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Biomedical subjects

B G Weniger

Publications and source records attributed to B G Weniger.

At least 19 recordsLinked to original sources
PubMed2001

Combination vaccines: postlicensure safety evaluation.

The success of immunizations in nearly eliminating many vaccine-preventable diseases has resulted in an increase in the need to study risks from vaccines, combination or otherwise. The well-known limitations associated with prelicensure trials have led many to hope that postlicensure studies can address safety issues. This article reviews measures that have been or should be taken to meet this expectation: establishment of clinical immunization safety assessment centers, standardization of case definitions for vaccine adverse events, use of the Vaccine Identification Standards Initiative to improve the accuracy and efficiency with which vaccination records are transferred, integration of vaccine safety monitoring into immunization registries, establishment (and enlargement) of the Vaccine Safety Datalink project, use of innovative analytic tools for better signal detection, and implementation of various methods to overcome confounding by contraindication. Only by investing in vaccine safety infrastructure at a level commensurate with investments in vaccine development can we hope to retain the public's confidence in immunization.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Safety and immunogenicity of varying dosages of trivalent inactivated influenza vaccine administered by needle-free jet injectors.

To evaluate the perceived pain, other adverse events, and immunogenicity of influenza virus vaccine administered by needle-free jet injector (JI) compared with that of vaccine administered by needle and syringe (N&S), we randomly assigned 304 healthy young adults to receive one of three dosages (0.5, 0.3, or 0.2 ml) of the 1998-1999 season vaccine administered by either of two JI devices or by N&S. In multivariate analysis, female gender and JI administration were associated with higher levels of pain reported at the time of vaccination as well as with the occurrence of local injection site reactions following vaccination. Immune response did not vary significantly by dosage but administration by one JI device was associated with higher post-vaccination H1N1 antibody titers.

Adult↗
PubMed2001

"Reverse engineering" a formulary selection algorithm to determine the economic value of pentavalent and hexavalent combination vaccines.

INTRODUCTION: Combination vaccines with overlapping, noncomplementary components are being introduced to reduce the number of separate injections required to immunize children. A vaccine selection algorithm using operations research techniques was developed as a tool for vaccine purchasers to assemble formularies of monovalent and combination vaccines that would satisfy the recommended immunization schedule. The algorithm weighs distinguishing features of economic consequence among competing vaccines to achieve the lowest overall cost to payers and/or to society for immunization. This method was adapted here to solve for the purchase price of several hypothetical future pentavalent and hexavalent combination vaccines that would permit each to "win" a place in such a lowest cost formulary. METHODS: Integer programming and an iterative bisection search method determined the maximum "inclusion price" of 4 vaccines not licensed in the United States as of September, 2001 [diphtheria-tetanus-acellular pertussis (DTPa)-Haemophilus influenzae type b (HIB)-hepatitis B (HBV), DTPa-HIB-inactivated polio vaccine (IPV), DTPa-HBV-IPV and DTPa-HIB-HBV-IPV], in competition with 15 existing formulations of licensed vaccines for these diseases at their March, 2000, federal contract discount prices. Both 5-visit and 6-visit scenarios were studied. Different preparation costs were assigned to lyophilized powder ($1.50), liquid ($0.75) and prefilled-syringe ($0.25) formulations/packaging. Injection costs were varied stepwise from $5 through $45 for each dose administered, shifting from a payer's to a societal perspective. RESULTS: Overall inclusion prices (maximum price for each candidate vaccine to be included in a lowest cost formulary) ranged from $9 to $129 per dose depending on cost assumptions and usage frequency (values would be higher if competing against private-sector vaccine prices). The range was $27 to $68 per dose for DTPa-HIB-HBV, at optimal utilization to avoid extra vaccination. Similarly, as injection costs varied from $5 to $45, DTPa-HIB-IPV ranged from $28 to $75. With the same assumptions, DTPa-HBV-IPV would earn a place in a best value formulary at prices from $35 to $76. As expected the inclusion prices for hexavalent DTPa-HIB-HBV-IPV, $40 to $123, were higher (reflecting more economic value) than for pentavalents. When the assumed injection costs rose to > or = $8, the more expensive HIB-HBV and DTPa-HIB tended to appear in lowest cost formularies, because their cost premium over separate monovalent and trivalent products was outweighed by the savings from one fewer injection. CONCLUSION: Reverse engineering the vaccine selection algorithm provides a tool to demonstrate the economic value of new combination vaccines and to make pricing decisions.

