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Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses, including La Crosse, Jamestown Canyon, Powassan, eastern equine encephalitis, and St. Louis encephalitis viruses, cause sporadic disease and occasional outbreaks. This report summarizes surveillance data for nationally notifiable domestic arboviruses reported to CDC for 2019. For 2019, 47 states and the District of Columbia (DC) reported 1,173 cases of domestic arboviral disease, including 971 (83%) WNV disease cases. Among the WNV disease cases, 633 (65%) were classified as neuroinvasive disease, for a national incidence of 0.19 cases per 100,000 population, 53% lower than the median annual incidence during 2009-2018. More Powassan and eastern equine encephalitis virus disease cases were reported in 2019 than in any previous year. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform recommended diagnostic testing, and promptly report cases to public health authorities. Because arboviral diseases continue to cause serious illness, and annual incidence of individual viruses continues to vary with sporadic outbreaks, maintaining surveillance is important in directing prevention activities. Prevention depends on community and household efforts to reduce vector populations and personal protective measures to prevent mosquito and tick bites such as use of Environmental Protection Agency-registered insect repellent and wearing protective clothing.*,†.

Problem/condition West Nile virus (WNV) is an arthropodborne virus (arbovirus) in the family Flaviviridae and is the leading cause of domestically acquired arboviral disease in the contiguous United States. An estimated 70%-80% of WNV infections are asymptomatic. Symptomatic persons usually develop an acute systemic febrile illness. Less than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. Reporting period 2009-2018. Description of system WNV disease is a nationally notifiable condition with standard surveillance case definitions. State health departments report WNV cases to CDC through ArboNET, an electronic passive surveillance system. Variables collected include patient age, sex, race, ethnicity, county and state of residence, date of illness onset, clinical syndrome, hospitalization, and death. Results During 2009-2018, a total of 21,869 confirmed or probable cases of WNV disease, including 12,835 (59%) WNV neuroinvasive disease cases, were reported to CDC from all 50 states, the District of Columbia, and Puerto Rico. A total of 89% of all WNV patients had illness onset during July-September. Neuroinvasive disease incidence and case-fatalities increased with increasing age, with the highest incidence (1.22 cases per 100,000 population) occurring among persons aged ≥70 years. Among neuroinvasive cases, hospitalization rates were >85% in all age groups but were highest among patients aged ≥70 years (98%). The national incidence of WNV neuroinvasive disease peaked in 2012 (0.92 cases per 100,000 population). Although national incidence was relatively stable during 2013-2018 (average annual incidence: 0.44; range: 0.40-0.51), state level incidence varied from year to year. During 2009-2018, the highest average annual incidence of neuroinvasive disease occurred in North Dakota (3.16 cases per 100,000 population), South Dakota (3.06), Nebraska (1.95), and Mississippi (1.17), and the largest number of total cases occurred in California (2,819), Texas (2,043), Illinois (728), and Arizona (632). Six counties located within the four states with the highest case counts accounted for 23% of all neuroinvasive disease cases nationally. Interpretation Despite the recent stability in annual national incidence of neuroinvasive disease, peaks in activity were reported in different years for different regions of the country. Variations in vectors, avian amplifying hosts, human activity, and environmental factors make it difficult to predict future WNV disease incidence and outbreak locations. Public health action WNV disease surveillance is important for detecting and monitoring seasonal epidemics and for identifying persons at increased risk for severe disease. Surveillance data can be used to inform prevention and control activities. Health care providers should consider WNV infection in the differential diagnosis of aseptic meningitis and encephalitis, obtain appropriate specimens for testing, and promptly report cases to public health authorities. Public health education programs should focus prevention messaging on older persons, because they are at increased risk for severe neurologic disease and death. In the absence of a human vaccine, WNV disease prevention depends on community-level mosquito control and household and personal protective measures. Understanding the geographic distribution of cases, particularly at the county level, appears to provide the best opportunity for directing finite resources toward effective prevention and control activities. Additional work to further develop and improve predictive models that can foreshadow areas most likely to be impacted in a given year by WNV outbreaks could allow for proactive targeting of interventions and ultimately lowering of WNV disease morbidity and mortality.

Two coronavirus disease 2019 (COVID-19) vaccines are currently authorized for use in the United States. The Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine on December 11, 2020, and for the Moderna COVID-19 vaccine on December 18, 2020; each is administered as a 2-dose series. The Advisory Committee on Immunization Practices issued interim recommendations for Pfizer-BioNTech and Moderna COVID-19 vaccines on December 12, 2020 (1), and December 19, 2020 (2), respectively; initial doses were recommended for health care personnel and long-term care facility (LTCF) residents (3). Safety monitoring for these vaccines has been the most intense and comprehensive in U.S. history, using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, and v-safe,* an active surveillance system, during the initial implementation phases of the COVID-19 national vaccination program (4). CDC conducted descriptive analyses of safety data from the first month of vaccination (December 14, 2020-January 13, 2021). During this period, 13,794,904 vaccine doses were administered, and VAERS received and processed† 6,994 reports of adverse events after vaccination, including 6,354 (90.8%) that were classified as nonserious and 640 (9.2%) as serious.§ The symptoms most frequently reported to VAERS were headache (22.4%), fatigue (16.5%), and dizziness (16.5%). A total of 113 deaths were reported to VAERS, including 78 (65%) among LTCF residents; available information from death certificates, autopsy reports, medical records, and clinical descriptions from VAERS reports and health care providers did not suggest any causal relationship between COVID-19 vaccination and death. Rare cases of anaphylaxis after receipt of both vaccines were reported (4.5 reported cases per million doses administered). Among persons who received Pfizer-BioNTech vaccine, reactions reported to the v-safe system were more frequent after receipt of the second dose than after the first. The initial postauthorization safety profiles of the two COVID-19 vaccines in current use did not indicate evidence of unexpected serious adverse events. These data provide reassurance and helpful information regarding what health care providers and vaccine recipients might expect after vaccination.

To improve recognition of coronavirus disease (COVID-19) and inform clinical and public health guidance, we randomly selected 600 COVID-19 case-patients in Colorado. A telephone questionnaire captured symptoms experienced, when symptoms occurred, and how long each lasted. Among 128 hospitalized patients, commonly reported symptoms included fever (84%), fatigue (83%), cough (73%), and dyspnea (72%). Among 236 nonhospitalized patients, commonly reported symptoms included fatigue (90%), fever (83%), cough (83%), and myalgia (74%). The most commonly reported initial symptoms were cough (21%–25%) and fever (20%–25%). In multivariable analysis, vomiting, dyspnea, altered mental status, dehydration, and wheezing were significantly associated with hospitalization, whereas rhinorrhea, headache, sore throat, and anosmia or ageusia were significantly associated with nonhospitalization. General symptoms and upper respiratory symptoms occurred earlier in disease, and anosmia, ageusia, lower respiratory symptoms, and gastrointestinal symptoms occurred later. Symptoms should be considered alongside other epidemiologic factors in clinical and public health decisions regarding potential COVID-19 cases.

