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)

A randomized double-blind study was performed to compare the side effects of long-term chemoprophylaxis of malaria with Fansidar (1 tablet a week) with those of a 300-mg weekly chloroquine regimen. This study was designed as a field trial with Austrian industrial workers in Nigeria and included 173 volunteers, 86 taking Fansidar and 87 taking chloroquine for 6 to 22 months. Only a few complaints were reported during that time, gastrointestinal disorders predominating in the Fansidar group and insomnia in the chloroquine group (3 cases each). The other complaints in both groups included one case each of skin rash and of visual disturbance, as well as one case of facial erythema after alcohol consumption in the Fansidar group and one of hair loss in the chloroquine group. Laboratory checks were performed at 3-monthly intervals, and included white and red cell counts, platelet counts and determination of GOT, GPT and alkaline phosphatase. There were no signs of drug-associated liver damage. In the Fansidar group there occurred a slight and transient decrease in the red cell count and in the chloroquine group a slight and transient decrease in the white cell count. Although statistically significant, these changes were without clinical significance. It is noteworthy that there were no cases of leucopenia in the Fansidar group. With the exception of one volunteer, who had discontinued his prophylactic drug regimen, malaria did not occur. Antibodies against blood stage parasites as determined by the indirect immunofluorescence test (IIFT), however, could be found at different stages of the study, which indicates that these two antimalarials are not causal prophylactic agents.
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PMID:Tolerability of long-term prophylaxis with fansidar: a randomized double-blind study in Nigeria. 615 20

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

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

The cultural context of forest onchocerciasis was studied in the Boulou and Baka ethnic communities in the Dja-Lobo Division of southern Cameroon. A 2-day survey used focus group interviews followed by a questionnaire administered to 212 randomly selected individuals in 8 communities (88 male and 124 females heads of household) to assess their knowledge about onchocerciasis. Most people (98%) had some knowledge about the disease. Minak was the term used for filariasis by most people (97%) and people knew (90%) that black fly (nyamendimi) was responsible for its transmission. Other vectors of the illness identified were mosquitoes, dirty water, sorcery, and taboo foods. 81% thought that maternal transmission was possible and 66% indicated that filariasis could be transmitted sexually. Virtually all respondents associated itching and rash with minak (filariasis) and more than 60% also recognized the swelling of the skin and leopard skin as manifestations of filariasis. Filariasis, malaria, worms, and blindness were placed in the middle category when the severity of various diseases was ranked by 20 Boulou adults. In contrast, the Baka did not think that filariasis caused blindness, nor that it is linked to eye-worms. However, the 212 individuals ranked blindness as the most severe among other diseases (filaria, malaria, diarrhea, and intestinal worms). 80% of the Boulou and Baka adults had had filariasis in the previous year, but only 5% of the Boulou children and none of the Baka children had had filariasis during that time period. With respect to intestinal worms, 71% of the Boulou adults and 60% of the Baka adults had had intestinal worms in the previous year, while more than 90% of the Boulou children and all of the Baka children had had intestinal worms. Of the 90% who revealed that they had had filariasis at least once before, 69% sought treatment. 54% had tried traditional treatment, while 50% had tried Notezine, 49% had tried Phenergan, and 38% had tried M.G. Lumiere.
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PMID:Ivermectin distribution and the cultural context of forest onchocerciasis in South Province, Cameroon. 864 8

A 30-year-old female entered the emergency room for medical advice because of progressive deterioration of general health with headache, arthralgias, myalgias and fever after a vacation of three weeks in Malaysia and Hong Kong. Because of persistent fever, lymphadenopathy, slight leuco- and thrombocytopenia and only insignificantly elevated humoral signs of an inflammatory process, the patient was treated symptomatically after exclusion of malaria. A viral disease was suspected. Two days later, an exanthema erupted suddenly on the trunk. Pinhead-sized livid, flat macules, increasing in size within hours and spreading to the extremities, were observed. Further investigations revealed a significantly elevated titer of IgG directed against rickettsia conorii, leading to the diagnosis of Mediterranean spotted fever. Under antibiotic treatment with tetracycline, the aforementioned findings regressed within few days, and the patient recovered completely.
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PMID:[Febrile status and exanthema following a trip to the jungle]. 869 32

From October 1991 to February 1992, an outbreak of acute fever (in which thick blood films were negative for malaria) spread rapidly in the city of Djibouti, Djibouti Republic, affecting all age groups and both nationals and foreigners. The estimated number of cases was 12,000. The clinical features were consistent with a non-haemorrhagic dengue-like illness. Serum samples from 91 patients were analysed serologically for flavivirus infection (dengue 1-4, West Nile, yellow fever, Zika, Banzi, and Uganda-S), and virus isolation was attempted. Twelve strains of dengue 2 virus were isolated. Dengue infection was confirmed by a 4-fold or greater rise in immunoglobulin (Ig) G antibody in paired serum specimens, the presence of IgM antibody, or isolation of the virus. Overall, 46 of the suspected cases (51%) were confirmed virologically or had serological evidence of a recent flavivirus infection. Statistical analysis showed that the presence of a rash was the best predictor of flavivirus seropositivity. In November 1992, Aedes aegypti was widespread and abundant in several districts of Djibouti city. A serological study of serum samples collected from Djiboutian military personnel 5 months before the epidemic showed that only 15/177 (8.5%) had flavivirus antibodies. These findings, together with a negative serosurvey for dengue serotypes 1-4 and yellow fever virus performed in 1987, support the conclusion that dengue 2 virus has only recently been introduced to Djibouti.
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PMID:Epidemic dengue 2 in the city of Djibouti 1991-1992. 875 61

