Serum bactericidal activity against circulating and reference strains of meningococcal serogroup B in the United States: A review of the strain coverage of meningococcal serogroup B (MenB) vaccines in adolescents and young adults.

Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and adolescents/young adults, and the most common type of IMD is caused by serogroup B (MenB). MenB is preventable among adolescents and young adults with the use of two licensed vaccines, MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Collegeville, PA) and MenB-4C (Bexsero®; GSK Vaccines, Srl, Italy). Because the effectiveness of MenB vaccination is dependent on broad vaccine coverage across circulating disease-causing strains, we reviewed the available clinical and real-world evidence regarding breadth of coverage of the two licensed vaccines in adolescents and young adults in the United States. Both vaccines protect against various MenB strains. More controlled data regarding breadth of coverage across MenB strains are available for MenB-FHbp compared with MenB-4C, whereas more observational data regarding US outbreak strain susceptibility are available for MenB-4C.

Control and Prevention of Invasive Pneumococcal Disease: A Current and Historical Perspective.

Although significant progress has been made in reducing the incidence of invasive pneumococcal disease (IPD) in children, IPD remains a continued threat. Since the introduction of pneumococcal conjugate vaccines (PCVs), rates of IPD and non-IPD have substantially decreased. However, serotype replacement reversed some of the benefits of PCV7 and, more recently, PCV13. Several replacement serotypes are antibiotic resistant, which is a cause of concern for providers. The introduction of the higher-valency conjugate vaccines PCV15 and PCV20 is expected to provide greater serotype coverage; unfortunately, these vaccines do not include some of the recently emerged serotypes. Recommendations for the use of the 23-valent polysaccharide vaccine in high-risk populations may be modified because of the effectiveness of the newer PCVs. Pediatricians must be aware of the new vaccine strategies for the prevention of IPD and the manifestations of IPD so that prompt empirical therapy can be initiated when treatment is required. [Pediatr Ann. 2023;52(3):e96-e101.].

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.

BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. METHODS: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. RESULTS: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. CONCLUSIONS: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Vaccine Development: From Laboratory to Policy.

Vaccines are one of the greatest public health achievements, protecting children and adults against numerous infectious diseases; however, the complex, rigorous process of vaccine development is unknown to many. A candidate vaccine undergoes extensive evaluation of safety and efficacy to meet licensure requirements before recommendations for use become policy. This time-consuming process involves an intricate collaboration among academia, public and private organizations, and federal agencies to ensure that safety is prioritized in every step. Vaccine safety continues to be monitored after licensure through a robust system. Yet, vaccine hesitancy remains a major challenge, especially now with the coronavirus disease 2019 (COVID-19) pandemic and concerns about the speed with which candidate vaccines are being developed. This article reviews the vaccine development process and the systems in place to ensure safety and effectiveness. A better understanding of these topics is necessary to address concerns and improve public acceptance of all vaccines, particularly COVID-19 vaccines. [Pediatr Ann. 2020;49(12):e509-e515.].

Association of sexually-transmitted infection and African-American race with Streptococcus agalactiae colonization in pregnancy.

