Efficacy of quinine-tetracycline for acute uncomplicated falciparum malaria in Thailand

Looareesuwan, S.; Wilairatana, Polrat; Vanijanonta, S; Kyle, Dennis E.; Webster, Kenneth

doi:10.1016/0140-6736(92)91690-a

Cited by 47 publications

(25 citation statements)

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“…9 %) showed patent P. vivax infection during the • As an example, quinine plus tetracycline has had much higher cure rates than quinine alone. (18,38) This provided the rationale for combining artesunate: a fast acting drug (parasite clearance in 2 days) but with a short half-lifc; with tetlacycline: il slow acting antibiotic (effect manifested in ahout 48h) but with a known hlond schizontocidal action. (12.…”

Section: Lab Findingsmentioning

confidence: 99%

“…Drug combinations have hccn extensively studied and used by natIOnal malaria control programs in many endemic areas, (17,20,(35)(36)(37)(38) e _ _ In one study in Brazil, 95% of 110 falciparum malaria patients l'rom the Amazon region were successfully treated with the comhination of quinmc plus tetracycline. (20) Since 1990, the combmation of quinme (3 days) and tetracyclinc (7 days The efficacy of 7-day and 5-day courses of oral artesunate (total dose = 0.6 g) to treat uncomplicated falciparum malaria was assessed in 80 Thai paticnts.…”

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Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

Duarte¹,

Fontes²,

Gyorkos³

et al. 1996

The American Journal of Tropical Medicine and Hygiene

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A triple 'blind randomized controlled trial was undertaken in a Brazilian Amazon region (Cuiabâ-MT), tn compare the effect;veness and side effects of oral artcsunate (7 days, total dose = 0.75 g) plus tetraeycline (7 days, total dose = 10.5 g) [AT) and oral quinine (3 days, total dose = 6 g) plus te(racydine (7 days, total dose = 10.5 g) [QT). Eligible patients had uncomph'c'ated P. falciparum malaria; age ~ 14 years; no previous malaria treatment related to ,the present attack; and, if women, indil,ation of absence of pregnancy. Clinical i\'lOEm and blood tests were pcrformt:d at baselinc (day 0) and thereafter at days 2, ·,l, 7, 14 and 28. EOE.:ctiveness was asscssed by cure rates (WHO criteria) and parasite dl!arance at day 2.176 patients were randomized, 88 to each group. 9\.\.1.6% of the AT group and 93.2% of the QT group completed the 7-day treatment. 81.8% of the AT group and 78.4% of the QT group completed follow-up visits to day 2g Groups had similar clinical characteristics at baseline. The incidence of side effects was much higher in the QT group (82%) th?n in the AT group (50%) [p 14 ans, aucun tnlltement antipaludéen relié à la crise présente; en cas de femmes, aucune 'ossesse indiquée. Un examen clinique et des prises de sang ont été faits au départ (jour 0) puis aux jours 2, 4, 7, 14· et 28 suivants. L'efficacité a été évaluée par les fréquences de guénson Il is to my family that 1 dedicate this thesis.'É dificil expressar min.~a gradidao à pessoas que, embora distante, se lïzeram as mais presentes durante meu perfodo na McGi11.Meu agradecimento e carinho para minha mae e mclhor amiga. Barhara, quem me deu motivaçao e auto-confiança para ir em [rente nas mais malucas situaçoes cm que me coloco, e me ensinou dedicaçâo através ùe seu proprio cxemplo ùe vida.Também quero dividir esta conquista corn minhas irmàs e irmàos, Eliane, Elisa.Elisete, Luiz e Waldeck Junior. tia e segunda mae. Neuza, meu pai, Waldc(,;k, c meus av6s, Archanjo e Elisa (em mem6ria). Pessoas que sempre foram so sorriso e carinho.

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Section: Lab Findingsmentioning

confidence: 99%

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confidence: 99%

Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

Duarte¹,

Fontes²,

Gyorkos³

et al. 1996

The American Journal of Tropical Medicine and Hygiene

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“…Development of quinine resistance in Plasmodium falciparum has been relatively slow and incomplete by comparison with those of the other principal antimalarial drugs, e.g., chloroquine, mefloquine, and sufadoxine-pyrimethamine. In areas with multidrug-resistant strains, 7-day regimens of quinine and tetracycline still provide cure rates well over 90% in patients with uncomplicated falciparum malaria (4,5). To date there is no convincing evidence of high-grade quinine resistance in the treatment of severe malaria (9).…”

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Quinine Pharmacokinetic-Pharmacodynamic Relationships in Uncomplicated Falciparum Malaria

