Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged ≤5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a two-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10 [IQR 0.03, 0.19]) than those with CM (0.24 [0.14, 0.69]; P=0.006) or asymptomatic malaria (0.19 [0.09, 0.46]; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL [4.7, 49.8]) and hepcidin/ferritin ratios (0.03 [0.01, 0.22]) than those with NTS alone (105.8 ng/mL [17.3, 233.3]; P=0.02 and 0.31 [0.06, 0.66]; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole (SCV), we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidinferroportin axis might mediate susceptibility to NTS in severely anemic children.

中文翻译：

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患有严重疟疾和非伤寒沙门氏菌菌血症的肯尼亚儿童的铁调素调节。

疟疾和侵袭性非伤寒沙门氏菌 (NTS) 是危及生命的感染，通常在非洲儿童中并存。铁调节激素铁调素在疟疾期间高度上调并控制铁的可用性，铁是细菌生长的关键营养素。我们调查了 1998 年 8 月至 2019 年 10 月期间所有 5 岁以下入院的儿科患者（n=75,034）中恶性疟原虫疟疾与 NTS 菌血症之间的关系。然后我们检测了五组铁调素和铁状态测量值：(1) 伴有严重疟疾性贫血 (SMA) 和 NTS 的儿童 (SMA+NTS，n=16)；和匹配的儿童 (2) SMA (n=33)；(3) NTS (n=33)；(4) 脑型疟疾 (CM, n=34)；(5) 社区儿童。SMA 和非疟疾严重贫血与 NTS 菌血症风险增加两倍或更多有关，而其他疟疾表型与 NTS 风险增加无关。SMA 患儿的铁调素/铁蛋白比率 (0.10 [IQR 0.03, 0.19]) 低于 CM (0.24 [0.14, 0.69]; P=0.006) 或无症状疟疾患儿 (0.19 [0.09, 0.46]; P=0.01)，表明抑制铁调素水平。SMA+NTS 患儿的铁调素水平（9.3 ng/mL [4.7, 49.8]）和铁调素/铁蛋白比值（0.03 [0.01, 0.22]）低于单独 NTS 患儿（105.8 ng/mL [17.3, 233.3]；P =0.02 和 0.31 [0.06, 0.66]；分别为 P=0.007）。由于 hepcidin 会降解含沙门氏菌的液泡 (SCV) 上的铁转运蛋白，我们假设 SMA 儿童中 hepcidin 的减少可能通过调节细菌生长所需的铁可用性来促进 NTS 生长。