[Mediterranean spotted fever in paediatric and adult patients: two clinical aspects of the same disease]. / La febbre bottonosa del Mediterraneo in età pediatricae in età adulta: due realtà cliniche differenti nella stessamalattia.

Mediterranean Spotted Fever is an acute febrile disease caused by Rickettsia conorii and transmitted to humans by the brown dog tick Rhipicephalus sanguineus. Nearly 400 cases are reported every year in Sicily, mainly from June to September. The aim of this study is to compare the clinical and laboratory features of two different groups of patients , one of adults and one of children. The analysis included all adult patients with MSF diagnosed at the Institute of Infectious Diseases, Paolo Giaccone University Polyclinic in Palermo, during the period January 2007- August 2010 and all the children diagnosed with MSF at the G. Di Cristina Children Hospital in Palermo during the period January 1997- December 2004. On admission, a complete physical and laboratory examination was carried out on every patient. An indirect immunofluorescence assay for Rickettsia conorii was performed in every case, a PCR assay was performed with blood samples from some adult patients. Analysis of the results confirms that MSF is a benign, and self-limiting disease in children, while severe complications can often arise in adults.

Universal varicella vaccination in the Sicilian paediatric population: rapid uptake of the vaccination programme and morbidity trends over five years.

Following the licensure of the Oka/Merck varicella vaccine in Italy in January 2003, the Sicilian health authorities launched a universal vaccination programme in all nine Local Health Units. A two-cohort vaccination strategy was adopted to minimise the shift of the mean age of varicella occurrence to older age groups, with the goal of vaccinating with one dose at least 80% of children in their second year of life and 50% of susceptible adolescents in their 12th year of life. Two studies were implemented in parallel to closely monitor vaccination coverage as well as varicella incidence.

Diagnostic problems and postnatal follow-up in congenital toxoplasmosis.

AIM: In order to assess the consequences of different clinical approaches in the prenatal management of congenital toxoplasmosis, we retrospectively reviewed 58 pregnant women with Toxoplasma seroconversion and prospectively enrolled their 59 infants, referred to us from 1999 to 2004. METHODS: Data on clinical, laboratory and demographic characteristics of the pregnant women were collected. Their children were entered into a 48-month follow-up programme in which clinical, instrumental, ophthalmologic and serologic evaluations were carried out at birth, at 1, 3, 6, 9, 15, 18, 24, 36 and at 48 months of life. Paediatric treatment with Spiramycin alone or alternated with Pyrimethamine-Sulphadiazine was administered according to the different clinical cases. RESULTS: Time of infection was dated in the first trimester for 24 women (41%), in the second trimester for 18 women (31%) and in the third trimester for 16 (28%). In the first trimester of pregnancy 20 of the 24 infected women had undergone amniocentesis, while the test had not been performed on any of the women infected in the third trimester. Serological follow-up revealed that 11 (19%) of the infants had been infected. An alternating regimen with Pyrimethamine-Sulphadoxine was administered to the infected children. All the infants were clinically asymptomatic, and the instrumental follow-up revealed specific toxoplasmosis anomalies in 4/11 infected children. CONCLUSION: Our results highlight issues and problems concerning current prenatal diagnostic tests and the therapeutic approach based on PCR testing of amniotic fluid alone. The incidence of ocular-cerebral lesions observed in children born to women with seroconversion in the third trimester raises questions about the diagnostic and therapeutic approach for these women and their offspring. Paediatric therapeutic protocol, with alternating Pyrimethamine-Sulphadiazine regimen, applied also to asymptomatic children born to women with inadequate prenatal diagnostic management, could prevent severe sequelae.

Diagnosis of congenital toxoplasmosis: pre- and post-natal evaluation in Sicilian (Italy) epidemiological area. Preliminary data.

