Evaluation of Pertussis Disease in Young Infants in India: A Hospital-Based Multicentric Observational Study.

OBJECTIVES: To evaluate the incidence of laboratory-confirmed pertussis (LCP) among infants hospitalized with acute respiratory infections (ARIs) and meeting the Centers for Disease Control and Prevention (CDC)-recommended clinical case definition. METHODS: An investigator-initiated active surveillance for clinically suspected cases (CSCs) of pertussis screened infants aged ≤6 mo hospitalized with ARIs during January 2020-April 2022 at seven centers across India. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect Bordetella pertussis in nasopharyngeal swabs. Infants were classified as having 'LCP' or 'probable pertussis' (PP). RESULTS: Among 1102 screened infants, 400 participants met the CDC-2020 clinical case definition for pertussis. Of these, 34/400 (8.5%) had LCP and 46/400 (11.5%) had PP. The proportion of participants with LCP and PP was similar among infants aged 0-3 and 4-6 mo [LCP: 0-3 mo, 21/248 (~9%); 4-6 mo, 13/152 (~9%); PP: 0-3 mo, 30/248 (~12%); 4-6 mo, 16/152 (~11%)]. Cough illness lasted ≥2 wk in 3/34 (~9%) and 34/46 (~74%) participants with LCP and PP, respectively. Notably, 80% CSCs had neither LCP nor PP, and a respiratory pathogen apart from B. pertussis was detected in ~32%. Ventilation was required in 12 participants with LCP/PP. CONCLUSIONS: In this first study from India based on revised CDC guidelines, the incidence of LCP was 8.5%; cough illness was not a predominant feature. Infants below the age appropriate for vaccination are prone to pertussis-related hospital admissions, ICU care, and ventilation. Maternal immunization may be evaluated for neonatal protection, in addition to other strategies, to decrease disease burden in this highly vulnerable group. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2019/12/022449.

Unique Properties of Yeast Probiotic Saccharomyces boulardii CNCM I-745: A Narrative Review.

Probiotics, both bacterial and yeast, have long been associated with a beneficial health history and human well-being. Among yeasts, Saccharomyces is a genus that is efficacious in rendering better human health, with Saccharomyces boulardii (S. boulardii) CNCM I-745 being classified as a probiotic agent. The present review highlights the unique properties of S. boulardii and its rolein the prevention of antibiotic-associated diarrhea (AAD) and pediatric acute gastroenteritis (PAGE) in comparison to bacterial probiotics. Its unique properties,such as viability over a wide pH range, inability to acquire antibiotic resistance genes, and property to achieve a steady state rapidly, have given S. boulardii an edge over bacterial probiotics. In AAD patients, prophylactic use of S. boulardii has shown a significantly lower risk of AAD (in comparison to controls) and restored the diversity of gut microbiota. Among Indian children with PAGE, S. boulardii CNCM I-745 was found superior to Lactobacillus rhamnosus GG and four strains of Bacillus clausii in shortening the duration of diarrhea and reducing the length of hospital stay. S. boulardii CNCM I-745 being considered a safe probiotic for use in children and adults also finds recommendations in several international guidelines for the management of acute diarrhea. The current review discusses evidence for the proven efficacy and safety of S. boulardii CNCM I-745 as a probiotic for preventing gastrointestinal disorders.

Phase III randomized clinical studies to evaluate the immunogenicity, lot-to-lot consistency, and safety of ROTAVAC® liquid formulations (ROTAVAC 5C & 5D) and non-inferiority comparisons with licensed ROTAVAC® (frozen formulation) in healthy infants.

