What's Hot This Year in Infectious Diseases Clinical Science.

The field of infectious diseases saw numerous exciting advances in 2023. Trials of new antibiotics and treatment regimens sought to address rising rates of antimicrobial resistance. Other studies focused on the most appropriate use of currently available treatments, balancing the dual goals of providing effective treatment and impactful antimicrobial stewardship. Improvements in disease prevention were made through trials of both new vaccines and new chemoprophylaxis approaches. Concerning trends this year included increasing rates of invasive group A streptococcal infections, medical tourism-associated cases of fungal meningitis, and the return of locally acquired malaria to the United States. This review covers some of these notable trials and clinical developments in infectious diseases in the past year.

Emerging Enterovirus A71 Subgenogroup B5 Causing Severe Hand, Foot, and Mouth Disease, Vietnam, 2023.

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Clinical and Epidemiological Characteristics of the 2022 Mpox Outbreak in Spain (CEME-22 Study).

Background: We conducted a multicentric national study (SEIMC-CEME-22), to describe the clinical and epidemiological profile of the mpox outbreak in Spain, including the management of the disease. Methods: This was a retrospective national observational study conducted by Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) and Foundation SEIMC-GESIDA. We included patients with a confirmed mpox diagnosis before 13 July 2022, and attended at the Spanish health network (the early phase of the outbreak). Epidemiological, clinical, and therapeutic data were collected. Results: Of a total of 1472 patients from 52 centers included, 99% of them were cisgender men, mostly middle-aged, and 98.6% were residents in Spain. The main suspected route of transmission was sexual exposure, primarily among MSM. Occupational exposure was reported in 6 patients. Immunosuppression was present in 40% of patients, mainly due to human immunodeficiency virus (HIV). Only 6.5% of patients had been vaccinated against orthopoxvirus. Virus sequencing was performed in 147 patients (all B.1 lineage). Rash was the most frequent symptom (95.7%), followed by fever (48.2%), adenopathies (44.4%) myalgias (20.7%), proctitis (17%), and headache (14.7%). Simultaneously diagnosed sexually transmitted infections included syphilis (n = 129), gonococcal infection (n = 91), HIV (n = 67), chlamydia (n = 56), hepatitis B (n = 14), and hepatitis C (n = 11). No therapy was used in 479 patients (33%). Symptomatic therapies and antibiotics were used in 50% of cases. The most used therapy regimens were systemic corticoids (90 patients), tecovirimat (6 patients), and cidofovir (13 patients). Smallpox immunoglobulins were used in 1 patient. Fifty-eight patients were hospitalized, and 1 patient died. Conclusions: Mpox outbreak in Spain affected primarily middle-aged men who were sexually active and showed a high rate of HIV infection. A range of heterogeneous therapeutics options was performed.

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection.

Rationale: Chronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF. Methods: pwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with S. maltophilia-negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) (n = 57), at (At) (n = 22), and after (Post) (n = 31) incident infection. We verified relative abundance data using S. maltophilia-specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis. Results: Twenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls (n = 56) based on Shannon Diversity Index (SDI, p = 0.04) and clustered based on Aitchison distance (PERMANOVA, p = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative (p = 0.004) and absolute (p = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively (p = 0.04) or absolute (p = 0.04), respectively. Conclusion: Microbial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.

Pathogen-Agnostic Advanced Molecular Diagnostic Testing for Difficult-to-Diagnose Clinical Syndromes-Results of an Emerging Infections Network Survey of Frontline US Infectious Disease Clinicians, May 2023.

During routine clinical practice, infectious disease physicians encounter patients with difficult-to-diagnose clinical syndromes and may order advanced molecular testing to detect pathogens. These tests may identify potential infectious causes for illness and allow clinicians to adapt treatments or stop unnecessary antimicrobials. Cases of pathogen-agnostic disease testing also provide an important window into known, emerging, and reemerging pathogens and may be leveraged as part of national sentinel surveillance. A survey of Emerging Infections Network members, a group of infectious disease providers in North America, was conducted in May 2023. The objective of the survey was to gain insight into how and when infectious disease physicians use advanced molecular testing for patients with difficult-to-diagnose infectious diseases, as well as to explore the usefulness of advanced molecular testing and barriers to use. Overall, 643 providers answered at least some of the survey questions; 478 (74%) of those who completed the survey had ordered advanced molecular testing in the last two years, and formed the basis for this study. Respondents indicated that they most often ordered broad-range 16S rRNA gene sequencing, followed by metagenomic next-generation sequencing and whole genome sequencing; and commented that in clinical practice, some, but not all tests were useful. Many physicians also noted several barriers to use, including a lack of national guidelines and cost, while others commented that whole genome sequencing had potential for use in outbreak surveillance. Improving frontline physician access, availability, affordability, and developing clear national guidelines for interpretation and use of advanced molecular testing could potentially support clinical practice and public health surveillance.

Sunflower Oil and Cholesterol Nanoemulsion: A Novel Carrier for Micafungin to Combat Multi-Resistant Candida auris.

