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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.

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

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.

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.

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.

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.

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.

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.

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 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.

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.

The formation of 10 to 40 μm Composite Gel MicroParticles (CGMPs) comprising ~100 nm drug containing nanoparticles (NPs) in a poly(ethylene glycol)(PEG) gel matrix is described. The CGMP particles enable targeting to the lung by filtration from the venous circulation. UV radical polymerization and Michael addition polymerization reactions are compared as approaches to form the PEG matrix. A fluorescent dye in the solid core of the NP was used to investigate the effect of reaction chemistry on the integrity of encapsulated species. When formed via UV radical polymerization, the fluorescence signal from the NPs indicated degradation of the encapsulated species by radical attack. The degradation decreased fluorescence by 90% over 15 minutes of UV exposure. When formed via Michael addition polymerization, the fluorescence was maintained. Emulsion processing using controlled shear stress enabled control of droplet size with narrow polydispersities. To allow for emulsion processing, the gelation rate was delayed by adjusting the solution pH. At a pH= 5.4 the gelation occurred at 3.5 hours. The modulus of the gels was tuned over the range of 5 to 50 kPa by changing the polymer concentration between 20 and 70 vol %. NPs aggregation during polymerization, driven by depletion forces, was controlled by the reaction kinetics. The ester bonds in the gel network enabled CGMP degradation. The gel modulus decreased by 50% over 27 days, followed by complete gel degradation after 55 days. This permits ultimate clearance of the CGMPs from the lungs. The demonstration of uniform delivery of 15.8 ± 2.6 μm CGMPs to the lungs of mice, with no deposition in other organs, is shown, and indicates the ability to target therapeutics to the lung while avoiding off-target toxic exposure.

Since 2012, three clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States. During 2012, 13 cases of meningococcal disease among MSM were reported by the New York City Department of Health and Mental Hygiene (1); over a 5-month period during 2012–2013, the Los Angeles County Department of Public Health reported four cases among MSM; and during May–June 2015, the Chicago Department of Public Health reported seven cases of meningococcal disease among MSM in the greater Chicago area. MSM have not previously been considered at increased risk for meningococcal disease. Determining outbreak thresholds* for special populations of unknown size (such as MSM) can be difficult. The New York City health department declared an outbreak based on an estimated increased risk for meningococcal infection in 2012 among MSM and human immunodeficiency virus (HIV)–infected MSM compared with city residents who were not MSM or for whom MSM status was unknown (1). The Chicago Department of Public Health also declared an outbreak based on an increase in case counts and thresholds calculated using population estimates of MSM and HIV-infected MSM. Local public health response included increasing awareness among MSM, conducting contact tracing and providing chemoprophylaxis to close contacts, and offering vaccination to the population at risk (1–3). To better understand the epidemiology and burden of meningococcal disease in MSM populations in the United States and to inform recommendations, CDC analyzed data from a retrospective review of reported cases from January 2012 through June 2015.

On February 2, 2015, the Rhode Island Department of Health was notified of a case of meningococcal disease in a male undergraduate student at Providence College. Three days later, a second case was reported in a male undergraduate with no contact with the first student, indicating an attack rate of 44 cases per 100,000 students, nearly 500 times higher than the national incidence of 0.15 cases per 100,000 among persons aged 17-22 years (Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC, unpublished data, 2013). Both cases were caused by a rare outbreak strain of Neisseria meningitidis serogroup B (ST-9069); neither case was fatal. In response to the outbreak, potential contacts received antibiotic chemoprophylaxis, and a mass vaccination campaign with a recently licensed serogroup B meningococcal (MenB) vaccine was implemented. In collaboration with CDC, the first phase of a meningococcal carriage evaluation was undertaken.

Objective We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Methods Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 “annual” boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). Results The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months. Conclusions A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response.

