Anand Prakash Dubey

Safety and immunogenicity of a tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine in adolescents and adults

The highest incidence of invasive meningococcal disease is in young children, with a second peak in adolescents/young adults. All five major disease-causing serogroups (A, B, C, W-135 and Y) have been described in Asia. Immunogenicity and safety of the investigational meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT, GlaxoSmithKline Biologicals) was evaluated in healthy, meningococcal conjugate vaccine-naïve adolescents in the Philippines, India and Taiwan. 1025 adolescents were randomized (3:1) to receive one dose of ACWY-TT or tetravalent ACWY polysaccharide vaccine (Mencevax™, Men-PS). Serum bactericidal activity using rabbit complement (rSBA) was measured. Local and systemic adverse reactions were recorded for 4 days. Safety data were pooled with results from a second, similarly designed study in adults for evaluation of grade 3 systemic events. The pre-specified immunogenicity criterion for non-inferiority to Men-PS was met. One month post-vaccination, ≥85.4%-97.1% had a vaccine response (post-titre ≥1:8 in initially seronegative and ≥4-fold increase in seropositive), versus 78.0%-96.6% after Men-PS, against each vaccine serogroup. Exploratory comparisons showed statistically significantly higher post-vaccination rSBA geometric mean titres against all serogroups following ACWY-TT versus Men-PS. Exploratory analysis showed no statistically significant differences between groups in grade 3 general symptoms; however, the statistical criterion for non-inferiority between pooled treatment groups in terms of the ratio of incidences of grade 3 general symptoms was not demonstrated. No SAEs were related to vaccination. ACWY-TT was immunogenic in Asian adolescents with a reactogenicity profile that was clinically acceptable and similar to that of licensed Men-PS. The results of this study indicate that ACWY-TT could be used as a third conjugate vaccine in the protection of adolescents against meningococcal disease.

Use of VSL#3 in the Treatment of Rotavirus Diarrhea in Children : Preliminary Results

We conducted a double-blind randomized placebo-controlled study to evaluate efficacy and tolerability of VSL♯3 (CD Pharma India) in the treatment of acute rotavirus diarrhea in children. The patients were randomly assigned to receive 4 days of oral treatment with VSL♯3 probiotic mixture or placebo in addition to usual care for diarrhea. Results: Out of 230 rotavirus-positive acute diarrhea children, 224 children completed the study, (113 in the drug group and 111 in the placebo group). At recruitment on Day 1, there were no significant differences between the 2 groups in terms of frequency of vomiting, mean loose stool frequency, stool consistency, and mean frequency of oral rehydration salts (ORS) and intravenous fluids administered. On Day 2, a lower mean stool frequency and improved stool consistency was noted in the drug group, which achieved statistical significance. This was also reflected in the lower volume of ORS administration in the drug group. Even on Day 3, mean loose stool frequency and frequency of ORS use and frequency of intravenous fluid use was significantly lower in the drug group. The differences in the frequency of loose stools persisted till 8 hours of Day 4. After this, as the placebo group also showed spontaneous improvement the difference between the 2 groups in terms of the overall stools frequency became comparable. However, the overall ORS requirement continued to be significantly lower in the drug group even on Day 4. The overall recovery rates were significantly better in the drug group compared with placebo. No side effects were noted with the use of the probiotic mixture. Use of probiotic mixture VSL♯3 in acute rotavirus diarrhea resulted in earlier recovery and reduced frequency of ORS administration reflecting decreased stool volume losses during diarrhea.

Immunogenicity of a single dose of tetravalent meningococcal serogroups A, C, W-135, and Y conjugate vaccine administered to 2- to 10-year-olds is noninferior to a licensed-ACWY polysaccharide vaccine with an acceptable safety profile

