Gustavo H. Dayan

Recent Resurgence of Mumps in the United States

BACKGROUND The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. METHODS We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. RESULTS A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. CONCLUSIONS Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps.

The History of Dengue Outbreaks in the Americas

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600-1946); Continental plan for the eradication of the Ae. aegypti (1947-1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971-1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000-2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread.

Live-attenuated Tetravalent Dengue Vaccine in Dengue-naïve Children, Adolescents, and Adults in Mexico City: Randomized Controlled Phase 1 Trial of Safety and Immunogenicity.

Background: Preliminary results in healthy, young US adults showed that a tetravalent, live-attenuated dengue vaccine (TDV) was safe and immunogenic, but no data are available in children. Methods: In a multicenter, randomized, controlled, observer-blinded study in the city of Mexico, children aged 2 to 5, 6 to 11, and 12 to 17 years (36 children per age group), and adults (n = 18) aged <45 years received the following: 3 injections of TDV at months 0, 3.5, and 12 (TDV-TDV-TDV), or 1 injection of yellow fever vaccine (YF) at month 0, and 2 injections of TDV at months 3.5 and 12 (YF-TDV-TDV). Adverse events and biologic safety (biochemistry and hematology) were documented. Plaque reduction neutralization test (PRNT50) antibody titers against the TDV parental viruses were measured 28 days after vaccination. Seropositivity was defined as antibody titers ≥10 1/dil. Results: No vaccine-related serious adverse events, other significant clinical adverse events, or clinically significant trends in biologic safety were observed. Reactogenicity did not increase with successive TDV injections, and mild-to-moderate injection site pain, headache, myalgia, and malaise were most commonly reported (14%–40% after each vaccination). After 3 TDV vaccinations, the seropositivity rate against each dengue serotype was in the range 77% to 92%, compared with 85% to 94% after completion of the YF-TDV-TDV regimen. Of the 2- to 11-year-old participants, 95% were seropositive against ≥3 serotypes after 3 vaccinations. Conclusions: A 3-dose TDV regimen had a favorable safety profile in children and adults and elicited neutralizing antibody responses against all 4 serotypes. These findings support the continued development of this vaccine.

The Cost of Containing One Case of Measles: The Economic Impact on the Public Health Infrastructure—Iowa, 2004

Background. In February 2004, students from a college in Iowa, with a high proportion of nonmedical exemptions to vaccination, traveled to India; one fourth of the students contracted measles while there. One exposed, susceptible student returned home during his infectious period, necessitating 2 months of containment efforts in Iowa. Objective. The objective of this study was to measure the direct costs of measles containment from a public health system perspective. Methods. We evaluated activities performed, personnel time/materials allocated, and direct costs incurred in 2004 US dollars by the Iowa public health infrastructure. The study period was defined as March 5, 2004 (when the Iowa Department of Public Health was first contacted about the case), through May 12, 2004 (when a final meeting was held on the containment effort). Results. A total of 2525 hours of personnel time were expended to review flight manifests, contact exposed passengers, set up vaccination clinics, trace >1000 potentially exposed contacts, and institute and enforce quarantine orders for vaccination refusers. Two thousand twenty-five phone calls were received from the public, and 2243 miles were driven by staff. The temporal distribution of personnel time was characterized by marked peaks at the report of potential secondary cases. The total estimated cost was

A Limited Measles Outbreak in a Highly Vaccinated US Boarding School

142452. Conclusions. The direct cost to the public health infrastructure of containing 1 case of measles was far greater than the estimated cost of uncomplicated individual illness (less than

Seroprevalence of Measles Antibody in the US Population, 1999–2004

100). Economic analyses of vaccine-preventable diseases may need to go beyond the costs of individual illness to account for the costs of protecting society.

Safety and Immunogenicity of a Recombinant Tetravalent Dengue Vaccine in 9–16 Year Olds: A Randomized, Controlled, Phase Ii Trial in Latin America

Objectives. We investigated a measles outbreak that began in March 2003 in a Pennsylvania boarding school with >600 students to identify all cases, including the source; implement outbreak control measures; and evaluate vaccine effectiveness. Methods. Measles was suspected in any person at the school with a generalized rash and fever during March 21 to May 28, 2003 and investigated with serologic testing. We reviewed vaccination history from school records and conducted a survey to determine country of measles vaccination. Vaccine effectiveness was calculated using the cohort method. Results. We identified 9 laboratory-confirmed cases at the school: 8 students and 1 staff member. Among them, 2 had never received any doses of measles-containing vaccine (MCV), 1 received 1 dose of MCV, and 6 received 2 doses of MCV. Three of the 6 who received 2 doses of MCV received both doses outside the United States. The source case had been infected in Lebanon. Two laboratory-confirmed spread cases were identified in New York City. Measles virus of genotype D4 was isolated in cases from the school and New York City. Of the 663 students in the school, 8 (1.2%) had never received any doses of MCV, 26 (3.9%) had received 1 dose, and 629 (94.9%) had received 2 doses before the outbreak. Vaccine effectiveness among students who had received 2 doses of MCV was 98.6%. However, students who received both doses outside the United States had a higher attack rate (3 of 75) than those who received both doses in the United States (3 of 509; rate ratio: 6.8; 95% confidence interval: 1.4–33.0). Conclusions. This is the largest measles outbreak to occur in a school in the United States since 1998, but it was limited to only 9 cases in a boarding school with >600 students. The limited extent of this outbreak highlights the high level of population immunity achieved in the United States through widespread implementation of a 2-dose measles-mumps-rubella vaccination strategy in school-aged children. States and schools should continue to enforce strictly the 2-dose measles-mumps-rubella vaccination requirement and, in an outbreak setting, consider revaccinating students who received measles vaccine outside of the United States. Continued vigilance by health care providers is needed to recognize measles cases.

Serologic response to inactivated poliovirus vaccine: a randomized clinical trial comparing 2 vaccination schedules in Puerto Rico.

BACKGROUND Endemic measles transmission was declared eliminated in the United States in 2000. To ensure that elimination can be maintained, high population immunity must be sustained and monitored. Testing for measles antibody was included in the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey, conducted during 1999-2004. METHODS A measles-specific immunoassay was used to measure the seroprevalence of measles antibody in NHANES participants 6-49 years of age. For analysis, participants were grouped by birth cohort. RESULTS During 1999-2004, the rate of measles seropositivity in the population overall was 95.9% (95% confidence interval [CI], 95.1%-96.5%). The highest seroprevalence of measles antibody was in non-Hispanic blacks (98.6% [95% CI, 98.0%-99.1%]). Those born during 1967-1976 had significantly lower levels of measles antibody (92.4% [95% CI, 90.8%-93.9%]) than did the other birth cohorts. Independent predictors of measles seropositivity in the 1967-1976 birth cohort were non-Hispanic/black race/ethnicity, more than a high school education, having health insurance, and birth outside the United States. CONCLUSIONS Measles seropositivity was uniformly high in the US population during 1999-2004. Nearly all population subgroups had evidence of measles seropositivity levels greater than the estimated threshold necessary to sustain measles elimination. Non-Hispanic whites and Mexican Americans born during 1967-1976 had the lowest measles seropositivity levels and represent populations that might be at increased risk for measles disease if the virus were reintroduced into the United States.

Cost-effectiveness of influenza vaccination in high-risk children in Argentina.

Background: The dengue virus is a member of the Flavivirus (FV) genus, which also includes the yellow fever virus. Dengue disease is caused by any 1 of 4 dengue virus serotypes and is a serious public health concern in Latin America. This study evaluated the safety and immunogenicity of a candidate recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in 9–16 year olds in Latin America. Methods: In this randomized, blinded, controlled study, volunteers received either 3 doses of CYD-TDV (n = 401) or placebo as first and second injection and tetanus/diphtheria/acellular pertussis vaccine as third injection (n = 199) at 0, 6 and 12 months. Adverse events were documented. Plaque reduction neutralization test antibody titers against the 4 CYD-TDV parental strains were measured before and 28 days after each dose. Seropositivity was defined as antibody titers ≥10 1/dil. Results: The number of adverse reactions decreased after each successive CYD-TDV dose. After each CYD-TDV dose, antibody titers against all 4 serotypes were higher than baseline and respective predose titers. After the third dose of CYD-TDV, 100%, 98.6% and 93.4% of participants were seropositive for at least 2, at least 3 or all 4 serotypes, respectively. Higher antibody titers were observed in participants in the CYD-TDV group who were FV-seropositive at baseline compared with those who were FV-seronegative. Conclusions: CYD-TDV had a favorable safety profile and elicited antibody responses against all 4 dengue virus serotypes in 9–16 year olds in Latin America. These findings support the continued development of CYD-TDV.

Effectiveness of Previous Mumps Vaccination During a Summer Camp Outbreak

BACKGROUND The World Health Organization (WHO) recommends the discontinuation of oral poliovirus vaccine after eradication of wild poliovirus. Studies assessing inactivated poliovirus vaccine (IPV) immunogenicity in tropical countries, using the WHO Expanded Programme on Immunization (EPI) schedule, have been limited. METHODS We conducted a randomized clinical trial in Ponce, Puerto Rico. Infants were assigned to 1 of 2 study arms: those in the EPI arm received IPV at 6, 10, and 14 weeks of age, and those in the US arm received IPV at 2, 4, and 6 months of age. Neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested on serum specimens obtained before administration of the first dose of IPV and 28-45 days after administration of the last dose of IPV. RESULTS Seroconversion rates for the EPI (n=225) and US (n=230) arms, respectively, were 85.8% and 99.6% for poliovirus type 1 (P<.001), 86.2% and 100% for poliovirus type 2 (P<.001), and 96.9% and 99.1% for poliovirus type 3 (P=.08). Seroconversion rates were lower among infants in the EPI arm who had high maternal antibody levels for all 3 poliovirus types (P<.001). CONCLUSIONS The EPI schedule resulted in lower seroconversion rates for poliovirus types 1 and 2. These results are relevant for tropical countries planning to use IPV in a posteradication environment.