As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy. Funding: The Spanish Agency for International Cooperation for Development (AECID) has provided generous support to the WHO Leishmaniasis program since 2005. This support permitted among many other activities regional meetings with the AFRO, EURO, PAHO and SEARO countries, and provided for short term contracts for IDV, MdB, MH and JS related to the preparation of the country profiles. Sanofi provided a grant for a regional meeting with the EMRO countries and various activities related to the control of cutaneous Leishmaniasis in the EMRO region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: alvarj@who.int . These authors contributed equally to this work " For a full list of the members of the WHO Leishmaniasis Control Team please see the Acknowledgments section.

/pdf/leishmaniasis-worldwide-and-global-estimates-of-its-3u3xol0yef.pdf

Leishmaniasis Worldwide and Global Estimates of Its Incidence

Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.

/pdf/drug-resistance-in-leishmaniasis-52uqk16ezk.pdf

Drug Resistance in Leishmaniasis

https://www.cell.com/trends/parasitology/pdf/S1471-4922(06)00239-X.pdf

Leishmaniasis and poverty.

In India, 320 patients with visceral leishmaniasis (209 in the state of Bihar and 11 in the neighboring state of Uttar Pradesh) received identical pentavalent antimony (Sb) treatment. Sb induced long-term cure in 35% (95% confidence interval [CI], 28%-42%) of those in Bihar versus 86% (95% CI, 79%-93%) of those in Uttar Pradesh. In Bihar, the center of the Indian epidemic, traditional Sb treatment should be abandoned.

/pdf/failure-of-pentavalent-antimony-in-visceral-leishmaniasis-in-4pb3323n1h.pdf

Failure of Pentavalent Antimony in Visceral Leishmaniasis in India: Report from the Center of the Indian Epidemic

Throughout the world, pentavalent antimonial compounds (Sb(v)) have been the mainstay of antileishmanial therapy for more than 50 years. Sb(v) has been highly effective in the treatment of Indian visceral leishmaniasis (VL: kala-azar) at a low dose (10 mg/kg) for short durations (6-10 days). But in the early 1980s reports of its ineffectiveness emerged, and the dose of Sb(v) was eventually raised to 20 mg/kg for 30-40 days. This regimen cures most patients with VL except in India, where the proportion of patients unresponsive to Sb(v) has steadily increased. In hyperendemic districts of north Bihar, 50-65% patients fail treatment with Sb(v). Important reasons are rampant use of subtherapeutic doses, incomplete duration of treatment and substandard drugs. In vitro experiments have established emergence of Sb(v) resistant strains of Leishmania donovani, as isolates from unresponsive patients require 3-5 times more Sb(v) to reach similarly effectiveness against the parasite as in Sb(v) responders. Anthroponotic transmission in India has been an important factor in rapid increase in the Sb(v) refractoriness. Pentamidine was the first drug to be used and cured 99% of these refractory patients, but over time even with double the amount of initial doses, it cures only 69-78% patients now and its use has largely been abandoned in India. Despite several disadvantages, amphotericin B is the only drug available for use in these areas and should be used as first-line drug instead of Sb(v). The new oral antileishmanial drug miltefosine is likely to be the first-line drug in future. Unfortunately, development of newer antileishmanial drugs is rare; two promising drugs, aminosidine and sitamaquine, may be developed for use in the treatment of VL. Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost.

Drug resistance in Indian visceral leishmaniasis.

Large scale therapeutic failure of antimony has been the outstanding feature of the current epidemic of Indian kala - azar. Because of the ineffectiveness of a regimen of sodium stibogluconate 10 mg/kg body weight for 6-10 days the World Health Organisation recommended a dosage of 20 mg/kg body weight for 20 days in new cases and for 40 days in relapses.1 Initial successes achieved with these regimens, however, have not been sustained.2,3 Against this background we examined the clinicoepidemiological factors contributing to the unresponsiveness of Indian kala-azar to the drug.

We studied 312 patients with Indian kala-azar (proved parasitologically) who had received one or more courses of antimony but had failed to recover. The mean weight of these patients was 38.8 (SD 13.3) kg; 169 patients weighed more than …

Clinicoepidemiological study of drug resistance in Indian kala - azar

In order to assess nutritional status of adolescent girls this community based cross-sectional study was done on 270 adolescent girls of a rural area of Varanasi selected by adopting appropriate sampling technique. Nutritional status of study subjects was assessed on the basis of clinical examination anthropometry and hemoglobin estimation. On clinical examination Vitamin A deficiency pallor dental caries and Iodine Deficiency Disorders were present in 13.70% 25.90% 13.33% and 4.44% adolescent girls respectively. As per proposed Asian and previous WHO criterias 68.52% adolescents girls were undernourished (BMI<18.5). As much as 19.63% 17.78% and 31.11% subjects suffered from chronic energy deficiency (CED) grade I II and III respectively. The average weight height and MAC were 73.63% 91.98% and 82.81% of the corresponding estimated reference values. Overall 30.74% girls were anaemic (Hb<12g%). Anaemia was significantly more in non-menstruating girls and subjects not using footwear during defecation. (authors)

Nutritional status of adolescent girls in rural area of Varanasi.

