Clinical Profile and Outcome of Severe Acute Respiratory Illness (SARI) in Children Amidst the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES:  Beginning in December 2019, COVID-19 rapidly emerged as a global pandemic. Though its severity in children was reported to be less than that in adults, data on its epidemiology in relation to severe acute respiratory illness (SARI) caused by other microbes needed to be generated. This study compares the clinical profile and outcome of children hospitalized with COVID-19-positive and negative SARI. METHODS:  This is a prospective observational analytical study involving children 1 month to 18 years old, hospitalized with COVID-19-positive and negative SARI during the pandemic. All eligible patients were enrolled after obtaining informed parental consent. Their clinical manifestations, investigations, and outcomes were documented on a predesigned case record form. A nasopharyngeal swab sample for COVID-19 reverse transcription polymerase chain reaction was sent, and results were noted. RESULTS:  From May 2020 to July 2021, 267 children were hospitalized with a diagnosis of SARI. Out of these, 146 (54.7%) were boys and 78.7% were under five years of age. Other presentations included fever and cough, breathlessness, nausea, vomiting, diarrhea, rash, seizures, and altered sensorium. Twenty-eight patients (10.5%) tested positive for COVID-19. COVID-19 patients were similar in terms of demographic characteristics and presenting symptoms to non-COVID-19 patients but had a lower absolute lymphocyte count (p = 0.019) and higher serum alanine transaminase levels (p = 0.013). Acute respiratory distress syndrome (OR, 4.3; 95% CI, 1.8-10.0), shock (OR, 3.9; 95% CI, 1.9-7.9), and need for intensive care unit admission (OR, 9.9; 95% CI, 6.9-14) were more common in COVID-19 SARI patients. Death occurred in 18% of COVID-19 and 9% of non-COVID-19 patients (p = 0.07). SARI nonsurvivors had significantly lower blood pH and platelet counts than survivors. CONCLUSIONS: Comparison of COVID-19-positive and negative SARI patients showed subtle differences between the two groups, with COVID-19-positive children having an increased severity of illness. Also, laboratory evidence of multiorgan dysfunction at admission was associated with higher mortality.

Acute demyelinating encephalomyelitis in a child with pulmonary tuberculosis.

Tuberculosis is a leading cause of mortality in children worldwide. One of the greatest challenges in its management is the difficulty of diagnosis as the manifestations are non-specific and often mimic other illnesses. Neurological infection occurs in approximately 1% of patients diagnosed with tuberculosis, and usually takes the form of tuberculous meningitis or tuberculoma. An 11-year-old girl who was diagnosed with acute disseminated encephalomyelitis, a rare immunological manifestation of tuberculosis, is presented. She recovered completely after a course of high-dose systemic corticosteroids in addition to anti-tuberculosis treatment. Considering the immense burden of this infectious disease, recognition and understanding of the uncommon manifestations are important to enable appropriate and timely treatment.Abbreviations: ADEM: acute disseminated encephalomyelitis; ATT: anti-tuberculosis therapy; CBNAAT: cartridge-based nucleic acid amplification test; CNS: central nervous system; CSF: cerebrospinal fluid; CT: computed tomography; FLAIR: fluid attenuated inversion recovery; IFN: interferon; MRI: magnetic resonance imaging; MTB: Mycobacterium tuberculosis; TB: tuberculosis; TNF: tumour necrosis factor.

The new Xpert Mycobacterium tuberculosis/rifampicin (MTB/Rif) Ultra assay in comparison to Xpert MTB/Rif assay for diagnosis of tuberculosis in children and adolescents.

