BackgroundRecent circumstantial evidence suggests that an increasing number of Iranian patients with cutaneous leishmaniasis are unresponsive to meglumine antimoniate (Glucantime), the first line of treatment in Iran. This study was designed to determine whether the clinical responses (healing, or non-healing) were correlated with the susceptibility of
Leishmania parasites to Glucantime.
Methods and FindingsIn vitro susceptibility testing was first performed on 185 isolated parasites in the intracellular mouse peritoneal macrophage model. A strong correlation between the clinical outcome and the in vitro effective concentration 50% (EC
50) values was observed. Parasites derived from patients with non-healing lesions had EC
50 values at least 4-fold higher than parasites derived from lesions of healing patients. A selection of these strains was typed at the molecular level by pulsed-field gels and by sequencing the pteridine reductase 1
(PTR1) gene. These techniques indicated that 28 out of 31 selected strains were
Leishmania tropica and that three were
Leishmania major. The
L. major isolates were part of a distinct pulsed-field group, and the
L. tropica isolates could be classified in three related additional pulsed-field groups. For each pulsed-field karyotype, we selected sensitive and resistant parasites in which we transfected the firefly luciferase marker to assess further the in vitro susceptibility of field isolates in the monocyte cell line THP1. These determinations confirmed unequivocally that patients with non-healing lesions were infected with
L. tropica parasites resistant to Glucantime. Additional characterization of the resistant isolates showed that resistance is stable and can be reversed by buthionine sulfoximine, an inhibitor of glutathione biosynthesis.
ConclusionsTo the authors' knowledge, this is the first report of proven resistant parasites contributing to treatment failure for cutaneous leishmaniasis and shows that primary Glucantime-resistant
L. tropica field isolates are now frequent in Iran.
Cutaneous leishmaniasis (CL) is a major health problem in endemic areas of Iran. The pentavalent antimony (SbV) based drug Glucantime is the first line of treatment for CL in Iran, but recently SbV-resistant Leishmania tropica isolates derived from unresponsive patients were reported. We show in this study that these resistant parasites are cross-resistant to the other SbV-containing drug Pentostam and at least for one isolate also to amphotericin B. However, these resistant isolates were shown to be sensitive to miltefosine and paromomycin. The latter two drugs could thus be useful alternatives for the treatment of leishmaniasis in Iran even for SbV-resistant isolates.
The Candida species recovered from oral cavity of 150 Iranian HIV/AIDS patients and their antifungal susceptibility profiles were reported. Candida albicans was the commonest Candida species, followed by C. dubliniensis, C. tropicalis, C. glabrata, C. kefyr and C. africana. All Candida isolates were susceptible to amphotericin B and caspofungin, while resistance to azoles was detected. The growing drug-resistance profile reported in clinical isolates of C. albicans and non-C. albicans strains is a serious problem in hospitals worldwide. Consequently, the suitable antifungal choice to treat the HIV/AIDS population with oral candidiasis needs to be rethought and new therapeutic options must urgently arise.
Strongyloides stercoralis is an intestinal nematode in humans, distributed through tropical and subtropical regions of the world. In most individuals, the infection has a chronic nature due to auto-infection at the low level. Accelerated auto-infection, mainly after an alteration in immune status, can cause a syndrome of severe hyper-infection or potentially fatal disseminated strongyloidiasis. Due to the increasing numbers of immunocompromised patients in Iran, strongyloidiasis is an emerging public health concern in the country. In the current study, which was carried out between 2003 and 2005, for the investigation on strongyloidiasis in HIV(+)/AIDS patients, a total of 781 patients were examined by agar plate culture, formalin ether concentration, and direct smear preparation of stool samples. According to the results, 2 out of 781 HIV( + )/AIDS patients were found infected with S. stercoralis, but both patients were at the progressive stage of AIDS and showing severe hyper-infection syndrome. In both cases, numerous rhabditiform and filariform larvae were found in fresh stool direct smears, and rapid and intensive development of parasite in agar plate cultures. In conclusion, in the progressive stages of AIDS, as a result of immunosuppression conditions or in the context of chemotherapy, S. stercoralis is capable of inducing overwhelming infection.
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