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The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

The low specificity of Ebola virus disease clinical signs increases the risk for nosocomial transmission to patients and healthcare workers during outbreaks. Reducing this risk requires identifying patients with a high likelihood of Ebola virus infection. Analyses of retrospective data from patients suspected of having Ebola virus infection identified 13 strong predictors and time from disease onset as constituents of a prediction score for Ebola virus disease. We also noted 4 highly predictive variables that could distinguish patients at high risk for infection, independent of their scores. External validation of this algorithm on retrospective data revealed the probability of infection continuously increased with the score.

Congregate homeless shelters are disproportionately affected by infectious disease outbreaks. We describe enterovirus epidemiology across 23 adult and family shelters in King County, Washington, USA, during October 2019–May 2021, by using repeated cross-sectional respiratory illness and environmental surveillance and viral genome sequencing. Among 3,281 participants >3 months of age, we identified coxsackievirus A21 (CVA21) in 39 adult residents (3.0% [95% CI 1.9%–4.8%] detection) across 7 shelters during October 2019–February 2020. We identified enterovirus D68 (EV-D68) in 5 adult residents in 2 shelters during October–November 2019. Of 812 environmental samples, 1 was EV-D68–positive and 5 were CVA21–positive. Other enteroviruses detected among residents, but not in environmental samples, included coxsackievirus A6/A4 in 3 children. No enteroviruses were detected during April 2020–May 2021. Phylogenetically clustered CVA21 and EV-D68 cases occurred in some shelters. Some shelters also hosted multiple CVA21 lineages.

Rocky Mountain spotted fever (RMSF) is a severe tickborne disease that can reach epidemic proportions in communities with certain social and ecologic risk factors. In some areas, the case-fatality rate of brown dog tick-associated RMSF is up to 50%. Because of the spread of brown dog tick–associated RMSF in the southwestern United States and northern Mexico, the disease has the potential to emerge and become endemic in other communities that have large populations of free-roaming dogs, brown dog ticks, limited resources, and low provider awareness of the disease. By using a One Health approach, interdisciplinary teams can identify communities at risk and prevent severe or fatal RMSF in humans before cases occur. We have developed a conceptual framework for RMSF prevention to enable communities to identify their RMSF risk level and implement prevention and control strategies.

Oropouche virus has recently caused outbreaks in South America and the Caribbean, expanding into areas to which the virus was previously not endemic. This geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents to the Americas. We review information on Oropouche virus, factors influencing its spread, transmission risk in the United States, and current status of public health response tools. On the basis of available data, the risk for sustained local transmission in the continental United States is considered low because of differences in vector ecology and in human–vector interactions when compared with Oropouche virus–endemic areas. However, more information is needed about the drivers for the current outbreak to clarify the risk for further expansion of this virus. Timely detection and control of this emerging pathogen should be prioritized to mitigate disease burden and stop its spread.

Wastewater testing can inform public health action as a component of polio outbreak response. During 2022–2023, a total of 7 US jurisdictions (5 states and 2 cities) participated in prospective or retrospective testing of wastewater for poliovirus after a paralytic polio case was identified in New York state. Two distinct vaccine-derived poliovirus type 2 viruses were detected in wastewater from New York state and New York City during 2022, representing 2 separate importation events. Of those viruses, 1 resulted in persistent community transmission in multiple New York counties and 1 paralytic case. No poliovirus was detected in the other participating jurisdictions (Connecticut, New Jersey, Michigan, and Illinois and Chicago, IL). The value of routine wastewater surveillance for poliovirus apart from an outbreak is unclear. However, these results highlight the ongoing risk for poliovirus importations into the United States and the need to identify undervaccinated communities and increase vaccination coverage to prevent paralytic polio.

Data on COVID-19 cases, deaths, hospitalizations, and vaccinations in Oklahoma, USA, have not been systematically described. The relationship between vaccination and COVID-19–related outcomes over time has not been investigated. We graphically described data collected during February 2020–December 2021 and conducted spatiotemporal modeling of monthly increases in COVID-19 cumulative death and hospitalization rates, adjusting for cumulative case rate, to explore the relationship. A 1 percentage point increase (absolute change) in the cumulative vaccination rate was associated with a 6.3% (95% CI 1.4%–10.9%) relative decrease in death outcome during April–June 2021, and a 1.9% (95% CI 1.1%–2.6%) relative decrease in death outcome and 1.1% (95% CI 0.5%–1.7%) relative decrease in hospitalization outcome during July–December 2021; the effect on hospitalizations was driven largely by data from urban counties. Our findings from Oklahoma suggest that increasing cumulative vaccination rates might reduce the increase in cumulative death and hospitalization rates from COVID-19.

Limited data exist on mortality rates after tuberculosis (TB) treatment in the United States. We analyzed mortality rates for all adults in Georgia, USA, who had a TB diagnosis and finished treatment during January 1, 2008–December 31, 2019. We obtained posttreatment mortality rate data from the National Death Index and calculated standardized mortality ratios (SMRs) for TB treatment survivors and the general Georgia population. Among 3,182 TB treatment survivors, 233 (7.3%) had died as of December 31, 2019. The overall TB cohort age- and sex-adjusted SMR was 0.89 (95% CI 0.73–1.05). The SMR among US-born TB treatment survivors was 1.56 (95% CI 1.36–1.77). In the TB cohort, US-born status, HIV co-infection, excess alcohol use, diabetes mellitus, and end-stage renal disease were associated with increased risk for death after TB treatment. TB treatment survivors could benefit from improved linkage to primary and HIV comprehensive care to prevent posttreatment death.

