Baseline Asymptomatic Malaria Infection and Immunogenicity of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein.

BACKGROUND: The effect of malaria infection on the immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein (GP) vaccine (rVSVΔG-ZEBOV-GP) (ERVEBO) is unknown. METHODS: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-2016 Ebola epidemic. In STRIVE's immunogenicity substudy, participants provided blood samples at baseline and at 1, 6, and 9-12 months. Anti-GP binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by polymerase chain reaction. RESULTS: Overall, 506 participants enrolled in the immunogenicity substudy and had ≥1 postvaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73 (14.6%). All GP enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants showed seroresponse by GP-ELISA (≥2-fold rise and ≥200 ELISA units/mL), while 81.5% showed seroresponse by PRNT (≥4-fold rise) at ≥1 postvaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months. CONCLUSION: Asymptomatic adults with or without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP, persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower.

Public Health Response to the Initiation and Spread of Pandemic COVID-19 in the United States, February 24-April 21, 2020.

From January 21 through February 23, 2020, a total of 14 cases of coronavirus disease 2019 (COVID-19) were diagnosed in six U.S. states, including 12 cases in travelers arriving from China and two in household contacts of persons with confirmed infections. An additional 39 cases were identified in persons repatriated from affected areas outside the United States (1). Starting in late February, reports of cases with no recent travel to affected areas or links to known cases signaled the initiation of pandemic spread in the United States (2). By mid-March, transmission of SARS-CoV-2, the virus that causes COVID-19, had accelerated, with rapidly increasing case counts indicating established transmission in the United States. Ongoing traveler importation of SARS-CoV-2, attendance at professional and social events, introduction into facilities or settings prone to amplification, and challenges in virus detection all contributed to rapid acceleration of transmission during March. Public health responses included intensive efforts to detect cases and trace contacts, and implementation of multiple community mitigation strategies. Because most of the population remains susceptible to infection, recognition of factors associated with amplified spread during the early acceleration period will help inform future decisions as locations in the United States scale back some components of mitigation and strengthen systems to detect a potential transmission resurgence. U.S. circulation of SARS-CoV-2 continues, and sustained efforts will be needed to prevent future spread within the United States.

Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Progress in Vaccine-Preventable and Respiratory Infectious Diseases-First 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006-2015.

The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006-2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus-associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful.

Cultivation of an Adaptive Domestic Network for Surveillance and Evaluation of Emerging Infections.

Accomplishments of this program have provided numerous dividends and might benefit areas outside infectious diseases.

Bacterial meningitis in the United States, 1998-2007.

BACKGROUND: The rate of bacterial meningitis declined by 55% in the United States in the early 1990s, when the Haemophilus influenzae type b (Hib) conjugate vaccine for infants was introduced. More recent prevention measures such as the pneumococcal conjugate vaccine and universal screening of pregnant women for group B streptococcus (GBS) have further changed the epidemiology of bacterial meningitis. METHODS: We analyzed data on cases of bacterial meningitis reported among residents in eight surveillance areas of the Emerging Infections Programs Network, consisting of approximately 17.4 million persons, during 1998-2007. We defined bacterial meningitis as the presence of H. influenzae, Streptococcus pneumoniae, GBS, Listeria monocytogenes, or Neisseria meningitidis in cerebrospinal fluid or other normally sterile site in association with a clinical diagnosis of meningitis. RESULTS: We identified 3188 patients with bacterial meningitis; of 3155 patients for whom outcome data were available, 466 (14.8%) died. The incidence of meningitis changed by -31% (95% confidence interval [CI], -33 to -29) during the surveillance period, from 2.00 cases per 100,000 population (95% CI, 1.85 to 2.15) in 1998-1999 to 1.38 cases per 100,000 population (95% CI 1.27 to 1.50) in 2006-2007. The median age of patients increased from 30.3 years in 1998-1999 to 41.9 years in 2006-2007 (P<0.001 by the Wilcoxon rank-sum test). The case fatality rate did not change significantly: it was 15.7% in 1998-1999 and 14.3% in 2006-2007 (P=0.50). Of the 1670 cases reported during 2003-2007, S. pneumoniae was the predominant infective species (58.0%), followed by GBS (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%). An estimated 4100 cases and 500 deaths from bacterial meningitis occurred annually in the United States during 2003-2007. CONCLUSIONS: The rates of bacterial meningitis have decreased since 1998, but the disease still often results in death. With the success of pneumococcal and Hib conjugate vaccines in reducing the risk of meningitis among young children, the burden of bacterial meningitis is now borne more by older adults. (Funded by the Emerging Infections Programs, Centers for Disease Control and Prevention.).

Benefits from immunization during the vaccines for children program era - United States, 1994-2013.

