Browsing by Author "Odhiambo, Eliud O."

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    Antibody correlates of risk of clinical malaria in an area of low and unstable malaria transmission in western Kenya
    (Springer Nature, 2025-03-04) Odhiambo, Eliud O.; Mellencamp, Kagan A.; Ondigo, Bartholomew N.; Hamre, Karen E. S.; Beeson, James G.; Opi, D. Herbert; Narum, David L.; Ayodo, George; John, Chandy C.; Microbiology and Immunology, School of Medicine
    Background: Defining antibody correlates of protection against clinical malaria in areas of low and unstable transmission is challenging because of limited malaria cases in these areas. Additionally, clinical malaria affects both adults and children in areas of low and unstable transmission, but it is unclear whether antibody correlates of protection against malaria differ with age. Methods: Blood samples were obtained from 5753 individuals in Kenyan highland area with low and seasonal malaria transmission in 2007 and recorded episodes of clinical malaria in this population from 2007 to 2017. Using a nested case-control study design, participants who developed clinical malaria (cases) were matched by age and village to those who did not (controls). Immunoglobulin (Ig)G, IgG1, IgG3, IgA and IgM responses to 16 Plasmodium falciparum antigens were compared in individuals < 5 years old (80 cases vs. 240 controls), 5-14 years old (103 cases vs. 309 controls) and ≥ 15 years old (118 cases vs. 354 controls). Antibody level was correlated with risk of clinical malaria, adjusted for malaria exposure markers. Results: In all age groups, most antibodies were not associated with risk of clinical malaria. In children < 5 years, higher levels of IgG to GLURP-R2 and MSP-2, IgG1 to GLURP-R2, and IgG3 to MSP-2 were associated with reduced risk of clinical malaria, while higher IgG3 levels to CSP were associated with increased risk of clinical malaria. In children 5-14 years and individuals ≥ 15 years, higher antibody levels to multiple P. falciparum antigens were associated with an increased risk of clinical malaria, and none were associated with decreased risk of clinical malaria. Conclusions: Antibody correlates of protection against clinical malaria were observed only in children < 5 years old in this area of low and unstable malaria transmission. In older children and adults in this area, some antibody responses correlated with increased risk of clinical malaria. Future studies in low malaria transmission areas should evaluate the comparative contributions of cellular and humoral immunity to protection from clinical malaria in young children versus older children and adults.
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    HIV infection drives IgM and IgG3 subclass bias in Plasmodium falciparum-specific and total immunoglobulin concentration in Western Kenya
    (BioMed Central, 2019-08-30) Odhiambo, Eliud O.; Datta, Dibyadyuti; Guyah, Bernard; Ayodo, George; Ondigo, Bartholomew N.; Abong’o, Benard O.; John, Chandy C.; Frosch, Anne E. P.; Pediatrics, School of Medicine
    BACKGROUND: HIV infection is associated with more frequent and severe episodes of malaria and may be the result of altered malaria-specific B cell responses. However, it is poorly understood how HIV and the associated lymphopenia and immune activation affect malaria-specific antibody responses. METHODS: HIV infected and uninfected adults were recruited from Bondo subcounty hospital in Western Kenya at the time of HIV testing (antiretroviral and co-trimoxazole prophylaxis naïve). Total and Plasmodium falciparum apical membrane antigen-1 (AMA1) and glutamate rich protein-R0 (GLURP-R0) specific IgM, IgG and IgG subclass concentrations was measured in 129 and 52 of recruited HIV-infected and uninfected individuals, respectively. In addition, HIV-1 viral load (VL), CD4+ T cell count, and C-reactive protein (CRP) concentration was quantified in study participants. Antibody levels were compared based on HIV status and the associations of antibody concentration with HIV-1 VL, CD4+ count, and CRP levels was measured using Spearman correlation testing. RESULTS: Among study participants, concentrations of IgM, IgG1 and IgG3 antibodies to AMA1 and GLURP-R0 were higher in HIV infected individuals compared to uninfected individuals (all p < 0.001). The IgG3 to IgG1 ratio to both AMA1 and GLURP-R0 was also significantly higher in HIV-infected individuals (p = 0.02). In HIV-infected participants, HIV-1 VL and CRP were weakly correlated with AMA1 and GLURP-R0 specific IgM and IgG1 concentrations and total (not antigen specific) IgM, IgG, IgG1, and IgG3 concentrations (all p < 0.05), suggesting that these changes are related in part to viral load and inflammation. CONCLUSIONS: Overall, HIV infection leads to a total and malaria antigen-specific immunoglobulin production bias towards higher levels of IgM, IgG1, and IgG3, and HIV-1 viraemia and systemic inflammation are weakly correlated with these changes. Further assessments of antibody affinity and function and correlation with risk of clinical malaria, will help to better define the effects of HIV infection on clinical and biological immunity to malaria.
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    Level and Duration of IgG and Neutralizing Antibodies to SARS-CoV-2 in Children with Symptomatic or Asymptomatic SARS-CoV-2 Infection
    (AAI, 2022-06-01) Khaitan, Alka; Datta, Dibyadyuti; Bond, Caitlin; Goings, Michael; Co, Katrina; Odhiambo, Eliud O.; Miller, Lucy; Zhang, Lin; Beasley, Stephanie; Poorbaugh, Josh; John, Chandy C.; Pediatrics, School of Medicine
    There are conflicting data about level and duration of Abs to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children after symptomatic or asymptomatic infection. In this human population, we enrolled adults and children in a prospective 6-mo study in the following categories: 1) symptomatic, SARS-CoV-2 PCR+ (SP+; children, n = 8; adults, n = 16), 2) symptomatic, PCR−, or untested (children, n = 27), 3) asymptomatic exposed (children, n = 13), and 4) asymptomatic, no known exposure (children, n = 19). Neutralizing Abs (nAbs) and IgG Abs to SARS-CoV-2 Ags and spike protein variants were measured by multiplex serological assay. All SP+ children developed nAb, whereas 81% of SP+ adults developed nAb. Decline in the presence of nAb over 6 mo was not significant in symptomatic children (100 to 87.5%; p = 0.32) in contrast to adults (81.3 to 50.0%; p = 0.03). Among children with nAb (n = 22), nAb titers and change in titers over 6 mo were similar in symptomatic and asymptomatic children. In children and adults, nAb levels postinfection were 10-fold lower than those reported after SARS-CoV-2 mRNA vaccination. Levels of IgG Abs in children to SARS-CoV-2 Ags and spike protein variants were similar to those in adults. IgG levels to primary Ags decreased over time in children and adults, but levels to three spike variants decreased only in children. Children with asymptomatic or symptomatic SARS-CoV-2 infection develop nAbs that remain present longer than in adults but wane in titer over time and broad IgG Abs that also wane in level over time. However, nAb levels were lower postinfection than those reported after immunization.
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    The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
    (BMC, 2021-09-17) Salgado, Christina; Ayodo, George; Macklin, Michael D.; Gould, Meetha P.; Nallandhighal, Srinivas; Odhiambo, Eliud O.; Obala, Andrew; Prudhomme O’Meara, Wendy; John, Chandy C.; Tran, Tuan M.; Medicine, School of Medicine
    Background: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. Methods: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. Results: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. Conclusions: This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.