Brucellosis with erythema nodosum-like manifestations diagnosed by isolated positivity of the ELISA test for anti-Brucella IgM.

Brucellosis is endemic in the Mediterranean area. In spite of the false negative results, the standard agglutination test remains the routine test for the diagnosis of brucellosis in southern Italy. We present a case of a patient with undulant fever and erythema nodosum-like skin lesions, with negative serum agglutination test, but isolated positivity of the ELISA test for anti-Brucella IgM. A diagnosis of brucellosis for this patient was supported by the anamnestic and clinical data, and by the response to therapy. This case and a review of the literature urge us to consider the ELISA test indispensable for the serological diagnosis of brucellosis.

Sensitive ELISA for IgG and IgM anti-albumin autoantibodies not influenced by HBsAg-associated polyalbumin receptors.

An enzyme immunoassay for the detection of IgG and IgM anti-polymerized albumin autoantibodies (AAA) is described. It was found that polyalbumin receptors on HBsAg particles interfere in the detection of IgG AAA when polymerized human albumin (pHSA), but not polymerized bovine albumin (pBSA), is used as coating antigen. Polyalbumin receptors do not appear to interfere in the detection of IgM AAA, with either pHSA or pBSA as coating antigen. All normal sera showed evidence of AAA, of both IgG and IgM classes. Levels of IgG and IgM AAA in sera from most type A and type B acute hepatitis patients were above the range of normal controls. ELISA detection of AAA distinct from HBsAg reactivity can help in understanding the role of these autoantibodies in HBV infection.

Effect of prednisone priming followed by alfa-interferon in treatment of children with chronic hepatitis B: an interim analysis of a controlled trial.

A six-month analysis of a controlled trial on the treatment of chronic hepatitis B in children shows that prednisone priming followed by alpha-interferon 2A was effective in 6 of 9 treated patients in reducing HBV replication and disease activity.

Outbreak of cutaneous larva migrans in Naples, southern Italy.

An outbreak of cutaneous larva migrans occurring in Naples, southern Italy, and involving 6 people is described. The infection was contracted in the area of Naples, through contact with material for dried floral arrangements most probably contaminated with dog or cat faeces. The factors that contributed to creating ideal conditions for the development and spread of this infection in this area are discussed.

Relation of changes in hepatitis B virus replication markers to the outcome of interferon treatment in patients with chronic hepatitis.

The relationship between the behavior of hepatitis B virus (HBV) replication markers and the response to treatment with recombinant alpha-2b interferon (IFN) was investigated in 11 patients with chronic hepatitis. At the end of 6 months of treatment, 4 patients showed a complete response to IFN: 2 more patients had seroconversion to HBeAb after 8 and 9 months of follow-up, respectively. The response to IFN was partial in the remaining patients. Pre-treatment levels of HBV DNA in patients showing complete response were lower than pre-treatment levels in patients with partial response: in addition, serum HBV DNA clearance during the treatment was associated with sustained remission more frequently than changes in the HBeAg/HBeAb system.

Quantitative viremia test for early prediction of a biochemical response in patients with chronic hepatitis C treated with interferon.

To evaluate the importance of the changes in viremia as an early predictor of the outcome of interferon (IFN) therapy, we assayed the levels of hepatitis C virus (HCV)-RNA in stored serum samples obtained from 34 patients with chronic hepatitis C who showed different biochemical responses to therapy. Serum samples obtained before the start of therapy and after 1 and 3 months were used, and viremia levels were determined by "branched DNA (bDNA)" technique. Viremia levels at 1 month of therapy were lower than pre-therapy levels in all 19 patients who had shown a persistent normalization of ALT during therapy (responder patients). The bDNA test was negative, i.e. the levels of viremia were below the sensitivity threshold of the method, in 12 (63.1%) patients at 1 month and in 13 (68.4%) at the 3rd month of therapy, whereas the bDNA test was negative in none of the 15 non-responder patients at the 1st month and in only 2 (13.3%) of them at the 3rd month of therapy. The bDNA test was superior to the ALT test both in predicting the non-response and the biochemical response to IFN after 1 month of therapy. The bDNA test results, instead, were not predictive of the duration of the response to IFN, either at the 1st or 3rd months of therapy. These results seem to indicate the usefulness of measuring the HCV-RNA levels at the beginning and after 1 month of IFN therapy in order to envisage or exclude a possible biochemical response early on in treatment.

Levels of anti-albumin autoantibodies in acute and chronic hepatitis B virus infection.

