{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:26:51Z","timestamp":1791440811298,"version":"4.3.3"},"reference-count":54,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,5]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Diagnostic escape via\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    ) histidine-rich protein 2 (\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    ) gene deletions is a major potential hurdle for global malaria elimination efforts. We investigated the prevalence of\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    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\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infections (i.e., rapid diagnostic test [RDT]-negative and positive by polymerase chain reaction [PCR]) had\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    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\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    exon 2 loci. Our analyses revealed novel amino acid repeat motifs (231\u2013293 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\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    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\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    parasites harboring a\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    deletion (adjusted relative risk ratio [aRRR] = 0.3; 95% CI = 0.1\u20131.0) and\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    parasites with intact\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    genes (aRRR = 0.4; 95% CI = 0.2\u20131.1) 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.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.24-0330","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T12:44:14Z","timestamp":1734439454000},"page":"601-609","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Characterization of Plasmodium falciparum Histidine-Rich Protein 2 Deletions and Their Impact on Malaria Interventions in Odisha, India"],"prefix":"10.4269","volume":"112","author":[{"given":"Stuti","family":"Mohanty","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbey M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Global Public Health, New York University, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swagatika","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya Ranjan","family":"Chhatria","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timir Kanta","family":"Padhan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjib","family":"Mohanty","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M.","family":"Carlton","sequence":"additional","affiliation":[{"name":"Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York;"},{"name":"Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle C.","family":"Ompad","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Global Public Health, New York University, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kessler","sequence":"additional","affiliation":[{"name":"Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York;"},{"name":"Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen Kishore","family":"Sahu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"World Malaria Report 2023","year":"2023"},{"key":"b2","series-title":"Guidelines for the Treatment of Malaria","year":"2015"},{"key":"b3","series-title":"Sci Rep","first-page":"14718","article-title":"Plasmodium falciparum parasites with histidine-rich protein 2 (pfhrp2) and pfhrp3 gene deletions in two endemic regions of Kenya","volume":"7","author":"Beshir","year":"2017"},{"key":"b4","series-title":"Am J Trop Med Hyg","first-page":"119","article-title":"A review of malaria diagnostic tools: Microscopy and rapid diagnostic test (RDT)","volume":"77","author":"Wongsrichanalai","year":"2007"},{"key":"b5","series-title":"Clin Microbiol Infect","first-page":"399","article-title":"Malaria rapid diagnostic tests in endemic settings","volume":"19","author":"Maltha","year":"2013"},{"key":"b6","series-title":"Clin Microbiol Rev","first-page":"97","article-title":"Update on rapid diagnostic testing for malaria","volume":"21","author":"Murray","year":"2008"},{"key":"b7","series-title":"Clin Microbiol Rev","first-page":"66","article-title":"Rapid diagnostic tests for malaria parasites","volume":"15","author":"Moody","year":"2002"},{"key":"b8","series-title":"Malar J","first-page":"298","article-title":"Genetic variation in histidine rich proteins among Indian Plasmodium falciparum population: Possible cause of variable sensitivity of malaria rapid diagnostic tests","volume":"11","author":"Kumar","year":"2012"},{"key":"b9","series-title":"J Clin Microbiol","first-page":"2773","article-title":"Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria","volume":"44","author":"Lee","year":"2006"},{"key":"b10","series-title":"Malar