The WHO pre-qualified rotavirus vaccine, ROTAVAC®, is derived naturally from the neonatal 116E rotavirus strain, and stored at -20°C. As refrigerator storage is preferable, immunogenicity and safety of liquid formulations kept at 2-8°C, having excipients to stabilize the rotavirus, with or without buffers, were compared with ROTAVAC® in different clinical studies. Study-1, the pivotal trial for this entire product development work, was a randomized, single-blind trial with two operationally seamless phases: (i) an exploratory phase involving 675 infants in which two formulations, ROTAVAC 5C (LnHRV-1.5 mL and LnHRV-2.0 mL) containing buffer and excipients to stabilize the virus against gastric acidity and temperature, were compared with ROTAVAC®. As the immune response of ROTAVAC 5C (LnHRV-2.0 mL) was non-inferior to ROTAVAC®, it was selected for (ii) confirmatory phase, involving 1,302 infants randomized 1:1:1:1 to receive three lots of LnHRV-2.0 mL, or ROTAVAC®. Primary objectives were the evaluation of non-inferiority and lot-to-lot consistency. The secondary objectives were to assess the safety and interference with the concomitant pentavalent vaccine. As it was separately established that buffers are not required for ROTAVAC®, in Study-2, the safety and immunogenicity of ROTAVAC 5D® (with excipients) were compared with ROTAVAC® and lot-to-lot consistency was assessed in another study. All lots elicited consistent immune responses, did not interfere with UIP vaccines, and had reactogenicity similar to ROTAVAC®. ROTAVAC 5C and ROTAVAC 5D® were immunogenic and well tolerated as ROTAVAC®. ROTAVAC 5D® had comparable immunogenicity and safety profiles with ROTAVAC® and can be stored at 2-8°C, leading to WHO pre-qualification.Clinical Trials Registration: Clinical Trials Registry of India (CTRI): CTRI/2015/02/005577CTRI/2016/11/007481 and CTRI/2019/03/017934.

The Efficacy and Safety of a Combination of Thiocolchicoside and Etoricoxib in Low Back Pain (ESCoTEL): A Randomized Active-Controlled Trial.

Background Low back pain (LBP) is a global health concern. Management of LBP aims at pain relief facilitating improvement of functional ability. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first line of therapy. However, the selection of NSAIDs is challenging given the range of underlying etiologies and severity. The current study aimed to compare the efficacy and safety of two available fixed-dose combinations (FDCs), namely, a dual FDC (DFC) of etoricoxib (60 mg) and thiocolchicoside (4 mg) versus a triple FDC (TFC) of chlorzoxazone (500 mg), diclofenac (50 mg), and paracetamol (325 mg). Methodology A total of 200 eligible adult subjects aged 18-70 years with a history of LBP and muscle spasm for ≤14 days and Wong-Baker Faces Pain score >4 were enrolled after obtaining written informed consent and randomized in a 1:1 allocation ratio to be treated with either DFC or TFC for 28 days. Efficacy was assessed based on the change in score from baseline (before treatment) to day 28 on the Wong-Baker Faces Pain Scale and the Oswestry Disability Index (ODI) questionnaire, as well as the proportion of subjects who improved upon treatment. Safety was assessed based on adverse events and clinical laboratory test results. Results A significant decrease in pain intensity (p < 0.001) and significant improvement in functional ability (p < 0.001) was observed after treatment with either DFC or TFC. The decrease in Wong-Baker Faces Pain score and ODI, from baseline, was comparable between the treatment groups. However, more subjects with very severe pain at baseline showed ≥30% improvement upon treatment with DFC than with TFC (~25% versus ~12%; p = 0.172). Also, significantly more crippled subjects with very severe functional disability showed improvement in the DFC group compared to the TFC group (~26% versus ~4%; p = 0.008). No adverse events or clinically relevant laboratory test results were evident. Conclusions Both DFC and TFC were comparable in efficacy and safety for the management of recent-onset LBP. However, significantly more subjects with very severe pain or functional disability showed improvement after 28 days when treated with DFC compared to TFC.

Antibody Persistence Following Administration of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T and IPV Vaccines and Safety and Immunogenicity of a Booster Dose of DTwP-IPV-HB-PRP~T Administered With an MMR Vaccine in Healthy Infants in India.

