Human Infection Research Articles

The alphavirus determinants of intercellular long extension formation.

The alphavirus chikungunya virus (CHIKV) is a serious human pathogen that can cause large-scale epidemics characterized by fever and joint pain and often resulting in chronic arthritis. Infection by alphaviruses including CHIKV and the closely related Semliki Forest virus (SFV) can induce the formation of filopodia-like intercellular long extensions (ILEs). ILEs emanate from an infected cell, stably attach to a neighboring cell, and mediate cell-to-cell viral transmission that is resistant to neutralizing antibodies. However, our mechanistic understanding of ILE formation is limited, and the potential contribution of ILEs to CHIKV virulence or human CHIKV infection is unknown. Here, we used well-characterized virus mutants and monoclonal antibodies with known epitopes to dissect the virus requirements for ILE formation. Our results showed that both the viral E2 and E1 envelope proteins were required for ILE formation, while viral proteins 6K and transframe, and cytoplasmic nucleocapsid formation were dispensable. A subset of CHIKV monoclonal antibodies reduced ILE formation by masking specific regions particularly on the E2 A domain. Studies of the viral proteins from different CHIKV strains showed that ILE formation is conserved across the four major CHIKV lineages. Sera from convalescent human CHIKV patients inhibited ILE formation in cell culture, providing the first evidence for ILE inhibitory antibody production during human CHIKV infections.IMPORTANCEChikungunya virus (CHIKV) infections can cause severe fever and long-lasting joint pain in humans. CHIKV is disseminated by mosquitoes and is now found world-wide, including in the Americas, Asia, and Africa. In cultured cells, CHIKV can induce the formation of long intercellular extensions that can transmit virus to another cell. However, our understanding of the formation of extensions and their importance in human CHIKV infection is limited. We here identified viral protein requirements for extension formation. We demonstrated that specific monoclonal antibodies against the virus envelope proteins or sera from human CHIKV patients can inhibit extension formation. Our data highlight the importance of evaluation of extension formation in the context of human CHIKV infection.

Detection of CRISPR‒Cas and type I R-M systems in Klebsiella pneumoniae of human and animal origins and their relationship to antibiotic resistance and virulence.

The clustered regularly interspaced short palindromic repeats (CRISPR)‒CRISPR-associated protein (Cas) and restriction‒modification (R-M) systems are important immune systems in bacteria. Information about the distributions of these two systems in Klebsiella pneumoniae from different hosts and their mutual effect on antibiotic resistance and virulence is still limited. In this study, the whole genomes of 520 strains of K. pneumoniae from GenBank, including 325 from humans and 195 from animals, were collected for CRISPR‒Cas systems and type I R-M systems, virulence genes, antibiotic resistance genes, and multilocus sequence typing detection. The results showed that host origin had no obvious influence on the distributions of the two systems (CRISPR‒Cas systems in 29.8% and 24.1%, type I R-M systems in 9.8% and 11.8% of human-origin and animal-origin strains, respectively) in K. pneumoniae. Identical spacer sequences from different hosts demonstrated there was a risk of human-animal transmission. All virulence genes (yersiniabactin, colibactin, aerobactin, salmochelin, rmpADC, and rmpA2) detection rates were higher when only the CRISPR‒Cas systems were present but were all reduced when coexisting with type I R-M systems. However, a lower prevalence of most antibiotic-resistance genes was found when the CRISPR‒Cas systems were alone, and when type I R-M systems were coexisting, some of the antibiotic resistance gene incidence rates were even lower (aminoglycosides, clindamycins, rifampicin-associated resistance genes, sulfonamides, methotrexates, beta-lactamases, and ultrabroad-spectrum beta-lactamases), and some of them were higher instead (quinolones, macrolides, tetracyclines, and carbapenems). The synergistic and opposed effects of the two systems on virulence and antibiotic-resistance genes need further study.IMPORTANCEK. pneumoniae is an important opportunistic pathogen responsible for both human and animal infections, and the emergence of hypervirulent and multidrug-resistant K. pneumoniae has made it difficult to control this pathogen worldwide. Here, we find that CRISPR‒Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, have synergistic and opposed effects on virulence and antibiotic resistance genes in K. pneumoniae. Moreover, this study provides insights into the distributions of the two systems in K. pneumoniae from different hosts, and there is no significant difference in the prevalence of the two systems among K. pneumoniae spp. In addition, this study also characterizes the CRISPR arrays of K. pneumoniae from different hosts, suggesting that the strains sharing the same spacer sequences have the potential to spread between humans and animals.

