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Query: UMLS:C0024530 (malaria)
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To compare the therapeutic efficacy of oral artesunate and artemether in combination with mefloquine for the treatment of multidrug resistant malaria, a trial was conducted in 540 adults and children on the Thai-Myanmar border. Three regimens were compared: artesunate (4 mg/kg/d for 3 d), artemether (4 mg/kg/d for 3 d), both in combination with mefloquine (25 mg/kg), and a single dose of mefloquine (25 mg/kg). The artesunate and artemether regimens gave very similar clinical and parasitological responses, and were both very well tolerated. There was no significant adverse effect attributable to the artemisinin derivatives. Fever and parasite clearance times with mefloquine alone were significantly longer (P < 0.001). After adjusting for reinfections the failure rates were 13.9% for the artesunate combination, 12.3% for the artemether combination and 49.2% for mefloquine alone (P < 0.0001; relative risk 3.8 [95% confidence interval 2.6-5.4]). Mefloquine should no longer be used alone for the treatment of multidrug resistant falciparum malaria in this area. Three-day combination regimens with artesunate or artemether are well tolerated and more effective.
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PMID:Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria. 856 May 31

Drug resistance is a major problem in malaria. The resistance mechanism remains unresolved but contributing factors are probably heavy drug use, parasite selection, cross resistance and genetic influences of drugs. Plasmodium ovale en P. malariae are sensitive to the current antimalarial drugs. P. vivax has some chloroquine resistant strains, notably on Papua New Guinea, Irian Jaya and other islands in the Pacific. The geographical distribution of P. falciparum strains resistant to proguanil and pyrimethamine is not well known. Chloroquine-resistant strains are found in South East Asia, the Amazon region (almost 100% resistance in both regions) and in Africa south of the Sahara (resistance not everywhere 100%). Sulfadoxine-pyrimethamine is not an effective treatment in South East Asia and the Amazon region; it is useful in tropical Africa. Mefloquine resistance is a problem mainly confined to Thailand. There is cross resistance between halofantrine and mefloquine. Decreased sensitivity to quinine was reported from Thailand, but it remains an effective drug, notably when given in combination with tetracycline or doxycycline. In cases of severe or complicated malaria intravenous quinine is still the preferred therapy. Resistance to artemisinine has not yet been reported. Pharmaceutical companies show little interest in antimalarial drug development, which in view of the increasing drug resistance is a matter of great concern.
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PMID:[Malaria and drug resistance]. 861 36

Three Dutch marine battalions (n=2289) serving in Western Cambodia during 1992-1993 used mefloquine as weekly malaria chemoprophylaxis. One battalion started with a loading dose. Full compliance with prophylaxis was reported by 86.3%, and possible mefloquine-related adverse events were reported by 30.2%. Sixty-four periods of malaria were diagnosed in 59 marines. During deployment, 31 Plasmodium falciparum and no Plasmodium vivax infections occurred. After return, there were 11 cases of falciparum malaria and 22 of vivax malaria, 16-72 days and 30-540 days, respectively, after stopping prophylaxis. Mefloquine-resistant parasites were isolated from 4 Dutch and 4 Khmer patients. Long-term mefloquine prophylaxis was well tolerated but not totally effective.
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PMID:Long-term malaria chemoprophylaxis with mefloquine in Dutch marines in Cambodia. 864 31

Increasing drug resistance in Plasmodium falciparum and a resurgence of malaria in tropical areas have effected a change in treatment of malaria in the last two decades. Symptoms of malaria are fever, chills, headache, and malaise. The prognosis worsens as the parasite counts, counts of mature parasites, and counts of neutrophils containing pigment increase. Treatment depends on severity, age of patient, degree of background immunity, likely pattern of susceptibility to antimalarial drugs, and the cost and availability of drugs. Chloroquine should be used for P. vivax, P. malariae, and P. ovale. P. vivax has shown high resistance to chloroquine in Oceania, however. Primaquine may be needed to treat P. vivax and P. ovale to rid the body of hypnozoites that survive in the liver. Chloroquine can treat P. falciparum infections acquired in North Africa, Central America north of the Panama Canal, Haiti, or the Middle East but not in most of Africa and some parts of Asia and South America. In areas of low grade resistance to chloroquine, amodiaquine can be used to effectively treat falciparum malaria. A combination of sulfadoxine-pyrimethamine is responsive to falciparum infections with high grade resistance to chloroquine. Mefloquine, halofantrine, or quinine with tetracycline can be used to treat multidrug-resistant P. falciparum. Derivatives of artemisinin obtained from qinghao or sweet wormwood developed as pharmaceuticals in China are the most rapidly acting of all antimalarial drugs. Children tend to tolerate antimalarial drugs well. Children who weigh less than 15 kg should not be given mefloquine. Health workers should not prescribe primaquine to pregnant women or newborns due to the risk of hemolysis. Chloroquine, sulfadoxine-pyrimethamine, quinine, and quinidine can be safely given in therapeutic doses throughout pregnancy. Clinical manifestations of severe malaria are hypoglycemia, convulsions, severe anemia, acute renal failure, jaundice, pulmonary edema, cerebral malaria, shock, and acidosis. Health workers should be prepared to treat these symptoms accordingly.
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PMID:The treatment of malaria. 904 53

