scholarly journals Increase in the proportion of Plasmodium falciparum with kelch13 C580Y mutation and decline in pfcrt and pfmdr1 mutant alleles in Papua New Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Naoko Yoshida ◽  
Masato Yamauchi ◽  
Ryosuke Morikawa ◽  
Francis Hombhanje ◽  
Toshihiro Mita
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
New Guinea ◽  
Therapeutic Effects ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
In The Wild ◽  
Nationwide Surveillance ◽  
Greater Mekong Subregion ◽  
C580y Mutation

Abstract Background The C580Y mutation in the Plasmodium falciparum kelch13 gene is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside the GMS, except for Guyana/Amazonia. In 2017, three parasites carrying the C580Y mutation were identified in Papua New Guinea (PNG). As the C580Y allele rapidly spread in the GMS, there is concern that this mutant is now spreading in PNG. Methods In 2020, a cross-sectional survey was conducted at two clinics in Wewak, PNG. Symptomatic patients infected with P. falciparum were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in kelch13, pfcrt, and pfmdr1 were determined. Parasite positivity was examined on day 3. The results were compared with those of previous studies conducted in 2002, 2003, and 2016–2018. Results A total of 94 patients were included in this analysis. The proportion of C580Y was significantly increased (2.2% in 2017, 5.7% in 2018, and 6.4% in 2020; p = 4.2 × 10–3). A significant upward trend was observed in the wild-type proportion for pfcrt (1.9% in 2016 to 46.7% in 2020; p = 8.9 × 10–16) and pfmdr1 (59.5% in 2016 to 91.4% in 2020; p = 2.3 × 10–6). Among 27 patients successfully followed on day 3, including three with C580Y infections, none showed positive parasitaemia. Conclusions Under the conditions of significant increases in pfcrt K76 and pfmdr1 N86 alleles in PNG, the increase in kelch13 C580Y mutants may be a warning indicator of the emergence of parasites resistant to the currently used first-line treatment regimen of artemether plus lumefantrine. Therefore, nationwide surveillance of molecular markers for drug resistance and assessment of its therapeutic effects are important.

scholarly journals Increased in the Prevalence of Plasmodium Falciparum With Kelch13 C580Y Mutations and the Decline in pfcrt and pfmdr1 Mutant Alleles in Papua New Guinea

2021 ◽  
Author(s):  
Naoko Yoshida ◽  
Masato Yamauchi ◽  
Ryosuke Morikawa ◽  
Francis Hombhanje ◽  
Toshihiro Mita
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
New Guinea ◽  
National Treatment ◽  
Upward Trend ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Nationwide Surveillance ◽  
Greater Mekong Subregion ◽  
C580y Mutation

Abstract BackgroundThe C580Y mutation in Plasmodium falciparum kelch13 (pfk13) is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside GMS, except for Guyana. In 2017, we identified three parasites carrying the C580Y mutation in Papua New Guinea (PNG). As the C580Y allele rapidly spread in the GMS, there is concern that this mutant is now spreading in PNG. MethodsIn 2020, we conducted a cross-sectional survey at two clinics in Wewak, PNG. Symptomatic patients infected with P. falciparum were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in pfk13, pfcrt, and pfmdr1 were determined. Parasite positivity was examined on day 3. ResultsA total of 94 patients were included in this analysis. The prevalence of C580Y was significantly increased (2.2% in 2017, 5.7% in 2018, and 6.4% in 2020; p = 4.2×10-3). A significant upward trend of wild-type prevalence was found for pfcrt (1.9% in 2016 to 46.7% in 2020; p = 8.9×10-16) and pfmdr1 (59.5% in 2016 to 91.4% in 2020; p = 2.3×10-6). Among 26 patients, including three with C580Y infections successfully followed on day 3, none showed positive parasitemia. ConclusionsUnder the conditions of significant increases in pfcrt K76 and pfmdr1 N86 alleles in PNG, the increase in pfk13 C580Y mutants may be a warning indicator of the emergence of parasites resistant to the currently used first-line treatment regimen of artemether plus lumefantrine. Therefore, nationwide surveillance of molecular markers for drug resistance and assessment of its therapeutic effect, are important.

scholarly journals Women's knowledge of maternal danger signs during pregnancy: Findings from a cross-sectional survey in Papua New Guinea

Midwifery ◽  
2019 ◽  
Vol 72 ◽  
pp. 7-13 ◽  
Author(s):  
LM Vallely ◽  
R Emori ◽  
H Gouda ◽  
S Phuanukoonnon ◽  
CSE Homer ◽  
...  
Keyword(s):  
Papua New Guinea ◽  
New Guinea ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Danger Signs ◽  
Women's Knowledge ◽  
Women’S Knowledge

scholarly journals Socio-economic status and behavioural and cardiovascular risk factors in Papua New Guinea: A cross-sectional survey

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0211068 ◽  
Author(s):  
Patricia Rarau ◽  
Justin Pulford ◽  
Hebe Gouda ◽  
Suparat Phuanukoonon ◽  
Chris Bullen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Papua New Guinea ◽  
Economic Status ◽  
New Guinea ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Socio Economic Status

scholarly journals Correction: Socio-economic status and behavioural and cardiovascular risk factors in Papua New Guinea: A cross-sectional survey

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212894
Author(s):  
Patricia Rarau ◽  
Justin Pulford ◽  
Hebe Gouda ◽  
Suparat Phuanukoonnon ◽  
Chris Bullen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Papua New Guinea ◽  
Economic Status ◽  
New Guinea ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Socio Economic Status

scholarly journals Plasmodium falciparum Isolates Carrying pfk13 Polymorphisms Harbor the SVMNT Allele of pfcrt in Northwestern Indonesia

