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Research Article

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

Stuti Mohanty Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;

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Abbey M. Jones Department of Epidemiology, School of Global Public Health, New York University, New York, New York;

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Swagatika Dash Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;

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Satya Ranjan Chhatria Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;

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Timir Kanta Padhan Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;

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Sanjib Mohanty Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;

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Jane M. Carlton Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York;
Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

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Danielle C. Ompad Department of Epidemiology, School of Global Public Health, New York University, New York, New York;

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Anne Kessler Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York;
Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

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Praveen Kishore Sahu Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India;

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DOI:
https://doi.org/10.4269/ajtmh.24-0330
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Ahead of Print
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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.

Author Notes

Financial support: This study was funded by the National Institute of Allergy and Infectious Diseases of the NIH under award number U19AI089676 as part of the International Centers of Excellence for Malaria Research U19 program. The content of this paper is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH.

Authors’ contributions: P. K. Sahu, A. Kessler, and J. M. Carlton conceived the pfhrp2 gene deletion study; D. C. Ompad and A. M. Jones conceived the modeling study; St. Mohanty performed the laboratory investigation and formal analysis with support from A. Kessler, S. Dash, S. R. Chhatria, and P. K. Sahu; A. M. Jones performed the epidemiologic analyses and modeling with support from D. C. Ompad. P. K. Sahu and A. Kessler supervised the study; J. M. Carlton acquired the funding; T. K. Padhan and Sa. Mohanty managed the sample and data collection from field sites and clinics; St. Mohanty, A. M. Jones, A. Kessler, J. M. Carlton, D. C. Ompad, and P. K. Sahu wrote the original draft of the manuscript; all the authors read and approved the final version of the manuscript.

Current contact information: Stuti Mohanty, Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India, E-mail: stutimohanty@gmail.com. Abbey M. Jones, School of Global Public Health, New York University, New York, NY, E-mail: amj593@nyu.edu. Swagatika Dash, Satyaranjan Chhatria, Timir Kanta Padhan, and Sanjib Mohanty, Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India, E-mails: dash.swagatika9@gmail.com, sranjanchhatria94@gmail.com, timir_pharma@yahoo.com, and sanjib.mohanty54@gmail.com. Jane M. Carlton, Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, MD, E-mail: janecarlton@jhu.edu. Danielle C. Ompad, School of Global Public Health, New York University, New York, NY, E-mail: danielle.ompad@nyu.edu. Anne Kessler, Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, MD, E-mail: akessl11@jh.edu. Praveen Kishore Sahu, Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital, Rourkela, Odisha, India, E-mail: praveenkishore.sahu@gmail.com or drpraveenksahu@cwshospital.org.

Address correspondence to Praveen Kishore Sahu, Department of Molecular Biology and Infectious Diseases, Community Welfare Society Hospital Rourkela, Jagda P.O., Northern Ave., Rourkela, Odisha, India 769005. E-mail: praveenkishore.sahu@gmail.com or drpraveenksahu@cwshospital.org
Copyright:
© The author(s) 2024
Received:
17 May 2024
|
Accepted:
12 Aug 2024
|
Published Online:
17 Dec 2024
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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