tetracycline and Parasitemia

Increasing rates of failure of artemisinin-based combination therapy have highlighted the possibility of emerging artemisinin resistance along the Thai-Cambodian border. We used an integrated in vivo-in vitro approach to assess the presence of artemisinin resistance in western Cambodia. This article provides additional data from a clinical trial that has been published in The New England Journal of Medicine.. Ninety-four adult patients from Battambang Province, western Cambodia, who presented with uncomplicated falciparum malaria were randomized to receive high-dose artesunate therapy (4 mg/kg/day orally for 7 days) or quinine-tetracycline. Plasma concentrations of dihydroartemisinin, in vitro drug susceptibility, and molecular markers were analyzed. Cases meeting all the following criteria were classified as artemisinin resistant: failure to clear parasites within 7 days of treatment or reemergence of parasites within 28 days of follow-up; adequate plasma concentrations of dihydroartemisinin; prolonged parasite clearance; and increased in vitro drug susceptibility levels for dihydroartemisinin.. Two (3.3%) of 60 artesunate-treated patients were classified as artemisinin resistant. Their parasite clearance times were prolonged (133 and 95 h, compared with a median of 52.2 h in patients who were cured). These patients had 50% inhibitory concentrations of dihydroartemisinin that were almost 10 times higher than the reference clone W2. Resistance did not appear to be mediated by the pfmdr1 copy number or selected PfATPase6 polymorphisms previously proposed to confer artemisinin resistance.. Artemisinin resistance has emerged along the Thai-Cambodian border. The potentially devastating implications of spreading resistance to a drug that currently has no successor call for further studies of this emerging problem.. ClinicalTrials.gov identifier NCT00479206.

Topics: Adolescent; Adult; Aged; Antimalarials; Artemisinins; Cambodia; Drug Resistance; Female; Humans; Malaria, Falciparum; Male; Middle Aged; Parasitemia; Plasma; Plasmodium falciparum; Quinine; Recurrence; Tetracycline; Thailand; Treatment Failure; Young Adult

The efficacy and toxicity of oral quinine combined with oral chloroquine were studied in 50 Thai men with uncomplicated falciparum malaria. All were treated for 7 days with quinine sulphate (10 mg salt/kg every 8 h). Twenty-five of the patients, selected at random, were also given oral tetracycline (4 mg/kg four times daily) over the same period and the remainder were given chloroquine (25 mg base/kg over the first 3 days). There were no serious adverse effects. Overall fever-clearance times (FCT) and parasite-clearance times (PCT) in the chloroquine and tetracycline groups were not significantly different, with mean (S.D.) values of 51 (33) and 41 (27) h for FCT and 80 (25) and 83 (21) h for PCT, respectively. Most of the patients (18 in each group) were followed for > or = 2 months. Recrudescence rates (R1) were significantly higher in the chloroquine group than in the tetracycline group (39% v. 6%; P = 0.02), all recrudescences occurring within 4 weeks (18-25 days) of starting treatment. Subsequent parasitaemia with Plasmodium vivax, however, occurred less frequently in the chloroquine group (11%) than in the tetracycline group (33%) (P = 0.11) and took longer to develop in the chloroquine group [51 or 59 days compared with a mean (S.D.) value of 29 (10) days in the tetracycline group; P = 0.01]. Within the chloroquine group, FCT and PCT were both shorter in those with cure than in those with R1 resistance, with mean (S.D.) values of 41 (25) and 70 (33) h for FCT (P = 0.09) and 72 (20) and 100 (18) h for PCT (P = 0.01), respectively. Chloroquine does not potentiate the clinical response to quinine against resistant strains of uncomplicated falciparum malaria, nor does it convey any useful antipyretic effect.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antimalarials; Chloroquine; Drug Therapy, Combination; Fever; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Middle Aged; Parasitemia; Quinine; Recurrence; Tetracycline; Thailand; Treatment Outcome

In this study, it was aimed to investigate the antimalarial activity of cinnamaldehyde (CIN) and cannabidiol (CBD) which have shown various biological activities such as potent antimicrobial activity and eravacycline (ERA), a new generation tetracycline derivative, in an in vivo malaria model. The cytotoxic activities of the active substances were determined by the MTT method against L929 mouse fibroblasts and their antimalarial activity were determined by the four-day test in an in vivo mouse model. In this study, five groups were formed: the CIN group, the CBD group, the ERA group, the chloroquine group (CQ) and the untreated group (TAG). 2.5 x 107 parasites/mL of P.berghei-infected erythrocyte suspension was administered IP to all mice. The determined doses of active substances were given to the mice by oral gavage in accordance with the four-day test and the parasitemia status in the mice was controlled for 21 days with smear preparations made from the blood taken from the tail end of the mice. The IC50 values, which express the cytotoxic activity values of the active substances were determined as 27.55 μg/mL, 16.40 μM and 48.82 μg/mL for CIN, CBD and ERA, respectively. The mean parasitemia rate in untreated mice was 33% on day nine and all mice died on day 11. On the ninth day, when compared with the TAG group, no parasites were observed in the CIN group, while the average parasitemia was 0.08% in the CBD group and 17.8% in the ERA group. Compared to the mice in the TAG group, the life expectancy of the other groups was prolonged by eight days in the CIN group, 12 days in the CBD group and eight days in the ERA group. It has been determined that all three active subtances tested in this study suppressed the development of Plasmodium parasites in an in vivo mouse model and prolonged the life span of the mice. It is thought that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining them with the existing and potential antimalarial molecules.

Topics: Animals; Antimalarials; Cannabidiol; Malaria; Mice; Parasitemia; Plant Extracts; Plasmodium berghei; Tetracycline

The resistance of Plasmodium falciparum to antimalarial drugs is one of the most worrisome problems in tropical medicine, but few clinical studies or observations have described confirmed cases of therapeutic failure. We report two cases of in vivo P. falciparum resistance (RIII response) to quinine in French Guiana, an Amazonian focal zone in which multi-resistant malaria is endemic. Both patients presented with uncomplicated malaria and were initially treated with intravenous quinine. Although absorption was normal, the treatment was not effective and the patients still had fever and significant parasitemia three days after the onset of treatment (day 3). The addition of intravenous tetracycline completely resolved the parasitemia within approximately 96 hours. These clinical reports confirm the necessity to combine quinine with tetracycline in this area, as recommended by the recent French regional antimalarial policy.

Topics: Absorption; Adult; Animals; Anti-Bacterial Agents; Antimalarials; Drug Resistance; Drug Therapy, Combination; French Guiana; Humans; Injections, Intravenous; Malaria, Falciparum; Male; Parasitemia; Plasmodium falciparum; Quinine; Tetracycline

Topics: Adrenal Cortex Hormones; Animals; Anorexia; Body Temperature; Ehrlichia; Ehrlichiosis; Fatal Outcome; Fluorescent Antibody Technique, Indirect; Ixodes; Leukocyte Count; Male; Norway; Parasitemia; Seasons; Sheep; Sheep Diseases; Tetracycline