Optimum dose of oral folic acid supplementation in transfusion-dependent thalassemia: a randomized controlled trial.

AIM AND OBJECTIVES: We compared the effect of different doses of oral folic acid (FA) supplementation (5 mg/day vs. 2.5 mg/day vs. 5 mg/week) on the proportion of children with folate excess (serum folate >20 ng/ml) and plasma homocysteine (Hcys) excess (>15 µmol/l) in transfusion-dependent thalassemia (TDT). MATERIALS AND METHODS: Children with TDT aged 5-18 years received oral FA in doses of 5 mg/day (Group 1), 2.5 mg/day (Group 2) and 5 mg/week (Group 3) for 9 months, after a wash-off period of 8 weeks. Folate levels (Serum and RBC) and plasma Hcys levels were measured after the therapy. RESULTS: Ninety children were randomized to receive one of the three interventions (30 per group). After wash-off period, the median serum folate levels were significantly lower and five children developed folate deficiency; the median [interquartile range (IQR)] serum folate levels (ng/dl) were comparable in the three groups [Group 1: 6.5 (3.3-14.2), Group 2: 5.1 (2.6-10.5) and Group 3: 4.8 (3.4-10.0)]. After 9 months of intervention, the median (IQR) serum folate levels (ng/ml) were comparable in all participants [Group 1: 18.0 (6.5-28), Group 2: 13.5 (6.4-24.5) and Group 3: 9.7 (5.3-22.5); p = 0.11]. Proportion of children with serum folate excess was 40%, 26.7% and 26.7% in Group 1, Group 2 and Group 3 (p = 0.48). Proportion of children with RBC folate excess was 92%, 86.7% and 86.7% in Group 1, Group 2 and Group 3 (p = 0.79). Hyperhomocysteinemia was seen in eight children with no significant difference between median Hcys levels in the groups (p = 0.75). CONCLUSION: Folic acid supplementation is recommended in TDT with 5 mg weekly dose being adequate.

Twice Weekly Vs. Thrice Weekly Low-Dose Prophylactic Factor VIII Therapy in Children with Hemophilia A: An Open Label Randomized Trial.

INTRODUCTION: Low dose factor VIII prophylactic therapy in hemophilia has not been well established till date. This randomized controlled trial compared the efficacy of twice vs. thrice weekly schedule of low dose prophylactic factor VIII in children with hemophilia A as evaluated by the bleeding rate and clinico-radiological evaluation. METHODS: Thirty-three children with severe hemophilia A (≤18 years) were randomized into two groups. Baseline evaluation included detailed history, clinical (HJHS 2.1 score and FISH score) and radiological examination (Pettersson score and ultrasound score). Group 1 received twice weekly factor VIII prophylaxis while group 2 received thrice weekly factor VIII prophylaxis, the dose being 10 U/kg in both groups. All participants were followed up over next 6 months to one year. Data regarding acute bleeding episodes and repeat clinico-radiological assessment at the end of follow up were recorded. RESULTS: We analyzed 14 children in twice weekly prophylaxis group and 16 children in thrice weekly prophylaxis group. Statistically insignificant difference was found between the bleeding rates in both the groups after prophylaxis with the median values of monthly bleeding rate being 0.17 and p-value of 0.79. The differences between the initial and final clinical and radiological scores within each group were found to be statistically significant. There was no significant difference in the clinical and radiological scores in between the groups. CONCLUSION: Twice weekly FVIII therapy is effective, easily administered prophylactic schedule to prevent long-term complications of hemophilia A. Lay summaryHemophilia A is one of the most common congenital coagulation factor deficiencies. Low dose factor VIII prophylaxis is recommended for hemophilia in resource-poor settings to reduce the bleeding episodes and improve the quality of life, although the optimal schedule for the same has not been well established. A randomized controlled trial on 33 children with hemophilia A (≤18 years) was done to compare the efficacy of twice versus thrice weekly schedule of prophylactic factor VIII. Group 1 received twice weekly factor VIII prophylaxis while group 2 received thrice weekly factor VIII prophylaxis, the dose in both groups being 10 U/kg. They were evaluated by the bleeding rate and clinical (HJHS 2.1 score and FISH score) and radiological scores (Pettersson score and ultrasound score). All participants were followed up over next 6 months to one year. Data regarding acute bleeding episodes and repeat clinico-radiological assessment at end of follow up were recorded. When analyzed, statistically insignificant difference was found between the bleeding rates after the two prophylaxis regimes. There was a significant improvement between initial and final clinical and radiological scores in both the groups and no difference was recorded in between the groups. To conclude, twice weekly FVIII therapy is effective, easily administered prophylactic schedule to prevent long-term complications of hemophilia A.

