Individuals with certain primary immunodeficiency disorders (PID) may be unable to clear poliovirus infection after exposure to oral poliovirus vaccine (OPV). Over time, vaccine-related strains can revert to immunodeficiency-associated vaccine-derived poliovirus (iVDPVs) that can cause paralysis in the patient and potentially spread in communities with low immunity. We reviewed the efforts for detection and management of PID patients with iVDPV infections and the epidemiology through an analysis of 184 cases reported to the World Health Organization (WHO) during 1962-2024 and a review of polio program and literature reports. Most iVDPV patients (79%) reported in the WHO Registry were residents in middle-income countries and almost half (48%) in the Eastern Mediterranean Region. Type 2 iVDPV was most frequently isolated (53%), but a sharp decline was observed after the switch to bivalent OPV in 2016, with only six cases reported during 2017-2024 compared to 63 during 2009-2016. Patients with common variable immunodeficiency have longer excretion of iVDPV than with other PID types. Implementation of sensitive sentinel surveillance to detect cases of iVDPV infection in high-risk countries and offer antiviral treatment to patients is challenged by competition with other health priorities and regulatory hurdles to the compassionate use of investigational antiviral drugs.

Preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), in colleges and universities requires mitigation strategies that address on- and off-campus congregate living settings as well as extracurricular activities and other social gatherings (1-4). At the start of the academic year, sorority and fraternity organizations host a series of recruitment activities known as rush week; rush week culminates with bid day, when selections are announced. At university A in Arkansas, sorority rush week (for women) was held during August 17-22, 2020, and consisted of on- and off-campus social gatherings, including an outdoor bid day event on August 22. Fraternity rush week (for men) occurred during August 27-31, with bid day scheduled for September 5. During August 22-September 5, university A-associated COVID-19 cases were reported to the Arkansas Department of Health (ADH). A total of 965 confirmed and probable COVID-19 cases associated with university A were identified, with symptom onset occurring during August 20-September 5, 2020; 31% of the patients with these cases reported involvement in any fraternity or sorority activity. Network analysis identified 54 gatherings among all linkages of cases to places of residence and cases to events, 49 (91%) were linked by participation in fraternity and sorority activities accounting for 42 (72%) links among gatherings. On September 4, university A banned gatherings of ≥10 persons, and fraternity bid day was held virtually. The rapid increase in COVID-19 cases was likely facilitated by on- and off-campus congregate living settings and activities, and health departments should work together with student organizations and university leadership to ensure compliance with mitigation measures.

BACKGROUND: Japanese encephalitis (JE) virus is an important cause of neurological disease in Asia. JE vaccine is recommended for travelers with higher JE risk itineraries. Inactivated Vero cell culture-derived JE vaccine (JE-VC) is the only JE vaccine currently available in the United States. An inactivated mouse brain-derived JE vaccine (JE-MB) previously was available but production was discontinued. One JE-VC dose administered to adults previously vaccinated with ≥3 doses of JE-MB provides good short-term protection for at least one month, but data on longer-term protection are limited. We evaluated non-inferiority of the JE virus neutralizing antibody response at 12-23 months in JE-MB-vaccinated adults administered one JE-VC dose compared with JE vaccine-naïve adults administered a JE-VC two-dose primary series. METHODS: We obtained archived sera from U.S. military personnel and performed a 50% plaque reduction neutralization test for anti-JE virus neutralizing antibodies. We compared the geometric mean titer (GMT) and seroprotection rate at 12-23 months after one JE-VC dose in previously JE-MB-vaccinated personnel and after the second JE-VC dose in previously JE vaccine-naïve personnel. Non-inferiority was concluded if the lower bound of the two-sided 95% confidence interval (CI) of the GMT ratio in previously vaccinated to vaccine-naïve personnel was >1/1.5. RESULTS: The GMT in previously JE-MB-vaccinated persons was 75 (95% CI 63-90) and in previously JE vaccine-naïve persons was 12 (95% CI 11-14), and seroprotection rates were 94% (235/250) and 54% (135/250), respectively. The ratio of GMTs was 6.3 (95% CI: 5.0-7.7), satisfying the criterion for non-inferiority. CONCLUSIONS: One JE-VC dose in previously JE-MB-vaccinated military personnel provides good protection for at least 1-2 years. The benefits of administration of a single JE-VC dose in previously JE-MB-vaccinated adults include a shorter time to completion of re-vaccination before travel, a decrease in the risk of adverse events, and reduced costs.

