A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Chickenpox attributable to a vaccine virus contracted from a vaccinee with zoster.

Five months after 2 siblings were immunized with varicella vaccine, 1 developed zoster. Two weeks later the second sibling got a mild case of chicken pox. Virus isolated from the latter was found to be vaccine type. Thus, the vaccine strain was transmitted from the vaccinee with zoster to his sibling. Vaccinees who later develop zoster must be considered contagious. varicella-zoster, zoster, vaccine, transmission, rash, PstI.

The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point.

In this study, we searched for evidence for reactivation of three latent herpesviruses, Epstein-Barr virus (EBV), herpes simplex virus type-1 (HSV-1), and human herpesvirus 6 (HHV-6), in West Point cadets experiencing two different stressors. Blood samples were obtained from cadets before and after a 6-week training period known as "Cadet Basic Training" (CBT), at a baseline prior to final examinations, and then once again during the week of final examinations. Antibody titers to latent HSV-1, EBV, and HHV-6 were determined as a measure of the steady-state expression of latent virus. EBV virus capsid antigen (VCA) IgG antibody titers were unchanged in blood samples obtained prior to and immediately after CBT. However, EBV antibody titers were significantly higher in the blood sample obtained during examination week than in the baseline period before examination; they were also higher than antibody titers before/after CBT. None of the serum samples were positive for EBV VCA IgM antibodies, indicating that the changes in antibody titers to EBV were not associated with recent EBV infections in the class. No significant changes in antibody titers to HSV-1 or HSV-6 were found over the identical time periods, including examination week. Academic stress but not CBT modulated the steady-state expression of latent EBV, resulting in the reactivation of latent virus. The same stressors, however, did not affect the steady-state expression of latent HSV-1 or HSV-6, at least as measured by changes in antibody titers. The data provide additional evidence of the impact of different psychological stressors on the steady-state expression of latent herpesviruses.

Viral gene expression in rat trigeminal ganglia following neonatal infection with varicella-zoster virus.

Newborn rats were injected intraperitoneally with uninfected human cells or cell infected with 56,000 pfu of varicella-zoster virus (VZV). Five to 6 weeks later, trigeminal ganglia were harvested and tested for VZV DNA and RNA by PCR. VZV gene 21 and 40 DNA were detected in most infected animals. Gene 21 RNA also was detected in ganglia from most infected animals, but not gene 40 RNA, paralleling previous observations in latently infected human ganglia. The neonatal rat may represent a useful new model for the study of VZV latency.

Varicella serological status of healthcare workers as a guide to whom to test or immunize.

Only 1.6% of 1,331 hospital workers were seronegative for varicella-zoster virus (VZV), including 8.7% of those with a negative history and 0.5% of those with a positive history. Seronegativity was inversely related to age but unrelated to job category, exposure at work to VZV, country of origin, race, or gender.

Recent advances in varicella-zoster virus infection.

Varicella-zoster virus has developed a complex strategy that allows it to remain latent in the body and avoid destruction by the immune system. Although varicella and zoster have been recognized since antiquity, several new clinical syndromes--including chronic chickenpox with persistent verrucous lesions and disseminated varicella without skin lesions--have been noted in patients with AIDS. Acyclovir has been the mainstay for treating severe varicella-zoster virus infections; however, newer antiviral agents, including valacyclovir and famciclovir, have expanded therapeutic options for treating adults with herpes zoster. The recently licensed live attenuated vaccine for varicella-zoster virus is effective in preventing chickenpox, and the vaccine's ability to stimulate immunity in seropositive adults suggests a promising strategy with which to modify the course of herpes zoster.

Lack of evidence of transmission of HIV-1 to family contacts of HIV-1 infected children.

