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Introduction: Leishmaniasis is a collective term used to describe various pathological conditions caused by an obligate intracellular protozoan of the genus Leishmania. It is one of the neglected diseases and has been given minimal attention by drug discovery and development stakeholders to narrow the safety and efficacy gaps of the drugs currently used to treat leishmaniasis. The challenge is further exacerbated by the emergence of drug resistance by the parasites.

Methods: Aiming to look for potential anti-leishmanial hits and leads, we screened Medicines for Malaria Venture (MMV) Pathogen Box compounds against clinically isolated Leishmania donovani strain. In this medium-throughput primary screening assay, the compounds were screened against promastigotes, and then against amastigote stages.

Results: From the total 400 compounds screened, 35 compounds showed >50% inhibitory activity on promastigotes in the initial screen (1 μM). Out of these compounds, nine showed >70% inhibition, with median inhibitory concentration (IC₅₀) ranging from 12 to 491 nM using the anti-promastigote assay, and from 53 to 704 nM using the intracellular amastigote assay. Identified compounds demonstrated acceptable safety profiles on THP-1 cell lines and sheep red blood cells, and had appropriate physicochemical properties suitable for further drug development. Two compounds (MMV690102 and MMV688262) were identified as leads. The anti-tubercular agent MMV688262 (delamanid) showed a synergistic effect with amphotericin B, indicating the prospect of using this compound for combination therapy.

Conclusion: The current study indicates the presence of additional hits which may hold promise as starting points for anti-leishmanial drug discovery and in-depth structure-activity relationship studies.

Oxidative stress is a common feature of tuberculosis (TB), and persons with reduced antioxidants are at more risk of TB. TB patients with relatively severe oxidative stress had also more advanced disease as measured by the Karnofsky performance index. Since adverse effects from anti-TB drugs are also mediated by free radicals, TB patients are prone to side effects, such as hearing loss. In previous articles, researchers appealed for clinical trials aiming at evaluating N-acetyl cysteine (NAC) in attenuating the dreaded hearing loss during multidrug-resistant TB (MDR-TB) treatment. However, before embarking on such trials, considerations of NAC's overall impact on TB treatment are crucial. Unfortunately, such a comprehensive report on NAC is missing in the literature and this manuscript reviews the broader effect of NAC on TB treatment. This paper discusses NAC's effect on mycobacterial clearance, hearing loss, drug-induced liver injury, and its interaction with anti-TB drugs. Based on the evidence accrued to date, NAC appears to have various beneficial effects on TB treatment. However, despite the favorable interaction between NAC and first-line anti-TB drugs, the interaction between the antioxidant and some of the second-line anti-TB drugs needs further investigations.

Objective: Preschool age children (PSAC) are excluded from community based praziquantel treatment programs mainly due to paucity of evidence on the magnitude of schistosomiasis, efficacy and safety of this treatment in PSAC. The aim of this study is to assess Schistosoma mansoni infection rate and evaluate response to praziquantel in PSAC. A facility based longitudinal study was employed from April to June 2016 at Erer Health Center, Eastern Ethiopia. Stool sample was examined for schistosomiasis in 236 PSAC and repeated after 4 weeks post-treatment in positive individuals. Treatment outcomes were recorded and interpreted.

Results: Out of the 236 study participants, 59 (25%) were infected with S. mansoni. Praziquantel treatment (40 mg/kg) resulted in 96.4% cure rate and 99.4% egg reduction rate. Children of 3-5 year old were significantly affected with S. mansoni infection. Nausea and fatigue were common mild adverse events within 4 h of treatment however moderate and severe adverse events and allergic reactions were not observed. In conclusion, praziquantel at 40 mg/kg, the dose utilized in standard care for school age children, is tolerable and efficacious in the treatment of S. mansoni infection in PSAC, which calls for the healthcare system to provide appropriate service for this population.