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including eastern equine encephalitis, Jamestown Canyon, La Crosse, Powassan, and St. Louis encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC for 2018 on nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because they are primarily nondomestic viruses typically acquired through travel. In 2018, 48 states and the District of Columbia (DC) reported 2,813 cases of domestic arboviral disease, including 2,647 (94%) WNV disease cases. Of the WNV disease cases, 1,658 (63%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis), for a national incidence of 0.51 cases of WNV neuroinvasive disease per 100,000 population. Because arboviral diseases continue to cause serious illness and have no definitive treatment, maintaining surveillance is important to direct and promote prevention activities. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform appropriate diagnostic testing, and report cases to public health authorities.

Background Most current evidence on risk factors for hospitalization because of coronavirus disease 2019 (COVID-19) comes from studies using data abstracted primarily from electronic health records, limited to specific populations, or that fail to capture over-the-counter medications and adjust for potential confounding factors. Properly understanding risk factors for hospitalization will help improve clinical management and facilitate targeted prevention messaging and forecasting and prioritization of clinical and public health resource needs. Objectives To identify risk factors for hospitalization using patient questionnaires and chart abstraction. Methods We randomly selected 600 of 1,738 laboratory-confirmed Colorado COVID-19 cases with known hospitalization status and illness onset during March 9–31, 2020. In April 2020, we collected demographics, social history, and medications taken in the 30 days before illness onset via telephone questionnaire and collected underlying medical conditions in patient questionnaires and medical record abstraction. Results Overall, 364 patients participated; 128 were hospitalized and 236 were non-hospitalized. In multivariable analysis, chronic hypoxemic respiratory failure with oxygen requirement (adjusted odds ratio [aOR] 14.64; 95% confidence interval [CI] 1.45–147.93), taking opioids (aOR 8.05; CI 1.16–55.77), metabolic syndrome (aOR 5.71; CI 1.18–27.54), obesity (aOR 3.35; CI 1.58–7.09), age ≥65 years (aOR 3.22; CI 1.20–7.97), hypertension (aOR 3.14; CI 1.47–6.71), arrhythmia (aOR 2.95; CI 1.00–8.68), and male sex (aOR 2.65; CI 1.44–4.88), were significantly associated with hospitalization. Conclusion We identified patient characteristics, medications, and medical conditions, including some novel ones, associated with hospitalization. These data can be used to inform clinical and public health resource needs.

As of March 2021, three COVID-19 vaccines had been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was 156 million fully vaccinated people. With high SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC from U.S. states in 2017 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because, in the continental United States, these viruses are acquired primarily through travel. In 2017, 48 states and the District of Columbia (DC) reported 2,291 cases of domestic arboviral disease, including 2,097 (92%) WNV disease cases. Among the WNV disease cases, 1,425 (68%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national rate of 0.44 cases per 100,000 population. More Jamestown Canyon and Powassan virus disease cases were reported in 2017 than in any previous year. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct and promote prevention activities.

Background The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. Methods Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. Results Among 15942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged, Infants aged

Zika virus infection during pregnancy can cause serious birth defects, including microcephaly and brain abnormalities (1). Population-based birth defects surveillance systems are critical to monitor all infants and fetuses with birth defects potentially related to Zika virus infection, regardless of known exposure or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed data from 15 U.S. jurisdictions conducting population-based surveillance for birth defects potentially related to Zika virus infection.* Jurisdictions were stratified into the following three groups: those with 1) documented local transmission of Zika virus during 2016; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents; and 3) less than one case of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents. A total of 2,962 infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] = 2.9-3.2) (2) met the case definition.† In areas with local transmission there was a non-statistically significant increase in total birth defects potentially related to Zika virus infection from 2.8 cases per 1,000 live births in the first half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural tube defects and other early brain malformations (NTDs)§ were excluded, the prevalence of birth defects strongly linked to congenital Zika virus infection increased significantly, from 2.0 cases per 1,000 live births in the first half of 2016 to 2.4 cases in the second half, an increase of 29 more cases than expected (p = 0.009). These findings underscore the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

Background Serogroup B meningococcal disease caused 7 US university outbreaks during 2013-2016. Neisseria meningitidis can be transmitted via asymptomatic nasopharyngeal carriage. MenB-FHbp (factor H binding protein), a serogroup B meningococcal (MenB) vaccine, was used to control a college outbreak. We investigated MenB-FHbp impact on meningococcal carriage. Methods Four cross-sectional surveys were conducted in conjunction with MenB-FHbp vaccination campaigns. Questionnaires and oropharyngeal swabs were collected from students. Specimens were evaluated using culture, slide agglutination, real-time polymerase chain reaction (rt-PCR), and whole genome sequencing. Adjusted prevalence ratios (aPRs) were calculated using generalized estimating equations. Results During each survey, 20%-24% of participants carried any meningococcal bacteria and 4% carried serogroup B by rt-PCR. The outbreak strain (ST-9069) was not detected during the initial survey; 1 student carried ST-9069 in the second and third surveys. No carriage reduction was observed over time or with more MenB-FHbp doses. In total, 615 students participated in multiple surveys: 71% remained noncarriers, 8% cleared carriage, 15% remained carriers, and 7% acquired carriage. Ten students acquired serogroup B carriage: 3 after 1 MenB-FHbp dose, 4 after 2 doses, and 3 after 3 doses. Smoking (aPR, 1.3; 95% confidence interval [CI], 1.1-1.5) and male sex (aPR, 1.3; 95% CI, 1.1-1.5) were associated with increased meningococcal carriage. Conclusions Carriage prevalence on campus remained stable, suggesting MenB-FHbp does not rapidly reduce meningococcal carriage or prevent serogroup B carriage acquisition. This reinforces the need for high vaccination coverage to protect vaccinated individuals and chemoprophylaxis for close contacts during outbreaks.