There is accumulating literature on waning acellular pertussis vaccine-induced immunity, confirming the results of studies assessing the duration of protection of pertussis vaccines.To evaluate the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine's effect over time among those 11 to 18 years old, while accounting for the transition from whole-cell to acellular pertussis vaccines for the childhood primary series.Extended, retrospective analysis of reported pertussis cases between January 1, 1990, and December 31, 2014, in the United States. The analysis included all nationally reported pertussis cases.US Tdap vaccination program and the transition from whole-cell to acellular pertussis vaccines.Rate ratios of reported pertussis incidence (defined as incidence among 11- to 18-year-old individuals divided by the combined incidence in all other age groups) modeled with segmented regression analysis and age-specific trends in reported pertussis incidence over time.Between 1990 and 2014, 356 557 pertussis cases were reported in the United States. Of those, 191 914 (53.8%) were female and 240 665 (67.5%) were white. Overall incidence increased from 1.7 in 100 000 to 4.0 in 100 000 between 1990 and 2003, while latter years were dominated by epidemic peaks. Incidence was highest among infants younger than 1 year throughout the analysis period. Pertussis rates were comparable among all other age groups until the late 2000s, when an increased burden of pertussis emerged among children 1 to 10 years old, resulting in the second highest age-specific incidence. By 2014, 11- to 18-year-old individuals once again had the second highest incidence. While slope coefficients from segmented regression analysis showed a positive impact of Tdap immediately following introduction (slope, -0.4959; P .001), a reversal in trends was observed in 2010 when rates of disease among 11- to 18-year-old individuals increased at a faster rate than all other age groups combined (slope, 0.5727; P .001).While the impact of Tdap among adolescents looked promising following vaccine introduction, our extended analysis found that trends in adolescent disease were abruptly reversed in 2010, corresponding directly to the aging of acellular pertussis-vaccinated cohorts. Despite the apparent limitations of Tdap, it remains the best prevention against disease in adolescents.

This study describes the serotype distribution and antibiotic resistance patterns among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil, during the period of 2000-2007, before introduction of the 10-valent pneumococcal conjugate vaccine. The active hospital-based surveillance showed a decline in the annual incidence rates of pneumococcal meningitis during the period of study, from 1.12 cases to 0.83 cases/100,000 persons for all age groups (P0.001), with an overall case-fatality rate of 28.6% (113 of 395) for all patients and 41.9% (57 of 136) for those5 years of age. Serotypes 14 (n=55; 13.9%), 3 (n=32; 8.1%), 23F (n=32; 8.1%), 19F (n=31; 7.8%), 6B (n=30; 7.6%), 18C (n=28; 7.1%), and 6A (n=20; 5%) were the most prevalent serotypes. In patients5 years the estimated projected coverage of 7-, 10- and 13-valent conjugate vaccines was 74.3%, 75.7% and 83.1%, respectively. Antimicrobial susceptibility testing revealed that 22.1% (n=88) of isolates were non-susceptible to penicillin, 56% were non-susceptible to trimethoprim/sulphamethoxazole, and 29.6% were non-susceptible to tetracycline. Nonsusceptibility to penicillin and cefotaxime was detected solely among serotype 14 isolates (n=4; 1%). This study provides an important baseline to assess the impact of conjugate vaccine implantation on the epidemiology of meningitis due to Streptococcus pneumoniae in Salvador, Brazil.

In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P.001). Route of administration did not significantly influence the occurrence of systemic AEs.The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.

In 2002, CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure anthrax vaccination for individuals at high risk for exposure to Bacillus anthracis spores. The AVP offered an opportunity to investigate hypothesized reasons for a reported gender difference in injection site adverse events (AEs) following anthrax vaccine adsorbed (AVA).To evaluate in women the impact of body mass index (BMI), pre-vaccination serum progesterone levels, and pre-vaccination anti-anthrax protective antigen immunoglobulin G concentrations (anti-PA IgG) on the occurrence of AEs following subcutaneous AVA vaccination.Participants' BMI was determined at enrollment. Also, pre-vaccination blood samples were assayed for serum progesterone and anti-PA IgG. Post-vaccination solicited AEs were recorded by participants using a 4-day diary card.Obese group had an elevated risk for arm soreness. Decreased pre-vaccination serum progesterone level was associated with arm swelling. Increased pre-vaccination anti-PA IgG was associated with itching on the arm; and within the obese group, was associated with arm swelling, lump or knot, redness, soreness, and warmth.In AVA vaccinated women, obesity was associated with arm soreness and decreased pre-vaccination serum progesterone levels were associated with increased rate of arm swelling. Increased pre-vaccination anti-PA IgG may be associated with an increased frequency of itching on the arm, and in obese women, may increase the occurrence of arm swelling, lump or knot, redness, and warmth. Administering AVA according to a woman's menstrual phase may reduce the occurrence of certain injection site reactions.

