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. 2010 May 17:9:129.
doi: 10.1186/1475-2875-9-129.

Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests

Joanne Baker  1 , Mei-Fong Ho, Anita Pelecanos, Michelle Gatton, Nanhua Chen, Salim Abdullah, Audrey Albertini, Frederic Ariey, John Barnwell, David Bell, Jane Cunningham, Djibrine Djalle, Diego F Echeverry, Dionicia Gamboa, Jeffery Hii, Myat Phone Kyaw, Jennifer Luchavez, Christopher Membi, Didier Menard, Claribel Murillo, Sina Nhem, Bernhards Ogutu, Pamela Onyor, Wellington Oyibo, Shan Qing Wang, James McCarthy, Qin Cheng
Affiliations

Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests

Joanne Baker et al. Malar J. .

Abstract

Background: Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region.

Methods: The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs.

Results: Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified.

Conclusions: The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

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Figures

Figure 1
Figure 1
Ratio of number of unique sequences to total sequences for pfhrp2 for countries with a minimum of 5 isolates. Numbers in brackets indicate the number of samples
Figure 2
Figure 2
The length of PfHRP2 (number of aa) in countries with ≥5 samples. Numbers in brackets indicate the number of samples. The dotted line indicates the global mean. ^ The mean number is significantly higher than the global mean (p < 0.05); # the mean number is significantly lower than the global mean (p < 0.05)
Figure 3
Figure 3
The number of type 2 repeat present in PfHRP2 in countries with ≥ 5 samples. Numbers in brackets indicate the number of samples. The dotted line indicates the global mean. ^ The mean number is significantly higher than the global mean (p < 0.05); # the mean number is significantly lower than the global mean (p < 0.05)
Figure 4
Figure 4
The number of Type 7 repeat present in PfHRP2 in countries with ≥5 samples. Numbers in brackets indicate the number of samples. The dotted line indicates the global mean. ^ The mean number is significantly higher than the global mean (p < 0.05); # the mean number is significantly lower than the global mean (p < 0.05)
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