Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4187 pregnant women with parasitemia attending 4 prenatal care clinics in rural Mangochi District, Malawi, were assigned to 1 of 4 regimens of antimalarial treatment and/or prophylaxis and followed through delivery. The aim was to examine maternal fever and to evaluate side effects and the frequency of adverse reproductive outcomes for their possible association with malaria or the antimalarial drug regimens. The regimens were 3 regimens for chloroquine (CQ), 1 of which was the current standard of care in Malawi, and a mefloquine (MQ) regimen. 25% of the pregnant women claimed to have had at least 1 febrile episode before their first prenatal care visit. Blood smear tests revealed the parasitemia prevalence rate at enrollment to be 44.4%. The sensitivity of fever to identify parasitemic pregnant women was 24%. Fever's specificity was 71%. Only high density parasitemia (10,000 parasites/sq m) was associated with fever (44.9% vs. 25.4% for no parasitemia; odds ratio [OR] = 2.54; p 0.000001). Other significant factors associated with high fever were low parity, enrollment in the rainy season, HIV seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal maternal height and weight, and literacy. The sensitivity of first or second pregnancy to identify parasitemic women was 71%. Its specificity was 57%. About 60% of women from both CQ and MQ treatment groups had side effects after a treatment dose. About 25% had side effects after a prophylactic dose. The leading side effects were itching, dizziness, and gastrointestinal disturbances. There were few serious side effects. Among all women, the spontaneous abortion rate was 1.2% and the stillbirth rate was 3.9%. Women in the CQ and MQ treatment groups had similar abortion and stillbirth rates. Based on these findings, the researchers concluded that using fever as a means to identify parasitemic women is unreliable. They recommend antimalarial treatment and/or prophylaxis for all pregnant women, but when resources are limited it should be administered to women in their first or second pregnancy.
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PMID:Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine. 870 37

The frequency and description of side effects secondary to the subcutaneous application of SPf66 malaria vaccine and placebo are reported for each dose of application in the participants of the vaccine efficacy trial in Brazil. Side effects evaluated two hours after each application were detected in 8.0%, 30.2% and 8.8%, for the 1st, 2nd and 3rd dose, respectively, in the SPf66 group, and in 7.0%, 8.5% and 2.9% in the placebo group. Local reactions such as mild inflammation, nodule and pain or erythema frequently accompanied by pruritus were the most common reactions detected in both groups (3.8%, 29.1% and 8.5% in the SPf66 group and 4.0%, 7.6% and 2.5% in the placebo group). Among vaccinees, local side effects after the 2nd dose were more frequent in females. Systemic side effects were expressed mainly through general symptoms referred by the participants and were most frequent after the 1st dose in both groups (4.3% in the SPf66 group and 3.0% in the placebo group). Muscle aches and fever were referred by few participants. No severe adverse reactions were detected for either dose of application or group.
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PMID:Safety evaluation of SPf66 malaria vaccine in Brazil. 888 74

Chlorpheniramine, a histamine H1 receptor antagonist, reverse chloroquine resistance in Plasmodium falciparum in vitro. However, the clinical significance of this remains unclear. We have evaluated the efficacy of chloroquine and a chloroquine-chlorpheniramine combination in 112 consecutive children with acute symptomatic uncomplicated falciparum malaria. There was no significant difference in the parasite and fever clearance times in the 2 treatment groups. However, the proportion of patients in whom parasitaemia increased 24 h after commencement of treatment was significantly higher in the chloroquine group than in the chloroquine-chlorpheniramine group (28.5% vs. 8.3%, chi 2 = 6.61, P < 0.01). There was also a higher proportion of children with RII and RIII responses to treatment in the chloroquine than in the chloroquine-chlorpheniramine group but the difference was not statistically significant. The cure rate on day 14 was higher in the chloroquine-chlorpheniramine group than in the chloroquine group. Chloroquine and its combination with chlorpheniramine were well tolerated, the only prominent adverse effect being pruritus, with equal incidence in both groups. Chlorpheniramine reversed chloroquine resistance in vitro in a similar manner to verapamil in isolates of P. falciparum obtained from the patients. Failure of a response in vivo to chloroquine correlated with resistance in vitro in patients treated with this drug. In contrast, all but one patient with isolates which were chloroquine resistant in vitro were successfully treated with chloroquine-chlorpheniramine combination. These data suggest the enhanced efficacy of chloroquine-chlorpheniramine combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria.
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PMID:Enhanced efficacy of chloroquine-chlorpheniramine combination in acute uncomplicated falciparum malaria in children. 950 91