BACKGROUND: Group B Streptococcus (GBS) remains a significant cause of neonatal infection, but the maternal risk factors for GBS colonization remain poorly defined. We hypothesized that there may be an association between antibiotic exposure during pregnancy and GBS colonization and/or the presence of inducible clindamycin resistance (iCLI-R) in GBS isolates from GBS-colonized pregnant women. METHODS: A retrospective cohort study was performed at Louisiana State University Health Sciences Center - Shreveport including demographic and clinical data from 1513 pregnant women who were screened for GBS between July 1, 2009 and December 31, 2010. RESULTS: Among 526 (34.8%) women who screened positive for GBS, 124 (23.6%) carried GBS strains with iCLI-R (GBS-iCLI-R). While antibiotic exposure, race, sexually-transmitted infection (STI) in pregnancy, GBS colonization in prior pregnancy and BMI were identified as risk factors for GBS colonization in univariate analyses, the only independent risk factors for GBS colonization were African-American race (AOR = 2.142; 95% CI = 2.092-3.861) and STI during pregnancy (AOR = 1.309; 95% CI = 1.035-1.653). Independent risk factors for GBS-iCLI-R among women colonized with GBS were non-African-American race (AOR = 2.13; 95% CI = 1.20-3.78) and younger age (AOR = 0.94; 95% CI = 0.91-0.98). Among GBS-colonized women with an STI in the current pregnancy, the only independent risk factor for iCLI-R was Chlamydia trachomatis infection (AOR = 4.31; 95% CI = 1.78-10.41). CONCLUSIONS: This study identified novel associations for GBS colonization and colonization with GBS-iCLI-R. Prospective studies will improve our understanding of the epidemiology of GBS colonization during pregnancy and the role of antibiotic exposure in alterations of the maternal microbiome.

The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19.

There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its 'oxidative immune-metabolic' physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.

Medical Foods for Inborn Errors of Metabolism: History, Current Status, and Critical Need.

Successful intervention for inborn errors of metabolism (IEMs) is a triumph of modern medicine. For many of these conditions, medical foods are the cornerstone of therapy and the only effective interventions preventing disability or death. Medical foods are designed for patients with limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foods or nutrients, whereby dietary management cannot be achieved by modification of the normal diet alone. In the United States today, access to medical foods is not ensured for many individuals who are affected despite their proven efficacy in the treatment of IEMs, their universal use as the mainstay of IEM management, the endorsement of their use by professional medical organizations, and the obvious desire of families for effective care. Medical foods are not sufficiently covered by many health insurance plans in the United States and, without insurance coverage, many families cannot afford their high cost. In this review, we outline the history of medical foods, define their medical necessity, discuss the barriers to access and reimbursement resulting from the regulatory status of medical foods, and summarize previous efforts to improve access. The Advisory Committee on Heritable Disorders in Newborns and Children asserts that it is time to provide stable and affordable access to the effective management required for optimal outcomes through the life span of patients affected with IEMs. Medical foods as defined by the US Food and Drug Administration should be covered as required medical benefits for persons of all ages diagnosed with an IEM.

In pursuit of control and elimination: update on hepatitis A and B epidemiology and prevention strategies.

PURPOSE OF REVIEW: This review describes the impact of recommendations for routine immunization of infants and children against hepatitis A and hepatitis B, the changing epidemiology of these infections, and the remaining challenges to controlling or eliminating these diseases in the United States. RECENT FINDINGS: Rates of hepatitis A and B have significantly declined because of childhood vaccination programs and long-term protection provided by infant immunization. However, hepatitis A immunization rates remain lower than other vaccines, and outbreaks continue to occur in part due to a growing number of susceptible adults. The Advisory Committee on Immunization Practice has updated pre and postexposure prophylaxis and travel recommendations for hepatitis A prevention in young infants, as well as recommendations to reduce ongoing perinatal transmission of hepatitis B. SUMMARY: Pediatric healthcare providers should continue to immunize all infants against hepatitis A and B and ensure that no child outgrows the pediatric practice without being vaccinated. To address hepatitis A, providers should be aware of new recommendations for unimmunized travelers, use vaccines to prevent and control outbreaks, and ensure postexposure prophylaxis. Universal vaccination of infants against hepatitis B should begin before hospital discharge. The prevention of perinatal transmission is critical for control and possible eradication of hepatitis B.

Glutathione Stimulates Vitamin D Regulatory and Glucose-Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency.

