Congenital cytomegalovirus infection: current strategies and future perspectives.

INTRODUCTION: Cytomegalovirus is the most common cause of congenital infections in humans and it produces considerable morbidity in newborns. AIMS: The present study reviews current concepts on epidemiology, clinical manifestations, diagnosis, treatment, future strategies and prognosis of children with congenital cytomegalovirus infection. RESULTS: Congenital cytomegalovirus infection can be symptomatic or not at birth, but about 10-20% of them all will exhibit neurological damage when followed up. Sensorineural hearing loss is the most frequent long-term consequence and is not manifest invariably at birth or in the neonatal period but in many cases becomes clinically apparent in later childhood. There are growing evidences that newborns with symptomatic congenital cytomegalovirus infection would benefit from treatment with either ganciclovir or valganciclovir, the most widely studied drugs in this setting. It is not yet clear if children with asymptomatic or pauci-symptomatic infection at birth would benefit from treatment. DISCUSSION: Studies evaluating treatment and long-term follow-up of infants with both symptomatic and asymptomatic infection are necessary, in order to definitely evaluate the short and long-term effectiveness and safety of both ganciclovir and valganciclovir and to identify risk factors associated to the development of long-term sequelae. In this way it will be possible to select those children that might benefit for treatment.

Pediatric hepatitis C infection: to treat or not to treat...what's the best for the child?

OBJECTIVES: Pediatric hepatitis C mainly occurs through mother to child transmission, to date. Children usually present a mild disease, but they are not spared from its long-term complications. Thus this infection cannot be underestimated in children and intervention is necessary. Current treatment is based on the administration of pegylated-interferon associated with ribavirin, but few studies evaluated the efficacy and safety of this therapeutic protocol. Moreover, there is still no clarity on who, when and how to treat pediatric patients. This article, based on the information in literature, provides an overview of the main aspects of the disease, with particular attention to treatment. METHODOLOGY AND RESULTS: We describe the different treatment options available. About the association peginterferon plus ribavirin, we analyze thirteen non-randomized studies and one trial, found in recent literature. These studies are not directly compared because of differences in age, type of infection (vertical or not), viral genotypes and duration of treatment, between groups enrolled. The overall sustained viral response rate ranges from 28.6% to 81.8%. The rate of treatment success is higher in children infected with genotypes 2 and 3 than with other genotypes. The therapy does not induce severe adverse effects and children present better tolerance to antiviral than adults. CONCLUSIONS: The pharmacological efficacy of peginterferon and ribavirin seems to be proven by data collected in studies cited, but there are different opinions about who, when and how to treat children infected. Thus, further research is needed to define the best management of vertical acquired hepatitis C.

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.

Acute cholestasis: atypical onset of Kawasaki disease.

Atypical onset of Kawasaki disease (KD) is a frequent problem leading to diagnostic mistake. Acute cholestasis and liver involvement occur occasionally as minor manifestation of KD. We report the case of a 6-year-old boy presenting fever, jaundice, abdominal pain, and ascites who subsequently developed typical KD clinical pattern just at the same time of echocardiographic coronary arteries anomalies. Abdominal radiological evaluation was normal and seroimmunologic markers resulted negative. Shortly after intravenous immunoglobulin and acetylsalicylic acid administration the clinical features disappeared. KD should be considered in differential diagnosis in children with cholestasis, abdominal pain and fever of unknown etiology.

Decreased chemiluminescence in leukocyte adhesion deficiency presenting with recurrent sepsis, amoebiasis and Candida albicans urinary tract infection.

Leukocyte adhesion deficiency (LAD) is a rare disorder of cellular immunity, generally due to various mutations producing reduced or altered expression of membrane integrins. The authors report a case of LAD due to integrins expression imbalance. LAD was suspected after recurrent sepsis, fungal infection and amoebiasis with persistent leukocytosis. Neutrophils were studied with chemiluminescence showing decreased functional activity: up to now, this seems the first chemiluminescence study of neutrophil function and the first report of amoebiasis at the onset in LAD.

Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome.

Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare disorder of unknown aetiology with neonatal onset, characterized by severe arthropathy, persistent skin rash and central nervous system disease. Joint involvement may vary from minimal swelling to destructive arthritis, with inability to stand or walk. The most striking findings of CINCA syndrome are cartilage anomalies with epiphyseal modifications and abnormal ossification, for which a pathogenetic role of tumour necrosis factor-alpha (TNF-alpha) is postulated. We describe a 4-year-old child affected with CINCA syndrome and presenting progressive joint disease, in whom non-steroidal anti-inflammatory drugs (NSAID) and systemic corticosteroidal therapy had been ineffective. Etanercept, anti-TNF-alpha therapy, was administered over a 6-month-period resulting in a dramatic improvement of the arthropathy. This good response to anti-cytokine treatment supports our hypothesis that TNF-alpha might play an important role in the pathogenesis of CINCA syndrome, which needs to be evaluated and confirmed in further studies.

Seizures in an interferon-treated child.

Interferon-treated patients can present seizures, which in most paediatric cases are related to fever. The case of chronic hepatitis C is described in which Interferon probably disclosed a latent epilepsy. The hypothesis is advanced that seizures can be provoked by Interferon therapy in subjects with a low convulsant threshold and, in those cases in which it cannot be substituted with another drug, antiepileptic therapy should be started after the first episode.

Childhood glomerulonephritis associated with varicella and streptococcal infection.

Varicella is a usually benign disease of childhood and its complications are uncommon in immunocompetent children. In recent years we have witnessed the increasing virulence of group A beta-haemolytic streptococci (GABHS). In particular, in 1993, 50% of new cases of invasive GABHS disease were associated with varicella infection and all were suppurative complications. Because also a non suppurative complication of varicella as glomerulonephritis associated with GABHS infection, has been published in only one case, we feel that it could be of interest to describe this condition in two other cases we have observed.

Cholestatic jaundice in infectious mononucleosis.

Jaundice is a less frequent sign in infectious mononucleosis, more often caused by hemolysis, rarely by hepatocytes damage. In subjects with erythrocyte plasmatic membrane defects such as spherocytosis, any infection could increase hemolysis. The authors describe the case of a young spherocytosis patient in whom Epstein-Barr virus caused an intense cholestatic jaundice and they discuss the possible damage mechanisms according to the recent studies on cholestasis pathogenesis.

Fetal infection from rubeovirus or cytomegalovirus: correlation among maternal serological profiles, invasive diagnostic procedures, and long-term follow-up.

Different variables influence the possibility that maternal viral infection may be transmitted to the fetus, although not all fetal infections result in fetal "illness" with consequent fetopathy. As concerns the fetus, prenatal diagnosis includes invasive techniques necessary for fetal tissue sampling. These techniques carry some risks. The fetal infectious risk, as determined by maternal clinico-serological profile and according to sonographic investigation, always should be weighed against the risks and benefits of invasive diagnostic procedures. The present study re-elaborates the criteria necessary for defining fetal risk as related to the maternal serological profile. In the 26 mothers with rubeola infection, the incidence of fetal mortality was 7.7%. Fetal prognosis worsens with the precocity of eruption. In these cases the esantema is the most reliable prognostic element as an indication to perform the invasive procedure. In the 15 patients with cytomegalovirus infection, no fetal or postnatal losses occurred. Morbidity occurred in 13.3% of cases, and the two ill fetuses were classified in the same risk group. In this group of patients, the maternal serological profile is a significant predictor of fetal morbidity.

[Haemophilus influenzae type b in meningitis: antibiotic resistance in pediatric patients]. / Haemophilus influenzae tipo b: antibioticoresistenza in una casistica pediatrica di meningiti purulente (1985-1994).

