Efficacy of Artemisinin-Based Combination Therapy for Treatment of Persons with Uncomplicated Plasmodium falciparum Malaria in West Sumba District, East Nusa Tenggara Province, Indonesia, and Genotypic Profiles of the Parasite

Asih, Puji B. S.; Dewi, Rita Marleta; Tuti, Sekar; Sadikin, Mohamad; Sumarto, Wajio; Sinaga, Bonar M.; Ven, A.J.A.M. van der; Sauerwein, Robert W.; Syafruddin, Din

doi:10.4269/ajtmh.2009.80.914

Cited by 16 publications

(19 citation statements)

References 23 publications

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“…In this study P. falciparum isolates frequently carried the allelic combination of pfcrt 76T and pfmdr1 86Y, but previous study showed artesunate (AS) and AQ combination therapy to be highly effective [10]. This finding suggests that the parasite haplotype 76T and pfmdr 1 86N is still sensitive to AQ treatment, particularly in combination with AS.…”

Section: Discussionmentioning

confidence: 82%

“…Resistance to CQ was first reported in 1975, resistance to SP appeared in 1978, and by 1997 treatment failures associated with both drugs had been documented in most provinces [5,6]. Molecular epidemiology studies conducted from 2003 to 2005 in several sentinel sites throughout the Indonesia archipelago indicated widespread distribution of mutant alleles associated with resistance to CQ resistance ( pfmdr1 86Y, Plasmodium falciparum chloroquine resistance (pfcrt) 76T) and SP ( dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps)) [7-10]. The mutant allele associated with chloroquine resistance, pfcrt 76T, seems to be nearly fixed among the P. falciparum isolates collected, and pfmdr1 1042D alleles were mainly found in the island of Flores [9].…”

Section: Introductionmentioning

confidence: 99%

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Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

Asih

Rogers²,

Susanti³

et al. 2009

Malar J

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BackgroundDrug resistant malaria poses an increasing public health problem in Indonesia, especially eastern Indonesia, where malaria is highly endemic. Widespread chloroquine (CQ) resistance and increasing sulphadoxine-pyrimethamine (SP) resistance prompted Indonesia to adopt artemisinin-based combination therapy (ACT) as first-line therapy in 2004. To help develop a suitable malaria control programme in the district of West Sumba, the seasonal distribution of alleles known to be associated with resistance to CQ and SP among Plasmodium falciparum isolates from the region was investigated.MethodsPlasmodium falciparum isolates were collected during malariometric surveys in the wet and dry seasons in 2007 using two-stage cluster sampling. Analysis of pfcrt, pfmdr1, pfmdr1 gene copy number, dhfr, and dhps genes were done using protocols described previously.Results and DiscussionThe 76T allele of the pfcrt gene is nearing fixation in this population. Pfmdr1 mutant alleles occurred in 72.8% and 53.3%, predominantly as 1042D and 86Y alleles that are mutually exclusive. The prevalence of amplified pfmdr1 was found 41.9% and 42.8% of isolates in the wet and dry seasons, respectively. The frequency of dhfr mutant alleles was much lower, either as a single 108N mutation or paired with 59R. The 437G allele was the only mutant dhps allele detected and it was only found during dry season.ConclusionThe findings demonstrate a slighly higher distribution of drug-resistant alleles during the wet season and support the policy of replacing CQ with ACT in this area, but suggest that SP might still be effective either alone or in combination with other anti-malarials.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

Asih

Rogers²,

Susanti³

et al. 2009

Malar J

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“…Of them, six treatment regimens were evaluated in Western Cambodia and one study was of a single dose of artesunate (see Additional file 8). In the remaining two studies [18,19] patients were treated with a three-day AS+AQ in Senegal and Indonesia and with PPRday3 documented as 10% (95%CI =6.3-15.6%) and 12.6% (95% CI=7.5-20.4%) respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Using this definition, nine outliers were identified, six of which were from the Pailin region, the epicentre for emerging artemisinin resistance in Cambodia and one of which was a short-course regimen. Of the remaining two studies, one by Asih et al from Indonesia conducted in 2005 to 2006, combined PCR positivity with microscopy, which may have accounted for higher than expected proportion of patients parasitaemic on Day 3 [19]. The remaining trial arm in a study by Adjuik et al was conducted in Senegal, although the Day 3 value was derived from a figure rather than actual data [18], (see Additional file 8).…”

