Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. We conducted a prospective, clinical study to compare the efficacy and safety of a 7-day course of oral albendazole with a single dose of oral ivermectin, or double doses, given 2 weeks apart, of ivermectin in Thai patients who developed this infection. Patients were regularly followed-up after initiation of treatment, until one year after treatment. Ninety patients were studied (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). The average duration of follow-up were 19 (range 2–76) weeks in albendazole group, 39 ( range 2–74) weeks in single dose ivermectin group, and 26 ( range 2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively. No serious adverse event associated with treatment was found in any of the groups. Therefore this study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis

Strategies for Diagnosis and Treatment of Suspected Leptospirosis: A Cost-Benefit Analysis

Symptoms and signs of leptospirosis are non-specific. A number of diagnostic tests for leptospirosis are available. We compared the cost-benefit of 5 management strategies: 1) no patients tested or given antibiotic treatment; 2) all patients given empirical doxycycline treatment; patients given doxycycline when a patient is tested positive for leptospirosis using: 3) lateral flow; 4) MCAT; 5) latex test. Outcomes were measured in duration of fever which is then converted to productivity losses to capture the full economic costs. Empirical doxycycline treatment was found to be the most efficient strategy, being both the least costly alternative and the one that resulted in the lowest average duration of fever. The significantly higher relative cost of using a diagnostic test as compared with presumptive treatment, and the limited sensitivity of all the diagnostic tests implied that only the latex test could be considered cost-effective when compared with the no-antibiotic-treatment option, and that all three tests were still inferior to empirical treatment

Evaluation of Combined Rapid Immunoglobulin M and Immunoglobulin G Lateral Flow Assays for the Diagnosis of Leptospirosis, Scrub Typhus, and Hantavirus Infection

Objective: Leptospirosis, scrub typhus, and hantavirus infection are commonly identified as causes of acute undifferentiated fever in rural parts of Asia. Although the characteristic presentations of these infections are well described, many of them present with nonspecific manifestations. Diagnosis is usually made by combined history of exposure, clinical features and positive antibody detection. The development of rapid antibody detection assay, using an immunochromatographic test (ICT) for the diagnosis of multi-diseases, has provided tools for more accurate diagnosis and appropriate antibiotic treatment of the acute undifferentiated fever syndrome. Methods: We evaluated the diagnostic performance of a commercially available combined rapid ICT for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection, using archived blood samples from 434 patients with laboratory-confirmed leptospirosis (131) or scrub typhus (128), and from patients with other causes of fever as the negative control (175). Polysaccharide of nonpathogenic Leptospira patoc, a chimeric recombinant protein cr56 and two other recombinant proteins, r21 and kr56, from different serotypes of Orientia tsutsugamushi, and 21kDa species-specific antigen and recombinant CNP antigen derived from the Soochong virus were used as antigens for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection in the combined ICT used in this study. Results: For the diagnosis of leptospirosis; in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 38.2% (95% CI, 29.9- 46.5%), and 99.0% (95% CI 97.9-100%); while in convalescent phase, the same were 84.6% (95%CI, 77.1- 92.0%), and 96.2% (95%CI, 92.5- 99.8%), respectively. For scrub typhus, in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 71.9% (95% CI, 64.1- 79.7%), and 97.4% (95% CI 95.6 - 99.2%); while in convalescent phase, the same were 84.6% (95%CI, 74.8- 94.4%), and 90.2% (95%CI, 85.3- 95.1%) respectively. For hantavirus infection, nine patients had detectable IgM for hantavirus infection. All these cases were diagnosed as scrub typhus by indirect immunofluorescent assay. Conclusion:  The performance of this combined ICT for leptospirosis and scrub typhus were comparable to those published data of other ICTs. However, the rapid test for the diagnosis of leptospirosis, using antigen detection, is needed. Hantavirus infection was not detected in this study population