Although a number of studies have documented that casual household contact does not result in the transmission of HIV, isolated cases of person-to-person transmission have been reported. We report a study of household transmission in which the families were unaware the children were infected with HIV and thus took no precautions to prevent transmission. Twenty-two family members of nine transfusion-associated HIV-infected children were studied for transmission of HIV in households. There was a total of 174 person-year of household exposure; 76 of these exposure years were before the diagnosis of HIV infection in the index child. All family members tested negative for HIV by ELISA. Sharing household facilities, and interactions with the infected child including kissing, bathing, sleeping with, and helping to bathe, dress, and eat, did not result in transmission. Interactions that could theoretically result in person-to-person transmission occurred in these households such as caring for nose bleeds, biting, and home health care procedures. The findings of this and other studies support the participation of HIV-infected infants and children in out-of-home care programs. It remains prudent, however, to observe current recommendations for prevention of HIV-1 for all individuals regardless of whether HIV status is known.

Enzyme-linked immunosorbent assay for detection of antibody to human herpesvirus 6.

The results obtained with an enzyme-linked immunosorbent assay (ELISA) for detection of human herpesvirus 6 (HHV-6) immunoglobulin G using a single 1:100 dilution of serum correlated well with those found by an indirect fluorescence microscopic assay (IFA) (r = 0.71). Concordant results were found in all 7 paired serum samples obtained from patients with acute primary infections and in 37 of 41 (90.24%) single serum samples. Fourteen serum samples (25%) which yielded nonspecific results by IFA were evaluable by ELISA. In a serologic survey using the ELISA, a disproportionate number of 12-month-old infants had low difference-of-optical-density values, suggesting that maternal antibody might persist beyond a year of age. This finding and the rises in antibody to HHV-6 found in patients with primary cytomegalovirus infections might lead to overestimation of HHV-6 infection rates in young children in seroprevalence studies. Other herpesvirus infections produced lesser effects on anti-HHV-6.

Management of neonates born to mothers with group B streptococcus colonization.

Approximately 20% of pregnant women harbor group B streptococcus (GBS) in the lower genital tract at the time of delivery. Intrapartum chemoprophylaxis of mothers with GBS colonization who have risk factors for neonatal GBS at delivery improves the outcome of the neonates. The recommendations for treating newborn infants of mothers who receive intrapartum chemoprophylaxis for GBS colonization and the recommendations for those who do not remain empiric, because clinical studies to support such recommendations are not available. An algorithm for treatment of neonates born to mothers with GBS colonization that is based on available data and empiric recommendations is presented. These guidelines are intended to guide medical practice and not to replace clinical judgment.

Children hospitalized for varicella: a prevaccine review.

OBJECTIVES: To describe varicella complications in healthy and previously ill children hospitalized for varicella and to explore trends in group A beta-hemolytic streptococcus complications of varicella. METHODS: A retrospective record review of children hospitalized for varicella between January 1, 1990, and March 31, 1994, was conducted in nine large acute care hospitals in Los Angeles County, California. RESULTS: We identified 574 children hospitalized for varicella in study hospitals during the 4.25-year study period (estimated risk of hospitalization, approximately 1 in 550 cases of varicella); 53% of the children were healthy before the onset of varicella and 47% were previously ill with underlying cancers or other chronic illnesses. Children were hospitalized for treatment of complications (n = 427, 74%) or for prophylactic antiviral therapy or observation (n = 147, 26%). Systems involved in complications included skin/soft tissue (45%), neurologic (18%), respiratory (14%), gastrointestinal (10%), and hematologic, renal, or hepatic (8% or less). The mean age of children with skin/soft tissue infections was 2.7 years (range < 1 to 16 years) compared with 4.7 years (< 1 to 18 years) for other complications. Children with skin/soft tissue and neurologic complications were more often previously healthy (p < 0.05), whereas those with respiratory complications were more often previously ill (p < 0.001). Hospitalizations for skin/soft tissue infections increased during the study period. The proportion of complications as a result of group A beta-hemolytic streptococcus infection increased from 4.7% before 1993 to 12.2% for the remainder of the study period (p = 0.02). CONCLUSIONS: Prior health status was predictive of the type of complications experienced by children with varicella requiring hospitalization. Our data suggest a recent increase in skin/soft tissue complications of varicella requiring hospitalization and an increase in the proportion of complications related to group A beta-hemolytic streptococcus. Wide-scale vaccine use should reverse this trend and reduce the overall impact of varicella on both healthy and previously ill children.

