Eugene D. Shapiro

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America

Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.

The Protective Efficacy of Polyvalent Pneumococcal Polysaccharide Vaccine

BACKGROUND Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccines protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine. METHODS From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subjects history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subjects vaccination history. RESULTS Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine (P less than 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P less than 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P less than 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15). CONCLUSIONS Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely.

The effectiveness of the varicella vaccine in clinical practice.

BACKGROUND A live attenuated varicella vaccine was approved for use in the United States in March 1995 and is recommended for all susceptible persons 12 months of age or older. METHODS To assess the effectiveness of the varicella vaccine, we conducted a case-control study with two controls per child with chickenpox, matched according to both age and pediatric practice. Children with potential cases of chickenpox were identified by active surveillance of pediatric practices in the New Haven, Connecticut, area. Research assistants visited the children on day 3, 4, or 5 of the illness, assessed the severity of the illness, and collected samples from lesions to test for varicella-zoster virus by polymerase chain reaction (PCR). RESULTS From March 1997 through November 2000, data collection was completed for 330 potential cases, of which 243 (74 percent) were in children who had positive PCR tests for varicella-zoster virus. Of the 56 vaccinated children with chickenpox, 86 percent had mild disease, whereas only 48 percent of the 187 unvaccinated children with chickenpox had mild disease (P<0.001). Among the 202 children with PCR-confirmed varicella-zoster virus and their 389 matched controls, 23 percent of the children with chickenpox and 61 percent of the matched controls had received the vaccine (vaccine effectiveness, 85 percent; 95 percent confidence interval, 78 to 90 percent; P<0.001). Against moderately severe and severe disease the vaccine was 97 percent effective (95 percent confidence interval, 93 to 99 percent). The effectiveness of the vaccine was virtually unchanged (87 percent) after adjustment for potential confounders by means of conditional logistic regression. CONCLUSIONS Varicella vaccine is highly effective as used in clinical practice.

Human Bocavirus Infection in Young Children in the United States: Molecular Epidemiological Profile and Clinical Characteristics of a Newly Emerging Respiratory Virus

Abstract BackgroundHuman bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as “children”) for HBoV MethodsChildren for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004 ResultsTwenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in ⩾50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period ConclusionsHBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children

Qualitative Analysis of Mothers' Decision-Making About Vaccines for Infants: The Importance of Trust

BACKGROUND. The high visibility of controversies regarding vaccination makes it increasingly important to understand how parents decide whether to vaccinate their infants. OBJECTIVE. The purpose of this research was to investigate decision-making about vaccinations for infants. DESIGN. We conducted qualitative, open-ended interviews. PARTICIPANTS. Subjects included mothers 1 to 3 days postpartum and again at 3 to 6 months. RESULTS. We addressed 3 topics: attitudes to vaccination, knowledge about vaccination, and decision-making. Mothers who intended to have their infants vaccinated (“vaccinators,” n = 25) either agreed with or did not question vaccination or they accepted vaccination but had significant concerns. Mothers who did not intend to vaccinate (“nonvaccinators,” n = 8) either completely rejected vaccination or they purposely delayed vaccinating/chose only some vaccines. Knowledge about which vaccines are recommended for children was poor among both vaccinators and nonvaccinators. The theme of trust in the medical profession was the central concept that underpinned all of the themes about decision-making. Promoters of vaccination included trusting the pediatrician, feeling satisfied by the pediatrician’s discussion about vaccines, not wanting to diverge from the cultural norm, and wanting to adhere to the social contact. Inhibitors included feeling alienated by or unable to trust the pediatrician, having a trusting relationship with an influential homeopath/naturopath or other person who did not believe in vaccinating, worry about permanent side effects, beliefs that vaccine-preventable diseases are not serious, and feeling that since other children are vaccinated their child is not at risk. CONCLUSION. Trust or lack of trust and a relationship with a pediatrician or another influential person were pivotal for decision-making of new mothers about vaccinating their children. Attempts to work with mothers who are concerned about vaccinating their infants should focus not only on providing facts about vaccines but also on developing trusting and positive relationships.

A Controlled Evaluation of the Protective Efficacy of Pneumococcal Vaccine for Patients at High Risk of Serious Pneumococcal Infections

The protective efficacy of pneumococcal vaccine against systemic pneumococcal infections in adults with the current indications for the vaccine was evaluated in a case-control study. Six (7%) of the 90 cases and 16 (18%) of the matched controls had received pneumococcal vaccine for an odds ratio of 0.33 (p less than 0.05). The vaccines protective efficacy was 67%, which remained virtually unchanged after adjusting for potential confounding variables. The vaccines efficacy was 77% for patients at moderately increased risk of pneumococcal infections, but 0% for patients who were severely immunocompromised. The vaccines protective efficacy was 70% (p less than 0.05) for all patients 55 years or older after controlling for indications for the vaccine in addition to age. Pneumococcal vaccine confers substantial protection against systemic pneumococcal infections on the elderly and patients with illnesses associated with a moderately increased risk of pneumococcal infections.