Summary Background Routine infant immunisation with seven-valent pneumococcal conjugate vaccine (PCV7) began in the USA in 2000. Although invasive pneumococcal disease has declined substantially, the programme's effect on hospital admissions for pneumonia is unknown. We therefore assessed the effect of the programme on rates of all-cause and pneumococcal pneumonia admissions. Methods Data from the Nationwide Inpatient Sample, the largest inpatient database available in the USA, were analysed with an interrupted time-series analysis that used pneumonia (all-cause and pneumococcal) admission rates as the main outcomes. Monthly admission rates estimated for years after the introduction of PCV7 vaccination (2001–2004) were compared with expected rates calculated from pre-PCV7 years (1997–1999). The year of vaccine introduction (2000) was excluded, and rates of admission for dehydration were assessed for comparison. Findings At the end of 2004, all-cause pneumonia admission rates had declined by 39% (95% CI 22–52) for children younger than 2 years, who were the target population of the vaccination programme. This annual decline in all-cause pneumonia admissions of 506 (291–675) per 100 000 children younger than 2 years represented about 41 000 pneumonia admissions prevented in 2004. During the 8 study years, 10 659 (2%) children younger than 2 years admitted with pneumonia were coded as having pneumococcal disease; these rates declined by 65% (47–77). This decline represented about 17 fewer admissions per 100 000 children in 2004. Admission rates for dehydration for children younger than 2 years remained stable over the study period. Interpretation The reduction in all-cause pneumonia admissions in children younger than 2 years provides an estimate of the proportion of childhood pneumonias attributable to Streptococcus pneumoniae in the USA that are vaccine preventable. Our results contribute to the growing body of evidence supporting the beneficial effects of the pneumococcal conjugate vaccines in children.

OBJECTIVE. Streptococcus pneumoniae is an important cause of otitis media in children. In this study we estimated the effect of routine childhood immunization with heptavalent pneumococcal conjugate vaccine on frequent otitis media (3 episodes in 6 months or 4 episodes in 1 year) and pressure-equalizing tube insertions. PATIENTS AND METHODS. The study population included all children who were enrolled at birth in TennCare or selected upstate New York commercial insurance plans as of July 1998 and continuously followed until 5 years old, loss of health plan enrollment, study outcome, or end of the study. We compared the risk of developing frequent otitis media or having pressure-equalizing tube insertion for 4 birth cohorts (1998–1999, 1999–2000, 2000–2001, and 2001–2002) by using Cox regression analysis. We used data from the National Immunization Survey to estimate the heptavalent pneumococcal conjugate vaccine uptake for children in these 4 birth cohorts in Tennessee and New York. RESULTS. The proportion of children in Tennessee and New York who received at least 3 doses of heptavalent pneumococcal conjugate vaccine by 2 years of age increased from ≤1% for the 1998–1999 birth cohort to ∼75% for the 2000–2001 birth cohort. By age 2 years, 29% of Tennessee and New York children born in 2000–2001 had developed frequent otitis media, and 6% of each of these birth cohorts had pressure-equalizing tubes inserted. Comparing the 2000–2001 birth cohort to the 1998–1999 birth cohort, frequent otitis media declined by 17% and 28%, and pressure-equalizing tube insertions declined by 16% and 23% for Tennessee and New York children, respectively. For the 2000–2001 to the 2001–2002 birth cohort, frequent otitis media and pressure-equalizing tubes remained stable in New York but increased in Tennessee. CONCLUSIONS. After heptavalent pneumococcal conjugate vaccine introduction, children were less likely to develop frequent otitis media or have pressure-equalizing tube insertions.