The Vaccines for Children (VFC) program was created by the Omnibus Budget Reconciliation Act of 1993 and first implemented in 1994. VFC was designed to ensure that eligible children do not contract vaccine-preventable diseases because of inability to pay for vaccine and was created in response to a measles resurgence in the United States that resulted in approximately 55,000 cases reported during 1989-1991. The resurgence was caused largely by widespread failure to vaccinate uninsured children at the recommended age of 12-15 months. To summarize the impact of the U.S. immunization program on the health of all children (both VFC-eligible and not VFC-eligible) who were born during the 20 years since VFC began, CDC used information on immunization coverage from the National Immunization Survey (NIS) and a previously published cost-benefit model to estimate illnesses, hospitalizations, and premature deaths prevented and costs saved by routine childhood vaccination during 1994-2013. Coverage for many childhood vaccine series was near or above 90% for much of the period. Modeling estimated that, among children born during 1994- 2013, vaccination will prevent an estimated 322 million illnesses, 21 million hospitalizations, and 732,000 deaths over the course of their lifetimes, at a net savings of $295 billion in direct costs and $1.38 trillion in total societal costs. With support from the VFC program, immunization has been a highly effective tool for improving the health of U.S. children.

The state of immunization 2013: we are the world.

Most vaccine-preventable diseases in the U.S. are at record low levels, and immunization coverage among toddlers and teenagers is high or increasing. However, importations of measles virus from other countries, resurgences of pertussis and mumps, and the 2009 pandemic of influenza A H1N1 are reminders that Americans remain vulnerable to vaccine-preventable diseases and that sustained support for public health and clinician efforts is needed. Geographic areas with high rates of exemptions from vaccinations required for school attendance place communities at risk for disease outbreaks. There has been much progress internationally in reducing the toll of vaccine-preventable diseases, through public-private partnerships like the Global Alliance for Vaccines and Immunizations (GAVI). Paralytic poliomyelitis is on the verge of eradication, with wild virus transmission continuing in only three countries - Nigeria, Afghanistan and Pakistan. Intensified efforts in those countries are critical. The Decade of Vaccines Collaboration offers an opportunity to strengthen immunization in every community and country.

Evaluation of universal antenatal screening for group B streptococcus.

BACKGROUND: Group B streptococcal disease is one of the most common infections in the first week after birth. In 2002, national guidelines recommended universal late antenatal screening of pregnant women for colonization with group B streptococcus to identify candidates for intrapartum chemoprophylaxis. METHODS: We evaluated the implementation of the guidelines in a multistate, retrospective cohort selected from the Active Bacterial Core surveillance, a 10-state, population-based system that monitors invasive group B streptococcal disease. We abstracted data from the labor and delivery records of a stratified random sample of live births and of all cases in which the newborn had early-onset group B streptococcal disease (i.e., disease in infants <7 days of age) in 2003 and 2004. We compared our results with those from a study with a similar design that evaluated screening practices in 1998 and 1999. RESULTS: We abstracted records of 254 births in which the infant had group B streptococcal disease and 7437 births in which the infant did not. The rate of screening for group B streptococcus before delivery increased from 48.1% in 1998-1999 to 85.0% in 2003-2004; the percentage of infants exposed to intrapartum antibiotics increased from 26.8% to 31.7%. Chemoprophylaxis was administered in 87.0% of the women who were positive for group B streptococcus and who delivered at term, but in only 63.4% of women with unknown colonization status who delivered preterm. The overall incidence of early-onset group B streptococcal disease was 0.32 cases per 1000 live births. Preterm infants had a higher incidence of early-onset group B streptococcal disease than did term infants (0.73 vs. 0.26 cases per 1000 live births); however, 74.4% of the cases of group B streptococcal disease (189 of 254) occurred in term infants. Missed screening among mothers who delivered at term accounted for 34 of the 254 cases of group B streptococcal disease (13.4%). A total of 61.4% of the term infants with group B streptococcal disease were born to women who had tested negative for group B streptococcus before delivery. CONCLUSIONS: Recommendations for universal screening were rapidly adopted. Improved management of preterm deliveries and improved collection, processing, and reporting of culture results may prevent additional cases of early-onset group B streptococcal disease.

Leveraging Rapid Response Activities to Build Public Health Capacity: Development of the Opioid Rapid Response Team Model.

As part of the federal response to the opioid crisis, the Opioid Rapid Response Team project (2018-2019) was created to provide rapid short-term assistance to requesting US jurisdictions responding to an acute opioid-related event. The project used an approach that maximized overall value by leveraging existing federal resources and harnessing opportunities to meet project-specific objectives while also enhancing general response capacity at the federal, state, and local levels. This tandem capacity building for both opioid rapid response and general response focused on systems and operations, workforce readiness, technical assistance, and partnerships. In this article, we demonstrate the ancillary value that issue-specific response activities can contribute to broader public health response capacity.