Human Leptospirosis Trends: Northeast Thailand, 2001–2012

The objective of this study was to determine the changing trend of leptospirosis over time in Thailand using two prospective hospital-based studies conducted amongst adult patients with acute undifferentiated fever (AUFI) admitted to Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima Province, Thailand between July 2001 to December 2002 and between July 2011 to December 2012. During the first period, leptospirosis (98 patients, 40%) and scrub typhus (59 patients, 24.1%) were the two major causes of AUFI. In the second period, scrub typhus (137 patients, 28.3%) was found to be more common than leptospirosis (61 patients, 12.7%). Amongst patients with leptospirosis, the proportion of male patients and the median age were similar. Leptospira interrogans serogroup Autumnalis was the major infecting serogroup in both study periods. The case fatality rate of leptospirosis was significantly higher in 2011–2012 as compared with the case fatality rate in 2001–2002 (19.7% vs. 6.3%, p < 0.001). In summary, we found that number of leptospirosis cases had decreased over time. This trend is similar to reportable data for leptospirosis complied from passive surveillance by the Ministry of Public Health, Thailand. However, the case fatality rate of severe leptospirosis has increased. Severe lung hemorrhage associated with leptospirosis remained the major cause of death

Additional file 1: Table S1. of An ELISA assay using a combination of recombinant proteins from multiple strains of Orientia tsutsugamushi offers an accurate diagnosis for scrub typhus

Correlation of IFA titer and ELISA in acute samples. Table S2. Distribution of IgG or IgM ELISA positive but diagnosed as scrub typhus negative. Figure S1. Correlation of IgG and IgM ELISA OD with single IFA titers at 400. One of the criteria to consider a patient as ST positive was based on IgG or IgM titer > = 400 of a single serum. The ELISA OD of patients was plotted against the IgG or IgM titer <400 (negative, open symbols) or > = 400 (positive, closed symbols). The mean OD of each group was plotted in red. The mean and standard deviation of ELISA OD of IgG (circles) or IgM (triangles). IFA positives (IFA titer > = 400) was significantly different from that of IFA negatives (t test, p < 0.0001). Figure S2. Correlation of IgG and IgM ELISA OD with ST cases. ST cases were determined by a combination of IFA and PCR results. The ELISA OD of patients who were determined as positives (closed symbols) and negatives (open symbols) were plotted. The mean and standard deviation of ELISA OD of each group was plotted in red. The mean OD of IgG (circles) or IgM (triangles) for determined positives and negatives was significantly different (t test, p < 0.0001). (DOCX 14 kb

Doxycycline versus Azithromycin for Treatment of Leptospirosis and Scrub Typhus▿

Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fever (<15 days), without an obvious focus of infection, at four hospitals in Thailand between July 2003 and January 2005. Patients were randomly allocated to receive either a 7-day course of doxycycline or a 3-day course of azithromycin. The cure rate, fever clearance time, and adverse drug events were compared between the two study groups. A total of 296 patients were enrolled in the study. The cause of acute fever was determined for 151 patients (51%): 69 patients (23.3%) had leptospirosis; 57 patients (19.3%) had scrub typhus; 14 patients (4.7%) had murine typhus; and 11 patients (3.7%) had evidence of both leptospirosis and a rickettsial infection. The efficacy of azithromycin was not inferior to that of doxycycline for the treatment of both leptospirosis and scrub typhus, with comparable fever clearance times in the two treatment arms. Adverse events occurred more frequently in the doxycycline group than in the azithromycin group (27.6% and 10.6%, respectively; P = 0.02). In conclusion, doxycycline is an affordable and effective choice for the treatment of both leptospirosis and scrub typhus. Azithromycin was better tolerated than doxycycline but is more expensive and less readily available

Costs, clinical outcomes and antibiotic prescription at various prevalence rates and for patients receiving no treatment, empirical treatment, diagnosis using the latex test and diagnosis with a test with 95% sensitivity and specificity.

<p>Costs, clinical outcomes and antibiotic prescription at various prevalence rates and for patients receiving no treatment, empirical treatment, diagnosis using the latex test and diagnosis with a test with 95% sensitivity and specificity.</p