Search Results (666)

Camelids are increasingly recognized as important livestock species. They are valuable sources of meat, fiber, and milk. Despite their growing popularity, many aspects of their reproductive physiology and pathology remain unclear. Their reproductive performance is reported to be low in many countries. Advances in camelid veterinary care have identified several disorders, some of which are species-specific. This article describes an approach to and the diagnosis of infertility and subfertility cases in alpacas, llamas, and camels referred to the authors over the past 35 years. Ultrasonography, endometrial cytology, and biopsy are the primary diagnostic tools for practitioners. However, laparoscopy, hysteroscopy, and cytogenetics are indicated for cases referred to theriogenologists. The incidence of congenital and acquired reproductive disorders is presented. A high incidence of congenital defects of the reproductive tract is found in South American camelids, which raises concerns about animal welfare. Acquired disorders are similar to those described in other species. Endometritis and endometrosis are major disorders contributing to infertility and early pregnancy loss. However, studies on uterine defense mechanisms and the pathogenesis of these disorders are lacking. Hydrobursitis, a common cause of infertility in dromedary camels, warrants further research. The implications of some contagious diseases (tuberculosis, campylobacteriosis, and brucellosis) in female infertility are discussed. These findings emphasize the importance of including camelid medicine in veterinary education to ensure a high standard of care for this species. Full article

Tuberculosis (TB) probably returned to being the world’s leading cause of death from a single infectious agent after three years during which it was replaced by COVID-19. Currently, there are two major, closely related challenges in TB treatment: a large number of cases of drug-resistant TB, as well as cases complicated by severe comorbidities. Materials and Methods: Our study included 219 patients with pulmonary multidrug-resistant TB (MDR-TB) who were treated in several clinics in St. Petersburg, Russian Federation. Of these patients, 47.0% had extensively drug-resistant TB (XDR-TB), and 48.4% had severe comorbidities. Univariate and multivariate exploratory analyses were performed to hypothesize factors affecting treatment success. Results: Both extensive drug resistance (XDR-TB) and the presence of comorbidity were significantly associated with a lower probability of successful treatment: OR = 0.56 (CI: 0.32–0.96, p = 0.033) and OR = 0.53 (CI: 0.30–0.91, p = 0.020), respectively. The use of bedaquiline was significantly associated with successful treatment in cases of XDR-TB: OR = 4.15 (CI: 1.32–16.20, p = 0.012). Only an insignificant opposite effect was identified for cases of non-XDR-TB: OR = 0.77 (p = 0.62). Resistance to thioamides was associated with unsuccessful treatment in cases complicated by comorbidity: OR = 0.46 (CI: 0.21–0.99, p = 0.044). Again, an only insignificant opposite effect was identified for cases without comorbidities: OR = 1.11 (p = 0.81). Almost all the patterns described above were replicated in the multivariate model. The following two differences with the univariate results were observed. First, the association between the use of bedaquiline and successful treatment became even more pronounced, and, as before, this was true only for XDR-TB: OR = 6.51 (CI: 1.98–26.04, p = 0.0036) for XDR-TB, and OR = 0.99 (p = 0.98) for non-XDR-TB. Second, the impact of comorbidities on treatment success remained significant only in conjunction with thioamide resistance. In addition, we found that the association between resistance to thioamides and unsuccessful treatment was especially pronounced in cases complicated by heart disease: OR = 0 (CI: 0–0.79, p = 0.0088). Conclusions: We confirmed that both XDR-TB and the presence of comorbidities are serious challenges in the treatment of tuberculosis. We also have reason to hypothesize that, first, bedaquiline can be a much more crucial component of therapy in cases of XDR-TB than in other cases of MDR-TB and, second, thioamides can play a positive role in cases complicated by comorbidities, especially by heart diseases. These findings should be considered as weak hypotheses that require further verification using independent data, as our analysis was exploratory rather than confirmatory. Full article

While pathogenic microbes, such as Yersinia pestis, Mycobacterium tuberculosis, Clostridium tetani, influenza A virus, and many others, have historically been the focus of scientific attention due to their role in causing severe diseases, beneficial microorganisms are being increasingly recognized for their essential contributions to human, animal, and plant health within the One Health framework, as well as their contributions to nutrition and the stability of ecosystems [...] Full article