To evaluate the usefulness of conventional serological methods with western blot assay (WB) in congenital toxoplasmosis diagnosis, we prospectively enrolled in a clinical and serological follow-up all pregnant women with Toxoplasma gondii infection and their offspring, referred to us from October 2004. Western blot and standard serological test were performed on sera collected from mother during pregnancy and from mother and child at birth, at postpartum month 1-3-6-9 and 12. At this point in time, 22 pregnant women and 14 infants have completed the follow-up. 4 newborns were infected and 2 had specific toxoplasmosis anomalies at the birth. In mothers without seroconversion, the WB performed during pregnancy demonstrates the highest accordance with postnatal follow-up whereas in 1 case the negative result of PCR analysis was not confirmed by postnatal observation. The detection of anti-T gondii IgG against 8 kDa accessory antigenic band and against the accessory band included between 35 and 40 kDa band in immunoblot assay was useful for diagnosis of acute phase but did not improve the evaluation of comparative postnatal profile. Althougth few infants have concluded the postnatal follow-up, the preliminary results showed a greater value of using a IgM and IgA WB test than other standard method for the early diagnosis of toxoplasmosis at birth also in child born to treated mothers. The comparative anti-T gondii IgG immunoblot profile of mother and child permitted us to reduce the time of ruling out infection in newborns born to mothers with probable or possible infection and/or when prenatal diagnosis is negative or not performed.

Hormonal, auxological and clinical follow-up in children with connatal HIV infection. Personal records.

AIM: HIV infection and antiretroviral drugs have relevant endocrine implications, affecting growth and pubertal development. Moreover stature impairment cannot depend only on decreased hormonal secretion. METHODS: We studied for 7 years growth, puberty, bone maturation, hormonal secretion [Growth Hormone (GH) basal and after stimulation with Clonidin and Insulin, Insulin-like Growth Factor 1 (IGF-1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), FSH, LH- gonadic hormones axis, ACTH, Cortisol, TSH, fT4, T4, T3, anti-thyroid antibodies, Leptin] of 10 HIV-infected children. RESULTS: In 3 patients stature was <-2 SDS in the first 2 years and in prepubertal age, with intervals of improved growth. The weight was >2 SDS in 6 children, <-2 SDS in 1 girl, while the other 3 patients had a weight <-2SDS only in the first 2 years of life. Height growth velocity was >10 degrees Centile all over the years of follow-up in 9 patients, while weight growth velocity was pathological in 5. Leptinemia showed higher levels at the beginning of follow up: 0.82-11.68 ng/L (M+/-DS: 3.29+/-4.15) than at the end of the study: 0.2-3 ng/L (M+/-DS: 1.65+/-1.01). Leptin levels showed a statistically significant correlation with CD4/CD8 count (P: 0.010; r: 0.916) and with the CDC stage (P: 0.006; r: 0.937), meaning a strong link to the severity of the disease. CONCLUSIONS: A good clinical control of HIV infection can guarantee growth within physiological centile in most of HIV-infected children. Over all IGFBP-3 and IGF-1 are good markers of growth, more usable than GH.

Viral gastroenteritis in children hospitalised in Sicily, Italy.

The aim of the present study was to describe the epidemiologic and clinical characteristics of acute viral gastroenteritis in hospitalised Italian children. A total of 215 stool specimens were collected from January to December 2003 from patients hospitalised in Palermo for acute diarrhoea. Samples were tested for group A rotavirus, astrovirus, adenovirus, norovirus, enteropathogenic bacteria, and parasites. Rotaviruses, mostly belonging to types G1-G4, were detected in 25.1% of samples, astrovirus in 7%, adenovirus in 6%, norovirus in 18.6%, and bacterial agents in 17.2%. No parasitic infections were diagnosed. Mixed infections represented 9.8% of all cases. The mean and median ages of children with rotavirus gastroenteritis were lower than those of children with other viruses (p = 0.029), with the highest median ages being found in astrovirus-infected patients. Vomiting and dehydration were more frequent among patients with viral infection (p < 0.01), and the severity score was significantly higher for children infected with astrovirus or group A rotavirus (p = 0.008). Rotavirus was the leading cause of prolonged hospitalisation (p = 0.005). In conclusion, viruses were confirmed in Italy as the most common cause of severe enteric illness in childhood, with rotavirus types G1-G4, which correspond to those included in the rotavirus vaccines being developed, playing the main role. Routine testing should be introduced for noroviruses, since they seem to represent an important cause of sporadic paediatric gastroenteritis.

