Search

Background: During the period of 1996-1999, we prospectively monitored 243 Javanese adults and children after arriving in Papua, Indonesia, and microscopically documented each new case of malaria by active surveillance., Methods: In a randomized, open-label, comparative malaria treatment trial, 72 adults and 50 children received chloroquine for each incident case of malaria, and 74 adults and 47 children received mefloquine., Results: Among 975 primary treatment courses, the cumulative 28-day curative efficacies were 26% and 82% for chloroquine against Plasmodium falciparum malaria and Plasmodium vivax malaria, respectively. Mefloquine cure rates were far superior (96% against P. falciparum malaria and 99.6% against P. vivax malaria)., Conclusions: Mefloquine is a useful alternative treatment for P. vivax malaria and P. falciparum malaria in areas such as Papua, where chloroquine is still recommended as the first-line therapeutic agent.

The clinical and parasitological characteristics of the first naturally acquired malarial infection have rarely been documented in humans. When 243 migrants from non-endemic Java were followed from the day of their arrival in Indonesian Papua, 217 (89%) were found to become infected with Plasmodium falciparum and/or P. vivax before they were lost to follow-up. The incidence of malarial infection in the children investigated (who were aged 6-10 years) was indistinguishable from that in the adults (aged >20 years), with 1.10 and 1.14 P. falciparum infections/person-year (relative risk=0.97; 95% confidence interval=0.72-1.29) and 1.47 and 1.49 P. vivax infections/person-year (relative risk=0.99; 95% confidence interval=0.72-1.29), respectively. During their first infections, the children had higher P. falciparum parasitaemias than the adults (with geometric means of 1318 and 759 parasites/microl, respectively; P=0.04) but similar P. vivax parasitaemias (with geometric means of 355 and 331 parasites/microl, respectively; P=0.76). At first infection, 56% of the subjects were febrile and 90% complained of symptoms. There were no differences between children and adults with respect to these two parameters, either for P. falciparum or P. vivax. These findings indicate that, with promptly diagnosed and treated uncomplicated malaria, migrant children and adults in north-eastern Indonesian Papua have an equal risk of malarial infection and of disease following their first infections with P. falciparum and P. vivax.

The epidemiology of infection by Plasmodium falciparum and P. vivax was investigated among Javanese migrants to an endemic region of Papua, Indonesia. A cohort of 243 migrants from Java was followed for malaria in a new settlement village in the endemic Armopa area of north-eastern Papua, beginning on the day each migrant arrived in the village. The subjects were monitored during home visits (three/week) and by the twice-monthly production of bloodsmears that were checked for malarial parasites. At the end of 33 months, 159 (65%) of the subjects remained under follow-up. The prevalence of parasitaemia in the village declined from 16% among those already living there when the study began in August 1996, to 5% when the study finished in June 1999. Over this period, 596 infections by P. falciparum and 723 by P. vivax occurred in the cohort, 22 and 27 of the subjects each experiencing at least six infections by P. falciparum and P. vivax, respectively. The incidence of malarial infection was higher during the first and second years post-migration (3.2 and 2.7 infections/person-year) than during the third (1.2 infections/person-year). Although the geometric mean parasite counts for P. falciparum increased over time (1209, 1478, and 1830 parasites/microl in the first, second and third years, respectively), the corresponding values for P. vivax (497, 535 and 490 parasites/microl) showed no such trend. Only one of the nine subjects who developed severe malaria (requiring intravenous quinine therapy) was a child, giving an odds ratio for a case of severe malaria being in an adult of 6.1 (P=0.08).

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.

The aim of this study was to evaluate the relationship among age, parasitemia status, spleen size, hematocrit, and antibody levels to Plasmodium vivax merozoite surface protein 1 (MSP1) in individuals chronically exposed to P. vivax. Subjects were recruited from the population of three adjacent villages on the Island of Flores in Indonesia where malaria transmission is hyperendemic and tropical splenomegaly syndrome is highly prevalent. Subjects were evaluated for spleen size, hematocrit, presence of parasitemia, and presence of antibodies to a recombinant peptide consisting of 90 amino acids from the carboxy terminus of MSP1. Fifty-seven percent of 2-4 year olds, 45% of 5-9 years old, and 7% of > or = 15 years old were parasitemic; 99% of the > or = 15 years old had splenomegaly, and 31% of them had Hackett 4 or 5 spleens. The frequency of antibody positivity to MSP1 antigen in ELISA increased with age reaching a maximum of 89% in > or = 20 years old. The frequency of antibody positivity to MSPI also increased with spleen size, and with a decline in the prevalence of parasitemia.

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.

The repeat region of the Plasmodium vivax circumsporozoite (CS) protein contains 20 copies of the nine-amino acid sequence DRA A/D GQPAG. A monoclonal antibody that passively protects monkeys against sporozoite challenge recognizes a four-amino acid linear sequence AGDR included within this nonamer, but when monkeys were immunized with a vaccine, NS1(81)V20, which contains 20 copies of the nonamer, they failed to produce antibodies to AGDR. To determine if natural exposure to sporozoites induces antibodies to AGDR, we tested sera from 176 individuals from a malaria-endemic area in Flores, Indonesia. Seventy-one percent of the adults had antibodies to the P. vivax repeat region; only 18% had detectable antibodies to AGDR. None of the subjects had antibodies to the P. vivax variant repeat ANGAGNQPG. We next tested sera from six human volunteers immunized with NS1(81)V20 and found that the vaccine, despite inducing antibodies against the nonamer, as it did in the monkeys, did not induce antibodies against AGDR. To further test our ability to raise anti-AGDR antibodies using synthetic peptides, we immunized Aotus monkeys and BALB/c mice with AGDR. Sera from the mice reacted strongly with both AGDR and a recombinant protein containing the 20 copies of the nonamer. Sera from the monkeys reacted only minimally with a protein (VIVAX-1) that contains monomeric AGDR within its sequence. Sera from the mice also bound air-dried P. vivax sporozoites, while sera from the monkeys did not.(ABSTRACT TRUNCATED AT 250 WORDS)