Cedric Brown

Mumps vaccination coverage and vaccine effectiveness in a large outbreak among college students--Iowa, 2006.

Following implementation of a routine childhood two-dose measles-mumps-rubella vaccination strategy, mumps disease levels dropped dramatically in the US and an elimination goal was set for 2010. However, a 2006 epidemic involved >5700 cases nationwide, with many reported among fully vaccinated college students. In an outbreak in two Iowa colleges, we investigated: (1) vaccination coverage using electronic records verified by provider records and (2) vaccine effectiveness assessed by comparison of dose-specific attack rates. Mumps was classified as typical (parotitis/orchitis) or atypical (parotid tenderness or submandibular/sublingual adenitis). Two-dose mumps vaccination coverage was 90% both for the student population (2128/2363) and case-students (97/108). Two-dose vaccine effectiveness was 76-88% with no significant difference for attack rates between one and two doses. Among two-dose vaccine recipients, 74% of the population (1482/2009) and 79% of the case-students (75/95) had received the second dose >10 years before. A large mumps outbreak occurred despite high two-dose vaccination coverage in a population most of whom had received the second dose >10 years before. Two-dose vaccine effectiveness was similar to previous one-dose estimates. Further studies are needed to examine the persistence of two-dose mumps vaccine-induced immunity and to determine whether US mumps elimination can be achieved with the current vaccination strategy.

Persistence of mumps antibodies after 2 doses of measles-mumps-rubella vaccine

BACKGROUND Since 1990, most US schoolchildren have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. The objective of the present study was to evaluate the short- and long-term mumps immunogenicity of MMR2. METHODS At enrollment in 1994-1995, children (n=308) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n=308) was vaccinated at age 9-11 years. Serum samples were collected over 12 years. Mumps antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 10). RESULTS Before MMR2, the geometric mean titer (GMT) for the younger group was 33; no subject was seronegative, but 16% had the lowest detectable titer. In response to MMR2, the GMT tripled to 97, and the proportion with low titers diminished to 3%. Four-fold boosts occurred among 54%, but only 3% were positive for immunoglobulin M. Twelve years after MMR2, the GMT declined to 46, the proportion with titers<or=10 was not significantly different from the pre-MMR2 proportion, and 5% were seronegative. The older group showed similar patterns, and at age 17 years both groups had comparable antibody levels. CONCLUSIONS The mumps antibody response to MMR2 was vigorous, but over a 12-year period titers declined to levels similar to pre-MMR2 titers. No advantage was apparent in delaying MMR2 from kindergarten to middle school.

Validity of parental report of influenza vaccination in young children seeking medical care.

BACKGROUND Despite frequent use of self-reported information to determine pediatric influenza vaccination coverage, little data are available on the validity of parental reporting of their childs influenza vaccination status and on factors affecting its accuracy. METHODS We compared parent reported influenza vaccination of children to documented reports of vaccination collected from medical records (the criterion standard) among children aged 6-59 months who presented to selected hospitals, emergency departments, and clinics in three U.S. counties with acute respiratory illness during three influenza seasons (November through May of 2004-2007). Demographic and epidemiologic data were collected from chart reviews and parental surveys. RESULTS Among 3072 children aged 6-59 months, 47.5% were reported by the parent to have received influenza vaccine and 39.5% of children had medical record verification of influenza vaccination. Sensitivity and specificity of parental reporting was 92.1% and 82.3%, respectively, when compared to the immunization record. However, 17.7% of children whose parents reported vaccination had no influenza vaccination documented in their medical records, and this proportion was even higher at 28.6%, among children with an underlying high-risk medical condition. Greater reporting accuracy was associated with younger age of child (6-23 months vs. 24-59 months), white non-Hispanic race/ethnicity, having health insurance, and having a mother with a college education. CONCLUSIONS Our findings indicate that although parental report of influenza vaccination is fairly reliable (∼76-96%), over reporting by parents often occurs and immunization record review remains the preferable method for determining vaccination status in children.

Enzyme-Linked Immunospot Assay Detection of Mumps-Specific Antibody-Secreting B Cells as an Alternative Method of Laboratory Diagnosis