Mycobacterium abscessus infection is challenging to treat. Extrapulmonary M. abscessus infections (EP-MAB) are less common than pulmonary M. abscessus infections. To evaluate treatment regimens, we retrospectively analyzed consecutive microbiologically confirmed EP-MAB cases diagnosed in France during 2012–2020. We studied 45 patients with EP-MAB, including 14 bone and joint infections, 10 skin and soft tissue infections, and 8 lymph node infections. Most (62%) patients had no reported immunodeficiency. In 27 patients, EP-MAB followed healthcare-associated (44%) or environmental (16%) injuries. Of the 45 isolates, 25 were subspecies abscessus, 10 bolletii, and 9 massiliense; 1 was unidentified. Cure was achieved for 36 (80%) patients who received a median antimicrobial regimen of 6 months; 22 (55%) also underwent surgery. Four patients died, and 5 were unavailable for follow-up. EP-MAB predominantly affects immunocompetent patients after an injury; outcomes are favorable. We propose a >6-month regimen of antimicrobial therapy with consideration for surgery and regular patient reassessment.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor–resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence–matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin’s stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.

The bacterium Vibrio parahaemolyticus is ubiquitous in tropical and temperate waters throughout the world and causes infections in humans resulting from water exposure and from ingestion of contaminated raw or undercooked seafood, such as oysters. We describe a nationwide outbreak of enteric infections caused by Vibrio parahaemolyticus in Australia during September 2021–January 2022. A total of 268 persons were linked with the outbreak, 97% of whom reported consuming Australia-grown oysters. Cases were reported from all states and territories of Australia. The outbreak comprised 2 distinct strains of V. parahaemolyticus, sequence types 417 and 50. We traced oysters with V. parahaemolyticus proliferation back to a common growing region within the state of South Australia. The outbreak prompted a national recall of oysters and subsequent improvements in postharvest processing of the shellfish.

We report a human case of severe fever with thrombocytopenia syndrome virus infection transmitted by a tick, confirmed by viral identification. Haemaphysalis aborensis, a tick species not native to Japan that has been observed to transmit the virus to humans, is now recognized as a potential vector of this virus in Japan.

Rocky mountain spotted fever (RMSF) causes significant illness and death in children. Although historically rare in California, USA, RMSF is endemic in areas of northern Mexico that border California. We describe 7 children with RMSF who were hospitalized at a tertiary pediatric referral center in California during 2017–2023. Five children had recent travel to Mexico with presumptive exposure, but 2 children did not report any travel outside of California. In all 7 patients, Rickettsia rickettsii DNA was detected by plasma microbial cell-free next-generation sequencing, which may be a useful diagnostic modality for RMSF, especially early in the course of illness, when standard diagnostic tests for RMSF are of limited sensitivity. A high index of suspicion and awareness of local epidemiologic trends remain most critical to recognizing the clinical syndrome of RMSF and initiating appropriate antimicrobial therapy in a timely fashion.

Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1–28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.

In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel lineage were documented in the Amazon Region of Brazil. We report the introduction of this lineage into Colombia and its co-circulation with another OROV lineage. Continued surveillance is needed to prevent further spread of OROV in the Americas.

Bourbon virus is a tickborne virus that can cause human disease. Cases have been reported in Kansas, Oklahoma, and Missouri, USA. We identified Bourbon virus–specific neutralizing antibodies in patients from North Carolina. Bourbon virus infections are likely more common than previously thought, highlighting the need for improved diagnostics and surveillance.

To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018–2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6–23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non‒medically attended illnesses) averted by multiple potential vaccination strategies: year-round versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831–10,868 for year-round, 10,175–11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects.

During the COVID-19 pandemic, widespread school closures were implemented globally based on the assumption that transmission among children in the school environment is common. However, evidence regarding secondary infection rates by school type and level of contact is lacking. Our study estimated the frequency of SARS-CoV-2 infection in school settings by examining the positivity rate according to school type and level of contact by using data from a large-scale school-based PCR project conducted in Okinawa, Japan, during 2021–2022. Our results indicate that, despite detection of numerous positive cases, the average number of secondary infections remained relatively low at ≈0.5 cases across all types of schools. Considering the profound effects of prolonged closures on educational access, balancing public health benefits against potential long-term effects on children is crucial.

We report acute Oropouche virus infections in 2 previously healthy women from a nonendemic region of Brazil outside the Amazon Basin. Infections rapidly progressed to hemorrhagic manifestations and fatal outcomes in 4–5 days. These cases highlight the critical need for enhanced surveillance to clarify epidemiology of this neglected disease.

We show the value of real-time data generated by a computerized decision support system in primary care in strengthening pneumonia surveillance. The system showed a 66% (95% CI 64%–67%) increase in community-acquired pneumonia from 2018 to 2023 for the population of France, 1 month before a national alert was issued.

