Managing of musculoskeletal infections in children.

OBJECTIVE: Epidemiological features of musculoskeletal infections are in continuous evolution. The incidence of emerging causative pathogen is arising. Nevertheless, up to 50% of osteoarticular infections shows negative cultures. Septic arthritis, with or without concurrent osteomyelitis, are most common in newborn while osteomyelitis frequently affects older patients. We retrospectively analyzed all the children affected by musculoskeletal infections treated at the Children's Hospital Bambino Gesù in ten years, focusing on the results of an early diagnostic and therapeutic management. MATERIALS AND METHODS: The study population consists of 150 children with acute septic arthritis, osteomyelitis and discitis, treated from 2006 to 2016, excluding patients with less than 12 months of follow-up and previous treatment sustained in others hospitals. A wide spectrum of data has been extracted from clinical charts, laboratory studies and imaging. Patients were categorized into 3 groups on the base of their age. The diagnostic and therapeutic protocol consisted of intravenous empirical treatment while diagnosis was ongoing then switched to oral treatment, according to the pathogen and the systemic symptoms. RESULTS: Only 31% of pathogens were identified. The most common was Staphylococcus aureus methicillin-sensible (MSSA) but an increase of cases caused by Kingella Kingae and Staphylococcus aureus methicillin-resistant (MRSA) was observed. The mean antibiotic treatment was 6.8 weeks. It's important to underline a significant correlation between age and C-reactive protein serum levels. CONCLUSIONS: Among others frequent pathogens, MRSA shows a high rate of physis involvement. Musculoskeletal infections represent a challenge in skeletally immature patients because of their potential severe complications. Timing of diagnosis and consequent targeted treatment is fundamental to avoid complications and functional sequelae.

HHV6 meningoencephalitis sequelae in previously healthy children.

INTRODUCTION: Human herpes virus 6 (HHV6) infection is a self-limiting illness occurring in early childhood. As with other herpes viruses, the encephalopathy associated with HHV6 is often attributable to the reactivation of a virus previously latent in human brain tissue. Previous reports on HHV6 encephalopathy dealt mainly with virus reactivation in immune-depressed older children and, above all, refer to encephalitis and not to meningoencephalitis. Complications are rare in healthy children. Encephalopathy has rarely been associated with HHV6 infection in children not affected by chronic disease. PURPOSE: The aim of this study was to evaluate sequelae of HHV6 meningoencephalitis in previously healthy children. RESULTS: We report three cases of HHV6 meningoencephalitis in previously healthy children followed for a 10-year period. Two of the patients presented invalidating sequelae. In detail, one patient developed speech disturbance and the other persistent hemiplegia and bilateral visual deficit. To our knowledge, this is the first case in which an ocular complication developed in the course of HHV6 meningoencephalitis. CONCLUSION: HHV6 meningoencephalitis can be associated with a wide range of clinical outcomes, from long-term neurological sequelae to a benign post-infectious clinical course.

Low genetic diversity in Polish populations of sibling ant species: Lasius niger (L.) and Lasius platythorax Seifert (Hymenoptera, Formicidae).

We present preliminary data on mitochondrial DNA diversity within and among populations of the ants Lasius niger and Lasius platythorax in Poland. Phylogenetic analysis based on the mitochondrial DNA markers: cytochrome c oxidase subunit I (cox1) and 16S ribosomal RNA (16S rRNA) confirms the species status of L. niger and L. platythorax. Intraspecific variability is low in both species, which might be a result of severe bottlenecks and rapid postglacial expansion into Central Europe.

Mucocutaneous manifestations in children with HIV infection and AIDS.

Mucocutaneous diseases are more frequent in HIV/AIDS-infected children than in the normal population. We analyze mucocutaneous disorders with atypical presentations in a large population of HIV-infected children, with or without full-blown AIDS, compared to a population of HIV seroreverted children. The majority of these cutaneous disorders have an infectious etiology and their frequency is related to the degree of deterioration of the immune system. Some diseases commonly observed in adults are rare in children; neoplasms are an exception.

Ganciclovir therapy for cytomegalovirus-associated liver disease in immunocompetent or immunocompromised children.

