Aetiology of severe Pneumonia in Gambian children

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Pneumonia is one of the most important causes of serious illness among children in The Gambia. We are doing research into what causes it and how it can be better prevented and treated. Pneumonia is caused by many different germs and it is important to know if possible what bug is causing the disease so that the right treatment can be given. Knowing what is causing pneumonia in Gambian children also helps in developing new treatments and ways of preventing pneumonia. Methods used for determining the causes of pneumonia have significant limitations. Better methods for collection material such as sputum and fluid from the nose, and the identification of pathogens are urgently needed, therefore. The children will be followed-up for at least 6 months and questions will be asked about daily life in the home. Some measurements will be taken of the goodness of the air using a small safe device you or your child can wear and using a small machine in the house

Technical Summary

Identification of the pathogens responsible for severe pneumonia in children is important for guiding treatment, identifying patterns of antimicrobial resistance, and planning prevention programmes. Conventional methods for determining the aetiology have significant limitations in sensitivity and specificity. There are difficulties both with obtaining appropriate clinical specimens and with analysing them meaningfully in the laboratory. Better methods for specimen collection and the identification of pathogens are urgently needed, therefore. We also need to be able to tell if an organism is causing disease or simply acting as a bystander.||This study is one of the severe pneumonia platform studies included in the QQ proposal. The objectives of this study are to |1. define the aetiology of severe pneumonia in Gambian children using the best available methods, |2. compare the utility of different specimen collection techniques, |3. assess the utility of molecular methods in determining aetiology |4. identify meaningful laboratory correlates of disease, and|5. To translate the findings of the study into practical approaches to improve diagnosis and treatment of patients||We will adopt a 4-dimensional strategy to the laboratory aspects of this challenge: |1. identification of all organisms present, |2. quantification of organisms, |3. measurement of organism markers of pathogenicity, and |4. measurement of markers of host-response to disease. |The ultimate aims of the work are to guide disease prevention work (including the development of vaccines) and to contribute to the development of practical diagnostic tools that will improve the outcome for children suffering from severe pneumonia and possibly other severe infections of childhood.

Publications

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Baggett HC (2017) Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Barger-Kamate B (2016) Pertussis-Associated Pneumonia in Infants and Children From Low- and Middle-Income Countries Participating in the PERCH Study. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Crawley J (2017) Standardization of Clinical Assessment and Sample Collection Across All PERCH Study Sites. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Deloria Knoll M (2017) Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Deloria Knoll M (2017) Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Deloria-Knoll M (2012) Identification and selection of cases and controls in the Pneumonia Etiology Research for Child Health project. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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DeLuca AN (2017) Safety of Induced Sputum Collection in Children Hospitalized With Severe or Very Severe Pneumonia. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Driscoll AJ (2017) Standardization of Laboratory Methods for the PERCH Study. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Driscoll AJ (2017) The Effect of Antibiotic Exposure and Specimen Volume on the Detection of Bacterial Pathogens in Children With Pneumonia. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

 
Description PERCH Project Methods
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description GAVI Hib Initiative Research Grant
Amount £445,000 (GBP)
Organisation Bill and Melinda Gates Foundation 
Department Global Alliance for Vaccination and Immunisation (GAVI)
Sector Charity/Non Profit
Country Switzerland
Start 07/2007 
End 06/2011
 
Description PERCH Project Grant
Amount £1,600,000 (GBP)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 10/2011 
End 12/2013
 
Description Child mortality research policy informal network 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Epidemiology and Population Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Facilitating informal interactions in this area and contributing to non-peer reviewed advocacy and policy discussion publications
Collaborator Contribution WHO CAH has been supportive of our work in this area, providing a sounding board and helping direct effortsIn addition to practical support in running a GCP trial, this Unit has engaged with us in contributing to broader issues of policy and ethics including by publication.LSHTM colleagues have actively engaged with us in informal exchange and development of thinking in child health policy. Recent attention is being given to the priority of newborn survival.
Impact Several non-peer reviewed policy discussion and advocacy publications: 1. Valuing children. Howie S, Howie R. Lancet; 2006, 368(9530): 117-18 (PMID 16829293 ) 2. Pneumonia and child mortality. Howie S, Adegbola R. Lancet; 2006, 368(9548): 1646 (PMID 17098074) 3. Conduct of clinical trials in developing countries. Stephen Howie. Lancet; 2007, 370(9587):562 (PMID: 17707742) 4. Assuring Trial Safety for Children. Stephen Howie, Jenny Mueller, Hilton Whittle. Lancet; 2008 Jul 5;372(9632):30 (PMID 18603156) 5. Childhood pneumonia in Hib and pneumococcal vaccinated communities. Mulholland K, Howie S, Adegbola R. PloS Medicine Comment 31 Mar 2009 on article http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050086
Start Year 2006
 
Description Child mortality research policy informal network 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution Facilitating informal interactions in this area and contributing to non-peer reviewed advocacy and policy discussion publications
Collaborator Contribution WHO CAH has been supportive of our work in this area, providing a sounding board and helping direct effortsIn addition to practical support in running a GCP trial, this Unit has engaged with us in contributing to broader issues of policy and ethics including by publication.LSHTM colleagues have actively engaged with us in informal exchange and development of thinking in child health policy. Recent attention is being given to the priority of newborn survival.
Impact Several non-peer reviewed policy discussion and advocacy publications: 1. Valuing children. Howie S, Howie R. Lancet; 2006, 368(9530): 117-18 (PMID 16829293 ) 2. Pneumonia and child mortality. Howie S, Adegbola R. Lancet; 2006, 368(9548): 1646 (PMID 17098074) 3. Conduct of clinical trials in developing countries. Stephen Howie. Lancet; 2007, 370(9587):562 (PMID: 17707742) 4. Assuring Trial Safety for Children. Stephen Howie, Jenny Mueller, Hilton Whittle. Lancet; 2008 Jul 5;372(9632):30 (PMID 18603156) 5. Childhood pneumonia in Hib and pneumococcal vaccinated communities. Mulholland K, Howie S, Adegbola R. PloS Medicine Comment 31 Mar 2009 on article http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050086
Start Year 2006
 
Description Child mortality research policy informal network 
Organisation World Health Organization (WHO)
Department Maternal, Newborn, Child and Adolescent Health
Country Switzerland 
Sector Public 
PI Contribution Facilitating informal interactions in this area and contributing to non-peer reviewed advocacy and policy discussion publications
Collaborator Contribution WHO CAH has been supportive of our work in this area, providing a sounding board and helping direct effortsIn addition to practical support in running a GCP trial, this Unit has engaged with us in contributing to broader issues of policy and ethics including by publication.LSHTM colleagues have actively engaged with us in informal exchange and development of thinking in child health policy. Recent attention is being given to the priority of newborn survival.
Impact Several non-peer reviewed policy discussion and advocacy publications: 1. Valuing children. Howie S, Howie R. Lancet; 2006, 368(9530): 117-18 (PMID 16829293 ) 2. Pneumonia and child mortality. Howie S, Adegbola R. Lancet; 2006, 368(9548): 1646 (PMID 17098074) 3. Conduct of clinical trials in developing countries. Stephen Howie. Lancet; 2007, 370(9587):562 (PMID: 17707742) 4. Assuring Trial Safety for Children. Stephen Howie, Jenny Mueller, Hilton Whittle. Lancet; 2008 Jul 5;372(9632):30 (PMID 18603156) 5. Childhood pneumonia in Hib and pneumococcal vaccinated communities. Mulholland K, Howie S, Adegbola R. PloS Medicine Comment 31 Mar 2009 on article http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050086
Start Year 2006
 
Description Immunology of zinc deficiency and supplementation in severe pneumonia 
Organisation Medical Research Council (MRC)
Department MRC International Nutrition Group
Country United Kingdom 
Sector Public 
PI Contribution Design and conduct of the randomised trial onto which the immunology add-on study has been added
Collaborator Contribution The MRC ING has brought nutritional expertise to this study and has added value with an immunological add-on study.
Impact A non-peer reviewed publication in the International Journal of Nutrition highlighting key areas of importance for zinc and severe pneumonia research (PMID 17209204)
Start Year 2006
 
