Distinct Signatures of Gut Microbiome and Metabolites Associated with Significant Fibrosis in Non-Obese NAFLD
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WO 2015/066625 Al 7 May 2015 (07.05.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/066625 Al 7 May 2015 (07.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12Q 1/04 (2006.01) G01N 33/15 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US2014/06371 1 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 3 November 20 14 (03 .11.20 14) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/898,938 1 November 2013 (01. 11.2013) (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: WASHINGTON UNIVERSITY [US/US] GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, One Brookings Drive, St. -
Title: Gut Microbiome Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients Wellinton M. Do Nasci
medRxiv preprint doi: https://doi.org/10.1101/2020.12.07.20245530; this version posted December 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Title: Gut microbiome profiles and associated metabolic pathways in HIV-infected treatment-naïve patients Wellinton M. do Nascimento1,2, Aline Machiavelli2, Luiz G. E. Ferreira3, Luisa Cruz Silveira1, Suwellen S. D. de Azevedo4, Gonzalo Bello4, Daniel P. Smith5, Melissa P. Mezzari5, Joseph Petrosino5, Rubens Tadeu Delgado Duarte6, Carlos R. Zaráte- Bládes2§*, and Aguinaldo R. Pinto1* 1 Laboratório de Imunologia Aplicada, LIA, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC, 88034-040, Brazil. 2 Laboratório de Imunoregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC, 88034-040, Brazil. 3 Hospital Regional Homero de Miranda Gomes, Rua Adolfo Donato da Silva, s/n, São José, SC, 88103-901, Brazil. 4 Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Av. Brasil, 4365, Rio de Janeiro, RJ, 21045-900, Brazil. 5 Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, United States. 6 Laboratório de Ecologia Molecular e Extremófilos, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC, 88034-040, Brazil. *contributed equally to this work NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. -
Robust Taxonomic Classification of Uncharted Microbial Sequences and Bins with CAT and BAT
bioRxiv preprint doi: https://doi.org/10.1101/530188; this version posted January 24, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Robust taxonomic classification of uncharted microbial sequences and bins with CAT and BAT F.A. Bastiaan von Meijenfeldt1,†, Ksenia Arkhipova1,†, Diego D. Cambuy1, Felipe H. Coutinho2,3, Bas E. Dutilh1,2,* 1 Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, The Netherlands. 2 Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Nijmegen, The Netherlands. 3 Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. * To whom correspondence should be addressed. Tel: +31 30 253 4212; Email: [email protected]. † These authors contributed equally to this work. Present Address: [Felipe H. Couthinho], Evolutionary Genomics Group, Departamento de Produccíon y Microbiología, Universidad Miguel Hernández, Campus San Juan, San Juan, Alicante 03550, Spain. ABSTRACT Current-day metagenomics increasingly requires taxonomic classification of long DNA sequences and metagenome-assembled genomes (MAGs) of unknown microorganisms. We show that the standard best-hit approach often leads to classifications that are too specific. We present tools to classify high- quality metagenomic contigs (Contig Annotation Tool, CAT) and MAGs (Bin Annotation Tool, BAT) and thoroughly benchmark them with simulated metagenomic sequences that are classified against a reference database where related sequences are increasingly removed, thereby simulating increasingly unknown queries. We find that the query sequences are correctly classified at low taxonomic ranks if closely related organisms are present in the reference database, while classifications are made higher in the taxonomy when closely related organisms are absent, thus avoiding spurious classification specificity. -
WO 2018/064165 A2 (.Pdf)