Low dose depot oral vitamin D3v. daily oral vitamin D3 for treating nutritional rickets: a randomised clinical trial.

We aimed to compare the efficacy of daily v. low dose depot oral vitamin D3 for treating nutritional rickets. We conducted a randomised controlled trial in the department of paediatrics of a tertiary care hospital catering to semi-urban and rural population in Delhi, India. We randomised sixty-six children aged 3 months to 5 years with nutritional rickets to receive either daily oral vitamin D3 drops (3-12 months: 2000 IU; > 12 months to 5 years: 4000 IU; n 33) for 12 weeks duration or a single oral depot dose of vitamin D3 granules (3-12 months: 60 000 IU; > 12 months to 5 years: 150 000 IU; n 33). Participants in both groups had comparable demographic characteristics, laboratory features and radiological severity of rickets. Thirty-three participants in each group received the assigned intervention and all were followed up till 12 weeks. At 12 weeks follow-up, children in both groups showed a significant improvement in all biochemical parameters (serum Ca, P, alkaline phosphatase (ALP), parathormone and 25(OH) vitamin D levels) as well as radiological healing. At 12 weeks, the mean serum 25(OH) vitamin D levels (nmol/l) were statistically comparable in both groups (daily: 120·2 (sd 83·2), depot: 108 (sd 74), P = 0·43) and 31 (93·9 %) children in each group had radiological healing (Thacher score < 1·5). Two children in each group persisted to have raised ALP, and one child each in the daily group continued to have hypocalcaemia and hypophosphataemia at 12 weeks. Low dose oral depot vitamin D3 is an effective alternative to daily oral vitamin D3 for nutritional rickets.

Can lung ultrasound differentiate between bacterial and viral pneumonia in children?

PURPOSE: This study evaluates whether LUS can differentiate between bacterial and viral pneumonia in children and thus affect their management. METHODS: The prospective, cross-sectional, analytical study included 200 children under 12 years of age (excluding neonates) with clinical suspicion of pneumonia who had undergone a chest radiograph (CR). The CR and LUS findings were classified as bacterial or viral pneumonia. The final diagnosis was made on the basis of a combination of clinical profile, available routine laboratory investigations and CR diagnosis which was taken as the gold standard for the study and LUS was compared with the gold standard. RESULTS: LUS has a high sensitivity (91%; 95% CI [84-96]) and specificity (91.3%; 95% CI [84-96]) in diagnosing bacterial pneumonia with a high positive predictive value (91.9%; 95% CI [85-96]) and negative predictive value (90.3%; 95% CI [82-95]). For diagnosing viral pneumonia, the sensitivity of LUS was 78.4%; (95% CI [68-86]), specificity was high (90.4%; 95% CI [83-95]) and so was the positive predictive value (87.3%; 95% CI [78-94]) and negative predictive value (91.3%; 95% CI [84-96]). CONCLUSION: LUS has a high accuracy in differentiating between bacterial and viral pneumonia in children and can help in their management by avoiding an ill-advised use of antibiotic therapy.

Procalcitonin Clearance, CD64, and HLA-DR as Predictors of Outcome in Febrile Neutropenic Children With Lymphoreticular Malignancies.

