Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14™) administered to 6-8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study.

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE's 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13). METHODS: This is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6-8 weeks old healthy infants at 6-10-14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study. FINDINGS: The safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13. INTERPRETATIONS: BE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine. The study was prospectively registered with clinical trial registry of India - CTRI/2020/02/023129.

Efficacy and Tolerability of Twice-Daily Dosing Schedule of Deferasirox in Transfusion-Dependent Paediatric Beta-Thalassaemia Patients: A Randomized Controlled Study.

Background: Deferasirox has proved good efficacy and acceptable safety for the management of thalassaemia patients. However, some patients are unresponsive or intolerant to once-daily administration of deferasirox even at a high dose. The current study evaluated the effectiveness and tolerability of twice-daily dosing of deferasirox among transfusion-dependent paediatric beta-thalassaemia patients. Methods: This prospective randomized single-blinded parallel study included all transfusion-dependent paediatric beta-thalassaemia patients prescribed with deferasirox, who visit the study site for their regular blood transfusions and follow-up. The enrolled patients were randomized into intervention and control groups by using a simple block randomization method. In the intervention group, the once-daily dosing of deferasirox was changed to twice-daily dosing with the same total daily dose. Whereas, in the control group, the patients continued with the once-daily deferasirox dosing. The serum ferritin levels of both groups were determined on the enrolment day and after 6 months of follow-up. Results: Forty-one patients were included for analysis. A statistically significant mean decrease in serum ferritin levels was detected in the intervention group, while the serum ferritin levels of the control group significantly increased from baseline. The twice-daily dosing of deferasirox was better tolerated by the thalassaemia patients when compared to once-daily dosing. Conclusion: This study concludes that twice-daily dosing of deferasirox with the same total daily dose significantly enhances the iron chelation efficacy and tolerability among transfusion-dependent paediatric beta-thalassaemia patients when compared to once-daily regimen.

COVID-19 vaccine triggered autoimmune hepatitis: case report.

Autoimmune hepatitis (AIH) is a non-contagious, chronic, inflammatory autoimmune disease in which one's own immune system attacks healthy, normal hepatic cells. The exact cause of AIH is unknown; however, the combination of genetic, environmental (eg, drugs and natural infection) and immunological factors may lead to AIH. AIH may also be potentiated with the use of vaccines: this case reports one such event following immunisation, along with 1 year of follow-up. A female patient in her late 20s presented to the hospital with yellowish discolouration of eyes, urine and stools. Her medical history revealed that she had been vaccinated with the first dose of a COVID-19 vaccine 10 days earlier. She had a history of asymptomatic COVID-19 infection 3 months ago and a history of chronic analgesic consumption for migraine. She was diagnosed as having AIH through extensive clinical and laboratory workup. This case may be an immediate enhancement of a hidden autoimmune disorder triggered by the vaccination. This adverse event following immunisation has an adequate temporal relationship with her COVID-19 vaccine. The causality can be categorised as 'indeterminate' and may be considered as a potential signal following COVID-19 vaccination.

A Rare Pediatric Case of Cefixime Induced Toxic Epidermal Necrolysis.

Cefixime is a third-generation cephalosporin that has been used for the treatment of a wide range of infections in children and adults. The incidence of cefixime induced toxic epidermal necrolysis (TEN) is less than 2% in adults, but it is infrequent among pediatric patients. We report a rare case of cefixime induced TEN in a 7-year-old boy. In this case, the child presented with symptoms of TEN after 2 days of administration of cefixime. This case highlights the need to select structurally different antibiotics in case of antibiotic-induced severe cutaneous adverse reaction (SCAR) to avoid recurrence of SCAR. Furthermore, concluded that irrational use of antibiotics could be disastrous as it can result in TEN as the incidence of antibiotics induced TEN ranges from 29% to 42%.

Adverse events following COVID-19 vaccination: first 90 days of experience from a tertiary care teaching hospital in South India.