BACKGROUND: Antibody persistence of a whole-cell pertussis-containing hexavalent vaccine (DTwP-IPV-HB-PRP~T) and its co- or sequential administration with measles, mumps, rubella (MMR) vaccine were evaluated. METHODS: Phase III, open-label, randomized, multicenter study in India. Healthy toddlers 12-24 months of age who had received DTwP-IPV-HB-PRP~T or separate DTwP-HB-PRP~T+IPV primary vaccination at 6-8, 10-12 and 14-16 weeks of age received a DTwP-IPV-HB-PRP~T booster concomitantly with MMR (N = 336) or 28 days before MMR (N = 340). Participants had received a first dose of measles vaccine. Immunogenicity assessment used validated assays and safety was by parental reports. All analyses were descriptive. RESULTS: All participants had prebooster anti-T ≥0.01 IU/mL and anti-polio 1 and 3 ≥8 1/dil, and ≥96.5% had anti-D ≥0.01 IU/mL, anti-HBs ≥10 mIU/mL, anti-polio 2 ≥8 1/dil and anti-PRP ≥0.15 µg/mL; for pertussis, antibody persistence was similar in each group. Postbooster immunogenicity for DTwP-IPV-HB-PRP~T was similar for each antigen in each group: ≥99.5% of participants had anti-D ≥0.01 IU/mL, anti-T ≥0.01 IU/mL, anti-polio 1, 2 and 3 >8 1/dil, anti-HBs ≥10 mIU/mL and anti-PRP ≥1 µg/mL; for pertussis, vaccine response was similar in each group [72.0%-75.9% (anti-PT), 80.8%-81.4% (anti-FIM), 77.6%-79.5% (anti-PRN), 78.2%-80.8% (anti-FHA)]. There was no difference in MMR immunogenicity between groups, and no difference in DTwP-IPV-HB-PRP~T booster immunogenicity based on the primary series. There were no safety concerns. CONCLUSIONS: DTwP-IPV-HB-PRP~T antibody persistence was similar to licensed comparators. Booster immunogenicity was robust after DTwP-IPV-HB-PRP~T with or without MMR, and MMR immunogenicity was not affected by coadministration with DTwP-IPV-HB-PRP~T. CLINICAL TRIALS REGISTRY INDIA NUMBER: CTRI/2020/04/024843.

Safety, immunogenicity and non-interference of concomitant Typhoid Vi capsular polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV®) and measles or measles-mumps-rubella vaccines in 8-9 months-old Indian children.

We evaluated safety, reactogenicity, and immunogenicity when the WHO-prequalified single-dose Typhoid Vi-polysaccharide conjugate vaccine, Typbar-TCV®, was administered concomitantly with measles (MV) or measles-mumps-rubella (MMR) vaccines in 8- or 9-month-old children. We enrolled 493 children who were randomized 2:1:1:1 to four groups to receive either TCV (0.5 mL intramuscularly) and MV (0.5 ml subcutaneously) concomitantly at 9 months of age (Group 1) with two subgroups given TCV booster 28 days (Group 1A) or 180 days (Group 1B) later, or MV on Day 0 and TCV on Day 28 (Group 2); or TCV at 8 months of age and MV 28 days later (Group 3), or MV only at 9 months of age (Group 4). All children received MMR at 15 months of age. We observed no statistically significant differences between group rates of solicited or unsolicited adverse events assessed throughout the study. Seroconversion rates for measles, mumps, and rubella antibodies were unaffected by concomitant administration with TCV, being similar in Groups 1, 2, and 3 and comparable to Group 4 (Control). IgG anti-Vi antibody titers were similar in all groups after primary Typbar-TCV® vaccination and were not increased by a second dose 28 days later. A small response to a booster dose of Typbar-TCV® given at 180 days did not achieve the high titers observed after the first dose, suggesting that booster vaccination may be more effective after a longer interval than 6 months. Typbar-TCV® can be safely co-administered with measles and MMR vaccines in children aged ≥9 months.Clinical trial registration number: CTRI/2014/04/004532.

Role of Lactobacillus reuteri DSM 17938 on Crying Time Reduction in Infantile Colic and Its Impact on Maternal Depression: A Real-Life Clinic-Based Study.