Background: Few studies have assessed the duration of humoral immunity following yellow fever (YF) vaccination in a non-endemic population. We evaluated seropositivity among U.S. resident travelers based on time post-vaccination. Methods: We identified serum samples from U.S. travelers with YF virus-specific plaque reduction neutralization testing (PRNT) performed at CDC from 1988-2016. Analyses were conducted to assess the effect of time since vaccination on neutralizing antibody titer counts. Results: Among 234 travelers who had neutralizing antibody testing performed on a specimen obtained >/=1 month after vaccination, 13 received multiple YF vaccinations and 221 had one dose of YF vaccine reported. All 13 who received more than one dose of YF vaccine had a positive PRNT regardless of the amount time since most recent vaccination. Among the 221 travelers with one reported dose of YF vaccine, 155 (70%) were vaccinated within 10 years (range 1 month-9 years) and 66 (30%) were vaccinated >/=10 years (range 10-53 years) prior to serum collection. Among the 155 individuals vaccinated <10 years prior to serum collection, 146 (94%) had a positive PRNT compared to 82% (54/66) of individuals vaccinated >/=10 years prior to serum collection (p = 0.01). Post-vaccination PRNT titers showed a time-dependent decrease. Individuals with immunocompromising conditions were less likely to have a positive PRNT (77%) compared to those who were not immunocompromised (92%; p = 0.04). Conclusion: Although the percentage of vaccinees with a positive PRNT and antibody titers decreased over time, a single dose of YF vaccine provided long-lasting protection in the majority of U.S. travelers. A booster dose could be considered for certain travelers who are planning travel to a high risk area based on immune competence and time since vaccination.

BACKGROUND: Powassan virus (POWV) is a tick-borne flavivirus that causes rare, but often severe, disease in humans. POWV neuroinvasive disease was added to the U.S. nationally notifiable disease list in 2001 and nonneuroinvasive disease was added in 2004. The only previous review of the epidemiology of POWV disease in the United States based on cases reported to the Centers for Disease Control and Prevention (CDC) covered the period from 1999 through 2005. METHODS: We describe the epidemiology and clinical features of laboratory-confirmed POWV disease cases reported to CDC from 2006 through 2016. RESULTS: There were 99 cases of POWV disease reported during the 11-year period, including 89 neuroinvasive and 10 nonneuroinvasive disease cases. There was a median of seven cases per year (range: 1-22), with the highest numbers of cases reported in 2011 (n = 16), 2013 (n = 15), and 2016 (n = 22). Cases occurred throughout the year, but peaked in May and June. Cases were reported primarily from northeastern and north-central states. Overall, 72 (73%) cases were in males and the median age was 62 years (range: 3 months-87 years). Of the 11 (11%) cases who died, all were aged >50 years. The average annual incidence of neuroinvasive POWV disease was 0.0025 cases per 100,000 persons. CONCLUSIONS: POWV disease can be a severe disease and has been diagnosed with increased frequency in recent years. However, this might reflect increased disease awareness, improved test availability, and enhanced surveillance efforts. Clinicians should consider POWV disease in patients presenting with acute encephalitis or aseptic meningitis who are resident in, or have traveled to, an appropriate geographic region.

