Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1ß, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

Quality Improvement Study With Low-Cost Strategies to Reduce Neonatal Admission Hypothermia.

Background Admission hypothermia is still an underappreciated major challenge for new-born survival in low-resource settings. The WHO recommends skin-to-skin contact as the simplest and safest way for maintaining the body temperature even during transportation. Quality improvement initiatives for hospitalised new-borns have shown benefits like a reduction in neonatal morbidity and mortality. This study was undertaken in a resource-constrained public hospital in southern India with an aim to reduce neonatal hypothermia at admission to <20%. Method It was a prospective, quality improvement study undertaken over 20 weeks. All neonates born in the selected delivery room (DR), requiring transportation to the neonatal intensive care unit, were included. The primary outcome indicators were the mean axillary temperature of neonates measured upon arrival at the neonatal intensive care unit and the percentage of neonates with hypothermia at admission. Improving the thermoregulatory practices and ambient DR temperature to >25˚C, transportation by the kangaroo method, and a portable infant warmer (PIW) were implemented in three successive Plan-Do-Study-Act (PDSA) cycles. Result In the third PDSA cycle, the mean admission temperature (36.51˚C ±0.82) was significantly (p<0.0001) higher when compared with the baseline phase (35.41˚C ±1.09), and there was a significant (p<0.001) reduction in hypothermia (33.33%). The aim was achieved in the last two weeks of the third cycle with a reduction in hypothermia to 17.6%. Conclusion Implementation of appropriate thermoregulatory practices and low-cost strategies like the kangaroo method and PIW using quality improvement methodology significantly reduced admission hypothermia.

Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probable in 55 (63%), and possible in 16 (18%). IgM detection in CSF had a sensitivity of 93% and specificity of 82% compared with PCR. Our findings suggest scrub typhus as an emerging common treatable cause of AES in children in southern India and highlight the importance of routine testing for scrub typhus in diagnostic algorithms. Our results also suggest the potential promise of IgM screening of CSF for diagnosis of AES resulting from scrub typhus.

Predictors of poor outcome in children with steroid sensitive nephrotic syndrome.

BACKGROUND AND OBJECTIVE: Nearly 50% of the children with steroid sensitive nephrotic syndrome (SSNS) have a frequently relapsing (FR) or steroid dependent (SD) course, experiencing steroid toxicities and complications of immunosuppression. The study aimed to compare parameters between children with infrequent relapsing (IFR) and FR/SD nephrotic syndrome and to identify the factors associated with a FR/SD course. METHODS: A retrospective analysis of medical records from 2009 to 2014, of children with SSNS attending the pediatric nephrology clinic in a tertiary care medical college and hospital. RESULTS: Out of 325 children (226 males) with SSNS, 213 were IFR and 112 were FRNS/SDNS. The median age of onset was 34 (IQR 24-48) months. The median time to the first relapse was 4 (IQR 3-7) months and 6 (IQR 4-12) months in FR/SD and IFR group respectively. Multivariate logistic regression analysis showed "adequate treatment (≥12 weeks) of the first episode" (odds ratio 0.56, 95% CI 0.34-0.91; p value=0.02) and "shorter median time to the first relapse" (odds ratio 1.04, 95% CI=1.01-1.08; p value=0.04) to be independent predictors of FR/SD course. An ROC curve was constructed which showed that time to first relapse <5.5 months was associated with a sensitivity of 69% and specificity of 60% in predicting a FR/SD course. CONCLUSION: Adequate treatment of the first episode is associated with less chance of an FR/SD course. After treatment of first episode, the first relapse occurring within 5.5 months may predict a frequently relapsing or steroid dependent course.