A retrospective study on 357 children admitted to four Pediatric Infectious Disease Centers in Rome, affected by acute meningitis, during 10 years period, between January, 1, 1985 and December, 31, 1994 was carried out. Haemophilus influenzae type b was detected in 110 patients; all children aged between 1 month and 5 years; the maximum incidence (74.5%) was observed in patients under two years. The following diagnostic criteria were utilized: Gram stain of CSF; Latex test on CSF, blood, urine; CSF and blood cultures. The in vitro sensitivity of 65 isolates was tested by using the Kirby-Bauer method. We detected 15.3% of strains resistant to Ampicillin and 1.5% resistant to CAF. We also observed a high number of Hib strains resistant to Erythromycin and Cotrimoxazole. Only one strain Ceftriaxone resistant was isolated, confirming the high in vitro sensibility Hib to III generation cephalosporins that still remain the first choice drugs in Hib meningitis.

[Haemophilus influenzae disease in childhood. Comment about case reports of meningitis]. / Patologia da Haemophilus influenzae in età pediatrica. Considerazioni su una casistica di meningiti.

The authors describe a series of Haemophilus influenzae meningitis in childhood, obtained with a retrospective analysis of the cases of bacterial meningitis admitted to Isolamento Pediatrico department of "A. Gemelli" Polyclinic in Rome, from January 1, 1970 to December 31, 1994. Haemophilus influenzae resulted the second agent in frequency (first was Neisseria meningitidis). Main features were: no patient was older than 5 years, and most of them were less than 2 years old; clinical feature was aspecific in the first year of life, it was typical of bacterial meningitis in older children; blood culture and detection of bacterial antigens in cerebrospinal fluid (CSF) were useful for etiological diagnosis, supporting CSF culture; clinical course was characterized by many complications, but no case was lethal and incidence of sequelae at discharge was low; C reactive protein was effective as index of inflammation and as indicator of arising complications; chosen antibiotics were efficacious, but frequency of antibiotic resistance, especially to beta-lactams, was found to be increasing; results of dexamethasone therapy were not of univocal interpretation. The authors are in favour of spreading of vaccination against Haemophilus influenzae in Italy, too, in order to eradicate this disease, as experiences in other countries are successful, and of setting up of the combined vaccines, in order to increase parents' compliance to vaccinal practices.

Varicella arthritis. Report of a case.

A rare case of varicella with bilateral acute arthritis of the knee is described. Clinical features and laboratory results of the patient are briefly compared with those of other sixteen cases previously published. The study of immune response shows a decrease of helper T cells (OKT4+) and an increase of suppressor/cytotoxic T cells (OKT8+) with a normal response of lymphocytes to PHA.

[Detection of virus A antibody through epidemiology and diagnosis of hepatitis A]. / Ricerca dell'anticorpo contro il virus A (= HAAb) per l'epidemiologia e la diagnosi dell'epatite A.

In the present work the Authors report the results of the research of HAAb in 383 subjects living in Rome with negative history for hepatitis (divided for age, sex and occupation) and in 64 acute non B hepatitis (HBsAg-). In the latter, the titer of HAAb was determined at the beginning and later during the course of the disease. A fractionation of 13 sera of these patients was done and the type of specific immunoglobulin was determined. Among the subject with negative history for hepatitis, 68.9% was positive during first 6 months of age 6.2% from 6 months to 5 y.o., 27.6% from 6 to 12 y.o., 45.4% from 12 to 17 y.o., 76.8% from 18 to 25 y.o., 82.2% from 26 to 45 y.o., 90.2% from 46 to 65 y.o.. There was no statistically significant difference either between males and females, or among various occupations. Among the 64 patients with non B hepatitis, 25 (39%) were hepatitis A (because they showed either a seroconversion for HAAb or a positive HAAb-IgM); 12 (18.7%) were non A-non B hepatitis because HAAb negative or HAAb positive but negative for HAAb-IgM; while 27 (42.2%) were impossible to classify because they showed a positivity for HAAb but not a seroconversion during the disease. The limit of the determination of HAAb and the utility of the research of IgM antibody for the diagnosis of hepatitis A are discussed.