BACKGROUND: Microbiological diagnosis of pediatric tuberculosis (TB) using conventional microbiological techniques has been challenging due to paucibacillary nature of the disease. Molecular methods using cartridge-based tests like Xpert, have immensely improved diagnosis. A novel next-generation cartridge test, Xpert Ultra, incorporates two additional molecular targets and claims to have much lower detection limit. We attempted to compare the two techniques in presumptive pediatric TB patients. OBJECTIVES: The aim of this study was to compare the diagnostic performance of Xpert MTB/Rif Ultra with Xpert MTB/Rif for the detection of pediatric TB. STUDY DESIGN: This is an observational comparative analytical study. METHODS: Children under 15 years of age with presumptive TB were enrolled. Appropriate specimens were obtained (sputum, induced sputum or gastric aspirate for suspected pulmonary TB, cerebrospinal fluid for suspected tubercular meningitis and pleural fluid for suspected tubercular pleural effusion), subjected to smear microscopy, mycobacterial culture, Xpert and Xpert ultra tests and other appropriate diagnostic investigations. RESULTS: Out of 130 enrolled patients, 70 were diagnosed with TB using a composite reference standard (CRS). The overall sensitivity of Xpert was 64.29% [95% confidence interval (CI) 51.93-75.93%] and that of Xpert Ultra was 80% (95% CI 68.73-88.61%) with 100% overall specificity for both. The sensitivity of Xpert and Xpert Ultra in pulmonary specimens (n = 112) was 66.67% and 79.37% and in extrapulmonary specimens (n = 18) was 42.86% and 85.71%, respectively. CONCLUSION: Our study found Ultra to be more sensitive than Xpert for the detection of Mycobacterium tuberculosis in children. Our findings support the use of Xpert Ultra as initial rapid molecular diagnostic test in children under evaluation for TB.

A 16-Year-Old-Girl With Asthma, Palpable Purpura, and Hypereosinophilia.

CASE PRESENTATION: A 16-year-old girl presented to the ED with complaints of loose stools, abdominal pain, and rash over her legs for the last 7 days. There was no history of fever, vomiting, oral ulcers, or mucosal bleeds. In the past, she had received a diagnosis of asthma. She had been taking oral montelukast every day for the past year and using a formoterol-budesonide dry powder inhaler irregularly, only during episodes of acute exacerbations. There was a history of significant but undocumented weight loss. On day 3 of hospital admission, she developed numbness over her right foot.

Early diagnosis of kidney injury in a paediatric population: a prospective cohort study (E-DRIP STUDY).

BACKGROUND: Renal Angina Index (RAI) is a bedside tool for risk stratification of patients to predict acute kidney injury (AKI). Kidney biomarkers are better indicators of real-time injury and give us lead time for diagnosing impending AKI. METHODS: We enrolled consecutive children aged 2 months-14 years admitted to a tertiary hospital in northern India over 2 years. RAI was calculated on day 0 (D0) and urinary (u) and plasma (p) neutrophil gelatinase-associated lipocalin (NGAL) were measured within 6 h of admission. Children were followed for the development of severe AKI on day 3 (D3) using Kidney Disease Improving Global Outcomes criteria to define and stage AKI. RESULTS: Of the 253 children enrolled and analysed, 44 (17.4%) developed D3-AKI (stage 1 in 52.2%, stage 2 in 20.5% and stage 3 in 27.3%). Renal angina (RAI ≥ 8) on D0 was present in 66.7% children who developed stage 2/3 D3-AKI vs. 43.5% in children who did not develop D3-AKI /stage 1 AKI (p = 0.065). Area under ROC (AUROC) curve for D0-RAI to predict D3-severe-AKI was 0.66 (95% CI, 0.55-0.77). AUROC curve for uNGAL and pNGAL to predict D3-severe-AKI was 0.62 (95% CI, 0.50-0.74) and 0.48 (95% CI, 0.35-0.61), respectively. The severe AKI group had greater requirement of ventilation and inotropic support with mortality being thrice higher compared to the non-AKI group. CONCLUSION: RAI ≥ 8 and uNGAL had a high negative predictive value but low sensitivity for predicting D3-severe-AKI. pNGAL had a poor predictive value for D3-severe-AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Bacterial Colonization of Home Nebulizers Used by Children With Recurrent Wheeze.

