Severe Pneumonia Studies Platform

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Pneumonia is the leading killer of young children worldwide and these studies are pursuing ways of preventing and treating it.
Vaccines are important for preventing pneumonia but current vaccines are unlikely to prevent more than half the deaths from pneumonia. Other measures are needed and it is likely that understanding how nutrition, things in the environment like cooking smoke, and social factors contribute to the chances of getting pneumonia will help us identify such measures. We are currently studying such factors with that aim.
We need to understand better what infections are causing pneumonia so that treatment can be improved and that future vaccines can be developed. Laboratory methods to identify these infections have been limited in the past, and newer molecular methods are giving us better insights into what organisms are causing severe pneumonia.
Unfortunately our best efforts will not prevent a substantial number of pneumonia cases, so we need to ensure that treatment can stop children with pneumonia dying. Our work focuses on treatments that can add value to antibiotics. Nutritional treatments such as zinc may do this and we are testing this possibility. We know that oxygen can save lives but it is usually not available to children in poor countries. We are working out ways to allow oxygen to be available to such children. Pneumonia and bacterial infections are an important causes of death and disease in newborn and young infants and this is an important area to develop further in future.

Technical Summary

The Severe Pneumonia Studies Platform hosts studies of the causes of and treatment for the leading cause of death in children. Reducing deaths from pneumonia is critical to the achievement of the 4th Millennium Development Goal, which is to reduce under-5 mortality two-thirds by 2015 compared to a 1990 baseline. This platform is designed to support research towards that aim and the aim of reducing pneumonia mortality further beyond 2015.
The platform has a case-control design and includes observational and interventional work, specifically: a study of risk factors for severe pneumonia (crowding, nutrition and indoor air pollution in particular), a study of aetiology using conventional and molecular methods, and a randomised trial of zinc adjunct treatment for severe pneumonia. In addition to this the platform hosts operational work on oxygen delivery for very severe pneumonia.
Understanding pneumonia aetiology better is important both for guiding treatment and for designing vaccines. Our understanding of aetiology has been limited by the low sensitivity of conventional culture, and these studies seek to improve our knowledge using molecular techniques. The strength of work conducted on the platform has enables us to participate in a large Gates-funded multi-country study of severe pneumonia, the Pneumonia Etiology for Child Health (PERCH) project. The PERCH study includes 7 countries and will give representative data on aetiology and risk factors in the context of the routine use of conjugate pneumococcal and Hib vaccines.
The use of currently available vaccines have the potential to reduce pneumonia mortality by up to half, but this will still leave a substantial burden of death that needs addressing. It is likely that social, environmental and nutritional factors are important in pneumonia mortality and identifying remedial risk factors in these areas is important.
Prevention alone will not be sufficient to reduce pneumonia deaths and improving case management will be crucial. Zinc adjunct treatment may lessen disease severity and hasten recovery and we are conducting an RCT to test this hypothesis. Oxygen reduces case fatality but most children do not have it available to them. We are undertaking operational research to understand and overcome barriers to successful oxygen treatment in children with severe pneumonia in the developing world.

Publications

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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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Bradley BD (2016) Implementation and 8-year follow-up of an uninterrupted oxygen supply system in a hospital in The Gambia. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

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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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Howie SR (2016) Global Hib vaccination: reasons to cheer and fear. in The Lancet. Global health

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Howie SR (2013) The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Howie SR (2014) Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Howie SR (2016) Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

 
Description Gambia Hib vaccine impact
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
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 Indoor Air Pollution Interventions for Child Pneumonia in The Gambia
Amount $130,000 (USD)
Organisation National Institute of Environmental Health Sciences 
Sector Public
Country United States
Start  
 
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 Immunology of zinc deficiency and supplementation in severe pneumonia 
Organisation Medical Research Council (MRC)
Department MRC International Nutrition Group
Country United Kingdom 
Sector Academic/University 
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 Indoor Air Pollution Harvard Collaboration 
Organisation Harvard University
Department Harvard T.H. Chan School of Public Health
Country United States 
Sector Academic/University 
PI Contribution Design and conduct of the severe pneumonia risk factor study in which this air pollution measurement component is applied
Collaborator Contribution Funding of a research assistant and field workers working in The Gambia
Impact Advances in methods for indoor air pollution exposure in children (PMID: 18422570)
Start Year 2007
 
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 Proteomic Collaboration Oxford 
Organisation University of Oxford
Department Wellcome Trust Centre for Human Genetics
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Design and conduct of epidemiological study to identify diagnostic biomarkers for pneumonia
Collaborator Contribution Design and conduct of proteomic laboratory analyses to identify diagnostic biomarkers for pneumonia
Impact Nil to date. Patent applications pending
Start Year 2009
 
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 Severe Acute Lower Respiratory Infections Working Group 
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 epidemiological studies of Severe ALRI
Collaborator Contribution Coordination of Working Group funded by BMGF, resources for meetings and the other activities associated with collaboration on global epidemiology of this disease
Impact This is a multi-disciplinary working group comprising clinicians epidemiologists and public health experts. Outputs: Global and regional estimates of hospitalised severe acute lower respiratory infections in young children in 2010: a systematic review and meta analysis. Harish Nair et al. Lancet 2013; Epub ahead of print Jan 29 doi:pii: S0140-6736(12)61901-1. 10.1016/S0140-6736(12)61901-1 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; 378:1917-30
Start Year 2010
 
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 WO2014006408 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact Nil to date
 
Title Oxygen delivery system 
Description A novel oxygen delivery system for use in developing country health facilities is under development. Funding has been secured under the MRC DPFS scheme to pursue this further 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2012
Development Status Under active development/distribution
Impact This product represents a development from earlier oxygen delivery work that has improved patient care in more than one health facility in The Gambia. The ultimate aim is to contribute to mortality reduction 
 
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