Neglected etiologies of prolonged febrile illnesses in tropical and subtropical regions: A systematic review.

BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments. METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias. RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles. CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.

[Zoonotic potential of brucellosis in marine mammals]. / Potentiel zoonotique de la brucellose des mammifères marins.

Introduction: Brucellosis in marine mammals (cetacean and pinnipeds) has emerged in a very significant way during the last two decades. Currently Brucella ceti and Brucella pinnipedialis are the two recognized species in marine mammals, but available information is still limited. Several genotypes have been identified, and studies on the relationship between sequence type (ST) and organ pathogenicity or tropism have indicated differences in pathogenesis between B. ceti sequences in cetaceans. The zoonotic potential of this disease is based on the identification of the main sources of introduction and spread of Brucella spp. in the marine environment as well as on the factors of exposure of marine mammals and humans to the bacteria. Bibliographic review: This article is a bibliographical review on marine mammal brucellosis, including the features, sources and transmission modes of each Brucella species, as well as their potential pathogenicity in animals and humans. Conclusion: Different genotypes of marine Brucella spp have been isolated from marine mammal species but without any evidence of pathology induced by these bacteria. Associated lesions are variable and include subcutaneous abscesses, meningo-encephalomyelitis, pneumonia, myocarditis, osteoarthritis, orchitis, endometritis, placentitis and abortion. The isolation of marine B. spp from marine mammal respiratory parasites associated to lung injury has raised the intriguing possibility that they may serve as a vector for the transmission of this bacterium.The severity of marine B. spp remains unknown due to the lack of an estimate of the prevalence of this disease in marine mammals. The number of suspected human cases is still very limited. However, by analogy with other germs of the genus Brucella responsible for abortion in ruminants and for a febrile and painful state in human beings, prevention measures are essential. The significant increase in the number of strandings coupled with a high seroprevalence in certain species of marine mammals must be considered for people in direct or indirect contact with these animals. Ongoing epidemiological monitoring combined with extensive post-mortem examinations (necropsy, bacteriology and sequencing) of all species of stranded marine mammals would deepen knowledge on the zoonotic potential of marine Brucella species.

Brucellosis: Unveiling the complexities of a pervasive zoonotic disease and its global impacts.

One zoonotic infectious animal disease is brucellosis. The bacteria that cause brucellosis belong to the genus Brucella. Numerous animal and human species are affected by brucellosis, with an estimated 500,000 human cases recorded annually worldwide. The occurrence of new areas of infection and the resurgence of infection in already infected areas indicate how dynamically brucellosis is distributed throughout different geographic regions. Bacteria originate from the blood and are found in the reticuloendothelial system, the liver, the spleen, and numerous other locations, including the joints, kidneys, heart, and genital tract. Diagnosis of this disease can be done by bacterial isolation, molecular tests, modified acid-fast stain, rose bengal test (RBT), milk ring test, complement fixation test, enzyme-linked immunosorbent assay, and serum agglutination test. The primary sign of a Brucella abortus infection is infertility, which can result in abortion and the birth of a frail fetus that may go on to infect other animals. In humans, the main symptoms are acute febrile illness, with or without localization signs, and chronic infection. Female cattle have a greater risk of contracting Brucella disease. Human populations at high risk of contracting brucellosis include those who care for cattle, veterinarians, slaughterhouse employees, and butchers. Antibiotic treatment of brucellosis is often unsuccessful due to the intracellular survival of Brucella and its adaptability in macrophages. A "one health" strategy is necessary to control illnesses like brucellosis.

Seroprevalence of brucellosis and associated risk factors in camels and its herders in selected districts of Somali Pastoral Region, Eastern Ethiopia.

