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.

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.

Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.

AIMS: Pharmacokinetic studies in the past have shown inadequate antituberculosis drug levels in children with the currently available dosing regimens. This study attempted to investigate the pharmacokinetics of isoniazid and rifampicin, when used in children, and to optimize their dosing regimens. METHODS: Data were collected from 41 children, aged 2-16 years, who were being treated with antituberculosis drugs for at least 2 months. Concentration measurements were done for 6 h and analysed using a nonlinear, mixed-effects model. RESULTS: Isoniazid pharmacokinetics were described by a one-compartment disposition model with a transit absorption model (fixed, n = 5). A mixture model was used to identify the slow and fast acetylator subgroups. Rifampicin was described by a one-compartment disposition model with a transit absorption model (fixed, n = 9). Body weight was added to the clearance and volume of distribution of both the drugs using an allometric function. Simulations with the isoniazid model showed that 84.9% of the population achieved therapeutic peak serum concentration with the planned fixed-dose combination regimen. Simulations with the rifampicin model showed that only about 28.8% of the simulated population achieve the therapeutic peak serum concentration with the fixed-dose combination regimen. A novel regimen for rifampicin, with an average dose of 35 mg kg-1 , was found to provide adequate drug exposure in most children. CONCLUSIONS: The exposure to isoniazid is adequate with present regimens. For rifampicin, a novel dosing regimen was developed to ensure adequate drug concentrations in children. However, further studies are required to assess the dose-effect relationship of higher doses of rifampicin.

Risk factors for acquisition of scrub typhus in children admitted to a tertiary centre and its surrounding districts in South India: a case control study.

BACKGROUND: Scrub typhus is a mite borne zoonosis common in the tropics with no good preventive strategy. Children are also affected leading to considerable morbidity and mortality. We conducted a case control study and a vector survey to determine the risk factors for acquisition of scrub typhus. METHODS: A case control study with a 1:2 case control ratio was conducted over a 2 year period at a tertiary care centre and its surrounding districts in South India. Cases were children < 15 years with confirmed scrub typhus. Controls were age and locality matched community controls without fever. Demographic, environmental and behavioural risk factors were obtained in cases and controls by an interview and an environmental survey. A vector survey was also undertaken in the immediate vicinity of the cases. RESULTS: Case Control study: 101 cases and 167 controls were analysed. On multivariate analysis, significant association was observed with environmental factors such as the presence of a water body within 100 m of the house (OR 3.56(1.36,9.75); p 0.011), cooking outside the house (OR 5.61 (1.51,23.01); p 0.011), owning pets (OR 3.33(1.16,9.09); p 0.031), and the presence of bushes within 5 m of the house (OR 2.78 (1.11,7.69); p 0.033). Of the behavioural factors, the child going to school by a vehicle (OR 3.12 (2.29,8.37); p 0.006) was associated with an increased risk. Drying clothes on a clothesline showed a trend towards protection from acquiring scrub typhus (OR 0.31 (0.08, 1.08); p 0.077). Vector survey:26 rodents were trapped in as many houses. Trombiculid mites were isolated in 24 houses with 9(34.6%) being able to transmit scrub typhus. 254 trombiculid mites belonging to four species and two genera were collected. Leptotrombidium deliense, (33.5%). Schoengastiella ligula, (11.0%) of the total mite specimens collected. S. ligula always co-existed with L. deliense. The estimated Chigger index for Leptotrombidium deliense and Schoengastiella ligula was 3.27and 1.08 per animal respectively. CONCLUSIONS: Our study highlights risk factors for scrub typhus, some of which may be modifiable. A clean peri-domestic environment free of vegetation, drying clothes on a clothesline and cooking indoors may decrease the risk of scrub typhus.

Sentinel Surveillance for Congenital Rubella Syndrome - India, 2016-2017.

Rubella infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). The 11 countries in the World Health Organization (WHO) South-East Asia Region are committed to the elimination of measles and control of rubella and CRS by 2020. Until 2016, when the Government of India's Ministry of Health and Family Welfare and the Indian Council of Medical Research initiated surveillance for CRS in five sentinel sites, India did not conduct systematic surveillance for CRS. During the first 8 months of surveillance, 207 patients with suspected CRS were identified. Based on clinical details and serologic investigations, 72 (34.8%) cases were classified as laboratory-confirmed CRS, four (1.9%) as congenital rubella infection, 11 (5.3%) as clinically compatible cases, and 120 (58.0%) were excluded as noncases. The experience gained during the first phase of surveillance will be useful in expanding the surveillance network, and data from the surveillance network will be used to help monitor progress toward control of rubella and CRS in India.

Scrub Typhus as a Cause of Acute Encephalitis Syndrome, Gorakhpur, Uttar Pradesh, India.

