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Biomedical subjects

E D Shapiro

Publications and source records attributed to E D Shapiro.

At least 55 records · Page 3Linked to original sources

Occult pneumococcal bacteremia: what happens to the child who appears well at reevaluation?

There is little information on the outcome of occult pneumococcal bacteremia in children who appear well at the time of first reevaluation. To determine the outcome of such children we reviewed the medical records of 364 children with blood cultures positive for Streptococcus pneumoniae managed at 2 hospitals in New Haven from 1973 to 1987. One hundred eighty of the 364 children were initially managed as outpatients; 111 of the 180 (62%) were afebrile and appeared well at the first reevaluation. Twenty-two of these 111 children (20%) were hospitalized and treated with intravenously administered antimicrobials at the first reevaluation visit; 2 of these 22 were still bacteremic, although no focal infection was found. Seventy-eight children (70%) were sent home after the first reevaluation visit with orally administered antimicrobials; 1 of these 78 children was still bacteremic and another subsequently was found to have meningitis that had been present at the first visit (culture of the cerebrospinal fluid obtained at the first visit subsequently grew S. pneumoniae). Eleven children (10%) were sent home from the reevaluation visit without antimicrobial treatment and none had persistent or recurrent pneumococcal infection. We conclude that the child who is afebrile and appears well at reevaluation for a blood culture positive for S. pneumoniae is unlikely to develop serious sequelae. Outpatient management with careful follow-up is essential for such children.

Bacteremia↗

Quantitative leukoviremia and immune complex-dissociated antigenemia as predictors of infection status in children born to mothers infected with human immunodeficiency virus type 1.

Four methods of culturing human immunodeficiency virus type 1 (HIV-1) from peripheral blood mononuclear cells and two serum antigen tests were assessed as predictors of infection status in children born to HIV-1-infected mothers. Of 36 infants whose cocultures were quantitative, all 15 who were deemed to be infected with HIV-1 (nine with symptoms, six without symptoms) by clinical criteria or persistence of Western blot reactive antibody had positive culture results, and all 21 uninfected seroreverters had negative culture results (sensitivity = 100%; specificity = 100%). Quantitative coculture was more sensitive than a technique in which cells were counted and stimulated with phytohemagglutin but not cocultivated with cells from seronegative donors, and more sensitive than two other qualitative techniques evaluated in samples from 80 children, in which cells were not enumerated before culture. The level of leukoviremia in children with symptoms did not differ appreciably from the level of leukoviremia in symptom-free infected children. Among those with positive results on quantitative coculture, only 40% also had free HIV-1 antigen in serum, whereas 86% had antigen in immune complexes. Among the methods evaluated, quantitative HIV-1 coculture was the best indicator of infection status in children.

AIDS Serodiagnosis↗

Early Lyme disease: a flu-like illness without erythema migrans.

The existence of a form of early Lyme disease characterized by a flu-like illness without erythema migrans is controversial. To confirm the existence and define the clinical characteristics of the flu-like illness without erythema migrans of localized Lyme disease, the authors studied patients from a Lyme disease endemic area of Connecticut who visited their primary care physicians with an undefined flu-like illness. Patients kept a diary of their symptoms. Acute and convalescent sera were obtained. The diagnosis of Lyme disease was based on the appearance of IgM or IgG antibodies to Borrelia burgdorferi as demonstrated by both enzyme-linked immunosorbent assay and immunoblot assay. Twenty-four untreated patients were studied. In five patients acute serologic evidence of Lyme disease developed. The flu-like illness in these five patients was characterized by fever and fatigue and resolved spontaneously in 5 to 21 days. Symptoms recurred in three of these five patients. The existence of a flu-like illness without erythema migrans of early Lyme disease has been clearly established. Prospective, controlled studies are needed to better define its incidence, characteristics, and prognosis so that appropriate diagnostic and therapeutic strategies can be developed.

Acute Disease↗

A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites.

BACKGROUND: Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern United States. Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten. METHODS: To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic. Children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days. Subjects were followed for one year for clinical manifestations of Lyme disease. Serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi. RESULTS: Of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo. Of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with B. burgdorferi. Erythema migrans developed in two subjects, both of whom had received placebo. There were no asymptomatic seroconversions and no late manifestations of Lyme disease. The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (P = 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent). CONCLUSIONS: Even in an area in which Lyme disease is endemic, the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated.

