Randomized, parallel placebo-controlled trial of primaquine for malaria prophylaxis in Papua, Indonesia.

Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attacking liver-stage parasites, a property distinguishing it from most chemoprophylactics and obviating 4-week postexposure dosing. A daily adult regimen of 30 mg primaquine prevented malaria caused by Plasmodium falciparum and P. vivax for 20 weeks in 95 of 97 glucose-6-phosphate dehydrogenase (G6PD)-normal Javanese transmigrants in Papua, Indonesia. In comparison, 37 of 149 subjects taking placebo in a parallel trial became parasitemic. The protective efficacy of primaquine against malaria was 93% (95% confidence interval [CI] 71%-98%); against P. falciparum it was 88% (95% CI 48%-97%), and >92% for P. vivax (95% CI >37%-99%). Primaquine was as well tolerated as placebo. Mild methemoglobinemia (mean of 3.4%) returned to normal within 2 weeks. Blood chemistry and hematological parameters revealed no evidence of toxicity. Good safety, tolerance, and efficacy, along with key advantages in dosing requirements, make primaquine an excellent drug for preventing malaria in nonpregnant, G6PD-normal travelers.

Identification of larval and adult Simulium yahense and Simulium sanctipauli based on species-specific enzyme markers and their distribution at different breeding habitats in Central Liberia.

Human-biting adults and late instar larvae of the Simulium damnosum complex from four ecologically different simuliid breeding habitats in the Firestone Rubber Plantation at Harbel, Liberia, were identified morphologically and the monthly species composition of each site was recorded. Samples of the predominant species found at each site were assayed electrophoretically for species-specific variants of phosphoglucomutase (PGM) and trehalase (TRE). Enzyme identifications of flies and larvae were compared with morphological identifications to determine the accuracy of field identifications relying upon morphological characters. Enzyme identifications confirmed the accuracy of over 98% of the adult female identifications. S. yahense was found to be the predominant human-biting species at each site over the 10 months of sampling, with S. sanctipauli comprising a small percentage of the biting fly population. Species-specific larval enzymes confirmed the accuracy of more than 96% of the larval identifications. S. yahense was the predominant larval species found in smaller, more shaded, cooler breeding waters, while S. sanctipauli predominated in the single large watercourse that was sampled. Normally allopatric, mixed populations of these two larval species were found to exist at all sites, but sympatry occurred primarily during the wet season months of May-October. Biting activity of S. sanctipauli was found to be greatest during wet season months, and generally reflected the increase of S. sanctipauli in the larval populations of habitats dominated by S. yahense. The low human-biting activity of S. sanctipauli at all sites and during times which fostered large populations of S. sanctipauli larvae may be an indication of this specie's zoophilic tendency. Circumstantial evidence of hybridization, the expression of PGM and TRE species-specific variants for both species, was found in adults and larvae morphologically identified as S. yahense. The frequency of this "hybrid" condition, based upon PGM and TRE, was calculated to be comparable to the frequency of hybridization as determined by larval chromosome inversions.

Quantitative studies of onchocerciasis transmission by Simulium yahense and Simulium sanctipauli in the Firestone Rubber Plantation at Harbel, Liberia.

Black fly vectors of onchocerciasis from three ecologically different Simuliid breeding habitats in the Firestone Rubber Plantation at Harbel, Liberia, were surveyed by human-biting collections conducted at weekly intervals over a 13-month period. Black flies were identified morphologically and the monthly and seasonal contribution of different vector species to the transmission of Onchocerca volvulus at each site was determined. Simulium yahense was identified as the predominant vector species at each site. Greatest populations of this species occurred during wet season (May-Oct), but its impact on transmission of onchocerciasis was most profound during dry season (Nov-Apr) when parity, infection, and infectivity were high. S. sanctipauli was the only other vector species captured, but biting populations of this species were small, and during wet season confined primarily to the vicinity of its breeding site in the Farmington River. Dry season populations of S. sanctipauli were also characterized by lower human-biting rates, and by higher rates of parity, infection, and infectivity. Monthly transmission potentials at each site were attributed primarily to S. yahense, with peak monthly transmission occurring during the dry season months of January-April. Against the WHO standard of 100 as a "tolerable" annual level of onchocerciasis transmission, annual transmission potentials for the three sampling sites were 94, 1,877, and 4,900, with highest values being calculated for S. yahense breeding sites.

