Scrub Typhus: A Spatial and Temporal Analysis from South India.

Scrub typhus is a zoonotic rickettsial disease caused by the bacterium Orientia tsutsugamushi. The non-specificity of presentation, low index of suspicion and the poor availability of diagnostic tests often lead to delayed diagnosis and significant morbidity and mortality. Temperature, humidity, rainfall and Normalized Difference Vegetation Index (NDVI) on the spatio-temporal clustering of scrub typhus cases in children in three contiguous administrative districts in South India over 5 years were studied. A total of 419 children were diagnosed with scrub typhus during the study period. A surge of children with scrub typhus was noted when the NVDI ranged between 0.6 and 0.8 µm. Temperature, humidity and rainfall had a major role in the incidence of scrub typhus.

Early Life Stress Affects Bdnf Regulation: A Role for Exercise Interventions.

Early life stress (ELS) encompasses exposure to aversive experiences during early development, such as neglect or maltreatment. Animal and human studies indicate that ELS has maladaptive effects on brain development, leaving individuals more vulnerable to developing behavioral and neuropsychiatric disorders later in life. This result occurs in part to disruptions in Brain derived neurotrophic factor (Bdnf) gene regulation, which plays a vital role in early neural programming and brain health in adulthood. A potential treatment mechanism to reverse the effects of ELS on Bdnf expression is aerobic exercise due to its neuroprotective properties and positive impact on Bdnf expression. Aerobic exercise opens the door to exciting and novel potential treatment strategies because it is a behavioral intervention readily and freely available to the public. In this review, we discuss the current literature investigating the use of exercise interventions in animal models of ELS to reverse or mitigate ELS-induced changes in Bdnf expression. We also encourage future studies to investigate sensitive periods of exercise exposure, as well as sufficient duration of exposure, on epigenetic and behavioral outcomes to help lead to standardized practices in the exercise intervention field.

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.

Distribution of Eschar in Pediatric Scrub Typhus.

BACKGROUND: Identifying an eschar in scrub typhus is useful for initiation of prompt and appropriate antibiotic therapy. METHODS: The distribution of eschars in all children <15 years of age admitted with confirmed scrub typhus over a 5 year period is described. RESULTS: Of 431 children admitted with scrub typhus, eschars were present in 176 (40.8%) children with the following distribution: head, face and neck, 33 (19.1%); axillae, 37 (21%); chest and abdomen, 21 (11.9%); genitalia, inguinal region and buttocks, 58 (33%); back, 8 (4.5%); upper extremities, 13 (7.4%); and lower extremities, 5 (2.8%). The commonest sites of eschars were scrotum (27 of 106; 25.5%) and axillae (15 of 106; 14.2%) in males and axillae (22 of 70; 31.4%) and groin (16 of 70; 22.9%) in females. Eschars were seen within skin folds in 100 of 176 (56.8%) children. CONCLUSION: Children should be carefully examined for the presence of eschar especially in the skin folds of the genitalia, axillae and groin to make an early diagnosis of scrub typhus.

Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification.

The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas1,2. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization3,4. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation5,6,7,8. Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization6,10. Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain.

Spectrum of COVID-19 Disease in Children: A Retrospective Analysis Comparing Wave 1 and Wave 2 from a Tertiary Hospital in South India.

OBJECTIVE: To describe COVID-19 in children and the differences between the two waves. METHODS: The electronic medical records of children younger than 16 y of age with laboratory-confirmed COVID-19 infection between June 1st 2020 and May 31st 2021 at Christian Medical College, Vellore were retrospectively reviewed. Demographic, clinical, and laboratory data were collected on a predesigned case record form and analyzed. RESULTS: A total of 988 children were diagnosed with confirmed COVID-19 during the study period. Of these, there were 585 children diagnosed during the 1st wave (June 2020-Feb 2021) and 403 children during the 2nd wave (March 2021-May 2021). It was found that loose stools and rash were significantly more frequent during the 1st wave and fever, cough, coryza, heart rate and temperature were significantly more during the 2nd wave. There was no significant difference between the two groups in terms of requirement of oxygen therapy, need for ICU admission, duration of ICU stay or hospital stay, or severity of illness. Mortality was significantly higher during the 2nd wave (0.3% vs. 2%). CONCLUSION: The COVID-19 pandemic among children during the 1st and 2nd waves were similar in severity, though there was a higher mortality during the 2nd wave.

Acute respiratory distress syndrome in paediatric scrub typhus.

Acute respiratory distress syndrome is a life-threatening complication of scrub typhus; we sought to describe its mortality and associated factors, namely eschar, hepatomegaly and severe thrombocytopenia, in a retrospective study in India of 65 children.

