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)

Mefloquine is an orally administered blood schizontocide. Initial dose-finding and comparative studies performed between 1977 and 1989 demonstrated efficacy of mefloquine as prophylaxis in nonimmune individuals and in the suppression and treatment of malaria in adults and children caused by multidrug-resistant Plasmodium falciparum. It was also effective against P. vivax infection, while data concerning the treatment of P. ovale and P. malariae infections were limited. In an attempt to delay the emergence of resistance to this promising antimalarial agent, mefloquine was combined with sulfadoxine and pyrimethamine. Although initial clinical trials indicated that this regimen was effective in preventing and treating falciparum malaria, recent treatment failures, the potential for severe dermatological reactions and lack of therapeutic advantage over mefloquine alone has prompted the World Health Organization to recommended that the combination be no longer used for treatment or prophylaxis of malaria. Mefloquine is generally well tolerated in both adults and children, with nausea, vomiting, diarrhoea, headache, dizziness, rash, pruritus and abdominal pain being the most common adverse effects, although it is difficult to distinguish between disease- and treatment-related events. The incidence of these adverse effects is similar to or lower than those observed with other antimalarial agents. Cardiovascular changes, such as bradycardia, occasionally occur. The most notable adverse effects associated with mefloquine are neuropsychiatric disturbances; precipitation of such events should be closely monitored and requires termination of prophylaxis or therapy. The eventual emergence of resistance to mefloquine, as with many other antimalarial agents, was inevitable. Mefloquine resistance is established in certain areas of Thailand and may be becoming a growing problem in other regions of the world. In order to preserve the efficacy of mefloquine in non-resistant areas, this useful agent should be used with care and only prescribed for prophylaxis in travellers and treatment in areas of multidrug-resistant plasmodia. Future options to combat mefloquine resistance may include the combination of mefloquine with other antimalarial agents such as qinghaosu derivatives. Thus, with cautious use and possible combination with other agents, mefloquine is likely to remain an important treatment option for falciparum malaria, a widespread parasitic disease for which an increasing number of drugs have proved inadequate.
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PMID:Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. 768 11

To facilitate the design of malaria prevention and control programs in tropical Africa, a qualitative investigation of treatment seeking behaviors and perceptions of the causes and symptoms of malaria was conducted in a rural area in South Western Uganda's Masaka District. Components of the investigation included focus group discussions involving 42 participants recruited from women's clubs and prenatal and child health clinics, semi-structured interviews with 395 female outpatients 13 years of age and above and adult women escorting young children to government subdispensaries for treatment of a new malaria episode, and household interviews with 64 mothers. In this rural community, there is no specific word for malaria; rather, the word "omusujja" is used to refer to malarial symptoms as well as any kind of fever. Respondents consistently identified omusujja as the most prevalent, serious disease in their community. They linked its causation to food and drink, environmental conditions, vectors such as mosquitoes, and other illnesses. There was widespread awareness that omusujja presents differently according to age group, e.g. fever, refusal to suck, crying, vomiting, and mouth sores in infants as compared to miscarriage, vomiting, weakness, chills, and joint pain in pregnant women. Treatment is initiated promptly, although it mainly consists of use of local herbs; if the herbs fail to reduce the fever, hospital care is sought. Preventive methods cited included boiling water, cleaning cooking utensils, avoiding raw mangoes and roasted maize, and keeping mosquitoes out of the home. Recommended is a health education campaign emphasizing the role of mosquitoes in malaria transmission and the need for prompt medical intervention.
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PMID:Recognition, treatment seeking behaviour and perception of cause of malaria among rural women in Uganda. 770 65

Malaria remains a major public health problem in large areas of the world. One of the major factors responsible for the resurgence is the emergence of Plasmodium falciparum, resistant to available antimalarials. An antimalarial, mefloquine, has been considered since its introduction as a promising alternative antimalarial drug to overcome the situation of widespread multidrug resistant P falciparum. Pharmacokinetic studies of mefloquine have been investigated in several groups of subjects either as mefloquine alone or as combined regimens. The oral absorption of mefloquine is relatively rapid, reaching peak concentrations within 24 hours. Metabolism takes place in the liver, with carboxymefloquine as a major metabolite. Mefloquine has a large apparent volume of distribution of 200 L and is highly bound (98%) to plasma proteins. The elimination is slow; the terminal half-life is 13 10 to 14 days in Thai patients with falciparum malaria. Vomiting within 1 hour of drug administration has an influence on blood concentrations of mefloquine and this may result in treatment failure. The whole blood concentrations of mefloquine on the first two days of treatment are important determinants of parasitological response. There appear to be no pharmacokinetic interactions between mefloquine and the other two components of Fansimef in patients with uncomplicated falciparum malaria. The advantage of this combination over mefloquine alone in multidrug resistant P falciparum is still debatable. However, recent data seem to support the higher efficacy of Fansimef over mefloquine alone. Concurrent administration of antibiotics, ie ampicillin and tetracycline with mefloquine results in a significant increase in maximum concentration, reduction of the apparent volume of distribution and shortening of the terminal elimination half-life of mefloquine. An antiemetic drug metoclopramide accelerates the absorption of mefloquine and increases the maximum concentration. In contrast, mefloquine concentrations are decreased in the presence of an antimalarial, artesunate. Primaquine has no effect on the pharmacokinetics of mefloquine when given concurrently.
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PMID:Clinical application of mefloquine pharmacokinetics in the treatment of P falciparum malaria. 772 Dec 26

