Molecular and serological detection of acute canine leptospirosis and associated predictive risk factors in and around Chennai, India.

Leptospirosis is a globally important re-emerging zoonotic disease affecting humans and many animal species including dogs. The present cross-sectional study aimed to diagnose acute leptospirosis among 210 suspected dogs using microscopic agglutination test (MAT) and polymerase chain reaction (PCR). Further, epidemiological risk factors were analyzed by univariate analysis and multivariate binomial logistic regression analysis. Out of the 210 dogs, anti-leptospiral antibody was detected in 123 (58.57 %; 95 % CI: 51.6-65.3) dogs by MAT (cut-off titer- ≥1:100), among which 67 (54.47 %; 95 % CI: 45.3-63.4) were seropositive to more than one serogroup. The predominant serogroups were Australis and Autumnalis in the study region. Whereas, acute leptospirosis was established in 49 (23.33 %, 95 % CI: 17.9-29.8) dogs based on ≥ 1:800 titer in unvaccinated dogs and ≥1:1600 titer in vaccinated dogs. The predictive risk factors of acute canine leptospirosis were adult dogs (1-5 years) (p = 0.001), north-east monsoon season (p = 0.011), outdoor management (p = 0.047), history of rodent exposure (p = 0.001) and history of contact with wet soil or stagnant water (p = 0.046). Among 49 acutely infected dogs, thirteen dogs were positive for urine PCR and one dog was positive for both urine as well as plasma PCR. Positive PCR amplicons were identified as Leptospira interrogans based on secY gene sequencing and phylogenetic analysis. This study enlightened about the occurrence of acute leptospirosis among suspected dogs with the above important predictive risk factors, which should be taken into consideration while history taking so that proper treatment strategies can be adopted for early recovery of the animal.

Sarangi S ，Vijaya Bharathi M ，Madhanmohan M ，Meenambigai TV ，Soundararajan C ，Manimaran K ，Senthilkumar TMA ... -  《-》

Insights into Leptospira spp. infection in pet cats in Croatia: Clinical, serological and molecular findings with emphasis on the potential important role of serogroup Pomona.

Leptospirosis, a globally re-emerging zoonosis caused by pathogenic Leptospira spp., poses a significant threat to public health. Leptospirosis in cats is often neglected due to its high underdiagnosis. Therefore, the role of cats in disease transmission and bacterial maintenance in the environment remains unclear. For this study, 54 serum samples, 54 urine samples and 27 EDTA-anticoagulated blood samples from pet cats presenting to the Veterinary Teaching Hospital due to health problems were used. The serum samples were tested for antibodies against 12 pathogenic serovars of Leptospira spp. using the microscopic agglutination test (MAT). EDTA-anticoagulated blood and urine samples were tested for the lipL32 gene of pathogenic Leptospira spp. by conventional (PCR) and real-time (qPCR) polymerase chain reaction. Agglutinating antibodies were detected in 18.52% (10/54) of the sera with a titre range of 1:50 to 1:12800. The most common serogroup was Pomona, followed by Sejroe, Icterohaemorrhagiae, Australis and Javanica. Leptospira spp. DNA was found in 1.85% (1/54) of the urine samples, while all EDTA-anticoagulated blood samples were negative. A statistically significant difference in seropositivity regarding lifestyle was found between outdoor/indoor and indoor-only cats, while the presence of another cat in the household significantly increased the likelihood of seropositivity. Cats with immunocompromising conditions showed a significantly increased risk of seropositivity, especially those undergoing immunosuppressive treatment. In addition, respiratory signs and changes in lung structure associated with the presence of leptospiral antibodies, and these cats were more likely to be infected with the Pomona serogroup. Moreover, cats with anaemia, leucocytosis, and thrombocytopenia were significantly more likely to have antibodies against Leptospira spp., while seropositive cats had significantly lower urine-specific gravity compared to seronegative cats. The results underline the importance of raising awareness of feline leptospirosis in veterinary care and recognising pet cats as potential carriers of leptospires. Further research is needed to clarify the specific role of the Pomona serogroup as a potentially highly evolutionary drifting serogroup in terms of pathogenicity and to clarify the zoonotic potential of infected cats, which is crucial for the implementation of effective public health measures and veterinary interventions.

