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1. 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, Afribiota Investigators, Laurence Barbot-Trystram, Robert Barouki, Alexandra Bastaraud, Jean-Marc Collard, Maria Doria, Serge Ghislain Djorie, Tamara Giles-Vernick, Bolmbaye Privat Gondje, Jean-Chrysostome Gody, Jean-Michel Héraud, Francis Allan Hunald, Nathalie Kapel, Jean-Pierre Lombart, Alexandre Manirakiza, Synthia Nazita Nigatoloum, Laura Wegener Parfrey, Lisette Raharimalala, Rindra Vatosoa Randremanana, Harifetra Mamy Richard Randriamizao, Frédérique Randrianirina, Annick Lalaina Robinson, Pierre-Alain Rubbo, Philippe Sansonetti, Laura Schaeffer, Ionela Gouandjika-Vassilache, Sonia Sandrine Vondo, and Inès Vigan-Womas

Subjects
stunting, environmental enteric dysfunction, flow cytometry, monocytes, regulatory T cells, Madagascar, Immunologic diseases. Allergy, RC581-607
Abstract

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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2. Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)

Author

Romaric Nzoumbou-Boko, Chris-Boris Gildas Panté-Wockama, Carine Ngoagoni, Nathalie Petiot, Eric Legrand, Ulrich Vickos, Jean-Chrysostome Gody, Alexandre Manirakiza, Christophe Ndoua, Jean-Pierre Lombart, and Didier Ménard

Subjects
Malaria, Plasmodium falciparum, Antimalarial drug resistance, Artemisinin, Pfkelch13, Bangui, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Over the last decade, artemisinin-based combination therapy (ACT) has contributed substantially to the decrease in malaria-related morbidity and mortality. The emergence of Plasmodium falciparum parasites resistant to artemisinin derivatives in Southeast Asia and the risk of their spread or of local emergence in sub-Saharan Africa are a major threat to public health. This study thus set out to estimate the proportion of P. falciparum isolates, with Pfkelch13 gene mutations associated with artemisinin resistance previously detected in Southeast Asia. Methods Blood samples were collected in two sites of Bangui, the capital of the Central African Republic (CAR) from 2017 to 2019. DNA was extracted and nested PCR were carried out to detect Plasmodium species and mutations in the propeller domain of the Pfkelch13 gene for P. falciparum samples. Results A total of 255 P. falciparum samples were analysed. Plasmodium ovale DNA was found in four samples (1.57%, 4/255). Among the 187 samples with interpretable Pfkelch13 sequences, four samples presented a mutation (2.1%, 4/187), including one non-synonymous mutation (Y653N) (0.5%, 1/187). This mutation has never been described as associated with artemisinin resistance in Southeast Asia and its in vitro phenotype is unknown. Conclusion This preliminary study indicates the absence of Pfkelch13 mutant associated with artemisinin resistance in Bangui. However, this limited study needs to be extended by collecting samples across the whole country along with the evaluation of in vitro and in vivo phenotype profiles of Pfkelch13 mutant parasites to estimate the risk of artemisinin resistance in the CAR.

Published
2020
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3. Impact of MenAfriVac on Meningococcal A Meningitis in Cameroon: A Retrospective Study Using Case-by-Case-Based Surveillance Data from 2009 to 2015

Author

Bouba Gake, Bonaventure Babinne Graobe, Bouba Abdouraman, Crescence Satou Ngah, Ahmadou Aissatou, Nelly-Michèle Gake, Elise Claudine Seukap, Elias Nchiwan Nukenine, Alain G. Etoundi Mballa, Marie-Christine Fonkoua, and Jean-Pierre Lombart

Subjects
Arctic medicine. Tropical medicine, RC955-962
Abstract

Meningococcal meningitis is a public health concern in Africa. Conjugated vaccine against serogroup A Neisseria meningitidis (MenAfriVac) was used in mass vaccination and was proved to have a good impact in the meningitis belt. There is a lack of information about the impact of this intervention in Cameroon after mass vaccination was undertaken. This study aimed at filling the gap in its unknown impact in Cameroon. A retrospective longitudinal study using biological monitoring data of case-by-case-based surveillance for meningitis was obtained from the National Reference Laboratories from 1 January 2009 to 20 September 2015. Immunization coverage data were obtained from Regional Public Health Delegations where immunizations took place. We compared the risks of vaccine serogroup occurrence before and after vaccinations and calculated the global impact using Halloran’s formula. Annual cases of meningitis A decreased gradually from 92 in 2011 to 34 in 2012 and then to 1 case in 2013, and since 2014, no cases have been detected. The impact was estimated at 14.48% (p=0.41) in 2012 and then at 98.63% (p

