Open-labeled Randomized Controlled Trial on Efficacy of Azithromycin Versus Doxycycline in Pediatric Scrub Typhus.

BACKGROUND: Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus. STUDY DESIGN: Open-label randomized controlled trial. METHODS: Children 1-14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ. RESULTS: We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83-1.08)]. On Kaplan-Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035). CONCLUSION: AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991.

Spectrum of Anemia in Indian children with Nephrotic Syndrome: a prospective observational study.

We aimed to estimate the prevalence of anemia in children with nephrotic syndrome (NS), determine its etiology, and correlate severity with disease duration and response to steroids. This was a prospective cohort study carried from 15th July 2019-14th July 2021 at the pediatric nephrology clinic, of a teaching hospital in India. We screened children aged 3 months-18 years with NS for eligibility. We excluded those suffering from chronic kidney disease and, on haematinics. All children underwent investigations for evaluation of nephrotic syndrome and anemia. To define the clinical phenotype of nephrotic syndrome, the patients were classified as infrequent relapsers, frequent relapsers, steroid dependent and steroid resistant NS as per ISPN guidelines. Children were followed up at least for a period of one year to define their response to steroids. A total of 125 children were finally analysed for all treatment outcomes. Of 125, 37 (30%) children presented with the first episode of NS. Remaining 88 were follow up cases of NS. Of 125 children, 41 (33%) were found to be anemic as per the WHO criteria. Iron deficiency anemia was found in 21 (51%) children. Steroid resistance was twice more prevalent in the anemic group compared to the non-anemic group, 7.3% vs 4.8% respectively, however this difference was not statistically significant, p = 0.65. Anemic group had a trend of higher no. of children receiving antihypertensives compared to non-anemics (38 (93%) vs. 67 (80%), p = 0.07. CONCLUSION: Iron deficiency anemia was the commonest cause of anemia and, anemia and need for anti-hypertensives to attain BP control and adequate proteinuria often coexisted in children suffering from nephrotic syndrome. WHAT IS KNOWN: • Anemia is a significant complication in children suffering from nephrotic syndrome. • Cause of anemia in nephrotic syndrome is multifactorial. WHAT IS NEW: • Iron deficiency anemia was the most common cause of anemia in Indian children with nephrotic syndrome. • Anemia and need for anti-hypertensives to attain adequate BP control and proteinuria often coexisted in children with nephrotic syndrome.

A wound inducible chalcone synthase gene from Dysoxylum gotadhora (DbCHS) regulates flavonoid biosynthesis.

Chalcone synthase (CHS) is a type III polyketide synthase and a key enzyme of the phenylpropanoid pathway that generates precursors for flavonoid biosynthesis. The tree species D. gotadhora is known for having an abundance of rohitukine, which has anti-inflammatory and immune-modulating effects. In this study, we used the leaves of D. gotadhora to clone CHS gene (DbCHS). The 1188-bp open reading frame (ORF) was part of the 1373-bp full-length DbCHS clone. Compared to other parts of the plant, DbCHS is expressed more in the leaves and fruits. This is linked to anti-microbial action against a panel of microbes in these tissues. The leaves and seeds extracts inhibit Bacillus subtilis, Streptococcus pyogenes, Bacillus cereus, and Candida albicans. When a plant is hurt, it leaves its tissues open to attack by microbes. To protect themselves, plants often make chemicals that kill microbes. We found that wounding had a big effect on the production of DbCHS. Based on these tests and the results of phylogenetic analysis and molecular docking, we believe that DbCHS is a wound-inducible enzyme that is needed to make flavonoids, which may give the plant antimicrobial properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01344-2.

Varicella vaccination in India's universal immunisation program -is it time?

We report two representative cases of complicated varicella in immunocompetent children highlighting the significant vaccine preventable varicella burden in the Indian population. A robust surveillance programme followed by incorporation of varicella vaccine in routine immunization would be the way forward to mitigate this illness.

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.

Challenges in management of atypical hemolytic uremic syndrome: Bottle neck in resource limited settings.

Treatment of atypical hemolytic uremic syndrome cases is challenging right from establishing correct and timely diagnosis to execution of management protocol. A seven-year-old male child from poor socioeconomic status was admitted with chief complaints of fever, 3 episodes of vomiting and passage of cola coloured urine. Based on clinical and laboratory findings, diagnosis was established. However, ADAMTS13 levels and genetic studies required for diagnosis could not be performed due to financial constraints and non-availability of these tests. TPE kits were arranged from charitable organizations. Six TPE procedures were performed using Cobe Spectra cell separator. Central venous catheter was placed in femoral vein. TPE kit was primed with compatible packed red blood cells before each procedure. Patient was non-cooperative and irritable in first three procedures and was sedated. A total of 1300ml plasma was exchanged in each procedure with group specific fresh frozen plasma. After second TPE procedure, patient started improving with decrease in plasma discoloration and periorbital edema. Renal function tests along with hematological parameters became normal after 6th TPE procedure. Patient was discharged in a stable condition. On follow up, C3 levels were normal with adequate platelet count and normal renal functions suggesting complete remission.

