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GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. : Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. : A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). : GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.

BackgroundIn sub-Saharan Africa, Plasmodium spp. infection prevalence very often overlaps with helminth infections, particularly with schistosomiasis which is reported to be the second parasitic infection after malaria in terms of prevalence. Interaction between both infections has been reported earlier. Schistosomiasis is typically a chronic disease, whereas malaria occurs in episodes, particularly in children. In this study, we assessed the effect of Schistosoma haematobium infection on clinical malaria among children.MethodsA longitudinal study was conducted from June 2016 to February 2018. Volunteers without any known chronic condition were included. Thick blood smear (TBS) was performed monthly at participants’ homes. For any medical concern including malaria-like symptoms and visible haematuria, participants were invited to come to CERMEL for diagnosis and treatment. Light microscopy was performed to detect malaria parasites and Schistosoma eggs, using TBS and urine filtration technique, respectively. Over the study course, participants found to be infected were treated accordingly. Schistosomiasis status was determined at the end of the follow-up.ResultsAmong the 351 volunteers included in the study, schistosomiasis status was available for 260. Mean age was 12.3 year (SD 4.6) with a 0.96 women-to-men sex ratio. Of those, 112/260 (43.1%) [37.0%–49.3%] participants were positive for S. haematobium, and a total of 132 (51%) children developed 230 malaria attacks. Those with schistosomiasis had a 1.5:1 [1.1–2.0] risk to develop malaria compared to their uninfected counterparts. The mean number of malaria episodes per child over the study course was higher among children with schistosomiasis compared to those without (2.03 vs 1.57, p-value=0.015).ConclusionS. haematobium infection was associated with increased susceptibility to develop malaria (by increasing the risk to develop a malaria episode) and, consequently, a higher malaria incidence.

BackgroundSchistosomiasis is a highly prevalent parasitic infection in Central Africa, where co-endemicity with other parasitic infections is common, and schistosomiasis outcomes can be affected by those other infections. Therefore, proper schistosomiasis control needs epidemiological data accounting for co-infections, too. In this present study, our objective was to determine the epidemiological situation around schistosomiasis in Lambaréné.MethodsA cross-sectional study was conducted among school-aged children living in Lambaréné. Urine filtration exam was performed for the detection of Schistosoma eggs. Kato-Katz and stool culture (Coproculture and Harada-Mori) techniques were used for the detection of soil-transmitted helminths. Detection of Plasmodium spp. and blood microfilariae was performed applying light microscopy. Risk factors for schistosomiasis and factors associated with schistosomiasis were investigated; haematology parameters evaluated.ResultsA total of 614 school children with available schistosomiasis status were included in the analysis. Mean age was 10.9 (SD=2.7) years, with a 0.95 boy-to-girl sex ratio. The prevalence of schistosomiasis was 26%. No risk factors except human-water contact were associated with schistosomiasis. Only Trichuris trichiura co-infection was associated with an increased odd (aOR=2.3, p-value=0.048) to be infected with schistosomiasis. Full blood counts showed a decrease of haemoglobin level and increase of WBC and platelet levels among the schistosoma-infected children. Haematuria was found associated with schistosomiasis (aOR=14.5, p-valueConclusionThe prevalence of schistosomiasis is moderate in Lambaréné where human-water contact remains the main risk factor and praziquantel is available for treatment. Trichuriasis is associated with increased risk to be infected. Children with schistosomiasis exhibit a distinct full blood count profile and haematuria is found to be more suitable to predict infection. However, it is desirable to implement comprehensive approaches beyond chemotherapy for schistosomiasis control in this area as recommended by WHO.

BackgroundDiarrhoeal disease remains the second leading cause of death in children under five years, being associated with about 525,000 deaths every year. The most common pathogens worldwide are Shigella spp/EIEC, rotavirus, adenovirus 40/41, ST-ETEC and Cryptosporidium spp. Public health interventions rely on estimates of pathogen-specific burden for prioritisation. Sadly, comprehensive data on the aetiology of diarrhoea in children is lacking for Gabon. This study aimed to identify the spectrum of pathogens found in Lambaréné, Gabon and provide baseline data on their prevalence, needed for implementation of effective control measures.MethodsA cross-sectional study was conducted at Albert Schweitzer and Georges Rawiri Regional hospitals in Lambaréné from February 2017 to February 2018. A consecutive sample of children under 5 year old with diarrhoea or a history of diarrhoea within the previous three days were prospectively studied. A single stool sample was collected from each study participant and processed using commercial rapid immunoassays to detect antigens of rotavirus, adenovirus, and Cryptosporidium spp. Multiplex PCR was used for Cryptosporidium spp., Giardia lamblia and Cyclospora cayetanensis detection, and characterisation of E. coli strains.ResultsOut of 188 participants who provided stool samples, one or more pathogens could be detected in 34.6% of the cases. The most prevalent parasites were Giardia lamblia (14.9%), Cryptosporidium spp. (11.7%), and Cyclospora cayetanensis (2.7%). Enteric viruses also were identified in these children: 10.6% and 1.6% of rotavirus and adenovirus, respectively. Multiple pathogens were detected in 5.3% of samples.ConclusionThis analysis of the causes of diarrhoea in children under 5 years of age in our setting showed three main pathogens: Giardia lamblia, Cryptosporidium spp. and rotavirus. Our study confirms major agents of acute diarrhoeal diseases in children, highlights research needs (Cryptosporidium) and supports the introduction of new tools such as the implementation of the rotavirus vaccine in the national immunisation programme.

