Jennifer B. Rosen

Mumps Outbreak in Orthodox Jewish Communities in the United States

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

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study

BACKGROUND In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1 - matched odds ratio) × 100%. FINDINGS We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86·0% (95% CI 75·5 to 92·3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85·6% (95% CI 70·6 to 93·5) and 96·5% (82·7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79·5%, 95% CI 30·3 to 94·8) and against antibiotic non-susceptible invasive pneumococcal disease (65·6%, 44·9 to 78·7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60·2% (95% CI 46·8 to 70·3). Vaccine effectiveness was similar among children with (81·4%, 95% CI 45·4 to 93·6) and without (85·8%, 74·9 to 91·9) underlying conditions. INTERPRETATION PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING Centers for Disease Control and Prevention.

Outbreak of Measles Among Persons With Prior Evidence of Immunity, New York City, 2011

BACKGROUND Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented. METHODS Suspected patients and contacts exposed during a measles outbreak in New York City in 2011 were investigated. Medical histories and immunization records were obtained. Cases were confirmed by detection of measles-specific immunoglobulin M and/or RNA. Tests for measles immunoglobulin G (IgG), IgG avidity, measurement of measles neutralizing antibody titers, and genotyping were performed to characterize the cases. RESULTS The index patient had 2 doses of measles-containing vaccine; of 88 contacts, 4 secondary patients were confirmed who had either 2 doses of measles-containing vaccine or a past positive measles IgG antibody. All patients had laboratory confirmation of measles infection, clinical symptoms consistent with measles, and high-avidity IgG antibody characteristic of a secondary immune response. Neutralizing antibody titers of secondary patients reached >80 000 mIU/mL 3-4 days after rash onset and that of the index was <500 mIU/mL 9 days after rash onset. No additional cases of measles occurred among 231 contacts of secondary patients. CONCLUSIONS This is the first report of measles transmission from a twice-vaccinated individual with documented secondary vaccine failure. The clinical presentation and laboratory data of the index patient were typical of measles in a naive individual. Secondary patients had robust anamnestic antibody responses. No tertiary cases occurred despite numerous contacts. This outbreak underscores the need for thorough epidemiologic and laboratory investigation of suspected cases of measles regardless of vaccination status.

Comparison of the Sensitivity of Laboratory Diagnostic Methods from a Well-Characterized Outbreak of Mumps in New York City in 2009

ABSTRACT A mumps outbreak in upstate New York in 2009 at a summer camp for Orthodox Jewish boys spread into Orthodox Jewish communities in the Northeast, including New York City. The availability of epidemiologic information, including vaccination records and parotitis onset dates, allowed an enhanced analysis of laboratory methods for mumps testing. Serum and buccal swab samples were collected from 296 confirmed cases with onsets from September through December 2009. All samples were tested using the Centers for Disease Control and Prevention (CDC) capture IgM enzyme immunoassay (EIA) and a real-time reverse transcription-PCR (rRT-PCR) that targets the short hydrophobic gene. A subset of the samples (n = 205) was used to evaluate 3 commercial mumps IgM assays and to assess the sensitivity of using an alternative target gene (nucleoprotein) in the rRT-PCR protocol. Among 115 cases of mumps with 2 documented doses of measles, mumps, and rubella (MMR) vaccine, the CDC capture IgM EIA detected IgM in 51% of serum samples compared to 9% to 24% using three commercial IgM assays. The rRT-PCR that targeted the nucleoprotein gene increased RNA detection by 14% compared to that obtained with the original protocol. The ability to detect IgM improved when serum was collected 3 days or more after symptom onset, whereas sensitivity of RNA detection by rRT-PCR declined when buccal swabs were collected later than 2 days after onset. Selection of testing methods and timing of sample collection are important factors in the ability to confirm infection among vaccinated persons. These results reinforce the need to use virus detection assays in addition to serologic tests.

Invasive Pneumococcal Disease Following the Introduction of 13-Valent Conjugate Vaccine in Children in New York City From 2007 to 2012.