Brucellosis poses a major public and animal health problem in many parts of the world, particularly in pastoral settings, however, seroepidemological studies are scarce. A cross-sectional study was conducted from December 2021 to April 2022 to estimate the prevalence of brucellosis and to identify the associated risk factors for camels and occupational individuals from three purposively selected districts of the Somali pastoral region in Eastern Ethiopia. Serum samples were serially diluted using the Rose Bengal Plate Test (RBPT) as a screening test and a competitive Enzyme-Linked Immunosorbent Assay (cELISA) test as a confirmatory test. From a total of 450 camels and 250 human serum samples tested, the overall seroprevalence was confirmed to be 2.9 % (95 % CI, 1.5-4.9) in camels and 2.0 % (95 % CI, 0.2-3.7) in humans. In camels, abortion and retained fetal membrane (RFM) were significant risk factors for Brucella seropositivity (p<0.05). However, in humans, RFM disposal differed significantly (p<0.05). The fact that brucellosis is found in both camels and humans highlights the importance of implementing a coordinated One Health approach to control and eliminate the disease. This would ensure improved public health and increased livestock productivity.

National epidemiology of culture-confirmed brucellosis in Israel, 2004-2022.

Brucellosis, a global zoonosis, is endemic in Israel. We used a national database of culture-confirmed cases (2004-2022) to analyse the trends of brucellosis. Of 2,489 unique cases, 99.8% were bacteraemic, 64% involved males, and the mean age was 30.5 years. Brucella melitensis was the dominant species (99.6%). Most cases occurred among the Arab sector (84.9%) followed by the Jewish (8.5%) and Druze (5.5%) sectors. The average annual incidence rates overall and for the Arab, Druze, and Jewish sectors were 1.6/100,000, 6.6/100,000, 5.5/100,000, and 0.18/100,000, respectively. The annual incidence rates among the Arab (incidence rate ratio (IRR) = 36.4) and the Druze (IRR = 29.6) sectors were significantly higher than among the Jewish sector (p < 0.001). The highest incidence rates among the Arab sector occurred in the South District, peaking at 41.0/100,000 in 2012. The frequencies of B. melitensis isolated biotypes (biotype 1 - 69.1%, biotype 2 - 26.0%, and biotype 3 - 4.3%) differed from most Middle Eastern and European countries. A significant switch between the dominant biotypes was noted in the second half of the study period. Efforts for control and prevention should be sustained and guided by a One Health approach mindful of the differential trends and changing epidemiology.

Brucella spp. in Wildlife of the Lombardy Region, Northern Italy.

Surveillance data collected in the period 2017-20 for Brucella spp. in wildlife of the Lombardy Region in northern Italy were used to describe the exposure of the wildlife species to Brucella spp. in wild boar (Sus scrofa), European brown hare (Lepus europaeus), fallow deer (Dama dama), red deer (Cervus elaphus), and roe deer (Capreolus capreolus). Among the tested species, wild boar (n=6,440) showed the highest percentage of seropositive samples (5.9%). Notably, wild boars of perifluvial area of the Po River showed higher percentages of positivity than those of the pre-Alpine district. In addition, during the hunting season in 2018, 95 organs (uterus or testes, spleen, and submandibular lymph nodes) from wild boar of the perifluvial area of the Po River were collected for bacteriological examination. Brucella suis was isolated in culture from 18.9% of tested lymph nodes. These serological and microbiological results highlight the presence of B. suis in wild boar and suggest the importance of wild boar as a reservoir for B. suis. Comparison of the spatial distribution of Brucella-seropositive wild boars with the location of backyard swine farms revealed a higher chance of contact between the two populations only in the areas where the lower percentage of seropositive samples was observed. Conversely, the high percentage of seropositive samples observed in the Po River area coupled with positive microbiological cultures suggest a greater risk of infection for the humans directly or indirectly involved in wild boar hunting activity. These results may serve as a basis to establish sound wildlife management and to adopt education campaigns aimed at reducing the risk of human infection in people involved in wild boar hunting related activities.

Investigation of hematologic findings related to brucellosis in Anatolian region.