Short report: case report of Cyclospora infection acquired in Indonesia and treated with cotrimoxazole.

A detailed chronology of unsuccessful efforts to diagnose and treat a sudden-onset case of chronic diarrhea acquired in Jakarta Indonesia, and ultimately attributed to Cyclospora is presented. A modified Kato technique was used to quantify Cyclospora oocysts during successive days prior to, during, and after successful cotrimoxazole therapy (160 mg of trimethoprim, 800 mg sulfamethoxazole twice a day for seven days) for this infection. Cyclospora was associated with 6.4% of the gastrointestinal illness and/or diarrhea cases that presented during a seven-month period to a Jakarta clinic that serves a small population of expatriates. Cyclospora and Giardia lamblia were identified with equal frequency during this period and were the dominant pathogenic intestinal parasite species found in this community.

Whole blood chloroquine concentrations with Plasmodium vivax infection in Irian Jaya, Indonesia.

Whole blood concentrations of self-administered chloroquine (CQ) and its metabolite desethylchloroquine (DCQ) were measured in 168 patients with microscopically confirmed infection by Plasmodium vivax in northeastern Irian Jaya, Indonesia. The study consisted of both survey and passive case detection in four separate villages between 1992 and 1994. The subjects were Javanese people 4-51 years old who had lived in the Arso region for up to two years. The sum of CQ and DCQ ranged from 0 to 8,342 ng/ml of whole blood, and 122 subjects (73%) had > or = 100 ng/ml of CQ plus DCQ, the estimated minimally effective concentration (MEC) in whole blood against chloroquine-sensitive P. vivax. Among 56 subjects reporting to a clinic with symptoms of malaria, 53 (95%) had ordinarily effective levels of chloroquine in blood. Among 109 largely asymptomatic malaria patients found by survey case detection, 69 (63%) had chloroquine blood levels greater than the MEC. Virtually all clinical and most subclinical vivax malaria in this region occurs despite ordinarily effective levels of chloroquine in blood.

Performance of the OptiMAL assay for detection and identification of malaria infections in asymptomatic residents of Irian Jaya, Indonesia.

The OptiMAL assay, a new immunochromatographic "dipstick" test for malaria based on detection of Plasmodium lactate dehydrogenase (pLDH), is purported to detect infections of approximately 200 parasites/microL of blood and to differentiate between Plasmodium falciparum and non-P. falciparum. We evaluated OptiMAL performance by comparing the test strip interpretations of two independent readers with consensus results obtained independently by expert malaria microscopists. Unbiased measures of sensitivity were derived by applying the OptiMAL test for detection and differentiation of light, asymptomatic infections by P. falciparum and Plasmodium vivax. OptiMAL readings were separated in time to determine whether the reaction signal was stable. Microscopy identified infections in 225 of 505 individuals screened; those with P. falciparum (n = 170) averaged 354 asexual forms/microL and P. vivax/Plasmodium malariae (n = 112) averaged 216 asexual forms/microL of blood. Concordance between OptiMAL and microscopy was 81% and 78% by the two independent readings. The assay's sensitivity for detection of any malaria species was 60.4% and 70.2% respectively and specificity was 97% and 89%. Most cases identified by microscopy as P. falciparum were graded as negative or non-falciparum by both OptiMAL readers. OptiMAL false negatives as well as misidentifications were related to low parasitemias (< 500/microL). The OptiMAL assay demonstrated 88-92% sensitivity for detecting infections of 500-1,000 parasites/microL, a range covering the mean parasitemia of primary symptomatic P. falciparum infections in malaria-naïve Indonesian transmigrants. This device was markedly less sensitive than expert microscopy for discriminating between malaria species and is presently unsuited for use as an epidemiological screening tool. The OptiMAL assay is not approved for diagnostic use but is commercially available for research purposes only.

