Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique.
Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique.
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DOI：
10.1038/s42003-023-04997-7
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发表时间：
2023-06-08
影响因子：
5.9
通讯作者：
Mayor, Alfredo
中科院分区：
文献类型：
--
作者：
da Silva, Clemente;Boene, Simone;Datta, Debayan;Rovira-Vallbona, Eduard;Aranda-Diaz, Andres;Cistero, Pau;Hathaway, Nicholas;Tessema, Sofonias;Chidimatembue, Arlindo;Matambisso, Gloria;Nhama, Abel;Macete, Eusebio;Pujol, Arnau;Nhamussua, Lidia;Galatas, Beatriz;Guinovart, Caterina;Enosse, Sonia;De Carvalho, Eva;Rogier, Eric;Plucinski, Mateusz M.;Colborn, James;Zulliger, Rose;Saifodine, Abuchahama;Alonso, Pedro L.;Candrinho, Baltazar;Greenhouse, Bryan;Aide, Pedro;Saute, Francisco;Mayor, Alfredo
莫桑比克是四个非洲国家之一，占全球疟疾死亡人数的一半以上，但对该国的寄生虫遗传结构知之甚少。我们对 2015 年和 2018 年在莫桑比克七个省收集的 2251 份疟疾感染的血液样本进行了恶性疟原虫扩增子和全基因组测序，以对抗疟疾耐药性标记进行基因分型，并使用全基因组微单倍体询问寄生虫种群结构。在这里，我们发现频率高于 5% 的唯一观察到的耐药相关标记是 pfmdr1-184F (59%)、pfdhfr-51I/59 R/108 N (99%) 和 pfdhps-437G/540E (89%)。与磺胺多辛-乙胺嘧啶抗性相关的 pfdhfr/pfdhps 五重突变体的频率从 2015 年的 80% 增加到 2018 年的 89% (p< 0.001)，与野生型寄生虫相比，pfdhps 突变体周围的微单倍型的预期杂合性较低，相关性较高，表明最近的选择。 pfdhfr/pfdhps 五重突变体也从北部的 72% 增加到南部的 95%（2018 年；p< 0.001）。这种耐药梯度伴随着北部pfdhps-436 (17%)突变的集中、恶性疟原虫感染遗传复杂性从南到北的增加(p = 0.001)以及区域分化的微单倍型特征。这里确定的寄生虫种群结构为指导抗疟干预措施和流行病学调查提供了见解。综合基因组学方法揭示了 2015 年和 2018 年在莫桑比克七个省收集的抗疟药物耐药性标记的时空分布以及恶性疟原虫的地理结构。
Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys. A comprehensive genomics approach reveals the spatial and temporal distribution of antimalarial drug resistance markers and geographic structure of P. falciparum parasites collected in seven provinces of Mozambique in 2015 and 2018.
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DOI：
10.1016/s2666-5247(20)30094-x
发表时间：
2020-09
期刊：
The Lancet. Microbe
影响因子：
--
作者：
Ehrlich HY;Jones J;Parikh S
通讯作者：
Parikh S
与柬埔寨恶性疟原虫疟疾双氢青蒿素-哌喹失败相关的遗传标记：基因型-表型关联研究。
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：
3
作者：
Chidimatembue A;Svigel SS;Mayor A;Aíde P;Nhama A;Nhamussua L;Nhacolo A;Bassat Q;Salvador C;Enosse S;Saifodine A;De Carvalho E;Candrinho B;Zulliger R;Goldman I;Udhayakumar V;Lucchi NW;Halsey ES;Macete E
通讯作者：
Macete E
影响因子：
11.8
作者：
Gupta H;Macete E;Bulo H;Salvador C;Warsame M;Carvalho E;Ménard D;Ringwald P;Bassat Q;Enosse S;Mayor A
通讯作者：
Mayor A
影响因子：
4.9
作者：
Humphreys, G. S.;Merinopoulos, I.;Hallett, R. L.
通讯作者：
Hallett, R. L.