Lyme Disease in Children in Southeastern Connecticut

BACKGROUND Although the incidence of Lyme disease is highest in children, there are few prospective data on the clinical manifestations and outcomes in children. METHODS We conducted a prospective, longitudinal, community-based cohort study of children with newly diagnosed Lyme disease in an area of Connecticut in which the disease is highly endemic. We obtained clinical and demographic information and performed serial antibody tests and follow-up evaluations. RESULTS Over a period of 20 months, 201 consecutive patients were enrolled; their median age was 7 years (range, 1 to 21). The initial clinical manifestations of Lyme disease were a single erythema migrans lesion in 66 percent, multiple erythema migrans lesions in 23 percent, arthritis in 6 percent, facial-nerve palsy in 3 percent, aseptic meningitis in 2 percent, and carditis in 0.5 percent. At presentation, 37 percent of the patients with a single erythema migrans lesion and 89 percent of those with multiple erythema migrans lesions had antibodies against Borrelia burgdorferi. All but 3 of the 201 patients were treated for two to four weeks with conventional antimicrobial therapy, which was administered orally in 96 percent. All had prompt clinical responses. After four weeks, 94 percent were completely asymptomatic (including the two patients whose parents had refused to allow antimicrobial treatment). At follow-up a mean of 25.4 months later, none of the patients had evidence of either chronic or recurrent Lyme disease. Six patients subsequently had a new episode of erythema migrans. CONCLUSIONS About 90 percent of children with Lyme disease present with erythema migrans, which is an early stage of the disease. The prognosis is excellent for those with early Lyme disease who are treated promptly with conventional courses of antimicrobial agents.

Influenza Vaccine Given to Pregnant Women Reduces Hospitalization Due to Influenza in Their Infants

BACKGROUND Infants aged <12 months are at high risk of hospitalization for influenza. Influenza vaccine is recommended for pregnant women and for most children; however, no vaccine is approved for infants aged <6 months. Effective approaches are needed to protect this vulnerable population. Vaccination of women during pregnancy may protect the infant through transfer of antibodies from the mother. Few studies have examined the effectiveness of this strategy, and those studies produced mixed results. METHODS In a matched case-control study, case patients were infants aged <12 months admitted to a large urban hospital in the northeastern United States because of laboratory-confirmed influenza from 2000 to 2009. For each case, we enrolled 1 or 2 control subjects who were infants who tested negative for influenza and matched cases by date of birth and date of hospitalization (within 4 weeks). Vaccine effectiveness was calculated on the basis of matched odds ratios and was adjusted for confounding. RESULTS The mothers of 2 (2.2%) of 91 case subjects and 31 (19.9%) of 156 control subjects aged <6 months, and 1 (4.6%) of 22 case subjects and 2 (5.6%) of 36 control subjects aged ≥6 months, had received influenza vaccine during pregnancy. The effectiveness of influenza vaccine given to mothers during pregnancy in preventing hospitalization among their infants, adjusted for potential confounders, was 91.5% (95% confidence interval [CI], 61.7%-98.1%; P = .001) for infants aged <6 months. The unadjusted effectiveness was 90.7% (95% CI, 59.9%-97.8%; P = .001). CONCLUSIONS Influenza vaccine given to pregnant women is 91.5% effective in preventing hospitalization of their infants for influenza in the first 6 months of life.

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology

Objective: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post–Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed? Methods: The authors analyzed published studies (1983–2003) using a structured review process to classify the evidence related to the questions posed. Results: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis. Conclusions: There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (≥8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post–Lyme syndrome (Level A).

A prospective study of recurrent febrile seizures

BACKGROUND Febrile seizures occur in about 2 to 4 percent of all children, approximately one third of whom will have recurrent febrile seizures. Little is known about predictors of recurrence. METHODS In this prospective study, we identified 347 children (1 month to 10 years of age) who presented with a first febrile seizure at one of four pediatric emergency departments. Information about these children was collected from medical records and interviews with the parents, and the children were followed for a median of 20 months to ascertain whether febrile seizures recurred. RESULTS Recurrent febrile seizures occurred in 94 of the 347 children (27 percent) with a cumulative risk of 25 percent at one year and 30 percent at two years. The duration of fever before the initial seizure was associated with the risk of recurrence at one year: for fever lasting less than 1 hour, the risk of recurrence was 44 percent; for fever lasting 1 to 24 hours, 23 percent; and for fever lasting more than 24 hours, 13 percent (P less than 0.001). With each degree of increase in temperature (in degrees Fahrenheit), from 101 degrees F (38.3 degrees C) to greater than or equal to 105 degrees F (40.6 degrees C), the risk of recurrence at one year declined, from 35 percent to 30, 26, 20, and 13 percent (P for trend = 0.024). An age of less than 18 months and a family history of febrile seizures were also associated with an increased risk of recurrence. A family history of epilepsy, complex febrile seizures, and neurodevelopmental abnormalities did not increase the risk of recurrent febrile seizures. CONCLUSIONS A shorter duration of fever before the initial febrile seizure and a lower temperature are associated with an increased risk of recurrence in children who have febrile seizures.