Prevalence of molecular markers of Plasmodium falciparum resistance to sulfadoxine–pyrimethamine during the intermittent preventive treatment in infants coupled with the expanded program immunization in Senegal

2011 ◽  
Vol 109 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Babacar Faye ◽  
Magatte Ndiaye ◽  
Jean Louis Ndiaye ◽  
Abiola Annie ◽  
Roger Clement Tine ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment

Reduced birth weight caused by sextuple drug resistant Plasmodium falciparum infection in early 2nd trimester

2021 ◽  
Author(s):  
Helle Hansson ◽  
Daniel T R Minja ◽  
Sofie L Moeller ◽  
John P A Lusingu ◽  
Ib C Bygbjerg ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Birth Weight ◽  
Birth Outcomes ◽  
Birth Outcome ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
First Trimester ◽  
Close Monitoring ◽  
The Impact ◽  
Mutant Haplotype

Abstract Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp-SP, we monitored birth outcomes in women followed from prior to conception or from the first trimester until delivery. Women infected with sextuple haplotypes in early 2 nd trimester specifically, delivered newborns with a lower birth weight (-267g, 95% CI -454; -59, p=0·01) compared to women who did not have malaria during pregnancy and women infected with less SP resistant haplotypes (-461g, 95% CI -877; -44, p=0·03). Thus, sextuple haplotype infections seems to impact the effectiveness of SP for IPTp and directly impact birth outcome by lowering birth weight. Close monitoring and targeted malaria control during early pregnancy is therefore crucial to improve birth outcomes.

scholarly journals Associations between Malaria-Preventive Regimens and Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Patience Nayebare ◽  
Victor Asua ◽  
Melissa D. Conrad ◽  
Richard Kajubi ◽  
Abel Kakuru ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Polymorphisms ◽  
Protective Efficacy ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Drug Susceptibility ◽  
Recent Trial ◽  
Content Type ◽  
High Level ◽  
Selection Of

ABSTRACT Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of Plasmodium falciparum genetic polymorphisms that alter susceptibility to these drugs. The prevalence of known genetic polymorphisms associated with altered drug susceptibility was determined in parasitemic samples, including 375 collected before IPTp drugs were administered, 125 randomly selected from those receiving SP, and 80 from those receiving DP. For women receiving DP, the prevalence of mixed/mutant sequences was greater in samples collected during IPTp than that in samples collected prior to the intervention for PfMDR1 N86Y (20.3% versus 3.9%; P < 0.001), PfMDR1 Y184F (73.0% versus 53.0%; P < 0.001), and PfCRT K76T (46.4% versus 24.0%; P < 0.001). Considering SP, prior to IPTp, the prevalence of all 5 common antifolate mutations was over 92%, and this prevalence increased following exposure to SP, although none of these changes were statistically significant. For two additional mutations associated with high-level SP resistance, the prevalence of PfDHFR 164L (13.7% versus 4.0%; P = 0.004), but not PfDHPS 581G (1.9% versus 3.0%; P = 0.74), was greater in samples collected during IPTp compared to those collected before the intervention. Use of IPTp in Uganda selected for parasites with mutations associated with decreased susceptibility to IPTp regimens. Thus, a potential drawback of IPTp is selection of parasites with decreased drug susceptibility.

scholarly journals Increased Prevalence of Mutant Allele Pfdhps 437G and Pfdhfr Triple Mutation in Plasmodium falciparum Isolates from a Rural Area of Gabon, Three Years after the Change of Malaria Treatment Policy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jacques-Mari Ndong Ngomo ◽  
Denise Patricia Mawili-Mboumba ◽  
Noé Patrick M’Bondoukwe ◽  
Rosalie Nikiéma Ndong Ella ◽  
Marielle Karine Bouyou Akotet
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Mutant Allele ◽  
Continuous Monitoring ◽  
Intermittent Preventive Treatment ◽  
Point Mutations ◽  
Preventive Treatment ◽  
Malaria Treatment ◽  
Pcr Rflp ◽  
Elevated Frequency