Adult↗

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.

Age Factors↗

Serologic evidence of active Epstein-Barr virus infection in Epstein-Barr virus-associated lymphoproliferative disorders of children with acquired immunodeficiency syndrome.

The DNA and nuclear antigens of Epstein-Barr virus (EBV) have been detected in specimens of tissue of non-Hodgkin lymphoma and lymphocytic interstitial pneumonitis from patients with acquired immunodeficiency syndrome. To determine whether there is serologic evidence of an active EBV infection in these disorders, we conducted a case-control study. The case patients were 10 children with acquired immunodeficiency syndrome and EBV genome-positive pneumonitis or lymphoma. We randomly selected one or, if available, two matched control patients with human immunodeficiency virus infection for each index patient and compared their EBV serologic profiles with those of the index case patient at the time of the biopsy. Ten case patients and 13 matched control patients were enrolled. All 10 case patients (100%) compared with 2 (15%) of 13 matched control patients had serologic evidence of either a primary or a reactivated EBV infection at the time the index patient had a biopsy performed (p less than 0.001). Therefore we found serologic and virologic evidence that EBV is etiologically related to EBV-associated lymphocytic interstitial pneumonitis and non-Hodgkin lymphoma in children with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration.

The term urinary tract infection (UTI) encompasses a broad range of clinical entities that share one characteristic: a positive urine culture. Clinical manifestations and responses to therapy are diverse even when comparable numbers of a particular bacterial species are identified on urine culture. These guidelines include discussion of acute uncomplicated cystitis, acute uncomplicated pyelonephritis, and complicated infections of the urinary tract. It is proposed that the finding of > or = 10(3) cfu/mL of urine defines significant bacteriuria in acute uncomplicated cystitis, > or = 10(4) cfu/mL in acute uncomplicated pyelonephritis and UTI in men, and > or = 10(5) cfu/mL in complicated UTI. The preferred clinical study design is prospective, randomized, and controlled with an active agent. Ideally, treatment with antimicrobial agents should eradicate the infecting organism, bring about the resolution of clinical signs and symptoms, have few adverse effects, and prevent reinfection.

Adult↗

Infections of the urinary tract.

There are many options for the treatment of the child with pyelonephritis. Many children can be successfully treated without hospitalization. Appropriate use of studies to image the urinary tract to detect renal damage and treatable anatomical and functional abnormalities is a key aspect of the management of such patients. With appropriate interventions (such as antimicrobial prophylaxis for vesicoureteral reflux or surgery for obstructive lesions), subsequent renal damage can be averted and the morbidity of recurrent infections often can be eliminated.

Bacterial Infections↗

Efficacy of Haemophilus influenzae type b vaccines in Massachusetts children 18 to 59 months of age.

Since 1987 Haemophilus influenzae b (Hib) conjugate vaccines have been licensed for use in children ages 18 months and older. Before licensure there were no clinical trials of a single dose of any conjugate vaccine in children ages 18 months or older. To fulfill this need we performed an age- and residence-matched case-control study of the efficacy of Hib vaccines. In our study population the protective efficacy (PE) of Hib-diphtheria toxoid conjugate vaccine was 88% (95% confidence interval, 45 to 98%). No vaccine failures were observed with Hib oligosaccharide CRM197 diphtheria protein conjugate vaccine, but usage was not sufficient to establish efficacy: PE = 100% (95% confidence interval, -37 to 100%). The protective efficacy of Hib capsular polysaccharide vaccine was 18% (95% confidence interval -487 to 89%). We conclude that for children ages 18 to 60 months a single dose of the Hib conjugate vaccine, PRP-D, is protective against invasive Hib infections. Consistent with most studies Hib polysaccharide vaccine provided suboptimal protection.

Bacterial Capsules↗

Predictive value of the human immunodeficiency virus 1 antigen test in children born to infected mothers.

