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Genetic variation in histidine rich proteins among Indian Plasmodium falciparum population: possible cause of variable sensitivity of malaria rapid diagnostic tests.

Kumar N, Singh JP, Pande V, Mishra N, Srivastava B, Kapoor R, Valecha N, Anvikar AR - Malar. J. (2012)

Bottom Line: PfHRP2 exhibited more polymorphism than PfHRP3.Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs.The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Malaria Research (ICMR), Sector 8, Dwarka, New Delhi, 110077, India.

ABSTRACT

Background: Rapid diagnostic tests (RDTs) have revolutionized the diagnosis of malaria. Among the various factors affecting RDTs sensitivity is genetic variation of the antigen used. The genetic variation in PfHRP2 and PfHRP3 proteins was studied among the Indian Plasmodium falciparum isolates.

Methods: One hundred and forty isolates of P. falciparum were collected from six geographical regions of India. Target genes encoding PfHRP2 and PfHRP3 antigens were sequenced to study genetic polymorphism. Minimum detection limit giving a positive rapid diagnostic test was also determined.

Results: Extensive variations were observed in amino acid repeat types of PfHRP2 and PfHRP3. PfHRP2 exhibited more polymorphism than PfHRP3. Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs.

Conclusion: The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity.

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Related in: MedlinePlus

Relationship between number of type 2 × type 7 amino acid repeats of PfHRP2 and average minimum detection limit of RDTs among six different geographical regions of India.
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Figure 2: Relationship between number of type 2 × type 7 amino acid repeats of PfHRP2 and average minimum detection limit of RDTs among six different geographical regions of India.

Mentions: Minimum parasitaemia that could be detected by RDTs was analysed in 62 samples. Extensive variations were observed in the minimum parasite detection limit (Table 2). The minimum level of parasitaemia that could be detected by RDTs ranged from 62 p/μl to 500 p/μl (Mean- 220.7 p/μl). About 75% of the isolates were predicted to be detected by RDTs at parasite density > 200 p/μl. The relationship between type 2 × type 7 amino acid repeats of PfHRP2 and average minimum detection limit of RDTs has been presented as Figure 2. It was observed that higher number of these repeats was associated with better sensitivity of HRP2 based RDTs. The same was confirmed by Baker’s logistic regression analysis.


Genetic variation in histidine rich proteins among Indian Plasmodium falciparum population: possible cause of variable sensitivity of malaria rapid diagnostic tests.

Kumar N, Singh JP, Pande V, Mishra N, Srivastava B, Kapoor R, Valecha N, Anvikar AR - Malar. J. (2012)

Relationship between number of type 2 × type 7 amino acid repeats of PfHRP2 and average minimum detection limit of RDTs among six different geographical regions of India.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475030&req=5

Figure 2: Relationship between number of type 2 × type 7 amino acid repeats of PfHRP2 and average minimum detection limit of RDTs among six different geographical regions of India.
Mentions: Minimum parasitaemia that could be detected by RDTs was analysed in 62 samples. Extensive variations were observed in the minimum parasite detection limit (Table 2). The minimum level of parasitaemia that could be detected by RDTs ranged from 62 p/μl to 500 p/μl (Mean- 220.7 p/μl). About 75% of the isolates were predicted to be detected by RDTs at parasite density > 200 p/μl. The relationship between type 2 × type 7 amino acid repeats of PfHRP2 and average minimum detection limit of RDTs has been presented as Figure 2. It was observed that higher number of these repeats was associated with better sensitivity of HRP2 based RDTs. The same was confirmed by Baker’s logistic regression analysis.

Bottom Line: PfHRP2 exhibited more polymorphism than PfHRP3.Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs.The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Malaria Research (ICMR), Sector 8, Dwarka, New Delhi, 110077, India.

ABSTRACT

Background: Rapid diagnostic tests (RDTs) have revolutionized the diagnosis of malaria. Among the various factors affecting RDTs sensitivity is genetic variation of the antigen used. The genetic variation in PfHRP2 and PfHRP3 proteins was studied among the Indian Plasmodium falciparum isolates.

Methods: One hundred and forty isolates of P. falciparum were collected from six geographical regions of India. Target genes encoding PfHRP2 and PfHRP3 antigens were sequenced to study genetic polymorphism. Minimum detection limit giving a positive rapid diagnostic test was also determined.

Results: Extensive variations were observed in amino acid repeat types of PfHRP2 and PfHRP3. PfHRP2 exhibited more polymorphism than PfHRP3. Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs.

Conclusion: The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity.

Show MeSH
Related in: MedlinePlus