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/064165 A2 05 April 2018 (05.04.2018) W !P O PCT (51) International Patent Classification: Published: A61K 35/74 (20 15.0 1) C12N 1/21 (2006 .01) — without international search report and to be republished (21) International Application Number: upon receipt of that report (Rule 48.2(g)) PCT/US2017/053717 — with sequence listing part of description (Rule 5.2(a)) (22) International Filing Date: 27 September 2017 (27.09.2017) (25) Filing Language: English (26) Publication Langi English (30) Priority Data: 62/400,372 27 September 2016 (27.09.2016) US 62/508,885 19 May 2017 (19.05.2017) US 62/557,566 12 September 2017 (12.09.2017) US (71) Applicant: BOARD OF REGENTS, THE UNIVERSI¬ TY OF TEXAS SYSTEM [US/US]; 210 West 7th St., Austin, TX 78701 (US). (72) Inventors: WARGO, Jennifer; 1814 Bissonnet St., Hous ton, TX 77005 (US). GOPALAKRISHNAN, Vanch- eswaran; 7900 Cambridge, Apt. 10-lb, Houston, TX 77054 (US). (74) Agent: BYRD, Marshall, P.; Parker Highlander PLLC, 1120 S. Capital Of Texas Highway, Bldg. One, Suite 200, Austin, TX 78746 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Meta Analysis of Microbiome Studies Identifies Shared and Disease
bioRxiv preprint doi: https://doi.org/10.1101/134031; this version posted May 8, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Meta analysis of microbiome studies identifies shared and disease-specific patterns Claire Duvallet1,2, Sean Gibbons1,2,3, Thomas Gurry1,2,3, Rafael Irizarry4,5, and Eric Alm1,2,3,* 1Department of Biological Engineering, MIT 2Center for Microbiome Informatics and Therapeutics 3The Broad Institute of MIT and Harvard 4Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute 5Department of Biostatistics, Harvard T.H. Chan School of Public Health *Corresponding author, [email protected] Contents 1 Abstract2 2 Introduction3 3 Results4 3.1 Most disease states show altered microbiomes ........... 5 3.2 Loss of beneficial microbes or enrichment of pathogens? . 5 3.3 A core set of microbes associated with health and disease . 7 3.4 Comparing studies within and across diseases separates signal from noise ............................... 9 4 Conclusion 10 5 Methods 12 5.1 Dataset collection ........................... 12 5.2 16S processing ............................ 12 5.3 Statistical analyses .......................... 13 5.4 Microbiome community analyses . 13 5.5 Code and data availability ...................... 13 6 Table and Figures 14 1 bioRxiv preprint doi: https://doi.org/10.1101/134031; this version posted May 8, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Gut Microbiome Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients
cells Article Gut Microbiome Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients Wellinton M. do Nascimento 1,2, Aline Machiavelli 1,2 , Luiz G. E. Ferreira 3, Luisa Cruz Silveira 1 , Suwellen S. D. de Azevedo 4 , Gonzalo Bello 4, Daniel P. Smith 5 , Melissa P. Mezzari 5 , Joseph F. Petrosino 5, Rubens Tadeu Delgado Duarte 6, Carlos R. Zárate-Bladés 2,*,†, and Aguinaldo R. Pinto 1,† 1 Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC 88034-040, Brazil; [email protected] (W.M.d.N.); [email protected] (A.M.); [email protected] (L.C.S.); [email protected] (A.R.P.) 2 Laboratório de Imunorregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC 88034-040, Brazil 3 Hospital Regional Homero de Miranda Gomes, Rua Adolfo Donato da Silva, s/n, São José, SC 88103-901, Brazil; [email protected] 4 Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, Rio de Janeiro, RJ 21045-900, Brazil; [email protected] (S.S.D.d.A.); gbello@ioc.fiocruz.br (G.B.) 5 Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; [email protected] (D.P.S.); [email protected] (M.P.M.); [email protected] (J.F.P.) 6 Laboratório de Ecologia Molecular e Extremófilos, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC 88034-040, Brazil; [email protected] Citation: do Nascimento, W.M.; * Correspondence: [email protected]; Tel.: +55-48-37215210 Machiavelli, A.; Ferreira, L.G.E.; Cruz † These authors contributed equally to this work. -
The Gut and Blood Microbiome in Iga Nephropathy and Healthy Controls Original Investigation
