A Double-Blind, Randomized Study of Azithromycin Compared to Chloroquine for the Treatment of Plasmodium Vivax Malaria in India

Abstract

Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.

Neglect of Plasmodium vivax malaria

“…In Thailand, a thorough examination of several thousand infections revealed almost no evidence of resistance [36][37][38][39][40]. Among 869 subjects evaluated in three separate studies in India, none showed evidence of resistance to CQ [41][42][43]. Survey work in Turkey [44,45] and in Vietnam [46] showed moderate levels of resistance (15% and 22% failure, respectively).…”

In VivoandIn VitroAntimalarial Properties of Azithromycin-Chloroquine Combinations That Include the Resistance Reversal Agent Amlodipine

“…These findings suggest that CQ might once again become a useful antimalarial drug, if used in combination, in areas where CQ resistance has waned. Similar to CQ, the macrolide azithromycin (AZ) has a long track record of tolerability and safety in both children and pregnant women, the populations most affected by malaria (19,20,34). As a widely used antibiotic, AZ has a very broad spectrum of activity against many important bacteria, including…”

“…Similar to CQ, the macrolide azithromycin (AZ) has a long track record of tolerability and safety in both children and pregnant women, the populations most affected by malaria (19,20,34). As a widely used antibiotic, AZ has a very broad spectrum of activity against many important bacteria, including Streptococcus, Staphylococcus, Chlamydia, and Neisseria, and is a first-line indication for the treatment of common infections, including community-acquired pneumonia, exacerbation of chronic bronchitis, pharyngitis, sinusitis, and several sexually transmitted diseases.…”

In Vitro Antimalarial Activity of Azithromycin, Artesunate, and Quinine in Combination and Correlation with Clinical Outcome

“…both in vitro (11,14) and in vivo for prophylaxis and treatment (1,3,4,6,8,10,15). Compared to other antibiotics used for malaria treatment (e.g., tetracyclines), azithromycin offers unique advantages due to its safety in children and experience with use in pregnant subjects (5), the populations most affected by malaria.…”