Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population.

Several genetic disorders are associated with either a permanent deficit or a delay in central nervous system myelination. We investigated 24 unrelated families (25 individuals) with deficient myelination after clinical and radiological evaluation. A combinatorial approach of targeting and/or genomic testing was employed. Molecular diagnosis was achieved in 22 out of 24 families (92%). Four families (4/9, 44%) were diagnosed with targeted testing and 18 families (18/23, 78%) were diagnosed using broad genomic testing. Overall, 14 monogenic disorders were identified. Twenty disease-causing variants were identified in 14 genes including PLP1, GJC2, POLR1C, TUBB4A, UFM1, NKX6-2, DEGS1, RNASEH2C, HEXA, ATP7A, SETBP1, GRIN2B, OCLN, and ZBTB18. Among these, nine (45%) variants are novel. Fourteen families (82%, 14/17) were diagnosed using proband-only exome sequencing (ES) complemented with deep phenotyping, thus highlighting the utility of singleton ES as a valuable diagnostic tool for identifying these disorders in resource-limited settings.

Resurgence of respiratory syncytial virus infection during COVID-19 pandemic in Pune, India.

INTRODUCTION: Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly in the context of the COVID-19 pandemic. OBJECTIVE: The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods. METHODS: We analyzed data from 15,381 patients tested for RSV between 2017 and 2023. RESULTS: Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses. CONCLUSION: Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses.

Maternal Colonization Versus Nosocomial Transmission as the Source of Drug-Resistant Bloodstream Infection in an Indian Neonatal Intensive Care Unit: A Prospective Cohort Study.

BACKGROUND: Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts. METHODS: We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates. RESULTS: Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate. CONCLUSIONS: Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI.

Comparative study of risk assessment for noncommunicable diseases among out patients visiting urban and rural health centers in Belagavi, Karnataka.

Purpose/Background: Hence, this comparative study of risk assessment was carried out among out patients visiting urban and rural health centers. This study aimed to find out and compare the risk factors for NCDs among out-patients visiting urban and rural health centers. Methods: This cross-sectional study was carried out in Urban health centre Rukmini Nagar and Rural health centre Vantamuri. Using convenient universal sampling, 200 out-patients from urban area and 200 from rural area were selected. The data were entered into MS-EXCEL and analyzed using SPSS software. Results: In urban area, males were more common (53.7%), whereas females were more common in rural areas (53.8%). Maximum study participants were laborers in urban area (24.5%), whereas home makers were common in rural area (40.5%). Most people in urban areas (11.5%) were indulged in smoking, whereas only 5% smoked in rural area. Participants in urban area had higher waist circumference (20.5%) than those in rural area (17.5%). Physical inactivity was more in rural area (68%), as compared to urban area (47%). 29.5% of participants were found to be at risk for NCDs in urban area, whereas 30% of those were found to be at risk in rural area. Conclusions: Awareness regarding ill effects of risk factors: smoking, alcohol consumption, physical inactivity, and obesity should be created among the community through health education and behavioral change communication to prevent its progression as a disease in future.

Screening of Extended Family Members of Thalassemia Major Children as a Thalassemia Preventive Strategy.

Background: Thalassemia is considered as the most common single gene disorder worldwide. Preventive measures include identification of thalassemia carriers (traits) through screening, genetic counselling and prenatal diagnosis to reduce the incidence. This study aims at estimating the prevalence of carrier status detection among the extended family members of children having thalassemia major so as to use it as a screening prevention strategy with appropriate counselling. Methods: This cross-sectional study was conducted in thalassemia unit of Pediatric Department of a tertiary care teaching hospital over a period of 18 months. Blood samples were collected from 117 extended family members (EFM) of 23 children with thalassemia major to carry out investigations such as Complete Blood Counts (CBC), Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT), Reticulocyte count, High Performance Liquid Chromatography(HPLC) and serum ferritin. Reports were analysed to find out the prevalence of carriers. Results: Among 117 EFM, 62 (52.9%) were males while 55(47.1%) were females. Mean age distribution in this study was 16.49 years (8.5). Prevalence of thalassemia trait (carrier) was 35%. NESTROFT test was positive in 57(48.7%) participants. The binary logistic regression found only positive NESTROFT test as a predictor (adjusted OR=0.022, P=0.001) of having raised HbA2 (HbA2≥3.5 %). Conclusion: Screening of thalassemia carrier by targeting extended family members of thalassemia major children could yield more carrier cases and targeted counselling could help effectively in decreasing the number of children born with thalassemia major. This strategy could be included in future plan of national prevention programme for thalassemia.

