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. 2020 Nov 2;19(1):388.
doi: 10.1186/s12936-020-03456-6.

Genetic variations in histidine-rich protein 2 and histidine-rich protein 3 of Myanmar Plasmodium falciparum isolates

Hương Giang Lê  1   2 , Jung-Mi Kang  1   2 , Jinyoung Lee  3 , Won Gi Yoo  4 , Moe Kyaw Myint  5 , Khin Lin  5 , Tong-Soo Kim  6 , Byoung-Kuk Na  7   8
Affiliations

Genetic variations in histidine-rich protein 2 and histidine-rich protein 3 of Myanmar Plasmodium falciparum isolates

Hương Giang Lê et al. Malar J. .

Abstract

Background: Malaria rapid diagnostic tests (RDTs) are precious tools to diagnose malaria. Most RDTs used currently are based on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in a patient's blood. However, concern has been raised in recent years that deletion of pfhrp2 in the parasite could affect the accuracy of PfHRP2-based RDTs. In addition, genetic variation in pfhrp2 might influence the accuracy and sensitivity of RDTs. In this study, the genetic variation in pfhrp2 and pfhrp3 in Myanmar P. falciparum isolates was analysed.

Methods: Blood samples were collected from malaria patients who were infected with P. falciparum in Mandalay, Naung Cho, Tha Beik Kyin, and Pyin Oo Lwin, Upper Myanmar between 2013 and 2015. The pfhrp2 and pfhrp3 were amplified by nested polymerase chain reaction (PCR), cloned and sequenced. Genetic variation in Myanmar pfhrp2 and pfhrp3 was analysed using the DNASTAR program. Comparative analysis of Myanmar and global pfhrp2 and pfhrp3 isolates was also performed.

Results: One-hundred and two pfhrp2 and 89 pfhrp3 were amplified from 105 blood samples, of which 84 pfhrp2 and 56 pfhrp3 sequences were obtained successfully. Myanmar pfhrp2 and pfhrp3 showed high levels of genetic variation with different arrangements of distinct repeat types, which further classified Myanmar pfhrp2 and pfhrp3 into 76 and 47 haplotypes, respectively. Novel amino acid changes were also found in Myanmar pfhrp2 and pfhrp3, but their frequencies were very low. Similar structural organization was shared by Myanmar and global pfhrp2 and pfhrp3, and differences in frequencies of repeat types and lengths were also observed between and among global isolates.

Conclusion: Length polymorphisms and amino acid substitutions generated extensive genetic variation in Myanmar pfhrp2 and pfhrp3. Comparative analysis revealed that global pfhrp2 and pfhrp3 share similar structural features, as well as extensive length polymorphisms and distinct organizations of repeat types. These results provide a better understanding of the genetic structure of pfhrp2 and pfhrp3 in global P. falciparum populations and suggest useful information to develop RDTs with improved quality.

Keywords: Genetic polymorphism; Histidine-rich protein 2; Histidine-rich protein 3; Myanmar; Plasmodium falciparum.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Genetic variation in Myanmar pfhrp2. Seventy-six unique haplotypes were identified in Myanmar pfhrp2. The haplotypes differ in the number and organization of 12 distinct repeat types. Each repeat type is displayed as a different color
Fig. 2
Fig. 2
Genetic variation in Myanmar pfhrp3. Forty-seven unique haplotypes were identified in Myanmar pfhrp3. The haplotypes differ in the number and organization of 11 distinct repeat types. Each repeat type is displayed as a different color
Fig. 3
Fig. 3
Frequencies of repeat types found in Myanmar pfhrp2 and pfhrp3. The frequency of each repeat type identified in Myanmar pfhrp2 and pfhrp3 is presented
Fig. 4
Fig. 4
Comparison of length polymorphisms in global pfhrp2 and pfhrp3 isolates. The blue dotted line indicates the mean amino acid length in global pfhrp2 and pfhrp3. The red lines represent the mean amino acid lengths of pfhrp2 and pfhrp3 calculated in P. falciparum isolates from each country
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