Geometric mean level of eosinophil, and ECP among hookworm positive (103) and negative participants (36).

ECP; Eosinophil cationic protein, Na; Necator americanus. Error bars are 95% confidence interval (CI).</p

Demographic and parasitological characteristics of the study population.

Demographic and parasitological characteristics of the study population.</p

Association between parasite infection status and ECP levels.

Association between parasite infection status and ECP levels.</p

Predicting hookworm infection with ECP level.

AUROC curve analysis using ECP levels as a classifier of hookworm infection status was used to predict hookworm infection. 95% Confidence Interval was computed with 2000 stratified bootstrap replicates. AUCROC; area under the receiver operating characteristic curve, ECP; eosinophil cationic protein, Na; hookworm.</p

STROBE statement.

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Adjusted associations between enteropathogen detection and symptoms of illness among children aged 6–59 months old in Greater Accra, Ghana.

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Correlation matrix between hemoglobin concentration, iron status biomarkers (SF and sTfR), and inflammatory biomarkers (CRP and AGP) among 262 children aged 6–59 months old in Greater Accra, Ghana.

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Table_1_GMZ2 Vaccine-Induced Antibody Responses, Naturally Acquired Immunity and the Incidence of Malaria in Burkinabe Children.docx

GMZ2 is a malaria vaccine candidate evaluated in a phase 2b multi-centre trial. Here we assessed antibody responses and the association of naturally acquired immunity with incidence of malaria in one of the trial sites, Banfora in Burkina Faso. The analysis included 453 (GMZ2 = 230, rabies = 223) children aged 12-60 months old. Children were followed-up for clinical malaria episodes for 12 months after final vaccine administration. Antibody levels against GMZ2 and eleven non-GMZ2 antigens were measured on days 0 and 84 (one month after final vaccine dose). Vaccine efficacy (VE) differed by age group (interaction, (12-35 months compared to 36-60 months), p = 0.0615). During the twelve months of follow-up, VE was 1% (95% confidence interval [CI] -17%, 17%) and 23% ([CI] 3%, 40%) in the 12 - 35 and 36 – 60 months old children, respectively. In the GMZ2 group, day 84 anti-GMZ2 IgG levels were associated with reduced incidence of febrile malaria during the follow up periods of 1-6 months (hazard ratio (HR) = 0.87, 95%CI = (0.77, 0.98)) and 7-12 months (HR = 0.84, 95%CI = (0.71, 0.98)) in the 36-60 months old but not in 12-35 months old children. Multivariate analysis involving day 84 IgG levels to eleven non-vaccine antigens, identified MSP3-K1 and GLURP-R2 to be associated with reduced incidence of malaria during the 12 months of follow up. The inclusion of these antigens might improve GMZ2 vaccine efficacy.</p

Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study

<div><p>The erythrocyte binding antigen region II (EBA-175 RII) is a <i>Plasmodium falciparum</i> ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth <i>in vitro</i>. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg) of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline). The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited <i>P</i>. <i>falciparum</i> growth <i>in vitro</i>, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended.</p><p>Trial registration</p><p>ClinicalTrials.gov. Identifier: <a href="https://clinicaltrials.gov/ct2/show/NCT01026246" target="_blank">NCT01026246</a></p></div

Adjusted associations of high and low relative gene target quantity and inflammation (CRP and AGP), iron deficiency (SF and sTfR), and anemia (Hb) among children aged 6–59 months old in Greater Accra, Ghana.

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