Piero Valentini

Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-α production in vitro and in vivo

Human newborns are susceptible to microbial infection related to incompletely defined aspects of the neonatal immune system. To characterize neonatal innate immunity, we studied production of two early response cytokines in response to Toll-like receptor (TLR)-activating microbial stimuli in vitro: the pro-inflammatory cytokine tumor necrosis factor (TNF)-α and IL-6, a multifunctional cytokine with antiinflammatory and Th2-polarizing properties. Neonatal cord blood responses to multiple TLR agonists, including poly dI:dC (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), and CpG DNA (TLR9), are characterized by a higher IL-6/TNF-α ratio than in adult peripheral blood. Robust LPS-induced IL-6 production is due to both neonatal cellular (monocyte-) and humoral (serum-) factors. Remarkably, serum collected from newborns during the first week of life demonstrates higher IL-6/TNF-α ratios than does cord blood, associated with elevations of the IL-6-inducible acute phase reactants CRP and LPS-binding protein in the first days of life. A high ratio of stimulus-induced IL-6/TNF-α production is likely to profoundly modulate both innate and adaptive immune responses in the human newborn.

An uncommon presentation for a severe invasive infection due to methicillin-resistant Staphylococcus aureus clone USA300 in Italy: a case report

BackgroundMethicillin resistant Staphylococcus aureus (MRSA) has been considered for many years a typical nosocomial pathogen. Recently MRSA has emerged as a frequent cause of infections in the community. More commonly, community-acquired (CA)-MRSA is a cause of infections of the skin and soft-tissues, but life-threatening infections such as necrotizing pneumonia and sepsis can occasionally occur.Case presentationThis report describes an uncommon presentation of invasive CA-MRSA infection in an adolescent without known risk factors. The presentation was typical for bacterial meningitis, but the clinical findings also revealed necrotizing pneumonia. Following the development of deep venous thrombosis, the presence of an inherited trombophilic defect (factor V Leiden) was detected. The patient was successfully treated with an antibiotic combination including linezolid and with anticoagulant therapy. CA-MRSA was isolated from both cerebrospinal fluid and blood. The isolates were resistant to oxacillin and other beta-lactam antibiotics and susceptible to the other antibiotics tested including erythromycin. Molecular typing revealed that the strains contained the Panton-Valentine leukocidin genes and type IV SCCmec, and were ST8, spa type t008, and agr type 1. This genetic background is identical to that of the USA300 clone.ConclusionThis report highlights that meningitis can be a new serious presentation of CA-MRSA infection. CA-MRSA strains with the genetic background of the USA300 clone are circulating in Italy and are able to cause severe infections.

Acute Necrotizing Encephalopathy during Novel Influenza A (H1N1) Virus Infection

A novel swine‐origin influenza A (H1N1) virus was recently identified in Mexico. Some cases of infection with neurological complications have been reported to date. We report a case of acute necrotizing encephalopathy associated with the novel H1N1 virus in a 2‐year‐old European girl who suddenly developed fever, seizures, and altered mental status. Brain and spinal cord magnetic resonance imaging showed bilateral symmetrical lesions of the insulae, thalami, geniculate bodies, and pons tegmentum suggestive of an acute necrotizing encephalopathy. An involvement of meninges and spinal cord was observed configuring an acute necrotizing meningoencephalomyelitis. ANN NEUROL 2010;68:111–114

Successful treatment with oral valganciclovir in immunocompetent infant with gastrointestinal manifestations of cytomegalovirus infection

A 3-month-old male infant was admitted to hospital with anemia. Follow-up controls revealed the presence of specific cytomegalovirus (CMV) antibodies. Virus was isolated from urine, blood, and saliva. At 7 months of age, he presented with melena. Polymerase chain reaction (PCR) of biopsy samples from the duodenum was positive for CMV. Anemia resolved after starting antiviral therapy with oral valganciclovir.

A 20-Year Retrospective Study of Pediatric Tuberculosis in Two Tertiary Hospitals in Rome

Background: Tuberculosis (TB) is among the top 10 causes of child death worldwide. Nevertheless, childhood disease has been neglected by tuberculosis control programs. Methods: This was a retrospective study of patients < 16 years of age diagnosed with active TB in 2 tertiary hospitals in Rome (Italy), between 1990 and 2009. Results: Two hundred fourteen cases of active tuberculosis were identified (132 definite, 82 probable). Pulmonary involvement was the most common form (75.5%), followed by lymphadenopathy (15.4%) and central nervous system TB (11%). Fever (51.86%) and cough (40%) were the most common presenting symptoms. A total of 23.4% of children were asymptomatic on admission. Sensitivities of the tuberculin skin test and the quantiferon test were 93.4% and 97%, respectively. Both tests performed in 52 children agreed in 49 cases (94%). Sensitivities for culture, Ziehl–Neelsen staining and polymerase chain reaction were 58%, 25% and 66.3%, respectively. The adult source case was identified in 28% of cases. History of contact with a patient with active TB was associated with pulmonary TB (P = 0.0014), whereas negative history of contact was associated with lymph node (P = 0.0064) and central nervous system TB (P = 0.05). Conclusions: Our study emphasizes the difficulty in managing children with suspected TB, because the absence of constitutional symptoms cannot exclude TB, and bacteriologic confirmation is the exception. Immunologic diagnosis can be a valuable tool to identify TB-infected children because the quantiferon test showed high sensitivity in all age groups. This is of primary importance because early identification of children with latent tuberculous infection and appropriate chemoprophylaxis represent, to date, the most important tool to reduce the burden of TB.

