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Objective To report the prevalence of polyparasitism during pregnancy in the Lambarene region of Gabon and its association with newborn birth weight. Method Pregnant women in their third trimester were recruited in a prospective study between November 2011 and March 2015. Parasite infection status was assessed microscopically in stool, urine and blood samples. Maternal demographic and obstetrical characteristics and newborns anthropometric data were collected. Multivariable logistic regression was used to assess the association between low birth weight and polyparasitism. Results 678 of 927 pregnant women were included for analysis with mean age (SD) of 25 (6.8) years. The analysis showed that 69% (468/678) were infected with at least one parasite (Plasmodium spp., Schistosoma spp., soil-transmitted helminths, filarial infections). This comprised of 38% with monoparasitism and 31% polyparasitism. The proportion of newborn babies with a weight below 2500 g (LBW) in our study was 21% (142/678). Compared to pregnant women without infection, women with monoparasitic infection had adjusted Odds Ratio confidence interval 95% CI (aOR [95%CI]) of 1.6 [0.95-2.73], those with two parasites had aOR 95%CI of 2.63 [1.51-4.62], and those with more than two parasites had aOR of 5.08 [2.5-10.38] for delivering a newborn with low birth weight. Conclusion In Lambarene, an endemic area for multiple parasite infections, there is a high prevalence of polyparasitism in pregnant women. Polyparasitism is associated with low birth weight. Therefore, there is an urgent need for active screening and treatment of parasite infections in pregnant women to assess the potential public health benefit of such interventions.

Gabon carries a high burden of both tuberculosis (TB) and smoking. This study examines the disease characteristics of smoking pulmonary TB patients in Lambaréné. We interviewed adult pulmonary TB patients in Lambaréné, between March 2016 and April 2019. Clinical and biological patient characteristics were collected. Bivariate and logistic regression analyses were performed to assess factors associated with smoking. The mean age of patients included was 31 years (±13). The proportion of smokers in our study was 30% (89/295). Smoking was significantly associated with patient-related diagnostic delay (adjusted odds ratio [AOR] = 8.18; 95% CI = 3.67-19.56), a higher number of pulmonary TB signs and symptoms (AOR = 2.74; 95% CI = 1.18-6.73), and a higher sputum mycobacterial load (AOR = 3.18; 95% CI = 1.33-8.11). The prevalence of smoking among TB patients is high, and leading to aggravated disease as compared with controls. Our study findings suggest that smoking patients should be regularly screened for TB, to reduce diagnostic delay and TB transmission within community. Smoking cessation activities should be included in the national TB control program in Gabon.

Schistosomiasis is a parasitic infection highly prevalent in Central Africa where it is co-endemic with many other parasitic infections, including soil-transmitted helminths (STHs). For its optimal control, there is a need of descriptive epidemiological data for each endemic region. The objective of the present study was to determine the epidemiological situation around schistosomiasis in Lambaréné, Gabon. A cross-sectional study was conducted among schoolchildren. One urine sample per day was collected on three consecutive days for the diagnosis of schistosomiasis using a urine filtration technique. One stool sample was collected for the detection of Schistosoma spp. and STH spp. eggs using the Kato-Katz technique, and for larvae, using the coproculture technique. A total of 614 schoolchildren were included in the analysis. The overall prevalence of schistosomiasis and STH infections was 26% (159/614) and 15% (70/473), respectively. Human-freshwater contact was the main risk factor for schistosomiasis in the area (relative risk (RR) = 2.96 [2.20-4.00], P < 0.001). Hematuria (RR = 5.53 [4.30-7.10], P < 0.001) and proteinuria (RR = 2.12 [1.63-2.75], P < 0.001) as well as infection with Trichuris trichiura (RR = 1.86 [1.33-2.61], P = 0.002) and Ascaris lumbricoides (RR = 1.96 [1.19-3.21], P = 0.039) were associated with an increased risk of schistosomiasis. Trichuris trichiura was the highest prevalent STH species in the area. Our study reports a moderate prevalence for schistosomiasis with human-water contact as the main risk factor, whereas the prevalence of STH infections appears to be low. Our results stress the need for the implementation of WHO recommendations for schistosomiasis control.

The objective of this pilot malacological survey was to identify the snail intermediate hosts for Schistosoma haematobium in endemic rural and semi-urban areas of Gabon. Snails were collected, morphologically identified, and tested for infection by cercarial shedding. Released cercariae were morphologically identified using low-power light microscopy. A total of six species of snails were collected throughout the study area, with Bulinus truncatus, B. forskalii, and Potadoma spp. being the most predominant species collected. Only the Bulinus species were tested for infection by cercarial shedding, of which only B. truncatus shed cercariae. Some B. truncatus shed mammalian schistosome cercariae, while others shed Gymnocephalus cercariae. Our results indicate that B. truncatus appears to be a potential intermediate host of schistosomiasis in Gabon, where cases of S. haematobium, S. guineensis, and S. intercalatum infection are reported. However, it will be important to further understand the species diversity and transmission dynamics of schistosomes.

Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30μg (n = 8) or 100μg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4+ T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4+ T cells were CD161+ memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1. In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4+ T cell responses that correlate with specific antibody levels. As these CD4+ T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity., Author summary Two hookworm vaccine candidate (Na-GST-1 and Na-APR-1) have been tested in Gabonese and found to be safe and to induce antibody response. We aimed to study the cellular immune responses among vaccinated and unvaccinated volunteers. We found that Na-GST-1 induced CD4+ T cell responses (IL-2, TNF) among the vaccinated volunteers that received the high vaccine dose (100 ug). Furthermore Na-GST-1 specific memory T cells were found to express the inhibitory molecule CTLA-4. These responses was not observed in those who received the low dose of the Na-GST-1 vaccine, or those who received Na-APR-1 or HBV. By blocking CTLA-4, we observed an increase in TNF production. Our data suggest that an intervention involving blockage of the CTLA-4 molecule in the vaccinated could be beneficial in endemic settings where vaccine responses have been shown to be lower compared to non-endemic settings.

Background Control of schistosomiasis remains a priority in endemic areas. Local epidemiological data are necessary for a tailored control programme, including data on population behaviour in relation to the disease. The objective of this study was to assess schistosomiasis-related knowledge, attitudes and practices in the general population of Lambaréné, a small city in Gabon, in order to optimise the design and implementation of a local control programme that is tailored to need. Methods The study was cross-sectional in nature. Eligible adults and children living in the study area who volunteered (with informed consent) to participate in the study were interviewed using standardised questionnaires, one of which was a simplified version of the primary questionnaire for participants aged 6–13 years. Data on the participants’ knowledge, attitudes and practices that enhance the risk for contracting schistosomiasis were collected. Results A total of 602 participants were included. The mean (± standard deviation) age was 21.2 (± 15.0) years, the female:male gender ratio was 1.6 and 289 (48%) participants completed the simplified version the questionnaire. Of the 602 participants, 554 (92%) reported past or current contact with freshwater, 218 (36%) reported a history of a diagnosis of schistosomiasis and 193 (32%) reported past intake of praziquantel medication. The overall levels of knowledge and adequate attitudes toward schistosomiasis among young adults and adults were 68 and 73%, respectively. The proportion of participants pursuing risk-enhancing practices (REP) was 60% among the whole study population. Location was significantly associated with differences in knowledge and REP levels. A history of confirmed schistosomiasis and larger family size were significantly associated with an increase in good knowledge and REP levels. However, the indication of freshwater-associated activities was only associated with a significant increase in the REP level. Conclusions The results of this survey reveal a high level of population exposure to schistosomiasis, which is in line with known prevalence of schistosomiasis in Lambaréné and its surroundings. The local population has a reasonable level of knowledge of and adequate attitudes toward schistosomiasis but the level of REP is high, particularly in areas where piped water is absent. In terms of interventions, improving hygiene should have the highest priority, but in a context where provision of safe water is difficult to achieve, the effectiveness of praziquantel treatment and the education of at-risk populations on the need for protective behaviours should be a prominent feature of any local control programme. Graphical abstract

Background Helminths can modulate the host immune response to Plasmodium falciparum and can therefore affect the risk of clinical malaria. We assessed here the effect of helminth infections on both the immunogenicity and efficacy of the GMZ2 malaria vaccine candidate, a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of P. falciparum. Controlled human malaria infection (CHMI) was used to assess the efficacy of the vaccine. Methodology In a randomized, double-blind Phase I clinical trial, fifty, healthy, lifelong malaria-exposed adult volunteers received three doses of GMZ2 adjuvanted with either Cationic Adjuvant Formulation (CAF) 01 or Alhydrogel, or a control vaccine (Rabies) on days (D) 0, D28 and D56, followed by direct venous inoculation (DVI) of 3,200 P. falciparum sporozoites (PfSPZ Challenge) approximately 13 weeks after last vaccination to assess vaccine efficacy. Participants were followed-up on a daily basis with clinical examinations and thick blood smears to monitor P. falciparum parasitemia for 35 days. Malaria was defined as the presence of P. falciparum parasites in the blood associated with at least one symptom that can be associated to malaria over 35 days following DVI of PfSPZ Challenge. Soil-transmitted helminth (STH) infection was assessed by microscopy and by polymerase chain reaction (PCR) on stool, and Schistosoma infection was assessed by microscopy on urine. Participants were considered as infected if positive for any helminth either by PCR and/or microscopy at D0 and/or at D84 (Helm+) and were classified as mono-infection or co-infection. Total vaccine-specific IgG concentrations assessed on D84 were analysed as immunogenicity outcome. Main findings The helminth in mono-infection, particularly Schistosoma haematobium and STH were significantly associated with earlier malaria episodes following CHMI, while no association was found in case of coinfection. In further analyses, the anti-GMZ2 IgG concentration on D84 was significantly higher in the S. haematobium-infected and significantly lower in the Strongyloides stercoralis-infected groups, compared to helminth-negative volunteers. Interesting, in the absence of helminth infection, a high anti-GMZ2 IgG concentration on D84 was significantly associated with protection against malaria. Conclusions Our results suggest that helminth infection may reduce naturally acquired and vaccine-induced protection against malaria. Vaccine-specific antibody concentrations on D84 may be associated with protection in participants with no helminth infection. These results suggest that helminth infection affect malaria vaccine immunogenicity and efficacy in helminth endemic countries., Author summary Helminths, mainly because of their immune regulatory effects, are able to impact the response induced by vaccines. In the context of clinical trial designs that measure accrual of natural infections during follow up or outcome of controlled human malaria infection (CHMI), their effect on vaccine efficacy can be measured. Indeed, most of such clinical trials on malaria vaccine candidates conducted in Africa, especially where the prevalence of helminths is high, have shown a certain limit in their efficacy and immunogenicity, as compared to results observed in European and U.S volunteers. The present analysis assessed the effect of helminths on GMZ2, a malaria vaccine candidate. We found a high level of anti-GMZ2 antibodies among volunteers not infected with helminths and protected against CHMI, indicating efficacy of the candidate vaccine in this population. We found a species-dependent effect of helminths on the level of post-immunization GMZ2-specific IgG concentration, and an association of helminths with an early onset of malaria in CHMI. Our findings reveal that helminths are associated with immunogenicity and may decrease the protective effect of antibodies induced by vaccination. Helminth infection status shall be determined when measuring the immunogenicity and efficacy of malaria vaccine candidates in helminth endemic countries.

In utero exposure to environmental factors can modify the development of allergies later in life whereby the mechanisms of the feto-maternal crosstalk still remain largely unknown. Murine studies revealed that inflammatory maternal signals elicited by chronic helminth infection within the placenta imprint a distinct gene expression profile related to the Vitamin-D-receptor (VDR)-inflammation-axis. We thus investigated whether pro- or anti- inflammatory immune responses as well as VDR and related gene expression within the placenta differ between women from helminth-endemic and non-endemic areas. A prospective pilot study was conducted in Munich, Germany (helminth non-endemic) and Lambaréné, Gabon (helminth-endemic). At delivery, clinical information alongside placenta tissue samples and maternal and cord blood were obtained for further laboratory analysis. Schistosoma haematobium infection was detected in 13/54 (23%) Gabonese women. RT PCR revealed significantly lower gene expression of VDR, Cyp27b1, Foxp3 and IL10 in Gabonese compared to German placentae as well as significantly lower levels of plasma IgG4 in newborns resulting in a significantly higher IgE/IgG4 ratio. These findings demonstrate that exposure in utero to different environments alters placental gene expression and thus possibly plays a role in the development and modulation of the immune system of the offspring.

Additional file 1. Overview of study visits over time with respect to the study phase and details of sample collection, describes the study phases and procedures.

Background Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (AS–AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. Methods A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS–AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. Results Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86–100) and 95% (95% CI 84–99) for AL and AS–AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. Conclusion This study showed that AL and AS–AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True

Background Sub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon. Methods Eligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR). Results A total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%. Conclusions The prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment. Trial registration clinicaltrials.gov Identifier NCT 02769103. Registered 11 May 2016, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02769013

In utero exposure to environmental factors can modify the development of allergies later in life whereby the mechanisms of the feto-maternal crosstalk still remain largely unknown. Murine studies revealed that inflammatory maternal signals elicited by chronic helminth infection within the placenta imprint a distinct gene expression profile related to the Vitamin-D-receptor (VDR)-inflammation-axis. We thus investigated whether pro- or anti- inflammatory immune responses as well as VDR and related gene expression within the placenta differ between women from helminth-endemic and non-endemic areas. A prospective pilot study was conducted in Munich, Germany (helminth non-endemic) and Lambaréné, Gabon (helminth-endemic). At delivery, clinical information alongside placenta tissue samples and maternal and cord blood were obtained for further laboratory analysis. Schistosoma haematobium infection was detected in 13/54 (23%) Gabonese women. RT PCR revealed significantly lower gene expression of VDR, Cyp27b1, Foxp3 and IL10 in Gabonese compared to German placentae as well as significantly lower levels of plasma IgG4 in newborns resulting in a significantly higher IgE/IgG4 ratio. These findings demonstrate that exposure in utero to different environments alters placental gene expression and thus possibly plays a role in the development and modulation of the immune system of the offspring.

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.

Background Malaria burden remains high in the sub-Saharan region where helminths are prevalent and where children are often infected with both types of parasites. Although the effect of helminths on malaria infection is evident, the impact of these co-infections is not clearly elucidated yet and the scarce findings are conflicting. In this study, we investigated the effect of schistosomiasis, considering soil-transmitted helminths (STH), on prevalence and incidence of Plasmodium falciparum infection. Methodology This longitudinal survey was conducted in school-age children living in two rural communities in the vicinity of Lambaréné, Gabon. Thick blood smear light microscopy, urine filtration and the Kato-Katz technique were performed to detect malaria parasites, S. haematobium eggs and, STH eggs, respectively. P. falciparum carriage was assessed at inclusion, and incidence of malaria and time to the first malaria event were recorded in correlation with Schistosoma carriage status. Stratified multivariate analysis using generalized linear model was used to assess the risk of plasmodium infection considering interaction with STH, and survival analysis to assess time to malaria. Main findings The overall prevalence on subject enrolment was 30%, 23% and 9% for S. haematobium, P. falciparum infections and co-infection with both parasites, respectively. Our results showed that schistosomiasis in children tends to increase the risk of plasmodium infection but a combined effect with Trichuris trichiura or hookworm infection clearly increase the risk (aOR = 3.9 [95%CI: 1.7–9.2]). The incidence of malaria over time was 0.51[95%CI: 0.45–0.57] per person-year and was higher in the Schistosoma-infected group compared to the non-infected group (0.61 vs 0.43, p = 0.02), with a significant delay of time-to first-malaria event only in children aged from 6 to 10-years-old infected with Schistosoma haematobium. Conclusions Our results suggest that STH enhance the risk for P. falciparum infection in schistosomiasis-positive children, and when infected, that schistosomiasis enhances susceptibility to developing malaria in young children but not in older children., Author summary Despite the progress made in the last decade, malaria remains a serious public health issue in sub-Saharan region, where it overlaps with helminths infections. The interactions between both are manifold and complex, requiring further investigation. We report here that Trichuris trichiura or hookworm associated with schistosomiasis increase the risk of Plasmodium falciparum infection; whilst schistosomiasis is independently associated with a malaria increase in young children, but not in the older children. Our finding is an additional evidence that optimizing helminth control mainly in children contributes to overcoming malaria in areas endemic for both parasitic infections where children are those who bear the highest burden of these infections.

Pregnancy-associated malaria (PAM) is a severe form of the disease caused by sequestration of Plasmodium falciparum-infected red blood cells (iRBCs) in the developing placenta. Pathogenesis of PAM is partially based on immunopathology, with frequent monocyte infiltration into the placenta. Neutrophils are abundant blood cells that are essential for immune defence but may also cause inflammatory pathology. Their role in PAM remains unclear. We analysed neutrophil alterations in the context of PAM to better understand their contribution to disease development. Pregnant women exposed to Plasmodium falciparum had decreased numbers of circulating neutrophils. Placental-like BeWo cells stimulated with malaria parasites produced the neutrophil chemoattractant IL-8 and recruited neutrophils in a trans-well assay. Finally, immunostaining of a PAM placenta confirmed neutrophil accumulation in the intervillous space. Our data indicate neutrophils may play a role in placental malaria and should be more closely examined as an etiological agent in the pathophysiology of disease.

In many tropical areas schistosomiasis is a major health problem causing hepatosplenic, intestinal or urogenital complaints. Hepatosplenic schistosomiasis mansoni is also characterized by blood coagulation abnormalities. Liver pathology plays a role in the development of haemostatic changes and the parasitic infection may directly affect coagulation. However, these contributing factors cannot be studied separately in hepatosplenic schistosomiasis infections. This pilot study provides insight in haemostatic changes in urinary schistosomiasis by studying coagulation parameters in schistosomiasis haematobium-infected Gabonese schoolchildren. Selection on urinary schistosomiasis patients without hepatosplenic complaints allows for the investigation of the direct effects of the parasite on haemostasis. Levels of von Willebrand Factor (VWF) antigen, active VWF and osteoprotegerin were elevated, indicating inflammation-mediated endothelial activation. In contrast to hepatosplenic schistosomiasis, thrombin–antithrombin complex and D-dimer levels were not affected. Despite its small sample size, this study clearly indicates that Schistosoma haematobium directly alters the activation status of the endothelium, without initiation of coagulation.

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.

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.

In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.)