AIMS: 25-Hydroxyvitamin D [25(OH)VD] deficiency/inadequacy is a major public health issue affecting more than 1 billion people worldwide. A convincing association exists between low levels of circulating 25(OH)VD and the poor health outcomes associated with chronic diseases. However, high supraphysiological doses of VD are needed to achieve the required 25(OH)VD levels in the blood, because many subjects respond poorly to supplementation. RESULTS: This study reports a link between 25(OH)VD deficiency and a reduction in glutathione (GSH) in obese adolescents. The improvement in GSH status that results from cosupplementation with VD and l-cysteine (LC; a GSH precursor) significantly reduced oxidative stress in a mouse model of 25(OH)VD deficiency. It also positively upregulated VD regulatory genes (VDBP/VD-25-hydroxylase/VDR) in the liver and glucose metabolism genes (PGC-1α/VDR/GLUT-4) in muscle, boosted 25(OH)VD, and reduced inflammation and insulin resistance (IR) levels in the blood compared with supplementation with VD alone. In vitro GSH deficiency caused increased oxidative stress and downregulation of VDBP/VD-25-hydroxylase/VDR and upregulation of CYP24a1 in hepatocytes and downregulation of PGC-1α/VDR/GLUT-4 in myotubes. This study demonstrates that improvement in the GSH status exerts beneficial effects on the blood levels of 25(OH)VD, as well as on the inflammation and IR in a VD-deficient mouse model. Thus, the VD supplements widely consumed by the public are unlikely to be successful unless the GSH status is also corrected. INNOVATION: These studies demonstrate a previously undiscovered mechanism by which GSH status positively upregulates the bioavailability of 25(OH)VD. CONCLUSION: Supplementation with a combination of VD and LC or GSH precursor, rather than supplementation with VD alone, is beneficial and helps achieve more successful VD supplementation. Antioxid. Redox Signal. 00, 000-000.

Vaccination during pregnancy: first line of defense for expecting mothers and vulnerable young infants.

PURPOSE OF REVIEW: Maternal vaccination is a well-tolerated and effective way to protect mothers, their developing fetuses, and their young infants from infectious diseases. Although influenza vaccine and diphtheria, tetanus, and acellular pertussis (Tdap) vaccine are recommended for all pregnant women, uptake rates in the United States remain low. This review will focus on the rationale, scientific evidence, and perceptions of vaccination during pregnancy. RECENT FINDINGS: Recent studies show that administration of influenza and Tdap vaccines during pregnancy is well tolerated and provides protection to the pregnant woman, her fetus, and young infant. Studies have shown that many pregnant women look to their obstetricians to guide their prenatal care. A strong provider recommendation remains the greatest impetus to increase vaccine uptake. Both healthcare providers and expectant mothers should continue to be educated on the importance and safety of the influenza and Tdap vaccines during pregnancy. SUMMARY: Providers play a central role in advising patients and their families about the importance of maternal vaccination. The strong recommendation of providers and the availability of maternal vaccines in OB/GYN offices are keys to improve vaccine uptake. Attention must be paid to further development of intervention techniques that address unique barriers such as vaccine cost, storage concerns, and misinformation about vaccine safety.

Mandatory influenza vaccination for all healthcare personnel: a review on justification, implementation and effectiveness.

PURPOSE OF REVIEW: As healthcare-associated influenza is a serious public health concern, this review examines legal and ethical arguments supporting mandatory influenza vaccination policies for healthcare personnel, implementation issues and evidence of effectiveness. RECENT FINDINGS: Spread of influenza from healthcare personnel to patients can result in severe harm or death. Although most healthcare personnel believe that they should be vaccinated against seasonal influenza, the Centers for Disease Control and Prevention (CDC) report that only 79% of personnel were vaccinated during the 2015-2016 season. Vaccination rates were as low as 44.9% in institutions that did not promote or offer the vaccine, compared with rates of more than 90% in institutions with mandatory vaccination policies. Policies that mandate influenza vaccination for healthcare personnel have legal and ethical justifications. Implementing such policies require multipronged approaches that include education efforts, easy access to vaccines, vaccine promotion, leadership support and consistent communication emphasizing patient safety. SUMMARY: Mandatory influenza vaccination for healthcare personnel is a necessary step in protecting patients. Patients who interact with healthcare personnel are often at an elevated risk of complications from influenza. Vaccination is the best available strategy for protecting against influenza and evidence shows that institutional policies and state laws can effectively increase healthcare personnel vaccination rates, decreasing the risk of transmission in healthcare settings. There are legal and ethical precedents for institutional mandatory influenza policies and state laws, although successful implementation requires addressing both administrative and attitudinal barriers.

