HBV whole-genome mutation profile in HIV-1/HBV coinfected patients in a long-term follow-up study.

PURPOSE: Human immunodeficiency virus (HIV-1)-infected patients frequently harbour hepatitis B and C viruses (HBV and HCV, respectively). Possible modifications of the natural history of hepatitis B may occur. The aim of this study was to characterise HBV diversity and evolutionary and mutational viral genome profiles in HIV-1/HBV coinfections. METHODS: HIV-1 and HBV markers determinations (Roche, FRG; Abbott, USA) and HBV genome-length retrospective analysis were performed in follow-up isolates from patients who were either stably HBsAg-negative with a low level of HBV DNA (occult hepatitis B infection, OBI) or HBsAg-positive with a high level of HBV DNA. Phylogenetic analysis (maximum likelihood method, MEGA5), statistical analysis and evolutionary rates calculation (d S/d N) were applied. RESULTS: Positive selection pressures in the PreS/S region and a significantly higher number of mutations in this region including the major hydrophilic region (MHR) and the "a" determinant were shown in HBsAg-negative (possibly OBI) compared to stably HBsAg-positive HIV-1/HBV subgenotypes D3/A2 coinfected patients. Mutants previously described in HIV-1/HBV coinfected patients were found. Known mutants Y100C, P127T and P120A associated to Y134H and S143T and new S mutants, which may potentially affect HBsAg expression and secretion and anti-HBs binding, were detected in baseline sera persisting up to the end of 9 years follow-up. Known mutations of BCP, Pre-C, C and X regions were also characterised. Natural mutants strictly known as being involved in diagnostic failure were not detected; however, numerous corresponding sites showed amino acid variations. CONCLUSIONS: Evolutionary and genotypic differences observed, particularly in the PreS/S region, between HBsAg-negative (OBI) and HBsAg-positive HIV-1/HBV coinfected patients, may contribute, in association with mutations of other genomic regions, to the HBsAg-negative phenotype.

Genotyping analyses of tuberculosis transmission among immigrant residents in Italy.

We used DNA fingerprinting to analyse tuberculosis (TB) epidemiology in immigrant patients living in two major northern Italian urban areas. The study population included 1999 TB patients (1500 Italian-born and 499 immigrants). Univariate and multivariate logistic regression models were used to identify risk factors related to clustering similar proportions of immigrant and Italian-born patients (46%) had infection with TB strains that belonged to genetic clusters. This supports the hypothesis that the disease in foreign patients is more likely to have arisen from reactivation of latent infection acquired in the country of origin than from recent transmission. Gender, age, human immunodeficiency virus infection and drug resistance were not significantly linked to TB clustering. Risk factors associated with strain clustering were country of origin (Somalia, adjusted OR (AOR) 3.19, p 0.017; Peru, AOR 2.86, p 0.014; and Senegal, AOR 2.60, p 0.045) and city of residence. Immigrant status in the larger urban area was an independent risk factor for infection with clustered TB, as reinforced by a subanalysis of the Senegalese group. In conclusion, variations in TB transmission were observed among immigrants from different countries and even within national groups, where living conditions have been found to exert a profound impact. These results emphasize the importance of improving social integration of immigrant subjects in order to limit risks of TB transmission in developed countries.

Recent acquired STD and the use of HAART in the Italian Cohort of Naive for Antiretrovirals (I.Co.N.A): analysis of the incidence of newly acquired hepatitis B infection and syphilis.

OBJECTIVE: To estimate the incidence of newly acquired syphilis (n-syphilis) and hepatitis B infection (n-hepatitis B) in I.Co.N.A. and to evaluate the impact of HAART, calendar date and risk group. METHODS: Cohort study: Incidence was calculated by person-years analyses. Poisson regression was used for the multivariate model. RESULTS: The rate of n-syphilis was 23.4/1,000 PYFU and it increased over time; HIV transmission risk was the most important predictor: men who have sex with men (MSM) had a considerable higher risk (RR 5.92, 95% CI 2.95-12.13 vs IDU/exIDU, p<0.0001). The rate of n-hepatitis B was 12.2/1,000 PYFU; it declined in recent years and halved per 10 years age. Patients with HIV-RNA<500 copies/ml had a 60% reduced risk of n-hepatitis B if they were treated with HAART compared with not treated individuals. CONCLUSIONS: In our population, the use of HAART was not associated with a higher risk of newly acquired sexually transmitted diseases (STD). Suppressive HAART was associated with a lower risk of HbsAg seroconversion. Incidence of n-hepatitis B has recently been declining possibly due to herd immunity provided by vaccination policies. The risk of acquiring n-syphilis has increased over time and it is higher in the population of MSM compared with other categories of HIV exposure.

Clustering of tuberculosis among senegalese immigrants in Italy.

OBJECTIVE: To study clustered Mycobacterium tuberculosis isolates as an indicator of recent TB transmission in a small urban setting in Italy, and to determine associated risk factors. METHODS: M. tuberculosis strains isolated between 1991 and 1997 were characterised by IS6110 restriction fragment length polymorphism (RFLP) analysis. RESULTS: One hundred and ninety-five isolates were available for RFLP analysis, which revealed 163 different patterns. Available cases were represented by 137 Italians (70%), 32 Senegalese (17%), and 26 other foreign-born cases (13%). A unique fingerprint pattern was found in 143 cases (73.3%), while 52 strains (26.7%) were grouped into 20 clusters. Nineteen cases (10%) were resident in the same quarter of Brescia with a high density of Senegalese immigrants (Area A). An increased probability of yielding clustered M. tuberculosis strains was associated with residence in Area A (OR 3.87, 95%CI 1.42-10.56; P = 0.02) and being Senegalese (OR = 5.96, 95%CI 1.48-23.97; P = 0.005). In the logistic regression analysis, being Senegalese was independently associated with yielding a clustered M. tuberculosis strain. CONCLUSIONS: Our results demonstrate a clustering of TB cases among Senegalese immigrants and suggest that RFLP analysis may be used to identify geographical areas where efforts can be targeted to interrupt TB transmission.

