The control of Leishmania infection relies primarily on chemotherapy till date. Resistance to pentavalent antimonials, which have been the recommended drugs to treat cutaneous and visceral leishmaniasis, is now widespread in Indian subcontinents. New drug formulations like amphotericin B, its lipid formulations, and miltefosine have shown great efficacy to treat leishmaniasis but their high cost and therapeutic complications limit their usefulness. In addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the parasite. In context to the limited drug options and unavailability of either preventive or prophylactic candidates, there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic disease. Notwithstanding significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from satisfactory. This review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.

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This study was conducted to find out the status of the ossicles in cases of chronic suppurative otitis media (CSOM). One hundred and fifty cases of CSOM, who underwent surgery, were included and their intra-operative ossicular chain findings noted. Ossicular erosion was found to be much more common in unsafe CSOM than in safe CSOM. Malleus was found to be the most resistant ossicle to erosion whereas incus was found to be the most susceptible.

Soon after the identification of Leishmania parasite as a causative agent, the pentavalent antimony compounds have been the mainstay to treat all forms of leishmaniasis. Due to growing incidences of antimony resistant parasites and unavailability of true antileishmanial compounds, few drugs like pentamidine (antimicrobial), amphotericin B (antifungal) or miltefosine (antitumor) are currently being used but these are associated with serious side effects. Unfortunately, the emergence of amphotericin B and miltefosine resistant parasites in clinical settings has further questioned their sustained use in leishmanial control. Moreover, the parameters of protective immunity are not well understood in leishmanial pathogenesis therefore, a vaccine candidate, either prophylactic or preventive, is still an unrealized goal. In addition, the emergence of insecticide resistance sand flies in disease endemic regions also stance a big threat for the current elimination strategies. Therefore, in lieu of the limited drug regimen and unavailability of a vaccine, the necessity of a true antileishmanial agent is always there. Although, leishmanial infections have been neglected for many decades but recent studies have identified potential drug targets that could be targeted to control the growth of parasites. In recent past many compounds derived from natural sources have also been shown to possess excellent antiparasitic potential; however, most of these studies are limited to primary evaluation and only a few have reached to clinical levels. In this review, we discuss the limitations of current drug regimen, explore possible drug targets of Leishmania species and summarize wide range of compounds isolated from various natural sources that are worth screening as antileishmanial drug candidates.

Background Community‐based primary‐level workers (PWs) are an important strategy for addressing gaps in mental health service delivery in low‐ and middle‐income countries. Objectives To evaluate the effectiveness of PW‐led treatments for persons with mental health symptoms in LMICs, compared to usual care. Search methods MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, ICTRP, reference lists (to 20 June 2019). Selection criteria Randomised trials of PW‐led or collaborative‐care interventions treating people with mental health symptoms or their carers in LMICs. PWs included: primary health professionals (PHPs), lay health workers (LHWs), community non‐health professionals (CPs). Data collection and analysis Seven conditions were identified apriori and analysed by disorder and PW examining recovery, prevalence, symptom change, quality‐of‐life (QOL), functioning, service use (SU), and adverse events (AEs). Risk ratios (RRs) were used for dichotomous outcomes; mean difference (MDs), standardised mean differences (SMDs), or mean change differences (MCDs) for continuous outcomes. For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥0.80 large clinical effects. Analysis timepoints: T1 (<1 month), T2 (1‐6 months), T3 ( >6 months) post‐intervention. Main results Description of studies 95 trials (72 new since 2013) from 30 LMICs (25 trials from 13 LICs). Risk of bias Most common: detection bias, attrition bias (efficacy), insufficient protection against contamination. Intervention effects *Unless indicated, comparisons were usual care at T2. “Probably”, “may”, or “uncertain” indicates "moderate", "low," or "very low" certainty evidence. Adults with common mental disorders (CMDs) LHW‐led interventions a. may increase recovery (2 trials, 308 participants; RR 1.29, 95%CI 1.06 to 1.56); b. may reduce prevalence (2 trials, 479 participants; RR 0.42, 95%CI 0.18 to 0.96); c. may reduce symptoms (4 trials, 798 participants; SMD ‐0.59, 95%CI ‐1.01 to ‐0.16); d. may improve QOL (1 trial, 521 participants; SMD 0.51, 95%CI 0.34 to 0.69); e. may slightly reduce functional impairment (3 trials, 1399 participants; SMD ‐0.47, 95%CI ‐0.8 to ‐0.15); f. may reduce AEs (risk of suicide ideation/attempts); g. may have uncertain effects on SU. Collaborative‐care a. may increase recovery (5 trials, 804 participants; RR 2.26, 95%CI 1.50 to 3.43); b. may reduce prevalence although the actual effect range indicates it may have little‐or‐no effect (2 trials, 2820 participants; RR 0.57, 95%CI 0.32 to 1.01); c. may slightly red...

BackgroundThough Nepal declared leprosy elimination in 2010, its burden is constantly rising in Terai communities for the past 2 years with 3000 new leprosy cases being diagnosed annually. Community’s perception is important for prevention and control of leprosy and enhancing quality of life of leprosy patients. Poor knowledge, unfavorable attitude and stigma create a hindrance to leprosy control. The main objective of this study was to assess the knowledge, attitude and stigma of leprosy amongst the community members living in Dhanusha and Parsa districts of Southern Central Nepal.MethodsA total of 423 individuals were interviewed using a structured questionnaire in Dhanusha and Parsa districts. Data was analyzed using both descriptive (frequency, percentage, median) and statistical inferences (Chi-square test, Kruskal Wallis H test, Mann Whitney U test, binary logistic regression) using SPSSvs20.ResultsAll respondents had heard about leprosy. Source of information on leprosy was mainly found to be health workers/hospitals (33.1%). Only 62.6% reported bacteria being its cause followed by other myths such as bad blood/curse/heredity/bad deeds (36%). Only 43.8% responded that leprosy is transmitted by prolonged close contact with leprosy patients and 25.7% reported religious rituals as the treatment. Only 42.1% had good knowledge and 40.9% had favorable attitude. Good knowledge of leprosy was highly associated with favorable attitude towards leprosy (P<0.001). The outcome variables- knowledge, attitude and EMIC score were found to have highly significant association with age, sex, ethnicity, religion, education and occupation of the respondents (P<0.001). Having knowledge on leprosy transmission was positively associated with favorable attitude towards leprosy (P<0.001).ConclusionsStrategizing the awareness programmes according to socio-demographic characteristics for enhancing the knowledge regarding leprosy cause, symptoms, transmission, prevention and treatment, can foster the positive community attitude towards leprosy affected persons. Enhancing positive attitude towards leprosy affected persons can reduce the community stigma, thus may increase their participation in the community. Positive attitude may further increase their early health seeking behaviour including their quality of life.

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