[Urinary schistosomiasis: remarks on a case]. / Considerazioni su un caso di schistosomiasi urinaria.

Urinary tract schistosomiasis is a parasitic disease caused by S. haematobium with a wide range of clinical manifestations related to the mucosal and submucosal granulomatous lesions of the bladder. It affects about 80 million people in Africa, Middle-East and India, while in Italy it is rarely seen among immigrants from endemic areas and returning travellers. The authors describe a case occurred in a 26 years old man, recently emigrated from a rural area of Ghana. He had the symptoms of a haemorrhagic cystitis. Cystoscopy and biopsy showed granulomatous lesions of bladder with calcified eggs. Microscopic examination of urine was positive for Schistosoma haematobium eggs. The therapy with Praziquantel (40 mg/Kg una tantum) was effective. The authors emphasized the risk of introduction of schistosomiasis in some regions of our country, in consideration of the presence of the intermediate host as well as of an appropriate climate.

[Pulmonary infection caused by Blastoschizomices capitatus]. / Infezione polmonare da Blastoschizomices capitatus.

Geotrichum capitatum, now known as Blastoschizomyces capitatus, can be responsible for several opportunistic infections (systemic infection or localized at lungs, liver, kidney, encephalitis or meningitis) in an immunocompromised host, especially in those patients affected by leukaemia or under immunosuppressive therapies. A 66-year-old woman with polimyosite under steroid and immunosuppressant therapy was hospitalized in ICU for an acute respiratory distress with moderate hypoxaemia and normocapnia. Pulmonary X-ray revealed a bilateral pneumonia. Hypoxaemia became severe 48 hours later and the patient underwent mechanical ventilation and empirical antibiotic therapy. Blood cultures, urine cultures and serological tests were negative, while yeast was identified by Gram's stain of bronchoaspirate. Before identifying the yeasts Fluconazole was added to therapy. At day 5 the clinical conditions remained severe and Candida spp were excluded: so Fluconazole was switched to liposomal Amphotericin B. At day 8 B. capitatus was identified. At day 26 the patient died of refractory respiratory insufficiency. B. capitatus infection is infrequent and its prognosis is severe, with a high mortality rate (>50%). Microbiological diagnosis requires time to characterize the yeast. At present no standard therapy is available although some authors report a good susceptibility to Amphotericin B and Voriconazole (100%), according to NCCLS guidelines.

Pulmonary tuberculosis in Italian children by age at presentation.

AIM: To evaluate the clinical characteristics, diagnostic methods and outcome of paediatric pulmonary tuberculosis (PTB) in relation to children's ages when observed. METHODS: Children under 15, who had been admitted to the Children's Hospital with PTB were prospectively evaluated. Our sample included patients with a positive tuberculin skin test and signs or symptoms of tuberculosis (TB), including abnormal chest X-rays which suggested PTB. We collected demographic, clinical, radiographic and microbiological data from the patients, in addition to carrying out contact investigations in order to find a source case. All the patients involved in this study were subjected to anti-tuberculosis treatment. RESULTS: Sixty-two patients (44% under 5) were eligible for inclusion in our study. Children with presenting symptoms were younger than asymptomatic patients (p<0.05). A source case was found in 38 patients out of 62 children (62%) and children under 5 were more likely to have a source case than that found with older children (p<0.05). Ghon complex (infiltrate + adenopathy) tended to occur in young children (median age of 3.25, p<0.05). Fourteen children (23%) had clinical specimens which tested positive for Mycobacterium tuberculosis (MT), and 20 (32%) for MT DNA according to a polymerase chain reaction (PCR). Resistant strains to 1 or more anti-tuberculosis drugs were found in 5 children and in 4 adult sources. The patients with minimal or no radiographic change during therapy displayed symptoms for a longer period of time and were infected by a resistant strain (p<0.05). CONCLUSION: Improvements in case detection, case management and contact investigations are necessary for controlling paediatric TB, especially in young children. Given that any diagnosis of TB in children is supported by epidemiological and clinical evidence rather than isolating MT, detection of the source case is important in selecting appropriate treatment.

