Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02448 (Fansidar)
 243 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most recent acquisitions on chemotherapy and chemoprophylaxis of malaria are reviewed. With regard to chemotherapy, candidate antimalarial compounds have been divided into four groups, according to their stages of development. Mefloquine and the combination of mefloquine with sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which halofantrine is the most promising one; b) the sesquiterpene lactones such as Qinghaosu, artemether, artesunate, artesunic acid and arteether which must be further tested in order to find more effective drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c) pyronaridine, which appears to be a promising antimalarial, effective also against chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d) enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-aminoquinolines, such as dabechin, piperaquine, hydroxypiperaquine, tripiperaquine, dichlor-quinazine and the Mannich base compounds, the 8-aminoquinolines, the 4-quinolinemethanols, the quinolones, the naphthoquinones, the quinazolines and the dihydrotriazines. Among the many antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as floxacrine, the antibiotics, antifungal agents or their metabolites, plant substances such as Yingzhaosu A and quassinoids have been mentioned. Malaria chemoprophylaxis, especially in chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of amodiaquine, the combination of sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), of pyrimethamine/dapsone (Maloprim), with or without chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of chloroquine with proguanil or chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Recent acquisitions on chemotherapy and chemoprophylaxis of malaria. 269 8

The effect of primaquine as a gametocytocidal drug was investigated in 218 P. falciparum (Pf) malaria cases detected during passive case detection (PCD) from August to December 1985 in two coastal villages of North Sumatra, where chloroquine-resistant and Fansidar-sensitive Pf was prevalent. Sulfonamide + pyrimethamine (SP) in combination with primaquine (Pr) was administered in Kuala Tanjung village and SP alone in Nana Siam village. Parasitologically confirmed Pf cases were followed up to observe the fluctuation of gametocytemia after the treatment. In 87 cases treated with SP alone, no significant change was observed in gametocyte positivity rate (GPR) and density on day 2 and day 7. In 131 cases treated with SP and Pr, no significant change was found on day 2 but significant reduction was observed in GPR and density on day 7. The gametocyte positive cases on day 7 were followed up weekly until gametocytes disappeared. SP alone did not reduce GPR from day 0 to week 2, then afterward GPR began to decline but was still 11.5% at week 5. On the other hand, SP with Pr reduced GPR from 77% on day 0 to 30% on day 7, after which GPR declined further to 7% at week 3. Reduction of parasite rate was observed in Kuala Tanjung after the PCD activities, reflecting a reduction in Pf prevalence rate from 18.6% in August 1985 to 2.9% in January 1986. These data indicate that a single dose of Pr 45 mg with SP was partially effective in reducing gametocytes and reducing malaria prevalence rate when administered through PCD activities.
 ...
PMID:Gametocytocidal effect of primaquine in a chemotherapeutic malaria control trial in North Sumatra, Indonesia. 269 82

A patient developed eosinophilic peripheral pulmonary infiltrates while receiving malaria prophylaxis with sulfadoxine-pyrimethamine (Fansidar). Withdrawal of Fansidar and treatment with corticosteroids led to rapid recovery. No exacerbation occurred after cessation of corticosteroids. Lymphocyte transformation testing gave a positive result in the presence of sulfadoxine but not pyrimethamine. It is concluded that drug hypersensitivity to sulfadoxine was the cause of the eosinophilic pneumonia in this patient.
 ...
PMID:Sulfadoxine specific lymphocyte transformation in a patient with eosinophilic pneumonia induced by sulfadoxine-pyrimethamine (Fansidar). 276 33

The itinerary of international travelers will largely determine the amount of pretravel counseling number of immunizations and type of malaria prophylaxis they will need. The countries visited are also the best predictor of traveler's diarrhea. Only yellow fever and cholera vaccines are required for entry into certain countries; the latter generally given only to satisfy entry requirements. Polio vaccine is important for some areas and is frequently neglected. For most malarious areas, chloroquine once per week is recommended. Fansidar should be prescribed weekly for very few travelers. Traveler's diarrhea is best prevented by avoiding high risk foods and beverages. Antibiotics, generally not recommended for prophylaxis, are very effective in treatment. Travelers should be reminded to advise physicians of their travel history during future medical encounters so that diseases, possibly contracted during travel, may be considered in diagnoses.
 ...
PMID:Counseling the international traveler. 279 6

Two randomised double-blind trials were conducted to examine the activity and tolerability of mefloquine alone and in combination with sulfadoxine/pyrimethamine (MSP). In one trial mefloquine was compared with chloroquine in 40 patients with Plasmodium vivax malaria and in the other one mefloquine was compared with MSP in 40 patients with P falciparum malaria. The former trial showed that both a single oral dose of 250 mg mefloquine and a single oral dose of 450 mg chloroquine (base) were highly effective in relieving symptoms of malaria and in clearing P vivax parasitaemia. No side-effects and no changes in laboratory variables attributable to the test drugs were observed. The other trial showed that a single oral dose of 750 mg mefloquine and a single oral dose of MSP (750 mg mefloquine plus 3 tablets of 'Fansidar', were equally effective in the treatment of falciparum malaria. 2/4 treatment failures in the mefloquine group and 2/3 treatment failures in the MSP group were due to low plasma drug levels resulting from vomiting soon after ingestion of the tablets. Gametocytes of P falciparum were unaffected by either mefloquine or MSP. 5 patients in each group had side-effects such as vomiting, skin rash, diarrhoea, and transient mental confusion. Mefloquine was well tolerated by patients with glucose-6-phosphate dehydrogenase deficiency or heterozygous haemoglobin E.
 ...
PMID:Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. 285 43