BACKGROUND: Febrile neutropenia (FN) is a dreaded complication of cancer chemotherapy. There has been a lot of improvement in supportive care in FN that has drastically reduced the infection-related mortality in these patients. The focus now is on reducing infection-related morbidity, healthcare costs and optimizing the quality of life of the child as well as their family during these episodes. In this study, biomarkers were studied as predictors of outcome so that outcome can be predicted earlier, and treatment modified accordingly. OBJECTIVE: To measure procalcitonin levels (at baseline and day 3), procalcitonin clearance, neutrophil CD64 expression levels (at baseline) and monocyte HLA-DR expression levels (at baseline), and their correlation with outcome. SETTING: Tertiary care hospital. STUDY TYPE: Cross-sectional observational study. POPULATION/PARTICIPANTS: Sixty-five episodes of FN in children below 12 years with lymphoreticular malignancies. Children receiving antibacterial and/or antifungal treatment within the last 7 days were excluded from the study. METHODS: The subjects recruited into the study had undergone complete clinical and laboratory evaluation as per hospital protocol. Procalcitonin (day 0 and 3), neutrophil CD64 expression, and monocytic HLA-DR expression levels were measured in these patients. RESULTS: Sixty-five episodes of FN were studied in children with lymphoreticular malignancy. It was found that procalcitonin and HLA-DR are very good markers of outcome, whereas CD64 although a good marker, was inferior to procalcitonin and HLA-DR in predicting outcome. Procalcitonin clearance was found to be superior to single value of procalcitonin. Furthermore, procalcitonin on day 3 was found to be a better predictor of outcome compared with its baseline value. Also, it was found that procalcitonin and HLA-DR had a significant correlation with baseline C-reactive protein levels. CONCLUSIONS: On the basis of the findings of the study we suggest that serial monitoring of procalcitonin levels be used in febrile neutropenic children with cancer. Procalcitonin levels on day 3 alone can be offered in resource poor setting. The role of HLA-DR and CD64 also seems promising and needs to be further explored in larger multicentric studies.

Early lactate measurements for predicting in-hospital mortality in paediatric sepsis.

AIM: We compared the performance of plasma lactate with high-sensitivity C-reactive protein (hs-CRP), and paediatric sepsis-related organ failure assessment (pSOFA) score for predicting mortality in septic children. METHODS: Serial plasma lactate and hs-CRP levels and pSOFA score was assessed during early hospital stay in septic children. RESULTS: Out of 149 participants, 45 died. Plasma lactate at 0 h and 6 h was significantly higher, and lactate clearance was significantly lower in non-survivors. The optimal cut-off of plasma lactate at 6h for identifying mortality was 2.5 mmol/L (sensitivity 85% and specificity 74%). pSOFA score had the best predictive ability for mortality (AUC 0.89) followed by hs-CRP at 0 h (AUC 0.86), hs-CRP at 48 h (AUC 0.83), plasma lactate levels at 6 h (AUC 0.83), and plasma lactate at 0 h (AUC 0.67). CONCLUSION: pSOFA score, hs-CRP and hyperlactemia at 6 h can identify septic children at risk of dying.

Serum and Urinary Hepcidin for Diagnosing Iron-deficiency Anemia in Under-5 Children.

Bone marrow iron estimation remains the gold standard for diagnosing iron-deficiency anemia (IDA); serum ferritin, total iron-binding capacity, and transferrin saturation are routinely used as surrogate markers of IDA. However, these tests are marred by problems like poor specificity and sensitivity. Recently, hepcidin, a protein hormone synthesized in the liver and excreted in urine, has been shown to be related to iron status. We estimated the serum and urinary hepcidin levels in healthy children 6 to 60 months of age with (n=30) and without IDA (n=30). The mean (SD) serum hepcidin levels in children with IDA were significantly lower than those in children without IDA (3.03 [1.06] vs. 4.78 [3.94] ng/mL; P=0.02). The mean (SD) urinary hepcidin levels were also significantly lower in children with IDA than those in children without IDA (2.29 [0.53] vs. 2.79 [0.75] ng/mL; P=0.004). Performance of urinary and serum hepcidin compared with serum ferritin (<12 µg/L) for diagnosing IDA in terms of area under the receiver operating characteristic curve was 0.704 (P=0.007) and 0.59 (P=0.22), respectively. Serum hepcidin is not useful for diagnosing IDA in under-5 children. In contrast, urinary hepcidin holds promise as a noninvasive diagnostic tool for IDA in under-5 children.

Glucose Homeostasis and Effect of Chelation on ß Cell Function in Children With ß-Thalassemia Major.