BACKGROUND: The COVID-19 vaccination program was introduced in India on 16 January 2021. The Government-issued fact sheet was the only source of information regarding Adverse Events Following Immunizations (AEFIs) for these vaccines. The objective of this study was to assess the AEFIs reported following COVID-19 vaccination in a tertiary care teaching hospital. MATERIALS AND METHODS: The spontaneous reporting method was used for data collection for a period of 3 months. A data collection form was designed to collect the data from the study population who reported adverse events. Collected data were analyzed and categorized by severity and seriousness. The causality assessment team performed causality assessment of the AEFIs using the World Health Organization's causality assessment algorithm. RESULTS: A total of 11,656 doses of COVID-19 vaccine were administered at the study site during the study period, of which 9292 doses were COVISHIELD™ and 2364 doses were COVAXIN™. In all, 445 AEFIs were reported from 269 subjects with an incidence rate of 3.48%. The majority of the subjects with AEFIs belonged to the age group of 18-45 years. Out of the total 445 AEFIs, 418 AEFIs were expected as per the fact sheets, 409 with COVISHIELD™ and 9 with COVAXIN™. Most of the AEFIs [62.02% (n = 276)] were observed at the system organ class of 'General disorders and administration site conditions'. After the causality assessment, out of 433 AEFIs to COVISHIELDTM vaccine, 94.22% (n = 408) of events were categorized to have 'consistent causal association with immunization'. Out of 12 adverse events following COVAXIN™, 8 (66.66%) events were categorized as 'consistent causal association with immunization'. All of them recovered from their adverse events without any sequelae. CONCLUSION: Spontaneous reporting is one of the cheapest methods that can be used for the reporting of AEFI. This method helps health care professionals to identify rare events and potential signals.

A Rare Case of Dapsone Hypersensitivity Syndrome and Leukemoid Reaction With Coexisting Hepatitis E in a Pediatric Patient.

Dapsone is extensively used for a variety of infectious, immunological, and hypersensitivity disorders. Dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome (DHS), which is potentially fatal. DHS is characterized by triad of eruptions, fever, and organ involvement (including liver, kidney, hematological system, etc.). DHS can develop several weeks to as late as 6 months after treatment initiation with dapsone. Here, we report a case of DHS and leukemoid reaction with coexisting hepatitis E in a 10-year-old girl. Three weeks prior to the current admission, she was treated with dapsone (1 mg/kg/day in two divided doses) for 8 days by a local doctor for lichen nitidus. She was managed successfully for DHS with intravenous (IV) steroids followed by the oral steroid. This case is being reported to highlight the importance to ensure timely diagnosis of DHS and its appropriate management. Patients started on dapsone for various clinical conditions need to be observed carefully for the development of the DHS. If this occurs, DHS can be mistaken for the progression of the primary disease. If dapsone is not withdrawn, it could have deleterious and potentially fatal effects due to major organ dysfunction.

Impact of educational intervention on the best immunization practices among practicing health care professionals in a south Indian city.

BACKGROUND AND AIMS: Maintaining the quality and safety of immunization is as important as the efficacy of vaccines in vaccine-preventable diseases (VPD) programs. The aim of this study was to determine the problems associated with different stages of vaccine use and to assess the outcome of an educational intervention on safety and quality use of vaccines among health care providers. METHODS: A pilot prospective interventional study was conducted over a period of 2 years at 271 sites in Mysuru, India. The study population was health care professionals (HCPs) involved in immunization and a sample of parents (one per site). A validated questionnaire was used as a study tool. An educational intervention on best immunization practice was conducted for the enrolled HCPs and the impact of the educational intervention was assessed using the study tool after 3 weeks. RESULTS: The total number of the study population was 594 (323 HCPs and 271 parents). Of these, 41.49% were working at community health care facility and 33.13% were enrolled from primary care centers. There were statistically significant improvements in post interventional assessment of all stages of the immunization process including storage (p -0.001), transportation (p -0.001), administration (p 0.001), monitoring and reporting of adverse events following immunization (AEFIs) (p -0.001), knowledge of AEFIs (p 0.001), and HCP-parent communication (p 0.001). AEFI reporting improved by 30% in the post education phase. CONCLUSION: Continuous education and motivation can result in positive behavioral changes on best immunization practices amongst HCPs involved in immunization, which may help to improve and maintain the safety and quality use of vaccines in immunization centers irrespective of the type of facility.

Impact of indirect education on knowledge and perception on cervical cancer and its prevention among the parents of adolescent girls: an interventional school-based study.

