37 results on '"Rindra Vatosoa Randremanana"'
Search Results
2. Three‐arm clinical trial of improved flour targeting intestinal microbiota (MALINEA)
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Muriel Vray, Laura Tondeur, Boris G. Hedible, Rindra Vatosoa Randremanana, Alexandre Manirakiza, Ramatoulaye Hamidou Lazoumar, Cassandre Van Platen, Antonio Vargas, André Briend, and Ronan Jambou
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Central African Republic ,Madagascar ,malnutrition ,microbiota ,Niger ,prebiotic ,Pediatrics ,RJ1-570 ,Gynecology and obstetrics ,RG1-991 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract The main objective of this project was to compare in the field conditions two strategies of re‐nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three‐arm, open‐label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo‐oligosaccharides (6 g/day if age ≥12 months and 4 g if age
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- 2024
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3. Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT)
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Suzanna C Francis, Tania Crucitti, Lindi Masson, Emma Michele Harding-Esch, Sarah Bernays, Chido Dziva Chikwari, Katharina Kranzer, Tsitsi Bandason, Karen Webb, Katherine Gill, Tanya Pidwell, David Anderson, Nicola Thomas, Janneke H H M van de Wijgert, Ayako Honda, Aina Harimanana, Elise Smith, Edina Sinanovic, Constance R S Mackworth-Young, Mutsawashe Chisenga, Eneyi Kpokiri, Linda Gail Bekker, Bich-Tram Huynh, Dimitri Rasoloson, Fezile Khumalo, Micaela Lurie, Phumla Radebe, Bahiah Meyer, Lyndon Mungur, Ashley Uys, Darryl Uys, Monalisa Manhanzva, Tinashe Mwaturura, Camille Fortas, Karabo Mahlangu, Rindra Vatosoa Randremanana, Stephanie Ramboarina, Théodora Mayouya Gamana, Reziky Mangahasimbola, Fatime Ramla Tanko, Jo-Anne Passmore, Conita Lombard, Celia Mehou-Loko, Yacoeb Ganief, Rezeen Daniels, Anda Madikida, Joseph F Chipanga, Patricia Makunyire, Felicia Mhangami, Jayjay Karumazondo, Jason Naidoo, Saberi Marias, Solange Rasoanandrianina, Dimitri Ravoavison, Patrick Andry Rakotonirina, Andrilaina Razakarivony, Hantamalala Randria, Alphonsine Rahantarimalala, Lala Rafetrarivony, Barivola Bernardson, Tsiry Rasolofomanana, Norohasina Randriamange, Antsanirina Nomenjanahary, Laurah Rabarisoa, Sahara Raveloson, Laura Randrianantenaina, Hanitratiavina Rakotonindriana, Fenosoa Voanarivolalao, Vaomalala Ranarinandra, and Farai Machinga
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Medicine - Abstract
Introduction A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test—called the Genital InFlammation Test (GIFT)—for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care.Methods and analysis We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical (‘diagnostic study’) and a qualitative, modelling and economic (‘an integration into care study’) part. The diagnostic study aims to evaluate GIFT’s performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms.Ethics and dissemination Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d’Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484).Trial registration number NCT05723484.
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- 2024
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4. Bubonic plague: can the size of buboes be accurately and consistently measured with a digital calliper?
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Josephine Bourner, Ravaka Randriamparany, Tsinjo Fehizoro Rasoanaivo, Emmanuelle Denis, Rindra Vatosoa Randremanana, Michel Vaillant, Alex Paddy Salam, Bronner P. Gonçalves, and Piero Olliaro
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Medicine (General) ,R5-920 - Abstract
Abstract Introduction Conducting clinical research on treatments for emerging infectious diseases is often complicated by methodological challenges, such as the identification of appropriate outcome measures to assess treatment response and the lack of validated instruments available to measure patient outcomes. In bubonic plague, some studies have assessed bubo size as an indicator of treatment success, a measure widely assumed to be indicative of recovery. Evaluating this outcome however is challenging as there is no validated method for measuring bubo size. The aim of this study is to assess the accuracy and inter- and intra-rater agreement of artificial bubo measurements using a digital calliper to understand whether a calliper is an appropriate measurement instrument to assess this outcome. Methods Study technicians measured 14 artificial buboes made from silicone overlaid with artificial silicone skin sheets over the course of two training sessions. Each artificial bubo was measured by each study technician once per training session, following a Standard Operating Procedure. The objectives of this study are to (i) evaluate the accuracy of individual measurements against the true size of the artificial bubo when using a digital calliper, (ii) understand whether the characteristics of the artificial bubo influence measurement accuracy and (iii) evaluate inter- and intra-rater measurement agreement. Results In total, 14 artificial buboes ranging from 52.7 to 121.6 mm in size were measured by 57 raters, generating 698 measurements recorded across two training sessions. Raters generally over-estimated the size of the artificial bubo. The median percentage difference between the measured and actual bubo size was 13%. Measurement accuracy and intra-rater agreement decreased as the size of the bubo decreased. Three quarters of all measurements had a maximum of 25% difference from another measurement of the same artificial bubo. Inter-rater agreement did not vary with density, size or presence of oedema of the artificial bubo. Conclusions The results of this study demonstrate the challenges for both individual and multiple raters to repeatedly generate consistent and accurate measurements of the same artificial buboes with a digital calliper.
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- 2023
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5. Socio-ecological risk factors associated with human flea infestations of rural household in plague-endemic areas of Madagascar.
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Adélaïde Miarinjara, Annick Onimalala Raveloson, Stephen Gilbert Mugel, Nick An, Andry Andriamiadanarivo, Minoarisoa Esther Rajerison, Rindra Vatosoa Randremanana, Romain Girod, and Thomas Robert Gillespie
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Plague is a flea-borne fatal disease caused by the bacterium Yersinia pestis, which persists in rural Madagascar. Although fleas parasitizing rats are considered the primary vectors of Y. pestis, the human flea, Pulex irritans, is abundant in human habitations in Madagascar, and has been found naturally infected by the plague bacterium during outbreaks. While P. irritans may therefore play a role in plague transmission if present in plague endemic areas, the factors associated with infestation and human exposure within such regions are little explored. To determine the socio-ecological risk factors associated with P. irritans infestation in rural households in plague-endemic areas of Madagascar, we used a mixed-methods approach, integrating results from P. irritans sampling, a household survey instrument, and an observational checklist. Using previously published vectorial capacity data, the minimal P. irritans index required for interhuman bubonic plague transmission was modeled to determine whether household infestations were enough to pose a plague transmission risk. Socio-ecological risk factors associated with a high P. irritans index were then identified for enrolled households using generalized linear models. Household flea abundance was also modeled using the same set of predictors. A high P. irritans index occurred in approximately one third of households and was primarily associated with having a traditional dirt floor covered with a plant fiber mat. Interventions targeting home improvement and livestock housing management may alleviate flea abundance and plague risk in rural villages experiencing high P. irritans infestation. As plague-control resources are limited in developing countries such as Madagascar, identifying the household parameters and human behaviors favoring flea abundance, such as those identified in this study, are key to developing preventive measures that can be implemented at the community level.
