Use of antibiotics in combination with standard anti-malarial drugs has been an important approach for treatment of drug-resistant, uncomplicated as well as complicated cases of malaria[
22]. Antibiotic treatment has been shown to prevent development of malaria infection, and also showed long-term protection in mice against subsequent malaria infections[
23]. Prescription of antibiotics in patients with presumed malaria associated febrile illness is high[
24]. Doxycycline, a tetracycline antibiotic, is one of the most prescribed, effective and affordable anti-malarial antibiotics[
9]. Although it is a slow-acting blood-schizontocide, it is safe and highly effective for treatment of malaria, when used in combination with a fast-acting anti-malarial drug. The anti-malarial use of doxycycline is especially suitable in areas with CQ and multidrug-resistant
P. falciparum malaria. However, doxycycline confers only partial protection against the sporozoite-induced malaria infections and also use of doxycycline is not recommended for pregnant women and children under eight years of age[
9]. Considering the proven records of safety and efficacy, tetracycline antibiotics with appropriate pharmacokinetic and pharmacodynamic profiles should be suitable for inclusion in new combination regimens for treatment of malaria. Attempts to acquire resistance against minocycline in experimental mouse malaria models suggested a slower development of resistance compared to other standard anti-malarial drugs[
25]. Recently, in an attempt to optimize anti-malarial efficacy of tetracycline several seven-position modified tetracycline analogues were identified with improved anti-malarial activity
in vitro against
P. falciparum and
in vivo in mouse malaria models[
26]. Tigecycline is actually a glycylcycline derivative of minocycline, the first clinically approved for treatment of skin and soft tissue infections, as well as intra-abdominal infections. Recent reports regarding prominent activity of tigecycline against several field isolates of
P. falciparum[
11‐
13] prompted the evaluation of this antibiotic
in vitro against CQ-susceptible and -resistant strains of
P. falciparum in combination with CQ. Tigecycline was found to be significantly more active against the resistant
P. falciparum strain than the susceptible. Further, low concentrations of tigecycline markedly and selectively sensitized the CQ-resistant (W2) strains to CQ action. It would be interesting to understand the mechanism for more prominent action of tigecycline against CQ-resistant strains and also potentiation of CQ action against resistant strains. Compared to earlier reports on delayed death of the malaria parasites with antibiotics[
6,
20,
27], tigecycline seems to show faster anti-malarial action
in vitro. However, in vitro activity of tetracycline observed in this activity was low compared to that reported earlier[
27]. This may be due delayed death of the parasite by tetracycline. Significant inhibition of
P. falciparum growth was noticed even with 24-hour exposure of
P. falciparum culture. A proteomic study with
in vitro culture of
P. falciparum schizonts treated with doxycycline indicated significant changes in mitochondria and apicoplast proteomes as distinct characteristic for antimalarial action of this antibiotic[
28]. Tigecycline inhibits protein synthesis by binding to the 30S ribosomal subunit of bacteria and blocks entry of aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation[
15]. Tigecycline inhibits the initial codon recognition step of tRNA accommodation and prevents rescue by the tetracycline-resistance protein TetM[
15]. It would interesting to know the mechanism for anti-malarial action of tigecycline.
In vivo in the
P. berghei mouse malaria model, treatment with very low doses (3.7 mg/kg) of tigecycline cause significant suppression of parasitaemia, while treatment with high dose of tigecycline (100 mg/kg) resulted in complete cures. Tigecycline also markedly potentiated the anti-malarial action of CQ
in vivo.