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Query: UMLS:C0024530 (malaria)
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A randomized double blind study was performed to evaluate the tolerance and the acceptance of mefloquine alone (Lariam) compared to a combined drug regimen consisting of mefloquine, sulfadoxine and pyrimethamine (MSP; Fansimef) in the prophylaxis of malaria. 175 Europeans travelling to different malaria endemic areas received either mefloquine alone (250 mg/week) or its combination with sulfadoxine (500 mg/week) plus pyrimethamine (25 mg/week). One person taking mefloquine and two taking MSP discontinued the drug intake because of moderate clinical side effects. Mild and moderate adverse clinical reactions predominantly concerning the gastro-intestinal tract and the autonomous nervous system were reported with a significantly higher occurrence in the MSP group. With both prophylactic regimens, reversibly elevated liver enzyme activities (glutamate oxalate transaminase and glutamate pyruvate transaminase [GPT]) were observed after prophylaxis. The increase of GPT serum activity correlated significantly with relatively high GPT levels before prophylaxis in both groups. This finding suggests a limited use of both regimens in cases of liver dysfunction. One case of mefloquine-resistant Plasmodium falciparum malaria was observed from West Africa; this patient was cured by a standard regimen of chloroquine.
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PMID:Tolerance of mefloquine alone and in combination with sulfadoxine-pyrimethamine in the prophylaxis of malaria. 269 82

Some 200 cases of malaria are officially reported yearly in Switzerland. It is estimated that 2000-8000 Swiss travellers are infected by the anopheles mosquito annually, with 90% protected by chemoprophylaxis. An attack of malaria appears to have a better prognosis when the symptoms start in Africa, since treatment is initiated immediately, than in industrialized countries where the mortality is 1-4%. Failure to inquire into travel history is often responsible for the delay in initiating treatment. Severe falciparum malaria is treated by repeated slow quinine infusions followed by 1500 mg sulfadoxine, 75 mg pyrimethamine and 750 mg mefloquine (single dose). This adult dose corresponds to 3 tablets of Lariam and 3 of Fansidar (or 3 of Fansimef). The increase in chloroquine resistance among falciparum strains has led to the use of Fansidar for chemoprophylaxis, followed by the use of mefloquine when Fansidar resistance occurs. The dosage of mefloquine is 250 mg weekly (1 tablet Lariam) for 4 weeks, followed by 1 tablet every fortnight. Treatment is continued for 1 month after return. If the risk of transmission is low, chemoprophylaxis may be replaced by prescription of a reserve drug to be taken in case of fever and headache. A sulfadoxine-pyrimethamine-mefloquine combination (i.e. 3 tablets Fansimef) has been tested in this indication. Ineffective chemoprophylaxis may lead to atypical clinical syndromes, e.g. anemia, hepatosplenomegaly and jaundice, without episodes of fever. HIV positive subjects may risk travelling in tropical countries if they have undergone correct chemoprophylaxis.
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PMID:[Malaria in Switzerland]. 306 91

A 42-year-old man was admitted to hospital with, previously wrongly diagnosed, fulminant falciparum malaria, 14 days after a two-week trip to Kenya. He had a high fever and was jaundiced, with severe anaemia and thrombocytopenia. He was given quinine intravenously and pyrimethamine/sulfadoxine (Fansidar) by mouth. He developed acute renal failure and increasingly severe cerebral symptoms, at times coma. An exchange transfusion and several plasmaphereses were, therefore, performed. The cerebral symptoms quickly abated during the exchange transfusion, but renal function failed to improve. Because of continuing fever, mefloquin (Lariam) and doxy-cycline (Vibramycin) were also administered. After several dialysis periods the patient improved gradually and was discharged after three weeks in generally good condition with normal renal function.
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PMID:[Exchange transfusion and (or) plasmapheresis: effective measures in severe tropical malaria?]. 328 61

