Dimitris A. Kafetzis

Etiology of community-acquired pneumonia in hospitalized school-age children: Evidence for high prevalence of viral infections

Abstract Background. Community-acquired pneumonia (CAP) in young children is most commonly associated with viral infections; however, the role of viruses in CAP of school-age children is still inconclusive. Methods. Seventy-five school-age children hospitalized with CAP were prospectively evaluated for the presence of viral and bacterial pathogens. Nasopharyngeal washes were examined by polymerase chain reaction for viruses and atypical bacteria. Antibody assays to detect bacterial pathogens in acute-phase and convalescent-phase serum samples were also performed. Results. A viral infection was identified in 65% of cases. Rhinovirus RNA was detected in 45% of patients; infection with another virus occurred in 31%. The most common bacterial pathogen was Mycoplasma pneumoniae, which was diagnosed in 35% of cases. Chlamydia pneumoniae DNA was not detected in any patient; results of serological tests were positive in only 2 patients (3%). Mixed infections were documented in 35% of patients, and the majority were a viral-bacterial combination. Conclusions. The high prevalence of viral and mixed viral-bacterial infections supports the notion that the presence of a virus, acting either as a direct or an indirect pathogen, may be the rule rather than the exception in the development of CAP in school-age children requiring hospitalization.

Preterm birth due to maternal infection: causative pathogens and modes of prevention

Preterm birth represents a major problem for modern obstetrics due to its increasing frequency and the accompanying socioeconomic impact. Although several maternal characteristics related to preterm birth have been identified, the etiology in most cases remains inadequately understood. Various microorganisms have been linked to the pathogenesis of preterm birth. Microbes may reach the amniotic cavity and fetus by ascending from the vagina and cervix, by hematogenous distribution through the placenta, by migration from the abdominal cavity through the fallopian tubes, or through invasive medical procedures. Organisms commonly cultured from the amniotic cavity following preterm delivery include Ureaplasma urealyticum, Mycoplasma hominis, Bacteroides spp., Gardnerella vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and group B hemolytic streptococci. Several trials have examined the effect of antibiotic administration to patients with preterm labor and intact membranes, preterm premature rupture of the membranes, genital mycoplasmal infection, asymptomatic bacteriuria, and bacterial vaginosis. The results of such studies, which were variable and often conflicting, are discussed here.

Maternal Genital Colonization with Ureaplasma urealyticum Promotes Preterm Delivery: Association of the Respiratory Colonization of Premature Infants with Chronic Lung Disease and Increased Mortality

BACKGROUND Infection of the chorioamnion with Ureaplasma urealyticum has been associated with low birth weight. Respiratory tract colonization in preterm infants has been associated with the development of chronic lung disease (CLD). The purpose of the present study was to determine the frequency of colonization of the mothers vagina and the preterm infants respiratory tract and to associate U. urealyticum with premature birth and with development of CLD in the newborn. METHODS The present prospective study involved 126 mothers with preterm delivery and 125 mothers with full-term delivery, as well as their offspring. Vaginal secretion specimens were obtained from each mother before delivery. Rhinopharyngeal secretion or tracheal lavage specimens were collected after the birth of each premature and full-term infant and then periodically during hospitalization. RESULTS Vaginal Ureaplasma colonization occurred among 36.5% of mothers with preterm delivery and among 38% of mothers with full-term delivery. The rate of vertical transmission was 33% and 17% for mothers with preterm delivery and mothers with full-term delivery, respectively. The transmission rate for infants, according to birth weight, was as follows: 60%, for infants with a birth weight of <1000 g; 50%, for infants with a birth weight of 1000-1500 g; and 15.3%, for infants with a birth weight of > or =1500 g (P=.001). The median gestational age of preterm infants born to colonized mothers was 28.5 weeks, and that of preterm infants born to noncolonized mothers was 32 weeks (P<.0001). The median birth weight of colonized preterm infants was 1135 g, and that of noncolonized infants was 1670 g (P<.0001). Twenty-four percent of preterm infants and 10% of full-term infants were colonized with U. urealyticum. Of colonized preterm infants, 27% developed CLD, compared with 9% of noncolonized infants (P=.03). Mortality was significantly higher among colonized preterm infants (P=.003). CONCLUSIONS The rate of vertical transmission is highest among preterm infants with a birth weight of <1500 g. Vaginal colonization with Ureaplasma organisms is associated with premature delivery. Colonization of the respiratory tract of infants is associated with the development of CLD and with increased mortality.

