磺胺多辛-乙胺嘧啶对赞比亚孕妇中恶性疟原虫的寄生虫学疗效及耐药相关分子标志物：一项观察性队列研究。

Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

机构信息

Department of Biological Sciences, University of Zambia, Lusaka, Zambia.

Africa University, Fairview Road, Old Mutare, Mutare, Zimbabwe.

出版信息

Malar J. 2021 Jan 22;20(1):61. doi: 10.1186/s12936-021-03596-3.

DOI:10.1186/s12936-021-03596-3

PMID:33482823

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7821718/

Abstract

BACKGROUND

The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population.

METHODS

Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population.

RESULTS

The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively.

CONCLUSION

The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

摘要

背景

世界卫生组织建议在疟疾中度至高度传播地区，于妊娠第 13 周至分娩期间，每 4 周用磺胺多辛-乙胺嘧啶（SP）进行一次间歇性预防治疗（IPTp）。然而，由于寄生虫耐药性，IPTp-SP 的效果在某些地区受到了影响，这就提高了寄生虫学和化学预防监测的重要性，并监测恶性疟原虫种群中 SP 耐药性标记物。

方法

2013 年 11 月至 2014 年 4 月，赞比亚恩切伦格的 1086 名孕妇在产前护理预约时接受了 IPTp-SP。在第 0 天和第 28 天治疗后采集血样，以检测疟原虫并估计 SP 对寄生虫血症的治疗和预防效果。对 96 份第 0 天疟疾阳性的随机样本进行分析，以估计恶性疟原虫种群中 SP 耐药性标记物的流行率。

结果

在第 0 天和第 28 天有配对血样的女性中，总体寄生虫学和预防失败率为 18.6%（95%CI 15.5, 21.8；590 例中有 109 例）。在第 0 天无症状寄生虫血症的孕妇中，第 28 天 PCR 未校正的寄生虫学失败率为 30.0%（95%CI 23.7, 36.2；207 例中有 62 例），第 28 天 PCR 校正的寄生虫学失败率为 15.6%（95%CI：10.6, 20.6；205 例中有 32 例）。在第 0 天检测为阴性的女性中，12.3%（95%CI 9.0, 15.6；383 例中有 47 例）在第 28 天出现寄生虫血症。在第 0 天检测为疟疾阳性的 96 个样本中，70.8%（95%CI 60.8, 79.2）含有 DHPS 双突变（Gly-437+Glu-540），92.7%（95%CI 85.3, 96.5）具有 DHFR 三突变（Asn-108+Ile-51+Arg-59）。在 68.8%（95%CI 58.6, 77.3）和 9.4%（95%CI 4.2, 16.0）的样本中分别发现了 quintuple 突变（DHFR 三突变+DHPS 双突变）和 sextuple 突变（DHFR 三突变+DHPS 双突变+Arg-581）。