Practical Approaches to Optimize Adolescent Immunization.

With the expansion of the adolescent immunization schedule during the past decade, immunization rates notably vary by vaccine and by state. Addressing barriers to improving adolescent vaccination rates is a priority. Every visit can be viewed as an opportunity to update and complete an adolescent's immunizations. It is essential to continue to focus and refine the appropriate techniques in approaching the adolescent patient and parent in the office setting. Health care providers must continuously strive to educate their patients and develop skills that can help parents and adolescents overcome vaccine hesitancy. Research on strategies to achieve higher vaccination rates is ongoing, and it is important to increase the knowledge and implementation of these strategies. This clinical report focuses on increasing adherence to the universally recommended vaccines in the annual adolescent immunization schedule of the American Academy of Pediatrics, the American Academy of Family Physicians, the Centers for Disease Control and Prevention, and the American Congress of Obstetricians and Gynecologists. This will be accomplished by (1) examining strategies that heighten confidence in immunizations and address patient and parental concerns to promote adolescent immunization and (2) exploring how best to approach the adolescent and family to improve immunization rates.

The Need to Optimize Adolescent Immunization.

The adolescent period heralds the pediatric patient's transition into adulthood. It is a time of dynamic development during which effective preventive care measures can promote safe behaviors and the development of lifelong health habits. One of the foundations of preventive adolescent health care is timely vaccination, and every visit can be viewed as an opportunity to update and complete an adolescent's immunizations.In the past decade, the adolescent immunization schedule has expanded to include 2 doses of quadrivalent meningococcal conjugate vaccine, 1 dose of tetanus, diphtheria, acellular pertussis, absorbed vaccine, 2 or 3 doses of human papillomavirus vaccine, depending on the child's age, and an annual influenza vaccine. In addition, during adolescent visits, health care providers can determine whether catch-up vaccination is needed to meet early childhood recommendations for hepatitis B; hepatitis A; measles, mumps, rubella; poliovirus; and varicella vaccines. New serogroup B meningococcal vaccines are now available for those at increased risk for meningococcal disease; in addition, these serogroup B meningococcal vaccines received a Category B recommendation for healthy adolescents, where individual counseling and risk-benefit evaluation based on health care provider judgements and patient preferences are indicated. This clinical report focuses on the epidemiology of adolescent vaccine-preventable diseases by reviewing the rationale for the annual universally recommended adolescent immunization schedule of the American Academy of Pediatrics, the American Academy of Family Physicians, the Centers for Disease Control and Prevention, and the American Congress of Obstetricians and Gynecologists. In addition, the barriers that negatively influence adherence to this current adolescent immunization schedule will be highlighted.

Update on barriers to human papillomavirus vaccination and effective strategies to promote vaccine acceptance.

PURPOSE OF REVIEW: This article provides a clinically relevant review and analysis of the latest research regarding barriers to human papillomavirus (HPV) vaccination and strategic efforts to promote this vaccine. RECENT FINDINGS: HPV vaccines are safe, effective, and could prevent the majority of HPV-attributable cancers, if vaccination coverage is high. However, uptake of HPV vaccine lags behind other vaccines recommended for 11 to 12-year olds. A lack of provider recommendation has consistently been found to be a key barrier to increasing vaccination rates. Lack of knowledge about the vaccine among parents coupled with an overestimation of parental vaccine hesitancy among providers also hinder vaccine uptake. Strongly recommending the vaccine as a safe, routine immunization that prevents cancer, and coadministering it with tetanus, diphtheria, and acellular pertussis vaccine and quadrivalent meningococcal conjugate vaccine, enhance vaccine uptake. In some cases, reminder and recall systems result in additional increases in vaccination rates. SUMMARY: Recent publications reveal new information about the implementation of HPV vaccines. Provider recommendation is a key approach, as is offering it routinely at the same time as other universally recommended adolescent immunizations. With the integration of these concepts into the clinical setting, adolescents can be better protected against HPV and its associated diseases.

