Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

Immunological markers for identifying recent HIV infection in North-West India.

Background & objectives: Being more efficient and widely used, limiting antigen (LAg)-avidity enzyme immunoassay (EIA) based on the recent infection testing algorithm (RITA) has been developed for differentiating recent and established HIV-1 infection. So far, LAg-avidity EIA has not been validated among the Indian population. Hence, the present study was planned to identify recent HIV infections in high risk patients in the North-West region of India using modified LAg-avidity RITA. Methods: Four hundred HIV-positive high risk patients registered on pre-antiretroviral therapy (ART) programme in the last one year, from five ART centres in North-Western States of India, were included for identifying the recent HIV infections. One hundred HIV-positive cases registered for pre-ART for greater than two years in ART centres were included for estimating false recent rate (FRR). Single-well LAg-avidity EIA-based modified RITA was used to identify recent HIV infection cases. Results: Of the 400 HIV-1-positive samples, 64 (16%) were found to have been infected within the past 130 days. The proportion of recent HIV infections was 16.8 per cent (18/107) among female sex workers, 10.7 per cent (9/84) among men who have sex with men and 17.7 per cent (37/209) among injecting drug users. The FRR was one per cent (1/100). Interpretation & conclusions: LAg-avidity EIA-based modified RITA provided good discrimination between recent and non-recent HIV infection, hence, it could be considered suitable for estimating HIV incidence in sentinel surveillance system in India.

Association of rheumatic fever & rheumatic heart disease with plausible early & late-stage disease markers.

BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

Differences in virulence repertoire and cell invasive potential of group A Streptococcus emm1-2 in comparison to emm1 genotype.

Group A streptococcus (GAS, Streptococcus pyogenes) type emm1 is widely associated with streptococcal invasive disease. This type is prevalent worldwide but is rare in India. Instead, emm1-2 type which is closely related to emm1 but is a distinct type is more prevalent. Although emm1 has been well characterized, information available on emm1-2 is rare. In this study we present a comparative study of both types. DNA microarray analysis showed segregation of emm1 and emm1-2 isolates into two distinct clusters. Out of 229 arrayed genes, 83-87% were present, 6-9% absent and 4-8% genes were ambiguous in emm1 isolates. emm1-2 strains harboured only 68-77%, 11-13% were absent and 10-20% ambiguous genes. Fourteen genes, present in all emm1, were completely absent in the emm1-2 isolates. sfb1 is a gene which encodes for Streptococcal fibronectin binding adhesin and invasin which has restricted distribution among different emm types of GAS. A variant of sfb1 (sfb1-2) was the only gene which was present in all emm1-2 isolates, but absent from all emm1 strains. Sfb1 and Sfb1-2 differ in sequences in the aromatic domain and the proline rich repeat region, whereas the fibronectin binding region was conserved and exhibited similar fibronectin binding activity. The presence of Sfb1-2 in emm1-2 strains was concomitant with significantly higher fibronectin-binding and invasion efficiency of HEp-2 cells when compared to emm1 isolates. The role of Sfb1-2 in invasion was confirmed by latex bead assay. emm1-2 isolates follow membrane ruffling mechanism during invasion and intracellularly follow classical endocytic pathway. Further studies are required to understand the correlation between the presence of emm1-2 isolates and the disease pattern in North India.

Which type of atrophic acne scar (ice-pick, boxcar, or rolling) responds to nonablative fractional laser therapy?

BACKGROUND: Few studies have examined the role of fractional lasers in individual acne scars (ice-pick, box car, rolling) using objective assessment tools in darkly pigmented skin. OBJECTIVE: To evaluate the effect of 1,540-nm fractional lasers on individual acne scars. METHODS AND MATERIALS: A prospective interventional study was conducted in 35 patients using a 1,540-nm fractional laser. Six sessions were performed with four passes per session and a dose varying from 70 to 100 mJ to maximize the DWR. A self-devised objective assessment tool with dose settings to optimize the depth-to-width ratio (DWR) and a visual analog scale (VAS) were used to count individual atrophic scars. Final results were assessed 6 months after final laser treatment. RESULTS: Acne scar reduction efficiency was used to validate the improvement of individual scars, a meaningful difference was considered as 51% or greater improvement. The boxcar scars (52.9%) responded better than the rolling (43.1%) and ice-pick scars (25.9%), with statistically significant improvement (p < .05) seen in boxcar scars after four sessions. Overall VAS scores revealed significant improvement (p < .001). CONCLUSION: Using an objective evaluation tool, an erbium-doped glass laser was found to improve atrophic acne scars, markedly so for boxcar and rolling scars. The VAS score overestimated improvement because of its subjective nature.

