Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To circumvent problems associated with polymorphic vaccine candidates for Plasmodium falciparum malaria, we evaluated recombinant proteins representing sequences from relatively high conserved regions of the precursor to the major merozoite surface proteins, gp190, for their ability to protect Saimiri monkeys against malaria challenge. Recombinant proteins represented amino acid residues 147 to 321 (p190-1) or 147 to 321 and 1060 to 1195 (p190-3), and their efficacy was compared with that of native gp190 and its processed products. All antigens were derived from P. falciparum K1, a Thai isolate, while the challenge strain was Palo Alto (from Uganda, Africa), which contains, with the exception of the N-terminal 375 amino acids, which are almost identical to the K1 sequence, essentially the MAD-20 allelic form of gp190. By 12 days following challenge, each control monkey required drug treatment. Three monkeys injected with p190-3 required therapy, while one cleared the parasites without therapy. Two monkeys injected with p190-1 received therapy on day 14, while the remaining two cleared the parasites without therapy. Of four animals injected with native gp190, because of health reasons unrelated to malaria, one was not challenged with parasites and one was removed from the study 8 days after challenge when its parasitemia was 1.1% (parasitemias in control animals ranged from 4.3 to 9%); the remaining two cleared the parasites after maximum parasitemias of 0.45 and 0.53%. The highest levels of antiparasite antibody were produced by animals immunized with native gp190. There was a significant correlation between monkeys which did not require drug treatment and antiparasite antibody. These results may suggest that native gp190 and/or its processed products can provide excellent protection against heterologous challenge and that antibody is important for protection. The challenge for vaccine development is to identify the protective sequence(s).
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PMID:Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. 189 56

Renal failure in malaria appears to be a complication less well known than anaemia and cerebral malaria. Thirty-one non-immune patients treated for Plasmodium falciparum malaria at Hannover Medical School were reviewed. Nine patients (29%) had acute renal failure, seven of whom required dialysis, and five patients needed mechanical ventilation. Cerebral symptoms were seen in nine patients, and three of the patients died. In a second series, information about patients who died of malaria in Germany and Austria was gathered. Thirty-six reports were obtained and analysed retrospectively. Thirty-four patients (94%) had acute renal failure. Eighteen patients received dialysis while five other patients with high central venous pressure or hyperkalaemia would have benefitted from dialysis. Cerebral involvement was seen in 34 patients, and 20 patients showed respiratory failure. It was concluded that renal failure in P. falciparum malaria is as common in non-immune adults as cerebral malaria. As untreated renal failure may have a deleterious influence on cerebral and respiratory functions, early dialysis-treatment in patients with severe P. falciparum malaria and signs of deteriorating renal function is recommended.
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PMID:Renal failure is a common complication in non-immune Europeans with Plasmodium falciparum malaria. 189 68

Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria transmission season 5 months prior to the attack, were included in the study. Lymphoproliferative responsiveness to purified soluble malarial antigens and to the unrelated antigen PPD was lost during the acute phase of the disease in most donors, but was regained during convalescence, except in four donors recrudescing or reinfected by day 30. In contrast to the suppression of antigenic responses, cellular responses to phytohaemagglutinin (PHA) remained virtually unaffected. All donors showed elevated plasma-levels of soluble IL-2 receptor during the acute phase of the disease which normalized during convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due to homing of this cell-population to lymphoid tissues. It was also found that acute-phase plasma was suppressive to PPD-induced proliferative responses, indicating an additional suppressive mechanism operating in vivo.
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PMID:Loss of cellular immune reactivity during acute Plasmodium falciparum malaria. 193 Nov 34

A total of 314 cases of Plasmodium falciparum malaria studied during 1980-88 in nine times monitoring revealed three RIII foci i.e. two in Jalpaiguri and one in Purulia districts. The studies showed a parasite clearance of 40 per cent and 32 per cent of P. falciparum cases within seventh day in Purulia and Jalpaiguri districts respectively, with a dosage of 25 mg per kg body weight, spread over three days in divided doses. Increase in transmission potential and prolonged drug pressure with single drug have been noted in association with development of resistance. Malaria parasite clearance time (MPCT) value of sensitive and resistant cases reach parallelism and malaria parasite recrudescence time (MPRT) value starts declining, giving an indication of stabilisation of genetic change in the parasite.
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PMID:Changing response of Plasmodium falciparum to chloroquine in West Bengal during 1980-1988. 194 Feb 14

The prevalence of Plasmodium falciparum malaria was evaluated in all near-term pregnant women and their newborns at the Macha Hospital in the Southern Province of Zambia during part of the rainy season, when malaria prevalence is at its peak. Peripheral parasitemia was noted in 19 (29%) of 65 newborns and in 40 (63%) of 63 mothers. All but one of the infected neonates had an infected mother, and 17 of 40 infected mothers gave birth to infected newborns. The parasite densities measured were uniformly low (less than 25,000/cc), and only seven of 19 infected neonates had fever within 48 hours of delivery suggestive of malaria infection. Parasitized newborns had a 469-gm lower average birthweight, but they did not have a higher incidence of prematurity or preterm delivery compared with uninfected newborns. In addition, the Apgar scores of infected and uninfected newborns were not significantly different. There was no correlation between neonatal parasitemia and either the sex of the child or the parity of the mother. Maternal chloroquine prophylaxis did not appear to be effective in preventing infection in the fetus or the gravida, and the emergence of chloroquine resistance may explain, in part, the greater prevalence of congenital malaria in endemic areas in recent years.
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PMID:Congenital malaria in a hyperendemic area. 195 68