Published
2021
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4. Emergence of Neisseria meningitidis Serogroup W, Central African Republic, 2015–2016

Author

Thierry Frank, Eva Hong, Jean-Robert Mbecko, Jean-Pierre Lombart, Muhamed-Kheir Taha, and Pierre-Alain Rubbo

Subjects
epidemics, serogroup W, meningitis/encephalitis, Neisseria meningitidis, Central African Republic, sub-Saharan Africa, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We analyzed data from the 2015 and 2016 meningitis epidemic seasons in Central African Republic as part of the national disease surveillance. Of 80 tested specimens, 66 belonged to meningococcal serogroup W. Further analysis found that 97.7% of 44 isolates belonged to the hyperinvasive clonal complex sequence type 11.

Published
2018
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5. Evidence of human leptospirosis cases in a cohort of febrile patients in Bangui, Central African Republic: a retrospective study, 2012–2015

Author

Pierre-Alain Rubbo, Marie-Estelle Soupé-Gilbert, Davy Martial Golongba, Florent Mbombo, Dominique Girault, Emmanuel Nakouné, Jean-Pierre Lombart, Sébastien Breurec, and Cyrille Goarant

Subjects
Leptospirosis, Bacteria, Infection, Central African Republic, Sub-Saharan Africa, Surveillance, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background In spite of a local favorable environment, leptospirosis has never been described in Central African Republic so far mainly because of the weakness of diagnostic tests and differential diagnostic strategy for febrile jaundice cases negative for yellow fever virus. Here we bring a complementary insight to conclusions of Gadia CLB et al. regarding the presence of leptospirosis in Central African Republic in YFV-negative febrile icteric patients. Methods Our study included 497 individuals presenting with fever and jaundice but negative for yellow fever infection, retrospectively selected from the national surveillance biobank for yellow fever in Institut Pasteur de Bangui, Central African Republic. A combination of serological (ELISA, agglutination) and molecular biology techniques (quantitative real-time polymerase chain reaction) was used to identify Leptospira or the patient’s immune response to the bacteria. Statistical analyses were done using the non parametric Mann-Withney U test with a 5% statistical threshold. Results ELISA test results showed 46 positive serum samples while 445 were negative and 6 remains equivocal. In addition, the reference microscopic agglutination test for leptospirosis diagnostic confirmed that 7 out of 32 samples tested were positive. Unfortunately, all 497 serum samples tested for leptospirosis were negative using the molecular techniques. Conclusions Unlike Gadia et al., we confirmed that leptospirosis is circulating in Central African Republic and therefore may be responsible for some of the unexplained cases of febrile jaundice in the country. Thus, leptospirosis needs to be investigated to improve identification of aetiological pathogens. Our study also suggests a need to improve sample transportation and storage conditions.

Published
2018
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6. Burkholderia cepacia meningitis in the Central African Republic

Author

Thierry Frank, Alain Farra, Pierre-Alain Rubbo, Jean-Robert Mbecko, Hugues Sanke, Anne Le Flèche-Matéos, Jean-Pierre Lombart, and Alain Berlioz-Arthaud

Subjects
meningitis, burkholderia cepacia, antibiotics, central african republic, Medicine
Abstract

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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7. Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)

Author

Carine Ngoagoni, Christophe Ndoua, Chris-Boris Gildas Panté-Wockama, Ulrich Vickos, Alexandre Manirakiza, Eric Legrand, Romaric Nzoumbou-Boko, Jean-Pierre Lombart, Didier Menard, Nathalie Petiot, Jean-Chrysostome Gody, Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Université de Bangui, Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris], Centre pédiatrique de Bangui, Programme national de Lutte contre le Paludisme [Bangui, République centrafricaine], This work was financed by the Institut Pasteur de Bangui and the Malaria Genetics and Resistance Unit at Institut Pasteur, Paris, and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, 030106 microbiology, Plasmodium falciparum, Drug Resistance, Protozoan Proteins, Gene mutation, medicine.disease_cause, lcsh:Infectious and parasitic diseases, Antimalarials, Lactones, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, medicine, Pfkelch13, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Antimalarial drug resistance, lcsh:RC109-216, Artemisinin, Mutation, biology, Research, Plasmodium ovale, biology.organism_classification, medicine.disease, Virology, Artemisinins, 3. Good health, Malaria, Central African Republic, Infectious Diseases, Parasitology, Bangui, Nested polymerase chain reaction, medicine.drug
Abstract

