UMLS:C0024530 - FACTA Search

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Query: UMLS:C0024530 (malaria)
44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine is considered essentially nontoxic when used for the chemosuppression of malaria, but gastrointestinal upsets, headache, blurring of vision, pruritus, and uritcaria may occur during chloroquine therapy. Recently, Bhargava et al. and Eronini and Eronini have reported the extrapyramidal syndrome (EPS) following chloroquine therapy in adults. The clinical manifestations included upward rolling of the eyeballs, retraction of neck and back, trismus with marked difficulty in speech, and coarse tremors. Observations of 4 instances of EPS in children following chloroquine therapy for malaria are reported. A 2-1/2 year old girl was admitted to the All India Institute of Medical Sciences Hospital with a 4 day history of intermittent high grade pyrexia with chills and rigors. Following treatment with oral chloroquine in the recommended therapeutic dosage, the fever responded, but the child became drowsy and developed paroxysms of involuntary movements of the tongue, torticollis, torsion dystonia of the limbs, and parosysms of tonic muscular spasms. She completely recovered spontaneously within 48 hours. The 2nd case was that of a 12-year old female brought to the hospital with a 15-day history of intermittent high grade fever with chills and rigors. The patient was started on chloroquine sulfate in the recommended therapeutic dose. After an interval of 4 days she developed coarse tremors of the hands, upward rolling of the eyeballs, episodic deviation of the angle of the mouth towards the left, and trismus. These symptoms disappeared spontaneously within 8 hours. A 6-year old girl, the 3rd case, developed episodes of opisthotonous, upward rolling of the eyeballs, protrusions of the tongue, intermittent writhing movements of the upper limbs, and drowsiness following the ingestion of 6 tablets of chloroquine sulfate for suspected diagnosis of malaria. She spontaneously recovered from EPS over a period of about 48 hours. The 4th case, a 7-year old boy, gave a history of high grade fever with chills and rigors of 1 day's duration. He developed drowsiness, tonic spasms of the neck, upward rolling of the eyeballs, and writhing contortions of all limbs about 2 hours following intravenous administration of 100 mg of chloroquine. 8 hours later an additional 100 mg chloroquine was given intravenously for the mistaken diagnosis of cerebral malaria. On examination the child was drowsy, had generalized stiffness, torticollis, and trismus. He recovered gradually over a 48-hour period without any specific therapy. The exact mechanism of production of EPS remains uncertain.
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PMID:Extrapyramidal syndrome following chloroquine therapy. 45 22

It is reported about a 56 years old woman returned from Mombaza, who was brought into hospital with high fever, jaundice and somnolence and died forty hours later in coma, anuria und hematemesis. The diagnosis of cerebral malaria resulted from autopsy. By the histological examination numerous microthrombi were observed exceptionally in certain cerebral areas, which are more vulnerable by hypoxia as other regions of the brain and other organs. The pathophysiology and the clinical importance of this correlationship are discussed.
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PMID:[A contribution to the intravascular coagulation in cerebral malaria (author's transl)]. 118 80

At a time when Fansimef, the fixed combination of mefloquine, sulfadoxine and pyrimethamine was considered for prophylaxis of falciparum malaria, a randomized double-blind study comparing the efficacy and tolerability of Fansimef with that of Lariam (mefloquine), Fansidar, chloroquine and placebo in malaria prophylaxis was performed in Thailand from July 1987 to January 1988. The study population of 602 adult males was recruited in Pak Tongchai District, some 360 km North-East of Bangkok, where multiresistant P. falciparum is endemic. All active treatments and placebo were given once weekly for 24 weeks with doses as follows: Fansimef: 125 mg mefloquine + 250 mg sulfadoxine + 12.5 mg pyrimethamine (1 half-strength tablet); Lariam: 125 mg mefloquine (1 half-strength tablet); Fansidar: 500 mg sulfadoxine + 25 mg pyrimethamine; chloroquine; 300 mg. A loading dose of 2 half-strength tablets was given in the Fansimef group in weeks 1 and 2 and in the Lariam group in weeks 1 to 4. The incidence of acute episodes of P. falciparum per 100 person months of prophylaxis was 0.17 each in the Fansimef and the Lariam groups, 1.18 in the Fansidar group, 0.69 in the chloroquine group and 0.64 in the placebo group (differences statistically not significant). Clinically adverse events were reported by 170 subjects (Fansimef 28, Lariam 29, Fansidar 41, choroquine 43, placebo 29; differences statistically not significant). The most frequent adverse events in all groups were headache, sleepiness, dizziness and weakness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial. 129 89