The introduction of Zika virus into the Region of the Americas (Americas) and the subsequent increase in cases of congenital microcephaly resulted in activation of CDC's Emergency Operations Center on January 22, 2016, to ensure a coordinated response and timely dissemination of information, and led the World Health Organization to declare a Public Health Emergency of International Concern on February 1, 2016. During the past year, public health agencies and researchers worldwide have collaborated to protect pregnant women, inform clinicians and the public, and advance knowledge about Zika virus (Figure 1). This report summarizes 10 important contributions toward addressing the threat posed by Zika virus in 2016. To protect pregnant women and their fetuses and infants from the effects of Zika virus infection during pregnancy, public health activities must focus on preventing mosquito-borne transmission through vector control and personal protective practices, preventing sexual transmission by advising abstention from sex or consistent and correct use of condoms, and preventing unintended pregnancies by reducing barriers to access to highly effective reversible contraception.

Dengue, chikungunya, and Zika viruses, primarily transmitted by Aedes species mosquitoes, have caused large outbreaks in the Americas, leading to travel-associated cases and local mosquito-borne transmission in the United States. We describe the epidemiology of dengue, chikungunya, and noncongenital Zika virus disease cases reported from U.S. states and territories in 2017, including 971 dengue cases, 195 chikungunya cases, and 1,118 Zika virus disease cases. Cases of all three diseases reported from the territories were reported as resulting from local mosquito-borne transmission. Cases reported from the states were primarily among travelers, with only seven locally acquired mosquito-transmitted Zika virus disease cases reported from Texas (n = 5) and Florida (n = 2). In the territories, most dengue cases (n = 508, 98%) were reported from American Samoa, whereas the majority of chikungunya (n = 39, 100%) and Zika virus disease (n = 620, 93%) cases were reported from Puerto Rico. Temporally, the highest number of Zika virus disease cases occurred at the beginning of the year, followed by a sharp decline, mirroring decreasing case numbers across the Americas following large outbreaks in 2015 and 2016. Dengue and chikungunya cases followed a more seasonal pattern, with higher case numbers from July through September. Travelers to the United States and residents of areas with active virus transmission should be informed of both the ongoing risk from dengue, chikungunya, and Zika virus disease and personal protective measures to lower their risk of mosquito bites and to help prevent the spread of these diseases.

Data on the duration of detectable Zika virus–specific IgM in infected persons are limited. Neutralizing antibody cross-reactivity occurs between Zika virus and related flaviviruses, but the degree to which this confounds diagnosis is uncertain. We tested serum specimens collected 12–19 months after illness onset from patients with confirmed Zika virus disease for Zika virus IgM and Zika virus and dengue virus neutralizing antibodies. Among 62 participants, 45 (73%) had detectable Zika virus IgM and 12 (19%) had an equivocal result. Although all patients tested had Zika virus neutralizing antibodies, 39 (63%) also had neutralizing antibodies against dengue virus; of those, 12 (19%) had 4-fold higher than Zika virus titer. Prolonged detection of IgM and neutralizing antibody cross-reactivity make it difficult to determine the timing of Zika virus infection and differentiate between related flaviviruses.

CDC has updated its interim guidance for persons with possible Zika virus exposure who are planning to conceive (1) and interim guidance to prevent transmission of Zika virus through sexual contact (2), now combined into a single document. Guidance for care for pregnant women with possible Zika virus exposure was previously published (3). Possible Zika virus exposure is defined as travel to or residence in an area of active Zika virus transmission (http://www.cdc.gov/zika/geo/index.html), or sex* without a condom† with a partner who traveled to or lived in an area of active transmission. Based on new though limited data, CDC now recommends that all men with possible Zika virus exposure who are considering attempting conception with their partner, regardless of symptom status,§ wait to conceive until at least 6 months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Recommendations for women planning to conceive remain unchanged: women with possible Zika virus exposure are recommended to wait to conceive until at least 8 weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Couples with possible Zika virus exposure, who are not pregnant and do not plan to become pregnant, who want to minimize their risk for sexual transmission of Zika virus should use a condom or abstain from sex for the same periods for men and women described above. Women of reproductive age who have had or anticipate future Zika virus exposure who do not want to become pregnant should use the most effective contraceptive method that can be used correctly and consistently. These recommendations will be further updated when additional data become available.

Monitoring of vaccine performance is necessary to identify outbreaks or emerging epidemiologic trends., In September 2013, local county health officials in Tallahassee, Florida, USA, were notified of a laboratory-confirmed pertussis case in a 1-year-old preschool attendee. During a 5-month period, 26 (22%) students 1–5 years of age, 2 staff from the same preschool, and 11 family members met the national case definition for pertussis. Four persons during this outbreak were hospitalized for clinical management of pertussis symptoms. Only 5 students, including 2 students with pertussis, had not received the complete series of vaccinations for pertussis. Attack rates in 1 classroom for all students who received the complete series of vaccinations for pertussis approached 50%. This outbreak raises concerns about vaccine effectiveness in this preschool age group and reinforces the idea that recent pertussis vaccination should not dissuade physicians from diagnosing, testing, or treating persons with compatible illness for pertussis.

Zika virus is a flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections also have been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-3). Most Zika virus infections are asymptomatic or result in mild clinical illness, characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis; Guillain-Barre syndrome, meningoencephalitis, and severe thrombocytopenia rarely have been associated with Zika virus infection (1). However, congenital Zika virus infection can result in fetal loss, microcephaly, and other birth defects (1,2). In 2016, a total of 5,168 noncongenital Zika virus disease cases were reported from U.S. states and the District of Columbia. Most cases (4,897, 95%) were in travelers returning from Zika virus-affected areas. A total of 224 (4%) cases were acquired through presumed local mosquitoborne transmission, and 47 (1%) were acquired by other routes. It is important that providers in the United States continue to test symptomatic patients who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas. All pregnant women and their partners should take measures to prevent Zika virus infection during pregnancy. A list of affected areas and specific recommendations on how to prevent Zika virus infection during pregnancy are available at https://www.cdc.gov/pregnancy/zika/protect-yourself.html.

Introduction The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Methods Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2–4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods—pertussis culture as the “gold standard,” composite reference standard analysis (CRS), and latent class analysis (LCA). Results Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Conclusions Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

We assessed IgM detection in Zika patients from the 2016 outbreak in Miami-Dade County, Florida, USA. Of those with positive or equivocal IgM after 12-19 months, 87% (26/30) had IgM 6 months later. In a survival analysis, ≈76% had IgM at 25 months. Zika virus IgM persists for years, complicating serologic diagnosis.

