Preparedness of primary and secondary health facilities in India to address major noncommunicable diseases: results of a National Noncommunicable Disease Monitoring Survey (NNMS).

BACKGROUND: The monitoring framework for evaluating health system response to noncommunicable diseases (NCDs) include indicators to assess availability of affordable basic technologies and essential medicines to treat them in both public and private primary care facilities. The Government of India launched the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular diseases and Stroke (NPCDCS) in 2010 to strengthen health systems. We assessed availability of trained human resources, essential medicines and technologies for diabetes, cardiovascular and chronic respiratory diseases as one of the components of the National Noncommunicable Disease Monitoring Survey (NNMS - 2017-18). METHODS: NNMS was a cross-sectional survey. Health facility survey component covered three public [Primary health centre (PHC), Community health centre (CHC) and District hospital (DH)] and one private primary in each of the 600 primary sampling units (PSUs) selected by stratified multistage random sampling to be nationally representative. Survey teams interviewed medical officers, laboratory technicians, and pharmacists using an adapted World Health Organization (WHO) - Service Availability and Readiness Assessment (SARA) tool on handhelds with Open Data Kit (ODK) technology. List of essential medicines and technology was according to WHO - Package of Essential Medicines and Technologies for NCDs (PEN) and NPCDCS guidelines for primary and secondary facilities, respectively. Availability was defined as reported to be generally available within facility premises. RESULTS: Total of 537 public and 512 private primary facilities, 386 CHCs and 334 DHs across India were covered. NPCDCS was being implemented in 72.8% of CHCs and 86.8% of DHs. All essential technologies and medicines available to manage three NCDs in primary care varied between 1.1% (95% CI; 0.3-3.3) in rural public to 9.0% (95% CI; 6.2-13.0) in urban private facilities. In NPCDCS implementing districts, 0.4% of CHCs and 14.5% of the DHs were fully equipped. DHs were well staffed, CHCs had deficits in physiotherapist and specialist positions, whereas PHCs reported shortage of nurse-midwives and health assistants. Training under NPCDCS was uniformly poor across all facilities. CONCLUSION: Both private and public primary care facilities and public secondary facilities are currently not adequately prepared to comprehensively address the burden of NCDs in India.

Baseline risk factor prevalence among adolescents aged 15-17 years old: findings from National Non-communicable Disease Monitoring Survey (NNMS) of India.

OBJECTIVE: To generate national estimates of key non-communicable disease (NCD) risk factors for adolescents (15-17 years) identified in the National NCD Monitoring Framework and, study the knowledge, attitudes and practices towards NCD risk behaviours among school-going adolescents. DESIGN AND SETTING: A community-based, national, cross-sectional survey conducted during 2017-2018. The survey was coordinated by the Indian Council of Medical Research-National Centre for Disease Informatics and Research with 10 reputed implementing research institutes/organisations across India in urban and rural areas. PARTICIPANTS: A multistage sampling design was adopted covering ages between 15 and 69 years-adolescents (15-17 years) and adults (18-69 years). The sample included 12 000 households drawn from 600 primary sampling units. All available adolescents (15-17 years) from the selected households were included in the survey. MAIN OUTCOME MEASURES: Key NCD risk factors for adolescents (15-17 years)-current tobacco and alcohol use, dietary behaviours, insufficient physical activity, overweight and obesity. RESULTS: Overall, 1402 households and 1531 adolescents completed the survey. Prevalence of current daily use of tobacco was 3.1% (95% CI: 2.0% to 4.7%), 25.2% (95% CI: 22.2% to 28.5%) adolescents showed insufficient levels of physical activity, 6.2% (95% CI: 4.9% to 7.9%) were overweight and 1.8% (95% CI: 1.0% to 2.9%) were obese. Two-thirds reported being imparted health education on NCD risk factors in their schools/colleges. CONCLUSION: The survey provides baseline data on NCD-related key risk factors among 15-17 years in India. These national-level data fill information gaps for this age group and help assess India's progress towards NCD targets set for 2025 comprehensively. Though the prevalence of select risk factors is much lower than in many developed countries, this study offers national evidence for revisiting and framing appropriate policies, strategies for prevention and control of NCDs in younger age groups.

National noncommunicable disease monitoring survey (NNMS) in India: Estimating risk factor prevalence in adult population.

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.

Insecticide susceptibility of Phlebotomus argentipes sandflies, vectors of visceral leishmaniasis in India.

