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

Abstract

BackgroundRapid 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.MethodsOne 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.ResultsExtensive 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.ConclusionThe results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity.

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China–Myanmar border area

“…Genetic diversity may be particularly important for PfHRP2-based RDTs, since most of the RDTs are based on this antigen (Mouatcho and Goldring, 2013). Studies to date have documented extensive size variations between parasite strains and a high degree of genetic diversity within this antigen (Baker et al, 2010b; Baker et al, 2005; Deme et al, 2014; Kumar et al, 2012; Lee et al, 2006; Rock et al, 1987). An extreme situation is that certain parasite isolates even harbor a deletion of the pfhrp2 gene, leading to false negative results in diagnosis with PfHRP2-based RDTs.…”

“…Since then, pfhrp2 deletion-associated poor performance of RDTs has been reported in many malaria-endemic regions (Cheng et al, 2014; Koita et al, 2012; Maltha et al, 2012; Pava et al, 2010; Wurtz et al, 2013). To date, unequivocal evidence for pfhrp2 and pfhrp3 gene deletions in P. falciparum isolates has been obtained in Peru (Gamboa et al, 2010; Maltha et al, 2012), Brazil (Houze et al, 2011), Senegal (Wurtz et al, 2013), and India (Kumar et al, 2012). Apart from gene deletion, PfHRP2 sequences in different regions showed differences in the number of amino acid repeats and even some rare amino acid variants (Baker et al, 2010b; Baker et al, 2005; Deme et al, 2014; Kumar et al, 2012; Lee et al, 2006).…”

“…To date, unequivocal evidence for pfhrp2 and pfhrp3 gene deletions in P. falciparum isolates has been obtained in Peru (Gamboa et al, 2010; Maltha et al, 2012), Brazil (Houze et al, 2011), Senegal (Wurtz et al, 2013), and India (Kumar et al, 2012). Apart from gene deletion, PfHRP2 sequences in different regions showed differences in the number of amino acid repeats and even some rare amino acid variants (Baker et al, 2010b; Baker et al, 2005; Deme et al, 2014; Kumar et al, 2012; Lee et al, 2006). Given the significance of PfHRP2-based RDTs in malaria diagnosis, systematic mapping of PfHRP2 diversity in global malaria endemic regions is highly demanded, especially in areas where poor performance or failure of PfHRP2-based RDTs have been reported (Cheng et al, 2014).…”

Development of Monoclonal Antibodies That Target 1-Cys Peroxiredoxin and Differentiate Plasmodium falciparum from P. vivax and P. knowlesi

“…However, the available RDTs are known to have certain deficiencies, such as the fact that HRP-2 is only expressed in P. falciparum and persists even after parasite clearance, thus causing false positive results [20]. The genetic variation of HRP-2 in different geographical regions has also been reported, a problem that affects the sensitivity of tests in the field [21, 22], and a large proportion of field isolates in the Peruvian Amazon lack this antigen [23]. On the other hand, pLDH-based tests were less efficient in detecting low parasite densities and yielded variable results in different studies [24], while aldolase targeting tests have been shown to lack sensitivity in recent comparative studies, possibly due to the low concentration of this antigen in the parasite [24].…”

Nuclear Peroxiredoxine: A promising Target for Drug & Diagnostic Solutions of Malaria

“…The development of alternative diagnostic method like rapid diagnostic test, (RDTs) has made it possible to provide rapid and accurate detection of malaria parasites in remote areas where microscopy facility is not available. Several factors affect the performance of malaria RDTs which include test factors & parasite factors but genetic variability [12,13] and genetic deletion of these diagnostic antigens have been also questioned their sensitivity & reliability [14]. So, there is also an urgent need Volume 3 Issue 2 -2016 to develop new reliable diagnostic target of malaria parasite.…”