Prolonged fecal shedding of replication-competent virus, lasting immune activation, and intestinal inflammation in a rhesus macaque after experimental SARS-CoV-2 infection

Infection of an adult rhesus macaque with SARS-CoV-2 led to viral RNAemia in nose, throat, and lungs. The animal also presented extended fecal shedding of viral genomic and subgenomic messenger RNA and replication-competent virus for more than 3 weeks after infection. Positron emission tomography revealed increased intestinal glucose metabolism which was histologically related to inflammation of the ileum. These findings highlight the potential of the virus to cause gastrointestinal infections in macaques like this is also regularly observed in COVID-19 patients and substantiates the probability of virus transmission via the fecal-oral route. This study further adds the importance of nonhuman primates as a valuable animal model to study SARS-CoV-2 infection in humans.

Genetic Characterization of Japanese Encephalitis Virus Isolates Circulating in Mosquitoes from Pig and Sheep Farms in Shanghai, China

Japanese encephalitis virus (JEV) is regarded as an emerging and reemerging pathogen that is a primary cause of viral encephalitis in humans. However, there is a scarcity of research on the prevalence of JEV genotypes across the different mosquito species in Shanghai. In this study, the diversity of mosquito species and prevalence of JEV in pig and sheep farms in Shanghai were surveyed in 2022. A total of 24,073 mosquitoes, belonging to four genera and seven species, were collected from pig and sheep enclosures in the Chongming, Jiading, Pudong, Fengxian, and Jinshan Districts of Shanghai. Culex tritaeniorhynchus was identified as the predominant species (87.09%, 20,965/24,073) with the highest JEV detection rate. Six strains of JEV were isolated in this study, and genetic analysis revealed that five strains (SH22-M5, SH22-M9, SH22-M14, SH22-M41, and SH22-M52) belonged to genotype I (GI), while one strain (SH22-M1) was classified as genotype III (GIII). The sequence homology was highest between SH22-M9 and SD-1 (99.87%) and between SH22-M14 and SD12 (99.53%). SH22-M5, SH22-M41, and SH22-M52 shared the highest sequence homology with the HEN07011 strain (99.73–99.93%). SH22-M1 was most closely related to SH18, with a sequence homology of 99.8%. Additionally, for the first time, the GI JEV strain was isolated from mosquitoes in sheep sties in this study. The findings highlight the necessity of enhancing the surveillance of JEV in pigs and other livestock farms, including sheep, as well as monitoring the mosquitoes present in these environments. It is recommended that livestock farming areas be kept separate from human habitation to reduce the risk of JEV infections in humans.

Pseudorabies virus as a zoonosis: scientific and public health implications.

Pseudorabies virus (PRV) is a herpes virus, also known as Aujeszky's disease virus (ADV), which can cause a highly infectious disease pseudorabies (PR) in a variety of mammals. In the past, it has been debated whether PRV can infect humans, but more and more cases of PRV infection have been reported since 2017. The illness has claimed many victims and left survivors with serious sequelae. This indicates that humans may ignore the zoonotic ability of PRV. This review aims to summarize the pathology and pathogenesis of PRV and speculate on how it infects humans. This paper provides a comprehensive overview of the progression of PRV, including its virology characteristics, genomic organization, and genetic evolution. It also synthesises the existing literature on PRV infection in humans, and analyses the factors contributing to PRV zoonosis. Finally, the pathogenesis of PRV-infected pigs and other mammals was summarized, and the pathogenesis of PRV-infected humans was speculated.