Plasmodium falciparum causes the most severe form of human malaria which directly results in over two million deaths per year. As there is not yet a useful vaccine against this disease the major form of treatment and control is the use of chemotherapeutic agents. Unfortunately the parasite has managed to devise mechanisms that allow it to evade the action of almost all the antimalarials in our arsenal. The antifolate drugs include the dihydrofolate inhibitors pyrimethamine and proguanil as well as the sulfones and sulfonamides. These antimalarials act on enzymes in the folate pathway. The mechanism of resistance to these compounds involve mutations in the target enzyme that decrease the affinity of binding of the drug. A second major group of antimalarials include the quinine-like compounds. Quinine was one of the first compounds used to treat malaria and the related drug chloroquine is the most important antimalarial. Mefloquine and halofantrine were developed in response to major problems with the spread of chloroquine resistance. Chloroquine resistance is due to the ability of the parasite to decrease the accumulation of the drug in the cell. The exact mechanism that allows this is still under investigation although at least one protein has been identified that affects the accumulation of this important antimalarial.
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PMID:Mechanisms of drug resistance in malaria. 877 Mar 61

Plasmodium falciparum in south-east Asia is highly resistant to chloroquine and sulfadoxine-pyrimethamine. Mefloquine used to be the chemosuppressant drug of choice in areas with chloroquine resistance. However, sensitivity to this drug has recently decreased in Thailand, Cambodia and Myanmar, and there is no suitable single alternative drug. We therefore investigated possible alternative combination therapies for multidrug resistant falciparum malaria. 120 male Thai patients at Makarm Malaria Clinic, Chantaburi, in eastern Thailand were allocated at random to receive either oral artemether (group A) or artesunate (group B) at a single dose of 300 mg on day 1, both followed by mefloquine, 750 and 500 mg at 24 and 30 h, respectively. Follow-up was on days 1, 2, 7, 14, 21, 28, 35 and 42. Patients in both groups had a rapid initial response to treatment; in most cases parasitaemia was cleared within 24 h, and fever was cleared within 24 h in 62% and 76.7% of the patients in groups A and B, respectively. 58 patients in group A and 57 in group B completed follow-up and cure rates were 98% and 97%, respectively. Reinfection could not be excluded for the 3 patients with recrudescences; all were cured with a repeated course of treatment. No serious adverse effect was observed in either group, only mild and transient nausea, vomiting and loss of appetite, with no significant difference between the 2 groups. These results suggest that a single oral dose of 300 mg of either artemether or artesunate followed by 1250 mg of mefloquine in 2 divided doses is effective against multiple drug resistant falciparum malaria. Either regimen can be considered as a suitable 'stand-by' in endemic areas of multiple drug resistant falciparum malaria.
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PMID:Artemether or artesunate followed by mefloquine as a possible treatment for multidrug resistant falciparum malaria. 888 93

Morbidity and mortality due to malaria remains an important health problem for travelers visiting endemic zones. In this population, typical episodes of chills and fever followed by diaphoresis are not always observed; inaugural signs may limited to low-grade fever accompanying digestive disorders. Early diagnosis is nevertheless essential to prevent progression to acute pernicious malaria. Blood smears, quantitative butty coat (QBC) test or the Parasight test can give rapid diagnosis. Chloroquine is the drug of choice for Plasmodium vivax, P. ovale or P. Malariae infection, but chloroquine-resistant P. falciparum is widespread in tropical zones and resistant P. vivax has been reported in Indonesia. Currently, halofantrine is the best treatment for P. falciparum infection, although cardiac toxicity may occur in patients with a long QT on the electrocardiogram. Mefloquine can be alternative. The sulfadoxine-pyrimethamine combination is also used in many tropical zones because of its low cost and availability, but many resistant strains of P. falciparum have been identified. Use of quinine is also widespread in tropical zones. This basic antimalarial is rapidly effective but is also rapidly eliminated, necessitating repeated oral doses. Intramuscular injection may provoke necrosis. The main indication for quinine is acute pernicious P. falciparum malaria, but the drug is also used for simple episodes of fever in many tropical zones. Symptomatic care including fluid replacement, oxygen, transfusion, diuretics, respiratory assistance and dialysis may also be required in some cases. Use of corticosteroids or exsanguinotransfusion remains a question of debate. When administered rapidly, fever should regress within a few days. Neurological sequellae are exceptional after acute pernicious malaria in adults but may occur approximately 5% of children, emphasizing the importance of associating chemoprophylaxis and protection against insect bites. There has been much publicity concerning a vaccine, but results to date have been disappointing.
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PMID:[Malaria: what treatment today?]. 909 64

