Global distribution of Leptospira serovar isolations and detections from animal host species: A systematic review and online database.

OBJECTIVES: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study. METHODS: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. RESULTS: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. CONCLUSIONS: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Prevalence and risk factors for Q fever, spotted fever group rickettsioses, and typhus group rickettsioses in a pastoralist community of northern Tanzania, 2016-2017.

BACKGROUND: In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community. METHODS: Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated. RESULTS: Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50). DISCUSSION: Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.

Symptom persistence and recovery among COVID-19 survivors during a limited outbreak in Canterbury, New Zealand: a prospective cohort study.

BACKGROUND: In Canterbury, near complete identification of coronavirus disease 2019 (COVID-19) cases during a limited outbreak provides unique insights into sequelae. AIMS: The current study aimed to measure symptom persistence, time to return to normal activity, generalised anxiety and health-related quality of life (HrQoL) among COVID-19 survivors compared with uninfected participants. METHODS: The authors conducted a prospective cohort study of people tested for COVID-19 by reverse transcriptase polymerase chain reaction of nasopharyngeal swabs from 1 March to 30 June 2020. They enrolled participants who tested positive and negative at a 1:2 ratio, and administered community-acquired pneumonia, 7-item generalised anxiety disorder (GAD-7) and HrQoL (RAND-36) questionnaires. RESULTS: The authors recruited 145 participants, 48 with COVID-19 and 97 without COVID-19. The mean time from COVID-19 testing to completing the health questionnaire was 306 days. The mean age of patients was 46.7 years, and 70% were women. Four (8%) COVID-19-positive and eight (8%) COVID-19-negative participants required hospitalisation. Fatigue (30/48 [63%] vs 13/97 [13%]; P < 0.001), dyspnoea (13/48 [27%] vs 6/97 [6%]; P < 0.001) and chest pain (10/48 [21%] vs 1/97 [1%]; P < 0.001) were persistent in those with COVID-19. Fewer COVID-19-positive participants returned to normal activity levels (35/48 [73%] vs 94/97 97%; P < 0.001), with longer times taken (median 21 vs 14 days; P = 0.007). The GAD-7 and RAND-36 scores of both groups were similar across all anxiety and HrQoL subscales. CONCLUSIONS: Persistent symptoms and longer recovery times were found in COVID-19 survivors, but not impaired generalised anxiety levels or HrQoL compared with COVID-19-uninfected participants.

Evaluation of pleural fluid cytology for the diagnosis of malignant pleural effusion: a retrospective cohort study.

BACKGROUND: Cytological examination of pleural fluid has good specificity, but imperfect sensitivity for the diagnosis of malignant pleural effusion (MPE). Published estimates of sensitivity vary and predictors of false negative cytology are not well established. AIMS: To estimate pleural fluid cytology sensitivity and identify risk factors for false negative cytology. METHODS: We conducted a retrospective cohort study of patients who had cytology testing of pleural fluid at Christchurch Hospital, New Zealand, from July 2017 to October 2019. Data on clinical and pleural fluid characteristics were collected. MPE was defined by positive pleural fluid cytology, tissue histology or multidisciplinary meeting consensus. We estimated sensitivity of the first pleural cytology assessment. We performed multivariate logistic regression to ascertain patient groups at greatest risk of false negative results. RESULTS: Initial pleural fluid cytology was diagnostic in 117 of 156 patients, providing a sensitivity (95% confidence interval (CI)) of 75.0% (67.4-81.6%). The sensitivity was 79.0% (66.8-88.3%) for lung cancer, 91.3% (72.0-98.9%) for breast cancer and 33.3% (95% CI 11.8-61.6%) for mesothelioma. Cloudy appearance of pleural fluid (odds ratio (OR) 0.12; 95% CI 0.03-0.54) and yellow/gold pleural fluid (OR 0.24; 95% CI 0.06-0.96) reduced the odds of false negative pleural cytology. Pleural thickening on computed tomography scan (OR 3.3; 95% CI 1.2-9.4) was a risk factor for false negative cytology. CONCLUSION: Sensitivity of pleural fluid cytology was greatest in primary lung and breast cancer, and lowest in mesothelioma. Clinicians should be alert to false negative results when suspecting mesothelioma or if pleural thickening is present.

Trends in fever case management for febrile inpatients in a low malaria incidence setting of Tanzania.