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and is associated with high morbidity and mortality, especially in resource-limited settings. In Mozambique, where both tuberculosis and HIV are highly prevalent, TBM poses significant diagnostic and therapeutic challenges. This study aimed to describe the clinical characteristics and to identify predictors of TBM mortality among persons living with HIV (PLWH) in a rural hospital in Mozambique. Methods: We conducted a retrospective cohort study at Carmelo Hospital of Chokwe (CHC) between 2015 and 2020. We included 372 PLWH diagnosed with TBM (PTBM); data on demographics, clinical presentation, and laboratory findings were extracted from patient records. TBM diagnosis was considered for confirmed cases based on a hospital-adapted algorithm incorporating clinical features, cerebrospinal fluid (CSF) analysis, TB-LAM, and Xpert MTB/RIF testing. Cox proportional hazard models were used to identify independent predictors of mortality, and Kaplan–Meier survival curves with log-rank tests were used to assess survival differences across clinical subgroups. Significance was considered at a p value ≤ 0.05 with an adjusted hazard ratio (AHR) 95% CI in the multivariate analysis. Results: Overall, 372 PTBM contributed to a total of 3720 person-months (PM) of treatment follow-up, corresponding to a mortality incidence of 3.76 deaths per 100 person-months. Factors independently associated with increased mortality included male sex (adjusted hazard ratio [aHR]: 1.80; 95% CI: 1.21–2.68; p = 0.004), BMI < 18.5 kg/m² (aHR: 2.84; 95% CI: 1.46–5.55; p = 0.002), Immunovirological failure to ART (aHR: 2.86; 95% CI: 1.56–5.23; p = 0.001), CSF opening pressure >40 cmH₂O (aHR: 2.67; 95% CI: 1.46–4.86; p = 0.001), and TBM severity grading III (aHR: 4.59; 95% CI: 1.79–11.76; p = 0.001). TBM involving other organs also significantly worsened survival (aHR: 2.03; 95% CI: 1.27–3.25; p = 0.003). Conclusions: TBM mortality in PLWH was driven by ART failure, high CSF pressure, and malnutrition. Male sex and severe neurology also increased risk. Urgent interventions are proposed: optimize ART, manage intracranial pressure, provide nutritional support, and use corticosteroids. An integrated care approach is essential to improving survival in resource-limited settings. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of infectious disease mortality worldwide. Global TB control efforts face several hurdles, including the lack of a broadly effective vaccine, limited sensitivity of current diagnostics, particularly for paucibacillary and extrapulmonary TB, and significant adverse effects associated with prolonged small-molecule drug regimens. The growing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains further underscores the urgent need for innovative therapeutic strategies. We outline characteristics of next-generation TB therapeutics. We show that antibody (Ab)-drug conjugates (ADCs) satisfy many of those desirable characteristics. Since a major hurdle to this approach lies in Mtb-specific Abs, we highlight an open-access resource comprising a broad panel of Mtb-specific mouse monoclonal antibodies targeting key factors involved in Mtb survival, immune evasion, and pathogenesis. These critical Mtb virulence factors include heat shock proteins (GroES, DnaK, and HspX), surface-associated or secreted proteins (LAM, Ag85, HBHA, Mpt64/CFP-21, and PhoS1/PstS1), cell wall/envelope-associated proteins (LprG/p27), and detoxifying enzymes (KatG and SodA). The resource provides full-length sequences of the immunoglobulin variable regions, enabling antibody engineering and facilitating translational TB research across vaccine design, diagnostic development, and immunotherapeutic applications, in addition to ADCs. This ADC targeted delivery strategy holds promise for overcoming TB heterogeneity and eliminating both active and dormant Mtb populations within a single therapeutic formulation and offers a novel avenue for precision TB treatment. Full article

