IgG Antibody Responses Are Preferential Compared With IgM for Use as Serological Markers for Detecting Recent Exposure to Plasmodium vivax Infection.
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ABSTRACT:
SUBMITTER: Longley RJ
PROVIDER: S-EPMC8214013 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAntibody responses as serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors that affect antibody responses in naturally infected people from endemic settings. To address this question, we studied IgG responses to novel serological exposure markers (SEMs) of P. vivax in three settings with different transmission intensity.MethodologyWe validated a panel of 34 SEMs in a Peruvian cohort with up to three years' longitudinal follow-up using a multiplex platform and compared results to data from cohorts in Thailand and Brazil. Linear regression models were used to characterize the association between antibody responses and age, the number of detected blood-stage infections during follow-up, and time since previous infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the previous 9 months.Principal findingsAntibody titers were associated with age, the number of blood-stage infections, and time since previous P. vivax infection in all three study sites. The association between antibody titers and time since previous P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the higher transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance for classifying recent exposure in all sites, with area under the ROC curve (AUC) = 0.83 in Thailand, AUC = 0.79 in Brazil, and AUC = 0.68 in Peru.ConclusionsIn low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In higher transmission settings, the accuracy of this approach diminishes substantially. We recommend using P. vivax SEMs in low transmission settings pursuing malaria elimination, but they are likely to be less effective in high transmission settings focused on malaria control.
| S-EPMC7909627 | biostudies-literature
Project description:Thailand is aiming for malaria elimination by the year 2030. However, the high proportion of asymptomatic infections and the presence of the hidden hypnozoite stage of Plasmodium vivax are impeding these efforts. We hypothesized that a validated surveillance tool utilizing serological markers of recent exposure to P. vivax infection could help to identify areas of ongoing transmission. The objective of this exploratory study was to assess the ability of P. vivax serological exposure markers to detect residual transmission "hot-spots" in Western Thailand. Total IgG levels were measured against a panel of 23 candidate P. vivax serological exposure markers using a multiplexed bead-based assay. A total of 4,255 plasma samples from a cross-sectional survey conducted in 2012 of endemic areas in the Kanchanaburi and Ratchaburi provinces were assayed. We compared IgG levels with multiple epidemiological factors that are associated with an increased risk of P. vivax infection in Thailand, including age, gender, and spatial location, as well as Plasmodium infection status itself. IgG levels to all proteins were significantly higher in the presence of a P. vivax infection (n = 144) (T-test, p < 0.0001). Overall seropositivity rates varied from 2.5% (PVX_097625, merozoite surface protein 8) to 16.8% (PVX_082670, merozoite surface protein 7), with 43% of individuals seropositive to at least 1 protein. Higher IgG levels were associated with older age (>18 years, p < 0.05) and males (17/23 proteins, p < 0.05), supporting the paradigm that men have a higher risk of infection than females in this setting. We used a Random Forests algorithm to predict which individuals had exposure to P. vivax parasites in the last 9-months, based on their IgG antibody levels to a panel of eight previously validated P. vivax proteins. Spatial clustering was observed at the village and regional level, with a moderate correlation between PCR prevalence and sero-prevalence as predicted by the algorithm. Our data provides proof-of-concept for application of such surrogate markers as evidence of recent exposure in low transmission areas. These data can be used to better identify geographical areas with asymptomatic infection burdens that can be targeted in elimination campaigns.
| S-EPMC8279756 | biostudies-literature
Project description:BACKGROUNDSerological tools for the accurate detection of recent malaria exposure are needed to guide and monitor malaria control efforts. IgG responses against Plasmodium vivax and P. falciparum merozoite surface protein-10 (MSP10) were measured as a potential way to identify recent malaria exposure in the Peruvian Amazon.METHODSA field-based study included 470 participants in a longitudinal cohort who completed a comprehensive evaluation: light microscopy and PCR on enrollment, at least 1 monthly follow-up by light microscopy, a second PCR, and serum and dried blood spots for serological analysis at the end of the follow-up. IgG titers against novel mammalian cell-produced recombinant PvMSP10 and PfMSP10 were determined by ELISA.RESULTSDuring the follow-up period, 205 participants were infected, including 171 with P. vivax, 26 with P. falciparum, 6 with infections by both species but at different times, and 2 with mixed infections. Exposure to P. vivax was more accurately identified when serological responses to PvMSP10 were obtained from serum (sensitivity, 58.1%; specificity, 81.8%; AUC: 0.76) than from dried blood spots (sensitivity, 35.2; specificity, 83.5%; AUC: 0.64) (PAUC < 0.001). Sensitivity was highest (serum, 82.9%; dried blood spot, 45.7%) with confirmed P. vivax infections occurring 7-30 days before sample collection; sensitivity decreased significantly in relation to time since last documented infection. PvMSP10 serological data did not show evidence of interspecies cross-reactivity. Anti-PfMSP10 responses poorly discriminated between P. falciparum-exposed and nonexposed individuals (AUC = 0.59; P > 0.05).CONCLUSIONAnti-PvMSP10 IgG indicates recent exposure to P. vivax at the population level in the Amazon region. Serum, not dried blood spots, should be used for such serological tests.FUNDINGCooperative agreement U19AI089681 from the United States Public Health Service, NIH/National Institute of Allergy and Infectious Diseases, as the Amazonian International Center of Excellence in Malaria Research.