Levels of anti-albumin autoantibodies (AAA) of the IgG class were determined by ELISA in sera of patients with acute and chronic hepatitis B virus (HBV) infection. Mean AAA levels were higher than normal in both acute and chronic hepatitis patients. AAA levels were higher than the upper normal limits in practically all patients with acute self-resolving hepatitis, and decreased to normal levels when the patients recovered. Enhanced IgG AAA levels were observed in many patients with chronic hepatitis and serological markers of HBV replication. Elevated AAA levels were not associated with either more elevated transaminase levels or more severe histological forms of chronic hepatitis. The results of this study suggest that the interaction of albumin with HBV determinants is involved in AAA elevations, probably by mediating an increase in albumin immunogenicity. Moreover, the fall in AAA levels in the recovery phase of acute hepatitis, the coexistence of elevated levels with HBeAg and HBV-DNA, and the lack of correlation between AAA levels and different evolutive forms of chronic hepatitis, seem to exclude AAA from playing a relevant role, be it protective or damaging, during HBV infection.

HBsAg carriers among blood donors in Italy; a retrospective survey of data from 189 blood banks.

Data of occasional or periodic blood donors from 189 banks scattered throughout Italy were retrospectively surveyed for the period between 1974 and 1977. The prevalence of HBsAg positive subjects (PHA or RIA) among occasional donors during 1975-1977 was about 3% with no appreciable annual variation. The rate of HBsAg positivity in southern Italy (i.e. Campania, 4.32%) was higher than in northern Italy (i.e. Trentino, 0.30%). Only 0.27% of the occasional donors showed both HBsAg positivity and elevated serum transaminases levels. Among periodic donors the rate of infection, as indicated by the appearance of HBsAg in serum subsequent to the last donation, was approximately 0.5% per year. Only one-tenth of the periodic donors who acquired HBsAg also had hypertransaminasemia.

Immunosuppressive therapy in chronic active hepatitis (CAH). A multicentric retrospective study on 867 patients. A report from a study group for CAH of the Italian Association for the study of the liver.

We retrospectively reviewed the clinical, biochemical and histological features of 867 patients with biopsy-proven CAH observed in 12 Italian Liver Units for at least one year. Either HBsAg positive or HBsAg negative patients (473 and 394 patients, respectively) were left untreated, or were treated with one of the following regimens: a) prednisolone or prednisone 10 to 30 mg daily, referred to as Steroids; b) azathioprine 50 to 100 mg daily; c) prednisolone or prednisone 10 to 20 mg daily associated with azathioprine 50 to 100 mg daily, referred to as Combination. The outcome was evaluated on the basis of clinical, biochemical and histological parameters. Among the 473 patients with HBsAg positive CAH those treated with combination, as compared to those untreated, more frequently, improved (P less than 0.001), and less frequently deteriorated (P less than 0.001). Under Steroids or Azathioprine improvement was more frequent than in untreated patients, but deterioration was not prevented. The results were similar among the 394 HBsAg negative patients. The data indicate that combination is effective in treating either HBsAg positive CAH or HBsAg negative CAH.

The etiology of chronic hepatitis in Italy: a multicenter study.

In a multicenter retrospective study, we reviewed the etiology of chronic hepatitis (CH) in Italy during the period 1980-1989, before the laboratory diagnosis of HCV hepatitis had become possible. Among the 5,461 patients investigated, 31.3% had HBV-CH, 5.5% HDV-CH, 3.0% serological markers of autoimmune hepatitis and 3.7% post-transfusion NANB CH. Alcohol abuse was considered responsible in 10.9% of the cases and a diagnosis of crytogenic CH was made in 42.5%. Considering that most cryptogenic cases were actually due to chronic HCV infection, we may assume that as many as two-thirds of our cases were due to a hepatitis virus infection. Some differences were observed between patients with chronic hepatitis of different etiologies. Drug abuse was frequently recorded only in HDV-CH; patients with HBV-CH and HCV-CH were younger than those in other etiological groups; a histological picture of chronic active hepatitis was more frequently recorded in HDV-CH and autoimmune CH. The only identifiable geographical differences observed were a higher prevalence of HDV-CH in the south and of alcoholic chronic liver diseases in the north. During the period under observation, we noted a clear reduction in the percentages of HBV chronic hepatitis cases after 1984 and, accordingly, the mean age of HBV-CH progressively increased from 1980 to 1989 by almost a year each year. This observation is in agreement with recent data suggesting a reduction in HBV endemicity in Italy in recent years.

Treatment of chronic active hepatitis (CAH): a retrospective review of 130 patients.

The authors review the course of disease in 130 patients (87 HBsAg-positive and 43 HBsAg-negative) with chronic active hepatitis (CAH) observed in the last six years. Patients were treated with prednisone (36 HBsAg-positive an 8 HBsAg-negative), azathioprine (7 HBsAg-positive and 12 HBsAg-negative) or a combination of prednisone and azathioprine (23 HBsAg-positive and 14 HBsAg-negative), or remained untreated (21 HBsAg-positive and 9 HBsAg-negative). Among HBsAg-positive patients improvement was observed in 54% of the 66 patients treated, and in none of the 21 untreated patients (P less than 0.001). Treatment did not modify the course of the disease in HBsAg-negative patients with CAH; this is probably related either to the small number of patients in each treatment group, or to geographical differences. Furthermore treatment was not effective in patients older than 40 years, whether HBsAg-positive or HBsAg-negative. Three out of 87 HBsAg-positive patients, and two out of the 43 HBsAg-negative patients had died by the end of the observation period irrespective of treatment. Full remission with clearance of HBsAg was observed only in one patient after 4 years of treatment with steroids.

