A retrospective study of Crimean-Congo hemorrhagic fever in Iraq.

Background: CCHF is transmitted via ticks biting and directly by contact with tissue or blood of infected patients or viremic animals. This study intends to determine the occurrence of CCHF in Iraq between 2015 and 2019. Methods: This study was designed as a retrospective and descriptive cross-sectional study. It was approved the occurrence of CCHF in Iraq with relation to some epidemiological and demographic data reported in the Iraqi Communicable Diseases Control Center (CDC)/zoonotic diseases section between 2015-2019. Results: Out of 206 suspected cases, only 17 were diagnosed as CCHF with a total fatality ratio of 52%, 25%, and 80% in 2015 and 2018 respectively. However, no mortality was reported during 2016, 2017, and 2019. The mean age of the patients was 33 years± 18 SD, in males mainly (76%). Moreover, the risk groups were 29 %, 23 %, 18 % 12 %, and 6 % for butchers, animal dealers, gainers, both housewives and students and children respectively. Conclusion: Strict precautions and precise surveillance should be implemented to control the disease and protect the community by improving the diagnosis and treatment of CCHF. The authors recommend another future study to detect the genotyping and sequencing of CCHFV in Iraq.

The Efficacy of Montelukast in Reducing the Risk of Warning Signs and Subsequent Dengue Shock Syndrome in Adult Dengue Fever Patients.

BACKGROUND: Dengue fever continues to pose significant health challenges globally, with recent outbreaks in Bihar, India, prompting a search for effective therapeutic interventions. This study assesses the effectiveness of Montelukast, traditionally used for asthma, in mitigating the severity of dengue fever symptoms and its progression to dengue shock syndrome (DSS). OBJECTIVE: To evaluate the impact of Montelukast on the prevalence of dengue warning signs and the incidence of DSS in adult patients. METHODS: A prospective observational study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India, from August 2022 to October 2023, enrolling 500 patients diagnosed with dengue fever. Participants were divided into two groups. About 250 were treated with Montelukast and 250 received standard care. Outcomes measured included the incidence of warning signs, DSS, length of hospital stay, and 30-day mortality. RESULTS: The Montelukast group exhibited a 24% lower prevalence of dengue warning signs compared to the control group, with 90 out of 250 patients (36%) in the Montelukast group versus 150 out of 250 patients (60%) in the control group (p < 0.001). The incidence of DSS was significantly reduced in the Montelukast group, with 4 out of 250 patients (1.6%) compared to 21 out of 250 patients (8.4%) in the control group (odds ratio: 0.178, p < 0.001). Furthermore, Montelukast users experienced shorter hospital stays (average 4.52 days vs. 6.54 days, T-statistic: -7.59, p = 1.58×10-13) and a reduced 30-day mortality rate, with 5 out of 250 patients (2%) in the Montelukast group versus 12 out of 250 patients (5%) in the control group (p < 0.03). CONCLUSION: Montelukast significantly lowers the incidence of dengue warning signs and DSS, shortens hospital stays, and decreases mortality rates among dengue patients, supporting its potential integration into existing dengue treatment protocols. This study highlights the need for further clinical trials to confirm these findings and fully understand the therapeutic mechanisms of Montelukast in dengue management.

Comparison of test performance of a conventional PCR and two field-friendly tests to detect Coxiella burnetii DNA in ticks using Bayesian latent class analysis.

Introduction: Coxiella burnetii (C. burnetii)-infected livestock and wildlife have been epidemiologically linked to human Q fever outbreaks. Despite this growing zoonotic threat, knowledge of coxiellosis in wild animals remains limited, and studies to understand their epidemiologic role are needed. In C. burnetii-endemic areas, ticks have been reported to harbor and spread C. burnetii and may serve as indicators of risk of infection in wild animal habitats. Therefore, the aim of this study was to compare molecular techniques for detecting C. burnetii DNA in ticks. Methods: In total, 169 ticks from wild animals and cattle in wildlife conservancies in northern Kenya were screened for C. burnetii DNA using a conventional PCR (cPCR) and two field-friendly techniques: Biomeme's C. burnetii qPCR Go-strips (Biomeme) and a new C. burnetii PCR high-resolution melt (PCR-HRM) analysis assay. Results were evaluated, in the absence of a gold standard test, using Bayesian latent class analysis (BLCA) to characterize the proportion of C. burnetii positive ticks and estimate sensitivity (Se) and specificity (Sp) of the three tests. Results: The final BLCA model included main effects and estimated that PCR-HRM had the highest Se (86%; 95% credible interval: 56-99%), followed by the Biomeme (Se = 57%; 95% credible interval: 34-90%), with the estimated Se of the cPCR being the lowest (24%, 95% credible interval: 10-47%). Specificity estimates for all three assays ranged from 94 to 98%. Based on the model, an estimated 16% of ticks had C. burnetii DNA present. Discussion: These results reflect the endemicity of C. burnetii in northern Kenya and show the promise of the PCR-HRM assay for C. burnetii surveillance in ticks. Further studies using ticks and wild animal samples will enhance understanding of the epidemiological role of ticks in Q fever.

