Reported changes in sexual behaviour and human papillomavirus knowledge in Peruvian female sex workers following participation in a human papillomavirus vaccine trial.

Limited data exist on the effect of clinical trial participation on sexual behavioural change. Two hundred female sex workers working in Lima, Peru received human papillomavirus (HPV) vaccine in either the standard (0, 2, 6 months) or modified (0, 3, 6 months) schedule. Participants received comprehensive screening and treatment for sexually transmitted infections (STIs), counselling on safe sex practices, education about HPV and the HPV vaccine, contraceptives (oral and condoms) and family planning at each visit. We assessed vaccine completion rates, change in sexual practices, and changes in HPV knowledge before and after participation in the vaccine trial. There were high rates of vaccine completion, 91% overall. The estimated number of reported new and total clients over a 30-day period decreased significantly (P < 0.001). Knowledge about HPV and HPV-related disease increased among all participants. In addition, all participants listed at least one preventive strategy during the month 7 follow-up survey.

Human papillomavirus prevalence, cervical abnormalities and risk factors among female sex workers in Lima, Peru.

Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infection. Questionnaires were administered to 200 FSWs aged 18-26 years in Lima, Peru, to gather risk behaviours, and cervical swab samples were collected for Pap smears and HPV DNA testing as part of a longitudinal study. Participants reported a median of 120 clients in the past month, and 99.2% reported using condoms with clients. The prevalence of any HPV in cervical samples was 66.8%; 34 (17.1%) participants had prevalent HPV 16 or 18, and 92 (46.2%) had one or more oncogenic types. Fifteen women had abnormal Pap smears, 13 of which were HPV DNA positive. Fewer years since first sex was associated with oncogenic HPV prevalence in a model adjusted for previous sexually transmitted infection (STI) status and condom use with partners (prevalence ratio = 0.77, 95% confidence interval [CI] = 0.60-0.97). Our data confirm the high rates of HPV transmission among FSWs in Peru, highlighting the need for early and effective strategies to prevent cervical cancer.

Underimmunization at discharge from the neonatal intensive care unit.

OBJECTIVE: The objectives of this study are to determine immunization rates at discharge from the neonatal intensive care unit (NICU) among infants 2 months of age and above and to evaluate risk factors for underimmunization. STUDY DESIGN: A retrospective cohort study was performed for infants in six NICUs in the Northern California Kaiser Permanente Medical Care Program. Immunization status at discharge was determined for all infants discharged on or after age 60 days. Logistic regression was used to identify risk factors for underimmunization at the time of discharge. RESULT: Of 668 infants discharged on or after age 60 days from the NICU, 51% were up-to-date for routine immunizations. Twenty-seven percent of infants had received no vaccines. Factors associated with higher immunization rates at discharge include history of mechanical ventilation, congenital heart disease and a diagnosis of apnea or bronchopulmonary dysplasia during the NICU stay, whereas surgery was associated with lower immunization rates. CONCLUSION: A significant proportion of infants discharged on or after 2 months of age in the NICU in this health system was unimmunized or underimmunized at discharge. Further efforts should be made to improve immunization rates prior to discharge.

Effect of food coupon incentives on timely completion of DTP immunization series in children from a low-income area in Karachi, Pakistan: a longitudinal intervention study.

This study introduced food/medicine vouchers as an incentive to mothers of infants visiting Expanded Program on Immunization (EPI) centers in a low socio-economic area. The timely completion of diphtheria, tetanus and pertussis vaccines combined (DTP) series immunization rates between intervention and control cohorts were compared. The DTP up-to-date immunization coverage at 18 weeks of age increased two-fold (RR 2.20, 95% CI: 1.95-2.48, p<0.001) in the incentive cohort compared to the no-incentive cohort. While increasing immunization coverage is a complex structural and behavioral process, food/medicine coupon may improve routine immunization coverage in developing countries.

Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.

OBJECTIVE: Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. STUDY DESIGN: We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. RESULT: A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, P<0.05). The incidence rate of sepsis evaluations was 40% lower after immunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (P<0.05). CONCLUSION: Despite an increase in fever and cardiorespiratory events after immunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.

Measles case fatality ratio in India a review of community based studies.

CONTEXT: Measles remains a major cause of child mortality in India. Measles case fatality ratios (CFRs) vary substantially between countries and even within the same community over time. We present a review of Indian community-based measles CFR studies conducted from 1975 to 2008. EVIDENCE ACQUISITION: PubMed, Cochrane Libraries, and all WHO databases were searched using a combination of terms. All community-based studies were abstracted into a database. RESULTS: We identified 25 studies with data on 27 communities. The median CFR was 1.63 per 100 cases (Q1= 0.00 and Q3= 5.06). Studies conducted after 1994 had significantly lower CFRs (P=0.031). Studies in rural settings had significantly higher CFRs compared to urban studies (P=0.015). No differences were found by study design or outbreak/endemic setting. CONCLUSIONS: This review suggests measles CFR may be declining in India. We hypothesize that increased measles vaccination coverage is the main factor contributing to the decline. Widespread vaccination increases both the average age of infection and the proportion of total measles cases previously vaccinated. Vitamin A treatment/supplementation is also likely to have contributed. In order to further reduce measles burden in India, vaccination and vitamin A treatment/supplementation coverage should be increased and a two dose vaccine strategy should be implemented in all areas.

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.

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.

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.

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.

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.

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.

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