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- 2024
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6. Determinants of COVID-19-related knowledge and disrupted habits during epidemic waves among women of childbearing age in urban and rural areas of the Malagasy Middle East
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Sitraka Rakotosamimanana, Reziky Tiandraza Mangahasimbola, Rila Ratovoson, and Rindra Vatosoa Randremanana
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Madagascar ,COVID-19 ,Maternal and child health ,Knowledge ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background With regard to the coronavirus disease (COVID-19) pandemic in Madagascar, little is known about the knowledge, the perceptions and the impacts of this disease on women of childbearing age. People’s knowledge of COVID-19 can have an impact on their attitudes towards seeking care. The aim of the current study is to determine the knowledge of COVID-19 and associated determinants among women of childbearing age in Moramanga. Methods A cross-sectional study based on questionnaire administration was used among women of childbearing age. Data collection was conducted from August to October 2021. A scoring method was applied to evaluate their knowledge level and perceptions about COVID-19 and its impacts on their lives. A binary stepwise logistic regression was performed to determine the sociodemographic determinants of their knowledge level about COVID-19. Results A total of 885 women of childbearing age from urban and rural Moramanga areas were interviewed. Approximately 49.8% (441/885) lived in urban areas, and 50.2% (444/885) lived in rural areas. Approximately 35.3% (322/885) of the participants had a good level of knowledge of COVID-19. Multivariate analysis showed that the probability of having a good level of knowledge of COVID-19 had a significant statistical association (p value
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- 2023
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7. Asymptomatic infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis among women in low- and middle-income countries: A systematic review and meta-analysis.
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Camille Fortas, Elisabeth Delarocque-Astagneau, Rindra Vatosoa Randremanana, Tania Crucitti, and Bich-Tram Huynh
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Public aspects of medicine ,RA1-1270 - Abstract
Syndromic management of sexually transmitted infections (STIs) is common in settings with limited access to diagnostic testing. However, this approach does not capture asymptomatic STIs. Untreated asymptomatic infections may result in serious complications and sequelae in women. We aimed to estimate the proportion and the prevalence of asymptomatic Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections among women in low- and middle-income countries. We searched Medline, Scopus, and Web of Science for articles published between 2000 and 2022. We used random effect models to compute the proportion and prevalence estimates and performed sub-group analysis. We evaluated the quality of each article using the Appraisal tool for Cross-Sectional Studies and performed sensitivity analyses. This study was registered with PROSPERO, CRD42022286673. Forty-eight eligible studies were included. The proportion of asymptomatic CT, NG, and TV infections were: 60.7% [95% Confidence Interval (CI): 50.4; 70.5], 53.3% [37.1; 69.1], and 56.9% [44.6; 68.9], respectively. The proportion of women with asymptomatic infections was the highest in Africa for the three pathogens. The pooled prevalence of asymptomatic CT, NG, and TV infection was 4.70 per 100 women [95%CI: 3.39; 6.20], 3.11 [1.34; 5.54], and 5.98 [3.46; 9.12], respectively. More than half of the women infected by CT, NG, or TV were asymptomatic. To avoid undiagnosed and untreated asymptomatic infections leading to complications, alternative approaches to syndromic management urgently need to be considered.
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- 2024
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8. SARS-CoV-2 Neutralizing Antibodies in Three African Countries Following Multiple Distinct Immune Challenges
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Diary Juliannie Ny Mioramalala, Rila Ratovoson, Paul Alain Tagnouokam-Ngoupo, Hermine Abessolo Abessolo, Joseph Marie Mindimi Nkodo, Georges Bouting Mayaka, Pierre Claude Tsoungui Atangana, Fanirisoa Randrianarisaona, Pulchérie Pélembi, Romaric Nzoumbou-Boko, Cathy Sandra Goimelle Coti-Reckoundji, Alexandre Manirakiza, Anjanirina Rahantamalala, Rindra Vatosoa Randremanana, Mathurin Cyrille Tejiokem, and Matthieu Schoenhals
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neutralizing antibodies ,natural infection ,vaccination ,healthcare worker ,COVID-19 ,Medicine - Abstract
Background: The COVID-19 pandemic has affected Madagascar, Cameroon, and the Central African Republic (CAR), with each experiencing multiple waves by mid-2022. This study aimed to evaluate immunity against SARS-CoV-2 strains Wuhan (W) and BA.2 (BA.2) among healthcare workers (HCWs) in these countries, focusing on vaccination and natural infection effects. Methods: HCWs’ serum samples were analyzed for neutralizing antibodies (nAbs) against W and BA.2 variants, with statistical analyses comparing responses between countries and vaccination statuses. Results: Madagascar showed significantly higher nAb titers against both strains compared to CAR and Cameroon. Vaccination notably increased nAb levels against W by 2.6-fold in CAR and 1.8-fold in Madagascar, and against BA.2 by 1.6-fold in Madagascar and 1.5-fold in CAR. However, in Cameroon, there was no significant difference in nAb levels between vaccinated and unvaccinated groups. Conclusion: This study highlights the complex relationship between natural and vaccine-induced immunity, emphasizing the importance of assessing immunity in regions with varied epidemic experiences and low vaccination rates.