Experimental infection and transmission of Leishmania major by laboratory-reared Phlebotomus bergeroti parrot.

The ability of colony-reared Phlebotomus bergeroti Parrot to successfully acquire and transmit Leishmania major (strain IPAP/EG 89/SI-177) was demonstrated in the laboratory. Female P. bergeroti were fed naturally on infected mice and artificially on infected blood suspension using a chick-skin membrane apparatus. Groups of sand flies, either infected on mice or by membrane feeding, were dissected and examined using light microscopy at 2-6, 8, 10, and 11 days postfeeding. Heavy promastigote infection of the thoracic and abdominal midgut was observed in 10% (2 of 20) of the naturally infected flies. Promastigote maturation was observed in 87% (81 of 93) of the artificially infected sand flies, with promastigotes observed in the cibarium and mouthparts at five days postinfection, and infective metacyclic stage promastigotes observed at eight days postinfection. Ten days postinfection, 31% (10 of 32) of the remaining artificially infected sand flies refed on an uninfected BALB/c mouse. Twenty-eight days following exposure to the infective sand flies, leishmanial lesions were observed on the pads of the mouse's front feet. The development of lesions on mouse foot pads clearly suggests the potential of P. bergeroti to serve as a vector for L. major.

Adaptation of a chloroquine-resistant strain of Plasmodium vivax from Indonesia to New World monkeys.

The spread of chloroquine-resistant Plasmodium vivax from Papua New Guinea and Indonesia poses a serious health threat to areas of Southeast Asia where this species of malaria parasite is endemic. A strain of P. vivax from Indonesia was adapted to develop in splenectomized Aotus lemurinus griseimembra, Aotus vociferans, Aotus nancymai, and Saimiri boliviensis monkeys. Transmission to splenectomized Saimiri monkeys was obtained via sporozoites. Chemotherapeutic studies indicated that the strain was resistant to chloroquine and amodiaquine while sensitive to mefloquine. Infections of chloroquine-resistant P.vivax in New World monkeys should be useful for the development of alternative treatments.

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Effect of mass treatment of a human population with ivermectin on transmission of Onchocerca volvulus by Simulium yahense in Liberia, West Africa.

The impact of mass treatment with ivermectin on the intensity of Onchocerca volvulus transmission by the black fly (Simulium yahense) was evaluated on the Liberian Agricultural Company rubber plantation in Liberia, West Africa. The adult pre-treatment prevalence of onchocerciasis was greater than 80%, and the average intensity of infection was 5.35 mf/mg of skin. The drug was administered at 2 annual intervals, reaching 58-60% of the approximately 14,000 people living in 73 camps. Landing/biting catches of black flies made in central and peripheral plantation zones indicated similar fly activity before and after ivermectin treatment (man hr index of 2.1 and 2.4 within the plantation, and 10 and 10.9 outside the plantation, respectively). The number of infected flies with developing larvae (L1, L2, L3 stages) of O. volvulus in treated areas was reduced by 93.4-95%; the number of infective flies with L3 larvae was reduced by 81.7-89.3%. Parasite loads of infected (L1, L2) and infective flies (L3 stages only) outside the plantation also decreased by 86.8% and 80%, respectively. Monthly transmission potential (MTP) showed a similar decrease: from 22.9 to 5.8 (74.6% reduction) in the treated area, and from 210 to 158.8 (24.4% reduction) in untreated areas. Mass treatment with ivermectin efficiently controlled, and at least temporarily interrupted, transmission of Onchocerca volvulus by black fly vectors.

Primaquine for prophylaxis against malaria among nonimmune transmigrants in Irian Jaya, Indonesia.

