Legionnaires' disease in transportation, construction and other occupations in 39 US jurisdictions, 2014-2016.

BACKGROUND: Certain workers are at increased risk for acquiring Legionnaires' disease compared with other workers. This study aims to identify occupations at increased risk for acquiring Legionnaires' disease. METHODS: Using data from the US Centers for Disease Control and Prevention's Supplemental Legionnaires' Disease Surveillance System, this study identified Legionnaires' disease confirmed patients ≥16 years of age in 39 states with reported symptom onset during 2014-2016. Age-adjusted and sex-adjusted incidence rate ratios (IRR) stratified by occupation group were calculated by comparing Legionnaires' disease patients in an occupation group (eg, transportation) to those in all other occupation groups (eg, non-transportation). RESULTS: A total of 2553 patients had a known occupation group. The two occupations with the highest burden were transportation (N=287; IRR=2.11) and construction (N=269; IRR=1.82). Truck drivers comprised the majority (69.7%) of the transportation occupation group and construction labourers comprised almost half (49%) of the construction occupation group. The healthcare support occupation had the highest IRR (N=75; IRR=2.16). CONCLUSION: Transportation and construction workers, who are generally not covered by guidance related to building water systems, have increased risk of Legionnaires' disease compared with other workers. One hypothesised risk factor for truck drivers is the use of non-genuine windshield cleaner in their vehicles. A simple intervention is to use genuine windshield cleaner with bactericidal properties (ie, includes isopropanol/methanol) which can reduce the risk of Legionella growth and transmission. To improve surveillance of Legionnaires' disease and identification of similar exposures, the authors encourage the collection of occupation and industry information for all patients with Legionnaires' disease.

Large Community Outbreak of Legionnaires Disease Potentially Associated with a Cooling Tower - Napa County, California, 2022.

Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission.

Rising Incidence of Legionnaires' Disease and Associated Epidemiologic Patterns, United States, 1992-2018.

Reported Legionnaires' disease (LD) cases began increasing in the United States in 2003 after relatively stable numbers for >10 years; reasons for the rise are unclear. We compared epidemiologic patterns associated with cases reported to the Centers for Disease Control and Prevention before and during the rise. The age-standardized average incidence was 0.48 cases/100,000 population during 1992-2002 compared with 2.71 cases/100,000 in 2018. Reported LD incidence increased in nearly every demographic, but increases tended to be larger in demographic groups with higher incidence. During both periods, the largest number of cases occurred among White persons, but the highest incidence was in Black or African American persons. Incidence and increases in incidence were generally largest in the East North Central, Middle Atlantic, and New England divisions. Seasonality was more pronounced during 2003-2018, especially in the Northeast and Midwest. Rising incidence was most notably associated with increasing racial disparities, geographic focus, and seasonality.

Epidemiologic Findings from Case Investigations and Contact Tracing for First 200 Cases of Coronavirus Disease, Santa Clara County, California, USA.

In January 2020, Santa Clara County, California, USA, began identifying laboratory-confirmed coronavirus disease among residents. County staff conducted case and contact investigations focused on households and collected detailed case demographic, occupation, exposure, and outcome information. We describe the first 200 test-positive cases during January 31-March 20, 2020, to inform future case and contact investigations. Probable infection sources included community transmission (104 cases), known close contact with a confirmed case-patient (66 cases), and travel (30 cases). Disease patterns across race and ethnicity, occupational, and household factors suggested multiple infection risk factors. Disproportionately high percentages of case-patients from racial and ethnic subgroups worked outside the home (Hispanic [86%] and Filipino [100%]); household transmission was more common among persons from Vietnam (53%). Even with the few initial cases, detailed case and contact investigations of household contacts capturing occupational and disaggregated race and ethnicity data helped identify at-risk groups and focused solutions for disease control.

Legionellosis Cluster Associated With Working at a Racetrack Facility in West Virginia, 2018.