Temperature and ST-segment morphology remote monitoring: new perspectives for implantable cardiac monitors in Brugada syndrome.

INTRODUCTION: Patients with Brugada syndrome (BrS) face an increased risk of ventricular arrhythmias and sudden cardiac death. Implantable cardiac monitors (ICMs) have emerged as effective tools for detecting arrhythmias in BrS. Technological advancements, including temperature sensors and improved subcutaneous electrocardiogram (subECG) signal quality, hold promise for further enhancing their utility in this population. METHODS AND RESULTS: We present a case of a 40-year-old man exhibiting a BrS type 2 pattern on 12-lead ECG, who underwent ICM insertion (BIOMONITOR IIIm, BIOTRONIK) due to drug-induced BrS type 1 pattern and a history of syncope, with a negative response to programmed ventricular stimulation. The device contains an integrated temperature sensor and can transmit daily vital data, such as mean heart rate and physical activity. Several months later, remote alerts indicated a temperature increase, along with transmitted subECGs suggesting a fever-induced BrS type 1 pattern. The patient was promptly advised to commence antipyretic therapy. Over the following days, remotely monitored parameters showed decreases in mean temperature, physical activity, and mean heart rate, without further recurrence of abnormal subECGs. CONCLUSION: ICMs offer valuable insights beyond arrhythmia detection in BrS. Early detection of fever using embedded temperature sensors may improve patient management, while continuous subECG morphological analysis has the potential to enhance risk stratification in BrS patients.

Optimized high-dose granulocyte transfusions for the treatment of infections in neutropenic patients: A single-center retrospective analysis.

BACKGROUND: Granulocyte transfusions for patients with prolonged neutropenia and severe infections has been a controversial practice. Previous studies suggest a benefit of high-dose granulocyte transfusions (≥0.6 × 109/kg), although, until recently, the consistent production of high-dose units has been challenging. Here, we present our experience and results utilizing high-dose granulocyte transfusions at a large, tertiary academic medical center for the treatment of infections in adult, neutropenic patients. STUDY DESIGN/METHODS: A retrospective chart review (2018-2021) was conducted for all patients who received high-dose granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. Gathered parameters included patient demographics, clinical history, infection status, dose, clinical outcomes, pre- and post-absolute neutrophil count (ANC), and transfusion times including time between granulocyte collection, administration, and posttransfusion ANC count. Gathered parameters were summarized using descriptive statistics, outcomes were assessed utilizing Kaplan-Meier curves/log-rank/regression testing. RESULTS: Totally 28 adult, neutropenic patients refractory to antimicrobial agents and/or G-CSF received a total of 173 granulocyte concentrates. Median ANC increased from 0.7 × 109/L pre-transfusion to 1.6 × 109/L posttransfusion. The mean granulocyte yield was 77.4 × 109 resulting in an average dose per kilogram of 0.90 × 109 ± 0.30 × 109 granulocytes. Composite day 42 survival and microbial response was 42.9% (n = 12/28) without significant adverse reactions. DISCUSSION: Here, we demonstrate the successful and safe implementation of high-dose granulocyte transfusions for neutropenic patients. Given the rapid and consistent production, distribution, and improved granulocyte quality, further investigations to determine the clinical efficacy of G-CSF primed granulocyte transfusions is now possible.

An Unusual Case of Fever in Paralytic Ileus.

Still's disease is frequently a condition of exclusion for patients with an unidentified cause of fever. Accompanying symptoms typically include fever, arthralgia, and a transient skin rash. The underlying pathophysiology indicates an autoimmune origin. Diagnosis is primarily clinical, often utilizing the Yamaguchi criteria. The case in question involves a 19-year-old male presenting with high-grade fever and paralytic ileus. The patient received intravenous glucocorticoids and cyclophosphamide, resulting in a rapid clinical improvement. During the follow-up, tofacitinib was initiated based on the clinical response observed.