OBJECTIVE: To assess the prevalence of impaired glucose tolerance in ß-thalassemia major and correlate it with chelation therapy. MATERIALS AND METHODS: Sixty-seven subjects with ß-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. RESULTS: The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). CONCLUSIONS: Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.

Glucose Homeostasis Markers in Beta-Thalassemia.

BACKGROUND: Glycosylated hemoglobin (HbA1c) has been a well-recognized marker of glucose homeostasis among thalassemics. Recently some studies have proposed the role of fructosamine as a better marker as compared with HbA1c. Hence, the study was carried out to find out which marker holds promise among Indian beta-thalassemic children. METHODS: In this case-control study, 60 diagnosed cases of beta-thalassemia major and equal number of normal controls who were ≥8 years of age were enrolled. HbA1c, fructosamine, and fasting insulin levels were measured in all. Oral glucose tolerance test was done as a gold standard and the measured parameters were compared. RESULTS: HbA1c was significantly higher in cases (7.10% [±0.47%]) than in controls (5.15% [±0.19%]) (P<0.001). Thalassemics with abnormal glucose tolerance had higher HbA1c level (7.34% [±0.57%]) than those with normal glucose tolerance (7.05% [±0.43%]) (P=0.05). Insulin resistance was noticed among thalassemics with abnormal glucose tolerance as compared with their normal counterparts (P=0.04). No significant difference was found in fructosamine levels between cases (239.80 [±31.80] µmol/L) and controls (234.10 [±21.34] µmol/L) (P=0.25) or between thalassemics with abnormal glucose tolerance (243.92 [±21.94] µmol/L) and their normal counterparts (238.77 [±33.93] µmol/L) (P=0.62). CONCLUSIONS: The use of HbA1c as a diagnostic marker for diabetes in hemolytic anemias has to be done with caution as its baseline values are higher in them. Despite this finding, HbA1c continues to be a good marker for worsening glucose homeostasis in thalassemics as higher values were found in thalassemics with abnormal glucose tolerance compared with their normal counterparts. The present study did not find any relationship of fructosamine levels with impaired glucose tolerance in beta-thalassemia.

Assessment of quality of life during treatment of pediatric oncology patients.

BACKGROUND: The objective of this study was to assess health-related quality of life (HRQOL) of pediatric cancer patients and their parents in North India. MATERIALS AND METHODS: Seventy-five cancer children were assessed for HRQOL, using Lansky play performance scale and health utility index-2 (HUI-2). Fifty-seven patients were followed-up after 4 months after therapy and reassessed. Their parents were also assessed using World Health Organisation (WHO) QOL BREF. Seventy five controls were also assessed and compared. RESULTS: Lansky and HUI-2 scores of patients, as well as WHO QOL BREF of parents were significantly poor in cancer patients when compared to controls. There was significant improvement after therapy in patients with lymphomas and miscellaneous tumors. Pain and self-care were found to be maximally affected domains on HUI-2. CONCLUSIONS: Large prospective multicenter studies may be undertaken and hence that need based interventions can be planned.

Missed phenotypic drug resistance in pediatric tuberculosis: A cause of concern in a resource-limited setting.

BACKGROUND: Multi-drug resistance (MDR) in pediatric tuberculosis (TB) is a growing global threat. Unavailability of conventional or molecular drug susceptibility test (DST) in resource-limited settings often impede the determination of the extent of first line anti-tubercular drugs deployed in national programs. MATERIALS AND METHOD: Pulmonary and extra pulmonary specimens were collected from clinically suspected pediatric TB cases, who were microbiologically confirmed. Resistance to first-line anti-TB was detected by 1% proportion method. KatG315 and inhA-15 genes were amplified by PCR and detection of mutations were done by sequencing. Genotypic resistance for rifampicin was detected by Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, California). RESULTS: Fifty-one cases of pediatric tuberculosis were confirmed microbiologically. Resistance to isoniazid, streptomycin, rifampicin and ethambutol were 5 (14%), 4 (11%), 2 (5.5%) and 2 (5.5%) respectively by 1% proportion method. Genotypic Rifampicin and isoniazid resistance was found in 2 (5.5%) and 7 (14%) samples respectively. CONCLUSION: Existing genotypic methods, detect targeted mutations conferring rifampicin resistance, however isoniazid (INH) resistance often go undetected. Since the resistance to pivotal anti-TB drugs are often encoded by multiple genes which may not be targeted by widely available molecular tests, discrepancies in molecular and culture-based DST reports should be interpreted with caution.

