Recommendations for the management of acute hepatitis B: position paper of the Italian Society for the Study of Infectious and Tropical Diseases (SIMIT).

PURPOSE: To develop recommendations for the management of acute hepatitis B by the Italian Society for the Study of Infectious and Tropical Diseases. METHODS: Development of the recommendations divided into three levels of evidence according to the GRADE system: A (high), B (medium) and C (low experts opinion), together with three recommendation levels: 1 (strong), 2 (medium), 3 (weak). RESULTS: The treatment with antivirals is in selected cases the mainstay of management of severe acute hepatitis, and should be started as a matter of urgency in order to prevent death. CONCLUSIONS: These recommendations are meant to provide the rationale and practical indications for the management of acute hepatitis B (AHB).

Factors associated with access to antiviral treatment in a multicentre cross-sectional study of patients with chronic hepatitis B in Italy.

A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1-1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1-2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2-6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02-2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4-10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5-0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5-0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5-0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3-0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.

Blood born viral infections, sexually transmitted diseases and latent tuberculosis in italian prisons: a preliminary report of a large multicenter study.

BACKGROUND: Recent screenings of inmates for Hepatitis C virus (HCV), Hepatitis B virus (HBV), human immunodeficiency virus (HIV), Syphilis and Latent Tuberculosis (LTB) did not provide sufficient information to improve healthcare strategies. AIM: To obtain valuable information on the endemicity of the above mentioned Infections in prisons of Italy. MATERIALS AND METHODS: A screening based on a peer-to-peer communication, followed by a month of blood sampling on a voluntary basis was performed to detect antibody to 4 of the 5 above mentioned infections and detect LTB by PPD (purified protein derivative) Skin Test. The present analysis regards data obtained in 9 of the 20 prisons. RESULTS: The percentage of patients who accepted the screening varied between jails (37.3-95.2%, median 62.2), but it was higher than 10.0-20.5% obtained in the same 9 prisons using traditional methods before our intervention. The participation to the screening reached 65.3% for HBV, 64.6% for HCV, 67.4%for HIV, 55.7% for TPHA (Treponema Pallidum Hemagglutination Assay) and 42.8% for LTB. HBsAg was detected in 4.4% of 2265 subjects, anti-HCV in 22.8% of 2241, anti-HIV in 3.8% of 2339 and TPHA in 2.1% of 1932; PPD Skin Test was positive in 17.2% of 1486 subjects. The screening identified 183 subjects with an unknown infection, 56 italian and 127 foreigners to be evaluated for clinical decisions: 35 with HBV chronic infection, 34 with HCV chronic infection, 3 anti-HIV positive, 14 with syphilis and 97 with LTB. CONCLUSIONS: The new approach to the screening, based on a peer-to-peer communication followed by blood sampling on a voluntary basis provided valuable information to improve the healthcare system in each single prison.

The model of response to viral haemorrhagic fevers of the National Institute for Infectious Diseases "Lazzaro Spallanzani".

Viral haemorrhagic fevers (VHF) are severe and life-threatening diseases caused by a range of viruses. However, only four agents of VHF are known to be readily capable of person-to-person spread: Lassa virus, Crimean/Congo haemorrhagic fever virus, Ebola and Marburg viruses. Diseases caused by these viruses are endemic only in few areas in the world, most notably Africa and some rural parts of the Middle East and Eastern Europe. Nonetheless, the increasing volume of international travel presents a greater likelihood for the importation of these infections or of suspected cases in non endemic countries. Four conditions can lead to the importation and to the subsequent recognition of VHF within Europe: 1) patients arriving as a result of a planned medical evacuation; 2) persons who became sick on route to their destination; 3) persons discovered ill when entering a country, for example during routine clinical examination at the airport; 4) persons becoming sick after their arrival. Public health implications and the risk of secondary spread of pathogens in the above reported circumstances are very different. Similarly, preparedness and response should vary. This paper summarizes the present knowledge on the four VHF capable of person-to-person spread, describes the high isolation area constructed at the Italian National Institute for Infectious Diseases Lazzaro Spallanzani in Rome to respond to the occurrence of VHF. A brief overview of procedures and equipment adopted is provided.

Antiretroviral therapy in HIV-infected individuals in clinical practice: are the criteria for initiating and choosing the type of drug regimen based only on immunologic and virologic values?

OBJECTIVES: To determine factors associated with beginning antiretroviral therapy and with the number of drugs used. METHODS: Longitudinal study of 3169 HIV-infected individuals naïve from antiretroviral drugs at enrollment in 65 infectious disease clinics in Italy. Initiation of antiretroviral therapy and number of drugs used (i.e., < 3 vs. > or = 3 drugs) were the main outcome measures. Adjusted odds ratios were calculated by logistic models to establish cofactors of these two measures. RESULTS: From January 1997 to December 1998, 1288 (40.6%) individuals started therapy, 58.0% of whom were given a triple combination regimen. This regimen became more frequent over time. By multivariate analysis, high levels of HIV-RNA and low CD4 counts were the most important independent predictors of starting any type of therapy. A significant association was also found with HIV exposure category, reason for being antiretroviral-naïve, presence/absence of liver disease, presence/absence of a new AIDS-defining disease, and clinical centre. High levels of HIV-RNA and low CD4 counts were also the most important predictors of starting with > or = 3 drugs, compared to < 3 drugs, and men had an independent higher probability of starting with > or = 3 drugs, compared to women. The probability of starting with > or = 3 drugs significantly increased with calendar time. CONCLUSIONS: CD4 and HIV-RNA were the main cofactors of initiating both any type of therapy and therapy with > or = 3 drugs. The large variability among clinical centres suggests that clinicians are uncertain as to the exact timing of beginning therapy and the specific regimen, especially among women.