In October 2018, the Centers for Disease Control and Prevention was notified of a cluster of Legionnaires' disease cases in workers at a racetrack facility. The objective of the resulting investigation was to determine the extent of the outbreak and identify potential sources of exposure to halt transmission. Case-finding and interviews were conducted among symptomatic racetrack workers who were known to be at the facility within 14 days prior to symptom onset. An environmental assessment of the facility and surrounding area was conducted for sources of potential Legionella exposure. In total, 17 legionellosis cases were identified. The environmental assessment revealed a poorly maintained hot tub in the jockey locker room as the most likely source. Further investigation identified deficiencies in the facility's ventilation systems, which suggested a transmission mechanism for workers who never entered the locker room floor. Considering indirect exposure routes via air handling systems can be useful for source identification and case-finding in legionellosis outbreaks.

Vital Signs: Health Care-Associated Legionnaires' Disease Surveillance Data from 20 States and a Large Metropolitan Area - United States, 2015.

BACKGROUND: Legionnaires' disease, a severe pneumonia, is typically acquired through inhalation of aerosolized water containing Legionella bacteria. Legionella can grow in the complex water systems of buildings, including health care facilities. Effective water management programs could prevent the growth of Legionella in building water systems. METHODS: Using national surveillance data, Legionnaires' disease cases were characterized from the 21 jurisdictions (20 U.S. states and one large metropolitan area) that reported exposure information for ≥90% of 2015 Legionella infections. An assessment of whether cases were health care-associated was completed; definite health care association was defined as hospitalization or long-term care facility residence for the entire 10 days preceding symptom onset, and possible association was defined as any exposure to a health care facility for a portion of the 10 days preceding symptom onset. All other Legionnaires' disease cases were considered unrelated to health care. RESULTS: A total of 2,809 confirmed Legionnaires' disease cases were reported from the 21 jurisdictions, including 85 (3%) definite and 468 (17%) possible health care-associated cases. Among the 21 jurisdictions, 16 (76%) reported 1-21 definite health care-associated cases per jurisdiction. Among definite health care-associated cases, the majority (75, 88%) occurred in persons aged ≥60 years, and exposures occurred at 72 facilities (15 hospitals and 57 long-term care facilities). The case fatality rate was 25% for definite and 10% for possible health care-associated Legionnaires' disease. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Exposure to Legionella from health care facility water systems can result in Legionnaires' disease. The high case fatality rate of health care-associated Legionnaires' disease highlights the importance of case prevention and response activities, including implementation of effective water management programs and timely case identification.

Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015.

Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities.

Patterns and Trends of Newly Diagnosed HIV Infections Among Adults and Adolescents in Correctional and Noncorrectional Facilities, United States, 2008-2011.

OBJECTIVES: We aimed to determine whether the patterns and trends of HIV infections newly diagnosed within correctional and noncorrectional facilities differ. METHODS: We classified persons newly diagnosed with HIV infection in the United States between 2008 and 2011 (n = 181,710) by correctional and noncorrectional facilities where diagnoses were first made, and stratified by sex, age group, race/ethnicity, transmission category, and diagnosis year. RESULTS: An estimated 9187 persons were newly diagnosed with HIV infection in 2008 to 2011 while incarcerated, representing approximately 5.1% of the 181,710 HIV infections diagnosed in the United States during this period. Of these incarcerated persons, 84% were male, 30% were aged 30 to 39 years, 59% were Black/African American, and 51% of the men had been exposed through male-to-male sexual contact. Yearly numbers of diagnoses declined by 9.9% in correctional versus 0.3% in noncorrectional facilities. The percentage with a late HIV diagnosis was significantly lower in correctional than in noncorrectional facilities (prevalence ratio = 0.52; 95% confidence interval = 0.49, 0.55). CONCLUSIONS: Initial HIV diagnosis occurred sooner after HIV infection onset in correctional than in noncorrectional settings, pointing to the need for efficient referral systems after release.

Decreased Ebola Transmission after Rapid Response to Outbreaks in Remote Areas, Liberia, 2014.

We measured the reproduction number before and after interventions were implemented to reduce Ebola transmission in 9 outbreaks in Liberia during 2014. We evaluated risk factors for secondary cases and the association between patient admission to an Ebola treatment unit (ETU) and survival. The reproduction number declined 94% from 1.7 (95% CI 1.1-2.6) to 0.1 (95% CI 0.02-0.6) after interventions began. The risk for secondary infections was 90% lower for patients admitted to an ETU (risk ratio 0.1, 95% CI 0.04-0.3) than for those who died in the community. The case-fatality rate was 68% (95% CI 60-74), and ETU admission was associated with a 50% reduction in death (hazard ratio 0.5, 95% CI 0.4-0.8). Isolation and treatment of Ebola patients had the dual benefit of interrupting community transmission and improving survival.

