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N A Halsey

Publications and source records attributed to N A Halsey.

At least 19 recordsLinked to original sources
PubMed2001

Combination vaccines: defining and addressing current safety concerns.

Combination vaccines have been in use for >50 years. Historical problems with vaccines, including intussusception after rotavirus vaccine, carrier suppression with tetanus toxoid conjugate vaccines, and decreased immunogenicity of some Haemophilus influenzae type b conjugate vaccines when mixed with acellular pertussis-diphtheria-tetanus, have contributed to some misperceptions about current vaccines. There is no evidence that adding additional vaccines through combination products increases the burden on the immune system, which has the capability of responding to many millions of antigens. Combining antigens usually does not increase adverse effects-in fact, it can lead to an overall reduction in adverse events. Combination products simplify immunization and allow for the introduction of new vaccines without requiring the vaccinee to make additional visits to his or her health care provider. Licensed combination vaccines undergo extensive testing before approval by the United States Food and Drug Administration to assure that the new products are safe and effective.

Autistic Disorder↗
PubMed2001

Safety of combination vaccines: perception versus reality.

BACKGROUND: Combination vaccines contain multiple antigens to protect against several diseases simultaneously and have simplified the delivery of childhood immunizations. Children are healthier today because of the use of combination vaccines, and the United States is benefiting from record low numbers of vaccine-preventable diseases. Despite obvious benefits, concerns and misconceptions exist regarding the safety and efficacy of combination vaccines. METHODS: A review of the pediatric literature to dispel the common misperceptions and potential barriers to combining vaccines. RESULTS: Assurance that combination vaccines approved by the United States Food and Drug Administration undergo extensive testing will help to alleviate concerns regarding safety and efficacy of combination vaccines. Food and Drug Administration standards are rigorous and require that combination vaccines be as safe and effective as each component of the vaccine administered separately. Combination vaccines have been available for >50 years, and lessons learned during this time are continuously applied to the development and use of new products. CONCLUSIONS: Children will benefit from new combination vaccines because fewer injections will be required to protect against vaccine-preventable diseases, allowing for the introduction of new vaccines into the immunization schedule and prevention of additional diseases.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12-13, 2000.

BACKGROUND: Parents and physicians are understandably concerned about the causes and treatment of autism, a devastating disease that affects the entire family. Although much has been learned about autism, there are many gaps in our knowledge about what causes the disorder and how it can be prevented. Autistic symptoms occur along a spectrum, often referred to as autistic spectrum disorder (ASD). Concern has been raised about a possible association between measles-mumps-rubella (MMR) vaccine and inflammatory bowel disease (IBD) and ASD, especially autism with regression. Also, increased requests for educational services related to ASD have raised concerns about possible increases in the incidence of ASD. METHODS: On June 12-13, 2000, the American Academy of Pediatrics (AAP) convened a conference titled "New Challenges in Childhood Immunizations" in Oak Brook, Illinois. At this conference, parents, practitioners, and scientists presented information and research on MMR vaccine and ASD. Attendees included representatives from select AAP committees and sections as well as federal and other organizations that address related issues. The multidisciplinary panel of experts reviewed data on what is known about the pathogenesis, epidemiology, and genetics of ASD and the available data on hypothesized associations with IBD, measles, and MMR vaccine. Supplemental information was requested from authors who have proposed the hypotheses and other experts in relevant areas. RESULTS: Autism is a complex disorder of uncertain and probably multiple etiologies. Genetic predisposition to ASD may involve as many as 10 genes. Many experts believe that the abnormal brain development in autism occurs before 30 weeks' gestation in most instances. In utero rubella is a known cause of autism. Animal model data support the biologic plausibility that exposure to yet unrecognized infectious or other environmental agents could cause ASD. Several factors may contribute to apparent increases in incidence of ASD in recent years. Most data indicate increased recognition and reporting as primary factors, but the epidemiologic data are insufficient to determine if there has been a true increase in the incidence of ASD. Increased reporting of ASD in recent years has occurred long after the introduction of MMR vaccine in the United States in 1971 and widespread use of this vaccine in the 1970s for routine immunization of children at 12 to 15 months of age. Appropriate detailed studies are needed to define the true incidence and prevalence of ASD. Epidemiologic studies in Europe indicate no association between MMR vaccine and ASD. Some children with ASD have gastrointestinal symptoms, but an increased rate of any specific gastrointestinal disorder in children with ASD has not been established. Studies to detect evidence of measles virus in intestinal tissue specimens from patients with IBD or autism with gastrointestinal symptoms have not used uniform techniques. Several laboratories have found no evidence of measles viruses in tissue specimens from patients with IBD, but 2 groups have found evidence of measles virus using different techniques. A group that found evidence of measles virus in affected tissue specimens from patients with IBD has also reported detecting portions of measles virus in peripheral blood lymphocytes and intestinal tissue specimens from patients with autism and gastrointestinal disorders. Finding a portion of a virus using molecular techniques does not constitute evidence for a causal relationship, because some viruses persist in unaffected hosts. Additional controlled studies in several laboratories are needed to determine if portions of measles virus persist in intestinal and other tissues of people with and without gastrointestinal disease and/or ASD. CONCLUSIONS: Although the possible association with MMR vaccine has received much public and political attention and there are many who have derived their own conclusions based on personal experiences, the available evidence does not support the hypothesis that MMR vaccine causes autism or associated disorders or IBD. Separate administration of measles, mumps, and rubella vaccines to children provides no benefit over administration of the combination MMR vaccine and would result in delayed or missed immunizations. Pediatricians need to work with families to ensure that children are protected early in the second year of life from these preventable diseases. Continued scientific efforts need to be directed to the identification of the causes of ASD.