Background: Meningococcal disease remains an important cause of invasive bacterial infections in children less than 5 years of age. Immunogenicity and safety of the investigational ACWY vaccine conjugated with tetanus toxoid (ACWY-TT, GlaxoSmithKline Biologicals) were evaluated in 1501 healthy 2- to 10-year-old children in the Philippines, India, Lebanon, and Saudi Arabia. Methods: Children were randomized (3:1) to receive ACWY-TT or licensed tetravalent meningococcal polysaccharide vaccine (Mencevax, GlaxoSmithKline, Men-PS). Diary cards were used to collect solicited symptoms for 4 days after vaccination. Serious adverse events were reported for 6 months. Serum bactericidal activity (rSBA, rabbit complement) was measured before and 1 month after vaccination in the first 75% of subjects enrolled in each country. Results: The statistical criteria for noninferiority in terms of rSBA vaccine responses were reached. Exploratory analyses showed that postvaccination rSBA titers ≥1:8 and ≥1:128 were significantly higher after ACWY-TT than Men-PS for serogroups C, W-135, and Y, and rSBA vaccine responses and geometric mean antibody titers were significantly higher for all 4 serogroups after administration of ACWY-TT. Noninferiority in terms of incidences of grade 3 general symptoms was not demonstrated. ACWY-TT was well tolerated with grade 3 events reported in <1% of subjects per group. No serious adverse events were considered related to vaccination. Conclusion: ACWY-TT was immunogenic in children between 2 to 10 years of age with a clinically acceptable safety profile that resembled licensed Men-PS. These data support a positive benefit/risk ratio for the ACWY-TT vaccine.

Patterns of diagnosis disclosure and its correlates in HIV-Infected North Indian children.

This facility-based cross-sectional study was conducted to determine the patterns of disclosure of HIV positive serostatus among 145 Indian children aged >5 years. Only 60 (41.4%) children were aware of their HIV-positive status. Disclosure was most frequently done by parents [51/60 (85%)] at a mean age of 9.1 ± 1.4 years. The rate of inaccurate disclosure was high [64/85 (75.3%)]. No information regarding their illness was given to 21/85 (24.7%) children. The most common reason for non-disclosure was that the child is too young [79/85 (92.9%)]. The factors favoring disclosure were increasing duration since diagnosis of HIV infection [odds ratio (OR) = 1.46; 95% confidence interval (CI) 1.11-1.93], non-perinatal mode of transmission (OR = 6.14; 95% CI 2.01-15.80), ART initiation (OR = 3.05; 95% CI 1.33-7.01), school enrolment (OR = 3.52; 95% CI 1.44-7.57) and caregiver educated beyond fifth grade (OR = 2.69; 95% CI 1.21-5.96). Detailed guidelines on disclosure are required focusing on children of school-going age with perinatal infection who are not on ART and with caregivers of low educational status.

Current Trends in the Management of Beta Thalassemia

The management of Beta Thalassemia, the commonest form of hemolytic anemia in children, has changed significantly in the last few years. With the availability of better transfusion regimen, iron chelation therapy, proper management of complications and good supportive care, it is now possible for a thalassemic child to have a near normal life span with a good quality of life.

Lipodystrophy and Metabolic Complications of Highly Active Antiretroviral Therapy

ObjectiveTo assess the metabolic drug toxicities of first-line, World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens, to estimate the prevalence of body fat redistribution and to identify associated risk factors.MethodsCross-sectional observational study. During 3 month period, 52 HIV infected children (25 on HAART; 27 not on HAART) were assessed. Their sociodemographic, clinical, and immunological data was recorded. Children were examined or the signs of fat redistribution (peripheral lipoatrophy and central lipohypertrophy). Liver function tests, fasting blood sugar, lipid profile, serum amylase, serum lactate, blood pH and bicarbonate levels were done in all patients.ResultsTwenty-two patients were on stavudine and three on zidovudine based HAART. None of the patients ever received any protease inhibitor. There were no cases of clinical or immunological failure. Children on HAART had significantly lower weight for age and body mass index but the mean height for age was similar between study groups. Only two cases of peripheral lipoatrophy were observed. Hypercholesterolemia was observed in four children on HAART but none without therapy. Hypertriglyceridemia was observed in three children on HAART and seven without therapy. Four cases of asymptomatic mild hyperlactatemia were observed. No case of any hyperglycemia or liver impairment was observed.ConclusionMetabolic abnormalities and lipodystrophy are emerging complications of HAART in Indian children and needs very close follow up. Future studies with larger sample size and longitudinal model are recommended.

Consensus statement of the Indian academy of pediatrics on integrated management of severe acute malnutrition

