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Biomedical subjects

H A Marwoto

Publications and source records attributed to H A Marwoto.

At least 19 recordsLinked to original sources
PubMed1992

Low immunogenicity of a Plasmodium vivax circumsporozoite protein epitope bound by a protective monoclonal antibody.

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)

Adolescent↗
PubMed1987

The pathology of lymphoreticular and genital tissues of silvered leaf monkeys (Presbytis cristata) experimentally infected with Wuchereria bancrofti.

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.

Animals↗
PubMed1986

Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum.

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.

Adolescent↗
PubMed1986

Identification of Brugia malayi in vectors with a species-specific DNA probe.

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.

Aedes↗
PubMed1986

In vitro growth inhibition of Plasmodium falciparum by sera from tropical splenomegaly syndrome patients.

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.

Adult↗
PubMed1985

RII and RIII type resistance of Plasmodium falciparum to combination of mefloquine and sulfadoxine/pyrimethamine in Indonesia.

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.

Adolescent↗
PubMed1985

The domestic cat as a host for Brugian filariasis in South Kalimantan (Borneo), Indonesia.

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.

Animals↗
PubMed1985

Antibody-mediated killing of suppressor T lymphocytes as a possible cause of macroglobulinemia in the tropical splenomegaly syndrome.

To investigate the pathogenesis of macroglobulinemia in the tropical splenomegaly syndrome (TSS), we assessed the functional activity of B lymphocytes and T cell subsets in a pokeweed mitogen-driven assay of immunoglobulin synthesis. Mononuclear cells from patients with TSS produced more IgM than cells from village or from distant controls. This appeared to result from a decrease in the number and/or activity of suppressor T cells of the T8+ phenotype. The lack of functional suppressor T lymphocytes was associated with the presence in sera from patients with TSS of IgM antibodies that specifically killed T8+, 9.3-, 60.1+ T cells from normal donors. These results support the hypothesis that macroglobulinemia in TSS results from defective immunoregulatory control of B cell function, and that this may be caused by lysis of suppressor T cells by specific lymphocytotoxic antibodies produced by patients with this syndrome.

Antibody Formation↗
PubMed1985

Evidence of possible natural infections of man with Brugia pahangi in South Kalimantan (Borneo), Indonesia.

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.

Acid Phosphatase↗
PubMed1984

Reduction of suppressor T lymphocytes in the tropical splenomegaly syndrome.

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.

Adolescent↗
PubMed1984

Prolonged incubation improves the micro-scale in-vitro test for drug sensitivity of Plasmodium falciparum.

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.

Adolescent↗
PubMed1984

Absence of malaria mortality in villagers with chloroquine-resistant Plasmodium falciparum treated with chloroquine.

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.

Adolescent↗
PubMed1984

Comparison of immunity to malaria in Sudan and Indonesia: crisis-form versus merozoite-invasion inhibition.

Immunity to falciparum malaria was compared in two populations from malarious areas of southern Sudan and Flores, Indonesia. In Sudan, splenomegaly in adults was rare and anti-plasmodium indirect fluorescent antibody (IFA) titers were low to moderate, 1:1,280 being the modal titer. Sudanese serum was profoundly inhibitory to cultured Plasmodium falciparum, reducing incorporation of radiolabeled hypoxanthine by 63-93% and severely retarding intraerythrocytic parasite development, resulting in moribund crisis-form parasites and virtually no healthy schizonts. In Flores, 64% of the serum donors had splenomegaly greater than or equal to Hackett spleen grade 4 or 5, and the modal IFA titer was 1:10,240. Sera from Indonesia did not retard intraerythrocytic parasite development, but inhibited merozoite erythrocyte invasion 22-87%. Anti-merozoite activity did not correlate with IFA titers. The differences in principal modes of anti-parasitic activity suggest that immunity to malaria in Sudan is based on cell-mediated immune mechanisms associated with crisis forms, merozoite neutralization being of secondary importance. In contrast, malaria immunity in Flores appears to be principally based on anti-merozoite antibody, which does not cause crisis forms and allows for development of reduced numbers of healthy schizonts. This less efficient mechanism may lead to a continuous low-grade parasitemia, which could explain the high specific malaria antibody titers and adult splenomegaly in Flores as compared to Sudan. This latter approach to immunity, being less efficient than the former, apparently results in chronic malaria infections with associated high Ig titers and splenomegaly.

Animals↗
PubMed1983

Opposing effects of filariasis and chronic malaria on immunoregulatory T lymphocytes.

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.

Adult↗