Dataset Information

CYP2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region.

ABSTRACT: Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals from the Brazilian Amazon region. The blood samples were collected from 220 unrelated Plasmodium vivax patients from five different endemic areas. Genotyping was performed using SNaPshot^® and real-time polymerase chain reaction methods. In all five areas, the rs1065852 (CYP2D6*10, C.100C > T), rs3892097 (CYP2D6*4, 1846C > T) and rs16947 (CYP2D6*2, C.2850G > A), as a homozygous genotype, showed the lowest frequencies. The rs28371725 (CYP2D6*41, 2988G > A) homozygous genotype was not detected, while the allele A was found in a single patient from Macapá region. No deviations from Hardy-Weinberg equilibrium were found, although a borderline p-value was observed (p = 0.048) for the SNP rs3892097 in Goianésia do Pará, Pará state. No significant associations were detected in these frequencies among the five studied areas. For the SNP rs3892097, a higher frequency was observed for the C/T heterozygous genotype in the Plácido de Castro and Macapá, Acre and Amapá states, respectively. The distribution of the CYP2D6 alleles investigated in the different areas of the Brazilian Amazon is not homogeneous. Further investigations are necessary in order to determine which alleles might be informative to assure optimal drug dosing recommendations based on experimental pharmacogenetics.

SUBMITTER: Salles PF

PROVIDER: S-EPMC8343396 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CYP2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region.

Salles Paula Ferreira PF Perce-da-Silva Daiana Souza DS Rossi Atila Duque AD Raposo Luisa Riehl LR Ramirez Ramirez Aina Danaisa AD Pereira Bastos Otílio Machado OM Pratt-Riccio Lilian Rose LR Cassiano Gustavo Capatti GC Baptista Andrea Regina Souza ARS Cardoso Cynthia Chester CC Banic Dalma Maria DM Machado Ricardo Luiz Dantas RLD

Frontiers in pharmacology 20210723

Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals ...[more]

PMID: 34366834

Similar Datasets

Project description:BackgroundPlasmodium vivax is the most widely distributed species causing the highest number of malaria cases in the world. In Brazil, P. vivax is responsible for approximately 84 % of reported cases. In the absence of a vaccine, control strategies are based on the management of cases through rapid diagnosis and adequate treatment, in addition to vector control measures. The approaches used to investigate P. vivax resistance to chloroquine (CQ) were exclusively in vivo studies because of the difficulty in keeping parasites in continuous in vitro culture. In view of the limitations related to follow-up of patients and to assessing the plasma dosage of CQ and its metabolites, an alternative approach to monitor chemo-resistance (QR) is to use molecular markers. Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene pvmdr1 are putative determinants of CQ resistance (CQR), but such SNPs in P. vivax isolates from patients with good response to treatment should be further explored. The aim of this study is to investigate the mutations in the gene, supposedly associated to QR, in P. vivax isolates from successfully cured patients, living in Brazilian endemic and non-endemic areas.MethodsBlood samples were collected from 49 vivax malaria patients from endemic (Amazon Basin: 45) and non-endemic (Atlantic Forest: four) Brazilian regions and analysed for SNPs in the CQR-related P. vivax gene (pvmdr1), using PCR-based methods.ResultsAmong the 49 isolates genetically characterized for the gene pvmdr1, 34 (70 %) presented at least one mutation. T958M mutant alleles were the most frequent (73 %) followed Y976F (15 %) and F1076L (12 %). Single mutation was detected in 24 (70.5 %) isolates and double mutations in ten (29.5 %). The most common single mutant genotype was the 958M/Y976/F1076 (79 %), followed by 976F/F1076 (21 %) whereas 958M/Y976/1076L (60 %) and 976F/1076L (40 %) double mutant genotypes were detected. Single mutant profile was observed only in isolates from Amazon Basin, although double mutants were found both in the Amazon and Atlantic Forest regions. Interestingly, the genotype 958M/Y976/1076L was present in all isolates from the Atlantic Forest in the Rio de Janeiro State.ConclusionsConsidering that primaquine (PQ) efficacy is highly dependent on concurrent administration of a blood schizontocidal agent and that PQ could not circumvent CQR, together with the fact that no pvmdr1 mutation should be expected in successfully cured patients, these findings seem to indicate that the pvmdr1 gene is not a reliable marker of CQR. Further investigations are needed to define a reliable molecular marker for monitoring P. vivax CQR in P. vivax populations.

Project description:BackgroundInformation on costs associated with malaria in pregnancy (MiP) in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon.Methods/principal findingsBetween January 2011 and March 2012 patient costs for the treatment of MiP were collected through an exit survey at a tertiary referral hospital and at a primary health care centre in the Manaus metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with malaria were interviewed after an outpatient consultation or at discharge after admission. Seventy-three interviews were included in the analysis. Ninety-six percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In 2010, the total median costs from the patient perspective were estimated at US $45.91 and US $216.29 for an outpatient consultation and an admission, respectively. When multiple P. vivax infections during the same pregnancy were considered, patient costs increased up to US $335.85, representing the costs of an admission plus an outpatient consultation. Provider direct and overhead cost data were obtained from several sources. The provider cost associated with an outpatient case, which includes several consultations at the tertiary hospital was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum malaria episode. The cost of an inpatient day and average admission of 3 days was US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis and treatment of all malaria cases reported in pregnant women in Manaus in 2010 (N = 364) were US $17,038.50, of which 92.4% (US$ 15,741.14) due to P. vivax infection.ConclusionDespite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P. falciparum. The information generated may help health policy decisions for the current control and future elimination of malaria in the area.

Project description:BACKGROUND:There is a growing body of evidence linking micronutrient deficiencies and malaria incidence arising mostly from P. falciparum endemic areas. We assessed the impact of micronutrient deficiencies on malaria incidence and vice versa in the Brazilian state of Amazonas. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated children <10 years old living in rural communities in the state of Amazonas, Brazil, from May 2010 to May 2011. All children were assessed for sociodemographic, anthropometric and laboratory parameters, including vitamin A, beta-carotene, zinc and iron serum levels at the beginning of the study (May 2010) and one year later (May 2011). Children were followed in between using passive surveillance for detection of symptomatic malaria. Those living in the study area at the completion of the observation period were reassessed for micronutrient levels. Univariate Cox-proportional Hazards models were used to assess whether micronutrient deficiencies had an impact on time to first P. vivax malaria episode. We included 95 children median age 4.8 years (interquartile range [IQR]: 2.3-6.6), mostly males (60.0%) and with high maternal illiteracy (72.6%). Vitamin A deficiencies were found in 36% of children, beta-carotene deficiency in 63%, zinc deficiency in 61% and iron deficiency in 51%. Most children (80%) had at least one intestinal parasite. During follow-up, 16 cases of vivax malaria were diagnosed amongst 13 individuals. Micronutrient deficiencies were not associated with increased malaria incidence: vitamin A deficiency [Hazard ratio (HR): 1.51; P-value: 0.45]; beta-carotene [HR: 0.47; P-value: 0.19]; zinc [HR: 1.41; P-value: 0.57] and iron [HR: 2.31; P-value: 0.16]). Upon reevaluation, children with al least one episode of malaria did not present significant changes in micronutrient levels. CONCLUSION:Micronutrient serum levels were not associated with a higher malaria incidence nor the malaria episode influenced micronutrient levels. Future studies targeting larger populations to assess micronutrients levels in P. vivax endemic areas are warranted in order to validate these results.

Project description:BackgroundChloroquine (CQ) and primaquine (PQ) are still the drugs of choice to treat Plasmodium vivax malaria in many endemic areas, Brazil included. There is in vivo evidence for the P. vivax resistance to CQ in the Brazilian Amazon, where the increase in the proportion of P. vivax malaria parallels the increase of unusual clinical complications related to this species. In this study, in vitro CQ and mefloquine (MQ)-susceptibility of P. vivax isolates from the Western Brazilian Amazon was tested using the double-site enzyme-linked lactate dehydrogenase immunodetection (DELI) assay.MethodsA total of 112 P. vivax isolates were tested in vitro for CQ-susceptibility and out of these 47 were also tested for MQ-susceptibility. The DELI assay was used to detect P. vivax growth at 48-hour short-term culture in isolates with ring stages ranging from 50 to %. Each isolate was tested in triplicate and geometric means of IC50's was obtained. Nineteen isolates were genetically characterized for pvdhfr, pvmrp1, pvmdr1 and pvdhps candidate genes likely related to CQ resistance (10 with IC50<40 nM and 9 with IC50 >100 nM).ResultsTwelve out of 112 isolates were considered resistant to CQ, resulting in 10.7% (IC95% 5.0-16.4), while 3 out of 47 (6.4%; IC95% 0.0-12.8) were resistant to MQ. A discrete correlation was observed between IC50's of CQ and MQ (Spearman=0.294; p=0.045). For pvdhps gene, a non-synonymous mutation was found at codon 382 (S→C) in 5/8 CQ-sensitive samples and 1/9 CQ-resistant samples (p=0.027). The other molecular markers were not associated to CQ-susceptibility.ConclusionsIn vitro CQ-resistance estimated in this study, estimated by the DELI test, was very similar to that observed in clinical trials, suggesting that in vitro procedures developed by capable local laboratories are useful in the surveillance of CQ-resistance in the Amazon; concurrent Amazon P. vivax strains with both CQ and MQ resistance may be common; and a non-synonymous mutation at pvdhps codon 382 (S→C) was associated to in vitro susceptibility to CQ, needing further studies to be confirmed.

Dataset Information

CYP2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region.

Publications

<i>CYP</i>2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets