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1. Cotrimoxazole versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in HIV-infected pregnant women in Bangui, Central African Republic: a Pragmatic Randomized Controlled Trial

Author

Aude Boulay, Samuel Gondje, Marie Yvette Batoumbou Ketta, Mirdad Kazanji, Alexandre Manirakiza, Laura Tondeur, Valérie Briand, Lenaig Le-Fouler, Ghislain Géraud Banthas Bata, Muriel Vray, Abdoulaye Sépou, Eugène Serdouma, Jean Methode Moyen, Olga Sakanga, Jean Pierre Lombart, Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Ministry of Health [Bangui], Hôpital de l'Amitié [Bangui], Institut Pasteur de la Guyane, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France, Université Paris Cité (UPC)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Paris Cité (UPC)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université (HESAM)-HESAM Université (HESAM)

Subjects
Adult, medicine.medical_specialty, 030231 tropical medicine, Maternity hospitals, HIV Infections, law.invention, 03 medical and health sciences, Antimalarials, Young Adult, 0302 clinical medicine, Randomized controlled trial, law, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Hiv infected, Sulfadoxine, Trimethoprim, Sulfamethoxazole Drug Combination, parasitic diseases, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, business.industry, Pregnant women, Public Health, Environmental and Occupational Health, medicine.disease, Sulfadoxine/pyrimethamine, 3. Good health, Malaria, Placental infection, Central African Republic, Drug Combinations, Infectious Diseases, Pyrimethamine, Pregnancy Complications, Parasitic, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Parasitology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, medicine.drug, Prophylaxis HIV
Abstract

International audience; OBJECTIVE: The main objective of the MACOMBA (Maternity and Control of Malaria-HIV co-infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than Sulphadoxine-Pyremethamine-IPTp (IPTp-SP) to prevent placental malaria infection (primary endpoint) among HIV-positive pregnant women with a CD4+ count ≥350 cells/mm(3) in Bangui, CAR.METHODS: MACOMBA is a multicenter, open-label randomized trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomized and 112 (59 and 53 in CTX and IPTp-SP arms, respectively) were assessed for placental infection defined by microscopic parasitemia or PCR.RESULTS: Thirteen women had a placental infection: 5 in the CTX arm (1 by microscopic placental parasitemia and 4 by PCR) and 8 by PCR in the SP-IPTp (8.5% vs 15.1%, p = 0.28). The percentage of newborns with low birthweight (< 2500 g) did not differ statistically between the two arms. Self-reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms.CONCLUSION: Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV-infected pregnant women, as currently recommended by WHO.

Published
2021
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2. Burkholderia cepacia meningitis in the Central African Republic

Author

Anne Le Flèche-Matéos, Pierre-Alain Rubbo, Alain Farra, Thierry Frank, Hugues Sanke, Alain Berlioz-Arthaud, Jean-Pierre Lombart, Jean-Robert Mbecko, Service de bactériologie [Bangui], Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], and Institut Pasteur [Paris] (IP)

Subjects
MESH: Meningitis, Bacterial / drug therapy, Imipenem, MESH: Burkholderia Infections / drug therapy, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Ceftazidime, MESH: Anti-Bacterial Agents / pharmacology, Burkholderia cepacia, MESH: Anti-Bacterial Agents / administration & dosage, Letter to the Editors, antibiotics, Microbiology, 03 medical and health sciences, 0302 clinical medicine, MESH: RNA, Ribosomal, 16S / genetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Bacteriology, Medicine, Meningitis, MESH: Burkholderia Infections / microbiology, 030212 general & internal medicine, Neck stiffness, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, biology, business.industry, Mortality rate, MESH: Child, Preschool, Outbreak, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, MESH: Drug Resistance, Multiple, Bacterial, medicine.disease, biology.organism_classification, MESH: Meningitis, Bacterial / diagnosis, MESH: Male, 3. Good health, MESH: Burkholderia Infections / diagnosis, Central African Republic, Burkholderia, MESH: Central African Republic, MESH: Meningitis, Bacterial / microbiology, MESH: Burkholderia cepacia / isolation & purification, business, medicine.drug
Abstract