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

The World Health Organization (WHO) has developed a diagnostic and treatment algorithm to facilitate the rapid identification and management of severely ill children in developing countries. 13 indicators are listed on Sick Child Charts: inability to drink, abnormal mental status (e.g., sleepiness), convulsions, wasting, edema, chest wall retraction, stridor, abnormal skin turgor, repeated vomiting, stiff neck, tender swelling behind the ear, pallor of the conjunctiva, and corneal ulceration. These indicators target the principal causes of child mortality: acute respiratory infection, malaria, measles, diarrheal disease, and malnutrition. The usefulness of the WHO algorithm was evaluated in 4 clinics in western Kenya's Siaya district and in the pediatric outpatient and inpatient departments of Siaya District Hospital. 770 (28%) of the 2799 children (mean age, 13 months) seen in these rural outpatient clinics had 1 or more of the 13 signs, most frequently repeated vomiting (13%). Children with any of these signs had a 2.3 times higher odds of hospitalization than those without such signs; however, 424 admitted children (54%) had none of the 13 signs. Pallor and chest wall retraction were most highly associated with hospital admission (odds ratio [OR], 8.6 and 5.3, respectively). Among the 1139 inpatients, 666 (58%) presented with at least 1 sign and 75 (7%) died, 67 (89%) of whom had at least 1 clinical sign at admission. Overall, the mortality risk associated with having at least 1 sign was 6.5 times higher than that for children with none of the signs. The signs most associated with mortality were abnormal mental status (OR, 59.6), poor skin turgor (OR, 5.6), pallor (OR, 4.3), repeated vomiting (OR, 3.6), chest wall retraction (OR, 2.7), and edema (OR, 2.4). Although studies in other settings are required to validate the WHO logarithm, this schema appears to be a feasible means for identifying high-risk children in developing countries.
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PMID:An evaluation of clinical indicators for severe paediatric illness. 906 Feb 22

The efficacy of chloroquine for treating uncomplicated Plasmodium falciparum malaria was evaluated in 98 children in Nigeria. Forty-three children failed chloroquine treatment (21 RI, 20 RII, 2 RIII) and were allocated at random to receive multiple doses of a combination of chloroquine and chlorpheniramine or a single dose of mefloquine orally. The parasite and fever clearance times were 2.7 +/- 1.0 d and 1.6 +/- 0.6 d, respectively, in children treated with the combination and 1.6 +/- 0.5 d and 1.1 +/- 0.3 d, respectively, for mefloquine treatment. The cure rate on day 14 was 81% among children receiving chloroquine/chlorpheniramine and 100% on days 14 and 28 with mefloquine. Three children who failed treatment with the combination responded promptly to mefloquine, with clearance of parasitaemia and fever within 48 h. Adverse effects following therapy were minimal, comprising drowsiness and pruritus in the combination group and abdominal discomfort in the mefloquine group. Isolates obtained from children who failed initial treatment with chloroquine were resistant to chloroquine but sensitive to mefloquine in vitro. The efficacy of this combination of chloroquine and chlorpheniramine confirmed previous reports of enhanced activity and it was effective in the management of mild to moderate chloroquine-resistant malaria. Although mefloquine is more effective in this respect, the combination, when developed, will be a valuable addition to the list of drugs for the management of chloroquine-resistant malaria.
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PMID:Comparative efficacy of chloroquine/chlorpheniramine combination and mefloquine for the treatment of chloroquine-resistant Plasmodium falciparum malaria in Nigerian children. 950 81

One hundred and eight children with acute, symptomatic, uncomplicated, falciparum malaria were randomized to receive chloroquine (for 3 days) plus chlorpheniramine alone (for seven days) (CQ-CP group; N = 55) or, in a sequential treatment, chloroquine plus chlorpheniramine for 3 days followed, on the fourth day, by a single oral dose of sulfadoxine-pyrimethamine (25 mg sulfadoxine/kg) (CQ-CP-SP group; N = 53). The mean (S.D.) parasite-clearance time in the CQ-CP group [2.1 (0.7) days; range = 1-5 days] was similar to that in the CQ-CP-SP [2.1 (0.8) days; range = 1-5 days]. The fever-clearance times were also similar: 1.2 (0.1) days (range = 1-3 days) v. 1.1 (0.4) days (range = 1-3 days). The cure rates on days 14, 21 and 28 were 98.2%, 96.3% and 92.7%, respectively in the CQ-CP group, and 100%, 100% and 96.2%, respectively, in the CQ-CP-SP group. The rates of gametocyte carriage were low and similar (5.4% in the CQ-CP group and 3.8% in the CQ-CP-SP group) throughout the duration of the study. Both treatment regimens were relatively well tolerated, the main adverse reactions being similar: sleepiness (on day 1) and pruritus (on days 1-3). No adverse effect was attributable to SP. The results indicate that sequential treatment, for 3 days with CQ and CP, followed by a single dose of SP, is effective and well tolerated in children with acute, uncomplicated, falciparum malaria and may be an alternative treatment for CQ- and/or SP-resistant falciparum malaria. Treatment with a CQ-CP combination (CQ and CP for 3 days and then CP alone for another 4 days) is also effective but requires continuing administration after the signs and symptoms of acute malaria have disappeared.
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PMID:Comparative efficacy of chloroquine plus chlorpheniramine alone and in a sequential combination with sulfadoxine-pyrimethamine, for the treatment of acute, uncomplicated, falciparum malaria in children. 1088 64

