Paul L. McCarthy

Clinical, virologic, and serologic evidence of Epstein-Barr virus infection in association with childhood pneumonia

To explore the association of Epstein-Barr virus infection with childhood pneumonia we studied two patients whose mononucleosis-like illnesses were accompanied by pneumonia; both had virologic and serologic evidence of current or recent EBV infection. We then analyzed the sera of 71 children (age range, 14 months to 9 years) with pulmonary infiltrates for the presence of four classes of antibody to EBV. Antibody responses consistent with current or recent EB virus infection were found in 15. Two children had IgM antibodies to the EBV viral antigen at titers ≥1:160, indicating current infection, and all 15 patients had antibody to components of the early antigen complex, suggesting recent infection. A fourfold rise or drop in one or more EBV-specific antibody classes was noted in eight patients within 30 days following onset of clinical illness. Few patients had clinical features suggesting infectious mononucleosis. Eight of the 15 with serologic evidence of current or recent EBV infection also had clinical or serologic evidence of infection with another pathogen-bacterial, viral, or mycoplasmal. Thus, in childhood pneumonia, EBV may be a primary, co-primary, or secondary pathogen; it may be reactivated in the course of infection with another agent, or possibly, by suppressing immune function, it may precipitate infection with some other organism.

The Reliability and Validity of the Pediatric Appropriateness Evaluation Protocol

Researchers at Yale-New Haven Hospital (New Haven, Connecticut) tested the reliability and validity of the Pediatric Appropriateness Evaluation Protocol (PAEP) through a comparison of inter-rater agreement between experienced pediatricians and less experienced clinicians. The PAEP is a diagnosis-independent instrument with 26 criteria in three categories used to assess appropriate hospital use in pediatrics. Pediatrician raters, using clinical judgment alone, and clinicians (fellows in pediatrics and nurse practitioners), using both clinical judgment and the PAEP, reviewed a sample of 47 days and judged which inpatient days were medically appropriate. A day was judged appropriate if any of the 26 criteria were fulfilled for that day and inappropriate if none of the criteria was fulfilled. The PAEP was found to be a reliable and valid instrument with a 93% sensitivity and a 78% specificity for detecting medically inappropriate days.

Kawasaki Disease Associated With Reactive Hemophagocytic Lymphohistiocytosis

We report a case of Kawasaki disease with significant coronary artery aneurysms subsequently associated with reactive hemophagocytic lymphohistiocytosis in a young child with low T-cell perforin expression and NK-cell dysfunction. The patient was treated with a selective T-cell costimulation modulator in an effort to regulate T-cells. This case is unique for several reasons: (1) the severe degree of coronary artery aneurysms; (2) low T-cell perforin and NK-cell values; and (3) treatment with a selective T-cell costimulation modulator, none of which has been described in prior cases.

Evaluation of Arthritis and Arthralgia in the Pediatric Patient

The records of 250 consecutive children presenting to a university pediatric service with joint complaints of unknown cause were reviewed to determine the frequency of diagnoses and the utility of laboratory data and physical examination findings. Eighteen per cent of children had orthopedic disorders (Group I), 17.6 per cent had autoimmune disorders (Group II), 19.6 per cent had joint complaints related to a bacterial infection (Group III), and 44 per cent had miscellaneous problems (Group IV). Autoimmune or infectious dis orders were eight times as likely if temperature was ≥38 C. and/or erythrocyte sedimentation rate was ≥30 mm/h was present than if absent (65% vs. 8% re spectively) ; the sensitivity of fever and/or elevated erythrocyte sedimentation rate was 93 per cent for Group II and III patients. The presence of rash was predictive of an autoimmune disorder in 67 per cent of the instances; a positive joint examination was seen disproportionately in Group I patients. A negative joint examination all but ruled out an infectious etiology. Other test results, such as diagnostic radiograms, WBC ≥ 15,000 per cu mm; or a positive ANA or rheumatoid factor were predictive but not sensitive indicators of selected groups. If the etiology of a childs joint complaints is unknown, the likelihood of an orthopedic, autoimmune or infectious disorder may be suggested by reviewing temperature and ESR data and skin and joint findings.

Predicting Fever Response of Children with Pneumonia Treated with Antibiotics

In order to study predictors of fever response in children with radiologic pulmonary infiltrates treated with antibiotics, 156 children with pneumonia were evaluated with slide test C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), blood cultures, acute and con valescent viral and mycoplasma titers, and then followed clinically. Both CRP (+) at a serum dilution of 1:50 and WBC ≥ 15,000 were better predictors of rapid resolution of fever while the patient was receiving antibiotics than were ESR ≥ 30 or temperature ≥ 40 C. WBC ≥ 15,000 was nearly as specific but more sensitive than CRP (+) 1:50 for resolution of fever in either 8, 12 or 24 hours. Positive blood or lung bacterial cultures, but not four-fold or greater viral or mycoplasma titer increases, were also associated with rapid resolution of fever. WBC ≥ 15,000 is useful in predicting rapid fever response in children with pneumonia treated with antibiotics.