Emerging Aeromonas spp. infections in Europe: characterization of human clinical isolates from German patients

Bacteria of the genus Aeromonas are widely distributed in water bodies around the world. Some Aeromonas species have been identified as human pathogens causing intestinal and a variety of extraintestinal infections. In Germany, information on diseases caused by Aeromonas is rare, because Aeromonas infections are not notifiable in Germany. To address this information gap and gain better insights, a successful collaboration with human medical diagnostic laboratories within Germany was established and several Aeromonas isolates from diseased patients were sent to the Aeromonas laboratory of the German Federal Institute for Risk Assessment. 52 clinical Aeromonas isolates, of which anonymized patients’ data were available, were selected for further characterization by MALDI-TOF MS, biochemical testing, and whole genome sequencing (WGS). Nearly half of the isolates were from patients older than 60 years, whereas only four isolates were from patients aged up to 10 years. 30 isolates originated from stools of patients with diarrhea/(gastro-)enteritis and 22 strains were from patients with diverse extraintestinal infections, such as wound infection, septicemia, bursitis, abscesses, cholangitis, urinary tract infections, and pneumonia. Taxonomical identification revealed following predominant species: A. veronii biovar sobria (18 isolates), A. caviae (17 isolates), and A. hydrophila (nine isolates). Two A. salmonicida isolates and one isolate each of A. dhakensis, A. bestiarum, and A. encheleia were also identified. Three closely related intestinal isolates could not be assigned to a recognized Aeromonas species. The clustering of strains based on virulence factor profile resulted in a grouping that closely resembles the clustering of the phylogenetic tree suggesting that the profiles are specific for each species. Our study on clinical Aeromonas isolates characterizes for the first time human pathogenic strains isolated in Germany. These bacteria are important microorganisms within the One Health context because of their ubiquitous presence in the environment and as a cause of opportunistic infections in humans and animals. Infections caused by Aeromonas bacteria show a seasonality with increased infection rates in warmer periods. In view of climate change, Aeromonas bacteria are regarded as emerging pathogens and research is required to determine the reservoirs in One Health sources from which human infections may arise.

A new chromosome-level genome assembly and annotation of Cryptosporidium meleagridis

Cryptosporidium spp. are medically and scientifically relevant protozoan parasites that cause severe diarrheal illness in infants, immunosuppressed populations and many animals. Although most human Cryptosporidium infections are caused by C. parvum and C. hominis, there are several other human-infecting species including C. meleagridis, which are commonly observed in developing countries. Here, we annotated a hybrid long-read Oxford Nanopore Technologies and short-read Illumina genome assembly for C. meleagridis (CmTU1867) with DNA generated using multiple displacement amplification. The assembly was then compared to the previous C. meleagridis (CmUKMEL1) assembly and annotation and a recent telomere-to-telomere C. parvum genome assembly. The chromosome-level assembly is 9.2 Mb with a contig N50 of 1.1 Mb. Annotation revealed 3,919 protein-encoding genes. A BUSCO analysis indicates a completeness of 96.6%. The new annotation contains 166 additional protein-encoding genes and reveals high synteny to C. parvum IOWA II (CpBGF). The new C. meleagridis genome assembly is nearly gap-free and provides a valuable new resource for the Cryptosporidium community and future studies on evolution and host-specificity.

Ancient genomes reveal a deep history of treponemal disease in the Americas.

Human treponemal infections are caused by a family of closely related Treponema pallidum that give rise to the diseases yaws, bejel, pinta and, most famously, syphilis1. Debates on both a common origin for these pathogens and the history of syphilis itself has weighed evidence for the "Columbian hypothesis"2, which argues for an American origin, against that for the "pre-Columbian hypothesis"3, which argues for presence of the disease in Eurasia in the Medieval period and possibly earlier. While molecular data has provided a genetic basis for distinction of the typed subspecies4, deep evolution of the complex has remained unresolved due to limitations in the conclusions that can be drawn from the sparse paleogenomic data currently available. Here we explore this evolutionary history through analyses of five pre- and peri-contact ancient treponemal genomes from the Americas that represent ancient relatives of the T. pallidum pallidum (syphilis), T. pallidum pertenue (yaws) and T. pallidum endemicum (bejel) lineages. Our data indicate unexplored diversity and an emergence of T. pallidum that post-dates human occupation in the Americas. Together these results support an American origin for all T. pallidum characterized at the genomic level, both modern and ancient.

Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type

Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53, but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors.

Antimicrobial Resistance Genes and Clonal Relationships of Duck-Derived Salmonella in Shandong Province, China in 2023

Salmonella is a major threat to both human and animal health. However, the diversity and antibiotic resistance of animal-derived Salmonella and their association with human infections remain largely unexplored. In this study, Salmonella strains were isolated, identified, and sequenced from dead embryos and cloacal swab samples obtained from 278 large-scale duck farms in 11 cities in Shandong Province. The results show that a total of 57 Salmonella strains were isolated, with the dominant sequence types (ST) being ST17 (15/57) and ST19 (9/57), while the dominant serotypes were S. Indiana (15/57) and S. Typhimurium (11/57). Furthermore, genomic analysis has revealed the presence of prevalent antibiotic resistance genes (ARGs), which are often associated with co-transfer mechanisms. Over 52.63% of the strains were observed to carry two or more ARGs, especially one Salmonella strain that carried twenty-eight distinct ARGs. Furthermore, core genome multilocus sequence typing analysis (cgMLST) indicated that the 57 Salmonella strains may have a close relationship, which could be clonally transmitted among different cities. The results demonstrated a close relationship between the Salmonella strains identified in diverse geographical regions, suggesting that these strains may have been widely disseminated through clonal transmission. The mutation analysis reveals significant mutations at parC (T57S), gyrA (S83F), parC (S80R), gyrA (D87N), and gyrA (S83Y). These findings emphasize the necessity for monitoring and controlling Salmonella infections in animals, as they may serve as a reservoir for ARGs with the potential to affect human health or even be the source of pathogens that infect humans.

Human and animal brucellosis and risk factors for human infection in Ethiopia: a systematic review and meta-analysis (2015–2024)

Background and objectiveBrucellosis is a neglected zoonotic disease caused by Brucella species. Unlike most developed nations, the problem of brucellosis in Ethiopia remains a public and animal health concern. This study was conducted to determine the magnitude of brucellosis in animals (mainly cattle, sheep, goats, dogs and camels) and humans, and to identify the risk factors for human brucellosis.MethodologyThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to conduct this systematic review and meta-analysis, which was performed from May 2024 to July 2024. Academic databases such as PubMed, ScienceDirect, Scopus, PubMed Central, Web of Science, and Google Scholar were searched to identify articles focusing on brucellosis in humans and animals in Ethiopia. Data extraction was performed according to predefined inclusion and exclusion criteria. The included articles were appraised using the appraisal tool for cross-sectional studies to assess study quality. Publication bias and small study effects were examined using funnel plot observation and Egger’s test, respectively. Statistical analysis was conducted using R software version 4.4.1.ResultsThirty-nine articles published between 2015 and 2024 were included in the final analysis from a total of 1,427 identified articles. The overall pooled seroprevalence of brucellosis was 5.0% (95% CI: 3.0, 6.0). The seroprevalence of brucellosis was higher in humans at 6.9% (95% CI: 4.9, 8.8) and lower in cattle at 3.5% (95% CI: 2.2, 4.7). There was high heterogeneity in the reports of brucellosis seroprevalence between studies (τ² = 0.0038, H² = 255.9, I² = 99.61%, Q-test = 1954.99, df = 56, p ≤ 0.001). Laboratory tests and study location were identified as factors contributing to potential sources of variation in the pooled seroprevalence. Drinking raw milk from aborted animals, touching aborted materials or fetuses, and occupation were among the risk factors for human brucellosis. No publication bias or small study effects were detected.ConclusionThe findings indicate that brucellosis continues to pose a significant zoonotic threat, particularly to humans, where the seroprevalence is notably higher than in animals. These results highlight the need for targeted public health interventions and greater awareness to reduce the incidence of brucellosis, especially among high-risk populations.