OBJECTIVE: To look for bacterial colonization of parts of home nebulizers used for children with recurrent wheeze and asthma. METHODS: Children aged 1 mo-12 y, using home nebulizers for recurrent cough and wheeze were enrolled from May to October, 2019. Caregivers were administered a structured questionnaire by a single researcher, during their hospital visit, to elicit information on their nebulizer cleaning practices. Samples were taken from nebulizer medicine chamber and tubing for bacterial culture and sensitivity. RESULT: Bacterial growth was observed in 17 culture samples obtained from medicine chamber and/or tubing of nebulizers used by 12 (20.3%) out of the 59 enrolled children. The bacteria isolated were Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus (Methicillin resistant S. aureus and Coagulase negative staphylococci) and these were resistant to many of the commonly used antimicrobials. Almost 20% parents had never cleaned the nebulizers. Diluent re-use was significantly associated with bacterial colonization of nebulizer parts [AOR (95% CI) 20.6 (2.26-188.5); P=0.007]. CONCLUSION: Home nebulizers, if not cleaned properly as per set protocols, may get colonized with potentially harmful bacteria. There is a need to increase awareness about their proper use amongst parents of children with recurrent wheeze.

Peripheral Perfusion Index as a Marker of Sepsis in Preterm Neonates.

BACKGROUND: Neonatal sepsis is a major contributor to neonatal mortality in India. Blood culture, the gold standard for the diagnosis of sepsis takes 48-72 h while the serological markers have suboptimal diagnostic test characteristics. Perfusion index (PI) is a real time, non-invasive marker that can detect microcirculatory changes before other clinical manifestation of sepsis. OBJECTIVE: To determine the diagnostic accuracy of PI in detecting hospital-acquired sepsis before overt clinical manifestations. STUDY DESIGN: A prospective observational study conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care hospital. PARTICIPANTS: Preterm neonates admitted to NICU. METHODS: PI was continuously monitored in all enrolled neonates. Clinical sepsis was defined using the NeonatalKrankenhaus-Infektions-Surveillance-System (NeoKISS). The time of fall of PI below 0.88 and time of clinical sepsis as per NeoKISS were noted and the difference was calculated. RESULTS: Among 65 preterm neonates (gestational age: 31.5 ± 2.6 weeks, birth weight: 1350, IQR 1100-1700 g), a total of 86 events of suspected sepsis were noted, of which 69 were sepsis screen positive. Fifteen events were associated with culture positive sepsis. PI yielded a sensitivity of 89.47% (95% CI 78.48-96.04%), specificity of 56% (95% CI 34.93-75.60%), positive predictive value of 82.26% (95% CI 74.70-87.92%) and negative predictive value of 70% (95% CI 50.36-84.29%) in detection of hospital-acquired sepsis. CONCLUSION: PI might serve as an early, non-invasive marker of hospital-acquired sepsis in preterm neonates.

Once-Daily vs. Twice-Daily Administration of Inhaled Budesonide for Mild and Moderate Well-Controlled Childhood Asthma: A Randomized, Controlled Trial.

OBJECTIVES: To compare median change in morning peak expiratory flow rate (PEFR) and clinical asthma control in children receiving total daily dosage of inhaled budesonide administered either as once-daily or divided twice-daily dose. METHODS: It was a randomized, parallel group, open label, noninferiority trial on 80 children aged 5-12 y with mild or moderate well-controlled asthma. Baseline parameters were recorded and subjects received inhaled budesonide either as once-daily or divided twice-daily dose. Primary outcome was median change in morning PEFR. Secondary outcomes included median change in evening and diurnal variation in PEFR, asthma symptom control as per Global Initiative for Asthma, 2017 and Asthma Control Questionnaire, and spirometric measurements taken at the clinic. RESULTS: The median [interquartile range (IQR)] increase in morning PEFR was more in children receiving once-daily as compared to those receiving twice-daily inhaled budesonide (by 6:00 L/min; IQR: -44.00-63.00 L/min vs. 4:00 L/min; IQR: -67.50-67.50 L/min, p 0.222; 95% CI: -1.37 to 19.08). Other spirometric variables and symptoms scores were also nonsignificant except median change in evening PEFR which was in favor of twice-daily regimen. CONCLUSION: Once-daily administration of inhaled budesonide is noninferior to twice-daily administration of equivalent daily dosage of inhaled budesonide.

