Genetic Characterization of Plasmodium falciparum Histidine-Rich Protein 2 Deletions and Their Impact on Malaria Interventions in Odisha, India.

IF 1.9 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Stuti Mohanty, Abbey M Jones, Swagatika Dash, Satya Ranjan Chhatria, Timir Kanta Padhan, Sanjib Mohanty, Jane M Carlton, Danielle C Ompad, Anne Kessler, Praveen Kishore Sahu
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引用次数: 0

Abstract

Diagnostic escape via Plasmodium falciparum (P. falciparum) histidine-rich protein 2 (pfhrp2) gene deletions is a major potential hurdle for global malaria elimination efforts. We investigated the prevalence of pfhrp2 gene deletions in 15 malaria-endemic villages in the state of Odisha, India, and modeled their impact on an ongoing in-country malaria intervention program. We found that 61.6% of subpatent P. falciparum infections (i.e., rapid diagnostic test [RDT]-negative and positive by polymerase chain reaction [PCR]) had pfhrp2 gene deletions, which were predominantly located in the exon 2 region (96.2%) and largely identified in samples from febrile individuals (82.6%). DNA sequencing and protein diversity features were characterized in a subset of samples from individuals with subpatent infections carrying intact pfhrp2 exon 2 loci. Our analyses revealed novel amino acid repeat motifs (231-293 amino acids), and these variant repeat sequences differed from those of RDT+/PCR+ samples. We also evaluated the state-sponsored mass screening and treatment intervention in the context of pfhrp2 gene deletions. We found that mass screening and treatment conducted alongside additional interventions (e.g., long-lasting insecticidal net distribution, indoor residual spraying) reduced the relative risk of infection for both P. falciparum parasites harboring a pfhrp2 deletion (adjusted relative risk ratio [aRRR] = 0.3; 95% CI = 0.1-1.0) and P. falciparum parasites with intact pfhrp2 genes (aRRR = 0.4; 95% CI = 0.2-1.1) when compared with the use of mass screening and treatment by RDT alone. Combined, our findings highlight the need for alternative diagnostic targets and tools as India moves toward its goal of malaria elimination by 2030.

印度奥里萨邦恶性疟原虫富组氨酸蛋白2缺失的遗传特征及其对疟疾干预的影响
恶性疟原虫富组氨酸蛋白2 (pfhrp2)基因缺失导致的诊断逃避是全球消除疟疾努力的一个主要潜在障碍。我们调查了印度奥里萨邦15个疟疾流行村庄中pfhrp2基因缺失的流行情况,并模拟了它们对正在进行的国内疟疾干预计划的影响。我们发现61.6%的亚隐性恶性疟原虫感染(即快速诊断试验[RDT]阴性和聚合酶链反应[PCR]阳性)存在pfhrp2基因缺失,主要位于外显子2区(96.2%),主要在发热个体样本中发现(82.6%)。在携带完整的pfhrp2外显子2位点的亚显性感染个体样本中,对DNA测序和蛋白质多样性特征进行了表征。我们的分析发现了新的氨基酸重复序列(231-293个氨基酸),这些变异重复序列与RDT+/PCR+样品不同。我们还评估了国家资助的pfhrp2基因缺失背景下的大规模筛查和治疗干预。我们发现,与其他干预措施(如长效杀虫蚊帐分发、室内滞留喷洒)一起进行的大规模筛查和治疗降低了携带pfhrp2缺失的两种恶性疟原虫感染的相对风险(调整后的相对风险比[aRRR] = 0.3;95% CI = 0.1-1.0)和携带完整pfhrp2基因的恶性疟原虫(aRRR = 0.4;95% CI = 0.2-1.1),与单独使用RDT进行大规模筛查和治疗相比。综上所述,我们的研究结果突出了印度在朝着2030年消除疟疾的目标迈进的过程中,对替代诊断目标和工具的需求。
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来源期刊
American Journal of Tropical Medicine and Hygiene
American Journal of Tropical Medicine and Hygiene 医学-公共卫生、环境卫生与职业卫生
CiteScore
6.20
自引率
3.00%
发文量
508
审稿时长
3 months
期刊介绍: The American Journal of Tropical Medicine and Hygiene, established in 1921, is published monthly by the American Society of Tropical Medicine and Hygiene. It is among the top-ranked tropical medicine journals in the world publishing original scientific articles and the latest science covering new research with an emphasis on population, clinical and laboratory science and the application of technology in the fields of tropical medicine, parasitology, immunology, infectious diseases, epidemiology, basic and molecular biology, virology and international medicine. The Journal publishes unsolicited peer-reviewed manuscripts, review articles, short reports, images in Clinical Tropical Medicine, case studies, reports on the efficacy of new drugs and methods of treatment, prevention and control methodologies,new testing methods and equipment, book reports and Letters to the Editor. Topics range from applied epidemiology in such relevant areas as AIDS to the molecular biology of vaccine development. The Journal is of interest to epidemiologists, parasitologists, virologists, clinicians, entomologists and public health officials who are concerned with health issues of the tropics, developing nations and emerging infectious diseases. Major granting institutions including philanthropic and governmental institutions active in the public health field, and medical and scientific libraries throughout the world purchase the Journal. Two or more supplements to the Journal on topics of special interest are published annually. These supplements represent comprehensive and multidisciplinary discussions of issues of concern to tropical disease specialists and health issues of developing countries
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