Rajendra Memorial Research Institute of Medical Sciences

BACKGROUND: Visceral leishmaniasis (kala-azar) affects large, rural, resource-poor populations in South Asia, Africa, and Brazil. Safe, effective, and affordable new therapies are needed. We conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin B, the present standard of care in Bihar, India. METHODS: In four treatment centers for visceral leishmaniasis, 667 patients between 5 and 55 years of age who were negative for the human immunodeficiency virus and had parasitologically confirmed visceral leishmaniasis were randomly assigned in a 3:1 ratio to receive paromomycin (502 patients) at a dose of 11 mg per kilogram of body weight intramuscularly daily for 21 days or amphotericin B (165 patients) at a dose of 1 mg per kilogram intravenously every other day for 30 days. Final cure was assessed 6 months after the end of treatment; safety assessments included daily clinical evaluations and weekly laboratory and audiometric evaluations. Noninferiority testing was used to compare 6-month cure rates, with a chosen margin of noninferiority of 10 percentage points. RESULTS: Paromomycin was shown to be noninferior to amphotericin B (final cure rate, 94.6% vs. 98.8%; difference, 4.2 percentage points; upper bound of the 97.5% confidence interval, 6.9; P<0.001). Mortality rates in the two groups were less than 1%. Adverse events, which were more common among patients receiving paromomycin than among those receiving amphotericin B (6% vs. 2%, P=0.02), included transient elevation of aspartate aminotransferase levels (>3 times the upper limit of the normal range); transient reversible ototoxicity (2% vs. 0, P=0.20); and injection-site pain (55% vs. 0, P<0.001); and in patients receiving amphotericin B, as compared with those receiving paromomycin, nephrotoxicity (4% vs. 0, P<0.001), fevers (57% vs. 3%), rigors (24% vs. 0, P<0.001), and vomiting (10% vs. <1%, P<0.001). CONCLUSIONS: Paromomycin was shown to be noninferior to amphotericin B for the treatment of visceral leishmaniasis in India. (ClinicalTrials.gov number, NCT00216346.)

The clinical value of amphotericin B, the mainstay therapy for visceral leishmaniasis in sodium antimony gluconate-nonresponsive zones of Bihar, India, is now threatened by the emergence of acquired drug resistance, and a comprehensive understanding of the underlying mechanisms is the need of the hour. We have selected an amphotericin B-resistant clinical isolate which demonstrated 8-fold-higher 50% lethal doses (LD(50)) than an amphotericin B-sensitive strain to explore the mechanism of amphotericin B resistance. Fluorimetric analysis demonstrated lower anisotropy in the motion of the diphenylhexatriene fluorescent probe in the resistant strain, which indicated a higher fluidity of the membrane for the resistant strain than for the sensitive strain. The expression patterns of the two transcripts of S-adenosyl-l-methionine:C-24-Δ-sterol methyltransferase and the absence of ergosterol, replaced by cholesta-5,7,24-trien-3β-ol in the membrane of the resistant parasite, indicate a decreased amphotericin B affinity, which is evidenced by decreased amphotericin B uptake. The expression level of MDR1 is found to be higher in the resistant strain, suggesting a higher rate of efflux of amphotericin B. The resistant parasite also possesses an upregulated tryparedoxin cascade and a more-reduced intracellular thiol level, which helps in better scavenging of reactive oxygen species produced by amphotericin B. The resistance to amphotericin B was partially reverted by the thiol metabolic pathway and ABC transporter inhibitors. Thus, it can be concluded that altered membrane composition, ATP-binding cassette transporters, and an upregulated thiol metabolic pathway have a role in conferring amphotericin B resistance in clinical isolates of Leishmania donovani.

BACKGROUND: Visceral leishmaniasis (VL) is a major public health problem in Bihar, accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. METHODS: An open, single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. RESULTS: The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good, with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients, including gastrointestinal toxicity and rise in aspertate amino transferase, alanine amino transferase, or serum creatinine levels, similar to previous clinical experience. CONCLUSION: This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic.