IMPORTANCE Invasive pneumococcal disease (IPD) is a leading cause of pneumonia, meningitis, and bacteremia in children. In March 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) was introduced to the routine childhood immunization schedule. The PCV13 contains 6 serotypes not included in the previously recommended 7-valent pneumococcal conjugate vaccine, including serotype 19A, the predominant cause of IPD prior to the introduction of PCV13. OBJECTIVES To describe changes in the epidemiology and incidence of IPD in children younger than 5 years in New York City (NYC) after the introduction of PCV13 and assess PCV13 coverage in NYC. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of population-based IPD surveillance data of the general population residing in NYC between January 1, 2007, and December 31, 2012. Invasive pneumococcal disease cases were identified by laboratory reporting of positive pneumococcal cultures from a normally sterile body site in NYC residents younger than 5 years. Isolates were serotyped. Participants included 468 cases younger than 5 years with IPD reported through routine surveillance to the NYC Department of Health and Mental Hygiene. MAIN OUTCOMES AND MEASURES Absolute differences and percentage changes in IPD incidence before and after the introduction of PCV13 by serotype grouping, age, and race/ethnicity. The number of PCV13 doses administered to children younger than 5 years was calculated using the NYC immunization information system. RESULTS There were 468 IPD cases from 2007 to 2012. The incidence of IPD decreased by 69.6% (95% CI, -79.3% to -55.5%) from 21.0 cases per 100 000 (2007-2009 mean) pre-PCV13 to 6.4 cases per 100 000 (2011-2012 mean) post-PCV13. Estimates of disease caused by serotypes included in the PCV13 decreased by 82.5% (95% CI, -90.0% to -69.3%), including a 79.7% reduction in serotype 19A (95% CI, -89.0% to -62.4%). Reductions in IPD incidence were seen in all age groups, with the largest reduction in children younger than 12 months (80.4%; P = .005). Incidence decreased significantly in all racial/ethnic groups. The percentage of children younger than 5 years in NYC with 1 or more doses of PCV13 increased from 47.8% in 2010 to 89.8% in 2012. CONCLUSIONS AND RELEVANCE The incidence of IPD in NYC children younger than 5 years and, particularly, the incidence of IPD caused by serotype 19A decreased dramatically following the introduction of PCV13, with reductions among all age and racial/ethnic groups. This represents a significant achievement for public health immunization programs and underscores the importance of achieving high immunization coverage.

Mumps vaccine effectiveness and risk factors for disease in households during an outbreak in New York City

BACKGROUND AND OBJECTIVES Mumps outbreaks have been reported among vaccinated populations, and declining mumps vaccine effectiveness (VE) has been suggested as one possible cause. During a large mumps outbreak in New York City, we assessed: (1) VE of measles-mumps-rubella vaccine (MMR) against mumps and (2) risk factors for acquiring mumps in households. METHODS Cases of mumps were investigated using standard methods. Additional information on disease and vaccination status of household contacts was collected. Case households completed follow-up phone interviews 78-198 days after initial investigation to ascertain additional cases. Mumps cases meeting the study case definition were included in the analysis. Risk factors for mumps were assessed, and VE was calculated using secondary household attack rates. RESULTS Three hundred and eleven households with 2176 residents were included in the analysis. The median age of residents was 13 years (range <1-85), and 462 (21.2%) residents met the study mumps case definition. Among 7-17 year olds, 89.7% received one or more doses of MMR vaccine, with 76.7% receiving two doses. Young adults aged 10-14 years (OR=2.4, CI=1.3-4.7) and 15-19 years (OR=2.5, CI=1.3-5.0) were at highest risk of mumps. The overall 2-dose VE for secondary contacts aged five and older was 86.3% (CI 63.3-94.9). CONCLUSIONS The two-dose effectiveness of MMR vaccine against mumps was 86.3%, consistent with other published mumps VE estimates. Many factors likely contributed to this outbreak. Suboptimal MMR coverage in the affected population combined with VE may not have conferred adequate immunity to prevent transmission and may have contributed to this outbreak. Achieving high MMR coverage remains the best available strategy for prevention of mumps outbreaks.

Mumps Outbreak Among a Highly Vaccinated University Community—New York City, January–April 2014

Background On 14 January 2014, a vaccinated student presented with parotitis. Mumps immunoglobulin M (IgM) testing was negative and reverse-transcription polymerase chain reaction (RT-PCR) testing was not performed, resulting in a missed diagnosis and the start of an outbreak at a New York City (NYC) university. Methods Mumps case investigations included patient interviews, medical records review, and laboratory testing including mumps serology and RT-PCR. Case patients were considered linked to the outbreak if they attended or had epidemiologic linkage to the university. Epidemiologic, clinical, and laboratory data for outbreak cases residing in NYC were analyzed. Results Fifty-six NYC residents with mumps were identified with onset between 12 January and 30 April 2014. Fifty-three cases (95%) were university students, 1 (2%) was a staff member, and 2 (4%) had epidemiologic links to the university. The median age was 20 years (range 18-37 years). All cases had parotitis. Three cases were hospitalized, including 1 of 2 cases with orchitis. Fifty-four (96%) cases had received ≥1 mumps-containing vaccine, 1 (2%) was unvaccinated due to religious exemption, and 1 (2%) had unknown vaccination status. Two of the 44 (5%) cases tested by serology were mumps IgM positive, and 27 of the 40 (68%) tested by RT-PCR were positive. Conclusions Mumps outbreaks can occur in highly vaccinated populations. Mumps should be considered in patients with parotitis regardless of vaccination status. RT-PCR is the preferred testing method; providers should not rely on IgM testing alone. High vaccination coverage and control measures likely limited the extent of the outbreak.