Background: In 2015, the number of infants born with microcephaly increased in Paraiba, Brazil, after a suspected Zika virus outbreak. We did a retrospective case-control investigation to assess the association of microcephaly and Zika virus. Methods: We enrolled cases reported to the national database for microcephaly and born between Aug 1, 2015, and Feb 1, 2016, on the basis of their birth head circumference and total body length. We identified controls from the national birth registry and matched them to cases by location, aiming to enrol a minimum of two controls per case. Mothers of both cases and controls were asked about demographics, exposures, and illnesses and infants were measured at a follow-up visit 1-7 months after birth. We took blood samples from mothers and infants and classified those containing Zika virus IgM and neutralising antibodies as evidence of recent infection. We calculated prevalence of microcephaly and odds ratios (ORs) using a conditional logistic regression model with maximum penalised conditional likelihood, and combined these ORs with exposure probability estimates to determine the attributable risk. Findings: We enrolled 164 of 706 infants with complete information reported with microcephaly at birth, of whom we classified 91 (55%) as having microcephaly on the basis of their birth measurements, 36 (22%) as small, 21 (13%) as disproportionate, and 16 (10%) as not having microcephaly. 43 (26%) of the 164 infants had microcephaly at follow-up for an estimated prevalence of 5.9 per 1000 livebirths. We enrolled 114 control infants matched to the 43 infants classified as having microcephaly at follow-up. Infants with microcephaly at follow-up were more likely than control infants to be younger (OR 0.5, 95% CI 0.4-0.7), have recent Zika virus infection (21.9, 7.0-109.3), or a mother with Zika-like symptoms in the first trimester (6.2, 2.8-15.4). Once Zika virus infection and infant age were controlled for, we found no significant association between microcephaly and maternal demographics, medications, toxins, or other infections. Based on the presence of Zika virus antibodies in infants, we concluded that 35-87% of microcephaly occurring during the time of our investigation in northeast Brazil was attributable to Zika virus. We estimate 2-5 infants per 1000 livebirths in Paraiba had microcephaly attributable to Zika virus. Interpretation: Time of exposure to Zika virus and evidence of infection in the infants were the only risk factors associated with microcephaly. This investigation has improved understanding of the outbreak of microcephaly in northeast Brazil and highlights the need to obtain multiple measurements after birth to establish if an infant has microcephaly and the need for further research to optimise testing criteria for congenital Zika virus infection. Funding: Centers for Disease Control and Prevention.

In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barre syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April-July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9-47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

In 2016, Zika virus disease developed in a man (patient A) who had no known risk factors beyond caring for a relative who died of this disease (index patient). We investigated the source of infection for patient A by surveying other family contacts, healthcare personnel, and community members, and testing samples for Zika virus. We identified 19 family contacts who had similar exposures to the index patient; 86 healthcare personnel had contact with the index patient, including 57 (66%) who had contact with body fluids. Of 218 community members interviewed, 28 (13%) reported signs/symptoms and 132 (61%) provided a sample. Except for patient A, no other persons tested had laboratory evidence of recent Zika virus infection. Of 5,875 mosquitoes collected, none were known vectors of Zika virus and all were negative for Zika virus. The mechanism of transmission to patient A remains unknown but was likely person-to-person contact with the index patient.

Information about the Zika virus disease incubation period can help identify risk periods and local virus transmission. In 2015-2016, data from 197 symptomatic travelers with recent Zika virus infection indicated an estimated incubation period of 3-14 days. For symptomatic persons with symptoms >2 weeks after travel, transmission might be not travel associated.

Zika virus is a mosquito-borne flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes. 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. Most Zika virus infections are asymptomatic. 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. Guillain-Barre syndrome, a rare autoimmune condition affecting the peripheral nervous system, also has been associated with Zika virus infection. 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. 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.

On July 12, 2016, the Utah Department of Health (UDOH) was notified by a clinician caring for an adult (patient A) who was evaluated for fever, rash, and conjunctivitis that began on July 1. Patient A had not traveled to an area with ongoing Zika virus transmission; had not had sexual contact with a person who recently traveled; and had not received a blood transfusion, organ transplant, or mosquito bites. Patient A provided care over several days to an elderly male family contact (the index patient) who contracted Zika virus abroad. The index patient developed septic shock with multiple organ failure and died in the hospital on June 25, 2016. The index patient's blood specimen obtained 2 days before his death had a level of viremia approximately 100,000 times higher than the average level reported in persons infected with Zika virus. Zika virus infection was diagnosed in patient A by real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing on a urine specimen collected 7 days after symptom onset. In addition, a serum specimen collected 11 days after symptom onset, after patient A's symptoms had resolved, was positive for antibodies to Zika virus by Zika immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (MAC-ELISA) and had neutralizing antibodies detected by plaque-reduction neutralization testing (PRNT). Working with Salt Lake and Davis County Health Departments, UDOH requested assistance from CDC with an investigation to determine patient A's exposures and determine a probable source of infection.