Of 51 consecutive children with cerebral malaria, fever, convulsions, and drowsiness were the commonest presenting symptoms. Decerebrate and decorticate postures and absent cornea reflex were the commonest brain stem signs. Opening lumbar cerebrospinal (CSF) pressure was raised in all but one of 24 children in whom it was reliably measured [mean 15.2 +/- 5.7 mmHg, range 6-24]. Hyponatraemia occurred in 17 (33%). Acute renal failure was not uncommon; the combination of hypercreatininaemia (plasma creatinine > 100 mumol/L) and hyperkalaemia (plasma potassium > 6.0 mumol/L) was fatal in 5 out of 7 patients in whom it occurred. Disturbances of acid-base status were present in all 40 children in whom it was assessed on admission. Mortality rate was 16% (8 patients). Neurological deficits occurred in 7 (14%) of the survivors and included cortical blindness [3], aphasia [3], hypertonia [3], hearing loss [2], and dystonia [1]. In addition to the present measures aimed at reducing morbidity and morality in children with cerebral malaria, efforts should be directed at rapid assessment of renal function and prompt correction of such dysfunction if found.
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PMID:Clinical study of cerebral malaria in African children. 1089 20

Artemether-lumefantrine (A-L), a new fixed-dose oral antimalarial drug, combines the fast onset of action of artemether (an artemisinin derivative) in terms of parasite clearance with the high cure rate of lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria. The extensive clinical trial database of A-L has allowed a comprehensive evaluation of its tolerability and safety in a total of 1869 patients (including 243 children aged 5-12 years and 368 children aged < 5 years). The most commonly reported and possibly related adverse effects following A-L therapy involved the gastro-intestinal (abdominal pain, anorexia, nausea, vomiting, diarrhoea) and central nervous (headache, dizziness) systems. Pruritus and rash were reported by < 2% of patients. More than 90% of the reported adverse events, many of which overlapped considerably with the clinical symptomatology or evolution of acute malaria, were rated mild to moderate in intensity. Compared to A-L, significantly higher incidences of vomiting and pruritus were observed with chloroquine, dizziness, nausea and vomiting with mefloquine, somnolence with pyrimethamine + sulfadoxine, and vomiting and dizziness with quinine. There were no serious or persistent neurological side-effects related to A-L administration. A-L did not lead to any clinically relevant alterations of the laboratory parameters. Serial electrocardiographic data were available for 713 patients. The frequency of QT interval prolongations was similar to or lower than that observed with chloroquine, mefloquine, or artesunate + mefloquine; these changes were considerably less frequent than with quinine or halofantrine. All patients with QT prolongation remained asymptomatic and no adverse clinical cardiac events were reported. Artemether-lumefantrine can thus be expected to show, both in children and in adults, a favourable safety profile for the treatment of acute, uncomplicated, P. falciparum malaria; it could as well be a reserve treatment option for travellers to endemic countries.
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PMID:An integrated assessment of the clinical safety of artemether-lumefantrine: a new oral fixed-dose combination antimalarial drug. 1112 48

The increasing resistance of Plasmodium falciparum to chloroquine (CQ) has created urgent needs for the evaluation of alternative antimalarial drugs that are effective, safe, readily available and affordable. Ketotifen, a histamine H(1)-receptor antagonist that reverses CQ resistance in P. falciparum in vitro, may potentially enhance the effects of CQ in vivo. The effects of oral treatment with CQ alone (30 mg/kg base given over 3 days) were compared with those of this CQ regimen combined with ketotifen fumarate (0.25 mg at presentation followed by 0.125 mg/kg every 8 h for 5 days). The subjects were 145 children aged 1-10 years who were suffering from acute, symptomatic, uncomplicated, P. falciparum malaria: 74 given CQ alone and 71 given CQ plus ketotifen (CQK). Although the mean fever-clearance time was significantly shorter following treatment with CQK than after treatment with CQ alone, all other therapeutic responses were similar in the two treatment groups. Among siblings in whom there was clustering of infections, the likelihood of cure was also similar in the two treatment groups. Retreatment of 17 CQ-treatment failures with CQK produced a cure in six children, and retreatment of 22 CQK-treatment failures with CQK produced a cure in eight children. Retreatment of all drug failures with a combination of amodiaquine plus pyrimethamine-sulfadoxine resulted in complete clearance of parasitaemia and symptoms within 2-3 days and a cure 'rate' of 100% on day 28. The prevalences and intensities of gametocytaemias on day 3 or days 3, 7 and/or 14 combined were similar in the two groups. Adverse drug reactions were always tolerable, and limited to pruritus, gastro-intestinal disturbances, drowsiness and weight gain; the latter two adverse effects were significantly more frequent in those treated with CQK than in those given CQ alone. Haematological and biochemical parameters were not adversely affected by either treatment regimen. The findings indicate that - at least at the dosing regimen used in the present study and among children with acute, uncomplicated, P. falciparum malaria from Ibadan - the addition of ketotifen to CQ produced little or no significant enhancement of the antimalarial effect of CQ.
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PMID:A randomized comparison of chloroquine and chloroquine plus ketotifen in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children. 1280 65

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