Heterogeneity and Hierarchy of Immune Response to Primary Immunization in HIV-Infected Children on HAART and the Impact of an Additional Dose of Vaccine.

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose.

Clinical Spectrum and Microbial Etiology of Bone and Joint Infections in Children: A Retrospective Analysis from South India.

Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5-105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5-8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.

Clinical, Microbiological Profile and Treatment Outcomes of Infants with BCG Adenitis: A Retrospective Study.

BACKGROUND: Bacille Calmette-Guérin (BCG) adenitis is an uncommon complication following BCG vaccination. In rare cases, infants can develop other complications. Controversy exists regarding the diagnosis and management of these cases. Not much information is available in literature regarding their microbiological and immunological characteristics. METHODS: Electronic medical records of children presenting to the Pediatric Infectious Diseases clinic in a tertiary care hospital from January 2011-December 2020 with a diagnosis of BCG adenitis were retrospectively reviewed. Their clinical, microbiological, treatment and follow-up data were noted and analyzed. FINDINGS: During the study period, 40 infants presented with a probable diagnosis of BCG adenitis with or without disseminated BCG. Median age at symptom onset was 4(2.5-5.9) months. Nine infants had disseminated disease at presentation. Fifteen infants were suspected to have underlying immune deficiency of whom 12 had proven defects in immune function. On multivariable logistic regression analysis, presence of disseminated disease was the only factor predictive of underlying immunodeficiency. Isoniazid monoresistance was seen in seven cases (32%) of the 22 samples sent for TB cultures. CONCLUSIONS: Though BCG adenitis runs a benign course, it could rarely be the first manifestation of an underlying immune defect. There is sizable isoniazid monoresistance, hence sending tissue samples for microbiologic evaluation is necessary to guide anti-tubercular therapy.

Accuracy and agreement of the Tuberculin Skin Test (TST) and the QuantiFERON-TB Gold In-tube test (QFT) in the diagnosis of tuberculosis in Indian children.

PURPOSE: Accurate diagnosis of TB in children is hampered by poor specificity of symptoms in endemic countries and the paucibacillary nature of childhood TB. This study was done to compare the accuracy and agreement of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-tube test (QFT) in diagnosing tuberculosis (TB) in a predominantly BCG-vaccinated population of children. METHODS: This retrospective cohort study enrolled all children aged 1-15 years who underwent TST and QFT testing as part of screening for TB. Children were classified according to the 2014 WHO case definition of TB, and statistical analysis was done to generate data on concordance between the TST and the QFT as well as sensitivity and specificity within WHO-defined groups. RESULTS: TST and QFT concordance was 83.9% overall (kappa 0.51), 79% in those with WHO-defined TB and 89% in those without TB. TST+/QFT-discordance was commoner than QFT+/TST- discordance across groups. The sensitivity of the TST vs. the QFT was 70.8% vs. 50% for WHO-defined TB, with comparable specificity at 89% vs. 90% respectively. CONCLUSIONS: The higher sensitivity of the cheaper and simpler TST supports its use for TB diagnosis in a normally nourished population of BCG-vaccinated children.

Candida utilis: a rare cause of septicemia in children.

Candida utilis is an emerging fungal pathogen in blood. The main aim of this study was to describe the prevalence, methods of speciation and antifungal susceptibility of Candida utilis at a tertiary care centre. METHODS: This was a retrospective study carried out at a tertiary care centre in South India. Over a period of 1 year, three Candida utilis were isolated from blood culture identified by MALDI-TOF MS Version 3.2 and were confirmed by ITS sequencing. Susceptibility testing was carried out by micro broth dilution. RESULTS: All three patients had a common risk factor of prolonged ICU stay but the source of infection could not be identified. Candida utilis isolates were identified by MALDI-TOF and confirmed by ITS sequencing. They were pansusceptible to all tested antifungal drugs. Among these, two patients who were treated in hospital had good clinical outcome and response to antifungal drugs. A third patient was lost to follow up. CONCLUSION: Candida utilis was predominantly seen between 0-3 month olds. Conventional methods of speciation were unable to identify C. utilis to species level. Rapid identification was done by MALDI-TOF MS and confirmed by sequencing. Rapid identification leads to prompt treatment and favours a good clinical outcome.

