Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

Pneumococcal population genomics changes during the early time period of conjugate vaccine uptake in southern India.

Streptococcus pneumoniae is a major cause of invasive disease of young children in low- and middle-income countries. In southern India, pneumococcal conjugate vaccines (PCVs) that can prevent invasive pneumococcal disease began to be used more frequently after 2015. To characterize pneumococcal evolution during the early time period of PCV uptake in southern India, genomes were sequenced and selected characteristics were determined for 402 invasive isolates collected from children <5 years of age during routine surveillance from 1991 to 2020. Overall, the prevalence and diversity of vaccine type (VT) and non-vaccine type (NVT) isolates did not significantly change post-uptake of PCV. Individually, serotype 1 and global pneumococcal sequence cluster (GPSC or strain lineage) 2 significantly decreased, whereas serotypes 6B, 9V and 19A and GPSCs 1, 6, 10 and 23 significantly increased in proportion post-uptake of PCV. Resistance determinants to penicillin, erythromycin, co-trimoxazole, fluoroquinolones and tetracycline, and multidrug resistance significantly increased in proportion post-uptake of PCV and especially among VT isolates. Co-trimoxazole resistance determinants were common pre- and post-uptake of PCV (85 and 93 %, respectively) and experienced the highest rates of recombination in the genome. Accessory gene frequencies were seen to be changing by small amounts across the frequency spectrum specifically among VT isolates, with the largest changes linked to antimicrobial resistance determinants. In summary, these results indicate that as of 2020 this pneumococcal population was not yet approaching a PCV-induced equilibrium and they highlight changes related to antimicrobial resistance. Augmenting PCV coverage and prudent use of antimicrobials are needed to counter invasive pneumococcal disease in this region.

Approach towards surveillance-based diagnosis of acute respiratory illness in India: Expert recommendations.

BACKGROUND: Emerging infectious diseases, often zoonotic, demand a collaborative "One-Health" surveillance approach due to human activities. The need for standardized diagnostic and surveillance algorithms is emphasized to address the difficulty in clinical differentiation and curb antimicrobial resistance. OBJECTIVE: The present recommendations are comprehensive diagnostic and surveillance algorithm for ARIs, developed by the Indian Council of Medical Research (ICMR), which aims to enhance early detection and treatment with improved surveillance. This algorithm shall be serving as a blueprint for respiratory infections landscape in the country and early detection of surge of respiratory infections in the country. CONTENT: The ICMR has risen up to the threat of emerging and re-emerging infections. Here, we seek to recommend a structured approach for diagnosing respiratory illnesses. The recommendations emphasize the significance of prioritizing respiratory pathogens based on factors such as the frequency of occurrence (seasonal or geographical), disease severity, ease of diagnosis and public health importance. The proposed surveillance-based diagnostic algorithm for ARI relies on a combination of gold-standard conventional methods, innovative serological and molecular techniques, as well as radiological approaches, which collectively contribute to the detection of various causative agents. The diagnostic part of the integrated algorithm can be dealt at the local microbiology laboratory of the healthcare facility with the few positive and negative specimens shipped to linked viral disease research laboratories (VRDLs) and other ICMR designated laboratories for genome characterisation, cluster identification and identification of novel agents.

Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries.

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8-68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7-48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4-34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5-94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7-84·3) compared with those without HIV (61·0%, 51·6-69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).

Clinical Spectrum and Microbial Etiology of Bone and Joint Infections in Children: A Retrospective Analysis from South India.

Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5-105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5-8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.

Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease: A Diagnostic Accuracy Study for Pediatric Tuberculosis.