ABSTRACT Although high measles, mumps, and rubella (MMR) vaccination coverage has been successful in dramatically reducing mumps disease in the United States, mumps (re)infections occasionally occur in individuals who have been either previously vaccinated or naturally infected. Standard diagnostics that detect virus or virus-specific antibody are dependable for confirming primary mumps infection in immunologically naïve persons, but these methods perform inconsistently for individuals with prior immune exposure. We hypothesized that detection of activated mumps-specific antibody-secreting B cells (ASCs) by enzyme-linked immunospot (ELISPOT) assay could be used as a more reliable diagnostic. To test this, a time course of virus-specific ASC responses was measured by ELISPOT assay following MMR vaccination of 16 previously vaccinated or naturally exposed adult volunteers. Mumps-specific ASCs were detectable in 68% of these individuals at some point during the first 3 weeks following revaccination. In addition, mumps-specific ASCs were detected in 7/7 previously vaccinated individuals who recently had been infected as part of a confirmed mumps outbreak. These data suggest that ELISPOT detection of mumps-specific ASCs has the potential for use as an alternative method of diagnosis when suspect cases cannot be confirmed by detection of IgM or virus. In addition, it was determined that mumps-specific memory B cells are detected at a much lower frequency than measles- or rubella-specific cells, suggesting that mumps infection may not generate robust B-cell memory.

A Fish Population Study of Third Sister Lake

Abstract The fish population of Third Sister Lake was removed by angling, netting and poison (rotenone). Fish were recovered after poisoning by intensive hand picking. An unknown number of fish, particularly those of the smaller sizes, did not come to the surface when killed by the poison and were therefore not recovered or included in the population analysis. A total of 15,454 fish weighing 866.6 pounds was recovered from all operations or 86.6 pounds per acre. Bluegills of legal length accounted for about 50 pounds per acre. Legal game fish made up approximately 70 per cent of the total weight of all fish. In 80 man-hours of hook and line fishing during the 22 days prior to poisoning, 431 fish weighing 153 pounds were captured. Approximately one fourth of the total number of legal largemouth bass and bluegills in the lake were removed by this angling effort which equaled 4.6 fish per hour. Coarse fish made up 16.3 per cent and forage fish 3.4 per cent of the weight of all fish.

Disparities Between Black and White Children in Hospitalizations Associated With Acute Respiratory Illness and Laboratory-confirmed Influenza and Respiratory Syncytial Virus in 3 US Counties—2002–2009

Few US studies have assessed racial disparities in viral respiratory hospitalizations among children. This study enrolled black and white children under 5 years of age who were hospitalized for acute respiratory illness (ARI) in 3 US counties during October-May 2002-2009. Population-based rates of hospitalization were calculated by race for ARI and laboratory-confirmed influenza and respiratory syncytial virus (RSV), using US Census denominators. Relative rates of hospitalization between racial groups were estimated. Of 1,415 hospitalized black children and 1,824 hospitalized white children with ARI enrolled in the study, 108 (8%) black children and 111 (6%) white children had influenza and 230 (19%) black children and 441 (29%) white children had RSV. Hospitalization rates were higher among black children than among white children for ARI (relative rate (RR) = 1.7, 95% confidence interval (CI): 1.6, 1.8) and influenza (RR = 2.1, 95% CI: 1.6, 2.9). For RSV, rates were similar among black and white children under age 12 months but higher for black children aged 12 months or more (for ages 12-23 months, RR = 1.7, 95% CI: 1.1, 2.5; for ages 24-59 months, RR = 2.2, 95% CI: 1.3, 3.6). Black children versus white children were significantly more likely to have public insurance or no insurance (85% vs. 43%) and a history of asthma/wheezing (28% vs. 18%) but not more severe illness. The observed racial disparities require further study.

An Experiment in the use of Derris Root (Rote-None) on the Fish and Fish-Food Organisms of Third Sister Lake

Abstract Sufficient powdered derris root (guaranteed rotenone content of 5 per cent) to make a concentration of 1:500,000 parts of water was applied to Third Sister Lake on May 6, 1941. Temperatures were unfavorably low and the treatment was not successful in the complete removal of fish. A second application on August 18, 1941 of a slightly greater concentration was sufficient to eradicate the remaining fish. There seemed to be little or no difference in the toleration of the different species of fish, however minnows and the young of game fish were killed in larger numbers at the beginning. It is believed this was the result of their location in shallow water rather than a difference in susceptibility to the poison. Not all fish came to the surface after death. Live fish taken from the lake before poisoning were placed in traps at different points and at various levels in the lake at the time of each poisoning in order to test vertical and horizontal distribution of the poison. In the first poisoning al...

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

ABSTRACT Vaccine manufacturing costs prevent a significant portion of the worlds population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. IMPORTANCE Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work describes a platform-enabling technology applicable to most vaccine-preventable diseases.

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.

Psychological Stress as a Trigger for Herpes Zoster: Might the Conventional Wisdom Be Wrong?

The causes for zoster remain largely unknown. Psychological stress is one commonly considered risk factor. We used self-controlled case series methods to look for increases in zoster following death or catastrophic health event occurring in a previously healthy spouse. We found no increase, although this stressor led to increased mental health visits.