Algorithms↗
PubMed2001

Economic value to parents of reducing the pain and emotional distress of childhood vaccine injections.

BACKGROUND: One reason that recommended childhood immunizations due at child health visits are deferred is to avoid the pain and emotional distress associated with the increasing number of injections required. This deferral leads to additional visits and costs and reduced immunoprotection against vaccine-preventable illnesses. To assess the economic value of combination vaccines that address this problem, we surveyed parents to determine the amount they would be willing to pay to avoid the pain and emotional distress experienced by their infants from injections. METHODS: A self-administered questionnaire was completed within 24 h of the vaccinations by 294 parents of children ages 11/2 to 7 months receiving vaccine injections at 26 outpatient child health centers. The willingness-to-pay (WTP) method was used to estimate the intangible cost of the pain and emotional distress of the 1 to 4 injections their child had received. Parents were asked how much of their own money they would have paid to avoid these injections, without any compromise in the safety and efficacy of the vaccinations. RESULTS: Wide variations in WTP amounts were observed, ranging from median values of $10 to $25 and average values of $57.06 to $79.28 to avoid the pain and emotional distress associated with eliminating all injections at visits in which one to four injections were administered. Parents placed greater value on reductions that avoided all injections than on reductions that avoided only some injections. Overall the median cost per injection avoided was $8.14, and the mean was $30.28. CONCLUSIONS: Parents have strong preferences for limiting vaccine injections. The economic cost of the pain and distress associated with such injections, reflected in the amounts they report they would be willing to pay to avoid them, represents a substantial component of the cost of disease control through immunization.

Adult↗
PubMed2000

The hidden costs of infant vaccination.

Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1-8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infant's vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of $25 to reduce injections from 4 to 3, $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean costs of $42 in medical utilization and $192 in work-loss among the families who experienced those events (Ns=62 and 35, respectively). When averaged among all 1657 study infants, vaccine-associated symptoms after the index vaccination visit resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct nonmedical costs, yielding total financial costs of $7.70. Parents of infants who had vaccine-associated symptoms said they would have paid a median of $50 to avoid these symptoms. Fever and fussiness were associated in logistic regression analysis with a two-fold increase in the odds of medical utilization, and fever with more than a three-fold increase in work loss. We conclude that multiple injections during a single clinic visit entail psychological costs. The psychological costs of vaccine-associated symptoms, as measured by willingness-to-pay methods, are higher than those resulting from multiple injections. The financial costs of medical utilization and work-loss resulting from common vaccine-associated symptoms are non-negligible and should be incorporated in economic analyses.

Cross-Sectional Studies↗
PubMed2000

Safety testing of needle free, jet injection devices to detect contamination with blood and other tissue fluids.

Needle free jet injection guns have been used extensively in both veterinary and human health to deliver both vaccine and drugs, but in recent years, concerns have mounted for their potential to transmit blood borne disease agents among consecutive vaccinates. A Ped-O-Jet type jet injection device was used to deliver serial subcutaneous injections of 0.5 mL saline (as a surrogate for vaccine) into calves and pigs, with intervening ejectates collected in vials to represent what the next vaccinate would have received. An enzyme linked immunosorbant assay was developed to detect species specific albumin as a marker for blood, using calibration standards from known dilutions of bovine or porcine blood. Assay sensitivity of 20 pL/mL corresponded to the estimated minimal chimpanzee infectious dose of 10 pL for hepatitis B virus. The methodology and available results for evaluating the safety of jet injector devices are reported.

Animals↗
PubMed1999

An integer programming model for vaccine procurement and delivery for childhood immunization: a pilot study.

The National Immunization Program of the Centers for Disease Control and Prevention has identified several challenges that must be faced in childhood immunization programs to deliver and procure vaccines to protect against the common preventable diseases. The biomedical challenge is how to combine and formulate products to take advantage of new vaccines without requiring additional injections. A programmatic challenge is to incorporate then into already crowded immunization schedules. The economic challenge is to make wise procurement choices from among a growing number of competing products. This paper reports the results of a pilot study using operations research methodologies to address the third of these challenges. The pilot is an integer programming model for procuring vaccines for a set of childhood diseases. The model is studied under various scenarios (minimum total cost, next lowest total cost, maximum total cost, minimum total cost with all manufacturers represented). The results of this pilot study demonstrate how a practical set of operations research tools can be developed to guide vaccine selection and procurement, which might stimulate the development of innovations in new vaccines to meet the challenges of disease control through immunization.

