Rubella immunity among pregnant women and the burden of congenital rubella syndrome (CRS) in India, 2022.

BACKGROUND: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. METHODS: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. RESULTS: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. CONCLUSION: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella.

Pertussis Vaccines Scarcely Provide Protection against Bordetella parapertussis Infection in Children-A Systematic Review and Meta-Analysis.

BACKGROUND: Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against Bordetella pertussis infections, but their effectiveness against Bordetella parapertussis remains debated due to conflicting study outcomes. METHODS: A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against B. parapertussis infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. RESULTS: The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against B. parapertussis infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain. CONCLUSIONS: These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against B. parapertussis. Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against B. parapertussis.

CrAss-Like Phages: From Discovery in Human Fecal Metagenome to Application as a Microbial Source Tracking Marker.

CrAss-like phages are a diverse group of bacteriophages genetically similar to the prototypical crAssphage (p-crAssphage), which was discovered in the human gut microbiome through a metagenomics approach. It was identified as a ubiquitous and highly abundant bacteriophage group in the gut microbiome. Initial co-occurrence analysis postulated Bacteroides spp. as the prospective bacterial host. Subsequent studies have confirmed multiple host species under Phylum Bacteroidetes and some Firmicutes. Detection of crAss-like phages in sewage-contaminated environmental water and robust correlation with enteric viruses and bacteria has culminated in their adoption as a microbial source tracking (MST) marker. Polymerase chain reaction (PCR) and real-time PCR assays have been developed utilizing the conserved genes in the p-crAssphage genome to detect human fecal contamination of different water sources, with high specificity. Numerous investigations have examined the implications of crAss-like phages in diverse disease conditions, including ulcerative colitis, obesity and metabolic syndrome, autism spectrum disorders, rheumatoid arthritis, atopic eczema, and other autoimmune disorders. These studies have unveiled associations between certain diseases and diminished abundance and diversity of crAss-like phages. This review offers insights into the diverse aspects of research on crAss-like phages, including their discovery, genomic characteristics, structure, taxonomy, isolation, molecular detection, application as an MST marker, and role as a gut microbiome modulator with consequential health implications.

Profile of cardiac lesions among laboratory confirmed congenital rubella syndrome (CRS) infants: a nationwide sentinel surveillance, India, 2016-22.

Background: The phenotypical profile of cardiovascular malformations in patients with congenital rubella syndrome (CRS) is varied. We aimed to describe the profile of cardiac defects among CRS patients detected in the sentinel CRS surveillance in India during 2016-22. Methods: Sentinel sites enrolled infants with suspected CRS based on presence of cardiac defects, hearing impairment, eye signs, or maternal history of febrile rash illness. Suspected CRS cases underwent detailed systemic examination, including echocardiography and serological investigation for rubella. Cardiac defects were categorized as 'Simple' or 'Complex' as per the National Heart, Lung, and Blood Institute classification. We compared the distribution of cardiac defects among laboratory confirmed CRS cases and seronegative discarded cases. Findings: Of the 4578 suspected CRS cases enrolled by 14 sites, 558 (12.2%) were laboratory confirmed. 419 (75.1%) laboratory confirmed cases had structural heart defects (simple defects: n = 273, 65.2%, complex defects: n = 144, 34.4%), with ventricular septal defect (42.7%), atrial septal defect (39.4%), patent ductus arteriosus (36.5%), and tetralogy of Fallot as the commonest defects (4.5%). Laboratory confirmed CRS cases had higher odds of left to right shunt lesions (OR = 1.58, 95% CI: 1.15-2.17). This was mainly on account of a significant association of PDA with CRS (OR = 1.77, 95% CI: 1.42-2.21). Mortality was higher among CRS patients with complex heart defects (HR = 2.04, 95% CI: 1.26-3.30). Interpretation: Three-fourths of the laboratory confirmed CRS cases had structural heart defects. CRS patients with complex cardiac defects had higher mortality. Detecting CRS infection early and providing timely intervention for cardiovascular defects is critical for the management of CRS patients. Funding: Ministry of Health and Family Welfare, Govt of India, through Gavi, the Vaccine Alliance.

An Update on Current Antiviral Strategies to Combat Human Cytomegalovirus Infection.

