Addition of Questions on Parental Factors to the WHO (Integrated Management of Childhood Illnesses) IMCI-HIV Algorithm Improves the Utility of the Algorithm for Diagnosis of HIV Infection in Children.

The WHO Integrated Management of Childhood Illnesses-HIV (IMCI-HIV) algorithm and its regional adaptation have shown variable performance in clinically identifying HIV-infected children with lack of validation in low prevalence areas. Addition of certain 'parental factors' (proxy indicators of parental HIV) may improve its utility. In this study, children aged 2 months to 5 years were enrolled into Group A (n = 1000, 'suspected symptomatic HIV infected' children as per the IMNCI-HIV algorithm) and group B (n = 50, children newly diagnosed with HIV infection). Parental factors were asked and HIV infection was tested for in Group A. For Group B, retrospective data were collected regarding IMNCI-HIV algorithm signs and parental factors. Utility of individual and various combinations of IMNCI-HIV signs and parental factors to predict HIV status was evaluated. Results showed that incorporating parental factors to IMNCI-HIV algorithm improved its sensitivity and positive predictive value in identifying HIV-infected children while maintaining the same sensitivity.

Addition of pyridoxine to prednisolone in the treatment of infantile spasms: A pilot, randomized controlled trial.

BACKGROUND: West syndrome is a catastrophic epilepsy syndrome characterized by infantile spasms, hypsarrhythmia, and developmental arrest or regression. AIM: The aim of this study was to explore the role of pyridoxine in the management of infantile spasms. SETTING AND DESIGN: This was a pilot, randomized, open-label trial conducted at a tertiary level hospital from November 2012 to March 2014. MATERIALS AND METHODS: Children aged 3 months to 3 years presenting with infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its variants on electroencephalogram (EEG) were enrolled. The study participants were randomized to receive either oral prednisolone (4 mg/kg/day) alone or 30 mg/kg/day of pyridoxine with oral prednisolone. The primary outcome measure was the proportion of children who achieved spasm freedom for 48 h on day-14 after treatment initiation, as per parental reports, in both the groups. The adverse effects were also monitored. The study was registered with clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT01828437). RESULTS: Sixty-two children were randomized into the two groups with comparable baseline characteristics. The proportion of children with spasm cessation on day-14 was similar in the two groups (39 vs. 37%, P = 0.98). The adverse effects were comparable in both the groups. CONCLUSIONS: The combination of pyridoxine with oral prednisolone was not found to be a beneficial therapy as compared to prednisolone alone in the treatment of infantile spasms in this pilot study. However, high dose pyridoxine may be safe in children with infantile spasms.

Development assessment of HIV exposed children aged 6-18 months: a cohort study from North India.

HIV exposed children are vulnerable to developmental delay irrespective of their HIV status due to combined effect of risk factors like poverty, prenatal drug exposure, stress and chronic illness in family and malnutrition. This cohort study assessed the development of 50 HIV exposed children aged 6-18 months at a Pediatric Centre of Excellence in HIV care in India. The development was assessed using Development Assessment Scale for Indian Infants (DASII) at enrolment, 3 and 6 months later. The development quotient (DQ) scores and proportion of children with developmental delay (DQ ≤ 70) were compared among two sub-groups, HIV infected (HI) and HIV exposed uninfected (HEU) children. The various social and clinical factors affecting development were studied by univariate and multivariate analysis. Prevalence of developmental delay was 2.4% in the HEU (n = 41), and 33.3% in HI (n = 9). The DQ of HI was significantly lower than that of HEU at all three assessments. The DQ of HI were also significantly lower compared to the HEU at ages 12.1-18 months (83.37 ± 20.73 vs 94.68 ± 5.13, p = 0.005) and 18.1-24 months (84.55 ± 15.35 vs 94.63 ± 5.86, p = 0.006) respectively. The development of HEU was adversely affected by lower socioeconomic status and presence of wasting. In addition, development of HI was also adversely influenced by presence of stunting and opportunistic infections, advanced disease stage and shorter ART duration. We conclude that with optimum care, HEU can have a normal development, while a considerable proportion of HI may continue to have delayed development.

Seroprevalence of transplacentally acquired measles antibodies in HIV-exposed versus HIV-unexposed infants at six months of age.