We studied SARS-CoV-2 binding and neutralizing antibody titers among previously infected persons in the United States over time. We assayed SARS-CoV-2 spike protein receptor-binding domain and neutralizing antibody titers for a convenience sample of residual clinical serum specimens that had evidence of prior SARS-CoV-2 infection gathered during January 2021–February 2022. We correlated titers and examined them by age group (65 years) across 4 different SARS-CoV-2 variant epochs. Among selected specimens, 30,967 had binding antibody titers and 744 had neutralizing titers available. Titers in specimens from children and adults correlated. In addition, mean binding antibody titers increased over time for all age groups, and mean neutralization titers increased over time for persons 16–49 and >65 years of age. Incorporating binding and neutralization antibody titers into infectious disease surveillance could provide a clearer picture of overall immunity and help target vaccination campaigns.

Highly pathogenic avian influenza A(H5N1) detected in dairy cows raises concerns about milk safety. The effects of pasteurization-like temperatures on influenza viruses in retail and unpasteurized milk revealed virus resilience under certain conditions. Although pasteurization contributes to viral inactivation, influenza A virus, regardless of strain, displayed remarkable stability in pasteurized milk.

We report a case of Burkholderia mallei causing glanders in a 73-year-old patient from the Northeast Region of Brazil. The patient was hospitalized with severe pneumonia. PCR and genomic sequencing confirmed B. mallei in pleural drainage. Genotyping revealed a novel genotype, emphasizing the need for genetic surveillance in zoonotic infections.

Dengue cases rose to record levels during 2023–2024. We investigated dengue in Valle del Cauca, Colombia, to determine if specific virus serotypes or lineages caused its large outbreak. We detected all 4 serotypes and multiple lineages, suggesting that factors such as climatic conditions were likely responsible for increased dengue in Colombia.

We recently expanded the viral genomic surveillance program in Minnesota, USA, to include human respiratory syncytial virus. We performed whole-genome sequencing of 575 specimens collected at Minnesota healthcare facilities during July 2023–February 2024. Subgroups A and B differed in their genomic landscapes, and we identified 23 clusters of genetically identical genomes.

Norovirus is a leading cause of acute gastroenteritis and imposes a substantial disease burden. In California, USA, norovirus surveillance is limited. We evaluated correlations between wastewater norovirus concentrations and available public health surveillance data. Wastewater surveillance for norovirus genotype GII in California provided timely, localized, and actionable data for public health authorities.

We report a suspected case of acute pulmonary coccidioidomycosis contracted in Peru, where the disease is not known to occur, in a patient from Switzerland. Although not confirmed by direct diagnostic testing, the clinical manifestations and serologic testing results of this case are highly suggestive of coccidioidomycosis.

In Slovenia, primary acellular pertussis vaccines (ACVs) containing pertactin (PRN) were mostly used during 1999–2016; ACVs without PRN were introduced in 2017. Among 123 Bordetella pertussis strains collected during 2002–2020, a total of 48 were PRN-deficient; 44 were collected after 2017. Changes to ACVs could increase PRN-deficient B. pertussis and infections.

We analyzed 3,081 invasive and noninvasive Streptococcus pyogenes cases (January 2005–December 2023) at a tertiary care hospital in southwest Germany. Absolute numbers of case-patients increased each year from 2005 until the COVID-19 pandemic. Odds ratios for invasive streptococcal disease were significantly influenced by year, male sex, and older age.

Analysis of clinical and environmental Vibrio cholerae O1 strains obtained during 2008–2015 in Nigeria showed that lineages Afr9 and Afr12 carrying cholera toxin and Vibrio pathogenicity island 1 can be isolated from water. Our findings raise concerns about the role of the environment in maintenance and emergence of cholera outbreaks in Nigeria.

We describe the case of a returned traveler to the United States from Ecuador who had an acute febrile illness, initially diagnosed as Oropouche fever. This illness was later confirmed to be a rare infection with Iquitos virus, a related bunyavirus that shares 2 of 3 genome segments with Oropouche virus.