A comparison of primaquine versus chloroquine for prophylaxis among nonimmune transmigrants from Java and Bali in the hyperendemic Arso region of Irian Jaya, Indonesia was conducted. Forty-five subjects received 0.5 mg of primaquine base/kg of body weight every other day, and 54 people in the same village received weekly 5 mg of chloroquine base/kg for 16-19 weeks beginning in December 1992. Plasmodium falciparum accounted for 18 of 30 infections with chloroquine, and four of five infections among subjects receiving primaquine. Plasmodium vivax was found in 12 people taking chloroquine but in just one person taking primaquine. The risk of malaria among people taking chloroquine relative to that among subjects taking primaquine was 3.96 (P = 0.014) for P. falciparum and 10.56 (P = 0.012) for P. vivax. Primaquine was better tolerated than chloroquine. The minimal protective efficacy for primaquine prophylaxis was 74% against P. falciparum and 90% against P. vivax among nonimmune children and adults living in Irian Jaya. These findings require confirmation with randomized, double-blinded, and placebo-controlled trials.

Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence and whole blood chloroquine levels.

To develop criteria for the diagnosis of resistance to chloroquine using an in vivo test, we examined published records of early clinical trials of quinine and chloroquine against Plasmodium vivax. These data established the timing of relapse by tropical P. vivax relative to therapy by these drugs. The first relapse occurred 17 days after initiating and three days after terminating quinine therapy. The median day of relapse was day 23, and 59% of the patients had relapsed by day 30 (n = 333). In contrast, no relapse occurred until day 36 following chloroquine treatment (n = 256). Data from our laboratory may help explain this difference; among 91 Indonesian patients with malaria, the mean whole blood levels of chloroquine (CQ) and desethylchloroquine (DCQ) were 141 ng/ml (95% confidence interval = 115-167) on day 28 after initiating standard therapy (25 mg base/kg in three doses over a 48-hr period). This exceeds the estimated minimal effective concentration of chloroquine (100 ng/ml of whole blood). Thus, chloroquine lingering in the blood for at least 28 days after starting standard therapy was sufficient to eliminate or at least suppress chloroquine-sensitive tropical P. vivax. We conclude that a parasitemia by P. vivax recurring in the 28 days after full compliance to standard chloroquine therapy demonstrates resistance. If the recurrence appears before day 16, it is almost certainly a recrudescence and between days 17 and 28 it may be either a recrudescence or a relapse by chloroquine-resistant parasites. Recurrences beyond day 28 could be relapse by chloroquine-sensitive P. vivax.

In vivo resistance to chloroquine by Plasmodium vivax and Plasmodium falciparum at Nabire, Irian Jaya, Indonesia.

A survey of resistance to chloroquine by Plasmodium vivax and P. falciparum was conducted during May 1995 at three mesoendemic villages 30 km southeast of Nabire, near the central northern coast of Irian Jaya, Indonesia. The prevalence of malaria at Urusumu (n = 157), Margajaya (n = 573), and Topo (n = 199) was 18%. 9%, and 9%, respectively, with spleen rates among children of 79%, 10%, and 27%. Infected patients among those screened formed a study population of 64 subjects eligible for a 28-day in vivo test of resistance to chloroquine. Sixty-three patients successfully completed the test; 45 males and 18 females 1-60 years of age, of whom 29 were Javanese transmigrants of five years residence in Irian Jaya and 34 were native to Irian Jaya. The seven-day day cumulative incidence of therapeutic failure for P. vivax and P. falciparum was 15% (n = 34) and 30% (n = 37). The 14- and 28-day estimates of cumulative incidence were 45% and 64% for P. vivax and 58% and 89% for P. falciparum. Almost all recurrences appeared in the face of ordinarily effective levels of chloroquine and its major metabolite, desethylchloroquine, in whole blood (> or = 100 ng/ml). Four infections by P. malariae in subjects enrolled in this study cleared by day 2 and none reappeared within 28 days. Chloroquine no longer provides effective therapy for falciparum or vivax malaria along the northern coast of Irian Jaya, Indonesia.