Carotid Intima-Media Thickness and Metabolic Complications in Children with HIV on Antiretroviral Therapy: A Cross-Sectional Study.

OBJECTIVES: To evaluate carotid intima media thickness (CIMT) in children with Human immunodeficiency virus (HIV) on anti-retroviral therapy (ART) and in controls. Also, to compare body mass index (BMI), body fat percentage, skin-fold thickness (SFT), waist-to-height ratio (WHtR), lipid profile, blood pressure, lipodystrophy syndrome (LDS), non-alcoholic fatty liver disease (NAFLD) in children with HIV and in controls and to determine association between lipid profile, LDS, liver amino-transferases, NAFLD, BMI, body fat percentage, SFT, WHtR and CIMT. METHODS: This cross-sectional study was done in 7 to 12 y old children attending the ART clinic and receiving ART for ≥6 mo according to 2018 National Aids Control Organization (NACO) guidelines. Thirty age and gender matched controls were enrolled from the pediatrics OPD. Weight, height, BMI, waist circumference, skin fold thickness and blood pressure were recorded. Lipid profile, liver amino-transferases, USG abdomen and CIMT were done with prior appointment. RESULTS: The present study had 43% females and 57% males (mean age of 9.33 ± 1.65 y). All cases were on combination ART (mean treatment duration: 59.1 mo). CIMT was significantly increased in cases as compared to controls 0.481 ± 0.087 mm vs. 0.418 ± 0.072 mm (p = 0.003). However, CIMT did not correlate with any other parameter. Cases had significantly higher body fat percentage (17% vs. 13.15%), systolic blood pressure (SBP), SFT, total cholesterol (TC) and low density lipoprotein- cholesterol (LDL-C) as compared to controls. NAFLD was seen in 3 cases (1%), lipohypertrophy in 7 (23%) cases and 5 (16%) controls. CONCLUSIONS: Children with HIV on ART have significantly higher CIMT and increased metabolic abnormalities.

Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children.

OBJECTIVE: To ascertain the effect of human immunodeficiency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. METHODS: Fifty-five children living with HIV infection (30 receiving ART for ≥ 2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo-18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. RESULTS: Mean (SD) serum MPO activity at 6 mo after ART [32.1 (± 19.9) U/L] was comparable to that at disease onset [17.2 (± 23.0) U/L], although it was significantly higher compared to that in children on ART ≥ 2 y [13.3 (± 15.8) U/L] and controls [12.1 (± 11.9) U/L]. Median fluorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was significantly higher than in the controls, as well as, children receiving ART ≥ 2 y. Stimulation index was highest in the control group [442.4 (341.9-562.9)], which was comparable to that in children on ART ≥ 2 y [304.2 (153.2-664.8)], but was significantly higher than the treatment-naïve cohort [266.1 (148.2-339.4)] and children on ART for 6 mo [318.8 (154.9-395.6)]. CONCLUSION: A hyperinflammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for ≥ 2 y normalized the impaired neutrophilic phagocytic functions.

Higher baseline natural killer cell counts are associated with a lower 8-day blast count and lower day 33 minimal residual disease in children with pediatric B-acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite advancements in treatment, a significant proportion of children relapse. Recently, immunotherapy has gained momentum and is becoming popular, especially for relapsed and refractory cases. NK cells are an important part of tumor immunity and are involved in the direct killing of tumor cells. Their role in B-ALL has not been explored. Therefore, this study was conducted to correlate the number of NK cells with standard prognostic parameters in B-ALL. METHODS: 25 subjects with newly diagnosed B-ALL between 0-14 years were recruited for the study from Pediatric OPD or emergency of the hospital. Along with a complete hemogram and peripheral smear examination, immunophenotyping by flow cytometry was done at the time of diagnosis for NK cell enumeration. The number of NK cells was correlated with standard prognostic parameters using the spearman correlation coefficient. RESULTS: Baseline NK cell percentage demonstrated a significant negative correlation with Prednisone poor day 8 blast response (P value = 0.02, r value = -0.44) and positive MRD (P value = 0.01, r value = -0.49) at day 33. A negative correlation was also noticed between NK cell percentage and unfavorable cytogenetics (hypodiploidy), although it was not significant (P value = 0.06, r value = -0.38). The number of NK cells did not correlate with age, gender and WBC count. Therefore, evaluating NK cells at diagnosis may serve as a simple and useful parameter for prognostication and risk stratification. CONCLUSION: It may be assumed that a higher percentage of NK cells is associated with improved outcomes and probably a better prognosis. NK numbers may serve as an early independent parameter predicting prognosis and survival in children with B-ALL, thus helping to decide individual therapeutic regimens.

