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.

中文翻译：

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循环免疫复合物和葡萄糖-6-磷酸脱氢酶缺乏症可预测乌干达重症疟疾儿童复发性黑水热


背景 最近，乌干达东部黑水热 （BWF） 的发病率出现了不明原因的增加。在这项研究中，我们评估了免疫复合物、葡萄糖-6-磷酸脱氢酶 （G6PD） 缺乏症以及重症疟疾 （SM） 儿童 BWF 发生和复发之间的关联。方法 2014 年至 2017 年，在乌干达中部和东部的 2 家医院招募了 6 个月至 <4 岁的 SM 住院儿童和社区儿童 （CC）。我们测量了血清循环免疫复合物 （cIC） 及其与 SM 并发症和出院后结局的关系，并评估了通过 G6PD 缺陷的作用介导。结果 共纳入 557 例 SM 患儿和 101 例 CC 患儿。平均年龄为 2.1 岁。SM 患儿的 cIC 水平高于 CC （P < .001）。控制年龄、性别和部位后，cIC 与严重贫血、黄疸和 BWF 相关： 校正比值比 （aOR），7.33 （95% 置信区间 [CI]，3.45-15.58），P < .0001;aOR，4.31 （95% CI，1.68–11.08），P = .002;和 aOR，分别为 5.21 （95% CI，2.06–13.18），P < .0001。cIC 预测 SM、严重贫血和 BWF 的再入院率：调整后的发病率比 （aIRR），2.11 （95% CI，1.33-3.34），P = .001;aIRR，8.62 （95% CI，2.80–26.59），P < .0001;和 aIRR，分别为 7.66 （95% CI，2.62–22.45），P < .0001。这种关系在男孩中最为明显，其中 G6PD 非洲等位基因 （A−） 的频率为 16.8%。G6PD 缺乏与男孩 cIC 增加相关 （P = .01），中介分析表明 G6PD 缺乏通过增加 cIC 导致复发性严重贫血和 BWF。结论 免疫复合物与溶血并发症相关，可预测 SM 幸存者的复发。