scholarly journals Plasmodium falciparum and Plasmodium vivax Genotypes and Efficacy of Intermittent Preventive Treatment in Papua New Guinea

2014 ◽  
Vol 58 (11) ◽  
pp. 6958-6961 ◽  
Author(s):  
Celine Barnadas ◽  
Nicolas Senn ◽  
Jonah Iga ◽  
Lincoln Timinao ◽  
Sarah Javati ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Papua New Guinea ◽  
Protective Efficacy ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
New Guinea ◽  
Content Type ◽  
Resistance Markers ◽  
Childhood Malaria

ABSTRACTIntermittent preventive treatment of infants (IPTi) reduces early childhood malaria-related morbidity. While genotypic drug resistance markers have proven useful in predicting the efficacy of antimalarial drugs in case management, there are few equivalent data relating to their protective efficacy when used as IPTi. The present data from an IPTi trial in Papua New Guinea demonstrate how these markers can predict protective efficacy of IPTi for bothPlasmodium falciparumandPlasmodium vivax.

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 Prevalence of Plasmodium falciparum Resistance Markers to Sulfadoxine-Pyrimethamine among Pregnant Women Receiving Intermittent Preventive Treatment for Malaria in Uganda

2015 ◽  
Vol 59 (9) ◽  
pp. 5475-5482 ◽  
Author(s):  
Anthony K. Mbonye ◽  
Josephine Birungi ◽  
Stephanie K. Yanow ◽  
Sandra Shokoples ◽  
Samuel Malamba ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Birth Weight ◽  
Pregnant Women ◽  
Intermittent Preventive Treatment ◽  
Melting Curve ◽  
Preventive Treatment ◽  
Melting Curve Analysis ◽  
Content Type ◽  
Lower Birth Weight ◽  
Resistance Markers

ABSTRACTThe aim of this study was to assess the prevalence of mutations inPlasmodium falciparumdihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes among pregnant women using sulfadoxine-pyrimethamine (SP) as an intermittent preventive treatment (IPTp). A molecular epidemiological study ofP. falciparumparasite resistance markers to SP was conducted from August 2010 to February 2012 in Mukono district in central Uganda. DNA was extracted from 413P. falciparum-positive samples. Real-time PCR, followed by melting curve analysis, was used to characterize point mutations in thePfdhfrandPfdhpsgenes that are associated with SP resistance. The prevalence of the single-nucleotide mutations inPfdhfrat codons 51I, 59R, and 108N and inPfdhpsat codons 437G and 540E was high (>98%), reaching 100% fixation after one dose of SP, while the prevalence of 581G was 3.3% at baseline, reaching 12.5% after one dose of SP. At baseline, the prevalence ofPfdhfrandPfdhpsquintuple mutations was 89%, whereas the sextuple mutations (including 581G) were not prevalent (3.9%), reaching 16.7% after one dose of SP. However, the numbers of infections at follow-up visits were small, and hence there was insufficient statistical power to test whether there was a true rise in the prevalence of this allele. The overall high frequency ofPfdhfrandPfdhpsquintuple mutations throughout pregnancy excluded further analyses of possible associations between certain haplotypes and the risk of lower birth weight and anemia. However, women infected withP. falciparumhad 1.3-g/dl-lower hemoglobin levels (P= 0.001) and delivered babies with a 400-g-lower birth weight (P= 0.001) compared to nonparasitemic women. Despite this, 44 women who wereP. falciparumpositive at baseline became negative after one or two doses of SP (i.e., 50.5%), implying that SP-IPTp still has some efficacy.P. falciparumresistance markers to SP are high in this population, whereasP. falciparuminfection was associated with poor birth outcomes.

scholarly journals The epidemiology of Plasmodium falciparum and Plasmodium vivax in East Sepik Province, Papua New Guinea, pre- and post-implementation of national malaria control efforts

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Johanna H. Kattenberg ◽  
Dulcie L. Gumal ◽  
Maria Ome-Kaius ◽  
Benson Kiniboro ◽  
Matthew Philip ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Papua New Guinea ◽  
Malaria Control ◽  
New Guinea

scholarly journals Increasing Prevalence of a Novel Triple-Mutant Dihydropteroate Synthase Genotype in Plasmodium falciparum in Western Kenya

2015 ◽  
Vol 59 (7) ◽  
pp. 3995-4002 ◽  
Author(s):  
Naomi W. Lucchi ◽  
Sheila Akinyi Okoth ◽  
Franklin Komino ◽  
Philip Onyona ◽  
Ira F. Goldman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Mutant Allele ◽  
Double Mutant ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Triple Mutant ◽  
Western Kenya ◽  
Content Type ◽  
Dihydropteroate Synthase

ABSTRACTThe molecular basis of sulfadoxine-pyrimethamine (SP) resistance lies in a combination of single-nucleotide polymorphisms (SNPs) in two genes coding forPlasmodium falciparumdihydrofolate reductase (Pfdhfr) andP. falciparumdihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. The continued use of SP for intermittent preventive treatment in pregnant women in many African countries, despite SP's discontinuation as a first-line antimalarial treatment option due to high levels of drug resistance, may further increase the prevalence of SP-resistant parasites and/or lead to the selection of new mutations. An antimalarial drug resistance surveillance study was conducted in western Kenya between 2010 and 2013. A total of 203 clinical samples from children with uncomplicated malaria were genotyped for SNPs associated with SP resistance. The prevalence of the triple-mutantPfdhfrC50I51R59N108I164genotype and the double-mutantPfdhpsS436G437E540A581A613genotype was high. Two triple-mutantPfdhpsgenotypes, S436G437E540G581A613andH436G437E540A581A613, were found, with the latter thus far being uniquely found in western Kenya. The prevalence of the S436G437E540G581A613genotype was low. However, a steady increase in the prevalence of thePfdhpstriple-mutantH436G437E540A581A613genotype has been observed since its appearance in early 2000. Isolates with these genotypes shared substantial microsatellite haplotypes with the most common double-mutant allele, suggesting that this triple-mutant allele may have evolved locally. Overall, these findings show that the prevalence of theH436G437E540A581A613triple mutant may be increasing in this population and could compromise the efficacy of SP for intermittent preventive treatment in pregnant women if it increases the resistance threshold further.

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