To the Editor: The high prevalence of tuberculosis (TB) underlines the important role of BCG (bacillus Calmette-Guerin) immunization. The vaccine, however, is not free from complications, which could be local or disseminated. Disseminated BCG infection as a result of TB vaccination is a rare complication with an incidence of 0.06 to 1.56 cases per million vaccinations; it occurs exclusively in patients with immune deficits. However, in these cases, the prognosis is unfavorable; up to 70% of patients die, despite intensive antituberculous treatment (1–4). A 4-month-old-girl exhibited enlargement of left axillary lymph nodes during a 1.5-month period. She was the second child of healthy parents, with no family history of genetic disorders or TB. She was vaccinated according to the regimen compulsory in Poland: the first dose of BCG and anti–hepatitis B virus (HBV) vaccination on the first day of life, followed by vaccination against diphtheria, tetanus, pertussis, poliomyelitis, and the second dose of anti-HBV after 6 weeks. BCG vaccination was performed intradermally in the upper part of left arm by administration of 0.1 mL Brazilian Moreau strain (Biomed, Lublin, Poland). On hospital admission, the patient was in reasonably good condition but pale, with grossly enlarged, adjacent left axillary lymph nodes and hepatosplenomegaly. Laboratory tests showed anemia, thrombocytopenia, elevated transaminase activity, a high C-reactive protein level, and high level of immunoglobulin M (IgM) class anti-cytomegalovirus (CMV) reactive antibodies. Based on clinical manifestations and biochemical and serologic signs, CMV infection was suspected. The patient was administered a 14-day regimen of ganciclovir (10 mg/kg/day); results of liver function tests and blood count normalized, and hepatosplenomegaly decreased. However, the lymph nodes continued to enlarge, and diagnostic excision and bone marrow aspiration were performed to exclude a neoplastic process. A histopathologic image of the excised lymph nodes showed caseating granulomas, and tuberculous lymphadenitis was suggested (Figure). Figure Digitally processed hematoxylin-eosin staining of the excised lymph nodes, showing caseating, tuberculosislike granulomas (original magnification ×100). At that time, a diagnosis of disseminated BCG infection as a complication of TB vaccination in a presumed immunocompromised patient was proposed. This idea was based on suggestive lymph node pathology, which showed caseating granulomas, a history of TB vaccination, and the exclusion of other pathologic changes. Flow cytometry measurements showed abnormally low expression of the α chain of the interferon (IFN)-γ receptor on peripheral blood lymphocytes. Only 20% lymphocytes expressed CD 119 (IFN-γ receptor outer subunit R1). Three-drug anti-tuberculous therapy (with rifampin, isoniazid, and streptomycin) was introduced despite chest and bone radiographs that were negative for infection, no abnormalities found on funduscopy, and negative results of Ziehl-Neelsen staining of lymph node tissue. Despite this therapy, the child's condition worsened; she exhibited a high temperature, hemolysis, and progressive neutropenia, thrombocytopenia, cholestasis, and renal failure. Uncontrolled sepsis developed, and she died. At postmortem examination, the diagnosis of disseminated BGC infection was made on the basis of multiple TB-like granulomas in the lungs, lymph nodes, meninges, liver, spleen, and kidneys. However, direct microbiologic confirmation of BCG infection was lacking because cultures were negative and Ziehl-Neelsen and periodic acid–Schiff staining did not show acid-fast bacilli, other bacteria, or fungi in these specimens. This case represents a rare complication of antituberculous vaccination, that is a progressive, disseminated BCG infection in a patient with deficiency of IFN-γ receptor. Concomitant CMV infection was diagnosed by positive IgM antibody response. Transient response to the ganciclovir treatment made the final diagnosis of BCG infection more difficult and probably postponed implementation of the anti-TB therapy. Until now ≈100 cases have been reported in the literature, most of them in infants and young children. These patients also had clear predisposition to other severe infections with intracellular microorganisms such as atypical mycobacteria, Salmonella spp., Listeria monocytogenes, and Leishmania spp (1–5). The INF-γ receptor is present on many cell types; however, its deficiency on macrophages may be responsible for the inhibition of phagocytosis and intracellular killing and the observed deficit of an antimycobacterial immunity. Among children with a clinical syndrome of IFN- γ–receptor deficiency, a clear genetic defect was identified in ≈20%. In our patient, the diagnosis was made by detection by flow cytometry of abnormally low expression of the α chain of the IFN-γ receptor on peripheral blood lymphocytes. This method appears to have high diagnostic value, given the fact that genetic methods are not always available and are expensive and often insensitive. The prognosis in patients with BCG infection secondary to IFN-γ–receptor deficiency is unfavorable. A few cases of successful treatment with allogenic bone marrow transplantation have been reported with long-term improvement of general condition and stable receipt of the graft as shown by molecular analysis of peripheral leukocytes (4,6–8). However, as specific and efficient therapy for this condition has not been as yet proposed, supportive measures with early diagnosis and institution of anti-TB and antimicrobial drug treatment appear to be important in managing this rare immune deficiency. The level of IFN-γ-receptor expression in populations known to be susceptible to TB, and its potential role in this phenomenon, appears to be a promising area of study.