BACKGROUND: Infantile colic is characterized by prolonged periods of inconsolable, incessant crying and persistent fussing in an otherwise healthy infant. It is a self-limiting condition, but causes significant stress to mothers. AIM: To observe the role of Lactobacillus reuteriDSM 17938 in reducing crying time in colicky infants in routine clinical practice. METHODS: This was a prospective observational multicentric clinic-based study. Each practitioner included approximately 30 infants < 5 months of age with infantile colic who were prescribed L. reuteri DSM 17938 for a period of 21 days. There were four physical consultations and two telephonic consultations. The parents were given a daily diary to record the duration of crying and fussing episodes and a questionnaire was administered during the consultations. RESULTS: A total of 120 infants with a mean age of 56.9 ± 34.2 days were included in this 28-day study. The mean crying time as reported by the parents in the subject diary reduced from 248.2 ± 101.2 min, 95% CI: 229.45, 266.94 at baseline to 45.6 ± 79.1 min 95% CI: 31.02, 60.31 at study end (P < 0.01). The clinical response (defined as reduction of 50% in crying time) was observed in 85% of subjects at study end. The fussiness and parental perception of colic recorded during the consultations were reduced by 66% and 72%, respectively, at study end. The maternal depression scores were reduced to 63% at study end. CONCLUSION: L. reuteri DSM 17938 was associated with a significant reduction in crying time in colicky infants, and showed improvement in maternal depression.

Effect of Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 on Acute Watery Diarrhea: A Randomized Double-Blind Placebo-Controlled Study in Indian Children.

PURPOSE: To assess the effect of combination probiotic Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 in outpatient management of acute watery diarrhea in children. METHODS: A randomized double-blind placebo-controlled study was conducted in 180 participants aged six months to five years with acute mild to moderate diarrhea. All were enrolled from six centers across India and centrally randomized to receive S. boulardii CNCM-I 3799 and B. subtilis CU-1 or a placebo along with oral rehydration salts and zinc supplementation. Each participant was followed up for three months to assess recurrence of diarrhea. RESULTS: The mean duration of diarrhea in the probiotic and placebo groups were 54.16 hours and 59.48 hours, respectively. The difference in the duration of diarrhea in those administered with probiotic or placebo within 24 hours of diarrhea onset was 25.21 hours. Furthermore, the difference in duration of diarrhea was 13.84 hours (p<0.05) for participants who were administered with probiotics within 48 hours. There were no significant differences in the stool frequencies between the two arms. After three months, 15% in the probiotic group and 18.5% in the placebo group reported episodes of diarrhea. The mean duration of diarrhea was considerably lower in the probiotic group, 31.02 hours versus 48 hours in placebo (p=0.017). CONCLUSION: S. boulardii CNCM-I 3799 and B. subtilis CU-1 combination was effective in reducing the duration of diarrhea when administered within 48 hours of diarrhea onset. Similarly, it reduced recurrence of diarrhea and its intensity in the subsequent three months.

A phase III randomized, open-label, non-inferiority clinical trial comparing liquid and lyophilized formulations of oral live attenuated human rotavirus vaccine (HRV) in Indian infants.

The human rotavirus vaccine (HRV; Rotarix, GSK) is available as liquid (Liq) and lyophilized (Lyo) formulations, but only Lyo HRV is licensed in India. In this phase III, randomized, open-label trial (NCT02141204), healthy Indian infants aged 6-10 weeks received 2 doses (1 month apart) of either Liq HRV or Lyo HRV. Non-inferiority of Liq HRV compared to Lyo HRV was assessed in terms of geometric mean concentrations (GMCs) of anti-RV immunoglobulin A (IgA), 1-month post-second dose (primary objective). Reactogenicity/safety were also evaluated. Seroconversion was defined as anti-RV IgA antibody concentration ≥20 units [U]/mL in initially seronegative infants (anti-RV IgA antibody concentration <20 U/mL) or ≥2-fold increase compared with pre-vaccination concentration in initially seropositive infants. Of the 451 enrolled infants, 381 (189 in Liq HRV and 192 in Lyo HRV group) were included in the per-protocol set. The GMC ratio (Liq HRV/Lyo HRV) was 0.93 (95% confidence interval [CI]: 0.65-1.34), with the lower limit of the 95% CI reaching ≥0.5, the pre-specified statistical margin for non-inferiority. In the Liq HRV and Lyo HRV groups, 42.9% and 44.3% (baseline) and 71.4% and 73.4% (1-month post-second dose) of infants had anti-RV IgA antibody concentration ≥20 U/mL, and overall seroconversion rates were 54.5% and 50.0%. Incidences of solicited and unsolicited adverse events were similar between groups and no vaccine-related serious adverse events were reported. Liq HRV was non-inferior to Lyo HRV in terms of antibody GMCs and showed similar reactogenicity/safety profiles, supporting the use of Liq HRV in Indian infants.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus is the most common cause of acute gastronenteritis and contributes to the high number of hospitalizations and deaths in young children worldwide.Vaccination against rotavirus has led to a significant decrease in rotavirus-related infections.The human rotavirus vaccine Rotarix (GSK) is currently used as a liquid or lyophilized formulation.In clinical trials conducted in European and North American infants, the liquid vaccine showed ability to induce immune response and safety comparable to the lyophilized formulation.Only the lyophilized vaccine is currently marketed in india.What is new?We compared the 2-dose liquid and lyophilized human rotavirus vaccines in indian infants in a phase III clinical trial:The ability to induce immune response for thw liquid formulation was not inferior to that observed for the lyophilized vaccine.The safety profiles of the 2 formulations were comparable.Why is this important?This study shows that the liquid human rotavirus vaccine can be administrated to infants from india.

