Rotarix: development of a live attenuated monovalent human rotavirus vaccine.
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Child↗
Biomedical subjects
David I Bernstein
Publications and source records attributed to David I Bernstein.
Transmissibility, infectivity and immunogenicity of a live human parainfluenza type 3 virus vaccine (HPIV3cp45) among susceptible infants and toddlers.
BACKGROUND: This study examined the transmissibility between young children of an intranasally administered live attenuated human parainfluenza virus type 3 (HPIV3)-cp45 vaccine candidate. METHODS: Eighty subjects were enrolled in playgroups among whom there was at least one infected vaccinee in close contact with a seronegative placebo recipient over 21 days without a confounding infection with wtHPIV3. Following vaccination viral cultures were obtained on nine occasions to detect shedding and transmission of HPIV3cp45. Serum antibody titers were measured before and 7 weeks after vaccination. RESULTS: No child fulfilled the criteria for transmission of HPIV3cp45 giving a risk of transmission of 0.04 (95% CI 0.01-0.19), hence establishing that HPIV3cp45 is less infectious than wtHPIV3 and risk of transmission is not a limitation to further clinical development of this vaccine candidate.
Antibodies, Viral↗
Efficacy of an acellular pertussis vaccine among adolescents and adults.
BACKGROUND: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. METHODS: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. RESULTS: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years. CONCLUSIONS: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.
Adolescent↗
Development of candidate rotavirus vaccines derived from neonatal strains in India.
The need for a rotavirus vaccine in India is based on the enormous burden associated with the >100,000 deaths due to rotavirus diarrhea that occur annually among Indian children. Two rotavirus strains identified during nosocomial outbreaks of rotavirus infection in New Delhi and Bangalore, India, more than a decade ago are being developed as live oral vaccines. Infected newborns had no symptoms, shed virus for up to 2 weeks after infection, mounted a robust immune response, and demonstrated protection against severe rotavirus diarrhea after reinfection. The 2 strains are naturally occurring bovine-human reassortants. The New Delhi strain, 116E, is characterized as having a P[11],G9 genotype, and the Bangalore strain, I321, is characterized as having a P[11],G10 genotype. The strains have been prepared as pilot lots for clinical trials to be conducted in New Delhi. This unique project, which is developing a new rotavirus vaccine in India with the use of Indian strains, an Indian manufacturer, and an Indian clinical development program, aims to expedite introduction of rotavirus vaccines in India.
Administration, Oral↗
Evaluation of imiquimod 5% cream to modify the natural history of herpes labialis: a pilot study.
BACKGROUND: Imiquimod is currently approved for the treatment of genital warts and has been shown to decrease recurrences of genital herpes in the guinea pig model of genital herpes. Therefore, we evaluated the safety and potential of topical imiquimod to decrease the rate of recurrence in humans with a history of recurrent herpes labialis. METHODS: Forty-seven subjects with recurrent herpes labialis applied imiquimod 5% (n=30) or vehicle cream (n=17) to recurrent lesion(s) on days 1, 3, and 5 of the study (day 1 of observation occurred within 48 h after recurrence of lesion). Subjects were seen at the study centers between each dose and 3 days after application of the final dose or until resolution of the lesion. RESULTS: After application to recurrent lesions, local erythema, edema, scabbing and/or flaking, pain, burning, and maximal lesion size were significantly greater in the imiquimod group than in the vehicle group. The study was terminated early because of severe local adverse events that occurred in 5 recipients of imiquimod. The median time until the next recurrence was, however, increased from 50 days in the vehicle group to 91 days in the imiquimod group (P=.018). CONCLUSIONS: Application of imiquimod 5% cream to herpes labialis lesions was associated with a delay in the time to the first recurrence after treatment, but severe local inflammation occurred in some individuals.
Administration, Topical↗
Safety and immunogenicity of glycoprotein D-adjuvant genital herpes vaccine.