The inability of most untreated patients with Kala-azar to control their visceral infections with Leishmania donovani has been attributed to a defective cell-mediated immune response to leishmanial antigens. We examined the in vitro response of T cells, including Leu-2+-depleted T cell populations, to determine whether unresponsiveness could be reversed. These studies on patients with visceral leishmaniasis in Bihar, north India, support previous observations regarding T cell unresponsiveness in patients with active disease: it is profound, it is specific, and it is reversible after successful chemotherapy. However, these studies also indicate that the specific unresponsiveness cannot be reversed by depletion of "suppressor" Leu-2+ T lymphocytes, nor by the addition of exogenously supplied human IL 2 to the cultures. One interpretation of these results is that in active cases of Kala-azar, there is an absence of Leishmania-specific T cells in the periphery. The possibility that reactive cells can be found in situ cannot be excluded. The observation that 13 of 25 family members of active cases were able respond to L. donovani in vitro or by skin testing suggests that the frequency of infection within an endemic area in Bihar is very high, and that assays for T cell responsiveness are far better epidemiologic tools for the detection of asymptomatic infection than is ELISA. Identification of such an exposed, Kala-azar-resistant population will be required to study host factors which influence the development of disease in infected individuals.

Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Urbanization and industrialization are responsible for environmental contamination in the air, water, and soil. These activities also generate large amounts of heavy metal ions in the environment, and these contaminants cause various types of health issues in humans and other animals. Hexavalent chromium, lead, and cadmium are toxic heavy metal ions that come into the environment through several industrial processes, such as tanning, electroplating, coal mining, agricultural activities, the steel industry, and chrome plating. Several physical and chemical methods are generally used for the heavy metal decontamination of wastewater. These methods have some disadvantages, including the generation of secondary toxic sludge and high operational costs. Hence, there is a need to develop a cost-effective and eco-friendly method for the removal of heavy metal ions from polluted areas. Biological methods are generally considered eco-friendly and cost-effective. This review focuses on heavy metal contamination, its toxicity, and eco-friendly approaches for the removal of heavy metals from contaminated sites.

Wnt/β-catenin (WβC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WβC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca2+ and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WβC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WβC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WβC signaling role in the abovementioned neurodegenerative diseases.

Hexavalent chromium is a highly soluble environmental contaminant. It is a widespread anthropogenic chromium species that is 100 times more toxic than trivalent chromium. Leather, chrome plating, coal mining and paint industries are the major sources of hexavalent chromium in water. Hexavalent chromium is widely recognised as a carcinogen and mutagen in humans and other animals. It is also responsible for multiorgan damage, such as kidney damage, liver failure, heart failure, skin disease and lung dysfunction. The fate of the toxicity of hexavalent chromium depends on its oxidation state. The reduction of Cr (VI) to Cr (III) is responsible for the generation of reactive oxygen species (ROS) and chromium intermediate species, such as Cr (V) and Cr (IV). Reactive oxygen species (ROS) are responsible for oxidative tissue damage and the disruption of cell organelles, such as mitochondria, DNA, RNA and protein molecules. Cr (VI)-induced oxidative stress can be neutralised by the antioxidant system in human and animal cells. In this review, the authors summarise the Cr (VI) source, toxicity and antioxidant defence mechanism against Cr (VI)-induced reactive oxygen species (ROS).

BACKGROUND: Poor access to diagnosis stymies control of visceral leishmaniasis (VL). Antibody-detecting rapid diagnostic tests (RDTs) can be performed in peripheral health settings. However, there are many brands available and published reports of variable accuracy. METHODS: Commercial VL RDTs containing bound rK39 or rKE16 antigen were evaluated using archived human sera from confirmed VL cases (n = 750) and endemic non-VL controls (n = 754) in the Indian subcontinent (ISC), Brazil, and East Africa to assess sensitivity and specificity with 95% confidence intervals. A subset of RDTs were also evaluated after 60 days' heat incubation (37°C, 45°C). Interlot and interobserver variability was assessed. RESULTS: All test brands performed well against ISC panels (sensitivity range, 92.8%-100%; specificity range, 96%-100%); however, sensitivity was lower against Brazil and East African panels (61.5%-91% and 36.8%-87.2%, respectively). Specificity was consistently > 95% in Brazil and ranged between 90.8% and 98% in East Africa. Performance of some products was adversely affected by high temperatures. Agreement between lots and readers was good to excellent (κ > 0.73-0.99). CONCLUSIONS: Diagnostic accuracy of VL RDTs varies between the major endemic regions. Many tests performed well and showed good heat stability in the ISC; however, reduced sensitivity against Brazilian and East African panels suggests that in these regions, used alone, several RDTs are inadequate for excluding a VL diagnosis. More research is needed to assess ease of use and to compare performance using whole blood instead of serum and in patients coinfected with human immunodeficiency virus.