Identification of potential universal vaccine candidates against group A Streptococcus by using high throughput in silico and proteomics approach.

Streptococcus pyogenes or group A Streptococcus (GAS) causes ~700 million human infections each year, resulting in over 500,000 deaths. The development of a commercial GAS vaccine is hampered due to high strain and serotype diversity in different geographical regions, and the generation of cross-reactive antibodies that may induce autoimmune disease. There is an urgent need to search for alternative vaccine candidates. High throughput multigenome data mining coupled with proteomics seems to be a promising approach to identify the universal vaccine candidates. In the present study, in silico analysis led to prediction of 147 proteins as universal vaccine candidates. Distribution pattern of these predicted candidates was explored in nonsequenced Indian GAS strains (n = 20) by using DNA array hybridization validating in silico analysis. High throughput analyses of surface proteins using 1D-SDS-PAGE coupled with ESI-LC-MS/MS was applied on highly (M49) and less (M1) invasive GAS strains of Indian origin. Comparative proteomics analysis revealed that highly invasive GAS M49 had metabolically more active membrane associated protein machinery than less invasive M1. Further, by overlapping proteomics data with in silico predicted vaccine candidate genes, 52 proteins were identified as probable universal vaccine candidates, which were expressed in these GAS serotypes. These proteins can further be investigated as universal vaccine candidates against GAS. Moreover, this robust approach may serve as a model that can be applied to identify the universal vaccine candidates in case of other pathogenic bacteria with high strain and genetic diversity.

High-precision mapping reveals the structure of odor coding in the human brain.

Odor perception is inherently subjective. Previous work has shown that odorous molecules evoke distributed activity patterns in olfactory cortices, but how these patterns map on to subjective odor percepts remains unclear. In the present study, we collected neuroimaging responses to 160 odors from 3 individual subjects (18 h per subject) to probe the neural coding scheme underlying idiosyncratic odor perception. We found that activity in the orbitofrontal cortex (OFC) represents the fine-grained perceptual identity of odors over and above coarsely defined percepts, whereas this difference is less pronounced in the piriform cortex (PirC) and amygdala. Furthermore, the implementation of perceptual encoding models enabled us to predict olfactory functional magnetic resonance imaging responses to new odors, revealing that the dimensionality of the encoded perceptual spaces increases from the PirC to the OFC. Whereas encoding of lower-order dimensions generalizes across subjects, encoding of higher-order dimensions is idiosyncratic. These results provide new insights into cortical mechanisms of odor coding and suggest that subjective olfactory percepts reside in the OFC.

Treatment adherence and its determinants among the rheumatic fever/rheumatic heart disease patients during COVID 19 pandemic - A cross sectional study from Chandigarh, India.

Background: Rheumatic heart disease/Rheumatic fever is a non - communicable disease being a major neglected health problem. Recurrent attacks of rheumatic fever can have catastrophic outcomes, therefore regular administration of antibiotics is recommended. During COVID 19 pandemic, people were afraid to approach hospitals hence the compliance and follow up of patients were affected. This study had planned to assess the treatment adherence of patients diagnosed with rheumatic fever/rheumatic heart disease during COVID 19 pandemic and to describe the socio demographic factors, clinical characteristics. This study also determines the factors associated with the treatment adherence. Methods: A cross sectional study was conducted among Rheumatic Fever/Rheumatic Heart Disease patients, attending Outpatient department at tertiary care hospital during COVID 19 pandemic. Mean score with confidence interval was calculated for quantitative data. P value less than 0.05 is significant. Results: The Mean (SD) age of the study participants was 41 ± 14.17 years. Treatment adherence was found to be 94.5 percent among Rheumatic Fever/Rheumatic Heart Disease patients during COVID 19 pandemic. 89.5% of injection benzathine penicillin users had an adherence rate above 80 percent. It was found that the presence of comorbidities (Diabetes/Hypertension/both Diabetes and Hypertension) had a statistically significant association with treatment adherence. Conclusions: Rheumatic Heart Disease is a disease of young and middle -age population affecting predominantly females. The overall adherence rate among Rheumatic Fever/Rheumatic Heart Disease patients was high. High time to maintain hospital-based registry to have follow up of patients.

Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance.