At its June 2015 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended that adolescents and young adults aged 16–23 years may be vaccinated with a serogroup B meningococcal (MenB) vaccine to provide short-term protection against most strains of serogroup B meningococcal disease. This report summarizes the deliberations of ACIP, the rationale for its decision, and recommendations for use of MenB vaccines in adolescents and young adults. Two MenB vaccines have recently been licensed by the Food and Drug Administration (FDA) for use in the United States and approved for use in persons aged 10–25 years: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, Inc.) and MenB-4C (Bexsero, Novartis Vaccines). Both MenB vaccines were licensed based on statutory regulations for accelerated approval, which enabled FDA to approve the MenB vaccines for serious or life-threatening diseases based on safety and demonstration that vaccine effectiveness, as measured by bactericidal antibody responses with assays using several MenB test strains that were representative of prevalent strains in the United States, is reasonably likely to predict clinical benefit. As a requirement for accelerated approval, confirmatory studies in the postmarketing period will be conducted to verify and further describe the effectiveness of the vaccines against an extended number of MenB strains that represent a broader diversity of endemic disease. Additional postlicensure safety data are also needed and will be reviewed by ACIP as they become available.

BACKGROUND: Pertussis is poorly controlled, with the highest rates of morbidity and mortality among infants. Although the source of infant pertussis is often unknown, when identified, mothers have historically been the most common reservoir of transmission. Despite high vaccination coverage, disease incidence has been increasing. We examined whether infant source of infection (SOI) has changed in the United States in light of the changing epidemiology. METHODS: Cases RESULTS: A total of 1306 infant cases were identified; 24.2% were CONCLUSIONS: In contrast to previous studies, our data suggest that the most common source of transmission to infants is now siblings. While continued monitoring of SOIs will optimize pertussis prevention strategies, recommendations for vaccination during pregnancy should directly increase protection of infants, regardless of SOI.

While PCR is the most common method used for detecting Bordetella pertussis in the United States, most laboratories use insertion sequence 481 (IS 481 ), which is not specific for B. pertussis ; therefore, the relative contribution of other Bordetella species is not understood. The objectives of this study were to evaluate the proportion of other Bordetella species misidentified as B. pertussis during a period of increased pertussis incidence, determine the level of agreement in Bordetella species detection between U.S. commercial laboratories and the CDC, and assess the relative diagnostic sensitivity of CDC's PCR assay when using a different PCR master mix. Specimens collected between May 2012 and May 2013 were tested at two U.S. commercial laboratories for B. pertussis and B. parapertussis detection. Every fifth specimen positive for IS 481 and/or IS 1001 with cycle threshold ( C T ) values of ≤35 was sent to CDC for PCR testing that identifies Bordetella species. Specimens with indeterminate or negative results in the CDC PCR were tested using an alternate PCR master mix. Of 755 specimens, there was agreement in species identification for 83.4% ( n = 630). Of the specimens with different identifications ( n = 125), 79.2% ( n = 99) were identified as indeterminate B. pertussis at CDC. Overall, 0.66% ( n = 5) of the specimens were identified as B. holmesii or B. bronchiseptica at CDC. Of 115 specimens with indeterminate or negative results, 46.1% ( n = 53) were B. pertussis positive when tested by an alternate master mix, suggesting a possible increase in assay sensitivity. This study demonstrates good agreement between the two U.S. commercial laboratories and CDC and little misidentification of Bordetella species during the 2012 U.S. epidemic.

In October 2014, the Food and Drug Administration (FDA) licensed the first serogroup B meningococcal (MenB) vaccine (MenB-FHbp [Trumenba, Wyeth Pharmaceuticals, Inc.]) as a 3-dose series. In January 2015, FDA licensed a second MenB vaccine (MenB-4C [Bexsero, Novartis Vaccines]) as a 2-dose series. Both vaccines were approved for use in persons aged 10-25 years. Following outbreaks of serogroup B meningococcal disease on two college campuses in 2013, both MenB vaccines were granted Breakthrough Therapy designations, which expedites drug development and review by FDA, and were licensed based on accelerated approval regulations. On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) recommended use of MenB vaccines among certain groups of persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease. This report summarizes information on MenB administration and provides recommendations and guidance for use of these vaccines among persons aged ≥10 years in certain groups who are at increased risk for serogroup B meningococcal disease, and reviews the evidence considered by ACIP to make these recommendations. Recommendations for broader use of MenB vaccines in adolescents and college students will be considered separately by ACIP.

Infants aged1 year are at highest risk for pertussis-related morbidity and mortality. In 2012, Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine was recommended for women during each pregnancy to protect infants in the first months of life; data on effectiveness of this strategy are currently limited.We conducted a case-control evaluation among pertussis cases2 months old with cough onset between 1 January 2011 and 31 December 2014 from 6 US Emerging Infection Program Network states. Controls were hospital-matched and selected by birth certificate. Mothers were interviewed to collect information on demographics, household characteristics, and healthcare providers. Provider-verified immunization history was obtained on mothers and infants. Mothers were considered vaccinated during pregnancy if Tdap was received ≥14 days before delivery; trimester was calculated using Tdap date, infant's date of birth, and gestational age. Odds ratios were calculated using multivariable conditional logistic regression; vaccine effectiveness (VE) was estimated as (1 - odds ratio) × 100%.A total of 240 cases and 535 controls were included; 17 (7.1%) case mothers and 90 (16.8%) control mothers received Tdap during the third trimester of pregnancy. The multivariable VE estimate for Tdap administered during the third trimester of pregnancy was 77.7% (95% confidence interval [CI], 48.3%-90.4%); VE increased to 90.5% (95% CI, 65.2%-97.4%) against hospitalized cases.Vaccination during pregnancy is an effective way to protect infants during the early months of life. With a continuing resurgence in pertussis, efforts should focus on maximizing Tdap uptake among pregnant women.

Objectives Several outbreaks of serogroup B meningococcal disease have occurred among university students in recent years. In the setting of high coverage of the quadrivalent meningococcal conjugate vaccine and prior to widespread use of serogroup B meningococcal vaccines among adolescents, we conducted surveys to characterize the prevalence and molecular characteristics of meningococcal carriage among university students. Methods Two cross-sectional oropharyngeal carriage surveys were conducted among undergraduates at a Rhode Island university. Isolates were characterized using slide agglutination, real-time polymerase chain reaction (rt-PCR), and whole genome sequencing. Adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression to determine risk factors for carriage. Results A total of 1837 oropharyngeal specimens were obtained from 1478 unique participants. Overall carriage prevalence was 12.7–14.6% during the two survey rounds, with 1.8–2.6% for capsular genotype B, 0.9–1.0% for capsular genotypes C, W, or Y, and 9.9–10.8% for nongroupable strains by rt-PCR. Meningococcal carriage was associated with being male, smoking, party or club attendance, recent antibiotic use (inverse correlation), and recent respiratory infections. Conclusions In this university setting, the majority of meningococcal carriage was due to nongroupable strains, followed by serogroup B. Further evaluation is needed to understand the dynamics of serogroup B carriage and disease among university students.