OBJECTIVES: To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients. METHODS: This multi-center study included patients older than 16 years of age who were followed up with a diagnosis of brucellosis. Patients' results, including white blood cell, hemoglobin, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet and eosinophil counts were analyzed at the initial diagnosis. RESULTS: In this study 51.3% of the patients diagnosed with brucellosis were male. The age median was 45 years for female and 41 years for male. A total of 55.1% of the patients had acute brucellosis, 28.2% had subacute, 7.4% had chronic and 9% had relapse. The most common hematologic findings in brucellosis patients were anemia (25.9%), monocytosis (15.9%), eosinopenia (10.3%), and leukocytosis (7.1%). Pancytopenia occurred in 0.8% of patients and was more prominent in the acute phase. The acute brucellosis group had lower white blood cell, hemoglobin, neutrophil, eosinophil, and platelet counts and mean platelet volume, and higher monocyte counts compared to subacute and chronic subgroups. CONCLUSION: It was noteworthy that in addition to anemia and monocytosis, eosinopenia was third most prominent laboratory findings in the study. Pancytopenia and thrombocytopenia rates were low.

Molecular and serological diagnosis of multiple bacterial zoonoses in febrile outpatients in Garissa County, north-eastern Kenya.

Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of non-malarial fevers in Kenya, yet their epidemiology remains unclear. We investigated brucellosis, Q-fever and leptospirosis in the venous blood of 216 malaria-negative febrile patients recruited in two health centres (98 from Ijara and 118 from Sangailu health centres) in Garissa County in north-eastern Kenya. We determined exposure to the three zoonoses using serological (Rose Bengal test for Brucella spp., ELISA for C. burnetti and microscopic agglutination test for Leptospira spp.) and real-time PCR testing and identified risk factors for exposure. We also used non-targeted metagenomic sequencing on nine selected patients to assess the presence of other possible bacterial causes of non-malarial fevers. Considerable PCR positivity was found for Brucella (19.4%, 95% confidence intervals [CI] 14.2-25.5) and Leptospira spp. (1.7%, 95% CI 0.4-4.9), and high endpoint titres were observed against leptospiral serovar Grippotyphosa from the serological testing. Patients aged 5-17 years old had 4.02 (95% CI 1.18-13.70, p-value = 0.03) and 2.42 (95% CI 1.09-5.34, p-value = 0.03) times higher odds of infection with Brucella spp. and Coxiella burnetii than those of ages 35-80. Additionally, patients who sourced water from dams/springs, and other sources (protected wells, boreholes, bottled water, and water pans) had 2.39 (95% CI 1.22-4.68, p-value = 0.01) and 2.24 (1.15-4.35, p-value = 0.02) times higher odds of exposure to C. burnetii than those who used unprotected wells. Streptococcus and Moraxella spp. were determined using metagenomic sequencing. Brucellosis, leptospirosis, Streptococcus and Moraxella infections are potentially important causes of non-malarial fevers in Garissa. This knowledge can guide routine diagnosis, thus helping lower the disease burden and ensure better health outcomes, especially in younger populations.

Factors influencing length of stay and costs in inpatient cases of human brucellosis as the primary diagnosis over a decade in Beijing, China.

Aims: In the year 2021, human brucellosis ranked fifth in terms of the number of cases among all statutorily notifiable infectious diseases in China, thus remaining a significant concern for public health. This study aims to provide insights into the financial burden of human brucellosis by examining hospital stays and associated costs for affected individuals. Methods: In this retrospective study, we gathered updated data from 467 inpatient cases primarily diagnosed with human brucellosis at eight major tertiary hospitals in Beijing, China, spanning from 2013 to 2023. To comprehensively explore the economic impact on individuals, we not only analyzed the duration of hospital stays and total costs but also examined various charge types, including drug, lab test, medical imaging, medical treatment, surgical procedures, medical supplies and consumables, inpatient bed care, nursing services, and other services costs. Statistical analysis was employed to compare differences among gender, age, ethnicity, type of health insurance, condition at admission, comorbidity index, the performance of surgery, and the site of infection. Results: Both the length of stay and total cost exhibited significant variations among insurance, surgery, and infection site groups. Utilization categories demonstrated significant differences between patients who underwent surgery and those who did not, as well as across different infection sites. Furthermore, multiple linear regression analysis revealed that the condition at admission, Elixhauser comorbidity index, infection site, and surgery influenced both hospital stay and total cost. In addition, age and insurance type were associated with total costs. Conclusion: By delving into various utilization categories, we have addressed a significant gap in the literature. Our findings provide valuable insights for optimizing the allocation and management of health resources based on the influencing factors identified in this study.

