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

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

Benefit-cost ratios for the different strategies.

*<p>The negative value is a result of the empirical treatment strategy being both less expensive and more effective than the <i>no –antibiotic</i>- treatment baseline</p

Test performance using acute sera [10],[14].

<p>Test performance using acute sera <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000610#pntd.0000610-Kemapunmanus1" target="_blank">[10]</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000610#pntd.0000610-Arimitsu1" target="_blank">[14]</a>.</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>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 (USD).

a<p>Cost of doxycycline (100 mg) 14 capsules in Thailand</p>b<p>Cost as of 2004 of lateral flow, MCAT, latex test.</p>c<p>Treatment of side effect symptoms such as antiemetic drug or antihistamine for rash.</p><p>With work loss, 1 day at minimum earning (5.25 USD) assumed.</p><p>There is no additional cost to patients not receiving antibiotics or to being cured.</p>d<p>Estimate of hospital costs, including intravenous antibiotics, other treatment.</p

Values and sources of inputs used in the decision model.

<p>Values and sources of inputs used in the decision model.</p