| S-EPMC7030819 | biostudies-literature
Project description:Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P. knowlesi, which also infects humans. P. vivax and P. knowlesi are co-endemic across much of South East Asia, making it important to design serological markers that minimize cross-reactivity in this region. To determine the degree of IgG cross-reactivity against a panel of P. vivax serological markers, we assayed samples from human patients with P. knowlesi malaria. IgG antibody reactivity is high against P. vivax proteins with high sequence identity with their P. knowlesi ortholog. IgG reactivity peaks at 7 days post-P. knowlesi infection and is short-lived, with minimal responses 1 year post-infection. We designed a panel of eight P. vivax proteins with low levels of cross-reactivity with P. knowlesi. This panel can accurately classify recent P. vivax infections while reducing misclassification of recent P. knowlesi infections.
| S-EPMC9245056 | biostudies-literature
Project description:The COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Serological testing for SARS-CoV-2-specific antibodies plays an important role in understanding and controlling the pandemic, notably through epidemiological surveillance. Well-validated and highly specific SARS-CoV-2 serological assays are urgently needed. We describe here the analytical and clinical performance of Vidas SARS-CoV-2 IgM and Vidas SARS-CoV-2 IgG, two CE-marked, emergency use authorization (EUA)-authorized, automated, qualitative assays for the detection of SARS-CoV-2-specific IgM and IgG, respectively. Both assays showed high within-run and within-laboratory precision (coefficients of variation < 11.0%) and very low cross-reactivity toward sera of patients with a past common coronavirus or respiratory virus infection. Clinical specificity determined on up to 989 prepandemic healthy donors was ≥99% with a narrow 95% confidence interval for both IgM and IgG assays. Clinical sensitivity was determined on up to 232 samples from 130 reverse transcriptase PCR (RT-PCR)-confirmed SARS-CoV-2 patients. The positive percent agreement (PPA) with SARS-CoV-2 PCR reached 100% at ≥16 days (Vidas SARS-CoV-2 IgM) and ≥32 days (Vidas SARS-CoV-2 IgG) of symptom onset. Combined IgM/IgG test results improved the PPA compared to each test alone. SARS-CoV-2 IgG seroconversion followed closely that of SARS-CoV-2 IgM and remained stable over time, while SARS-CoV-2 IgM levels rapidly declined. Interestingly, SARS-CoV-2-specific IgM and IgG responses were significantly higher in COVID-19 hospitalized versus nonhospitalized patients. Altogether, the Vidas SARS-CoV-2 IgM and IgG assays are highly specific and sensitive serological tests suitable for the reliable detection of past acute SARS-CoV-2 infections.
| S-EPMC8092742 | biostudies-literature
Project description:Plasmodium vivax causes the most geographically widespread human malaria, accounting annually for 70-80 million clinical cases throughout the tropical and subtropical regions of the world's continents. We have analyzed the DNA sequences of the Csp (circumsporozoite protein) gene in 24 geographically representative strains of P. vivax and 2 of P. simium, which parasitizes several species of New World monkeys. The Csp sequences are of two types, VK210 and VK247, which differ by three diagnostic amino acid replacements, one in each of the 5' and 3' terminal regions [5' nonrepeat (NR) and 3' NR] of the gene and in an insertion sequence that precedes the 3' NR region. The central region of the gene consists of approximately 38 repetitive "motifs," which are alternatively four and five amino acids long, which also are diagnostically different between the VK210 and VK247 types. There are very few synonymous substitutions within and between the two types of strains, which we hypothesize reflects that the worldwide spread of P. vivax is very recent. The two P. simium Csp sequences belong one to each of the two VK types and are genetically indistinguishable from the corresponding P. vivax strains, suggesting that at least two host transfers have occurred between humans and New World monkeys. We exclude as unlikely the possibility that the two types of sequences could have independently arisen in humans and platyrrhines by natural selection. There are reasons favoring each of the two possible directions of host transfer between humans and monkeys.
