A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

Clinical and Infection Prevention Applications of Severe Acute Respiratory Syndrome Coronavirus 2 Genotyping: An Infectious Diseases Society of America/American Society for Microbiology Consensus Review Document.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged into a world of maturing pathogen genomics, with >2 million genomes sequenced at this writing. The rise of more transmissible variants of concern that affect vaccine and therapeutic effectiveness has led to widespread interest in SARS-CoV-2 evolution. Clinicians are also eager to take advantage of the information provided by SARS-CoV-2 genotyping beyond surveillance purposes. Here, we review the potential role of SARS-CoV-2 genotyping in clinical care. The review covers clinical use cases for SARS-CoV-2 genotyping, methods of SARS-CoV-2 genotyping, assay validation and regulatory requirements, clinical reporting for laboratories, and emerging issues in clinical SARS-CoV-2 sequencing. While clinical uses of SARS-CoV-2 genotyping are currently limited, rapid technological change along with a growing ability to interpret variants in real time foretell a growing role for SARS-CoV-2 genotyping in clinical care as continuing data emerge on vaccine and therapeutic efficacy.

Clinical and Infection Prevention Applications of Severe Acute Respiratory Syndrome Coronavirus 2 Genotyping: an Infectious Diseases Society of America/American Society for Microbiology Consensus Review Document.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged into a world of maturing pathogen genomics, with more than 2 million genomes sequenced at the time of writing. The rise of more transmissible variants of concern that impact vaccine and therapeutic effectiveness has led to widespread interest in SARS-CoV-2 evolution. Clinicians are also eager to take advantage of the information provided by SARS-CoV-2 genotyping beyond surveillance purposes. Here, we review the potential role of SARS-CoV-2 genotyping in clinical care. The review covers clinical use cases for SARS-CoV-2 genotyping, methods of SARS-CoV-2 genotyping, assay validation and regulatory requirements, and clinical reporting for laboratories, as well as emerging issues in clinical SARS-CoV-2 sequencing. While clinical uses of SARS-CoV-2 genotyping are currently limited, rapid technological change along with a growing ability to interpret variants in real time foretells a growing role for SARS-CoV-2 genotyping in clinical care as continuing data emerge on vaccine and therapeutic efficacy.

Molecular Testing for Acute Respiratory Tract Infections: Clinical and Diagnostic Recommendations From the IDSA's Diagnostics Committee.

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses, and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judgment and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. Here, we summarize the current state of the art with respect to the diagnosis of viral and bacterial RTIs, provide a practical framework for diagnostic decision making using selected patient-centered vignettes, and make recommendations for future studies to advance the field.

Systematic Hospital-Based Travel Screening to Assess Exposure to Zika Virus1.

We queried hospital patients about international travel in the previous 30 days to assess potential importation of emerging infections. We used 12 months of deidentified data to analyze patient demographics, travel destinations, and diagnoses for exposure to Zika virus. Our approach could be used to analyze potential infectious disease exposures.

Global Diversity within and between Human Herpesvirus 1 and 2 Glycoproteins.

UNLABELLED: Human herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large-genome DNA viruses that establish a persistent infection in sensory neurons and commonly manifest with recurring oral or genital erosions that transmit virus. HSV encodes 12 predicted glycoproteins that serve various functions, including cellular attachment, entry, and egress. Glycoprotein G is currently the target of an antibody test to differentiate HSV-1 from HSV-2; however, this test has shown reduced capacity to differentiate HSV strains in East Africa. Until the recent availability of 26 full-length HSV-1 and 36 full-length HSV-2 sequences, minimal comparative information was available for these viruses. In this study, we use a variety of sequence analysis methods to compare all available sequence data for HSV-1 and HSV-2 glycoproteins, using viruses isolated in Europe, Asia, North America, the Republic of South Africa, and East Africa. We found numerous differences in diversity, nonsynonymous/synonymous substitution rates, and recombination rates between HSV-1 glycoproteins and their HSV-2 counterparts. Phylogenetic analysis revealed that while most global HSV-2 glycoprotein G sequences did not form clusters within or between continents, one clade (supported at 60.5%) contained 37% of the African sequences analyzed. Accordingly, sequences from this African subset contained unique amino acid signatures, not only in glycoprotein G, but also in glycoproteins I and E, which may account for the failure of sensitive antibody tests to distinguish HSV-1 from HSV-2 in some African individuals. Consensus sequences generated in the study can be used to improve diagnostic assays that differentiate HSV-1 from HSV-2 in global populations. IMPORTANCE: Human herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large DNA viruses associated with recurring oral or genital erosions that transmit virus. Up to 12 HSV-1 and HSV-2 glycoproteins are involved in HSV cell entry or are required for viral spread in animals, albeit some are dispensable for replication in vitro. The recent availability of comparable numbers of full-length HSV-1 and HSV-2 sequences enabled comparative analysis of gene diversity of glycoproteins within and between HSV types. Overall, we found less glycoprotein sequence diversity within HSV-2 than within the HSV-1 strains studied, while at the same time, several HSV-2 glycoproteins were evolving under less selective pressure. Because HSV glycoproteins are the focus of antibody tests to detect and differentiate between infections with the two strains and are constituents of vaccines in clinical-stage development, these findings will aid in refining the targets for diagnostic tests and vaccines.