OBJECTIVES: In 2010, WHO published guidelines emphasising parasitological confirmation of malaria before treatment. We present data on changes in fever case management in a low malaria transmission setting of northern Tanzania after 2010. METHODS: We compared diagnoses, treatments and outcomes from two hospital-based prospective cohort studies, Cohort 1 (2011-2014) and Cohort 2 (2016-2019), that enrolled febrile children and adults. All participants underwent quality-assured malaria blood smear-microscopy. Participants who were malaria smear-microscopy negative but received a diagnosis of malaria or received an antimalarial were categorised as malaria over-diagnosis and over-treatment, respectively. RESULTS: We analysed data from 2098 participants. The median (IQR) age was 27 (3-43) years and 1047 (50.0%) were female. Malaria was detected in 23 (2.3%) participants in Cohort 1 and 42 (3.8%) in Cohort 2 (p = 0.059). Malaria over-diagnosis occurred in 334 (35.0%) participants in Cohort 1 and 190 (17.7%) in Cohort 2 (p < 0.001). Malaria over-treatment occurred in 528 (55.1%) participants in Cohort 1 and 196 (18.3%) in Cohort 2 (p < 0.001). There were 30 (3.1%) deaths in Cohort 1 and 60 (5.4%) in Cohort 2 (p = 0.007). All deaths occurred among smear-negative participants. CONCLUSION: We observed a substantial decline in malaria over-diagnosis and over-treatment among febrile inpatients in northern Tanzania between two time periods after 2010. Despite changes, some smear-negative participants were still diagnosed and treated for malaria. Our results highlight the need for continued monitoring of fever case management across different malaria epidemiological settings in sub-Saharan Africa.

On the robustness of latent class models for diagnostic testing with no gold standard.

It is difficult to estimate sensitivity and specificity of diagnostic tests when there is no gold standard. Latent class models have been proposed as a potential solution as they provide estimates without the need for a gold standard. Using a motivating example of the evaluation of point of care tests for leptospirosis in Tanzania, we show how a realistic violation of assumptions underpinning the latent class model can lead directly to substantial bias in the estimates of the parameters of interest. In particular, we consider the robustness of estimates of sensitivity, specificity, and prevalence, to the presence of additional latent states when fitting a two-state latent class model. The violation is minor in the sense that it cannot be routinely detected with goodness-of-fit procedures, but is major with regard to the resulting bias.

Incidence of Typhoid and Paratyphoid Fevers Among Adolescents and Adults in Yangon, Myanmar.

BACKGROUND: Accurate estimates of typhoid disease burden are needed to guide policy decisions, including on vaccine use. Data on the incidence of enteric fever in Myanmar are scarce. We estimated typhoid and paratyphoid fever incidence among adolescents and adults in Yangon, Myanmar, by combining sentinel hospital surveillance with a healthcare utilization survey. METHODS: We conducted a population-based household health care utilization survey in the Yangon Region 12 March through 5 April 2018. Multipliers derived from this survey were then applied to hospital-based surveillance of Salmonella Typhi and Paratyphi A bloodstream infections from 5 October 2015 through 4 October 2016 at Yangon General Hospital (YGH) to estimate the incidence of typhoid and paratyphoid fevers among person ≥12 years of age. RESULTS: A total of 336 households representing 1598 persons were enrolled in the health care utilization survey, and multipliers were derived based on responses to questions about healthcare seeking in the event of febrile illness. Of 671 Yangon residents enrolled over a 1-year period at YGH, we identified 33 (4.9%) with Salmonella Typhi and 9 (1.3%) with Salmonella Paratyphi A bloodstream infection. After applying multipliers, we estimated that the annual incidence of typhoid was 391 per 100 000 persons and paratyphoid was 107 per 100 000 persons. CONCLUSIONS: Enteric fever incidence is high in Yangon, Myanmar, warranting increased attention on prevention and control, including consideration of typhoid conjugate vaccine use as well as nonvaccine control measures. Research on incidence among infants and children, as well as sources and modes of transmission is needed.

Legionnaires' disease caused by Legionella longbeachae: Clinical features and outcomes of 107 cases from an endemic area.