Outbreaks of acute encephalitis syndrome (AES) have been occurring in Gorakhpur Division, Uttar Pradesh, India, for several years. In 2016, we conducted a case-control study. Our findings revealed a high proportion of AES cases with Orientia tsutsugamushi IgM and IgG, indicating that scrub typhus is a cause of AES.

Pneumococcal serotypes associated with invasive disease in under five children in India & implications for vaccine policy.

BACKGROUND & OBJECTIVES: Streptococcus pneumoniae is a major cause of morbidity and mortality especially in children less than five years, particularly in India. We present data on S.pneumoniae infections in children less than five years age group, with response to its serotype distribution, antibiotic resistance profile and available vaccines expected coverage. METHODS: Children aged less than five, who were suspected for invasive pneumococcal disease were included in the study and their sterile body fluids were investigated for the presence of S. pneumoniae. Invasive S. pneumoniae isolates from sterile body fluids were identified by bile solubility and optochin susceptibility test. Pneumococcal serotyping was performed with co-agglutination technique and reconfirmed with multiplex PCR. RESULTS: The most common pneumococcal serotypes causing invasive infections in children less than five years of age were 14, 19F, 5, 6A and 6B. Of the 114 S. pneumoniae isolates studied, 110 (96.4%) were non-susceptible to co-trimoxazole and 30 per cent were non-susceptible to erythromycin, 5.2 per cent of the isolates were non-susceptible to penicillin and only 0.8 per cent was non-susceptible to cefotaxime. INTERPRETATION & CONCLUSIONS: Our results indicate that PCV-10 can protect against 64 per cent of serotypes causing invasive pneumococcal infections. Use of PCV-13 in this region can provide increase in protection upto 74.6 per cent against serotypes causing invasive pneumococcal infections. Incorporating PCV-13 in the Universal Immunization Programme may provide incremental protection against IPD serotypes in the southern region of the country.

A systematic review of hepatitis E virus infection in children.

A systematic review was conducted, seeking all literature relevant to the epidemiology, clinical and laboratory features, and outcome of hepatitis E virus (HEV) infection in children. Transmission is thought to be primarily from fecal-oral transmission, with the role of transmission from animal reservoirs not being clear in children. Worldwide, seroprevalence is <10% up to 10 years of age, with the exception of 1 of 5 studies from India and the sole study from Egypt. Seroprevalence increases with age, but it is not clear if it is increasing over time. The clinical presentation of HEV infection has broad similarities to hepatitis A virus (HAV) infection, with most cases being subclinical. However, HEV differs from HAV in that infectivity is lower, perinatal transmission can result in neonatal morbidity and even mortality, and a chronic carrier state exists, accounting for chronic hepatitis in some pediatric solid organ transplant recipients.

Approach to fever in children.

BACKGROUND: Fever in children is one of the most common reasons for outpatient visits as well as in-patient evaluation, often causing anxiety among parents and caregivers. Fever can be a standalone feature or be associated with other localising symptoms and signs like rash, lymphadenopathy, or any other organ system involvement with or without a focus of infection. The etiologies of fever vary depending on the clinical setting and epidemiology. India being a tropical country, sees a distinct spectrum of tropical infections. Physicians need to stay updated on the prevalent diseases in their region and the unique factors that may influence the clinical presentations and course of fever in the cohort of children they manage. The challenge lies in balancing the benefit of early treatment for severe diseases versus the harms of unnecessary investigations and treatment for self-resolving illnesses. OBJECTIVES: This review aims to provide a comprehensive overview of fever in children, covering its etiology, clinical features, and management strategies. This review offers an algorithmic approach to fever tailored to the Indian setting to guide physicians in identifying the disease based on clinical symptoms and signs, ordering essential laboratory investigations, and initiating appropriate management promptly. CONTENT: The review categorises fever into various segments like fever with localising signs like rash, lymphadenopathy, fever due to infection localised to a particular organ system, and fever without a focus including fever of unknown origin. It delves into the diverse etiological factors contributing to fever in each of these categories, encompassing infectious and non-infectious origins. It gives pointers to identify the etiology from history, examination, and confirm them with judicious use of diagnostic investigations with emphasis on identifying the red flag signs that require immediate attention, especially in vulnerable groups like neonates and young infants.

Heterogeneity and Hierarchy of Immune Response to Primary Immunization in HIV-Infected Children on HAART and the Impact of an Additional Dose of Vaccine.

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose.

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.

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.

Prospective multi-centre sentinel surveillance for Haemophilus influenzae type b & other bacterial meningitis in Indian children.

BACKGROUND & OBJECTIVES: Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance. METHODS: Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per µl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens. RESULTS: A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively). INTERPRETATION & CONCLUSIONS: Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.

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.

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.

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.

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.

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.