BACKGROUND: Two previous trials have suggested that a herpes simplex virus (HSV) type 2 glycoprotein D (gD) vaccine combined with the adjuvants alum and 3'-O-deacylated-monophosphoryl lipid A (MPL) is well tolerated and provides protection against genital herpes disease in women with no preexisting HSV antibody. METHODS: The safety and immunogenicity of this vaccine were evaluated in a large, multicenter, double-blind, randomized, placebo-controlled trial. The effects of sex and preexisting HSV immunity were sought. RESULTS: When solicited symptoms that continued after the initial 4 days of observation were excluded, the incidence of unsolicited symptoms occurring during the 7 months after vaccination (the primary analysis period) was 22.1% in vaccine recipients and 21.9% in placebo recipients. Significant increases in the number of local and systemic symptoms were found in vaccine recipients within 4 days after vaccination. However, most symptoms were mild to moderate in severity and were short lived. Women reported symptoms more frequently than did men, but preexisting immunity had little effect. The vaccine induced higher titers of HSV gD antibody on enzyme-linked immunosorbent assays than did natural infection with HSV. CONCLUSION: The vaccine was generally safe, well tolerated, and immunogenic.
Adjuvants, Immunologic↗
The non-nucleoside antiviral, BAY 38-4766, protects against cytomegalovirus (CMV) disease and mortality in immunocompromised guinea pigs.
New antiviral drugs are needed for the treatment of cytomegalovirus (CMV) infections, particularly in immunocompromised patients. These studies evaluated the in vitro and in vivo activity of the non-nucleosidic CMV inhibitor, BAY 38-4766, against guinea pig cytomegalovirus (GPCMV). Plaque reduction assays indicated that BAY 38-4766 was active against GPCMV, with an IC(50) of 0.5muM. Yield reduction assays demonstrated an ED(90) and ED(99) of 0.4 and 0.6muM, respectively, of BAY 38-4766 against GPCMV. Guinea pigs tolerated oral administration of 50mg/kg/day of BAY 38-4766 without evidence of biochemical or hematologic toxicity. Plasma concentrations of BAY 38-4766 were high following oral dosing, with a mean peak level at 1-h post-dose of 26.7mg/ml (n=6; range, 17.8-35.4). Treatment with BAY 38-4766 reduced both viremia and DNAemia, as determined by a real-time PCR assay, following GPCMV infection of cyclophosphamide-immunosuppressed strain 2 guinea pigs (p<0.05, Mann-Whitney test). BAY 38-4766 also reduced mortality following lethal GPCMV challenge in immunosuppressed Hartley guinea pigs, from 83% (20/24) in placebo-treated guinea pigs, to 17% (4/24) in BAY 38-4766-treated animals (p<0.0001, Fisher's exact test). Mortality differences were accompanied by reduction in DNAemia in Hartley guinea pigs. Based upon its favorable safety, pharmacokinetic, and therapeutic profiles, BAY 38-4766 warrants further investigation in the GPCMV model.
Animals↗
Pediatricians' intention to administer human papillomavirus vaccine: the role of practice characteristics, knowledge, and attitudes.
PURPOSE: The objective of this study was to examine pediatrician characteristics and attitudes associated with intention to recommend two hypothetical human papillomavirus (HPV) vaccines. METHODS: A survey instrument mailed to a random sample of 1000 pediatricians assessed provider characteristics, HPV knowledge, and attitudes about HPV vaccination. Intention to administer each of two HPV vaccines types (a cervical cancer/genital wart vaccine and a cervical cancer vaccine) to girls and boys of three different ages (11, 14, and 17 years) was assessed. Linear mixed modeling for repeated measures and multivariable linear regression models were performed to identify variables associated with intention to recommend vaccination. RESULTS: The mean age of participants (n = 513) was 42 years and 57% were female. Participants were more likely to recommend vaccination to girls vs. boys and older vs. younger children, and were more likely to recommend a cervical cancer/genital wart vaccine than a cervical cancer vaccine (p < .0001). Variables independently associated with intention to recommend a cervical cancer/genital wart vaccine were: higher estimate of the percentage of sexually active adolescents in one's practice (beta .084, p = .002), number of young adolescents seen weekly (beta 1.300, p = .015), higher HPV knowledge (beta 1.079, p = .015), likelihood of following the recommendations of important individuals and organizations regarding immunization (beta .834, p = .001), and fewer perceived barriers to immunization (beta -.203, p = .001). CONCLUSIONS: Vaccination initiatives directed toward pediatricians that focus on modifiable predictors of intention to vaccinate, such as HPV knowledge and attitudes about vaccination, may facilitate adherence to emerging national immunization guidelines.