Candida auris is an emerging, multidrug-resistant yeast that causes systemic infections, mainly in hospitalized or immunosuppressed patients. This pathogen has a high mortality and morbidity rate. This study aims to evaluate the antifungal potential of micafungin (MICA) encapsulated in a nanoemulsion (NEM) against four clades of C. auris and other non-C. auris species. The antifungal potential of MICA and NEM was evaluated by determining mature biofilm inhibition (0.78-50 µg/mL). The antifungal activities of MICA and NEM (5.92 mg/Kg) were evaluated using an in vivo model of Galleria mellonella. The results showed that NEM intensified the antibiofilm action of MICA, especially in 48 h mature biofilms. In vivo results displayed a higher effectiveness of NEM against all clades of C. auris tested, inhibiting the fungal load in the hemolymph and tissues of G. mellonella with a difference of 3 log10. In addition, C. auris infection caused granulomas surrounded by hemocytes, mainly at the lower and upper ends. Conversely, C. albicans developed pseudohyphae, biofilms, filaments, and chlamydospores. In conclusion, encapsulation of MICA in a nanoemulsion enhances its antifungal activity against mature biofilms of C. auris. This strategy may be considered a therapeutic approach for the control of infections and the dissemination of this new global health threat.

Emerging Burkholderia Musculoskeletal Infections With Delayed Diagnosis in Non-endemic Regions Affect Patient Morbidity: A Case Series of 10 Patients With a Review of the Literature.

INTRODUCTION:  Burkholderia infection commonly presents as bacteraemic pulmonary disease; however, it is notorious for its wide variety of presentations in chronic cases, including musculoskeletal manifestations. It is common in patients living in endemic areas with comorbidities such as diabetes and who have chronic alcoholism. It was previously under-reported due to a low index of suspicion. Now, there is an increasing trend of diagnosis of these infections in non-endemic areas because of various factors, such as MALDI-TOF, molecular tests, and PCR. MATERIALS AND METHODS: This is a single tertiary centre study of 10 patients, diagnosed with Burkholderia infection and treated at our institution between 2021 and 2023 and followed up for a minimum of six months. Information was collected from outpatient and inpatient records. RESULTS: In this study, the mean age of the patients was 45 years, with eight males and two females. Out of 10, seven patients had comorbidities. However, only one patient has a history of travelling to an endemic area. All our patients were treated operatively, and the course of intervention and the planning of the surgical procedure were decided according to clinico-radiological findings. Six out of 10 patients suffering from Burkholderia species infections have a history of prolonged ICU stay, four of them tested positive for Burkholderia pseudomallei and the remaining two tested positive for Burkholderia cepacia, with a mean average time of 24.6 days. Diabetes was the most common comorbidity in 70% of the patients. The knee was the most commonly affected joint, showing involvement in 60% of patients. We have done surgical intervention in all patients. In our study, we have given IV antibiotics for a minimum of six weeks to all patients, followed by oral antibiotic therapy for three to six months on the basis of regular follow-up of clinico-haematologic parameters. CONCLUSION: Infections caused by Burkholderia species should be considered a potential causative agent of musculoskeletal infections in non-endemic areas without prior history of travelling to endemic areas. It may present with a chronic, mild course; a high index of suspicion is required, and it is important that due suspicion translates to prompt diagnosis and appropriate treatment to mitigate the course of the disease and associated morbidities in patients.

Vaccine Development.

This article considers ethical considerations surrounding pediatric vaccine development for pandemic preparedness, examines some historical cases of pediatric vaccines developed during past smallpox, influenza, and 2019 coronavirus disease pandemics, and discusses the current state of vaccine development for pandemic preparedness, including vaccines against smallpox/mpox, influenza, anthrax, and Ebola that are included in the US Strategic National Stockpile and vaccines being developed against priority pathogens identified by the World Health Organization.

Candida auris Outbreak in a Multidisciplinary Hospital in Romania during the Post-Pandemic Era: Potential Solutions and Challenges in Surveillance and Epidemiological Control.

Candida auris is a newly emerging yeast, which is raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals, and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analyzed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could only be traced in 10 patients, according to the epidemiologic investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first positive case detected.

Recurrent Clostridioides difficile Infection and Outcome of Fecal Microbiota Transplantation Use: A Population-Based Assessment.

Background: Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality. Methods: A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and ≥1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt. Results: A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI. Conclusions: These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.

Investigating the impact of vaccine hesitancy on an emerging infectious disease: a mathematical and numerical analysis.

Throughout the last two centuries, vaccines have been helpful in mitigating numerous epidemic diseases. However, vaccine hesitancy has been identified as a substantial obstacle in healthcare management. We examined the epidemiological dynamics of an emerging infection under vaccination using an SVEIR model with differential morbidity. We mathematically analyzed the model, derived R0, and provided a complete analysis of the bifurcation at R0=1. Sensitivity analysis and numerical simulations were used to quantify the tradeoffs between vaccine efficacy and vaccine hesitancy on reducing the disease burden. Our results indicated that if the percentage of the population hesitant about taking the vaccine is 10%, then a vaccine with 94% efficacy is required to reduce the peak of infections by 40%. If 60% of the population is reluctant about being vaccinated, then even a perfect vaccine will not be able to reduce the peak of infections by 40%.

Developing technology-based interventions for infectious diseases: ethical considerations for young sexual and gender minority people.

Compared to their heterosexual and cisgender peers, young sexual and gender minority (YSGM) people are more likely to contract sexually transmitted infections (STIs; e.g., HIV) and to face adverse consequences of emerging infections, such as COVID-19 and mpox. To reduce these sexual health disparities, technology-based interventions (TBIs) for STIs and emerging infections among YSGM adolescents and young adults have been developed. In this Perspective, we discuss ethical issues, ethical principles, and recommendations in the development and implementation of TBIs to address STIs and emerging infections among YSGM. Our discussion covers: (1) confidentiality, privacy, and data security (e.g., if TBI use is revealed, YSGM are at increased risk of discrimination and family rejection); (2) empowerment and autonomy (e.g., designing TBIs that can still function if YSGM users opt-out of multiple features and data collection requests); (3) evidence-based and quality controlled (e.g., going above and beyond minimum FDA effectiveness standards to protect vulnerable YSGM people); (4) cultural sensitivity and tailoring (e.g., using YSGM-specific models of prevention and intervention); (5) balancing inclusivity vs. group specificity (e.g., honoring YSGM heterogeneity); (6) duty to care (e.g., providing avenues to contact affirming healthcare professionals); (7) equitable access (e.g., prioritizing YSGM people living in low-resource, high-stigma areas); and (8) digital temperance (e.g., being careful with gamification because YSGM experience substantial screen time compared to their peers). We conclude that a community-engaged, YSGM-centered approach to TBI development and implementation is paramount to ethically preventing and treating STIs and emerging infections with innovative technology.

Benford´s Law with small sample sizes: A new exact test useful in health sciences during epidemics / Ley de Benford con muestras pequeñas: una prueba exacta nueva útil ciencias de la salud durante epidemias

Abstract Benford or "first digit" law has been used successfully to evaluate epidemiological surveillance systems, especially during epidemics. Conventional statistical methods for evaluation (x2 and log-likelihood ratio) are controversial when the number of data is small (n <7). In this methodological note a new test is proposed to evaluate compliance with Benford's law with small samples, which can be used with biomedical, medical and public health data.

Resumen La ley de Benford o de los "primeros dígitos" ha sido usada exitosamente para evaluar los sistemas de vigilancia epidemiológica, en especial durante epidemias. Los métodos estadísticos convencionales para la evaluación (x 2 y razón de log-verosimilitud) son controversiales cuando los datos son poco (n<7). En esta nota metodológica se propone una nueva prueba para evaluar el cumplimiento de la ley de Benford con muestras pequeñas, que puede ser usada con datos de biomedicina, medicina y salud pública.

As novas facetas e a ameaça da gripe aviária no mundo globalizado / New aspects and the threat of an avian flu epidemic in a globalized world

A influenza ou, como é conhecida comumente, a gripe, é uma doença infecciosa aguda causada por um grupo de vírus (com mesmo nome) que acomete várias espécies de animais, desde felinos até aves, passando por humanos. Há cerca de 10 anos têm sido descritos, inicialmente em Hong Kong, surtos de gripe causados por vírus aviários em populações humanas. A seguir, foram descritos surtos na Holanda e no Canadá. Portanto, indaga-se: o mundo corre o risco de um novo surto semelhante ao de 1918, porém com uma população mundial quatro a cinco vezes maior? Qual a velocidade de disseminação desse vírus, visto que as viagens internacionais já não são feitas em navios lentos, mas sim em jatos supersônicos que dão a volta ao mundo em algumas horas? Antes de tudo, o que torna esse vírus tão problemático? Para nós, profissionais de laboratório, é preocupante a questão do diagnóstico etiológico dessas infecções. Como ressaltamos, os quadros de gripe podem ser causados por vários agentes. Portanto, o diagnostico etiológico, básico para intervenções terapêuticas e para que se defina a ocorrência da epidemia, passa a ter relevância ainda maior.

Influenza, or as it is best known, "flu", is an acute respiratory infection caused by a virus that affects many different animal species from felines to birds, including humans.Ten years ago, initialy in Hong Kong and after that in Holand and Canada, outbreaks of avian flu have been increasingly reported in human beings. The question is innevitable: are we in the surge of a new flu pandemic like the one we had in 1918? The perspective is even worse now that we have five times the world population and the international travels are no longer made in slow-going ships but instead in super fast jet planes. For us, laboratory professionals, the question of the laboratory diagnosis is crucial. Considering that so many different viruses are associated with respiratory infections and therapeutic measures depend on this definition, this subject assumes an even greater interest.