Background Over the last decade, artemisinin-based combination therapy (ACT) has contributed substantially to the decrease in malaria-related morbidity and mortality. The emergence of Plasmodium falciparum parasites resistant to artemisinin derivatives in Southeast Asia and the risk of their spread or of local emergence in sub-Saharan Africa are a major threat to public health. This study thus set out to estimate the proportion of P. falciparum isolates, with Pfkelch13 gene mutations associated with artemisinin resistance previously detected in Southeast Asia. Methods Blood samples were collected in two sites of Bangui, the capital of the Central African Republic (CAR) from 2017 to 2019. DNA was extracted and nested PCR were carried out to detect Plasmodium species and mutations in the propeller domain of the Pfkelch13 gene for P. falciparum samples. Results A total of 255 P. falciparum samples were analysed. Plasmodium ovale DNA was found in four samples (1.57%, 4/255). Among the 187 samples with interpretable Pfkelch13 sequences, four samples presented a mutation (2.1%, 4/187), including one non-synonymous mutation (Y653N) (0.5%, 1/187). This mutation has never been described as associated with artemisinin resistance in Southeast Asia and its in vitro phenotype is unknown. Conclusion This preliminary study indicates the absence of Pfkelch13 mutant associated with artemisinin resistance in Bangui. However, this limited study needs to be extended by collecting samples across the whole country along with the evaluation of in vitro and in vivo phenotype profiles of Pfkelch13 mutant parasites to estimate the risk of artemisinin resistance in the CAR.

Published
2020
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8. Impact of MenAfriVac on Meningococcal A Meningitis in Cameroon: A Retrospective Study Using Case-by-Case-Based Surveillance Data from 2009 to 2015

Author

Crescence Satou Ngah, Elias Nchiwan Nukenine, Bouba Gake, Bouba Abdouraman, Bonaventure Babinne Graobe, Jean-Pierre Lombart, Elise Claudine Seukap, Ahmadou Aissatou, Alain G. Etoundi Mballa, Marie-Christine Fonkoua, and Nelly-Michèle Gake

Subjects
medicine.medical_specialty, Surveillance data, Article Subject, business.industry, Neisseria meningitidis, Public health, RC955-962, Retrospective cohort study, General Medicine, medicine.disease_cause, medicine.disease, Microbiology, Vaccination, Environmental health, Arctic medicine. Tropical medicine, Medicine, Parasitology, Mass vaccination, business, MenAfriVac, Meningitis, Research Article
Abstract

Meningococcal meningitis is a public health concern in Africa. Conjugated vaccine against serogroup A Neisseria meningitidis (MenAfriVac) was used in mass vaccination and was proved to have a good impact in the meningitis belt. There is a lack of information about the impact of this intervention in Cameroon after mass vaccination was undertaken. This study aimed at filling the gap in its unknown impact in Cameroon. A retrospective longitudinal study using biological monitoring data of case-by-case-based surveillance for meningitis was obtained from the National Reference Laboratories from 1 January 2009 to 20 September 2015. Immunization coverage data were obtained from Regional Public Health Delegations where immunizations took place. We compared the risks of vaccine serogroup occurrence before and after vaccinations and calculated the global impact using Halloran’s formula. Annual cases of meningitis A decreased gradually from 92 in 2011 to 34 in 2012 and then to 1 case in 2013, and since 2014, no cases have been detected. The impact was estimated at 14.48% ( p = 0.41 ) in 2012 and then at 98.63% ( p < 0.0001 ) after the end of vaccinations in 2013. This survey confirms the effectiveness of the MenAfriVac vaccine in Cameroon as expected by the WHO. The surveillance must be pursued and enhanced to monitor coming immunizations measures with multivalent conjugated vaccines for this changing threat.

Published
2021

9. 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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10. Validation of a New Rapid Detection Test for Detection of Neisseria meningitidis A/C/W/X/Y Antigens in Cerebrospinal Fluid

Author

Ali Elhaj Mahamane, E. Begaud, Aziza Razki, Eva Hong, Yves Germani, Alain Agnememel, Jean-Pierre Lombart, Fati Sidikou, Aude Terrade, Berthe-Marie Njanpop-Lafourcade, Paul O. Verhoeven, Muhamed-Kheir Taha, Cyrille H. Haddar, Bruno Pozzetto, Mireille Dosso, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), BioSpeedia [Paris], Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris] (IP), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Agence de Médecine Préventive, Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES), Institut Pasteur de Bangui, Institut Pasteur du Maroc, Université Jean Monnet [Saint-Étienne] (UJM), Institut Pasteur [Paris], and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)