In different countries opinions differ as to which chemotherapeutic methods should be used for malaria prophylaxis. It has long been the opinion of the Nordic countries, that WHO should give an official recommendation and the result is reflected now in the publication "Vaccination certificate requirements and health advice for internation travel." The malaria-endemic regions of the world are divided into 3 categories: regions without risk and no need for prophylaxis, low risk regions (A) with predominantly vivax inflections, risk regions (B) with predominantly chloroquine sensitive P. falciparum, and high risk regions (C) with often both chloroquine as well as sulfa/pyrimethamine resistance. Chloroquine is a sufficient prophylaxis for A-regions. For B-regions proguanil should be added and for C-regions only mefloquine is given. Proguanil was reintroduced basically because of Swedish research results in Liberia. An American initiative recommends for all regions, A-C, chemorprophylaxis as an alternative. However, a precondition is an observant traveller and clear instructions for self-treatment. Travellers who fall ill in a B-region should choose between Fansidar, mefloquine and quinine for self-treatment. Mefloquine has the least serious side effects, whereas quinine is therapeutically more safe. Fansidar very seldom gives any side effects. For C-regions only mefloquine is recommended for self-treatment. Nordic colleagues have recommended to double prophylaxis (chloroquine + Paludrine) treatment for the entire African tropical region. For short-time travellers to Kenya, Tanzania and Uganda, 6 tablets Lariam should be added. Only chloroquine is recommended for India and the Amazon region of South America. No chemoprophylaxis can guarantee full protection. Insect protection is therefore more important than ever. Malaria decreases the unspecific immune defense system. Surprisingly, repeated tests have shown that the AIDS frequency is not higher in patients with chronic malaria than for persons without plasmodia in the blood. In WHO's new little yellow booklet, a page concerning prophylaxis against AIDS appears. Equipment that is not new should be steamed or cooked for a least 20 minutes or treated with chemical disinfectants for at least 30 minutes. These measures should be enough to prevent HIV-infection.
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PMID:[Malaria and HIV prevention in WHO's "little gem"]. 338 44

Prophylactic drug monitoring of mefloquine and its carboxylic acid metabolite were studied in two patients with end-stage renal disease undergoing long-term hemodialysis treatment. The patients, short-term travellers to areas where malaria is endemic, took 250 mg of mefloquine (Lariam) once weekly for 2 weeks before and during their 3-week stay abroad and for one week after their return. Pre- and postdialysis blood samples were drawn before their departure and after their return. The concentration-time profiles of mefloquine and its metabolite in plasma samples taken before and after the 3- to 4-h dialysis sessions were similar. Mefloquine and its metabolite could not be detected in the dialysate. These findings show that mefloquine and its metabolite are not, or are very poorly, removed by hemodialysis. Concentrations in plasma and accumulation kinetics were similar to those reported for healthy volunteers and were associated with high prophylactic efficacy against malaria. No special dosage adjustments have to be made in patients undergoing hemodialysis treatment to achieve concentrations in plasma similar to those in healthy volunteers. The prophylactic dose of mefloquine could be given before, during, or after the hemodialysis session.
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PMID:Influence of hemodialysis on plasma concentration-time profiles of mefloquine in two patients with end-stage renal disease: a prophylactic drug monitoring study. 748 43

Two studies were conduct in Thailand in order to find appropriate falciparum malaria prophylactic drug regimens. The first study was done during June - September 1987 with 363 soldiers who received Fansimef (MSP) 1 tab/week (group 1), 337 soldiers who received MSP 1 tab/2 week (group 2) and 165 soldiers who received chloroquine 300 mg base weekly plus Fansidar 1 tab/week (group 3). At the end of the study there were 9 and 13 falciparum malaria episodes in groups 1 and 2, respectively, with incidence rates of 0.8 and 1.8 cases/100 person-months (P-M). In group 3, the corresponding values were 30 episodes and an incidence of 7.2/100 P-M. For the second study which lasted from October 1987 - January 1988 in the same area, 498 soldiers were given Fansimef 1/2 tab/week (group 4), 499 soldiers were given Lariam 1/2 tab/week (group 5) and 247 soldiers were given chloroquine plus Fansidar (group 6). Thirty malaria episodes were found in group 4, for an incidence of 2.0/100 P-M. In group 5, 23 episodes were found, for an incidence of 1.6/100 P-M. In group 6, 74 episodes occurred, ie an incidence of 12.2/100 P-M. The incidence rates of malaria among Fansimef 1 tab weekly, Fansimef half dose weekly or Lariam half dose weekly were not significantly different but were different from chloroquine plus Fansidar groups. Adverse events in each group were mild.
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PMID:Prevention of Plasmodium falciparum malaria by Fansimef and Lariam in the northeastern part of Thailand. 793 38