Kawasaki disease: an overview.

Purpose of review Kawasaki disease is an acute, self-limited vasculitis of childhood. The increasing frequency of the disease as well as the deficiency of specific diagnostic means renders its diagnosis and treatment an area of intense investigation. The purpose of this review is to summarize all the known features of Kawasaki disease and also give an insight to the latest findings. Recent findings Kawasaki disease is one of the leading causes of acquired heart disease in children while its cause remains essentially unknown. Viruses, bacterial conventional as well as superantigens, and genetic polymorphisms have been implicated in the etiology of the disease. Markers of inflammation, such as CCL2 and CCXCL10, contribute to the pathology and the diagnosis of Kawasaki disease. Intravenous administration of immunoglobulin remains the mainstay of therapy for Kawasaki disease. Nevertheless, forms of the disease refractory to intravenous administration of immunoglobulin therapy may respond to aspirin, corticosteroids, cyclophosphamide, and/or plasmapheresis. Summary The present review covers evidence regarding the history of Kawasaki disease, the epidemiology, etiology, pathology, genetic influences, and long-term sequela. It also includes an evaluation of contemporary diagnostic techniques and optimal therapeutic approaches with an emphasis on recent publications.

The impact of the heptavalent pneumococcal conjugate vaccine on the epidemiology of acute otitis media complicated by otorrhea.

Background: The heptavalent pneumococcal conjugate vaccine (PCV7) has a considerable effect on the epidemiology of pneumococcal disease. The aim of this observational hospital-based study was to examine the effect of the PCV7 (introduced in our settings in 2004) on the epidemiology of spontaneously draining acute otitis media. Methods: Results of all middle ear fluid cultures (n = 3446) obtained from children with acute otitis media complicated with otorrhea before the introduction of immunization (between 2000 and 2003) were compared with those (n = 2134) obtained during a similar post-PCV7 period (between 2005 and 2008). Results of cultures obtained between 2006 and 2008 were examined prospectively, whereas those obtained in previous years were retrospectively reviewed. Results: Following PCV7 immunization, the rates of otorrhea visits per 10,000 emergency department visits decreased by 38% from 133 to 83 (95% confidence interval of the difference, 42–53; P < 0.001), mainly as a result of the decrease in the incidence of pneumococcal disease (48% decrease—25 vs. 13 per 10,000 emergency department visits; P < 0.001). Otorrhea due to Haemophilus influenzae decreased by 20% (20–16 per 10,000 visits; P < 0.001). Serotype 19A accounted for 1 of 47 (2%) pneumococcal strains in 2006, for 5 of 34 (15%) in 2007, and for 13 of 53 (25%) in 2008 (P for trend: 0.001). In the postvaccine years, penicillin-resistant pneumococcal strains (minimum inhibitory concentration ≥2 &mgr;g/mL) increased from 4% to 13% (P < 0.001). However, the proportion of pneumococci resistant to macrolides decreased (44% vs. 35%; P = 0.01). Conclusions: After the introduction of immunization, otorrhea incidents decreased considerably, mainly because of the decrease in pneumococcal disease. H. influenzae is now the predominant organism. Serotype 19A has increased significantly and is the most common nonvaccine pneumococcal serotype. Penicillin resistance has increased in recent years.