Despite high national vaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines among U.S. adolescents, rates of adolescent pertussis disease are increasing. We estimated the duration of protection after Tdap vaccination and the possible effects of the change from whole-cell to acellular childhood pertussis vaccines in the United States during the 1990s.We conducted a retrospective cohort analysis among 11- to 18-year-olds enrolled in two integrated health-care delivery systems during 2005-2012. Cases met the Council of State and Territorial Epidemiologists' confirmed or probable definition or a polymerase chain reaction-positive suspect definition. We estimated vaccine effectiveness (VE) overall and by time since Tdap receipt. We stratified VE estimates by primary series pertussis vaccine received (based on birth year): mixed-vaccine cohort (1987-1997) and acellular vaccine cohort (1998-2001).The overall Tdap VE was 57% (95% confidence interval [CI]: 42%-68%); the VE in the mixed-vaccine and acellular cohorts was 65% (95% CI: 44%-78%) and 52% (95% CI: 30%-68%), respectively. Tdap VE within2 years post vaccination (69%, 95% CI: 54%-79%) was significantly different from VE ≥2 years post vaccination (34%, 95% CI: 1%-55%, p value .01). VE was significantly higher2 years post vaccination compared with ≥2 years post vaccination in both mixed-vaccine (87%, 95% CI: 58%-96%, and 52%, 95% CI: 13%-73%; p value = .04) and acellular cohorts (62%, 95% CI: 41%-76%, and 21%, 95% CI: -30% to 52%; p value = .01).Although Tdap vaccination remains the best pertussis prevention method for adolescents, protection wanes within 2 years regardless of the type of childhood primary vaccine. Vaccines with longer duration of protection could decrease pertussis burden.

Despite guidelines and medications available for the management of chemotherapy-induced nausea and vomiting (CINV), many patients with cancer are persistently affected by this dreadful adverse effect. It is not only physically and mentally draining, but financially strenuous as well. Along with these concerns, health-related consequences as dehydration, epigastric pain, and anorexia can arise. Therefore, compliance becomes a big issue in this patient population. It is important for healthcare professionals to educate patients and incorporate strategies by not only addressing but also individualizing treatment regimens and determining risk factors for potential CINV. By making formulary considerations using patient-centered and evidence-based treatment, patient outcomes can improve. Overall, it is necessary to understand the impact of CINV on quality of life and addressing it actively can significantly enhance care of patients with cancer.

Background In 2012, >48000 pertussis cases were reported in the United States. Many cases occurred in vaccinated persons, showing that pertussis vaccination does not prevent all pertussis cases. However, pertussis vaccination may have an impact on disease severity. Methods We analyzed data on probable and confirmed pertussis cases reported through Enhanced Pertussis Surveillance (Emerging Infections Program Network) between 2010 and 2012. Surveillance data were collected through physician and patient interview and vaccine registries. We assessed whether having received an age-appropriate number of pertussis vaccines (AAV) (for persons aged ≥3 months) was associated with reduced odds of posttussive vomiting, a marker of more clinically significant illness, or of severe pertussis (seizure, encephalopathy, pneumonia, and/or hospitalization). Adjusted odds ratios were calculated using multivariable logistic regression. Results Among 9801 pertussis patients aged ≥3 months, 77.6% were AAV. AAV status was associated with a 60% reduction in odds of severe disease in children aged 7 months-6 years in multivariable logistic regression and a 30% reduction in odds of posttussive vomiting in persons aged 19 months-64 years. Conclusions Serious pertussis symptoms and complications are less common among AAV pertussis patients, demonstrating that the positive impact of pertussis vaccination extends beyond decreasing risk of disease.

Background Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well described. Methods All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described. Annualized incidence rates among MSM and non-MSM were compared through calculation of the relative risk and 95% confidence intervals. Isolates from meningococcal disease cases among MSM were characterized using standard microbiological methods and whole-genome sequencing. Results Seventy-four cases of meningococcal disease were reported among MSM and 453 among non-MSM. Annualized incidence of meningococcal disease among MSM was 0.56 cases per 100000 population, compared to 0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1-5.1). Among the 64 MSM with known status, 38 (59%) were infected with human immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6) the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were serogroup C sequence type 11. Conclusions MSM are at increased risk for meningococcal disease, although the incidence of disease remains low. HIV infection may be an important factor for this increased risk. Routine vaccination of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in accordance with Advisory Committee on Immunization Practices recommendations should be encouraged.

Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections.

Although pertussis disease is vaccine preventable, Washington State experienced a substantial rise in pertussis incidence beginning in 2011. By June 2012, the reported cases reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011. We assessed the molecular epidemiology of this statewide epidemic using 240 isolates collected from case patients reported from 19 of 39 Washington counties during 2012 to 2013. The typing methods included pulsed-field gel electrophoresis (PFGE), multilocus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), and pertactin gene ( prn ) mutational analysis. Using the scheme PFGE-MLVA-MLST- prn mutations-Prn deficiency, the 240 isolates comprised 65 distinct typing profiles. Thirty-one PFGE types were found, with the most common types, CDC013 ( n = 51), CDC237 ( n = 44), and CDC002 ( n = 42), accounting for 57% of them. Eleven MLVA types were observed, mainly comprising type 27 ( n = 183, 76%). Seven MLST types were identified, with the majority of the isolates typing as prn2-ptxP3-ptxA1-fim3-1 ( n = 157, 65%). Four different prn mutations accounted for the 76% of isolates exhibiting pertactin deficiency. PFGE provided the highest discriminatory power ( D = 0.87) and was found to be a more powerful typing method than MLVA and MLST combined ( D = 0.67). This study provides evidence for the continued predominance of MLVA 27 and prn2-ptxP3-ptxA1 alleles, along with the reemergence of the fim3-1 allele. Our results indicate that the Bordetella pertussis population causing this epidemic was diverse, with a few molecular types predominating. The PFGE, MLVA, and MLST profiles were consistent with the predominate types circulating in the United States and other countries. For prn , several mutations were present in multiple molecular types.

