Potentially Modifiable Factors Associated with Death of Infants and Children with Severe Pneumonia Routinely Managed in District Hospitals in Malawi

RESEARCH ARTICLE Potentially Modifiable Factors Associated with Death of Infants and Children with Severe Pneumonia Routinely Managed in District Hospitals in Malawi Penelope M. Enarson1,2*, Robert P. Gie2,3, Charles C. Mwansambo4, Alfred E. Chalira4, Norman N. Lufesi4, Ellubey R. Maganga5, Donald A. Enarson1,2, Neil A. Cameron6, Stephen M. Graham1,7 1 International Union Against Tuberculosis and Lung Disease, Paris, France, 2 Desmond Tutu TB Centre, Stellenbosch University, Tygerberg, South Africa, 3 Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa, 4 Ministry of Health, Lilongwe, Malawi, 5 UNICEF Malawi, Lilongwe, Malawi, 6 Division of Community Health, The Department of Interdisciplinary Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa, 7 Centre for International Child Health, University of Melbourne Department of Paediatrics and Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Australia OPEN ACCESS Citation: Enarson PM, Gie RP, Mwansambo CC, Chalira AE, Lufesi NN, Maganga ER, et al. (2015) Potentially Modifiable Factors Associated with Death of Infants and Children with Severe Pneumonia Routinely Managed in District Hospitals in Malawi. PLoS ONE 10(8): e0133365. doi:10.1371/journal. pone.0133365 Editor: Eric Brian Faragher, Liverpool School of Tropical Medicine, UNITED KINGDOM Received: October 17, 2014 * Abstract Objective To investigate recognised co-morbidities and clinical management associated with inpatient pneumonia mortality in Malawian district hospitals. Accepted: June 26, 2015 Published: August 3, 2015 Copyright: © 2015 Enarson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The CLHP was primarly funded by the MoH of Malawi, who contributed 69% of the running costs comprising facilities and human resources that are part of the existing health system. The Bill and Melinda Gates Foundation funded the remaining 31% of the costs, 21% of which was investment and 79% operating costs. The Bill & Melinda Gates Foundation grant ID#: 413 http://www.gatesfoundation.org/Pages/ home.aspx). The external funders had no role in Methods Prospective cohort study, of patient records, carried out in Malawi between 1st October 2000 and 30th June 2003. The study included all children aged 0-59 months admitted to the paediatric wards in sixteen district hospitals throughout Malawi with severe and very severe pneumonia. We compared individual factors between those that survived (n = 14 076) and those that died (n = 1 633). Results From logistic regression analysis, predictors of death in hospital, adjusted for age, sex and severity grade included comorbid conditions of meningitis (OR =2.49, 95% CI 1.50-4.15), malnutrition (OR =2.37, 95% CI 1.94-2.88) and severe anaemia (OR =1.41, 95% CI 1.031.92). Requiring supplementary oxygen (OR =2.16, 95% CI 1.85-2.51) and intravenous fluids (OR =3.02, 95% CI 2.13-4.28) were associated with death while blood transfusion was no longer significant (OR =1.10, 95% CI 0.77-1.57) when the model included severe anaemia. PLOS ONE | DOI:10.1371/journal.pone.0133365 August 3, 2015 1 / 13 Factors Associated with Outcome in Children with Severe Pneumonia study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Conclusions This study identified a number of challenges to improve outcome for Malawian infants and children hospitalised with pneumonia. These included improved assessment of co-morbidities and more rigorous application of standard case management. Introduction Pneumonia is consistently estimated to be the single major cause of death in infants and young children (1–59 months of age) and almost all these deaths occur in low-income countries. [1–3] It is estimated that approximately 50% of all deaths due to pneumonia in children occur in sub-Saharan Africa. [4] However, there are a number of acknowledged limitations to attributing a death to a single disease entity. [5–7] First, in infants and young children with severe pneumonia, co-morbidities such as malnutrition or HIV infection are common and increase the risk of death. [8,9] Second, there is clinical overlap with diseases such as severe anaemia, malaria or septicaemia that may result in death being wrongly attributed to pneumonia. [10,11] Finally, it is also recognised that bacterial pneumonia can occur as a co-infection or secondary complication in children with other infections such as measles, severe malaria or tuberculosis. [12–14] Nonetheless, health workers in high mortality settings are required to manage sick children according to standard case-management protocols on the basis of clinical findings with very limited diagnostic support. The World Health Organization (WHO) has clear clinical case-management guidelines that aim to identify the child with pneumonia among the many infants and young children that present to health services with an acute respiratory illness, and then to classify the pneumonia case further by age and by severity. [15] These classifications determine whether the child with pneumonia is managed as an inpatient or outpatient and the choice of antibiotic treatment. [11] In general terms, the choice of penicillin is primarily aimed to treat pneumonia due to Streptococcus pneumoniae, while a broad spectrum antibiotic is recommended as first-line antibiotic treatment for cases where pneumonia is associated with a high risk of mortality and/or is often due to a wider range of bacterial pathogens, including Gram negative bacteria. The latter group include very young infants (<2 months of age), malnourished children and children with very severe pneumonia. [11,15] Therefore children 2 to 59 months of age classified as having very severe pneumonia are to be given chloramphenicol for treatment; those classified as having severe pneumonia are not. The WHO case-management guidelines also aim to avoid the unnecessary use of antibiotics for upper respiratory tract illness only. We recently reported outcomes from a prospective implementation programme that included 47,228 Malawian children admitted to district hospitals in Malawi for severe and very severe pneumonia over a five year period. [16, 17] We have further analysed data from a subset of this cohort to determine the individual factors including demographics of the study population, recognised co-morbidities and clinical management that were associated with inpatient death. Methods Study participants We revi (...truncated)