Fenozan B07, a 1,2,4-trioxane endoperoxide with potent blood schizontocidal activity against drug-sensitive and drug-resistant rodent malaria parasites, exerted a modest potentiating action when administered with chloroquine (CQ) to mice infected with parasites of the CQ-resistant P. yoelii ssp. NS, but not when given to mice infected with the CQ-sensitive P. berghei N strain. The reason why this potentiation may be of particular value in the treatment of severe falciparum malaria is discussed. Mefloquine and halofantrine displayed a similar level of potentiation with Fenozan B07 against the CQ-resistant parasites. However, antagonism was shown by combinations of Fenozan B07 with pyronaridine or the 8-aminoquinoline WR 238 605 when used against CQ-resistant parasites. Mefloquine with Fenozan B07 is also antagonistic against a highly mefloquine-resistant line of P. yoelii ssp. NS. The reasons behind such antagonism are not known. The importance is stressed of using carefully selected drug combinations of novel antimalarials, rather than single drugs, in order to impede the selection of drug-resistant parasites, but only after adequate, preclinical, toxicity testing.
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PMID:The chemotherapy of rodent malaria. LIV. Combinations of 'Fenozan B07' (Fenozan-50F), a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane, with other drugs against drug-sensitive and drug-resistant parasites. 909 27

Parasitic diseases are closely related to the lack of sanitation (unavailability of potable water, inadequate disposal of human waste, lack of latrines) or the absence of personal hygiene. They are also closely linked to warm and humid climates, and are therefore considered tropical diseases. This chapter addresses chronic hookworm parasitosis and malaria, and their effect on women's health. Of all Helminthes, hookworms cause the most severe anemia because of iron deficiency due to chronic blood loss. Worldwide, an estimated 51% of pregnant women suffer from anemia-almost twice as many as non-pregnant women. In severe cases (Hb < 70 g/l) the risk of perinatal maternal and child death increases up to 500-fold. Anemia due to maternal deficiency affects the fetus, causes retarded intrauterine growth, and reduces fetal ability to absorb iron provided by the mother. Hookworms are nematodes that infect roughly 1 billion people. Their preferred habitat is the jejunum, where they attach to the mucous tissue to feed, and secrete an anticoagulant causing bleeding. Hookworm infections often begin in childhood. The worm enters the body through the skin and reaches the highest number at the end of adolescence and young adulthood. Little attention has been given to the treatment of pregnant women because of unavailability of safe antiparasitic drugs and fear of teratogenesis. However, there are new treatments, and the anthelminthic drugs may be administered in schools and organized women's groups in communities. During pregnancy anthelminthic treatment can improve maternal, fetal and infant health. Treatment given every 4 months has been shown to interrupt the transmission cycle of the parasite and help to improve the iron status of all women. Therapeutic strategies should be linked to other measures, such as promoting the use of shoes, introduction of potable water, education and treatment of the population at large, especially the school-age population. An estimated 267 million people are annually infected by malaria, a parasitic disease caused by Protozoa of the genus Plasmodium. Malaria is transmitted by the Anopheles mosquito and is highly prevalent in tropical and subtropical regions located between 40 degrees latitude North and 30 degrees latitude South. It causes acute attacks that leave the human body in such a poor state that health problems resulting from these attacks become chronic. Due to the high mortality and morbidity associated with it, malaria is considered the most serious of tropical diseases and a major public-health dilemma. Pregnant women are at high risk of becoming infected, as well as children in their first years of life. In pregnant women, malaria can cause anemia which can be the major cause of maternal mortality, especially during the first pregnancy. Malaria can also cause fetal anemia which frequently results in retarded intrauterine growth and low birth weight. Prophylactic treatment with antimalarial drugs during pregnancy is recommended in areas where the disease is endemic. The prophylactic treatment should focus primarily on primiparous women who are most susceptible. Chloroquine is safe and effective for antimalarial prophylaxis, and is not teratogenic. Proguanil is also safe for prophylactic use during pregnancy, particularly in areas where P. falciparum is resistant to chloroquine. Mefloquine may be used during the third trimester of pregnancy, only if other antimalarial drugs are unavailable or ineffective.
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PMID:Effects of chronic parasitosis on women's health. 925 75

Individuals from industrialized nations frequently travel to countries with malaria, so health care providers need to be familiar with current recommendations for prevention of malaria. Changes in drug susceptibility of malaria parasites and evolving knowledge of how well drugs are tolerated necessitate periodic review of guidelines for prophylaxis of malaria, especially of chloroquine-resistant Plasmodium falciparum malaria. Mefloquine is the drug of choice for chemoprophylaxis for most travelers, with doxycycline and chloroquine being less effective alternatives. Mefloquine is well tolerated at prophylactic dosages, but anecdotal reports have raised concerns about its adverse effects. Resistance to this drug has emerged in parts of Southeast Asia and may spread to other regions of the world. The major disadvantages of doxycycline are the need for daily dosing, its contraindication for young children and pregnant women, and its adverse effects. Chloroquine is effective for prophylaxis only in Central America, the Caribbean, and parts of the Middle East. Few new drugs will be available in the near future because of reduced funding for antimalarial drug research and development; therefore, the usefulness of currently available drugs needs to be prolonged by rational use. Increased efforts should be made to ensure that alternative drugs will be available for prevention of malaria.
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PMID:Update on prevention of malaria for travelers. 980 26


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