Adolescent↗
Prevalence of diarrheagenic Escherichia coli in acute childhood enteritis: a prospective controlled study.
OBJECTIVE: Since diarrheagenic E. coli are not identified by common clinical laboratory techniques, we hypothesized that these organisms might be an unrecognized cause of enteritis in children in the U.S. STUDY DESIGN: 1327 children with acute gastroenteritis were identified prospectively by active surveillance in the Emergency Department (ED) and the inpatient units at Cincinnati Children's Hospital Medical Center. Stool samples were evaluated for diarrheagenic E. coli using a panel of DNA probes and adherence pattern to HEp-2 cells. Stool samples from a reference group of 555 well children were studied for comparison. RESULTS: Gene probe studies, but not HEp-2 cell adherence, demonstrated that enteroaggregative, diffusely adherent and enteropathogenic E. coli were associated with clinical illness. Each was isolated significantly more often from study subjects in the ED than controls. In children <1 year of age, enteroaggregative E. coli were isolated significantly more often from both inpatients (4.7%, Odds Ratio = 3.4, 95% confidence intervals 1.3-9.1, p <0.03) and ED patients (10.0%, Odds Ratio = 7.2, 95% confidence intervals 2.9-18.2, p <0.001) than from well children (1.4%). CONCLUSIONS: Diarrheagenic E. coli , especially enteroaggregative E. coli , may be an important, unrecognized cause of childhood diarrhea in the U.S.
Adolescent↗
Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis.
BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo in patients with SAR. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 565 patients aged 12 to 80 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms and completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Olopatadine spray (0.4% and 0.6%) was significantly superior to placebo for percentage change from baseline in overall reflective (P = .004 and P < .001, respectively) and instantaneous (P = .02 and P = .003, respectively) TNSSs. Also, 0.6% olopatadine was significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny and itchy nose, and itchy eyes; the instantaneous assessments of watery eyes; and the overall and all 7 domain scores of the RQLQ (P < .05). Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs (reflective and instantaneous) and in quality-of-life variables in patients with SAR. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.
Administration, Intranasal↗
Lack of correlation between regional pollen counts and percutaneous reactivity to tree pollen extracts in patients with seasonal allergic rhinitis.
BACKGROUND: Although seasonal patterns of tree pollination have been reported, it is unknown if aerobiologic data correlate with patterns of in vivo sensitization. OBJECTIVE: To evaluate the relationship between regional tree pollen exposure and patterns of in vivo percutaneous reactivity to specific tree pollen extracts in a local patient population with seasonal allergic rhinitis. METHODS: Patients with spring seasonal allergic rhinitis and percutaneous sensitivity to 1 or more regional tree pollens were studied. Tree pollen counts were collected at the same urban site from 1997 to 2002 and at a suburban site in 2002. Patients underwent skin prick testing with commercial extracts of 15 indigenous tree species. Serum specific IgE measurements were assayed in a subset of sensitized patients. RESULTS: Of 127 patients who reported symptoms consistent with seasonal allergic rhinitis during the spring pollen season, 93 qualified based on demonstration of at least 1 positive skin prick test result. Mean 5-year pollen counts (1997-2001) and 2002 urban counts were highly correlated (Spearman r = 0.95, P < .001), indicating that year-to-year pollen counts were consistent. No significant correlation was found between mean seasonal pollen counts (urban site, 1997-2001) and frequencies of skin prick test reactivity to specific tree pollen allergens (Spearman r = -0.03, P = .93). No significant relationship was found between 5-year mean tree pollen counts and positive serum specific IgE tests for specific tree pollens (Spearman r = -0.42, P = .30). Eight of 15 species elicited percutaneous reactions in more than 50% of patients (ie, satisfying definition of a major in vivo allergen). However, 6 of the 8 major tree allergens each represented 5% or less of 5-year mean total tree pollen counts. CONCLUSION: No correlation was found between overall frequencies of in vivo sensitization to tree pollen allergens in a local population and regional pollen exposure data.
