Onychomycosis is more common in women of 20-40 years of age. Distolateral subungual onychomycosis and candidal onychomycosis are the most common clinical presentations, and Candida and T. rubrum are the major pathogens in Pakistan.

A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156 and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC50 values ≤ 5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.

We report a randomized, double-blind study, comparing the relative efficacy and tolerability of oral terbinafine, given for 1, 2 or 4 weeks, in tinea capitis. Of 161 evaluable patients, 53 were treated with terbinafine for 1 week, 51 for 2 weeks and 57 for 4 weeks. Isolated pathogens included Trichophyton violaceum (71.5%), T. tonsurans (14.9%), T. verrucosum (4.3%), Microsporum audouinii (4.3%), M. canis (2.5%), T. schoenleinii (1.9%) and T. mentagrophytes (0.6%). The final evaluation, at 12 weeks, showed cure rates of 73.6, 80.4 and 85.9%, in the respective groups. The adverse effects noted, were not drug related. In our opinion, terbinafine given for 1, 2 or 4 weeks, is equally effective for most cases of tinea capitis.

T. violaceum is the predominant pathogen causing tinea capitis in this part of the world, and gives rise to a varied clinical picture.