title: High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.
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.
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit.|Busitema University Faculty of Health Sciences, Mbale Campus.
authors.forename: Peter
authors.initials: P
authors.lastname: Olupot-Olupot
authors.affiliation: Soroti Regional Referral Hospital, Soroti, Uganda.
authors.forename: Charles
authors.initials: C
authors.lastname: Engoru
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
authors.forename: Sophie
authors.initials: S
authors.lastname: Uyoga
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit.
authors.forename: Rita
authors.initials: R
authors.lastname: Muhindo
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
authors.forename: Alex
authors.initials: A
authors.lastname: Macharia
authors.affiliation: Makerere College of Health Sciences, Department of Paediatrics, Kampala, and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kiguli
authors.affiliation: Makerere College of Health Sciences, Department of Paediatrics, Kampala, and.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Opoka
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
authors.forename: Samuel
authors.initials: S
authors.lastname: Akech
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
authors.forename: Carolyne
authors.initials: C
authors.lastname: Ndila
authors.affiliation: St Mary's Hospital, Lacor, Uganda.
authors.forename: Richard
authors.initials: R
authors.lastname: Nyeko
authors.affiliation: Joint Malaria Programme, Teule Hospital, Muheza, Tanzania; and.
authors.forename: George
authors.initials: G
authors.lastname: Mtove
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit.
authors.forename: Julius
authors.initials: J
authors.lastname: Nteziyaremye
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit.|Busitema University Faculty of Health Sciences, Mbale Campus.
authors.forename: Martin
authors.initials: M
authors.lastname: Chebet
authors.affiliation: Medical Research Council, Clinical Trials Unit, University College London, and.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: George
authors.affiliation: Medical Research Council, Clinical Trials Unit, University College London, and.
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Babiker
authors.affiliation: Medical Research Council, Clinical Trials Unit, University College London, and.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit.|Busitema University Faculty of Health Sciences, Mbale Campus.|Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.|Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit.|Busitema University Faculty of Health Sciences, Mbale Campus.|Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.|Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Maitland
mesh_terms: D000367:Age Factors; D015415:Biomarkers; D001742:Blackwater Fever / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology* / Q000469:parasitology; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006453:Hemoglobinopathies / Q000150:complications / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D063868:Patient Outcome Assessment; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D012720:Severity of Illness Index; D063189:Symptom Assessment; D014454:Uganda / Q000453:epidemiology; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D005954:Glucosephosphate Dehydrogenase
keywords: African child; blackwater fever; haemoglobinopathies; hemoglobinuria; malaria