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.).

Valganciclovir for symptomatic congenital cytomegalovirus disease.

BACKGROUND: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). CONCLUSIONS: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

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.

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.

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.

Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP).

This report summarizes the epidemiology of human papillomavirus (HPV) and associated diseases, describes the licensed HPV vaccines, provides updated data from clinical trials and postlicensure safety studies, and compiles recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of HPV vaccines. Persistent infection with oncogenic HPV types can cause cervical cancer in women as well as other anogenital and oropharyngeal cancers in women and men. HPV also causes genital warts. Two HPV vaccines are licensed in the United States. Both are composed of type-specific HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein using recombinant DNA technology produces noninfectious virus-like particles (VLPs). Quadrivalent HPV vaccine (HPV4) contains four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18. Bivalent HPV vaccine (HPV2) contains two HPV type-specific VLPs prepared from the L1 proteins of HPV 16 and 18. Both vaccines are administered in a 3-dose series. ACIP recommends routine vaccination with HPV4 or HPV2 for females aged 11 or 12 years and with HPV4 for males aged 11 or 12 years. Vaccination also is recommended for females aged 13 through 26 years and for males aged 13 through 21 years who were not vaccinated previously. Males aged 22 through 26 years may be vaccinated. ACIP recommends vaccination of men who have sex with men and immunocompromised persons (including those with HIV infection) through age 26 years if not previously vaccinated. As a compendium of all current recommendations for use of HPV vaccines, information in this report is intended for use by clinicians, vaccination providers, public health officials, and immunization program personnel as a resource. ACIP recommendations are reviewed periodically and are revised as indicated when new information and data become available.

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.

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.

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.

Decision-making process for conditions nominated to the recommended uniform screening panel: statement of the US Department of Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and Children.

PURPOSE: The US Secretary of Health and Human Services provides guidance to state newborn screening programs about which conditions should be included in screening (i.e., the "Recommended Uniform Screening Panel"). This guidance is informed by evidence-based recommendations from the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. This report describes the Advisory Committee's revised decision-making process for considering conditions nominated to the panel. METHODS: An expert panel meeting was held in April 2012 to revise the decision matrix, which helps to guide the recommendation process. In January 2013, the Advisory Committee voted to adopt the revised decision matrix. RESULTS: The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominated conditions. CONCLUSION: The revised decision matrix will bring increased quality, transparency, and consistency to the process of modifying the recommended uniform screening panel and will now allow formal evaluation of the challenges that state newborn screening programs face in adopting screening for new conditions.

Child and adolescent immunizations: selected review of recent US recommendations and literature.

PURPOSE OF REVIEW: To provide a clinically relevant summary of the latest research and recommendations regarding childhood and adolescent immunizations. RECENT FINDINGS: Childhood vaccination has dramatically reduced pediatric morbidity and mortality in the United States. Recent research on childhood and adolescent immunizations has focused on expanding the use of current vaccines for additional subpopulations as well as the development of new vaccines. In particular, data confirming the safety and immunogenicity of vaccines in various groups of children have shaped national guidelines. Furthermore, studies on vaccine uptake, cost-effectiveness, and impact of vaccination have reinforced the importance of adhering to these guidelines. More work needs to be done by providers and parents to increase vaccination coverage rates to better protect children and adolescents from these serious diseases. In this article, selected recent publications and recommendations on the following vaccines are reviewed: influenza, meningococcal conjugate, childhood and adolescent/adult formulations of diphtheria and tetanus toxoids and acellular pertussis, pneumococcal conjugate, and human papillomavirus. SUMMARY: Research on childhood and adolescent vaccinations continues to shape future guidelines. Through this work, we can learn how to optimize the protection of all children and adolescents against vaccine-preventable diseases.

Update on adolescent immunizations: selected review of US recommendations and literature.