Subjects
Microbiology (medical), 030231 tropical medicine, Meningitis, Meningococcal, Neisseria meningitidis, rapid diagnostic test, medicine.disease_cause, Sensitivity and Specificity, Rapid detection, cerebrospinal fluid, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Antigen, Positive predicative value, parasitic diseases, Multiplex polymerase chain reaction, medicine, Humans, 030212 general & internal medicine, validation, Antigens, Bacterial, Rapid diagnostic test, business.industry, Bacteriology, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 3. Good health, Africa, France, business, Meningitis
Abstract

International audience; Meningococcal meningitis remains a life-threatening disease worldwide, with high prevalence in the sub-Saharan meningitis belt. A rapid diagnosis is crucial for implementing adapted antimicrobial treatment. We describe the performances of a new immunochromatographic test (MeningoSpeed, BioSpeedia, France) for detecting and grouping Neisseria meningitidis. Cerebrospinal fluids (CSFs) were collected from 5 African countries and France. For the rapid diagnostic test (RDT), the CSF sample was deposited on each of the 3 cassettes for a total volume of 90 μl. The results of the RDT were compared to those of a reference multiplex PCR assay detecting the major serogroups of N. meningitidis on 560 CSF specimens. Five specimens were found uninterpretable by RDT (0.9%). The results of interpretable specimens were as follows: 305 positive and 212 negative samples by both techniques, 14 positive by PCR only, and 24 positive by RDT only (sensitivity, specificity, and positive and negative predictive values of 92.7%, 93.8%, 95.6%, and 89.8%, respectively, with an accuracy of 93.2% and a kappa test of 0.89; P < 0.05). From 319 samples positive by PCR for serogroups A, C, W, X, or Y, the grouping results were concordant for 299 specimens (sensitivity of 93.0%, 74.4%, 98.1%, 100%, and 83.3% for serogroups A, C, W, X, and Y, respectively). The MeningoSpeed RDT exhibited excellent performances for the rapid detection of N. meningitidis antigens. It can be stored at room temperature, requires a minimal amount of CSF, is performed in 15 minutes or less, and is easy to use at bedside.

Published
2020
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11. Emergence of Neisseria meningitidis Serogroup W, Central African Republic, 2015–2016

Author

Jean-Robert Mbecko, Eva Hong, Muhamed-Kheir Taha, Thierry Frank, Jean-Pierre Lombart, Pierre-Alain Rubbo, Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris] (IP), This work was supported by the French Ministry of Foreign Affairs and Institut Pasteur, Bangui, Central African Republic, and Paris, France., and Institut Pasteur [Paris]

Subjects
0301 basic medicine, Microbiology (medical), Male, sub-Saharan Africa, Adolescent, Epidemiology, 030106 microbiology, lcsh:Medicine, Biology, Meningitis, Meningococcal, Neisseria meningitidis, medicine.disease_cause, Serogroup, epidemics, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Meningitis/encephalitis, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, serogroup W, Child, Emergence of Neisseria meningitidis Serogroup W, Central African Republic, 2015–2016, bacteria, Sequence (medicine), Disease surveillance, Neisseria meningitidis serogroup, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], lcsh:R, Dispatch, meningococci, Infant, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 3. Good health, Bacterial Typing Techniques, Central African Republic, Infectious Diseases, Child, Preschool, surveillance, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, meningitis/encephalitis, Meningitis, Multilocus Sequence Typing
Abstract

International audience; We analyzed data from the 2015 and 2016 meningitis epidemic seasons in Central African Republic as part of the national disease surveillance. Of 80 tested specimens, 66 belonged to meningococcal serogroup W. Further analysis found that 97.7% of 44 isolates belonged to the hyperinvasive clonal complex sequence type 11.

Published
2018
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12. Biological Profile of HIV-Positive Patients in Bangui, Central African Republic, in 2017

Author

Jean-Pierre Lombart, Alain Farra, Alexandre Manirakiza, Brice Martial Yambiyo, Yawo Tufa Nyasenu, Rodolphe Mambely-Nzako, Fernand Didier Padou, Pierre-Alain Rubbo, Pulchérie Pelembi, Ferdinand Yapou, Alain Berlioz-Arthaud, and Marie-Joëlle Mandeng

Subjects
Creatinine, medicine.medical_specialty, Leukopenia, business.industry, Human immunodeficiency virus (HIV), Total population, Neutropenia, medicine.disease_cause, medicine.disease, Antiretroviral therapy, chemistry.chemical_compound, chemistry, Biological profile, Internal medicine, medicine, medicine.symptom, business, Viral load
Abstract

Background: The biological profile of HIV-positive patients is essential for diagnosing treatment failure and the prognosis of infection. We determined the virological and immunological profiles and biological anomalies of HIV-positive people on antiretroviral therapy (ART) in Bangui, Central Afri-can Republic. Methods: We conducted an analytical, descriptive study be-tween 4 April and 30 September 2017 of all patients who had received ART for more than 12 months and who attended the Medical Analysis Laboratory of the Institut Pasteur in Bangui for a complete biological work-up, including viral load. A blood sample was taken for quantification of RNA HIV-1, CD4 lymphocytes and blood count in two tubes containing ethylenediamine te-traacetic acid, and another sample was taken in a dry tube for measurement of creatinine and transaminases. Results: The total population comprised 1748 patients, with a mean age of 38.7 years (±14.3; median, 41 years; range, 2 - 79 years); 33.3% of patients were between 40 and 49 years old. Females predo-minated (71.3%), for a sex ratio of 0.4. Immunological failure was observed in 20.2% of patients (CD4 < 200 cells/μL), and 44.5% of patients had a load of RNA HIV-1 ≥ 1000 copies/mL. The main haematological anomalies were anaemia (28.0%), leukopenia (26.7%), neutropenia (42.1%) and lymphopenia (27.2%). Blood creatinine was abnormal in 61.0% of patients, ALAT in 57.0% and ASAT in 66.9%. Conclusion: The abnormalities observed in this study concerned the haematopoietic system, the liver and the kidneys. As other or-gans and systems may be affected, periodic multidisciplinary biological and clinical follow-up is necessary for people living with HIV in order to improve their management.

Published
2018
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13. Trends of HIV Viral Load in Patients under Combined Antiretroviral Treatment in Bangui, Central African Republic

Author

Alexandre Manirakiza, Pierre-Alain Rubbo, Yawo Tufa Nyasenu, Aubin Béré, Gilles Ngaya, Brice Martial Yambiyo, Sandrine Moussa, Pulchérie Pelembi, Jean-Pierre Lombart, Rodolphe Mambely-Nzako, Davy Martial Golongba, Alain Berlioz-Arthaud, Marie-Joëlle Mandeng, Serge Ghislain Djorie, and Alain Farra

Subjects
Cart, medicine.medical_specialty, business.industry, medicine.disease, Virus, Plasma viral load, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Statistical significance, medicine, In patient, business, Prospective cohort study, Viral load
Abstract

Background: The success of antiretroviral therapy requires better virological monitoring. We described the virological profile of patients on combined antiretroviral therapy (cART) for HIV/AIDS in Bangui, Central African Republic (CAR). Methods: In this prospective cohort study of patients who had been on combined antiretroviral therapy treatment (cART) for at least 12 months in Bangui, only one HIV plasma viral load per patient was realized at the Institut Pasteur of Bangui, between April 4th and November 28th, 2017. Sociodemographic and biological data were collected. Blood samples were taken for viral load. The biocentric generic human immunodeficiency virus (HIV) load test was used to quantify a ribonucleic acid (RNA) HIV-1. Data were analyzed with Stata software version 14. Chi-squared test was used to analyse viral load according to sex and age. The level of significance was set at P ≤ 0.05. Results: A total of 3569 patients were recruited, with a mean age of 40 years (median, 42 years; range, 1 - 84), patients aged 40 - 49 predominating (34.2%). The sex ratio was 0.4. No virus was detectable in plasma from 49.2% of patients, while 42.4% had virological failure (viral load, ≥1000 copies/mL) according to WHO criteria. The risk for virological failure decreased with age (P = 0.001) and was higher among females than males (P = 0.001). Conclusions: The rate of virological failure among patients on cART is very high in the CAR, despite the availability of and access to monitoring of HIV plasma viral load in Bangui. Therefore, adherence to treatment should be evaluated and reinforced in Bangui, CAR.

Published
2018
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14. 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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15. Evidence of human leptospirosis cases in a cohort of febrile patients in Bangui, Central African Republic: a retrospective study, 2012–2015

Author

Jean-Pierre Lombart, Davy Martial Golongba, Pierre-Alain Rubbo, Marie-Estelle Soupé-Gilbert, Dominique Girault, Florent Mbombo, Sébastien Breurec, Cyrille Goarant, Emmanuel Nakouné, Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Nouvelle-Calédonie, Université des Antilles et de la Guyane - UFR des sciences médicales (UAG UFR SM), Université des Antilles et de la Guyane (UAG), and This work was supported by the Institut Pasteur International Network (ACIP grant 2012-A22) and Institut Pasteur of Bangui. National surveillance of yellow fever is funded by the WHO.