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- 2024
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9. An Entomological Investigation during a Recent Rift Valley Fever Epizootic/Epidemic Reveals New Aspects of the Vectorial Transmission of the Virus in Madagascar
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Luciano Michaël Tantely, Soa Fy Andriamandimby, Maminirina Fidelis Ambinintsoa, Manou Rominah Raharinirina, Jean Théophile Rafisandratantsoa, Jean-Pierre Ravalohery, Aina Harimanana, Nirina Nantenaina Ranoelison, Judickaelle Irinantenaina, Miamina Fidy Ankasitrahana, Dany Bakoly Ranoaritiana, Laurence Randrianasolo, Rindra Vatosoa Randremanana, Vincent Lacoste, Philippe Dussart, and Romain Girod
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Rift Valley fever ,mosquito biology ,outbreak ,virus detection ,Madagascar ,Medicine - Abstract
A Rift Valley fever (RVF) outbreak occurred in at least five regions of Madagascar in 2021. The aim of this study was to provide an overview of the richness, abundance, ecology, and trophic preferences of mosquitoes in the Mananjary district and to investigate the distribution of mosquitoes that were RT-PCR-positive for RVFV. Three localities were prospected from 26 April to 4 May 2021, using light traps, BG-Sentinel traps baited with an artificial human odor, Muirhead-Thomson pit traps, and indoor pyrethroid spray catches. A total of 2806 mosquitoes belonging to at least 26 species were collected. Of 512 monospecific pools of mosquitoes tested with real-time RT-PCR, RVFV was detected in 37 pools representing 10 mosquito species. The RVFV-positive species were as follows: Aedes albopictus, Ae. argenteopunctatus, Anopheles coustani, An. gambiae s.l., An. mascarensis, An. squamosus/cydippis, Culex antennatus, Cx. decens, Cx. Tritaeniorhynchus, and Uranotaenia spp. Of the 450 tested engorged females, 78.7% had taken a blood meal on humans, 92.9% on cattle, and 71.6% had taken mixed (human–cattle) blood meals. This investigation suggests the potential role of mosquitoes in RVFV transmission within this epizootic/epidemic context and that the human populations at the three study sites were highly exposed to mosquitoes. Therefore, the use of impregnated mosquito nets as an appropriate prevention method is recommended.
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- 2024
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10. The Re-Emergence of Rift Valley Fever in Mananjary District, Madagascar in 2021: A Call for Action
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Aina Nirina Harimanana, Soa Fy Andriamandimby, Dany Bakoly Ranoaritiana, Laurence Randrianasolo, Judickaelle Irinantenaina, Nirina Nantenaina Ranoelison, Jean Théophile Rafisandrantatsoa, Miamina Fidy Ankasitrahana, Antso Hasina Raherinandrasana, Manuela Vololoniaina Andriamahatana, Michael Luciano Tantely, Romain Girod, Philippe Dussart, Vincent Lacoste, and Rindra Vatosoa Randremanana
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cattle ,disease outbreaks ,humans ,Madagascar ,One Health approach ,rift valley fever ,Medicine - Abstract
An epizootic of rift valley fever (RVF) was suspected on 21 February 2021 in various districts of Madagascar, with a lab confirmation on 1 April 2021. A cross-sectional survey aiming to detect cases of RVF in humans and to study the circulation of rift valley fever virus (RVFV) in animals was conducted from 22 April to 4 May 2021 in the district of Mananjary. Blood samples from cattle and humans were tested using serological and molecular techniques. In cattle, the circulation of RVFV was confirmed between 5 February and 4 May 2021. The positivity rates of anti-RVFV IgG and IgM were 60% and 40%, respectively. In humans, the circulation of RVFV was observed from 1 April to 5 May 2021. The positivity rate of RVFV was estimated to be 11.7% by combining the results of the molecular and serological approaches. Of the 103 individuals who agreed to participate in the survey, 3 were determined to be positive by RT-PCR, and 10 had anti-RVFV IgM. Among them, one was positive for both. Given that previous studies have reported the circulation of RVFV during inter-epidemic periods and the occurrence of outbreaks due to imported RVFV in Madagascar, our findings suggest the importance of strengthening RVF surveillance from a “One Health” perspective by conducting syndromic and risk-based surveillance at the national and regional levels.
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- 2024
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11. Linear epitope mapping of the humoral response against SARS-CoV-2 in two independent African cohorts
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Inès Vigan-Womas, Jean-Louis Spadoni, Thomas Poiret, Fabien Taïeb, Fanirisoa Randrianarisaona, Rokhaya Faye, Adji Astou Mbow, Aboubacry Gaye, Ndongo Dia, Cheikh Loucoubar, Diary Juliannie Ny Mioramalala, Rila Ratovoson, Rindra Vatosoa Randremanana, Amadou Alpha Sall, Moussa Seydi, Josselin Noirel, Gabriel Moreau, Arnaud Simon, Pavlo Holenya, Jean-Philippe Meyniel, Jean-François Zagury, and Matthieu Schoenhals
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Medicine ,Science - Abstract
Abstract Profiling of the antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in African populations is scarce. Here, we performed a detailed IgM and IgG epitope mapping study against 487 peptides covering SARS-CoV-2 wild-type structural proteins. A panel of 41 pre-pandemic and 82 COVID-19 RT-PCR confirmed sera from Madagascar and Senegal were used. We found that the main 36 immunodominant linear epitopes identified were (i) similar in both countries, (ii) distributed mainly in the Spike and the Nucleocapsid proteins, (iii) located outside the RBD and NTD regions where most of the reported SARS-CoV-2 variant mutations occur, and (iv) identical to those reported in European, North American, and Asian studies. Within the severe group, antibody levels were inversely correlated with the viral load. This first antibody epitope mapping study performed in patients from two African countries may be helpful to guide rational peptide-based diagnostic assays or vaccine development.
