Population-Based Surveillance of Pneumococcal Infections in Children with Sickle Cell Disease before and after Prevnar 7® and Prevnar 13® Licensure: Implications for Expanded Vaccination

Before prophylactic antibiotic use, approximately 1/10 children <5 years old with sickle cell disease (SCD) developed invasive pneumococcal disease (IPD) with a high risk of meningitis and death. Although the emergence of penicillin-resistance in IPD threatened benefits of penicillin prophylaxis, after licensure of the 7-valent pneumococcal polysaccharide vaccine (PCV7) in 2000, IPD rates in children with SCD decreased by over 2/3. In 2010, PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C, 23F) was licensed in children, and in 2021, two additional conjugated vaccines were approved for use in adults: PCV15 (VAXNEUVANCE®, PCV13+: 22F, 33F) and PCV20 (PREVNAR20®, PCV13+: 8, 10A, 11A, 12F, 15B, 22F, 33F). IPD rates in children with SCD over 24 years in Atlanta were evaluated to describe trends in age of infection, frequency of antibiotic resistance, non-vaccine IPD serotype distribution after vaccine licensures, and estimates for serotype coverage by newer vaccines. IPD among children with SCD, ages 0 to 4 years and 5 to 9 years, residing in the Metropolitan area of Atlanta, Georgia, USA, from 1/1/1994 through 7/31/2018, were compared to the general population. The Centers for Disease Control and Prevention (CDC)-funded Georgia Emerging Infections Program (GA EIP) Active Bacterial Core Surveillance network included initially 8 counties in 1994 and from 1997 onward, 20 counties (total populations of approximately 3.8 and 5.1 million, respectively). Two registries of patients with SCD seen at least once at one of 3 pediatric hospitals serving the region were merged and matched with GA EIP data. The serotyping and antibiotic susceptibility testing were conducted at the CDC. The study was approved by the Emory University Institutional Review Board. Data from 3 periods: pre PCV period (94-99), PCV7 period (00-09) and PCV13 period (10-18) were analyzed. Compared to the pre PCV period, overall, IPD rates decreased in children with SCD vs 91% in the RP for 0-4 years; and 80% in children with SCD vs 78% in the RP for 5-9 years (table1). The difference in IPD rates between patients with SCD and the general population increased over time: pre PCV period, relative risk (RR)=24.22 (95 % Confidence Interval [CI] 17.43,32.88), P<.001; PCV 7 period, RR=32.17 (95 %CI 22.17,45.37), P<.001; PCV 13 period, RR=39.18 (95 %CI 22.35,64.69) P<.001. Meningitis and deaths from IPD decreased significantly in all populations examined but remained significantly higher in patients with SCD compared to RP (table 2). The mean age at IPD diagnosis for the 3 periods examined increased both in SCD and in the RP. For those with SCD (n=50), pre-PCV7 period mean age was :2.7 standard deviation (+/-) 2.3 years; for the PCV 13 period: n=19; 3.7 years +/-2.2 years p= 0.0877; for the RP: Pre-PCV period: n=1025; 1.3 +/-1.6 years; PCV 13 period: n=213; 2.2 +/-2.3 years. Overall absolute IPD rates declined for all age groups examined (table 1). Prior to PCV7 licensure, IPD in patients with SCD were significantly less likely to be penicillin susceptible (MIC <0.06 µg/mL) compared to the RP: 41.9% (18/43) vs 60.0% (476/793) RR=0.70 (95% CI 0.49,1.00), p=0.025. This difference was no longer present after PCV licensure (PCV 13 period , SCD 52.9% [9/17], vs RP 48.6% [70/144]). Non PCV serotypes IPD rates increased after PCV7 licensure but remained stable after PCV13 licensure; 16% of non PCV13 serotypes during all time periods are included in PCV15, whereas PCV20 may cover between 29% and 50% depending on related serotypes cross protection (table3). Although significantly less frequent compared with pre-PCV-era, IPD can be severe in patients with SCD. Increase in IPD age was seen in both SCD and RP. Lower rates of penicillin non-susceptibility may may reflect lower exposure to penicillin prophylaxis. Newer vaccines may offer expanded coverage for children with SCD. Ongoing surveillance will help determine their effect. Vaccines that cover all serotypes are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

