Search

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/μl in the first, second and third years, respectively), the corresponding values for P. vivax (497, 535 and 490 parasites/μl) 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). [ABSTRACT FROM AUTHOR]

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/μl, respectively; P=0.04) but similar P. vivax parasitaemias (with geometric means of 355 and 331 parasites/μl, 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. . [ABSTRACT FROM AUTHOR]

Investigates the effectiveness of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) for the treatment of uncomplicated malaria in Indonesia. Prevalence of malaria; Cumulative incidence of therapeutic failure of SP and CQ; Resistance of Plasmodium falciparum to CQ and SP.

We surveyed adults in a randomly selected sample of 1,000 households in 50 villages in nine malarial sub-districts in Purworejo, central Java, Indonesia from May to July 2001. The survey assessed malaria knowledge, attitudes, and practices in communities experiencing epidemic malaria to begin exploring broad strategies for controlling the disease in the region. A pre-tested survey instrument consisting of 93 questions addressed demographic characteristics, socioeconomic factors, knowledge and perceptions of malaria, burden and severity of disease, treatment-seeking behavior, malaria prevention practices, and perceptions of government malaria control efforts. The survey was taken by in-person interview of all subjects. Most (97%) subjects were aware of malaria and more than two-thirds correctly identified mosquitoes as the vector. Forty-one percent of households in both forest/hilly and agricultural/urban areas reported malaria illness in the past year. Thirty-six percent (357 households) owned at least one bed net, 92% of these had been purchased by the owners. However, only 36% of households with bed nets affirmed their use as a means of preventing malaria. Nearly all respondents reported a willingness to accept spraying of residual insecticides for malaria prevention, yet less than 5% were willing to pay a nominal fee (US $3) for this service. Fifty-two percent of respondents reported self-treatment of malaria illness without visiting a health facility. This assessment of knowledge, attitudes, and practices showed a broad awareness of malaria and its consequences among residents of malarial areas in the Menoreh Hills of Central Java.

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.

After more than 50 years of effective management, resurgent malaria threatens residents in the Menoreh Hills and the foothills of the Dieng Plateau of Central Java, Indonesia. The Dieng Plateau dominates the highland center of Central Java. The steep Menoreh Hills, surrounded by rice paddy habitats, cover approximately 500 km2 with no peaks greater than 1,000 m. We studied epidemic malaria in Purworejo district, one of the three districts containing the Menoreh Hills. Between 1986 and 1995, the annual parasite incidence (API) in Purworejo ranged from 2 to 11 cases per 1,000 residents per year and was typically approximately 5 per 1,000. In 2000 the API was 44.5. This sharp increase was confined to subdistricts in and around the Menoreh Hills and Dieng Plateau foothills. The primary vectors of malaria, those favoring steep, forested hillsides on Java, were Anopheles maculatus and Anopheles balabacensis. Deterioration of vector control activity, followed by a severe economic downturn in 1997, may explain the epidemic. Malaria in the Menoreh Hills and lower Dieng Plateau threatens surrounding areas of rice paddy inhabited by Anopheles aconitus as well as a nearby coastal habitat where the even more efficient vector Anopheles sundaicus occurs in abundance. Most of the 130 million people living on Java never experienced the hyper- and holoendemic malaria that occurred throughout most of the island before the effective DDT spraying and chloroquine treatment campaigns of the 1950s. Reintroduced endemic malaria threatens the island of Java.

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)

The effect of parasitic infections on immunoregulatory T lymphocytes was evaluated by means of quantitative determinations of total T cell and T-cell subset populations present in peripheral blood of patients with lymphatic filariasis, with the malaria-induced tropical splenomegaly syndrome (TSS), and with both infections. Total T-cell numbers were similar to control values in patients without TSS, and reduced in donors with TSS. OKT4+/OKT8+ T-cell ratios were decreased in microfilaremic donors without TSS (0.76 +/- 0.08) and elevated in patients with TSS without microfilaremia (1.97 +/- 0.16). Patients with dual infections tended to yield results similar to uninfected control donors. Thus, filariasis and chronic malaria (TSS) have opposing effects on the normal balance of immunoregulatory T lymphocytes. In patients with TSS, the imbalance appears to result from a decrease in the absolute number of circulating T cells with suppressor/cytotoxic phenotype.

Blood from 9 humans, 6 domestic cats (Felis domesticus), and 5 silvered leaf monkeys (Presbytis cristatus) from South Kalimantan (Borneo), Indonesia, with known filarial infections was examined for determination ofacid phosphatase activity of the microfilarae (mff). The findings suggest 1) that Brugia parasites from domestic cats and silvered leaf monkeys can be speciated by acid phosphatase activity and that speciation by acid phosphatase assay corresponds to that based upon adult worm morphology and 2) that Brugia mff from humans have acid phosphatase activity characteristic of that of B. pahangi microfilariae from cat and monkey. Thus B. pahangi may infect man in South Kalimantan.

