Seroprevalence of SARS-CoV-2-specific anti-spike IgM, IgG, and anti-nucleocapsid IgG antibodies during the second wave of the pandemic: A population-based cross-sectional survey across Kashmir, India.

Background: Within Kashmir, which is one of the topographically distinct areas in the Himalayan belt of India, a total of 2,236 cumulative deaths occurred by the end of the second wave. We aimed to conduct this population-based study in the age group of 7 years and above to estimate the seropositivity and its attributes in Kashmir valley. Methods: We conducted a community-based household-level cross-sectional study, with a multistage, population-stratified, probability-proportionate-to-size, cluster sampling method to select 400 participants from each of the 10 districts of Kashmir. We also selected a quota of healthcare workers, police personnel, and antenatal women from each of the districts. Households were selected from each cluster and all family members with age 7 years or more were invited to participate. Information was collected through a standardized questionnaire and entered into Epicollect 5 software. Trained healthcare personnel were assigned for collecting venous blood samples from each of the participants which were transferred and processed for immunological testing. Testing was done for the presence of SARS-CoV-2-specific anti-spike IgM, IgG antibodies, and anti-nucleocapsid IgG antibodies. Weighted seropositivity was estimated along with the adjustment done for the sensitivity and specificity of the test used. Findings: The data were collected from a total of 4,229 participants from the general population within the 10 districts of Kashmir. Our results showed that 84.84% (95% CI 84.51-85.18%) of the participants were seropositive in the weighted imputed data among the general population. In multiple logistic regression, the variables significantly affecting the seroprevalence were the age group 45-59 years (odds ratio of 0.73; 95% CI 0.67-0.78), self-reported history of comorbidity (odds ratio of 1.47; 95% CI 1.33-1.61), and positive vaccination history (odds ratio of 0.85; 95% CI 0.79-0.90) for anti-nucleocapsid IgG antibodies. The entire assessed variables showed a significant role during multiple logistic regression analysis for affecting IgM anti-spike antibodies with an odds ratio of 1.45 (95% CI 1.32-1.57) for age more than 60 years, 1.21 (95% CI 1.15-1.27) for the female gender, 0.87 (95% CI 0.82-0.92) for urban residents, 0.86 (95% CI 0.76-0.92) for self-reported comorbidity, and an odds ratio of 1.16 (95% CI 1.08-1.24) for a positive history of vaccination. The estimated infection fatality ratio was 0.033% (95% CI: 0.034-0.032%) between 22 May and 31 July 2021 against the seropositivity for IgM antibodies. Interpretation: During the second wave of the SARS-CoV-2 pandemic, 84.84% (95% CI 84.51-85.18%) of participants from this population-based cross-sectional sample were seropositive against SARS-CoV-2. Despite a comparatively lower number of cases reported and lower vaccination coverage in the region, our study found such high seropositivity across all age groups, which indicates the higher number of subclinical and less severe unnoticed caseload in the community.

Acceptance of COVID-19 vaccine among healthcare workers before the launch of vaccine in India: An online survey.

BACKGROUND: COVID-19 has led to significant morbidity and mortality globally in addition to unprecedented disruption in economic activities. Vaccination against it is considered to be the only sustainable way out of this pandemic. The study was conducted to estimate vaccine acceptance among doctors in India using an online survey. MATERIALS AND METHODS: A cross-sectional study using a purposive sampling method was conducted two weeks before vaccine rollout. A pretested questionnaire developed using Google forms was shared by social media groups targeting doctors only.The questions collected information regarding socio-demographic details, knowledge, attitude and practices towards COVID-19 vaccination. Data was downloaded and analysed using SPSS-v23. Chi-square test and fisher exact test was used and P < 0.05 was considered significant. RESULTS: A total of 511 records were included in the final analysis of which 340 (66.53%) reported to be either definitely or probably willing to accept COVID-19 vaccine. One third of respondents were working in COVID-19 designated hospitals (37.2%), 30% were posted in non COVID-19 hospitals, 25.1% had no direct contact with COVID-19 patients while 7.7% doctors were involved in testing COVID-19 diagnosis. Subjects who perceived a higher risk of contracting COVID-19, those who perceived that vaccine would be effective against COVID-19 and those who felt that vaccine will not have any serious side effects were more likely to accept the vaccine. CONCLUSION: There is an urgent need to address any apprehensions regarding COVID-19 vaccines. A tailored and intensified advocacy program for doctors is needed before the launch of vaccine.