Efficacy of polyethylene glycol 3350 as compared to lactulose in treatment of ROME IV criteria-defined pediatric functional constipation: A randomized controlled trial.

BACKGROUND AND AIMS: Functional constipation is a common childhood problem, with a prevalence of approximately 3% worldwide. The aim of the study was to compare the efficacy of polyethylene glycol (PEG) 3350 and lactulose in the treatment of pediatric functional constipation. METHODS: A total of 100 subjects with functional constipation were enrolled and centrally randomized to receive PEG 3350 (0.7-1.5 mg/kg/day) or lactulose (0.7-2.0 g/kg/day). RESULTS: There was a significant increase in median (min, max) stool frequency within 1 week in the PEG 3350 group as compared to the lactulose group (1 [0, 3] to 8 [3, 39] vs. 1 [0, 3] to 7 [1, 17]) (p-value < 0.01). The trend was maintained at week 2, week 3 (p-value < 0.01), and week 4 (p-value = 0.05) with the PEG 3350 group reporting higher weekly median stool frequency than the lactulose group. The PEG group reported significant reduction in painful bowel movements from 68.8% subjects at baseline to 43.8% at the end of first week, whereas the lactulose group reported an increase from 48.9% to 73.3% (p-value = 0.05). Other parameters of constipation, i.e. straining, large diameter stool, and large fecal mass as reported subjectively by parents, significantly decreased from baseline to the end of the study in the PEG 3350 arm compared to those in the lactulose arm. At the end of week 4, there was a statistically significant reduction in all the ROME IV-defined criteria between the two groups. CONCLUSION: This study proved that the PEG 3350 treatment group had early symptom relief and significant improvement compared to the lactulose group in pediatric functional constipation. TRIAL REGISTRATION: Clinical Trials Registry India (CTRI/2018/01/011061).

Specific Probiotics for the Treatment of Pediatric Acute Gastroenteritis in India: A Systematic Review and Meta-Analysis.

Pediatric acute gastroenteritis (PAGE) is a significant cause of morbidity, mortality and healthcare costs in many countries, but differences in PAGE vary from country-to-country; thus, we limited our analysis to 1 country. Probiotics have been recommended as an adjunct to standard treatment, but the choice of probiotic is unclear. PubMed, Google Scholar, and reviews were searched from inception to May 2020 for randomized controlled trials (RCTs) in India using probiotics for a treatment for PAGE. Meta-analyses using subgroups of identical probiotic types (≥2 RCT/type) were conducted for primary outcomes (duration of diarrhea, cured by day 3, rapidity of response, and length of hospital stay). Twenty-two RCTs were included in the systematic review (N = 4059 participants) including 5 single-strained probiotics and 3 multi-strained mixtures. For the meta-analyses, 17 RCT (20 treatment arms) were included. Saccharomyces boulardii CNCM I-745 had the strongest effect on shortening the duration of diarrhea (standardized mean difference, -1.86 d; 95% confidence interval, -2.8 to -0.9), while both Lactobacillus rhamnosus GG and a mixture of 4 Bacillus clausii strains (O/C, SIN, N/R, T) significantly reduced the duration of diarrhea (-1.7 and -1.4 d, respectively). S. boulardii and L. rhamnosus GG significantly reduced hospital stays (-1.8 and -1.1 d, respectively), while B. clausii had no effect. The frequency of stools/day was significantly reduced by day 4 for S. boulardii and by day 5 for L. rhamnosus GG. In India, 2 types of probiotics (S. boulardii CNCM I-745 and L. rhamnosus GG) significantly shortened both the duration of diarrhea and hospitalization stays in pediatric patients with PAGE. While these 2 probiotic strains were safe and effective for children in India, further research is needed to confirm if other probiotic strains or mixtures may be effective.