International audience; Burkholderia cepacia causes frequent infections in immunocompromised and hospitalized patients, with a significant mortality rate. This bacterial species has also been associated with epidemic outbreaks due to contamination of antiseptic solutions and parenteral and nebulized medications. In 2016, in the town of Bongonon in the north of the Central African Republic (CAR), a three-year-old boy with febrile meningeal syndrome (fever, neck stiffness and altered general condition) was admitted for a medical consultation provided by the nongovernmental organization MSF-Spain. On 20 March 2016, a sample of the boy's cerebrospinal fluid was sent to the Bacteriology Laboratory of the Pasteur Institute of Bangui for analysis. Conventional bacteriology showed that the isolate was a Gram-negative bacillus, which was identified as B. cepacia by using API 20 NE, with 99.9%confidence. In addition, the strain presented an acquired resistance to ticarcillin-clavulanate, ceftazidime and imipenem but remained susceptible to cotrimoxazole. As B. cepacia had never previously been isolated from cerebrospinal fluid in Africa, we chose to identify the strain by 16S rRNA gene sequencing. The molecular data showed that the isolate belonged to B. cepacia group. This is the first report of a case of meningitis caused by B. cepacia in CAR and developing countries.

Published
2019
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3. Development and Evaluation of a Dipstick Diagnostic Test for Neisseria meningitidis Serogroup X

Author

Laurence A. Mulard, Bouba Gake, Mélanie Denizon, Jean-Pierre Lombart, Adèle Kacou-N′douba, François Traincard, Odile Ouwe Missi Oukem-Boyer, Ali Elhaji Mahamane, Sylvie Dartevelle, Muhamed-Kheir Taha, Alain Agnememel, Mireille Dosso, Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris] (IP), Centre Collaborateur de l'OMS pour les méningites bactériennes - WHO Collaborating Center Bacterial Meningitis (CC-OMS - WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris Diderot - Paris 7 (UPD7), Ingénierie des Anticorps (plate-forme) - Antibody Engineering (Platform), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Chimie des Biomolécules - Chemistry of Biomolecules, Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES), Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Côte d'Ivoire, Centre Pasteur du Cameroun, The research work was supported by funding from the Fondation Total, including a fellowship to A.A., Institut Pasteur [Paris], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
Microbiology (medical), Epidemiology, MESH: Cerebrospinal Fluid, Meningitis, Meningococcal, Neisseria meningitidis, MESH: Africa, Serogroup, medicine.disease_cause, Likelihood ratios in diagnostic testing, Chromatography, Affinity, MESH: Neisseria meningitidis, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Antigen, Predictive Value of Tests, Conjugate vaccine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Humans, Medicine, 030212 general & internal medicine, MESH: Diagnostic Tests, Routine, Cerebrospinal Fluid, Antigens, Bacterial, 0303 health sciences, Rapid diagnostic test, MESH: Humans, Diagnostic Tests, Routine, 030306 microbiology, business.industry, MESH: Meningitis, Meningococcal, Dipstick, MESH: Serogroup, MESH: Chromatography, Affinity, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Predictive Value of Tests, 3. Good health, MESH: France, Africa, France, African meningitis belt, business, Meningitis, MESH: Antigens, Bacterial
Abstract

