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Lancet (London, England) Mar 2023Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial.
BACKGROUND
Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine.
METHODS
We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179.
FINDINGS
From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min.
INTERPRETATION
Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered.
FUNDING
European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Adult; Young Adult; Pyrimethamine; Sulfadoxine; Pregnancy Outcome; Antimalarials; Azithromycin; Pregnancy Complications, Parasitic; Quinolines; Drug Combinations; Kenya; Tanzania
PubMed: 36913959
DOI: 10.1016/S0140-6736(22)02535-1 -
The Journal of Infectious Diseases Feb 2022The Plasmodium falciparum dihydrofolate reductase (PfDHFR) inhibitors pyrimethamine and cycloguanil (the active metabolite of proguanil) have important roles in malaria...
BACKGROUND
The Plasmodium falciparum dihydrofolate reductase (PfDHFR) inhibitors pyrimethamine and cycloguanil (the active metabolite of proguanil) have important roles in malaria chemoprevention, but drug resistance challenges their efficacies. A new compound, P218, was designed to overcome resistance, but drug-susceptibility data for P falciparum field isolates are limited.
METHODS
We studied ex vivo PfDHFR inhibitor susceptibilities of 559 isolates from Tororo and Busia districts, Uganda, from 2016 to 2020, sequenced 383 isolates, and assessed associations between genotypes and drug-susceptibility phenotypes.
RESULTS
Median half-maximal inhibitory concentrations (IC50s) were 42 100 nM for pyrimethamine, 1200 nM for cycloguanil, 13000 nM for proguanil, and 0.6 nM for P218. Among sequenced isolates, 3 PfDHFR mutations, 51I (100%), 59R (93.7%), and 108N (100%), were very common, as previously seen in Uganda, and another mutation, 164L (12.8%), had moderate prevalence. Increasing numbers of mutations were associated with decreasing susceptibility to pyrimethamine, cycloguanil, and P218, but not proguanil, which does not act directly against PfDHFR. Differences in P218 susceptibilities were modest, with median IC50s of 1.4 nM for parasites with mixed genotype at position 164 and 5.7 nM for pure quadruple mutant (51I/59R/108N/164L) parasites.
CONCLUSIONS
Resistance-mediating PfDHFR mutations were common in Ugandan isolates, but P218 retained excellent activity against mutant parasites.
Topics: Antimalarials; Drug Resistance; Folic Acid Antagonists; Humans; Malaria, Falciparum; Plasmodium falciparum; Polymorphism, Genetic; Proguanil; Pyrimethamine; Tetrahydrofolate Dehydrogenase; Uganda
PubMed: 34460932
DOI: 10.1093/infdis/jiab435 -
BMC Pregnancy and Childbirth Mar 2022Low birth weight is a public health problem in Africa with the cause attributable to malaria in pregnancy. World Health Organization recommends the use of intermittent...
BACKGROUND
Low birth weight is a public health problem in Africa with the cause attributable to malaria in pregnancy. World Health Organization recommends the use of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine to prevent malaria during pregnancy. The objective of this study was to evaluate the prevalence and trajectories of birth weight and the direct impact and relationship between sulfadoxine-pyrimethamine and birth weight in Ghana since 2003.
METHOD
This study used secondary data obtained from the Demographic and Health Survey conducted in Ghana since 2003. Low birth weight was defined as weight < 2500 g irrespective of the gestational age of the foetus, while normal birth weight was between 2500 g to < 4000 g and macrosomia was = > 4000 g. In all the analysis, we adjusted for clustering, stratification and weighting to reduce bias and improve precision of the estimates. Analysis was performed on each survey year as well as the pooled dataset. The generalized ordered partial proportional odds model was used due to violations of the parallel regression model assumptions. Efforts were made to identify all confounding variables and these were adjusted for. Predictive analysis was also executed.
