Polymorphisms in genes associated with drug resistance of Plasmodium vivax in India

Anantabotla, Vamsi Mohan; Antony, Hiasindh Ashmi; Parija, Subhash Chandra; Rajkumari, Nonika; Kini, Jyoti R.; Manipura, Radhakrishna; Nag, Vijaya Lakshmi; Gadepalli, Ravi; Chayani, Nirupama; Patro, Somi

doi:10.1016/j.parint.2019.03.001

Cited by 19 publications

(21 citation statements)

References 30 publications

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“…Similarly, F1076 L has not been found to be associated with CQR both in vivo and in vitro drug assays [ 66 ]. In this study, F1076 L reached high prevalence of 85.8%, which was concordant with previous reports from other Asian areas including India, Thailand and Myanmar [ 23 , 60 , 61 ]. The frequency of F1076 L mutation in asymptomatic infections in Laiza township was twice as much as that in Shwegyin township of Myanmar [ 8 ].…”

Section: Discussionsupporting

confidence: 93%

“…The frequency of F1076L mutation in asymptomatic infections in Laiza township was twice as much as that in Shwegyin township of Myanmar [8]. The single mutation haplotype 976Y/997K/1076L was the most prevalent at the China-Myanmar border, similar to a previous report from India [60], but differed from a report from Yunnan, China, which showed WT as the dominant [67]. These geographical variations in pvmdr1 gene may suggest different drug selection pressure imposed on P. vivax population in these Asian countries.…”

Section: Discussionsupporting

confidence: 86%

“…Other studies found that lysine (K) insertion at position 10 of pvcrt - o gene may be associated with CQR [ 20 , 23 ]. This study observed a prevalence of 34% of K10 insertion in the pvcrt - o gene, higher than that found in India (9.4%) and Thailand (0%) [ 60 – 62 ], but lower than that detected in other regions of Myanmar (48.3–72.7%) [ 23 ]. A recent study showed correlation of CQR with increased expression of pvcrt [ 29 ], which could not be evaluated with the DBS samples.…”

Section: Discussioncontrasting

confidence: 68%

“…The molecular mechanisms underlying CQR are not well understood, but mutations in pvmdr1 and expression of pvcrt - o were implicated. For pvmdr1 , the Y976 F mutation has been reported in P. vivax isolates from many malaria-endemic regions around the world [ 60 – 64 ], and is associated with a decrease in in vitro sensitivity to CQ [ 20 ]. In this study, the Y976 F mutation was relatively rare, with 5.5% detected only in samples from symptomatic infections.…”

Section: Discussionmentioning

confidence: 99%

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Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border

Zhao

Wang

Soe

et al. 2020

Malar J

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Background: In the Greater Mekong sub-region, Plasmodium vivax has become the predominant species and imposes a major challenge for regional malaria elimination. This study aimed to investigate the variations in genes potentially related to drug resistance in P. vivax populations from the China-Myanmar border area. In addition, this study also wanted to determine whether divergence existed between parasite populations associated with asymptomatic and acute infections. Methods: A total of 66 P. vivax isolates were obtained from patients with acute malaria who attended clinics at the Laiza area, Kachin State, Myanmar in 2015. In addition, 102 P. vivax isolates associated with asymptomatic infections were identified by screening of volunteers without signs or symptoms from surrounding villages. Slide-positive samples were verified with nested PCR detecting the 18S rRNA gene. Multiclonal infections were further excluded by genotyping at msp-3α and msp-3β genes. Parasite DNA from 60 symptomatic cases and 81 asymptomatic infections was used to amplify and sequence genes potentially associated with drug resistance, including pvmdr1, pvcrt-o, pvdhfr, pvdhps, and pvk12. Results: The pvmdr1 Y976F and F1076L mutations were present in 3/113 (2.7%) and 97/113 (85.5%) P. vivax isolates, respectively. The K10 insertion in pvcrt-o gene was found in 28.2% of the parasites. Four mutations in the two antifolate resistance genes reached relatively high levels of prevalence: pvdhfr S58R (53.4%), S117N/T (50.8%), pvdhps A383G (75.0%), and A553G (36.3%). Haplotypes with wild-type pvmdr1 (976Y/997K/1076F) and quadruple mutations in pvdhfr (13I/57L/58R/61M/99H/117T/173I) were significantly more prevalent in symptomatic than asymptomatic infections, whereas the pvmdr1 mutant haplotype 976Y/997K/1076L was significantly more prevalent in asymptomatic than symptomatic infections. In addition, quadruple mutations at codons 57, 58, 61 and 117 of pvdhfr and