Molecular epidemiology study of exogenous reinfection in an area with a low incidence of tuberculosis.

In geographical areas with a low incidence of tuberculosis, recurrent tuberculosis is generally due to reactivation of the disease. However, the relative contribution of tuberculosis reinfection increases in parallel with the incidence of disease and is likely to depend on the epidemiological context: factors such as the spread of multidrug resistance, human immunodeficiency virus (HIV) infection, and immigration from developing countries could modify disease transmission in areas at low risk for tuberculosis. A molecular epidemiology study was performed in Lombardy, Northern Italy, where the incidence of tuberculosis is 17.5 cases per 100,000 persons. A total of 2,452 cases of culture-confirmed tuberculosis in 2,127 patients were studied. A group of 32 patients (1.5%), each of whom had two episodes of tuberculosis with cure as the outcome of the first episode and with more than 6 months between the two episodes, were studied by means of restriction fragment length polymorphism DNA fingerprinting analysis. For 5 of the 32 patients (16%), the DNA fingerprinting patterns of Mycobacterium tuberculosis strains responsible for the second episode did not match those of the corresponding isolates of the first episode, indicating exogenous reinfection. Two of these patients developed multidrug-resistant tuberculosis during the second episode, and in three cases the isolates belonged to clusters of M. tuberculosis strains spreading in the community. A fourfold-increased risk for reinfection was observed in immigrant patients compared to Italian subjects. In contrast, a higher risk of relapse rather than reinfection was evidenced in HIV-positive subjects and in patients infected with multidrug-resistant tuberculosis. Episodes of tuberculosis reinfection in areas with a low incidence of tuberculosis are rare compared to those in high-incidence geographical regions. In populations that have immigrated from high-risk areas, reinfection may represent a considerable contributor to the rate of recurrent tuberculosis. This finding emphasizes the importance of containing the spread of epidemic strains in close communities, in order to prevent changes in global tuberculosis trends for developed countries.

A case of costochondral abscess due to Corynebacterium minutissimum in an HIV-infected patient.

Corynebacterium minutissimum, known as the causative agent of erythrasma, has recently been reported as a clinically significant pathogen in the immunocompromised host. We report for the first time the possible involvement of a multidrug-resistant C. minutissimum strain in a costochondral abscess occurring in an HIV-infected patient.

Outcome of multidrug-resistant tuberculosis in human immunodeficiency virus-infected patients.

Among 324 cases of culture-proven tuberculosis from 1988 to 1996 in a hospital in Milan, Italy, 90 (27.8%) were due to Mycobacterium tuberculosis strains resistant to isoniazid and rifampin. Sixty-one of 69 isolates tested had identical restriction fragment length polymorphism patterns. The prevalent strain tested susceptible only to ethionamide and was also resistant to ethambutol, streptomycin, cycloserine, amikacin, kanamycin, terizodone, ofloxacin, rifabutin, rifapentin, and KRM 1648. The median survival time was 94 days. Multivariate analysis showed a trend toward better outcome in the period 1994-1996 (hazard ratio, 4.16; P<.001), and extrapulmonary localization of tuberculosis was the only other independent predictor of a negative outcome (hazard ratio, 2.1; P = .019). The delay from symptoms to beginning of therapy did not seem to be a determining factor in survival time. Standard antituberculosis therapy with four drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) had a higher efficacy than did other regimens with fewer drugs but without a statistically significant difference.

Tuberculosis among immigrants from developing countries in the province of Milan, 1993-1996.

SETTING: The Province of Milan, which has high rates of immigration from developing countries, and the Villa Marelli Institute (VMI), Reference Centre for Tuberculosis Control of Lombardy. OBJECTIVE: To describe epidemiology and clinical patterns of tuberculosis among immigrants from developing countries (IDCs) in the Province from 1993 to 1996. DESIGN: Retrospective analysis of the registries of the Regional Bureau for Public Health and of the VMI concerning immigrant patients with active TB living in the Province. Restriction fragment length polymorphism (RFLP) analysis of the available strains to detect recent transmission among immigrants. RESULTS: IDCs represented 22.8% of all TB cases. The standardised incidence rate was eight times higher in IDCs compared to Italians. Of 596 cases notified in IDCs, 524 (87.9%) had been referred at least once to the VMI. Of these, 77.2% were diagnosed within 5 years of arrival, and 86.6% were brought to medical attention because of symptoms. RFLP fingerprinting demonstrated that the mean period of stay in Italy was significantly higher in clustered than in non clustered patients (61.5 versus 37.3 months). Spread to the native population was episodic. CONCLUSIONS: The incidence of TB is higher among more recent immigrants (i.e., Peruvians). TB cases are largely due to reactivation of infection occurring in the country of origin. Preventive measures for early diagnosis of disease or chemoprophylaxis of dormant infection are not regularly performed, but should be implemented for those immigrants at high risk.