Seroprevalence and molecular detection of brucellosis among Pakistani women with spontaneous abortion.

Background: Human brucellosis is a neglected disease transmitted to humans from animals such as cattle, goats, dogs, and swine. The causative agents are bacteria of the genus Brucella, intracellular pathogens usually confined to the reproductive organs of their animal hosts causing sterility and abortions. The objective of the study was to determine the seroprevalence of brucellosis among women with spontaneous abortions (SAW) and compare this seroprevalence with that of healthy pregnant women (HPW). Methods: The case-control study was designed to determine the seroprevalence and molecular detection of brucellosis in women who suffered from spontaneous abortion and healthy pregnant women of the Haripur District of Pakistan. A total of 770 blood samples (n = 385 for each group) were collected from 9 public and 11 private hospitals in Haripur District from December 2021-March 2023. Data on demographic features, epidemiological variables, and risk factors were collected from each participant by structured questionnaires. Initial screening for brucellosis was performed by Rose Bengal Plate Test followed by qRT-PCR for molecular detection of the genus-specific BCSP-31 gene of Brucella. Results: The study showed that anti-Brucella antibodies were more found in SAW 23.63% (91/385) than in HPW 1.29% (5/385). Brucella specific DNA was amplified in 89.01% (81/91) seropositive samples of SAW. Demographic features and risk factors such as age, urbanicity, socioeconomic status, education, occupation, and animal contact were found significantly associated with brucellosis (p ≤ 0.05). Consumption of unpasteurized raw milk (OR = 18.28, 95%CI: 8.16-40.94) was found highly concomitant with seroprevalence. Conclusion: This study reports the first evidence of involvement of brucellosis in spontaneous abortions in women of Pakistan. The study can be used to develop strategies for risk management during pregnancy, to raise awareness for brucellosis, and develop control programs.

Neurobrucellosis: laboratory features, clinical characteristics, antibiotic treatment, and clinical outcomes of 21 patients.

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Knowledge-attitude and practice of Anthrax and brucellosis: Implications for zoonotic disease surveillance and control in pastoral communities of Afar and Somali region, Ethiopia.

BACKGROUND: Anthrax and brucellosis are endemic national priority zoonotic diseases in Ethiopia. This study assess the possible factors explaining the current limited information available on animal and human cases in pastoral communities. METHODS: Two questionnaire surveys gathered data from 509 pastoralists and 51 healthcare providers between February and April 2019 in five districts of Afar and the Somali region (SRS). RESULTS: Among the 51 healthcare providers, 25 (49%) and 38 (74.5%) had heard of brucellosis, and anthrax, respectively. Of those, only 3 (12%) and 14 (36.8%) knew the symptoms of brucellosis and Anthrax. None of the Health Extension Workers knew any disease symptoms. Healthcare providers recalled two human cases of brucellosis and 39 cases of Anthrax in the last 12 months, based on symptom-based diagnosis. Pastoralists had a moderate level of knowledge about diseases in their animals, with over half (52.4%; n = 267/509) understanding that animals can transmit diseases to people. Overall, 280 out of 508 (55.1%) and 333 out of 507 (65.7%) pastoralists had heard of brucellosis and Anthrax, respectively. Among the latter, 282 (51.3%) knew at least one preventive measure for Anthrax. However, disease knowledge among women was poor. Despite their knowledge, pastoralists engaged in risky unprotected animal handling, animal product consumption/usage as well as husbandry behaviors exposing them to pathogens and favoring the spread of diseases. They identified Anthrax as the most important zoonosis (47.6%) and as one of top three diseases suspected to cause mortality in their livestock. Pastoralists highlighted lack of vaccine coverage, availability and their timely administration. Both, pastoralists and healthcare providers stated the lack of disease awareness and the unavailability of drugs in the market as important challenges. Health facilities lacked protocols and standard operating procedures for managing zoonotic diseases, and did not have access to laboratory confirmation of pathogens. CONCLUSION: Our study revealed significant under-reporting of Anthrax and brucellosis, and weak prevention and response in humans, mostly associated with poor disease knowledge of healthcare providers. Ability to respond to animal outbreaks was limited by vaccine and drugs availability, timely vaccine administration and the mobility of pastoralists.

