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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The therapeutic efficacy and toxicity of a combination of low dose mefloquine (15 mg/kg) plus artesunate 10 mg/kg in one day (MA) was compared with the currently used regimen of high dose mefloquine (25 mg/kg) (MQ) in 552 patients with uncomplicated falciparum malaria in an area of multi-drug resistance on the Thai-Burmese border. MA gave faster clinical and parasitological responses and prevented early treatment failure; 15 patients in the MQ group (6%) were early failures (< 9 d) compared with none receiving MA (P = 0.0001). Overall failure rates by day 28 were 19% in the MA group and 24% in with MQ group (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.54-1.12). In the subgroup of patients who required re-treatment, MA proved significantly more effective than MQ; failure rates were 25% and 52% respectively (RR = 0.49, 95% CI = 0.29-0.83). Treatment failures were associated with mefloquine treatment in the previous month (RR = 1.72, 95% CI = 1.09-2.70) and diarrhoea (RR = 1.55, 95% CI = 1.05-2.28). Gastrointestinal side-effects and dizziness were more likely in the MQ group. There was no evident adverse effect associated with artesunate. A single day's treatment with artesunate augments the antimalarial efficacy of mefloquine.
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PMID:Single day mefloquine-artesunate combination in the treatment of multi-drug resistant falciparum malaria. 803 79

During November-December, 1991, clinicians administered either 15 mg/kg mefloquine or 25 mg/kg mefloquine to 57 and 53 patients, respectively, to treat falciparum malaria. The patients were at the referral hospital in Site 8, a Khmer refugee camp on the border between Thailand and Cambodia. The 2 groups responded essentially the same, except the 15 mg/kg group had a lower mean hemoglobin level than the 25 mg/kg group (9.4 g/dl vs. 10 g/dl; p = .03). Parasitological failure rates on day 28 and 42 were not significantly different between the 2 groups. On day 28, they were 50% for the 15 mg/kg group and 43.4% for the 25 mg/kg group. They were especially high at day 42 (62% and 56%, respectively). Patients in the 25 mg/kg group were more likely to experience adverse effects of mefloquine (13% vs. 7% for vomiting, 26% vs. 19% for diarrhea, and dizziness 74% vs. 70%), but the differences were not significant. The mean serum mefloquine level was basically the same for both groups (2165 mcg/l in 15 mg/kg group and 2284 mcg/l in the 25 mg/kg group). 13 of 19 patients tested had serum mefloquine concentrations greater than 2000 mcg/1 on day 2, yet they experienced parasitological failure. This concentration traditionally indicated successful treatment. People who vomited within an hour of receiving mefloquine had much lower serum mefloquine levels than those who did not vomit (1289 mcg/l vs. 2300 mcg/l; p = .03). Patients who experienced dizziness on day 2 had much higher serum mefloquine levels than those who were not dizzy (2394 mcg/l vs. 1371 mcg/l; p = .006). On day 2, the mean ratio between the levels of the (SR)-(-) and (RS)-(+) enantiomers of mefloquine stood at 3.37, suggesting that differences exist in their pharmacokinetics. The 7-day retreatment regimen with quinine and tetracycline was successful in 93% of the 50 patients who experienced parasitological failure.
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PMID:Falciparum malaria in eastern Thailand: a randomized trial of the efficacy of a single dose of mefloquine. 813 Dec 53

A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border. Mefloquine gave > or = 86% (95% confidence interval [CI], 59%-94%) protection against Plasmodium falciparum and complete protection against Plasmodium vivax infections. Mefloquine prophylaxis was well tolerated; use of an initial loading dose (10 mg/kg) was associated with transient dizziness, but there were no other significant adverse effects on the mother, the pregnancy, or infant survival or development (followed for 2 years). Falciparum malaria was associated with maternal anemia and a mean reduction in birth weight in gravidae I, II, and III of 225 g (95% CI, 26-423). Maternal anemia at delivery (hematocrit < 30%) was associated with increased infant mortality: 26% versus 15% (relative risk, 1.9; 95% CI, 1.1-3.2). Mefloquine is safe and effective for antimalarial prophylaxis in the second half of pregnancy.
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PMID:Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study. 779 76