Fluconazole orally dispersible tablets for the treatment of patients with oropharyngeal candidiasis.

The efficacy and tolerability of fluconazole orally dispersible tablets (ODT) in the treatment of oropharyngeal candidiasis was evaluated in this multicentre non-comparative study. A total of 89 adults with signs and symptoms of oropharyngeal candidiasis were enrolled; 70 of whom completed therapy with fluconazole ODT 100 mg once daily for 7 - 14 days. Acquired immunodeficiency syndrome (AIDS)/ AIDS-related complex was an underlying illness in 69% of patients (61). An antimicrobial and corticosteroid therapy was given in 52% (46) and 20% (18) of patients, respectively. Of the 60 patients who had baseline signs and symptoms of infection and a culture positive for Candida albicans, 90% (54) were cured or had improved at the end of therapy, and the fungal pathogen was eradicated in 19/57 (33%) patients. At the 4-week posttreatment follow-up, signs and symptoms of oropharyngeal candidiasis were absent in 73% (27/37) patients. The adverse events and laboratory abnormalities recorded during the study period were attributable to underlying illnesses rather than to fluconazole therapy. These results indicate that this novel dosage form of fluconazole is effective and well tolerated in the treatment of oropharyngeal candidiasis.

[Diagnostic imaging in AIDS-related pulmonary Kaposi's sarcoma]. / Diagnostica per immagini del sarcoma di Kaposi polmonare nell'AIDS.

INTRODUCTION: Kaposi's sarcoma is an uncommon multifocal angiogenic lesion but the most frequent tumor (15%) in HIV+ patients: it is found in homosexual HIV+ men in 95% of cases and appears as cutaneous-mucous lesions in most patients; the respiratory system is involved in 20% of cases. We investigated the yield of conventional radiography, CT and HRCT in the diagnostic imaging of pulmonary Kaposi's sarcoma. MATERIAL AND METHODS: We retrospectively reviewed the findings of 205 patients with cutaneous Kaposi's sarcoma. Chest radiography (two projections) had been performed in all of them, chest CT in 23, HRCT in 7, and tracheobronchial endoscopy in 20. RESULTS: The respiratory system was involved in 22% of the patients with cutaneous-mucous Kaposi's sarcoma. The pulmonary pattern was perivasculobronchial interstitial thickening with bilateral and symmetrical ilifugal involvement in 78% of cases, associated with multiple perivascular nodular opacities (< 1 cm) in 19 patients. Pleural effusion was seen in 52% of cases, while 3 patients had plaque thickening of visceral pleura; mediastinal adenopathy was found in 8.6% of cases. Endoscopy detected 14 tracheobronchial Kaposi's lesions. Kaposi's involvement of the respiratory system was confirmed histologically in 26 autopsy cases. CONCLUSIONS: In our experience, conventional radiology and clinical-history data permit to evaluate early pleuropulmonary involvement of Kaposi's sarcoma and to follow its evolution. CT and HRCT unquestionably detect the typical signs earlier than conventional radiology and yield further information on disease extent.

A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection.

This study assessed the activity and tolerability of an HIV-protease inhibitor, saquinavir, alone or in combination with zidovudine. A total of 92 previously untreated HIV-infected patients with CD4 cell counts < 300 cells/mm3 participated in a parallel, randomized double-blind study. Patients were randomized to receive one of five treatments, each three times a day: 600 mg of saquinavir; 200 mg of zidovudine; 75, 200 or 600 mg of saquinavir in combination with 200 mg of zidovudine. The primary treatment period was 16 weeks, with monthly extensions in patients who did not show major disease progression or toxicity. The main measures of the efficacy of therapy used were changes in CD4 cell counts and in the concentration of HIV-1 RNA in the plasma (as determined by quantitative polymerase chain reaction). The 600 mg dose of saquinavir in combination with zidovudine induced a 1.6 log (after 4 weeks) and a 0.7 log (after 16 weeks) median reduction in plasma RNA concentration; this reduction was greater than those seen in the other four treatment groups. The combination of 600 mg of saquinavir with zidovudine also resulted in a larger and more sustained improvement in the CD4 cell count than either saquinavir or zidovudine monotherapy or the other combination therapies. In the group receiving 200 mg of saquinavir in combination with zidovudine, the maximal median change in CD4 cell count occurred at week 2 (85 cells/mm3), and by week 16 had fallen to 15 cells/mm3. In the group receiving 600 mg of saquinavir plus zidovudine, the median change in CD4 cell count remained high for the 16-week period (median change of 48 cells/mm3 at week 2 and 61 cells/mm3 at week 16). Saquinavir was safe and very well tolerated, either alone or in combination with zidovudine. The incidence of adverse events was greater in the four groups receiving zidovudine therapy, and all the most commonly reported adverse events have previously been associated with zidovudine therapy. Few changes in laboratory values occurred during the study, except for known zidovudine-associated toxicities. The most frequent abnormalities were raised aspartate aminotransferase and alanine aminotransferase levels, depressed calcium levels, and abnormally high or low phosphate levels. Despite the low oral bioavailability of saquinavir, combined virological and immunological data show definite antiviral activity in vivo for the combination of saquinavir at 600 mg plus zidovudine at 200 mg (each three times daily). The combination of drugs with different mechanisms of action represents an advance in the treatment of HIV infection.