Contains fulltext : 171915.pdf (Publisher’s version ) (Open Access) Infections with helminths and Plasmodium spp. overlap in their geographical distribution. It has been postulated that helminth infections may influence malarial transmission by altering Plasmodium falciparum gametocytogenesis. This cross-sectional study assessed the effect of helminth infections on P. falciparum gametocyte carriage and on humoral immune responses to sexual stage antigens in Gabon. Schistosoma haematobium and filarial infections as well as P. falciparum asexual forms and gametocyte carriage were determined. The antibody responses measured were to sexual (Pfs230, Pfs48/45) and asexual P. falciparum antigens (AMA1, MSP1, and GLURP). A total of 287 subjects were included. The prevalence of microscopically detectable P. falciparum asexual parasites was higher in S. haematobium-infected subjects in comparison to their uninfected counterparts (47% versus 26%, P = 0.003), but this was not different when filarial infections were considered. Plasmodium falciparum gametocyte carriage was similar between Schistosoma- or filaria-infected and uninfected subjects. We observed a significant decrease of Pfs48/45 immunoglobulin G titer in S. haematobium-infected subjects (P = 0.037), whereas no difference was seen for Pfs230 antibody titer, nor for antibodies to AMA1, MSP1, or GLURP. Our findings suggest an effect of S. haematobium on antibody responses to some P. falciparum gametocyte antigens that may have consequences for transmission-blocking immunity.

Background Characterising the effect of natural acquired immunity and sickle cell anaemia on the pattern of Plasmodium falciparum parasitaemia may be useful to understand the pathophysiological mechanisms of protection against malaria. Controlled human malaria infection (CHMI) by direct venous inoculation of aseptic, purified, cryopreserved sporozoites (Pf-SPZ challenge) is a new tool which can be used to investigate the pathophysiology of malaria. Methods The study was performed in Lambarene, Gabon, one of seven African partners in the EDCTP-funded CHMI platform. Adults aged 18–35 from three groups NI: 5 non-immune (NI), 11 semi-immunes with haemoglobin AA (IA), and 9 semi-immunes with haemoglobin AS (IS) received 3,200 sporozoites after a curative treatment course with clindamycin. Capillary blood samples were taken daily up to Day 28 to determine parasitaemia by real-time quantitative polymerase chain reaction (RT-qPCR). Treatment was administered for a malaria episode or at Day 28, whichever came first. Results Parasitaemia was detected in 5 (100%) subjects in the NI group, 9 (82%) in the IA group and 7 (78%) in the IS group. All volunteers in the NI group showed similar patterns with parasitaemia starting around Day 8 and rising quickly. Patterns for parasitaemia in the immune groups (IA and IS) were highly heterogeneous. Although time points of initial parasitaemia and duration of parasitaemia varied, all semi-immunes managed to control parasitaemia for at least several days. There were no discernible differences in patterns between the IS and IA group, including the area under curve of parasitaemia over time. Conclusions No parasitaemia was detected in 20% of the semi-immunes, likely due to liver stage immunity. The highly variable patterns of parasitaemia did not allow us to discern immune mechanisms against blood stages. Haemoglobin AS had no visible effect on parasite dynamics at the low parasitaemia encountered.

Background Malaria remains the first cause of death in Africa. In endemic area, it overlaps with other infections including helminths infections. It has been shown that there are interactions between the two parasites infection. Lambarene is the endemic area for urogenital schistosomiasis, which co-exist with P. falciparum malaria. Therefore, we decide to assess for the first time the effect of schistosomiasis infection on malaria infection burden. Methods In order to assess the effect of S. haematobium on malaria infection burden, a cross-sectional study was conducted in school children aged 6–16 years old. One blood smear was performed and 3 urine samples were obtained to assess the presence of infections. Chi-square test and generalised linear model were used to compare the risk to be infected by P. falciparum parasite and Mann-Whitney-Wilcoxon test to compare the parasitaemia of P. falciparum . Demographic data was also collected. Results A total of 741 children were included. The overall prevalence was 20% and 31% for P. falciparum microscopic carriage and S. haematobium infection, respectively. Co-infection of both was found in 65 (9%) participants. S. haematobium and P. falciparum are highly prevalent in PK compared to Bindo and Makouke areas. At univariable analysis, schistosomiasis-infected subjects have an odd of 2.11 [1.46–3.07] to be infected by P. falciparum parasite compared to non-infected subjects. Locality was found to confound the association which remains significant after adjustment for age, gender and locality (aOR=1.69, [1.13–2.59]). The effect of S. haematobium on the P. falciparum parasitaemia outcome was also assessed. There is no effect of Schistosoma infection on malaria parasite density (p-value=0.92). Conclusions S. haematobium infection increases the risk of being infected with P. falciparum but doesn9t affect the parasitaemia density of P. falciparum malaria in our study population.