Verbal autopsy uses a caretaker interview to determine the cause of death. We conducted a study of the major causes of child death in Namibia to determine the validity of this method. A questionnaire, including signs and symptoms of the diagnoses of interest was administered to the caretaker in 135 deaths of children < 5 years old who were identified from hospital records. The 243 diagnoses included malnutrition (77), diarrhoea (73), pneumonia (36), malaria (33), and measles (24). Sensitivity and specificity of various algorithms of reported signs and symptoms were compared to the medical diagnoses. An algorithm for malnutrition (very thin or swelling) had 73 per cent sensitivity and 76 per cent specificity. An algorithm for cerebral malaria (fever, loss of consciousness or convulsion) had 72 per cent sensitivity and 85 per cent specificity, while for all malaria deaths the same algorithm had low sensitivity (45 per cent) and high specificity (87 per cent). For diarrhoea, loose or liquid stools had high sensitivity (89 per cent), but low specificity (61 per cent). Cough with dyspnoea or tachypnoea had 72 per cent sensitivity and 64 per cent specificity. An algorithm for measles (age > or = 120 days, rash) had 71 per cent sensitivity and 85 per cent specificity. The study results suggest verbal autopsy data can be useful to ascertain the leading causes of death in childhood, but may have limitations for health impact evaluation.
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PMID:Validation study of a verbal autopsy method for causes of childhood mortality in Namibia. 900 66

In preparation for a recently reported, independent field trial of SPf66 malaria vaccine efficacy in Thailand, we first established the safety and immunogenicity of two clinical lots of U.S. manufactured lots of SPf66 in a series of overlapping Phase I studies. The vaccine was produced in approved laboratories using good manufacturing practices. Two clinical lots of alum-adsorbed SPf66 were evaluated in a combined, open-label, Phase I clinical trial involving 50 healthy, malaria-experienced Karen adults and children. Volunteers were grouped by age and immunized sequentially. Group 1 had 30 adults. Group 2 had 10 children 8-15 years of age, and Group 3 had 10 children 2-6 years of age. The SPf66 vaccine was well tolerated in this malaria-experienced population. The most common side effects were erythema, induration, warmth, and tenderness at the site of injection, which typically resolved within 24-48 hr. One adult volunteer developed an acute urticarial rash following the third dose. Among adults, and to a lesser extent older children females had more local reactions than their male counterparts. Seroconversion to SPf66 by enzyme-linked immunosorbent assay occurred in 76% of volunteers receiving two or three doses. This vaccine was safe and immunogenic in malaria-experienced Karen adults and children. This study establishes the comparability of U.S.-manufactured SPf66 with that of Colombian origin, and is important for interpreting the efficacy results of U.S.-manufactured SPf66 in the same study population.
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PMID:Phase I trial of the SPf66 malaria vaccine in a malaria-experienced population in Southeast Asia. 918 Jun 3

Imported dengue is increasingly observed in non endemic countries. We report a retrospective study of 44 cases of dengue fever diagnosed in nine french university hospitals between 1994 and 1997. The patients were aged between 13 and 67 years. Most of them were tourists and had been traveling for a few weeks, in French West Indies and French Guyana (18), South-East Asia (10), India (7) or Polynesia (4). Only, two contracted the disease in Africa. The onset of symptoms preceded the return or followed it within 7 days. The most frequent clinical presentation was a febrile and painful syndrome. Cutaneous manifestations (rash or macular exanthem) were observed in 59% of cases, digestive symptoms in 50%, pharyngitis and/or cough in 25%, microadenopathy in 20%, moderate mucous haemorrhagic manifestations in 16% and neuropsychiatric manifestations in 14%. The common biological abnormalities were thrombocytopenia (84%), leukopenia (59%), and elevated transminases (57%). The diagnosis, orientated by negativity of malaria smears, the knowledge of an epidemic in the visited country, or occurrence of similar cases in the entourage, were argued by serological results: presence of anti-DEN IgM in 25 cases, serological conversion (anti- DEN IgG) in 7 cases or very high seropositivity (anti-DEN IgG > 1/1280) in 12 cases. No virus isolation was obtained.
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PMID:[Imported dengue: study of 44 cases observed from 1994 to 1997 in 9 university hospital centers. Infectio-Sud-France group]. 1041 36

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.
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PMID:Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid. 1051 44


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