Increase in the proportion of Plasmodium falciparum with kelch13 C580Y mutation and decline in pfcrt and pfmdr1 mutant alleles in Papua New Guinea.
Increase in the proportion of Plasmodium falciparum with kelch13 C580Y mutation and decline in pfcrt and pfmdr1 mutant alleles in Papua New Guinea.
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巴布亚新几内亚携带kelch13 C580Y突变的恶性疟原虫比例增加，携带pfcrt和pfmdr1突变等位基因的比例下降。
DOI：
10.1186/s12936-021-03933-6
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发表时间：
2021-10-19
期刊：
影响因子：
3
通讯作者：
Mita T
中科院分区：
文献类型：
--
作者：
Yoshida N;Yamauchi M;Morikawa R;Hombhanje F;Mita T
恶性疟原虫 kelch13 基因中的 C580Y 突变是大湄公河次区域 (GMS) 青蒿素耐药菌株中最常见的突变。直到 2017 年，除圭亚那/亚马逊地区外，大湄公河次区域以外的地区尚未发现这种病毒。 2017 年，巴布亚新几内亚 (PNG) 发现了三种携带 C580Y 突变的寄生虫。由于 C580Y 等位基因在 GMS 中迅速传播，人们担心这种突变体现在正在巴布亚新几内亚传播。 2020 年，在巴布亚新几内亚韦瓦克的两家诊所进行了一项横断面调查。根据国家治疗政策，感染恶性疟原虫的有症状患者接受蒿甲醚加本芴醇治疗。治疗前采集血样，并测定 kelch13、pfcrt 和 pfmdr1 的多态性。第 3 天检查寄生虫阳性。结果与 2002 年、2003 年和 2016-2018 年进行的先前研究的结果进行了比较。本次分析共有 94 名患者。 C580Y的比例显着增加（2017年为2.2%，2018年为5.7%，2020年为6.4%；p = 4.2 × 10–3）。 pfcrt（2016年为1.9%，2020年为46.7%；p = 8.9 × 10–16）和pfmdr1（2016年为59.5%，2020年为91.4%）野生型比例呈显着上升趋势； p = 2.3 × 10–6)。在第 3 天成功随访的 27 名患者中，包括 3 名 C580Y 感染患者，没有一人显示出阳性寄生虫血症。在巴布亚新几内亚 pfcrt K76 和 pfmdr1 N86 等位基因显着增加的情况下，kelch13 C580Y 突变体的增加可能是出现对目前使用的蒿甲醚加本芴醇一线治疗方案耐药的寄生虫的警告指标。因此，在全国范围内监测耐药性分子标志物并评估其治疗效果非常重要。在线版本包含可在 10.1186/s12936-021-03933-6 获取的补充材料。
The C580Y mutation in the Plasmodium falciparum kelch13 gene is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside the GMS, except for Guyana/Amazonia. In 2017, three parasites carrying the C580Y mutation were identified in Papua New Guinea (PNG). As the C580Y allele rapidly spread in the GMS, there is concern that this mutant is now spreading in PNG. In 2020, a cross-sectional survey was conducted at two clinics in Wewak, PNG. Symptomatic patients infected with P. falciparum were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in kelch13, pfcrt, and pfmdr1 were determined. Parasite positivity was examined on day 3. The results were compared with those of previous studies conducted in 2002, 2003, and 2016–2018. A total of 94 patients were included in this analysis. The proportion of C580Y was significantly increased (2.2% in 2017, 5.7% in 2018, and 6.4% in 2020; p = 4.2 × 10–3). A significant upward trend was observed in the wild-type proportion for pfcrt (1.9% in 2016 to 46.7% in 2020; p = 8.9 × 10–16) and pfmdr1 (59.5% in 2016 to 91.4% in 2020; p = 2.3 × 10–6). Among 27 patients successfully followed on day 3, including three with C580Y infections, none showed positive parasitaemia. Under the conditions of significant increases in pfcrt K76 and pfmdr1 N86 alleles in PNG, the increase in kelch13 C580Y mutants may be a warning indicator of the emergence of parasites resistant to the currently used first-line treatment regimen of artemether plus lumefantrine. Therefore, nationwide surveillance of molecular markers for drug resistance and assessment of its therapeutic effects are important. The online version contains supplementary material available at 10.1186/s12936-021-03933-6.
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DOI：
10.1016/s1473-3099(16)30409-1
发表时间：
2017-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amato R;Lim P;Miotto O;Amaratunga C;Dek D;Pearson RD;Almagro-Garcia J;Neal AT;Sreng S;Suon S;Drury E;Jyothi D;Stalker J;Kwiatkowski DP;Fairhurst RM
通讯作者：
Fairhurst RM
影响因子：
6.7
作者：
Miotto O;Sekihara M;Tachibana SI;Yamauchi M;Pearson RD;Amato R;Gonçalves S;Mehra S;Noviyanti R;Marfurt J;Auburn S;Price RN;Mueller I;Ikeda M;Mori T;Hirai M;Tavul L;Hetzel MW;Laman M;Barry AE;Ringwald P;Ohashi J;Hombhanje F;Kwiatkowski DP;Mita T
通讯作者：
Mita T
影响因子：
3.2
作者：
Mita, Toshihiro;Kaneko, Akira;Bjorkman, Anders
通讯作者：
Bjorkman, Anders
影响因子：
4.9
作者：
Nair, Shalini;Li, Xue;Anderson, Tim J. C.
通讯作者：
Anderson, Tim J. C.
影响因子：
7.7
作者：
Mathieu, Luana C.;Cox, Horace;Musset, Lise
通讯作者：
Musset, Lise