The emergence of Neisseria meningitidis serogroup X (NmX) in the African meningitis belt has urged the development of diagnostic tools and vaccines for this serogroup, especially following the introduction of a conjugate vaccine against N. meningitidis serogroup A (NmA). We have developed and evaluated a new rapid diagnostic test (RDT) for detecting the capsular polysaccharide (cps) antigen of this emerging serogroup. Whole inactivated NmX bacteria were used to immunize rabbits. Following purification by affinity chromatography, the cpsX-specific IgG antibodies were utilized to develop an NmX-specific immunochromatography dipstick RDT. The test was validated against purified cpsX and meningococcal strains of different serogroups. Its performance was evaluated against that of PCR on a collection of 369 cerebrospinal fluid (CSF) samples obtained from patients living in countries within the meningitis belt (Cameroon, Côte d'Ivoire, and Niger) or in France. The RDT was highly specific for NmX strains. Cutoffs of 10 5 CFU/ml and 1 ng/ml were observed for the reference NmX strain and purified cpsX, respectively. Sensitivity and specificity were 100% and 94%, respectively. A high agreement between PCR and RDT (Kappa coefficient, 0.98) was observed. The RDT gave a high positive likelihood ratio and a low negative likelihood (0.07), indicating almost 100% probability of declaring disease or not when the test is positive or negative, respectively. This unique NmX-specific test could be added to the available set of RDT for the detection of meningococcal meningitis in Africa as a major tool to reinforce epidemiological surveillance after the introduction of the NmA conjugate vaccine.

Published
2015
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4. Changes in Systemic Regulatory T Cells, Effector T Cells, and Monocyte Populations Associated With Early-Life Stunting

Author

Zo, Andriamanantena, Fanirisoa, Randrianarisaona, Maheninasy, Rakotondrainipiana, Prisca, Andriantsalama, Ravaka, Randriamparany, Rindra, Randremanana, Frédérique, Randrianirina, Sophie, Novault, Darragh, Duffy, François, Huetz, Milena, Hasan, Matthieu, Schoenhals, Philippe J, Sansonetti, Pascale, Vonaesch, Inès, Vigan-Womas, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénie microbienne moléculaire, This project was funded by the Total Foundation, Institut Pasteur (PTR Immunohealth), Odyssey Re-Insurance company and the Petram Foundation. ZA was supported through a Calmette and Yersin traineeship grant from Institut Pasteur, and a Nutricia Research Foundation Fellowship Grant. PV was supported by an Early Postdoctoral Fellowship (Grant No. P2EZP3_152159), an Advanced Postdoctoral Fellowship (Grant No. P300PA_177876) as well as a Return Grant (Grant No. P3P3PA_17877) from the Swiss National Science Foundation, a Roux-Cantarini Fellowship (2016), a L’Oréal-UNESCO for Women in Science France Fellowship (2017) and a stipend through the Forschungsfonds of the University of Basel., Afribiota Investigators: Laurence Barbot-Trystram, Hôpital Pitié-Salpêtrière, Paris, France, Robert Barouki, Hôpital Necker- Enfants maladies, Paris, France, Alexandra Bastaraud, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Jean-Marc Collard, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Maria Doria, Institut Pasteur, Paris, France, Darragh Duffy, Institut Pasteur, Paris, France, Serge Ghislain Djorie, Institut Pasteur de Bangui, Bangui, Central African Republic, Tamara Giles-Vernick, Institut Pasteur, Paris, France, Bolmbaye Privat Gondje, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Jean-Chrysostome Gody, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Milena Hasan, Institut Pasteur, Paris, France, Jean-Michel Héraud, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Francis Allan Hunald, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU-JRA), Antananarivo, Madagascar, Nathalie Kapel, Hôpital Pitié-Salpêtrière, Paris, France, Jean-Pierre Lombart, Institut Pasteur de Bangui, Bangui, Central African Republic, Alexandre Manirakiza, Institut Pasteur de Bangui, Bangui, Central African Republic, Synthia Nazita Nigatoloum, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Laura Wegener Parfrey, University of British Columbia, Vancouver, Canada, Lisette Raharimalala, Centre de Santé Materno-Infantile, Tsaralalana, Antananarivo, Madagascar, Maheninasy Rakotondrainipiana, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Rindra Vatosoa Randremanana, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Harifetra Mamy Richard Randriamizao, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU-JRA), Antananarivo, Madagascar, Frédérique Randrianirina, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Annick Lalaina Robinson, Centre Hospitalier Universitaire Mère Enfant de Tsaralalana, Antananarivo, Madagascar, Pierre-Alain Rubbo, Institut Pasteur de Bangui, Bangui, République Centrafricaine, Philippe Sansonetti, Institut Pasteur, Paris, France, Laura Schaeffer, Institut Pasteur, Paris, France, Ionela Gouandjika-Vassilache, Instiut Pasteur de Bangui, Bangui, République Centrafricaine, Pascale Vonaesch, Institut Pasteur, Paris, France, Sonia Sandrine Vondo, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Inès Vigan-Womas, Institut Pasteur de Madagascar, Antananarivo, Madagascar., and Vougny, Marie-Christine