Tuberculous meningitis (TBM) is a severe illness that is predominantly observed in countries with a high burden of tuberculosis. It is primarily found in infants and human immunodeficiency virus (HIV)-infected adults, and, if left untreated, causes irreversible damage to the host’s nerve and brain tissue, often leading to mortality. Current methods of TBM detection relies on cerebrospinal fluid (CSF) culture, which may only yield results in up to 6 weeks, is not very sensitive, and requires a biological safety level III laboratory to conduct. Other detection methods are equally not very sensitive and laborious. This research investigates the detection of interferon-gamma (IFN-γ) protein biomarker using fluoroimmunoassay with an optical biosensor and a custom-manufactured chip. The glass-surface of the chip was treated with 3-aminopropyltriethoxysilane (APTES) and incubated with glutaraldehyde to prepare for immobilization, after which a sandwich ELISA format was used to perform a dilution series by immobilizing the capture antibody, IFN-γ protein, and fluorescein isothiocyanate (FITC)-stained detection antibody onto the chip. The optical biosensor excited the FITC-stained antibodies to capture the emission light at multiple exposures, which were then merged to create a high dynamic range (HDR) image for image processing. The results from the optical biosensor were verified with a Zeiss LSM780 confocal microscope (Carl Zeiss (Pty) Limited, Cape Town, South Africa). The system demonstrated the capability to rapidly identify the biomarker, detect the binding sites, and quantify IFN-γ in blood serum. This fluorescent optical sensor proposes a possible approach for the development of a point-of-care system for TBM, providing a quicker and simpler method for the early detection of TBM. Full article

Coinfection with HIV, active tuberculosis, and COVID-19 is rare but markedly increases mortality risk and complicates treatment due to the interactions between these infections. Management requires a multidisciplinary approach that integrates antiretroviral therapy, antituberculous drugs, antibiotics, and supportive care for COVID-19. We report the case of a 28-year-old male with HIV (viral load 30 copies, CD4 count 303), active tuberculosis, and a history of resolved syphilis, who presented with severe respiratory decompensation and hypoxemia (SpO₂ 55%), requiring orotracheal intubation. Initial treatment included broad-spectrum antibiotics, antiretrovirals, and antituberculous therapy. Despite the critical illness, the patient demonstrated progressive clinical improvement, was successfully extubated after a spontaneous breathing trial, and continued recovery under supplemental oxygen. This case underscores the clinical complexity of triple coinfection and highlights the potential for favorable outcomes when management is timely and multidisciplinary. Full article

Neglected tropical diseases (NTDs) constitute a group of infectious diseases that severely affect the health of impoverished populations, and the health, economies, and health systems of affected countries. Leishmaniasis and human African trypanosomiasis (HAT) are particularly notable, and malaria, despite not being neglected, is part of the “big three” (HIV, tuberculosis, and malaria) with high incidence, increasing the probability of infection by NTDs. Therefore, efforts are ongoing in the search for new drugs targeting the enzyme N-myristoyltransferase (NMT), a potential drug target that has been explored. Thus, we provide a review here that highlights the epidemiological data for these diseases and the importance of discovering new drugs against these agents. Here, the importance of NMT and its inhibitors is clear, with this study highlighting thiochromene, pyrazole, thienopyridine, oxadiazole, benzothiophene, and quinoline scaffolds, identified by computational methods followed by biological assays to validate the findings; for example, this study shows the action of the aminoacylpyrrolidine derivative 13 against Leishmania donovani NMT (IC₅₀ of 1.6 nM) and the pyrazole analog 23 against Plasmodium vivax NMT (IC₅₀ of 9.48 nM), providing several insights that can be used in drug design in further work. Furthermore, the selectivity and improvement in activity are related to interactions with the residues Val⁸¹, Phe⁹⁰, Tyr²¹⁷, Tyr³²⁶, Tyr³⁴⁵, and Met⁴²⁰ for leishmaniasis (LmNMT); Tyr²¹¹, Leu⁴¹⁰, and Ser³¹⁹ for malaria (PvNMT); and Lys²⁵ and Lys³⁸⁹ for HAT (TbNMT). We hope our work provides valuable insights that research groups worldwide can use to search for innovative drugs to combat these diseases. Full article