Xiaolan Guo,1 Dansen Wu,1 Xiaoping Chen,2 Jing Lin,1 Jialong Chen,1 Liming Wang,1 Songjing Shi,1 Huobao Yang,1 Ziyi Liu,3 Donghuang Hong1,4 1Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 2Computer Science and Mathematics, Fujian University of Technology, Fuzhou, Fujian, People’s Republic of China; 3Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Ziyi Liu, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai, 200127, People’s Republic of China, Email liu-ziyi@sjtu.edu.cn Donghuang Hong, Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134, Dongjie Street, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email hongdh2003@fjmu.edu.cnPurpose: The objective of this study was to identify the risk factors associated with Carbapenem-resistant Enterobacteriaceae (CRE) colonization in intensive care unit (ICU) patients and to develop a predictive risk model for CRE colonization.Patients and Methods: In this study, 121 ICU patients from Fujian Provincial Hospital were enrolled between January 2021 and July 2022. Based on bacterial culture results from rectal and throat swabs, patients were categorized into two groups: CRE-colonized (n = 18) and non-CRE-colonized (n = 103). To address class imbalance, Synthetic Minority Over-sampling Technique (SMOTE) was applied. Statistical analyses including T-tests, Chi-square tests, and Mann–Whitney U-tests were employed to compare differences between the groups. Feature selection was performed using Lasso regression and Random Forest algorithms. A Logistic regression model was then developed to predict CRE colonization risk, and the results were presented in a nomogram.Results: After applying SMOTE, the dataset included 198 CRE-colonized patients and 180 non-CRE-colonized patients, ensuring balanced groups. The two groups were comparable in most clinical characteristics except for diabetes, previous emergency department admission, and abdominal infection. Eight independent risk factors for CRE colonization were identified through Random Forest, Lasso regression, and Logistic regression, including Acute Physiology and Chronic Health Evaluation (APACHE) II score > 16, length of hospital stay > 31 days, female gender, previous carbapenem antibiotic exposure, skin infection, multi-site infection, immunosuppressant exposure, and tracheal intubation. The risk prediction model for CRE colonization demonstrated high accuracy (87.83%), recall rate (89.9%), precision (85.6%), and an AUC value of 0.877. Patients were categorized into low-risk (0– 90 points), medium-risk (91– 160 points), and high-risk (161– 381 points) groups, with corresponding CRE colonization rates of 1.82%, 7.14%, and 58.33%, respectively.Conclusion: This study identified independent risk factors for CRE colonization and developed a predictive model for assessing the risk of CRE colonization.Keywords: carbapenem-resistant Enterobacteriaceae, intensive care unit, colonization, risk factors, risk prediction model

Kridsanai Gulapa, Dararat Eksombatchai, Tananchai Petnak, Viboon Boonsarngsuk Division of Pulmonary Medicine and Pulmonary Critical Care Medicine, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Dararat Eksombatchai, Division of Pulmonary Medicine and Pulmonary Critical Care Medicine, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Bangkok, 10400, Thailand, Email Dararat.eks@mahidol.ac.thBackground: COVID-19 infection is associated with an increased risk of severe illness and adverse outcomes in individuals with immunocompromising conditions. Immunocompromised patients may have difficulty with viral clearance, which can lead to persistent infection and potential relapses in viral replication.Case Presentation: Herein, we present four cases of persistent COVID-19 pneumonia in immunocompromised patients, including those with diffuse large B-cell lymphoma, polyarteritis nodosa, and end-stage renal disease post-kidney transplant. Three patients had previously received rituximab. Notably, all patients in this cohort demonstrated positive anti-receptor binding-domain immunoglobulin G (IgG) and negative anti-nucleocapsid IgG values.Conclusion: Persistent COVID-19 infection should be considered in the differential diagnosis of immunocompromised patients who exhibit ongoing symptoms or lack of improvement in chest X-ray findings following initial COVID-19 treatment. Early recognition, beyond the diagnosis of post-COVID organizing pneumonia, may significantly improve clinical outcomes with timely and appropriate treatment.Keywords: COVID-19 pneumonia, persistent COVID-19, immunocompromised patients, SAR-CoV-2

Sara Alfakeeh,1,* Reema Fahad Alghanem,1,* Shahad Bin Obaid,1,* Alya Alsuwayhib,1,* Ghaida Al Kawabah,1,* Reem Abanamy,1– 3,* Mohammad Bosaeed1– 3,* 1College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 3King Abdullah International Medical Research Center, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Mohammad Bosaeed, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, 11426, Saudi Arabia, Email bosaeedmo@mngha.med.saPurpose: Brucella endocarditis is a rare complication with a high mortality risk. This research aims to evaluate patients diagnosed with Brucella Endocarditis and review clinical characteristics, diagnosis, and treatment strategies to serve as a foundation for future research in managing Brucella endocarditis and improving patient care and outcomes.Patients and Methods: This retrospective study reviewed the medical records of patients diagnosed with Brucella endocarditis from 2011 to 2022. The study included patients of all ages and genders who were diagnosed based on positive serum serology or blood culture in conjunction with clinical presentation. Diagnostic criteria for endocarditis were based on evidence of endocardial involvement, as confirmed by echocardiographic findings consistent with infective endocarditis. Descriptive statistics were used for data analysis.Results: Nine patients were included in this study. The most common presenting symptom was shortness of breath. Treatment regimens included Doxycycline and Rifampicin, always in combination with other antibiotics. Surgical intervention was necessary for two-thirds of the patients. Complications, such as septic shock, stroke, and heart failure, were observed in most cases. Six patients achieved clinical and microbiological cures, while one-third of the patients died. The deaths were primarily attributed to patients being deemed unsuitable for surgery due to a high surgical risk, based on their comorbidities and clinical assessments.Conclusion: This study highlights the importance of initiating an appropriate antibiotic regimen in a timely manner. Particularly in patients with pre-existing heart diseases, surgical intervention can significantly improve patient outcomes and reduce complications associated with Brucella endocarditis.Keywords: brucellosis, Brucella endocarditis, Brucella complication, Saudi Arabia