INTRODUCTION: An estimated 1.2 million children develop tuberculosis (TB) every year with 240,000 dying because of missed diagnosis. Existing tools suffer from lack of accuracy and are often unavailable. Here, we describe the scientific and clinical methodology applied in RaPaed-TB, a diagnostic accuracy study. METHODS: This prospective diagnostic accuracy study evaluating several candidate tests for TB was set out to recruit 1000 children <15 years with presumptive TB in 5 countries (Malawi, Mozambique, South Africa, Tanzania, India). Assessments at baseline included documentation of TB signs and symptoms, TB history, radiography, tuberculin skin test, HIV testing and spirometry. Respiratory samples for reference standard testing (culture, Xpert Ultra) included sputum (induced/spontaneous) or gastric aspirate, and nasopharyngeal aspirate (if <5 years). For novel tests, blood, urine and stool were collected. All participants were followed up at months 1 and 3, and month 6 if on TB treatment or unwell. The primary endpoint followed NIH-consensus statements on categorization of TB disease status for each participant. The study was approved by the sponsor's and all relevant local ethics committees. DISCUSSION: As a diagnostic accuracy study for a disease with an imperfect reference standard, Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease (RaPaed-TB) was designed following a rigorous and complex methodology. This allows for the determination of diagnostic accuracy of novel assays and combination of testing strategies for optimal care for children, including high-risk groups (ie, very young, malnourished, children living with HIV). Being one of the largest of its kind, RaPaed-TB will inform the development of improved diagnostic approaches to increase case detection in pediatric TB.

Epidemiology and outcomes of pneumococcal sepsis in children with nephrotic syndrome in a developing country.

BACKGROUND: Pneumococcal infections are common in children with nephrotic syndrome. Knowledge of the commonly available serotypes and antibiotic susceptibility will help in prevention and appropriate management of pneumococcal sepsis, especially in resource-limited countries. METHODS: Demographic, clinical, and laboratory data on children with nephrotic syndrome and pneumococcal infections were extracted from the electronic medical records. RESULTS: Sixty-three isolates of pneumococci obtained from 60 children with nephrotic syndrome, over a period of 14 years, were included in the study. This represented 18% of all pneumococcal infections occurring in children during the same period. Commonly available vaccines covered up to 58% of all the serotypes causing infection. Severe disease, with shock, intensive care admission and/or meningitis, was observed in 38% children and mortality was observed in 10%. Resistance to commonly used antibiotics was not observed, except for erythromycin. CONCLUSIONS: Pneumococcal sepsis was observed to be common in children with nephrotic syndrome and results in significant morbidity and mortality. Commonly used antibiotics were observed to be effective in management of the infections.

Clinical, Microbiological Profile and Treatment Outcomes of Infants with BCG Adenitis: A Retrospective Study.

BACKGROUND: Bacille Calmette-Guérin (BCG) adenitis is an uncommon complication following BCG vaccination. In rare cases, infants can develop other complications. Controversy exists regarding the diagnosis and management of these cases. Not much information is available in literature regarding their microbiological and immunological characteristics. METHODS: Electronic medical records of children presenting to the Pediatric Infectious Diseases clinic in a tertiary care hospital from January 2011-December 2020 with a diagnosis of BCG adenitis were retrospectively reviewed. Their clinical, microbiological, treatment and follow-up data were noted and analyzed. FINDINGS: During the study period, 40 infants presented with a probable diagnosis of BCG adenitis with or without disseminated BCG. Median age at symptom onset was 4(2.5-5.9) months. Nine infants had disseminated disease at presentation. Fifteen infants were suspected to have underlying immune deficiency of whom 12 had proven defects in immune function. On multivariable logistic regression analysis, presence of disseminated disease was the only factor predictive of underlying immunodeficiency. Isoniazid monoresistance was seen in seven cases (32%) of the 22 samples sent for TB cultures. CONCLUSIONS: Though BCG adenitis runs a benign course, it could rarely be the first manifestation of an underlying immune defect. There is sizable isoniazid monoresistance, hence sending tissue samples for microbiologic evaluation is necessary to guide anti-tubercular therapy.

Effect of Nutritional Supplementation on Illness Outcome in Adolescents with HIV on HAART: A Randomized, Double-Blind Clinical Trial.