Recommendations for Updating Fever and Inflammation of Unknown Origin From a Modified Delphi Consensus Panel.

Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients. Methods: A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies. Results: Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO. Conclusions: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.

Forecasting deep learning-based risk assessment of vector-borne diseases using hybrid methodology.

BACKGROUND: Dengue fever is rapidly becoming Malaysia's most pressing health concern, as the reported cases have nearly doubled over the past decade. Without efficacious antiviral medications, vector control remains the primary strategy for battling dengue, while the recently introduced tetravalent immunization is being evaluated. The most significant and dangerous risk increasing recently is vector-borne illnesses. These illnesses induce significant human sickness and are transmitted by blood-feeding arthropods such as fleas, parasites, and mosquitos. A thorough grasp of various factors is necessary to improve prediction accuracy and typically generate inaccurate and unstable predictions, as well as machine learning (ML) models, weather-driven mechanisms, and numerical time series. OBJECTIVE: In this research, we propose a novel method for forecasting vector-borne disease risk using Radial Basis Function Networks (RBFNs) and the Darts Game Optimizer (DGO) algorithm. METHODS: The proposed approach entails training the RBFNs with historical disease data and enhancing their parameters with the DGO algorithm. To prepare the RBFNs, we used a massive dataset of vector-borne disease incidences, climate variables, and geographical data. The DGO algorithm proficiently searches the RBFN parameter space, fine-tuning the model's architecture to increase forecast accuracy. RESULTS: RBFN-DGO provides a potential method for predicting vector-borne disease risk. This study advances predictive demonstrating in public health by shedding light on effectively controlling vector-borne diseases to protect human populations. We conducted extensive testing to evaluate the performance of the proposed method to standard optimization methods and alternative forecasting methods. CONCLUSION: According to the findings, the RBFN-DGO model beats others in terms of accuracy and robustness in predicting the likelihood of vector-borne illness occurrences.

Detection of influenza A(H3N2) viruses with polymerase acidic subunit substitutions after and prior to baloxavir marboxil treatment during the 2022-2023 influenza season in Japan.

Baloxavir marboxil (baloxavir), approved as an anti-influenza drug in Japan in March 2018, can induce reduced therapeutic effectiveness due to PA protein substitutions. We assessed PA substitutions in clinical samples from influenza-infected children and adults pre- and post-baloxavir treatment, examining their impact on fever and symptom duration. During the 2022-2023 influenza season, the predominant circulating influenza subtype detected by cycling-probe RT-PCR was A(H3N2) (n=234), with a minor circulation of A(H1N1)pdm09 (n=10). Of the 234 influenza A(H3N2) viruses collected prior to baloxavir treatment, 2 (0.8%) viruses carry PA/I38T substitution. One virus was collected from a toddler and one from an adult, indicating the presence of viruses with reduced susceptibility to baloxavir, without prior exposure to the drug. Of the 54 paired influenza A(H3N2) viruses collected following baloxavir treatment, 8 (14.8%) viruses carried E23K/G, or I38M/T substitutions in PA. Variant calling through next-generation sequencing (NGS) showed varying proportions (6 to 100 %), a polymorphism and a mixture of PA/E23K/G, and I38M/T substitutions in the clinical samples. These eight viruses were obtained from children aged 7-14 years, with a median fever duration of 16.7 hours and a median symptom duration of 93.7 hours, which were similar to those of the wild type. However, the delayed viral clearance associated with the emergence of PA substitutions was observed. No substitutions conferring resistance to neuraminidase inhibitors were detected in 37 paired samples collected before and following oseltamivir treatment. These findings underscore the need for ongoing antiviral surveillance, informing public health strategies and clinical antiviral recommendations for seasonal influenza.

Six adenoviral vectored African swine fever virus genes protect against fatal disease caused by genotype I challenge.

