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

Cultural drivers and health-seeking behaviours that impact on the transmission of pig-associated zoonoses in Lao People's Democratic Republic

Pig rearing is an important income source in the Lao People’s Democratic Republic (PDR), with many smallholder farmers using traditional free-range pig production systems. Despite the potentially significant health risks posed by pig production regarding pig-associated zoonoses, information on the sociocultural drivers of these zoonoses is significantly lacking. This review summarises the existing sociocultural knowledge on eight pig-associated zoonoses suspected to be endemic in Southeast Asia: brucellosis, Q fever (Coxiella burnetii), trichinellosis, hepatitis E virus, leptospirosis, Japanese encephalitis, Streptococcus suis and Taenia solium taeniasis-cysticercosis. It summarises current knowledge on these diseases grouped according to their clinical manifestations in humans to highlight the propensity for underreporting. A literature search was conducted across multiple databases for publications from 1990 to the present day related to the eight pig-associated zoonoses and the risk and impact connected with them, with Lao PDR as a case study. Many of these pig-associated zoonoses have similar presentations and are often diagnosed as clinical syndromes. Misdiagnosis and underreporting are, therefore, substantial and emphasise the need for more robust diagnostics and appropriate surveillance systems. While some reports exist in other countries in the region, information is significantly lacking in Lao PDR with existing information coming mainly from the capital, Vientiane. The disease burden imposed by these zoonoses is not only characterised by morbidity and mortality, but directly impacts on livelihoods through income reduction and production losses, and indirectly through treatment costs and lost work opportunities. Other factors crucial to understanding and controlling these diseases are the influence of ethnicity and culture on food-consumption practices, pig rearing and slaughter practices, hygiene and sanitation, health-seeking behaviours and, therefore, risk factors for disease transmission. Published information on the knowledge, attitudes and beliefs of people regarding pig zoonoses and their risk factors is also extremely limited in Lao PDR and the broader Southeast Asian region. The need for more transdisciplinary research, using a One Health approach, in order to understand the underlining social determinants of health and their impacts on health-seeking behaviours, disease transmission and, ultimately, disease reporting, cannot be more emphasized

Activation of the coagulation cascade in patients with leptospirosis.

BACKGROUND: Disseminated intravascular coagulation (DIC) is common among patients with sepsis. Leptospirosis is an important cause of sepsis in tropical areas, and pulmonary hemorrhage associated with thrombocytopenia is the major cause of death, but the coagulopathy in severe leptospirosis has not been further characterized. The aim of this study was to evaluate coagulation factors and the presence of DIC in patients with leptospirosis in northeast Thailand. METHODS: We measured plasma concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complexes, and prothrombin fragment 1,2 and evaluated the DIC score in 79 patients with culture-confirmed and/or serologically confirmed leptospirosis and in 33 healthy Thai control subjects. RESULTS: The median concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complexes, and prothrombin fragment 1,2 were significantly elevated in a cohort of 79 patients with leptospirosis, compared with healthy control subjects (

Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial.

BACKGROUND: Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. METHODS: For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials.com, number ISRCTN86140460. FINDINGS: We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). INTERPRETATION: Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. FUNDING: Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust

Trimethoprim-sulfamethoxazole versus trimethoprimsulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): A multicentre, double-blind, non-inferiority, randomised controlled trial

Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials. com, number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients

Trimethoprim-sulfamethoxazole versus trimethoprimsulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): A multicentre, double-blind, non-inferiority, randomised controlled trial

Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials. com, number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients