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Publications (260)
Background
Soil-transmitted helminths (STH) affect approximately 1.5 billion people globally. The current STH control strategy is annual or twice-annual preventive chemotherapy, typically school-based deworming targeting children and women of reproductive age. Mathematical modeling suggests that it may be possible to interrupt STH transmission thro...
Soil-transmitted helminths (STH) are one of the most prevalent enteric infections world-wide. To control STH-related morbidity, the World Health Organization recommends targeted deworming and improvements in water, sanitation and hygiene. Current surveillance strategies for STH focus on identifying and quantifying eggs in stool samples via microsco...
Background
One-fifth of the global population is infected with soil-transmitted helminths (STH). Mass drug administration (MDA) with deworming medication is widely implemented to control morbidity associated with STH infections. However, surveillance of human infection prevalence by collecting individual stool samples is time-consuming, costly, oft...
Poor birth outcomes in low- and middle income countries are associated with maternal vitamin D deficiency and chronic helminth infections. Here, we investigated whether maternal Schistosoma haematobium affects maternal or cord vitamin D status as well as birth outcomes. In a prospective cross-sectional study of pregnant women conducted in Lambaréné...
A Stakeholder engagement meeting on the implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda was held in Nairobi, Kenya, on 27 September 2023. Representatives from the respective National Malaria Control Programmes, the World Health Organization (WHO) Geneva, Africa Regional and Kenya offices, research...
One-fifth of the global population is infected with soil-transmitted helminths (STH). Mass drug administration (MDA) with deworming medication is widely implemented to control morbidity associated with STH infections. However, surveillance of human infection prevalence by collecting individual stool samples is time-consuming, costly, often stigmati...
Background
Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the Wo...
Background
The African continent is currently facing an epidemiological transition characterized by a shift from communicable to non-communicable diseases. Prominent amongst the latter are allergies and asthma. In that context, wheeze has multiple potential contributory factors that could include some of the endemic helminth infections, as well as...
The complement system is considered the first line of defense against pathogens. Hijacking complement regulators from blood is a common evasion tactic of pathogens to inhibit complement activation on their surfaces. Here, we report hijacking of the complement C4b-binding protein (C4bp), the regulator of the classical and lectin pathways of compleme...
Objectives
Current guidelines for the control of soil-transmitted helminths (STH) recommend deworming children and other high-risk groups, primarily using school-based deworming (SBD) programmes. However, targeting individuals of all ages through community-wide mass drug administration (cMDA) may interrupt STH transmission in some settings. We comp...
Background
Antibody and cellular memory responses following vaccination are important measures of immunogenicity. These immune markers were quantified in the framework of a vaccine trial investigating the malaria vaccine candidate GMZ2.
Methods
Fifty Gabonese adults were vaccinated with two formulations (aluminum Alhydrogel and CAF01) of GMZ2 or a...
Background
Annual mass drug administrations (MDA) of ivermectin will strongly reduce Onchocerca volvulus microfilariae (mf) in the skin and in the onchocerciasis patients’ eyes. Ivermectin treatment will also affect the expression of immunity in patients, such that activated immune defenses may help control and contribute to clearance of mf of O. v...
Background
Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the Wo...
Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially...
Background
Despite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster...
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 asex...
Sequestration of Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen in the placenta results in poor pregnancy outcomes, including low birth weight and maternal anemia. Antigen-specific antibody-mediated immunity is acquired during successive pregnancies. Thus, evaluating VAR2CSA-specific IgG profiles among pregnant women wil...
The high prevalence of sickle cell disease in some human populations likely results from the protection afforded against severe Plasmodium falciparum malaria and death by heterozygous carriage of HbS. P. falciparum remodels the erythrocyte membrane and skeleton, displaying parasite proteins at the erythrocyte surface that interact with key human pr...
Malaria during pregnancy is a major cause of maternal morbidity as well as fetal and neonatal mortality. Previous studies including our own suggested that placental and peripheral cytokines and chemokines levels measured at delivery can be used as biomarkers for pregnancy outcomes. However, the timing of malaria infection during pregnancy matters a...
Background
Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed...
Background Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions between different parasite species. Intestinal protozoa and helminths could modulate anti-malarial immunity, for example, there...
Background: Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and consequently, the possibility of immune-mediated interactions between different parasite species. Intestinal protozoa and helminths could modulate anti-malarial immunity, for example, there...
The World Health Organization’s Neglected Tropical Disease Roadmap has accelerated progress towards eliminating select neglected tropical diseases (NTDs). This momentum has catalyzed research to determine the feasibility of interrupting transmission of soil-transmitted helminths (STH) using community-wide mass drug administration (MDA). This study...
Aims:
Schistosomiasis and malaria are endemic in sub-Saharan Africa where Schistosoma haematobium (Sh) and Plasmodium falciparum (Pf) coinfections are thus frequent. We explored the effect of Sh infection on antibody responses directed to Pf merozoite antigens and on malaria susceptibility in Beninese children.
Methods and results:
268 children...
Introduction:
Plasmodium falciparum infected erythrocytes bind to specific endothelial cell receptors via members of PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich inter-domain region (CIDR) domains found in the N-terminal region of all PfEMP1. CIDRα1 domains bind EPCR, CIDR...
Background
Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial i...
Background
Sickle cell trait (HbAS) confers partial protection against malaria by reducing the adhesion of Plasmodium falciparum-infected erythrocytes to host receptors, but little is known about its potential protection against placental malaria.
Methods
Using flow cytometry, we assessed the recognition of HbAA and HbAS VAR2CSA-expressing infecte...
Malaria transmission remains high in Sub-Saharan Africa despite large-scale implementation of malaria control interventions. A comprehensive understanding of the transmissibility of infections to mosquitoes may guide the design of more effective transmission reducing strategies. The impact of P. falciparum sexual stage immunity on the infectious re...