| S-EPMC1266129 | biostudies-literature
Project description:Dengue virus (DENV) and Zika virus (ZIKV) belong to the flavivirus genus and are antigenically closely related. They also share the same mosquito vector and can cause similar symptoms upon infection. However, DENV and ZIKV infections lead to different clinical sequelae and treatments; therefore, clinicians need rapid and accurate diagnostics capable of distinguishing between the two diseases. METHODS:We employed the immuno-magnetic assay technology on a microfluidic cartridge (ViroTrack Sero Zika IgG/IgM) for diagnosis of ZIKV infection based on the aggregation of magnetic nanoparticles. We carried out three serological studies including samples from the Dominican Republic, USA, and Nicaragua, aimed at detecting ZIKV-specific IgG and IgM using the ViroTrack Sero Zika IgG/IgM test. RESULTS:The seroconversion results were comparable with ZIKV IgG and IgM reactivity measured by the commercial ZIKV ELISA kit. The sensitivity and specificity for both ZIKV IgG and IgM tested by the ViroTrack Sero Zika IgG/IgM was approximately 98% and 93%, respectively. CONCLUSION:Serological detection of ZIKV infection by the new ViroTrack Sero Zika IgG/IgM test shows promising performance and limited cross-reactivity with DENV.
| S-EPMC7345115 | biostudies-literature
Project description: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.
| S-EPMC4966634 | biostudies-literature
Project description:Background: Malaria is a public health problem in parts of Thailand, where Plasmodium falciparum and Plasmodium vivax are the main causes of infection. In the northwestern border province of Tak parasite prevalence is now estimated to be less than 1% by microscopy. Nonetheless, microscopy is insensitive at low-level parasitaemia. The objective of this study was to assess the current epidemiology of falciparum and vivax malaria in Tak using molecular methods to detect exposure to and infection with parasites; in particular, the prevalence of asymptomatic infections and infections with submicroscopic parasite levels. Methods: Three-hundred microlitres of whole blood from finger-prick were collected into capillary tubes from residents of a sentinel village and from patients at a malaria clinic. Pelleted cellular fractions were screened by quantitative PCR to determine parasite prevalence, while plasma was probed on a protein microarray displaying hundreds of P. falciparum and P. vivax proteins to obtain antibody response profiles in those individuals. Results: Of 219 samples from the village, qPCR detected 25 (11.4%) Plasmodium sp. infections, of which 92% were asymptomatic and 100% were submicroscopic. Of 61 samples from the clinic patients, 27 (44.3%) were positive by qPCR, of which 25.9% had submicroscopic parasite levels. Cryptic mixed infections, misdiagnosed as single-species infections by microscopy, were found in 7 (25.9%) malaria patients. All sample donors, parasitaemic and non-parasitaemic alike, had serological evidence of parasite exposure, with 100% seropositivity to at least 54 antigens. Antigens significantly associated with asymptomatic infections were P. falciparum MSP2, DnaJ protein, putative E1E2 ATPase, and three others.
2014-06-22 | GSE55265 | GEO
Project description:Malaria is a public health problem in parts of Thailand, where Plasmodium falciparum and Plasmodium vivax are the main causes of infection. In the northwestern border province of Tak parasite prevalence is now estimated to be less than 1% by microscopy. Nonetheless, microscopy is insensitive at low-level parasitaemia. The objective of this study was to assess the current epidemiology of falciparum and vivax malaria in Tak using molecular methods to detect exposure to and infection with parasites; in particular, the prevalence of asymptomatic infections and infections with submicroscopic parasite levels.Three-hundred microlitres of whole blood from finger-prick were collected into capillary tubes from residents of a sentinel village and from patients at a malaria clinic. Pelleted cellular fractions were screened by quantitative PCR to determine parasite prevalence, while plasma was probed on a protein microarray displaying hundreds of P. falciparum and P. vivax proteins to obtain antibody response profiles in those individuals.Of 219 samples from the village, qPCR detected 25 (11.4%) Plasmodium sp. infections, of which 92% were asymptomatic and 100% were submicroscopic. Of 61 samples from the clinic patients, 27 (44.3%) were positive by qPCR, of which 25.9% had submicroscopic parasite levels. Cryptic mixed infections, misdiagnosed as single-species infections by microscopy, were found in 7 (25.9%) malaria patients. All sample donors, parasitaemic and non-parasitaemic alike, had serological evidence of parasite exposure, with 100% seropositivity to at least 54 antigens. Antigens significantly associated with asymptomatic infections were P. falciparum MSP2, DnaJ protein, putative E1E2 ATPase, and three others.These findings suggest that parasite prevalence is higher than currently estimated by local authorities based on the standard light microscopy. As transmission levels drop in Thailand, it may be necessary to employ higher throughput and sensitivity methods for parasite detection in the phase of malaria elimination.
| S-EPMC4342942 | biostudies-literature