The disposition of sulfadoxine was studied in the presence of pyrimethamine in 18 healthy Thai subjects who had been suffering from falciparum malaria in the 6 months prior to the study, and in 12 Thai patients with acute malaria. The volunteers were administered an oral dose of 500 mg sulfadoxine + 25 mg pyrimethamine (1 Fansidar tablet). They were classified retrospectively as responders (Group I, n = 8) or nonresponders (Group II, n = 10) according to previous response to treatment with Fansidar. The patients were treated with 3 Fansidar tablets corresponding to 1500 mg sulfadoxine and 75 mg pyrimethamine. Five of them were completely cured. Seven patients showed R I or R II resistance. In all cases blood samples were collected up to 288 h post dose. The resultant plasma was analyzed for active (i.e. unchanged) and total sulfadoxine using a modified Bratton-Marshall method. In the healthy volunteers the plasma concentration time course of total sulfadoxine was similar for responding and nonresponding subjects. However, in nonresponders active sulfadoxine tended to show shorter half-lives (harmonic means were 212 h vs 267 h, respectively). Furthermore, significantly higher amounts of metabolites (mainly N4-acetylsulfadoxine) were present in plasma of nonresponders. In contrast to these findings, in malaria patients, plasma concentrations of active and total sulfadoxine were even higher in nonresponders as compared to the subjects who could be successfully cured. Furthermore, in this case there was no increase of the amount of metabolites in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Plasma concentrations of sulfadoxine in healthy and malaria infected Thai subjects. 290 23

A 12-year-old boy developed a phototoxic rash with subsequent progression to Stevens-Johnson syndrome due to prophylactic ingestion of antimalarials (chloroquine and sulfadoxine-pyrimethamine; Fansidar). The patient recovered from his skin symptoms after 4 weeks during which he received systemic corticosteroids and antibiotics. This unusual combination of two different patterns of adverse cutaneous drug reactions was most probably caused by the sulfonamide component of Fansidar.
 ...
PMID:An unusual combination of phototoxicity and Stevens-Johnson syndrome due to antimalarial therapy. 291 79

In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000-8,000 users, and that fatal reactions occur in 1 per 11,000-25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.
 ...
PMID:Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. 293 35

A small-scale trial was carried out in the Upper Kinabatangan district of Sabah, Malaysia, to determine the effect of using permethrin-impregnated bednets on malaria transmission. A total of 306 nylon bednets with cotton borders, impregnated at a dose estimated to have been 0.062 g permethrin/m2 of nylon netting, were distributed to 139 households in five villages. At the time of distributing bednets, mass drug administration with Fansidar plus primaquine was also administered to the human population to clear all parasitaemias due to Plasmodium falciparum Welch. In another village, for comparison, mass drug administration was the only intervention. After intervention measures in December 1984 and January 1985, the parasite rates in children declined in all villages during the first month, significantly more in the villages with impregnated bednets than in the control, thus proving that the nets had an impact on malaria. However, after about 2 months, parasite rates started to increase again. After 4-6 months, parasite rates in the villages with bednets approached the rate in the control village without nets. The increase in parasite rates was paralleled by a significant deterioration in the quality, physical condition and the degree of non-utilization of bednets. Entomological evaluation proved the efficacy of permethrin-impregnated nets for controlling Anopheles balabacensis Baisas and other anophelines. Bioassays (1 h exposure) of permethrin-impregnated bednets gave 100% mortality initially and 44-61% mortality after 85-106 days. Mosquito collections in treated bednets were significantly reduced for at least 217 days. The project failed to achieve prolonged suppression of malaria transmission for a combination of entomological, sociological and practical reasons which are discussed in relation to the objectives and implementation of future bednet studies.
 ...
PMID:The influence of permethrin-impregnated bednets and mass drug administration on the incidence of Plasmodium falciparum malaria in children in Sabah, Malaysia. 297 56

Heterogeneity within isolates of Plasmodium falciparum in regard to drug susceptibility is described from studies with three Thai isolates and some clones derived from them. One isolate (T9), which before cloning was resistant in vitro to chloroquine and pyrimethamine, contained a diverse assortment of clones, some of which were sensitive to one or other, or both, of these drugs. Another isolate (CH150) was initially sensitive to mefloquine in vitro, but, on recrudescence of infection in the patient, developed a number of clones all of which had diminished susceptibility to mefloquine. Drug pressure in a laboratory culture of CH150 resulted in a similar change in susceptibility. Hence resistant clones are thought to have been present as a minority component of the original isolate CH150. On testing uncloned isolates at different times after growth in culture, drug susceptibility showed considerable variability, but clones remained stable. Reaction in vitro of these isolates to some other drugs (amodiaquine, Fansidar, quinine) is also described, and the results are discussed in relation to changes in drug resistance of malaria parasites which may occur in laboratory cultures and under field conditions.
 ...
PMID:Variability in drug susceptibility amongst clones and isolates of Plasmodium falciparum. 305 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>