BACKGROUND AND OBJECTIVE: Legionella longbeachae is a predominant cause of Legionnaires' disease in some parts of the world, particularly in Australasia. Clinical reports of L. longbeachae infection are limited to case reports or small case series, and culture-confirmed cases. METHODS: We reviewed the clinical characteristics and outcomes of L. longbeachae pneumonia in a large case series from Christchurch, New Zealand during a 4-year period when both PCR and cultures were used as routine diagnostic tools for Legionnaires' disease. Cases of Legionella pneumophila pneumonia were reviewed for comparison. RESULTS: A total of 107 cases of L. longbeachae infection were identified by PCR and/or culture. The median age was 65 years (range 25-90 years), 63% were male, and most became unwell during spring or summer. Presenting clinical features were similar to those reported for community-acquired pneumonia, with headache, myalgia and diarrhoea being common. Elevated C-reactive protein, hyponatraemia and abnormal liver function tests were also common. History of productive cough, involvement of both lungs, and high bacterial load were independently associated with culture of Legionella from lower respiratory samples. One quarter required intensive care unit admission, and 5% died. Among patients given antimicrobial therapy before admission, those given agents without anti-Legionella activity were more likely to be admitted to the intensive care unit. Limited comparisons were made with the 19 L. pneumophila cases over the same time period. CONCLUSION: Characteristics of L. longbeachae pneumonia are broadly similar to those reported for community-acquired pneumonia from a variety of other populations, except for the spring/summer seasonality.

Complications of atypical pneumonia: A case of Legionella longbeachae empyema.

Legionella longbeachae is the most common cause of Legionnaires' disease in Australasia. Legionella species are considered a rare cause of pleural infection, and empyema and lung abscess due to L. longbeachae has not previously been reported. Our patient presented with a 2-3 week history of breathlessness, lethargy, dry cough and headaches. Initial chest radiograph showed extensive left sided consolidation with an associated pleural effusion. An area of necrotising pneumonia evident on computed tomography scan evolved into a multiloculated intrapulmonary abscess. Sputum culture isolated L. longbeachae, which prompted culture of pleural fluid on buffered charcoal yeast extract agar and isolation of the organism. This case provides evidence that L. longbeachae can cause both empyema and lung abscess, and in areas where it is prevalent, increased use of Legionella specific agar for pleural fluid culture should be considered.

SunGold Kiwifruit Consumption Restores Adequate to Optimal Vitamin C Status in People with a History of Severe Respiratory Infections.

Severe respiratory infections are characterised by depleted vitamin C and elevated inflammation and oxidative stress. The aim of this study was to recruit people with a history of severe respiratory infections to undergo a six-week intervention with SunGold kiwifruit to determine if this could restore adequate vitamin C status. Secondary outcomes included changes in inflammatory and oxidative stress biomarkers, self-reported fatigue and subjective mood, and the incidence, duration and severity of respiratory symptoms. The total cohort comprised 20 adults (65% female, age range 31-84 years). The participants had a low median fruit and vegetable intake of 2.3 servings/day and a correspondingly low vitamin C intake of 46 mg/day. Circulating vitamin C status was a median of 45 µmol/L and was in the hypovitaminosis range in 25% of the cohort. Following intervention with two SunGold kiwifruit/day (equivalent to ~300 mg vitamin C), there was an increase in plasma vitamin C concentrations to >60 µmol/L (p < 0.05). Approximately 20% of the participants were unable to reach adequate vitamin C status (≥50 µmol/L), possibly due to current smoking, which enhances vitamin C turnover, and a strong inverse correlation between body weight and vitamin C status (r = -0.734, p < 0.05). Following the intervention, there were indications towards decreases in the inflammatory biomarkers C-reactive protein and TNFα (p > 0.05), but no changes in oxidative stress biomarkers (F2isoprostanes, protein carbonyls). There were decreases in fatigue and depression (p < 0.05) and a lower number of individual respiratory symptoms reported during the kiwifruit intervention phase (8.5 vs. 10, p = 0.05). Overall, the consumption of two SunGold kiwifruit per day for six weeks was able to restore adequate to saturating vitamin C status in ~80% of the participants. Smokers and people with higher body weight may need larger doses and/or longer duration of supplementation. The contribution of vitamin C to reducing fatigue, depression, and number of respiratory symptoms warrants further investigation.

Impact of routine systematic polymerase chain reaction testing on case finding for Legionnaires' disease: a pre-post comparison study.

