Leptospirosis Pulmonary Hemorrhage Syndrome In Salvador, Brazil From 2003 - 2012

ABSTRACT Objective: Leptospirosis pulmonary hemorrhage syndrome (LPHS) is a severe form of leptospirosis, with a case fatality rate exceeding 50%. Recently, LPHS has become the principal cause of mortality in leptospirosis patients in Salvador, Brazil. This study aims to describe the epidemiology of LPHS since 2003, characterize its clinical presentation, and identify risk factors. Methods: Patients admitted between January 1, 2003 and December 31, 2012 in the active hospital-based surveillance who met the clinical case definition for leptospirosis were included in the study. A standardized questionnaire was used to collect data from patient charts and in-person interviews. Unadjusted logistic regression models identified individual-level risk factors. Maps showing spatial distribution and clustering of leptospirosis cases were created to identify areas of high risk. Results: We identified 1,316 patients meeting our case definition, which included 113 LPHS, 184 NHPL, and 1019 NPL cases. Males were at greater risk for LPHS in all age groups. The LPHS-associated mortality was 65.5% (95% CI: 56.33-73.63), compared to 30.4% and 6.2% for NHPL and NPL cases, respectively. A lower microagglutination test (MAT) titer compared for LPHS compared to NPL cases in the acute phase suggests the absence of an early robust immune response. A high-risk LPHS cluster (p= 0.01) was identified and rat sightings was associated with NHPL patients (OR: 2.77, 95% CI: 1.23-6.23). Limited unique clinical correlates observed in patients with pulmonary manifestations compared to non-pulmonary forms of leptospirosis. Conclusion: We describe the clinical features and epidemiology of LPHS in Salvador, Brazil, since its emergence in 2003. Few clinical correlates were identified between LPHS and NHPL patients, suggesting that leptospirosis is a disease on a clinical spectrum. Multidimensional control measures focusing on areas of high risk are necessary to reduce the burden of leptospirosis

Measles Virus Infection of Primary Respiratory Epithelial Cells Derived from Rhesus Macaques

Measles remains a leading vaccine-preventable cause of child mortality globally. Although a live-attenuated vaccine against measles virus (MV) is available, measles has been difficult to control. MV is a respiratory infection typically spread by aerosol droplets which target respiratory epithelial cells as initial sites of viral entry and replication. Primary tracheal and nasal epithelial cells (rmTECs/NECs) derived from rhesus macaques serve as an ideal system to study MV infection in the respiratory tract, because: 1) rmTECs/NECs are polarized and differentiated to mimic respiratory epithelium in vivo and 2) rhesus macaques are the only susceptible host to MV infection other than humans. We have optimized a method for culturing well-differentiated polarized rmTECs/NECs and shown that both WT and vaccine strains of MV successfully infect cells from both apical and basolateral surfaces. Though no significant difference in viral infection was observed with an increased duration of infection, viral titers maintained high. Evidence of infection was characterized by observations of changes in cell morphology and titering of infectious virus in the supernatant. A working in vitro model of the respiratory system is important in bringing greater appreciation and understanding for the development of a respiratory vaccine against measles

Measles Virus Infection of Primary Respiratory Epithelial Cells Derived from Rhesus Macaques

Measles remains a leading vaccine-preventable cause of child mortality globally. Although a live-attenuated vaccine against measles virus (MV) is available, measles has been difficult to control. MV is a respiratory infection typically spread by aerosol droplets which target respiratory epithelial cells as initial sites of viral entry and replication. Primary tracheal and nasal epithelial cells (rmTECs/NECs) derived from rhesus macaques serve as an ideal system to study MV infection in the respiratory tract, because: 1) rmTECs/NECs are polarized and differentiated to mimic respiratory epithelium in vivo and 2) rhesus macaques are the only susceptible host to MV infection other than humans. We have optimized a method for culturing well-differentiated polarized rmTECs/NECs and shown that both WT and vaccine strains of MV successfully infect cells from both apical and basolateral surfaces. Though no significant difference in viral infection was observed with an increased duration of infection, viral titers maintained high. Evidence of infection was characterized by observations of changes in cell morphology and titering of infectious virus in the supernatant. A working in vitro model of the respiratory system is important in bringing greater appreciation and understanding for the development of a respiratory vaccine against measles

Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. While neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of TLR2 and TLR4 on peripheral neutrophils compared to healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation) regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.National Institute of Allergy and Infectious Diseases at the National Institutes of Health, United States Department of Health & Human Services, National Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [U01AI088752, AI 089992, AG 042489]; American Society for Tropical Medicine and Hygiene Gorgas Memorial Institute Research Award; Fogarty International Center, Global Health Equity Scholars Fellowship [R25 TW009338]; Fundacao Oswaldo Cruz/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-Ciencia Sem Fronteiras Bolsa Jovens Talentos12 month embargo; published online 22 July 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes