The Immunogenicity of Monovalent Oral Poliovirus Vaccine Type 1 (mOPV1) and Inactivated Poliovirus Vaccine (IPV) in the EPI Schedule of India.

BACKGROUND: In 2016, the Global Polio Eradication Initiative (GPEI) recommended the cessation of using type 2 oral poliovirus vaccine (OPV) and OPV, with countries having to switch from the trivalent to bivalent OPV (bOPV) with the addition of inactivated poliovirus vaccine (IPV) in their routine immunization schedule. The current GPEI strategy 2022-2026 includes a bOPV cessation plan and a switch to IPV alone or a combination of vaccine schedules in the future. The focus of our study was to evaluate the immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV-only schedules. METHODS: This was a three-arm, multi-center randomized-controlled trial conducted in 2016-2017 in India. Participants, at birth, were randomly assigned to the bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth and at 14, 18, and 22 weeks old were analyzed with a standard microneutralization assay for all the three poliovirus serotypes. RESULTS: The results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after the completion of the schedule at 18 weeks were 99.5% (97.0-99.9), 100.0% (97.9-100.0), and 96.0% (92.0-98.1) in Arms A (4bOPV + IPV), B (4mOPV1 + IPV), and C (3IPV), respectively. Type 2 and type 3 seroconversions at 18 weeks were 80.0% (73.7-85.1), 76.9% (70.3-82.4); 93.2% (88.5-96.1), 100.0% (98.0-100.0); and 81.9% (75.6-86.8), 99.4% (96.9-99.9), respectively, in the three arms. CONCLUSIONS: This study shows the high efficacy of different polio vaccines for serotype 1 in all three schedules. The type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type-specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on the epidemiology from time to time.

A Comprehensive Echocardiographic Assessment of Neonatal Right Ventricular Function in Neonatal Intensive Care Unit Babies.

Background The right ventricle (RV) in the fetus is the predominant chamber, accounting for about 60% of the total cardiac output. The majority of the RV outflow volume is diverted from the pulmonary artery via the ductus arteriosus to the descending aorta. After birth, the RV undergoes extensive structural and functional modifications. The RV undergoes an improper transition from fetal to neonatal circulation in sick neonatal intensive care unit (NICU) babies. Functional echocardiography is now commonly being used in most NICUs as it is a noninvasive and bedside investigation that gives an immediate evaluation of hemodynamics and can be taken into consideration as an extension of clinical assessment to study a critically unwell neonate. Therefore, a study of RV functions in NICU neonates will help in better understanding the neonatal cardiopulmonary response to different diseases. Thus, this study aimed to assess RV functions in neonates getting admitted to the NICU of a tertiary care institute. Methodology This observational, cross-sectional study was approved by the Research & Recognition Committee of Dr. D. Y. Patil Vidyapeeth, Pune. In total, 35 cases of term neonates admitted to the NICU at Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune who fulfilled the inclusion criteria were enrolled in this study after obtaining consent from their parents. Two-dimensional echocardiography was performed by a trained pediatric cardiologist, and the findings were substantiated by a neonatologist trained in echocardiography. Results Our study found a strong association between tricuspid inflow velocity and neonates with sepsis. Similarly, a significant association was observed between abnormal tricuspid Inflow velocity (E/A and E/E') and neonates requiring inotropic support. Conclusions Data on the normal values of different echocardiographic parameters of the systolic and diastolic function of the RV during the neonatal phase of life are currently limited. Our data offer preliminary insights into this topic. Early echocardiography and intervention are advisable, especially in neonates with sepsis and requiring inotropic support.

A Case Report on CNS Hemophagocytic Lymphohistiocytosis in an Infant With Dengue Hemorrhagic Fever.

