TUBERCOLOSI POLMONARE, EXTRAPOLMONARE E DISSEMINATA A CONFRONTO: ANALISI CLINICA ED EPIDEMIOLOGICO-MOLECOLARE NELL'AREA URBANA DI MILANO, 1996-2010.

Pulmonary, extrapulmonary and disseminated tuberculosis compared: clinical and molecular-epidemiological analysis into the metropolitan area of Milan, 1996-2010. BACKGROUND: The increases in lymphonodal extra-pulmonary tuberculosis (LEPTB), other extrapulmonary tuberculosis (EPTB) and disseminated TB (DTB) have been attributed to human immunodeficiency virus co-infection. The decline of AIDS cases due to the efficacy of HAART could have repercussions on the change of host-related risk factors for these forms of TB. Therefore, we carried out a study to compare epidemiological and microbiological characteristics between DTB, EPTB and PTB patients in Italy. A correlation between molecular profile of Mycobacterium tuberculosis clinical isolates and site of TB was assessed. METHODS: A cohort of PTB, LEPTB EPTB, DTB patients was compared. Enrollees were assessed for TB risk, medical records were reviewed, A 14-year retrospective analysis was carried out on tuberculosis (TB) patients diagnosed into metropolitan area of Milan. Characteristics of epidemiological, microbiological and clinical features were obtained from medical case records. The genotypic profile of the available clinical isolates was obtained by Spoligotyping method. The association with the correspondent lineages was based on SPOLDB4.0 database. Risk factors for being either a DTB, or an EPTB patient relative to a PTB patient were identified using logistic regression analysis. RESULTS: 1579 TB cases were analysed. PTB were clearly prevalent with 1219 episodes (77.2%), EPTB were 130 (8.2%), LEPTB amounted to 115 (7.3%) as well as those DTB (7.3%). Among EPTB the most frequent were genitourinary (42.3%), bone (23.1%) and CNS (14.6%). Age> 50 years was associated with EPTB (2.41 [1.45 to 4.02], p <0.001). According to gender, the female sex is associated with LEPTB (1.80 [1.20 to 2.70], p <0.005). The risk of developing LEPTB was more than four times for Africans (4.62 [2.52 to 8.46], p <0.0001), whereas patients coming from Eastern Europe had a higher risk of having PTB. The Asian subjects (3.39 [1.56 to 7.36], p <0.002), Africans 3.48 [1.83 to 6.64], p <0.0001 and South America patients (1.97 [1.06 to 3 , 66], p <0.031) had a significantly higher risk of developing DTB. For HIV infected patients the risk of having other than tuberculosis in lung was significantly higher: about doubled in LEPTB (2.18 [0.99 to 4.80], p <0.053) and more than six times to those DTB (6.63 [3.79 to 11.57], p <0.0001). For extrapulmonary localization in the CNS and gastrointestinal there was a significant association with HIV infection (7.88 [3.07 to 20.23], p <0.0001) which is not found in the genito-urinary and bone forms (0.74 [0.21 to 2.52], p <0.65). Pulmonary forms were significantly associated with an increased risk of multidrug-resistance than disseminated ones (0.21 [0.05 to 0.92], p <0.039). Of 1579 M. tuberculosis clinical isolates, based on Spoligopattern, 1420 (89.9%) were uniquely associated with a STI known, distributed into 13 major lineage. The most represented family was T genotype with 518 isolates (36.4%), followed by families H, Latin And Mediterranean, U and Beijing respectively comprising 235 (16.5%), 209 (14.7%), 153 (10.8%) and 93 (6.5%) strains. These five lineage aggregated about 85% of the total isolates. Stratifying the lineages respect to the sites of disease specific differences emerged. Multivariate analysis confirmed EAI (3.78 [1.08 to 13.26], p <0.038), Beijing (3.94 [1.15 to 13.51], p <0.029) and CAS (4.64 [1.38 to 15.61], p <0.013) were significantly associated with LEPTB. CONCLUSION: Overall EPTB and DTB differed substantially from the more frequent PTB. Inside the heterogeneous group of EPTB, LEPTB showed peculiarities as follows: they were significantly prevalent among female, in younger, Africans and HIV patients. Three genotypes, EAI, CAS and Beijing, were preferentially associated with LEPTB.