The sensitivity of Plasmodium falciparum infections to pyrimethamine-sulfadoxine was studied in 18 Indonesian patients in Jayapura, Irian Jaya. In 16 of the 18 patients parasitaemia was cleared by day 6 and the patients remained without parasitaemia through day 28. Two of the 18 patients had late recrudescences consistent with RI-type resistance; one each on days 14 and 21. Pyrimethamine-sulfadoxine is still an effective antimalarial for most patients with falciparum malaria in Jayapura.

Three hundred and twenty-five domestic cats (Felis catus) from six villages of the Hulu Sungai Tengah and Banjar Regency of South Kalimantan (Borneo), Indonesia, were examined for filarial nematodes. Parasites were found in 66 cats, of which 61 (92.4%) had Brugia pahangi, four (6.1%) has B. malayi and one (1.5%) had Dirofilaria repens. Infection rates ranged from 11% to 22% in cats from secondary forest/rice-field habitats, from 15% to 30% in open village/rice-field habitats, to 50% in an open coastal village. In all cases the infection rate of B. malayi in man was greater than in cats from the same collecting area. The number of B. pahangi microfilariae per 20 microliter cat blood ranged from 34 at 1000 hours to 571 at 2200 hours. The results of this study suggest that in this region of Indonesia the domestic cat is not an important host for maintaining B. malayi.

A candidate Plasmodium falciparum sporozoite vaccine, R32tet32, which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum, has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet32 antibody titers greater than or equal to 1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites.

2 of 36 Plasmodium falciparum infections were resistant (RII and RIII) in vivo to the combination of mefloquine (M) and sulfadoxine-pyrimethamine (SP) in Jayapura, Irian Jaya, Indonesia. Expected absorption of mefloquine and pyrimethamine was confirmed in the one resistant patient from whom sera were available, and the isolate from this patient was sensitive to mefloquine in vitro. Only 2 of 41 infections studied at the same time were resistant in vivo to SP. There was no clinical advantage of MSP compared with SP, and limited observations suggest there may be a disadvantage.

We carried out a series of malaria studies in Robek , Flores, Indonesia, a coastal village of 900 farmers and fishermen where malaria is hyperendemic by parasite rate and holoendemic by spleen rate. The studies showed that: (i) 28 of 31 isolates (90%) of Plasmodium falciparum were resistant to chloroquine in vitro, (ii) 3 of 12 isolates (25%) were resistant at the R-11 level in vivo, (iii) 376 P. falciparum infections occurred in 301 individuals during one year, (iv) no villagers who were treated with chloroquine for P. falciparum infections during the year died, and (v) increasing the dosage of chloroquine base from 15 to 25 to 37.5 mg/kg led to improved clearing of parasitaemia. We conclude that chloroquine can still be used as the primary antimalarial in Robek , but the dosage may have to be increased to clear parasitaemia.

In the standard micro-scale in-vitro test for detecting resistance of Plasmodium falciparum to chloroquine, isolates are incubated for 24-28 h in medium that does not contain serum. The effect of prolonging incubation to 48 h and of adding human AB serum to the culture medium of P falciparum from Irian Jaya, Indonesia was studied. Addition of serum was not associated with any advantages or disadvantages. Production of schizonts was increased when incubation was prolonged. This facilitated reading of the malaria smears and interpretation of the results. The percentage of successful tests (greater than or equal to 20 schizonts/200 asexual parasites in control wells) increased from 31% at 28 h incubation to 94% at 48 h. Among the 7 (44%) isolates which were chloroquine-resistant in vivo, only 1 met the criteria for a positive test at 28 h incubation, but at 48 h all 7 did. To achieve optimum results from the micro-scale in-vitro test in Jayapura, Irian Jaya, isolates should be incubated for 48 h.

Wild and domestic animals trapped from forests, villages, and rice fields in South Kalimantan (3 degrees 20' S, 115 degrees 02' E, 25 m) were examined for blood parasites using Giemsa stained thick and thin blood films and Nuclepore filter preparations of peripheral vein and heart puncture blood. Presbytis cristatus (silvered leaf monkey) (25%) and Felis catus (domestic cat) (7%) were infected with Brugia malayi and B. pahangi. In addition, P. cristatus was infected with Wuchereria kalimantani (35%); Cardiofilaria sp. (1%) and Dirofilaria sp. (1%). Microfilariae of Cardiofilaria were also recovered from Callosciurus notatus (squirrel), Pitta sordida (bird), Pycnonotus goiavier (bird) and Gallus gallus (bird). Paradoxurus hermaphroditus (civet) and Muntiacus muncak (barking deer), were positive for Dirofilaria sp. Bos indicus (cow) for Onchocerca sp. and Nectarinia jugularis (bird) for Splendidofilaria sp. Plasmodium coatneyi was found in 22% of the P. cristatus examined. Plasmodium sp. was also recovered from Zaocys fuscus and Ahaetulla prasina (reptile); Muscicapa sp. Lonchura malacca, Orthotomus sericeus, Rhipidura javanica, Treron vernans, Pycnonotus melanoleucus and G. gallus (bird). In addition 39% of the Cynopterus brachyotis and 29% of C. horsfieldi (fruit bats) were infected with Hepatocystis pteropi. A single G. gallus was infected with Leucocytozoon sabrazesi and another with Trypanosoma sp.

The discovery of the silvered leaf monkey, Presbytis cristata, as a suitable experimental host for the human filarial parasite, Wuchereria bancrofti, opened the door for major advances in our understanding of the disease caused by this parasite. To study the pathogenesis of bancroftian filariasis in this model, 15 adult P. cristata which had been experimentally infected with 250 infective third-stage larvae of the parasite were examined. After inoculation with larvae, the monkeys were maintained under study for periods of 2 to 3 years, at which time all had achieved patent infections. At necropsy, Wuchereria-induced macroscopic lesions were not detected in experimentally infected monkeys. Microscopic findings included nematodiasis, microfilariasis, lymphadenitis, lymphangiectasis, perilymphangitis, splenitis, orchitis, periorchitis, epididymitis and funiculitis. Sections of normal adult worms were most often found in lymphatic vessels near lymph nodes, or in the lymphatics of the male genital system. These worms caused microfiliariasis in some regional lymph nodes. Inflammatory responses to filariae were most prominent in proximity to degenerated and dead worms, whereas intact, normal appearing adult worms elicited only minimal cellular response.

On the basis of morphological characteristics of adult and microfilarial stages, Wuchereria kalimantani sp. n. (Nematoda: Filarioidea) is described. The parasites were recovered from the inguinal lymph nodes and testes of silvered leaf monkeys (Presbytis cristatus) from a rubber estate, Banjar Regency, South Kalimantan (Borneo), Indonesia. Adult males are characterized by having more than 24 caudal papillae, a left spicule with a simple lamina, four pairs of sessile caudal papillae, a blunt tail, a mean overall length of 41 mm, and sheathed microfilariae with a nude tail tip; accordingly, the parasite is placed in the genus Wuchereria. This is the second species of Wuchereria described on the basis of both adult and embryonic forms, and is the first such species that has been found to infect primates naturally.

Sera from tropical splenomegaly syndrome (TSS) and non-TSS patients from the same village were examined for their ability to inhibit the in vitro growth of Plasmodium falciparum. Using synchronized malaria cultures, sera from both groups inhibited parasite development only if added before merozoite reinvasion of erythrocytes had occurred. There was no significant difference in the degree or apparent mechanism of inhibition caused by TSS and non-TSS sera. These results suggest that the aberrant immune response that results in TSS may not be associated with the elaboration of unique serum factors that differentially inhibit growth of the parasite in vitro.

We evaluated the potential value of a cloned sequence of genomic DNA of Brugia malayi as a species-specific probe. Clone pBm 15 reacted with all stages of 8 different geographic isolates of B. malayi and cross-hybridized with microfilariae of B. timori. It did not hybridize with Wuchereria bancrofti or with B. pahangi, W. kalimantani, Dirofilaria repens, Breinlia booliati or Cardiofilaria species, animal filariids that can be sympatric with B. malayi. P32-labeled clone pBm 15 correctly identified mosquitoes infected even with 1 infective larva of B. malayi. This specific DNA probe should be an invaluable tool to monitor control programs of Brugian filariasis.

To study the pathogenesis of tropical splenomegaly syndrome, we compared immunologic findings in patients from Flores, Indonesia, with those obtained in local residents without splenomegaly and in controls. Villagers with tropical splenomegaly syndrome had markedly elevated levels of total IgM, higher titers of IgM antibodies to Plasmodium vivax, and reduced levels of circulating T lymphocytes. The latter were caused by a decrease in the total number of T cells with the suppressor/cytotoxic phenotype (T8+). Levels of B lymphocytes were similar in all groups. All immunologic abnormalities reverted toward normal in patients treated weekly for 9 to 26 months with chloroquine phosphate. These findings suggest that overproduction of immunoglobulins in patients with tropical splenomegaly syndrome is caused by an imbalance in the normal ratio of helper: suppressor T cells that regulate B-lymphocyte function, and that this imbalance is due to a decrease in suppressor T lymphocytes.