Min Zhao,1 Changyi Yang,1 Linhong Zhu,1 Xiaoqian Guo,1 Haiyan Ma,2 Yuanhao Luo,3 Qi Wang,4 Juanjuan Chen4 1Department of Periodontology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2School of Stomatology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 4Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of ChinaCorrespondence: Juanjuan Chen; Qi Wang, Email ery_juanjuanchen@lzu.edu.cn; ery_wangqery@lzu.edu.cnIntroduction: Our study investigated the disparities and correlations between oral microbiota and metabolites in pregnant patients with and without periodontitis.Methods: Subgingival plaque samples from all subjects were collected for shotgun metagenomic sequencing and broad-target metabolomics analysis.Results: Forty pathogens, including Porphyromonas gingivalis, Fusobacterium nucleatum, Eubacterium saphenum, Gemella morbillorum, Tannerella forsythia, Streptococcus anginosus group, Selenomonas sputigena etc, were significantly enriched in pregnant patients with periodontitis (PPP). Conversely, symbiotic species such as Morococcus cerebrosus, Streptococcus vestibularis, S. salivarius, S. mitis, and S. pneumoniae were significantly more abundant in healthy controls (HCs). A total of 87 predicted functional modules (PFMs) exhibited significant differences between the two groups; eight PFMs showed high enrichment in PPP with involvement of PPP-enriched species within these pathways. The remaining 79 PFMs encompassing ribonucleotide biosynthesis, carbohydrate, and amino acid metabolism were highly abundant in HCs. For oral microbial metabolome, a total of 105 metabolites related to 150 KEGG pathways displayed significant differences between the two groups. Pathways such as pyruvate metabolism, folate biosynthesis, vascular smooth muscle contraction, and AMPK/mTOR signaling pathway along with their associated metabolites were found to be enriched in PPP, while carbohydrate metabolism predominated among HCs. Spearman’s rank correlation analysis revealed significant positive associations between species enriched in PPP and metabolites enriched in PPP, but significant negative associations between species enriched in PPP and metabolites enriched in HCs.Discussion: Our findings provide potential biomarkers for distinguishing periodontitis during pregnancy while offering valuable insights into mechanisms exploration and clinical intervention.Keywords: Pregnancy-induced periodontitis, oral microbiota composition, predicted functional modules, microbial metabolites profiling, biomarkers identification

Yongru Chen,1 Chongyue Chen,1 Wei Chen,2,3 Wei Gai,4 Yafeng Zheng,4 Yuxin Guo,4 Zhaoning Wang,1 Yongsong Chen,1 Zhiming Cai1,5,6 1The First Affiliated Hospital of Shantou University, Shantou, Guangdong, People’s Republic of China; 2Department of Urology, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen, People’s Republic of China; 3Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen, People’s Republic of China; 4WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 5BGI Genomics, BGI Shenzhen, Shenzhen, People’s Republic of China; 6Carson International Cancer Center, Shenzhen University, Shenzhen, People’s Republic of ChinaCorrespondence: Zhiming Cai, Carson International Cancer Center of Shenzhen University, No. 1066, Xueyuan Road, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86 136 0253 0322, Email caizhiming2000@163.com Yongsong Chen, The First Affiliated Hospital of Shantou University, No. 57, Changping Road, Shantou, Guangdong Province, People’s Republic of China, Tel +86 0754-88905000, Email yongsongchen@126.comPurpose: This study aimed to evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) in sepsis patients who received early empirical antibiotic treatment.Patients and Methods: A retrospective analysis was conducted on clinical data from sepsis patients diagnosed in the Emergency Intensive Care Unit (EICU) between April 2019 and May 2023. All patients underwent standard conventional microbiological testing. Patients were categorized into either the mNGS group or the control group based on whether they underwent mNGS tests. Baseline variables were matched using propensity scores.Results: Out of 461 sepsis patients screened, 130 were included after propensity matching, with 65 patients in each group. Despite prior antibiotic treatment, 57 cases (87.69%) in the mNGS group had positive mNGS results, exceeding the culture detection rate (52.31%). Besides, a higher proportion of patients in the mNGS group experienced antibiotic adjustments compared to the control group (72.31% vs 53.85%). Mortality rates were also compared based on the duration of antibiotic exposure before mNGS sampling. Patients exposed to antibiotics for less than 24 hours had a lower mortality rate compared to those exposed for over 8 days (22.22% vs 42.86%). COX multivariate analysis identified mNGS testing, underlying diseases, lymphocyte percentage, infection site (respiratory and bloodstream) as independent risk factors for mortality in sepsis patients.Conclusion: With increased antibiotic exposure time, the positive rate of culture testing significantly decreased (44.44% vs 59.52% vs 35.71%, P = 0.031), whereas the positive rate of mNGS remained stable (77.78% vs 88.10% vs 92.86%, P = 0.557). mNGS demonstrated less susceptibility to antibiotic exposure. Early mNGS detection positively impacted the prognosis of sepsis patients.Keywords: metagenomic next-generation sequencing, sepsis, antibiotic management, clinical value, prognosis