[Analysis on personal protection in occupational population at high risk for brucellosis and influencing factor in China].

Objective: To understand the current status of personal protection in occupational population at high risk for brucellosis in China and provide evidence for the evaluation of implementation of National Brucellosis Prevention and Control Plan (2016-2020). Methods: Four counties in Shanxi Province and Xinjiang Uygur Autonomous Region were selected to conduct a questionnaire survey in occupational population at high risk for brucellosis from December 2019 to July 2020 by using cross-sectional survey methods. Results: A total of 2 384 persons at high risk for brucellosis were surveyed, and the standardized utilization rate of personal protective equipment (PPE) was 20.13% (480/2 384). The utilization rate of glove, mask, rubber shoe, and work cloth were 38.26% (912/2 384), 31.80% (758/2 384), 32.01% (763/2 384) and 30.87% (736/2 384),respectively. There were significant differences in the utilization rate and standardized utilization rate of the four types of PPE among populations in different age, occupation, educational level and area groups (all P<0.001). The utilization rate and standardized utilization rate of PPE were lower in people over 60 years old, women, farmers, and those with lower educational level. The results of multivariate analysis showed that occupation and area were the influencing factors for the standardized utilization of PPE, the standardized utilization rates of PPE were higher in herdsmen and veterinarians. The standardized utilization rate of PPE in Yanggao County and Huocheng County was significantly higher than that in Zuoyun County and Hunyuan County. Conclusions: The utilization rate of the four types of PPE in occupational population at high risk for brucellosis was not high in China, and the standardized utilization rate was low, lower than the requirement in National Brucellosis Prevention and Control Plan, and there were significant differences among different areas. It is urgent to distribute PPE to occupational population at high risk for brucellosis and carry out health education about PPE utilization. Meanwhile, it is necessary to strengthen information exchange or sharing among different areas.

Impact of herd mobility on brucellosis seroprevalence and spread risk resulting from cross-border transhumance.

BACKGROUND: Cross-border livestock mobility through transhumance is mainly practiced in West African countries for seasonal access to resources and market. Cross-border herds are involved in the dynamic of transboundary animal diseases among them brucellosis taken as model. Brucellosis is a zoonotic disease causing abortion. OBJECTIVES: This study explores the seroprevalence of brucellosis according to mobility and infection spread between Mali and Côte d'Ivoire in the context of seasonal cross-border transhumance. METHODS: From February to April 2021, a transversal serological survey of brucellosis was conducted on 521 cattle from 111 transhumant herds and 283 cattle from 59 sedentary herds, all from Mali. RESULTS: The global individual seroprevalence for Brucella spp. in transhumant and sedentary cattle from Mali was 8.2% (95% CI = 6.0-10.5). At herd level, seroprevalence was 21.2% with a significant variation between transhumant (11.7%) and sedentary (39.0%) herds. For herds in transhumance, cattle seropositivity was associated with a previous infection suspected by herdsmen odds ratio (OR = 4.4; 95% CI = 1.1-18.1) and unknown abortion aetiology (OR = 4.3; 95% CI = 1.0-17.3). The departure region (coming from Sikasso) and previous brucellosis infection or unexplained abortion could be used to predict Brucella infection in transhumant herds with a probability of around 60%. The risk of brucellosis introduction in host regions was high despite the individual animal seroprevalence of 3.6% and a low sale rate in transhumant cattle. CONCLUSIONS: The findings suggest that testing transhumant during border control and survey of cattle markets and sales could improve risk control of the spread of disease at regional scale.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

A Multidisciplinary "One Health" Tool for Tackling Brucellosis.