Mumps outbreak in Orthodox Jewish communities in the United States.

BACKGROUND: By 2005, vaccination had reduced the annual incidence of mumps in the United States by more than 99%, with few outbreaks reported. However, in 2006, a large outbreak occurred among highly vaccinated populations in the United States, and similar outbreaks have been reported worldwide. The outbreak described in this report occurred among U.S. Orthodox Jewish communities during 2009 and 2010. METHODS: Cases of salivary-gland swelling and other symptoms clinically compatible with mumps were investigated, and demographic, clinical, laboratory, and vaccination data were evaluated. RESULTS: From June 28, 2009, through June 27, 2010, a total of 3502 outbreak-related cases of mumps were reported in New York City, two upstate New York counties, and one New Jersey county. Of the 1648 cases for which clinical specimens were available, 50% were laboratory-confirmed. Orthodox Jewish persons accounted for 97% of case patients. Adolescents 13 to 17 years of age (27% of all patients) and males (78% of patients in that age group) were disproportionately affected. Among case patients 13 to 17 years of age with documented vaccination status, 89% had previously received two doses of a mumps-containing vaccine, and 8% had received one dose. Transmission was focused within Jewish schools for boys, where students spend many hours daily in intense, face-to-face interaction. Orchitis was the most common complication (120 cases, 7% of male patients ≥12 years of age), with rates significantly higher among unvaccinated persons than among persons who had received two doses of vaccine. CONCLUSIONS: The epidemiologic features of this outbreak suggest that intense exposures, particularly among boys in schools, facilitated transmission and overcame vaccine-induced protection in these patients. High rates of two-dose coverage reduced the severity of the disease and the transmission to persons in settings of less intense exposure.

Rapid response to Ebola outbreaks in remote areas - Liberia, July-November 2014.

West Africa is experiencing its first epidemic of Ebola virus disease (Ebola). As of February 9, Liberia has reported 8,864 Ebola cases, of which 3,147 were laboratory-confirmed. Beginning in August 2014, the Liberia Ministry of Health and Social Welfare (MOHSW), supported by CDC, the World Health Organization (WHO), and others, began systematically investigating and responding to Ebola outbreaks in remote areas. Because many of these areas lacked mobile telephone service, easy road access, and basic infrastructure, flexible and targeted interventions often were required. Development of a national strategy for the Rapid Isolation and Treatment of Ebola (RITE) began in early October. The strategy focuses on enhancing capacity of county health teams (CHT) to investigate outbreaks in remote areas and lead tailored responses through effective and efficient coordination of technical and operational assistance from the MOHSW central level and international partners. To measure improvements in response indicators and outcomes over time, data from investigations of 12 of 15 outbreaks in remote areas with illness onset dates of index cases during July 16-November 20, 2014, were analyzed. The times to initial outbreak alerts and durations of the outbreaks declined over that period while the proportions of patients who were isolated and treated increased. At the same time, the case-fatality rate in each outbreak declined. Implementation of strategies, such as RITE, to rapidly respond to rural outbreaks of Ebola through coordinated and tailored responses can successfully reduce transmission and improve outcomes.

Congenital rubella syndrome in child of woman without known risk factors, New Jersey, USA.

We report a case of congenital rubella syndrome in a child born to a vaccinated New Jersey woman who had not traveled internationally. Although rubella and congenital rubella syndrome have been eliminated from the United States, clinicians should remain vigilant and immediately notify public health authorities when either is suspected.

Viruses detected among sporadic cases of parotitis, United States, 2009-2011.