At the Bangkok Hospital for Tropical Diseases in Thailand, health workers collected blood samples from male patients with acute uncomplicated falciparum malaria so researchers could compare the efficacy of artesunate (700 mg over 5 days) with the standard antimalarial treatment (600 mg quinine at 8 hour intervals plus 250 mg tetracycline at 6 hour intervals for 7 days). All 31 patients in the artesunate group had a much more rapid initial response than the 33 in the quinine-tetracycline group (mean parasite clearance time [PCT] = 37 hours; mean fever clearance time [FCT] = 31 vs. 73 and 55 hours, respectively) (p = 0.000001 for PCT; p = 0.000041 for FCT). In both groups, the mean PCT and mean FCT did not differ with level of pretreatment parasitemia. The cure rates on day 28 did not differ significantly (96.7% for the artesunate group, 100% for the quinine-tetracycline group). Five men in the artesunate group and nine in the quinine-tetracycline group had Plasmodium vivax in the peripheral blood between days 13 and 24, suggesting that these two regimens are not effective during the intrahepatic stage of plasmodia. 29 patients in the quinine-tetracycline group had tinnitus, while no one in the artesunate group did (p = 0.000001). Nausea and dizziness were common in both groups (45% for the artesunate group and 60% for the quinine-tetracycline group; 52% and 48%, respectively). Vomiting was more common in the quinine-tetracycline group (91% vs. 26%; p = 0.000005). Seven patients in the artesunate group had bradycardia, mostly during days 2-7. Convulsions occurred in one patient in the artesunate group 21 days after the first dose. They may have been caused by malaria, but artemisinin compounds have had central nervous system effects. These findings suggest that 700 mg artesunate is an effective antimalarial in areas with multiple-drug resistant parasites. Health workers should monitor its side effects, especially neurotoxicity, closely.
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PMID:Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria. 820 43

In 1991 and 1992, a prospective randomized trial was conducted on the northern Thai-Cambodian border. That trial compared the efficacy and tolerance of two mefloquine regimens for the treatment of uncomplicated Plasmodium falciparum malaria in an area with multi-drug-resistant P. falciparum. The resolution of fever and other symptoms was faster with high-dose mefloquine (25 mg/kg of body weight [M25 group; n = 68]) than with the conventional 15-mg/kg dose (M15 group; n = 71). There were no early treatment failures (days 7 to 9) in the M25 group, but there were 5 (7%) treatment failures in the M15 group (P = 0.03). The incidences of treatment failures by day 28 were 40% with the M15 group and 11% with the M25 group (P = 0.0004). By day 42, these values had risen to 50 and 27%, respectively (P = 0.01). The risk of treatment failure was highest in children (relative risk, 2.1; 95% confidence interval, 1.3 to 3.4) and patients with posttreatment diarrhea (relative risk, 2.0; 95% confidence interval, 1.3 to 3.1). Over half of the recrudescences in the M25 group occurred between days 28 and 42, whereas 17% of the recrudescences in the M15 group occurred between days 28 and 42 (P = 0.02). Thus, the sensitivity of assessment was significantly increased with longer follow-up. Treatment failure was associated with a delayed parasite clearance and an inadequate hematological recovery. Upper gastrointestinal side effects and dizziness were significantly more common in the M25 group, but overall, the high dose was relatively well tolerated, in particular by children. An increase in the dose to 25 mg/kg can prolong the therapeutic use of mefloquine in areas with multi-drug-resistant P.falciparum malaria where high-grade resistance to mefloquine is still rare.
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PMID:Comparison of two mefloquine regimens for treatment of Plasmodium falciparum malaria on the northeastern Thai-Cambodian border. 823 16

The antimalarial efficacy of halofantrine was compared with mefloquine in an open-label, randomized comparative trial in adult male patients with acute uncomplicated falciparum malaria. Twenty-eight patients received halofantrine and 27 received mefloquine. Halofantrine was administered in 3 doses of 500 mg at 6 hour intervals and mefloquine was administered in divided doses of 1,250 mg or 1,500 mg depending on whether the patients weighed less than or more than 60 kg. The patients were followed for 42 days and observed for drug tolerance and evidence of recrudescence. Response to treatment was favorable with both drugs, but three patients (two treated with halofantrine and one with mefloquine) did not completely eliminate malaria parasites from peripheral blood films in seven days. The parasite and fever clearance times were 75.6 and 55.7 hours, and 80.1 and 61.3 hours, respectively for halofantrine and mefloquine. However, 12 patients recrudesced during the 42 day follow-up period. Nine of these had been treated with halofantrine and three with mefloquine. The 42-day cure rate for the two drugs was 56% and 84%, respectively. The side-effects of halofantrine and mefloquine were comparable and transient. These are diarrhea, dizziness, orthostatic hypotension and black out. However, vomiting was found to be more common in mefloquine group (41% vs 22%).
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PMID:Clinical trials with halofantrine in acute uncomplicated falciparum malaria in Thailand. 836 5