Adherence to antihypertensive therapy and its determinants among patients attending primary care hospitals of Kashmir, India.

BACKGROUND: Adherence to antihypertensive therapy is an important factor in determining the clinical course of hypertension. This study was planned to estimate adherence to antihypertensive therapy and its determinants among OPD patients attending two primary care hospitals in Kashmir valley. METHODS: This study employed a cross-sectional study design. All subjects who reported to OPD between October and December 2020 and had been prescribed antihypertensive medications for at least 1 year were included. Sociodemographic information was collected on a pretested schedule and adherence to medications was assessed by using the-14 item Hill-Bone HBP Compliance to High Blood Pressure Therapy Scale (HB-HBP). Mann-Whitney test and Spearman's rank correlation coefficient were used. RESULTS: A total of 406 subjects were included in the final analysis with a mean age of 58 years for women and 56 years for men. The sample comprised 54% women. More than 60% of subjects were currently married, urban area residents, and belonged to middle strata of social class. The mean score obtained in the HB-MAS (maximum score 56) was 19.26 (SD ± 4.3). Subjects aged 60 years and above, those belonging to lower socioeconomic class, and subjects prescribed three or more drugs with more than once-daily dosing regimen had higher odds of having poor adherence. CONCLUSION: There is suboptimal adherence among OPD patients at primary care level. There is a need for enhanced counselling regarding medication adherence particularly for elderly, poor, illiterate persons and those prescribed multiple medicines with more than once-daily dosing.

Spontaneous generation of prions and transmissible PrP amyloid in a humanised transgenic mouse model of A117V GSS.

Inherited prion diseases are caused by autosomal dominant coding mutations in the human prion protein (PrP) gene (PRNP) and account for about 15% of human prion disease cases worldwide. The proposed mechanism is that the mutation predisposes to conformational change in the expressed protein, leading to the generation of disease-related multichain PrP assemblies that propagate by seeded protein misfolding. Despite considerable experimental support for this hypothesis, to-date spontaneous formation of disease-relevant, transmissible PrP assemblies in transgenic models expressing only mutant human PrP has not been demonstrated. Here, we report findings from transgenic mice that express human PrP 117V on a mouse PrP null background (117VV Tg30 mice), which model the PRNP A117V mutation causing inherited prion disease (IPD) including Gerstmann-Sträussler-Scheinker (GSS) disease phenotypes in humans. By studying brain samples from uninoculated groups of mice, we discovered that some mice (≥475 days old) spontaneously generated abnormal PrP assemblies, which after inoculation into further groups of 117VV Tg30 mice, produced a molecular and neuropathological phenotype congruent with that seen after transmission of brain isolates from IPD A117V patients to the same mice. To the best of our knowledge, the 117VV Tg30 mouse line is the first transgenic model expressing only mutant human PrP to show spontaneous generation of transmissible PrP assemblies that directly mirror those generated in an inherited prion disease in humans.

Strengthening the Use of Partograph in High Caseload Public Health Facilities in India through an Integrated Quality Improvement Approach.

BACKGROUND: The effective implementation of evidence-based practices including the use of partograph to improve maternal and newborn outcomes is critical on account of increased institutional delivery. However, despite clear guidelines, partograph use in India is not widely practiced. MATERIALS AND METHODS: Quality improvement (QI) efforts along with training and mentoring were operationalized in a total of 141 facilities across 26 high priority districts of India. Assessments were conducted across baseline, intervention period, and end line. These included reviewing the availability of partograph and staff competency in filling them at baseline and end line, as well as reviewing monthly data for use and completeness of filling. The monthly data were tabulated quarter wise to study trends. Competency scores were tabulated to show the difference across assessments. RESULTS: An overall upward trend from 29% to 61% was seen in the practice of partograph use. Simultaneously, completeness in filling up the partograph increased from 32% to 81%. Staff competency in filling partograph improved considerably: proportion of staff scoring low decreased over the intervention period from 63% to 2.5% (P < 0.0001), and the proportion scoring high increased from 13% to 72% (P < 0.0001) from baseline to end line. CONCLUSION: The integrated approach of training, mentoring, and QI can be used in similar settings to strengthen partograph use.

Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS.

Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.

A naturally occurring variant of the human prion protein completely prevents prion disease.

Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.

Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP) gene (PRNP) and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.