Subjects
systemic immune cells, MESH: Humans, [SDV.IMM] Life Sciences [q-bio]/Immunology, flow cytometry, MESH: T-Lymphocytes, Regulatory, MESH: Th17 Cells, MESH: Child, Preschool, stunting, MESH: T-Lymphocyte Subsets, MESH: Growth Disorders, MESH: Monocytes, T-Lymphocytes, Regulatory, regulatory T cells, T-Lymphocyte Subsets, Child, Preschool, MESH: Child, environmental enteric dysfunction, Madagascar, Humans, Th17 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Child, monocytes, Growth Disorders
Abstract

International audience; Stunting and environmental enteric dysfunction (EED) may be responsible for altered gut and systemic immune responses. However, their impact on circulating immune cell populations remains poorly characterized during early life. A detailed flow cytometry analysis of major systemic immune cell populations in 53 stunted and 52 non-stunted (2 to 5 years old) children living in Antananarivo (Madagascar) was performed. Compared to age-matched non-stunted controls, stunted children aged 2-3 years old had a significantly lower relative proportion of classical monocytes. No significant associations were found between stunting and the percentages of effector T helper cell populations (Th1, Th2, Th17, Th1Th17, and cTfh). However, we found that HLA-DR expression (MFI) on all memory CD4+ or CD8+ T cell subsets was significantly lower in stunted children compared to non-stunted controls. Interestingly, in stunted children compared to the same age-matched non-stunted controls, we observed statistically significant age-specific differences in regulatory T cells (Treg) subsets. Indeed, in 2- to 3-year-old stunted children, a significantly higher percentage of memory Treg, whilst a significantly lower percentage of naive Treg, was found. Our results revealed that both innate and adaptive systemic cell percentages, as well as activation status, were impacted in an age-related manner during stunting. Our study provides valuable insights into the understanding of systemic immune system changes in stunted children.

Published
2022
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5. Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models