Benvin I ，Fitz D ，Mojčec Perko V ，Maurić Maljković M ，Đurić V ，Habuš J ，Štritof Z ，Perharić M ，Hađina S ，Zečević I ，Turk N ... -  《-》

Leptospira seroprevalence and associated risk factors among slaughterhouse workers in Western Bahr El Ghazal State, South Sudan.

Leptospirosis is a neglected re-emerging and occupational zoonotic disease worldwide. In Africa, contact with livestock is postulated as a potential source of environmental contamination and a source of human Leptospira exposure, though pathways remain unknown. Recently, we confirmed Leptospira exposure and shedding among slaughtered cattle in Western Bahr El Ghazal. In the current study, we sought to determine corresponding occupational leptospiral seropositivity, associated risk factors and the prevalence of febrile illness among slaughterhouse workers. Between 27th February and 30th March 2023, we collected blood and interviewed 250 consenting slaughterhouse workers of the same facilities from which the cattle samples were collected. The workers were screened for leptospiral antibodies using the Microscopic agglutination test (MAT), based on a panel of 12 including those previously reported in livestock in South Sudan and the East African Region. Of the 250 participants, 16 were seropositive 16/250, (6.4%, 95% CI = 3.2-10.2). Two seropositive individuals 0.8% (2/250) had MAT titers ≥ 800, indicative of probable recent leptospiral infection. Moreover, 42.4% (106/250) of the respondents reported experiencing fever in the past one month and 36.0% (90/250) sought medical attention. Among those seeking medical care for febrile illnesses, diagnostic tests revealed 9.2% (23/250) with malaria, 7.6% (19/250) with typhoid, 16.8% (42/250) with both malaria and typhoid coinfections, 1.6% (4/250) with brucellosis, and no cases of leptospirosis had been considered. Most seropositive individuals reacted to serovar L. borgpetersenii Tarassovi 2.4% (6/250) and L. interrogans sv Australis 2.4% (6/250). The factors associated with seropositivity included flaying, with persons who flay animals having 14.9 times, (95% CI, 2.5-88.9) greater odds of being seropositive than persons who do not flay animals (P = 0.003), people who wore an apron/overall were 10.6 times (95% CI, 1.6-67.6) more likely to be seropositive than people who did not wear an apron/overall (P = 0.012). An increase in the number of carcasses handled per day by one increases the odds of exposure by 2.7 times (95% CI, 1.6-4.5), (P = 0.001). Finding seropositive workers in cattle slaughter facilities in Western Bahr El Ghazal, South Sudan, and similar serogroups as previously found in the cattle slaughtered at these facilities implies activities like animal slaughter that bring humans into close contact with animals could be one pathway for human Leptospira exposure in South Sudan. This could also highlight leptospirosis as a potential public health threat to those in frequent contact with cattle, including farmers, those in animal transportation, and veterinarians. The role of leptospirosis in cases of undifferentiated fever in South Sudan may also be worth investigating, especially in cases where occupational exposure is suspected. Further research including animals, the general public, farmers, and hospitalized patients is proposed to fully understand the burden of human leptospirosis. Including the serovar and serogroup Tarassovi and Australis in future vaccine development and serodiagnostic panels for South Sudan is highly recommended.

Onafruo D ，Dreyfus A ，Erume J ，Kankya C ，Jubara A ，Kokas I ，Odoch T ，Munyeme M ，Alinaitwe L ，Kitale E ，Marin P ，Sabbath E ，Klein J ... -  《PLoS Neglected Tropical Diseases》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》