Risk factors for invasive group A streptococcal infections in children with varicella: a case-control study.

OBJECTIVE: To identify characteristic clinical manifestations and potential risk factors for invasive group A streptococcal (GAS) disease in children with varicella. DESIGN AND PARTICIPANTS: A case-control study was conducted in Los Angeles and Orange Counties, CA. Cases were children with varicella who developed invasive GAS disease between January 1 and May 3, 1994 (n = 25). Controls were acquaintance, neighborhood or schoolmate children with uncomplicated varicella during the study period (n = 62). Cases were compared with controls with regard to underlying illness, child care practices, parental home health practices, health care-seeking behaviors, sociodemographic characteristics and clinical characteristics. RESULTS: Controlling for age we found that cases were more likely than controls: (1) to be cared for in the home vs. out-of-home child care (odds ratio (OR), 4.4 (95% confidence interval (95% CI), 1.1 to 17)); (2) to report having asthma (OR, 6.2 (95% CI, 1.2 to 41.0)) and to be taking albuterol (OR, 11.6 ((95% CI, 1.0 to 581)); (3) to be secondary varicella cases within a household (OR, 7.3 (95% CI, 2.2 to 25)); (4) to report fever after Day 2 of varicella; and (5) to have contacted their health care provider later than controls (Day 3.8 rather than Day 1.7, P < 0.001). CONCLUSIONS: To our knowledge this is the first case-control study exploring potential risk factors for invasive GAS disease in children with varicella. Both previously healthy children with varicella and those with underlying medical problems, including asthma, may be at increased risk for GAS complications. Interventions should be targeted to parents and health care providers to increase awareness of early signs and symptoms of invasive GAS disease in children with varicella. Additional studies are needed to confirm the associations suggested by this study between GAS complications of varicella and asthma, in-home child care, secondary vs. primary varicella household cases and delayed contact with medical care providers.

Frequent recurrence and persistence of varicella-zoster virus infections in children infected with human immunodeficiency virus type 1.

OBJECTIVE: To examine complications and treatment of varicella-zoster virus (VZV) infections in children infected with human immunodeficiency virus type 1 (HIV-1). METHODS: Cases of VZV infection were identified retrospectively by reports to the department of health services and review of medical charts. The CD4+ cell counts were correlated with severity and frequency of VZV episodes. RESULTS: We identified 117 episodes of VZV infection in 73 HIV-1-infected children between Aug. 21, 1986, and Dec. 1, 1993. The most common complications were recurrence and persistence; 38 children (53%) had 69 recurrent episodes of VZV infection. The majority of children (61%) had zoster during the first recurrent episode, and 32% had a disseminated eruption typical of varicella. There was a strong association between an increasing number of episodes of VZV infection and low CD4+ cell count (p = 0.0008). In a subgroup followed for at least 2 years after their primary varicella episode, 10 of 22 children had a recurrence. Persistence of VZV infection was documented in 10 of 73 children, whereas other complications were rare. Thirty-three children (45%) were hospitalized and received acyclovir intravenously. CONCLUSION: Primary, recurrent, and persistent VZV infections are a frequent cause of morbidity and hospitalization for HIV-1-infected children. Studies of improved preventive and therapeutic agents are urgently needed in this population.

Abnormalities of measles antibody response in human immunodeficiency virus type 1 (HIV-1) infection.