Pharmacology of L-prolyl-L-leucyl-glycinamide (PLG): a review.

AIM: The aim was to determine the epidemiology of ocular trauma in a large teaching hospital in northern India over 4 years from 2010 to 2014. MATERIALS AND METHODS: This prospective, hospital-based, observational study was conducted at the Ophthalmology and Emergency Outpatient Departments of S. S. Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, from March 2012 to February 2016. Detailed history was taken with special consideration to time, place and session of trauma, mode of injury, and type and nature of traumatic agent. All patients were thoroughly examined as per the standard clinical procedures to identify the type, extent, and severity of injury and impact on ocular structure and vision. Follow-up period was 6 months. Statistical analysis was based on age, sex, residence, marital status, occupation, per capita income, type of trauma and nature of damage, etc. RESULTS: Out of 402 patients, 293 (72.9%) were male and 109 (27.1%) were female. Overall male-to-female sex ratio was 2.7:1. Patients were aged between 2 and 70 years (mean: 26.48 ± 15.88, median: 23 years). The most vulnerable age group was 6–15 years (24.38%) followed by 16–25 years (23.88%). Maximum patients belonged to rural background (61.94%). The extent of ocular trauma was 3.93% (95% confidence interval: 3.23–4.63). Majority of participants were single (78.11%) and rest were married. About 112 (27.9%) participants were illiterate and 24.4% had primary education only. One hundred and eighty-eight (46.8%) participants belonged to lower and lower middle socioeconomic status. The cases were clustered in Rs. 1000–5000 per capita income. Most of the injuries occurred in summer season (46.18%) and in afternoon between 12.00 and 17.59 h (48.8%). Majority of trauma occurred away from home (66.20%) mainly on street (28.6%) and playground (9.2%). The most common injury was nonoccupational (82.3%) including sports related (23.9%) and road traffic accident (23.6%). Mechanical injuries were accounted for 89.3% of all eye injuries, and most common source was wooden object (24.9%) followed by metallic objects (20.9%). Traumatic agents were blunt and sharp in 56% and 17% of cases, respectively. Majority of traumatic agents were solid (82.1%). Seven percent of victims were drowsy during trauma and 98.4% of participants were not using any protective device at the time of injury. In 60.7% of cases, time elapsed between injury and treatment was between 1 and 24 h. Around 44.5% had isolated ocular trauma and rest 55.5% were polytrauma cases. Three hundred and sixty-eight (91.5%) participants had unilateral involvement and 8.5% had bilateral involvement. Almost 52.8% had injuries of adnexa and 32.8% had globe injuries. More than half of the study participants had ≥3 ocular structure involvement. After 6 months, 14.8% of the right eyes and 25.5% of the left eyes showed poor outcome. CONCLUSION: This study highlights epidemiology of ocular trauma in northern India. Mass health education and awareness about risk of ocular trauma, morbidity caused by delayed presentation, and need to adopt safety or preventive strategies should be focused, especially during travel, playground, and at workplace.

The epidemiology of ocular trauma in Northern India: A teaching hospital study.

In order to assess nutritional status of adolescent girls of a slum community of Varanasi and factors influencing them, this study was carried out on 70 girls belonging to the age group 13 to 18 years The study subjects were selected from Sunderpur, an urban community of Varanasi, by adopting appropriate sampling methodology The approach adopted for the study was a cross sectional one The tools in the study were pre-designed and pre-tested schedule, weighing scale, steel anthoropometric rod and measuring tape The techniques of the study included interview method, clinical examination and anthropometry In all, 700% adolescent girls had BMI 6) indicated role of familial support in prevention of undernutrition in adolescent girls

C. P. Mishra

Papers

Clinicoepidemiological study of drug resistance in Indian kala - azar

Nutritional status of adolescent girls in rural area of Varanasi.

Pharmacology of L-prolyl-L-leucyl-glycinamide (PLG): a review.

The epidemiology of ocular trauma in Northern India: A teaching hospital study.

Nutritional status of adolescent girls of a slum community of Varanasi.