Chrysanthi Skevaki

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.

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.

Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells.

BackgroundHuman rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro.MethodsMonolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry.ResultsRV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation.ConclusionRV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

Tuberculosis in Neonates and Infants

Tuberculosis is one of the leading infectious causes of death and as such represents a major global health problem. Infants may develop congenital tuberculosis from an infectious mother or, most commonly, they may acquire postnatal disease by contact with an infectious adult source. Important epidemiologic, pathogenetic, and clinical data regarding the management of infantile disease are reviewed.Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smears and cultures, examination of the cerebrospinal fluid, and polymerase chain reaction, as well as the more recent interferon-γ assay.Pregnant women with a positive Mantoux skin test but normal chest x-ray should either start chemoprophylaxis during gestation or after delivery depending on the likelihood of being recently infected, their risk of progression to disease, as well as their clinical evidence of disease. Pregnant women with a positive Mantoux skin test and chest x-ray or symptoms indicative of active disease should be treated with non-teratogenic agents during gestation; all household contacts should also be screened. When tuberculosis is suspected around delivery, the mother should be assessed by chest x-ray and sputum smear; separation of mother and offspring is indicated only if the mother is non-adherent to medical treatment, needs to be hospitalized, or when drug-resistant tuberculosis is involved.According to the American Academy of Pediatrics, treatment of latent infection is highly effective with isoniazid administration for 9 months. This regimen may be extended to 12 months for immunocompromised patients. When drug resistance is suspected, combination therapies, which usually consist of isoniazid with rifampin (rifampicin), are administered until the results of susceptibility tests become available. Organisms resistant to isoniazid only may be treated with rifampin alone for a total of 6–9 months.All infants with tuberculosis disease should be started on four agents (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) until drug susceptibility is assessed. For susceptible intrathoracic tuberculosis, isoniazid, rifampin, and pyrazinamide are administered for a total of 2 months, at which point pyrazinamide is withdrawn and the other two agents are continued for another 4–10 months depending on the severity of the disease. The same regimen may be applied in extrapulmonary tuberculosis with the exception of skeletal, miliary, and CNS disease, which require daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin for 1–2 months, followed by isoniazid and rifampin daily or twice weekly for another 10 months. When drug-resistant tuberculosis is suspected, a regimen of isoniazid, rifampin, and pyrazinamide plus either streptomycin or ethambutol should be initially prescribed, until the results of susceptibility tests become available. HIV-seropositive infants with pulmonary tuberculosis should receive isoniazid, rifampin, pyrazinamide, and ethambutol or an aminoglycoside for 2 months, followed by isoniazid and rifampin for a total of at least 12 months.Apart from conventional antimycobacterial agents, novel therapeutic modalities, which stimulate the host immune system such as interleukin-2 (IL-2), IL-12, interferon-γ, and tumor necrosis factor antagonists have been tested with promising results.

Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release.

Background Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved.

The significance of ureaplasma urealyticum as a pathogenic agent in the paediatric population

Purpose of review Ureaplasma urealyticum is a frequent commensal in the lower genital tract of sexually active women. It may be transmitted perinatally from the colonized mother to her offspring, often resulting in prematurity and neonatal disease. The microorganism also sustains a causative role for infectious diseases in older children. Recent findings U. urealyticum infection can be diagnosed by culture, polymerase chain reaction, and the detection of specific antibodies. Neonatal infection has been implicated in various pathological conditions including pneumonia, chronic lung disease, central nervous system disorders, sepsis, osteomyelitis and even death. Older children may present with wheezing, pneumonitis, pertussis-like syndrome and different forms of arthritis. Large well-designed trials have demonstrated that the regular administration of antibiotics to vaginally colonized women are not beneficial in terms of preventing preterm labour. Macrolide-containing antibiotic regimens are, however, recommended for preterm premature rupture of the membranes. Erythromycin treatment of ureaplasma respiratory colonized premature infants shows no reduction in the incidence of chronic lung disease. Treatment of central nervous system infections, sepsis and arthritides includes tetracyclines, fluoroquinolones and anti-inflammatory agents, respectively. Summary This review covers recent evidence concerning the role of U. urealyticum as a pathogen during childhood. It also includes an evaluation of contemporary diagnostic techniques and optimal therapeutic approaches.

Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features

BackgroundHuman rhinoviruses, major precipitants of asthma exacerbations, induce lower airway inflammation and mediate angiogenesis. The purpose of this study was to assess the possibility that rhinoviruses may also contribute to the fibrotic component of airway remodeling.MethodsLevels of basic fibroblast growth factor (bFGF) mRNA and protein were measured following rhinovirus infection of bronchial epithelial cells. The profibrotic effect of epithelial products was assessed by DNA synthesis and matrix metalloproteinase activity assays. Moreover, epithelial cells were exposed to supernatants from cultured peripheral blood mononuclear cells, obtained from healthy donors or atopic asthmatic subjects and subsequently infected by rhinovirus and bFGF release was estimated. bFGF was also measured in respiratory secretions from atopic asthmatic patients before and during rhinovirus-induced asthma exacerbations.ResultsRhinovirus epithelial infection stimulated mRNA expression and release of bFGF, the latter being positively correlated with cell death under conditions promoting rhinovirus-induced cytotoxicity. Supernatants from infected cultures induced lung fibroblast proliferation, which was inhibited by anti-bFGF antibody, and demonstrated increased matrix metalloproteinase activity. Rhinovirus-mediated bFGF release was significantly higher in an in vitro simulation of atopic asthmatic environment and, importantly, during rhinovirus-associated asthma exacerbations.ConclusionsRhinovirus infection induces bFGF release by airway epithelium, and stimulates stroma cell proliferation contributing to airway remodeling in asthma. Repeated rhinovirus infections may promote asthma persistence, particularly in the context of atopy; prevention of such infections may influence the natural history of asthma.

Human Milk and Allergic Diseases: An Unsolved Puzzle.

There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development.