Background
In the Fluid-Expansion-as-a-Supportive-Treatment (FEAST) trial an unexpectedly-high proportion of participants from Eastern Uganda presented with blackwater fever (BWF).
Methods
We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of three malaria-protective red blood cell polymorphisms in BWF-cases versus both trial (non-BWF) and population-controls.
Findings
Of 3,170 trial participants 394 (12.4%) had BWF. The majority (318; 81.0%) presented in Eastern Uganda: the subjects of further analysis. BWF cases typically presented with both clinical jaundice 254/318 (80%) and severe-anaemia (Hb <5g/dl) 238/310 (77%). Plasmodium falciparum parasitaemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum Histidine Rich Protein-2 [192/246 (78.0%) versus 811/1154 (70.3%); p=0.014], suggesting recent anti-malarial treatment. Overall, 282/318 (88.7%) received transfusions, with 94/282 (33.3%) and 9/282 (3.4%) receiving 2 or 3 transfusions respectively. By day-28, 39/318 (12.3%) BWF cases and 154/1554 (9.9%) non-BWF controls had died (P=0.21) and 7/255 (3.0%) versus 13/1212 (1%; p=0.036) had severe anaemia. We found no association with G6PD deficiency. The prevalence of both the sickle cell trait [10/218 (4.6%)] and homozygous +thalassaemia [8/216 (3.7%)] were significantly lower among cases than population controls [334/2123 (15.7%) and 141/2114 (6.6%), respectively], providing further support for the role of malaria.
Interpretation
We report the emergence of BWF in Eastern Uganda, a condition that according to local investigators was rare until the last 5 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.