Subjects
Male, 0301 basic medicine, Serology, Cohort Studies, 0302 clinical medicine, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Direct agglutination test, Child, Aged, 80 and over, Leptospira, Surveillance, Sub-Saharan Africa, biology, Yellow fever, Middle Aged, Jaundice, Leptospirosis, 3. Good health, Central African Republic, Infectious Diseases, Child, Preschool, Female, medicine.symptom, Infection, Research Article, Adult, medicine.medical_specialty, Adolescent, Fever, 030106 microbiology, 030231 tropical medicine, Enzyme-Linked Immunosorbent Assay, Emergence, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, Agglutination Tests, Internal medicine, Yellow Fever, medicine, Humans, lcsh:RC109-216, Aged, Retrospective Studies, Bacteria, Diagnostic Tests, Routine, business.industry, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, Etiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience; BACKGROUND: In spite of a local favorable environment, leptospirosis has never been described in Central African Republic so far mainly because of the weakness of diagnostic tests and differential diagnostic strategy for febrile jaundice cases negative for yellow fever virus. Here we bring a complementary insight to conclusions of Gadia CLB et al. regarding the presence of leptospirosis in Central African Republic in YFV-negative febrile icteric patients.METHODS: Our study included 497 individuals presenting with fever and jaundice but negative for yellow fever infection, retrospectively selected from the national surveillance biobank for yellow fever in Institut Pasteur de Bangui, Central African Republic. A combination of serological (ELISA, agglutination) and molecular biology techniques (quantitative real-time polymerase chain reaction) was used to identify Leptospira or the patient's immune response to the bacteria. Statistical analyses were done using the non parametric Mann-Withney U test with a 5% statistical threshold.RESULTS: ELISA test results showed 46 positive serum samples while 445 were negative and 6 remains equivocal. In addition, the reference microscopic agglutination test for leptospirosis diagnostic confirmed that 7 out of 32 samples tested were positive. Unfortunately, all 497 serum samples tested for leptospirosis were negative using the molecular techniques.CONCLUSIONS: Unlike Gadia et al., we confirmed that leptospirosis is circulating in Central African Republic and therefore may be responsible for some of the unexplained cases of febrile jaundice in the country. Thus, leptospirosis needs to be investigated to improve identification of aetiological pathogens. Our study also suggests a need to improve sample transportation and storage conditions.

Published
2018
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16. Plasma virion reverse transcriptase activity and heat dissociation-boosted p24 assay for HIV load in Burkina Faso, West Africa

Author

Joséphine Braun, François Simon, Gary E Corrigan, Véronique Lemée, Muriel Vray, Jean-Christophe Plantier, Anatole Kafando, Rasmata Ouédraogo-Traoré, and Jean Pierre Lombart

Subjects
Hot Temperature, Immunology, HIV Core Protein p24, Enzyme-Linked Immunosorbent Assay, HIV Infections, Sensitivity and Specificity, Virus, Burkina Faso, Blood plasma, Humans, Immunology and Allergy, biology, Virion, virus diseases, RNA, Viral Load, biology.organism_classification, Nucleotidyltransferase, Virology, HIV Reverse Transcriptase, Reverse transcriptase, Infectious Diseases, Lentivirus, Feasibility Studies, RNA, Viral, Viral disease, Viral load
Abstract

In resource-limited settings, the requirement for inexpensive, easy-to-perform viral load monitoring has increased with greater antiretroviral drug availability.To evaluate feasibility, in Burkina Faso, of a simple assay for plasma HIV reverse transcriptase (RT) activity quantification compared to heat dissociation-boosted (HDB) p24 antigen and RNA-based quantifications in plasma samples from HIV-infected patients.: Plasma viraemia was quantified by RT activity, HDB-p24 and RNA copies in 84 samples from 70 HIV-1 group M-infected patients (82% non-B subtype, 93% treatment naive), including serial samples from nine patients.RT activity detected 86% of plasma samples containing measurable RNA copies; corresponding to 0, 93 and 100% of samples with 1.7-4.0 log(10), 4.1-4.8 log(10) and 4.9-6.7 log(10) RNA copies/ml, respectively. HDB-p24 detected 77% of plasma samples containing measurable RNA copies; corresponding to 27, 80 and 86% of samples with 1.7-4.0 log(10), 4.1-4.8 log(10) and 4.9-6.7 log(10) RNA copies/ml, respectively. Measurement error based on one-way analysis of variance between RT activity and HDB-p24 values with RNA copies showed good agreement with RT activity (ME,10%), however poorer agreement was obtained with HDB-p24 values (ME,10%). Patient follow up showed a similar pattern of viraemia with RNA and RT activity assays.Field trials in Burkina Faso support the practical use of plasma RT activity assay as an affordable alternative for HIV viral load determination in regions where RNA detection remains difficult to perform. HDB-p24 use requires further evaluation before being considered as an alternative method in African HIV-infected patient follow up.