Original Investigation The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls Neal B. Shah ,1 Sagar U. Nigwekar ,2 Sahir Kalim,2 Benjamin Lelouvier,3 Florence Servant ,3 Monika Dalal,1 Scott Krinsky,2 Alessio Fasano ,4 Nina Tolkoff-Rubin,2 and Andrew S. Allegretti 2 Key Points A higher microbiome load, possibly originating from different body sites, may be playing a pathogenic role in IgA nephropathy. Several microbiome taxonomic differences between patients with IgA nephropathy and healthy controls are observed in blood and stool. Striking differences between the blood and gut microbiome confirm that the blood microbiome does not directly reflect the gut microbiome. Abstract Background IgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption, and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in patients with IgAN in relation to healthy controls. Methods We conducted a case-control study with 20 patients with progressive IgAN, matched with 20 healthy controls, and analyzed bacterial DNA quantitatively in blood using 16S PCR and qualitatively in blood and stool using 16S metagenomic sequencing. We conducted between-group comparisons as well as comparisons between the blood and gut microbiomes. Results Higher median 16S bacterial DNA in blood was found in the IgAN group compared with the healthy controls group (7410 versus 6030 16S rDNA copies/ml blood, P50.04). a-andb-Diversity in both blood and stool was largely similar between the IgAN and healthy groups. In patients with IgAN, in comparison with healthy controls, we observed higher proportions of the class Coriobacteriia and species of the genera Legionella, Enhydrobacter,andParabacteroides in blood, and species of the genera Bacteroides, Escherichia-Shigella,andsome Ruminococcus in stool. -
Identification of the Core Bacteria in Rectums of Diarrheic and Non-Diarrheic Piglets
www.nature.com/scientificreports OPEN Identifcation of the core bacteria in rectums of diarrheic and non- diarrheic piglets Jing Sun1,3,4,5*, Lei Du1,5, XiaoLei Li2,5, Hang Zhong1, Yuchun Ding1,3,4, Zuohua Liu1,3,4 & Liangpeng Ge1,3,4* Porcine diarrhea is a global problem that leads to large economic losses of the porcine industry. There are numerous factors related to piglet diarrhea, and compelling evidence suggests that gut microbiota is vital to host health. However, the key bacterial diferences between non-diarrheic and diarrheic piglets are not well understood. In the present study, a total of 85 commercial piglets at three pig farms in Sichuan Province and Chongqing Municipality, China were investigated. To accomplish this, anal swab samples were collected from piglets during the lactation (0–19 days old in this study), weaning (20–21 days old), and post-weaning periods (22–40 days), and fecal microbiota were assessed by 16S rRNA gene V4 region sequencing using the Illumina Miseq platform. We found age-related biomarker microbes in the fecal microbiota of diarrheic piglets. Specifcally, the family Enterobacteriaceae was a biomarker of diarrheic piglets during lactation (cluster A, 7–12 days old), whereas the Bacteroidales family S24–7 group was found to be a biomarker of diarrheic pigs during weaning (cluster B, 20–21 days old). Co-correlation network analysis revealed that the genus Escherichia-Shigella was the core component of diarrheic microbiota, while the genus Prevotellacea UCG-003 was the key bacterium in non-diarrheic microbiota of piglets in Southwest China. Furthermore, changes in bacterial metabolic function between diarrheic piglets and non-diarrheic piglets were estimated by PICRUSt analysis, which revealed that the dominant functions of fecal microbes were membrane transport, carbohydrate metabolism, amino acid metabolism, and energy metabolism. -
Gut Microbiota and Host Reaction in Liver Diseases
Microorganisms 2015, 3, 759-791; doi:10.3390/microorganisms3040759 OPEN ACCESS microorganisms ISSN 2076-2607 www.mdpi.com/journal/microorganisms Review Gut Microbiota and Host Reaction in Liver Diseases Hiroshi Fukui Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, 840 Shijo-cho Kashihara, 634-8522 Nara, Japan; E-Mail: [email protected]; Tel.: +81-744-22-3051; Fax: +81-744-24-7122 Academic Editor: Carl Gordon Johnston Received: 3 September 2015 / Accepted: 21 October 2015 / Published: 28 October 2015 Abstract: Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. -
The Gut and Blood Microbiome in Iga Nephropathy and Healthy Controls