BACKGROUND: Legionnaires' disease cannot be clinically or radiographically distinguished from other causes of pneumonia, and specific tests are required to make the diagnosis. Currently, testing occurs erratically and, instead, clinicians rely on empiric treatment strategies and ignore public health implications of the diagnosis. We aimed to measure the increase in case detection of Legionnaires' disease following the introduction of routine polymerase chain reaction (PCR) testing of respiratory specimens. PCR is the most sensitive diagnostic tool for Legionnaires' disease. METHODS: In a quasi-experimental study in Christchurch, New Zealand, we compared the number of cases of Legionnaires' disease requiring hospitalization diagnosed during a 2-year period before the introduction of a routine PCR testing strategy (November 2008-October 2010) with a similar period after the introduction (November 2010-October 2012). With this testing strategy, all respiratory specimens from hospitalized patients with pneumonia sent to the region's sole tertiary-level laboratory were tested for Legionella by PCR, whether requested or not. RESULTS: During November 2008 to October 2010, there were 22 cases of Legionnaires' disease compared with 92 during November 2010 to October 2012. Of 1834 samples tested since November 2010, 1 in 20 was positive, increasing to 1 in 9 during peak Legionella season (November to January). Increasing bacterial load was associated with increasing disease severity. CONCLUSIONS: In our region, the burden of Legionnaires' disease is much greater than was previously recognized. Routine PCR testing provides results within a clinically relevant time frame and enables improved characterization of the regional epidemiology of Legionnaires' disease.

Prevalence of concurrent deep vein thrombosis in patients with lower limb cellulitis: a prospective cohort study.

BACKGROUND: Lower limb cellulitis and deep vein thrombosis share clinical features and investigation of patients with cellulitis for concurrent DVT is common. The prevalence of DVT in this group is uncertain. This study aimed to determine the prevalence of deep vein thrombosis (DVT) in patients with lower limb cellulitis and to investigate the utility of applying the Wells algorithm to this patient group. METHODS: Patients admitted with lower limb cellulitis prospectively underwent a likelihood assessment for DVT using the Wells criteria followed by investigation with D-dimer and ultrasonography of ipsilateral femoral veins as appropriate. Diagnoses of contralateral DVT or pulmonary embolism during admission were recorded. RESULTS: 200 patients assessed for DVT. 20% of subjects were high risk by Wells criteria. D-dimer was elevated in 74% and 79% underwent insonation of the affected leg. Ipsilateral DVT was found in 1 patient (0.5%) and non-ipsilateral VTE in a further 2 (1%). CONCLUSIONS: Deep vein thrombosis rarely occurs concurrently with lower limb cellulitis. The Wells score substantially overestimates the likelihood of DVT due to an overlap of clinical signs. Investigation for DVT in patients with cellulitis is likely to yield few diagnoses and is not warranted in the absence of a hypercoaguable state. TRIAL REGISTRATION: ACTRN: 12610000792022 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=320662).

Etiologic Investigation of Patients Diagnosed with Bacteriologically Unconfirmed Tuberculosis in Tanzania.

Globally, half of patients with pulmonary tuberculosis (PTB) are diagnosed clinically without bacteriologic confirmation. In clinically diagnosed PTB patients, we assessed both the proportion in whom PTB could be bacteriologically confirmed by reference standard diagnostic tests and the prevalence of diseases that mimic PTB. We recruited adult patients beginning treatment of bacteriologically unconfirmed PTB in Moshi, Tanzania, in 2019. We performed mycobacterial smear, Xpert MTB/RIF Ultra, and mycobacterial culture, fungal culture, and bacterial culture on two induced sputum samples: fungal serology and computed tomography chest scans. We followed participants for 2 months after enrollment. We enrolled 36 (63%) of 57 patients with bacteriologically unconfirmed PTB. The median (interquartile range) age was 55 (44-67) years. Six (17%) were HIV infected. We bacteriologically confirmed PTB in 2 (6%). We identified pneumonia in 11 of 23 (48%), bronchiectasis in 8 of 23 (35%), interstitial lung disease in 5 of 23 (22%), pleural collections in 5 of 23 (22%), lung malignancy in 1 of 23 (4%), and chronic pulmonary aspergillosis in 1 of 35 (3%). After 2 months, 4 (11%) were dead, 21 (58%) had persistent symptoms, 6 (17%) had recovered, and 5 (14%) were uncontactable. PTB could be bacteriologically confirmed in few patients with clinically diagnosed PTB and clinical outcomes were poor, suggesting that many did not have the disease. We identified a high prevalence of diseases other than tuberculosis that might be responsible for symptoms.