Pukrittayakamee

Wanwimolruk

Stepniewska

et al. 2003

Antimicrob Agents Chemother

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The relationships between the pharmacokinetic properties of quinine during a 7-day treatment course and the therapeutic response were studied in 30 adult patients with uncomplicated falciparum malaria monitored for >28 days. All patients received a 7-day oral quinine regimen either alone (n ‫؍‬ 22) or in combination with rifampin (n ‫؍‬ 8). The median fever clearance time was 58.5 h, and the mean ؎ standard deviation parasite clearance time was 73 ؎ 24 h. After recovery, six patients had recrudescences of Plasmodium falciparum malaria and seven had delayed appearances of P. vivax infection between days 16 and 23. Between the patients with and without recrudescences, there were no significant differences either in fever clearance time or parasite clearance time or in the overall pharmacokinetics of quinine and 3-hydroxyquinine. Patients for whom the area under the concentration-time curve from 3 to 7 days for quinine in plasma was <20 g ⅐ day/ml had a relative risk of 5.3 (95% confidence interval ‫؍‬ 1.6 to 17.7) of having a subsequent recrudescence of infection (P ‫؍‬ 0.016). Modeling of these data suggested an average minimum parasiticidal concentration of quinine in plasma of 3.4 g/ml and an MIC of 0.7 g/ml for uncomplicated falciparum malaria in Thailand. To ensure a cure, the minimum parasiticidal concentration must be exceeded during four asexual cycles (>6 days).The cinchona alkaloids have been important antimalarial drugs for more than 350 years. The principal alkaloid, quinine, still remains effective against chloroquine-resistant falciparum malaria, and it is widely used. Development of quinine resistance in Plasmodium falciparum has been relatively slow and incomplete by comparison with those of the other principal antimalarial drugs, e.g., chloroquine, mefloquine, and sufadoxine-pyrimethamine. In areas with multidrug-resistant strains, 7-day regimens of quinine and tetracycline still provide cure rates well over 90% in patients with uncomplicated falciparum malaria (4, 5). To date there is no convincing evidence of high-grade quinine resistance in the treatment of severe malaria (9). The pharmacokinetic properties of and therapeutic responses to quinine vary with age, pregnancy, immunity, and disease severity (2,8,14). As patients recover from malaria, the total apparent volume of distribution of quinine expands and systemic clearance increases (13). As a result, concentrations in plasma fall. In areas with resistant strains of P. falciparum in order to achieve good therapeutic responses in children, the dose of quinine must be increased after the 3rd day of treatment to compensate for this decline in the concentration in plasma which occurs with recovery (2). These observations suggest that quinine concentrations must remain above levels which inhibit parasite multiplication throughout the course of treatment to eradicate the infection from the body (14). Knowledge of the in vivo minimum parasiticidal concentrations and MICs (14) of quinine in patients with malaria are necessary for optimization of d...

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“…Re-treatment with mefloquine again increases the risk of severe neuropsychiatric reactions. 9 The combination of quinine and tetracycline over a seven-day period provides an alternative that remains Ն 80% effective, 10 but compliance is poor, and tetracycline cannot be given to young children and pregnant women (who comprise a significant proportion of treatment failures). Although oral artesunate is the most widely used of the artemisinin derivatives, an oral formulation of artemether is also available.…”

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Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria.

Price¹,

Vugt²,

Nosten³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. The therapeutic efficacy and toxicity of artesunate (2mg/kg/day for five days, then 1 mg/kg/day for two days: total ϭ 12 mg/kg) was compared with that of artemether (4 mg/kg followed by 2 mg/kg/day for two days, then 1 mg/kg/day for four days: total ϭ 12 mg/kg) for the treatment of recrudescent multidrug-resistant falciparum malaria in an open randomized trial in 443 patients living on the western border of Thailand. Parasite and fever clearance times were similar in both groups; within 48 hr 94% (95% confidence interval [CI] ϭ 91-96%]) of the treated patients were aparasitemic and 93% (95% CI ϭ 89-96%) were afebrile. Symptom resolution and resolution of hepatomegaly were slightly slower in the artesunate group; adjusted hazards ratio ϭ 1.5 (95% CI ϭ 1-2.0, P Ͻ 0.01) and 2.2 (95% CI ϭ 1.4-8, P ϭ 0.04), respectively. There was no significant difference in times to resolution or development of anemia or splenomegaly between treatment groups. By day 28, 3% (95% CI ϭ 0.3-5%) of the patients treated with artesunate and 6% of those treated with artemether (95% CI ϭ 2-9%) had recurrent infections (P ‫؍‬ 0.3). Both regimens were very well tolerated, with no significant adverse effects attributable to either derivative. Overall, these data suggest that the two oral artemisinin derivatives are safe, highly effective, and result in equivalent therapeutic responses in the treatment of drug-resistant falciparum malaria.On the western border of Thailand, Plasmodium falciparum has developed resistance to nearly all the available antimalarial drugs. Mefloquine has been the treatment of choice for uncomplicated falciparum malaria in this region since 1985, but nearly 50% of the patients now fail with high dose (25mg/kg) mefloquine when given alone. 1 These recrudescent infections have a higher failure rate when retreated with mefloquine again, and constitute the reservoir and driving force for drug resistance. 2The artemisinin derivatives are the most potent antimalarial compounds available for human use. 3 They have excellent efficacy against multidrug-resistant strains of P. falciparum and they are very well tolerated. Although more than a million people have now been treated with artemisinin, or one of its derivatives, there is still no consensus concerning the most appropriate dose, treatment regimen, or choice of derivative. The antimalarial efficacy of oral artesunate in uncomplicated malaria appears to be a function of the duration of therapy. 4,5 Recrudescence rates are unacceptably high in patients given less than five days of treatment. Combined treatment with mefloquine improves efficacy and allows shorter courses of artesunate to be given. 6,7 Since 1994, a combination regimen (MAS3) of mefloquine (25 mg/kg) plus a three-day course of artesunate (12 mg/kg) has become the treatment of choice for uncomplicated falciparum malaria in this area.1 The recrudescence rate by day 63 with this treatment is less than 10%, 8 but patients whose infections do recur are symptomatic and their management poses a difficult p...

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Efficacy of quinine-tetracycline for acute uncomplicated falciparum malaria in Thailand

Cited by 47 publications

References 5 publications

Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

Quinine Pharmacokinetic-Pharmacodynamic Relationships in Uncomplicated Falciparum Malaria

Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria.

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