Molecular Epidemiology of Measles in California, United States-2019.

In 2019, the United States (US) experienced the highest number of measles importations and cases in the postelimination era. More than a quarter of imported cases entered the US through California. Measles surveillance efforts in California resulted in the identification of 26 importations, 6 outbreaks, and 72 cases in 2019. Only genotype B3 and D8 measles strains were detected. Genotype-specific differences were noted in the incidence of vaccine failures, hospitalizations, and severe complications among cases. A targeted whole genome sequencing approach provided higher-resolution discrimination between epidemiologically linked and sporadically introduced strains than conventional N450 sequencing. Our report underscores the importance of ensuring appropriate measles vaccination status, especially prior to international travel to measles-endemic regions, and highlights the value of a strong measles surveillance system in minimizing outbreaks and preserving measles elimination status in the US.

Measles transmission during a large outbreak in California.

A large measles outbreak in 2014-2015, linked to Disneyland theme parks, attracted international attention, and led to changes in California vaccine policy. We use dates of symptom onset and known epidemic links for California cases in this outbreak to estimate time-varying transmission in the outbreak, and to estimate generation membership of cases probabilistically. We find that transmission declined significantly during the course of the outbreak (p = 0.012), despite also finding that estimates of transmission rate by day or by generation can overestimate temporal decline. We additionally find that the outbreak size and duration alone are sufficient in this case to distinguish temporal decline from time-invariant transmission (p = 0.014). As use of a single large outbreak can lead to underestimates of immunity, however, we urge caution in interpretation of quantities estimated from this outbreak alone. Further research is needed to distinguish causes of temporal decline in transmission rates.

Increased Risk of Late-onset Streptococcus pneumoniae Meningitis in Adults With Prior Head or Spine Surgeries.

In a case-control study within the Kaiser Permanente Northern California adult population, prior head or spine surgery was associated with increased Streptococcus pneumoniae meningitis outside of the postoperative period (no prior head or spine surgery; odds ratio, 6.0 [95% confidence interval, 1.9-18.6]). Among the cases, only 33.3% had received any prior pneumococcal vaccinations.

Barriers to Receipt of Prenatal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine Among Mothers of Infants Aged <4 Months with Pertussis - California, 2016.

Vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended for all pregnant women to protect infants who are too young for vaccination from severe pertussis-related outcomes (1-3). However, Tdap vaccine coverage among pregnant women remains suboptimal in California (4). California mothers whose infants developed pertussis in 2016 and their prenatal care providers were interviewed to ascertain possible reasons for low Tdap vaccine coverage. Mothers who were offered Tdap vaccination on-site during a routine prenatal visit were more likely to be vaccinated than were mothers who were referred off-site for vaccination. Mothers insured by Medicaid were less likely to receive Tdap vaccine than were mothers with private insurance, even when the vaccine was stocked on-site. Nearly all vaccinated mothers received Tdap vaccine in their prenatal clinic. Incorporating Tdap vaccination into routine prenatal care visits is an effective means to increase prenatal Tdap vaccination coverage.

Measles control in Australia - threats, opportunities and future needs.

Control of measles was the focus of a national workshop held in 2015 in Sydney, Australia, bringing together stakeholders in disease control and immunisation to discuss maintaining Australia's measles elimination status in the context of regional and global measles control. The global epidemiology of measles was reviewed, including outbreaks in countries that have achieved elimination, such as the Disneyland outbreak in the United States and large outbreaks in Sydney, Australia. Transmission of measles between Australia and New Zealand occurs, but has not been a focus of control measures. Risk groups, the genetic and seroepidemiology of measles as well as surveillance, modelling and waning vaccine-induced immunity were reviewed. Gaps in policy, research and practice for maintaining measles elimination status in Australia were identified and recommendations were developed. Elimination of measles globally is challenging because of the infectiousness of measles and the need for 2-dose vaccine coverage rates in excess of 95% in all countries to achieve it. Until this occurs, international travel will continue to permit measles importation from endemic countries to countries that have achieved elimination. When measles cases are imported, failure to diagnose and isolate cases places the health system at risk of measles outbreaks. Vaccine funding models can result in gaps in vaccine coverage for adults and migrants. Australia introduced a whole-of-life immunisation register in 2016 and catch-up vaccination for at-risk communities, which will improve measles control. Research on diagnosis, immunology, case management and modelling of vaccination strategies are important to ensure continued control of measles.