OBJECTIVE: To assess the effect of macronutrient and micronutrient supplementation on body mass index (BMI), hemoglobin (Hb), CD4 count, triglyceride levels, and morbidity among adolescents with human immunodeficiency virus (HIV) living in India. METHODS: A prospective, randomized, double-blinded, placebo-controlled trial was conducted among 80 adolescents (10-19 y) with HIV on highly active antiretroviral therapy (HAART) for a minimum of 6 mo using simple randomization. Participants in the intervention arm received 400 kcal and 15 g protein as a powder daily and multivitamin tablets thrice weekly for 3 mo. Those in the placebo arm received a similar-appearing sachet containing 100 kcal and 2 g protein daily and a placebo tablet thrice weekly. Weight, height, BMI, Hb, CD4 count, triglycerides, and number of intercurrent illnesses were measured at 3 and 6 mo. RESULTS: At 6 mo, the intervention group showed an increase in weight from 36.4 ± 10.9 kg to 39.7 ± 8.5 kg and a significant increase in BMI from 16.6 ± 2.3 kg/m2 to 17.5 ± 2.3 kg/m2. Increase in CD4 count in the placebo arm was more than that in the intervention arm, but the difference between the arms was not statistically significant. Intervention group showed a pronounced rise in Hb from 9.7 ± 2.3 g/dL to 11.4 ± 1.6 g/dL, significant reduction in triglyceride levels from 99.2 ± 92.7 mg/dL to 81.0 ± 12.8 mg/dL and reduction in intercurrent illnesses from 32.5% to none. CONCLUSIONS: Nutritional supplementation of adolescents with HIV on HAART improves BMI, hemoglobin, and reduces triglyceride levels and intercurrent illnesses.

Accuracy and agreement of the Tuberculin Skin Test (TST) and the QuantiFERON-TB Gold In-tube test (QFT) in the diagnosis of tuberculosis in Indian children.

PURPOSE: Accurate diagnosis of TB in children is hampered by poor specificity of symptoms in endemic countries and the paucibacillary nature of childhood TB. This study was done to compare the accuracy and agreement of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-tube test (QFT) in diagnosing tuberculosis (TB) in a predominantly BCG-vaccinated population of children. METHODS: This retrospective cohort study enrolled all children aged 1-15 years who underwent TST and QFT testing as part of screening for TB. Children were classified according to the 2014 WHO case definition of TB, and statistical analysis was done to generate data on concordance between the TST and the QFT as well as sensitivity and specificity within WHO-defined groups. RESULTS: TST and QFT concordance was 83.9% overall (kappa 0.51), 79% in those with WHO-defined TB and 89% in those without TB. TST+/QFT-discordance was commoner than QFT+/TST- discordance across groups. The sensitivity of the TST vs. the QFT was 70.8% vs. 50% for WHO-defined TB, with comparable specificity at 89% vs. 90% respectively. CONCLUSIONS: The higher sensitivity of the cheaper and simpler TST supports its use for TB diagnosis in a normally nourished population of BCG-vaccinated children.

Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants.

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

Development of a Multiplex Real-Time PCR Assay for Mycobacterium bovis BCG and Validation in a Clinical Laboratory.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live attenuated vaccine which can result in local or disseminated infection, most commonly in immunocompromised individuals. Differentiation of BCG from other members of the Mycobacterium tuberculosis complex (MTBC) is required to diagnose BCG disease, which requires specific management. Current methods for BCG diagnosis are based on mycobacterial culture and conventional PCR; the former is time-consuming and the latter often unavailable. Further, there are reports that certain BCG strains may be associated with a higher rate of adverse events. This study describes the development of a two-step multiplex real-time PCR assay which uses single nucleotide polymorphisms to detect BCG and identify early or late BCG strains. The assay has a limit of detection of 1 pg BCG boiled lysate DNA and was shown to detect BCG in both pure cultures and experimentally infected tissue. Its performance was assessed on 19 suspected BCG clinical isolates at Christian Medical College in Vellore, India, taken from January 2018 to August 2020. Of these 19 isolates, 10 were identified as BCG (6 early and 4 late strains), and 9 were identified as other MTBC members. Taken together, the results demonstrate the ability of this assay to identify and characterize BCG disease from cultures and infected tissue. The capacity to identify BCG may improve patient management, and the ability to discriminate between BCG strains may enable BCG vaccine pharmacovigilance. IMPORTANCE Vaccination against tuberculosis with bacillus Calmette-Guérin (BCG) can lead to adverse events, including a rare but life-threatening complication of disseminated BCG. This complication often occurs in young children with immunodeficiencies and is associated with an ∼60% mortality rate. A rapid method of reliably identifying BCG infection is important because BCG requires treatment unique to tuberculosis. BCG is resistant to the first-line antituberculosis drug pyrazinamide. Additionally, diagnosis of BCG disease would lead to further investigation of a possible underlying immune condition. We have developed a diagnostic assay to identify BCG which improves upon previously published methods and can reliably identify BCG from bacterial culture or directly from infected tissue. This assay can also differentiate between strains of BCG, which have been suggested to be associated with different rates of adverse events. This assay was validated on 19 clinical isolates collected at Christian Medical College in Vellore, India.