Acute disseminated encephalomyelitis due to a zoonotic co-infection.

Acute disseminated encephalomyelitis (ADEM) is a post-infectious, autoimmune, demyelinating neurological illness, usually attributed to infection with viruses. We describe a case of ADEM occurring in a child with Leptospira-Brucella co-infection. The 12-year-old girl developed a biphasic febrile illness with encephalopathy. On evaluation, she was found to have serological evidence of Brucella and Leptospira infections. Persistence of neurological symptoms after initiating treatment for the co-infection led us to do a magnetic resonance imaging scan of the brain which showed typical findings suggestive of ADEM. Patient responded appropriately to treatment of ADEM with glucocorticoids. The high prevalence of these zoonotic infections in developing countries, and the risk that these may lead to ADEM highlights the importance of detailed evaluation of such cases for proper treatment and better outcomes.

ADEM is a serious neurological disease which occurs as an uncommon complication of certain infections that lead to formation of antibodies which attack the cells of the nervous system. It usually occurs after viral infections, but we came across a 12-year-old girl with ADEM who tested positive for simultaneous infection with two different micro-organisms, both not viruses. These microbes, called Leptospira and Brucella, are common in developing countries and usually lead to infection in individuals in close contact with animals, or with consumption of infected, unpasteurized animal products. Neurological symptoms are uncommon in both infections. However, our case highlights that both infections can occur together and lead to serious neurological illness which needs proper evaluation and a different kind of treatment so that patient has better recovery.

Magnetic Resonance Imaging in Subacute Sclerosing Panencephalitis: Two Case Reports and Review of Literature.

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive neurodegenerative disease caused by the measles virus. This study investigated the magnetic resonance imaging (MRI) findings in SSPE by retrospective review of two cases diagnosed by typical periodic electroencephalographic (EEG) features, clinical symptoms and elevated measles antibody titre in cerebrospinal fluid (CSF). MRI revealed lesions of high signal intensity on T2-weighted images involving the periventricular or subcortical white matter in both the patients. Both these patients were given sodium valproate for seizures. However, the disease proved fatal in both these cases eventually.

Clinical Spectrum and Outcome of Acute Encephalitis Syndrome in Children with Scrub Typhus: A Series of Eight Cases from India.

Scrub typhus has reemerged with a different geographical distribution and varied clinical presentation like acute encephalitis syndrome (AES), which is a less known entity in scrub typhus. In this case series, we studied the clinical profile and outcome of eight patients who presented with AES and a positive scrub serology without any other identifiable cause of encephalopathy. All these patients had fever, altered sensorium, and nuchal rigidity, while seizures were present in six (75%) patients and papilledema in two (25%) patients. Complications like shock, pulmonary edema, and gastrointestinal (GI) bleed were observed in three (37%) patients. All patients except for one responded well to the treatment and recovered completely. Scrub typhus should be suspected early in patients presenting with AES. How to cite this article: Kaur P, Jain R, Kumar P, Randev S, Guglani V. Clinical Spectrum and Outcome of Acute Encephalitis Syndrome in Children with Scrub Typhus: A Series of Eight Cases from India. Indian J Crit Care Med 2020;24(9):885-887.

Epidemiology of Coronavirus Infection in Children and Their Impact on Lung Health: Finding From a Birth Cohort Study.

