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.

Performance of SD Bioline Tsutsugamushi assays for the diagnosis of scrub typhus in Thailand.

OBJECTIVE: To assess the diagnostic capacity of a commercially available test (SD Bioline Tsutsugamushi assay) to aid with the diagnosis of scrub typhus in febrile patients in Thailand. MATERIAL AND METHOD: A commercially available lateral-flow-format immunochromatographic test (ICT) for the detection of O. tsutsugamushi IgM, IgG and IgA antibodies was evaluated, using archived serum samples from 102 laboratory confirmed scrub typhus patients and from 63 patients with other causes of fever as the negative control. RESULTS: The sensitivity, specificity of this rapid immunochromatographic test were 66.7% (95% CI, 57.1 to 75.1%) and 98.4% (95% CI 91.5 to 99.7%) respectively. False positive ICT result occurred in one patient with influenza A infection. Among patients with scrub typhus, 17 out of 38 patients (44.7%, 95% CI 30.2 to 60.3%) with negative IgM antibody test by IFA (titer < 1:50) had positive ICT test. Compared to IFA IgG, 33 out of 54 patients (66.1%, 95% CI 47.8 to 72.9%) with negative IgG antibody test by IFA (titer < 1:50) had positive ICT test. CONCLUSION: This rapid ICT test for the diagnosis of scrub typhus was more sensitive than the standard IFA in acute phase specimens.

Performance of Leptospira immunoglobulin M ELISA and rapid immunoglobulin G immunochromatographic assays for the diagnosis of leptospirosis.

Using archived samples, we assessed the diagnostic capacity of two commercially available tests (an ELISA IgM and a rapid immunochromatographic test, ICT) for the detection of Leptospira spp. IgM and IgG antibodies to aid with the diagnosis of acute leptospirosis in febrile patients in Thailand. The sensitivities of the ELISA for the detection of IgM and the rapid immunochromatographic test for the detection of IgG were 60.7% (95% CI, 50.3 to 70.2%), and 83.2% (95% CI 73.9 to 89.6%) respectively. False positive ICT result occurred in one patient with influenza B infection. The positive rates of both assays were high after the first week of onset of fever up to third weeks of illness.

Strategies for diagnosis and treatment of suspected leptospirosis: a cost-benefit analysis.

BACKGROUND: Symptoms and signs of leptospirosis are non-specific. Several diagnostic tests for leptospirosis are available and in some instances are being used prior to treatment of leptospirosis-suspected patients. There is therefore a need to evaluate the cost-effectiveness of the different treatment strategies in order to avoid misuse of scarce resources and ensure best possible health outcomes for patients. METHODS: The study population was adult patients, presented with uncomplicated acute febrile illness, without an obvious focus of infection or malaria or typical dengue infection. We compared the cost and effectiveness 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. The framework used is a cost-benefit analysis, accounting for all direct medical costs in diagnosing and treating patients suspected of leptospirosis. Outcomes are measured in length of fever after treatment which is then converted to productivity losses to capture the full economic costs. FINDINGS: Empirical doxycycline treatment was the most efficient strategy, being both the least costly alternative and the one that resulted in the shortest duration of fever. The limited sensitivity of all three diagnostic tests implied that their use to guide treatment was not cost-effective. The most influential parameter driving these results was the cost of treating patients with complications for patients who did not receive adequate treatment as a result of incorrect diagnosis or a strategy of no-antibiotic-treatment. CONCLUSIONS: Clinicians should continue treating suspected cases of leptospirosis on an empirical basis. This conclusion holds true as long as policy makers are not prioritizing the reduction of use of antibiotics, in which case the use of the latex test would be the most efficient strategy.

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.

Radiographic chest findings and clinical correlations in leptospirosis.