The finding that severe measles occurs in immunized as well as nonimmunized human immunodeficiency virus (HIV)-infected individuals suggests that both immunologic memory and the initial response to measles may be impaired by HIV infection. That the initial response is affected was supported by the finding that post-measles immunization titers of HIV-infected babies were significantly lower (p = 0.01) than those of normal babies. Poor immunologic memory was evidenced in HIV-infected children by lower titers than in normal children (p < 0.001) and by a continuing decline in measles antibody that was not arrested by reimmunization. Impaired memory appeared to be associated with defective avidity maturation. HIV-infected babies and infants or children had a significantly lower avidity index (AI) than age-matched normal children (p < 0.01). HIV-infected adults, who were infected with HIV following infection with measles, did not have AI values significantly different from normal adults (p = 0.18) but had significantly greater values than did HIV-infected babies and children (p < 0.01). Thus, in contrast to infants and children who were infected with HIV before measles immunization, the adult immune response to measles was less affected.

Factors related to immunization status among inner-city Latino and African-American preschoolers.

OBJECTIVE: To identify factors associated with undervaccination at 3 months and 24 months among low-income, inner-city Latino and African-American preschool children. DESIGN: Interviews with a representative sample of inner-city families using a cross-sectional, multi-stage, cluster-sample design combined with a replicated quota sampling approach. SETTING: South Central and East Los Angeles areas in inner-city Los Angeles. POPULATION: Eight hundred seventeen Latino and 387 African-American families with children between 12 and 36 months of age. MAIN OUTCOME VARIABLES: Being fully immunized or up-to-date (UTD) at 3 months (1 diphtheria-tetanus-pertussis vaccine and 1 oral polio vaccine) and 24 months of age (4 diphtheria-tetanus-pertussis vaccines, 3 oral polio vaccines, and 1 measles-mumps-rubella vaccine). METHODS: Logistic regressions of UTD immunization status at 3 and 24 months by population and health care system factors. RESULTS: Seventy percent of Latino children and 53% of African-American children were UTD at 3 months of age. At 24 months of age, 42% of Latino children and 26% of African-American children were UTD on their immunizations. Receipt of the first immunizations by 3 months was associated with smaller family size, and evidence of connection to prenatal care. Latino children were less likely to be UTD at 24 months if they obtained well child care from private providers versus public clinics (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.26, 0.79). There was also a trend for Latino children to be less well immunized if they were in health maintenance organizations versus public clinics (0.31, 0.05 < P < .1). African-American children were more likely to be UTD at 24 months if they were UTD at 3 months (OR = 5.56, 95% CI = 1.43, 21.6), had more health visits (OR = 1.13, 95% CI = 1.01, 1.27), and were less likely to be UTD at 24 months if they were on Medicaid versus private insurance (OR = 0.26, 95% CI = 0.08, 0.90). IMPLICATIONS: Both African-American and Latino children in inner-city Los Angeles have low immunization rates at 3 and 24 months. Prenatal care and family size are strongly associated with being UTD by 3 months; however, family and child characteristics are relatively unimportant predictors of being UTD at 24 months of age. Important risk factors for underimmunization at 2 years of age in the inner-city, low-income communities studied include type of health insurance and source of well child care, with the public sector having higher rates than private doctors' offices or health maintenance organization/managed care plans.

Unrecognized human immunodeficiency virus type 1 infection in a cohort of transfused neonates: a retrospective investigation.

OBJECTIVE: To retrospectively identify unrecognized human immunodeficiency virus type 1 (HIV-1) infection among a cohort of children transfused as neonates before donated blood was routinely screened for HIV-1 antibody. METHODS: Records at a large, private, metropolitan hospital were reviewed to identify children who were transfused as neonates between January 1980 and March 1985 and discharged alive from the hospital. Multiple data sources were used to locate these children. Parents or guardians were contacted, and their children were offered HIV-1 antibody testing and physical examination. RESULTS: Of the 775 children identified as having received transfusions during the project period, 644 (83%) were located, and 443 (69%) were evaluated for HIV-1 infection. Among those evaluated, 33 (7%) had antibody to HIV-1, including 14 whose infections had not been previously diagnosed. At the time of enrollment, 13 children infected with HIV-1 were asymptomatic an average of 63 months after transfusion. CONCLUSION: HIV-1 antibody testing should be considered for all children, regardless of clinical status, who were transfused before routine blood donor screening was implemented in March 1985, particularly in areas with a high incidence of acquired immunodeficiency syndrome during those years.