Global distribution of Leptospira serovar isolations and detections from animal host species: a systematic review and online database.

Objectives: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, currently data are fragmented. We aimed to systematically review the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions, and to identify geographic regions in need of study. Methods: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterized by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. Results: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n=39), Icterohaemorrhagiae (n=29), Pomona (n=28), Australis (n=25), and Ballum (n=25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. Conclusions: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.

Background: We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania. Methods: We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use. Results: Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each). Conclusions: Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.

Prevalence and risk factors for human leptospirosis at a hospital serving a pastoralist community, Endulen, Tanzania.

BACKGROUND: Leptospirosis is suspected to be a major cause of illness in rural Tanzania associated with close contact with livestock. We sought to determine leptospirosis prevalence, identify infecting Leptospira serogroups, and investigate risk factors for leptospirosis in a rural area of Tanzania where pastoralist animal husbandry practices and sustained livestock contact are common. METHODS: We enrolled participants at Endulen Hospital, Tanzania. Patients with a history of fever within 72 hours, or a tympanic temperature of ≥38.0°C were eligible. Serum samples were collected at presentation and 4-6 weeks later. Sera were tested using microscopic agglutination testing with 20 Leptospira serovars from 17 serogroups. Acute leptospirosis cases were defined by a ≥four-fold rise in antibody titre between acute and convalescent serum samples or a reciprocal titre ≥400 in either sample. Leptospira seropositivity was defined by a single reciprocal antibody titre ≥100 in either sample. We defined the predominant reactive serogroup as that with the highest titre. We explored risk factors for acute leptospirosis and Leptospira seropositivity using logistic regression modelling. RESULTS: Of 229 participants, 99 (43.2%) were male and the median (range) age was 27 (0, 78) years. Participation in at least one animal husbandry practice was reported by 160 (69.9%). We identified 18 (7.9%) cases of acute leptospirosis, with Djasiman 8 (44.4%) and Australis 7 (38.9%) the most common predominant reactive serogroups. Overall, 69 (30.1%) participants were Leptospira seropositive and the most common predominant reactive serogroups were Icterohaemorrhagiae (n = 20, 29.0%), Djasiman (n = 19, 27.5%), and Australis (n = 17, 24.6%). Milking cattle (OR 6.27, 95% CI 2.24-7.52) was a risk factor for acute leptospirosis, and milking goats (OR 2.35, 95% CI 1.07-5.16) was a risk factor for Leptospira seropositivity. CONCLUSIONS: We identified leptospirosis in approximately one in twelve patients attending hospital with fever from this rural community. Interventions that reduce risks associated with milking livestock may reduce human infections.

A Randomized Trial of Nafamostat for Covid-19.

BACKGROUND: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with coronavirus disease 2019 (Covid-19). Participants were randomly assigned to usual care or usual care plus nafamostat. The primary end point was death (any cause) or receipt of new invasive or noninvasive ventilation or vasopressor support within 28 days after randomization. Analysis was with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to falling numbers of eligible patients. RESULTS: We screened 647 patients in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal) and enrolled 160 participants from May 2021 to August 2022. In the intention-to-treat population, the primary end point occurred in 8 (11%) of 73 patients with usual care and 4 (5%) of 82 with nafamostat. The median adjusted odds ratio for the primary end point for nafamostat was 0.40 (95% credible interval, 0.12 to 1.34) with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%. For usual care compared with nafamostat, hyperkalemia occurred in 1 (1%) of 67 and 7 (9%) of 78 participants, respectively, and clinically relevant bleeding occurred in 1 (1%) of 73 and 7 (8%) of 82 participants. CONCLUSIONS: Among hospitalized patients with Covid-19, there was a 93% posterior probability that nafamostat reduced the odds of death or organ support. Prespecified stopping criteria were not met, precluding definitive conclusions. Hyperkalemia and bleeding were more common with nafamostat. (Funded by ASCOT and others; ClinicalTrials.gov number, NCT04483960.)