Distribution of Mutations Associated with Antifolate and Chloroquine Resistance among Imported Plasmodium vivax in the State of Qatar

Almeida

et al. 2018

Malar J

BackgroundThe resistance of Plasmodium vivax to chloroquine has become an obstacle to control strategies based on the use of anti-malarials. The current study investigated the association between P. vivax CQ-resistance in vivo with copy number variation and mutations in the promoter region in pvcrt-o and pvmdr1 genes.MethodsThe study included patients with P. vivax that received supervised treatment with chloroquine and primaquine. Recurrences were actively recorded during this period.ResultsAmong the 60 patients with P. vivax, 25 were CQ-resistant and 35 CQ-susceptible. A frequency of 7.1% of multi-copy pvcrt-o was observed in CQ-susceptible samples and 7.7% in CQ-resistant at D0 (P > 0.05) and 33.3% in CQ-resistant at DR (P < 0.05). For pvmdr1, 10.7% of the CQ-susceptible samples presented multiple copies compared to 11.1% in CQ-resistant at D0 and 0.0% in CQ-resistant at DR (P > 0.05). A deletion of 19 bp was found in 11/23 (47.6%) of the patients with CQ-susceptible P. vivax and 3/10 (23.1%) of the samples with in CQRPv at D0. At day DR, 55.5% of the samples with CQRPv had the 19 bp deletion. For the pvmdr-1 gene, was no variation in the analysed gene compared to the P. vivax reference Sal-1.ConclusionsThis was the first study with 42-day clinical follow-up to evaluate the variation of the number of copies and polymorphisms in the promoter region of the pvcrt-o and pvmdr1 genes in relation to treatment outcomes. Significantly higher frequency of multi-copy pvcrt-o was found in CQRPv samples at DR compared to CQ-susceptible, indicating parasite selection of this genotype after CQ treatment and its association with CQ-resistance in vivo.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2411-5) contains supplementary material, which is available to authorized users.

Section: Discussioncontrasting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Chloroquine resistance is associated to multi-copy pvcrt-o gene in Plasmodium vivax malaria in the Brazilian Amazon

Almeida

et al. 2018

Malar J

Pathogens and Global Health

“…The World Health Organization (WHO) estimates that 3.3 billion people are at risk of malaria infection, 219 million clinical cases and 435,000 deaths globally in 2017 [1]. Qatar has been free from local malaria transmission since 1970 [2], however, an influx of migrant workers from malaria-endemic countries, representing a major threat for re-introduction of local drug resistance malaria transmission [3][4][5][6]. In addition to the flow of imported cases, the receptivity and risk of malaria reintroduction are evident by the presence of the mosquito vectors, Anopheles stephensi and An.…”

Section: Introductionmentioning

confidence: 99%

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

Bansal

Bharti

Acharya

et al. 2019

Self Cite

Malaria remains a significant public health challenge and is of global importance. Imported malaria is a growing problem in non-endemic areas throughout the world and also in Qatar due to a massive influx of migrants from endemic countries. Antimalarial drug resistance is an important deterrent in our fight against malaria today. Molecular markers mirror intrinsic antimalarial drug resistance and their changes precede clinical resistance. Thus, in the present study, molecular markers of sulphadoxine-pyrimethamine (Pfdhfr and Pfdhps) and artemisinin (PfATPase6 and Pfk13) were sequenced to determine the drug resistance genotypes among 118 imported P. falciparum isolates in Qatar, between 2013 and 2016. All the isolates had mutant Pfdhfr alleles, with either double mutant (51I/108N) (59.3%) or triple mutant (51I, 59R and 108N) (30.6%) genotypes. I164L substitution was not found in this study. In case of Pfdhps, majority of the samples were carriers of either single (S436A/ A437G/ K540E) mutant (47.2%) or double (S436A/K540E, A437G/K540E, K540E/A581G) mutant (39.8%). A single novel point mutation (431V) was observed in the samples originated from Nigeria and Ghana. Polymorphisms in PfATPase6 were absent and only one non-synonymous mutation in Pfk13 was found at codon G453A from a sample of Kenyan origin. High levels of sulphadoxinepyrimethamine resistance in the present study provide potential information about the spread of antimalarial drug resistance and will be beneficial for the treatment of imported malaria cases in Qatar.

“…Émigrés constitute the majority of residents in GCC countries, reaching > 80% in Qatar [8]. In the last two decades there has been an increase in the flow of migrant workers to Qatar, associated with a positive trend in reported cases of imported malaria [7,9,10]. In addition to the increase in imported cases, the receptivity and risk of malaria reintroduction is evident by the presence of the mosquito vectors, Anopheles stephensi and An.…”

Section: Introductionmentioning

confidence: 99%

“…The chronic nature of asymptomatic malaria infection, most common in adults, in conjunction with population mobility, creates a threat to effective, long-term malaria elimination [12]. Imported asymptomatic infection often carries drug resistant strains of the Plasmodium parasite, and the transmissible stages [9,13], posing an imminent threat to receptive areas where transmission has been interrupted or targeted for elimination [14]. An improved understanding of transmission rates, Plasmodium species involved, extent of genetic diversity, and the possession of drug resistant strains of imported malaria, would permit the deployment of effective cross-border measures to limit impacts on regions targeted for elimination.…”

Section: Introductionmentioning

confidence: 99%

Influx of diverse, drug resistant and transmissible Plasmodium falciparum into a malaria-free setting in Gulf Cooperation (GCC) countries.

Al-Rumhi

Al-Hashami

Al-Hamidhi

et al. 2020

Preprint

Self Cite

Background Successful malaria control programs have interrupted local malaria transmission in almost all the Gulf Cooperation Council (GCC) countries. However, a massive influx of imported malaria via migrant workers from endemic areas sustains a threat for the re-introduction of local transmission. Here we examined the origin of imported malaria into one of the GCC countries (Qatar) and assessed the extent of genetic diversity, and carriage of drug resistance genes of imported Plasmodium falciparum and it’s potential to re-introduce the disease. Methods We examined imported malaria reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated total parasite and gametocyte density using qPCR and qRT-PCR, respectively. In addition, we examined ten neutral microsatellites and four drug resistance genes, Pfmrp1, Pfcrt, Pfmdr1 and Pfkelch13 , to assess the extent of diversity of imported P. falciparum and its potential carriage of drug resistance genotypes respectively. Results The majority of imported malaria comprised P. vivax , while P. falciparum and mixed species infections ( P. falciparum /P. vivax ) were less frequent. The main origin of P. vivax was the Indian subcontinent, while P. falciparum was most apparent among expatriates from Africa. Imported P. falciparum was highly diverse carrying multiple genotypes as well as early and late gametocytes. We observed a high prevalence of SNPs implicated in drug resistance among imported P. falciparum , with some novel SNPs in Pfkelch13 . Conclusions The high influx of genetically diverse P. falciparum, with multiple drug resistance marker gene mutations and high capacity of producing gametocytes, sustains threat for re-introduction of drug resistant malaria into GCC countries. This scenario highlights the impact of current globalisation of movement of humans in reintroducing malaria infections to areas targeted for elimination.