African swine fever virus causes a lethal hemorrhagic disease in domestic swine and wild boar for which currently licensed commercial vaccines are only available in Vietnam. Development of subunit vaccines is complicated by the lack of information on protective antigens as well as suitable delivery systems. Our previous work showed that a pool of eight African swine fever virus genes vectored using an adenovirus prime and modified vaccinia virus boost could prevent fatal disease after challenge with a virulent genotype I isolate of the virus. Here, we identify antigens within this pool of eight that are essential for the observed protection and demonstrate that adenovirus-prime followed by adenovirus-boost can also induce protective immune responses against genotype I African swine fever virus. Immunization with a pool of adenoviruses expressing individual African swine fever virus genes partially tailored to genotype II virus did not protect against challenge with genotype II Georgia 2007/1 strain, suggesting that different antigens may be required to induce cross-protection for genetically distinct viruses. IMPORTANCE: African swine fever virus causes a lethal hemorrhagic disease in domestic pigs and has killed millions of animals across Europe and Asia since 2007. Development of safe and effective subunit vaccines against African swine fever has been problematic due to the complexity of the virus and a poor understanding of protective immunity. In a previous study, we demonstrated that a complex combination of eight different virus genes delivered using two different viral vector vaccine platforms protected domestic pigs from fatal disease. In this study, we show that three of the eight genes are required for protection and that one viral vector is sufficient, significantly reducing the complexity of the vaccine. Unfortunately, this combination did not protect against the current outbreak strain of African swine fever virus, suggesting that more work to identify immunogenic and protective viral proteins is required to develop a truly effective African swine fever vaccine.

Serological and molecular survey of Q fever in the dog population of the Campania region, southern Italy.

Q fever is a re-emerging zoonosis whose epidemiological cycle in ruminants is well defined, while the role of other species (including pets) is still debated. In this study, the serological and molecular prevalence of Coxiella burnetii in a sample of dogs in the Campania region, southern Italy was evaluated. A seroprevalence of 5.97 % (16/268) was observed using a commercial multispecies ELISA, compared to only 2.7 % (5/197) at the molecular level. No risk factors correlated with higher levels of exposure except for the size of the animal (small dogs showed significantly higher seroprevalence). Positive samples were further evaluated for reactivity to phase I and II antigens using IFA and phase-specific ELISAs (for specific IgG detection). Two animals showed antibodies against both phases of infection, suggesting that Coxiella burnetii seroconversion in dogs follows similar dynamics to those observed in ruminants. One of the five samples that showed positive results in real-time PCR was confirmed at the PCR endpoint and showed similarity with other Coxiella spp. strains detected in tick and dog samples when sequenced. In this study, we demonstrated exposure to Coxiella burnetii for different categories of dogs in southern Italy, including pet dogs living indoors. Since reports of transmission of infection from pets to humans have been described in both rural and urban areas, careful surveillance of these species is also necessary. In the lack of additional information, comprehending the risk to humans requires monitoring of wild and domestic animal populations.

Tracking the shift in enteric fever trends and evolving antibiotic sensitivity patterns.

Objective: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) . Study Design: Retrospective study. Participant: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital. Interventions: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed. Results: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3). Conclusion: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever. Funding: None declared.

Efficiency of recombinant Ybgf in a double antigen-ELISA for the detection of Coxiella antibodies in ruminants.

Q fever is a zoonosis whose main reservoirs are domestic ruminants. Surveillance in these species is carried out mainly with serological tests, which, however, have limited diagnostic performance, and their manufacturing requires laboratories equipped with high biosafety requirements for antigen production. Recombinant ELISAs do not depend on these requirements and, being based on a single antigen, can reduce potential false positivity by identifying antibodies specific to a phase of infection. The aim of this study was to apply a new technology (dual antigen test) to a recombinant protein (Ybgf), an antigen produced in recombinant form and already used in previous studies for the design of an indirect ELISA. The successfully produced recombinant antigen was used to coat 96-well plates and, at the same time, another antigen aliquot was conjugated with HRP to obtain an HRP-conjugated Ybgf. After setting the test conditions, the results obtained with the recombinant double antigen test were compared with those obtained with a commercial assay (considered as reference assay) testing a total of 514 ruminant samples (280 goats and 234 cattle). A concordance of 86.2 and a Cohen's Kappa value of 0.72 were obtained, with no significant difference between the two species tested. Notably, the test proved to be highly specific, having correctly identified 250 out of 253 animals. This research represents an additional effort to use recombinant antigens to enhance serological methods in veterinary medicine. In a "one-health scenario", improving the performance of serological tests used in veterinary practice also means improving the surveillance of this infection.

p67 gene alleles sequence analysis reveals Theileria parva parasites associated with East Coast fever and Corridor disease in buffalo from Zambia.