Ganciclovir therapy was given intravenously to 20 children with cytomegalovirus (CMV)-associated liver disease, of whom 6 were immunocompetent and 14 were immunocompromised (9 had AIDS and 5 had solid tumors). Immunocompetent children had isolated liver disease diagnosed at birth (4 children), or systemic congenital CMV infection including liver disease (2 children). Ganciclovir was used following two regimens: A) 5 mg/kg twice daily for 8 to 86 days (mean 21); B) 7.5 mg/kg twice daily for 14 days followed by 10 mg/kg three times weekly for three months. CMV infection was diagnosed by viral isolation, detection of viral antigens, and/or CMV DNA from blood and urine. All immunocompetent children had negative CMV culture and CMV DNA detection from blood and/or urine after 14 weeks of treatment. However, the three children who were treated with regimen B showed normal ALT levels at the end of the maintenance course, whereas the children who received ganciclovir with regimen A had normal ALT levels only after about 1 year. All children with tumors initiated regimen B, but only three, who had negative CMV detection and markedly decreased ALT levels, received full treatment; of the remaining two children, one recovered after only an initial course, and the other had therapy interrupted because of hepatic failure and died 9 days later. In contrast, the children with AIDS received several ganciclovir courses for different periods at the lower dosage: they generally improved during treatment but did not recover completely, and five children died with active CMV infections. Based on our study, CMV-associated liver disease can be efficiently treated with ganciclovir both in immunocompetent and immunodeficient children. However, a single ganciclovir course including a higher dosage and prolonged therapy appeared to be more effective than several courses with lower dosages.

Rapid progression of HIV disease in children with cytomegalovirus DNAemia.

OBJECTIVE: In HIV-1-infected children, active cytomegalovirus (CMV) infection can cause severe clinical manifestations and accelerate progression of HIV disease. However, sufficient quantities of blood samples may not be available either for culture or detection of CMV DNA or antigens in white blood cells. The aim of this study was to investigate the diagnostic and prognostic significance of detecting CMV DNA in serum samples from HIV-1-infected children. DESIGN: Sera from 55 children (18 boys), aged 2-130 months (mean, 49.8 months), with perinatal HIV-1 infection and clinical manifestations attributable to CMV infection were tested for CMV DNA by nested polymerase chain reaction and for class-specific CMV antibodies [immunoglobulin (Ig) G, IgA, IgM] by enzyme-linked immunosorbent assay. The children were followed up for 2 days to 59 months (mean, 25.5 months). RESULTS: CMV infection was demonstrated in 43 children (74.5%), 18 of whom (42%) were positive for CMV DNA. During the follow-up, 13 children with CMV infection (30.2%) died, including 11 (84.6%) who were positive for CMV DNAemia just before death. Of these children, seven died soon after hospitalization without antiviral treatment, and four died despite therapy with ganciclovir or foscarnet. Post-mortem CMV inclusions were revealed in seven out of eight children who underwent autopsy. The two other children who died also had progressive CMV disease and received ganciclovir until death. In comparison with CMV-seropositive children without CMV DNAemia, children with CMV DNAemia showed significantly shorter mean survival time (42.5 versus 60 months; P < 0.01), lower final CD4+ T-cell count (218 versus 499 x 10(6)/1; P < 0.01) and higher mortality rate (P < 0.0001). CONCLUSIONS: The detection of CMV DNA in serum is of value for diagnosis of active CMV infection in HIV-1-positive children, and CMV DNAemia is a good prognostic indicator of severe outcome of HIV disease.

Detection of IgM antibodies to human herpesvirus 6 in Romanian children with nonprogressive human immunodeficiency virus disease.

