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Clin Infect Dis. 2017 Apr 1;64(7):939-946. doi: 10.1093/cid/cix003.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

Author information

1
Mbale Regional Referral Hospital Clinical Research Unit.
2
Busitema University Faculty of Health Sciences, Mbale Campus.
3
Soroti Regional Referral Hospital, Soroti, Uganda.
4
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
5
Makerere College of Health Sciences, Department of Paediatrics, Kampala, and.
6
St Mary's Hospital, Lacor, Uganda.
7
Joint Malaria Programme, Teule Hospital, Muheza, Tanzania; and.
8
Medical Research Council, Clinical Trials Unit, University College London, and.
9
Faculty of Medicine, Imperial College, London, United Kingdom.

Abstract

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 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls.

Results:

Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia 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%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria.

Conclusions:

We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.

KEYWORDS:

African child; blackwater fever; haemoglobinopathies; hemoglobinuria; malaria

PMID:
28362936
PMCID:
PMC5848229
DOI:
10.1093/cid/cix003
[Indexed for MEDLINE]
Free PMC Article

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