Adolescent↗
Psychological, behavioral, and interpersonal impact of human papillomavirus and Pap test results.
BACKGROUND: The purpose of this study was to explore the short-term psychological, behavioral, and interpersonal impact of human papillomavirus (HPV) and Pap results in adolescent and young adult women. METHODS: Sexually active young women 14-21 years of age were recruited using a purposeful sampling strategy from a hospital-based teen health center. Participants underwent HPV DNA and Pap testing at baseline. At a follow-up visit 2 weeks later, they received test results and participated in individual interviews designed to examine the impact of test results. Interview data were analyzed using framework analysis, a qualitative analytical method. RESULTS: The mean age of the 100 participants was 17.2 years, and 82% were black. Fifty-one percent were HPV positive, and 23% had abnormal Pap tests. Psychological responses consisted of affective reactions to abnormal results, empowerment through knowledge of results, and self-confidence to prevent future disease. Personal behavioral intentions encompassed safe sexual behaviors, partner monitoring, and return for screening. Anticipated interpersonal consequences focused on the impact of communication about test results on relationships. Psychosocial and behavioral responses were influenced by the personal meaning participants derived from HPV and Pap results (e.g., perceptions of personal risk and anticipated stigma), cognitive understanding of test results, and such factors as coping mechanisms, locus of control, and relationship quality. CONCLUSIONS: An understanding of young women's responses to HPV and Pap test results may help guide clinical interventions designed to prevent possibly harmful psychosocial and interpersonal responses to HPV and Pap testing but promote healthy sexual behaviors and regular screening.
Adolescent↗
Human papillomavirus vaccines and adolescents.
PURPOSE OF REVIEW: This review will describe human papillomavirus (HPV) vaccines in development, summarize data regarding safety and efficacy of these vaccines, and discuss key issues related to HPV vaccine implementation. RECENT FINDINGS: Evidence from epidemiologic and genetic studies has confirmed that HPV infection is a necessary cause of cervical cancer and contributes to the development of other cancers. HPV infection also may cause nonmalignant conditions such as external genital warts and recurrent respiratory papillomatosis. Over the past decade, several vaccines that target common HPV types have entered clinical trials. These vaccines are classified as prophylactic or therapeutic. The goal of prophylactic vaccines is to prevent primary or persistent HPV infections, and thus prevent cervical cancer and/or genital warts. Recent evidence indicates that prophylactic vaccines are well tolerated, highly immunogenic and effective in preventing persistent HPV infection and cervical intraepithelial neoplasia (CIN). Questions remain, however, concerning vaccine efficacy against HPV-related diseases other than cervical cancer, the duration of protection, vaccine acceptability and feasibility of vaccine delivery in the developing world. The goal of therapeutic vaccines is to prevent progression of HPV infection, induce regression of CIN or condylomata, or eradicate residual cervical cancer. Although therapeutic vaccines appear to induce both humoral and cell-mediated immunity, they have not consistently demonstrated clinical efficacy. SUMMARY: HPV vaccines in development have the potential to reduce the substantial morbidity and mortality associated with cervical cancer and other HPV-associated diseases. Large-scale efficacy studies that are planned or underway will provide additional information about vaccine tolerance and efficacy.
Adolescent↗
Nonmedical costs associated with rotavirus disease requiring hospitalization.