Maternal and neonatal characteristics of an immigrant population in an Italian hospital

Objective. The objective of this study was to evaluate clinical and epidemiological characteristics of the maternal and neonatal immigrant population and to compare it with the Italian population in the Agostino Gemelli Hospital (Rome). Methods. This study was a prospective population-based study. We compared 595 newborns from immigrant mothers with 2413 newborns from Italian mothers. Neonatal characteristics included in this study were sex, gestational age, birth weight, Apgar score, transfer to pathology units, minor pathologies, and type of breastfeeding at discharge. Maternal characteristics included nationality, age, parity, type of delivery, twin birth, and pathology during the pregnancy. Results. Immigrant newborns comprised 20% of the total births included in the study. No statistically significant differences were found between immigrant and Italian newborns in gestational age, birth weight, or Apgar score. Immigrant newborns were transferred to the Paediatric Infectious Disease Unit more frequently than Italian newborns, had a significantly higher incidence of hyperbilirubinemia and a higher rate of exclusive and prevalent breastfeeding at discharge. Immigrant mothers came predominantly from Eastern Europe, were younger and had caesarean sections less frequently than Italian mothers. Conclusion. No significant differences in biological and clinical characteristics or in medical practice were found between groups, except for a higher frequency of neonatal hyperbilirubinemia and an inclination among immigrant mothers toward breastfeeding.

Role of spiramycin/cotrimoxazole association in the mother-to-child transmission of toxoplasmosis infection in pregnancy.

The purpose of this report is to evaluate the efficacy and safety of spiramycin/cotrimoxazole in the mother-to-child transmission of Toxoplasma gondii infection. We retrospectively analysed 76 infants born to mothers with toxoplasmosis during pregnancy and estimated the risk of mother-to-child transmission considering the gestational age at the time of infection. Seventy-six mothers were given spiramycin, cotrimoxazole and folinic acid; only two babies (2.6%) were infected by Toxoplasma and none of them showed signs or symptoms of congenital infection or interference of sulphamid on tetrahydrofolate reductase (THFR) either at birth or during follow-up. Treatment did not need to be stopped in any mother because of adverse drug effects. Our results seem to encourage the use of spiramycin/cotrimoxazole in women with toxoplasmosis during pregnancy.

Incomplete Kawasaki syndrome followed by systemic onset-juvenile idiopathic arthritis mimicking Kawasaki syndrome.

A 3-month-old child was first treated for incomplete Kawasaki syndrome with three cycles of intravenous immunoglobulins and aspirin, then with methylprednisolone which led to fever remission. The same child was re-hospitalized after a 10-month-period of well-being for the suspicion of a new episode of Kawasaki syndrome, which appeared to be immunoglobulin-resistant: extensive testing failed to provide an alternative diagnosis of any infectious or infiltrative disease. Diagnosis of systemic onset-juvenile idiopathic arthritis was postulated upon the long persistence of fever and inflammatory signs, which subsided only after starting corticosteroid treatment.

Accuracy of QuantiFERON-TB Gold Test for Tuberculosis Diagnosis in Children

Objectives To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in children with suspected active or latent TB infection (LTBI). Methods A retrospective study was conducted on 621 children (0–14 years old) evaluated for TB infection or disease. Following clinical assessment, children were tested with the QFT-IT assay. Results Among the 140 active TB suspects, we identified 19 cases of active disease. The overall sensitivity for active TB was 87.5%, ranging from 62.5% in children 25–36 months old to 100% in children older than 49 months. The overall specificity for active TB was 93.6%. Among the 481 children tested for LTBI screening, 38 scored positive and all but 2 had at least one risk factor for TB infection. Among the 26 children with indeterminate results, bacterial, viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB related extra-pulmonary infections in 12 (46.1%). Conclusions Our results indicate that the childrens response to QFT-IT associates to active TB and risk factors for LTBI. Moreover, we show that mitogen response is also found in children of 1 year of age, providing support for QFT-IT use also in young children.

Involvement of type I immune responses in swine-origin H1N1 influenza virus infection

Swine-origin H1N1 influenza virus (S-OIV) appeared in 2009 with a higher incidence rate among children. Although fever was the most common symptom, some complicated cases occurred. We evaluated the percentages of effector T cells, B cells, and regulatory T cells in peripheral blood from 5 children infected by S-OIV (1 with acute necrotizing encephalitis, 2 with pneumonia, and 2 without complications), 5 children with seasonal influenza, and 5 healthy children. We found higher percentages of T-bet(+) CD4(+)CD8(+) T cells, monocytes, and B cells, granzyme B(+) and perforin(+) CD4(+), and CD8(+) T cells in affected children with both seasonal and H1N1 influenza than in controls, whereas both groups demonstrated similar percentages of CD4(+)CD25(+)Foxp3(+) regulatory T cells. In infected children with complications we observed high percentages of perforin(+) and interferon-γ(+) CD4(+) and CD8(+) T cells associated with low percentages of T regulatory cells. Our data suggest a dysregulation of antipathogen type I immune responses in complicated S-OIV infections.