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Title: Community-acquired pneumonia in Malawian adults : aetiology and predictors of mortality
Author: Aston, S. J.
ISNI:       0000 0004 6422 6770
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Background Community-acquired pneumonia (CAP) is one of the commonest causes of adult hospitalisation in sub-Saharan Africa, but recent data describing its epidemiology, microbial aetiology and outcome are limited. Focusing particularly on Malawi, the overall aim of this thesis was to describe the aetiology and outcome of CAP in sub-Saharan African to determine the key predictors of mortality. Methods Firstly, a systematic review of studies of CAP in adults in sub-Saharan Africa was performed to describe CAP aetiology, estimate the mortality rate and identify risk factors associated with death. Secondly, a prospective observational study of adults hospitalised with clinically diagnosed CAP to Queen Elizabeth Central Hospital, Blantyre, Malawi was completed to describe microbial aetiology using modern diagnostic modalities, determine outcome and identify prognostics factors. Thirdly, having identified in preliminary analyses of the prospective cohort that hypoxaemia was an independent risk factor for mortality, a study of the effectiveness of supplemental oxygen delivery by oxygen concentrator to correct hypoxaemia in adults with suspected CAP was performed. Results In both the systematic review and the prospective cohort the predominant burden of hospitalised CAP was in young (average age 38 and 35, respectively) and HIV-positive (52% and 78%) patients with limited chronic cardiovascular and pulmonary comorbidity. Streptococcus pneumoniae (27% and 21%) and Mycobacterium tuberculosis (19% and 23%) were the most commonly identified causes. The overall mortality rate for hospitalised patients in the systematic review was 9.5%, but data describing prognostic factors were limited. In the prospective cohort (n=459), death by day 30 occurred in 14.6% and was associated with: male sex (aOR 2.57); pre-presentation symptom duration (aOR 1.11 per day increase); inability to stand (aOR 4.28); heart rate (aOR 1.02 per beat/minute rise); oxygen saturations (aOR 0.95 per % rise); white cell count (aOR 0.91 per 109/L rise); haemoglobin (aOR 0.90 per g/dL rise). A newly derived four parameter mortality risk prediction tool based on male sex, oxygen saturations < 90%, inability to stand and heart rate ≥125 /min predicted 30-day mortality with reasonable accuracy (area under the receiver-operating curve (AUROC) 0.79) whilst existing tools performed poorly (CURB65: AUROC 0.60; SMRT-CO: AUROC 0.66). Hypoxaemia was corrected in 86.4% (n=59) of adults with suspected CAP with supplemental oxygen at standard flow-rate of 5 litres/minute. Failure to attain normoxaemia was associated with a more than four-fold increase in the risk of death (RR 4.25). Conclusions The major burden of hospitalised CAP in low-resource, sub-Saharan African settings is seen in young and HIV-positive adults, many of whom have TB. Extrapolating CAP assessment and treatment algorithms from well-resourced settings where the epidemiology and aetiology of disease is very different is flawed. If validated, locally derived severity assessment tools may provide a rational basis on which to stratify CAP management. Strategies to increase early detection and treatment of TB and to improve supportive care, in particular the correction of hypoxaemia, hold considerable promise for improving CAP outcomes and should be evaluated in clinical trials.
Supervisor: Gordon, S. B. ; Heydernan, R. S. ; Mwandumba, H. C. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral