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Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi

Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blo...

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Autores principales: Msefula, Chisomo L., Olgemoeller, Franziska, Jambo, Ndaru, Segula, Dalitso, Van Tan, Trinh, Nyirenda, Tonney S., Nedi, Wilfred, Kennedy, Neil, Graham, Matthew, Henrion, Marc Y. R., Baker, Stephen, Feasey, Nicholas, Gordon, Melita, Heyderman, Robert S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663031/
https://www.ncbi.nlm.nih.gov/pubmed/31314752
http://dx.doi.org/10.1371/journal.pntd.0007539
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author Msefula, Chisomo L.
Olgemoeller, Franziska
Jambo, Ndaru
Segula, Dalitso
Van Tan, Trinh
Nyirenda, Tonney S.
Nedi, Wilfred
Kennedy, Neil
Graham, Matthew
Henrion, Marc Y. R.
Baker, Stephen
Feasey, Nicholas
Gordon, Melita
Heyderman, Robert S.
author_facet Msefula, Chisomo L.
Olgemoeller, Franziska
Jambo, Ndaru
Segula, Dalitso
Van Tan, Trinh
Nyirenda, Tonney S.
Nedi, Wilfred
Kennedy, Neil
Graham, Matthew
Henrion, Marc Y. R.
Baker, Stephen
Feasey, Nicholas
Gordon, Melita
Heyderman, Robert S.
author_sort Msefula, Chisomo L.
collection PubMed
description Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials.
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spelling pubmed-66630312019-08-05 Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi Msefula, Chisomo L. Olgemoeller, Franziska Jambo, Ndaru Segula, Dalitso Van Tan, Trinh Nyirenda, Tonney S. Nedi, Wilfred Kennedy, Neil Graham, Matthew Henrion, Marc Y. R. Baker, Stephen Feasey, Nicholas Gordon, Melita Heyderman, Robert S. PLoS Negl Trop Dis Research Article Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials. Public Library of Science 2019-07-17 /pmc/articles/PMC6663031/ /pubmed/31314752 http://dx.doi.org/10.1371/journal.pntd.0007539 Text en © 2019 Msefula et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Msefula, Chisomo L.
Olgemoeller, Franziska
Jambo, Ndaru
Segula, Dalitso
Van Tan, Trinh
Nyirenda, Tonney S.
Nedi, Wilfred
Kennedy, Neil
Graham, Matthew
Henrion, Marc Y. R.
Baker, Stephen
Feasey, Nicholas
Gordon, Melita
Heyderman, Robert S.
Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi
title Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi
title_full Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi
title_fullStr Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi
title_full_unstemmed Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi
title_short Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi
title_sort ascertaining the burden of invasive salmonella disease in hospitalised febrile children aged under four years in blantyre, malawi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663031/
https://www.ncbi.nlm.nih.gov/pubmed/31314752
http://dx.doi.org/10.1371/journal.pntd.0007539
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