India is an endemic country for dengue. The incidence of hemophagocytic lymphohistiocytosis (HLH) with dengue in children has been well-reported. However, central nervous system (CNS) HLH associated with dengue has not been described in the literature yet. We hereby report a novel case of CNS HLH triggered by dengue infection. An eight-month-old, well-grown male infant with uneventful antenatal, perinatal, and neonatal history was admitted with a history of febrile illness associated with cough, cold, vomiting, and loose motions and one episode of hematochezia and hepatosplenomegaly on examination. Investigations revealed bi-cytopenia, hyper-ferritinemia, deranged coagulation profile, liver function test, and hypo-fibrinogenemia. Dengue non-structural protein 1 ( NS1) antigen was positive. The child was given dexamethasone and continued supportive care with a diagnosis of dengue shock syndrome. The child showed an overall transient improvement, however, he had rebound fever followed by right focal convulsion on Day 9 of steroids. MRI brain revealed areas of diffusion-restricted embolic infarcts with diffuse leptomeningeal enhancement and mild cerebral edema, and CSF showed a total leukocyte count of 80 cells with 75% lymphocytic picture, histiocytes with hemophagocytosis, confirmatory of CNS HLH. Intrathecal methotrexate, hydrocortisone, and intravenous (IV) etoposide were started. However, the child succumbed to his illness. CNS involvement in dengue-triggered HLH needs to be suspected despite subtle neurological signs and aggressively managed following a multi-departmental approach to ensure the best clinical and neuro-developmental outcomes.

Incidence, Clinical Features, and Outcomes of Transient Tachypnea of the Newborn at a Tertiary Care Center in Western India.

Background Transient tachypnea of the newborn (TTN) is a self-limiting, benign condition leading to respiratory distress shortly after birth. It is among the leading cause of respiratory distress in term and late preterm neonates. The disease is transient and resolves by three to four days in most neonates. Objective The objective of this study was to study the incidence of TTN, its clinical features, predictors of outcomes and duration of hospital stay in these neonates suffering from it. Methods This was a prospective study done at a tertiary care center carried out between August 2019 to July 2021. The study subjects were late pre-term (34 to 36 weeks of gestation) and term neonates with respiratory distress who were admitted to the neonatal intensive care unit (NICU). The diagnosis was based on clinical features, radiological features, and clinical course in NICU. Results The total number of cases with TTN was 74. The incidence of TTN was 16 per 1000 live births. 63.5% were male, 75.7% were term births, 70.3% were born via lower section cesarean section (LSCS), and 66.2% were normal birth weight (≥2.5 kg) infants. A high incidence of TTN was found in late pre-term babies, babies born via LSCS, and male sex. None of the neonates required ventilatory support, either noninvasive or invasive. Conclusion Delivery by LSCS and male sex were risk factors for the development of TTN. The distress in TTN is usually mild to moderate, and in most cases, oxygen supplementation suffices. Higher Downes' score at presentation, low birth weight, preterm, and delivery by LSCS were found to be predictors for a longer duration of distress and thus the longer duration of NICU stay. Although severe complications for TTN have been reported in the literature, they are rare. Careful observation can decrease not only a lot of unnecessary investigations but also allow clinicians at secondary and primary centers to better care for neonates with TTN.

Study of Stem Cells in Human Milk.

Stem cells are cells that have the ability to self-renew into an undifferentiated cell state, which can further delineate into distinct cell types. There are various sources of stem cells in the human body; some of them include cord blood, placental tissue, bone marrow, adipose tissue, dental pulp, etc.  Breast milk could become an important source of stem cells in the near future because of its non-invasive isolation technique. Based on this nature, this study was conducted to isolate stem cells from breast milk and to show further potential implications of these cells. The total number of cells isolated from the milk ranged from 1.5 × 105 cells to 3 × 105 cells. As there was prolongation in the lactation period, the number of cells in the milk lowered significantly. There was no significant difference in the cell count in various gestational age groups. The cytochemistry analysis of these cells with their specific cell markers confirmed the presence of a homogenous population of mesenchymal stem cells. Further differentiation of these breast milk stem cell analyses showed transformation into adipocytes, chondrocytes, and osteoblasts in different culture mediums. So the presence of mesenchymal stem cells in human milk, which are multipotent in nature, makes it an important source of stem cells for further regenerative therapies, tissue culture techniques, and gene therapies. Due to this nature, these cells can be redirected to produce various tissues in the human body.

Effect of nutritional counselling for using anthropometric indices among Indians.

Malnutrition in children under 5 years is a major public health problem in developing countries. Malnutrition complex comprises of under-nutrition including multiple conditions like acute, chronic malnutrition, micronutrient deficiencies and nutrition related to obesity. Therefore, it is of interest to report data on the individualized nutritional counselling on nutritional status among mild to moderately malnourished children aged 2 - 5 years at one, three and six month follow up. Their dietary habits will help to determine the aetiology of mild/moderate malnutrition.150 Children attending outpatient department of the Department of Paediatrics of D Y Patil Medical College and admitted with mild/moderate malnutrition were included in the study after taking informed consent from their parents. The children were randomly allocated into 4 groups (group 1 - 4). The groups consisted of children where dedicated nutritional counselling was provided at 1 month, 1 and 3 month follow up and where-in no dedicated counselling was provided. A diet chart was provided with counselling. Group 4 followed up with routine care without any dietary intervention. Detailed dietary, socio economic history, clinical examination with anthropometry was done followed-up at 1, 3, 6 months from date of inclusion. Majority (57.3%) belonged to lower socio-economic class according to Kuppuswamy scale. The mean birth weight was 2.4 kg, age 34.5 months and age of weaning 7.6 months. Data shows that 70% children had mild malnutrition and 30% moderate malnutrition. At 6 month follow up amongst 105 children with mild malnutrition, 82 still had mild malnutrition, 4 normal, 19 had moderate malnutrition. Under-five childhood malnutrition is highly prevalent in poor socioeconomic strata of the society. Nutritional counselling provided by trained healthcare providers in existing settings are effective in improving nutritional status, daily calorie/protein intake, prevention of malnutrition. Prevention/treatment of co-existing illness bears equal importance.

Protocol for Infant Massage in Home Settings: An e-Delphi Approach for Consensus Guidance Integrating Traditional Wisdom with Modern Medicine.

Infant massage is a highly prevalent traditional practice in India and other parts of Asia. Clear guidance on safe and effective uses of infant massage is lacking especially in the contemporary times when the traditional knowledge is on the verge of extinction and preparations may differ from in the past. This paper presents a consensus guidance in the form of a standardized protocol for routine massage of infants in home settings. Furthermore, a feasible method to develop an integrative protocol involving traditional and modern medicine experts is described. A modified e-Delphi method was used to develop the protocol. A group of seventeen experts, including academicians and practitioners from disciplines as modern paediatrics, Ayurveda paediatrics, Physiotherapy and Naturopathy participated in three rounds of a Delphi study to evolve the consensus guidance. The present protocol for massage of infants born beyond 34 weeks of gestation and weighing above 1.8 kg is recommended for use by care givers. This provides guidance on the preparation for infant massage such as when to begin massaging the infant, checking fitness of the infant for massage, the appropriate time, environment, person and substance for infant massage and a detailed description of the procedure for infant massage. Paediatricians, obstetricians and other child care practitioners can use this protocol to guide care givers on how to peform infant massage.

Test Anxiety among School-Going Children and Adolescents, Factors Affecting and Impact on Quality of Life: A Multicenter Study.

OBJECTIVE: To assess test anxiety (TA) and factors affecting TA in school-going children. To observe the impact of TA on quality of life (QOL). METHOD: A multi-centric cross-sectional observational study was conducted in Indian schools from 6 different states in both rural and urban settings. Indian school children 9 to 18-y-old were the subjects. Demographic data, including age, gender, and socioeconomic status, were obtained. Children were administered Test Anxiety Inventory (TAI) and PedsQL (Pediatric Quality of Life). TAI score (and factors affecting it in both rural and urban children) and QOL scores were assessed. RESULTS: Data on 2158 children were analyzed (1162 boys). The mean age was 13.8 ± 1.8 y, and the mean TAI score was 48.3 ± 10.2. TAI score was significantly higher in girls and rural children (p < 0.05 for both). Based on the TAI score, high, medium, and low-anxiety clusters were generated. Proportion of children with high, medium and low-anxiety scores were 18%, 48%, and 34%, respectively. Children with low anxiety had better QOL in all subdomains (p < 0.05). Regression analysis indicated increasing age, low QOL, urban living, and lower maternal education as significant predictors of high anxiety (p < 0.05). CONCLUSION: Girls and rural children had higher TA. Two-thirds of children studied had moderate to high TA. Increasing age, urban living, QOL, and maternal education had an impact on TA. Evaluating TA and developing appropriate strategies for stress-reduction in school children is necessary.

High Burden of Bloodstream Infections Associated With Antimicrobial Resistance and Mortality in the Neonatal Intensive Care Unit in Pune, India.

