Clinical characteristics and risk factors of human leptospirosis in Argentina (1999-2005)

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-11-12T11:49:21Z No. of bitstreams: 1 Vanasco N Clinical characteristics and risk....pdf: 244738 bytes, checksum: c222162978cf0b6a2679cce149ed1100 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-11-12T12:05:28Z (GMT) No. of bitstreams: 1 Vanasco N Clinical characteristics and risk....pdf: 244738 bytes, checksum: c222162978cf0b6a2679cce149ed1100 (MD5)Made available in DSpace on 2015-11-12T12:05:28Z (GMT). No. of bitstreams: 1 Vanasco N Clinical characteristics and risk....pdf: 244738 bytes, checksum: c222162978cf0b6a2679cce149ed1100 (MD5) Previous issue date: 2008Instituto Nacional de Enfermedades Respiratorias. INER “Dr. E. Coni”. Administración Nacional de Laboratorios e Institutos de Salud. ANLIS Dr. Carlos G. Malbrán. Santa Fe, Argentina / Facultad de Bioquímica y Ciencias Biológicas. Santa Fe, ArgentinaInstituto Nacional de Enfermedades Respiratorias. INER “Dr. E. Coni”. Administración Nacional de Laboratorios e Institutos de Salud. ANLIS Dr. Carlos G. Malbrán. Santa Fe, ArgentinaFacultad de Bioquímica y Ciencias Biológicas. Santa Fe, ArgentinaFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Weill Medical College of Cornell University. Division of International Medicine and Infectious Disease. NY, USAINTA. Rafaela, ArgentinaThere is scarce data on the burden of leptospirosis and its epidemiological characteristics in Argentina. This study aimed to evaluate distribution of leptospirosis cases and identify risk factors for the disease during national laboratory-based surveillance. From January 1999 to December 2005, 812 suspected cases were referred to the national reference laboratory, of which 182 and 463 had respectively, laboratory confirmed and unconfirmed diagnosis of leptospirosis. The diagnosis of leptospirosis was discarded in 167 cases. The most prevalent presumptive infecting serogroup was Icterohaemorrhagie followed by Pomona, Ballum and Canicola. The majority of cases occurred during the worm and rainy months. Confirmed cases were predominantly adults and males, who presented with fever, headache and myalgias. Severe clinical manifestations included jaundice and acute renal insufficiency. Conjunctival suffusion, a hallmark clinical sign of leptospirosis, was found in 55% of confirmed cases, and 43% of the cases with discarded diagnosis (p=0.036). After multivariate analyses, age >30 years (OR=2.16; 1.05-4.41), occupation in a rural setting (OR=3.41; 1.45-8.06), contact with contaminated surface water (OR=2.17; 1.01-4.68), and contact with floods (OR=4.49; 1.17-17.25) were significantly associated with leptospirosis. In conclusion, although activities associated with rural occupations remain important risk factors in Argentina, exposures occurring during flooding events have emerged to be the major risk factor for leptospirosis

14-3-3 proteins regulate exonuclease 1-dependent processing of stalled replication forks

Replication fork integrity, which is essential for the maintenance of genome stability, is monitored by checkpoint-mediated phosphorylation events. 14-3-3 proteins are able to bind phosphorylated proteins and were shown to play an undefined role under DNA replication stress. Exonuclease 1 (Exo1) processes stalled replication forks in checkpoint-defective yeast cells. We now identify 14-3-3 proteins as in vivo interaction partners of Exo1, both in yeast and mammalian cells. Yeast 14-3-3-deficient cells fail to induce Mec1-dependent Exo1 hyperphosphorylation and accumulate Exo1-dependent ssDNA gaps at stalled forks, as revealed by electron microscopy. This leads to persistent checkpoint activation and exacerbated recovery defects. Moreover, using DNA bi-dimensional electrophoresis, we show that 14-3-3 proteins promote fork progression under limiting nucleotide concentrations. We propose that 14-3-3 proteins assist in controlling the phosphorylation status of Exo1 and additional unknown targets, promoting fork progression, stability, and restart in response to DNA replication stress