The prevalence of human herpesvirus 6 (HHV-6) infection and the course of human immunodeficiency virus (HIV) disease were investigated in 25 Romanian children with nosocomial HIV-1 infection. HHV-6 IgM and IgG antibodies were detected by enzyme immunoassay (EIA) and immunofluorescence assay (IFA) at the beginning of the study and after 18 months, concomitantly with collection of virologic, immunologic and clinical data. The initial HHV-6 seropositivity was 92% by EIA and 76% by IFA, whereas final testing showed 100% positivity by EIA and 84% by IFA. Positive HHV-6 IgM antibodies were detected in 10 children (40%) by EIA and IFA. Of these 9 children (36%) by EIA and 6 (24%) by IFA had both initial and final IgM antibodies. Children with HHV-6 IgM antibodies had a higher prevalence of pneumonitis than those without (100% vs. 53.3%; P < 0.01). In addition they more frequently showed positive p24 antigen detection (67% vs. 40%) and positive HIV-1 culture (80% vs. 69%). Nevertheless the patients with HHV-6 IgM antibodies showed a slight increase in the final mean CD4+ T cell count (from 1.140 to 1.185 x 10(6)/liter), whereas those with HHV-6 IgG alone showed a statistically significant (P = 0.01) decrease (from 1.395 to 968 CD4+ T-cells x 10(6)/liter). Therefore current or recent HHV-6 infection, as revealed by positive HHV-6 IgM antibodies, appeared to be associated with the development of pneumonitis but not with progression of HIV disease. A possible competitive inhibition of HIV-1 by HHV-6 or a stimulating effect of HHV-6 on CD4+ T-cell production may be suggested.

Cytomegalovirus-associated stage 4S neuroblastoma relapsed stage 4.

Neuroblastoma is one of the most frequent solid tumors in childhood, rarely recurrent after five years from diagnosis. Cytomegalovirus (CMV), a major pathogen causing congenital birth defects and severe opportunistic diseases, has been shown to have teratogenic, immunodepressive and oncogenic properties. The case of a girl with stage 4S neuroblastoma diagnosed at three months and relapsed as stage 4 five years later is reported. In both circumstances, active CMV infection was revealed by positive CMV-specific IgM and IgA antibodies, CMV-DNAemia and CMV culture. At three months, the patient presented with subcutaneous nodules, hepatosplenomegaly and increased aminotransferase levels, and the opsolonus-myoclonus syndrome. Mental retardation developed later on. At 5 years, relapsed neuroblastoma was preceded by a mononucleosis-like syndrome concomitant with active CMV infection and decreased levels of immune cells and natural killer activity. Clinical, virologic, and immunologic findings suggest an immune-mediated pathogenic role for CMV in this tumor.

Active or recent parvovirus B19 infection in children with Kawasaki disease.

Because parvovirus B19 occasionally causes some of the features typical of Kawasaki disease, we investigated B19 involvement in 15 children with Kawasaki disease. Active or recent B19 infection, as shown by B19-DNAaemia, positive B19-specific IgM antibodies, or both, was diagnosed in 10 patients (67%). A high frequency of all major criteria for diagnosis of Kawasaki disease (60%), anaemia (60%), coronary aneurysms (30%), and arthropathy (30%) was found in children with B19-associated Kawasaki disease. Thus B19 may have a pathogenic role in the development of Kawasaki disease, with other predisposing factors.

Multiple viral infections in HIV-infected children with chronically-evolving hepatitis.

Hepatic involvement was investigated in 31 children with perinatal HIV-1 infection, who were followed for 2-82 months (mean 30.5). Liver disease, as revealed by increased aminotransferase levels, liver biopsy or necroscopy, was diagnosed in 18 children (58%), of which 7 (22.5%) had acute hepatitis and 11 (35.5%) showed chronic liver disease. Overall, 40 persistently active or recurrent viral infections, as demonstrated by positive culture and/or detection of serum DNA, specific IgM, IgA and high levels of IgG, were revealed in the children with liver disease, while 12 similar infections were detected in 13 children without liver disease (p < 0.001). In particular, the children with liver disease showed a significantly (p < 0.002) higher incidence of cytomegalovirus (CMV) infections than children without liver disease (13 versus 3). Moreover, hepatitis C and B virus infections were revealed only in children with liver disease (5 and 1 patients, respectively). Clinical outcome showed a significantly (p < 0.001) higher mean survival in the children without liver disease than those with liver disease (47.5 versus 18.2 months). In fact, nine of the children with liver disease (50%) died, as opposed to only one of the children without liver disease (7.7%; p = 0.01). Based on these findings, liver disease is indicative of a poor prognosis in children with HIV infection, being related to the presence of multiple active viral infections.