BACKGROUND & OBJECTIVES: Measles infection is reported to be more severe, prolonged and associated with a higher complication rate in children with HIV infection. Reports indicate that infants born to HIV-infected women [HIV exposed infants (HEI)] may be more vulnerable to measles. The World Health Organization recommends measles vaccination starting at six months of age in these infants who may be HIV-infected themselves. However, in India, they are given measles vaccination at nine months of age like all other infants. In this study, the seroprevalence of transplacentally acquired measles antibodies was compared in HEI and unexposed infants (HUnI) at six months of age and the proportion of HEI undergoing seroconversion after immunization with measles vaccine was assessed. METHODS: In this prospective longitudinal study, measles IgG antibodies were estimated in serum of 49 HEI and 50 HUnI aged 6-7 months. Measles vaccine was then administered to HEI. Assessment for measles IgG antibodies was repeated 8-12 wk post-immunization. RESULTS: Measles IgG antibodies were detected in two of 49 (4.1%) HEI and 16 of 50 (32%) HUnI. HEI were 11 times more likely to lack measles antibodies as compared to HUnI (odds ratio=11.05, 95% confidence interval=2.989-40.908). Post-vaccination, seroprevalence of measles antibodies increased to 38.5 per cent (PInterpretation & conclusions: Most HEI lacked measles antibodies at six months age and were, therefore, more vulnerable to measles than HUnI. Seroconversion in response to a single dose of measles vaccine administered at six months age was low in these infants, signifying the need of additional dose(s) of measles/measles-containing vaccine.

Coexistence of celiac disease & type 1 diabetes mellitus in children.

BACKGROUND & OBJECTIVES: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) tend to co-exist due to similar underlying genetic predisposition. Failure to recognize CD in patients with T1DM predisposes them to complications. The present study was aimed to assess children with T1DM for the presence of CD. METHODS: This was a retrospective analysis of the records of children with T1DM attending paediatric endocrinology clinic at a tertiary care hospital in north India from January 2006 to May 2014. All children were screened for CD at the time of diagnosis of T1DM using IgA anti-tissue transglutaminase (anti-tTG) levels in serum. Seropositive children were subjected to upper gastrointestinal endoscopy and duodenal biopsy for histopathological confirmation. The children also underwent thyroid function testing (TFT); those with deranged TFT were evaluated for thyroid-specific antibodies. RESULTS: Positive serology for CD was present in 43 of 126 children with T1DM whose records were reviewed [34.1%; 95% confidence interval (CI): 25.9-43.1]. Confirmed CD was diagnosed in 17 (13.5%; CI: 8.1-20.7) of the children screened and 17 of 40 (42.5%; CI: 27.1-59.1) seropositive participants. Four out of 17 children with coexisting CD and T1DM also had autoimmune thyroiditis with overt hypothyroidism. The children with confirmed CD were more likely to have short stature [odds ratios (OR)-3.16; 95% CI: 1.09-9.20, P<0.05] and hypothyroidism (OR-6.4; 95% CI: 1.52-26.90, P<0.05). INTERPRETATION & CONCLUSIONS: Our study showed a higher proportion of CD in children with T1DM as compared to that reported in general population. Regular screening of children with T1DM for CD is needed to improve metabolic control and prevent long-term complications.

Acute Intermittent Porphyria in children: A case report and review of the literature.

Acute Intermittent Porphyria (AIP), an autosomal dominant inborn error of heme metabolism, typically presents in adulthood, most often in women in the reproductive age group. There are limited reports on the clinical presentation in children, and in contrast to the adults, most of the reported pediatric cases are male. While acute abdominal pain is the most common presenting symptom in children, seizures are commonly seen and may precede the diagnosis of AIP. As an example, we report a 9year old developmentally normal pre-pubertal boy who presented with acute abdominal pain, vomiting and constipation followed by hyponatremia, seizures, weakness and neuropathy. After a diagnostic odyssey, his urine porphobilinogen was found to be significantly elevated and genetic testing showed a previously unreported consensus splice-site mutation IVS4-1G>A in the HMBS gene confirming the diagnosis of AIP. Here, we discuss the clinical presentation in this case, and 15 reported pediatric cases since the last review 30years ago and discuss the differential diagnosis and challenges in making the diagnosis in children. We review the childhood-onset cases reported in the Longitudinal Study of the Porphyrias Consortium. Of these, genetically and biochemically confirmed patients, 11 of 204 (5%) reported onset of attacks in childhood. Most of these patients (91%) reported recurrent attacks following the initial presentation. Thus, AIP should be considered in the differential diagnosis of children presenting with unexplained abdominal pain, seizures, weakness and neuropathy.