Malaria in a nonimmune population after extended chloroquine or primaquine prophylaxis.

Extended chemoprophylaxis against endemic malaria raises concern with regard to susceptibility after ceasing use of the drug. In this study, we measured attack rates of malaria among adult men for 28 weeks after they ended one year of prophylaxis using either weekly chloroquine (5 mg base/kg, n = 20), daily primaquine (0.5 mg base/kg, n = 30), or a placebo of primaquine (n = 41). The 28-week incidence densities, times to parasitemia, parasite densities, and symptoms of primary post-prophylaxis infections were not significantly different among the former primaquine, chloroquine, and placebo groups. However, the incidence of Plasmodium falciparum infection in the post-chloroquine group was significantly greater than in the post-primaquine group during the first (P = 0.03) and second (P = 0.02) months post-prophylaxis. Six of 10 primary P. falciparum and three of 10 P. vivax infections occurred in the former chloroquine group within one month after ending prophylaxis and the mean time to infection was 30-35 days. In contrast, only one P. falciparum and no P. vivax infections occurred during the first month after ending primaquine prophylaxis. The mean time to first parasitemia by either species of malaria parasite in this group was 72-77 days. There was no indication that daily use of primaquine for one year placed subjects at greater risk of malaria infection or to more severe clinical symptoms of malaria than subjects who had taken placebo or chloroquine, despite the potential for some degree of immunity to have been acquired in these latter two groups during the year-long prophylaxis period. The results do suggest that chloroquine suppressed P.falciparum infections until drug levels decreased, and that primaquine had effectively prevented the establishment of liver-stage parasites.

Survey of in vivo sensitivity to chloroquine by Plasmodium falciparum and P. vivax in Lombok, Indonesia.

A malariometric survey was conducted in 14 villages of Sekotong district, in Lombok, Indonesia during October 1994. Point prevalence of malaria ranged from 0% to 15% in the surveyed villages, averaging 6% overall, and Plasmodium falciparum accounted for 63% of the infections. Forty-nine patients with uncomplicated malaria and parasite counts ranging from 40 to 10,800 asexual forms/microliter were enrolled in a 28-day in vivo test of chloroquine sensitivity. All subjects received a supervised therapeutic regimen of chloroquine (25 mg base/kg over a 48-hr period) and parasitemia and symptoms were closely monitored for 28 days. Asexual parasites were eliminated within four days in the 29 P. falciparum and 20 P. vivax study patients enrolled. The cumulative incidence of therapeutic failure (recurrent symptomatic parasitemia) among P. falciparum cases at days 7, 14, and 28 was 7%, 10%, and 14% (4 of 29), respectively. However in all four cases, parasitemias recurred against chloroquine blood levels below the minimally effective concentration (MEC) of 200 ng/ml and do not confirm chloroquine resistance. All 20 P. vivax parasitemias were sensitive to chloroquine and the blood remained clear, with the exception of one case in which an asymptomatic parasitemia appeared on day 28. Parasitemias by P. falciparum and P. vivax that were observed before supervised therapy, but in the presence of whole blood chloroquine above normally suppressive MEC levels, suggest resistance to suppressive or prophylactic regimens of chloroquine.

Identification and genetic comparison of leishmanial parasites causing viscerotropic and cutaneous disease in soldiers returning from Operation Desert Storm.