BACKGROUND: The burden of dengue virus (DENV) infection across geographical regions of India is poorly quantified. We estimated the age-specific seroprevalence, force of infection, and number of infections in India. METHODS: We did a community-based survey in 240 clusters (118 rural, 122 urban), selected from 60 districts of 15 Indian states from five geographical regions. We enumerated each cluster, randomly selected (with an Andriod application developed specifically for the survey) 25 individuals from age groups of 5-8 years, 9-17 years, and 18-45 years, and sampled a minimum of 11 individuals from each age group (all the 25 randomly selected individuals in each age group were visited in their houses and individuals who consented for the survey were included in the study). Age was the only inclusion criterion; for the purpose of enumeration, individuals residing in the household for more than 6 months were included. Sera were tested centrally by a laboratory team of scientific and technical staff for IgG antibodies against the DENV with the use of indirect ELISA. We calculated age group specific seroprevalence and constructed catalytic models to estimate force of infection. FINDINGS: From June 19, 2017, to April 12, 2018, we randomly selected 17 930 individuals from three age groups. Of these, blood samples were collected and tested for 12 300 individuals (5-8 years, n=4059; 9-17 years, n=4265; 18-45 years, n=3976). The overall seroprevalence of DENV infection in India was 48·7% (95% CI 43·5-54·0), increasing from 28·3% (21·5-36·2) among children aged 5-8 years to 41·0% (32·4-50·1) among children aged 9-17 years and 56·2% (49·0-63·1) among individuals aged between 18-45 years. The seroprevalence was high in the southern (76·9% [69·1-83·2]), western (62·3% [55·3-68·8]), and northern (60·3% [49·3-70·5]) regions. The estimated number of primary DENV infections with the constant force of infection model was 12 991 357 (12 825 128-13 130 258) and for the age-dependent force of infection model was 8 655 425 (7 243 630-9 545 052) among individuals aged 5-45 years from 30 Indian states in 2017. INTERPRETATION: The burden of dengue infection in India was heterogeneous, with evidence of high transmission in northern, western, and southern regions. The survey findings will be useful in making informed decisions about introduction of upcoming dengue vaccines in India. FUNDING: Indian Council of Medical Research.

Miltefosine has previously been shown to cure 97% of cases of visceral leishmaniasis (VL) in Indian adults. Because approximately one-half of cases of VL occur in children, we evaluated use of the adult dosage of miltefosin (2.5 mg/kg per day for 28 days) in 80 Indian children (age, 2-11 years) with parasitologically confirmed infection in an open-label clinical trial. Clinical and parasitological parameters were reassessed at the end of treatment and 6 months later. One patient died of intercurrent pneumonia on day 6. The other 79 patients demonstrated no parasites after treatment, had marked clinical improvement, and were deemed initially cured. Three patients had relapse, and 1 patient was lost to follow-up. The final cure rate was 94% for all enrolled patients and 95% for evaluable patients. Side effects included mild-to-moderate vomiting or diarrhea (each in approximately 25% of patients) and mild-to-moderate, transient elevations in the aspartate aminotransferase level during the early treatment phase (in 55%). This trial indicates that miltefosine is as effective and well tolerated in Indian children with VL as in adults and that it can be recommended as the first choice for treatment of childhood VL in India.

BACKGROUND: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May-June 2020 and 7.1% in August-September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. METHODS: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. RESULTS: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0-25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5-27.8%). CONCLUSIONS: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.

