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.

Oral sex practices, oral human papillomavirus and correlations between oral and cervical human papillomavirus prevalence among female sex workers in Lima, Peru.

Few data exist on oral human papillomavirus (HPV) prevalence in female sex workers (FSWs). Information regarding oral sex practices of 185 Peruvian FSWs, 18-26 years of age, was obtained via survey and compared with HPV testing results of oral rinse samples. Oral HPV prevalence was 14/185 (7.6%); four (28.9%) HPV genotypes were carcinogenic. One hundred and eighty-two participants reported having had oral sex; 95% reported condom use during oral sex with clients and 9.5% with partners. Women who had oral sex more than three times with their partners in the past month were more likely to have oral HPV than women who had oral sex three times or less (P = 0.06). Ten (71.4%) women with oral HPV were HPV-positive at the cervix; conversely 8.3% of women with cervical HPV were HPV-positive in the oral cavity. The prevalence of oral HPV was relatively low, considering the high rates of oral sex practiced by these women.

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.

Infection in a neonate caused by Pichia fabianii: importance of molecular identification.

Pichiafabianii, an uncommon yeast species recovered from clinical specimens, was documented as the cause of an infection in a 5-week-old female twin delivered at 25 and 3/7 weeks. She developed respiratory distress syndrome and necrotizing enterocolitis. At the time of the infection, she was febrile, thrombocytopenic, and still was requiring minimal ventilatory support. Blood cultures drawn on two consecutive days were positive for a germ tube negative yeast. Phenotypic methods including carbohydrate fermentations and assimilations (API 20C AUX) did not identify the yeast. Sequencing of D1/D2 domain of the large subunit rDNA was performed in one laboratory and sequencing a subunit of D2 performed in a second laboratory identified the yeast as P. fabianii. The organism was susceptible in vitro to amphotericin B, fluconazole and 5-fluorocytosinc. The patient responded to amphotericin B and removal of her vascular catheter. This case illustrates that there are an increasing number of fungi that may be pathogenic. Phenotypic tests may fail to identify them, emphasizing the need for commercially available, molecular based assays for identification.

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.

Safety and immunogenicity of a recombinant Borrelia burgdorferi outer surface protein A vaccine against lyme disease in healthy children and adolescents: a randomized controlled trial.

OBJECTIVE: A recombinant lipoprotein outer surface protein A (OspA) Lyme disease (LD) vaccine (LYMErix) has been shown to be safe and effective in preventing LD in adults and in adolescents 15 years of age and older. Children are at risk for developing LD. This clinical study was conducted to address the safety and immunogenicity of LD vaccine in children 4 to 18 years of age. METHODS: A randomized, placebo-controlled clinical trial was conducted at 17 investigational sites in Lyme-endemic areas in the United States. Immunogenicity data from this study also were compared with data obtained from the adult efficacy study. A total of 4090 healthy children and adolescents (age range: 4-18; mean age: 10.4 years) were randomized; 4087 were vaccinated, and a subset of 301 children participated in the immunogenicity analysis. Children were randomized to receive either 30 microgram of LD vaccine (N = 3063) or placebo (N = 1024) on a 0, 1, 12-month schedule. Safety assessments evaluated both solicited (local: redness, swelling, and pain; general: fever, headache, fatigue, arthralgia, and rash) and unsolicited adverse events. Serum specimens were collected at month 0 or month 2, and months 6, 12, and 13. RESULTS: Solicited reactogenicity data revealed a higher incidence of local injection site reactions and general symptoms (fever, headache, fatigue, and arthralgia) in vaccine than placebo recipients. The majority of events were limited in duration (mean: 2-3 days) and were mild to moderate in severity. The total IgG anti-OspA geometric mean titer (GMT) in the pediatric vaccine recipients at month 13 was as good as and statistically higher than the GMT in the adult cohort at month 13 (27 485 enzyme-linked immunosorbent assay units [EL.U]/mL vs 8216 EL.U /mL). All of the pediatric vaccine recipients attained a level of antibody concentration >/=1400 EL.U/mL (proposed seroprotective level) compared with 90% of adults attaining levels >/=1400 EL.U/mL in the efficacy trial. CONCLUSIONS: LD vaccine administered on a 0, 1, 12-month schedule generally is well tolerated and immunogenic in children 4 to 18 years of age. The safety profile consists of mild to moderate local injection site reactions and flu-like symptoms of limited duration and did not worsen with subsequent injections. IgG GMT at month 13 was threefold higher than the month 13 GMT obtained in the adult efficacy study. This higher immune response in children should provide protection against LD.

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.

Foundations for effective strategies to control sexually transmitted infections: voices from rural Kenya.

Achieving maximal benefit from clinic-based, sexually transmitted infection (STI) control strategies requires that persons seek treatment at public clinics. Community-based, ethnographic research methods were used to examine patterns of health-seeking behavior for sexually transmitted infections in western Kenya. Illness narratives of sexually transmitted infections provided the basis for an analysis of sequential steps in health-seeking behavior, namely recognition, classification, overcoming stigma, identification of treatment options and selection of a course of therapy. A variety of terms were used to identify STI, including multiple terms referring to "women's disease". The stigma associated with STI, reflected in the terminology, was based on a set of beliefs on the causes, contagiousness and sequelae of STI, and resulted in delays in seeking treatment. Five commonly used treatment options were identified, with multiple sources of care often used concurrently. The desire for privacy, cost and belief in the efficacy of traditional medicines strongly influenced health-seeking behaviour. A belief that sexually transmitted infections must be transmitted in order to achieve cure was professed by several respondents and promoted by a traditional healer. Implications for STI control strategies are derived, including the development of educational messages and the design of clinics.

PIP: Data on health-seeking behavior were collected in Vihiga and Homa Bay Districts of western Kenya, as part of formative research for a sexually transmitted disease (STD) control and HIV/AIDS home care project with the main goal of securing information to guide project design and implementation. Community-based, ethnographic research methods were used from January 1995 to June 1996, including key informant interviews, focus group discussions, and in-depth interviews. Illness narratives of STDs provided the basis for an analysis of sequential steps in health-seeking behavior, namely recognizing, classifying, overcoming stigma, identifying treatment options, and selecting a course of therapy. A range of terms were used to identify STDs, including multiple terms referring to "women's disease." Stigma associated with STDs was based upon a set of beliefs of the causes, contagiousness, and sequelae of STDs, and resulted in treatment seeking delays. 5 commonly used treatment options were identified, with multiple sources of care often used concurrently. The desire for privacy, cost, and belief in the efficacy of traditional medicines strongly influenced health-seeking behavior. The belief that STDs must be transmitted in order to achieve cure was held by several respondents and promoted by a traditional healer. Implications for STD control strategies are considered, including the development of educational messages and clinic design.

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.