The clinical efficacy of intramuscular artemether was studied in 144 children suffering from severe non cerebral malaria. Fifty-three children with chloroquine-resistant and 27 children with sulfadoxinepyrimethamine-resistant falciparum malaria were also studied. Greater than 95% of pre-treatment parasitaemia was cleared by 24 h after commencement of treatment in all groups. The parasite and fever clearance times were 35.4 +/- 8.0 and 18.6 +/- 6.3 h respectively, in children suffering from severe non cerebral malaria 36.3 +/- 7.9 and 15.6 +/- 3.8 h, respectively, in the chloroquine-resistant and 36.8 +/- 8.8 and 16.5 +/- 4.2 h, respectively, in the sulfadoxine-pyrimethamine-resistant groups. The cure rate in all groups on day 14 was 100%. Side effects following treatment were minimal and comprised pain with mild tenderness at site of injection in two children and bradycardia, on the second or third day of treatment, in another two patients. No patient had pruritus. These data suggest that artemether is rapidly effective in falciparum malaria in children irrespective of previous drug treatment and especially in chloroquine- or sulphadoxinepyrimethamine-resistant infection and in this study was without deleterious side effects.
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PMID:Efficacy of artemether in severe falciparum malaria in African children. 913 65

In preparation for an efficacy trial of malaria vaccine SPf66 in Thailand, a series of overlapping Phase I trials were conducted of US-manufactured SPf66. Here, two clinical lots were evaluated for safety and immunogenicity in a combined open-label trial. Eleven healthy, malaria naive, 18-44 year-old Thai men and women received three doses by subcutaneous injection in alternate arms at 0, 1 and 6 months. Safety was assessed by monitoring local and systemic reactogenicity and laboratory parameters. Common side effects were mild erythema, induration and tenderness at the site of injection which resolved within 24-48 h. At third immunization, two volunteers developed acute bilateral reactions with induration, erythema and pruritus limited to the sites of the second and third immunizations. Eight of 11 volunteers sero-converted by ELISA, six of whom would be classified as high responders by Colombian standards. Eight of 11 volunteers developed a lymphoproliferative response to the SPf66 antigen. Side effects were more common and antibody and lymphoproliferative responses greatest, among the four female volunteers. This initial study of SPf66 malaria vaccine in Asia constitutes an essential link between the initial Phase I study in the US and subsequent field studies in a semi-immune population in a malaria endemic area of Thailand. This study further establishes comparability of US-manufactured SPf66 with that of Colombian provenance and substantiates the validity of the subsequent negative efficacy results of SPf66 in a field trial in Thailand.
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PMID:SPf66 malaria vaccine is safe and immunogenic in malaria naive adults in Thailand. 924 86

The efficacy of chloroquine for treating uncomplicated Plasmodium falciparum malaria was evaluated in 98 children in Nigeria. Forty-three children failed chloroquine treatment (21 RI, 20 RII, 2 RIII) and were allocated at random to receive multiple doses of a combination of chloroquine and chlorpheniramine or a single dose of mefloquine orally. The parasite and fever clearance times were 2.7 +/- 1.0 d and 1.6 +/- 0.6 d, respectively, in children treated with the combination and 1.6 +/- 0.5 d and 1.1 +/- 0.3 d, respectively, for mefloquine treatment. The cure rate on day 14 was 81% among children receiving chloroquine/chlorpheniramine and 100% on days 14 and 28 with mefloquine. Three children who failed treatment with the combination responded promptly to mefloquine, with clearance of parasitaemia and fever within 48 h. Adverse effects following therapy were minimal, comprising drowsiness and pruritus in the combination group and abdominal discomfort in the mefloquine group. Isolates obtained from children who failed initial treatment with chloroquine were resistant to chloroquine but sensitive to mefloquine in vitro. The efficacy of this combination of chloroquine and chlorpheniramine confirmed previous reports of enhanced activity and it was effective in the management of mild to moderate chloroquine-resistant malaria. Although mefloquine is more effective in this respect, the combination, when developed, will be a valuable addition to the list of drugs for the management of chloroquine-resistant malaria.
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PMID:Comparative efficacy of chloroquine/chlorpheniramine combination and mefloquine for the treatment of chloroquine-resistant Plasmodium falciparum malaria in Nigerian children. 950 81

The effect of combining promethazine with chloroquine was examined against Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays from volunteers given promethazine. The combination of chloroquine plus promethazine (1 x 10(-6) M) reversed chloroquine resistance in standard P. falciparum clones and patient parasite isolates from Nigeria. The combination reduced the 50% inhibitory concentrations (IC50s) for chloroquine against resistant parasites by 32-92%. Coadministration of promethazine with chloroquine also demonstrated a dose-dependent effect in Aotus monkeys infected with chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20 mg/kg of body weight for seven days), which normally has no effect on parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one monkey, parasitemia was suppressed at the lowest promethazine dose, but re-treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some animals followed by recrudescence. Re-treatment at higher doses cured one monkey and resulted in initial clearance and delayed recrudescence 28 or 63 days after treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10 parasites/microl of blood) and subsequently cleared without re-treatment. An in vitro bioassay model was developed to examine the effects of clinically achievable doses of promethazine on parasites susceptibilities in vitro. Plasma samples taken at hourly intervals from patients given a single oral dose of 25 mg of promethazine decreased the IC50 values for chloroquine by 20-58% with the most significant reductions occurring in plasma obtained from volunteers 3-4 hr after ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug demonstrated no effect on chloroquine susceptibility, suggesting that study of the pharmacokinetic disposition and potential interaction is warranted to optimize the dose regimen in patients for antimalarial efficacy. Historic use of this drug combination for treatment or prevention of chloroquine-associated pruritus or as an antiemetic suggest that the combination is safe and effective when used at standard dosages. The results from this study demonstrate that promethazine is a potent modulator of chloroquine resistance. Clinical evaluation of therapeutic regimens is required to validate clinical efficacy of this promising combination for treatment of uncomplicated chloroquine-resistant malaria.
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PMID:In vitro and in vivo reversal of chloroquine resistance in Plasmodium falciparum with promethazine. 959 52