The rise of colistin-resistant bacteria isolated from animals

<p>Colistin is one of the most widely used antibiotics in the animal sector and is frequently used as an animal growth promoter. Colistin, is also the last resort for treatment of human infections caused by carbapenem-resistant bacteria. Its intensive and systematic use may have led to the occurrence and spread of colistin-resistant bacteria in animals and humans. As the discovery of new antibiotics is rare, preserving the activity of colistin has become a priority for public health authorities. Monitoring of global prevalence, mechanisms driving colistin resistance, reservoirs, and mobile genetic elements carried by colistin-resistant bacteria are essential steps in the fight against the rise of colistin-resistant bacteria. In this mini-review, we conducted a literature review on phenotypic and genotypic colistin resistance in animals and evaluated the genetic relatedness of colistin-resistant plasmids and bacteria found in animals and humans. According to phylogenetic analysis of <em>mcr</em>-producing bacteria genomes, it seems that there is indeed a transmission of <em>mcr-8.1</em>-producing bacteria between humans and animals, animals and animals, and between humans and humans.</p>

Modeling of randomized hepatitis C vaccine trials: Bridging the gap between controlled human infection models and real-word testing

Abstract Global elimination of chronic hepatitis C (CHC) remains difficult without an effective vaccine. Since injection drug use is the leading cause of hepatitis C virus (HCV) transmission in Western Europe and North America, people who inject drugs (PWID) are an important population for testing HCV vaccine effectiveness in randomized-clinical trials (RCTs). However, RCTs in PWID are inherently challenging. To accelerate vaccine development, controlled human infection (CHI) models have been suggested as a means to identify effective vaccines. To bridge the gap between CHI models and real-world testing, we developed an agent-based model simulating a two-dose vaccine to prevent CHC in PWID, representing 32,000 PWID in metropolitan Chicago and accounting for networks and HCV infections. We ran 500 trial simulations under 50% and 75% assumed-vaccine efficacy (aVE) and sampled HCV infection status of recruited in silico PWID. The mean estimated vaccine efficacy (eVE) for 50% and 75% aVE was 48% (standard deviation (SD ±12) and 72% (SD±11), respectively. For both conditions, the majority of trials (∼71%) resulted in eVEs within 1SD of the mean, demonstrating a robust trial design. Trials that resulted in eVEs >1SD from the mean (lowest eVEs of 3% and 35% for 50% and 75% aVE, respectively), were more likely to have imbalances in acute infection rates across trial arms. Modeling indicates robust trial design and high success rates of finding vaccines to be effective in real-life trials in PWID. However, with less effective vaccines (aVEs∼50%) there remains a higher risk of concluding poor vaccine efficacy due to post-randomization imbalances.

The rise of colistin-resistant bacteria isolated from animals

<p>Colistin is one of the most widely used antibiotics in the animal sector and is frequently used as an animal growth promoter. Colistin, is also the last resort for treatment of human infections caused by carbapenem-resistant bacteria. Its intensive and systematic use may have led to the occurrence and spread of colistin-resistant bacteria in animals and humans. As the discovery of new antibiotics is rare, preserving the activity of colistin has become a priority for public health authorities. Monitoring of global prevalence, mechanisms driving colistin resistance, reservoirs, and mobile genetic elements carried by colistin-resistant bacteria are essential steps in the fight against the rise of colistin-resistant bacteria. In this mini-review, we conducted a literature review on phenotypic and genotypic colistin resistance in animals and evaluated the genetic relatedness of colistin-resistant plasmids and bacteria found in animals and humans. According to phylogenetic analysis of <em>mcr</em>-producing bacteria genomes, it seems that there is indeed a transmission of <em>mcr-8.1</em>-producing bacteria between humans and animals, animals and animals, and between humans and humans.</p>