BACKGROUND: Antimicrobial resistance (AMR) is a growing threat to newborns in low- and middle-income countries (LMIC). METHODS: We performed a prospective cohort study in 3 tertiary neonatal intensive care units (NICUs) in Pune, India, to describe the epidemiology of neonatal bloodstream infections (BSIs). All neonates admitted to the NICU were enrolled. The primary outcome was BSI, defined as positive blood culture. Early-onset BSI was defined as BSI on day of life (DOL) 0-2 and late-onset BSI on DOL 3 or later. RESULTS: From 1 May 2017 until 30 April 2018, 4073 neonates were enrolled. Among at-risk neonates, 55 (1.6%) developed early-onset BSI and 176 (5.5%) developed late-onset BSI. The majority of BSIs were caused by gram-negative bacteria (GNB; 58%); among GNB, 61 (45%) were resistant to carbapenems. Klebsiella spp. (n = 53, 23%) were the most common cause of BSI. Compared with neonates without BSI, all-cause mortality was higher among neonates with early-onset BSI (31% vs 10%, P < .001) and late-onset BSI (24% vs 7%, P < .001). Non-low-birth-weight neonates with late-onset BSI had the greatest excess in mortality (22% vs 3%, P < .001). CONCLUSIONS: In our cohort, neonatal BSIs were most commonly caused by GNB, with a high prevalence of AMR, and were associated with high mortality, even in term neonates. Effective interventions are urgently needed to reduce the burden of BSI and death due to AMR GNB in hospitalized neonates in LMIC.

Implementation of the Comprehensive Unit-Based Safety Program to Improve Infection Prevention and Control Practices in Four Neonatal Intensive Care Units in Pune, India.

Objective: To implement the Comprehensive Unit-based Safety Program (CUSP) in four neonatal intensive care units (NICUs) in Pune, India, to improve infection prevention and control (IPC) practices. Design: In this quasi-experimental study, we implemented CUSP in four NICUs in Pune, India, to improve IPC practices in three focus areas: hand hygiene, aseptic technique for invasive procedures, and medication and intravenous fluid preparation and administration. Sites received training in CUSP methodology, formed multidisciplinary teams, and selected interventions for each focus area. Process measures included fidelity to CUSP, hand hygiene compliance, and central line insertion checklist completion. Outcome measures included the rate of healthcare-associated bloodstream infection (HA-BSI), all-cause mortality, patient safety culture, and workload. Results: A total of 144 healthcare workers and administrators completed CUSP training. All sites conducted at least 75% of monthly meetings. Hand hygiene compliance odds increased 6% per month [odds ratio (OR) 1.06 (95% CI 1.03-1.10)]. Providers completed insertion checklists for 68% of neonates with a central line; 83% of checklists were fully completed. All-cause mortality and HA-BSI rate did not change significantly after CUSP implementation. Patient safety culture domains with greatest improvement were management support for patient safety (+7.6%), teamwork within units (+5.3%), and organizational learning-continuous improvement (+4.7%). Overall workload increased from a mean score of 46.28 ± 16.97 at baseline to 65.07 ± 19.05 at follow-up (p < 0.0001). Conclusion: CUSP implementation increased hand hygiene compliance, successful implementation of a central line insertion checklist, and improvements in safety culture in four Indian NICUs. This multimodal strategy is a promising framework for low- and middle-income country healthcare facilities to reduce HAI risk in neonates.

Prevalence and perceptions of infant massage in India: study from Maharashtra and Madhya Pradesh states.

BACKGROUND: Knowledge of the prevailing infant care practices and their effects is important to inform practice and public programs. Infant massage is a traditional practice in India but remains less studied. This study was conducted to study the prevalence and perceptions of infant massage practices in two states of India. METHODS: A total of 1497 caretakers of children under 18 months of age were interviewed in a cross-sectional study at immunisation units of medical schools in Maharashtra (MH) and Madhya Pradesh (MP) states and through home visits in villages in MH during March through August 2018. RESULTS: Infant massage was a prevalent practice (93.8% [95%CI: 92.4,94.9]) in both study states - 97.9%[95%CI:96.9,98.8] in MH and 85.3%[95%CI: 81.9,88.3] in MP - and the prevalence did not vary between male (94.5%) and female (93.5%) infants (p = 0.44). Massage was mostly initiated in the first week of life (82%); it is widely viewed as a traditional practice. It was common to massage the baby once daily (77%), before bathing (77%), and after feeding (57%). Massage was mostly conducted using oils (97%). In MH, preferred oils were a sesame oil-based proprietary traditional medicine oil (36%) and coconut oil (18%) while olive (29%) and mustard (20%) oils were most popular in MP. Commonly reported application techniques included gentle massage with minimal pressure, pressing (30%) and manually stretching certain joints (60%). Commonly reported perceived benefits of infant massage included increased bone strength, better sleep and growth, while no harm was perceived (95%). CONCLUSION: Infant oil massage is a highly prevalent traditional practice in MH and MP. Clear guidance on the use of massage, choice of oil, and techniques for application is required to optimize benefits and minimize risks of this popular traditional practice.