[Diagnosis of HCV infection by 3rd-generation ELISA in HCV-RNA positive hypertransaminasemic patients with 2nd-generation ELISA negative results]. / Diagnosi di infezione da HCV con ELISA di 3 generazione in pazienti con ipertransaminasemia cronica HCV-RNA positivi ma negativi all'ELISA di 2 generazione.

To evaluate the improved sensitivity of 3rd-generation assays for the detection of ani-HCV antibodies in diagnosing cases of HCV infection, we have re-tested by 3rd-generation ELISA test (ELISA-3) serum samples from immunocompetent patients with chronic hypertransaminasemia who were HCV-RNA positive but tested negative with 2nd-generation ELISA (ELISA-2). Out of 21 HCV-RNA positive/ELISA-2 negative samples, 3 (14.3%) were ELISA-3 positive. Among the ELISA-3 reactive samples, two were indeterminate by RIBA-3 (one was reactive with c1 00 and the other with c22), and one was negative. These results demonstrate that even in the clinical setting ELISA-3 improves the diagnosis of HCV infection. The improvement seems to be related to a better reactivity of HCV peptides rather than to the inclusion of the new determinant NS5. However, the sensitivity of the tests for the detection of anti-HCV antibodies remains to be improved.

Biochemical response to interferon of chronic hepatitis in drug-addict patients infected with human immunodeficiency virus.

The effects of IFN treatment were retrospectively evaluated for 18 drug-addict patients with symptomatic HIV infection and chronic hepatitis C. Most of the patients were receiving concomitant treatment with zidovudine. Seven out of the 18 patients (39%) stopped IFN after less than three months, most of them for non-compliance. Among the 11 patients who completed a 6-12 month period of IFN treatment, 3 (27%) normalized and maintained normal ALT levels during therapy: for 2 of them the response was sustained after IFN discontinuation. The response to IFN therapy was neither correlated to the CD4+ levels nor to the clinical stage of the HIV infection. Instead, the response seemed to be influenced by pre-therapy ALT levels and liver histology. Tolerance to IFN treatment was good. These data show that IFN may be indicated in the therapy of chronic HCV infection for HIV-positive patients.

[Congenital cytomegalic disease. Current possibilities and prospects of prevention]. / Malattia citomegalica congenita. Possibilità attuali e prospettive di prevenzione.

Congenital CMV infection occurs frequently as a consequence of primary maternal CMV infection during pregnancy: clinical abnormalities are present at birth or may become apparent later in about 25% of infected infants. Transmission of CMV to the fetus occurs less frequently as a consequence of CMV reactivation in immune mothers, and is rarely associated with clinical manifestations at birth or long-term sequelae. The incidence of congenital CMV infection can be reduced by avoiding primary infection during pregnancy and knowledge of the epidemiology of CMV infection allows physicians to inform pregnant women on major risk factors. Since vaccination of nonimmune women could prevent congenital disease, the development of a suitable and safe CMV vaccine would be desirable. New anti-viral agents with anti-CMV activity are expected to be lifesaving in infants with disseminated visceral disease; moreover, if safe, they could be used to treat CMV disease prenatally. If effective anti-CMV drugs were available the development of simple, rapid and inexpensive methods for the early diagnosis of congenital CMV infection would become more urgent. Instruction of parents, family doctors and all those involved in child care can improve prevention of congenital CMV infection.

[Prevention of congenital toxoplasmosis]. / Prevenzione della toxoplasmosi congenita.

Toxoplasma gondii can be transmitted from mother to fetus during primary maternal infection acquired after or, possibly, slightly before conception. The incidence of congenital infection is highest in the third trimester, while severity is greatest when maternal infection is acquired during the first trimester. About 50 per cent of mothers who acquire the infection during gestation, if not treated, will give birth to infected infants. Incidence of congenital toxoplasmosis varies from 0.5 to 6.5 cases per 1000 live births. Serologic screening before or very early in pregnancy is required to identify seronegative women who are at risk to acquire the infection during pregnancy. Prevention of congenital toxoplasmosis is obtained by educating pregnant women at risk about how to prevent the infection and by diagnosing acute infection of mother. Every mother who demonstrates seroconversion for toxoplasmosis during pregnancy has to be treated as soon as possible. Therapy is based on spiramycin that achieves high concentrations in the placenta; if the fetus is infected pyrimethamine plus sulphonamides are administered since fourth month. Chemotherapy of the infected pregnant mother reduces the incidence of congenital toxoplasmosis and the severity of the disease in the newborn. Intrauterine infection can be detected by fetal blood sampling, by amniocentesis and ultrasound examination; prenatal diagnosis is mandatory if an abortion is being considered.