Peripheral blood mononuclear cells (PBMC) from a large proportion of 34 healthy adult native residents in a malaria endemic area showed null or marginal proliferative response (low-responders) to schizont-enriched Plasmodium falciparum malaria antigen (M.Ag) but good response to pokeweed mitogen. In contrast, substantial proliferative response to M.Ag was observed in 8/8 adult temporary residents with a history of one to three acute malaria episodes. Purified CD4+ T cells preferentially responded to M.Ag, however in low-responders CD4+ T cell proliferation was poor. Moreover, no inhibition of CD4+ T cell proliferation was observed when graded numbers of CD8+ T cells were added in culture. The addition of recombinant interleukin 2 (rIL-2) to M.Ag restored the proliferative response of low-responders' PBMC. This response was M.Ag-specific when CD4+ T cells grown in M.Ag plus rIL-2, but not in rIL-2 alone, were tested in secondary cultures.
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PMID:Interleukin-2 reverses T cell unresponsiveness to Plasmodium falciparum-antigen in malaria immune subjects. 197 25

To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.
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PMID:Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen. 198 42

Detection of Plasmodium falciparum malaria by a specific DNA probe is a highly promising means for epidemiological surveillance of human malaria. However, none of presently available DNA probe methods could detect as little as a few parasites in infected blood. By amplification of a specific 206 base pairs P. falciparum DNA sequence using the polymerase chain reaction (PCR), as little as 0.01 picogram DNA or one-half of a parasite was sufficient for a specific detection. A PCR procedure for detection of P. falciparum in infected blood without prior DNA extraction was also developed which was sensitive for a single parasite. The procedure was simple and should be applicable for a large scale epidemiological study involving a very low parasitemia situation.
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PMID:A novel detection of a single Plasmodium falciparum in infected blood. 199 2

A longitudinal study was carried out in Burkina Faso to investigate the natural development of the immune response to Plasmodium falciparum malaria. Three bleedings were carried out before, during, and after the seasonal peak of transmission. Detailed antigen mapping and antibody prevalence of the 248 collected serum samples were established by immunoblotting on the basis of several epidemiological and biological parameters. An improved Western immunoblotting system was used to analyze up to 67 serum samples on each nitrocellulose sheet. This system allowed us to perform the entire study with strictly comparable conditions. Two different blood-stage antigens (exoantigens and somatic antigens) were used to analyze the distribution of different classes and subclasses of immunoglobulins according to the age of the individuals, the presence or absence of a malarial attack, the transmission period, the origin of parasite isolates, and the response to intraerythrocytic stages. Although this analysis emphasizes strong individual variations, reactions with two major antigens of 115 and 103 kDa were especially noted. These antigens induced high antibody levels and prevalences but were probably not involved in protection. The prevalence of immunoglobulin G (IgG) antibodies differed by isotype. Most of antigens stimulating IgG production were also responsible for the IgM antibody response. The role played by these antibodies in the development of natural immunity against malaria is discussed.
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PMID:Development of natural immunity in Plasmodium falciparum malaria: study of antibody response by Western immunoblotting. 203 69

The efficacy of a loading dose of 20 mg of chloroquine per kg of body weight per os given at intervals during the first day was evaluated in 27 patients in Madagascar with Plasmodium falciparum malaria. The conventional regimen of 25 mg/kg over 3 days (schedule 1) was thus compared with a regimen of 30 mg/kg over 2 days (schedule 2; one dose of 10 mg/kg followed by two doses of 5 mg/kg at 6-h intervals on the first day and two doses of 5 mg/kg at 12-h intervals on the second day) in terms of their clinical and parasitological efficacies, tolerance, and drug concentration-time curves. At 24 h schedule 2 gave higher chloroquine levels in blood, which induced a more rapid decrease in parasitemia. The time required for a 50% decrease in the initial parasitemia was shorter in patients on schedule 2 (14.3 +/- 1.6 h) than it was in patients on schedule 1 (35.5 +/- 5.4 h; P less than 0.01). Moreover, negative blood smears were obtained more rapidly with schedule 2 (50.8 +/- 3.7 h) than with schedule 1 (72 +/- 8.7 h). As predicted by the drug concentration-time curve, no high, potentially toxic peak drug concentration appeared and no adverse effects were observed with the loading dose regimen (schedule 2). These findings support the idea that a loading dose of 20 mg/kg given at intervals during the first 12 h is well tolerated and can be used to obtain a more rapid decrease in parasitemia and to shorten the treatment time of uncomplicated chloroquine-susceptible falciparum malaria in the field.
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PMID:Efficacy of a loading dose of oral chloroquine in a 36-hour treatment schedule for uncomplicated plasmodium falciparum malaria. 203 90


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