Environmental factors potentially associated with mumps transmission in yeshivas during a mumps outbreak among highly vaccinated students: Brooklyn, New York, 2009-2010.

During 2009–2010, a large US mumps outbreak occurred affecting two-dose vaccinated 9th–12th grade Orthodox Jewish boys attending all-male yeshivas (private, traditional Jewish schools). Our objective was to understand mumps transmission dynamics in this well-vaccinated population. We surveyed 9th-12th grade male yeshivas in Brooklyn, NY with reported mumps case-students between 9/1/2009 and 3/30/2010. We assessed vaccination coverage, yeshiva environmental factors (duration of school day, density, mixing, duration of contact), and whether environmental factors were associated with increased mumps attack rates. Ten yeshivas comprising 1769 9th–12th grade students and 264 self-reported mumps cases were included. The average yeshiva attack rate was 14.5% (median: 13.5%, range: 1–31%), despite two-dose measles-mumps-rubella vaccine coverage between 90–100%. School duration was 9–15.5 h/day; students averaged 7 h face-to-face/day with 1–4 study partners. Average daily mean density was 6.6 students per 100 square feet. The number of hours spent face-to-face with a study partner and the number of partners per day showed significant positive associations (p < 0.05) with classroom mumps attack rates in univariate analysis, but these associations did not persist in multivariate analysis. This outbreak was characterized by environmental factors unique to the yeshiva setting (e.g., densely populated environment, prolonged face-to-face contact, mixing among infected students). However, these features were present in all included yeshivas, limiting our ability to discriminate differences. Nonetheless, mumps transmission requires close contact, and these environmental factors may have overwhelmed vaccine-mediated protection increasing the likelihood of vaccine failure among yeshiva students.

Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geocoding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8–91.9%; adjusted estimate: 82.5%, 95% CI 65.6–91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Varicella Outbreak Surveillance in Schools in Sentinel Jurisdictions, 2012–2015

BACKGROUND In 2007, a routine second dose of varicella vaccine was recommended in the United States for children aged 4 to 6 years to better control varicella-zoster virus circulation and outbreaks. Sentinel varicella outbreak surveillance was established to assess feasibility of surveillance and describe outbreaks that are occurring. METHODS Through the Centers for Disease Control and Prevention Epidemiology Laboratory Capacity funding, health departments conducted active surveillance for varicella outbreaks in schools from 2012 to 2015. Outbreaks of varicella were defined as ≥5 cases in a school within at least 1 incubation period (21 days). School nurses, healthcare providers, or laboratories reported cases and outbreaks of varicella to health departments; demographic, vaccination, and clinical data were collected. RESULTS Georgia, Houston, Maine, Minnesota, New York City, and Philadelphia participated in all 3 years; Puerto Rico and West Virginia participated in 2012 to 2013; and Kansas and Arkansas participated in 2014 to 2015. Twenty-nine outbreaks including 262 cases were reported. The median size of the outbreaks was 7 cases (range, 5-31 cases), and the median duration was 31 days (range, 4-100 days). Of the case-patients associated with larger outbreaks (≥8 cases), 55.4% were unvaccinated, and 15.7% and 18.1% had received 1 or 2 doses of vaccine, respectively. In small outbreaks (5-7 cases), 33.3% of case-patients were unvaccinated, and 16.7% and 38.5% had received 1 or 2 doses of vaccine, respectively. CONCLUSIONS The majority of cases associated with outbreaks occurred in undervaccinated children (unvaccinated and 1-dose vaccine recipients). Outbreaks with a greater proportion of 2-dose vaccine recipients were smaller. Varicella outbreak surveillance is feasible, and continued monitoring of outbreaks remains important for describing the epidemiology of varicella during the 2-dose varicella vaccination program.