COVID-19 Antibody Response in Patients with Thalassemia.

Background The coronavirus disease 2019 (COVID-19) can severely affect people with comorbidities such as those with diabetes, hypertension, chronic lung disease, cancer, and hemoglobinopathies. Studies assessing the clinical characteristics and immune response to COVID-19 infection in patients with thalassemia are limited. Objectives The primary objective of the study was to study the clinical pattern and the immunoglobulin G (IgG) antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with transfusion-dependent thalassemia (TDT) compared to patients without thalassemia. The secondary objective wasto study the relationship of COVID-19 severity with IgG antibody titers. Setting, Design, and Participants This case-control study was conducted at a tertiary care hospital between January 2021 and August 2022. A total of 30 patients with TDT (mean age: 12.7 years, SD: 4.7) and 30 patients without thalassemia (mean age: 13.9 years, SD: 7) who tested positive for COVID-19 in the preceding six weeks were recruited. Methods Serum samples from the cases and controls were collected after 6, 12, and 24 weeks of COVID-19 infection for IgG antibody estimation using chemiluminescent immunoassay. Outcome variables The primary variable was comparative analysis of antibody levels and clinical profile of COVID-19 in cases and controls. The secondaryvariable was association of the severity of COVID-19 with the antibody titers produced. Results Symptomatic individuals among cases (n=12) were significantly lesser than controls (n=22) (p=0.009). The median IgG titers of cases and controls were comparable at six weeks (p=0.40), but the titers were significantly lower for cases at 12 weeks (p=0.011) and 24 weeks (p=0.006). There was significant fall in titers from 6 to 12 and 24 weeks in both the groups. The titers were not affected by COVID-19 severity and pre-existing comorbidities. Conclusion Patients with TDT manifest with mild or asymptomatic COVID-19 and mount a comparable IgG antibody response to COVID-19 akin to controls. However, this serological response could not sustain over three to six months advocating the need for protection through vaccination.

Seroprotection With Three Dose vs Four Dose Schedule for Hepatitis B Vaccination in Children Living With Human Immunodeficiency Virus: Follow-up Data at 36-42 Months From a Randomized Controlled Trial.

OBJECTIVE: To compare the long-term seroprotection (anti-HBs ≥10 IU/L) in children living with HIV (CLHIV) receiving a 3- or 4-dose double-strength (20 µg) recombinant Hepatitis B virus (rHBV) vaccination. METHODS: We present anti-retroviral therapy (ART) clinic based follow-up data collected from January, 2021 to August, 2022, from CLHIV who had received either 3-dose or 4-dose double-strength (20 µg) rHBV vaccination, after 36-42 months and assessed for anti-HBs titres, naïve and memory T-helper lymphocytes, CD4 counts and HIV viral load. Children found unprotected after primary immunization, were administered a single double-strength rHBV vaccine booster dose (20 µg) and seroprotection was reassessed after 4 and 12 weeks. RESULTS: Out of 50 children initially vaccinated, 45 were followed up 36-42 months after primary immunization; median (IQR) anti-HBs titres (IU/L) were 230 (80.5 - 305.7) in the 3-dose group (n=23) and 263.5 (47.1-332.9) in the 4-dose group (n=22) (P=0.33). 19 and 20 children in the 3-dose and 4-dose group, respectively, were seroprotected (P=0.24). Anti-HBs titres at 36-42 months correlated with CD4 counts at baseline, anti-HBs titres at 1 and 6 months after completion of primary immunization and percentage of memory T-helper lymphocytes. All the five children (3-dose group: 4; 4-dose group: 1) who received rHBV vaccine booster dose attained seroprotection one-month later. CONCLUSION: Three-dose double strength rHBV vaccination schedule offers comparable seroprotection to a 4-dose double strength rHBV vaccination schedule in CLHIV receiving ART.