Introduction: The course of HBV infection and the outcome of interferon alpha (IFNα) therapy of patients with chronic hepatitis B, is determined by the antiviral immune response of the host. The aim of the study was to investigate 1) the correlation between IL-6 and IL-12 serum levels and biochemical and histopathological changes in children with chronic hepatitis B, 2) predictive value of pre-treatment serum levels of these cytokines in patients treated with interferon alpha and 3) changes in serum levels of these cytokines after interferon alpha treatment. Methods: Serum levels of IL-6, IL-12 (heterodimer p70) and IL-12 (heterodimer p70 & p40 subunit) were determined by specific ELISA in 39 children with chronic hepatitis B on the first and the last day of IFNα therapy. Results: Serum levels of IL-6, IL-12 (p70) and IL-12 (p70&p40) were respectively within the following ranges of values: 0-1.7 pg/mL, 3.0-85.1pg/mL, 93.7-442.7 pg/mL and they showed no correlation with biochemical and histopathological changes. The pre-treatment cytokines levels in patients who responded and those who did not respond to IFNα therapy did not differ statistically. There was no statistical difference between the end and pre-treatment cytokines levels in both groups. Conclusions: Serum levels of IL-6 and IL-12 do not reflect the inflammatory activity of hepatitis and have no predictive value of positive response to the IFNα therapy in children with chronic hepatitis B. Serum IL-6 and IL-12 levels at the end of INFa treatment do not inform of their role in immunological changes which take place while inhibition of HBV replication or virus clearance.

One hundred children with chronic hepatitis B, aged 1-17.3 years participated in the study. The results of treatment with interferon alpha (IFN-alpha) were evaluated. An attempt was made to define the factors predicting positive response to treatment. Three million units of IFN-alpha 2a or 2b were given by subcutaneous injections to analysed patients 3 times a week for 20 weeks. Positive treatment outcome reflected in HbeAg elimination was observed in 46% of children. High AlAT activity preceding therapy had a statistically significant effect on positive treatment outcome. The inhibition of HBV replication caused by the treatment was permanent and it coexisted with the normalisation of AlAT activity in blood serum. Full response to therapy with IFN-alpha measured with the elimination of HbeAg and HbsAg was observed in 14% of children. It was favoured by high AlAT activity before treatment and short HBV duration.

Objective: To assess the side-effects of interferon-alpha (IFN-alpha) therapy in children with chronic hepatitis B.Methods: This prospective study was performed on one hundred children by interviewing the patients and their parents; clinical examinations and laboratory investigations were performed during and after therapy.Results: The most frequent side-effects of IFN-alpha therapy were fever, flu-like symptoms, and headaches. Lowering of the mean haemoglobin level, leukocyte and platelet count was significant, but transient during INF-alpha treatment. No increase in autoantibody titres or significant alterations in thyroid function was observed. Twelve months after treatment, hepatitis Be antigen (HBeAg) elimination and alanine aminotransferase (ALT) normalization was achieved in 46% of the children; HBeAg and hepatatis B surface antigen (HBsAg) elimination, together with ALT normalization, was achieved in 14% of the cases.Conclusion: The side-effects of the IFN-alpha therapy in children such as fever, flu-like symptoms and bone marrow suppression are common, but transient and mild.

Subdural empyemas are a rare, life-threatening complication of cerebrospinal meningitis. Two cases of subdural empyemas which occurred as early complications after cerebrospinal meningitis in infants are presented. Utilization of modern diagnostic methods, such as US and CT allowed to establish an early diagnosis, which made it possible to institute appropriate treatment, involving evacuation of the purulent content with local application of antibiotics followed by intravenous antibiotics well penetrating the fluid-filled compartments of the CNS. Early institution of treatment gave a chance of complete recovery in both presented cases.

The purpose of this review was to evaluate possible differentiation between various causes of different types of cholestatic jaundice in children. Analyses were performed in 33 infants from 3 weeks to 3.5 years old with symptoms of cholestatic jaundice. The most frequent causes of cholestasis were congenital atresia of extrahepatic bile ducts (30%) and the CMV infection (20%). On the basis of the performed examinations it should be concluded that in order to differentiate between the causes of cholestatic jaundice it is necessary to do a series of tests as there is no specific diagnostic method which would be effective.