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- 2023
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12. Factors associated with anaemia among preschool- age children in underprivileged neighbourhoods in Antananarivo, Madagascar
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Mirella Malala Randrianarisoa, Maheninasy Rakotondrainipiana, Ravaka Randriamparany, Prisca Vega Andriantsalama, Anjasoa Randrianarijaona, Azimdine Habib, Annick Robinson, Lisette Raharimalala, Francis Allen Hunald, Aurélie Etienne, Jean-Marc Collard, Frédérique Randrianirina, Robert Barouki, Clement Pontoizeau, Alison Nestoret, Nathalie Kapel, Philippe Sansonetti, Pascale Vonaesch, and Rindra Vatosoa Randremanana
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Anaemia ,Factors ,Underprivileged neighbourhoods ,Children ,Antananarivo ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Anaemia occurs in children when the haemoglobin level in the blood is less than the normal (11 g/dL), the consequence is the decrease of oxygen quantity in the tissues. It is a prevalent public health problem in many low-income countries, including Madagascar, and data on risk factors are lacking. We used existing data collected within the pathophysiology of environmental enteric dysfunction (EED) in Madagascar and the Central African Republic project (AFRIBIOTA project) conducted in underprivileged neighbourhoods of Antananarivo to investigate the factors associated with anaemia in children 24 to 59 months of age. Methods Children included in the AFRIBIOTA project in Antananarivo for whom data on haemoglobin and ferritin concentrations were available were included in the study. Logistic regression modelling was performed to identify factors associated with anaemia. Results Of the 414 children included in this data analysis, 24.4% were found to suffer from anaemia. We found that older children (adjusted OR: 0.95; 95% CI: 0.93–0.98) were less likely to have anaemia. Those with iron deficiency (adjusted OR: 6.1; 95% CI: 3.4–11.1) and those with a high level of faecal calprotectin (adjusted OR: 2.5; 95% CI: 1.4–4.4) were more likely to have anaemia than controls. Conclusions To reduce anaemia in the children in this underprivileged area, more emphasis should be given to national strategies that improve children’s dietary quality and micronutrient intake. Furthermore, existing measures should be broadened to include measures to reduce infectious disease burden.
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- 2022
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13. Factors Associated with Carriage of Enteropathogenic and Non-Enteropathogenic Viruses: A Reanalysis of Matched Case-Control Data from the AFRIBIOTA Site in Antananarivo, Madagascar
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Iony Manitra Razanajatovo, Lova Andrianomiadana, Azimdine Habib, Mirella Malala Randrianarisoa, Helisoa Razafimanjato, Maheninasy Rakotondrainipiana, Prisca Andriantsalama, Ravaka Randriamparany, Soa Fy Andriamandimby, Pascale Vonaesch, Philippe Jean Sansonetti, Vincent Lacoste, Rindra Vatosoa Randremanana, Jean-Marc Collard, Jean-Michel Heraud, and on behalf of the Afribiota Investigators
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enteric viruses ,stunting ,Madagascar ,Africa ,Medicine - Abstract
Environmental Enteric Dysfunction (EED) is an associate driver of stunting in poor settings, and intestinal infections indirectly contribute to the pathophysiology underlying EED. Our work aimed at assessing whether enteric viral carriage is determinant to stunting. A total of 464 healthy and asymptomatic children, aged 2 to 5 years, were recruited, and classified as non-stunted, moderately stunted, or severely stunted. Among the recruited children, 329 stool samples were obtained and screened for enteric and non-enteric viruses by real-time polymerase chain reaction. We statistically tested for the associations between enteric viral and potential risk factors. Approximately 51.7% of the stool samples were positive for at least one virus and 40.7% were positive for non-enteric adenoviruses. No statistical difference was observed between virus prevalence and the growth status of the children. We did not find any statistically significant association between viral infection and most of the socio-demographic risk factors studied, except for having an inadequate food quality score or an over-nourished mother. In addition, being positive for Ascaris lumbricoides was identified as a protective factor against viral infection. In conclusion, we did not find evidence of a direct link between stunting and enteropathogenic viral carriage in our population.
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- 2023
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14. Influence of Sociospatial determinants on knowledge, attitudes and practices related to the plague in a population living in endemic areas in the central highlands, Madagascar
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Sitraka Rakotosamimanana, Feno Jacob Rakotoarimanana, Vaomalala Raharimanga, François Taglioni, Josélyne Ramamonjisoa, Rindra Vatosoa Randremanana, Minoarisoa Rajerison, and Fanjasoa Rakotomanana
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Plague ,Madagascar ,Central highlands ,KAP scores ,Sociospatial determinants ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Plague is endemic to the central highlands of Madagascar. Sporadic human cases or outbreaks can occur annually in these areas. In Madagascar, the associations between endemicity and the knowledge, attitudes and practices (KAP) of the population with regard to this disease remain poorly documented. The aim of this study was to assess KAP related to plague among the population living in the central highlands. Methods A cross-sectional survey was conducted in the general population from June to August 2017. Based on the reported cases of plague between 2006 and 2015 in two central highland districts, a KAP questionnaire was administered in the population. Based on the proportion of correct answers provided by respondents, KAP scores were classified into three KAP categories: low (< Mean - SD), medium (Mean ± SD) and good (> Mean + SD). Multivariate analyses were performed to determine the associations between population KAP scores related to plague and sociodemographic and epidemiological factors. In addition, individual interviews and focus groups with health professionals were conducted to assess plague perception. Results A total of 597 individuals participated in the survey; 20% (n = 119) had a good KAP score, 62% (n = 370) a medium KAP score and 18% (n = 108) a low KAP score. Among the 119 respondents with good KAP scores, 80% (n = 95) resided in Ambositra district, and 20% (n = 24) resided in Tsiroanomandidy district. According to the health professionals in the two districts, populations in endemic areas are well aware of the plague. There were significant associations (p
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- 2021
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15. Changes in Systemic Regulatory T Cells, Effector T Cells, and Monocyte Populations Associated With Early-Life Stunting
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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
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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.
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- 2022
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16. High prevalence of small intestine bacteria overgrowth and asymptomatic carriage of enteric pathogens in stunted children in Antananarivo, Madagascar.