Tuberculosis of the central nervous system in children: 32 years survey.

AIM: In order to study the impact of clinical and diagnostic parameters on the clinical outcome of children with central nervous system tuberculosis (CNS-TB), we retrospectively reviewed all cases of CNS-TB diagnosed over a 32-year period at the Children's Hospital of Palermo, Italy. METHODS: Data were collected with regard to the clinical, laboratory and demographic characteristics of patients, as well as the results of radiological investigations and data on clinical outcome. In relation to the date of introduction of new diagnostic methods (indirect as well direct) and to the change of treatment periods, the authors compared the clinical outcome of patients admitted prior and after 1984. They also classified the patients into 3 different stages of illness according to the severity of the disease on admission. RESULTS: We identified 80 patients with CNS-TB. The mean age of the children was 3 years with 54% of patients younger than 5 years. The contact source was documented in 40 patients (50%). The mean duration of symptoms prior to admission was 22 days (range 5 days - 3 months). Mantoux skin test was positive on admission in 50 patients (62%). CSF smear microscopy and culture were positive in 29% and 45% of patients respectively. PCR for Mycobacterium tuberculosis introduced in 1994 was positive in 11 out of 13 tested patients. Determination of CSF gdT lymphocytes composition applied in 7 patients shows a predominance of Vg9/Vd2 T lymphocytes. Fifteen subjects (19%) died; 11 (13%) suffered from permanent sequelae. The died children and those with permanent sequelae were younger than the others (p<0.05). Prior to 1984, none of the patients were identified during early stage of illness and 4 out of 37 patients with stage II illness died. After 1985, 44% of children were in stage I and 2 out of 4 patients with stage III died (p<0.05). CONCLUSIONS: Stage of disease and young age are still the decisive factors in the clinical outcome of children with CNS-TB. The availability of new advanced methods has improved the identification of patients with CNS-TB in stage I and therefore the possibility of an early treatment of such patients.

Treatment of human brucellosis with rifampin plus minocycline.

In order to evaluate the efficacy and tolerability of a high intravenous dose of rifampin plus oral minocycline (administered daily for 3 weeks) for the treatment of acute brucellosis, we retrospectively reviewed the outcome of 239 consecutive patients (135 adults and 104 children) diagnosed and treated over a 17-year period in Italy. The combination used resulted in 100% response and a relapse rate lower than 2%. Fifty-two (30 adults and 22 children) (29.8%) complained of mild adverse effects including an increase in aspartate aminotransferase (>250 IU) observed in 12 cases and considered related to rifampin and in 11 cases a reversible hyperpigmentation of the tongue attributed to minocycline. A randomized prospective comparative study should be performed to confirm our encouraging results.

Monocyte and lymphocyte apoptosis resistance in acute and chronic brucellosis and its possible implications in clinical management.

This study evaluated the level of susceptibility of monocytes and lymphocytes to spontaneously induced and CH11-induced apoptosis in 16 patients with Brucella infection. The expression of some immunological and apoptotic markers was evaluated. Before therapy, monocytes showed a high level of resistance to spontaneously induced or CH11-induced apoptosis in all patients. In patients with acute infection, this resistance persisted for 10-20 days after treatment was initiated, then decreased; in chronically infected patients, it persisted after 45 days of treatment. Lymphocytes were also more resistant to CH11-induced apoptosis. The level of activated CD8(+) T lymphocytes was high in patients with acute infection. The data indicate that the CD95-mediated apoptotic pathway is not involved in CH11 resistance. Lymphocytes are not infected by Brucella, so their resistance to apoptosis may be due to a soluble factor released by infected monocytes. The evaluation of levels of susceptibility to CH11-induced apoptosis in monocytes may be used to test the effectiveness of the therapy.