Risk Markers for Pertussis Among Infants <4 Months of Age: Understanding the Hispanic Disparity.

OBJECTIVES: Hispanic infants are at greater risk of pertussis compared with other racial/ethnic groups. Studies have shown that the source of Bordetella pertussis infection for most infants is household members. Using a case-control study, we examined risk markers for pertussis among Hispanic and non-Hispanic infants and evaluated whether maternal parity, a proxy for household size, contributes to the ethnic disparity. METHODS: We evaluated infants born in California during 2013-2014; cases were infants reported to California Department of Public Health with pertussis occurring before 4 months of age, and controls were infants who survived to at least 4 months of age without pertussis. Bivariate comparisons and multivariate logistic regression models were used to identify risk markers for pertussis in Hispanic and non-Hispanic infants. RESULTS: Increased maternal parity was associated with greater risk of pertussis, with a clear dose response observed with increasing risk for additional prior births. Teenage mothers were more likely to have infants with pertussis. These were both independent risk factors across all racial/ethnic groups, even when adjusting for important covariates. Preterm birth and Medicaid insurance were also identified as independent risk markers among Hispanic infants only. CONCLUSIONS: Infants of all races/ethnicities with older siblings or born to younger mothers are at increased risk of pertussis. Among Hispanic infants, prematurity and Medicaid insurance were independent risk markers for pertussis. These factors highlight the need to ensure prompt immunization of pregnant women with Tdap at the earliest opportunity starting at 27 weeks gestation.

Pertussis in California: A Tale of 2 Epidemics.

INTRODUCTION: California experienced pertussis epidemics in 2010 and 2014, with more than 9000 and 11,000 reported cases, respectively. Using an ecologic study design, we compared age-specific pertussis incidence for persons ≤20 years of age in California in 2010 and 2014 to describe any changes in disease burden that may be attributable to changes in pertussis vaccination policy that occurred during interepidemic years. METHODS: We evaluated California pertussis surveillance data for reported pertussis cases 20 years of age and younger with disease onset from January 1, 2010 to December 31, 2010 or from January 1, 2014 to December 31, 2014. Age-specific pertussis rates were calculated for each of the epidemic years. Characteristics of each age group were compared across epidemic years and age-specific rate ratios (RRs) and associated 95% confidence intervals (CIs) were calculated. RESULTS: In both years, the highest disease rate was reported in infants <6 months of age; however, the incidence of pertussis declined significantly among infants <6 months of age in 2014 compared with 2010 (RR 0.58, 95% CI: 0.53-0.63). Incidence remained stable among infants ≥6 months of age, children and adolescents <12 years of age (RR 1.1, 95% CI: 0.5-1.3). Adolescents 12-18 years of age had significantly higher rates of pertussis in 2014 compared with 2010, with the highest rates observed among 14- to 16-year-olds (RR 6.5, 95% CI: 5.4-7.8). CONCLUSIONS: A 42% reduction (53%-63%) in pertussis incidence among infants <6 months of age in 2014 after the routine prenatal Tdap vaccination recommendation suggested that an increase in prenatal Tdap coverage has been having some impact on infant pertussis. The excess number of cases observed in 2014 compared with 2010 occurred almost exclusively among the 12- to 17-year-old age group. Among older children, the peak age of pertussis is shifting, consistent with aging of the acellular pertussis vaccine cohort.

An Observational Study of Severe Pertussis in 100 Infants ≤120 Days of Age.

BACKGROUND: Pertussis in young infants is a unique, severe, afebrile, cough illness that is frequently fatal. METHODS: All pertussis cases ≤120 days of age admitted to a pediatric intensive care unit in California between October 1, 2013, and April 25, 2015, were evaluated. RESULTS: Of 100 pertussis patients ≤120 days of age admitted to pediatric intensive care unit, there were 5 deaths. The white blood cell counts in the fatal cases were significantly higher than in the nonfatal cases. Thirty-four percent of patients were intubated, 18% received inotropic and/or vasoactive support, 22% received steroid, 4% received extracorporal membrane oxygenation, and 3% underwent exchange blood transfusion. The median age at the time of illness onset in the patients who died was 23 days. CONCLUSIONS: These data, as well as data from previous California studies, suggest updated strategies for the management of severe pertussis. These include perform serial white blood cell counts, treat all presumptive cases with azithromycin, evaluate for pulmonary hypertension, intubate and administer oxygen for apneic episodes and administer inotropic/vasoactive agents for cardiogenic shock. Do not administer steroids or nitric oxide. Criteria for exchange blood transfusion therapy for leukocytosis with lymphocytosis are suggested.