JustificationSevere acute malnutrition (SAM) is a major public health issue. It afflicts an estimated 8.1 million under-five children in India causing nearly 0.6 million deaths. The improved understanding of pathophysiology of SAM as well as new internationally accepted growth charts and newer modalities of integrated intervention have necessitated a relook at IAP recommendations.ProcessA National Consultative Meeting on Integrated Management of Severe Acute Malnutrition was held in Mumbai on 16th and 17th October, 2010. It was attended by the invited experts in the field. Extensive discussions were held as per the program. The participants were then divided into six groups for detailed discussions. The groups deliberated on various issues pertaining to the task assigned and presented recommendations of the groups in a plenary session. The participants made a list of recommendations after extensive discussions. A Writing Committee was formed and was entrusted with the task of drawing a Consensus Statement on the basis of these Recommendations. After multiple deliberations, the following Consensus Statement was adopted.ObjectivesTo critically evaluate the current global evidence to formulate a consensus among stakeholders regarding diagnosis and management of SAM.RecommendationsAn integrated management of malnutrition is likely to yield more dividends. Thus, management of SAM should constitute an important component of Integrated Management of Neonatal and Childhood Illnesses (IMNCI) program. Determination of SAM on the basis of Z-scores using WHO Growth charts is considered statistically more appropriate than cut-offs based on percentage weight deficit of the median. Considering the fact that many children with SAM can be successfully managed on outpatient basis and even in the community, it is no more considered necessary to advise admission of all children with SAM to a healthcare facility. Management of SAM should not be a stand-alone program. It should integrate with community management therapeutic programs and linkages with child treatment center, district hospitals and tertiary level centers offering inpatient management for SAM and include judicious use of ready-to-use-therapeutic Food (RUTF). All sections of healthcare providers need to be trained in the integrated management of SAM.

Study of pulmonary function tests in thalassemic children.

The present study aimed to investigate pulmonary function tests (PFTs) in children with thalassemia and to assess the relation between the degree respiratory impairment with the body iron status. High resolution computed tomography of chest (CHRCT) and bronchoalveolar lavage (BAL) was performed to study the cause of pulmonary dysfunction. Thirty-one children with thalassemia over 8 years were included. PFTs were studied including lung volumes and carbon monoxide diffusion capacity (DLco). Patients with abnormal PFTs and/or impaired DLco were further subjected to CHRCT and BAL. Total cell count was measured; differential count was performed on Giemsa and PAP smears. Iron laden macrophages were identified on Perls stain. PFTs were normal in 51.61%, diffusion capacity impaired in 41.16%, restriction in 16.12%, while obstruction in 3.22% of cases, respectively. There was significant inverse correlation between DLco and serum ferritin. Through multivariate regression analysis, ferritin was found to be a strong predictor for forced vital capacity and total lung capacity. Bronchial dilatation and areas of air trapping were the predominant CHRCT findings. Iron laden macrophages were demonstrated in 14 of 15 patients in BAL. A significant correlation between serum ferritin and DLco, forced vital capacity, total lung capacity, and the presence of iron laden macrophages in BAL indicates that iron plays a major role in the etiopathogenesis of these abnormalities.

Immunogenicity and safety of a tetravalent dengue vaccine in healthy adults in India: A randomized, observer-blind, placebo-controlled phase II trial.

Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo-controlled, Phase II study, adults aged 18–45 years were randomized 2:1 to receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration. Immunogenicity was assessed using a 50% plaque reduction neutralization test (PRNT50) at baseline and 28 days after each study injection. 189 participants were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%. Seropositivity rates for each serotype increased after each CYD-TDV injection with a more pronounced increase after the first injection. In the CYD-TDV group, geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third injection compared with baseline but remained similar to baseline in the placebo group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to 24.6-fold higher after the third injection compared with baseline in those who were dengue seropositive and dengue seronegative, respectively. Pain was the most commonly reported solicited injection site reaction after the first injection in both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently after subsequent injections. No serious adverse events were vaccine-related, no immediate unsolicited adverse events, and no virologically-confirmed cases of dengue, were reported during the study. The immunogenicity and safety of CYD-TDV was satisfactory in both dengue seropositive and seronegative Indian adults.

Celiac Disease in a Child With β-Thalassemia Major: A Need for Improved Screening and Awareness

Growth failure is one of the most common problems in children with thalassemia with multiple etiologies. We present a case of celiac disease, an underdiagnosed cause of growth failure in a child with beta-thalassemia major. A 10-year-old boy on a hypertransfusion regimen was referred for early onset growth failure. Serology for hepatitis B, hepatitis C, and HIV was negative. Serum zinc levels were normal. Thyroid function tests and growth hormone secretion, evaluated with clonidine stimulation test were normal. Malabsorption syndrome was suspected, even in the absence of gastrointestinal symptoms. Tissue transglutaminase were highly raised >300 IU/mL (normal values <15 U/L). Characteristic mucosal lesions on jejunal biopsy confirmed the diagnosis of celiac disease. Institution of a gluten-free diet resulted in rapid gain in weight and improvement in height velocity.