Survey of in Vivo Sensitivity to Chloroquine by Plasmodium falciparum and P. vivax in Lombok, Indonesia

Dj, Fryauff; Jk, Baird; Candradikusuma, Didi; Masbar, S; Ma, Sutamihardja; Leksana, B; Tuti, Sekar; Marwoto, Harijani A.; Richie, Thomas L.; Romzan, Ali

doi:10.4269/ajtmh.1997.56.241

Cited by 30 publications

(29 citation statements)

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“…28 Studies in Indonesia have found that the majority of people given a standard therapeutic dose achieve and then maintain whole blood levels of chloroquine plus desethychloroquine greater than the MEC of 100 ng/ml through the 28-day test period. 23,24,29 This was not apparent in our study, in which the mean day 28 level of chloroquine plus desethychloroquine (26.8 ng/ml) following standard treatment was significantly lower than that of five other ethnic populations in the region (Fryauff DJ, unpublished data). It seems possible that variant patterns of chloroquine absorption, metabolism, and elimination may characterize different racial/ethnic groups.…”

Section: Discussionmentioning

confidence: 53%

Chloroquine-resistant Plasmodium vivax in transmigration settlements of West Kalimantan, Indonesia.

Fryauff¹,

Tuti²,

Mardi³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Section: Discussionmentioning

confidence: 53%

Chloroquine-resistant Plasmodium vivax in transmigration settlements of West Kalimantan, Indonesia.

Fryauff¹,

Tuti²,

Mardi³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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“…Since early reports in the late 1950s, CQ resistance has been identified in most regions of the world where malaria is endemic. This problem has been investigated in several islands of the Indonesian archipelago such as Lombok, 1 Java, 2 and Irian Jaya, [3][4][5] where the first Indonesian case of CQ-resistant P. falciparum was described. 6 To understand the mechanism of CQ resistance in malaria parasites, a search for the responsible gene(s) has been launched.…”

mentioning

confidence: 99%

Plasmodium falciparum mdr1 mutations and in vivo chloroquine resistance in Indonesia.

Gómez-Saladín

Fryauff²,

Taylor³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Mutations in the Pfmdr1 gene are reported to be associated with chloroquine resistance in some Plasmodium falciparum isolates. A polymerase chain reaction/restriction fragment length polymorphism method was used for the detection of Pfmdr1 mutations in chloroquine-resistant field isolates of P. falciparum collected in Irian Jaya. The frequency of Pfmdr1 mutations was significantly higher in chloroquine-resistant P. falciparum parasites than background frequencies observed in the same location. The 7G8 mutation was identified in some parasites although always in a mixed genotype status. Chloroquine-resistant P. falciparum specimens were characterized using the World Health Organization 28-day criteria, supplemented by demonstrating adequate chloroquine absorption and genetic analysis.Resistance of Plasmodium falciparum to chloroquine (CQ) and other antimalarial drugs is a widespread phenomenon that challenges current control efforts. Since early reports in the late 1950s, CQ resistance has been identified in most regions of the world where malaria is endemic. This problem has been investigated in several islands of the Indonesian archipelago such as Lombok, 1 Java, 2 and Irian Jaya, [3][4][5] where the first Indonesian case of CQ-resistant P. falciparum was described. 6 To understand the mechanism of CQ resistance in malaria parasites, a search for the responsible gene(s) has been launched. In 1989 two P. falciparum genes homologous to the mammalian multiple drug resistance (MDR) gene were identified, mapped to chromosome V, 7 and named Pfmdr1 and Pfmdr2. 8 This discovery, coupled with the fact that the calcium channel blocker verapamil reverses CQ resistance, 9 gave support to the theory that a mechanism similar to multiple drug resistance in mammalian tumor cells, in which over expression and amplification of the MDR gene confers drug resistance to tumor cells via an efflux mechanism, operates in P. falciparum. The product of the Pfmdr1 gene, Pglycoprotein homolog 1 (Pgh1) has been localized to the membrane of the digestive vacuole of mature blood stage parasites. 10 This model predicted that the Pfmdr1 gene would be amplified and/or over expressed in CQ-resistant isolates but several studies obtained mixed results. [11][12][13][14][15] Considerable controversy has been generated by conflicting reports that tested a second model: that mutations in the Pfmdr1 gene confer CQ resistance. DNA sequencing of the Pfmdr1 gene from reference strains and field isolates has revealed several point mutations that correlated with CQ resistance. 16 These mutations were classed into two genotypes: the K1 genotype, resulting in an asparagine (Asn) to tyrosine (Tyr) change at position 86 and the 7G8 genotype, with four point mutations resulting in amino acid substitutions at positions 184, 1034, 1042, and 1246. Shortly after a rapid polymerase chain reaction (PCR) and restriction digest method for the detection of these two genotypes in field isolates was developed;17 field studies applied this technique and confirmed ...