BACKGROUND. Since introduction of the heptavalent pneumococcal conjugate vaccine in the United States in 2000, rates of invasive pneumococcal disease have declined. However, the national impact of heptavalent pneumococcal conjugate vaccine on pneumonia and otitis media remains unknown. OBJECTIVES. We compared national rates of outpatient visits for pneumonia and otitis media in children before and after heptavalent pneumococcal conjugate vaccine introduction. METHODS. Rates of ambulatory visits for pneumococcal and nonspecific pneumonia, otitis media, and other acute respiratory infections were compared before (1994–1999) and after (2002–2003) heptavalent pneumococcal conjugate vaccine introduction using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. To evaluate vaccine effects while accounting for temporal variability, ratios of pneumococcal-related disease rates in children RESULTS. After the introduction of heptavalent pneumococcal conjugate vaccine, otitis media visit rates declined by 20% in children aged CONCLUSIONS. After heptavalent pneumococcal conjugate vaccine introduction, national rates of otitis media visits declined significantly in children

Laboratory technicians, laboratory supervisors, decontamination/remediation workers, and environmental investigators are at increased risk for repeated occupational exposure to Bacillus anthracis. In 2002, the Advisory Committee on Immunization Practices (ACIP) recommended pre-exposure vaccination for these occupational groups.To determine (1) the factors that influenced an individual's decision to either accept or decline Anthrax Vaccine Adsorbed (AVA), and (2) if laboratory workers' concern about AVA safety was related to their information needs and trust in the information provided.We conducted a decision-making survey of 404 participants at 44 Laboratory Response Network laboratories located throughout the United States. All participants were enrolled between October 2002 and December 2004, and all were eligible to receive AVA according to the 2002 ACIP recommendations. Chi-square tests and multivariate logistic regression were used in the analyses.The response rate of eligible individuals at participating laboratories was 94% (404/430). Sixty-six percent of respondents accepted and 34% declined AVA. Laboratory workers who declined AVA were more likely to rate their risk of exposure to inhalation anthrax as low (OR = 6.9; 95%CI 1.7, 28.3), report being very concerned (OR = 4.1; 95%CI 1.8, 9.3) or concerned (OR = 2.0; 95%CI 1.3, 3.1) about the safety of the vaccine, report that they did not trust the information provided in the Vaccine Information Statement (VIS) (OR = 2.3; 95%CI 1.1, 4.5), and to be enrolled in the study during 2002 (OR = 24.7; 95%CI 6.4, 95.3) or 2003 (OR = 5.0; 95%CI 2.5, 9.8), the first 2 years of the study. Furthermore, we found a significant association between a participant's level of concern about the safety of AVA and their perception that they received enough information and/or trusted the information in the VIS.Low perceived necessity, concern about the safety of the vaccine, and a lack of trust in the VIS were associated with the decision of laboratory workers to decline AVA. Results of this decision-making study may be used to try to improve acceptance rates of AVA among persons considered at high risk, and may inform educational efforts for other adult vaccines.

Purpose The CDC's Anthrax Vaccine and Antibiotic Availability Program was implemented under an Investigational New Drug (IND) application to provide additional post-exposure prophylaxis for individuals potentially exposed to Bacillus anthracis in the fall of 2001. Participants were provided with two options: (1) 40 additional days of antimicrobial prophylaxis (i.e., ciprofloxacin, doxycycline, or amoxicillin); or (2) 40 additional days of antimicrobial prophylaxis plus three doses of anthrax vaccine adsorbed (AVA). Methods Participants were monitored for adverse events (AEs). Participants were asked to complete 2-week AE diaries for 6 weeks post-enrollment, and approximately 2 months after enrollment, active surveillance was conducted through telephone interviews with 1113 (64%) participants. Results A total of 1727 of approximately 10 000 previously prophylaxed persons enrolled to receive 40 additional days of antibiotics. Of these, 199 opted at enrollment to receive three doses of AVA in addition to the additional 40 days of antibiotic. Overall, 28% of participants reported at least one AE on their diaries. Results varied by surveillance mechanism, the diary data indicated differences in the proportion reporting AEs between participants receiving antibiotic only and participants receiving antibiotic and AVA. However, during the active 2-month telephone follow-up, the rates of AEs reported for both the antibiotic only and antibiotic plus AVA treatment regimens were similar. Additionally, ciprofloxacin and doxycycline had similar AE profiles, with only rigors reported significantly more often among ciprofloxacin recipients. Conclusions Overall, the rates of AEs experienced by all participants were acceptable given the seriousness of potential B. anthracis exposure. Copyright © 2005 John Wiley & Sons, Ltd.