Introduction: The Epizootiological Investigation Form (EIF) is a document issued for every notified human brucellosis case, with the aim to convey information from public health to veterinary authorities for farm animals epidemiologically linked with the patient. We assessed the integration of EIF to the routine collaboration among stakeholders and the efficiency in directing the veterinary efforts to identify Brucella-infected animals. Methods: EIFs were evaluated for the implementation, timeliness, and completeness of the shared information provided by the public health and the veterinary authorities. The efficiency of EIFs in identifying infected farms was compared with the Brucella infection rate of routinely screened farms in the frame of the national brucellosis program. Results: During 2017-2022, 344 EIFs were issued for equal number of human brucellosis cases and 118 (34.3%) were circulated successfully among all stakeholders, whereas 226 (65.7%) went missing. The highest rate of intersectoral circulation occurred in May (47.8%, p = 0.007). Veterinary investigation was performed, and result was provided in 62 (57.4%) of the 108 circulated EIFs that disclosed the contact details of the epidemiologically linked animal farms. Brucella was detected at a significantly higher rate (51.7%) in the investigated sheep and goats' farms than the infection rate (2.7%) of the national brucellosis program (p < 0.00001). Among the screened bovine herds, two were found infected of the eight tested (25%). The circulation among all competent authorities of EIFs with a farm screening outcome required a median (interquartile range) of 50 days (22, 88). The likelihood of a "complete" EIF per human case differed among geographic Regions (p = 0.010), and was higher for patients diagnosed in April (p = 0.001) and occupied as stockbreeders (p = 0.025). Conclusions: EIF is a useful tool for pinpointing suspected animals for brucellosis screening. Training of the collaborating personnel is essential for improving the implementation of EIF in the everyday practice.

One Health approach for Brucella canis: Serological and molecular detection in animal-hoarding individuals and their dogs.

Animal hoarding disorder (AHD) is classified as a psychiatric obsessive-compulsive condition characterized by animal accumulation and often accompanied by unsanitary conditions and animal cruelty. Although AHD may increase pathogen transmission and spread, particularly for zoonotic diseases, human and dog exposure in such cases has yet to be fully established. Accordingly, this study aimed to assess Brucella canis in 19 individuals with AHD (11 households) and their 264 dogs (21 households) in Curitiba, the eighth largest city in Brazil, with approximately 1.8 million habitants. Anti-B. canis antibodies were detected by the 2-mercaptoethanol microplate agglutination test (2ME-MAT) and by a commercial lateral flow immunoassay (LFIA), while molecular detection of previously positive seropositive samples was performed by conventional PCR. Although all the human samples were 2ME-MAT negative, 12/264 (4.5%, 95% Confidence Interval: 2.0-7.0%) dog samples were 2ME-MAT and LFIA positive, with 2ME-MAT titers ranging from 20 to 640. At least one dog in 4/21 (19.0%, 95% CI: 2.0-46.0%) households was seropositive. Despite the absence of seropositivity in individuals with AHD and the comparatively low seroprevalence in dogs, B. canis circulation and outbreaks should be considered in such human populations due to the high burden and recurrent character of B. canis exposure in high-density dog populations and the constant introduction of susceptible animals.

Comparative Analysis of Pediatric Brucellosis Cases With and Without Bacteremia.

Introduction: Brucellosis, which is among the endemic regions of Turkey, is a common zoonotic disease. The gold standard in diagnosing brucellosis is culture. We aimed to compare demographic characteristics, risk factors, and clinical and laboratory variables between cases with culture positivity and undetected in culture. Materials and Methods: This single-center study was conducted between January 2007 and April 2022. Clinical and laboratory data of patients with brucella growth in blood culture and patients without growth were compared. Results: A total of 150 patients were included in the study. The median age was 10 (1-18 years). Of the patients, 66 (44%) were female and 84 (56%) were male. Forty (26.7%) of the patients were bacteremic and 110 (73.3%) were nonbacteremic. In the bacteremic group, white blood cell count, platelet, and hemoglobin counts were lower, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were higher. In clinical evaluation, fever, hepatomegaly, splenomegaly, and abdominal pain were more common in the bacteremic group. Conclusion: The distinction between bacteremic and nonbacteremic brucellosis can be predicted using laboratory values such as white blood cells, hemoglobin counts, platelet, ALT, and AST, and clinical findings such as fever, abdominal pain, hepatomegaly, and splenomegaly.