OBJECTIVE: To determine the clinical presentations, radiographic chest findings, and their correlation in patients with leptospirosis. DESIGN: A cross sectional study. SETTING: Between July 2001- December 2002 at 3 hospitals in North Eastern Thailand. MATERIAL AND METHOD: Two hundred and forty patients with laboratory confirmed leptospirosis. RESULTS: Two hundred and nine (87.1%) patients were males. The mean age was 37.53 years (range 13-76). The median duration of fever was 3 days (range 1-13). Overall, 154 patients (64.2%) had respiratory symptoms and 26 (10.8%) patients had hemoptysis. Jaundice was detected in 76 (31.7%) patients, hypotension in 50 (20.8%), renal dysfunction in 80 (30%), and multiorgan dysfunction in 62 (25.8%) on admission. One hundred and fifty-four (64.17%) patients had abnormal chest radiographs on admission (classified as cardiovascular, pulmonary, and mixed cardio-pulmonary involvement in 40 (25.97%), 41 (26.62%), and 73 (47.4%) patients, respectively). Jaundice was significantly associated with the likelihood of having abnormal chest radiography on admission. Air- space nodules detected on the chest radiograph were significantly more common in patients with renal dysfunction and patients who required mechanical ventilation. CONCLUSION: Pulmonary and cardiovascular involvements are common in leptospirosis. Air-space nodules detected by chest radiography may indicate severe leptospirosis.

Haemodynamics in leptospirosis: effects of plasmapheresis and continuous venovenous haemofiltration.

BACKGROUND: Haemodynamics in leptospirosis may differ from that of sepsis because of frequently obeserved myocarditis and severe cholestatic jaundice. A haemodynamic study was therefore made in 10 patients with severe leptospirosis. METHODS AND RESULTS: All patients had pulmonary complications with a chest X-ray showing either pulmonary oedema or infiltration. Renal failure was present in nine patients. Three patterns of haemodynamics were revealed. The first pattern was observed in six patients who showed increased cardiac index, decreased systemic vascular resistance, normal pulmonary capillary wedge pressure, normal pulmonary vascular resistance and hypotension. The pattern resembled that of sepsis. The second pattern shown in two patients with haemoptysis consisted of a normal cardiac index, normal systemic vascular resistance, normal blood pressure, normal pulmonary capillary wedge pressure and increased pulmonary vascular resistance. The third pattern was observed in two patients with severe jaundice who had hypotension, a relatively low cardiac index, increased systemic vascular resistance and normal pulmonary capillary wedge pressure, and pulmonary vascular resistance. Plasmapheresis performed in two patients and continuous venovenous haemofiltration performed in two patients improved systemic haemodynamics and normalized blood pressure with a resolution of lung signs.

An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis.

BACKGROUND: Leptospirosis is an important cause of fever in the rural tropics. Since 1996, there has been a marked increase in the incidence of leptospirosis in northeastern Thailand. Although leptospirosis generally is susceptible to antibiotics, there is no consensus regarding the optimal treatment for severe leptospirosis. METHODS: An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium (hereafter known as "penicillin G"), and doxycycline for the treatment of suspected severe leptospirosis was conducted. The study involved 540 patients admitted to 4 hospitals in northeastern Thailand. RESULTS: A total of 264 patients (48.9%) had leptospirosis confirmed by serologic testing or culture. The overall mortality rate was 5%. There were no significant differences between the antibiotics with regard to associated mortality, defervescence, or time to resolution of abnormal findings of laboratory tests either among all study participants or among the subgroup of patients with confirmed leptospirosis. A total of 132 patients had rickettsial infection diagnosed, and, for these patients, treatment with doxycycline was superior to treatment with penicillin G. CONCLUSIONS: Doxycycline or cefotaxime is a satisfactory alternative to penicillin G for the treatment of severe leptospirosis.

Possible scrub typhus coinfections in Thai agricultural workers hospitalized with leptospirosis.

Possible coinfections with Orientia tsutsugamushi the causative agent of scrub typhus, were prospectively evaluated in rice farmers hospitalized with leptospirosis in Northeast Thailand. Of 22 adults with leptospirosis diagnosed by the microscopic agglutination test, 9 also had serologic evidence of scrub typhus. Of 9 individuals with possible coinfections, 5 had signs or symptoms typical of scrub typhus and atypical of leptospirosis. Patients who appeared to have mixed infections had significantly higher median platelet counts and significantly lower median serum bilirubin and creatinine concentrations (P < 0.05, Mann-Whitney U test) than did individuals with leptospirosis alone. One patient with serologic evidence of scrub typhus and leptospirosis was treated only with penicillin, to which scrub typhus is not sensitive. Respiratory distress worsened during therapy, and the patient died of respiratory failure. Physicians should consider the possibility of scrub typhus infection in leptospirosis patients who respond poorly to treatment or who have atypical disease manifestations.