OBJECTIVES: Indoor residual spraying (IRS) with insecticides is the main vector control intervention for the elimination of visceral leishmaniasis in India. After a change in IRS policy in 2015 due to widespread resistance of Phlebotomus argentipes to DDT, IRS with DDT was replaced with alpha-cypermethrin IRS in 2016. The objective of the present study was to evaluate the susceptibility of P. argentipes to DDT and its alternatives, namely malathion and pirimiphos-methyl (organophosphates); alpha-cypermethrin, deltamethrin, lambda-cyhalothrin and permethrin (pyrethroids), and bendiocarb and propoxur (carbamates), in support of visceral leishmaniasis elimination in India. METHODS: Phlebotomus argentipes sandflies were collected from the visceral-leishmaniasis endemic states of Bihar, Jharkhand and West Bengal. In the WHO tube tests, the phenotypic susceptibility of F1, 2-day old, non-blood fed females were determined against filter papers impregnated with DDT 4%, malathion 5%, pirimiphos-methyl 0.25%, alpha-cypermethrin 0.05%, deltamethrin 0.05%, lambda-cyhalothrin 0.05%, permethrin 0.75%, bendiocarb 0.1% and propoxur 0.1%, which were sourced from Universiti Sains Malaysia. The knockdown of sandflies after 1-h exposure and mortality at 24 h after the 1-h exposure period were scored. RESULTS: Mean mortality of P. argentipes 24 h after exposure in tube tests was 22.6% for DDT and ≥ 98% for other insecticide-impregnated papers tested. CONCLUSION: Phlebotomus argentipes continues to be highly resistant to DDT with no reversal of resistance after DDT's withdrawal from IRS. P. argentipes was fully susceptible to pyrethroid, organophosphate and carbamate insecticides tested. Regular monitoring is warranted for insecticide resistance management in sandfly vectors.

The usefulness of trained field workers in diagnosis of post-kala-azar dermal leishmaniasis (PKDL) and clinico-epidemiological profile in highly endemic areas of Bihar.

BACKGROUND: Surveillance of post-kala-azar dermal leishmaniasis (PKDL) is critical to the elimination of visceral leishmaniasis (VL). In this study we assessed the feasibility of using trained field workers for detecting suspected PKDL cases. METHODS: A cross-sectional study using a multistage sampling technique was conducted in the Araria district of Bihar. Trained field workers were utilized for identification of suspected PKDL case. RESULTS: We investigated 57 099 individuals from 11 300 households. The trained field workers were useful in identifying 107 (18%) probable PKDL cases. The calculated PKDL prevalences were 18.7/10 000 and 9.7/10 000 for probable and confirmed PKDL cases, respectively. The median duration of onset of PKDL was 23 months (interquartile range 16.5-56.5). The younger age group developed PKDL significantly more often compared with the older age group (p=0.007). Of the 107 patients, 25 (55.5%) were positive by microscopy of slit skin smear and 42 (93.3%) by polymerase chain reaction. Of 45 patients, 33 (73%) PKDL cases were cured after full treatment. The risk of not being cured with incomplete treatment was three times higher than with complete treatment (relative risk 3.12 [95% confidence interval 1.23 to 8.67], p=0.004). CONCLUSIONS: We conclude that the prevalence of PKDL is high and the use of trained field workers may be feasible to actively detect PKDL cases in VL-endemic areas of Bihar, India.

Computational prediction and analysis of potential antigenic CTL epitopes in Zika virus: A first step towards vaccine development.

The Zika virus disease is an Aedes mosquito-borne disease caused by the ZIKA virus. The unavailability of vaccines or proper chemotherapeutic treatment emphasizes the need for the development of preventive and therapeutic vaccines. T cell specific epitopes have been used as vaccine candidates to generate desired immune responses against a variety of viral pathogens. Herein, the immune-informatics approach was used for the screening of potential major histocompatibility complex class I restricted epitopes, which may be competent to generate a cell-mediated immune response in humans. A total of 63 epitopes were identified, which revealed a comprehensive binding affinity to the 42 different human leukocyte antigen class I supertypes: A01, A02, A08, A23, A24, A25, A26, A29, A30, A32, A66, A68, A69, A80, B07, B08, B14, B15, B27, B35, B39, B40, B42, B45, B46, B48, B51, B53, B54, B57, B58, B83, C12, C03, C04, C05, C06, C07, C08, C12, C14, and C15, and which had no homologs in humans. By combining the human leukocyte antigen binding specificity and population coverage, nine promiscuous epitopes located in Capsid 1 Protein (MVLAILAFL(P1)), Envelop Protein (RLKGVSYSL (P2) and RLITANPVI (P3)), NS2A (AILAALTPL (P4)), NS4B (LLVAHYMYL (P5) and LVAHYMYLI (P6)) and NS5 (SLINGVVRL (P7), ALNTFTNLV (P8) and YLSTQVRYL (P9)) were shortlisted. Most of these consensus epitopes revealed 100% conservancy in all Zika virus strains and were very less conserved against the human proteome. The combination of the selected epitopes accounted for an optimal coverage in the world wide population (>99%) independent of ethnicity. Structural analysis of these selected epitopes by the PatchDock web server showed their preferential mode of presentation to the T cell receptor. All these results recommended the possibility of a combined epitope vaccine strategy and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates.

Snowball Vs. House-to-House Technique for Measuring Annual Incidence of Kala-azar in the Higher Endemic Blocks of Bihar, India: A Comparison.

