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Table of Contents
LETTER TO THE EDITOR
Year : 2019  |  Volume : 56  |  Issue : 1  |  Page : 85-86

Deletions in the Plasmodium falciparum histidine-rich protein 2 gene: An emerging threat to the elimination of malaria in India


Cell Biology Laboratory and Malaria Parasite Bank, ICMR–National Institute of Malaria Research, New Delhi–110 077, India

Date of Submission28-Feb-2019
Date of Web Publication7-May-2019

Correspondence Address:
Dr Vineeta Singh
Cell Biology Laboratory and Malaria Parasite Bank, ICMR–National Institute of Malaria Research, New Delhi–110 077
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-9062.257781

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How to cite this article:
Singh V, Kojom LP. Deletions in the Plasmodium falciparum histidine-rich protein 2 gene: An emerging threat to the elimination of malaria in India. J Vector Borne Dis 2019;56:85-6

How to cite this URL:
Singh V, Kojom LP. Deletions in the Plasmodium falciparum histidine-rich protein 2 gene: An emerging threat to the elimination of malaria in India. J Vector Borne Dis [serial online] 2019 [cited 2019 Nov 19];56:85-6. Available from: http://www.jvbd.org/text.asp?2019/56/1/85/257781



Dear Editor,

The advent of immunochromatographic rapid diagnostic tests (RDTs) as part of strategies for control and elimination of malaria has greatly improved the management of this infectious disease in endemic countries[1]. RDTs rely on the recognition of malarial antigens in circulating blood like parasite lactate dehydrogenase (pLDH), aldolase which are produced by all the five human malarial species, and histidine-rich protein 2 (HRP2) which is more specific to Plasmodium falciparum[2]. RDTs targeting PfHRP2 constitute the bulk of RDTs available commercially given that P. falciparum is the most prevalent and dangerous malaria species across the world[1].

Malaria is highly prevalent in India and accounts for 68% of cases and 65% of deaths in the Southeast Asia region[1]. In India, P. falciparum (Pf) and P. vivax (Pv) are the species mainly responsible for malaria cases and deaths[3]. The country has outlined the elimination objectives defined by the World Health Organization (WHO) in the Global Technical Strategy 2016–2030. The WHO is aiming for the elimination of malaria by 2025–2030 in at least 20–30 countries which were malaria endemic in 2015[1]. Malaria elimination in India calls for a complete understanding of the current scenario of burden inflicted by the disease as well as massive scaling-up of different fight/control strategies including a reliable diagnosis of malaria cases[4].

RDTs are an essential part of diagnosis policies in India as witnessed by increase in their utilization in the last few years[5]. However, their utilization, especially those targeting PfHRP2, could probably become an important future diagnostic challenge given the possibility of falsenegative results due to the presence of deletions in gene encoding PfHRP2 protein[6]. The utilization of PfHRP2-based RDTs is no longer recommended in some Latin American countries where a high proportion of falsenegative results were attributed to PfHRP2 gene deletions[7]. Some studies in India have reported the circulation of strains with deleted PfHRP2 gene which was responsible for 65.5–100% of false-negative results[8],[9],[10]. The misclassification of P. falciparum with P. vivax mixed infections as P. vivax single infection using RDTs targeting PfHRP2 or other malarial antigens is another diagnostic consequence of PfHRP2 gene deletions. The successive consequences of misdiagnosis would lead to disease complications or deaths due to delay in providing an effective and reliable antimalarial treatment.

Thus, the protection/safeguard of diagnostic effectiveness of RDTs through ongoing surveillance of deletions in PfHRP2 gene is of utmost importance in India to achieve the target of malaria elimination by 2030.

Conflict of interest: None.



 
  References Top

1.
World Malaria Report 2018. Geneva, Switzerland: World Health Organization 2018; p. 210. Available from: https://apps.who.int/ iris/bitstream/handle/10665/275867/9789241565653-eng.pdf? ua=1 (Accessed on January 16, 2019).  Back to cited text no. 1
    
2.
Moody A. Rapid diagnostic tests for malaria parasites. Clin Microbiol Rev 2002; 15(1): 66–78. doi: 10.1128/CMR.15.1.66-78.2002  Back to cited text no. 2
    
3.
Gupta B, Gupta P, Sharma A, Singh V, Dash AP, Das A. High proportion of mixed-species Plasmodium infections in India revealed by PCR diagnostic assay. Trop Med Int Health 2010; 15 (7): 819–24. doi: org/10.1111/j.1365–3156. 2010. 02549x.  Back to cited text no. 3
    
4.
Patankar S, Sharma S, Rathod PK, Duraisingh MT. Malaria in India: The need for new targets for diagnosis and detection of Plasmodium vivax. Proteomics Clin Appl 2018; 12(4): e1700024. doi: 10.1002/prca.201700024.  Back to cited text no. 4
    
5.
Behera S. Diagnostic challenges of malaria in India. Available from: http://www.apiindia.org/pdf/medicine_update_2017/ mu_006.pdf. (Accessed on February 23, 2019).  Back to cited text no. 5
    
6.
Gendrot M, Fawaz R, Dormoi J, Madamet M, Pradines B. Genetic diversity and deletion of Plasmodium falciparum histidinerich protein 2 and 3: A threat to diagnosis of P. falciparum malaria. Clin Microbiol Infect 2018; pii: S1198-743X(18)30631-1. doi: 10.1016/j.cmi.2018.09.009.  Back to cited text no. 6
    
7.
Gamboa D, Ho MF, Bendezu J, Torres K, Chiodini PL, Barnwell JW, et al. A large proportion of P. falciparum isolates in the Amazon region of Peru lack Pfhrp2 and Pfhrp3: Implications for malaria rapid diagnostic tests. PLoS One 2010; 5: e8091. doi: 10.1371/journal.pone.0008091.  Back to cited text no. 7
    
8.
Kumar N, Pande V, Bhatt RM, Shah NK, Mishra N, Srivastava B, et al. Genetic deletion of HRP2 and HRP3 in Indian Plasmodium falciparum population and false negative malaria rapid diagnostic test. Acta Trop 2013; 125: 119–21. doi: 10.1016/ j.actatropica.2012.09.015.  Back to cited text no. 8
    
9.
Bharti PK, Chandel HS, Ahmad A, Krishna S, Udhayakumar V, Singh N. Prevalence of Pfhrp2 and/or Pfhrp3 gene deletion in Plasmodium falciparum population in eight highly endemic states in India. PLoS One 2016; 11(8): e0157949. doi: https:// doi.10.1371/journal.pone.0157949.  Back to cited text no. 9
    
10.
Pati P, Dhangadamajhi G, Bal M, Ranjit M. High proportions of Pfhrp2 gene deletion and performance of HRP2-based rapid diagnostic test in Plasmodium falciparum field isolates of Odisha. Malar J 2018; 17: 394. doi.org/10.1186/s12936-018-2502-3.  Back to cited text no. 10
    




 

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