Objective To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS. Data sources We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older. Study selection We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013. Data extraction We abstracted relevant data, assessed each study's internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates. Results rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear. Conclusions For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

BACKGROUND Infants are at greatest risk for severe pertussis. In 2006, the Advisory Committee on Immunization Practices recommended that adolescents and adults, especially those with infant contact, receive a single dose of Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine). To assess the effectiveness of cocooning, we conducted a case-control evaluation of infant close contacts. METHODS Pertussis cases aged

At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection. ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease (1), including persons who have persistent (e.g., genetic) deficiencies in the complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5-C9); persons receiving eculizumab (Soliris, Alexion Pharmaceuticals) for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria (because the drug binds C5 and inhibits the terminal complement pathway); and persons with functional or anatomic asplenia (including persons with sickle cell disease). Routine vaccination with meningococcal conjugate vaccine is also recommended for all healthy adolescents in the United States (1). This report summarizes the evidence considered by ACIP in recommending vaccination for HIV-infected persons, and provides recommendations and guidance for use of meningococcal conjugate vaccines (serogroups A, C, W, and Y) among HIV-infected persons aged ≥2 months; the majority of meningococcal disease among HIV-infected persons is caused by these four serogroups.

Zika virus is a mosquito-borne flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections have also been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-5). Most Zika virus infections are asymptomatic (1,6). Clinical illness, when it occurs, is generally mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. However, Zika virus infection during pregnancy can cause adverse outcomes such as fetal loss, and microcephaly and other serious brain anomalies (1-3). Guillain-Barre syndrome, a rare autoimmune condition affecting the peripheral nervous system, also has been associated with Zika virus infection (1). Following the identification of local transmission of Zika virus in Brazil in May 2015, the virus has continued to spread throughout the Region of the Americas, and travel-associated cases have increased (7). In 2016, Zika virus disease and congenital infections became nationally notifiable conditions in the United States (8). As of September 3, 2016, a total of 2,382 confirmed and probable cases of Zika virus disease with symptom onset during January 1-July 31, 2016, had been reported from 48 of 50 U.S. states and the District of Columbia. Most cases (2,354; 99%) were travel-associated, with either direct travel or an epidemiologic link to a traveler to a Zika virus-affected area. Twenty-eight (1%) cases were reported as locally acquired, including 26 associated with mosquito-borne transmission, one acquired in a laboratory, and one with an unknown mode of transmission. Zika virus disease should be considered in patients with compatible clinical signs or symptoms who traveled to or reside in areas with ongoing Zika virus transmission or who had unprotected sex with someone who traveled to those areas. Health care providers should continue to educate patients, especially pregnant women, about the importance of avoiding infection with Zika virus, and all pregnant women should be assessed for possible Zika virus exposure at each prenatal visit (2).

BACKGROUND:In the United States, the proportion of Bordetella pertussis isolates lacking pertactin, a component of acellular pertussis vaccines, increased from 14% in 2010 to 85% in 2012. The impact on vaccine effectiveness (VE) is unknown.METHODS:We conducted 2 matched case-control evaluations in Vermont to assess VE of the 5-dose diphtheria, tetanus, and acellular pertussis vaccine (DTaP) series among 4- to 10-year-olds, and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) among 11- to 19-year-olds. Cases reported during 2011 to 2013 were included. Three controls were matched to each case by medical home, and additionally by birth year for the Tdap evaluation. Vaccination history was obtained from medical records and parent interviews. Odds ratios (OR) were calculated by using conditional logistic regression; VE was estimated as (1-OR) × 100%. Pertactin status was determined for cases with available isolates.RESULTS:Overall DTaP VE was 84% (95% confidence interval [CI] 58%–94%). VE within 12 months of dose 5 was 90% (95% CI 71%–97%), declining to 68% (95% CI 10%–88%) by 5–7 years post-vaccination. Overall Tdap VE was 70% (95% CI 54%–81%). Within 12 months of Tdap vaccination, VE was 76% (95% CI 60%–85%), declining to 56% (95% CI 16%–77%) by 2–4 years post-vaccination. Of cases with available isolates, >90% were pertactin-deficient.CONCLUSIONS:Our DTaP and Tdap VE estimates remain similar to those found in other settings, despite high prevalence of pertactin deficiency in Vermont, suggesting these vaccines continue to be protective against reported pertussis disease.

Background During 9 May 2010-7 May 2011, an outbreak of pertussis-like illness (incidence, 80 cases per 100 000 persons) occurred in Franklin County, Ohio. The majority of cases were identified by IS481-directed polymerase chain reaction (PCR), which does not differentiate among Bordetella species. We sought to determine outbreak etiology and epidemiologic characteristics. Methods We obtained demographic, clinical, and vaccination-related data from the Ohio Disease Reporting System and Impact Statewide Immunization Information System. We tested sera from 14 patients for anti-pertussis toxin (PT) antibodies and used species-specific PCR on 298 nasopharyngeal specimens. Results Reported cases totaled 918. IS481 results were available for 10 serologically tested patients; 5 of 10 had discordant anti-PT antibody and IS481 results, suggestive of Bordetella holmesii, which lacks PT and harbors IS481. We identified specific Bordetella species in 164 of 298 specimens tested with multitarget PCR; B. holmesii and Bordetella pertussis were exclusively detected among 48 (29%) and 112 (68%), respectively; both were detected in 4 (2%). Among 48 patients with B. holmesii infections, 63% were aged 11-18 years, compared with 35% of 112 patients with B. pertussis infections (P = .001). Symptoms were similar among B. holmesii- and B. pertussis-infected patients. Adolescent pertussis ("Tdap") booster vaccinations were more effective against B. pertussis than B. holmesii (effectiveness: 67% and 36%, respectively; 95% confidence intervals, 38%-82% and -33% to 69%, respectively). Conclusions We report the first documented mixed outbreak of B. pertussis and B. holmesii infections. Bordetella holmesii particularly affected adolescents. Although laboratory capacity limitations might inhibit routine use of multitarget PCR for clinical diagnosis, focused testing and enhanced surveillance might improve understanding the burden of B. holmesii infection.

