Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments.
Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments.
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在撒哈拉以南非洲检测到的高度多样化的丙型肝炎菌株对直接作用抗病毒治疗的敏感性未知。
DOI：
10.1002/hep.30342
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发表时间：
2019-04
期刊：
影响因子：
--
通讯作者：
Thomson EC
中科院分区：
文献类型：
--
作者：
Davis C;Mgomella GS;da Silva Filipe A;Frost EH;Giroux G;Hughes J;Hogan C;Kaleebu P;Asiki G;McLauchlan J;Niebel M;Ocama P;Pomila C;Pybus OG;Pépin J;Simmonds P;Singer JB;Sreenu VB;Wekesa C;Young EH;Murphy DG;Sandhu M;Thomson EC
由世界卫生组织领导的根除丙型肝炎病毒（HCV）的全球计划概述了使用高效的直接作用抗病毒药物（DAA）到2030年实现消除。在撒哈拉以南非洲（SSA）识别活动性疾病个体并调查病毒多样性的广度至关重要，因为该地区的基因型（很少进行临床试验）与世界其他地区的基因型不同。我们在乌干达进行了一项基于人群的巢式病例对照研究，并从刚果民主共和国（DRC）获得了额外的样本，以估计HCV的患病率，评估使用血清学和分子技术进行疾病检测的策略，并表征病毒的遗传多样性。使用下一代和桑格测序，我们旨在鉴定在东非和中非流行的菌株。共有7，751名乌干达患者接受了HCV初步筛查，并获得了20份PCR阳性样本进行测序。发现血清学检测对HCV的特异性差异显着。在乌干达检测到的HCV毒株包括基因型（g）4k、g4p、g4q和g4s以及一种新发现的未分配的g7 HCV毒株。在来源于DRC的患者中鉴定出另外两种未分配的g7菌株（一种部分开放阅读框序列和一种完全开放阅读框序列）。这些g4和g7菌株含有非结构（ns）蛋白3和5A多态性与其他基因型的DAA抗性。因此，临床研究适用于研究感染患者的治疗反应。总结：尽管在资源充足的国家，HCV的患病率和基因型在患者中得到了很好的表征，但在高度多样化的g4和g7毒株流行的SSA中，迫切需要进行临床试验。
The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.
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影响因子：
64.8
作者：
Gurdasani, Deepti;Carstensen, Tommy;Tekola-Ayele, Fasil;Pagani, Luca;Tachmazidou, Ioanna;Hatzikotoulas, Konstantinos;Karthikeyan, Savita;Iles, Louise;Pollard, Martin O.;Choudhury, Ananyo;Ritchie, GrahamR. S.;Xue, Yali;Asimit, Jennifer;Nsubuga, Rebecca N.;Young, Elizabeth H.;Pomilla, Cristina;Kivinen, Katja;Rockett, Kirk;Kamali, Anatoli;Doumatey, Ayo P.;Asiki, Gershim;Seeley, Janet;Sisay-Joof, Fatoumatta;Jallow, Muminatou;Tollman, Stephen;Mekonnen, Ephrem;Ekong, Rosemary;Oljira, Tamiru;Bradman, Neil;Bojang, Kalifa;Ramsay, Michele;Adeyemo, Adebowale;Bekele, Endashaw;Motala, Ayesha;Norris, Shane A.;Pirie, Fraser;Kaleebu, Pontiano;Kwiatkowski, Dominic;Tyler-Smith, Chris;Rotimi, Charles;Zeggini, Eleftheria;Sandhu, Manjinder S.
通讯作者：
Sandhu, Manjinder S.
影响因子：
9.4
作者：
Iles JC;Njouom R;Foupouapouognigni Y;Bonsall D;Bowden R;Trebes A;Piazza P;Barnes E;Pépin J;Klenerman P;Pybus OG
通讯作者：
Pybus OG
影响因子：
3.7
作者：
Lu L;Xu Y;Yuan J;Li C;Murphy DG
通讯作者：
Murphy DG
影响因子：
3.4
作者：
Gray RR;Parker J;Lemey P;Salemi M;Katzourakis A;Pybus OG
通讯作者：
Pybus OG
影响因子：
14.2
作者：
Salmona, M.;Caporossi, A.;Maylin, S.
通讯作者：
Maylin, S.