Measles control in the United States: problems of the past and challenges for the future.

Elimination of indigenous measles from the United States has been a public priority since 1978. To assess the progress made toward this goal, we review the epidemiology of measles from 1963 to the present. From the 1970s through early into the recent measles epidemic, the majority of measles cases were in highly vaccinated, school-age children. This was due primarily to a 1 to 5% primary measles-mumps-rubella vaccine failure rate and nonrandom mixing patterns among school-age populations. To eliminate susceptible individuals in the school-age populations, a second dose of measles vaccine is now recommended between 5 and 6 years or 11 and 12 years by both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics. Later in the epidemic, measles cases surged among unimmunized preschool children, especially among the poor in inner-city areas. Immunization rates have been documented to be low among preschool populations because of missed opportunities to administer vaccines at all health visits and barriers to access to immunizations. To raise immunization rates, the age for the first measles-mumps-rubella immunization was lowered to 12 to 15 months of age, federal immunization funding has increased, and new standards for immunization delivery have been developed and promulgated.

Virologic, immunologic, and clinical evaluation of human immunodeficiency virus antibody status of symptom-free children born to infected mothers.

STUDY OBJECTIVE: To determine the prevalence of infection by the human immunodeficiency virus (HIV) in a population of symptom-free children who were born to HIV-infected mothers and who subsequently underwent seroreversion from an HIV antibody-positive to an HIV antibody-negative status. DESIGN: Cohort. SETTING: Pediatric HIV program in a community setting. PATIENTS: We used HIV DNA polymerase chain reaction (PCR) and coculture to detect the presence or absence of HIV in peripheral blood mononuclear cells of 134 children aged 6 to 53 months. All children had HIV antibody at birth and underwent a subsequent seroreversion to antibody-negative status. RESULTS: In 134 children with HIV antibody-negative status, 219 of 220 culture results and 242 of 247 HIV-1 DNA PCR assay results were negative. Six positive laboratory results were obtained for six different children, each of whom had negative results on multiple assays. For HIV-infected children, 56 of 62 cultures and 99 of 104 PCR evaluations showed positive results. There was no clinical or laboratory evidence of HIV infection in the group with HIV antibody-negative status. CONCLUSION: We were unable to find evidence of latent HIV type 1 infection in this cohort of symptom-free children who underwent seroreversion to HIV antibody-negative status. The loss of maternal HIV antibody in these children indicates the absence of HIV infection. False-positive PCR and culture results occurred sporadically, indicating that repeated analysis of HIV seropositivity in infants and children is necessary.

Pneumonia in the neonatal intensive care unit. Diagnosis by quantitative bacterial tracheal aspirate cultures.

Growth of > or = 10(5) colonies of bacteria per milliliter obtained at bronchoscopy in children and adults correlates with bacterial pneumonia. To determine whether quantitative tracheal aspirate cultures aid in diagnosis of pneumonia in the neonatal intensive care unit setting, tracheal aspirates were obtained from 25 infants who had recently undergone endotracheal intubation; 15 of the infants had suspected pneumonia and 10 control infants had undergone intubation for suspected apnea of prematurity (4 infants) or elective surgery (6 infants). Studies also were performed to detect Mycoplasma, Ureaplasma, viruses, and Pneumocystis. Tracheal aspirates from 2 of 15 infants with suspected pneumonia grew > or = 10(5) bacteria, and 1 was positive for respiratory syncytial virus. These infants were considered to have pneumonia. In 12 infants whose tracheal aspirates grew < 10(5) bacteria, respiratory decompensation later was explained by other causes in 11 infants, and there was one false-negative culture. There were three false-positive tracheal aspirates in the control group. We conclude that tracheal aspirates of infants who have recently had an endotracheal tube placed may be useful for diagnosing pneumonia and for identifying the causative agent.