Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Leonard CM[original query] |
---|
Dynamics of IgG antibody response against Plasmodium antigens among Nigerian infants and young children
Leonard CM , Uhomoibhi P , Abubakar A , Ogunniyi A , Mba N , Greby SM , Okoye MI , Iriemenam NC , Ihekweazu C , Steinhardt L , Rogier E . Front Immunol 2023 14 1208822 BACKGROUND: Plasmodium falciparum malaria is a leading cause of child mortality in Nigeria. Neonates are born with maternal antibodies from placental transfer which may protect against malaria infection in the first months of life. The IgG dynamics of the transition from passively transferred antimalarial antibodies to actively acquired IgG from natural exposure have not been well elucidated. METHODS: Blood samples collected during a 2018 Nigeria nationwide HIV/AIDS household survey were available for 9,443 children under 5 years of age, with a subset of infants under 2 months of age having maternal samples available (n=41). Samples were assayed for the P. falciparum HRP2 antigen and anti-malarial IgG antibodies. LOESS regression examined the dynamics in IgG response in the first 5 years of life. Correlation with maternal IgG levels was assessed for mother/child pairs. RESULTS: Consistent decreases were observed in median IgG levels against all Plasmodium spp. antigen targets for the first months of life. At a population level, P. falciparum apical membrane antigen-1 (AMA1) and merozoite surface protein-1 19kD (PfMSP1) IgG decreased during the first 12 months of life before reaching a nadir, whereas IgGs to other targets only declined for the first 4 months of life. Seropositivity showed a similar decline with the lowest seropositivity against AMA1 and PfMSP1 at 10-12 months, though remaining above 50% during the first 2 years of life in higher transmission areas. No protective association was observed between IgG positivity and P. falciparum infection in infants. Maternal antibody levels showed a strong positive correlation with infant antibody levels for all P. falciparum antigens from birth to 2 months of age, but this correlation was lost by 6 months of age. DISCUSSION: Maternally transferred anti-malarial IgG antibodies rapidly decline during the first 6 months of life, with variations among specific antigens and malaria transmission intensity. From 3-23 months of age, there was a wide range in IgG levels for the blood-stage antigens indicating high individual variation in antibody production as children are infected with malaria. Non-falciparum species-specific antigens showed similar patterns in waning immunity and correlation with paired mother's IgG levels compared to P. falciparum antigens. |
Non-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018
Herman C , Leonard CM , Uhomoibhi P , Maire M , Moss D , Inyang U , Abubakar A , Ogunniyi A , Mba N , Greby SM , Okoye MI , Iriemenam NC , Maikore I , Steinhardt L , Rogier E . Nat Commun 2023 14 (1) 1360 Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples (n = 31,234) were collected from children aged 0-14 years during a 2018 nationwide HIV survey and assayed for Plasmodium antigenemia, Plasmodium DNA, and IgG against Plasmodium MSP1-19 antigens. Of all children, 6.6% were estimated to have Pm infection and 1.4% Po infection with no Pv infections detected. The highest household wealth quintile was strongly protective against infection with Pm (aOR: 0.11, 95% CI: 0.05-0.22) or Po (aOR= 0.01, 0.00-0.10). Overall Pm seroprevalence was 34.2% (95% CI: 33.3-35.2) with lower estimates for Po (12.1%, 11.6-12.5) and Pv (6.3%, 6.0-6.7). Pm seropositivity was detected throughout the country with several local government areas showing >50% seroprevalence. Serological and DNA indicators show widespread exposure of Nigerian children to Pm with lower rates to Po and Pv. |
Missed plasmodium ovale infections among symptomatic persons in Angola, Mozambique, and Ethiopia
Leonard CM , Hwang J , Assefa A , Zulliger R , Candrinho B , Dimbu PR , Saifodine A , Plucinski M , Rogier E . Open Forum Infect Dis 2022 9 (7) ofac261 The majority of symptomatic malaria in sub-Saharan Africa is caused by Plasmodium falciparum. Infection with Plasmodium ovale is often not recorded and not considered clinically relevant. Here, we describe 8 cases of P ovale infection from 3 African countries-all of which were misdiagnosed at the presenting health facility. |
Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015.
Leonard CM , Assefa A , McCaffery JN , Herman C , Plucinski M , Sime H , Mohammed H , Kebede A , Solomon H , Haile M , Murphy M , Hwang J , Rogier E . Malar J 2022 21 (1) 70 BACKGROUND: Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting. METHODS: The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual's RDT results. Dose-response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey. RESULTS: Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively). CONCLUSIONS: There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings. |
Missed Plasmodium falciparum and Plasmodium vivax Mixed Infections in Ethiopia Threaten Malaria Elimination.
Leonard CM , Mohammed H , Tadesse M , McCaffery JN , Nace D , Halsey ES , Girma S , Assefa A , Hwang J , Rogier E . Am J Trop Med Hyg 2021 106 (2) 667-670 Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia. This study investigated whether mixed infections were missed by microscopy from a 2017 therapeutic efficacy study at two health facilities in Ethiopia. All patients (N = 304) were initially classified as having single-species P. falciparum (n = 148 samples) or P. vivax infections (n = 156). Dried blood spots were tested for Plasmodium antigens by bead-based multiplex assay for pan-Plasmodium aldolase, pan-Plasmodium lactate dehydrogenase, P. vivax lactate dehydrogenase, and histidine-rich protein 2. Of 304 blood samples, 13 (4.3%) contained both P. falciparum and P. vivax antigens and were analyzed by polymerase chain reaction for species-specific DNA. Of these 13 samples, five were confirmed by polymerase chain reaction for P. falciparum/P. vivax co-infection. One sample, initially classified as P. vivax by microscopy, was found to only have Plasmodium ovale DNA. Plasmodium falciparum/P. vivax mixed infections can be missed by microscopy even in the context of a therapeutic efficacy study with multiple trained readers. |
Spatial distribution of Plasmodium falciparum and P. vivax in northern Ethiopia by microscopy, rapid diagnostic test, laboratory antibody and antigen data
Leonard CM , Assefa A , Sime H , Mohammed H , Kebede A , Solomon H , Drakeley C , Murphy M , Hwang J , Rogier E . J Infect Dis 2021 225 (5) 881-890 BACKGROUND: Determining malaria transmission within regions of low, heterogenous prevalence is difficult. A variety of malaria tests exist and range from identification of diagnostic infection to testing for prior exposure. This study describes concordance of multiple malaria tests using data from a 2015 household survey conducted in Ethiopia. METHODS: Blood samples (n= 2,279) from three regions in northern Ethiopia were assessed for Plasmodium falciparum and P. vivax by microscopy, rapid diagnostic test (RDT), multiplex antigen assay, and multiplex assay for IgG antibodies. Geospatial analysis was conducted with spatial scan statistics and kernel density estimation to identify hotspots of malaria by different test results. RESULTS: Prevalence of malaria infection was low (1.4% by RDT, 1.0% by microscopy, and 1.8% by laboratory antigen assay). For P. falciparum, overlapping spatial clusters for all tests and an additional five unique IgG clusters were identified. For P. vivax, clusters identified for bead antigen assay, microscopy, and IgG with partial overlap. CONCLUSIONS: Assessing the spatial distribution of malaria exposure using multiple metrics can improve the understanding of malaria transmission dynamics in a region. The relative abundance of antibody clusters indicates that in areas of low-transmission, IgG antibodies are a more useful marker to assess malaria exposure. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 06, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure