Risk factors associated with poor prognosis from acute lower respiratory infections (ALRI) in young children in low and middle income countries: analysis of published and unpublished data

Pneumonia is the leading infectious cause of death worldwide in children 1-59 months. Although childhood pneumonia mortality has declined gradually since 2000, it remains the major cause of childhood mortality beyond the neonatal period. The highest pneumonia mortality rates are in low- and middle-income countries (LMICs); 49% of pneumonia deaths occurred in just 5 countries: India, Nigeria, Pakistan, Democratic Republic of Congo, and Ethiopia. In some countries in Africa and Southeast Asia, the highest incidences and mortalities from child pneumonia are due to poor socioeconomic conditions and health-related factors such as HIV and malnutrition. The WHO revised its pneumonia management guidelines to facilitate pneumonia case distinguished from ALRIs and other diseases. However, despite the widespread implementation of the Integrated Management of Childhood Illnesses algorithm, high vaccination coverage, and improved nutrition, a substantial burden of disease remains due to other common and preventable risk factors. The purpose of this study was to investigate the evidence on potential risk factors that can predict poor prognosis (death) in young children presenting to hospital with pneumonia in LMICs. This was accomplished by evaluating the evidence from two sources: published and unpublished data. In the first part of this thesis, I analysed data from published studies to investigate risk factors associated with in-hospital pneumonia child mortality. Starting with a systematic review and meta-analysis, I obtained pooled estimates for different risk factors associated with in-hospital pneumonia child mortality that were related to child, mother, socioeconomic status, and environmental factors in addition to health-related factors. In the second part of the thesis, I analysed data from the WHO PREPARE dataset. A univariate analysis of risk factors showed that the association between increased respiratory rate and increased CFR extended beyond the WHO threshold for all age groups (with very high respiratory rate associated with a further increase in risk). Oxygen saturation also showed an interesting observation of a non-existent clear threshold at 90%, and CFR seems to keep falling until about 95% SpO2. I then developed a multi-variable model for poor prognosis (death) in young children admitted to hospital with pneumonia. Hypoxaemia had the greatest odds of child mortality, followed by malnutrition. However, interaction among the involved variables complicated the model and needs more detailed study. I then adopted a decision-tree classification approach to take into account these complex relationships and presented results in a simple format which has potential to be implemented in a clinical context. Dividing the sample into two different tracks (infant = 12 months), the results demonstrate that the importance of the child’s age in terms of the relative importance of presenting symptoms. Being able to discriminate between cases based on their age followed by presenting signs may help refine treatment plans and case management more quickly. The presence of hypoxaemia, malnutrition and raised respiratory rate were the most discriminating clinical signs for poor outcome. The investigated pneumonia risk factors are often the result of children’s exposure to multiple deprivations. Actions must target the most vulnerable children and ensure all children living within high mortality countries have access to protective, preventive, and curative services. However, it is quite clear from the results in this thesis that many poor pneumonia prognoses in children could be avoided by using simple equipment such as pulse oximeters to supplement clinical signs and identify children with pneumonia at high risk of mortality