Kidney360 Publish Ahead of Print, published on June 9, 2021 as doi:10.34067/KID.0000132021 The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls Neal B. Shaha; Sagar U. Nigwekarb; Sahir Kalimb; Benjamin Lelouvierc; Florence Servantc; Monika Dalala; Scott Krinskyb; Alessio Fasanod; Nina Tolkoff-Rubinb; Andrew S. Allegrettib aDepartment of Medicine, Division of Hospital Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA bDivision of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA cVaiomer SAS, Labège, France dDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, MassGeneral Hospital for Children, Boston, MA, USA Corresponding author: Neal B. Shah Department of Medicine, Division of Hospital Medicine, Johns Hopkins Bayview Medical Center 5200 Eastern Avenue, MFL East Tower, room 260, Baltimore, MD 21224, USA. Tel: (410) 550-5018. Fax: (410) 550-2972. E-mail: [email protected]. 1 Copyright 2021 by American Society of Nephrology. KEY POINTS A higher microbiome load possibly originating from different body sites may be playing a pathogenic role in IgA Nephropathy. Several microbiome taxonomic differences between IgA Nephropathy and healthy controls are observed in blood and stool. Striking differences between the blood and gut microbiome confirm that the blood microbiome does not directly reflect the gut microbiome. ABSTRACT Background: IgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in IgAN patients in relation to healthy controls. Methods: We conducted a case control study with 20 progressive IgAN patients matched with 20 healthy controls, analyzing bacterial DNA quantitatively in blood by 16S PCR and qualitatively in blood and stool by 16S metagenomic sequencing. -
Resource Represents ~75% of the Genus-Level Bacterial and Archaeal Taxa Present in the Rumen
RESOURCE OPEN Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection Rekha Seshadri1,9 , Sinead C Leahy2,8,9 , Graeme T Attwood2, Koon Hoong Teh2,8, Suzanne C Lambie2,8, Adrian L Cookson2, Emiley A Eloe-Fadrosh1, Georgios A Pavlopoulos1, Michalis Hadjithomas1, Neha J Varghese1, David Paez-Espino1 , Hungate1000 project collaborators3, Rechelle Perry2, Gemma Henderson2,8, Christopher J Creevey4, Nicolas Terrapon5,6 , Pascal Lapebie5,6, Elodie Drula5,6, Vincent Lombard5,6, Edward Rubin1,8, Nikos C Kyrpides1, Bernard Henrissat5–7, Tanja Woyke1 , Natalia N Ivanova1, William J Kelly2,8 Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents ~75% of the genus-level bacterial and archaeal taxa present in the rumen. Climate change and feeding a growing global population are the two of the flow of carbon through the rumen by lignocellulose degrada- 1 biggest challenges facing agriculture . -
Stunted Childhood Growth Is Associated with Decompartmentalization of the Gastrointestinal Tract and Overgrowth of Oropharyngeal Taxa
Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa Pascale Vonaescha,b, Evan Morienc,d,e, Lova Andrianonimiadanaf, Hugues Sankeg, Jean-Robert Mbeckog, Kelsey E. Huush, Tanteliniaina Naharimanananirinai, Bolmbaye Privat Gondjej, Synthia Nazita Nigatoloumj, Sonia Sandrine Vondoj, Jepthé Estimé Kaleb Kandouk, Rindra Randremananal, Maheninasy Rakotondrainipianal, Florent Mazelc,d,e, Serge Ghislain Djoriek, Jean-Chrysostome Godyj, B. Brett Finlayh,1, Pierre-Alain Rubbog,1, Laura Wegener Parfreyc,d,e,1, Jean-Marc Collardf, Philippe J. Sansonettia,b,m,2, and The Afribiota Investigators3 aUnité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France; bUnité INSERM 1202, Institut Pasteur, 75015 Paris, France; cDepartment of Botany, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; dDepartment of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; eBiodiversity Research Centre, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; fUnitédeBactériologieExpérimentale, Institut Pasteur de Madagascar, BP 1274 Ambatofotsikely, 101 Antananarivo, Madagascar; gLaboratoires d’Analyses Médicales, Institut Pasteur de Bangui, BP 923 Bangui, Central African Republic; hMichael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; iCentre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona, BP 4150, 101 Antananarivo, Madagascar; jComplexe Pédiatrique de Bangui, BP 923 Bangui, Central