A questionnaire survey was conducted in the Dakar region (Senegal) between August and October 1992 to investigate diagnosis and treatment practices for uncomplicated malaria attacks in the health care facilities. The sample consisted of 208 prescribers in the operational sense i.e. 20% of the following professional categories: medical doctors, health care technicians, birth attendants, qualified nurses, and auxiliary nurses. A thick smear was mentioned as a diagnostic element by 23% of the practitioners; chloroquine remained the first choice drug for 80% of the personnel but 13% declared prescribing parenteral quinine for uncomplicated malaria in patients without vomiting; halofantrine and the association sulfadoxine-pyrimethamine-mefloquine are prescribed by respectively 7 and 1% of the personnel, also in the public sector; chloroquine is prescribed in an effective dose (25-40 mg/kg) by 74% of the personnel for adults and by 43% for children; quinine base in a dose below 25 mg/kg by 100% of personnel for adults and by 99% for children; nearly half of the prescribers do not take into account the children's weight; 13% of the practitioners prescribe useless expensive symptomatic treatments and 45 to 73% ignore the price of the common antimalarials, allowing for a 10% error; health care workers have a bad knowledge of the results of chemosensitivity surveys. The development of a national malaria control programme that emphasises permanent training of the health care workers and control of therapeutic information seems mandatory.
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PMID:[Diagnostic and therapeutic management of uncomplicated malaria attacks in the Dakar region, Senegal]. 772 63

Plasmodium falciparum in Thailand is highly resistant to chloroquine and sulfadoxine/pyrimethamine and there is increasing resistance to the alternative antimalarials, quinine and mefloquine. In eastern Thailand, the cure rates of mefloquine at 750 and 1250 mg were 30% and 55%, respectively. The use of drug combinations may be necessary in areas where drug-resistant parasites exist. 159 male Thai patients in Chantaburi, eastern Thailand, were allocated at random to receive either oral artemether at a single dose of 300 mg on the first day followed by mefloquine 750 mg at 24 h and 500 mg at 30 h (group A), or oral artemether at a single dose of 300 mg on the first day, mefloquine 750 mg at 24 h and placebo at 30 h (group B). The follow-up was on days 1, 2, 7, 14, 21, 28, 35 and 42. Most patients in both groups had a rapid initial response to treatment, parasitaemia being cleared within 24 h and fever cleared within 48 h in both groups. The cure rates were 97% and 90%, respectively, for groups A and B. No serious adverse effect was seen in either group; mild and transient nausea, vomiting and loss of appetite were noted. The adverse effects did not differ between the 2 groups. The results suggested that a single oral dose of artemether (300 mg) can markedly improve the cure rate of mefloquine at a dose of 750 or 1250 mg in multiple drug-resistant falciparum malaria.
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PMID:Artemether-mefloquine combination in multidrug resistant falciparum malaria. 777 52

All children 2 years and younger with diagnosis of gastroenteritis (diarrhea and vomiting) admitted to the Eldoret District Hospital between the February and June 1992 were enrolled. ELISA test was performed for HIV for each of the 57 children. In addition, relevant tests were carried out in all cases, such as hemogram, stool for ova and cysts, blood slide for malaria parasites, and urinalysis. The ELISA results were confirmed by the Western blot for all positive cases. A total of 57 children, 32 (56.1%) males and 25 (43.9%) females were studied. All the children were 2 years or younger, with 61.4% under 9 months old. The difference with respect to distribution of HIV positivity and negativity in those under 9 months and those above 9 months was significant (p 0.001). 29 of the 57 infants (50.9%) were ELISA and Western blot positive. Of the positive cases, 23 (79.3%) were 9 months or younger, with 6 (20.7%) between 9 months and 24 months (p 0.001). Of the 33 (58.3%) patients with diarrhea of less than 14 days' duration, 12 (36.70%) were seropositive, and of the 24 (41.7%) with diarrhea of more than 14 days, 17 (70.8%) were HIV positive. The difference in the duration of diarrhea in both the positive and negative cases in the 2 groups was significant. There were 34 patients who presented with diarrhea and vomiting alone of whom 15 (44.1%) were positive for HIV, while there were 10 who presented with diarrhea and either malnutrition or pneumonia with 8 (80%) positive for HIV. Diarrhea lasting more than 14 days was a significant parameter, as 70.8% of the patients in this category were seropositive for HIV compared to 36.7% in those with diarrhea of less than 14 days' duration (p 0.02). In addition, children 0-9 months old had a higher incidence of HIV seropositivity than the older age group, especially the age group 5-9 months, 73.6% of whom were seropositive.
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PMID:HIV seropositivity in children admitted with diarrhoea at Eldoret District Hospital, Kenya. 782 Dec 40