Published
2005
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17. 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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18. Epidemiologic pattern of meningococcal meningitis in northern Cameroon in 2007–2010: contribution of PCR-enhanced surveillance

Author

Pascal Boisier, Denis Massenet, Bouba Gake, Clifford Ebong, François Azowé, Jean-Pierre Lombart, and Jacques Birguel

Subjects
Biology, Meningitis, Meningococcal, Neisseria meningitidis, medicine.disease_cause, Microbiology, Polymerase Chain Reaction, law.invention, Haemophilus influenzae, law, Streptococcus pneumoniae, medicine, Humans, Cameroon, Polymerase chain reaction, Cerebrospinal Fluid, Public Health, Environmental and Occupational Health, General Medicine, medicine.disease, Virology, Latex fixation test, Bacterial Typing Techniques, Infectious Diseases, Gram staining, Multilocus sequence typing, Parasitology, Original Article, Meningitis, Sentinel Surveillance
Abstract

Monitoring acute bacterial meningitis in northern Cameroon.Health professionals collected cerebrospinal fluid (CSF) specimens from patients presenting with clinical symptoms of meningitis. Specimens were tested using gram stain, latex agglutination test, and culture. A PCR assay completed the diagnostic testing. Multilocus sequence typing (MLST) was performed on some Neisseria meningitidis (Nm) isolates.From 2007 through 2010, of the 1429 CSF specimens tested, 292 (20·4%) were positive, either for Nm (205), Streptococcus pneumoniae (Sp) (57), or Haemophilus influenzae (Hi) (30). From 2007 through 2009, the serogroup W135 represented 98·8% of 164 case isolates. Until 2008, most serogroup W135 isolates presented the sequence-type ST-2881 usually associated with sporadic cases. Since 2009, the ST-11 (an epidemic-associated clone) became predominant, although no epidemic occurred. Serogroup A ST-7 was observed in 2010 and caused a localized epidemic. Using the detection PCR on turbid CSF, a 2·7-fold increase in cases with etiologic diagnosis was obtained, compared to culture. All tested meningococcal isolates (42) were susceptible to ampicillin, chloramphenicol, and cefotaxim.Resurgence of serogroup A and recent increase in ST-11 among serogroup W135 isolates were worrying when considered with the epidemic wave of serogroup A meningitis, which affected neighboring countries and the serogroup W135 epidemic in Niger in 2009-2010.

Published
2013

19. Les enfants présentant un retard de croissance présentent une colonisation ectopique de l'intestin grêle par des bactéries buccales, qui provoquent une malabsorption des lipides dans des modèles expérimentaux

Author

Vonaesch, P., Araújo, J. R., Gody, J. C., Mbecko, J. R., Sanke, H., Andrianonimiadana, L., Naharimanananirina, T., Ningatoloum, S. N., Vondo, S. S., Gondje, P. B., Rodriguez-Pozo, A., Rakotondrainipiana, M., Kandou, K. J. E., Nestoret, A., Kapel, N., Djorie, S. G., Finlay, B. B., Wegener Parfrey, L., Collard, J. M., Randremanana, R. V., Sansonetti, P. J., Afribiota Investigators, 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
Mouth, Multidisciplinary, Bacteria, lipid malabsorption, [SDV]Life Sciences [q-bio], [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Models, Theoretical, Lipid Metabolism, Lipids, Gastrointestinal Microbiome, Mice, Cross-Sectional Studies, Malabsorption Syndromes, stunted child growth, Child, Preschool, Intestine, Small, environmental enteric dysfunction, low-grade inflammation, Animals, Humans, Leukocyte L1 Antigen Complex, small intestine, Growth Disorders
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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20. 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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21. 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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22. Immunoglobulin recognition of fecal bacteria in stunted and non-stunted children: findings from the Afribiota study