A Population-Based Study of Recurrent Symptomatic Bordetella pertussis Infections in Children in California, 2010-2015.

BACKGROUND: Natural infection with Bordetella pertussis is thought to result in 4-20 years of immunity against subsequent symptomatic pertussis infection. However, these estimates are based on studies in unvaccinated or whole-cell pertussis-vaccinated children. We conducted a population-based study of pertussis infection and reinfection during a 5-year period in California in an cohort vaccinated exclusively with acellular pertussis (aP) vaccine. METHODS: California surveillance data were reviewed to identify all children with 2 reported incidents of pertussis with symptom onset between 1 January 2010 and 31 December 2015. Case investigation reports were reviewed, and children with ≥2 episodes of symptomatic pertussis infection that met the case definition were included. RESULTS: Of 26259 pertussis cases reported in children (aged <18 years), 27 children met the inclusion criteria. Recurrent cases occurred among children of all ages; 5 (19%) were <6 months of age at the time of their first illness. The time from initial infection to reinfection was <1 year in 11 (41%) cases. Twenty-one children (78%) had received ≥3 doses of diphtheria and tetanus toxoids and aP vaccine at the time of their first pertussis infection, 1 (4%) had received 1 dose, and 5 (19%) were unvaccinated. CONCLUSIONS: Recurrent cases of pertussis infection are extremely rare. Based on this surveillance data, approximately 0.1% of children who were infected with pertussis experienced a clinically significant second episode of pertussis within 4 years. More research is needed to understand the immune response to B. pertussis infection in children vaccinated with aP vaccines.

Perinatal transmission in infants of mothers with chronic hepatitis B in California.

AIM: To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in California. METHODS: Retrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%. RESULTS: A total of 17687 infants were born to HBsAg positive mothers in California between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%CI: 6.05-361.32, P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%CI: 12.22-247.55, P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection. CONCLUSION: In California, transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/mL is associated with high risk of perinatal infection.

Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012-2015.

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.

Subacute Sclerosing Panencephalitis: The Devastating Measles Complication That Might Be More Common Than Previously Estimated.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles. We reviewed California cases from 1998-2015 to understand risk factors for SPPE and estimate incidence. METHODS: SSPE cases had clinically compatible symptoms and measles antibody detection in cerebrospinal fluid (CSF) or medical record documentation of SSPE. Cases were identified though a state death certificate search, Centers for Disease Control and Prevention reports, or investigations for undiagnosed neurologic disease. Measles detection in CSF was performed by serology at the California Department of Public Health or at clinical laboratories. RESULTS: Seventeen SSPE cases were identified. Males outnumbered females 2.4:1. Twelve (71%) cases had a history of measles-like illness; all 12 had illness prior to 15 months of age. Eight (67%) children were exposed to measles in California. SSPE was diagnosed at a median age of 12 years (3-35 years), with a latency period of 9.5 years (2.5-34 years). Among measles cases reported to CDPH during 1988-1991, the incidence of SSPE was 1:1367 for children <5 years, and 1:609 for children <12 months at time of measles disease. CONCLUSIONS: SSPE cases in California occurred at a high rate among unvaccinated children, particularly those infected during infancy. Protection of unvaccinated infants requires avoidance of travel to endemic areas, or early vaccination prior to travel at age 6-11 months. Clinicians should be aware of SSPE in patients with compatible symptoms, even in older patients with no specific history of measles infection. SSPE demonstrates the high human cost of "natural" measles immunity.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older - United States, 2017.

In October 2016, the Advisory Committee on Immunization Practices (ACIP) voted to approve the Recommended Adult Immunization Schedule for Adults Aged 19 Years or Older-United States, 2017. The 2017 adult immunization schedule summarizes ACIP recommendations in two figures, footnotes for the figures, and a table of contraindications and precautions for vaccines recommended for adults. These documents are available at https://www.cdc.gov/vaccines/schedules. The full ACIP recommendations for each vaccine can be found at https://www.cdc.gov/vaccines/hcp/acip-recs/index.html. The 2017 adult immunization schedule was also reviewed and approved by the American College of Physicians (https://www.acponline.org), the American Academy of Family Physicians (https://www.aafp.org), the American College of Obstetricians and Gynecologists (http://www.acog.org), and the American College of Nurse-Midwives (http://www.midwife.org).