PURPOSE OF REVIEW: To provide a clinically relevant synopsis of recent research findings as well as updated recommendations from the American Academy of Pediatrics (AAP) and Advisory Committee on Immunization Practices (ACIP) regarding adolescent immunizations. RECENT FINDINGS: Coverage rates for the adolescent vaccinations continue to lag behind those of the childhood vaccinations, despite their importance. Recent research has focused on the reasons for suboptimal adolescent vaccination rates as well as strategies for improvement. By more fully understanding the barriers to immunization, efforts can be implemented to address these concerns and to ensure that all eligible adolescents receive their vaccinations. In addition, much work has focused on the duration of protection induced by childhood and adolescent vaccinations and the need for booster doses in older adolescents. Because immunity has been found to wane after vaccination, these booster doses can serve to more fully protect adolescents. This article reviews selected recent publications on human papillomavirus, meningococcal conjugate, and tetanus and diphtheria toxoids and acellular pertussis vaccines. SUMMARY: Adolescent vaccinations will continue to be studied and this research will serve to shape future recommendations. Through this work, we can learn the best methods to optimize the protection of all adolescents against these very serious diseases.

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.].

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.

Update on child and adolescent immunizations: selected review of US recommendations and literature.

PURPOSE OF REVIEW: To provide a clinically relevant synopsis of recent research findings as well as updated guidelines from the American Academy of Pediatrics and Advisory Committee on Immunization Practices regarding child and adolescent immunizations. RECENT FINDINGS: Childhood vaccinations have served to dramatically reduce pediatric morbidity and mortality in the USA. Much of the recent research has focused on the improvement of current vaccines as well as on the development of new vaccines. By improving the safety, efficacy and immunogenicity of vaccinations, children can be more fully protected. Additionally, recommendations have broadened as vaccinations have been proven well tolerated and effective for a growing number of subpopulations. Although more groups of children are now included in vaccination recommendations, efforts must continue to ensure that all eligible children receive their vaccinations. This article reviews selected recent publications on influenza, human papillomavirus, the childhood and adolescent/adult formulations of diphtheria and tetanus toxoids and acellular pertussis, meningococcal conjugate and pneumococcal vaccines. The relationship between febrile seizures and childhood immunizations is explored. SUMMARY: The research on childhood and adolescent vaccinations is continuously growing and will serve to shape future recommendations. Through their findings, we can learn how to optimize the protection of all children and adolescents against these very serious diseases.

Adherence to CLSI recommendations for testing of Staphylococcus aureus isolates in Louisiana hospitals: report of a clinical failure and results of a questionnaire study.

We report a case of failure of clindamycin therapy due to inducible clindamycin resistance. We surveyed and found that only 52% of reporting hospitals in the state of Louisiana were performing the D test for inducible clindamycin resistance according to guidelines recommended by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards).

Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 2.

PURPOSE OF REVIEW: To provide a clinically relevant synopsis of research findings regarding childhood and adolescent vaccines. RECENT FINDINGS: Vaccine coverage is relatively static or improving for the vaccines included in the 2010 annual harmonized immunization schedules. Providers should be reviewing patients' immunization records at each visit to take advantage of any opportunity to administer indicated, age-appropriate vaccines. There have been infectious disease outbreaks among highly immunized populations, although unvaccinated or undervaccinated individuals continue to play large roles in the spread of disease. Infants, many of whom are too young to be vaccinated, continue to bear a large disease burden, which underscores the importance of cocooning and, in some cases, vaccination of pregnant women. Influenza, measles, mumps, and rubella, varicella, hepatitis A, meningococcal conjugate, human papillomavirus, diphtheria and tetanus toxoids and acellular pertussis, and tetanus and diphtheria toxoids and acellular pertussis vaccines are reviewed in this second of two articles. SUMMARY: New research on childhood and adolescent vaccines is anticipated to shape the practice of pediatric providers. Research will continue to provide the science to optimize protection and to promote the health and well being of all children and adolescents.