Tuberculosis and AIDS: a retrospective, longitudinal, multicentre study of Italian AIDS patients. Italian group for the study of tuberculosis and AIDS (GISTA)

We report the results of a retrospective, longitudinal, multicentre study which estimated the cumulative incidence of tuberculosis in patients who eventually develop AIDS, investigated the characteristics of AIDS patients in relation to the development of tuberculosis, and endeavoured to determine the degree of HIV-induced immunosuppression at which tuberculosis occurs. The Infectious Disease Units of 23 hospitals located in 11 of the 20 regions of Italy participated in this study. We investigated 1691 patients with AIDS diagnosed in 1988 and 1989 and reported to the National AIDS Registry by participating units before the end of December 1990. By that time M. tuberculosis had been cultured from 193 patients (11.4%). Compared with intravenous drug users (the largest HIV transmission category), only homosexual men had a statistically significant lower risk of tuberculosis (relative risk = 0.65; 95% confidence interval 0.43-0.99). The median count of CD4+ lymphocytes at the time tuberculosis was diagnosed was 82/mm3 (range 1-752); only four patients (2.1%) had CD4+ lymphocyte counts of more than 500/mm3, and 36 (18.7%) of over 200/mm3. We conclude that in Italy the proportion of AIDS patients who develop tuberculosis is higher than in other industrialised countries and differences in the incidence of tuberculosis among various HIV-transmission categories are less marked than in other western countries. Tuberculosis associated with HIV infection may occur in those with widely differing CD4+ counts, although the risk increases consistently in proportion to the degree of immunosuppression.

Tuberculosis in HIV-infected subjects in Italy: a multicentre study. The Gruppo Italiano di Studio Tubercolosi e AIDS.

OBJECTIVES: To evaluate the strength of the association between tuberculosis and HIV infection in Italy, to assess the pattern of this association in relation to HIV transmission categories, and to describe clinical presentation of tuberculosis in a large group of Italian HIV-infected subjects. DESIGN: Multicentre review of clinical records. SETTING: Twenty-one infectious disease hospital units in nine of the 20 administrative regions of Italy. PATIENTS, PARTICIPANTS: All HIV-infected adults observed by each participating unit (in- and outpatients) between 1985 and 1989. MAIN OUTCOME MEASURE: Culture-proven tuberculosis. RESULTS: A total of 306 cases of tuberculosis were observed. Of these, 85 were pulmonary, 167 extrapulmonary, and 54 both pulmonary and extrapulmonary. The proportion of HIV-infected subjects diagnosed with tuberculosis increased during the study period from three out of 1380 (0.2%) in 1985 to 152 out of 6504 subjects (2.3%) in 1989 (P less than 0.0001). Two hundred and twenty-six of the 2760 (8.19%) patients with AIDS had tuberculosis within 12 months of AIDS diagnosis; the proportion of AIDS patients with tuberculosis remained stable after 1985. Compared with AIDS patients who were intravenous drug users, only homosexual AIDS patients had a significantly lower proportion of tuberculosis (178 out of 1958 versus 30 out of 522; P less than 0.02). CONCLUSIONS: Our data show that tuberculosis is quite common among HIV-infected subjects in Italy, and suggest that the risk of tuberculosis in these subjects has not changed. There are some differences between the pattern of the association between tuberculosis and HIV infection in Italy, compared with other industrialized countries.

The efficacy and safety of imipenem/cilastatin in the treatment of severe bacterial infections.

We have assessed the efficacy and safety of imipenem/cilastatin in a non-comparative study of 27 immunocompromised patients suffering from severe bacterial infections. Moreover in two groups of 14 patients the efficacy of imipenem/cilastatin versus a standard broad spectrum antibiotic therapy has also been compared. Clinical and microbiological efficacy and side effects have been evaluated.

A case of falciparum malaria acquired in Italy.

The first case of Plasmodium falciparum malaria acquired in Italy after the eradication of the disease is reported. The P. falciparum strain was sensitive to chloroquine in vitro and in vivo. It seems most likely that an infective mosquito of tropical origin was responsible for transmission.

Post-varicella acute transverse myelitis.

This report of a case of acute transverse myelitis, after otherwise uneventful varicella, further stresses the importance that the possibility of this relatively rare complication should be kept in mind in patients developing a paraplegic syndrome late in the course of the disease.