BACKGROUND: As the most common cause of severe diarrhea among children, rotavirus has a significant economic impact. Previous studies focused on the direct medical costs of rotavirus infections; however, nonmedical costs account for the majority of the financial burden from this disease. Herein, we report the results from the largest prospective study in the United States determining the nonmedical costs of severe rotavirus infections. METHODS: Prospective, active, gastroenteritis case surveillance was conducted between November 1997 and December 1999 at 3 pediatric medical centers. Rotavirus infection was identified for 548 children admitted between 2 weeks and 5 years of age. Detailed information about nonmedical costs during the prehospitalization, hospitalization and posthospitalization periods was obtained through interviews. RESULTS: The average nonmedical cost per case of rotavirus disease was USD $448.77, including $359.04 for missed work, $56.66 for transportation, $11.90 for oral rehydration solutions, $9.59 for diapers, $6.83 for child care changes, $3.82 for special foods and $0.93 for formula changes. More than one-half of these expenses (53%) occurred outside the hospitalization period, and 80% of the cost was attributable to missed work. CONCLUSIONS: With an estimated 50,000 hospitalizations attributable to rotavirus each year in the United States, the nonmedical costs of severe rotavirus infections may exceed USD $22 million annually. Previous cost effectiveness analyses of rotavirus vaccines substantially underestimated this burden, suggesting that the nonmedical costs associated with mild to moderate rotavirus disease have been similarly underestimated. These findings are needed to assess accurately the cost effectiveness of future rotavirus immunization strategies.
Antigens, Viral↗
Use of active surveillance to validate international classification of diseases code estimates of rotavirus hospitalizations in children.
OBJECTIVE: National estimates of hospitalizations for rotavirus, the leading cause of acute gastroenteritis (AGE) in children, have been used to establish the need for rotavirus vaccines. A previous method directly estimated discharges by using the rotavirus-specific International Classification of Diseases (ICD) code, but this method has not been validated. Our study evaluated the sensitivity of the rotavirus ICD code among children hospitalized for AGE by using active surveillance for rotavirus at a tertiary children's hospital. DESIGN: We compared data for rotavirus-coded hospital discharges in 2000-2001 at Cincinnati Children's Hospital Medical Center with data on laboratory-confirmed cases of rotavirus obtained from active surveillance. We estimated additional rotavirus hospitalizations by extrapolating the proportion of rotavirus-positive results from active-surveillance cases to those with an unknown rotavirus status. RESULTS: Of 767 cases of AGE-related discharge codes, 103 (13%) were coded as rotavirus, 91% (94 of 103) of which were laboratory-confirmed diagnoses. Among all children discharged with an AGE-related illness, 260 (34%) were enrolled in active surveillance, of whom 155 (60%) tested positive for rotavirus. An additional 47 laboratory-confirmed rotavirus-case patients not enrolled in active surveillance yielded a total of 202 rotavirus cases and a maximum sensitivity of the rotavirus code of 47%. Extrapolation indicated that an additional 170 untested children might be rotavirus-positive, yielding a total of 372 rotavirus hospitalizations and a minimum sensitivity of the rotavirus code of 25%. CONCLUSIONS: Measurement of rotavirus-coded hospital discharges alone seems to greatly underestimate the true burden of rotavirus-associated hospitalizations. The numbers of national rotavirus hospitalization discharges may be substantially greater than previously estimated.
Acute Disease↗
Lack of induction of autoantibody responses following immunization with cytomegalovirus (CMV) glycoprotein B (gB) in healthy CMV-seronegative subjects.
Possible correlations have been proposed between autoimmune diseases, such as systemic lupus erythematosus (SLE), and infection with human cytomegalovirus (CMV). The recent observation that an adenovirus expressing the immunodominant envelope glycoprotein of CMV, glycoprotein B (gB), may be capable of inducing autoantibodies in certain mouse strains has prompted interest in exploring potential relationships between gB immunization and autoimmune disease. We examined whether a recombinant CMV gB vaccine, or a gB canarypox vectored vaccine (ALVAC-CMVgB), administered to a total of 76 CMV-seronegative subjects, was capable of inducing cross-reactive antibodies to Smith antigen (Sm), ribonucleoprotein complex (RNP), and the U1-70 kDa component of the RNP complex. Using immunofluorescence, EIA and immunoblot analyses, we failed to identify induction of autoantibodies following vaccination with gB, whether administered alone as a purified protein subunit with adjuvant, or in combination with expression in a vectored approach using a recombinant canarypox. These data reinforce the favorable safety profile of CMV gB vaccines.
Adolescent↗
Longitudinal risk of herpes simplex virus (HSV) type 1, HSV type 2, and cytomegalovirus infections among young adolescent girls.