Serological Response to COVID-19 and Its Association With Measles-Rubella (MR)-Containing Vaccines.

BACKGROUND AND OBJECTIVES:  Epidemiological studies suggest that coronavirus disease 2019 (COVID-19) has a less severe disease course and a more favorable prognosis among children. Childhood vaccines and heterologous immunity have been suggested as reasons for this. Additionally, the structural similarity between the measles, rubella, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus particles may affect immune responses. The objective of this study was to compare COVID-19 antibody titers and disease severity between measles-rubella (MR) vaccinated and unvaccinated children. Additionally, we aimed to evaluate and compare the antibody response in recipients of a single dose and two doses of the MR vaccine. METHODS:  The study was prospective and comparative and included 90 COVID-19-positive children aged nine months to 12 years. The study was registered under the clinical trials registry of India (CTRI/2021/01/030363). COVID-19 antibody titers were measured at two weeks, six weeks, and 12 weeks, along with the assessment of MR antibody titers. COVID-19 antibody titers and disease severity were compared between MR-vaccinated and MR-unvaccinated children. The comparison of COVID-19 antibody titers between recipients of a single dose and two doses of MR vaccine was also conducted. RESULTS: The results showed significantly higher median COVID-19 antibody titers at all time points during follow-up in the MR-vaccinated group (P<0.05). However, the two groups had no significant difference in the disease severity. Moreover, there was no difference in the antibody titers of MR one dose and two dose recipients. CONCLUSION: Exposure to even a single dose of MR-containing vaccine enhances the antibody response against COVID-19. However, randomized trials are necessary to further explore this subject.

Correlation of T-regulatory Cells and Iron Status in ß-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent ß-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficient evidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in ß-thalassemia major patients. Methods In this study, 20 ß-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70% cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

Chemotherapy-Induced Oxidative Stress in Pediatric Acute Lymphoblastic Leukemia.

Introduction Plasma antioxidant capacity in children receiving chemotherapy decreases due to the effect of the disease and chemotherapy. Increased oxidative stress (OS) predisposes to an increased risk for chemotherapy-related toxicity and febrile neutropenic episodes. Materials and methods We conducted this case-control study in the hematology-oncology unit of the department of pediatrics of a tertiary hospital in Delhi, India, from November 2017 to March 2019 to compare OS between children with acute lymphoblastic leukemia (ALL) and healthy controls. We estimated the trends in OS as measured by the plasma total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) levels at baseline and at the completion of induction I (four weeks), induction II (eight weeks), and induction IIA-consolidation (16 weeks) phases of chemotherapy in children with ALL. We also assessed the change in OS during different phases of initial treatment and studied the association between OS and the hematological toxicity of chemotherapy (determined by the need for blood component therapy and the number of febrile neutropenic episodes) and serum cobalamin and folate levels. Results OS was significantly higher in children with ALL at diagnosis (n=23) compared to controls (n=19). The median (interquartile range (IQR)) TAC levels (mM) were significantly lower (1.21 (1.05-1.26) versus 1.28 (1.26-1.32), P=0.006), and TBARS levels (nmol/mL) were significantly higher (312.0 (216.6-398.0) versus 58.5 (46.2-67.2), P<0.001) in children with ALL at diagnosis compared to controls. OS was highest at the end of the induction I phase (four weeks) despite the patients being in clinical and hematological remission. OS at the completion of intensive chemotherapy (16 weeks) was higher than at diagnosis. A significant correlation was found between serum folate levels and TAC levels at baseline (P=0.03). Serum cobalamin levels, the need for blood component therapy, and the number of febrile neutropenic episodes did not have any association with OS. Conclusion Children with ALL had significantly higher OS compared to controls, indicating that underlying disease affects the oxidative balance unfavorably. Chemotherapy itself increases oxidative stress.