Basem M Alraddadi,1,2 Emily LG Heaphy,3 Muhannad S Alzahrani,1 Mouad Alqadi,1 Moayad Sami Qashqari,1 Mohammed S Alhuthali,1 Mohammad Kamal Al Hroub,4 Lama Hefni,1 Abeer N Alshukairi,1,2 Yasser Aldabbagh,5 Mohammed Qutub6 1Medicine Department, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 2Medicine Department, Al Faisal University, Riyadh, Saudi Arabia; 3Research- Jeddah Department, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Infection Control & Hospital Epidemiology Department, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 5Department of Medicine, Al-Moosa Health Group, Al-Ahsa, Saudi Arabia; 6Pathology and Laboratory Medicine Department, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi ArabiaCorrespondence: Emily LG Heaphy, King Faisal Specialist Hospital and Research Center- Jeddah, Al Rawdah Road, P.O. Box 40047, Jeddah, 21499, Saudi Arabia, Email emily.lg.heaphy@gmail.comPurpose: The study aimed to determine the impact of Carbapenem-resistant Enterobacterales (CRE) colonization status on development of CRE infection and 30-day mortality outcomes in high-risk patients.Patients and Methods: This retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Center in Jeddah, Saudi Arabia from October 2022 to July 2023. It included all patients aged 14 years and older admitted to the intensive care unit (ICU), the renal transplant unit and the oncology units who were screened for CRE colonization upon hospital admission.Results: Overall, 246 patients comprised the study population and 37 patients (56.8% ICU, 13.5% renal transplant unit, and 29.7% oncology units) had a positive CRE screening test. The majority of the isolates (59.5%) were OXA-48. Almost one-third (32.1%) of the patients had diabetes mellitus and 55.3% had any underlying immunosuppression. Eight (3.3%) patients had a confirmed CRE infection and 35 (14.2%) patients died within 30 days of screening. A positive CRE screening test significantly increased the likelihood of 30-day mortality for this high-risk patient population (adjusted odds ratio [AOR] = 3.06, 95% CI = 1.10– 8.51, p = 0.03).Conclusion: A substantial percentage of the high-risk patients had a positive CRE screening test at the time of hospital admission and CRE-colonization status predicted 30-day mortality. Further studies are needed to determine the best practices for CRE screening as a strategy to prevent infection and mortality.Keywords: carbapenem-resistant enterobacterales, CRE, epidemiology, OXA-48, Saudi Arabia

Lihong Zhou,1 Yan Yong,1 Hao Li,2 Qin Hu1 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Zhejiang Chinese and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Tuberculosis Laboratory, Zhejiang Chinese and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qin Hu, Zhejiang Tuberculosis Diagnosis and Treatment Center, Zhejiang Chinese and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-13968146922, Fax +86-571-56109821, Email qinhu19832023@163.comPurpose: The diagnosis of tuberculosis located in the peripheral zone remains challenging and requires ultrasound bronchoscopy-guided maneuvers. We assessed the precision of CapitalBioTM Mycobacterium nucleic acid detection test (CapitalBio MTB test) and Mycobacterium tuberculosis isothermal RNA amplification test (MTB-RNA) using endobronchial ultrasonography with a guide sheath (EBUS-GS) for peripheral pulmonary tuberculosis (PTB) and compared it with those of acid-fast bacilli (AFB) smear and MTB culture tests.Patients and Methods: This retrospective analysis included 287 patients suspected of peripheral pulmonary tuberculosis who underwent EBUS-GS examinations, medical examination results of AFB smears, MTB culture, CapitalBio MTB test, and MTB-RNA were analyzed. We evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC), and its diagnostic accuracy for peripheral PTB was evaluated in comparison with the final clinical diagnosis.Results: The overall sensitivity, specificity, PPV, NPV, and AUC of CapitalBio MTB test were 44.83%, 100.00%, 100.00%, 54.07%, and 0.72, respectively; those of MTB-RNA were 22.99%, 100.00%, 100.00%, 45.75%, and 0.61, respectively, and those for parallel test (CapitalBio MTB test or MTB-RNA) were 46.55%, 100.00%, 100.00%, 54.85%, and 0.73, respectively. These values for AFB smear were 9.2%, 97.35%, 84.21%, 41.04%, and 0.53, respectively, and those of MTB culture were 31.03%, 100.00%, 100.00%, 48.50%, and 0.69, respectively.Conclusion: The CapitalBio MTB test showed the best diagnostic performance compared with AFB smear, MTB culture, and MTB-RNA assays and was similar to the parallel test (CapitalBio MTB test or MTB-RNA). The CapitalBio MTB test combined with EBUS-GS had satisfactory diagnostic accuracy for diagnosing peripheral PTB.Keywords: sensitivity, specificity, receiver operating characteristic curve, endobronchial ultrasonography, polymerase chain reaction, nucleic acid molecular testing