BACKGROUND: Cross-sectional seroprevalence studies indicate that infections with herpes simplex virus (HSV) types 1 (HSV-1) and 2 (HSV-2) and cytomegalovirus (CMV) are common. However, data on the rates of acquisition of these infections are limited. METHODS: A 3-year longitudinal study of HSV-1, HSV-2, and CMV seroprevalence was conducted in a cohort of 174 adolescent girls (age at enrollment, 12-15 years). RESULTS: At study entry, 41% of the girls reported a history of sexual activity, and by the end of the study, 73% reported a history of sexual activity. At enrollment, 71% of all participants were seropositive for CMV, 44% were seropositive for HSV-1, and 7% were seropositive for HSV-2. By the end of the study, 81% of the girls were seropositive for CMV, 49% were seropositive for HSV-1, and 14% were seropositive for HSV-2. Among girls with a history of sexual activity, 15.5% were HSV-2 seropositive at the beginning of the study, and 18.9% were HSV-2 seropositive at the end of the study. The attack rates, based on the number of cases per 100 person-years, were 13.8 for CMV infection and 3.2 for HSV-1 infection (among all girls) and 4.4 for HSV-2 infection (among girls with a history of sexual activity). Participants with preexisting HSV-1 antibodies were associated with a significantly lower attack rate for HSV-2 infection. A generalized estimating equation model indicated that participants with a longer history of sexual activity and those who had more sexually transmitted diseases during the 6-month periods before the study visits were more likely to be HSV-2 seropositive. CONCLUSIONS: This longitudinal study of adolescent girls found high baseline CMV and HSV-1 seroprevalence rates and substantial attack rates for all 3 pathogens.
Adolescent↗
Vaccination success rate and reaction profile with diluted and undiluted smallpox vaccine: a randomized controlled trial.
CONTEXT: Additional smallpox vaccine doses are needed to augment current US national stockpile. Aventis Pasteur smallpox vaccine (APSV), initially manufactured in the 1950s from the New York Board of Health vaccinia strain in a frozen preparation, appears as effective as lyophilized vaccine but the effectiveness of diluted doses of APSV is unclear. OBJECTIVE: To compare the vaccination success rate and the reaction profile of various APSV dilutions. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized controlled trial of 340 healthy vaccinia-naive adults aged 18 to 32 years from 3 academic medical centers who were vaccinated with 1 of 3 strengths of APSV dilutions (undiluted, 1:5, and 1:10) between October 9, 2002, and February 24, 2003. Volunteers were followed up every 3 to 5 days until the vaccination site healed for bandage changes, vaccine response assessment, and adverse event evaluation, followed by 1- and 2-month clinic evaluations and 6-month telephone interview. MAIN OUTCOME MEASURES: Successful vaccination, defined by presence of a vesicle or pustule at the inoculation site 6 to 11 days postvaccination, and local and systemic reactions to vaccination. RESULTS: A total of 340 volunteers were vaccinated (vaccine dose: undiluted, n = 113; 1:5 dilution, n = 114; and 1:10 dilution, n = 113). Following vaccination, 99.4% (95% confidence interval [CI], 97.9%-99.9%) of all volunteers had successful vaccinations. Success rates did not differ between the dilution groups (undiluted, 100.0%; 95% CI, 96.8%-100.0%; 1:5 dilution, 98.2%; 95% CI, 93.8%-99.8%; 1:10 dilution, 100.0% 95% CI, 96.8%-100.0%; P =.33). Overall, 99.7% of volunteers reported at least 1 local symptom at the vaccination site, and 61.8% had axillary lymphadenopathy, 15.0% developed satellite lesions, and 7.6% developed a rash away from the vaccination site. Fever developed in 21.5%. No differences were noted in local or systemic reactions between the 3 dilution groups (P>.05 for each comparison). A total of 25% of volunteers missed scheduled duties due to vaccine-related symptoms. CONCLUSIONS: Even at diluted doses, APSV is an effective smallpox vaccine, allowing for expansion of the current stockpile. However, reactogenicity was not reduced with dilution of the vaccine and, as with other smallpox vaccines, may impair daily activities.
Adult↗