Author

Pascale Vonaesch, Nathalie Kapel, Michel Dede, André Rodriguez-Pozo, Amee R. Manges, Alison Nestoret, Afribiota Investigators, Azimdine Habib, B. Brett Finlay, Philippe J. Sansonetti, Kelsey E. Huus, Jean-Marc Collard, University of British Columbia (UBC), Pathogénie microbienne moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité des Helminthiases [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This research was supported by grants from the Canadian Institutes of Health Research (CIHR), the Bill and Melinda Gates Foundation and the Total Foundation. Work in PJS’s laboratory is supported by grants from the European Research Commission. Work in BBF’s laboratory was supported by grants from CIHR. KEH was supported by a CIHR Vanier Graduate scholarship, a Killam fellowship and a Four-Year Fellowship. PV was supported by a Swiss National Science Foundation Early and Advanced Postdoctoral Fellowship as well as Return Grant, a Roux-Cantarini Postdoctoral Fellowship and a fellowship from L’Oréal-UNESCO for Women in Science., We are deeply grateful to the children and families who participated in Afribiota and to the large team of community health workers, nurses, doctors, technicians, administrators, and others without whom this study would not have been possible. We would like to thank Andy Johnson and Justin Wong at UBC for their invaluable assistance in the flow cytometry facility, as well as Lisa Thorson and Adrian Carney for their help in arranging and receiving sample shipments at the Michael Smith Laboratories. We are further grateful to Vincent Guillemot and Antoine Menard at the Institut Pasteur for their advice on biostatistic analysis and to the members of the Sansonetti research group and the Finlay laboratory for their support and feedback., The Afribiota Investigators are: (in alphabetical order): Emilson Jean Andriatahirintsoa, Alexandra Bastaraud, Jean-Marc Collard, Maria Doria, Serge Ghislain Djorie, Aurélie Etienne, Brett Finlay, Tamara Giles-Vernick, Jean-Chrysostome Gody, Bolmbaye Privat Godje, Ionela Gouandjika-Vassilache, Francis Allan Hunald, Nathalie Kapel, Jean-Pierre Lombart, Alexandre Manirakiza, Synthia Nazita Nigatoloum, Lisette Raharimalala, Maheninasy Rakotondrainipiana, Rindra Randremanana, Harifetra Mamy Richard Randriamizao, Frédérique Randrianirina, Annick Robinson, Pierre-Alain Rubbo, Philippe Sansonetti, Laura Schaeffer, Inès Vigan-Womas, Sonia Sandrine Vondo, Pascale Vonaesch & Laura Wegener-Parfrey, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Collège de France - Chaire Microbiologie et Maladies infectieuses

Subjects
Male, Immunoglobulin A, medicine.disease_cause, Immunoglobulin G, Feces, Medical microbiology, RNA, Ribosomal, 16S, Growth Disorders, 2. Zero hunger, Stunting, 0303 health sciences, Sub-Saharan Africa, biology, Campylobacter, 3. Good health, Central African Republic, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Child, Preschool, Environmental Enteric dysfunction, lcsh:QR100-130, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Microbiology (medical), medicine.medical_specialty, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Microbiology, lcsh:Microbial ecology, 03 medical and health sciences, Haemophilus, Madagascar, medicine, Humans, Microbiome, 030304 developmental biology, Bacteria, 030306 microbiology, Research, Malnutrition, Undernutrition, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, medicine.disease, Fecal coliform, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Background Child undernutrition is a global health issue that is associated with poor sanitation and an altered intestinal microbiota. Immunoglobulin (Ig) A mediates host-microbial homeostasis in the intestine, and acutely undernourished children have been shown to have altered IgA recognition of the fecal microbiota. We sought to determine whether chronic undernutrition (stunting) or intestinal inflammation were associated with antibody recognition of the microbiota using two geographically distinct populations from the Afribiota project. Fecal bacteria from 200 children between 2 and 5 years old in Antananarivo, Madagascar, and Bangui, Central African Republic (CAR), were sorted into IgA-positive (IgA+) and IgA-negative (IgA−) populations by flow cytometry and subsequently characterized by 16S rRNA gene sequencing to determine IgA-bacterial targeting. We additionally measured IgG+ fecal bacteria by flow cytometry in a subset of 75 children. Results Stunted children (height-for-age z-score ≤ −2) had a greater proportion of IgA+ bacteria in the fecal microbiota compared to non-stunted controls. This trend was consistent in both countries, despite the higher overall IgA-targeting of the microbiota in Madagascar, but lost significance in each country individually. Two of the most highly IgA-recognized bacteria regardless of nutritional status were Campylobacter (in CAR) and Haemophilus (in both countries), both of which were previously shown to be more abundant in stunted children; however, there was no association between IgA-targeting of these bacteria and either stunting or inflammatory markers. IgG-bound intestinal bacteria were rare in both stunted and non-stunted children, similar to levels observed in healthy populations. Conclusions Undernourished children carry a high load of intestinal pathogens and pathobionts. Our data suggest that stunted children have a greater proportion of IgA-recognized fecal bacteria. We moreover identify two putative pathobionts, Haemophilus and Campylobacter, that are broadly targeted by intestinal IgA. This study furthers our understanding of host-microbiota interactions in undernutrition and identifies immune-recognized microbes for future study.

Published
2020
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