In vivo responses to antimalarials by Plasmodium falciparum and Plasmodium vivax from isolated Gag Island off northwest Irian Jaya, Indonesia.
(17/1555)
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. (+info)
Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.
(18/1555)
A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative. Parasite prevalence (all species) decreased with age (from a high of 83% among children 1-4 years old to 60% among children 10-14 years old). Even more dramatic decreases were noted in the prevalence of high density falciparum infection (from 37% among children 12-23 months old to < 1% among 10-14-year-old children) and in clinical malaria (20% to 0.3% in the same age groups). Children < 1 year of age accounted for 55% of all cases of anemia detected. Anemia was consistently associated with high density infection in children < 10 years of age (20% to 210% increased risk relative to aparasitemic children). These results demonstrate the relationship between high-density malaria infection and two clinical manifestations of malarial illness. (+info)
Role of eicosanoids in the pathogenesis of murine cerebral malaria.
(19/1555)
Because microvascular damage is a common feature of cerebral malaria, we have examined the role eicosanoid metabolites (prostaglandins and leukotrienes) in experimental cerebral malaria. Eighty ICR mice were infected with Plasmodium berghei ANKA, with 40 uninfected mice as controls. Half of the infected mice were treated on days 4 and 5 with aspirin, a prostaglandin synthesis inhibitor. Infected mice started to die of cerebral malaria on day 6, and by day 17, all infected mice died. In contrast, all infected mice treated with aspirin died by day 12. Infected mice had increased phospholipase A2 mRNA expression in the spleen and cyclooxygenase 1 (COX1) and COX2 expression in the brain. At the peak of cerebral malaria, infected mice had higher serum leukotriene B4 levels than control mice, and aspirin-treated infected mice had higher serum leukotriene B4 levels than untreated infected mice. These results suggest that prostaglandins are protective whereas leukotrienes are detrimental in cerebral malaria. (+info)
Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.
(20/1555)
The frequency of cytokine-producing peripheral blood mononuclear cells was assessed in 28 subjects with microfilaremic loiasis and in 14 amicrofilaremic individuals. In addition, a subgroup of seven microfilaremic individuals coinfected with Plasmodium malariae was evaluated. By using flow cytometry for the intracellular detection of cytokines, a more pronounced T helper (Th)2 cell-type response with the expansion of interleukin (IL)-4, IL-10, and IL-13 expressing CD4+ cells in the microfilaremic compared with the amicrofilaremic group was noted. Expression of IL-5 was equivalent in both groups as was the frequency of Th2-type cytokines expressing CD8+ cells and of Th1-type cytokines (interferon [IFN]-gamma, IL-2, IFN-gamma/IL-2) producing CD4+ and CD8+ cells. Th0-type cytokine-expressing cells, represented by IL-4/IFN-gamma, IL-10/IFN-gamma, and IL-13/IFN-gamma, were equally distributed within groups. Coinfection of P. malariae did not significantly alter the cytokine expression compared with microfilaremic individuals without P. malariae infections. By identifying a large panel of cytokine-producing T cell subpopulations, a Th2-driven immune response in microfilaremic Loa loa patients was noted. (+info)
A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies.
(21/1555)
A nested polymerase chain reaction (PCR) assay that uses Plasmodium genus-specific primers for the initial PCR (nest 1) amplification and either genus- or species-specific primers for the nest 2 amplifications was tested on laboratory and field samples. With in vitro cultured Plasmodium falciparum-infected blood samples, it was capable of detecting six parasites/microl of blood using DNA prepared from 25-microl blood spots on filter paper. The assay was evaluated on fingerprick blood samples collected on filter paper from 129 individuals living in a malaria-endemic area in Malaysia. Malaria prevalence by genus-specific nested PCR was 35.6% (46 of 129) compared with 28.7% (37 of 129) by microscopy. The nested PCR detected seven more malaria samples than microscopy in the first round of microscopic examination, malaria in three microscopically negative samples, six double infections identified as single infections by microscopy and one triple infection identified as a double infection by microscopy. The nested PCR assay described is a sensitive technique for collecting accurate malaria epidemiologic data. When coupled with simple blood spot sampling, it is particularly useful for screening communities in remote regions of the world. (+info)
Plasticity of immune responses suppressing parasitemia during acute Plasmodium chabaudi malaria.
(22/1555)
gammadelta T cells have a crucial role in cell-mediated immunity (CMI) against P. chabaudi malaria, but delta-chain knockout (KO) (deltao/o) mice and mice depleted of gammadelta T cells with mAb cure this infection. To address the question of why mice deficient in gammadelta T cells resolve P. chabaudi infections, we immunized deltao/o mice by infection with viable blood-stage parasites. Sera from infection-immunized mice were tested for their ability to protect JHo/o, deltao/o double KO mice passively against P. chabaudi challenge infection. The onset of parasitemia was significantly delayed in mice receiving immune sera, compared with saline or uninfected serum controls. Immune sera were then fractionated into Ig-rich and Ig-depleted fractions by HPLC on a protein G column. Double KO mice were passively immunized with either fraction and challenged with P. chabaudi. The onset of parasitemia was significantly delayed in recipients of the Ig-rich fraction compared with recipients of the Ig-poor fraction of immune sera. We conclude that deltao/o mice, which are unable to activate CMI against the parasite, suppress P. chabaudi infection by a redundant Ab-mediated process. (+info)
Plasmodium falciparum isolates from infected pregnant women and children are associated with distinct adhesive and antigenic properties.
(23/1555)
Plasmodium falciparum malaria during pregnancy is an important cause of maternal and infant morbidity and mortality. Accumulation of large numbers of P. falciparum-infected erythrocytes in the maternal blood spaces of the placenta may be mediated by adhesion of infected erythrocytes to molecules presented on the syncytiotrophoblast surface. In this study, isolates from placentas and peripheral blood of infected pregnant women and from children were tested for binding to purified receptors and for agglutination with adult sera. Results suggest that adhesion to chondroitin sulfate A may be involved in placental parasite sequestration in most cases, but other factors are also likely to be important. Agglutination assay results suggest that parasites infecting pregnant women are antigenically distinct from those common in childhood disease. The prevalence of agglutinating antibodies to pregnancy isolates was generally low, but it was highest in multigravidae who are likely to have had the greatest exposure. (+info)
Antiparasite adherence activity in Thai individuals living in a P. falciparum endemic area.
(24/1555)
Two types of antimalaria antibodies in the serum of 54 villagers living in a malaria endemic area of Thailand were determined by indirect immunofluorescence assay in order to define the status of malaria immunity within the group. Antibodies to parasite-derived antigens in the membrane of ring stage-infected erythrocytes were very high (> or = 1:1,250) in 44%, moderate to low (< or = 1:250) in 37% of the sera, and the rest did not have the antibody. However, all the sera had antibodies to antigens of the intraerythrocytic mature parasites, showing a very high level in 65% and moderate to low levels in 37% of the sera. Sera with high antibody titers to either type of antigen significantly inhibited cytoadherence of P. falciparum-infected erythrocytes. All the sera variably inhibited rosette formation of the parasites but showed no association with the antibody titers. These results suggest that the antibodies to cytoadherence and rosette formation can be elicited and sustained in the malaria experienced host while living in the endemic area. This may be a natural preventive mechanism against the severity of P. falciparum infection in the infected host. How long the antiparasite adherence activity will last remains to be investigated. (+info)