Efficacy of zinc as an adjunct therapy in the management of severe pneumonia among Gambian children

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Pneumonia is one of the most important causes of death among children in The Gambia. Malnourished children are thought to be deficient of an important micronutrient called zinc. Deficiency of zinc was found to be associated with loss of bodys protection to severe infection including pneumonia. The bodys capacity to fight against severe or very severe pneumonia may be improved by giving zinc to malnourished children. We are doing research to find out if zinc supplementation improves child hood pneumonia among malnourished children.In this study children suffering from malnutrition and severe or very severe pneumonia will be included if it is likely to be zinc deficient as well. Participants will receive either zinc plus multivitamins or only multivitamins, along with other treatment for pneumonia. We will take blood samples at the beginning and after 6 months, if the child is included in a 6 months follow-up study. These samples of blood will be used to see if the subject has enough blood or malaria, and the zinc and iron status will be determined. In the 6 months follow-up study, a health worker will visit the subjects 6 days a week to supervise intake of trial medicines. He/She will also collect information on the childs health on each weekly visit, and measure the childs height and weight each month for 6 months.

Technical Summary

Zinc is the most abundant trace metal inside most cells. It is a functionally essential component of more than 200 enzymes, pervading all metabolic pathways. The beneficial role of zinc in the maintenance and regeneration of pulmonary epithelial cells, cellular growth and differentiation, improvement of immune status, recovery from acute diarrhoea, and prevention of severe ALRI or pneumonia in children suggests the potential benefit of zinc in the treatment of pneumonia in children. Stunted children are at increased risk of zinc deficiency and severe infections including severe pneumonia. We will conduct a double blind randomized clinical trial of zinc as an adjunct treatment of severe or very severe pneumonia among stunted children. Four hundred and eighty stunted children 2 to 24 months of age presenting with severe or severe pneumonia will be randomized to receive zinc plus multivitamins or multivitamins only with antibiotics for treatment of severe or very severe pneumonia. Proportion of children failing to recover from severe pneumonia on day-5 post-enrolment or from very severe pneumonia on day-10 post enrolment will be compared between the groups. To confirm that stunted Gambian children are zinc deficient, we will continue zinc supplementation in a subgroup of 130 children for 6 months after recovery from severe or very severe pneumonia and measure the impact of zinc supplementation on linear growth and immune competence. If zinc is found to be efficacious as an adjunct treatment of severe or very severe pneumonia in chronically malnourished children, it will have far-reaching implication for child survival in many developing countries.

Publications

10 25 50

publication icon
Howie SR (2011) Blood sample volumes in child health research: review of safe limits. in Bulletin of the World Health Organization

publication icon
Puchalski Ritchie LM (2009) Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

publication icon
Ritchie L. M. Puchalski (2009) Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study in INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE

publication icon
Rutherford ME (2009) Preventive measures in infancy to reduce under-five mortality: a case-control study in The Gambia. in Tropical medicine & international health : TM & IH

 
Description Indoor Air Pollution Interventions for Child Pneumonia in The Gambia
Amount $130,000 (USD)
Organisation National Institute of Environmental Health Sciences 
Sector Academic/University
Country United States
Start  
 
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 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