\nSuman Rijal and colleagues highlight lessons from a regional collaboration to eliminate visceral leishmaniasis and identify priorities for the post-elimination plan

OBJECTIVE: We sought to estimate visceral leishmaniasis (VL) burden in Bangladesh, India, and Nepal and document care-seeking behaviour for VL to provide baseline information for monitoring the VL elimination program and identify options for improved case finding and management. DESIGN: A cross-sectional study using cluster sampling (clusters being villages) of 4 VL endemic districts was used in order to document all current and existing VL cases over the preceding 12 mo. Extended (in-depth) interviews were conducted in a subsample of households to explore (a) VL-related knowledge, attitudes, and practices of the population; (b) use of VL care by patients; and (c) delay between onset of symptoms, diagnosis, and start of treatment, as well as treatment interruption. Findings were discussed with national program managers and policy makers to develop improved strategies. RESULTS: Screening for VL was done in 18,933 households (106,425 inhabitants). The estimated annual incidence of VL in the endemic districts was on average 22 times higher than the elimination target of less than one case per 10,000 inhabitants in 2015. This incidence varied widely between study sites, from 9.0 to 29.8 per 10,000 inhabitants. The percentage of newly detected cases through the household screening was high in the districts least covered by health-care services (particularly Rajshahi, Bangladesh, 49%; and to a lesser extent Vaishali in Bihar, India, 32.5%), and much lower in districts with greater availability of VL care (Muzaffarpur, India, 3.8%). On average 267 houses had to be visited, i.e., at least three to four working days per health worker, to identify a new VL (ranging from 1,432 houses in Muzaffarpur, India to only 166 houses in Rajshahi, Bangladesh). Knowledge of the disease and its vectors was good in India and Nepal but poor in Bangladesh (Rajshahi) where very little attention has been given to VL over the last decades. Although all socio-demographic indicators showed high levels of poverty, people in India preferred private medical practitioners for the treatment of VL, whereas in Nepal, and even more in Bangladesh, the public health-care sector was preferred. Delays between onset of symptoms and diagnosis as well as start of treatment was high. Reported non-adherence to treatment was particularly high in the more under-served districts and was mainly due to lack of resources. DISCUSSION: The findings suggest that (a) house-to-house screening may be useful in highly endemic districts with a poor passive case detection system, but further evidence on case finding adapted to local conditions has to be collected; (b) strengthening the quality of the public health sector is imperative in the three countries, especially in India, with its largely unregulated private-sector provision of VL care.

Illustrated keys for the identification of the fourth-instar larvae and adult females of the mosquito species of tribe Aedini in Thailand are presented, along with the geographic distribution of the species and the known habitats of their immature stages. The keys are the first to encompass the recent revisionary studies of tribe Aedini. One hundred and seventy-five species of Aedini belonging to 38 genera and 18 subgenera are recognized in Thailand. Two species of genus Armigeres, two of genus Collessius, and one of genus Downsiomyia are undescribed. Himalaius simlensis [formerly Aedes (Finlaya) simlensis], Hopkinsius (Yamada) albocinctus [formerly Aedes (Finlaya) albocinctus], Downsiomyia nipponica and Downsiomyia saperoi [formerly species of Aedes (Finlaya)], and Hulecoeteomyia pallirostris [formerly Ochlerotatus (Finlaya) pallirostris] are new country records. Aedimorphus (formerly a subgenus of Aedes), Cancraedes, and Rhinoskusea (formerly subgenera of Ochlerotatus) are recognized as genera, and genus Petermattinglyius includes species previously included in Diceromyia (formerly a subgenus of Aedes) in Thailand. Heteraspidion, Huangmyia, Stegomyia, and Xyele are newly recognized subgenera of genus Stegomyia (formerly a subgenus of Aedes), which includes eight species without subgeneric placement. Two unidentified and unplaced species were discovered in Thailand.