Theileriosis caused by Theileria parva infections is responsible for high cattle mortalities in Zambia. Although infected buffalo are a risk to cattle, the characterization of T. parva parasites occurring in this host in Zambia has not been reported. Furthermore, considering the advances in the development of a p67 subunit vaccine, the knowledge of p67 genetic and antigenic diversity in both cattle and buffalo associated T. parva is crucial. Therefore, blood samples from buffalo (n=43) from Central, Eastern and Southern provinces, and cattle (n=834) from Central, Copperbelt, Eastern, Lusaka, and Southern provinces, were tested for T. parva infection and the parasites characterized by sequencing the gene encoding the p67 antigen. About 76.7 % of buffalo and 19.3 % of cattle samples were PCR positive for T. parva. Three of the four known p67 allele types (1, 2 and 3) were identified in parasites from buffalo, of which two (allele types 2 and 3) are associated with T. parva parasites responsible for Corridor disease. Only allele type 1, associated with East Coast fever, was identified from cattle samples, consistent with previous reports from Zambia. Phylogenetic analysis revealed segregation between allele type 1 sequences from cattle and buffalo samples as they grouped separately within the same sub-clade. The high occurrence of T. parva infection in buffalo samples investigated demonstrates the risk of Corridor disease infection, or even outbreaks, should naïve cattle co-graze with infected buffalo in the presence of the tick vector. In view of a subunit vaccine, the antigenic diversity in buffalo associated T. parva should be considered to ensure broad protection. The current disease control measures in Zambia may require re-evaluation to ensure that cattle are protected against buffalo-derived T. parva infections. Parasite stocks used in 'infection and treatment' immunization in Zambia, have not been evaluated for protection against buffalo-derived T. parva parasites currently circulating in the buffalo population.

Antibiotic resistance trends in high-risk lineages of Salmonella enterica serovar Typhi: A study spanning pre to post COVID-19 pandemic.

OBJECTIVES: The aim of this study was to understand the status of extensively drug-resistance (XDR) genotype in Salmonella enterica serotype Typhi (S. Typhi) recovered during the pre to post COVID-19 pandemic period using Multiplex PCR. METHODS: A longitudinal descriptive study was carried out during five years. Antibiotic susceptibility testing was performed according to the Clinical Laboratory Standards Institute antimicrobial susceptibility testing guidelines. The identification of S. Typhi, the detection of their high-risk lineages and XDR genotype was done using single nucleotide polymorphism-based multiplex PCR. RESULTS: A total of four hundred nine (n = 409) S. Typhi isolates were recovered during pre to post COVID-19 pandemic period. Among them, 30.81% belonged to the pre COVID-19 period while 69.19% to the post COVID-19 period. Different trends in antibiotic resistance in S. Typhi isolates with high prevalence of XDR-S. Typhi were observed. However, there was comparatively different frequency of their occurrence among the S. Typhi isolates recovered during pre to post COVID-19 pandemic period. Multiplex PCR showed that the majority of S. Typhi isolates were the H58 haplotype or genotype 4.3.1 which contained XDR genotype. CONCLUSIONS: The increasing episodes of XDR-S. Typhi causing typhoid fever in endemic areas is alarming. The antibiotic resistance in food and water borne pathogens greatly contribute to the dissemination of the antimicrobial resistance in pathogenic bacteria, which has now been considered as a global concern.

Forecasting and mapping dengue fever epidemics in China: a spatiotemporal analysis.

BACKGROUND: Dengue fever (DF) has emerged as a significant public health concern in China. The spatiotemporal patterns and underlying influencing its spread, however, remain elusive. This study aims to identify the factors driving these variations and to assess the city-level risk of DF epidemics in China. METHODS: We analyzed the frequency, intensity, and distribution of DF cases in China from 2003 to 2022 and evaluated 11 natural and socioeconomic factors as potential drivers. Using the random forest (RF) model, we assessed the contributions of these factors to local DF epidemics and predicted the corresponding city-level risk. RESULTS: Between 2003 and 2022, there was a notable correlation between local and imported DF epidemics in case numbers (r = 0.41, P < 0.01) and affected cities (r = 0.79, P < 0.01). With the increase in the frequency and intensity of imported epidemics, local epidemics have become more severe. Their occurrence has increased from five to eight months per year, with case numbers spanning from 14 to 6641 per month. The spatial distribution of city-level DF epidemics aligns with the geographical divisions defined by the Huhuanyong Line (Hu Line) and Qin Mountain-Huai River Line (Q-H Line) and matched well with the city-level time windows for either mosquito vector activity (83.59%) or DF transmission (95.74%). The RF models achieved a high performance (AUC = 0.92) when considering the time windows. Importantly, they identified imported cases as the primary influencing factor, contributing significantly (24.82%) to local DF epidemics at the city level in the eastern region of the Hu Line (E-H region). Moreover, imported cases were found to have a linear promoting impact on local epidemics, while five climatic and six socioeconomic factors exhibited nonlinear effects (promoting or inhibiting) with varying inflection values. Additionally, this model demonstrated outstanding accuracy (hitting ratio = 95.56%) in predicting the city-level risks of local epidemics in China. CONCLUSIONS: China is experiencing an increasing occurrence of sporadic local DF epidemics driven by an unavoidably higher frequency and intensity of imported DF epidemics. This research offers valuable insights for health authorities to strengthen their intervention capabilities against this disease.