Comparison of Scrub Typhus With and Without Meningitis.

OBJECTIVE: To compare the children admitted with scrub typhus with and without meningitis. METHODS: All children admitted with scrub typhus over a 62 mo period were reviewed. Statistical analysis was performed to compare those with and without meningitis for demographic, clinical, investigations and outcome parameters. RESULTS: Four hundred twenty seven children were admitted with scrub typhus and 63 (14.8%) had meningitis. The mean cerebrospinal fluid white blood cell (CSF WBC) count was 71 cells/cu.mm. with mean lymphocyte proportion of 92%. The mean CSF protein was 67 mg/dl and mean CSF glucose, 55 mg/dl. Of those who had meningitis, 24 (38.1%) had seizures, 17 (27%) had altered sensorium and 37 (58.7%) had nuchal rigidity. Finding an eschar, being male, breathing difficulty, and hepatomegaly were significantly more common in those without meningitis. Children with meningitis also had shorter duration of fever at presentation (median [IQR] 7 [3] days vs. 10 [4] days; p = 0.028). Headache and vomiting were significantly more common in those with meningitis. Hemoglobin and platelet were significantly lower in those without meningitis. Duration of hospitalization was significantly longer in those with meningitis, whereas acute respiratory distress syndrome (ARDS) was significantly more common in those without meningitis. There was no neurological deficit in both the groups. There was no mortality in the meningitis group compared to 3.6% mortality in the non-meningitis group (p = 0.213). CONCLUSIONS: Meningitis occurs in 15% of those with scrub typhus; those with meningitis have good neurological outcome with little mortality; those without meningitis have more complications and poorer outcome.

Impact of pre-hospital care on the outcome of children arriving with agonal breathing to a pediatric emergency service in South India.

BACKGROUND: Data on the prehospital interventions received by critically ill children at arrival to Paediatric Emergency Services (PES) is limited in developing countries. This study aims to describe the pre-hospital care scenario, transport and their impact on outcome in non-traumatic, acutely ill children presenting in PES with agonal breathing. METHODS: Prospective observational study done on children aged below 15 years arriving in PES with agonal breathing due to non-trauma related causes. RESULTS: Out of 75 children studied, 69% were infants. The duration of illness among 65% of them (75) was less than 3 days. Majority of them (81%) had received treatment prior to arrival. Government sector physicians (72%), half of them (51%) being pediatricians were the major treating doctors. 37% of the children had arrived to the Emergency in an ambulance. Cardiopulmonary Resuscitation (CPR) was given to 27% on arrival in PES. Other interventions included fluid boluses to correct shock (92%) and inotrope infusion (56%). Sepsis (24%) and pneumonia (24%) were the most common diagnoses. Out of 75, 57 (76%) children who were stabilized and shifted to PICU and among them 27 (47%) survived to discharge. Normal blood pressure (p=0.0410) and non-requirement of CPR (0.0047) and inotropic infusion (0.0459) in PES were associated with a higher chance of survival. CONCLUSION: 36% (27/75) of children who arrived to our PES with agonal breathing survived to hospital discharge. Survival was significantly better among those who did not need CPR.

Neuroregression as an initial manifestation in a toddler with acquired pernicious anaemia.

The aetiology spectrum for neuroregression in infants and toddlers is diverse. Vitamin B12 deficiency-mediated neuroregression is less commonly considered as a differential. Prevalence of pernicious anaemia in the general population is 0.1% and is extremely rare in children. We describe a 35-month-old toddler with neuroregression, seizures, coarse tremors, bleating cry and neuropathy. His clinical symptomatology mimicked grey matter degenerative illness and infantile tremor syndrome, a nutritional deficiency-mediated movement disorder. His vitamin B12 level was low and serum homocysteine level was elevated. Haematological manifestations were not overt and anti-intrinsic factor antibody was positive. With parenteral vitamin B12 therapy, there was a dramatic response with clinical and laboratory translation. This report emphasises the need for a high index of suspicion and screening for markers of vitamin B12 deficiency in all children with unexplained acute or subacute neuroregression, seizures and movement disorders as it is potentially reversible.

Syndrome of insulin resistance with acanthosis nigricans, acral hypertrophy and muscle cramps in an adolescent - a rare diagnosis revisited.

The authors report a 14-y-old boy with insulin resistance, acanthosis nigricans, acral hypertrophy and muscle cramps. While there was a dramatic response of the muscle cramps to phenytoin therapy, some other features of metabolic syndrome did not respond to phenytoin therapy alone.