Human papillomavirus epidemiology and vaccine recommendations: selected review of the recent literature.

PURPOSE OF REVIEW: This article provides a clinically relevant review and analysis of the latest research and recommendations regarding human papillomavirus (HPV) vaccine. RECENT FINDINGS: Although studies have found that bivalent and quadrivalent HPV vaccines are well tolerated and effective, high-risk HPV types not included in these vaccines are responsible for a significant burden of disease worldwide. Clinical trials have found that the recently licensed 9-valent vaccine, which includes five additional high-risk HPV types, is well tolerated and efficacious. This vaccine was added to the Advisory Committee on Immunization Practices HPV vaccination recommendations in 2015. A two-dose series in girls and boys 9-14 years old with a 6- or 12-month interval between doses has been shown to result in antibody titers noninferior to those measured after the three-dose series in women 16-26 years old. The Food and Drug Administration is considering these data. SUMMARY: Recent publications highlight the safety and effectiveness of HPV vaccines, the licensure of the 9-valent HPV vaccine, and the revision of HPV vaccine recommendations.

Yellow Fever Vaccine Booster Doses: Recommendations of the Advisory Committee on Immunization Practices, 2015.

On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.

Immunizing adolescents: a selected review of recent literature and US recommendations.

PURPOSE OF REVIEW: To provide a clinically relevant synopsis of the latest research and recommendations regarding adolescent immunizations. RECENT FINDINGS: Immunization is an important and effective strategy for preventing morbidity and mortality in adolescents. Although there has been progress in recent years, coverage rates in the US remain suboptimal, particularly for the human papillomavirus vaccine. Much work has been done to better understand and address the barriers to adolescent immunization, so that all teens may be protected against serious vaccine-preventable diseases. In addition, several recent studies have focused on the effectiveness of current adolescent vaccines and the development of new vaccines to protect against additional types of human papillomavirus and serotype B Neisseria meningitidis. Decreased pertussis vaccine effectiveness has led to new recommendations for pregnant women, including adolescents, to protect them and their young infants. The present review highlights selected literature on acellular pertussis, meningococcal, and human papillomavirus vaccines. Research findings on various strategies to improve adolescent vaccine uptake are also discussed in this review. SUMMARY: Research on adolescent immunizations and their delivery continues to have an impact on clinical practice and will shape future guidelines. Through this work, we can learn how best to protect adolescents against vaccine-preventable diseases.

Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices.

During its February 2015 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended 9-valent human papillomavirus (HPV) vaccine (9vHPV) (Gardasil 9, Merck and Co., Inc.) as one of three HPV vaccines that can be used for routine vaccination. HPV vaccine is recommended for routine vaccination at age 11 or 12 years. ACIP also recommends vaccination for females aged 13 through 26 years and males aged 13 through 21 years not vaccinated previously. Vaccination is also recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously. 9vHPV is a noninfectious, virus-like particle (VLP) vaccine. Similar to quadrivalent HPV vaccine (4vHPV), 9vHPV contains HPV 6, 11, 16, and 18 VLPs. In addition, 9vHPV contains HPV 31, 33, 45, 52, and 58 VLPs. 9vHPV was approved by the Food and Drug Administration (FDA) on December 10, 2014, for use in females aged 9 through 26 years and males aged 9 through 15 years. For these recommendations, ACIP reviewed additional data on 9vHPV in males aged 16 through 26 years. 9vHPV and 4vHPV are licensed for use in females and males. Bivalent HPV vaccine (2vHPV), which contains HPV 16, 18 VLPs, is licensed for use in females. This report summarizes evidence considered by ACIP in recommending 9vHPV as one of three HPV vaccines that can be used for vaccination and provides recommendations for vaccine use.