A case-control study was conducted to understand the risk factors associated with kala-azar in disease-endemic areas of Bihar, India. A total of 134 kala-azar cases treated at the Rajendra Memorial Research Institute of Medical Sciences in Patna and 406 healthy controls selected randomly from the neighborhoods of cases in their native villages were included in the study. Univariate analysis showed that education, a history of other diseases in the previous year, a history of kala-azar in the family, type of walls in houses, presence of a granary inside houses, presence of vegetation around houses, bamboo trees near houses, and irregular spraying around houses with DDT were risk factors. Multivariate analysis showed that a history of other diseases in the previous year (odds ratio [OR] = 3.6, P = 0.002), a history of kala-azar in the family (OR = 1.8, P = 0.03), mud-plastered walls in houses, (OR = 2.4, P = 0.0001], a granary inside houses (OR = 4.3, P = 0.0001), presence of bamboo trees around houses (OR = 2.3, P = 0.001), and houses not sprayed with DDT in the past six months (OR = 3.4, P = 0.0001) were significant risk factors for kala-azar. These results will be useful in developing kala-azar control programs for identifying intervention strategies such as better housing, regular and proper insecticide spraying, and promoting health awareness to the community residing in disease-endemic areas for reducing transmission and incidence of this disease.

BACKGROUND: The primary objective of National NCD monitoring survey (NNMS) was to generate national-level estimates of key NCD indicators identified in the national NCD monitoring framework. This paper describes survey study protocol and prevalence of risk factors among adults (18-69 years). MATERIALS AND METHODS: NNMS was a national level cross-sectional survey conducted during 2017-18. The estimated sample size was 12,000 households from 600 primary sampling units. One adult (18-69 years) per household was selected using the World Health Organization-KISH grid. The study tools were adapted from WHO-STEPwise approach to NCD risk factor surveillance, IDSP-NCD risk factor survey and WHO-Global adult tobacco survey. Total of 8/10 indicators of adult NCD risk factors according to national NCD disease monitoring framework was studied. This survey for the first time estimated dietary intake of salt intake of population at a national level from spot urine samples. RESULTS: Total of 11139 households and 10659 adults completed the survey. Prevalence of tobacco and alcohol use was 32.8% (95% CI: 30.8-35.0) and 15.9% (95% CI: 14.2-17.7) respectively. More than one-third adults were physically inactive [41.3% (95% CI: 39.4-43.3)], majority [98.4% (95% CI: 97.8-98.8)] consumed less than 5 servings of fruits and / or vegetables per day and mean salt intake was 8 g/day (95% CI: 7.8-8.2). Proportion with raised blood pressure and raised blood glucose were 28.5% (95% CI: 27.0-30.1) and 9.3% (95% CI: 8.3-10.5) respectively. 12.8% (95% CI: 11.2-14.5) of adults (40-69 years) had ten-year CVD risk of ≥30% or with existing CVD. CONCLUSION: NNMS was the first comprehensive national survey providing relevant data to assess India's progress towards targets in National NCD monitoring framework and NCD Action Plan. Established methodology and findings from survey would contribute to plan future state-based surveys and also frame policies for prevention and control of NCDs.

Large-scale antimony resistance in the treatment of visceral leishmaniasis (VL) in north Bihar, India, has led to the development of miltefosine as an alternative therapy. In a pilot study and later in three Phase II studies involving 249 patients, oral miltefosine, 100-150 mg/day for 28 days, was shown to cure approximately 90% patients with reasonable safety. In the pivotal Phase III trial, 299 patients were treated at three centres with amphotericin B as the comparator drug (99 patients). In this trial 38% and 20% patients had mild to moderate vomiting and diarrhoea respectively, similar to previous studies. Asymptomatic transient elevation of hepatic transaminases and mild renal dysfunction were observed in 15% and 10% patients respectively. The final cure rate was 94% with miltefosine and 97% with amphotericin B; based on these results, the drug was approved in India. Subsequently in two paediatric studies involving 119 patients in the age group of 2-11 years, the safety and efficacy of miltefosine (2.5 mg/kg daily for 28 days) was established with a cure rate (94%) similar to that seen in adults. Miltefosine is the first oral antileishmanial drug with a high degree of safety and efficacy for the treatment of VL.