In this birth cohort, coronavirus acute respiratory infection was detected in 6.5% of the episodes; the commonest strain was OC43, followed by NL63, HKU1, and 229E. Children with coronavirus acute respiratory infection during infancy had significantly decreased forced expiratory volume in 0.5 seconds, forced expiratory flow between 25% and 75% of forced vital capacity, and peak expiratory flow at 3 years of age.

Allergic bronchopulmonary aspergillosis without asthma or cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an immunological disease complicating asthma or cystic fibrosis. An 8-year-old girl with no previous respiratory morbidity was diagnosed with ABPA on the basis of a raised eosinophil count and total and specific serum IgE levels combined with a positive skin-prick test for aspergillus and typical CT images of finger-in-glove hilar opacities and hyperattenuating mucous. She responded to treatment with itraconazole and corticosteroids and remains well. As far as we are aware, she is only the second child to be diagnosed with ABPA without asthma or cystic fibrosis.

Wheezing in Preschool Children and Total IgE Levels: A Birth Cohort Study.

OBJECTIVES: To evaluate association between total IgE levels and wheezing in preschool children from India. METHODS: Data were collected in a prospective birth cohort study related to wheezing till three years of age. Total IgE was measured at enrolment, at one year and two years of age and correlated with wheezing episodes. RESULTS: A total of 310 (167 boys) children were enrolled. Total IgE levels increased with age (P<0.001). Overall, 101 (32.6%) children had 182 episodes of wheezing. The median (IQR) total IgE levels in children with wheezing and without wheezing were similar at one year [42.1 (12.7, 93.5) vs 41.9 (17.1, 96.7) kU/L; P=0.39] and two years of age [62.8 (32.4, 212.0) vs 75 (25.8, 173.0) kU/L, P=0.92). CONCLUSION: Total IgE levels increased with age and were not different in preschool children with and without wheezing.

Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study.

INTRODUCTION: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. METHODS: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. RESULTS: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV1.0), forced expiratory volume in 0.75 s (FEV0.75), forced expiratory volume in 0.5 s (FEV0.5), forced expiratory flow between 25% and 75% of FVC (FEF25-75), and maximal expiratory flow at 25% of FVC (MEF25) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF50 or TEF25/peak TEF) at 3 years was significantly increased in children who had ARI in infancy. CONCLUSIONS: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.

Normative Data of Infant Pulmonary Function Testing: A Prospective Birth Cohort Study from India.

OBJECTIVE: To develop a normal reference range of Infant pulmonary function test (IPFT) indices for Indian children. STUDY DESIGN: Prospective birth cohort study. SETTING: Division of Pediatric Pulmonology of a tertiary-care institute in India from August 2012 to March 2017. PARTICIPANTS: All neonates born at the institute during the study period were screened for eligibility. MEASUREMENT: IPFT at baseline and every 6-month until 36-months of age. MAIN OUTCOME MEASURE(S): Tidal breathing flow-volume loop (TBFVL), Rapid thoracoabdominal compression (RTC), and Raised volume RTC (RVRTC) indices at baseline and follow-up. RESULTS: 310 newborns were enrolled in the cohort; 281 of them (169 male) had completed 36-months of follow-up at the end of the study period. There was no influence of gender on the baseline IPFT indices. Tidal volume per unit body weight (VT/kg) significantly increased from baseline to 36 months of age (P<0.001) while the peak ratio (tPTEF/tE) initially decreased in first 18-months of age (P<0.001), after that returned to the baseline value by 36 months of age. RTC indices did not change significantly from baseline values. In RVRTC, the ratio of forced expiratory volume in 0.5s to forced vital capacity (FEV0.5/FVC) was significantly decreased from baseline to 36 months of age (P=0.002). CONCLUSIONS: Normal values for various IPFT indices for TBFVL, RTC, and RVRTC from neonates to the age of 36-month are provided. These data may be used as normative data for healthy neonates and children of Indian origin.