In Gabon, sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment during pregnancy (IPTp-SP) and for uncomplicated malaria treatment through ACTs drug. P. falciparum strains resistant to SP are frequent in areas where this drug is highly used and is associated with the occurrence of mutations on Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes. The aim of the study was to compare the proportion of mutations on Pfdhfr and Pfdhps genes in isolates collected at Oyem in northern Gabon, in 2005 at the time of IPTp-SP introduction and three years later. Point mutations were analyzed by nested PCR-RFLP method. Among 91 isolates, more than 90% carried Pfdhfr 108N and Pfdhfr 59R alleles. Frequencies of Pfdhfr 51I (98%) and Pfdhps 437G (67.7%) mutant alleles were higher in 2008. Mutations at codons 164, 540, and 581 were not detected. The proportion of the triple Pfdhfr mutation and quadruple mutation including A437G was high: 91.9% in 2008 and 64.8% in 2008, respectively. The present study highlights an elevated frequency of Pfdhfr and Pfdhps mutant alleles, although quintuple mutations were not found in north Gabon. These data suggest the need of a continuous monitoring of SP resistance in Gabon.

scholarly journals Origins of the Recent Emergence of Plasmodium falciparum Pyrimethamine Resistance Alleles in Madagascar

2010 ◽  
Vol 54 (6) ◽  
pp. 2323-2329 ◽  
Author(s):  
Valérie Andriantsoanirina ◽  
Christiane Bouchier ◽  
Magali Tichit ◽  
Martial Jahevitra ◽  
Stéphane Rabearimanana ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Single Mutation ◽  
Wild Type ◽  
Triple Mutant ◽  
Asian Origin ◽  
Recent Emergence ◽  
Malaria During Pregnancy ◽  
Mutation Allele

ABSTRACT The combination of sulfadoxine-pyrimethamine is recommended for use as intermittent preventive treatment of malaria during pregnancy and is deployed in Africa. The emergence and the spread of resistant parasites are major threats to such an intervention. We have characterized the Plasmodium falciparum dhfr (pfdhfr) haplotypes and flanking microsatellites in 322 P. falciparum isolates collected from the Comoros Islands and Madagascar. One hundred fifty-six (48.4%) carried the wild-type pfdhfr allele, 19 (5.9%) carried the S108N single-mutation allele, 30 (9.3%) carried the I164L single-mutation allele, 114 (35.4%) carried the N51I/C59R/S108N triple-mutation allele, and 3 (1.0%) carried the N51I/C59R/S108N/I164L quadruple-mutation allele. Microsatellite analysis showed the introduction from the Comoros Islands of the ancestral pfdhfr triple mutant allele of Asian origin and its spread in Madagascar. Evidence for the emergence on multiple occasions of the I164L single-mutation pfdhfr allele in Madagascar was also obtained. Thus, the conditions required to generate mutants with quadruple mutations are met in Madagascar, representing a serious threat to current drug policy.

scholarly journals Multiplicity of Plasmodium falciparum infection following intermittent preventive treatment in infants

2010 ◽  
Vol 9 (1) ◽  
pp. 244 ◽  
Author(s):  
Ulrike Buchholz ◽  
Robin Kobbe ◽  
Ina Danquah ◽  
Philipp Zanger ◽  
Klaus Reither ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Falciparum Infection ◽  
Plasmodium Falciparum Infection

scholarly journals Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

2018 ◽  
Vol 1 ◽  
pp. 1
Author(s):  
James Abugri ◽  
Felix Ansah ◽  
Kwaku P. Asante ◽  
Comfort N. Opoku ◽  
Lucas A. Amenga-Etego ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Chloroquine Resistance ◽  
Nucleotide Polymorphisms ◽  
Chloroquine Resistance Transporter ◽  
Significant Difference ◽  
Quadruple Mutant ◽  
Study Sites