Background: Stigma is a major barrier to tuberculosis (TB) control worldwide. However, there is limited evidence of TB-related stigma not only toward patients but also toward their family members in Saudi Arabia. This study aims to assess the level of TB-related stigma and associated factors among individuals with TB and their families in Jazan, Saudi Arabia. Methods: A cross-sectional survey was conducted among 404 participants (272 adult patients with TB and their 132 family members). Participants were interviewed using a structured questionnaire adapted from validated TB-related stigma scales, covering sociodemographic factors and perceived stigma. Sociodemographic factors were used to compare stigma grades. Collected data were analyzed using the Statistical Package for the Social Sciences. Frequencies and percentages were used to describe qualitative variables, while the χ²-test was applied to compare TB-related stigma levels according to demographic factors. p < 0.05 was considered statistically significant. Results: Most participant patients had pulmonary TB (78.7%), while 21.3% had extrapulmonary TB. More than half of them (50.7%) experienced severe stigma, while 23.5% had mild stigma. Levels of TB-related stigma differed significantly according to the patients’ age groups (p = 0.011), residence (p < 0.001), occupation (p = 0.022), and type of TB, which was higher among those with pulmonary TB (p = 0.003). Moreover, 24.2% of family members experienced severe stigma, while 25% had mild stigma. Perceived stigma showed a negative impact on the management of TB. Levels of stigma differed significantly among family members according to their residence (p < 0.001) and marital status (p = 0.018). Conclusions: TB-related stigma is widespread among individuals with TB and their family members in Saudi Arabia. This stigma has significant negative impacts on the management of TB. Levels of perceived stigma are higher among younger patients, those living in urban areas, unemployed patients, and patients with pulmonary TB. Among family members, the stigma levels are higher for those living in urban areas and single individuals. Full article

Background: Pulmonary tuberculosis (TB) is increasingly recognized as a risk factor for chronic obstructive pulmonary disease (COPD), but its impact on COPD onset and severity remains poorly characterized, particularly in low- and middle-income countries. This multicenter study aimed to assess the impact of prior pulmonary TB on COPD onset, severity, the timing of the first severe exacerbation, and progression among Romanian patients with and without a history of pulmonary TB. Methods: This retrospective multicenter study included adults hospitalized for their first severe COPD exacerbation at two tertiary care centers in Romania between April 2020 and April 2025. Patients were grouped based on smoking status and prior TB history. Propensity score matching was used to control for confounding factors. Clinical characteristics, spirometry, and radiological TB patterns were analyzed comparatively between patients with prior TB and TB-naïve patients. Results: Among 403 COPD patients, those with prior TB had significantly earlier COPD onset (mean age 48.67 ± 6.42 vs. 65.61 ± 5.14 years in smokers, p < 0.001) and shorter intervals to their first severe COPD exacerbation compared to patients without prior TB (6.35 ± 4.71 vs. 15.14 ± 6.93 years in smokers, p < 0.001). COPD prevalence was higher among TB survivors compared to those without TB history, especially in smokers (OR = 5.73; 95% CI, 3.30–9.94, p < 0.001), versus non-smokers (OR =2.23; 95% CI, 1.37–3.64, p = 0.001). Radiological severity of TB lesions significantly influenced COPD prevalence among smokers (OR = 10.79, p < 0.001). Conclusions: Prior pulmonary TB substantially accelerates COPD onset, exacerbation timing, and disease severity, particularly in smokers. This multicenter comparative study demonstrates that prior pulmonary TB significantly accelerates COPD onset, exacerbation timing, and disease severity, especially among smokers. Recognizing TB history as a significant COPD risk factor underscores the importance of targeted COPD screening and tailored management in populations with high TB prevalence. Full article

Predictive models use historical data to predict a future event and can be applied to a wide variety of tasks. A broader evaluation of the cattle literature is required to better understand predictive model performance across various health challenges and to understand data types utilized to train models. This narrative review aims to describe predictive model performance in greater detail across various disease outcomes, input data types, and algorithms with a specific focus on accuracy, sensitivity, specificity, and positive and negative predictive values. A secondary goal is to address important areas for consideration for future work in the beef cattle sector. In total, 19 articles were included. Broad categories of disease were covered, including respiratory disease, bovine tuberculosis, and others. Various input data types were reported, including demographic data, images, and laboratory test results, among others. Several algorithms were utilized, including neural networks, linear models, and others. Accuracy, sensitivity, and specificity values ranged widely across disease outcome and algorithm categories. Negative predictive values were greater than positive predictive values for most disease outcomes. This review highlights the importance of utilizing several performance metrics and concludes that future work should address prevalence of outcomes and class-imbalanced data. Full article

