Effects of Tetracycline against Chloroquine-Resistant and Chloroquine-Sensitive Plasmodium Falciparum *

Kh, Rieckmann; Rd, Powell; Jv, McNamara; Willerson, D.; Lass, L; Frischer, Henri; Pe, Carson

doi:10.4269/ajtmh.1971.20.811

Cited by 58 publications

(30 citation statements)

References 5 publications

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“…Thirty years ago, tetracycline and its derivatives were found to have antimalarial activity (43), as demonstrated by in vitro (6,30) and clinical (54) studies. The IC 50 for tetracyclines in our experiments was close to those reported by other authors: 39 M for oxytetracycline (6), 32 M for tetracycline (55), and 11 M for doxycycline (40).…”

Section: Discussionmentioning

confidence: 99%

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In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron

Pradines

Rogier

Fusaı̈

et al. 2001

Antimicrob Agents Chemother

106

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The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated on Plasmodium falciparum clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro activity against P. falciparum, which increased after a prolonged exposure (96 or 144 h). In the presence of iron (FeCl 3 ), only the activities of tetracyclines and norfloxacin were decreased. Their in vitro activity against intraerythrocytic stages of multidrug-resistant P. falciparum and their efficacy in vivo favor the use of antibiotics as antimalarial drugs. However, due to their slow antimalarial action and to the fact that they act better after prolonged contact, they probably need to be administered in conjunction with a rapidly acting antimalarial drug, such as a short course of chloroquine or quinine.

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Section: Discussionmentioning

confidence: 99%

“…Thirty years ago, tetracyclines were found to have antimalarial activity (43). Experimental observations obtained in vitro (3,40) and in clinical studies (4,16) proved the antimalarial activity of doxycycline.…”

mentioning

confidence: 99%

In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron

Pradines

Rogier

Fusaı̈

et al. 2001

Antimicrob Agents Chemother

106

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“…17 Of twelve American volunteers given tetracycline (2 or 4 gm/day for 7 or 14 days), only 4 subjects (33.3%) were fully sensitive; a cure rate consistent with our vivax data. Tetracycline or doxycycline monotherapy resulted in slow mean parasite and fever clearance times against P. falciparum 17-20 (PCT 5 days, FCT 3-5 days) [17][18][19][20] and P. vivax (PCT 7 days, FCT 6 days) 17 malaria. Our study has re-documented the slow parasite clearance times of falciparum (x ϭ 4 days), and vivax malaria (x ϭ 5 days), but our mean fever clearance times were faster, just over 2 days for both species.…”

Section: Discussionmentioning

confidence: 99%

“…16 Doxycycline and tetracycline have modest antimalarial activity against vivax or falciparum malaria. [17][18][19][20] However, combining either drug for seven days with quinine, mefloquine, or artesunate resulted in treatment efficacies exceeding 94% against falciparum malaria in Thailand, [21][22][23][24] and the addition of three days of doxycycline to standard-dose chloroquine improved the cure rate of chloroquine from 36% to 75% in Gabonese adults with falciparum malaria. 25 Doxycycline has now replaced tetracycline for use in combination with quinine against falciparum malaria 15 because of its therapeutic advantage of twice-daily dosing and low cost (US$ 3.14/100 generic capsules in Indonesia).…”

Section: Introductionmentioning

confidence: 99%

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Taylor¹,

Widjaja²,

Richie³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n ϭ 30), doxycycline (100 mg every 12 hours [7 days], n ϭ 20), or chloroquine with doxycycline (n ϭ 39); corresponding numbers for vivax malaria (n ϭ 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/ RIII Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.

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“…9 Thirty years ago, tetracyclines were found to have antimalarial activity. 10 Experimental observations obtained in vitro 11,12 and in clinical studies 13 showed antimalarial activity of tetracycline and its derivatives. Tetracycline depresses the activity of dihydroorotate dehydrogenase of the pyrimidine pathway in P. falciparum, 14 presumably due to inhibition of enzyme protein synthesis.…”

mentioning

confidence: 99%

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

Pradines

Spiegel²,

Rogier³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71 50% inhibitory concentration (IC 50 ) values for doxycycline ranged from 0.7 to 108.0 M and the geometric mean IC 50 for the 71 isolates was 11.3 M (95% confidence interval ϭ 9.5-13.4 M). The activity of doxycycline did not differ significantly (P ϭ 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in vitro activity of doxycycline against intraerythrocytic stages of multidrug-resistant P. falciparum, its action against the preerythrocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the other antimalarial drugs, and its original potential site of action are factors that favor its use as antimalarial drug.The current options for reducing the morbidity and mortality of malaria are chemoprophylaxis and chemotherapy. Therefore, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria.

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Effects of Tetracycline against Chloroquine-Resistant and Chloroquine-Sensitive Plasmodium Falciparum *

Cited by 58 publications

References 5 publications

In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron

In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

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