Author

Vonaesch, Pascale, Araújo, João, Gody, Jean-Chrysostome, Mbecko, Jean-Robert, Sanke, Hugues, Andrianonimiadana, Lova, Naharimanananirina, Tanteliniaina, Ningatoloum, Synthia Nazita, Vondo, Sonia Sandrine, Gondje, Privat Bolmbaye, Rodriguez-Pozo, Andre, Rakotondrainipiana, Maheninasy, Kandou, Kaleb Jephté Estimé, Nestoret, Alison, Kapel, Nathalie, Djorie, Serge Ghislain, Finlay, B. Brett, Wegener Parfrey, Laura, Collard, Jean-Marc, Randremanana, Rindra Vatosoa, Sansonetti, Philippe, Collard, Jean-Marc, Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Swiss Tropical and Public Health Institute [Basel], Université de Lausanne = University of Lausanne (UNIL), University of Basel (Unibas), Centre pédiatrique de Bangui, Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHUJRA), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of British Columbia (UBC), Collège de France (CdF (institution)), This project was funded by the Total Foundation, the Institut Pasteur, Bill and Melinda Gates Foundation Grant OPP1204689, the Fondation Petram, Nutricia Foundation Grant NRF 2016-10, and a donation from the Odyssey Re-Insurance Company. P.V. was supported by Swiss National Science Foundation Early Postdoctoral Fellowship P2EZP3_152159, Advanced Postdoctoral Fellowship P300PA_177876, and Return Grant P3P3PA_17877, a Roux-Cantarini fellowship (2016), a L’Oréal–UNESCO for Women in Science France fellowship (2017), and an Excellence Scholarship from the University of Basel (Forschungsfonds, 2019). Her group is funded through the NCCR Microbiomes, a National Centre of Competence in Research, funded by the Swiss National Science Foundation (grant number 180575). Work in the group of L.W.P. is funded by Human Frontier Science Program Grant RGY0078/2015. P.J.S. is a Howard Hughes Medical Institute Senior Foreign Scholar and CIFAR scholar in the human microbiome consortium., We thank all children and their families who participated in the Afribiota project. Further, we thank the Afribiota Consortium, the participating hospitals in Bangui and Antananarivo, the Institut Pasteur, the Institut Pasteur de Madagascar, the Institut Pasteur de Bangui, and members of the scientific advisory boards for their continuous support, and we thank the Centre de Recherche Translationelle and the Direction Internationale of the Institut Pasteur (especially Paméla Palvadeau, Jane Lynda Deuve, Cécile Artaud, Nathalie Jolly, Sophie Jarrijon, Mamy Ratsialonina, and Jean-François Damaras) for help in setting up and steering the Afribiota project. We also thank J.-M.C., Pierre-Alain Rubbo, Dieu-Merci Welekoi-Yapondo, L.A., Laurence Arowas, and Marie-Noelle Ungeheuer for managing the biobank, the members of the animal facility at the Institut Pasteur for taking care of the mice, the Centre d’Immunolgoie Humaine of the Institut Pasteur, especially Milena Hasan, Tarshana Stephen, and Esma Karkeni, for help with setting up the LUMINEX assays at their platform, Asmaa Tazi for identification of the bacteria by MALDI-TOF spectroscopy, Estelle Martineau at the Platform Spectrometries Capacités at the University of Nantes for quantification of the fermentation products, Kelsey Huus for critical reading of the manuscript, and Munir Winkel for streamlining of the R code., and Liste of Afribiota Inverstigators : Laurence Barbot-Trystram, Hôpital Pitié-Salpêtrière, Paris, France Robert Barouki, Hôpital Necker- Enfants maladies, Paris, France Alexandra Bastaraud, Institut Pasteur de Madagascar, Antananarivo, Madagascar Jean-Marc Collard, Institut Pasteur de Madagascar, Antananarivo, Madagascar Maria Doria, Institut Pasteur, Paris, France Darragh Duffy, Institut Pasteur, Paris, France B. Brett Finlay, University of British Columbia, Vancouver, Canada Serge Ghislain Djorie, Institut Pasteur de Bangui, Bangui, Central African Republic Tamara Giles-Vernick, Institut Pasteur, Paris, France Bolmbaye Privat Gondje, Complexe Pédiatrique de Bangui, Bangui, Central African Republic Jean-Chrysostome Gody, Complexe Pédiatrique de Bangui, Bangui, Central African Republic Milena Hasan, Institut Pasteur, France Francis Allen Hunald, Service de Chirurgie pédiatrique, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU-JRA), Antananarivo, Madagascar Nathalie Kapel, Hôpital Pitié-Salpêtrière, Paris, France Jean-Pierre Lombart, Institut Pasteur de Bangui, Bangui, Central African Republic Alexandre Manirakiza, Institut Pasteur de Bangui, Bangui, Central African Republic Synthia Nazita Nigatoloum, Complexe Pédiatrique de Bangui, Bangui, Central African Republic Laura Wegener Parfrey, University of British Columbia, Vancouver, Canada Lisette Raharimalala, Centre de Santé Materno-Infantile, Tsaralalana, Antananarivo, Madagascar Maheninasy Rakotondrainipiana, Institut Pasteur de Madagascar, Antananarivo, Madagascar Rindra Vatosoa Randremanana, Institut Pasteur de Madagascar, Antananarivo, Madagascar Harifetra Mamy Richard Randriamizao, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU-JRA), Antananarivo, Madagascar Frédérique Randrianirina, Institut Pasteur de Madagascar, Antananarivo, Madagascar Annick Robinson, Centre Hospitalier Universitaire Mère Enfant de Tsaralalana, Antananarivo, Madagascar Pierre-Alain Rubbo, Institut Pasteur de Bangui, Bangui, République Centrafricaine Philippe Sansonetti, Institut Pasteur, Paris, France Laura Schaeffer, Institut Pasteur, Paris, France Ionela Gouandjika-Vassilache, Institut Pasteur de Bangui, Bangui, République Centrafricaine Pascale Vonaesch, Institut Pasteur, Paris, France Sonia Sandrine Vondo, Complexe Pédiatrique de Bangui, Bangui, Central African Republic Inès Vigan-Womas, Institut Pasteur de Madagascar, Antananarivo, Madagasca