Tuberculosis and parasitic infections, including Toxocara, frequently coexist in many regions worldwide, yet their interaction remains poorly understood. Tuberculosis triggers a type 1 immune response characterized by IL-12, IFN-γ, and TNF-α production, while toxocariasis elicits a type 2 response, mediated by cytokines such as IL-4, IL-5, IL-13, and IL-33. The coexistence of these divergent immune pathways can disrupt immune regulation and impair the host’s ability to control both infections, potentially leading to persistent hypereosinophilia. We illustrate this complex interplay through a real-world case involving a heavy smoker in whom Toxocara infection likely reactivated latent tuberculosis, resulting in severe, unexplained hypereosinophilia and late-onset asthma with recurrent exacerbations. After excluding other causes and completing full antituberculosis therapy along with three courses of antiparasitic treatment and systemic corticosteroids, hypereosinophilia persisted. The introduction of benralizumab, a biologic therapy targeting IL-5Rα, led to a rapid reduction in eosinophils to normal ranges and significant clinical improvement. This case underscores the diagnostic and therapeutic challenges posed by the intersection of common infections and highlights that even a neglected parasitic infection such as toxocariasis can underlie severe respiratory complications with eosinophilia, where paradoxically biologic therapy may ultimately provide a very effective intervention. Full article

The shortage of organs for use in transplantation has contributed to the development of an international commercial market for organ transplantation. Unfortunately, transplant tourism (TT) is associated with risks for surgical complications, poor graft outcome, increased mortality, and infectious complications. TT increases the risk of several viral (HIV and hepatitis B and C viruses), bacterial (Mycobacterium tuberculosis, Pseudomonas sp., Enterococcus sp., Escherichia coli, and Acinetobacter sp.), fungal (Aspergillus sp., Zygomycetes, Ramichloridium sp., Scedosporium apiospermum, and Trichosporon sp.), and parasitic (Plasmodium sp., Trypanosoma cruzi and Strongyloides sp., and Microsporidia sp.) infections. This paper presents a case report of an anonymous patient who travelled to Pakistan and underwent a commercial kidney transplant. He developed infection from extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC). Moreover, we reviewed all published cases of bacterial, viral, and fungal infections in kidney transplant recipients who bought their organs abroad. Full article

Background: Tuberculosis (TB) remains a major global health challenge, including in Thailand, where both asymptomatic and symptomatic cases sustain transmission. The disease burden increases treatment complexity and mortality, requiring integrated care and coordinated policies. Methods: We developed a deterministic compartmental model to examine the transmission dynamics of TB in Thailand, incorporating both latent and active stages of infection, as well as vaccination coverage. The model was calibrated using national TB incidence data, and sensitivity analysis revealed that the TB transmission rate was the most influential parameter affecting the basic reproduction number (R₀). We evaluated the impact of several intervention strategies, including increased treatment coverage for latent and active TB infections and improved vaccination rates. Results: Our analysis indicates that among the single interventions, scaling up effective treatment for latent TB infections produced the greatest reduction in asymptomatic and symptomatic cases, while enhanced treatment for active TB cases was second most effective for reducing both asymptomatic and symptomatic cases. Importantly, our results indicate that combining multiple interventions yields significantly greater reductions in overall TB incidence than any single approach alone. Our findings suggest that a modest investment in integrated TB control can substantially reduce TB transmission and disease burden in Thailand. However, complete eradication of TB would require a comprehensive and sustained investment to achieve near-universal coverage of both preventive and curative strategies. Conclusions: TB remains a significant public health threat in Thailand. Targeted interventions and integrated strategies are key to reducing disease burden and improving treatment outcomes. Full article

The P1104A variant in the TYK2 gene is recognized as the first common monogenic cause of tuberculosis, and recent studies also suggest a potential role in COVID-19 severity. However, its frequency and impact in admixed Latin American populations remain underexplored. Therefore, we investigated the P1104A/TYK2 variant in a cohort comprising 1826 RT-PCR-confirmed COVID-19 patients from Southern Brazil. Cases were stratified by severity into non-severe (n = 1190) and severe (n = 636). Three homozygous individuals were identified—one non-severe and two severe cases—although no statistically significant association with disease severity was observed. The frequency of the C allele in the COVID-19 cohort (2.85%) was significantly higher than in Brazilian population databases, including “DNA do Brasil” (1.81%, p < 0.001) and ABraOM (2.34%, p = 0.03), but lower than in the multi-ancestry gnomAD database (3.71%, p = 0.01), possibly reflecting ancestry bias. We also observed associations between COVID-19 severity and sex (p = 0.003), age (p < 0.001), obesity (p < 0.001), diabetes (p < 0.001), and hypertension (p < 0.001). Future studies in larger and more diverse cohorts are needed to characterize the prevalence of the variant in admixed populations and assess its contribution to COVID-19 susceptibility. Full article