Human cytomegalovirus (HCMV) remains an essential global concern due to its distinct life cycle, mutations and latency. As HCMV is a herpesvirus, it establishes a lifelong persistence in the host through a chronic state of infection. Immunocompromised individuals are at risk of significant morbidity and mortality from the virus. Until now, no effective vaccine has been developed to combat HCMV infection. Only a few antivirals targeting the different stages of the virus lifecycle and viral enzymes are licensed to manage the infection. Therefore, there is an urgent need to find alternate strategies to combat the infection and manage drug resistance. This review will provide an insight into the clinical and preclinical antiviral approaches, including HCMV antiviral drugs and nucleic acid-based therapeutics.

Congenital rubella syndrome surveillance in India, 2016-21: Analysis of five years surveillance data.

Background: In India, facility-based surveillance for congenital rubella syndrome (CRS) was initiated in 2016 to estimate the burden and monitor the progress made in rubella control. We analyzed the surveillance data for 2016-2021 from 14 sentinel sites to describe the epidemiology of CRS. Method: We analyzed the surveillance data to describe the distribution of suspected and laboratory confirmed CRS patients by time, place and person characteristics. We compared clinical signs of laboratory confirmed CRS and discarded case-patients to find independent predictors of CRS using logistic regression analysis and developed a risk prediction model. Results: During 2016-21, surveillance sites enrolled 3940 suspected CRS case-patients (Age 3.5 months, SD: 3.5). About one-fifth (n = 813, 20.6%) were enrolled during newborn examination. Of the suspected CRS patients, 493 (12.5%) had laboratory evidence of rubella infection. The proportion of laboratory confirmed CRS cases declined from 26% in 2017 to 8.7% in 2021. Laboratory confirmed patients had higher odds of having hearing impairment (Odds ratio [OR] = 9.5, 95% confidence interval [CI]: 5.6-16.2), cataract (OR = 7.8, 95% CI: 5.4-11.2), pigmentary retinopathy (OR = 6.7, 95 CI: 3.3-13.6), structural heart defect with hearing impairment (OR = 3.8, 95% CI: 1.2-12.2) and glaucoma (OR = 3.1, 95% CI: 1.2-8.1). Nomogram, along with a web version, was developed. Conclusions: Rubella continues to be a significant public health issue in India. The declining trend of test positivity among suspected CRS case-patients needs to be monitored through continued surveillance in these sentinel sites.

Detection of Echovirus-18 in Children Suspected With SARS-CoV-2 Infection With Multisystem Inflammatory Syndrome: A Case Report From India.

There have been several reports across the globe regarding the presentation of a severe multi-system hyperinflammatory syndrome, resembling Kawasaki disease (KD), in the pediatric population during the SARS-CoV-2 pandemic. The exact pathophysiology is still unclear; however, children typically demonstrate multi-organ dysfunction and less respiratory system involvement compared to adults. The limited literature is available at present for the identification and management of such patients. In this study, we investigated four cases in children ages 11-15 years that fulfilled the case definition for the pediatric multi-system inflammatory syndrome. All were found negative for SARS-CoV-2 from oropharyngeal swabs and stool. As they were having symptoms of diarrhea, tests for bacterial and enteric viral infections were performed after SARS-CoV-2 testing. Molecular analysis revealed that all the children were infected with enterovirus (Echovirus-18). Early and exact diagnosis is vital for timely, effective, and potentially life-saving management of such cases.

Looking beyond Pertussis in Prolonged Cough Illness of Young Children.

Pertussis, commonly known as whooping cough, is one of the most poorly controlled vaccine-preventable diseases in the world. South-East Asia is estimated to contribute the most to childhood disease burden while this remains largely unexplored in India. The clinical diagnosis of pertussis in young children is a challenge as the classical four-stage presentation with paroxysmal cough or whoop may be absent. It is also difficult to differentiate from other respiratory infections which can cause pertussis-like illness. Children below two years with prolonged cough illness attending an urban pediatric center in western India, were evaluated for pertussis and viral infections by molecular methods. Bordetella pertussis and B. holmesii were confirmed in three each of 45 suspected cases, and RSV-A and hMPV were the most common viruses that were detected. These organisms can mimic mild cases of pertussis and need to be considered in differential diagnosis of prolonged cough illness in young children. The accurate etiology of prolonged cough illness needs to be detected and documented to ensure appropriate management and accurate estimates of disease burden.

Draft Whole-Genome Sequences of Two Multidrug-Resistant Salmonella enterica Serovar Senftenberg Sequence Type 14 Strains Resistant to Ciprofloxacin, Ceftriaxone, and/or Azithromycin, Isolated from Kolkata, India.