Autistic Disorder↗
PubMed1999

Antibody-dependent cell-mediated cytotoxicity can protect PBMC from infection by cell-associated HIV-1.

We have developed a novel in vitro assay system to study the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in protection against HIV-1 infection by cell-associated virus. HIV-1-infected NK-resistant cells are mixed with specific antibody and unstimulated PBMC and ADCC is allowed to occur over several hours. The PBMC are then activated and cultured to allow virus replication in newly infected T cells. To ensure that ADCC is the only mechanism by which protection could occur we have used haptenated (TNP) infected cells and anti-hapten antibody. Anti-hapten sera completely protected PBMC from infection by haptenated HIV-1-infected cells in ADCC protection assays. F(ab')2 fragments of anti-hapten IgG showed no protection, confirming that ADCC was responsible for protection by anti-hapten IgG. PCR analysis for HIV-1 DNA confirmed the elimination of infected cells. We believe this to be the first direct demonstration that ADCC alone can protect PBMC from infection by cell-associated HIV-1.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1999

Clinical case definitions for Argentine hemorrhagic fever.

Argentine hemorrhagic fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic.

Adult↗
PubMed1999

Hepatitis B vaccine administered to children and adolescents at yearly intervals.

OBJECTIVE: Hepatitis B vaccines are usually administered on a schedule of 0, 1 to 2, and 6 months. Longer intervals between the second and third doses have been studied, but the effectiveness of hepatitis B vaccine administered at intervals of >2 months between the first and second doses have not been studied. Our objective was to compare the antibody response in recipients of Engerix-B hepatitis B vaccine administered at 12-month intervals to the response to vaccine administered at 0-, 1-, and 6-month intervals. METHODS: A total of 389 children, 5 through 16 years of age, were randomized to receive Engerix-B (10 mg) at a schedule of either 0-, 1-, and 6-month intervals or 0-, 12-, and 24-month intervals. Blood was drawn before and 1 month after the third dose. RESULTS: Immediately before the third dose of vaccine, 92.3% of children who received vaccine on the 0-, 1-, and 6-month schedule and 88.8% of children who received the 0-, 12-, and 24-month schedule had antibody to hepatitis B surface (anti-HBs) antigen concentrations >/=10 mIU/mL. Of the children in the 0-, 1-, and 6-month schedule, 95% received the third dose according to protocol versus 90% of those in the 0-, 12-, 24-month schedule. The geometric mean anti-HBs concentration just before the third dose for recipients of the 0-, 1-, and 6-month schedule (117.9 mIU/mL) was somewhat lower than that for the children who had received vaccine on the 0-, 12-, and 24-month schedule (162.1 mIU/mL). One month after the third dose, >98% of all children had anti-HBs concentrations >/=10 mIU/mL and high geometric mean antibody concentrations were observed in both groups: 5687 mIU/mL for children on the 0-, 1-, and 6-month schedule and 3159 mIU/mL for children on the 0-, 12-, and 24-month schedule. Body mass index was correlated inversely with final antibody concentration, but age was not a factor after adjustment for body mass index. DISCUSSION: Engerix-B administered on a 0-, 12-, and 24-month schedule is highly immunogenic. Providers should consider this alternate immunization schedule for children who are at low risk of immediate exposure to hepatitis B infections.