We studied 50 cases of complicated falciparum malaria in order to evaluate the different clinical presentations. Thirty five had cerebral malaria while 15 presented with extracerebral features including diarrhea and vomiting (n = 6), hepatitis (n = 4), acute renal failure (n = 3), and gastrointestinal bleeding (n = 2). These cases were treated with quinine. Mortality was higher in extracerebral form (33.3%) as compared to cerebral malaria (22%). Our study suggests that even though cerebral malaria remains the single most important cause of high mortality in complicated falciparum malaria, extracerebral presentation of falciparum malaria is equally life threatening and should be viewed seriously.
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PMID:Complicated falciparum malaria. 789 Mar 45

Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.
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PMID:Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. 793 Jul 43

Halofantrine is a phenanthrenemethanol antimalarial that is effective against asexual forms of multidrug-resistant Plasmodium falciparum malaria. It has no action on gametocytes or hypnozoites in the liver. The drug is administered as a racemic mixture but the (+)- and (-)-enantiomers show no difference in activity in vitro. Three formulations for oral administration are available for human use, i.e. tablets, capsules and suspension. Toxicity studies in animals suggest that halofantrine has very low toxicity both in short term and long term animal studies, and there has been no evidence of mutagenicity in these studies. Phase I, II and III clinical trials of halofantrine conducted in several tropical countries found the drug to be well tolerated and effective against multidrug-resistant P. falciparum malaria when 500mg was administered every 6 hours for 3 doses. The majority of clinical adverse effects reported, including nausea, vomiting, abdominal pain, diarrhoea, orthostatic hypotension, prolongation of QTc interval, pruritus and rash, have been mild and transient. There is wide interindividual variation in halofantrine absorption. The maximal plasma concentration (Cmax) is achieved approximately 6 hours after oral administration. Bioavailability is not dose-proportional for doses over 500mg, but there is a dose-proportional increase in Cmax and area under the plasma concentration-time curve (AUC) for doses between 250 and 500mg. In patients with malaria the bioavailability of halofantrine is decreased. The mean half-life of absorption is 4 hours and Cmax is significantly lower than that obtained in healthy individuals. Furthermore, halofantrine absorption is enhanced when the drug is taken with fatty food. Therefore, halofantrine should be taken with food to ensure optimal absorption in patients with malaria. The terminal elimination half-life is 5 days in patients with malaria. Halofantrine is biotransformed in the liver to its major metabolite N-debutyl-halofantrine. Plasma concentrations of this metabolite are observed soon after administration of halofantrine, but in much lower concentrations. The elimination half-life is similar to that of halofantrine. There have been increasing reports of halofantrine treatment failure, particularly in the eastern part of Thailand. The majority of treatment failures have been associated with incomplete drug absorption. The dose-dependent cardiotoxic effects (e.g. cardiac arrhythmia) are a major concern, particularly when the bioavailability of the drug cannot be predicted. Ongoing and future studies should aim at developing more appropriate drug formulation(s) and/or optimising dosage regimens. This will allow therapeutic concentrations to be achieved with minimum adverse effects, particularly cardiotoxicity.
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PMID:Clinical pharmacokinetics of halofantrine. 795 74

To assess the validity of clinical criteria, we investigated 2096 outpatients diagnosed as malaria cases by nurses at a rural health subcentre in a highly endemic area of Papua New Guinea. 73% of the children < 10 years old had a positive blood slide for any species of Plasmodium and 32% had > or = 10,000 P. falciparum parasites per microL. For adults the frequencies were 51% and 9%, respectively. Stepwise logistic regression identified spleen size, no cough, temperature, no chest indrawing, and normal stools as significant predictors for a positive blood slide in children; no cough and normal stools predicted a positive blood slide in adults. Fever, no cough, vomiting, and enlarged spleen were significant predictors for a P. falciparum parasitaemia > or = 10,000/microL in children; in adults the only predictor was vomiting. In children the association of no cough and enlarged spleen had the best predictive value for a positive blood slide, and a temperature > or = 38 degrees C had the best predictive value for a P. falciparum parasitaemia > or = 10,000 microL. In adults, no major symptom had a good predictive value for a positive blood slide but vomiting had the best predictive value for a P. falciparum parasitaemia > or = 10,000/microL. When microscopy is not available, these findings can help in areas of high endemicity to determine which patients with a history of fever are most likely to have malaria and, more importantly, for which patients another diagnosis should be strongly considered.
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PMID:Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area? 799 31


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