For a majority of patients with non-small cell lung cancer with EGFR mutations, treatment with EGFR inhibitors (EGFRi) induces a clinical response. Despite this initial reduction in tumor size, residual disease persists that leads to disease relapse. Elucidating the preexisting biological differences between sensitive cells and surviving drug-tolerant persister cells and deciphering how drug-tolerant cells evolve in response to treatment could help identify strategies to improve the efficacy of EGFRi. In this study, we tracked the origins and clonal evolution of drug-tolerant cells at a high resolution by using an expressed barcoding system coupled with single-cell RNA sequencing. This platform enabled longitudinal profiling of gene expression and drug sensitivity in response to EGFRi across a large number of clones. Drug-tolerant cells had higher expression of key survival pathways such as YAP and EMT at baseline and could also differentially adapt their gene expression following EGFRi treatment compared with sensitive cells. In addition, drug combinations targeting common downstream components (MAPK) or orthogonal factors (chemotherapy) showed greater efficacy than EGFRi alone, which is attributable to broader targeting of the heterogeneous EGFRi-tolerance mechanisms present in tumors. Overall, this approach facilitates thorough examination of clonal evolution in response to therapy that could inform the development of improved diagnostic approaches and treatment strategies for targeting drug-tolerant cells. SIGNIFICANCE: The evolution and heterogeneity of EGFR inhibitor tolerance are identified in a large number of clones at enhanced cellular and temporal resolution using an expressed barcode technology coupled with single-cell RNA sequencing.

Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin®).

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

FUT2 gene as a genetic susceptible marker of infectious diseases: A Review.

Some blood group antigens are reported as a susceptibility marker for some diseases. For instance, HBGA (Histo-blood group antigen) which is controlled by gene FUT2 also considered as a susceptible marker. The FUT2 gene which exhibits the expression of alpha-1, 2-L-fucosyltransferase enzyme also leads to HBGA expression for the gut, and it provides a composition of the phenotypical profile that exists in some populations with unique histories of evolution and it can be considered as a marker of the genetic population. It is found to have an association with many diseases which is discussed in this review. Polymorphic mutations are known to inhibit and reduce its function which are population specific. Detailed understanding and deeper knowledge of its role in the pathogenesis and prevention of many diseases is required. FUT2 may also have a potential role in the case of COVID-19 as a susceptible marker due to its association with respiratory diseases and the ABO blood group. There is an utmost need for this kind of review knowing its importance and owing to limited collective information.

Lupus Miliaris Disseminatus Faciei: Response to Combination of Isotretinoin and Oral Minipulse.

A 32-year-old man presented with multiple reddish and skin-colored asymptomatic skin lesions over his face and ears present for a year. These lesions appeared in crops at variable intervals, healing with scarring over the next few months. He had received doxycycline and azithromycin for about 6 months without any relief. No history of flushing, worsening of lesions on sun exposure, or eating spicy food, was reported. He had no chronic illness or prolonged usage of any medication. The patient neither had abdominal pain, respiratory distress, or uveitis to suggest sarcoidosis nor accounted any personal or family history of tuberculosis. (SKINmed. 2022;20:307-310).

Harnessing machine learning models for non-invasive pre-diabetes screening in children and adolescents.

BACKGROUND AND OBJECTIVES: Pre-diabetes has been identified as an intermediate diagnosis and a sign of a relatively high chance of developing diabetes in the future. Diabetes has become one of the most frequent chronic disorders in children and adolescents around the world; therefore, predicting the onset of pre-diabetes allows a person at risk to make efforts to avoid or restrict disease progression. This research aims to create and implement a cross-validated machine learning model that can predict pre-diabetes using non-invasive methods. METHODS: We have analysed the national representative dataset of children and adolescents (5-19 years) to develop a machine learning model for non-invasive pre-diabetes screening. Based on HbA1c levels the data (n = 26,567) was segregated into normal (n = 23,777) and pre-diabetes (n = 2790). We have considered eight features, six hyper-tuned machine learning models and different metrics for model evaluation. The final model was selected based on the area under the receiver operator curve (AUC), Cohen's kappa and cross-validation score. The selected model was integrated into the screening tool for automated pre-diabetes prediction. RESULTS: The XG boost classifier was the best model, including all eight features. The 10-fold cross-validation score was highest for the XG boost model (90.13%) and least for the support vector machine (61.17%). The AUC was highest for RF (0.970), followed by GB (0.968), XGB (0.959), ETC (0.918), DT (0.908), and SVM (0.574) models. The XGB model was used to develop the screening tool. CONCLUSION: We have developed and deployed a machine learning model for automated real-time pre-diabetes screening. The screening tool can be used over computers and can be transformed into software for easy usage. The detection of pre-diabetes in the pediatric age may help avoid its enhancement. Machine learning can also show great competence in determining important features in pre-diabetes.

Group A Streptococcus Infections: Their Mechanisms, Epidemiology, and Current Scope of Vaccines.

Group A streptococci (GAS) are gram-positive, cocci-shaped bacteria that cause a wide variety of infections and are a cause of significant health burden, particularly in lower- and middle-income nations. The GAS genome contains a number of virulence factors such as the M-protein, hyaluronic acid, C5a peptidase, etc. Despite its significant health burden across the globe, a proper vaccine against GAS infections is not yet available. Various candidates for an effective GAS vaccine are currently being researched. These are based on various parts of the streptococcal genome. These include candidates based on the N-terminal region of the M protein, the conserved C-terminal region of the M protein, and other parts of the streptococcal genome. The development of a vaccine against GAS infections is hampered by certain challenges, such as extensive genetic heterogeneity and high protein sequence variation. This review paper sheds light on the various virulence factors of GAS, their epidemiology, the different vaccine candidates currently being researched, and the challenges associated with M-protein and non-M-protein-based vaccines. This review also sheds light on the current scenario regarding the status of vaccine development against GAS-related infections.

Persistence of immunity and impact of third dose of inactivated COVID-19 vaccine against emerging variants.

This is a comprehensive report on immunogenicity of COVAXIN® booster dose against ancestral and Variants of Concern (VOCs) up to 12 months. It is well known that neutralizing antibodies induced by COVID-19 vaccines wane within 6 months of vaccination leading to questions on the effectiveness of two-dose vaccination against breakthrough infections. Therefore, we assessed the persistence of immunogenicity up to 6 months after a two or three-dose with BBV152 and the safety of a booster dose in an ongoing phase 2, double-blind, randomized controlled trial (ClinicalTrials.gov: NCT04471519). We report persistence of humoral and cell mediated immunity up to 12 months of vaccination, despite decline in the magnitude of antibody titers. Administration of a third dose of BBV152 increased neutralization titers against both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, Delta Plus and Omicron) with a slight increase in B cell memory responses. Thus, seronversion rate remain high in boosted recipients compared to non-booster, even after 6 months, post third dose against variants. No serious adverse events observed, except pain at the injection site, itching and redness. Hence, these results indicate that a booster dose of BBV152 is safe and necessary to ensure persistent immunity to minimize breakthrough infections of COVID-19, due to newly emerging variants.Trial registration: Registered with the Clinical Trials Registry (India) No. CTRI/2021/04/032942, dated 19/04/2021 and on Clinicaltrials.gov: NCT04471519.

Measuring and predicting personal and household Black Carbon levels from 88 communities in eight countries.

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10-5 m-1) of collected PM2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10-5 m-1, respectively. The correlation between BC and PM2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC.

Multinational prediction of household and personal exposure to fine particulate matter (PM2.5) in the PURE cohort study.

INTRODUCTION: Use of polluting cooking fuels generates household air pollution (HAP) containing health-damaging levels of fine particulate matter (PM2.5). Many global epidemiological studies rely on categorical HAP exposure indicators, which are poor surrogates of measured PM2.5 levels. To quantitatively characterize HAP levels on a large scale, a multinational measurement campaign was leveraged to develop household and personal PM2.5 exposure models. METHODS: The Prospective Urban and Rural Epidemiology (PURE)-AIR study included 48-hour monitoring of PM2.5 kitchen concentrations (n = 2,365) and male and/or female PM2.5 exposure monitoring (n = 910) in a subset of households in Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania and Zimbabwe. PURE-AIR measurements were combined with survey data on cooking environment characteristics in hierarchical Bayesian log-linear regression models. Model performance was evaluated using leave-one-out cross validation. Predictive models were applied to survey data from the larger PURE cohort (22,480 households; 33,554 individuals) to quantitatively estimate PM2.5 exposures. RESULTS: The final models explained half (R2 = 54%) of the variation in kitchen PM2.5 measurements (root mean square error (RMSE) (log scale):2.22) and personal measurements (R2 = 48%; RMSE (log scale):2.08). Primary cooking fuel type, heating fuel type, country and season were highly predictive of PM2.5 kitchen concentrations. Average national PM2.5 kitchen concentrations varied nearly 3-fold among households primarily cooking with gas (20 µg/m3 (Chile); 55 µg/m3 (China)) and 12-fold among households primarily cooking with wood (36 µg/m3 (Chile)); 427 µg/m3 (Pakistan)). Average PM2.5 kitchen concentration, heating fuel type, season and secondhand smoke exposure were significant predictors of personal exposures. Modeled average PM2.5 female exposures were lower than male exposures in upper-middle/high-income countries (India, China, Colombia, Chile). CONCLUSION: Using survey data to estimate PM2.5 exposures on a multinational scale can cost-effectively scale up quantitative HAP measurements for disease burden assessments. The modeled PM2.5 exposures can be used in future epidemiological studies and inform policies targeting HAP reduction.

Seroprevalence of Dengue Infection Using IgG Capture ELISA in India, 2017-2018.

We conducted a nationally representative population-based survey in 60 districts from 15 Indian states covering all five geographic regions during 2017-2018 to estimate the age specific seroprevalence of dengue. Of the 12,300 sera collected, 4,955 were positive for IgG antibodies against dengue virus using IgG Indirect ELISA indicating past dengue infection. We tested 4,948 sera (seven had inadequate volume) positive for IgG antibodies on indirect ELISA using anti-dengue IgG capture ELISA to estimate the proportion of dengue infections with high antibody titers, suggestive of acute or recent secondary infection. Of the 4,948 sera tested, 529 (10.7%; 95% CI: 9.4-12.1) were seropositive on IgG capture ELISA. The proportions of dengue infections with high titers were 1.1% in the northeastern, 1.5% in the eastern, 6.2% in the western, 12.2% in the southern, and 16.7% in the northern region. The distribution of dengue infections varied across geographic regions, with a higher proportion of infections with high antibody titer in the northern and southern regions of India. The study findings could be useful for planning facilities for clinical management of dengue infections.

Immunity against diphtheria among children aged 5-17 years in India, 2017-18: a cross-sectional, population-based serosurvey.

BACKGROUND: Diphtheria is re-emerging as a public health problem in several Indian states. Most diphtheria cases are among children older than 5 years. In this study, we aimed to estimate age-specific immunity against diphtheria in children aged 5-17 years in India. METHODS: We used residual serum samples from a cross-sectional, population-based serosurvey for dengue infection done between June 19, 2017, and April 12, 2018, to estimate the age-group-specific seroprevalence of antibodies to diphtheria in children aged 5-17 years in India. 8309 serum samples collected from 240 clusters (122 urban and 118 rural) in 60 selected districts of 15 Indian states spread across all five geographical regions (north, northeast, east, west, and south) of India were tested for the presence of IgG antibodies against diphtheria toxoid using an ELISA. We considered children with antibody concentrations of 0·1 IU/mL or greater as immune, those with levels less than 0·01 IU/mL as non-immune (and hence susceptible to diphtheria), and those with levels in the range of 0·01 to less than 0·1 IU/mL as partially immune. We calculated the weighted proportion of children who were immune, partially immune, and non-immune, with 95% CIs, for each geographical region by age group, sex, and area of residence (urban vs rural). FINDINGS: 29·7% (95% CI 26·3-33·4) of 8309 children aged 5-17 years were immune to diphtheria, 10·5% (8·6-12·8) were non-immune, and 59·8% (56·3-63·1) were partially immune. The proportion of children aged 5-17 years who were non-immune to diphtheria ranged from 6·0% (4·2-8·3) in the south to 16·8% (11·2-24·4) in the northeast. Overall, 9·9% (7·7-12·5) of children residing in rural areas and 13·1% (10·2-16·6) residing in urban areas were non-immune to diphtheria. A higher proportion of girls than boys were non-immune to diphtheria in the northern (17·7% [12·6-24·2] vs 7·1% [4·1-11·9]; p=0·0007) and northeastern regions (20·0% [12·9-29·8] vs 12·9% [8·6-19·0]; p=0·0035). INTERPRETATION: The findings of our serosurvey indicate that a substantial proportion of children aged 5-17 years were non-immune or partially immune to diphtheria. Transmission of diphtheria is likely to continue in India until the immunity gap is bridged through adequate coverage of primary and booster doses of diphtheria vaccine. FUNDING: Indian Council of Medical Research.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial.

BACKGROUND: To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel). METHODS: We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 µg with Algel-IMDG, 6 µg with Algel-IMDG, or 6 µg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519). FINDINGS: Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 µg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 µg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 µg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 µg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 µg with Algel-IMDG, 6 µg with Algel-IMDG, and 6 µg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups. INTERPRETATION: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. FUNDING: Bharat Biotech International.