Centers for Disease Control and Prevention, U.S.↗
PubMed1999

Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Herpes in the time of AIDS: a comparison of the epidemiology of HIV-1 and HSV-2 in young men in northern Thailand.

OBJECTIVES: To compare the epidemiologic pattern of HIV-1, a recently introduced sexually transmitted disease (STD) agent in Thailand, with the pattern of HSV-2, a well-established STD agent, so that future trends for both viruses can be better understood. METHODS: We obtained questionnaire data and determined HSV-2 (by specific gG-2) and HIV-1 seroreactivity in a cohort of 1,115 young male army conscripts who entered service in northern Thailand in 1991. RESULTS: Seroprevalence of HIV-1 and HSV-2 was 6.9% and 14.9%, respectively. For HSV-2-seropositive men who reported previous genital ulcers, HIV-1 seroprevalence was 32%. For most variables, there was a close correspondence between the prevalence ratios for HIV-1 and for HSV-2, except that prevalence ratios for HIV-1 tended to be greater than the corresponding ratios for HSV-2. The seroprevalence of both viruses was strongly related to early and frequent contact with female sex workers (FSWs), infrequent use of condoms with FSWs, and residence in the upper north region of Thailand. When differences in sexual behavior between the upper north and lower north were controlled for, the seroprevalence of both viruses still differed significantly by region. CONCLUSIONS: Although the seroprevalence levels of HSV-2 and HIV-1 were quite different in this cohort of Thai army conscripts in 1991, the patterns of infection in terms of demographic, residential, and behavioral variables were similar. Seroprevalence studies of HSV-2 in other populations, particularly where the HIV-1 epidemic is just beginning, may be useful in predicting which subgroups might be most vulnerable to the epidemic and could therefore benefit the most from public health intervention. Where differences in the patterns of the two viruses have been noted, we hypothesize that the pattern for HIV-1 will evolve toward that seen for HSV-2.

Adult↗
PubMed1999

HIV-1 and other sexually transmitted infections in a cohort of female sex workers in Chiang Rai, Thailand.

OBJECTIVES: To determine demographic and behavioural factors and sexually transmitted infections (STIs) associated with prevalent HIV-1 infection among brothel based and other female sex workers (FSWs) in Chiang Rai, northern Thailand. METHODS: Data were collected from questionnaires, physical examinations, and laboratory evaluations on Thai FSWs enrolled in a prospective cohort study in Chiang Rai, Thailand, from 1991 to the end of 1994. RESULTS: HIV-1 seroprevalence was 32% among 500 women: 47% for 280 brothel workers and 13% for 220 other FSWs (p < 0.001); 96% of infections were due to HIV-1 subtype E. At enrolment, other STIs were common: chlamydia, 20%; gonorrhoea, 15%; active syphilis (serological diagnosis), 9%; genital ulcer, 12%; seroreactivity to Haemophilus ducreyi, 21%, and herpes simplex virus type 2 (HSV-2), 76%. On multiple logistic regression analysis, HIV-1 was associated with brothel work, birth in upper northern Thailand, initiation of commercial sex at < 15 years of age, syphilis, HSV-2 seropositivity, and genital ulcer. CONCLUSIONS: Young Thai FSWs working in brothels in northern Thailand in the early phase of the HIV epidemic have been at very high risk for HIV-1 infection and several other STIs. Programmes are needed to prevent girls and young women from entering the sex industry and to reduce the risk of infection with HIV-1 and other STIs.

Adolescent↗
PubMed1998

HIV-1 seroconversion in a prospective study of female sex workers in northern Thailand: continued high incidence among brothel-based women.

OBJECTIVES: To determine the incidence of HIV-1 infection, temporal trends in incidence, and risk factors for seroconversion in a cohort of female commercial sex workers (CSW) in upper northern Thailand, the region of Thailand with the highest rates of HIV-1 infection. METHODS: CSW were enrolled from 1991 through 1994 and evaluated prospectively with interviews, physical examination, testing for sexually transmitted diseases (STD), and serologic testing for HIV-1 infection. RESULTS: The incidence of HIV-1 seroconversion in the first year of follow-up was 20.3 per 100 person-years among 126 brothel-based CSW and 0.7 per 100 person-years among 159 other CSW who worked in other venues such as bars or massage parlors. Incidence remained elevated among brothel-based CSW who were enrolled later in the study compared with those who enrolled earlier. Through 1996, 30 women seroconverted. In a multivariable proportional hazards model, seroconversion was significantly associated (P < 0.05) with brothel-based sex work (adjusted risk ratio, 7.3) and Chlamydia trachomatis cervical infection (adjusted risk ratio, 3.3). CONCLUSION: Despite national HIV control efforts and declining rates of infection among young men in Thailand, brothel-based CSW may continue to be at high risk for HIV-1 infection. Additional efforts are needed to provide alternative economic choices for young women, to ensure universal condom use during commercial sex, and to develop new prevention technologies.