RESULTS
The overall prevalence of low birth weight was 9% while that of macrosomia was 13%. The low birth weight for 2003 was 12% while in 2008 it was 21% and then 68% in 2014. The mean birth weight of the children in 2014 was 3.16 (3.14, 3.19), 2008 was 3.37 (3.28, 3.45) and 2003 was 3.59 (3.49, 3.69) while that of the pooled data was 3.28 (3.25, 3.30). The adjusted model (taking into consideration all confounding variables) showed that non-uptake of SP could result in 51% odds of giving birth to a low-birth-weight compared with normal birth weight child. An insignificant result was observed between macrosomia and low birth weight.
CONCLUSION
There is higher probability that low birth weight could increase over the next couple of years if measures are not taking to reverse the current trajectories. The uptake of sulfadoxine-pyrimethamine should continue to be encouraged and recommended because it has a direct beneficial effect on the weight of the child.
Topics: Adult; Antimalarials; Birth Weight; Demography; Drug Combinations; Female; Fetal Macrosomia; Ghana; Humans; Infant, Low Birth Weight; Malaria; Models, Statistical; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine
PubMed: 35305604
DOI: 10.1186/s12884-022-04565-7 -
Malaria Journal Jul 2017Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia.
METHODS
A systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature. Comprehensive meta-analysis software was used to perform all meta-analyses. The Cochrane Q and the I were used to evaluate heterogeneity of studies. Random effects model was used to combine studies showing heterogeneity of Cochrane Q p < 0.10 and I > 50.
RESULTS
Twenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Overall, a significant high treatment success of 92.9% (95% CI 89.1-96.6), p < 0.001, I = 98.39% was noticed. However, treatment success was higher in falciparum malaria patients treated with artemether-lumefantrine than chloroquine for Plasmodium vivax patients [98.1% (97.0-99.2), p < 0.001, I = 72.55 vs 94.7% (92.6-96.2), p < 0.001, I = 53.62%]. Seven studies reported the adverse drug reactions to anti-malarial treatment; of 822 participants, 344 of them were exposed to adverse drug reactions with a pooled event rate of 39.8% (14.1-65.5), p = 0.002.
CONCLUSIONS
On the basis of this review, anti-malarial treatment success was high (92.9%) and standard regimens showed good efficacy against Plasmodium falciparum (98.1%) and P. vivax (94.7%) infections in Ethiopia, but associated with high rates of adverse drug reactions (ADRs). However, these ADRs were not serious enough to discontinue anti-malarial treatment. The results of this study suggest that the current anti-malarial medications are effective and safe; however, greater priority should be placed on the discovery of new anti-malarial drugs to achieve successful outcomes as resistance seems inevitable since cases of anti-malarial drug resistance have been reported from other areas of the world.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Chloroquine; Drug Combinations; Ethanolamines; Ethiopia; Fluorenes; Humans; Malaria, Falciparum; Malaria, Vivax; Primaquine; Pyrimethamine; Sulfadoxine; Treatment Failure
PubMed: 28673348
DOI: 10.1186/s12936-017-1922-9 -
Malaria Journal Aug 2020Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern...
Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India.
BACKGROUND
Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015-2016 after 3-4 years of ASP use, are reported.
METHODS
Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16-185, pfdhps 436-632 and K13 407-689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism.
RESULTS
Sulfadoxine-pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively.
CONCLUSION
The frequency of P. falciparum with reduced susceptibility to sulfadoxine-pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.
Topics: Adolescent; Adult; Aged; Antimalarials; Artesunate; Child; Child, Preschool; Drug Combinations; Drug Resistance; Humans; India; Infant; Malaria, Falciparum; Middle Aged; Mutation; Plasmodium falciparum; Protozoan Proteins; Pyrimethamine; Sulfadoxine; Young Adult
PubMed: 32795288
DOI: 10.1186/s12936-020-03274-w -
Clinical Pharmacology and Therapeutics Sep 2022Endogenous biomarkers for transporter-mediated drug-drug interaction (DDI) predictions represent a promising approach to facilitate and improve conventional DDI...