Piaopiao Ying,1 Jiajing Chen,2 Yinchai Ye,3 Chang Xu,4 Jianzhong Ye5 1Department of General Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Department of Nephrology, Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University, Taizhou, People’s Republic of China; 3Department of General Medicine, The Health Center of Eryuan Town, Wenzhou, People’s Republic of China; 4Department of Intensive Care Medicine, Ningbo No. 2 hospital, Ningbo, People’s Republic of China; 5Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Chang Xu, Department of Intensive Care Medicine, Ningbo No. 2 hospital, Ningbo, 41 Xibei Street, Ningbo, 315010, People’s Republic of China, Email xc95121@163.com Jianzhong Ye, Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, People’s Republic of China, Email jzye89@163.comObjective: This study aimed to investigate the correlation between computed tomography (CT) derived body composition and 30-day mortality in patients with pulmonary infections caused by carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae).Methods: A total of 89 eligible participants from a tertiary teaching hospital, enrolled between January 1, 2016, and December 31, 2020, were included in the study. We analyzed the relationship between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), and skeletal muscle (SM) and 30-day mortality in patients infected with carbapenem-resistant K. pneumoniae (CRKP) in the pulmonary region. Furthermore, we established Cox regression models and a personalized nomogram model to predict the probability of 30-day mortality in these infected patients.Results: Individuals with high VAT exhibited a higher likelihood of 30-day all-cause mortality (P< 0.01) and 30-day mortality due to CRKP infection (P< 0.01) compared to those with low VAT. Similar results were observed for TAT. After adjusting for significant comorbidities and other clinical characteristics, Cox regression analysis revealed that male gender (adjusted HR = 4.37; 95% CI = 0.96– 19.92, P=0.06), vasopressor use (adjusted HR = 3.65; 95% CI = 1.04– 12.85, P=0.04), and VAT (adjusted HR = 1.16; 95% CI = 1.01– 1.34, P=0.03) were independent risk factors for 30-day all-cause mortality among these infectious patients.Conclusion: The study results highlight the significant prognostic value of CT-quantified visceral adipose tissue in patients with CRKP pulmonary infection. Individuals with high VAT are more prone to mortality within 30 days compared to those with low VAT.Keywords: body composition, carbapenem-resistant Klebsiella pneumoniae, mortality, visceral adipose tissue, pulmonary infection

Shanshan Jin,1,2,&ast; Hui Xie,1,&ast; Ruilan Wang1,2 1Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200080, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruilan Wang, Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200080, People’s Republic of China, Email wangyusun@hotmail.comAbstract: Community-acquired Klebsiella pneumoniae meningitis (CA-KPM) can rapidly progress to invasive infection in healthy individuals. We present the case of a 54-year-old man with a history of acute suppurative otitis media and uncontrolled type 2 diabetes mellitus (T2DM), who had been treated with oral antibiotics intermittently and irregularly for one month. His symptoms did not improve and continued to worsen, leading to fever and coma. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) identified Klebsiella pneumoniae (KP) after 24 hours in the intensive care unit (ICU). Subsequent CSF culture confirmed a hypervirulent KP (hvKp) strain with capsular genotype K2 and sequence type (ST) 375. Fortunately, the patient made a full recovery with targeted antimicrobial therapy and was discharged. Despite the delayed diagnosis, the outcome was favorable. This case highlights the importance of clinicians, particularly otolaryngologists, maintaining a high index of suspicion for CA-KPM in patients with both otitis media and T2DM, emphasizing the need for timely multidisciplinary consultation.Keywords: Klebsiella pneumoniae, hypervirulent, case report, meningitis, community-acquired

Abstract Background The COVID-19 pandemic has been the most significant health challenge of the last century. Multiple and successive waves of COVID-19 cases, driven particularly by the emergence of new SARS-CoV-2 variants, have kept the world in a constant state of alert. Methods We present an observational, descriptive, cross-sectional study aimed at identifying SARS-CoV-2 variants circulating during two local waves of COVID-19 cases in southern Bahia, Brazil (late 2021 and late 2022), and analyzing the association between the detected variants and the epidemiological and clinical characteristics of the disease. For this purpose, data and nasopharyngeal samples from individuals in southern Bahia, Brazil, with suspected COVID-19 were included. Viral detection was performed by RT-qPCR, and SARS-CoV-2 variants were identified by next-generation viral sequencing. Results A total of 368 nasopharyngeal samples were tested. Approximately 23% of the samples from late 2021 tested positive for SARS-CoV-2, while in 2022, the positivity rate was about 56%. All sequenced samples from 2021 were identified as the Delta variant, while in 2022, all samples were classified as the Omicron variant. Overall, individuals who tested positive for SARS-CoV-2 in 2022 were younger than those who tested positive in 2021. Moreover, we observed significant differences in the clinical spectrum of SARS-CoV-2 infection when comparing the two periods. Individuals who presented with anosmia/ageusia were more likely to test positive for SARS-CoV-2 infection in 2021 but not in 2022. Additionally, fever, dry cough, pharyngalgia, headache, and rhinorrhea were more frequent among individuals infected with the Omicron variant than among those infected with the Delta variant. Conclusions The profile of COVID-19 in southern Bahia differed when analyzing two distinct waves of the pandemic in the region. These differences are likely related to the variants, which may differ in transmissibility and virulence, thereby altering the dynamics of the pandemic. This underscores the importance of genomic surveillance in better understanding the behavior of viral infections.