Visceral Leishmaniasis during Childhood in Southern Greece

Records were reviewed of 82 immunocompetent children (median age, 2. 5 years) from southern Greece who were diagnosed with visceral leishmaniasis from 1986 through 1998. Forty-nine (58%) patients originated from the city of Athens; of them, 46 (94%) lived by hills bordering the city. The median interval from the onset of symptoms to admission was 10 days. Fever and splenomegaly were observed in >95% of the patients. Thrombocytopenia was the most frequent hematological finding (80%). All patients were treated with meglumine antimonate; 20 (24%) of them were partially treated on an outpatient basis. Rapid clinical response was noted in all patients but one. Five patients relapsed; 3 responded to reintroduction of meglumine antimonate, 1 responded to liposomal amphotericin B, and 1 underwent splenic artery ligation. We conclude that pentavalent antimonials remain the first choice of treatment for visceral leishmaniasis in immunocompetent children in areas where resistance has not become a problem. It is possible to treat affected patients with outpatient administration of these agents, making them feasible options for therapy.

Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus

Background Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro‐inflammatory and remodelling‐associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus‐induced inflammation and remodelling are less known.

IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion

Background and aims:  Epidemiological evidence examining the role of atopy and/or allergy in the pathogenesis of otitis media with effusion (OME) is inconclusive. The aim of this study was to assess any increased risk for OME attributable to allergy‐related factors, in a well‐characterized population using a case‐control design and multivariate analysis.

PASSAGE OF CEPHALOSPORINS AND AMOXICILLIN INTO THE BREAST MILK

ABSTRACT. Kafetzis, D. A., Siafas C. A., Georgakopoulos P. A., and Papadatos C. J. (Second Department of Pediatrics University of Athens, and Third Department of Obstetrics and Gynecology, Maternity Hospital “Marika Iliadi”, Athens, Greece). Passage of cephalosporins and amoxicillin into the breast milk. Acta Paediatr Scand, 70:285, 1981.–The concentrations of five cephalosporins and amoxicillin in breast milk were studied in 42 voluntarily participating lactating mothers using standard assay methods. Each mother received one single dose of 1 g of either an orally or intravenously administered antibiotic. Amoxicillin, cephalexin, and cefadroxil were given orally, and peak milk concentrations averaged 0.81±0.33 µg/ml at 5 hours, 0.50±0.23 ug/ml at 4 hours, and 1.64±0.73 µg/ml at 6 hours, respectively. Cephalothin, cephapirin and cefotaxime were given as an i.v. bolus injection, and peak milk concentrations at 2 hours averaged 0.47±0.14 ug/ml, 0.43±0.16 µg/ml and 0.32±0.09 ug/ml, respectively. The high concentrations of cefadroxil can be explained by its low rate of elimination and higher fat solubility. Milk/serum ratios for all antibiotics were increasing as serum concentrations were diminishing, especially with cephalothin and cephapirin whose serum concentrations are rapidly declining. The significance of bactericidal concentrations in breast milk remains to be evaluated.

Viral infections in children undergoing hematopoietic stem cell transplant

Background. Although viral infection is a major clinical problem for hematopoietic stem cell transplant recipients, there are few large series reporting on these infections in the pediatric population. We performed a retrospective analysis of the impact of viral infections in this patient population in our center, managed by a uniform antiviral prophylaxis protocol. Methods. We reviewed the medical records of consecutive children and adolescents who received hematopoietic stem cell transplantation at the Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center in Houston, TX, from July, 1992 to August, 1996. Results. During the study period there were 70 episodes of viral infections in 96 transplants. The viruses most commonly encountered were cytomegalovirus (24), varicella‐zoster (21) and herpes simplex (10). Fifty of these episodes resulted in clinically apparent diseases, affecting 39 patients. The Kaplan‐Meier estimated probability for the development of viral diseases was 62%. Ten percent of these patients died as a direct result of the infectious process, all within 4 months of transplant. Significant factors for development of viral disease were the development of acute graft‐vs.‐host disease and the duration of preengraftment neutropenia. Conclusions. Viruses are common pathogens after hematopoietic stem cell transplantation in the pediatric population. Despite routine antiviral prophylaxis the morbidity and mortality of viral infections remain high. Enhancement of immune recovery after hematopoietic stem cell transplantation together with the development of new classes of antiviral agents may impact the incidence and prognosis of viral infections in this setting.