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Title: Towards an evidence base in the treatment of severe febrile illness in East African children
Author: Nadjm, Behzad
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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Febrile illness is the primary cause of childhood outpatient attendance, admission to hospital and death in Africa. This series of studies were aimed at ascertaining the treatable causes of infection in children admitted to a district hospital typical of those found throughout East Africa, in an area of high transmission of malaria. The studies were also designed to determine the clinical correlates of infection and predictors of mortality, looking in particular at malaria, invasive bacterial disease and HIV infection. These studies also explored to what extent clinical examination by one group of staff was replicable by another. After informed consent a detailed history and structured examination was performed on all children admitted to the hospital. Blood was drawn for culture, microscopy for malaria, HIV testing, full blood count, bedside haemoglobin, blood glucose and lactate measurement and HRP-2 based rapid diagnostic test for falciparum malaria. Outcomes were recorded at death or discharge. Sufficient data was available on 3,639 children including 184 deaths (5.1%). Invasive bacterial disease was detected in 341 children (9.4%) and HIV in 142 (3.9%). Children with HIV and those with evidence of recent malaria were significantly more likely to have invasive bacterial disease. The most common organisms isolated were non-typhi Salmonella (46.9%), Strep, pneumoniae (16.4%) and Haemophilus influenzae b (11.4%). The most frequently encountered pathogen was P. falciparum, with 2,195 children found to have asexual parasitaemia (60.3%). Falciparum parasitaemia was detected in 100 children with invasive bacterial disease (29.3%). Falciparum malaria was detected in over half (51.6%) of childhood deaths, invasive bacterial disease was documented in 31.5%. In children with a positive blood slide for malaria, WHO severe malaria criteria identified 91.6% of the children that died. A multivariate analysis showed that signs of malnutrition, respiratory distress, altered consciousness, hypoxia according to pulse oximetry, hypoglycaemia, raised blood lactate, invasive bacterial disease and female sex were all associated with an increased risk of death. In children with negative blood slides signs of malnutrition, respiratory distress, altered consciousness, hypoglycaemia, raised blood lactate and invasive bacterial disease were all independently associated with mortality by multivariate analysis. WHO defined criteria of syndromes which would warrant antibiotics predicted 56% of cases of coinfection with invasive bacterial disease and malaria and 69.7% of cases of invasive bacterial disease in slide negative children. Treating all children with severe malaria for bacterial disease would result in 71% of children with coinfection being treated. In children with negative slides including severe anaemia or prostration as syndromes requiring antibiotic therapy would have resulted in 74.7% of children with invasive bacterial disease receiving antibiotic therapy. There was moderate agreement between staff over the presence of clinical signs in children, with hospital nurses performing as well as hospital clinical officers. Agreement was better in children over 18 months of age and in children who were not crying during examination. Current WHO guidelines on antibiotic use performed poorly in this setting. Gram negative infections were the most common cause of invasive infection and many of these are likely to be resistant to penicillin and other commonly used antibiotics. Consideration should be given to expanding the indications for antibiotic use and using more broad-spectrum antibiotics in severely ill children.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available