmed by immunofluorescence using air-dried sporozoites. CS antibodies to P. falciparum were present in less than 50% of the population less than 30 years of age. These data support further testing of this protein as a candidate vivax vaccine.
    Matched MeSH terms: Plasmodium vivax/immunology*
  13. Lee WC, Malleret B, Lau YL, Mauduit M, Fong MY, Cho JS, et al.
    Blood, 2014 May 01;123(18):e100-9.
    PMID: 24652986 DOI: 10.1182/blood-2013-12-541698
    Rosetting phenomenon has been linked to malaria pathogenesis. Although rosetting occurs in all causes of human malaria, most data on this subject has been derived from Plasmodium falciparum. Here, we investigate the function and factors affecting rosette formation in Plasmodium vivax. To achieve this, we used a range of novel ex vivo protocols to study fresh and cryopreserved P vivax (n = 135) and P falciparum (n = 77) isolates from Thailand. Rosetting is more common in vivax than falciparum malaria, both in terms of incidence in patient samples and percentage of infected erythrocytes forming rosettes. Rosetting to P vivax asexual and sexual stages was evident 20 hours postreticulocyte invasion, reaching a plateau after 30 hours. Host ABO blood group, reticulocyte count, and parasitemia were not correlated with P vivax rosetting. Importantly, mature erythrocytes (normocytes), rather than reticulocytes, preferentially form rosetting complexes, indicating that this process is unlikely to directly facilitate merozoite invasion. Although antibodies against host erythrocyte receptors CD235a and CD35 had no effect, Ag-binding fragment against the BRIC 4 region of CD236R significantly inhibited rosette formation. Rosetting assays using CD236R knockdown normocytes derived from hematopoietic stem cells further supports the role of glycophorin C as a receptor in P vivax rosette formation.
    Matched MeSH terms: Plasmodium vivax/immunology*
  14. Idris ZM, Chan CW, Mohammed M, Kalkoa M, Taleo G, Junker K, et al.
    Parasit Vectors, 2017 Apr 26;10(1):204.
    PMID: 28441959 DOI: 10.1186/s13071-017-2139-z
    BACKGROUND: Seroepidemiology can provide evidence for temporal changes in malaria transmission and is an important tool to evaluate the effectiveness of control interventions. During the early 2000s, Vanuatu experienced an acute increase in malaria incidence due to a lapse in funding for vector control. After the distribution of subsidised insecticide-treated nets (ITNs) resumed in 2003, malaria incidence decreased in the subsequent years. This study was conducted to find the serological evidence supporting the impact of ITN on exposure to Anopheles vector bites and parasite prevalence.

    METHODS: On Ambae Island, blood samples were collected from 231 and 282 individuals in 2003 and 2007, respectively. Parasite prevalence was determined by microscopy. Antibodies to three Plasmodium falciparum (PfSE, PfMSP-119, and PfAMA-1) and three Plasmodium vivax (PvSE, PvMSP-119, and PvAMA-1) antigens, as well as the Anopheles-specific salivary antigen gSG6, were detected by ELISA. Age-specific seroprevalence was analysed using a reverse catalytic modelling approach to estimate seroconversion rates (SCRs).

    RESULTS: Parasite rate decreased significantly (P vivax co-dominance. Significant (P vivax antigens (except PvAMA-1; P = 0.153), consistent with the more pronounced decrease in P. falciparum prevalence. Seroprevalence to gSG6 also decreased significantly (P vivax transmission was less clear.

    CONCLUSIONS: Serological markers pointed to the effectiveness of ITNs in reducing malaria prevalence on Ambae Island between 2003 and 2007. The recombinant gSG6 antigen originally developed to indicate exposure to the Afrotropical vector An. gambiae may be used in the Pacific to complement the traditional measure of entomological inoculation rate (EIR).

    Matched MeSH terms: Plasmodium vivax/immunology
  15. 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/immunology*
  16. Müller-Sienerth N, Shilts J, Kadir KA, Yman V, Homann MV, Asghar M, et al.
    Malar J, 2020 Jan 17;19(1):31.
    PMID: 31952523 DOI: 10.1186/s12936-020-3111-5
    BACKGROUND: Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information.

    METHODS: Using the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species.

    RESULTS: Using sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38.

    CONCLUSIONS: Using the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.

    Matched MeSH terms: Plasmodium vivax/immunology*
  17. Othman AS, Marin-Mogollon C, Salman AM, Franke-Fayard BM, Janse CJ, Khan SM
    Expert Rev Vaccines, 2017 Jul;16(7):1-13.
    PMID: 28525963 DOI: 10.1080/14760584.2017.1333426
    INTRODUCTION: Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
    Matched MeSH terms: Plasmodium vivax/immunology*
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