Diagnostic Accuracy of Recombinant Immunoglobulin-like Protein A-Based IgM ELISA for the Early Diagnosis of Leptospirosis in the Philippines

Background Leptospirosis is an important but largely under-recognized public health problem in the tropics. Establishment of highly sensitive and specific laboratory diagnosis is essential to reveal the magnitude of problem and to improve treatment. This study aimed to evaluate the diagnostic accuracy of a recombinant LigA protein based IgM ELISA during outbreaks in the clinical-setting of a highly endemic country. Methodology/Principal Findings A prospective study was conducted from October 2011 to September 2013 at a national referral hospital for infectious diseases in Manila, Philippines. Patients who were hospitalized with clinically suspected leptospirosis were enrolled. Plasma and urine were collected on admission and/or at discharge and tested using the LigA-IgM ELISA and a whole cellbased IgM ELISA. Sensitivity and specificity of these tests were evaluated with cases diagnosed by microscopic agglutination test (MAT), culture and LAMP as the composite reference standard and blood bank donors as healthy controls: the mean+3 standard deviation optical density value of healthy controls was used as the cut-off limit (0.062 for the LigA-IgM ELISA and 0.691 for the whole cell-based IgM ELISA). Of 304 patients enrolled in the study, 270 (89.1%) were male and the median age was 30.5 years; 167 (54.9%) were laboratory confirmed. The sensitivity and ROC curve AUC for the LigA-IgM ELISA was significantly greater than the whole cell-based IgM ELISA (69.5% vs. 54.3%, p<0.01; 0.90 vs. 0.82, p<0.01) on admission, but not at discharge. The specificity of LigA-IgM ELISA and whole cell-based IgM ELISA were not significantly different (98% vs. 97%). Among 158 MAT negative patients, 53 and 28 were positive by LigA- and whole cell-based IgM ELISA, respectively; if the laboratory confirmation was re-defined by LigA-IgM ELISA and LAMP, the clinical findings were more characteristic of leptospirosis than the diagnosis based on MAT/ culture/LAMP. Conclusions/Significance The newly developed LigA-IgM ELISA is more sensitive than the whole cell-based IgM based ELISA. Although the final diagnosis must be validated by more specific tests, LigAIgM ELISA could be a useful diagnostic test in a real clinical-setting, where diagnosis is needed in the early phase of infection

Leptospirosis and Leptospires - The silent assassins

Leptospirosis is one of the most common yet under reported zoonoses. Leptospires, the etiological agents of leptospirosis are ubiquitous pathogens, with a world-wide distribution, causing a spectrum of disease ranging from a mild influenza-like illness to Weil’s disease, which manifests itself in multi-organ failure. The following chapter reports on the epidemiology and transmission of the disease in humans and animals. The chapter will also delineate the symptoms observed in humans and animals and in concluding outline unresolved and evolving issues for microbiologists, epidemiologists and public health officials

Cholera in Oceania

For approximately 200 years, cholera has been feared globally as a disease that can cause rapid-onset epidemics. The causative organisms, Vibrio cholerae O1 and O139 serogroups, are endemic to Southern Asia, but appear to spread globally in waves resulting in seven recognised pandemics to date. The current seventh pandemic has seen the introduction of V. cholerae O1 El Tor into the Oceania region. Since 1962 there have been five large outbreaks at a frequency of approximately one per decade. There have also been regular small outbreaks and clusters of disease throughout the region during the seventh pandemic. The most recent outbreak of cholera in the region occurred in Papua New Guinea in 2009–2011, and this was the largest outbreak to occur in the region to date. In Oceania the majority of people live in high-income settings (Australia and New Zealand) so the risk of cholera transmission is low. Despite this, an estimated 6.5 million people living in the region are at risk of cholera. The most important risk factors are inadequate access to safe water and lack of appropriate sanitation and hygiene measures. However, many other factors may contribute to cholera transmission risk, and people living in Pacific Island countries may be at increased risk in the future due to climate change. Strengthening health delivery services in the region will ensure countries are better equipped to handle future cholera outbreaks; and further understanding the epidemiology of cholera and the causative agent in the region could help prevent future transmission