A retrospective analysis of respiratory virus transmission before and during the COVID-19 pandemic in Pune the western region of India.

Background: SARS-CoV-2 was first reported in China in December 2019 and quickly spread across the world. Non-pharmaceutical interventions (NPIs) are the key to control the transmission of respiratory viruses. To stop the spread, NPI is widely recommended and is still followed by most countries. Methods: At the National Influenza Center of the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), the surveillance of severe acute respiratory illness and acute respiratory illness cases for influenza and other respiratory viruses is in place. In this study, we analyzed surveillance data on respiratory viruses and/or SARS-CoV-2 testing from January 2017 to December 2021. Multiplex real-time PCR was used to detect the respiratory viruses. Results: Our findings indicate that during the pandemic, the positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus, and human coronavirus declined significantly. Conclusion: The annual distinct seasonal outbreaks of influenza, RSV, and other respiratory viruses as observed during the pre-COVID-19 period were not observed during the COVID-19 pandemic in years 2020 and 21. Social distancing, lock-downs, and non-pharmaceutical interventions may play an important role in the reduction of respiratory viruses. Understanding the seasonal respiratory virus decline could help public health experts prepare for future respiratory virus pandemics.

Clinical Profile of SARS-CoV-2-Infected Neonates.

Background There are conflicting data on the mother-to-child transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and few studies have described the clinical course of neonates infected with SARS-CoV-2. Objectives This study investigates the mother-to-child transmission rate and clinical profile of SARS-CoV-2-infected newborns. Methods Data on 304 newborns of 301 mothers with coronavirus disease 2019 (COVID-19) were prospectively collected and analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) determined the presence of SARS-CoV-2 in the placenta, umbilical cord stump, and nasopharyngeal swabs collected within 24h of birth. Clinical and laboratory data of SARS-CoV-2-infected newborns was entered in a structured proforma. Results A total of 20 neonates (6.5%) were positive for SARS-CoV-2, of which 12 were positive only in the nasopharyngeal swab, four cases had the umbilical stump positive, three were positive in the placenta, and one case was positive in all the three specimens collected. Six of the 20 SARS-CoV-2-positive neonates developed severe symptoms. The SARS-CoV-2-positive symptomatic neonates required a more extended stay in hospital compared to their non-symptomatic infected counterparts. Conclusions A proportion of the babies born to SARS-CoV2-infected mothers tested positive and some of these newborns had severe symptoms.

Clinical Profile and Outcome of Hospitalized Confirmed Cases of Omicron Variant of SARS-CoV-2 Among Children in Pune, India.

Background The Omicron variant of SARS-CoV-2 infection was seen to be more infectious but less severe in children than adults with reduced hospitalization rates. There is a paucity of data on hospitalized children with confirmed Omicron variant. Objective We describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of children with confirmed Omicron variant of SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, India. Methodology Children who tested positive for SARS-CoV-2 - Omicron variant and were admitted between 1st December 2021 and 28th February 2022 were included in the study. Results Out of a total of 37 Covid-positive children admitted during the study period, 16 underwent genome sequencing of which 14 were confirmed to be Omicron variant and two were Delta variant. The age range was one month to 12 years and seven (50%) were male. Common presenting features were fever (n=13, 93%), cough (n=7, 50%), seizures (n=7, 50%) and coryza (n=5, 36%). Comorbidities noted were epilepsy (n=3, 21%) and one each with Thalassemia Major, suspected inborn error of metabolism (IEM), operated anorectal malformation with hypospadias, chronic suppurative otitis media with complications (mastoiditis and facial nerve palsy), neonatal cholestasis and intracranial bleed with dural venous sinus thrombosis. Malnutrition was noted in 42%, pallor in 10 cases (71%). Severe anaemia (n=10, 71%), elevated ferritin (n=6, 43%), positive C-Reactive Protein (n=4, 28%) and deranged D-dimer (n=11, 78%) were noted. The Neutrophil to Lymphocyte ratio (NLR) was >3.3 in five (36%) children. Four (28%) had evidence of pneumonia on the chest radiograph. Oxygen therapy was needed in nine (64%) while two children (14%) required mechanical ventilation. There were two deaths (14%) in children with multiorgan dysfunction and refractory shock. Intravenous immunoglobulin and methylprednisolone were administered to one patient respectively (14%). The median hospital stay was 10 days (Interquartile range = 8). Conclusion Hospitalized children with Omicron variant of SARS-CoV-2 who have underlying comorbidities may have severe presentations needing ICU care. Mortality rates are low with appropriate ICU care.