Sphaeropsidin A Loaded in Liposomes to Reduce Its Cytotoxicity and Preserve Antifungal Activity Against Candida auris

Candida species constitute the most common cause of fungal infections in humans; the emergence of resistance and biofilm formation by Candida species further threaten the limited availability of antifungal agents. Over the past decade, C. auris has caused significant outbreaks worldwide and has emerged as a human pathogenic fungus that causes diseases ranging from superficial to life-threatening disseminated infections. Despite the recent advances in antifungal research, the mechanisms of drug resistance in C. auris remain poorly understood even as its ability to form biofilms poses a significant therapeutic challenge. The purpose of this research was to elucidate the fungal properties of Sphaeropsidin A (SphA), a secondary metabolite derived from Diplodia fungi, with a specific focus on its efficacy against C. auris. This study revealed that SphA and its liposomal encapsulated (SphA-L) form are fungistatic with time-kill kinetics highlighting their efficacy and significantly inhibited the formation of C. auris biofilms. Our investigation into the antifungal mechanism of this drug revealed notable alterations in ROS production and the disruption of the Candida cell cycle. Our findings show that SphA-L impairs key pathogenic traits of C. auris, such as its ability to adhere to human epithelial cell lines, while exhibiting no harmful effects on human cells, highlighting its potential as a future therapeutic agent. In Caenorhabditis elegans infection models, both ShpA and SphA-L displayed effective antifungal activity, significantly reducing the C. auris fungal load and improving nematode survival rates, underscoring their promise as antifungal candidates. Overall, the potent antifungal effects of SphA and SphA-L against C. auris encourage further research.

Loop-Mediated Isothermal Amplification-Based Workflow for the Detection and Serotyping of Salmonella spp. in Environmental Poultry Flock Samples

Salmonella spp. is one of the most important foodborne pathogens worldwide. Given the fact that poultry and poultry products are the main source of human infection, Salmonella control in these farms is of utmost importance. To better control this pathogen in farms, boot swabs are used to sample farm environments but the analysis of these swabs is mainly based on culture-dependent methods. In the present study, a novel loop-mediated isothermal amplification (LAMP) method was developed for the rapid screening of Salmonella spp. in boot swab samples from broiler flock environments. Four different DNA extraction protocols were evaluated in depth, including a simple thermal lysis, a chelex-based protocol and two thermal lysis protocols followed by the purification of magnetic beads made of silica (“glass milk”) in order to determine the most suitable alternative for potential on-site, farm analyses. The methodology evaluation included a blind interlaboratory assay and as a proof-of-concept, a naked-eye colorimetric assay was also included. Following the final methodology, it was possible to reach an LoD50 of 1.8 CFU/25 g of the samples, with a high relative sensitivity (95.7%), specificity (100%) and accuracy (96.6%) along with Cohen’s kappa of concordance with respect to the ISO standard 6579-1:2017 of 0.9, with an RLOD of 1.3. In addition to this, due to the relevance of certain serotypes with the genus Salmonella spp., a serotype LAMP panel for the specific identification of S. Typhimurium, S. Enteritidis, S. Infantis, S. Hadar and S. Virchow was also developed. Even though some degree of cross-reactivity among the primers developed was observed, all the serotypes could be accurately identified based on their melt curve analysis profile. Taken together, in the present study, a rapid Salmonella spp. screening method, suitable for farm applications, was developed, along with a serotyping panel that could be used in a laboratory setup for the identification of the most relevant serotypes of the genus, taking advantage of real-time amplification followed by melt curve analysis.