Endogenous biomarkers for transporter-mediated drug-drug interaction (DDI) predictions represent a promising approach to facilitate and improve conventional DDI investigations in clinical studies. This approach requires high sensitivity and specificity of biomarkers for the targets of interest (e.g., transport proteins), as well as rigorous characterization of their kinetics, which can be accomplished utilizing physiologically-based pharmacokinetic (PBPK) modeling. Therefore, the objective of this study was to develop PBPK models of the endogenous organic cation transporter (OCT)2 and multidrug and toxin extrusion protein (MATE)1 substrates creatinine and N -methylnicotinamide (NMN). Additionally, this study aimed to predict kinetic changes of the biomarkers during administration of the OCT2 and MATE1 perpetrator drugs trimethoprim, pyrimethamine, and cimetidine. Whole-body PBPK models of creatinine and NMN were developed utilizing studies investigating creatinine or NMN exogenous administration and endogenous synthesis. The newly developed models accurately describe and predict observed plasma concentration-time profiles and urinary excretion of both biomarkers. Subsequently, models were coupled to the previously built and evaluated perpetrator models of trimethoprim, pyrimethamine, and cimetidine for interaction predictions. Increased creatinine plasma concentrations and decreased urinary excretion during the drug-biomarker interactions with trimethoprim, pyrimethamine, and cimetidine were well-described. An additional inhibition of NMN synthesis by trimethoprim and pyrimethamine was hypothesized, improving NMN plasma and urine interaction predictions. To summarize, whole-body PBPK models of creatinine and NMN were built and evaluated to better assess creatinine and NMN kinetics while uncovering knowledge gaps for future research. The models can support investigations of renal transporter-mediated DDIs during drug development.
Topics: Biomarkers; Cimetidine; Creatinine; Drug Interactions; Humans; Organic Cation Transport Proteins; Pharmaceutical Preparations; Pyrimethamine; Trimethoprim
PubMed: 35527512
DOI: 10.1002/cpt.2636 -
Parasites & Vectors Jun 2024Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial.
BACKGROUND
Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.
METHODS
This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
RESULTS
Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
CONCLUSIONS
A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
Topics: Humans; Child; Praziquantel; Pyrimethamine; Animals; Adolescent; Artesunate; Female; Male; Schistosomiasis mansoni; Schistosoma haematobium; Schistosomiasis haematobia; Schistosoma mansoni; Drug Therapy, Combination; Kenya; Artemisinins; Treatment Outcome; Anthelmintics; Sulfalene; Drug Combinations; Parasite Egg Count
PubMed: 38943214
DOI: 10.1186/s13071-024-06359-6 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Apr 2019Malaria is a parasitic disease which threatens human life and health seriously. Sulfadoxine-pyrimethamine (SP) has been recommended for intermittent preventive treatment... (Review)
Review
Malaria is a parasitic disease which threatens human life and health seriously. Sulfadoxine-pyrimethamine (SP) has been recommended for intermittent preventive treatment of malaria in children and pregnant women, and also used as a compound component of artemisinin based therapy. The mechanisms of SP resistance in involve point mutations in the genes encoding dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), and the drug pressure can also lead to the mutations in the two genes of To provide the information for the formulation of anti-malarial strategies, this article reviews the discovery, application, effect of SP, and the resistance mechanism and research progress of the related genes in .
Topics: Antimalarials; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Humans; Malaria, Falciparum; Mutation; Plasmodium vivax; Pyrimethamine; Research; Sulfadoxine; Tetrahydrofolate Dehydrogenase
PubMed: 31544425
DOI: 10.16250/j.32.1374.2018290 -
International Journal of Environmental... Oct 2022A significant gap exists between high rates of antenatal care attendance and low uptake of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine...