Six Leishmania major and seven L. tropica parasites were isolated and identified from participants in Operation Desert Shield/Storm. A complete enzyme analysis (21 enzymes) revealed that there was enzyme polymorphism among the isolates of each species group. Any one Desert Storm L. major isolate could differ from any other for 1-3 enzymes, and any L. tropica isolate could differ from any one other for up to eight enzymes. Enzyme polymorphism data from other L. major and L. tropica isolates from Africa and the Middle East region were obtained and combined with the Desert Storm data to produce population enzyme polymorphism estimates. Results from these population data indicated that L. major parasites could be expected to differ from each other for as many as eight enzymes and still be L. major, and similarly, L. tropica isolates could differ for as many as 14 enzymes. These expected isolate variation extremes have not been observed among the isolates studied. All L. major and most L. tropica isolates were from patients who, as expected, presented with cutaneous disease, but the Desert Storm and two Kenyan patients infected with L. tropica presented with a viscerotropic disease, the symptoms of which are unlike those of classic visceral leishmaniasis. Such unrecognized presentation for these L. tropica-infected patients indicates that both parasite and patient can play critical roles in disease manifestations. The Desert Storm isolates are, as indicated, either L. major or L. tropica.

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

Malariometric surveys were conducted during July 1996 in native Dayak villages and predominantly Javanese transmigration settlements in Ketapang district of West Kalimantan, Indonesia. Malaria prevalence ranged from 0.9% to 2.7% in Dayak villages and from 1% to 20% in the transmigration settlements. Plasmodium falciparum accounted for 67% of the cases among Dayaks but P. vivax was dominant among transmigrants, accounting for more than 72% of the infections. Chloroquine sensitivity/resistance was assessed by 28-day in vivo testing of uncomplicated malaria infections and measurement of chloroquine blood levels in cases where parasitemias reappeared within the 28-day test period. Resistance was based on the appearance of asexual parasites against chloroquine plus desethylchloroquine levels exceeding the minimally effective whole blood concentrations proposed for sensitive parasite strains (P. vivax, 100 ng/ml; P. falciparum, 200 ng/ml). All parasitemias cleared initially within four days of beginning supervised chloroquine therapy (25 mg base/kg over a 48-hr period), but asexual parasites reappeared within 28 days in 27 of 52 P. vivax and three of 12 P. falciparum cases. Chloroquine blood levels at the time of recurrent parasitemias revealed resistance in 12 of the 27 P. vivax cases and in one of the three P. falciparum cases. Genotypes of nine of the 12 recurrent P. vivax isolates matched with their primary isolates and ruled out reinfection. These findings establish the presence of chloroquine-resistant P. vivax on the island of Borneo. The pattern of malaria and the high frequency of chloroquine resistance by P. vivax at the West Kalimantan location may relate to demographic, ecologic, agricultural, and socioeconomic changes associated with transmigration.

Epidemiology of cutaneous leishmaniasis at a focus monitored by the multinational force and observers in the northeastern Sinai Desert of Egypt.

A longitudinal epidemiologic study of cutaneous leishmaniasis (CL) transmission was conducted between July 1989 and June 1991 in a 1,200-km2 sector of the northeastern Sinai Desert monitored by the Multinational Force and Observers (MFO), an international peace keeping mission between Egypt and Israel. The occurrence of human cases, sand fly density, rodent collection, and isolations of Leishmania confirmed only one of four surveyed locations as a significant focus of CL transmission. Phlebotomus papatasi, the only anthropophilic sand fly species encountered at this focus, comprised more than 96% of the sand fly population and attained human landing densities exceeding 100 sand flies/person/hr during 1990. Seasonal activity of this species ranged from April to November, with highest densities occurring during the period May-September. A peak promastigote infection rate of 2.4% (13 of 534) was observed in P. papatasi during July 1990. Twelve of the 60 (20%) persons at risk during the six months of intense sand fly activity at this site developed lesions consistent with CL; L. major was isolated from nine (75%) of these cases. Leishmania major infection was acquired by two of 22 (9%) sentinel hamsters used during the same period. More than 97% of the 897 wild rodents trapped at this site were desert gerbil species. Leishmania major was the only Leishmania isolated from human, sand fly, wild rodent (Gerbillus pyramidum), and sentinel hamster infections that originated at site Check point 1-Delta, the focus of CL transmission within jurisdiction of the MFO. The altered ecology of this area, created by construction of a dam, may contribute significantly to the transmission dynamics of CL at this focus.

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

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.

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

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 < 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.