BACKGROUND: India has almost 225 million adolescent girls and they seem to be at a disadvantage, both economically and by their lack of knowledge on human papilloma virus (HPV) vaccine, when compared to adolescent girls of other Asian countries. AIM: To assess the prevalence of HPV vaccination and to identify the impact of education in improving the knowledge and perception about the HPV infection and vaccination among the parents of adolescent girls. METHODOLOGY: The prospective interventional study was conducted in four schools within a South Indian City, Mysuru. The informed consent form and the questionnaire were sent home with the identified adolescent girls during the pre-interventional phase. Educational sessions were conducted for the students in their school and an education leaflet was distributed to their parents. Three weeks later, questionnaires were re-administered to the parents via the enrolled girls and their responses were collected. RESULTS: The prevalence of HPV vaccination in the study population was 4.4%. There was a statistically significant improvement in knowledge in the post-interventional phase of the study (p = 0.001), but could not identify a significant change in their perception (p = 0.479). Parents belonging to the socioeconomic class of upper middle and upper lower showed better improvement at the end of the study, with a percentage improvement of 58.93% and 48.44%, respectively. CONCLUSION: The study proved that the healt care professional can target school children to communicate effectively to their parents on the importance of HPV vaccine as the study clearly observed a positive behavioral change among the study population.

Effectiveness and tolerability of twice daily dosing of deferasirox in unresponsive and intolerant transfusion-dependent beta-thalassemia patients: A narrative review.

Chronic iron overload in beta-thalassemia patients after continuous blood transfusions has caused notable morbidity and mortality in these patients. The once-a-day oral iron chelator, deferasirox has established efficacy and bearable safety in adults and pediatric thalassemia patients. It is now extensively used for the management of transfusional hemosiderosis. However, a number of studies have revealed a few patients continued to be none respondent or intolerant toward the once-a-day regimen of deferasirox even after the administration of maximum dose recommended by the World Health Organization. In the literature, there were three studies showing the boon of twice in a day dosing of deferasirox among transfusional-dependent beta thalassemia patients. Therefore, a nonsystematic review was conducted on above three studies to ascertain the enhanced effectiveness and tolerability of twice per day regimen of deferasirox with the same total dose as that of once daily regimen of deferasirox in unresponsive or intolerant transfusion-dependent beta-thalassemia (TDT) patients. All the above studies concluded that the twice per day regimen of deferasirox was more efficacious and tolerable among TDT patients when compared to the once-a-day regimen with the same total daily dose. Although there was a significant good results from these studies, there is a need to conduct either muticenter study or randomized control study in a larger number of patients for the better confirmation of the results as all the above studies were conducted in the small number of TDT patients.

Active surveillance of adverse events following immunization (AEFI): a prospective 3-year vaccine safety study.

BACKGROUND: Vaccines used in national immunization programs are considered safe and effective but immunization safety has become as important as the efficacy of vaccination programs. The objective of the study was to detect adverse events following immunization (AEFIs) to all vaccines administered to a pediatric population in India. METHODS: The prospective active vaccine safety surveillance study enrolled eligible children in the age group 0-5 years receiving vaccination from the immunization center at JSS Hospital, Mysuru. Study participants were monitored at the site for 30 min following vaccination and a telephonic survey was made after 8 days to identify all AEFIs. Causality assessment of the AEFIs were done using a new algorithm developed by the safety and vigilance department of the World Health Organization. RESULTS: The incidence of reported AEFIs was 13.7%. The most frequently reported AEFI was fever (n = 3095, 93.2%) with an incidence of 109.7 per 1000 doses of vaccine administered, followed by persistent crying (n = 69, 2.4 per 1000 doses of vaccine) and diarrhea (n = 57, 2.0 per 1000 doses of vaccine). The majorly implicated vaccine for AEFIs was Pentavac® followed by BCG. Consistent causal association to immunization was observed in 93.4% of cases. CONCLUSIONS: A high incidence rate of AEFI was observed in our study population when compared with previous published studies. AEFI surveillance studies help to detect changes in the frequency of adverse events, which may be an alert to consider vaccine quality or identify a specific risk among the local population.

Probable blueberry-induced haemolysis in a G6PD deficient child: A case report.

BACKGROUND: Blueberry is a North American native fruit increasingly popular as a source of health-promoting bioactive compounds. However, there is evidence in the literature stating that blueberries should be avoided in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. CASE PRESENTATION: We report the first case of a G6PD deficient child who developed haemolysis approximately after half a day following the intake of fresh blueberry. He presented with the complaints of the passage of orange coloured urine and hurried breathing. The child had haemoglobin of 7.9 g/dl on admission day and the laboratory results were indicative of haemolytic process. OUTCOMES AND IMPLICATIONS: During the stay in the hospital, the child was managed conventionally, and he improved both clinically and symptomatically. The child was discharged after four days of treatment and diet counselling was provided to his parents. RECOMMENDATIONS: Our report should encourage further research on this fruit regarding the mechanism behind the development of haemolytic anaemia. Also, it is important in the case of G6PD deficient patients to take lifelong precautions to avoid the foods that can trigger haemolysis.