OPPORTUNITIES FOR SCIENCE GROWTH AMIDST THE COVID-19 PANDEMIC

Dear reader, The 21st year of the 21st century will go down in history as the boundary that divided the coronavirus (COVID-19) pandemic and post-pandemic world. It is the efforts of medical academic institutions and the dedicated medical professionals all around the world that have demonstrated a high readiness to overcome the modern challenges of the pandemic that has engulfed all the humanity. The world has received a new vector in the development of science to understand the strategy to combat the "plague" of the 21st century. First, it is the creation of specific prevention of COVID-19 at a record pace: on January 10, 2020, the information on the sequencing of SARS-CoV-2 virus (also known as 2019-nCoV) was received, and on December 11, 2020, vaccination against COVID-19 started among healthcare professionals in the United States. Currently, more than 2 billion people worldwide have been vaccinated against SARS-CoV-2 [1]. No deaths have been reported in the UK for 25 days (as of June 3, 2021), nevertheless changes in the SARS-CoV-2 genome and the emergence of new virus strains continue, and reports from high-incidence regions such as India are still alarming. The pandemic of the SARS-CoV-2 virus, which as of today has infected more than 171 million and killed more than 3.5 million people globally, has been a major test for newer vaccines that differ from the previous ones. The organization and conduct of clinical research are becoming more important than ever. The article by Andriy Cherkas is dedicated to this topic [2]. Pfizer, Moderna, AstraZeneca and Johnson-Johnson vaccines developed and tested in clinical trials were made possible following the results of fundamental research by Katalin Karikó and Drew Weisman, which began almost 30 years ago [2] and ushered in the fifth era of vaccination [3, 4].

Introduction of newer vaccines in national immunization programme in India: a challenge

Immunization significantly reduces the incidence of communicable diseases in children and improves the quality of life of children. Many developing countries including India, is lagging behind in sufficient coverage of routine immunization among children. Currently, India manufactures about 43% of the global vaccines. Newer vaccine research can be promoted only when there is conducive environment, funding and subsequent chances of vaccine being introduced in the universal immunization programme (UIP). Government of India has a National Vaccine Policy which was developed after the recommendations made by National Technical Advisory Group on Immunization.This policy addresses the issues to streamline the process on new and underutilized vaccine and also suggests to strengthen the institutional framework, processes, evidence base and framework required for decision making for strengthening of UIP in India. Government of India laid some standard guidelines and few criteria for the introduction of new vaccine in UIP. While planning to introduce a newer vaccine, cost effectiveness of the vaccination program should be kept in mind.

Awareness and attitudes of mothers towards new vaccines in the childhood vaccination programme in delhi state: a cross sectional study

Background: With the introduction of newer antigens in the childhood immunization programme in several states, the nationwide UIP is eventually going to be further expanded to increase the number of diseases against which children will be protected through the vaccination programme. However, despite the best intentions of the government, a poor awareness of the new vaccines among the caregivers may defeat this purpose and only result in poor coverage and poor uptake. This study was carried out to assess the awareness of mothers regarding the new vaccines introduced in the childhood vaccination programme in Delhi State. Methods: The study was conducted in the immunization clinic of a tertiary care hospital of Delhi. A total sample of 388 mothers was interviewed. The data was analyzed using SPSS ver 20. Results: Only 18.3% (95% CI, 14.76-22.46) of the participants were aware that newer vaccines have been introduced into the programme. 48.2% (95% CI 43.27- 53.16) of the respondents were unaware about the same, while 33.5% (95% CI, 28.99-38.35) claimed to have heard about it but were not sure whether newer vaccines had been introduced. It was observed that as the education status of mothers improved, their awareness regarding newer vaccines in the programme also increased. The knowledge regarding age of administration, number of doses etc. was very poor. However multiple pricks during a single vaccination visit was not a disincentive for the mother to get the child vaccinated. The willingness to buy a vaccine that was not available free of cost from the hospital, increased with increasing education level of the mother. Conclusions: There is a requirement of focused publicity campaigns to increase the awareness and thereby uptake of the new vaccines among caregivers.

Practicing pediatrician’s perspective on the immunization schedules: a short survey

Background: The practicing pediatrician is left in a dilemma regarding the need for the newer vaccines and conflicting scientific data from vaccine manufacturers. This study is aimed at evaluating the pediatrician’s perspective regarding the immunization schedule.Methods: A brief questionnaire was framed to bring out the most common issues faced by the pediatrician in immunization schedules.Results: About 77 percent of respondents felt that our National Immunization is inadequate. About 37 percent and 28 percent of respondents felt that the next vaccine that is to be introduced in the National Immunization Schedule is Pneumococcal vaccine and Rotavirus vaccine respectively. Nearly half of the respondents trusted IAP as the single most important influencing factor in choosing a newer vaccine. About 76 percent of respondents felt that the immunization schedules are influenced by vaccine makersConclusions: The practicing pediatrician who had always looked at IAP Immunization schedule as his bible in office practice is now beginning to doubt its authenticity. The threat of not having a consensus on Immunization is detrimental. It is the duty of IAP to clear the air regarding the controversies it had faced in the immunization schedule.