Indian Academy of Pediatrics Guidelines on Screen Time and Digital Wellness in Infants, Children and Adolescents.

JUSTIFICATION: Screen-based media have become an important part of human lifestyle. In view of their easy availability and increasing use in Indian children, and their excessive use being linked to physical, developmental and emotional problems, there is a need to develop guidelines related to ensure digital wellness and regulate screen time in infants, children, and adolescents. OBJECTIVES: To review the evidence related to effects of screen-based media and excessive screen time on children's health; and to formulate recommendations for limiting screen time and ensuring digital wellness in Indian infants, children and adolescents. PROCESS: An Expert Committee constituted by the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines. A detailed review document was circulated to the members, and the National consultative meet was held online on 26th March 2021 for a day-long deliberation on framing the guidelines. The consensus review and recommendations formulated by the Group were circulated to the participants and the guidelines were finalized. CONCLUSIONS: Very early exposure to screen-based media and excessive screen time (>1-2h/d) seems to be widely prevalent in Indian children. The Group recommends that children below 2 years age should not be exposed to any type of screen, whereas exposure should be limited to a maximum of one hour of supervised screen time per day for children 24-59 months age, and less than two hours per day for children 5-10 years age. Screen time must not replace other activities such as outdoor physical activities, sleep, family and peer interaction, studies and skill development, which are necessary for overall health and development of the children and adolescents. Families should ensure a warm, nurturing, supportive, fun filled and secure environment at home, and monitor their children's screen use to ensure that the content being watched is educational, age-appropriate and non-violent. Families, schools and pediatricians should be educated regarding the importance of recording screen exposure and digital wellness as a part of routine child health assessment, and detect any signs of cyberbullying or media addiction; and tackle it timely with expert consultation if needed.

Spectrum of Multiorgan Dysfunction in Scrub Typhus Infection.

OBJECTIVES: We planned this study to determine the clinical spectrum and compare incidence of multiorgan dysfunction in children hospitalized with scrub typhus with other etiologies of tropical fever. DESIGN: Prospective cohort study. SETTING: Pediatric emergency and PICU services of a university teaching hospital situated in the sub-Himalayan region. PATIENT: Children aged 2 months to 14 years with acute undifferentiated fever of more than 5 days. INTERVENTIONS: Detailed fever workup was performed in all children. We compared scrub typhus IgM positive children (cases) with remaining febrile children who were negative for scrub IgM assay (controls) for mortality and morbidity. MAIN RESULTS: We enrolled 224 febrile children; 76 children (34%) were positive for scrub typhus IgM ELISA. Scrub typhus group had a significantly higher incidence of multiorgan dysfunction [OR 3.5 (95% CI 2.0-6.3); p < 0.001] as compared to non-scrub typhus group requiring supportive care. The incidence of altered sensorium [OR 8.8 (95% CI 3.1-24.9)], seizures [OR 3.0 (95% CI 1.1-8.3)], acute respiratory distress syndrome [OR 17.1 (95% CI 2.1-140.1)], acute renal failure (5% vs. 0%), meningitis [OR 6.2 (95% CI 1.2-31.6)], thrombocytopenia [OR 2.8 (95% CI 1.5-5.1)], transaminitis [OR 2.7 (95% CI 1.6-4.8)], requirement of oxygen [OR 17.8 (95% CI 4.0-80.3)], positive pressure support [OR 3.7 (95% CI 1.2-10.5)] and shock requiring inotropes [OR 3.0 (95% CI 1.3-6.7)] was significantly higher in scrub typhus group as compared to the non-scrub typhus group (Table 1). CONCLUSIONS: Pediatric scrub typhus who were hospitalized had severe systemic manifestations when compared to other causes of fever.

Recurrent Intracranial Bleed in 3 Siblings: Short of a Shot of Vitamin K!

We present a family who suffered recurrent sibling losses due to vitamin K deficiency bleed. The index child was asymptomatic at presentation, had normal clinical examination, and was investigated for coagulation disorders in view of previous 3 sibling losses as a result of intracranial hemorrhage. His investigations showed deranged coagulogram and clotting factors' assay. The baby was given vitamin K1 1 mg intramuscularly following which his coagulogram and clotting factors' assay returned to normal. The genetic analysis did not identify any inherited cause of bleeding tendency. The significant family history, exclusive breastfeeding, no diarrhea, failure to thrive or drug use, no prophylaxis with vitamin K at birth, recovery of clotting factors on vitamin K administration, and a corroborative molecular analysis confirmed diagnosis of vitamin K deficiency in the index child. This case gives a strong reminder not to miss birth dose of vitamin K in any neonate.

Effect of fetal growth restriction on urinary podocalyxin levels at birth in preterm neonates.