Adolescent↗
PubMed1998

HIV-1 subtype E incidence and sexually transmitted diseases in a cohort of military conscripts in northern Thailand.

OBJECTIVES: To determine the rate of and risk factors for HIV-1 seroconversion and describe sexually transmitted disease (STD) prevalence rates for young men in northern Thailand. METHODS: Data were collected from self-administered questionnaires and serologic testing at enrollment in a prospective study in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 men selected by lottery for military conscription. RESULTS: A total of 14 men seroconverted to HIV-1 envelope subtype E. The overall HIV-1 incidence rate was 1.1 (95% confidence interval [CI], 0.6-1.8) per 100 person-years (PY) of follow-up. However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions (adjusted rate ratio [RR] = 2.69; 95% CI, 0.8-12.2). On multivariate analyses, the behavioral factors associated with HIV-1 seroconversion were frequency of sex with female sex workers (FSWs; p = .04), receptive anal sex (adjusted RR = 6.73; 95% CI, 1.8-21.7), and large amount of alcohol consumption (adjusted RR = 3.12; 95% CI, 1.0-10.9). Genital ulceration was the STD most strongly associated with seroconversion. The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with FSWs and was generally higher for men from the upper north. CONCLUSION: Young men in northern Thailand are at high risk for HIV-1, primarily through sex with FSWs; and other STDs are highly associated with HIV-1 incidence. As HIV-1 infection extends into the general population, intervention programs are needed to address the problem of sexual transmission apart from commercial sex venues.

Adult↗
PubMed1998

HIV prevalence, risk, and partner serodiscordance among pregnant women in Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.

CONTEXT: Most prior studies of the human immunodeficiency virus (HIV) epidemic in Thailand have focused on commercial sex encounters; however, because the epidemic increasingly concerns stable heterosexual relationships, determining risk factors for this form of transmission is warranted. OBJECTIVES: To determine temporal trends in HIV prevalence, risk factors for HIV seropositivity, and rates of partner serodiscordance for pregnant women in Bangkok, Thailand. DESIGN: Retrospective review of hospital antenatal clinic HIV test results from 1991 through 1996. Baseline demographic and behavioral risk factors for HIV were assessed for subjects enrolled from November 1992 through March 1994. SETTING: Two Bangkok hospitals with routine antenatal clinic HIV counseling and testing. PARTICIPANTS: The HIV-positive pregnant women enrolled in a perinatal HIV transmission study and their partners and HIV-negative pregnant controls. RESULTS: From 1991 through 1996, antenatal clinic HIV seroprevalence increased from 1.0% to 2.3%. On multivariate analysis of data from 342 HIV-positive and 344 HIV-negative pregnant women, more than 1 lifetime sex partner, history of a sexually transmitted disease, and a high-risk sex partner were the most important factors for seropositivity (all P<.001). Twenty-six percent of partners of HIV-positive women were HIV negative. Women reporting more than 1 lifetime sex partner were more likely to have an HIV-negative partner than women reporting only 1 (45% vs 8%; relative risk, 5.5; 95% confidence interval, 3.2-9.5; P<.001); women reporting no high-risk behaviors were less likely to have an HIV-negative partner (10% vs 44%; relative risk, 0.2; 95% confidence interval, 0.1-0.4; P<.001). CONCLUSIONS: Prevalence of HIV in pregnant women has increased steadily in Bangkok from 1991 through 1996. Sex with current partners was the only identified risk exposure for about half (52%) of the HIV-positive women. Although few HIV-positive pregnant women reported high-risk behaviors, more than 1 lifetime partner and a partner with high-risk behavior were strong risk factors for seropositivity. Together with the unexpected finding that one fourth of partners of seropositive pregnant women were seronegative, these data emphasize that women in the general population are at risk for HIV because of the risk behavior of both current and previous partners.