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Jean-Marc Collard, Lova Andrianonimiadana, Azimdine Habib, Maheninasy Rakotondrainipiana, Prisca Andriantsalama, Ravaka Randriamparany, M A N Rabenandrasana, François-Xavier Weill, Nathalie Sauvonnet, Rindra Vatosoa Randremanana, Vincent Guillemot, Pascale Vonaesch, Philippe J Sansonetti, and Afribiota Investigators
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Environmental Enteric Dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries and is also associated with poor sanitation and certain gut infections possibly resulting in an abnormal gut microbiota, small intestinal bacterial overgrowth (SIBO) and stunting. We investigated bacterial pathogen exposure in stunted and non-stunted children in Antananarivo, Madagascar by collecting fecal samples from 464 children (96 severely stunted, 104 moderately stunted and 264 non-stunted) and the prevalence of SIBO in 109 duodenal aspirates from stunted children (61 from severely stunted and 48 from moderately stunted children). SIBO assessed by both aerobic and anaerobic plating techniques was very high: 85.3% when selecting a threshold of ≥105 CFU/ml of bacteria in the upper intestinal aspirates. Moreover, 58.7% of the children showed more than 106 bacteria/ml in these aspirates. The most prevalent cultivated genera recovered were Streptococcus, Neisseria, Staphylococcus, Rothia, Haemophilus, Pantoea and Branhamella. Feces screening by qPCR showed a high prevalence of bacterial enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, such as Shigella spp., enterotoxigenic Escherichia coli, enteropathogenic E. coli and enteroaggregative E. coli. These pathogens were detected at a similar rate in stunted children and controls, all showing no sign of severe diarrhea the day of inclusion but both living in a highly contaminated environment (slum-dwelling). Interestingly Shigella spp. was the most prevalent enteropathogen found in this study (83.3%) without overrepresentation in stunted children.
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- 2022
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17. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Rindra Vatosoa Randremanana, Mihaja Raberahona, Mamy Jean de Dieu Randria, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Agathe Legrand, Tsinjo Fehizoro Rasoanaivo, Ravaka Randriamparany, Théodora Mayouya-Gamana, Reziky Mangahasimbola, Josie Bourner, Alex Salam, Annelies Gillesen, Tansy Edwards, Matthieu Schoenhals, Laurence Baril, Peter Horby, and Piero Olliaro
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Plague ,Bubonic plague ,Pneumonic plague ,Streptomycin ,Ciprofloxacin ,Medicine (General) ,R5-920 - Abstract
Abstract Background Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides. Methods A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague ‘seasons’. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11. Discussion If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022. Trial registration ClinicalTrials.gov NCT04110340 . Registered on 1 October 2019
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- 2020
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18. The impact of COVID-19 on clinical research for Neglected Tropical Diseases (NTDs): A case study of bubonic plague.
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Tsinjo Fehizoro Rasoanaivo, Josephine Bourner, Ravaka Niaina Randriamparany, Théodora Mayouya Gamana, Voahangy Andrianaivoarimanana, Mily Harijaona Raherivelo, Harivelo Randriamampionona, Minoarisoa Rajerison, Mihaja Raberahona, Alex Paddy Salam, Tansy Edwards, Piero L Olliaro, and Rindra Vatosoa Randremanana
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundAmong the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue.MethodsTo understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron'I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment.ResultsDuring the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases.DiscussionCOVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.
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- 2021
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19. Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa
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Pascale Vonaesch, Munir Winkel, Nathalie Kapel, Alison Nestoret, Laurence Barbot-Trystram, Clément Pontoizeau, Robert Barouki, Maheninasy Rakotondrainipiana, Kaleb Kandou, Zo Andriamanantena, Lova Andrianonimiadana, Azimdine Habib, Andre Rodriguez-Pozo, Milena Hasan, Inès Vigan-Womas, Jean-Marc Collard, Jean-Chrysostome Gody, Serge Djorie, Philippe J. Sansonetti, Rindra Vatosoa Randremanana, and on behalf of the Afribiota Investigators
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environmental enteric dysfunction ,stunted child growth ,Sub-Saharan Africa ,anemia ,biomarker ,alpha-1-antitrypsin ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2–5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.
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- 2022
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20. High prevalence of intestinal parasite infestations among stunted and control children aged 2 to 5 years old in two neighborhoods of Antananarivo, Madagascar.
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Azimdine Habib, Lova Andrianonimiadana, Maheninasy Rakotondrainipiana, Prisca Andriantsalama, Ravaka Randriamparany, Rindra Vatosoa Randremanana, Rado Rakotoarison, Inès Vigan-Womas, Armand Rafalimanantsoa, Pascale Vonaesch, Philippe J Sansonetti, Jean-Marc Collard, and Afribiota Investigators
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThis study aimed to compare the prevalence of intestinal parasite infestations (IPIs) in stunted children, compared to control children, in Ankasina and Andranomanalina Isotry (two disadvantaged neighborhoods of Antananarivo, Madagascar), to characterize associated risk factors and to compare IPI detection by real-time PCR and standard microscopy techniques.Methodology/principal findingsFecal samples were collected from a total of 410 children (171 stunted and 239 control) aged 2-5 years. A single stool sample per subject was examined by simple merthiolate-iodine-formaldehyde (MIF), Kato-Katz smear and real-time PCR techniques. A total of 96.3% of the children were infested with at least one intestinal parasite. The most prevalent parasites were Giardia intestinalis (79.5%), Ascaris lumbricoides (68.3%) and Trichuris trichiura (68.0%). For all parasites studied, real-time PCR showed higher detection rates compared to microscopy (G. intestinalis [77.6% (n = 318) versus 20.9% (n = 86)], Entamoeba histolytica [15.8% (n = 65) versus 1.9% (n = 8)] and A. lumbricoides [64.1% (n = 263) versus 50.7% (n = 208)]). Among the different variables assessed in the study, age of 4 to 5 years (AOR = 4.61; 95% CI, (1.35-15.77)) and primary and secondary educational level of the mother (AOR = 12.59; 95% CI, (2.76-57.47); AOR = 9.17; 95% CI, (2.12-39.71), respectively) were significantly associated with IPIs. Children drinking untreated water was associated with infestation with G. intestinalis (AOR = 1.85; 95% CI, (1.1-3.09)) and E. histolytica (AOR = 1.9; 95% CI, (1.07-3.38)). E. histolytica was also associated with moderately stunted children (AOR = 0.37; 95% CI, 0.2-0.71). Similarly, children aged between 4 and 5 years (AOR = 3.2; 95% CI (2.04-5.01)) and living on noncemented soil types (AOR = 1.85; 95% CI, (1.18-2.09)) were associated with T. trichiura infestation.Conclusions/significanceThe prevalence of IPIs is substantial in the studied areas in both stunted and control children, despite the large-scale drug administration of antiparasitic drugs in the country. This high prevalence of IPIs warrants further investigation. Improved health education, environmental sanitation and quality of water sources should be provided.
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- 2021
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21. Dietary diversity of 6- to 59-month-old children in rural areas of Moramanga and Morondava districts, Madagascar.
