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吡喹酮治疗妊娠曼氏血吸虫对后代血吸虫抗原免疫应答的影响:一项随机、安慰剂对照试验的结果。

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial.

机构信息

Faculty of Veterinary Medicine, Makerere University, Kampala, Uganda.

出版信息

BMC Infect Dis. 2011 Sep 2;11:234. doi: 10.1186/1471-2334-11-234.

DOI:10.1186/1471-2334-11-234
PMID:21888656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3176493/
Abstract

BACKGROUND

Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown.

METHODS

In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy.

RESULTS

Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel.

CONCLUSIONS

Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated.

TRIAL REGISTRATION

ISRCTN: ISRCTN32849447.

摘要

背景

由于子宫内致敏或抗体经胎盘转移,患有血吸虫病的女性的后代可能对血吸虫表现出免疫反应。妊娠期间使用吡喹酮治疗可增强母体对血吸虫抗原的免疫反应,并减少虫体负荷。妊娠期间使用吡喹酮治疗对后代的反应的影响尚不清楚。

方法

在乌干达进行的一项妊娠期间驱虫治疗试验(ISRCTN32849447;http://www.controlled-trials.com/ISRCTN32849447/elliott)中,检测了感染曼氏血吸虫的女性的后代对血吸虫虫体(SWA)和虫卵(SEA)抗原的细胞因子和抗体反应,分别在脐带血和 1 岁时进行检测。研究了与母体反应和治疗前感染强度的关系,并比较了在妊娠期间接受或未接受吡喹酮治疗的女性的后代之间的反应。

结果

在所研究的 388 名曼氏血吸虫感染的女性中,有 215 名女性的 1 岁婴儿获得了样本。所有婴儿的粪便检查均未发现曼氏血吸虫卵。脐带和婴儿样本对血吸虫抗原的细胞因子产生反应的能力非常低,除了脐带 IL-10 反应较强外。脐带和婴儿的细胞因子反应与母体反应无关。与预期的一样,脐带血中针对 SWA 和 SEA 的免疫球蛋白(IgG)水平很高,与母体抗体相关。然而,1 岁时 IgG 水平已经下降,几乎检测不到。妊娠期间使用吡喹酮治疗对 SWA 或 SEA 的脐带血和 1 岁时的细胞因子反应或抗体水平均无影响,除了 SWA 的 IgG1,其在接受治疗母亲的婴儿中升高,反映了母体水平。有一些证据表明,母体感染强度与 SWA 脐带血 IL-5 和 IL-13 对 SWA 的反应以及 SEA 中 IL-5 的反应呈正相关,并且这种关联受吡喹酮治疗的影响。

结论

尽管对母体感染强度和母体免疫反应有很强的影响,但妊娠期间感染妇女的吡喹酮治疗对 1 岁时后代的抗血吸虫免疫反应没有影响。治疗是否会影响后代在初次感染血吸虫时的反应还有待阐明。

试验注册

ISRCTN:ISRCTN32849447。

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