Addressing bottlenecks in Lassa fever treatment: overcoming the ribavirin parenteral formulation challenge.

Ribavirin ampoule formulation remains a major challenge in managing Lassa fever disease. Lassa fever is an endemic viral hemorrhagic fever in the West Africa subregion, which has high-dose ribavirin as the standard of care. The high-dose therapy required makes the 200 mg/ml ampoule dosing of ribavirin a daunting task to administer, especially during disease outbreaks. This commentary highlights the challenges and makes a passionate call for vial dosage adjustment to fit the high-dose requirement of Lassa fever disease.

A rare missense p.C125Y mutation in the TNFRSF1A gene identified in a Chinese family with tumor necrosis factor receptor-associated periodic fever syndrome.

Background: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disorder with a low incidence in Asia. The most frequent clinical manifestations include fever, rash, myalgia, joint pain and abdominal pain. Misdiagnosis rates are high because of the clinical and genetic variability of the disease. The pathogenesis of TRAPS is complex and yet to be fully defined. Early genetic diagnosis is the key to precise treatment. Methods: In this study, a Chinese family with suspected TRAPS were analyzed by genome-wide SNP genotyping, linkage analysis and targeted sequencing for identification of mutations in causative genes. To study the pathogenicity of the identified gene mutation, we performed a conservation analysis of the mutation site and protein structure analysis. Flow cytometry was used to detect TNFRSF1A shedding and quantitative real-time PCR were used to assess the activation of unfolded protein response (UPR) in the mutation carriers and healthy individuals. Results: A typical TRAPS family history, with a pattern of autosomal dominant inheritance, led to the identification of a rare mutation in the TNFRSF1A gene (c.G374A [p.Cys125Tyr]) with unknown significance. The patient responded well to corticosteroids, and long-term therapy with colchicine effectively reduced the inflammatory attacks. No amyloid complications occurred during the 6-year follow-up. In silico protein analysis showed that the mutation site is highly conversed and the mutation prevents the formation of intrachain disulfide bonds in the protein. Despite a normal shedding of the TNFRSF1A protein from stimulated monocytes in the TRAPS patients with p.C125Y mutation, the expression of CHOP and the splicing of XBP1 was significantly higher than healthy controls, suggesting the presence of an activation UPR. Conclusion: This is the first report of a Chinese family with the rare p.C125Y mutation in TNFRSF1A. The p.C125Y mutation does not result in aberrant receptor shedding, but instead is associated with an activated UPR in these TRAPS patients, which may provide new insights into the pathogenesis of this rare mutation in TRAPS.

Malaria Tropica: An Autopsy Case Report With a Discussion on the Presence of Malaria in Bulgaria.

Malaria is an infectious disease caused by several types of parasitic plasmodia and transmitted to humans through Anopheles mosquitoes. The disease has long been widespread and has caused a significant number of deaths and decreased life quality from sequelae worldwide. As understanding of the disease increased immensely at the beginning of the 20th century, eradication plans were implemented to decrease disease transmission. This led to the successful eradication of malaria across predominantly industrialized countries, with multiple geographic areas remaining malaria endemic zones to this day. With climate changes and migration, the risk of reintroduction of malaria to malaria-free zones has risen due to relatively easy travel to endemic zones and importation of cases. On the one hand, this is a significant public health risk and, on the other, a challenge to the medical system, as healthcare workers in malaria-free zones are often ill-prepared to recognize, diagnose, and treat malaria cases. Herein, we present an autopsy and histopathology case report of tropical (falciparum) malaria, complicated with blackwater fever (malignant malaria) with prevalent gross and histopathological changes, including hemomelanin deposition in the spline, liver, and bone marrow; visible parasitic forms in the remaining red blood cells; Durk's granulomas, sludge, and petechial hemorrhages in the central nervous system; and hemoglobin casts within the renal tubular structures. We also discuss the history and risk of reintroducing malaria into a malaria-free zone - Bulgaria.