In the absence of a suitable malaria case definition, reliable surveillance data on the impact of malaria are not available. Determinants of case loads, including population movements, environmental changes, lack of political commitment and resources, and resistance to antimalarials and residual insecticides, work towards global deterioration. Some 90% of the Plasmodium falciparum burden is carried by Africa south of the Sahara. There, in 1992, the number of children under five years of age and exposed to high risk was about 106 million. Assuming a malaria attack rate of 0.5-1.5 per child per year, and a case fatality rate of 2%, annual clinical cases and malaria deaths in this population alone come to 53-160 million and 1-3 million, respectively. Roche, a pharmaceutical company with major research efforts in tropical medicine, in collaboration with research centers and international institutions, has recently set up a tropical medicine unit that coordinates and concentrates corporate efforts in this field. The unit aims to make affordable and innovative products available which are effective against major tropical diseases. A commercial product of the unit is Lariam, a major antimalarial used alone or in simultaneous or sequential combinations. The single dose combination of Lariam plus Fansidar (Fansimef) is particularly useful for stand-by or emergency oral therapy. Artemisinine, or its derivatives, followed by one to two doses of Lariam are effective against severe and multiresistant P. falciparum malaria. A new Roche peroxide antimalarial is currently in phase II clinical trials. The unit is also involved in research and development of malaria sporozoite and asexual blood stage vaccine candidates.
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PMID:Commitment of Roche in malaria and other tropical diseases. 825 5

One hundred and five healthy nonimmunes in Colombia took part in a randomize, double-blind comparison of 250 mg of Lariam (L) (active ingredient: mefloquine) on alternate weeks or one tablet of Fansidar (F) (active ingredients: sulfadoxine and pyrimethamine) weekly for malaria prophylaxis during at least six months. Volunteers also gave blood for determination of drug concentrations after six months and/or 24-27 months of prophylaxis. Twenty-five volunteers withdrew involuntarily when they lost their jobs in the company. Two who took L withdrew due to moderate diarrhea and mild nausea or headache, weakness, drowsiness and anxiety. One volunteer stopped taking F due to severe unilateral hypostatic eczema and slight S-T depressions on the ECG. The rest completed at least six (range 6-36) months of prophylaxis. The mean half-life for L was 26 days. The AUCs in the time interval 0-14 days for L varied between 19.3-31.5 mumol x days/l. For the main metabolite, the corresponding range was 28.8-81.3 mumol x days/l. The range of trough concentrations at day 0 and 14 were 0.95-2.01 mumol/l for L and 1.69-5.62 mumol/l for the metabolite. No differences in tolerability and efficacy were noted between L and F. Our kinetic results do not indicate that enzymatic induction or inhibition would be important during long-term prophylaxis with mefloquine. This favors a continued use of the drug for very long periods of time (= years).
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PMID:Comparative tolerability and kinetics during long-term intake of Lariam and Fansidar for malaria prophylaxis in nonimmune volunteers. 825 6

Stand-by therapy is the first treatment of a presumptive malaria by the traveller. Goals and possible indications are listed and the mode of application described. Information of the traveller by the physician is time consuming but very important for the correct use of stand-by therapy. The central message is the instruction to visit a doctor within 12 to 25 hours after intake of stand-by therapy, to avoid the risk of missing other diseases with similar symptoms. Fansimef and Lariam, recommended in Switzerland for stand-by therapy of malaria, are shortly reviewed.
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PMID:[Emergency treatment of malaria during travel]. 837 76

The development of acute neuropsychiatric symptoms in a 10-year-old boy subsequent to his return from travel abroad in Africa, where he had taken the antimalarial agent mefloquine (Lariam), is reported. A 4-week course of cognitive-behavioral therapy was used to effectively treat this substance-induced anxiety disorder, which had been caused by treatment with mefloquine. A review of the literature about adverse neuropsychiatric effects of mefloquine and the differential diagnosis of malaria is provided. In an age in which international travel is occurring with increasing frequency, it is important to obtain travel histories, including exposure to prophylactic medication, when patients present with acute-onset psychiatric symptoms.
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PMID:Case study: neuropsychiatric symptoms associated with the antimalarial agent mefloquine. 939 47


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