A significant gap exists between high rates of antenatal care attendance and low uptake of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) in Senegal. This study aims to investigate whether IPTp-SP is delivered per Senegal's national guidelines and to identify factors affecting the delivery of IPTp-SP at antenatal care visits. A secondary analysis was conducted using the 2014 and 2016 Senegal's Service Provision Assessment. The study sample consists of 1076 antenatal care across 369 health facilities. Multiple logit regression models were used to estimate the probability of receiving IPTp-SP during the antenatal care visit based on prior receipt of IPTp-SP and gestational age during the current pregnancy. At an antenatal care visit, the probability of receiving IPTp-SP is 84% (95% CI = [83%, 86%]) among women with no IPTp-SP history and 85% (95% CI = [79%, 92%]) among women with one prior dose. Women who visit a facility in the top quintile of the proportion of IPTp trained staff have a nearly 4-fold higher odds of receiving IPTp compared to those who visit a facility in the bottom quintile (95% CI = [1.54, 9.80]). The dose and timing of IPTp-SP provided in antenatal care settings in Senegal did not always conform with the national guideline. More training for providers and patient engagement is warranted to improve the uptake of IPTp-SP in antenatal care visits.
Topics: Antimalarials; Cross-Sectional Studies; Drug Combinations; Female; Humans; Malaria; Male; Pregnancy; Pregnancy Complications, Parasitic; Prenatal Care; Pyrimethamine; Senegal; Sulfadoxine
PubMed: 36232166
DOI: 10.3390/ijerph191912866 -
Infection, Genetics and Evolution :... Mar 2019Pyrimethamine resistance is a major concern for the control of human haemoprotozoa, especially Plasmodium species. Currently, there is little understanding of how...
Pyrimethamine resistance is a major concern for the control of human haemoprotozoa, especially Plasmodium species. Currently, there is little understanding of how pyrimethamine resistance developed in Plasmodium vivax in the natural field conditions. Here, we present for the first time evidence of positive selection pressure on a dihydrofolate reductase locus and its consequences on the emergence and the spread of pyrimethamine resistance in P. vivax in the Punjab province of Pakistan. First, we examined the dihydrofolate reductase locus in 38 P. vivax isolates to look for evidence of positive selection pressure in human patients. The S58R (AGA)/S117N (AAC) double mutation was most common, being detected in 10/38 isolates. Single mutation S117N (AAC), I173L (CTT) and S58R (AGA) SNPs were detected in 8/38, 2/38 and 1/38 isolates, respectively. The F57L/I (TTA/ATA) and T61M (ATG) SNPs were not detected in any isolates examined. Although both soft and hard selective sweeps have occurred with striking differences between isolates, there was a predominance of hard sweeps. A single resistance haplotype was present at high frequency in 9/14 isolates, providing a strong evidence for single emergence of resistance by the single mutation, characteristics of hard selective sweeps. In contrast, 5/14 isolates carried multiple resistance haplotypes at high frequencies, providing an evidence of the emergence of resistance by recurrent mutations, characteristics of soft selective sweeps. Our phylogenetic relationship analysis suggests that S58R (AGA)/S117N (AAC) and S117N (AAC) mutations arose multiple times from a single origin and spread to multiple different cities in the Punjab province through gene flow. Interestingly, the I173L (CTT) mutation was present on a single haplotype, suggesting that it arises rarely and has not spread between cities. Our work shows the need for responsible use of existing and new antimicrobial drugs and their combinations, control the movement of infected patients and mosquito vector control strategies.
Topics: Alleles; Antimalarials; Drug Resistance; Gene Frequency; Genome, Protozoan; Haplotypes; High-Throughput Nucleotide Sequencing; Humans; Malaria, Vivax; Mutation; Parasitic Sensitivity Tests; Phylogeny; Plasmodium vivax; Polymorphism, Single Nucleotide; Pyrimethamine; Tetrahydrofolate Dehydrogenase
PubMed: 30594654
DOI: 10.1016/j.meegid.2018.12.032