Adherence to antiretroviral therapy and its determinants in children with HIV infection - Experience from Paediatric Centre of Excellence in HIV Care in North India.

The objective of this study is to assess adherence to antiretroviral therapy (ART) in HIV-infected children using the pill count method, and determine factors leading to adherence failure. Records of 106 children living with HIV (CLHIV) age <15 years and on ART for >6 months were reviewed. Average adherence to ART by pill count method over preceding six months was calculated and re-assessed by 3-day recall method. The caregivers of 105 children and one child himself were interviewed about the problems encountered while giving ART. Median age of enrolled children was 104 (inter-quartile range [IQR] 77.3-133.8) months. Median duration of ART was 25 (IQR 16-35) months. The desired adherence level of >95% during six months of review assessed by pill count was achieved in 95.3% children. The 3-day recall method yielded >95% adherence in 99% children (p ≤ .001). Caregivers of 59 children (56.2%) reported multiple problems while administering drugs. In most instances, problems encountered were related to family/caregivers, the commonest being multiple caregivers, job constraints and death/illness in the family. In conclusion, we found a very high level of adherence to ART in CLHIV. Poor adherence was mainly associated with issues related to the family/caregivers.

A Randomized controlled trial on safety and efficacy of single intramuscular versus staggered oral dose of 600 000IU Vitamin D in treatment of nutritional rickets.

OBJECTIVE: Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. METHODS: Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. RESULTS: No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. CONCLUSION: Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets.

High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Distal ulnar changes in children with thalassemia and deferiprone related arthropathy.

BACKGROUND: Regular blood transfusion and iron chelation are the standard of care for children with thalassemia. Deferiprone is an effective oral iron chelator but is known to cause significant arthropathy. Though clinical and radiographic features of deferiprone related arthropathy have been described, the long-term effects are not known. PROCEDURE: Routine radiographs of left wrist and hand done for bone age estimation in 40 children with thalassemia were evaluated and revealed unique radiographic changes in 13 children (10 males: 3 females) with previous or current deferiprone related arthropathy. Subsequently, these children underwent radiographs of both the knee joints. RESULTS: The changes on wrist X-ray included lucency and thinning of the ulnar metaphysis, small ulnar epiphysis, deformation and impaired growth of the physeal cartilage leading to reduced distance between the epiphysis and metaphysis. The knee radiograph showed subchondral flattening of femoral and tibial condyles with irregular articular margins. CONCLUSIONS: Bony dysplasia, deformation and impaired growth of ulnar epiphyses, metaphyses and physes may be an expression of deferiprone related arthropathy in children with thalassemia major.

Report of a novel Indian case of congenital erythropoietic porphyria and overview of therapeutic options.

Congenital erythropoietic porphyria is a rare disorder of heme biosynthesis, resulting from decreased enzymatic activity of uroporphyrinogen III synthase. Clinical manifestations are heterogenous, of variable severity, and with occasional phenotypic-genotypic correlation. A 14-month-old boy developed fever, extensive dermatitis, and reddish colored urine. Anemia, erythrodontia, hepatosplenomegaly, and massive urinary elimination of predominantly type I porphyrins was suggestive of congenital erythropoietic porphyria. Although hemolysis remained mild and compensated, facial and digital mutilation developed indicative of moderate clinical phenotype. Mutational analysis revealed compound heterozygosity of mutant alleles, including a novel mutation (p.Pro190Leu). The child received supportive management and underwent facial reconstruction successfully.

A novel mutation in thyrotropin (thyroid-stimulating hormone) gene in congenital hypothyroidism.

A 3-year-old girl had global developmental delay with dysmorphic facies. In addition, she was found to have congenital hypothyroidism. In view of the associated dysmorphism, a karyotype analysis was done. It revealed a novel translocation mutation, 46XX t(1;14) (p22;q32). The association of this mutation with congenital hypothyroidism has been postulated in our case report. To the best of our knowledge, this mutation has never been described before in cases of congenital hypothyroidism.

Management of nutritional rickets in Indian children: a randomized controlled trial.

