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Abstract Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. PfAMA1’s polymorphic nature impacts vaccine-induced protection. To address polymorphism, three Diversity Covering (DiCo) protein sequences were designed and tested in a staggered phase Ia/b trial. A cohort of malaria-naive adults received PfAMA1-DiCo adjuvanted with Alhydrogel® or GLA-SE and a cohort of malaria-exposed adults received placebo or GLA-SE adjuvanted PfAMA1 DiCo at weeks 0, 4 and 26. IgG and GIA levels measured 4 weeks after the third vaccination are similar in malaria-naive volunteers and placebo-immunised malaria-exposed adults, and have a similar breadth. Vaccination of malaria-exposed adults results in significant antibody level increases to the DiCo variants, but not to naturally occurring PfAMA1 variants. Moreover, GIA levels do not increase following vaccination. Future research will need to focus on stronger adjuvants and/or adapted vaccination regimens, to induce potentially protective responses in the target group of the vaccine.

During the season of high malaria transmission, most children are infected by Plasmodium, which targets red blood cells (RBCs), affecting haematological parameters. To describe these variations, we examined the haematological profiles of two groups of children living in a malaria-endemic area. A cross-sectional survey was conducted at the peak of the malaria transmission season in a rural area of Burkina Faso. After informed consent and clinical examination, blood samples were obtained from the participants for malaria diagnosis and a full blood count. Of the 414 children included in the analysis, 192 were not infected with Plasmodium, whereas 222 were asymptomatic carriers of Plasmodium infection. The mean age of the infected children was 41.8 months (range of 26.4-57.2) compared to 38.8 months (range of 22.4-55.2) for the control group (p = 0.06). The asymptomatic infected children tended to have a significantly lower mean haemoglobin level (10.8 g/dL vs. 10.4 g/dL; p < 0.001), mean lymphocyte count (4592/µL vs. 5141/µL; p = 0.004), mean platelet count (266 x 103/µL vs. 385 x 103/µL; p < 0.001) and mean RBC count (4.388 x 106/µL vs. 4.158 x 106/µL; p < 0.001) and a higher mean monocyte count (1403/µL vs. 1192/µL; p < 0.001) compared to the control group. Special attention should be applied when interpreting haematological parameters and evaluating immune responses in asymptomatic infected children living in malaria-endemic areas and enrolled in vaccine trials.

Abstract Background In the current context of tailoring interventions to maximize impact, it is important that current data of clinical epidemiology guide public health programmes and health workers in the management of severe disease. This study aimed at describing the burden of severe malaria at hospital level in two areas with distinct malaria transmission intensity. Methods A hospital-based surveillance was established in two regional hospitals located in two areas exposed to different malaria transmission. Data on paediatric severe malaria admissions were recorded using standardized methods from August 2017 to August 2018 with an interruption during the dry season from April to June 2018. Results In total, 921 children with severe malaria cases were enrolled in the study. The mean age was 33.9 (± 1.3) and 36.8 (± 1.6) months in lower malaria transmission (LMT) and higher malaria transmission (HMT) areas (p = 0.15), respectively. The geometric mean of asexual P. falciparum density was significantly higher in the LMT area compared to the HMT area: 22,861 trophozoites/µL (95% CI 17,009.2–30,726.8) vs 11,291.9 trophozoites/µL (95% CI 8577.9–14,864.5). Among enrolled cases, coma was present in 70 (9.2%) participants. 196 patients (21.8%) presented with two or more convulsions episodes prior to admission. Severe anaemia was present in 448 children (49.2%). Other clinical features recorded included 184 (19.9%) cases of lethargy, 99 (10.7%) children with incoercible vomiting, 80 (8.9%) patients with haemoglobinuria, 43 (4.8%) children with severe hypoglycaemia, 37 (4.0%) cases where child was unable to drink/suck, 11 (1.2%) cases of patients with circulatory collapse/shock, and 8 cases (0.9%) of abnormal bleeding (epistaxis). The adjusted odds of presenting with coma, respiratory distress, haemoglobinuria, circulatory collapse/shock and hypoglycaemia were significantly higher (respectively 6.5 (95%CI 3.4–12.1); 1.8 (95%CI 1.0–3.2); 2.7 (95%CI 1.6–4.3); 5.9 (95%CI 1.3–27.9); 1.9 (95%CI 1.0–3.6)) in children living in the HMT area compared to those residing in the LMT area. Overall, forty-four children died during hospitalization (case fatality rate 5.0%) with the highest fatalities in children admitted with respiratory distress (26.0%) and those with hypoglycaemia (25.0%). Conclusion The study showed that children in the HMT area have a higher risk of presenting with coma, shock/dehydration, haemoglobinuria, hypoglycaemia, and respiratory distress. Case-fatality rate is higher among patients with respiratory distress or hypoglycaemia. Hospital surveillance provides a reliable and sustainable means to monitor the clinical presentation of severe malaria and tailor the training needs and resources allocation for case management.