We report draft whole-genome sequences of two multidrug-resistant Salmonella enterica serovar Senftenberg sequence type 14 strains resistant to ciprofloxacin, ceftriaxone, and/or azithromycin, which were isolated from neonatal stool and goat meat in Kolkata, India. The genome characteristics, as well as the antimicrobial resistance genes, plasmid types, and integrons, are presented in this report.

Pertussis seroprevalence in mother-infant pairs from India: role of maternal immunisation.

OBJECTIVE: To evaluate pertussis antibody status of pregnant women and their newborns, and the impact of antenatal immunisation. DESIGN: Observational study. SETTING: Hospitals in urban western India. PARTICIPANTS: Pregnant women and their newborns. METHODS: Pertussis antibody titres in mothers and their newborns were determined. Vaccinated and unvaccinated mothers and their newborns were compared for baseline characteristics, geometric mean titres (GMTs) and placental transfer ratio of antibodies. Multivariate logistic regression was performed to understand the influence of different factors on protective antibody titres. RESULTS: Of 284 mother-infant pairs, 75 mothers and 73 of their newborns were seropositive for anti-pertussis toxin (PT) IgG antibodies. 94 women were vaccinated in pregnancy; 51 (54.3%) of these mothers and newborns were PT IgG positive, compared with 24 (12.3%) of the women (and 22 newborns) not vaccinated in pregnancy. Women vaccinated in pregnancy and their newborns had higher GMT (30.88 and 32.54 IU/mL), compared with women who were not vaccinated (12.63%, 2.24 IU/mL) and their newborns (11.58%, 2.53 IU/mL). Placental transfer ratios in newborns of mothers vaccinated in pregnancy and those who had childhood immunisation or natural immunity were similar (1.05 and 1.12, respectively). Protective titres of antibodies at birth (>20 IU/mL) were observed in 72.3% vs 21% of newborns of vaccinated and unvaccinated pregnant women, respectively; influenced by mother's vaccination status and seropositivity. CONCLUSION: Protection against pertussis is low in newborns of mothers who are only immunised during childhood. Vaccination early in pregnancy boosts maternal and neonatal immunity.

Outbreak of cholera in a remote village in western India.

Background & objectives: Atypical El Tor strains of Vibrio cholerae are frequently implicated in outbreaks of cholera. It is important to understand genetic variations of such strains which impact clinical and epidemiological outcomes. The present study was carried out to characterize an outbreak of cholera which occurred between July 8 and 13, 2018, in a remote settlement in Nashik district, Maharashtra. Methods: A large number of acute diarrhoea cases were reported in Rahude village, Nashik, Maharashtra since July 8, 2018. Molecular characterization of the isolated strains of V. cholerae was done. Results: 195 cases of cholera were detected from a population of 850 (attack rate 22.9%) with two deaths (Case Fatality Ratio of 1.03). A non-haemolytic polymyxin B sensitive strain of V. cholerae O1 Ogawa was isolated from 5/14 fecal samples. Molecular characterization of the isolates indicated that this strain was an altered El Tor (AET) strain. Deletion of the trinucleotide 'GTA' in the rstB gene, a unique feature of classical strains, was observed. Interpretation & conclusions: A cholera outbreak caused by a non-haemolytic polymixin B sensitive AET strain, occurred from July 8 to 13, 2018, in a remote settlement in western India. The molecular characterization of the outbreak strains highlighted an assortment of genetic determinants, stressing the need to monitor the genetic attributes of V. cholerae O1 in outbreaks for better understanding and mapping of clinical and epidemiological changes.

Evidence-Based Health Behavior Interventions for Cholera: Lessons from an Outbreak Investigation in India.

In rural India, since 2014, the Swachh Bharat Abhiyan (Clean India Mission) has ensured construction of more than 100 million toilets and is now focusing on reinforcement of sanitation behaviors. We report a cholera outbreak in a remote village in western India where open defecation was implicated in causation. A water pipeline was damaged in the vicinity of a stream flowing from a site of open defecation. Despite the availability of a toilet facility in the majority of households (75%), open defecation was widely practiced (62.8%). Many reported not washing hands with soap and water before eating (78.5%) and after defecation (61.1%). The study emphasizes the need for focused health behavior studies and evidence-based interventions to reduce the occurrence of cholera outbreaks. This could be the last lap in the path toward achieving the United Nations Sustainable Development Goal 6, which aims to "ensure availability and sustainable management of water and sanitation for all."

Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019-20.

BACKGROUND: India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal. METHODS: We conducted serosurveys in 2019-20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS. RESULT: The seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4-84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49-232.41) and 65.47 per 100,000 live births (95% CI: 41.60-104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225-23,100) and 50,028 (95% CI: 48,234-51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively. CONCLUSIONS: Our findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.

Active support after natural disasters: a review of a microbiologist's role.

In the aftermath of a natural disaster, multispecialty rapid response teams are deployed to support health-related relief work. Microbiologists are often part of such teams, along with public health specialists, clinicians and entomologists, and can contribute to the response in multiple ways. The role of a microbiologist is critical not only for laboratory diagnosis of infectious diseases, but also for situational analysis and evaluation, planning, prevention and control. The task begins with risk assessment, specifically for identification of diseases epidemic and endemic to the area. Evaluation of existing laboratory setups and establishment of services where none exist is a priority, including facilitation of a tiered laboratory system. Training of laboratory staff at short notice in field settings, biosafety and biomedical waste management are niche areas where microbiologists can contribute. Emerging focus areas include establishment of modular laboratories, infection prevention and control in community evacuation centres and considerations for reopening of healthcare facilities closed due to extensive natural damage. A trained and efficient microbiologist will prove a valuable asset to provide timely and useful support for infectious disease diagnosis, prevention, control and management in the wake of natural disasters.

Epidemiology of Congenital Rubella Syndrome (CRS) in India, 2016-18, based on data from sentinel surveillance.

BACKGROUND: Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India. METHODOLOGY/PRINCIPAL FINDINGS: We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation. CONCLUSIONS/SIGNIFICANCE: About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country.

Kinetics of viral RNA, immunoglobulin-M & G antibodies in Kyasanur forest disease.

Background & objectives: Kyasanur forest disease (KFD) is an infectious disease discovered in Karnataka State of India in 1957; since then, the State has been known to be enzootic for KFD. In the last few years, its presence was observed in the adjoining five States of the Western Ghats of India. The present study was conducted to understand the kinetics of viral RNA, immunoglobulin M (IgM) and IgG antibody in KFD-infected humans for developing a diagnostic algorithm for KFD. Methods: A prospective follow up study was performed among KFD patients in Sindhudurg district of Maharashtra State, India. A total of 1046 suspected patients were tested, and 72 KFD patients were enrolled and followed for 17 months (January 2016 to May 2017). Serum samples of KFD patients were screened for viral RNA, and IgM and IgG antibodies. Results: KFD viral positivity was observed from 1st to 18th post-onset day (POD). Positivity of anti-KFD virus (KFDV) IgM antibodies was detected from 4th till 122nd POD and anti-KFDV IgG antibodies detected from 5th till 474th POD. A prediction probability was determined from statistical analysis using the generalized additive model in R-software to support the laboratory findings regarding viral kinetics. Interpretation & conclusions: This study demonstrated the presence of KFD viral RNA till 18th POD, IgM antibodies till 122nd POD and IgG till the last sample collected. Based on our study an algorithm was recommended for accurate laboratory diagnosis of KFDV infection. A sample collected between 1 and 3 POD can be tested using KFDV real-time reverse transcriptase polymerase chain reaction (RT-PCR); between 4 and 24 POD, the combination of real-time RT-PCR and anti-KFDV IgM enzyme-linked immunosorbent assay (ELISA) tests can be used; between POD 25 and 132, anti-KFDV IgM and IgG ELISA are recommended.

Molecular aspects of the teratogenesis of rubella virus.

Rubella or German measles is an infection caused by rubella virus (RV). Infection of children and adults is usually characterized by a mild exanthematous febrile illness. However, RV is a major cause of birth defects and fetal death following infection in pregnant women. RV is a teratogen and is a major cause of public health concern as there are more than 100,000 cases of congenital rubella syndrome (CRS) estimated to occur every year. Several lines of evidence in the field of molecular biology of RV have provided deeper insights into the teratogenesis process. The damage to the growing fetus in infected mothers is multifactorial, arising from a combination of cellular damage, as well as its effect on the dividing cells. This review focuses on the findings in the molecular biology of RV, with special emphasis on the mitochondrial, cytoskeleton and the gene expression changes. Further, the review addresses in detail, the role of apoptosis in the teratogenesis process.