INTRODUCTION: Rickets is usually attributed to vitamin D deficiency. However, recent studies have implicated dietary calcium deficiency in its etiology. Information on relative efficacy of calcium, vitamin D or both together in healing of rickets is limited. OBJECTIVE: To study effect of treatment with calcium, vitamin D or a combination of these two on healing of nutritional rickets in young children. DESIGN: Randomized controlled trial. METHODS: Sixty-seven cases of nutritional rickets in the age group of 6 months to 5 years were randomly allocated to receive vitamin D (600 000 IU single intramuscular dose), calcium (75 mg/kg/day elemental calcium orally) or a combination of the above two for a period of 12 weeks. The demographic parameters, nutritional status, dietary calcium and phytate intake were assessed for all. Radiographs (wrist and knee) and biochemical parameters (serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxycholecalciferol and parathyroid hormone) were evaluated at baseline, 6 and 12 weeks for evidence of healing. RESULTS: Mean dietary intake of calcium in all cases was low (204 ± 129 mg/day). Mean serum 25-hydroxycholecalciferol D level was 15.9 ± 12.4 ng/ml, and 82.1% of patients had serum vitamin D levels <20 ng/ml, indicative of vitamin D deficiency. After 6 and 12 weeks of treatment, radiological and biochemical evidence of healing rickets was observed in all treatment groups, albeit to a variable extent. The combined end point of normal serum alkaline phosphatase and complete radiological healing at 12 weeks was observed in 50% subjects on combination therapy as compared with 15.7% subjects on vitamin D alone and 11.7% on calcium alone. CONCLUSIONS: Children with rickets had a low serum vitamin D level and a low dietary calcium intake. The best therapeutic response was seen with a combination of vitamin D and calcium than either of them given alone. TRIAL REGISTRATION NUMBER: CTRI/2010/091/000448.

Transition of Care of Pediatric Patients with Special Needs to Adult Care Settings: Children with Diabetes Mellitus and Other Endocrine Disorders.

Childhood onset endocrine disorders need long-term medical, psychological and social management. Over time, many illnesses evolve, while others may witness onset of new complications. Thus, the components of the care change as the child grows into adolescence and then adulthood. The transition of children and adolescents with chronic endocrine disorders to adult care continues to be a major challenge. Pediatric and adult healthcare teams should together design a transitional care plan that is developmentally appropriate and responsive to the needs of young adults. The preparation for transition to adult care should begin early in adolescence and involve both the adolescent and his parents. A structured and planned transitional care bridges the gap between pediatric and adult care teams, promote ongoing engagement and build trust with the new healthcare teams. Combined pediatric-adult care transition model for endocrine conditions has yielded high adherence rates and patient satisfaction.

Daily vs. monthly oral vitamin D3 for treatment of symptomatic vitamin D deficiency in infants: a randomized controlled trial.

OBJECTIVES: Compare the efficacy and safety of daily vs. monthly oral vitamin D3 in treating symptomatic vitamin D deficiency in infants. METHODS: 90 infants with symptomatic vitamin D deficiency were randomized into Daily (D) [46 infants] and Bolus (B) [44 infants] groups to receive oral vitamin D3, daily (2000 IU/day) and bolus (60,000 IU/month) for three months respectively. Both groups received daily oral calcium @50 mg/kg/day. Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol [25(OH)D], parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 and 12 weeks. At the end of 12 weeks, 78 infants were available for evaluation of efficacy and safety of both regimens. RESULTS: Both regimens led to a statistically significant increase in Ca and P levels and fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no inter-group difference. Infants in group D had statistically significant higher mean 25(OH)D levels as compared to group B at 4 weeks (group D 130.89 ± 43.43 nmol/L, group B - 108.25 ± 32.40 nmol/L; p - 0.012) and 12 weeks (group D - 193.69 ± 32.47 nmol/L, group B - 153.85 ± 33.60 nmol/L; p<0.001). Eight infants [group D - 6/41 (14.6 %); group B - 2/37 (5.4 %), p=0.268] developed mild asymptomatic hypercalcemia without hypercalciuria at 12 weeks that corrected spontaneously within a week. CONCLUSIONS: Both daily and monthly oral vitamin D3 in equivalent doses are efficacious and safe for treating symptomatic vitamin D deficiency in infants.

Short-Term Adverse Drug Reactions to Antiretroviral Therapy in Children with HIV: A Cohort Study.