Description Metabolomic Analysis in Severe Pneumonia 
Organisation Georgetown University
Department Lombardi Comprehensive Cancer Center
Country United States 
Sector Academic/University 
PI Contribution Design and conduct of the severe pneumonia aetiology study to which this metabolomic component has been added
Collaborator Contribution Metablomic analysis of samples for the Severe Pneumonia Aetiology Study
Impact Abstract to ISPPD-7 conference; publication 20844590
Start Year 2008
 
Description RSV Global Estimates Network (RSV GEN) 
Organisation University of Edinburgh
Department Global Public Health Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Contribution of expertise, time and data to global estimates of RSV disease
Collaborator Contribution Coordination of Network/Working Group
Impact A global estimate of RSV burden paper is being written
Start Year 2013
 
Description University Edinburgh-CHERG pneumonia collaborative group 
Organisation University of Edinburgh
Department Centre for Population Health Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We contribute local data to global analyses of childhood pneumonia
Collaborator Contribution This Group led by Harry Campbell brings together pneumonia researchers from around the world to synthesise global data on childhood pneumonia to guide policy and practice. As part of this group we are able to have our local data contribute to global analyses
Impact The global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Harish Nair, W. Abdullah Brooks , Anna Roca , James A Berkley , Shabir A Madhi , James Mark Simmerman , Aubree Gordon , Masatoki Sato , Stephen Howie , Anand Krishnan , Maurice Ope , Kim A Lindblade , Phyllis Carosone-Link , Marilla Lucero , Walter Ochieng , Laurie Kamimoto , Erica Dueger , Niranjan Bhat , Sirenda Vong , Evropi Theodoratou , Malinee Chittaganpitch , Osaretin Chimah , Angel Balmaseda , Philippe Buchy , Eva Harris , Valerie Evans , Masahiko Katayose , Bharti Gaur , Cristina O'Callaghan-Gordo , Doli Goswami , Wences Arvelo , Marietjie Venter , Thomas Briese , Rafal Tokarz , Marc-Alain Widdowson , Anthony W Mounts , Robert F Breiman , Daniel R Feikin , Keith P Klugman , Sonja J Olsen , PhD; Bradford D Gessner , Peter F Wright , Igor Rudan , Shobha Broor , Eric A F Simões , Harry Campbell. Lancet 2011; in press (accepted 2 July 2011)
Start Year 2010
 
Description genome-wide gene expression in severe pneumonia 
Organisation University of Edinburgh
Department Division of Pathway Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We designed the clinical and epidemiological aspects of the study
Collaborator Contribution Sharing of skills in bioinformatics
Impact Nil publications as yet
Start Year 2008
 
Title Biomarker patent application 
Description Using a clinical and epidemiological platform for severe pneumonia study in The Gambia and proteomic analysis expertise in Oxford a biomarker for severe and bacterial pneumonia was discovered and validated 
IP Reference PCT/GB2013/051768 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact Nil to date
 
Description Gambia government-MRC meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact reporting on and discussing research results and plans and priorities

Progress towards consensus on priorities and activities
Year(s) Of Engagement Activity 2006,2007,2009
 
Description Gambia government-MRC meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact reporting on and discussing research results and plans and priorities

Progress towards consensus on priorities and activities
Year(s) Of Engagement Activity 2006,2007,2009
 
Description Gambian radio 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Field Coordinator for the Severe Pneumonia Studies does radio talk back shows on several radio stations in The Gambia once or twice a year. The purpose of these is to raise awareness about pneumonia and about our research, as well as to dispell common misconceptions about MRC research in general.

These radio programmes are well received. It is clear to the field team that people they are encountering in the community are more likely to have some basic knowledge about pneumonia and are keener to participate in research projects.
Year(s) Of Engagement Activity 2008,2009
 
Description TAMA - Unit information dissemination newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Type Of Presentation Paper Presentation
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact An interview detailing the scope of pneumonia-related research at the Unit.
Report about oxygen project

Not known
Year(s) Of Engagement Activity 2009,2013
 
Description World Pneumonia Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact MRC supported the Ministry of Health in organising rallies in Banjul, Bansang and Basse to mark the first World Pneumonia Day. MRC staff including SH spoke at the rallies. Subsequent WPDs have been observed similarly, notably 2011 and 2012

These World Pneumonia Day activities were covered by Gambian news media and given wide exposure in the country.
Year(s) Of Engagement Activity 2009,2011,2012