Acute Disease↗
PubMed1998

Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.

BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.

AIDS-Related Opportunistic Infections↗
PubMed1998

Dose-response to a two-component acellular pertussis vaccine in infants and comparison with whole-cell vaccine.

In an effort to determine the optimal dose of pertussis toxoid (PT) and filamentous haemagglutinin (FHA) for use in acellular pertussis vaccines we compared the immunogenicity and safety of acellular pertussis vaccine combined with diphtheria and tetanus toxoids containing 12.5 microg (DTaP-12.5) or 25 microg (DTaP-25) each of PT and FHA with a whole cell pertussis vaccine in infants immunized at 2, 4 and 6 months of age. Recipients of acellular vaccines developed higher anti-FHA concentrations and more rapid anti-PT serological responses that infants who received whole cell pertussis vaccine combined with diphtheria and tetanus toxoids (DPT). A dose response was noted; infants immunized with DTaP-25 developed significantly (P<0.03) higher anti-FHA and anti-PT levels than infants who received DTaP-12.5. No rise in the agglutinin titres was noted for recipients of the acellular vaccines although this vaccine stimulated increases in agglutinins when given as the fourth or fifth dose to children who had received three doses of DTP. The rates of erythema, induration, pain, irritability, crying, increased sleepiness, and decreased appetite were significantly (P</=0.05) lower in infants who received acellualr vaccines than in infants who received DTP. When the data from the injections at 2, 4 and 6 months of age were combined, no significant differences in the rates of any adverse event were noted for recipients of DTaP-12.5 or DTaP-25. The rates of most adverse reactions following DTP decreased from the first to the third immunization except fever, which increased. For acellular vaccine recipients, the rates of fever and erythema increased somewhat from the first to the third injection but remained far below the rates following DTP. The acellular vaccine was safe and immunogenic, and a dose-response effect was demonstrated.

Adhesins, Bacterial↗
PubMed1998

Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group.

Argentine hemorrhagic fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious.

Adolescent↗
PubMed1998

Cultural feasibility studies in preparation for clinical trials to reduce maternal-infant HIV transmission in Haiti.

A cultural feasibility study is defined as one that investigates scientific as well as ethical, behavioral, and social issues in the design of clinical trials. The value of such a broadly defined assessment is illustrated through the presentation of two case studies conducted to prepare for clinical trials to reduce maternal-infant HIV transmission on Cité Soleil, Haiti. The first study addressed issues surrounding a trial of breast-feeding and exclusive bottle-feeding among HIV seropositive mothers. The second study focused on the implementation of a double-blind trial of HIV immune globulin and standard immune globulin to be administered to infants of seropositive mothers shortly after birth. Both cases used focus group interviews with mothers and in-depth interviews with key informants to investigate AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community reactions and repercussions to the trial. Findings point to the difficulties posed by attempts to conduct trial involving complex research designs in socially disadvantaged populations. Recommendations highlight the need to consider the community-wide impact of a trial, and the need to undertake extensive educational preparation of participants to ensure informed consent and adherence to protocols.

Bottle Feeding↗