Archive for August 13, 2015

Current immunological and molecular tools for leptospirosis: diagnostics, vaccine design, and biomarkers for predicting severity.

Ann Clin Microbiol Antimicrob. 2015 Jan 16;14:2.

Rajapakse S1, Rodrigo C2, Handunnetti SM3, Fernando SD4.

Author information

1Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo, 08, Sri Lanka. senaka@med.cmb.ac.lk

2Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo, 08, Sri Lanka. chaturaka.rodrigo@gmail.com

3Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka. shiromah@gmail.com

4Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. ferndeep@gmail.com

Abstract

Leptospirosis is a zoonotic spirochaetal illness that is endemic in many tropical countries. The research base on leptospirosis is not as strong as other tropical infections such as malaria.

However, it is a lethal infection that can attack many vital organs in its severe form, leading to multi-organ dysfunction syndrome and death.

There are many gaps in knowledge regarding the pathophysiology of leptospirosis and the role of host immunity in causing symptoms.

This hinders essential steps in combating disease, such as developing a potential vaccine. Another major problem with leptospirosis is the lack of an easy to perform, accurate diagnostic tests. Many clinicians in resource limited settings resort to clinical judgment in diagnosing leptospirosis.

This is unfortunate, as many other diseases such as dengue, hanta virus, rickettsial infections, and even severe bacterial sepsis, can mimic leptospirosis. Another interesting problem is the prediction of disease severity at the onset of the illness.

The majority of patients recover from leptospirosis with only a mild febrile illness, while a few others have severe illness with multi-organ failure.

Clinical features are poor predictors of potential severity of infection, and therefore the search is on for potential biomarkers that can serve as early warnings for severe disease.

This review concentrates on these three important aspects of this neglected tropical disease: diagnostics, developing a vaccine, and potential biomarkers to predict disease severity.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299796/pdf/12941_2014_Article_60.pdf

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August 13, 2015 at 3:23 pm

Leptospirosis in humans.

Curr Top Microbiol Immunol. May 2015;387:65-97.

Haake DA1, Levett PN.

Author information

1Division of Infectious Diseases, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA, dhaake@ucla.edu

Abstract

Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding.

Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine.

Although many wild and domestic animals can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis.

The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change.

Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic.

Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age.

High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10.

Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever.

Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to multisystem organ failure have widespread hematogenous dissemination of pathogens.

Nonoliguric (high output) renal dysfunction should be supported with fluids and electrolytes. When oliguric renal failure occurs, prompt initiation of dialysis can be life saving.

Elevated bilirubin levels are due to hepatocellular damage and disruption of intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of bile caniliculi.

Hemorrhagic complications are common and are associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive alveolar hemorrhage has a fatality rate of >50 %.

Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Peña-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005).

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442676/pdf/nihms690013.pdf

August 13, 2015 at 3:21 pm

Polymerase chain reaction-based assays for the diagnosis of human brucellosis.

Ann Clin Microbiol Antimicrob. 2014 Aug 1;13:31.

Wang Y, Wang Z, Zhang Y, Bai L, Zhao Y, Liu C, Ma A, Yu H.

Abstract

Polymerase chain reaction (PCR) is an in vitro technique for the nucleic acid amplification, which is commonly used to diagnose infectious diseases.

The use of PCR for pathogens detection, genotyping and quantification has some advantages, such as high sensitivity, high specificity, reproducibility and technical ease.

Brucellosis is a common zoonosis caused by Brucella spp., which still remains as a major health problem in many developing countries around the world.

The direct culture and immunohistochemistry can be used for detecting infection with Brucella spp. However, PCR has the potential to address limitations of these methods.

PCR are now one of the most useful assays for the diagnosis in human brucellosis. The aim of this review was to summarize the main PCR techniques and their applications for diagnosis and follow-up of patients with brucellosis.

Moreover, advantages or limitation of the different PCR methods as well as the evaluation of PCR results for treatment and follow-up of human brucellosis were also discussed.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236518/pdf/s12941-014-0031-7.pdf

August 13, 2015 at 3:18 pm


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