Serum leptin and interleukin-6 levels in pediatric patients with HIV.

Recent therapeutic approaches have improved the prognosis of children with HIV. Many new efforts could be involved in their quality of life and therefore could need additional diagnostic strategies. Leptin regulates pubertal development; furthermore a continuous immune stimulus, as in chronic infectious diseases, can enhance leptin's secretion by the action of cytokines such as interleukin (IL)-6. To clarify this role in patients infected with HIV, we assayed leptin and IL-6 and evaluated the influence of HIV severity on its secretion. IL-6 (380.5 +/- 257.6 pg/ml; range: 22-900 pg/ml) showed a significant correlation with leptinemia, HIV-1 RNA, and viremia related to the stage of HIV disease. The difference in leptinemia from a control group (3 +/- 3.2 ng/ml; range: 1-12 ng/ml in HIV patients; 6.72 +/- 8 ng/ml in the controls) did not reach statistical significance, nor did it correlate with pubertal stage, BMI, viremia, CD4 or anti-retroviral therapy. There was a statistically significant correlation between leptinemia and the stage of the HIV disease, and with IL-6 level. We want to stress the role of immunological factors in enhancing leptin secretion.

Pediatric visceral leishmaniasis in Western Sicily, Italy: a retrospective analysis of 111 cases.

The clinical and epidemiological characteristics of 111 consecutive cases of visceral leishmaniasis identified from 1980 to 2000 in a Sicilian pediatric hospital were analyzed retrospectively. The mean age of the patients was 1.7 years. All children were HIV negative, but 15% were severely malnourished. Fever and splenomegaly were present in all cases and hepatomegaly in 101 (90.1%) cases. Thrombocytopenia and anemia were both observed in 78 (70.2%) cases and leukopenia in 47 (42.3%) cases. A bone marrow aspirate was obtained in all cases; Leishmania amastigotes were detected in 89 (80.2%) cases. Initial treatment consisted of meglumine antimoniate in 99 (89.2%) patients and amphotericin B in 12 (10.8%) patients. Only two children treated with meglumine antimoniate relapsed. The findings highlight the differences between the cases of visceral leishmaniasis observed in the Mediterranean basin and those observed in other regions. The use of the term "Mediterranean visceral leishmaniasis", rather than the term "kala-azar", is proposed for cases observed in the Mediterranean area.

Efficacy and safety of clarithromycin as treatment for Mediterranean spotted fever in children: a randomized controlled trial.

Fifty-one children with Mediterranean spotted fever (MSF) were randomized to receive either clarithromycin, 15 mg/kg/day orally in 2 divided doses, or chloramphenicol, 50 mg/kg/day orally in 4 divided doses, for 7 days. Mean time to defervescence was 36.7 h in the clarithromycin group and 47.1 h in the chloramphenicol group (P=.047). Clarithromycin could be an acceptable therapeutic alternative to chloramphenicol and to tetracyclines for children aged <8 years with MSF.

Change of Th0 to Th1 cell-cytokine profile following tuberculosis chemotherapy.

T cells mediate protection against tuberculosis, but little is known about their role during chemotherapy of patients with active disease. Here we examined the cytokine profile of CD4 T cells before and after four months of chemotherapy in six initial skin test anergic cases. Purified protein derivative (PPD) and 16-kDa antigen-reactive CD4 T-cell clones prior to therapy resided mostly in disease-associated body fluids and were of the Th0 (interferon (IFN)-gamma + interleukin (IL)-4) secreting profile. In contrast, the majority of postchemotherapy CD4 T-cell clones originated from blood and were of the IFN-gamma secreting Th1 type. However, the recognition of several peptides derived from the 16-kDa antigen was not significantly different between the Th1 and Th0 clones. We conclude that chemotherapy shifts CD4 T cells from the affected body fluids to the blood circulation, accompanied by a change from Th0 to Th1 cytokine profile.

Ligand-specific alphabeta and gammadelta T cell responses in childhood tuberculosis.

The alphabeta and gammadelta T cell responses were analyzed in the peripheral blood of children affected by active tuberculosis (TB) and in healthy children who tested positive (PPD+) or negative (PPD-) for purified protein derivative. PPD+ healthy and diseased children responded equally well to PPD in vitro. In contrast, only 18% of PPD+ TB patients responded to peptide p38G derived from the 38-kDa protein of Mycobacterium tuberculosis. Analysis of the whole gammadelta T cell population and of its Vgamma9/Vdelta2 subset showed similar frequencies in PPD+ children with TB and in healthy PPD+ and PPD- children. Vgamma9/Vdelta2 cells from children with TB responded to 5 different phosphoantigens similarly to those from healthy PPD+ children, but healthy PPD- children responded very poorly. Chemotherapy had contrasting effects on the tested lymphocyte population, represented by increase of alphabeta and decline of Vgamma9/Vdelta2 T cell responses. T cell responses in childhood TB may be similar to those in adult TB.

Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy.

The specificity of CD4 T lymphocytes was investigated in 6 patients affected by tuberculosis who had negative tuberculin purified protein derivative (PPD) skin tests at diagnosis. Polyclonal CD4 T cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4 cell lines from the disease site responded to PPD and to the 16- and 38-kDa proteins and derived epitopes in vitro. Four months after chemotherapy, the patients became responsive to PPD. The proliferative response to PPD and to the 16- or 38-kDa proteins and their derived peptides decreased in CD4 T cell lines from the disease site and increased in lines from the peripheral blood. These results indicate that CD4 T cells recognizing a vast array of M. tuberculosis epitopes are compartmentalized at the site of disease in anergic patients but appear in peripheral blood after chemotherapy.

[Descriptive analysis of measles epidemic in Palermo, from September 1996 to June 1997. Failure of a vaccination campaign]. / Analisi descrittiva di un'epidemia di morbillo a Palermo dal settembre 1996 al giugno 1997. Insuccesso di una campagna vaccinale.

BACKGROUND: The authors report 1642 measles cases observed from September 1996 to June 1997 at the "G. Di Cristina" Children's Hospital. 34% of patients were hospitalized at the Division of Infectious Diseases. METHODS: The records of children admitted with measles to emergency area were retrospectively collected. The medical records (anamnestic, clinical and laboratory findings) of hospitalized children were obtained from schedules which since 1993 were performed to perspectively collect the exanthematous diseases. International criteria for the definition of measles case were applied. The variables considered were: background, demographic data, seasonal distribution, clinical presentation, complications and days of hospital stay. RESULTS: The results of this research showed that the outbreak involved predominantly infants. The complications accounted for 72% of measles hospitalized cases. Four cases of encephalitis were observed. A total of 1692 days of hospital stay was reported. CONCLUSIONS: These data show the failure in measles control adopted by the Sicilian Region and confirm the difficulties to achieve high percentage of parents participation to the infant recommended vaccination program.

Clinical and laboratory findings of boutonneuse fever in Sicilian children.

UNLABELLED: The spectrum of signs and symptoms of 645 consecutive children diagnosed from 1984 to 1996 with boutonneuse fever (BF), a mild rickettsial disease caused by Rickettsia conorii endemic in the Mediterranean basin, are reported. The major clinical features were fever (97.2%), exanthema (96.1%) and "tache noire" (71.8%). The large series examined permitted the authors to observe some rare or disregarded clinical features of the disease: cases with papulovesicular exanthema, reported previously only in adults who had been infected by R. conorii in Africa; and cases in which the only symptom was an isolated lymphadenopathy. CONCLUSION: R. conorii infection should be considered in patients with lymphadenopathy who live in or have travelled to an endemic area, even when other, more specific features, are not present. Also pox-like vesicular lesions may be caused by this organism, awaiting confirmation by using culture techniques instead of serology. The serological confirmation of BF by immuno fluorescent antibody test is possible only late in the illness.