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Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia.

Basuki S - Malar. J. (2014)

Bottom Line: They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment.The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. uemura@nagasaki-u.ac.jp.

ABSTRACT

Background: Mutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed.

Methods: After obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected.

Results: Pfdhfr and pfdhps genotypes from 24 P. falciparum-infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the pfdhfr/pfdhps combined haplotypes of ANRNI/SGTGA (n = 6), ANRNL/SGTGA (n = 4), and ANRNI/SGEAA(588F) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.

Conclusion: Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

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Study site, Banjar district, South Kalimantan Province, Indonesia.
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Figure 1: Study site, Banjar district, South Kalimantan Province, Indonesia.

Mentions: The study was conducted at Sei Pinang and Aranio subdistricts, Banjar district, South Kalimantan Province, Indonesia (Figure 1) from October 2009 to August 2010, and was approved by the Ethical Committees, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia and Institute of Tropical Medicine, Nagasaki University, Japan. Total population of the study site subdistricts was 25,975 in 2008 and the most common occupations were farmers and mining workers. Both subdistricts have high prevalence of malaria. Written informed consent was obtained from each participant, or from caretakers if participants were under 12 years of age, after explanation in the local language of the study procedure.


Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia.

Basuki S - Malar. J. (2014)

Study site, Banjar district, South Kalimantan Province, Indonesia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4222776&req=5

Figure 1: Study site, Banjar district, South Kalimantan Province, Indonesia.
Mentions: The study was conducted at Sei Pinang and Aranio subdistricts, Banjar district, South Kalimantan Province, Indonesia (Figure 1) from October 2009 to August 2010, and was approved by the Ethical Committees, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia and Institute of Tropical Medicine, Nagasaki University, Japan. Total population of the study site subdistricts was 25,975 in 2008 and the most common occupations were farmers and mining workers. Both subdistricts have high prevalence of malaria. Written informed consent was obtained from each participant, or from caretakers if participants were under 12 years of age, after explanation in the local language of the study procedure.

Bottom Line: They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment.The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. uemura@nagasaki-u.ac.jp.

ABSTRACT

Background: Mutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed.

Methods: After obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected.

Results: Pfdhfr and pfdhps genotypes from 24 P. falciparum-infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the pfdhfr/pfdhps combined haplotypes of ANRNI/SGTGA (n = 6), ANRNL/SGTGA (n = 4), and ANRNI/SGEAA(588F) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.

Conclusion: Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

Show MeSH
Related in: MedlinePlus