Immunogenicity and safety of an intramuscular split-virion quadrivalent inactivated influenza vaccine in individuals aged ≥ 6 months in India.

A quadrivalent split-virion inactivated influenza vaccine (IIV4; Fluzone® Quadrivalent, Sanofi Pasteur) has been available in the US since 2013 for individuals aged ≥ 6 months. Here, we describe the results of an open-label, multicenter trial (WHO Universal Trial Number U1111-1143-8370) evaluating the immunogenicity and safety of IIV4 in Indian children aged 6-35 months and 3-8 years, adolescents aged 9-17 years, and adults aged ≥ 18 years (n = 100 per group). Post-vaccination hemagglutination inhibition titers for all strains in all age groups were ≥ 8 fold higher than at baseline (range, 8-51). At least 70% of participants in all age groups seroconverted or had a significant increase in titer for each strain. The most common solicited reactions were injection-site pain and tenderness, plus fever in participants 6-23 months and myalgia in older children and adolescents. All injection-site reactions and most systemic reactions were grade 1 or 2 and resolved within 3 days. Only three vaccine-related unsolicited adverse events were reported, all of which were grade 1 or 2 and transient. No immediate adverse events, adverse events leading to study discontinuation, adverse events of special interest, or serious adverse events were reported. This study showed that IIV4 was well tolerated and highly immunogenic in all age groups. This adds important data on the safety, tolerability, and immunogenicity of influenza vaccines in India.

Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine in Children 6-17 Years of Age in India: An Open-label Trial.

In an open-label study in India, 200 healthy participants 6-17 years of age received 13-valent pneumococcal conjugate vaccine (PCV13). PCV13 elicited robust functional antibody immune responses. No adverse events were reported by caregivers at the 1-month follow-up visit. The immunogenicity results together with the known favorable risk-benefit profile of PCV13 support extension of the indication to this age group in India.

Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized, controlled phase III study in Indian infants.

BACKGROUND: Rotavirus remains the leading cause of diarrhoea among children <5years. We assessed immunogenic non-inferiority of a tetravalent bovine-human reassortant rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5. METHODS: Phase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6-8, 10-12, and 14-16weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above -10%. Each subject was evaluated for solicited adverse events 7days and unsolicited & serious adverse events 28days following each dose of vaccination. RESULTS: Of 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, -14.08% (95%CI: -20.4; -7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the -10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles. CONCLUSION: BRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants.

Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants.

Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6-10-14 weeks (W) of age (n = 112) or 2-4-6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6-10-14W group: 25.2%; 2-4-6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6-10-14W group) and 22.3% (2-4-6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule.

Airway Diseases Education and Expertise (ADEX ) in Pediatrics: Adaptation for Clinical Practice in India.

JUSTIFICATION: Asthma and allergic rhinitis together are part of the concept of one airway, one disease or united airway disease. The management of allergic airway diseases should address this united concept and manage the issue by educating the patients and their parents and health care providers, along with environmental control measures, pharmacotherapy and immunotherapy. Here, we present recommendations from the module of Airway Diseases Education and Expertise (ADEX) that focused on allergic rhinitis, asthma and sleep disorder breathing as a single entity or Allergic Airway Disease. PROCESS: A working committee was formed by the collaboration of Pediatric Allergy Association of India (PAAI) and Indian Academy of Pediatrics (IAP) Allergy and Applied Immunology chapter to develop a training module on united airway disease. OBJECTIVE: To increase awareness, understanding and acceptance of the concept of United Airway disease and to educate the primary health care providers for children and public health officials, in the management of united airway diseases. RECOMMENDATIONS: Recommendations for diagnosis, management and follow-up of Allergic airway disease are presented in this document. A better compliance by linking education of child, parent, grandparents and other health care providers, and scientific progress by collaboration between practitioners, academicians, researchers and pharmaceutical companies is suggested.

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.