Evaluation of immunogenicity, safety and breakthrough following administration of live attenuated varicella vaccine in two doses three months apart regimen in Indian children.

BACKGROUND: In India, where varicella outbreaks are reported at a younger age, a two-dose vaccine schedule administered at an early age could be highly efficacious in preventing varicella infection. The aim of this study was to evaluate the immunogenicity and safety of live attenuated varicella vaccine (VR 795 Oka strain) in a two-dose, 3 months apart regimen. METHODOLOGY: Healthy children (⩾ 12 months and ⩽12 years; mean age: 4.4 years) of either sex were included. Geometric mean titers (GMT) were measured at baseline and 28 days post first- and second-dose, and seroprotection rates were measured 28 days post first and second dose. The incidence of breakthrough (BT) infections post vaccination was determined from 42 days post first and second dose of vaccine up to 12 months. Adverse events (AEs) were monitored and recorded throughout the study period. RESULTS: Of 305 subjects enrolled, 217 were seronegative. The seroconversion rate (a change from a seronegative to a seropositive condition) was 93.3% post first-dose and 100% post two-doses. High levels (9 times) of GMT were reported since post first-dose to post second-dose in children aged 12-18 months, 18-60 months (99.43%); and in and above 60 months (99.02%). The extent of rise of anti-VZV IgG antibody titer post 28 days of first-dose at two-fold, three-fold and four-fold rise was 93.39%, 90.56% and 80.66%, respectively and 100% 4-fold rise post second-dose. A single case, a day after the first-dose of vaccination of mild BT infection, was observed after close contact with a severe case. AEs were mild and none of the serious AEs were related to the study drug. CONCLUSION: The two-dose schedule of varicella vaccine was safe and immunogenic when given 3 months apart. However, further comparative studies and follow up for both dosing schedules are needed to validate the advantage of early dosing.

Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children.

INTRODUCTION: Hepatitis A virus infection is more severe in adults than children. Although vaccination can protect adults, current childhood programs cover a large population more successfully. Childhood vaccination is, therefore, a solution to protecting adults if it induces lasting immunity. Fifteen-year protection has been demonstrated in children, but longer-term data are only available for adults. We aimed to predict long term persistence of antibody in children beyond 15 years and assess if immunological mechanisms triggered by vaccination support longer-term protection. METHODS: Long-term clinical studies using hepatitis A (HAV) or A/B vaccines (HAB) containing 720 or 1440 Enzyme-linked immunosorbent assay Units (EU) of hepatitis A virus antigen were identified. Duration of persistence of antibodies and possible protection was determined by descriptively comparing antibody geometric mean concentration (GMC) kinetics, as well as GMC (95% confidence interval) at 15 years post-vaccination across studies. Immunological mechanism studies describing hepatitis A vaccination were identified. RESULTS: One study in children 12-15 years (2-dose HAB 720) and four in adults (2-dose HAV 1440 and 3-dose HAB 720) showed comparable GMC kinetics and per year rates of change up to 15 years. At 15 years, the GMC in children [414.7 mEU/ml (336.9; 510.5)] was in the same range as in adults [range 282.6 (217.6; 367.0) to 550.1 (416.0; 727.4)]. Based on these data, mathematical model predictions from adult studies (showing > 85% protected at 50 years) were deemed likely to also apply to children. Studies identified, both humoral and cell-mediated responses are induced following vaccination. CONCLUSION: Based on comparable antibody data in adults and children up to 15 years, similar longer-term antibody persistence is expected in children with 2-dose inactivated hepatitis A 720 containing vaccine at least up to 50 years. Accordingly, improving routine childhood hepatitis A vaccination coverage could protect against more severe disease in adulthood. Fig. 1 Plain language summary TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT00875485, NCT01000324, NCT01037114, NCT00289757, NCT00291876.