BACKGROUND: Small-for-gestational-age (SGA) neonates are at a higher risk of adult-onset metabolic disorders because of fetal programming in the presence of growth restriction. Nephrogenesis may also be affected in fetal growth restriction. This study hypothesized that urinary podocalyxin levels, a marker of nephrogenesis, would be lower among preterm SGA neonates as compared to appropriate-for-gestational-age (AGA) controls. METHODS: This cross-sectional study enrolled gestation-matched SGA (n = 90) and AGA (n = 45) neonates born at 260-366 weeks of gestation. The SGA group comprised of 45 neonates with birth weight between 3rd and 10th centile and 45 neonates with birth weight <3rd centile. The primary outcome of the study was the difference in urinary podocalyxin levels between SGA and AGA neonates. Glomerular and tubular functions were also assessed. RESULTS: Urinary podocalyxin levels were similar in SGA and AGA neonates (ng/mg of creatinine; median [interquartile range]: 28.7 [4.8-70.2] vs. 18.7 [3.1-55.9]), P value 0.14). No correlation was observed between birth weight centile and urinary podocalyxin levels (r: -0.06). Glomerular filtration rate, fractional excretion of sodium, and serum ß-2-microglobulin levels were comparable across the study groups. CONCLUSIONS: Glomerular development as assessed by urinary podocalyxin levels and renal functions are comparable in SGA and AGA preterm neonates. IMPACT: Neonates born with fetal growth restriction are at a higher risk of adult-onset metabolic disorders because of fetal programming. This cross-sectional study investigated the effect of presence and severity of fetal growth restriction on glomerular development by measuring urinary podocalyxin levels in preterm infants. This study did not observe any effect of the presence or severity of fetal growth restriction on urinary podocalyxin levels and other markers of glomerular and renal tubular functions.

Changing Clinicoradiologic Spectrum of Intracranial Neurotuberculosis in Children: A Cross-sectional Study.

BACKGROUND: Neurotuberculosis is among the most severe type of tuberculosis with high mortality and morbidity in all age groups. Various sociodemographic and disease-/treatment-related factors have emerged over the years that can affect clinical and radiologic features of neurotuberculosis. OBJECTIVE: To investigate various clinical and neuroradiologic presentations of neurotuberculosis. METHODOLOGY: This cross-sectional study was done in a tertiary care center of northern India. The patients between the ages of 3 months and 18 years with newly diagnosed neurotuberculosis were enrolled after taking informed consent. RESULTS: A total of 78 patients (37% males) were enrolled. Fifty-six patients (72%) had tubercular meningitis (TBM) and 22 (28%) isolated tuberculomas. Very high percentage of patients in both the groups was BCG vaccinated. In the tubercular meningitis group, fever (68%), headache (59%), and vomiting (54%) were the most common complaints whereas in the tuberculoma group, seizures (95.5%) were the main complaint and systemic symptoms were rare. In tubercular meningitis patients, cerebrospinal fluid-based studies showed cartridge-based nucleic acid amplification test (Xpert MTB/RIF) positivity for Mycobacterium tuberculosis in 17.6% cases, whereas on gastric aspirate and sputum examination, acid-fast bacilli were seen in 30.7% and cartridge-based nucleic acid amplification test was positive in 19% patients. On neuroimaging, hydrocephalus was seen in 44.6% of tubercular meningitis patients, infarcts in 32%, and basal exudates in 12% patients only; coexistent tuberculomas were seen in 53%. CONCLUSION: Compared with the available literature, the present study showed a smaller percentage of children <5 years of age, stage III tubercular meningitis cases, and typical neuroradiologic findings like hydrocephalus and basal exudates and more tuberculomas associated with tubercular meningitis.

Using Telemedicine During the COVID-19 Pandemic.

Telemedicine is the delivery of health care services using information or communication technology. In the current pandemic scenario, telemedicine can supplement health-care delivery in the absence of in-person visit. The Government of India has recently launched the e-sanjeevani OPD, a National teleconsultation service, which has been adopted by many state governments as mandatory for health-care providers. With Indian Medical Association issuing an advisory against the use of telemedicine except in few situations, a lot of confusion exists in the mind of a pediatrician. Despite the uncertain situation, we have to remember that other diseases shall not stall in the face of a pandemic. Since telemedicine is an evolving subject, training of medical professionals, clear guidelines and good quality internet service systems will go a long way in increasing the acceptability of telemedicine in the Indian population. We herein discuss issues related to using telemedicine during the SARS-CoV-2 pandemic.

Clinicoepidemiological and Genotyping Correlation of Pediatric Scrub Typhus from Chandigarh, India.

OBJECTIVE: We studied the clinical phenotypes and prevalent genotypes of Orientia tsutsugamushi in our area using indirect immunofluorescence assay (IFA). METHODS: We prospectively screened all febrile children presenting to our hospital over three years. From among children who were scrub typhus positive by ELISA we selected a sample of convenience for IFA testing to determine the genotypes of O. tsutsugamushi using four strains namely Boryong, Gilliam, Karp and Kato. RESULTS: Of all scrub positive patients (n=77), we tested 14 samples using IFA and all 14 samples were IFA positive. Karp genotype (n=7) was most prevalent followed by Kato (3), Boryong (1) and Gilliam (1) genotypes; 2 patients were positive for mixed genotype. There was high prevalence of organ dysfunction among IFA positive children. Three most common organ dysfunctions included hematological derangement in all, liver involvement in 10 (71%), and encephalopathy and shock in 4 each. CONCLUSIONS: Karp was the most prevalent genotype of O. tsutsugamushi in our area.