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每日服用复方新诺明预防对马拉维暴露于HIV但未感染的儿童针对恶性疟原虫疟疾感染的抗体介导免疫自然发展的影响。

The effect of daily co-trimoxazole prophylaxis on natural development of antibody-mediated immunity against P. falciparum malaria infection in HIV-exposed uninfected Malawian children.

作者信息

Longwe Herbert, Jambo Kondwani C, Phiri Kamija S, Mbeye Nyanyiwe, Gondwe Thandile, Hall Tom, Tetteh Kevin K A, Drakeley Chris, Mandala Wilson L

机构信息

Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi.

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

出版信息

PLoS One. 2015 Mar 25;10(3):e0121643. doi: 10.1371/journal.pone.0121643. eCollection 2015.

DOI:10.1371/journal.pone.0121643
PMID:25807475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4373908/
Abstract

BACKGROUND AND OBJECTIVES

Co-trimoxazole prophylaxis, currently recommended in HIV-exposed, uninfected (HEU) children as protection against opportunistic infections, also has some anti-malarial efficacy. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection.

METHODS

Using an enzyme-linked immunosorbent assay, we measured antibodies to 8 Plasmodium falciparum antigens (AMA-1, MSP-119, MSP-3, PfSE, EBA-175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIV-unexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age.

RESULTS

Compared to HIV-uninfected children, HEU children had significantly lower levels of specific IgG against AMA-1 at 6 months (p = 0.001), MSP-119 at 12 months (p = 0.041) and PfSE at 6 months (p = 0.038), 12 months (p = 0.0012) and 18 months (p = 0.0097). No differences in the IgG antibody responses against the rest of the antigens were observed between the two groups at all time points. The breadth of specificity of IgG response was reduced in HEU children compared to HUU children during the follow up period.

CONCLUSIONS

Co-trimoxazole prophylaxis seems to reduce IgG antibody responses to P. falciparum blood stage antigens, which could be as a result of a reduction in exposure of those children under this regime. Although antibody responses were regarded as markers of exposure in this study, further studies are required to establish whether these responses are correlated in any way to clinical immunity to malaria.

摘要

背景与目的

目前推荐对暴露于人类免疫缺陷病毒(HIV)但未感染(HEU)的儿童使用复方新诺明进行预防,以预防机会性感染,其也具有一定的抗疟功效。我们确定每日使用复方新诺明进行预防是否会影响抗体介导的针对恶性疟原虫血液期感染的免疫自然发育。

方法

我们采用酶联免疫吸附测定法,测量了33名HEU儿童和31名未暴露于HIV且未感染(HUU)儿童在6、12和18月龄时采集的血清样本中针对8种恶性疟原虫抗原(AMA-1、MSP-119、MSP-3、PfSE、EBA-175RII、GLURP R0、GLURP R2和CSP)的抗体。

结果

与未感染HIV的儿童相比,HEU儿童在6月龄时针对AMA-1的特异性IgG水平显著较低(p = 0.001),在12月龄时针对MSP-119的特异性IgG水平显著较低(p = 0.041),在6月龄(p = 0.038)、12月龄(p = 0.0012)和18月龄(p = 0.0097)时针对PfSE的特异性IgG水平显著较低。在所有时间点,两组之间针对其余抗原的IgG抗体反应均未观察到差异。在随访期间,与HUU儿童相比,HEU儿童IgG反应的特异性广度降低。

结论

复方新诺明预防似乎会降低对恶性疟原虫血液期抗原的IgG抗体反应,这可能是由于在该方案下这些儿童的暴露减少所致。尽管在本研究中抗体反应被视为暴露的标志物,但需要进一步研究以确定这些反应是否以任何方式与疟疾临床免疫力相关。

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