We undertook to develop a tool based on the FIM instrument to predict the number of nursing hours required to care for stroke patients in an acute inpatient rehabilitation program. The initial study to evaluate the feasibility of using the FIM instrument revealed that the total FIM score had a strong inverse relation to the level of care indicated by the Patient Care Index (PCI) at days 1, 5, 7, 10, 15, and 20 of rehabilitation (rs = -.76 to -.87). The results warranted continued investigation of the FIM instrument as a guide for nurse staffing decisions. Based on data from the initial study, five categories of FIM score ranges were designated that demonstrated the most accuracy of placing patients at the correct level of care. Special care considerations unique to institutional settings were identified and incorporated into the tool's final format, as were the calculations to determine the amount of assistance needed. The study reported here was undertaken to evaluate the level of care indicated by the adapted tool, compared with that of the PCI, in a sample of 67 stroke admissions. Spearman correlations revealed a moderate relationship (rs = .49 to .54) between the amount of care determined by the Patient Acuity and Staffing tool and through the PCI at the first, second, and third team meetings. We conclude that the system is an effective, efficient guide for scheduling nurse staffing on the stroke rehabilitation unit.

The purpose of this study was to evaluate the feasibility of using the Functional Independence Measure (FIM) to predict staffing needs of stroke patients in an acute inpatient rehabilitation program. The Patient Care Index (PCI) was concurrently administered with the FIM on all stroke admissions to a stroke rehabilitation unit over a 3-month period. One hundred fourteen patients 18 years of age or older admitted to the unit with a medical diagnosis of stroke were included in the sample. Total FIM score had a strong inverse relationship to the level of care indicated by the PCI at Days 1, 5, 7, 10, 15, and 20 of rehabilitation (rs = —.76 to —.87). Total FIM score and the need for staff supervision for safety were the two factors predictive of the level of nursing care. The FIM has potential to guide nurse-staffing decisions.

Balance and imbalance between oxidant stress and antioxidants contributes to the manifestations of human immunodeficiency virus (HIV) infection. Previously, we demonstrated a characteristic cytokine pattern in marrow supernatant from HIV patients who underwent diagnostic examinations.In this report, we have determined the protein nitrotyrosine (pNT) concentration (an indicator of nitric oxide-superoxide interaction) as well as the concentration of the redox enzyme thioredoxin (Trx) in marrow supernatant from HIV patients, healthy controls, and other patients, and in serum from comparable subjects.pNT concentrations were similar in serum and marrow supernatant and did not differ between subject subsets. Trx concentrations in both marrow supernatant and serum were higher for HIV patients than for other subjects; serum Trx concentrations were significantly higher than marrow Trx concentrations for the non-HIV patients and controls. The ratios of pNT/Trx concentrations in serum were similar in all subsets tested. In marrow aspirate, however, these ratios differed widely and significantly, with the highest values observed in non-HIV patients and the lowest in HIV patients. Only for HIV patients were serum and marrow supernatant pNT/Trx ratios similar. In HIV patients, marrow Trx concentrations correlated with CD4 count, CD4/CD8 ratio, and marrow colony-forming unit E (CFU-E) concentration; marrow pNT concentration correlated with the concentration of tumor necrosis factor in marrow supernatant, and with platelet count. No correlations were observed in other subject subsets.These findings suggest that there is a degree of local regulation of the redox state of the marrow microenvironment that varies with the patients' clinical statuses, and which is associated with effects on hematopoiesis.