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Sulphadoxine-pyrimethamine (SP) which was the second line antimalarial drug in Ghana, was now adopted for intermittent preventive treatment of malaria in pregnancy (IPTp). Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we employed restriction fragment length polymorphism polymerase chain reaction to genotype and compare single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter ( pfcrt, PF3D7_0709000), multidrug resistance ( pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase ( pfdhfr, PF3D7_0417200) and dihydropteroate synthase ( pfdhps, PF3D7_0810800) genes. Parasites were collected from children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) in 2012-2013 and 2016-2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10.2% and 65.1% of infections, respectively. The majority of the isolates harboured the antifolate resistance-associated pfdhfr alleles 51I (83.4%), 59R (85.9 %) and 108N (90.5%). Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G, which was more common in Accra compared to Kintampo for the 2016-2017 isolates. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination (I 51 R 59 N 108/ G 437). CQ resistance alleles decreased during the 12 years after CQ withdrawal, but an mediate SP resistance alleles increased. Conclusion: Surveillance of the prevalence of resistance alleles is necessary in monitoring the efficacy of antimalarial drugs.

scholarly journals Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
M. Andreína Pacheco ◽  
Kristan A. Schneider ◽  
Qiuying Cheng ◽  
Elly O. Munde ◽  
Caroline Ndege ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mutant Allele ◽  
Intermittent Preventive Treatment ◽  
Low Frequency ◽  
Preventive Treatment ◽  
Parasite Clearance ◽  
Drug Formulation ◽  
Drug Pressure ◽  
Lack Of Information ◽  
In Pregnancy

Abstract Background Sulfadoxine-pyrimethamine (SP) is the only anti-malarial drug formulation approved for intermittent preventive treatment in pregnancy (IPTp). However, mutations in the Plasmodium falciparum dhfr (Pfdhfr) and dhps (Pfdhps) genes confer resistance to pyrimethamine and sulfadoxine, respectively. Here, the frequencies of SP resistance-associated mutations from 2005 to 2018 were compared in samples from Kenyan children with malaria residing in a holoendemic transmission region. Methods Partial sequences of the Pfdhfr and Pfdhps genes were amplified and sequenced from samples collected in 2005 (n = 81), 2010 (n = 95), 2017 (n = 43), and 2018 (n = 55). The frequency of known mutations conferring resistance to pyrimethamine and sulfadoxine were estimated and compared. Since artemisinin-based combination therapy (ACT) is the current first-line treatment for malaria, the presence of mutations in the propeller domain of P. falciparum kelch13 gene (Pfk13) linked to ACT-delayed parasite clearance was studied in the 2017/18 samples. Results Among other changes, the point mutation of Pfdhps S436H increased in frequency from undetectable in 2005 to 28% in 2017/18. Triple Pfdhfr mutant allele (CIRNI) increased in frequency from 84% in 2005 to 95% in 2017/18, while the frequency of Pfdhfr double mutant alleles declined (allele CICNI from 29% in 2005 to 6% in 2017/18, and CNRNI from 9% in 2005 to undetectable in 2010 and 2017/18). Thus, a multilocus Pfdhfr/Pfdhps genotype with six mutations (HGEAA/CIRNI), including Pfdhps S436H, increased in frequency from 2010 to 2017/18. Although none of the mutations associated with ACT-delayed parasite clearance was observed, the Pfk13 mutation A578S, the most widespread Pfk13 SNP found in Africa, was detected in low frequency (2.04%). Conclusions There were changes in SP resistance mutant allele frequencies, including an increase in the Pfdhps S436H. Although these patterns seem consistent with directional selection due to drug pressure, there is a lack of information to determine the actual cause of such changes. These results suggest incorporating molecular surveillance of Pfdhfr/Pfdhps mutations in the context of SP efficacy studies for intermittent preventive treatment in pregnancy (IPTp).

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