Individual level of Pfs230 and Pfs48/45 antibody densities in the present and an independent cohort study [24] from Burkina Faso and best model fits of antibody profiles using estimated antibody half-lives.
Plasma samples of the independent cohort study were collected in June, August and December of the same year (2002) as described elsewhere [24]....
Levels of Pfs230 and Pfs48/45 antibody densities per gametocyte carriage status and age of study participants.
(TIF)
NANP6 antibody density by age and concurrent gametocyte density.
Antibody densities of study participants were measured in subsamples of n = 37, n = 97 and n = 157 samples in age groups 1–4, 5–14 and ≥15 years of age respectively. Error bars show horizontal lines from top indicating maximum antibody density, 75% percentile, median (50% percentile),...
Supplemental methods.
(PDF)
Background
Among the Plasmodium species that infect humans, adverse effects of P. falciparum and P. vivax have been extensively studied and reported with respect to poor outcomes particularly in first time mothers and in pregnant women living in areas with unstable malaria transmission. Although, other non-falciparum malaria infections during pregn...
Association between Plasmodium spp infection and anemia at enrolment.
* Proportion of women who developed the corresponding outcome from each type of infection group is presented. **P. falciparum, non-falciparum and mixed infections groups were compared with no malaria infection.
(DOCX)
Plasmodium spp. infections at enrolment and pregnancy outcomes.
(DOCX)
Plasmodium spp. infections in the peripheral blood and pregnancy outcomes.
(DOCX)
Plasmodium spp. infections in the placental blood and pregnancy outcomes.
(DOCX)
Risk factors for non-falciparum malaria infections at enrolment.
OR = Odd ratio; *Crude ORs for parity, gestational age, season of enrolment are adjusted for all other Covariates (parity, gestational age, mother’s age, season of enrolment)
(DOCX)
Risk factors for non-falciparum malaria infections at delivery.
OR = Odd ratio; *Crude ORs for parity, gestational age, season of delivery are adjusted for all other Covariates (parity, gestational age, mother’s age, season of enrolment).
(DOCX)
Prevalence of P. malariae and P. ovale infections during the pregnancy according to parity and age of the woman, and the season of sample collection.
*P value.
(DOCX)
Paired peripheral and placental samples of all P. ovale involved infections.
(DOCX)
Paired peripheral and placental samples of mono-infection of P. ovale.
(DOCX)
Hybrid trials that include both clinical and implementation science outcomes are increasingly relevant for public health researchers that aim to rapidly translate study findings into evidence-based practice. The DeWorm3 Project is a series of hybrid trials testing the feasibility of interrupting the transmission of soil transmitted helminths (STH),...
Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those trea...
Hybrid trials that include both clinical and implementation science outcomes are increasingly relevant for public health researchers that aim to rapidly translate study findings into evidence-based practice. The DeWorm3 Project is a series of hybrid trials testing the feasibility of interrupting the transmission of soil transmitted helminths (STH),...
Both γδ T cells and CD4+ T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previou...
Significance
This paper aims to discover how diverse malaria parasites are in children from an African village. DNA sequencing shows that they are highly diverse with respect to the genes encoding the surface coat. Indeed, every child has a malaria infection with a different set of these genes. Importantly, this paper shows by computational methods...
Background:
The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired...
Background Malaria is a major public health problem particularly in Africa. Despite the relatively good immunogenicity profile of the vaccine candidates in naive population, most of them are poorly immunogenic in malaria endemic population. This could be due to an induction of various immune regulatory mechanisms. It has recently been shown that hi...
Background:
Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investiga...
Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: lon...
Significance
Chronic helminth infections are accompanied by profound immune regulation. In humans, helminth-induced immune reactivity has not been thoroughly investigated in trial settings. We assessed the effect of anthelmintic treatment on immune responses in a whole community in a placebo-controlled randomized controlled trial. We show increased...
We conducted a genome-wide association study (GWAS) of antibody responses directed to three Plasmodium falciparum vaccine candidate antigens (MSP1, MSP2 and GLURP) previously associated with different patterns of protection against malaria infection in Senegalese children. A total of 174 950 single-nucleotide polymorphisms (SNPs) were tested for as...
Maternal parasitoses modulate fetal immune development, manifesting as altered cellular immunological activity in cord blood that may be linked to enhanced susceptibility to infections in early life. Plasmodium falciparum typifies such infections, with distinct placental infection-related changes in cord blood exemplified by expanded populations of...
The disease caused by Plasmodium falciparum (Pf) involves different clinical manifestations that, cumulatively, kill hundreds of thousands every year. Placental malaria (PM) is one such manifestation in which Pf infected erythrocytes (IE) bind to chondroitin sulphate A (CSA) through expression of VAR2CSA, a parasite-derived antigen. Protection agai...
Background:
Plasmodium falciparum gametocytes are essential for malaria transmission. Malaria control measures that aim at reducing transmission require an accurate characterization of the human infectious reservoir.
Methods:
We longitudinally determined human infectiousness to mosquitoes and P. falciparum carriage by an ultrasensitive RNA-based...
We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the PACOME clinical...
Placental malaria is caused by Plasmodium falciparum-infected erythrocytes that bind to placental tissue. Binding is mediated by VAR2CSA, a parasite antigen coded by the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation. Antibody-mediated immunity to placental malaria is ac...
Background:
Molecular, as opposed to microscopic, detection measures the real prevalence of Plasmodium falciparum infections. Such occult infections are common during pregnancy but their impact on pregnancy outcomes is unclear. We performed a longitudinal study to describe that impact.
Methods:
In a cohort of 1037 Beninese pregnant women, we use...