BACKGROUND: Sporadic cases of parotitis are generally assumed to be mumps, which often requires a resource-intensive public health response. This project surveyed the frequency of viruses detected among such cases. METHODS: During 2009-2011, 8 jurisdictions throughout the United States investigated sporadic cases of parotitis. Epidemiologic information, serum, and buccal and oropharyngeal swabs were collected. Polymerase chain reaction methods were used to detect a panel of viruses. Anti-mumps virus immunoglobulin M (IgM) antibodies were detected using a variety of methods. RESULTS: Of 101 specimens, 38 were positive for a single virus: Epstein-Barr virus (23), human herpesvirus (HHV)-6B (10), human parainfluenza virus (HPIV)-2 (3), HPIV-3 (1), and human bocavirus (1). Mumps virus, enteroviruses (including human parechovirus), HHV-6A, HPIV-1, and adenoviruses were not detected. Early specimen collection did not improve viral detection rate. Mumps IgM was detected in 17% of available specimens. Patients in whom a virus was detected were younger, but no difference was seen by sex or vaccination profile. No seasonal patterns were identified. CONCLUSIONS: Considering the timing of specimen collection, serology results, patient vaccination status, and time of year may be helpful in assessing the likelihood that a sporadic case of parotitis without laboratory confirmation is mumps.

Mumps antibody levels among students before a mumps outbreak: in search of a correlate of immunity.

BACKGROUND: In 2006, a mumps outbreak occurred on a university campus despite ≥ 95% coverage of students with 2 doses of measles-mumps-rubella (MMR) vaccine. Using plasma samples from a blood drive held on campus before identification of mumps cases, we compared vaccine-induced preoutbreak mumps antibody levels between individuals who developed mumps (case patients) and those who did not develop mumps (nonpatients). METHODS: Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms. Antibody titers were measured by plaque reduction neutralization assay using Jeryl Lynn vaccine virus and the outbreak virus Iowa-G/USA-06 and by enzyme immunoassay (EIA). RESULTS: Preoutbreak Jeryl Lynn virus neutralization titers were significantly lower among case patients than unexposed nonpatients (P = .023), and EIA results were significantly lower among case patients than exposed nonpatients (P = .007) and unexposed nonpatients (P = .009). Proportionately more case patients than exposed nonpatients had a preoutbreak anti-Jeryl Lynn titer < 31 (64% vs 27%, respectively; P = .065), an anti-Iowa-G/USA-06 titer < 8 (55% vs 14%; P = .033), and EIA index standard ratio < 1.40 (64% vs 9%; P = .002) and < 1.71 (73% vs 14%, P = .001). DISCUSSION: Case patients generally had lower preoutbreak mumps antibody levels than nonpatients. However, titers overlapped and no cutoff points separated all mumps case patients from all nonpatients.

Recent resurgence of mumps in the United States.

BACKGROUND: The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. METHODS: We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. RESULTS: A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. CONCLUSIONS: Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps.

Travel-associated cases of Legionnaires' disease in the United States, 2015-2016.

BACKGROUND: Recent travel is associated with ~20% of reported Legionnaires' disease (LD) cases worldwide. METHODS: We analyzed LD cases reported to the Centers for Disease Control and Prevention (CDC) during 2015-2016. Travel-associated cases met case criteria for confirmed LD in someone who spent ≥1 night away from home during the 10 days before symptom onset. Most analyses were limited to travel-associated, public accommodation stay (TAPAS) cases. We used reported travel dates to estimate the number of TAPAS cases acquired during travel. RESULTS: Of 12,200 LD cases reported among U.S. residents, 12.3% were travel-associated; 8.7% were TAPAS. Median patient age for TAPAS cases was 61 years; 64.4% were male; 67.3% were white; 77.9% were non-Hispanic; 96.1% were hospitalized; 4.5% died. Among 887 TAPAS cases involving U.S. destinations, an estimated 29.8% were acquired during travel; 4.28 TAPAS cases were reported, and an estimated 1.10 TAPAS cases were acquired during travel, per 10,000,000 hotel room nights booked. Sixty-eight U.S. TAPAS clusters were detected. CONCLUSIONS: While acquisition during travel accounted for a relatively small proportion of all LD cases, clusters of TAPAS cases were frequently detected. Prompt notification of these cases to CDC facilitates cluster detection and expedites intervention.

Substance P receptor expression on lymphocytes is associated with the immune response to respiratory syncytial virus infection.

