{"doi":"10.1093/infdis/jiae431","title":"Circulating Immune Complexes and Glucose-6-Phosphate Dehydrogenase Deficiency Predict Recurrent Blackwater Fever in Ugandan Children With Severe Malaria","abstract":"BACKGROUND: Recently, there has been an unexplained increase in the incidence of blackwater fever (BWF) in Eastern Uganda. In this study, we evaluated the association between immune complexes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the occurrence and recurrence of BWF in children with severe malaria (SM). METHODS: Between 2014 and 2017, children aged 6 months to <4 years hospitalized with SM and community children (CC) were recruited at 2 hospitals in Central and Eastern Uganda. We measured serum circulating immune complexes (cIC) and their relationship to SM complications and postdischarge outcomes, and evaluated effect mediation through G6PD deficiency. RESULTS: In total, 557 children with SM and 101 CC were enrolled. The mean age was 2.1 years. Children with SM had higher cIC levels than CC (P < .001). After controlling for age, sex, and site, cIC were associated with severe anemia, jaundice, and BWF: adjusted odds ratio (aOR), 7.33 (95% confidence interval [CI], 3.45-15.58), P < .0001; aOR, 4.31 (95% CI, 1.68-11.08), P = .002; and aOR, 5.21 (95% CI, 2.06-13.18), P < .0001, respectively. cIC predicted readmissions for SM, severe anemia, and BWF: adjusted incidence rate ratios (aIRR), 2.11 (95% CI, 1.33-3.34), P = .001; aIRR, 8.62 (95% CI, 2.80-26.59), P < .0001; and aIRR, 7.66 (95% CI, 2.62-22.45), P < .0001, respectively. The relationship was most evident in boys where the frequency of the G6PD African allele (A-) was 16.8%. G6PD deficiency was associated with increases in cIC in boys (P = .01) and mediation analysis suggested G6PD deficiency contributes to recurrent severe anemia and BWF via increased cIC. CONCLUSIONS: Immune complexes are associated with hemolytic complications and predict recurrences in SM survivors.","journal":"The Journal of Infectious Diseases","year":2024,"id":466258,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9385,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1082704,"name":"Kagan A. Mellencamp","orcid":"0000-0003-3994-3869","position":1,"is_corresponding":false},{"id":269837,"name":"Robert O. Opoka","orcid":"0000-0003-3240-2058","position":2,"is_corresponding":false},{"id":269828,"name":"Dibyadyuti Datta","orcid":"0000-0002-1693-935X","position":3,"is_corresponding":false},{"id":1146820,"name":"Giselle Lima-Cooper","orcid":"0000-0001-5168-9125","position":4,"is_corresponding":false},{"id":920007,"name":"Claire Liepmann","orcid":null,"position":5,"is_corresponding":false},{"id":748974,"name":"Julian Sherman","orcid":null,"position":6,"is_corresponding":false},{"id":481595,"name":"Ana Rodrı́guez","orcid":"0000-0002-0060-3405","position":7,"is_corresponding":false},{"id":1092097,"name":"Caroline Kazinga","orcid":null,"position":8,"is_corresponding":false},{"id":310457,"name":"Russell E. Ware","orcid":"0000-0001-9582-0594","position":9,"is_corresponding":false},{"id":1298454,"name":"Michael G Goings","orcid":null,"position":10,"is_corresponding":false},{"id":3855,"name":"Marcus V. G. de Lacerda","orcid":"0000-0003-3374-9985","position":11,"is_corresponding":false},{"id":899526,"name":"Marco Abreu","orcid":"0000-0002-5659-1255","position":12,"is_corresponding":false},{"id":309714,"name":"Tae-Hwi Schwantes-An","orcid":null,"position":13,"is_corresponding":false},{"id":91693,"name":"Chandy C. John","orcid":null,"position":14,"is_corresponding":false},{"id":445533,"name":"Andrea L. Conroy","orcid":"0000-0002-5328-6511","position":15,"is_corresponding":false},{"id":466930,"name":"Ruth Namazzi","orcid":"0000-0003-2459-6526","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:04:54.606394Z","pmid":"39208451","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}