Subjects
[SDV] Life Sciences [q-bio], stunted child growth, lipid malabsorption, [SDV]Life Sciences [q-bio], environmental enteric dysfunction, low-grade inflammation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, small intestine, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract

International audience; Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

Published
2022
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6. Factors Associated with Stunted Growth in Children Under Five Years in Antananarivo, Madagascar and Bangui, Central African Republic

Author

Pascale, Vonaesch, Serge Ghislain, Djorie, Kaleb Jephté Estimé, Kandou, Maheninasy, Rakotondrainipiana, Laura, Schaeffer, Prisca Vega, Andriatsalama, Ravaka, Randriamparany, Bolmbaye Privat, Gondje, Synthia, Nigatoloum, Sonia Sandrine, Vondo, Aurélie, Etienne, Annick, Robinson, Francis Allen, Hunald, Lisette, Raharimalala, Tamara, Giles-Vernick, Laura, Tondeur, Frédérique, Randrianirina, Alexandra, Bastaraud, Jean-Chrysostome, Gody, Philippe Jean, Sansonetti, Rindra Vatosoa, Randremanana, Inès, Vigan-Womas, Pathogénie microbienne moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Unité d'Epidémiologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre pédiatrique de Bangui, Centre Hospitalier Universitaire Mère-Enfant de Tsaralalàna (CHUMET), Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHUJRA), Anthropologie et écologie de l’émergence des maladies - Anthropology and Ecology of Disease Emergence, Institut Pasteur [Paris], Centre de Biologie Clinique [Antananarivo] (IPM), Laboratoire d'hygiène des aliments et de l'environnement [Antananarivo, Madagascar] (IPM), Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar], The epidemiological part of AFRIBIOTA was funded by the Total Foundation and the Fondation Petram. PV was supported by an Early Postdoctoral Fellowship (Grant No. P2EZP3_152159), an Advanced Postdoctoral Fellowship (Grant No. P300PA_177876) as well as a Return Grant (Grant No. P3P3PA_17877) from the Swiss National Science Foundation, a Roux-Cantarini Fellowship (2016) and a L’Oréal-UNESCO for Women in Science France Fellowship (2017). PJS is a HHMI Senior Foreign Scholar. The funders had no role in study design or collection, analysis, and interpretation of data and in writing this manuscript., AFRIBIOTA Investigators: Laurence Barbot-Trystram, Hôpital Pitié-Salpêtrière, Paris, France, Robert Barouki, Hôpital Necker-Enfants maladies, Paris, France, Alexandra Bastaraud, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Jean-Marc Collard, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Maria Doria, Institut Pasteur, Paris, France, Aurélie Etienne, Institut Pasteur, Paris, France/Institut Pasteur de Madagascar, Madagascar, Serge Ghislain Djorie, Institut Pasteur de Bangui, Bangui, Central African Republic, Tamara Giles-Vernick, Institut Pasteur, Paris, France, Bolmbaye Privat Gondje, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Jean-Chrysostome Gody, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Francis Allen Hunald, Service de Chirurgie pédiatrique, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU-JRA), Antananarivo, Madagascar, Nathalie Kapel, Hôpital Pitié-Salpêtrière, Paris, France, Jean-Pierre Lombart, Institut Pasteur de Bangui, Bangui, Central African Republic, Alexandre Manirakiza, Institut Pasteur de Bangui, Bangui, Central African Republic, Synthia Nazita Nigatoloum, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Lisette Raharimalala, Centre de Santé Materno-Infantile, Tsaralalana, Antananarivo, Madagascar, Maheninasy Rakotondrainipiana, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Rindra Randremanana, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Harifetra Mamy Richard Randriamizao, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU-JRA), Antananarivo, Madagascar, Frédérique Randrianirina, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Annick Robinson, Centre Hospitalier Universitaire Mère Enfant de Tsaralalana, Antananarivo, Madagascar, Pierre-Alain Rubbo, Institut Pasteur de Bangui, Bangui, République Centrafricaine, Philippe Sansonetti, Institut Pasteur, Paris, France, Laura Schaeffer, Institut Pasteur, Paris, France, Ionela Gouandjika-Vassilache, Institut Pasteur de Bangui, Bangui, République Centrafricaine, Pascale Vonaesch, Institut Pasteur, Paris, France, Sonia Sandrine Vondo, Complexe Pédiatrique de Bangui, Bangui, Central African Republic, Inès Vigan-Womas, Institut Pasteur de Madagascar, Antananarivo, Madagascar. We wish to thank further all families and fieldworkers who contributed to this study, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), and Vigan-Womas, Inès

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Stunted growth, Nutritional Status, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, MESH: Madagascar, MESH: Pregnancy, Pregnancy, MESH: Risk Factors, MESH: Child, Prevalence, Madagascar, Humans, Child, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Children, Growth Disorders, MESH: Prevalence, MESH: Humans, digestive, oral, and skin physiology, MESH: Child, Preschool, Infant, Undernutrition, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Growth Disorders, MESH: Nutritional Status, MESH: Case-Control Studies, MESH: Infant, Central African Republic, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, MESH: Central African Republic, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract

Objectives With a fourth of all under-five children affected, stunting remains one of the biggest health challenges worldwide. Even though the main underlying factors are known, the exact pathways to stunting varying in affected regions, and interventions thus need to be tailored to the local contexts. This study aimed assessing and comparing factors associated with stunting in two understudied sub-Saharan urban contexts with some of the highest stunting prevalence globally: Bangui, Central African Republic (~ 36%) and Antananarivo, Madagascar (42%). Methods We performed a case–control study on 175 + 194 stunted and 237 + 230 non-stunted control children aged 2–5 years and matched for age, gender and district of residency. Factors associated with stunting were identified using a standardized, paper questionnaire delivered by trained interviewers. Statistical analysis was done using logistic regression modelling. Results In both sites, formal maternal education lowered the risk of being stunted and restricted access to soap, suffering of anaemia and low birth weight were associated with higher risk of stunting. Short maternal stature, household head different from parents, diarrhoea and coughing were associated with an increased risk and continuing breastfeeding was associated with a lower risk of stunting in Antananarivo. Previous severe undernutrition and dermatitis/ fungal skin infections were associated with higher and changes in diet during pregnancy with lower risk of stunting in Bangui. Conclusions Our results suggest maternal education, antenatal care, iron supplementation and simple WASH interventions such as using soap and infection control as general and breastfeeding (Antananarivo) or better nutrition (Bangui) as area-specified interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s10995-021-03201-8.

Published
2021
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