Quinine-tetracycline for multidrug resistant falciparum malaria

Parasitology and Tropical Medicine Association of Thailand, Bangkok, Thailand.
The Southeast Asian journal of tropical medicine and public health (Impact Factor: 0.72). 04/1996; 27(1):15-8.
Source: PubMed


Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine and sulfadoxine/ pyrimethamine. Quinine-tetracycline has been used as a second line treatment for uncomplicated falciparum malaria, but duration of treatment varies from place to place. The 7-days course of this combination has been shown to be very effective. However, due to the cinchonism adverse effects, the patient compliance has not been satisfactory. We have evaluated the efficacy of a 7-days course of tetracycline in combination with either 5 or 7-days course of quinine. Ninety male Thai patients who were admitted to the Bangkok Hospital for Tropical Diseases were randomized to receive tetracycline 250 mg qid for 7 days in combination with either quinine 600 mg tid for 5 days (Q5T7; group A) or quinine 600 mg tid for 7 days (Q7T7; group B). The patients were hospitalized for 28 days. Patients in both groups had a comparable initial response to treatment, with the clearance of fever and parasites within 4 days. There were 46 and 40 patients in group A and B, respectively, who completed the 28 day of follow-up. The cure rates were 87 and 100%, respectively for group A and B. No serious adverse effects were found in either group; transient nausea, vomiting and tinnitus were common findings. The incidence of adverse effects was not different between the two groups. The results from the present study suggest that a short course treatment of quinine (Q5T7) had significantly decreased the cure rate. In areas with quinine resistant falciparum malaria, a full course of 7-days quinine, in combination with 7-days course of tetracycline is recommended for hospital treatment. However, an alternative shorter course of antimalarials is suggested for home treatment.

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    • "A more recent report shows 23% recrudescence in pregnant women after quinine treatment (McGready et al., 1998), which may be an indication that quinine resistance in Thailand is stabilizing, perhaps because of the widespread use of quinine combinations and alternative drugs. In Africa, quinine resistance remains at very low levels, and even in Southeast Asia, cure rates with quinine combinations (for example, quinine-tetracycline) remain high (Watt et al., 1992; Looareesuwan et al., 1994; Bunnag et al., 1996). "

    African journal of pharmacy and pharmacology 02/2013; 7(5):148-156. DOI:10.5897/AJPPX12.015 · 0.84 Impact Factor
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    • "The most frequent adverse event associated with quinine treatment is cinchonism, which is characterized by tinnitus, nausea, headache and blurred vision. Combinations of quinine with some antibiotics (e.g., tetracycline, doxycyline, clindamycin and azithromycin) significantly improved the treatment efficacy compared to quinine alone in the treatment of drug-resistant malaria [20-22]. The continued use of quinine is however challenged by poor tolerability and poor compliance associated with the duration of treatment and the complex dosing regimes [23,24]. "
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    ABSTRACT: Artemisinin-based combinations are recommended for treatment of uncomplicated falciparum malaria, but are costly and in limited supply. Clindamycin plus quinine is an alternative non-artemisinin-based combination recommended by World Health Organization. The efficacy and safety of clindamycin plus quinine is not known. This systematic review aims to assess the efficacy of clindamycin plus quinine versus other anti-malarial drugs in the treatment of uncomplicated falciparum malaria. All randomized controlled trials comparing clindamycin plus quinine with other anti-malarial drugs in treating uncomplicated malaria were included in this systematic review. Databases searched included: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. Two authors independently assessed study eligibility, extracted data and assessed methodological quality. The primary outcome measure was treatment failure by day 28. Dichotomous data was compared using risk ratio (RR), in a fixed effects model. Seven trials with 929 participants were included. Clindamycin plus quinine significantly reduced the risk of day 28 treatment failure compared with quinine (RR 0.14 [95% CI 0.07 to 0.29]), quinine plus sulphadoxine-pyrimethamine (RR 0.17 [95% CI 0.06 to 0.44]), amodiaquine (RR 0.11 [95% CI 0.04 to 0.27]), or chloroquine (RR 0.11 [95% CI 0.04 to 0.29]), but had similar efficacy compared with quinine plus tetracycline (RR 0.33 [95% CI 0.01 to 8.04]), quinine plus doxycycline (RR 1.00 [95% CI 0.21 to 4.66]), artesunate plus clindamycin (RR 0.57 [95% CI 0.26 to 1.24]), or chloroquine plus clindamycin (RR 0.38 [95% CI 0.13 to 1.10]). Adverse events were similar across treatment groups but were poorly reported. The evidence on the efficacy of clindamycin plus quinine as an alternative treatment for uncomplicated malaria is inconclusive. Adequately powered trials are urgently required to compare this combination with artemisinin-based combinations.
    Malaria Journal 01/2012; 11(1):2. DOI:10.1186/1475-2875-11-2 · 3.11 Impact Factor
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    • "The most common antibiotics used against malaria are tetracycline and doxycycline. A standard treatment for patients with infections by chloroquineresistant P. falciparum strains is a 7-day course of quinine–tetracycline combinations (Bunnag et al., 1996). Quinine–doxycycline and chloroquine– doxycycline were effective in treating chloroquineresistant uncomplicated falciparum malaria patients (Taylor et al., 2001). "
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    ABSTRACT: Azithromycin, an azalide analog of erythromycin was assayed for its in vitro activity against multidrug-resistant Plasmodium falciparum K1 strain by measuring the 3H-hypoxanthine incorporation. Azithromycin caused inhibitory effects on the parasite growth with IC50 and IC90 values of 8.4+/-1.2 microM and 26.0+/-0.9 microM, respectively. Erythromycin inhibited growth of P. falciparum with IC50 and IC90 values of 58.2+/-7.7 microM and 104.0+/-10.8 microM, respectively. The activity of antimalarial drugs in combination with azithromycin or erythromycin against P. falciparum K1 were compared. Combinations of chloroquine with azithromycin or erythromycin showed synergistic effects against parasite growth in vitro. Combinations of quinine-azithromycin and quinine-erythromycin showed potentiation. Additive effects were observed in mefloquine-azithromycin and mefloquine-erythromycin combinations. Similar results were also produced by pyronaridine in combination with azithromycin or erythromycin. However, artesunate-azithromycin and artesunate-erythromycin combinations had antagonistic effects. The in vitro data suggest that azithromycin and erythromycin will have clinical utility in combination with chloroquine and quinine. The worldwide spread of chloroquine-resistant P. falciparum might inhibit the ability to treat malaria patients with chloroquine-azithromycin and chloroquine-erythromycin in areas of drug-resistant. The best drug combinations against multidrug-resistant P. falciparum are quinine-azithromycin and quinine-erythromycin.
    Acta Tropica 01/2007; 100(3):185-91. DOI:10.1016/j.actatropica.2006.10.008 · 2.27 Impact Factor
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