Nyirenda Tonney S, Nyirenda James T, Tembo Dumizulu L, Storm Janet, Dube Queen, Msefula Chisomo L, Jambo Kondwani C, Mwandumba Henry C, Heyderman Robert S, Gordon Melita A, Mandala Wilson L
Pathology Department, College of Medicine, University of Malawi, Blantyre, Malawi
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Clin Vaccine Immunol. 2017 Jul 5;24(7). doi: 10.1128/CVI.00057-17. Print 2017 Jul.
Invasive nontyphoidal (iNTS) infections are commonly associated with infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to Typhimurium were reduced in febrile -infected children (median, -0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], = 0.052). In relation to SBA, C3 deposition on Typhimurium was significantly reduced in febrile -infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], = 0.048). WBBA with respect to Typhimurium was significantly reduced in febrile -infected children (median, 0.25 log10 [IQR, -0.73, 1.13], = 0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10 [IQR, -1.68, -0.16]). In relation to WBBA, Typhimurium-specific NRBA was reduced in febrile -infected children (median, 8.8% [IQR, 3.7, 20], = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). infection impairs humoral and cellular immunity to Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further.
侵袭性非伤寒沙门菌（iNTS）感染通常与疟疾感染相关，但这种关联的免疫基础尚不清楚。我们推测，疟疾感染会损害宿主对非伤寒沙门菌的体液免疫和细胞免疫，从而增加宿主对iNTS感染的易感性。我们在马拉维布兰太尔的一个社区卫生中心前瞻性招募了6至60个月大的儿童，并将他们分为以下几组：单纯性疟疾发热组、疟疾发热阴性组和非疟疾发热阴性组。检测了鼠伤寒血清型特异性血清杀菌活性（SBA）、全血杀菌活性（WBBA）、补体C3沉积和中性粒细胞呼吸爆发活性（NRBA）水平。与非疟疾发热阴性儿童（中位数为-1.42 log10[四分位间距{IQR}，-2.0，-0.47]，P = 0.052）相比，疟疾发热感染儿童的鼠伤寒SBA水平降低（中位数为-0.20 log10[IQR，-1.85，0.32]）。与SBA相关，与非疟疾发热阴性儿童（中位数为29%[IQR，11.8，48.0]，P = 0.048）相比，疟疾发热感染儿童鼠伤寒上的C3沉积显著减少（中位数为7.5%[IQR，4.1，15.0]）。与非疟疾发热阴性儿童（中位数为-1.0 log10[IQR，-1.68，-0.16]）相比，疟疾发热感染儿童的鼠伤寒WBBA显著降低（中位数为0.25 log10[IQR，-0.73，1.13]，P = 0.0001）。与WBBA相关，与非疟疾发热阴性儿童（中位数为40.5%[IQR，33，65.8]）相比，疟疾发热感染儿童鼠伤寒特异性NRBA降低（中位数为8.8%[IQR，3.7，20]，P = 0.0001）。疟疾感染会损害儿童疟疾发作期间对鼠伤寒沙门菌的体液免疫和细胞免疫，这可能解释了在疟疾流行地区儿童中观察到的iNTS风险增加。体液免疫受损的潜在机制尚不完全清楚，应进一步探索。