Review of long term immunogenicity and tolerability of live hepatitis A vaccine.

Hepatitis A represents one of the major public health problems worldwide including India. Vaccination is the most effective way to prevent hepatitis A infection. Two types of hepatitis A vaccines-live attenuated (H2 strain) and inactivated (killed) are available for use in clinical practice in India with former having advantage of a single-dose compared to two-dose killed vaccine. One of the important characteristic of an ideal vaccine includes its ability to provide life-long protection. In this article we reviewed the available long-term (≥10 years follow-up) published data on live attenuated hepatitis A (H2 strain) vaccine. The data from country of origin of the vaccine (China) and India establish the long-term immunogenicity, protection, and tolerability. Based on the results of several clinical trials showing long-term protection, single dose of live attenuated hepatitis vaccine can be widely used to protect high-risk population against hepatitis A virus infection and related complications.

Micronutrient-fortified infant cereal improves Hb status and reduces iron-deficiency anaemia in Indian infants: an effectiveness study.

Anaemia affects approximately 69 % of Indian children aged 6-12 months, with Fe deficiency (ID) being a common cause. The effectiveness of micronutrient-fortified infant cereal in improving Fe status and neurodevelopment was evaluated in non-anaemic and mildly anaemic Indian infants. An intervention group (IC) enrolled at age 6 months consumed 50 g/d of rice-based cereal providing 3·75 mg Fe/d as ferrous fumarate for 6 months (n 80) and was compared with a matched static cross-sectional control group (CG) without intervention enrolled at age 12 months (n 80). Mean Hb was higher in IC (118·1 (sd 10·2) g/l) v. CG (109·5 (sd 16·4) g/l) at age 12 months (adjusted mean difference: 9·7 g/l; 95 % CI 5·1, 14·3; P < 0·001), while geometric mean serum ferritin tended to be higher (27·0 (-1 sd 13·4, +1 sd 54·4) v. 20·3 (-1 sd 7·5, +1 sd 55·0) ng/ml); P = 0·085) and soluble transferrin receptor was lower (1·70 (-1 sd 1·19, +1 sd 2·43) v. 2·07 (-1 sd 1·29, +1 sd 3·33) mg/l; P = 0·014). Anaemia (23 v. 45 %; P = 0·007) and ID (17 v. 40 %; P = 0·003) were lower in IC v. CG. Bayley Scales of Infant and Toddler Development Third Edition scores for language (P = 0·003), motor development (P = 0·018), social-emotional (P = 0·004) and adaptive behaviour (P < 0·001), but not cognitive development (P = 0·980), were higher in IC v. CG. No significant difference in anthropometric Z-scores was observed between the groups. Consuming a micronutrient-fortified infant cereal daily for 6 months during complementary feeding promoted better Fe status while reducing the risk for anaemia and ID and was associated with superior neurodevelopmental scores.

Increasing Burden of Hepatitis A in Adolescents and Adults and the Need for Long-Term Protection: A Review from the Indian Subcontinent.