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Nivo Heritiana Rakotonirainy, Valérie Razafindratovo, Chitale Rabaoarisoa Remonja, Randza Rasoloarijaona, Patrice Piola, Charlotte Raharintsoa, and Rindra Vatosoa Randremanana
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Medicine ,Science - Abstract
BACKGROUND:A dietary imbalance or a disregard for the nutritional needs of children during early childhood can affect their growth. From the age of six months, breast milk is no longer able to meet the energy and micronutrient needs of children; the consumption of adequate complementary foods is therefore essential. Various indicators have been used to assess the quality of children's diets, and the dietary diversity score is a good indicator of children's diets. The objective of this study was to describe the dietary practices of children in rural areas of Moramanga and Morondava, Madagascar, and to identify the determinants of low dietary diversity to prioritize nutritional interventions. METHODS:We collected dietary data in 2014 on children aged 6-59 months in a study on the determinants of chronic malnutrition using the 24-hour recall method. Data on the characteristics of households and mothers were also collected. We carried out bivariate and multivariate analyses to identify the determinants of low dietary diversity scores for children. RESULTS:We included 1824 children: 893 from Moramanga and 931 from Morondava. Approximately 42.1% [95% CI: 39.0-45.4] of the children from Moramanga and 47.6% [95% CI: 44.4-50.8] of those from Morondava had a poorly diversified diet, consisting mainly of foods rich in carbohydrates and poor in meat products. Poor maternal education was associated with a high likelihood of having a non-varied diet in both study areas; the adjusted odds ratios were 2.2 [95% CI: 1.3-3.8] and 4.0 [95% CI: 2.5-6.4] for children from mothers with lower education levels for Moramanga and Morondava, respectively. For children recruited in Morondava, having low household socioeconomic status (adjusted OR: 1.8, 95% CI: 1.2-2.8) and belonging to a household without livestock was associated with a low dietary diversity score (adjusted OR: 1.8, 95% CI 1.2-2.7). CONCLUSION:Our results show the need to improve girls' education, adapt nutrition education programs for mothers based on their level of education, and strengthen poverty reduction programs.
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- 2018
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22. Correction: The importance of public health, poverty reduction programs and women's empowerment in the reduction of child stunting in rural areas of Moramanga and Morondava, Madagascar.
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Chitale Rabaoarisoa Remonja, Rado Rakotoarison, Nivo Heritiana Rakotonirainy, Reziky Tiandraza Mangahasimbola, Alain Berthin Randrianarisoa, Ronan Jambou, Inès Vigan-Womas, Patrice Piola, and Rindra Vatosoa Randremanana
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0186493.].
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- 2017
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23. The importance of public health, poverty reduction programs and women's empowerment in the reduction of child stunting in rural areas of Moramanga and Morondava, Madagascar.
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Chitale Rabaoarisoa Remonja, Rado Rakotoarison, Nivo Heritiana Rakotonirainy, Reziky Tiandraza Mangahasimbola, Alain Berthin Randrianarisoa, Ronan Jambou, Inès Vigan-Womas, Patrice Piola, and Rindra Vatosoa Randremanana
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Medicine ,Science - Abstract
Malnutrition accounts for 45% of mortality in children under five years old, despite a global mobilization against chronic malnutrition. In Madagascar, the most recent data show that the prevalence of stunting in children under five years old is still around 47.4%. This study aimed to identify the determinants of stunting in children in rural areas of Moramanga and Morondava districts to target the main areas for intervention.A case-control study was conducted in children aged from 6 to 59.9 months, in 2014-2015. We measured the height and weight of mothers and children and collected data on child, mother and household characteristics. One stool specimen was collected from each child for intestinal parasite identification. We used a multivariate logistic regression model to identify the determinants of stunting using backwards stepwise methods.We included 894 and 932 children in Moramanga and in Morondava respectively. Stunting was highly prevalent in both areas, being 52.8% and 40.0% for Moramanga and Morondava, respectively. Stunting was most associated with a specific age period (12mo to 35mo) in the two study sites. Infection with Trichuris trichiura (aOR: 2.4, 95% CI: 1.1-5.3) and those belonging to poorer households (aOR: 2.3, 95% CI: 1.6-3.4) were the major risk factors in Moramanga. In Morondava, children whose mother had activities outside the household (aOR: 1.7, 95% CI: 1.2-2.5) and those perceived to be small at birth (aOR: 1.6, 95% CI: 1.1-2.1) were more likely to be stunted, whereas adequate birth spacing (≥24months) appeared protective (aOR: 0.4, 95% CI: 0.3-0.7).Interventions that could improve children's growth in these two areas include poverty reduction, women's empowerment, public health programmes focusing on WASH and increasing acceptability, and increased coverage and quality of child/maternal health services.
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- 2017
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24. Etiologies, Risk Factors and Impact of Severe Diarrhea in the Under-Fives in Moramanga and Antananarivo, Madagascar.
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Rindra Vatosoa Randremanana, Richter Razafindratsimandresy, Todisoa Andriatahina, Arthur Randriamanantena, Lovaniaina Ravelomanana, Frédérique Randrianirina, and Vincent Richard
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Medicine ,Science - Abstract
Diarrheal disease remains a leading cause of death in children in low-income countries. We investigated the etiology, risk factors and effects on nutritional status of severe diarrhea in children from two districts in Madagascar.We performed a matched case-control study in 2011 to 2014, on children under the age of five years from Moramanga and Antananarivo. The cases were children hospitalized for severe diarrhea and the controls were children without diarrhea selected at random from the community. Stool samples were collected from both groups. Anthropometric measurements were made during follow-up visits about one and two months after enrolment.We enrolled 199 cases and 199 controls. Rotavirus infection was the most frequently detected cause of diarrhea. It was strongly associated with severe diarrhea (OR: 58.3; 95% CI: 7.7-439.9), accounting for 42.4% (95% CI: 37.6-43.1) of severe diarrhea cases. At the household level, possession of cattle (OR = 0.3; 95% CI: 0.1-0.6) and living in a house with electricity (OR = 0.4; 95% CI: 0.2-0.8) were protective factors. The presence of garbage around the house was a risk factor for severe diarrhea (OR = 3.2; 95% CI: 1.9-5.4). We found no significant association between severe diarrhea and the nutritional status of the children at follow-up visits, but evident wasting at enrolment was associated with a higher risk of severe diarrhea (OR = 9; 95% CI: 4.5-17.9).Severe childhood diarrhea is mostly caused by rotavirus infection. An anti-rotavirus vaccine has already been introduced in Madagascar and should be promoted more widely. However, post-licensing surveillance is required. Interventions to improve the nutritional status of children, preventive measures focused on household and personal hygiene and nutritional rehabilitation during severe diarrheal disease should be reinforced.