An affordable, highly immunogenic Neisseria meningitidis serogroup A meningococcal conjugate vaccine (PsA-TT) was licensed for use in sub-Saharan Africa in 2009. In 2010, Burkina Faso became the first country to implement a national prevention campaign, vaccinating 11·4 million people aged 1-29 years. We analysed national surveillance data around PsA-TT introduction to investigate the early effect of the vaccine on meningitis incidence and epidemics.We examined national population-based meningitis surveillance data from Burkina Faso using two sources, one with cases and deaths aggregated at the district level from 1997 to 2011, and the other enhanced with results of cerebrospinal fluid examination and laboratory testing from 2007 to 2011. We compared mortality rates and incidence of suspected meningitis, probable meningococcal meningitis by age, and serogroup-specific meningococcal disease before and during the first year after PsA-TT implementation. We assessed the risk of meningitis disease and death between years.During the 14 year period before PsA-TT introduction, Burkina Faso had 148 603 cases of suspected meningitis with 17 965 deaths, and 174 district-level epidemics. After vaccine introduction, there was a 71% decline in risk of meningitis (hazard ratio 0·29, 95% CI 0·28-0·30, p0·0001) and a 64% decline in risk of fatal meningitis (0·36, 0·33-0·40, p0·0001). We identified a statistically significant decline in risk of probable meningococcal meningitis across the age group targeted for vaccination (62%, cumulative incidence ratio [CIR] 0·38, 95% CI 0·31-0·45, p0·0001), and among children aged less than 1 year (54%, 0·46, 0·24-0·86, p=0·02) and people aged 30 years and older (55%, 0·45, 0·22-0·91, p=0·003) who were ineligible for vaccination. No cases of serogroup A meningococcal meningitis occurred among vaccinated individuals, and epidemics were eliminated. The incidence of laboratory-confirmed serogroup A N meningitidis dropped significantly to 0·01 per 100 000 individuals per year, representing a 99·8% reduction in the risk of meningococcal A meningitis (CIR 0·002, 95% CI 0·0004-0·02, p0·0001).Early evidence suggests the conjugate vaccine has substantially reduced the rate of meningitis in people in the target age group, and in the general population because of high coverage and herd immunity. These data suggest that fully implementing the PsA-TT vaccine could end epidemic meningitis of serogroup A in sub-Saharan Africa.None.

Background After the Department of Defense implemented a mandatory anthrax vaccination program in 1998 concerns were raised about potential long-term safety effects of the current anthrax vaccine. The CDC multicenter, randomized, double-blind, placebo-controlled Anthrax Vaccine Adsorbed (AVA) Human Clinical Trial to evaluate route change and dose reduction collected data on participants’ quality of life. Our objective is to assess the association between receipt of AVA and changes in health-related quality of life, as measured by the SF-36 health survey (Medical Outcomes Trust, Boston, MA), over 42 months after vaccination. Methods 1562 trial participants completed SF-36v2 health surveys at 0, 12, 18, 30 and 42 months. Physical and mental summary scores were obtained from the survey results. We used Generalized Estimating Equations (GEE) analyses to assess the association between physical and mental score difference from baseline and seven study groups receiving either AVA at each dose, saline placebo at each dose, or a reduced AVA schedule substituting saline placebo for some doses. Results Overall, mean physical and mental scores tended to decrease after baseline. However, we found no evidence that the score difference from baseline changed significantly differently between the seven study groups. Conclusions These results do not favor an association between receipt of AVA and an altered health-related quality of life over a 42-month period.

Background In 2002 CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure vaccination with Anthrax Vaccine Adsorbed (AVA) for persons at high risk of exposure to Bacillus anthracis spores. There has been concern that AVA could be associated with long term impairment of physical and/or mental health. Objectives To ascertain whether physical and mental functional status, as measured by the SF-36v2 health survey (Medical Outcomes Trust, Boston, MA), of AVA recipients and controls changed differently over time. Methods We enrolled 437 exposed (received AVA) and 139 control subjects. The exposed group received AVA under then-current Advisory Committee on Immunization Practices (ACIP) recommendations. SF-36v2 surveys were completed at 0, 12, and 30 months. SF-36v2 physical and mental scores both range from 0 to 100 with an estimated national average of 50 points. Results For physical scores, the average change from baseline was −0.53 for exposed vs. −0.67 for controls at 12 months ( p = 0.80) and −1.09 for exposed vs. −1.97 for controls at 30 months ( p = 0.23). For mental scores, the average change from baseline was −1.50 for exposed vs. −1.64 for controls at 12 months ( p = 0.86) and −2.11 for exposed vs. −0.24 for controls at 30 months ( p = 0.06). In multivariable analysis, the difference in mental score change between exposed vs. controls at 30 months was less pronounced ( p = 0.37) but other findings were similar to univariate analyses. Conclusions These results do not favor an association between receipt of AVA and an altered health related quality of life over a 30-month period.

BACKGROUND AND OBJECTIVES: We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. METHODS: We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. RESULTS: Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. CONCLUSIONS: A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.

Resurgence of pertussis was not directly correlated with changes in vaccine composition or schedule., Since the 1980s, pertussis notifications in the United States have been increasing. To determine the types of Bordetella pertussis responsible for these increases, we divided 661 B. pertussis isolates collected in the United States during 1935–2009 into 8 periods related to the introduction of novel vaccines or changes in vaccination schedule. B. pertussis diversity was highest from 1970–1990 (94%) but declined to ≈70% after 1991 and has remained constant. During 2006–2009, 81.6% of the strains encoded multilocus sequence type prn2-ptxP3-ptxS1A-fim3B, and 64% were multilocus variable number tandem repeat analysis type 27. US trends were consistent with those seen internationally; emergence and predominance of the fim3B allele was the only molecular characteristic associated with the increase in pertussis notifications. Changes in the vaccine composition and schedule were not the direct selection pressures that resulted in the allele changes present in the current B. pertussis population.