Our objective was to examine the utility of the human immunodeficiency virus (HIV-1) antigen test as an early predictor of HIV-1 infection among children born to infected mothers and to collect information about its performance as a diagnostic test. The Abbott HIVAG-1 Enzyme Immunoassay was used to analyze serial serum samples from patients enrolled in a longitudinal cohort study of children born to mothers infected with HIV-1. There were 85 subjects who were followed from birth whose HIV-1 infection status could be definitely determined as of March, 1990. Of these 22 (26%) were infected with HIV-1 and 63 (74%) were uninfected. Overall the sensitivity of the test was 77% (95% confidence interval (CI), 55 to 92%) and the specificity was 97% (95% CI, 89 to 99%). The positive predictive value of a single positive test was 89% (95% CI, 67 to 99%) and of two or more positive tests was 100% (95% CI, 50 to 100%). The sensitivity of the test varied greatly with age. For 36 children from whom sera were collected during the first month of life the specificity of the antigen test was 100% but the sensitivity was only 20%. Overall in the first 6 months of life the sensitivity was less than 50%. The Abbott HIV-1 antigen test is useful as an early predictor of HIV-1 infection in children whose mothers are infected.

Child, Preschool↗

Outcome of children with occult bacteremia caused by Haemophilus influenzae type b.

For better definition of the clinical course and outcome of children with occult bacteremia caused by Haemophilus influenzae type b (Hib), we reviewed the medical records of children who were initially managed as outpatients and subsequently found to be bacteremic. At Yale-New Haven Hospital (1971 to 1987) and the Children's Hospital of Philadelphia (1982 to 1987), 69 previously healthy children were identified with occult Hib bacteremia. Their median age was 14 months (range, 4 to 89 months). Thirty-six (52%) of the 69 were either febrile and/or had a focus of serious infection at follow-up (meningitis (17), pneumonia (5), epiglottitis (3), cellulitis (5), and septic arthritis (3)). Although the remaining 33 children (48%) were afebrile and appeared well on reevaluation, 3 of these 33 were still bacteremic and another 5 subsequently developed focal Hib infections. These 8 children were significantly younger (median age, 8.5 months) than the 25 children who remained well (median age, 16 months; P = 0.03). Of the 28 children who had initially been treated with antimicrobials to which their organism was known to be susceptible, 12 (43%) were improved at reevaluation and remained well; 7 (23%) of the 31 patients who had not received such antimicrobials improved and remained well (P = 0.17). Children initially managed as outpatients and later found to have had Hib bacteremia are at risk of subsequently developing a serious focal infection.

Ambulatory Care↗

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 vaccine's 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 subject's history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject's 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.

Adolescent↗

Group day care and the risk of serious infectious illnesses.

Group day care attendance has been associated with an increased risk of infectious illnesses. With the exception of illnesses caused by Haemophilus influenzae type b (H. influenzae) and Neisseria Meningitidis (N. meningitidis), most studies have examined relatively mild illnesses. A matched case-control study was conducted to study the association between group day care attendance and serious infectious illnesses (requiring hospitalization). Cases were children aged 3 months to 59 months hospitalized for an infectious illness at Yale-New Haven Hospital from June 1984 through November 1986. Each case was matched to a control by date of birth and regular pediatrician, and their parents were interviewed. Data from 193 matched pairs were analyzed using conditional logistic regression. The matched odds ratio (OR) for the association between group day care attendance and serious infectious illness was 1.39 (95% confidence interval (CI) 0.87-2.20). For pairs in which the case had an H. influenzae infection (n = 46), the odds ratio was 8.00 (95% CI 1.00-63.85), and for N. meningitidis (n = 9) the odds ratio was 2.00 (95% CI 0.39-10.27). In the remaining 138 pairs, the odds ratio was 1.27 (95% CI 0.76-2.12). In infants less than 12 months of age (n = 64) the odds ratio for group day care and illnesses (excluding H. influenzae and N. meningitidis) was 1.66 (95% CI 0.73-3.80) and it was 1.06 (95% CI 0.55-2.05) for older children (n = 74). The data suggested an association between day care attendance and invasive bacterial infections other than H. influenza and N. meningitidis, OR = 2.00 (95% CI 0.81-4.94) but not for local bacterial infections, OR = 1.00 (95% CI 0.25-4.00) or infections of presumed viral etiology, OR = 1.00 (95% CI 0.49-2.05). Important predictors of serious infections (excluding H. influenzae and N. meningitidis) were passive smoking (OR = 3.96, 95% CI 2.16-7.24) and sharing a bedroom (OR = 2.31, 95% CI 1.23-4.33). These findings do not suggest that group day care attendance poses a large risk of serious infections (other than H. influenzae or N. meningitidis) to young children; however, at least one preventable factor, passive smoking, may.

Child↗