J","first-page":"129","article-title":"Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: Implications for the performance of malaria rapid diagnostic tests","volume":"9","author":"Baker","year":"2010"},{"key":"b11","series-title":"Clin Microbiol Infect","first-page":"580","article-title":"Genetic diversity and deletion of Plasmodium falciparum histidine-rich protein 2 and 3: A threat to diagnosis of P. falciparum malaria","volume":"25","author":"Gendrot","year":"2019"},{"key":"b12","series-title":"J Infect Dis","first-page":"870","article-title":"Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests","volume":"192","author":"Baker","year":"2005"},{"key":"b13","series-title":"Malar J","first-page":"109","article-title":"Detection of high prevalence of Plasmodium falciparum histidine-rich protein 2\/3 gene deletions in Assosa zone, Ethiopia: Implication for malaria diagnosis","volume":"20","author":"Alemayehu","year":"2021"},{"key":"b14","series-title":"Malar J","first-page":"207","article-title":"HRP2 and HRP3 cross-reactivity and implications for HRP2-based RDT use in regions with Plasmodium falciparum hrp2 gene deletions","volume":"20","author":"Kong","year":"2021"},{"key":"b15","series-title":"Malar J","first-page":"392","article-title":"Impact of Plasmodium falciparum gene deletions on malaria rapid diagnostic test performance","volume":"19","author":"Gatton","year":"2020"},{"key":"b16","series-title":"Emerg Infect Dis","first-page":"462","article-title":"Major threat to malaria control programs by Plasmodium falciparum lacking histidine-rich protein 2, eritrea","volume":"24","author":"Berhane","year":"2018"},{"key":"b17","series-title":"Bull World Health Organ","first-page":"558","article-title":"Prevalence of Plasmodium falciparum lacking histidine-rich proteins 2 and 3: A systematic review","volume":"98","author":"Thomson","year":"2020"},{"key":"b18","series-title":"Malar J","first-page":"276","article-title":"Impact of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions on malaria control worldwide: A systematic review and meta-analysis","volume":"20","author":"Molina-de la Fuente","year":"2021"},{"key":"b19","series-title":"Malar J","first-page":"26","article-title":"Plasmodium falciparum histidine-rich protein 2 and 3 genes deletion in global settings (2010-2021): A systematic review and meta-analysis","volume":"21","author":"Jejaw Zeleke","year":"2022"},{"key":"b20","series-title":"Trends Parasitol","first-page":"112","article-title":"HRP2: Transforming malaria diagnosis, but with caveats","volume":"36","author":"Poti","year":"2020"},{"key":"b21","series-title":"Malar J","first-page":"1","article-title":"A review of the WHO malaria rapid diagnostic test product testing programme (2008-2018): Performance, procurement and policy","volume":"18","author":"Cunningham","year":"2019"},{"key":"b22","series-title":"PLoS One","first-page":"e8091","article-title":"A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: Implications for malaria rapid diagnostic tests","volume":"5","author":"Gamboa","year":"2010"},{"key":"b23","series-title":"Sci Rep","first-page":"2797","article-title":"Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru","volume":"3","author":"Akinyi","year":"2013"},{"key":"b24","series-title":"Am J Trop Med Hyg","first-page":"194","article-title":"False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene","volume":"86","author":"Koita","year":"2012"},{"key":"b25","series-title":"J Clin Microbiol","first-page":"2694","article-title":"Combined deletions of pfhrp2 and pfhrp3 genes result in Plasmodium falciparum malaria false-negative rapid diagnostic test","volume":"49","author":"Houz\u00e9","year":"2011"},{"key":"b26","series-title":"Malaria Situation in India","year":"2020"},{"key":"b27","series-title":"PLoS One","first-page":"e0157949","article-title":"Prevalence of pfhrp2 and\/or pfhrp3 gene deletion in Plasmodium falciparum population in eight highly endemic states in India","volume":"11","author":"Bharti","year":"2016"},{"key":"b28","series-title":"Malar J","first-page":"394","article-title":"High proportions of pfhrp2 gene deletion and performance of HRP2-based rapid diagnostic test in Plasmodium falciparum field isolates of Odisha","volume":"17","author":"Pati","year":"2018"},{"key":"b29","series-title":"Indian J Med Res","first-page":"123","article-title":"Eliminating malaria in India by 2027: The countdown begins!","volume":"148","author":"Narain","year":"2018"},{"key":"b30","series-title":"J Vector Borne Dis","first-page":"53","article-title":"Malaria elimination drive in Odisha: Hope for halting the transmission","volume":"56","author":"Pradhan","year":"2019"},{"key":"b31","series-title":"Glob Health Action","first-page":"1886458","article-title":"The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: Study protocol for a cluster-assigned quasi-experimental study","volume":"14","author":"Ompad","year":"2021"},{"key":"b32","series-title":"Trans R Soc Trop Med Hyg","first-page":"1229","article-title":"Learnings from two independent malaria elimination demonstration projects in India","volume":"115","author":"Rajvanshi","year":"2021"},{"key":"b33","series-title":"Sci Rep","first-page":"22998","article-title":"The effectiveness of malaria camps as part of the malaria control program in Odisha, India","volume":"13","author":"Ompad","year":"2023"},{"key":"b34","series-title":"Guidelines for Diagnosis and Treatment of Malaria in India 2014","year":"2014"},{"key":"b35","series-title":"J Clin Microbiol","first-page":"2411","article-title":"Applied genomics: Data mining reveals species-specific malaria diagnostic targets more sensitive than 18S rRNA","volume":"49","author":"Demas","year":"2011"},{"key":"b36","series-title":"Proc Natl Acad Sci USA","first-page":"E1791","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children","volume":"109","author":"Lavstsen","year":"2012"},{"key":"b37","series-title":"Nucleic Acids Res","first-page":"3784","article-title":"ExPASy: The proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"Gasteiger","year":"2003"},{"key":"b38","series-title":"Sci Rep","first-page":"1709","article-title":"Plasmodium falciparum histidine-rich protein (PfHRP2 and 3) diversity in Western and Coastal Kenya","volume":"9","author":"Nderu","year":"2019"},{"key":"b39","series-title":"Malar J","first-page":"46","article-title":"Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: A systematic review and meta-analysis","volume":"19","author":"Kojom","year":"2020"},{"key":"b40","series-title":"J Vector Borne Dis","first-page":"273","article-title":"Prevalence of Pfhrp2\/3 gene deletions among false negative rapid antigen test results in central India","volume":"58","author":"Kumari","year":"2021"},{"key":"b41","series-title":"Response Plan to pfhrp2 Gene Deletions","year":"2019"},{"key":"b42","article-title":"False-negative RDT results and P. falciparum histidine-rich protein 2\/3 gene deletions 2019","year":"2019"},{"key":"b43","series-title":"Surveillance Template Protocol for pfhrp2\/pfhrp3 Gene Deletions","year":"2020"},{"key":"b44","series-title":"Trop Med Infect Dis","first-page":"265","article-title":"Factors affecting the performance of HRP2-based malaria rapid diagnostic tests","volume":"7","author":"Marti\u00e1\u00f1ez-Vendrell","year":"2022"},{"key":"b45","series-title":"ACS Infect Dis","first-page":"140","article-title":"Optical spectrophotometry as a promising method for quantification and stage differentiation of Plasmodium falciparum parasites","volume":"9","author":"Baptista","year":"2023"},{"key":"b46","series-title":"Sci Rep","first-page":"6307","article-title":"Glutamate dehydrogenase: A novel candidate to diagnose Plasmodium falciparum through rapid diagnostic test in blood specimen from fever patients","volume":"10","author":"Kori","year":"2020"},{"key":"b47","series-title":"Current Topics and Emerging Issues in Malaria Elimination","first-page":"12","author":"Dieng","year":"2021"},{"key":"b48","series-title":"PLoS One","first-page":"e0238749","article-title":"Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: A nationwide study of symptomatic malaria patients","volume":"15","author":"Amoah","year":"2020"},{"key":"b49","series-title":"PLoS One","first-page":"e0171150","article-title":"Histidine-rich protein 2 (pfhrp2) and pfhrp3 gene deletions in Plasmodium falciparum isolates from select sites in Brazil and Bolivia","volume":"12","author":"Rachid Viana","year":"2017"},{"key":"b50","series-title":"Acta Trop","first-page":"26","article-title":"Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China-Myanmar border area","volume":"152","author":"Li","year":"2015"},{"key":"b51","series-title":"Malar J","first-page":"34","article-title":"Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: Impact on rapid malaria diagnostic tests","volume":"12","author":"Wurtz","year":"2013"},{"key":"b52","series-title":"Emerg Infect Dis","first-page":"2043","article-title":"Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and relatedness to other global isolates, Djibouti, 2019-2020","volume":"28","author":"Rogier","year":"2022"},{"key":"b53","series-title":"N Engl J Med","first-page":"1191","article-title":"Increasing prevalence of artemisinin-resistant HRP2-negative malaria in eritrea","volume":"389","author":"Mihreteab","year":"2023"},{"key":"b54","series-title":"Malar J","first-page":"371","article-title":"Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam","volume":"21","author":"Thang","year":"2022"}],"container-title":["The American Journal of Tropical Medicine and 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