Université de Paris, MERIT, IRD, 75006, Paris, France.
Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
Malar J. 2022 Mar 26;21(1):107. doi: 10.1186/s12936-022-04124-7.
Despite decades of prevention efforts, the burden of malaria in pregnancy (MiP) remains a great public health concern. Sulfadoxine-pyrimethamine (SP), used as intermittent preventive treatment in pregnancy (IPTp-SP) is an important component of the malaria prevention strategy implemented in Africa. However, IPTp-SP is under constant threat from parasite resistance, thus requires regular evaluation to inform decision-making bodies.
In two malaria endemic communities in the Volta region (Adidome and Battor), a cross-sectional hospital-based study was conducted in pregnant women recruited at their first antenatal care (ANC) visit and at delivery. Basic clinical and demographic information were documented and their antenatal records were reviewed to confirm IPTp-SP adherence. Peripheral and placental blood were assayed for the presence of Plasmodium falciparum parasites by quantitative polymerase chain reaction (qPCR). One hundred and twenty (120) positive samples were genotyped for mutations associated with SP resistance.
At first ANC visit, P. falciparum prevalence was 28.8% in Adidome and 18.2% in Battor. At delivery, this decreased to 14.2% and 8.2%, respectively. At delivery, 66.2% of the women had taken at least the recommended 3 or more doses of IPTp-SP and there was no difference between the two communities. Taking at least 3 IPTp-SP doses was associated with an average birth weight increase of more than 360 g at both study sites compared to women who did not take treatment (p = 0.003). The Pfdhfr/Pfdhps quintuple mutant IRNI-A/FGKAA was the most prevalent (46.7%) haplotype found and the nonsynonymous Pfdhps mutation at codon A581G was higher at delivery among post-SP treatment isolates (40.6%) compared to those of first ANC (10.22%). There was also an increase in the A581G mutation in isolates from women who took 3 or more IPTp-SP.
This study confirms a positive impact following the implementation of the new IPTp-SP policy in Ghana in increasing the birth weight of newborns. However, the selection pressure exerted by the recommended 3 or more doses of IPTp-SP results in the emergence of parasites carrying the non-synonymous mutation on codon A581G. This constant selective pressure calls into question the time remaining for the clinical utility of IPTp-SP treatment during pregnancy in Africa.
尽管几十年来一直在努力预防，但妊娠疟疾（MiP）的负担仍然是一个重大的公共卫生问题。磺胺多辛-乙胺嘧啶（SP）作为妊娠间歇性预防治疗（IPTp-SP），是在非洲实施的疟疾预防策略的重要组成部分。然而，SP 易受到寄生虫耐药性的威胁，因此需要定期评估以告知决策机构。
在沃尔特地区（阿迪多梅和巴托尔）的两个疟疾流行社区，对首次产前保健（ANC）就诊和分娩时招募的孕妇进行了一项横断面医院为基础的研究。记录了基本的临床和人口统计学信息，并对其产前记录进行了回顾，以确认是否遵循了 IPTp-SP 方案。通过定量聚合酶链反应（qPCR）检测外周血和胎盘血中恶性疟原虫寄生虫的存在。对 120 个阳性样本进行了与 SP 耐药性相关的突变基因分型。
首次 ANC 就诊时，阿迪多梅的疟原虫流行率为 28.8%，巴托尔为 18.2%。分娩时，这一比例分别下降至 14.2%和 8.2%。分娩时，66.2%的妇女至少服用了推荐的 3 剂或更多剂量的 IPTp-SP，两个社区之间没有差异。与未接受治疗的妇女相比，在两个研究地点，至少服用 3 剂 IPTp-SP 与平均出生体重增加超过 360g 相关（p=0.003）。在所研究的地点，发现最常见的是 Pfdhfr/Pfdhps 五重突变 IRNI-A/FGKAA （46.7%），与首次 ANC 相比，分娩时接受 SP 治疗的寄生虫中，密码子 A581G 处的非同义 Pfdhps 突变更高（40.6%）（10.22%）。在接受 3 剂或更多 IPTp-SP 的妇女的分离物中，也发现了 A581G 突变的增加。
本研究证实，加纳实施新的 IPTp-SP 政策后，新生儿的出生体重增加，产生了积极影响。然而，推荐的 3 剂或更多剂量的 IPTp-SP 产生的选择压力导致携带非同义突变密码子 A581G 的寄生虫的出现。这种持续的选择压力，使 IPTp-SP 治疗在非洲的妊娠期间的临床应用时间受到质疑。