Severe generalized pruritus is a common drawback in chloroquine therapy of malaria in black Africans. In a cross-sectional study, we evaluated the knowledge, attitude and practice of 117 Nigerian hospital workers, who historically itch to chloroquine, to the use of prednisolone to prevent chloroquine pruritus in malaria. Ninety per cent of respondents had a positive family history of chloroquine induced pruritus. Seventy-five per cent (92) of the subjects were aware of the anti-pruritic action of prednisolone, but only 43% (n = 40) have ever used it during malaria. Among the prednisolone users (n = 40), 25 (62.5%) had total prevention, 25% (n = 10) had marked pruritus attenuation, but no effect was seen in 12.5% (n = 5). The modal prednisolone dose causing inhibition of itching was 10 mg orally given once. Concurrent prednisolone increased compliance with chloroquine in 68% of all who used the combination, and there was no evidence of malaria recurrence.
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PMID:Knowledge, attitude and practice of prednisolone prevention of chloroquine induced pruritus among Nigerian health workers. 980 39

Background: The objectives of this study were (1) to compare the efficacy of Lariam (mefloquine) with that of Fansimef (mefloquine, sulfadoxine, and pyrimethamine), Fansidar (sulfadoxine and pyrimethamine), chloroquine, and placebo in suppressing asexual parasitemia in semi-immune persons living in an area endemic for Plasmodium falciparum malaria; and (2) to compare the tolerance of these drugs when taken over a prolonged period of time. Method: A randomized double-blind comparative placebo-controlled study was undertaken in the village of Biasso, 60 km from Abidjan in the southern part of the Ivory Coast, a region where P. falciparum malaria is endemic. Four hundred and ninety nine male volunteers (five parallel groups), who were inhabitants of Biasso, were involved. The main outcome measures concerned the incidence of malaria breakthroughs (acute malaria attacks) and the incidence of parasitemia. Results: Within this strictly defined epidemiologic context, prophylaxis, taken once weekly, proved to be fully protective (parasitic index: 0) in the Lariam, Fansidar, and Fansimef groups throughout the whole study period. Prophylaxis with chloroquine proved incompletely protective (parasitic index: 2.5) The most frequent side effects were pruritus (5.6%), diarrhea (1.2%) and headache (0.06%). No significant differences in the incidence of side effects in each group (chi-square test) was observed. All side effects were transient and judged to be mild by the investigators. Conclusions: Excellent efficacy was observed in the prophylaxis of P. falciparum malaria with Lariam, Fansidar, and Fansimef as compared to the partial protection provided by chloroquine. Safety and tolerance were comparable in all groups during the whole period of observation (5 months).
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PMID:Mefloquine in the Prophylaxis of P. Falciparum Malaria. 981 95

In the face of growing chloroquine resistance of Plasmodium falciparum, efforts to prolong the clinical usefulness of the drug have partly concentrated on its combination with potential resistance-reversing compounds. However, clinical studies on such combinations have been limited. We have compared the efficacy of halofantrine, an arylaminoalcohol effective in chloroquine resistant malaria, and a combination of chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist which reverses chloroquine resistance of P. falciparum in vitro and in vivo, in 100 children with acute symptomatic uncomplicated falciparum malaria in an area in Nigeria where the rate of chloroquine resistance is 35-45%. Both chloroquine plus chlorpheniramine and halofantrine produced similar parasite and fever clearance times and cure rates (96%). Both treatment regimens were relatively well tolerated. Pruritus was commoner in patients treated with chloroquine plus chlorpheniramine than in those treated with halofantrine. Intravascular haemolysis occurred in one patient, and abdominal pain with or without diarrhoea occurred in 4 patients, treated with halofantrine. In vitro, the chloroquine resistance of P. falciparum isolates obtained from the patients was reversed by verapamil. All patients with isolates which were chloroquine-resistant in vitro were cured by either therapy. These results indicate that chloroquine plus chlorpheniramine is as effective as halofantrine and is without overt deleterious effect in treating acute uncomplicated chloroquine-resistant falciparum malaria in children, and may be a clinically useful alternative for this purpose in Nigeria.
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PMID:Comparative efficacy of chloroquine plus chlorpheniramine and halofantrine in acute uncomplicated falciparum malaria in Nigerian children. 985 Apr 4


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