Thirty-three female patients suffering from acute uncomplicated falciparum malaria were treated with intramuscular artemether for 5 days during May-October 1990. Fourteen patients received 160 mg as an initial dose, followed by 80 mg daily for 4 days. Nineteen patients with low body weight (mean weight of 36.5 kg) were given artemether at 3.2/kg as a loading dose and followed by 1.6 mg/kg/dose for another 4 days. The geometric mean of parasitemia was 17,378/microliters (range 640-234,720). The mean fever (FCT) and parasite clearance time (PCT) were 41.8 and 49.4 hours, respectively. Two patients had probable intercurrent infection with FCT of over 7 days. Thirty-one patients had completed the 28-day follow-up. The cure rate was 90.3% (28/31). Three patients had RI type of response. Mild and transient adverse effects were experienced in eleven patients; these consisted of pain at the injection sites, vomiting, dizziness, abdominal pain, palpitation and diarrhea. These symptoms may in part be due to symptom complex of malaria. The MIC of chloroquine, quinine, quinidine and mefloquine was performed in all patients but only 25 isolates were successfully cultured and tested. The MIC of all tested drugs were shown to be higher than that of previous studies, suggesting that there is a rapid increase of mefloquine resistant strains of falciparum malaria. In conclusion, artemether proves to be effective against multiple drug resistant falciparum malaria (including mefloquine resistant strains) and can be considered as an alternative antimalarial to mefloquine. The drug was well tolerated in female patients with mild and transient side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intramuscular artemether in female patients with uncomplicated falciparum malaria. 836 6

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too toxic for humans, has been the antimalarial of choice for 40 years. While a range of serious CNS effects have been documented during chloroquine therapy, the incidence is unclear (extrapyramidal symptoms occur with an incidence of 1 in 5000). Amodiaquine has a higher incidence of mild CNS effects than chloroquine. Mefloquine therapy causes dose-related transient dizziness. Serious CNS events during mefloquine therapy occur in 1:1200 Asians and 1:200 Caucasians/Africans. Risk factors include dosage, concomitant drug use/interactions, previous history of a CNS event and disease severity. Retreatment (within a month) increases the risk in Asians 7-fold. Studies indicate that the frequency of serious CNS events with mefloquine prophylaxis (1:10,000) is similar to that with chloroquine (1:13,600). Quinine causes cinchonism at standard therapeutic doses. High-tone hearing loss occurs, but irreversible auditory or ocular effects are very rare. The artemisinin derivatives are associated with dose-dependent brain lesions in rodent, canine and nonhuman primates. At low doses, histological injury has been demonstrated, without clinical neurological signs. No significant toxicity has been reported in humans. Other antimalarial drugs are seldom associated with CNS adverse events. Data do not suggest a need to diminish the correct use of the quinoline derivatives. Irreversible effects are extremely rare and usually associated with overdosing or prior history of a serious CNS event. Concomitant therapeutic use of 2 drugs from the same family, or retreatment with the same drug, should be avoided. Onset of drug-associated serious CNS events requires drug discontinuation and future avoidance of the drug.
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PMID:CNS adverse events associated with antimalarial agents. Fact or fiction? 852 12

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

From June until October 1993, a battalion of Dutch marines was stationed in Cambodia for a United Nations deployment. In 73 volunteers who used mefloquine as malaria chemoprophylaxis, possible mefloquine-related adverse events were monitored with special emphasis on QT prolongation. All participants started mefloquine chemoprophylaxis with a loading dose (250 mg a day for three days) one week before departure, followed by a weekly dose (250 mg) for approximately 25 weeks. One month before (t - 1) and one (t + 1) and three (t + 3) months after mefloquine prophylaxis was started, an at rest electrocardiogram was made. Frequency, PR-, and QT-intervals were measured; blood samples for liver transaminases, total white blood cell count, and mefloquine concentration were obtained after one and three months. Adverse events such as dizziness, headache, coordination problems, and nausea were spontaneously reported in one (1.4%) and three (4.1%) persons at t + 1 and t + 3, respectively, while specific questioning revealed adverse events in nine (12.3%) and five (6.9%) persons, respectively, at the same time point. Three months after starting chemoprophylaxis, the heart rate at rest and total white blood cell count were lower (P < 0.05), while the QTc-interval was longer and levels of liver transaminases increased (P < 0.05), although both were still within the normal range. There was no extreme prolongation of the QTc-interval or increased levels of liver transaminases that resulted in a need to stop the chemoprophylaxis. No accumulation of mefloquine in the serum occurred, and no relationship was observed between the incidence of adverse events and serum mefloquine concentrations. The incidence of self reported mefloquine-related adverse events was low. In conclusion, mefloquine chemoprophylaxis was safe and well-tolerated in this group.
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PMID:Tolerance of mefloquine chemoprophylaxis in Dutch military personnel. 878 Apr 66


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