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“…15 A seven-day in vivo study in Irian Jaya showed no distinction between long-and short-term exposure groups treated with CQ, but did show a clear difference in their response to S/P. 2 Whole blood levels of CQ plus DCQ, measured on day 2 of treatment in the Gag Island population, were low relative to other populations surveyed, 10,12,13,[16][17][18] and reinfections may account for the majority of therapeutic failures seen. Relative to adults, the significantly lower drug levels that we measured in children suggest that poor drug absorption, rather than immature or undeveloped immunity, may account for the higher frequency of therapeutic failures seen in this group.…”

Section: Discussionmentioning

confidence: 99%

In vivo responses to antimalarials by Plasmodium falciparum and Plasmodium vivax from isolated Gag Island off northwest Irian Jaya, Indonesia.

Fryauff¹,

Sumawinata²,

Purnomo³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. There is renewed interest in the rich nickel and cobalt deposits of Pulau Gag, an isolated but malarious island off the northwest coast of Irian Jaya. In preparation for an expanded workforce, an environmental assessment of malaria risk was made, focusing upon malaria prevalence in the small indigenous population, and the in vivo sensitivity of Plasmodium falciparum and P. vivax to chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P), the respective first-and second-line drugs for uncomplicated malaria in Indonesia. During April-June 1997, mildly symptomatic or asymptomatic malaria infections were found in 24% of 456 native residents. Infections by P. falciparum accounted for 60% of the cases. Respective day 28 cure rates for CQ (10 mg base/kg on days 0 and 1; 5 mg/kg on day 2) in children and adults were 14% and 55% (P Ͻ 0.005). Type RII and RIII resistance characterized only 5% of the CQ failures. Re-treatment of 36 P. falciparum CQ treatment failures with S/P (25 mg/kg and 1.25 mg/kg, respectively) demonstrated rapid clearance and complete sensitivity during the 28-day follow-up period. More than 97% of the P. vivax malaria cases treated with CQ cleared parasitemia within 48 hr. Three cases of P. vivax malaria recurred between days 21 and 28, but against low drug levels in the blood. The low frequency of RII and RIII P. falciparum resistance to CQ, the complete sensitivity of this species to S/P, and the absence of CQ resistance by P. vivax are in contrast to in vivo and in vitro test results from sites on mainland Irian Jaya.

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Survey of in Vivo Sensitivity to Chloroquine by Plasmodium falciparum and P. vivax in Lombok, Indonesia

Cited by 30 publications

References 0 publications

Chloroquine-resistant Plasmodium vivax in transmigration settlements of West Kalimantan, Indonesia.

Chloroquine-resistant Plasmodium vivax in transmigration settlements of West Kalimantan, Indonesia.

Plasmodium falciparum mdr1 mutations and in vivo chloroquine resistance in Indonesia.

In vivo responses to antimalarials by Plasmodium falciparum and Plasmodium vivax from isolated Gag Island off northwest Irian Jaya, Indonesia.

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