Sero-prevalence and risk factors associated with occurrence of anti-Brucella antibodies among slaughterhouse workers in Uganda.

INTRODUCTION: Brucellosis is a febrile zoonosis occurring among high-risk groups such as livestock keepers and abattoir workers and is a public health priority in Uganda. The technical complexities of bacteriological and molecular methods make serological approaches the cornerstone of diagnosis of human brucellosis in resource limited settings. Therefore, proper application and interpretation of serological tests is central to achieve a correct diagnosis. MATERIALS AND METHODS: We conducted a cross-sectional study to estimate the seroprevalence and factors associated with anti-Brucella antibodies among slaughterhouse workers processing ruminants and pigs in three regions of the country with serial testing using a combination of the Rose Bengal Test (RBT) and the BrucellaCapt test. An authorized clinician collected 543 blood samples from consenting abattoir workers as well as attribute medical and social demographic data. Univariable and multivariable logistic regression were used to determine factors associated with anti-Brucella sero-positivity. RESULTS AND DISCUSSION: The sero-prevalence among ruminant slaughterhouse workers ranged from 7.3% (95% CI: 4.8-10.7) using BrucellaCapt to 9.0% (95% CI: 6.3-12.7) using RBT. Slaughterhouse workers from the Eastern regions (AOR = 9.84, 95%CI 2.27-69.2, p = 0.006) and those who graze animals for alternative income (AOR = 2.36, 95% CI: 1.91-6.63, p = 0.040) were at a higher risk of exposure to Brucella. Similarly, those who wore Personal Protective Equipment (AOR = 4.83, 95%CI:1.63-18.0, p = 0.009) and those who slaughter cattle (AOR = 2.12, 95%CI: 1.25-6.0, p = 0.006) were at a higher risk of exposure to Brucella. Those who slaughter small ruminants (AOR = 1.54, 95%CI: 1.32-4.01, p = 0.048) were also at a higher risk of exposure to Brucella. CONCLUSIONS AND RECOMMENDATIONS: Our study demonstrates the combined practical application of the RBT and BrucellaCapt in the diagnosis of human brucellosis in endemic settings. Both pharmaceutical (e.g., routine testing and timely therapeutic intervention), and non-pharmaceutical (e.g., higher index of suspicion of brucellosis when investigating fevers of unknown origin and observation of strict abattoir hygiene) countermeasures should be considered for control of the disease in high-risk groups.

Molecular epidemiological characteristics of osteoarthritis-associated Brucella melitensis in China: evidence from whole-genome sequencing-based analysis.

BACKGROUND: Brucellosis, developing complications including arthritis, spondylitis, sacroiliitis, and osteomyelitis, is one of the most common zoonotic diseases in the current world which causes economic losses to the livestock industry and is a great public health concern. Brucella melitensis are the main pathogen of brucellosis epidemics in China, most of which are located in northern China. However, there is limited knowledge about the epidemiology of osteoarthritis-associated brucellosis. This study was aimed to reveal the prevalence of osteoarthritis-associated brucellosis in Inner Mongolia and also to investigate the molecular characteristics of B. melitensis isolates. METHODS AND RESULTS: In 2018, the osteoarthritis symptoms of brucellosis in the Brucellosis department of a hospital in Inner Mongolia were investigated. Twenty osteoarthritis-associated B. melitensis strains, isolated from the inpatients in Inner Mongolia during 2013-2017, were subjected to whole genome sequencing. The multilocus sequence type (MLST) and core genome SNP (cgSNP) analysis were conducted to detect molecular epidemiological characteristics. The incidence of brucellosis osteoarthritis symptoms in males (85/120, 70.8%) was significantly higher than that in females (35/120, 29.2%), and the age of patients was concentrated between 41 and 60 years old. In silico analyses indicated ST8 was the prevalent sequence type and the transmission of osteoarthritis-associated B. melitensis among different geographical areas. All strains carry virulence genes, including cgs, lpsA, manCoAg, pgm, pmm, virB4, wbdA and wboA. CONCLUSION: Our study showed the close epidemiologically connection of osteoarthritis-associated B. melitensis strains in northern China. And ST8 was the prevalent sequence type which need our attention.