AIDS Serodiagnosis↗
PubMed1998

Addressing the challenges to immunization practice with an economic algorithm for vaccine selection.

The biotechnology revolution is producing a growing bounty of new vaccines which pose difficult choices in selecting among many products. Some major public and private purchasers of vaccine may offer individual physicians and clinics their choice in assembling vaccine inventories. Others might purchase only a limited stock of products that would satisfactorily immunize a typical child. In either case, current vaccine selection decisions are based principally on purchase price alone without systematic consideration of other factors of fiscal consequence. As a potential tool for decision making, we developed an economic algorithm for vaccine selection that would minimize the overall costs of disease control through immunization by considering: (1) purchase price, (2) number of doses needed, (3) preparation time, (4) route of administration, (5) cold storage needs, (6) shelf life, (7) earliest age of full immunity, (8) adverse events frequency, and (9) efficacy of protection. To demonstrate the algorithm, variables (1) to (4) above were incorporated into a pilot binary-integer linear programming model that satisfied the recommended immunization schedule for diphtheria, tetanus, pertussis, Haemophilus influenzae b, and hepatitis B, using eleven vaccines (DTaP, DTaP-Hib, Hib, HepB and Hib-HepB) from four manufacturers. Five (or six) opportunities to vaccinate were modeled at (1), 2, 4, 6, 12-18, and 60 months of life, assuming US$40 per clinic visit, $15 per injection, and $0.50 per minute of nurse preparation time. Vaccine costs were varied using actual March and September 1997 US Federal vaccine prices, as well as estimates for unpriced new vaccines. Over 16,000 distinct vaccine stocking lists by vaccine type and brand were possible. Including a 1-month visit, the lowest-cost 'solution' of the algorithm was $529.41 per child in the March cost-assumption case, and $490.32 in the September one (both included four doses of DTaP-Hib, three HepB, and one DTaP). Without a 1-month visit, the lowest-cost solution in the March case cost $486.67 (four DTaP, two Hib-HepB, one DTaP-Hib, and one HepB), while the September case cost $450.32 (four DTaP-Hib, three HepB, and one DTaP). Ensuring at least one product was selected from each of the four manufacturers increased costs about $13.00, and the needed injections rose from eight to nine. The most economical selection of vaccines to use cannot be intuitively predicted, as permutations are large and solutions are sensitive to minor changes in costs and constraints. A transparent, objective selection method that weighs the economic value of distinguishing features among competing vaccines might offer the 'best value' to vaccine purchasers, while also creating strong market incentives for continuing innovation and competition in the vaccine industry.

Adolescent↗
PubMed1996

Detection of HIV type 1 env subtypes A, B, C, and E in Asia using dried blood spots: a new surveillance tool for molecular epidemiology.

Global surveillance of HIV-1 subtypes for genetic characterization is hampered by the biohazard of processing and the difficulties of shipping whole blood or cells from many developing country regions. We developed a technique for the direct automated sequencing of viral DNA from dried blood spot (DBS) specimens collected on absorbent paper, which can be mailed unrefrigerated in sturdy paper envelopes with low biohazard risk. DBS were collected nonrandomly from HIV-1-infected, mostly asymptomatic, patients in five Asian countries in 1991, and shipped via airmail or hand carried without refrigeration to Bangkok, and then transshipped to North America for processing. After more than 2 years of storage, including 6 months at ambient temperatures, proviral DNA in the DBS was amplified by nested PCR, and a 389-nucleotide segment of the C2-V3 env gene region was sequenced, from which 287 base pairs were aligned and subtyped by phylogenetic analysis with neighbor-joining and other methods. From southern India, there were 25 infections with subtype C and 2 with subtype A. From Myanmar (Burma), we identified the first subtype E infection, as well as six subtype BB, a distinct cluster within subtype B that was first discovered in Thailand and that has now appeared in China, Malaysia, and Japan. From southwest China, one BB was identified, while a "classical" B typical of North American and European strains was found in Indonesia. From Thailand, five DBS of ambiguous serotype were identified as three B, one BB, and one E. A blinded control serotype E specimen was correctly identified, but a serotype BB control was not tested. Most HIV-1 in southern India appears to be env subtype C, with rare A, as others have reported in western and northern India. The subtypes BB and E in Myanmar, and the BB in China, suggest epidemiological linkage with these subtypes in neighboring Thailand. DBS are a practical, economical technique for conducting large-scale molecular epidemiological surveillance to track the global distribution and spread of HIV-1 variants.

China↗