Hepatitis A, an acute inflammatory liver disease caused by hepatitis A virus (HAV) infection from close contact with infected people, is highly endemic in the Indian subcontinent. Due to poor sanitary conditions, most of the population is exposed to the virus in childhood. At this age, the disease is asymptomatic and provides life-long protection against the disease. Due to rapid socioeconomic development in some areas, however, pockets of the population are reaching adolescence/adulthood without prior exposure to the virus and are thus susceptible to infection. At these ages, infection carries a higher risk of symptomatic disease and complications including mortality. This review of epidemiology and burden of disease studies in the Indian subcontinent, published since 2005, shows increasing evidence of a shift from high to intermediate endemicity in high-income-typically urban-populations. The prevalence of anti-HAV antibodies (previously reported at > 90%) is lower now in adolescents and young adults (e.g., around 80% in Bangladesh and 55% in 5-15 years in India). As a result, HAV is responsible for more acute viral hepatitis predominantly in this age group (e.g., > 15 years: 3.4% in 1999 to 12.3% in 2003 or high socioeconomic status 13-20 years: 27% in 1999 to 62% in 2003), with a greater clinical and economic burden. Numerous outbreaks due to HAV have been reported [e.g., Sri Lanka (2009-2010): > 13,000 affected; Kashmir (2015-2017): 12 outbreaks; Kerala (2012-2016): 84 outbreaks] from water or food contamination. Due to current shifts in endemicity, a growing proportion of the population is no longer exposed in childhood. As the disease remains highly endemic, it also provides a source for more severe disease in susceptible people at an older age and for outbreaks. Well-tolerated and effective vaccines are available and help prevent disease burden and provide long-term protection. These should now be used more widely to protect more patients from the growing disease burden of hepatitis A. FUNDING: GlaxoSmithKline Biologicals SA. Plain language summary available for this article-please see Fig. 1 and the following link: https://doi.org/10.6084/m9.figshare.9963044.Fig. 1Plain Language Summary. Highlights the context of the article, the endemicity shift and the burden of hepatitis A in adolescents and adults and steps to be taken to address the impact of this disease.

Safety and immunogenicity of Bio Pox™, a live varicella vaccine (Oka strain) in Indian children: A comparative multicentric, randomized phase II/III clinical trial.

Varicella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasizing the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™ [a][a] Please note that this article refers to the product named VARIVAX as manufactured by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB Life Sciences Limited, Mumbai, and not the product VARIVAX® owned by Merck Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have asked us to make clear that the product manufactured by Changchun Keygen Biological Products Ltd. is unrelated to and is not sponsored, endorsed or otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit. Seroconversion percentage in children having pre-vaccination anti VZV IgG titer <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio Pox™ and 77% for Varivax™ (p = 0.692). The seroconversion rate in the group receiving Bio Pox™ was non-inferior to the group that received Varivax™. There were mild local reactions for both the vaccines; none of the patient had fever or required hospitalization or medication. The Bio Pox™ was found to be safe and immunogenic in children against VZV infection.

Immunogenicity and safety of a novel MMR vaccine (live, freeze-dried) containing the Edmonston-Zagreb measles strain, the Hoshino mumps strain, and the RA 27/3 rubella strain: Results of a randomized, comparative, active controlled phase III clinical trial.

This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the single-dose and multi-dose formulations of a novel MMR vaccine (live, freeze-dried) developed by M/s Cadila Healthcare Limited, India (Cadila MMR vaccine), containing the Hoshino mumps strain, compared to that of an existing MMR vaccine (live, freeze-dried) developed by M/s Serum Institute of India Limited, India (Serum MMR vaccine). These two vaccines have similar measles and rubella strains, but different mumps strains (Hoshino in Cadila MMR vaccine, and L-Zagreb in Serum MMR vaccine). Three hundred and twenty-eight subjects of either sex, aged 15-18 months, were randomized in a 2:1 ratio to receive either the Cadila or Serum MMR vaccine. Immunogenicity assessments (IgG antibodies against measles, mumps, and rubella viruses) were done at baseline and 42 d after vaccination. Solicited (local and systemic) and unsolicited adverse events were recorded for up to 42 d following vaccination. The Cadila MMR vaccine was found to be non-inferior to the Serum MMR vaccine in terms of end-of-study proportion of subjects seropositive for anti-measles antibodies (100.0% in both groups), anti-mumps antibodies (94.5% vs. 94.0%), and anti-rubella antibodies (95.5% vs. 91.0%). Both vaccines were well tolerated by all study participants; the most common adverse event reported in both groups was fever, followed by rash. The results of this phase III clinical trial show that the novel Cadila MMR vaccine is non-inferior to the Serum MMR vaccine.