OBJECTIVES: To carry out an active surveillance for adverse drug reactions (ADRs) in children with HIV infection newly initiated on antiretroviral therapy (ART), determine risk factors for their occurrence, and assess their influence on adherence to ART. METHODS: All children newly initiated on ART from 1st March 2014 to 30th June 2019 at a tertiary care children's hospital in New Delhi, were actively monitored for ADRs to ART for a period of 6 mo after ART initiation. The frequency, spectrum, and severity of ADRs, their influence on adherence, and risk factors for their occurrence were analyzed. RESULTS: Among the 174 enrolled children, ADRs were observed in 78 (44.8%) children during the first 6 mo after ART initiation. Total numbers of episodes of ADR observed were 108 (0.62 episodes of ADR/child). Sixty percent of events were of grade 1 severity, 19.4% events were of grade 2 and 3 each, while 1 (0.9%) event was of grade 4 severity. Adherence to ART was adversely affected in 21.8% of ADRs. Gastrointestinal symptoms (49.1%) were most frequent among all the events observed. Zidovudine, lopinavir/ritonavir, efavirenz and nevirapine based regimes were significantly associated with hematological, gastrointestinal, neurological, and dermatological ADRs, respectively. Children with immunological suppression were at a higher risk of developing ADRs as compared to those without it [RR 1.9 (95% CI (1.1-3.2)]. CONCLUSIONS: ADRs to ART are very frequent; most of them are mild and self-limiting. However, they can adversely impact adherence to ART. Anticipatory guidance, ongoing monitoring, and provision of symptomatic treatment will help tide over most ADRs and reduce their adverse impact upon ART adherence.

Hearts don't lie: Cardiac tuberculosis diagnosed on fine-needle aspiration cytology.

Cardiac involvement in tuberculosis is relatively rare when compared to other organs and often involves the pericardium leading to constrictive pericarditis. Myocardial tuberculoma is exceedingly rare and only seldom cases have yet been reported. Our report is of a case diagnosed on fine-needle aspiration cytology.

Insulin Resistance in children on Sodium Valproate - A hospital based cross-sectional study in Indian children.

Our objective was to compare the point prevalence of insulin resistance (IR) in children taking sodium valproate (VPA) and phenytoin sodium (PS) monotherapy for >1 year. 150 children, aged 6-18 years, were categorized (50 each) into - group A (VPA), group B (PS) and group C (healthy controls age-sex matched with group A). Groups were compared for metabolic complications and risk factors assessed. The point prevalence of IR and non-alcoholic fatty liver disease was significantly higher in children on VPA (12% and 34% respectively) than on PS and healthy controls, regardless of age, sex, pubertal and nutritional status. The presence of central obesity, acanthosis, hypertension, dyslipidaemia was significantly associated with IR but none showed an independent association on multivariate analysis. Therapy with VPA makes children susceptible to metabolic complications. Close monitoring will facilitate early detection and timely intervention.

Viewpoints from the National Consultation on Addressing Acute Malnutrition on Mainstreaming Community-Based Program for Management of Acute Malnutrition in India.

High burden of acute malnutrition among children less than 5 years is a major public health problem in India. A "Two-days National Consultation on Addressing Acute Malnutrition" was organized to gather experiences and evidence from 13 states of India on prevention and management of acute malnutrition among children and documenting viewpoints from experts and government counterparts on the same. The consultation centered around five key themes of addressing acute malnutrition; 1) capacity building, 2) strengthening screening, 3) nutritional care of wasting, 4) tracking progress, and 5) scale-up. The paper highlights the experiences and key recommendations around the above key themes. It emerged that there is a need to further accelerate the efforts toward strengthening existing platforms and services to address acute malnutrition among children. Regular trainings of the frontline workers, increased convergence, regular monitoring, and continued service delivery during the pandemic should be undertaken for better outcomes.

Henoch-Schönlein purpura with uveitis: an unusual case and review of literature.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with IgA dominant immune complex deposition. It is characterized by a triad of palpable purpura (without thrombocytopenia), abdominal pain and arthritis. Uveitis is rarely associated with HSP with only 3 cases reported in literature. All these cases were in adult population and were associated with nephritis. However, this association is not reported in paediatric age group. We are reporting a case of an 11-year-old child of recurrent HSP with uveitis.