Fever without apparent source on clinical examination.

PURPOSE This review discusses recent literature that has focused on the epidemiology, clinical and laboratory evaluation and treatment of episodes of acute illnesses associated with fever and also of prolonged episodes of fever in children. RECENT FINDINGS Articles addressed the epidemiology of invasive pneumococcal disease in children in other countries that have not yet initiated vaccination with the conjugated pneumococcal vaccine. From the United States there was a report of the decreased occurrence of invasive pneumococcal disease in patients being provided primary care who had been vaccinated with conjugated pneumococcal vaccine. Another report outlined the experience at childrens hospitals with invasive pneumococcal disease in the years pre- and post-introduction of pneumococcal vaccine. One of the studies found that there was a slight increase in pneumococcal disease caused by non-vaccine serotypes. Another group of articles focused on serious bacterial infections in infants with fever who are positive for respiratory syncytial virus (RSV). All studies found a significant occurrence of urinary tract infections in these patients. One report found that bacteremia may occur in such patients if less than 28 days of age. Finally articles from Turkey, Thailand, and Italy give excellent discussions about the range of diagnoses and key clinical findings that may be seen in children with prolonged fever. SUMMARY In the review period, there was a particular emphasis on invasive disease caused by S. pneumoniae and the impact of vaccination with conjugated pneumococcal vaccine, on the occurrence of serious bacterial infection in febrile infants with RSV infections, and on the broad spectrum of diagnoses in children with prolonged fever in varying geographic locales.

Fever without apparent source on clinical examination, lower respiratory infections in children, and enterovirus infections.

This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. Klig reviews recent literature about lower respiratory tract infection in children. Finally, Kennedy and Kahn discuss recent developments in infectious diseases pertinent to office practice.

Peripheral white blood cell counts and bacterial meningitis: implications regarding diagnostic efficacy in febrile children.

In order to investigate the clinical value of peripheral white blood cell variables for the diagnosis of bacterial meningitis among young, febrile children, we compared total peripheral white counts, total segmented neutrophil counts, total band counts, and the ratio of immature-to-total neutrophils (I:T ratio) among 46 children with bacterial meningitis, 130 children with aseptic meningitis, and 56 febrile children with culture confirmed extrameningeal bacterial infection. Children with bacterial meningitis were comparable to those with aseptic meningitis with respect to median total white blood cell counts and median total segmented neutrophil counts but had a significantly higher median total band count (1760/μI VS 378/μl p=0.0001) and a significantly higher median I:T ratio (0.40 vs 0.09, P<0.001). In contrast, children with bacterial meningitis were comparable to those with an extrameningeal bacterial infection with respect to median total band count but had a significantly lower median total peripheral white count (10,650/μl VS 15,300/μl p=0.0013), a lower median total segmented neutrophil count (4511/μI VS 6796/μI p=0.023), and a significantly higher median I:T ratio (0.40 vs 0.15, p<0.001). Children with meningitis who were bacteremic at presentation had a significantly lower total white cell count (p=0.001) and significantly higher I:T ratio (p=0.005) when compared with children who had an extrameningeal infection and concurrent bacteremia at presentation. As a diagnostic marker, an I:T ratio>0.12 was found to be more strongly associated with (odds ratio: 5.6; 95% confidence interval: 2.6, 11.9), and more sensitive for, bacterial meningitis (82%) than were a total peripheral white cell count>15,000/μl (OR: 0.8; 95% CI: 0.3,1,6; sensitivity: 22%) or a total band count>1500/μI (OR: 4 3; 95% CI: 2.2, 8.5; sensitivity: 59%). Multiple logistic regression analysis indicated that the I:T ratio was a significant independent predictor of bacterial meningitis after controlling for meningeal signs and physician impression of illness severity at presentation. We conclude that the I:T ratio is a valuable clinical adjunct for the identification of febrile children with underlying bacterial meningitis.

Fever without apparent source on clinical examination, infectious diseases, and lower respiratory infections in children.

This section focuses on issues in infectious diseases that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children, and the evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews recent literature about lower respiratory tract infection in children. Jeffrey Kahn and Eugene Shapiro discuss recent developments in pediatric infectious diseases concerning neonatal herpes infections, poliovirus immunization schedule, and group B streptococcus screening and treatment.

A Computer Program for Calculating Subject-by-Subject Kappa or Weighted Kappa Coefficients

This computer program calculates individual subject kappa or weighted kappa coefficients for each of the following three types of categorical data: (a) nominal (dichotomous/polychotomous), (b) ordinal (dichotomous /continuous), and (c) mixed scales of measurement (containing both nominal and ordinal features). Additional output includes criteria for determining levels of both statistical and clinical significance as well as specific tests of examiner bias.