Section: Discussionmentioning

confidence: 99%

Early parasitological response following artemisinin-containing regimens: a critical review of the literature

Das

Price

Bethell

et al. 2013

Malar J

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BackgroundParasitaemia on Day 3 has been proposed as a useful alert of potential artemisinin resistance, however, the normal variation of parasite clearance observed in artemisinin-based combination therapy clinical trials is poorly documented.MethodsThe trends in early parasitological response following treatment with an artemisinin anti-malarial regimen were reviewed. A PubMed literature search identified all studies using an artemisinin regimen for uncomplicated falciparum malaria published between January 2000 and December 2011. Data from clinical studies were extracted for analysis using a standardized questionnaire.ResultsIn total 65,078 patients were enrolled into 213 clinical trials with 413 treatment arms containing either an artemisinin derivative alone (n=26) or in combination with a partner drug (n=387). The proportion of patients remaining parasitaemic at 24, 48 and 72 hours was documented in 115 (28%), 167 (40%) and 153 (37%) treatment arms, respectively. Excluding resistance studies in Cambodia, the median proportion of patients still parasitaemic was 53.8% [range 3–95, IQR=30.5-69.2] on Day 1, 6% [range 0–65.9, IQR=2-11.5] on Day 2 and 0 [range 0–12.6, IQR=0-2] on Day 3. Comparing studies from 2000 to 2005 and 2006 to 2011, the median proportion of patients reported to remain parasitaemic at 72 hours decreased in Africa (1.2% vs 0%, p=0.007), but increased in Asia (0.4% vs 3.9%, p=0.076). In 95% of studies the proportion of patients with peripheral parasitaemia was less than 6% at 72 hours.ConclusionsThese results highlight the normal distribution of early parasitological responses following ACT, and the influence that heterogeneity in study design, host and parasite factors have in confounding a surveillance system based on Day 3 parasite positivity. Greater understanding of factors influencing parasite clearance is crucial, but will require analysis of pooled data from individual patient records.

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“…Although very little is known of the malaria vector bionomics in this area, one entomologic survey documented 11 species of anophelines occurring in this district: Anopheles sundaicus, Anopheles subpictus, Anopheles barbirostris, Anopheles hyrcanus, Anopheles aconitus, Anopheles flavirostris, Anopheles annularis, Anopheles maculatus, Anopheles tessellatus, Anopheles vagus, and Anopheles kochi. 18 These species occurred in relative abundance in accordance with their respective preferred habitats including coastal marshes and ponds, seasonal rice paddies, and forested hillsides. This setting is typical for many rural malaria-endemic areas in Indonesia, particularly high risk coastal zones.…”

Section: Methodsmentioning

confidence: 99%

Impact of a Spatial Repellent on Malaria Incidence in Two Villages in Sumba, Indonesia

Syafruddin¹,

Bangs²,

Sidik³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. A randomized, double-blinded, placebo-controlled study was conducted to examine the effect of spatial repellent (SR) in households at risk of malaria in Indonesia. Following presumptive radical cure for malaria in 180 adult men representing sentinels of new infection in four clusters within two villages, all households were given either metofluthrin or placebo mosquito coils. Weekly blood smear screening and human-landing mosquito catches were done throughout the 6 months intervention. Malaria infections occurred in 61 subjects living in placebo households and 31 subjects living in SR coil households, suggesting a 52% protective effect of SR. Likewise, anopheles indoor human landing rates were 32% lower in homes receiving SR coils. Differences in the malaria attack rate between SR-and placebo-treated homes was significant when not accounting for the effects of clustering. When the analysis was adjusted for intra-cluster correlation, the differences between SR-and placebo-treated homes were not statistically significant. The findings provide evidence of SR public health benefit and support a larger trial statistically powered to detect those effects.

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Efficacy of Artemisinin-Based Combination Therapy for Treatment of Persons with Uncomplicated Plasmodium falciparum Malaria in West Sumba District, East Nusa Tenggara Province, Indonesia, and Genotypic Profiles of the Parasite

Cited by 16 publications

References 23 publications

Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

Early parasitological response following artemisinin-containing regimens: a critical review of the literature

Impact of a Spatial Repellent on Malaria Incidence in Two Villages in Sumba, Indonesia

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