Background. Pertussis is among the most poorly controlled bacterial vaccine-preventable diseases in the United States. In 2006, a tetanus, reduced-dose diphtheria, and acellular pertussis (Tdap) booster was recommended for adolescents and adults. Tdap vaccines were licensed on the basis of antibody response without vaccine effectiveness data. Methods. From 30 September 2007 through 19 December 2007, a pertussis outbreak occurred at a nursery through twelfth grade school on St. Croix, US Virgin Islands. We screened all students for cough and collected clinical history, including Tdap receipt. Coughing students were offered diagnostic testing. We defined clinical case patients as students with cough ≥14 days in duration plus either whoop, paroxysms, or post-tussive vomiting, and we defined confirmed case patients as students with any cough with isolation of Bordetella pertussis or those with clinical cases and polymerase chain reaction or serological evidence of pertussis; other clinical cases were classified as probable. Results. There were 51 confirmed or probable cases among 499 students (attack rate, 10%). Disease clustered in grades 6-12, with a peak attack rate of 38% among 10th graders. Of 266 students aged ≥11 years with complete data, 31 (12%) had received Tdap. Forty-one unvaccinated students (18%) had confirmed or probable pertussis, compared with 2 (6%) of the vaccinated students (relative risk, 2.9); vaccine effectiveness was 65.6% (95% confidence interval, -35.8% to 91.3%; P = .092). Conclusions. This first evaluation of Tdap vaccine effectiveness in the outbreak setting suggests that Tdap provides protection against pertussis. Increased coverage is needed to realize the full benefit of the vaccine program. Serological testing was an important tool for case identification and should be considered for inclusion in the Council of State and Territorial Epidemiologists case definition.

Background Routine childhood immunization with pneumococcal conjugate vaccines (PCV7s) began in 2000 in the United States. Despite vaccine shortages, reductions in invasive pneumococcal disease occurred rapidly during 2000–2002. Age-appropriate PCV7 coverage was estimated and characteristics associated with undervaccination were identified for children in the 1998–2002 birth cohorts. Methods Data were analyzed for 85,135 children aged 19–35 months in the 2001–2004 National Immunization Surveys. To obtain PCV7 coverage estimates by birth cohorts, a pooled analysis was conducted by combining individual survey years that sampled children with appropriate birth dates. Logistic regression models were used to identify factors associated with age-appropriate vaccination. Results The proportion of children receiving the primary 3-dose PCV7 series by age 12 months increased from 45.5% (±0.6) among children born in 2000 to 62.1% (±0.7) among those born in 2002. By age 24 months, an estimated 30.7% (±0.6), 38.0% (±0.6), and 49.0% (±1.1) of children born in 2000, 2001 and 2002, respectively, had received all four PCV7 doses; however, only 15.0% (±0.4), 16.1% (±0.4) and 24.4% (±0.6) of children were age-appropriately immunized. Among children born in 1998 and 1999, 10.1% ±0.5) and 37.6% (±0.7), respectively, received one or more catch-up doses during their second year of life. Lower age-appropriate PCV7 coverage was independently associated with black race, Hispanic ethnicity, receiving vaccinations from public health providers, and low household income. Conclusions The dramatic reductions in pneumococcal-related diseases from direct and indirect vaccine effects occurred when few children had received the recommended complete vaccine schedule, and there were substantial racial and socioeconomic disparities in coverage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of hemorrhagic stroke with 30-day mortality between 33 and 45%. Delayed cerebral ischemia (DCI) is the chief cause of morbidity and mortality in patients who survive the initial aSAH. DCI accounts for almost 50% of deaths in patients surviving to treatment of the ruptured aneurysm. The mechanisms for brain injury after aSAH and the brain's response to this injury are not fully understood in humans. MicroRNAs (miRs) are 22- to 25-nucleotide single-stranded RNA molecules that inhibit the expression of specific messenger RNA targets. In this work, miR profiling of human cerebrospinal fluid from eight patients after aSAH was performed daily for 10 days with the goal of identifying changes in miR abundance. Using the nanoString nCounter Expression Assay, we identified two specific clusters of miR that were differentially regulated over time. Quantitative RT-PCR was performed on select miRs from each cluster. The first cluster contained miRs known to be present in blood and decreased in abundance over time. miRs in this group include miR-92a and let-7b. The second cluster contained several poorly characterized miRs that increased in abundance over time. miRs in this group included miR-491. This second cluster of miRs may be released into the CSF by the brain itself as a result of the initial SAH. Temporal changes in the abundance of specific miRs in human CSF after aSAH may provide novel insight into the role of miRs in brain injury and the brain's response.

Multiple school-associated pertussis outbreaks were reported in Maine from 2010 to 2011. These outbreaks were associated with an overall increase in pertussis cases statewide. Waning of protection in students recently vaccinated with tetanus, diphtheria, and acellular pertussis (Tdap) has been implicated in the increase in reported rates of pertussis nationally.We conducted a retrospective cohort study to evaluate Tdap vaccine effectiveness (VE) among students aged 11-19 years in two schools reporting outbreaks in 2011. All pertussis cases reported from August through November, 2011 at the two schools were included. Vaccination history was verified using provider information, state vaccine registry data, and parental verification. Attack rates (AR) were calculated. VE and duration of protection was calculated as VE=1-(ARvaccinated/ARunvaccinated)×100% using a log binomial regression model.Of 416 students enrolled, 314 were included in the analyses. Twenty-nine cases collectively in Schools A and B. Tdap coverage was 65% at School A and 42% at School B before the start of the outbreak. Among students enrolled in the study, attack rates were 11.9% and 7.7% at Schools A and B, respectively. Overall VE was 68.5% (95% confidence interval (CI) 37.7-86.2). VE was 70.4% (95% CI 17.5-89.4) for School A and 65.2% (95% CI -19.2 to 89.9) for School B. VE2 years versus ≥2 years from outbreak onset was not significantly different.Tdap was moderately effective in preventing disease among vaccinated students. Vaccine coverage of 65% or less was suboptimal and might contribute to outbreaks. Waning VE was not demonstrated. Increased vaccination coverage rates as well as further evaluation of the role of acellular vaccine on VE is needed.

Background. A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN – ) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed. Methods. We retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis. Results. Among 753 isolates, 640 (85%) were PRN – . The age distribution differed between cases caused by PRN – B. pertussis and cases caused by B. pertussis producing pertactin (PRN + )( P =. 01). The proportion reporting individual pertussis symptoms was similar between the 2 groups, except a higher proportion of PRN + case-patients reported apnea (P= .005). Twenty-two case-patients were hospitalized; 6% in the PRN + group compared to 3% in the PRN – group (P= .11). Case-patients having received at least 1 pertussis vaccine dose had a higher odds of having PRN – B. pertussis compared with unvaccinated case-patients (adjusted OR = 2.2; 95% confidence interval [CI], 1.3– 4.0). When restricted to case-patients at least 1 year of age and those age-appropriately vaccinated, the adjusted OR increased to 2.7 (95% CI, 1.2–6.1). Conclusions. The significant association between vaccination and isolate pertactin production suggests that the likelihood of having reported disease caused by PRN – compared with PRN + strains is greater in vaccinated persons. Additional studies are needed to assess whether vaccine effectiveness is diminished against PRN – strains.

Background Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n = 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n = 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.