The kinetics and magnitude of SP receptor expression was determined for bronchoalveolar leukocyte cell subsets from BALB/c mice in the primary immune response to respiratory syncytial virus (RSV) and human parainfluenza virus-3 (PIV3) infection, and in the secondary immune response to RSV and PIV3 challenge. In both the primary and secondary responses to infection, expression of substance P (SP) receptors was markedly increased by infection, especially for T lymphocytes, compared to B220+, CD11b+ and CD14+ cells. CD4+ T lymphocytes predominantly expressed SP receptors in the secondary response. These results suggest that SP receptor expression may be important in the development of primary and secondary immune responses to respiratory virus infections.

The economic burden of sixteen measles outbreaks on United States public health departments in 2011.

BACKGROUND: Despite vaccination efforts and documentation of elimination of indigenous measles in 2000, the United States (US) experienced a marked increase in imported cases and outbreaks of measles in 2011. Due to the high infectiousness and potential severity of measles, these outbreaks require a vigorous response from public health institutions. The effort and resources required to respond to these outbreaks are likely to impose a significant economic burden on these institutions. OBJECTIVE: To estimate the economic burden of measles outbreaks (defined as ≥ 3 epidemiologically linked cases) on the local and state public health institutions in the US in 2011. METHODS: From the perspective of local and state public health institutions, we estimated personnel time and resources allocated to measles outbreak response in local and state public health departments, and estimated the corresponding costs associated with these outbreaks in the US in 2011. We used cost and resource utilization data from previous studies on measles outbreaks in the US and, relying on outbreak size classification based on a case-day index, we estimated costs incurred by local and state public health institutions. RESULTS: In 2011, the US experienced 16 outbreaks with 107 confirmed cases. The average duration of an outbreak was 22 days (range: 5-68). The total estimated number of identified contacts to measles cases ranged from 8936 to 17,450, requiring from 42,635 to 83,133 personnel hours. Overall, the total economic burden on local and state public health institutions that dealt with measles outbreaks during 2011 ranged from an estimated $2.7 million to $5.3 million US dollars. CONCLUSION: Investigating and responding to measles outbreaks imposes a significant economic burden on local and state health institutions. Such impact is compounded by the duration of the outbreak and the number of potentially susceptible contacts.

Elimination of endemic measles, rubella, and congenital rubella syndrome from the Western hemisphere: the US experience.

IMPORTANCE: To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE: To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS: Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES: Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS: Since 2001, US reported measles incidence has remained below 1 case per 1,000,000 population. Since 2004, rubella incidence has been below 1 case per 10,000,000 population, and CRS incidence has been below 1 case per 5,000,000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE: The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

An outbreak of measles in an undervaccinated community.

Measles is readily spread to susceptible individuals, but is no longer endemic in the United States. In March 2011, measles was confirmed in a Minnesota child without travel abroad. This was the first identified case-patient of an outbreak. An investigation was initiated to determine the source, prevent transmission, and examine measles-mumps-rubella (MMR) vaccine coverage in the affected community. Investigation and response included case-patient follow-up, post-exposure prophylaxis, voluntary isolation and quarantine, and early MMR vaccine for non-immune shelter residents >6 months and <12 months of age. Vaccine coverage was assessed by using immunization information system records. Outreach to the affected community included education and support from public health, health care, and community and spiritual leaders. Twenty-one measles cases were identified. The median age was 12 months (range, 4 months to 51 years) and 14 (67%) were hospitalized (range of stay, 2-7 days). The source was a 30-month-old US-born child of Somali descent infected while visiting Kenya. Measles spread in several settings, and over 3000 individuals were exposed. Sixteen case-patients were unvaccinated; 9 of the 16 were age-eligible: 7 of the 9 had safety concerns and 6 were of Somali descent. MMR vaccine coverage among Somali children declined significantly from 2004 through 2010 starting at 91.1% in 2004 and reaching 54.0% in 2010 (χ(2) for linear trend 553.79; P < .001). This was the largest measles outbreak in Minnesota in 20 years, and aggressive response likely prevented additional transmission. Measles outbreaks can occur if undervaccinated subpopulations exist. Misunderstandings about vaccine safety must be effectively addressed.