The Burden and Spectrum of Paediatric Severe Malaria and Aetiology of Dark Urine Syndrome in Eastern Uganda

Olupot-Olupot, Peter (2015). The Burden and Spectrum of Paediatric Severe Malaria and Aetiology of Dark Urine Syndrome in Eastern Uganda. PhD thesis The Open University.



From May 2011 - April 2012, I prospectively conducted paediatric ward admissions surveillance (WSS) and described both the in-patient burden and clinical spectrum of severe P. falciparum malaria (SM) in children admitted to Mbale Regional Referral Hospital (Mbale RRH). Furthermore, epidemiology, clinical features and the outcomes of dark urine syndrome (DUS) were described using both retrospective dark urine epidemiological study (REDUES); (FEAST trial ISRCTN 69856593) and the prospective dark urine epidemiological study (PRODUES) nested in the WSS. Overall 10,208/23,217 (44.0%) children were enrolled in the WSS, a majority 87% were under 5 years of age. Malaria 6,714/10,208 (65. 8%) and DUS 1,087/10,208 (10.6%) were among the common diagnoses. Neonatal conditions accounted for 947/9,551 (10.0%) admissions. The in-hospital mortality was high 655 (6.4%); with higher case fatality rate (CFR) 13.2% in neonates compared to 3.7% in older children, P=0.0001. The WHO criteria for surveillance of severe malaria were fulfilled in 662 admissions or 10% of all malaria cases. The common clinical presentations included respiratory distress 554/662 (83.7%), shock 411/662 (62.1%), clinical jaundice 177/662 (26.7%), severe anaemia 169/662 (25.5%), hyperlactataemia 134/662 (20. 3%) and DUS 93/662 (14.0%); features similar to, but also varying from those reported from other settings. The mortality in SM was high 63/662 (9.5%) but consistent with other reports, with higher CFR in patients with multiple features. In the REDUES, 394/3,170 (12.4%) had DUS with a majority 318/394 (81.0%) presenting to Eastern Uganda. Complications of DUS included clinical jaundice in 256/318 (80.5%) and severe anaemia (Hb <5g/dL) in 238/310 (77.0%). Current malaria infection 147/300 (49.0%) was lower than evidence of recent infection 192/246 (78. 0%). G6PD was marginally higher in DUS 35/224 (15.6%) v 53/489 (10.8%) in those without DUS. Mortality at 48hours (10.4% v 8.9%, P=0.402) and at 28 days (12.3% v 9.9%, P=0.211) was similar in children with and without DUS respectively. PRODUES enrolled 268 strictly defined cases in whom use of antimalarials 129/268 (48.1%) and herbs 52/268 (19.4%) were common. Haemoglobinuria 92/165 (55.8%) and myoglobinuria 59/165 (36.0%), markers of massive haemolysis and muscle cell injury respectively were found; possibly related to the pathophysiology of malaria. In conclusion, the spectrum of SM in children at Mbale RRH was similar to, but also varied from current descriptions from other sites. The DUS was linked to malaria with innate characteristics and drugs being risk factors.

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