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- 2016
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25. Spatial analysis of pulmonary tuberculosis in Antananarivo Madagascar: tuberculosis-related knowledge, attitude and practice.
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Sitraka Rakotosamimanana, Vatsiharizandry Mandrosovololona, Julio Rakotonirina, Joselyne Ramamonjisoa, Justin Rasolofomanana Ranjalahy, Rindra Vatosoa Randremanana, and Fanjasoa Rakotomanana
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Medicine ,Science - Abstract
Tuberculosis infection may remain latent, but the disease is nevertheless a serious public health issue. Various epidemiological studies on pulmonary tuberculosis have considered the spatial component and taken it into account, revealing the tendency of this disease to cluster in particular locations. The aim was to assess the contribution of Knowledge Attitude and Practice (KAP) to the distribution of tuberculosis and to provide information for the improvement of the National Tuberculosis Program.We investigated the role of KAP to distribution patterns of pulmonary tuberculosis in Antananarivo. First, we performed spatial scanning of tuberculosis aggregation among permanent cases resident in Antananarivo Urban Township using the Kulldorff method, and then we carried out a quantitative study on KAP, involving TB patients. The KAP study in the population was based on qualitative methods with focus groups.The disease still clusters in the same districts identified in the previous study. The principal cluster covered 22 neighborhoods. Most of them are part of the first district. A secondary cluster was found, involving 18 neighborhoods in the sixth district and two neighborhoods in the fifth. The relative risk was respectively 1.7 (p
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- 2014
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26. Viral etiology of influenza-like illnesses in Antananarivo, Madagascar, July 2008 to June 2009.
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Norosoa Harline Razanajatovo, Vincent Richard, Jonathan Hoffmann, Jean-Marc Reynes, Girard Marcellin Razafitrimo, Rindra Vatosoa Randremanana, and Jean-Michel Heraud
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Medicine ,Science - Abstract
In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs).From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation.In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation.
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- 2011
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27. SARS‐CoV‐2 infection rate in Antananarivo frontline health care workers, Madagascar
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Rila Ratovoson, Mihaja Raberahona, Rado Razafimahatratra, Lova Randriamanantsoa, Emmanuel Harizaka Andriamasy, Perlinot Herindrainy, Norosoa Razanajatovo, Soa Fy Andriamandimby, Andoniaina Rakotonaivo, Fanirisoa Randrianarisaona, Philippe Dussart, Jean Michel Heraud, Mamy Jean de Dieu de Randria, Matthieu Schoenhals, and Rindra Vatosoa Randremanana
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Adolescent ,SARS-CoV-2 ,Epidemiology ,Health Personnel ,Public Health, Environmental and Occupational Health ,COVID-19 ,Cohort Studies ,Infectious Diseases ,Madagascar ,Humans ,Female ,Prospective Studies - Abstract
Health care workers (HCWs) represent a vulnerable population during epidemic periods. Our cohort study aimed to estimate the risk of infection and associated factors among HCWs during the first wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Madagascar.A prospective cohort study was carried out in three hospitals that oversaw the first cases of COVID-19. Monthly ELISA-based serological tests were conducted, and nasopharyngeal swabs were collected in the case of symptoms linked to COVID-19 for RT-PCR analysis. Survival analyses were used to determine factors associated with SARS-CoV-2 infection.The study lasted 7 months from May 2020. We included 122 HCWs, 61.5% of whom were women. The median age was 31.9 years (IQR: 26.4-42.3). In total, 42 (34.4%) had SARS-CoV-2 infections, of which 20 were asymptomatic (47.6%). The incidence of SARS-CoV-2 infection was 9.3% (95% CI [6.5-13.2]) person-months. Sixty-five HCWs presented symptoms, of which 19 were positive by RT-PCR. When adjusted for exposure to deceased cases, infection was more frequent in HCWs younger than 30 years of age (RR = 4.9, 95% CI [1.4-17.2]).Our results indicate a high incidence of infection with SARS-CoV-2 among HCWs, with a high proportion of asymptomatic cases. Young HCWs are more likely to be at risk than others. Greater awareness among young people is necessary to reduce the threat of infection among HCWs.
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- 2022
28. Sociospatial determinants of knowledge and perceptions of COVID-19 impacts among childbearing women in urban and rural areas of the Malagasy middle east
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Sitraka RAKOTOSAMIMANANA, Reziky Tiandraza MANGAHASIMBOLA, Rila RATOVOSON, and Rindra Vatosoa RANDREMANANA
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Background With regard to the coronavirus disease (COVID-19) pandemic in Madagascar, little is known about the knowledge and perceptions of and impacts on childbearing women. People's knowledge of COVID-19 can have an impact on their attitudes towards seeking care. The aim of the current study is to determine the knowledge of COVID-19 and associated determinants of childbearing women in Moramanga. Methods A cross-sectional study based on questionnaire administration was used in urban and rural areas of Moramanga, a district located 112 km from the capital, among childbearing women. Data collection was conducted from August to October 2021. A scoring method was applied to evaluate their knowledge level and perceptions about COVID-19 and its impacts on their lives. A binary stepwise logistic regression was performed to determine the sociodemographic and sociospatial determinants of their knowledge level towards COVID-19. Results A total of 885 childbearing women from urban and rural Moramanga areas were interviewed. Approximately 49.8% (441/885) lived in urban areas, and 50.2% (444/885) lived in rural areas. Approximately 35.3% (322/885) of the participants had a good level of knowledge of COVID-19. Multivariate analysis showed that the probability of having good level of knowledge of COVID-19 had a significant statistical association (p value with living in an urban area [AOR: 2.86; 95% CI (1.87–4.40)], telephone ownership [AOR: 1.71; 95% CI (0.16–1.1)], radio ownership [AOR 2.22; 95% CI (1.44–3.43)], watching TV [AOR = 1.95; 95% CI (1.34–2.83)] and reading journal paper [AOR = 3.74 95% CI (1.69–8.3)]. Conclusions Levels of knowledge about COVID-19 among women of reproductive age in the middle east area of Madagascar are related to sociospatial determinants. Almost a third of the sample had a good level of knowledge of COVID-19. Access to information and telecommunication technologies increases the chances of being better informed about the disease. To avoid the negative repercussions of COVID-19 and infectious disease epidemics on maternal and child health, it is necessary to improve the awareness of childbearing women and other categories of the population about these diseases. This implies taking into account the geographic and demographic characteristics of the populations.
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- 2023
29. Using a multiplex serological assay to estimate time since SARS-CoV-2 infection and past clinical presentation in Malagasy patients
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Mame Diarra Bousso Ndiaye, Lova Tsikiniaina Rasoloharimanana, Solohery Lalaina Razafimahatratra, Rila Ratovoson, Voahangy RASOLOFO, Paulo Ranaivomanana, Laurent Raskine, Jonathan Hoffmann, Rindra Vatosoa Randremanana, Niaina Rakotosamimanana, and Matthieu Schoenhals
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Background: The world is facing a 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, efficient serological assays are needed to accurately describe the humoral responses against the virus. These tools could potentially provide temporal and clinical characteristics and are thus paramount in developing-countries lacking sufficient ongoing COVID-19 epidemic descriptions.Methods: We developed and validated a Luminex xMAP® multiplex serological assay targeting specific IgM and IgG antibodies against the SARS-CoV-2 Spike subunit 1 (S1), Spike subunit 2 (S2), Spike Receptor Binding Domain (RBD) and the Nucleocapsid Protein (NP). Blood samples collected periodically for 12 months from 43 patients diagnosed with COVID-19 in Madagascar were tested for these antibodies. A random forest algorithm was used to build a predictive model of time since infection and symptom presentation.Findings: The performance of the multiplex serological assay was evaluated for the detection of SARS-CoV-2 anti-IgG and anti-IgM antibodies. Both sensitivity and specificity were equal to 100% (89.85-100) for S1, RBD and NP (S2 had a lower specificity = 95%) for IgG at day 14 after enrolment. This multiplex assay compared with two commercialized ELISA kits, showed a higher sensitivity. Principal Component Analysis was performed on serologic data to group patients according to time of sample collection and clinical presentations. The random forest algorithm built by this approach predicted symptom presentation and time since infection with an accuracy of 87.1% (95% CI = 70.17-96.37, p-value = 0.0016), and 80% (95% CI = 61.43-92.29, p-value = 0.0001) respectively. Interpretation: This study demonstrates that the statistical model predicts time since infection and previous symptom presentation using IgM and IgG response to SARS-CoV2. This tool may be useful for global surveillance, discriminating recent- and past- SARS-CoV-2 infection, and assessing disease severity.
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- 2022
30. Stunted Child Growth Is Associated With Small Intestinal Colonization by Oral Bacteria Driving Lipid Malabsorption and Inflammation in vitro
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Pascale Vonaesch, João R. Araújo, Jean-Chrysostome Gody, Jean-Robert Mbecko, Hugues Sanke, Lova Andrianonimiadana, Tanteliniaina Naharimanananirina, Cynthia Nigateloum, Sonia Vondo, Privat Gondje, Andre Rodriguez-Pozo, Maheninasy Rakotondrainipiana, Kaleb Jephté Estimé Kandou, Alison Nestoret, Nathalie Kapel, Serge Ghislain Djorie, Laura Wegener Parfrey, Jean-Marc Collard, Rindra Vatosoa Randremanana, Philippe J. Sansonetti, and Afribiota Investigators
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- 2022
31. Factors Associated with Stunted Growth in Children Under Five Years in Antananarivo, Madagascar and Bangui, Central African Republic
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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
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[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.
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- 2021
32. Additional file 1 of An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Rindra Vatosoa Randremanana, Mihaja Raberahona, Mamy Jean De Dieu Randria, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Legrand, Agathe, Tsinjo Fehizoro Rasoanaivo, Ravaka Randriamparany, Mayouya-Gamana, Théodora, Reziky Mangahasimbola, Bourner, Josie, Salam, Alex, Gillesen, Annelies, Tansy Edwards, Schoenhals, Matthieu, Baril, Laurence, Horby, Peter, and Olliaro, Piero
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humanities ,3. Good health - Abstract
Additional file 1. : Patient information sheet. Informed consent form (ADULTS). Informed consent form (CHILDREN AND PROXY).
33. Additional file 2 of An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Rindra Vatosoa Randremanana, Mihaja Raberahona, Mamy Jean De Dieu Randria, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Legrand, Agathe, Tsinjo Fehizoro Rasoanaivo, Ravaka Randriamparany, Mayouya-Gamana, Théodora, Reziky Mangahasimbola, Bourner, Josie, Salam, Alex, Gillesen, Annelies, Tansy Edwards, Schoenhals, Matthieu, Baril, Laurence, Horby, Peter, and Olliaro, Piero
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3. Good health - Abstract
Additional file 2. Case Report Form (CRF).
34. Additional file 2 of An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Rindra Vatosoa Randremanana, Mihaja Raberahona, Mamy Jean De Dieu Randria, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Legrand, Agathe, Tsinjo Fehizoro Rasoanaivo, Ravaka Randriamparany, Mayouya-Gamana, Théodora, Reziky Mangahasimbola, Bourner, Josie, Salam, Alex, Gillesen, Annelies, Tansy Edwards, Schoenhals, Matthieu, Baril, Laurence, Horby, Peter, and Olliaro, Piero
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3. Good health - Abstract
Additional file 2. Case Report Form (CRF).
35. Additional file 1 of An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Rindra Vatosoa Randremanana, Mihaja Raberahona, Mamy Jean De Dieu Randria, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Legrand, Agathe, Tsinjo Fehizoro Rasoanaivo, Ravaka Randriamparany, Mayouya-Gamana, Théodora, Reziky Mangahasimbola, Bourner, Josie, Salam, Alex, Gillesen, Annelies, Tansy Edwards, Schoenhals, Matthieu, Baril, Laurence, Horby, Peter, and Olliaro, Piero
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humanities ,3. Good health - Abstract
Additional file 1. : Patient information sheet. Informed consent form (ADULTS). Informed consent form (CHILDREN AND PROXY).
36. 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
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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
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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.
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- 2022
37. Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models
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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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