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 86%

Section: Discussioncontrasting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border

Zhao

Wang

Soe

et al. 2020

Malar J

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“…Unlike other well-described mutations in the Pvmdr1 gene, the role of the K10 insertion in Pvcrt-o in chloroquine resistance in P. vivax is unclear because this mutation is present in some studies and absent in others [3,5,7,16,34,41]. In Thailand, the K10 insertion was found in 2008 [16], but was not detected again until recently [7,42].…”

Section: Discussionmentioning

confidence: 94%

Molecular Detection of Antimalarial Drug Resistance in Plasmodium vivax from Returned Travellers to NSW, Australia during 2008–2018

et al. 2020

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To monitor drug resistance in Plasmodium vivax, a multidrug resistance 1 (Pvmdr1) gene and a putative transporter protein (Pvcrt-o) gene were used as molecular markers for chloroquine resistance. The biomarkers, the dihydrofolate reductase (Pvdhfr) gene and the dihydropteroate synthetase (Pvdhps) gene, were also used for the detection of resistance to sulphadoxine-pyrimethamine (SP); this drug is often accidentally used to treat P. vivax infections. Clinical blood samples (n = 120) were collected from patients who had been to one of eight malaria-endemic countries and diagnosed with P. vivax infection. The chloroquine resistance marker, the Pvmdr1 gene, showed F976:L1076 mutations and L1076 mutation. A K10 insertion in the Pvcrt-o gene was also found among the samples successfully sequenced. A combination of L/I57:R58:M61:T117 mutations in the Pvdhfr gene and G383:G553 mutations in the Pvdhps gene were also observed. Mutations found in these genes indicate that drug resistance is present in these eight countries. Whether or not countries are using chloroquine to treat P. vivax, there appears to be an increase in mutation numbers in resistance gene markers. The detected changes in mutation rates of these genes do suggest that there is still a trend towards increasing P. vivax resistance to chloroquine. The presence of the mutations associated with SP resistance indicates that P. vivax has had exposure to SP and this may be a consequence of either misdiagnosis or coinfections with P. falciparum in the past.

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In Vitro and In Silico Anti‐plasmodial Evaluation of Newly Synthesized β‐Carboline Derivatives

et al. 2021

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Series of novel thiourea and guanidine conjugated β-carbolines along with other analogues of this class were designed and synthesized for in vitro antimalarial activity against Plasmodium falciparum to overcome the threat of resistance to anti-malarial drug. Among them, two guanidine conjugated β-carbolines 7 a and 7 c showed promising activities against both sensitive and resistant strains Pf3D7 and PfINDO with the IC 50 values ranging from 0.6-1.0 μM. The relative activities were further supported by in silico docking and binding studies of the synthesized scaffolds against specific targets, revealing that DHFR and FP3 may act as a potential target for 7 a and 7 c respectively.

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Polymorphisms in genes associated with drug resistance of Plasmodium vivax in India

Cited by 19 publications

References 30 publications

Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border

Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border

Molecular Detection of Antimalarial Drug Resistance in Plasmodium vivax from Returned Travellers to NSW, Australia during 2008–2018

In Vitro and In Silico Anti‐plasmodial Evaluation of Newly Synthesized β‐Carboline Derivatives

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