Effectiveness of Prenatal Versus Postpartum Tetanus, Diphtheria, and Acellular Pertussis Vaccination in Preventing Infant Pertussis.

BACKGROUND: Most severe and fatal cases of pertussis occur in infants <8 weeks of age, before initiation of the primary pertussis vaccine series. Women are recommended to receive tetanus, diphtheria, and acellular pertussis (Tdap) vaccine at the start of the third trimester of each pregnancy to optimize transplacental transfer of antibodies to the fetus. This recommendation was made by the Advisory Committee for Immunization Practices based on immunogenicity data, and no studies in the United States have yet evaluated the effectiveness of this strategy in reducing pertussis incidence in infants. METHODS: We evaluated a cohort of mothers with documented Tdap vaccination histories in the California Immunization Registry to determine whether infants whose mothers received Tdap vaccine at 27-36 weeks gestation had a lower risk of pertussis at <8 weeks of age than infants born to women who received Tdap vaccine within 14 days post partum. RESULTS: Tdap vaccination received at 27-36 weeks gestation was found to be 85% (95% confidence interval, 33%-98%) more effective than postpartum Tdap vaccination at preventing pertussis in infants <8 weeks of age . Vaccination at 27-36 weeks gestation was more effective at preventing pertussis in infant than vaccination during the second trimester. CONCLUSIONS: Tdap vaccination at 27-36 weeks gestation was 85% more effective than postpartum vaccination at preventing pertussis in infants <8 weeks of age. Efforts should be made by prenatal care providers to provide Tdap vaccine to pregnant women during routine prenatal visits at the earliest opportunity between 27 and 36 weeks gestation.

Effectiveness of Prenatal Tetanus, Diphtheria, and Acellular Pertussis Vaccination on Pertussis Severity in Infants.

BACKGROUND: All US women are recommended to receive a tetanus, diphtheria, and acellular pertussis (Tdap) vaccine at 27-36 weeks gestation during each pregnancy to reduce the risk of pertussis to their infants. The impact of this strategy on severity of disease among infected infants has not been evaluated. METHODS: We use a retrospective cohort study design evaluating whether pertussis-infected infants born in 2011-2015 whose mothers received Tdap vaccine during pregnancy had less severe pertussis, resulting in a lower risk of hospitalization or intensive care unit admission compared with infants born to unvaccinated mothers. RESULTS: Infected infants of vaccinated mothers were significantly less likely to be hospitalized and had significantly shorter hospital stays compared with infants born to unvaccinated mothers, after adjustment for chronological and gestational age and receipt of diphtheria and tetanus toxoids and acellular pertussis vaccine. Unadjusted and adjusted vaccine effectiveness for preventing hospitalization among infants with pertussis was 72% (95% confidence interval [CI], 49%-85%) and 58% (95% CI 15%-80%), respectively. No infants born to vaccinated mothers required intubation or died of pertussis. CONCLUSIONS: Infants with pertussis whose mothers received Tdap during pregnancy had a significantly lower risk of hospitalization and intensive care unit admission and shorter hospital stays. Prenatal Tdap vaccination is a critical strategy for reducing the morbidity and mortality from pertussis.

The Effect of Contact Investigations and Public Health Interventions in the Control and Prevention of Measles Transmission: A Simulation Study.

BACKGROUND: Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission. METHODS AND FINDINGS: The synthetic population was created to simulate California`s population in terms of population demographics, household, workplace, school, and neighborhood characteristics using California Department of Finance 2010 census data. Parameters for the model were obtained from a review of the literature, California measles case surveillance data, and expert opinion. Eight different scenarios defined by the use of three different public health interventions were evaluated: (a) post-exposure measles, mumps, and rubella (MMR) vaccine, (b) post-exposure immune globulin (IG), and (c) voluntary isolation and home quarantine in the presence or absence of public health response delays. Voluntary isolation and home quarantine coupled with one or two other interventions had the greatest reduction in the number of secondary cases infected by the index case and the probability of escape situations (i.e., the outbreak continues after 90 days). CONCLUSIONS: Interrupting contact patterns via voluntary isolation and home quarantine are particularly important in reducing the number of secondary cases infected by the index case and the probability of uncontrolled outbreaks.