Serological prevalence of the Coxiella burnetii infection in humans in the age group of 0–20 years in some regions of North Macedonia

The aim of this study was to identify the seroprevalence of Coxiella burnetii in humans and to examine the variation of infection in females and males in the age group of 0–20 years in some regions of North Macedonia. Blood samples were collected from 142 random people from five regions. These patients were tested for antibodies against C. burnetii phase II antigen by enzyme-linked immunosorbent assay (ELISA). Positive test was based on the cut-off value, which in this case was over 0.5 optical density (OD). Of 74 female serums examined, seven samples resulted positive (9.45%), and of 68 male serums examined, five resulted positive (7.35%). In total, the infection percentage was approximate in both sexes; the differences depended on the regions. These findings on Q fever in humans can be used to improve the visibility of this zoonotic disease especially in North Macedonia, where very little information is available on C. burnetii infections. These findings will help local health authorities to focus on the origin of the problem and facilitate the application of preventive measures.

Cat scratch disease in children with nocturnal fever: A case report

BACKGROUND Cat scratch disease (CSD) is the most common human infection caused by Bartonella henselae (B. henselae ). The main manifestation is self-limited lymphadenopathy that primarily affects adolescents, and typically resolves without treatment within 2-4 months. However, individuals with compromised immune systems or immunodeficiency require specific antibacterial therapy following diagnosis. Due to its low incidence, nonspecific clinical manifestations, and diagnostic limitations, this condition often poses challenges for clinicians in terms of missed diagnoses and misdiagnoses. CASE SUMMARY The child was ultimately diagnosed with CSD. The primary manifestations included nocturnal fever, enlargement of lymph nodes in the neck, axilla and groin, and suspected brucellosis; however, both brucellosis tests conducted during the course of the illness yielded negative results. Bone marrow cytology indicated stimulated proliferation. Lymph node biopsy indicated hyperplasia of lymphoid tissue in the cervical lymph nodes (right), with combined immunohistochemical findings indicating reactive hyperplasia. Immunohistochemical analysis revealed CD20 B (+), CD3 T (+), BCL-6 (+), and BCL-2 (). CD21 FDC networks were present and Ki67 expression in the germinal center was ~80%. Blood next-generation sequencing indicated B. henselae sequence number was 3. Serological test results demonstrated positive antibody response to B. henselae IgG (+), B. henselae IgM (+), Bartonella quintana (B. quintana ) IgG () and B. quintana IgM (), and the final diagnosis was CSD. CONCLUSION In patients presenting with fever at night and swollen lymph nodes of unknown origin, CSD should be considered.

Immune Response and Histopathological Changes of Serratia rubidaea in Mice

Serratia rubidaea is a zoonotic opportunistic pathogen that causes respiratory tract infection, septicemia, and encephalitis in humans and animals. The current study aimed to estimate the immunological response (IgG, IL-6by ELISA test and Delayed Type Hypersensitivity (DTH)-Skin Test and histopathological lesions (intestine, liver, kidney, and spleen) by using twenty-four Swiss mice divided into three equal groups (8/each).The first group(G1) as control negative given PBS (pH 7.2) 0.1ml S/C, the second group(G2) immunized by killed whole cell antigen Serratia rubidaea (KWCA SR) (1.2 ×109CFU ml) S/C and the third group(G3) immunized by sonicated whole cell antigen Serratia rubidaea (SWCASR) (1000 μg/ml) S/C. A booster dose was given after 14 days of immunization to the G2 and G3 the same as the immunizing dose. At 21 and 28 days of immunization, IgG and IL-6 concentrations were increased significantly (P≤0.05) in the groups G2 and G3 compared to the negative control group. DTH-Skin Tests of G2 and G3 groups showed increased induration diameter after 24 and 48 hours. and a decrease at 72 hours. Histopathological lesions showed mild to moderate changes in immunized groups compared with the positive control group in all organs. In conclusion, it was found that KWCASR and SWCASR induce humoral (IgG) and cellular immune responses(IL-6,DTH), which reduce the pathological lesions in the immunized mice.

Assessment of Knowledge, Awareness, and Practices of Human Papillomavirus Infection and Vaccination Among Medical and Dental Students: A Cross-Sectional Study

Assessment of Knowledge, Awareness, and Practices of Human Papillomavirus Infection and Vaccination Among Medical and Dental Students: A Cross-Sectional Study