BACKGROUND: Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to-house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar's χ² statistics (64; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission. CONCLUSION/SIGNIFICANCE: Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination programme as cost-effective approach for estimation of kala-azar burden.

Development of PLGA-PEG encapsulated miltefosine based drug delivery system against visceral leishmaniasis.

Targeted drug delivery systems are ideal technology to increase the maximum mechanism of action with smaller dose, we have developed miltefosine encapsulated PLGA­PEG nanoparticles (PPEM) to target macrophage of infected tissues against Leishmania donovani. The structural characterization of PLGA­PEG by transmission electron microscopy (TEM) has shown a size range of 10 to 15 nm. Synthesis and drug encapsulation confirmed by dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR) and confirmed NP encapsulation. The dose of nano encapsulated miltefosine decreased by fifty percent as compared to that of a conventional miltefosine and Amphoterecin B. The inhibition of amastigotes in the splenic tissue with nano encapsulated miltefosine (23.21 ± 23) was significantly more than the conventional miltefosine (89.22 ± 52.7) and Amphoterecin B (94.12 ± 55.1). This study signifies that there is an increased contact surface area of the nano encapsulated drug and significant reduction in size, improved the efficacy in both in vitro and in vivo study than that of the conventional miltefosine, Amphoterecin B.

Asymptomatic infection with visceral leishmaniasis in a disease-endemic area in bihar, India.

A prospective study was carried out in a cohort of 355 persons in a leishmaniasis-endemic village of the Patna District in Bihar, India, to determine the prevalence of asymptomatic persons and rate of progression to symptomatic visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were positive for leishmaniasis by any of the three tests (rK39 strip test, direct agglutination test, and polymerase chain reaction) used. Point prevalence of asymptomatic VL was 110 per 1,000 persons and the rate of progression to symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75-15.01, P = 0.09) among case-contacts of VL compared with neighbors. High prevalence of asymptomatic persons and clinical VL cases and high density of Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic areas.

Estimation of under-reporting of visceral leishmaniasis cases in Bihar, India.

We estimated the level of under-reporting of visceral leishmaniasis (VL) cases by comparing the actual reported cases with those expected as estimated using age- and sex-stratified incidence proportions obtained in a cohort of 31,324 persons. The average incidence proportion of VL cases in study population was 5.7/1,000 (95% confidence interval [CI] = 4.88-6.54) and 1.09/1,000 persons (95% CI = 0.99-1.20) based on the reported cases in two primary health centers. The overall magnitude of VL cases not reported to the government agencies was higher by a factor 4.17 (95% CI = 3.75-4.63) than for reported cases. The levels of under-reporting were 4.74 (95% CI = 4.11-5.47) in males and 3.51 (95% CI = 2.99-4.11) in females with no significant difference (P > 0.05). It was significantly higher in persons >or= 30 years of age than in persons 30 years of age (P < 0.05).

A controlled, randomized nonblinded clinical trial to assess the efficacy of amphotericin B deoxycholate as compared to pentamidine for the treatment of antimony unresponsive visceral leishmaniasis cases in Bihar, India.

BACKGROUND: There is significant variation in Amphotericin B (AMB) efficacy and relapses in antimony unresponsive visceral leishmaniasis (VL) cases over a period of time (10-15 years). Keeping in mind the above mentioned view this study was undertaken with an objective to assess the magnitude of cure and relapse rates of AMB in the treatment of antimony unresponsive VL cases. METHODS: In a controlled, randomized nonblinded clinical trial, we evaluated the cure and relapse rate of Amphotericin B deoxycholate as compared to pentamidine. A total of 82 sodium stibogluconate (SSG) unresponsive and parasitologically confirmed VL cases were included in this study and randomized into two groups, test (Amphotericin B) and control (Pentamidine). Both the groups were treated with recommended dosages (as per World Health Organization guidelines) of respective medicines. All the patients were followed up on 1st, 2nd, and 6th month after end of treatment. RESULTS: Apparent cure rate in the Amphotericin B group was found to be 95% (39/41) compared with 83% (34/41) in the Pentamidine group, which shows significant statistical difference (p = 0.05). The ultimate cure rate was found 92% (38/41) in the Amphotericin B group compared to 73% (30/41) in the Pentamidine group, which shows a significant statistical difference (Yates corrected chi-square = 4.42, p = 0.04). Similarly, significant statistical difference was observed in the relapse rate of the Amphotericin group compared to the Pentamidine group (p = 0.03). CONCLUSIONS: AMB may still be the drug of choice in the management of resistant VL cases in Bihar, India. This is due to its consistent apparent cure rate (95%), low relapse rate (2.5%), and cost effectiveness compared with other available antileishmanial drugs. It is a safe drug even in case of pregnancy. Efforts should be taken to form a future strategy so that this drug and coming newer drugs do not meet a similar fate as has happened to SSG and pentamidine over a span of 10-15 years.