An Eight-Year Profile of Children with Influenza A(H1N1) in a Large Hospital in India.

As influenza virus A(H1N1) continues to circulate, reports from India have documented mainly respiratory involvement in children. This retrospective chart review of children at a medical college found that from August 2009 to July 2017, 855 children aged 3 months to 15 years had H1N1 influenza of whom 310 (36.3%) were admitted and 29 (9.4% admissions) died. In 2009-12, 76.5% patients presented in August-October but from 2015 to 2017, 89.3% came in January-March. The proportion of under-fives increased from 54.0% in 2009-10 to 77.7% in 2015-17. Among admitted children, 82.6% were under 5 years, 96.1% had respiratory symptoms and 11% had seizures. Six children had encephalopathy of whom four died; two survivors had severe neurological sequelae. Other features included gastroenteritis, otitis media, myositis and hepatitis. Complications included shock (10.7%) and acute respiratory distress syndrome (6.1%). Evidence of bacterial/fungal infection was present in 71 (22.9%). Oxygen was required by 123 children (39.7%), high-dependency/intensive care by 47 (15.2%), 17 (5.5%) received high-flow oxygen and 29 (9.4%) required mechanical ventilation. There were no significantly increased odds of needing intensive care or of dying in children with underlying diseases or among different age groups but those with underlying central nervous system (CNS) diseases had higher odds of needing high-dependency/intensive care [odds ratio (OR) 2.35, p = 0.046]. Significantly, children with CNS symptoms had nearly seven times higher odds of needing mechanical ventilation (OR 6.85, p < 0.001) and over three times higher odds of dying (OR 3.31, p = 0.009).Lay summaryH1N1 Influenza ("swine flu") emerged as a global pandemic in 2009 and continues to affect children all over the world. This review of records from a medical college hospital in southern India found that 855 children aged 3 months to 15 years came with H1N1 influenza over 8 years from August 2009 to July 2017. In 2009-12, over three-quarters of them presented in the rainy season but from 2015-17, almost 90% came in the winter and spring, suggesting a change in the seasonality of the outbreaks, which could impact the choice of dates for annual influenza vaccination. The proportion under 5 years of age increased from 54% in 2009-10 to 78% in 2015-17, suggesting possible immunity in children exposed to earlier outbreaks. Over a third of the children needed admission of whom almost 40% needed oxygen, one-sixth needed high-dependency/intensive care and 1 in 11 admitted children died, emphasizing the severity of this disease. While most children had respiratory symptoms, all organs of the body were affected; 11% of those admitted had seizures and 6 had encephalitis. Children admitted with central nervous system symptoms had an almost 7-fold higher risk of needing high-dependency/intensive care and an over 3-fold higher risk of dying.

Methicillin-resistant Staphylococcus aureus (MRSA)-associated juvenile osteomyelitis of mandible: a rare variant.

Mandibular osteomyelitis in paediatric population presents as painful swelling with progressive trismus. Often the aetiology for this form of progressive osteomyelitis is inconclusive. The infective aetiology in this condition is difficult to assign as bone tissue culture is found to be seldom positive. We present a case of an 11-year-old girl, with hearing and speech impairment, who presented with report of painful right-sided mandibular swelling with progressive trismus. Clinical, radiographic and histopathological findings were suggestive of sclerotic osteomyelitis. Bone tissue culture grew Methicillin-resistant Staphylococcus aureus, indicating a rare infective variant. Unlike the common belief, where osteomyelitic mandible needs a combination of medical and surgical management, our case was managed conservatively with only antibiotic therapy. Our patient responded well to the treatment with reduction in pain and gradual improvement in the mouth opening. Radiographically the mandibular involvement also showed complete regression.

Clinical Spectrum of Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection.

OBJECTIVES: To compare the clinical profile, treatment, and outcomes of PCR-positive and PCR-negative antibody-positive critically ill children with multisystem inflammatory syndrome (MIS-C). METHODS: This retrospective observational study was done at a tertiary care coronavirus disease 19 (COVID-19) pediatric intensive care unit in India. The baseline characteristics, clinical profile, treatment, and outcomes in seventeen critically ill children diagnosed with MIS-C were analyzed from 1 July to 31 October, 2020. RESULTS: Sixteen out of 17 children presented with hypotensive shock and respiratory distress. Mean (SD) age of PCR-negative antibody-positive and PCR-positive children was 11 (4.4) and 5 (3.7) years, respectively (P=0.007). The former group had significantly higher mean (SD) D-dimer levels [16,651 (14859) ng/mL vs 3082 (2591) ng/mL; P=0.02]. All received intensive care management and steroid therapy; 7 children received intravenous immunoglobulin. 14 children survived and 3 died. CONCLUSIONS: The outcome of children with MIS-C was good if recognized early and received intensive care.

Hospital-based sentinel surveillance for bacterial meningitis in under-five children prior to the introduction of the PCV13 in India.

INTRODUCTION: A hospital-based sentinel surveillance network for bacterial meningitis was established in India to estimate the burden of bacterial meningitis, and the proportion of major vaccine-preventable causative organisms. This report summarises the findings of the surveillance conducted between March 2012, and September 2016 in eleven hospitals. METHODS: We enrolled eligible children with bacterial meningitis in the age group of one to 59 months. CSF samples were collected and processed for biochemistry, culture, latex agglutination, and real-time PCR. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. RESULTS: Among 12 941 enrolled suspected meningitis cases, 586 (4.5%) were laboratory confirmed. S. pneumoniae (74.2%) was the most commonly detected pathogen, followed by H. influenzae (22.2%), and N. meningitidis (3.6%). Overall 58.1% of confirmed bacterial meningitis cases were children aged between one, and 11 months. H. influenzae meningitis cases had a high (12.3%) case fatality rate. The serotypes covered in PCV13 caused 72% pneumococcal infections, and the most common serotypes were 14 (18.3%), 6B (12.7%) and 19F (9.9%). Non-susceptibility to penicillin was 57%. Forty-five (43.7%) isolates exhibited multidrug resistance, of which 37 were PCV13 serotype isolates. CONCLUSIONS: The results are representative of the burden of bacterial meningitis among under-five children in India. The findings were useful in rolling out PCV in the National Immunization Program. The non-susceptibility to penicillin and multidrug resistance was an important observation. Timely expansion of PCV across India will significantly reduce the burden of antimicrobial resistance. Continued surveillance is needed to understand the trend after PCV expansion in India.

Hospital-based sentinel surveillance for Streptococcus pneumoniae and other invasive bacterial diseases in India (HBSSPIBD): design and methodology.

INTRODUCTION: Streptococcus pneumoniae is one of the frequently isolated organisms and an important aetiological agent of invasive bacterial diseases (IBD) like pneumonia, meningitis and sepsis. As a measure to control the burden of IBD, the Government of India introduced Pneumoccocal Conjugate Vaccine-13 (PCV-13) in the Universal Immunization Program in high burden districts of five states in a phased manner from 2017 onwards. It is essential to understand the trend of circulating pneumococcal serotypes associated with IBD in the prevaccination and postvaccination scenarios to decide on the expansion of vaccination programmes and PCV reformulation. This manuscript describes the protocol for hospital-based sentinel surveillance for S. pneumoniae and other organisms causing IBD across various geographical regions in India. METHODS AND ANALYSIS: Hospital-based surveillance is established in selected hospitals to recruit children aged 1-59 months with symptoms of pneumonia and other IBD. Diagnostic criteria were adapted from standard WHO case definitions. Case Report Forms (CRFs) are used to collect data from the enrolled children. Blood, cerebrospinal fluid (CSF) and other normally sterile body fluids are collected and subjected to microscopy, cytology, latex agglutination, biochemistry, bacteriological culture and real-time PCR as applicable. Pneumococcal isolates are serotyped and tested for assessing antimicrobial resistance patterns. Data will be analysed by simple descriptive statistics to estimate the proportion of pneumonia and other IBD due to S. pneumoniae, Hemophilus influenzae type b and Neisseria meningitidis. Prevalence of bacterial infection, circulating pneumococcal serotypes, antibiotic resistance patterns, serotype variability across seasons and regions will be described in terms of percentage with 95% confidence interval. ETHICS AND DISSEMINATION: The institutional review boards of the coordinating centre, all sentinel sites, regional and national reference laboratories approved the project. The results will be published in peer-reviewed journals and shared with stakeholders for deciding on revising vaccination strategy appropriately.

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.