Abstract Objective To analyze the genotypes of VZV in Jiangsu province to identify vaccine strains and wild strains, providing a molecular biological background for the effective prevention and control of varicella. Method Stratified sampling was used to collect herpes fluid or throat swab from patients diagnosed with varicella. ORF22 was carried out, and the restriction enzyme site of ORF38, ORF54 and ORF62 were detected. Results All 207 virus strains were Clade 2 type by sequencing the PCR products of ORF22. The sequencing results showed that five SNP sites changed compared to the Dumas reference strain(Clade 1). From A to G at 37,902, from T to c at 38,055, from A to C at 38,081, and from G to A at 38,177, from G to A at 39,394. The prevalent VZV genotypes in Jiangsu is consistent with the P-Oka. The restriction enzyme site analysis of PCR amplification products from ORF38 (PstI), ORF54 (BglI), ORF62 (SmaI) showed that all 207 virus strains were wild-type. There were two different types of the wild strains, and 183 strains (88.4%) were PstI (+), BglI (+), SmaI (-). The wild strains between different regions showed no significant differences (χ2 = 0.05, P = 0.982). Conclusions The prevalent VZV genotypes are Clade 2 and the prevalent virus strains are wild strains in Jiangsu Province, the primary wild strain observed is mainly PstI (+), BglI (+), SmaI (-).

Abstract Background Reticuloendotheliosis virus (REV) is an oncogenic immunosuppressive retrovirus that infects different kinds of avian species; posing significant economic losses to the poultry industry worldwide. Methods In Egypt, there is an unidentified disease associated with the runting-stunting syndrome with neoplasia, suspected to be REV, that has been continuously monitored in several breeder flocks. To diagnose and analyze REV by cell cultures, enzyme-linked immunosorbent assay (ELISA), histopathological investigation, the polymerase chain reaction (PCR) test, and sequencing analysis, 200 blood samples, and 50 tissue specimens were collected. The current study targets the occurrence and genetic characteristics of a viral neoplastic disease, resembling REV infection, circulating in breeder flocks from 2022 to 2023 in the Ismailia, El-Sharqia, and El-Dakahliya governorates. Result Here, REV was isolated on chicken embryo fibroblast cell culture; exhibiting cell aggregation, rounding, and cell detachments. Collectively, only 70 serum samples were positive for anti‐REV antibodies with seroprevalence rates of 35% based on the ELISA test. The histopathological observation demonstrated lymphoreticular tumors in the liver, spleen, and other examined organs. The immunohistochemical staining method confirmed the REV-positive signals in all examined organs (liver, kidney, spleen, bursa, ovaries) except for the heart. The PCR assay of the LTR gene assessed 370 base pairs with only 5 positive samples with a percentage of 16.6%. Three positive samples were further sequenced and submitted to the Genbank under accession numbers (PP763709, PP763710, PP763711). Phylogenetic analysis of the REV-LTR gene showed that our three isolates (Sharquia-1-REV, Ismilia-2-REV, Mansoura-3-REV) are REV subtype III which predominantly circulated in breeders in Egypt. These three isolates are highest similar to American, Chinese, and Taiwanese REV reference strains, and other Egyptian strains with nucleotide identity percentages of 100%, 99%, and 99%; respectively, and on the amino acid identity level were with (99–100%), (98%, 99%), (99%, 100%); respectively. Conclusions This study established that REV infection was extensively distributed in the breeders and became one of the causes of the clinical outbreaks of tumors, raising awareness of REV as the causative agent of avian oncogenic disease in Egypt.

Abstract Background This case report describes the treatment of a 12-year-old indigenous Brazilian girl from the Maxakali group with rabies using the adapted Milwaukee Protocol. Case presentation The patient suffered a superficial bat bite on her right elbow, reported on April 5, 2022. Despite receiving immunoglobulin, a vaccine, and antiviral medications such as amantadine and sapropterin, the patient succumbed to the disease 25 days after hospital admission. The report highlights the inherent challenges in treating rabies due to the virus’s neurotropic nature and the difficulties in delivering antiviral drugs to the central nervous system. The case underscores the need for early antiviral intervention and calls for more studies to validate and improve treatment protocols for rabies in vulnerable populations, particularly those with genetic and immunological susceptibilities like the Maxakali indigenous group. Conclusion The findings suggest that while the Milwaukee Protocol offers some hope, significant obstacles remain in achieving successful outcomes in rabies cases.

Abstract Background Rotavirus B (RVB) causes diarrhea in humans and pigs. Although various RVB strains were identified in humans and various animals globally, little is known about the epidemiology RVB infection in Africa. In this study, we attempted to examine the prevalence of RVB infection in pig populations in Zambia. Methods Metagenomic analyses were conducted on pig feces collected in Zambia to detect double stranded RNA viruses, including RVB. To clarify the prevalence of RVB infection in pig populations in Zambia, 147 fecal samples were screened for the RVB detection by RT-qPCR. Full genome sequence of a detected RVB was determined by Sanger sequencing and genetically analyzed. Results The metagenomic analyses revealed that RVB sequence reads and contigs of RVB were detected from one fecal sample collected from pigs in Zambia. RT-qPCR screening detected RVB genomes in 36.7% (54/147) of fecal samples. Among 54 positive samples, 13 were positive in non-diarrheal samples (n = 48, 27.1%) and 41 in diarrheal samples (n = 99, 41.4%). Genetic analyses demonstrated that all the segments of ZP18-18, except for VP4, had high nucleotide sequence identities (80.6–92.6%) with all other known RVB strains detected in pigs. In contrast, the VP4 sequence of ZP18-18 was highly divergent from other RVB strains (

Abstract Purpose This study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022. Methods This observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis. Results Among 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab. Conclusion Among Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes. Trial registration The study was registered with clinicaltrial.gov (NCT05917951).