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Inke N. D. Lubis ◽  
Hendri Wijaya ◽  
Munar Lubis ◽  
Chairuddin P. Lubis ◽  
Khalid B. Beshir ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Artemisinin Combination Therapy ◽  
Drug Susceptibility ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Content Type ◽  
Treatment Groups ◽  
Greater Mekong Subregion

ABSTRACT Artemisinin-based combination therapy (ACT) is the first-line antimalarial regimen in Indonesia. Susceptibility of Plasmodium falciparum to artemisinin is falling in the Greater Mekong subregion, but it is not known whether the efficacy of current combinations is also threatened in nearby Sumatera. We evaluated the genetic loci pfcrt, pfmdr1, and pfk13, considered to be under selection by artemisinin combination therapy, among 404 P. falciparum infections identified by PCR detection in a cross-sectional survey of 3,731 residents of three regencies. The pfcrt haplotype SVMNT (codons 72 to 76) was the most prevalent and displayed significant linkage disequilibrium with the pfmdr1 haplotype YY (codons 86 and 184) (odds ratio [OR] 26.7; 95% confidence interval [CI], 5.96 to 239.4; P < 0.001). This contrasts with Mekong countries, where the CVIET haplotype of pfcrt predominates. Among 231 evaluable isolates, only 9 (3.9%) showed any evidence of nonsynonymous gene variants in the propeller domain of pfk13. The Thr474Ala variant was seen in six individuals, and Cys580Tyr was identified with low confidence in only a single isolate from an asymptomatic individual. Among a subset of 117 symptomatic P. falciparum-infected individuals randomized to receive either dihydroartemisinin-piperaquine or artemether-lumefantrine, the treatment outcome was not associated with pretreatment genotype. However, submicroscopic persistent parasites at day 28 or day 42 of follow-up were significantly more likely to harbor the pfmdr1 haplotype NF (codons 86 and 184) than were pretreatment isolates (P < 0.001 for both treatment groups). Current ACT regimens appear to be effective in Sumatera, but evidence of persistent submicroscopic infection in some patients suggests further detailed studies of drug susceptibility should be undertaken.

scholarly journals Relationship between markers of inflammation and anaemia in children of Papua New Guinea

2012 ◽  
Vol 16 (2) ◽  
pp. 289-295 ◽  
Author(s):  
Naomi Shinoda ◽  
Kevin M Sullivan ◽  
Katie Tripp ◽  
Jürgen G Erhardt ◽  
Bridgette MH Haynes ◽  
...  
Keyword(s):  
Papua New Guinea ◽  
Acute Phase ◽  
Acute Phase Protein ◽  
New Guinea ◽  
Protein Biomarkers ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Markers Of Inflammation ◽  
Phase Protein ◽  
Nationally Representative

AbstractObjectiveTo assess the association of the acute-phase protein biomarkers, C-reactive protein (CRP) and α1-acid glycoprotein (AGP), with anaemia in children aged 6–59·9 months in Papua New Guinea.DesignA nationally representative household-based cross-sectional survey of children aged 6–59·9 months was used to assess the relationships between various combinations of elevated CRP (>5 mg/l) and AGP (>1·2 g/l) with anaemia. Logistic regression was used to determine if other factors, such as age, sex, measures of anthropometry, region, urban/rural residence and household size, modified or confounded the acute-phase protein–anaemia association.SettingPapua New Guinea.SubjectsA total of 870 children aged 6–59·9 months from the 2005 Papua New Guinea National Micronutrient Survey were assessed.ResultsThe following prevalence estimates were found: anaemia 48 %; elevated CRP 32 %; and elevated AGP 33 %. Children with elevated CRP had a prevalence of anaemia of 66 % compared with children with normal CRP who had a prevalence of 40 %. Corresponding estimates for AGP were 61 % and 42 %, respectively. Similar results were found with combinations of elevated CRP and AGP. The higher prevalence of anaemia in children with elevated CRP and/or AGP was still present after controlling for confounders.ConclusionsElevated levels of CRP and AGP were significantly associated with a higher prevalence of anaemia in the children surveyed. There are no expert group recommendations on whether to or how to account for markers of inflammation in presenting results on anaemia prevalence. Additional research would be helpful to clarify this issue.

scholarly journals Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea

2019 ◽  
Author(s):  
Olivo Miotto ◽  
Makoto Sekihara ◽  
Shin-Ichiro Tachibana ◽  
Masato Yamauchi ◽  
Richard D Pearson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Sensitivity ◽  
New Guinea ◽  
Clinical Samples ◽  
Sequencing Data ◽  
Cross Sectional ◽  
Genetic Features ◽  
Parasite Populations ◽  
Flanking Regions ◽  
C580y Mutation

AbstractThe rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the kelch13 C580Y mutation is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.

scholarly journals Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea

2020 ◽  
Vol 16 (12) ◽  
pp. e1009133 ◽  
Author(s):  
Olivo Miotto ◽  
Makoto Sekihara ◽  
Shin-Ichiro Tachibana ◽  
Masato Yamauchi ◽  
Richard D. Pearson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Sensitivity ◽  
New Guinea ◽  
Clinical Samples ◽  
Sequencing Data ◽  
Cross Sectional ◽  
Genetic Features ◽  
Parasite Populations ◽  
Flanking Regions ◽  
C580y Mutation

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.

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