Early-onset symptomatic neonatal COVID-19 infection with high probability of vertical transmission.

BACKGROUND: There are few reports of COVID-19 in neonates and most are suspected to be due to postnatal transmission. Vertical transmission has been proven in only a couple of cases so far. METHODS: We describe early-onset, severe COVID-19 disease in a neonate with very strong evidence of vertical transmission of SARS-CoV-2. RESULTS: A COVID-19 suspected mother, who tested negative by RT-PCR for COVID, but tested positive for SARS-CoV-2 by serology, delivered a term baby. The neonate was kept in strict isolation. Molecular tests for SARS-CoV-2 on umbilical stump, placenta, and nasopharyngeal aspirate of the neonate, collected at birth were positive. On day 2, the neonate developed clinical features of COVID in the form of fever, poor feeding, and hyperbilirubenemia along with elevated inflammatory markers. Antibiotics were started empirically pending cultures. Blood, CSF, and urine cultures were sterile. Baby tested RT-PCR positive for SARS-CoV-2 on two more occasions before testing positive for antibodies and was discharged on day 21 of life. CONCLUSION: This report highlights a very strong possibility of vertical transmission of COVID-19 from a mildly symptomatic, RT-PCR negative but antibody-positive mother with significant symptomatic, early-onset neonatal infection.

Severe Malnutrition and Anemia Are Associated with Severe COVID in Infants.

BACKGROUND: COVID-19 is uncommon and less severe in children than adults. It is thought that infants may be at higher risk for severe disease than older children. There is a paucity of literature on infants with COVID, particularly those with severe disease. OBJECTIVE: We describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of infants with confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, India. METHODOLOGY: Infants who tested positive for SARS-CoV-2 and were admitted between 1 April 2020 and 7 August 2020 were included in the study. RESULTS: A total of 13 infants were admitted during the study period. The median age was 8 months (IQR 6) and nine were male. Common presenting features were fever (n = 8, 62%), poor feeding, irritability, and runny nose (n = 3, 23%). Comorbidities noted were severe acute malnutrition (SAM) in three cases (23%) and nutritional megaloblastic anemia, iron deficiency anemia, sickle thalassemia and renal calculi in one case (8%) each. There was a history of low birth weight in two cases (15%). Pallor was noted in three cases (23%), SAM in three cases (23%) and tachypnea and respiratory distress in four cases (30%). Severe anemia, thrombocytopenia, elevated ferritin, abnormal procalcitonin, abnormal C Reactive Protein and deranged D-dimer was noted in three cases (23%) each. Neutrophil-lymphocyte ratio was normal in all cases. Three infants (43%) had evidence of pneumonia on the chest radiograph, of which one had adult respiratory distress syndrome (ARDS) like pattern, one infant had cardiomegaly and perihilar infiltrates. Hydroxychloroquine and azithromycin were given to five patients (38%), Intravenous Immunoglobulin and methylprednisolone were administered to one patient (8%). One infant died of ARDS with multi-organ dysfunction with refractory shock and hemophagocytic lymphohistiocytosis. CONCLUSION: SAM and anemia may be associated with severe COVID in infants.

Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process.

Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order to ensure product quality and uniformity. Of particular challenge is the powder blends with low drug loads (<5% w/w) where the measurement of the signal-to-noise and, in turn, precision limit the ability of the method. We evaluate both near-infrared (NIR) and Raman spectroscopy for use in PAT applications by measuring pharmaceutical blends of varying active ingredient concentrations. Both spectrometers are equipped with a fiber-optically coupled probe head for noncontact measurement of powder blends. A mockup of the interface between the spectrometer and powders within the feed frame of a rotary tablet press is used to simulate the movement of powder blends from the mixer to the press. A port on the feed frame allows measurement by NIR or Raman spectroscopy of the blends just before tablet compression. For our model compound, Raman spectroscopy is shown to have a lower limit-of-detection and less day-to-day variability than NIR spectroscopy. Raman spectroscopy was chosen as the PAT platform to support process development, and working distance and spot size were both optimized for use in the feed-frame of a tablet press. Sufficient limit-of-detection was achieved for monitoring active pharmaceutical ingredient concentrations (API) down to 1% w/w during a semicontinuous manufacturing of tablets. An innovative optimization-based model (EIOT) was used to trend API concentration and demonstrated that the process could be capable of detecting out-of-trend material.