Utility of QuantiFERON®-TB gold In-Tube test compared with tuberculin skin test in diagnosing tuberculosis in Indian children with malnutrition.

This prospective cohort study was conducted to compare the accuracy of QuantiFERON®-TB (QFT) Gold In-Tube test and tuberculin skin test (TST) in diagnosing tuberculosis (TB) in predominantly bacille Calmette-Guerin-vaccinated children with a high incidence of malnutrition. The sensitivity of the QFT versus the TST was 69.6% versus 52.9% for WHO-defined TB, with specificity of 86% versus 78.3%, respectively. The concordance of the TST and QFT was 79% overall (κ = 0.430), 62.5% in those with WHO-defined TB and 85.7% in those without TB. Majority of the QFT+/TST - discordance was seen in children with TB, whereas majority of the TST+/QFT - discordance was seen in those without TB. The TST was more likely to be negative in children with moderate-to-severe malnutrition (P = 0.003) compared to the QFT, which was more likely to be positive in younger children. The significantly better performance of the QFT in malnourished children and those at younger ages supports its use for TB diagnosis in these subpopulations.

Comparison of Scrub Typhus Meningitis with Acute Bacterial Meningitis and Tuberculous Meningitis.

OBJECTIVE: To compare scrub typhus meningitis with bacterial and tuberculous meningitis. METHODS: Children aged <15 years admitted with meningitis were screened and those who fit criteria for diagnosis of scrub typhus meningitis (n=48), bacterial meningitis (n=44) and tuberculous meningitis (n=31) were included for analysis. Clinical features, investigations and outcomes were compared between the three types of meningitis. RESULTS: Mean age, duration of fever at presentation, presence of headache and, altered sensorium and presence of hepatomegaly/splenomegaly were statistically significantly different between the groups. Scrub typhus had statistically significant thrombocytopenia, shorter hospital stay and a better neurological and mortality outcome. CONCLUSION: Sub-acute presentation of meningitis in older age group children, and good outcome is associated with scrub typhus when compared to bacterial and tuberculous meningitis.

Spectrum of Pediatric Tuberculosis in a Tertiary Care Setting in South India.

BACKGROUND: Pediatric tuberculosis (TB) is often underdiagnosed with poor estimate of its true burden. Availability of Xpert MTB/RIF assay enhances diagnostic capacity of pediatric TB. METHODS: A 3-year retrospective review of hospital records was done for all children diagnosed with confirmed and unconfirmed TB. Comparison was made between intrathoracic, single-site extrathoracic and disseminated TB. RESULTS: In total, 274 children had TB with 130 (47.4%) having confirmed TB. Pulmonary (23.4%), lymph node (23%) and central nervous system (12.8%) TB were the three commonest forms. HIV TB coinfection was 2.9%. Mycobacterial culture was positive in 90 (32.8%) and XPert MTB/RIF in 85 patients (31%). Mycobacterial confirmation was obtained in 45 (56.3%) intrathoracic TB, 69 (45.4%) extrathoracic TB and 16 (38.1%) disseminated TB. Correlation between positive Xpert and mycobacterial culture was poor (kappa 0.38). Rifampicin resistance was present in 25 (19.2%) of the 130 microbiologically confirmed TB. CONCLUSION: Extrathoracic TB is common in children. Mycobacterial confirmation in pediatric TB is improved with use of Xpert.

Successful Treatment of Cutaneous Leishmaniasis with Topical Paramomycin in a Child After Treatment Failure with Systemic Fluconazole.

It is challenging to find safe, nonscarring and noninvasive treatment of facial cutaneous leishmaniasis (CL) in children. Herein, we report a child with CL from a region endemic for Leishmania tropica, whose lesion persisted after treatment with oral fluconazole but responded to topical paromomycin. Paromomycin should be considered early for treatment of Old World CL and is a well-tolerated and effective mode of therapy for facial lesions.

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.