Genome Sequencing and Analysis of Geographically Diverse Clinical Isolates of Herpes Simplex Virus 2.

UNLABELLED: Herpes simplex virus 2 (HSV-2), the principal causative agent of recurrent genital herpes, is a highly prevalent viral infection worldwide. Limited information is available on the amount of genomic DNA variation between HSV-2 strains because only two genomes have been determined, the HG52 laboratory strain and the newly sequenced SD90e low-passage-number clinical isolate strain, each from a different geographical area. In this study, we report the nearly complete genome sequences of 34 HSV-2 low-passage-number and laboratory strains, 14 of which were collected in Uganda, 1 in South Africa, 11 in the United States, and 8 in Japan. Our analyses of these genomes demonstrated remarkable sequence conservation, regardless of geographic origin, with the maximum nucleotide divergence between strains being 0.4% across the genome. In contrast, prior studies indicated that HSV-1 genomes exhibit more sequence diversity, as well as geographical clustering. Additionally, unlike HSV-1, little viral recombination between HSV-2 strains could be substantiated. These results are interpreted in light of HSV-2 evolution, epidemiology, and pathogenesis. Finally, the newly generated sequences more closely resemble the low-passage-number SD90e than HG52, supporting the use of the former as the new reference genome of HSV-2. IMPORTANCE: Herpes simplex virus 2 (HSV-2) is a causative agent of genital and neonatal herpes. Therefore, knowledge of its DNA genome and genetic variability is central to preventing and treating genital herpes. However, only two full-length HSV-2 genomes have been reported. In this study, we sequenced 34 additional HSV-2 low-passage-number and laboratory viral genomes and initiated analysis of the genetic diversity of HSV-2 strains from around the world. The analysis of these genomes will facilitate research aimed at vaccine development, diagnosis, and the evaluation of clinical manifestations and transmission of HSV-2. This information will also contribute to our understanding of HSV evolution.

Clinical differences between Raoultella spp. and Klebsiella oxytoca.

Purpose: Raoultella spp. is a genus of bacteria that is known to be closely related to Klebsiella. It has been debated whether Raoultella should be reclassified as a subgroup of Klebsiella. The aim of this study is to compare clinical aspects of Raoultella and Klebsiella oxytoca, a species of Klebsiella that is known to be bacteriologically similar to Raoultella spp. Methods: Using data collected at a tertiary care hospital in the United States, we identified 43 patients with Raoultella infection and 1173 patients with Klebsiella oxytoca infection. We compared patient demographics (age and sex), hospitalization status, isolation sites and antibiotic resistance profiles between the two species. Results: There was no significant difference in patient demographics between the two bacteria species. The proportions of intensive care unit (ICU) admission were higher among patients with Raoultella infection (p=0.008). The most common site of isolation was urine for both species (39.5% of all patients with Raoultella spp. vs. 59.3% for K. oxytoca). The second most common site of isolation was blood stream for Raoultella spp. (23.3%) and respiratory tract for K. oxytoca (10.8%). Except for the high proportion of resistant isolates of Raoultella spp. for Trimethoprim/sulfamethoxazole, the antibiotic susceptibility profiles were similar between the two bacteria species. Both were susceptible to ciprofloxacin and meropenem. Conclusion: While there are no significant differences in the patient demographics and antibiotic susceptibility profiles between Raoultella spp. and K. oxytoca, Raoultella may cause more serious infection requiring ICU admissions. Also, Raoultella may cause blood stream infection more frequently than K. oxytoca.

Headache, Fever, and Myalgias in an HIV-Positive Male with a History of Tuberculosis: Epstein-Barr Virus Aseptic Meningitis.

BACKGROUND: We describe a case of EBV aseptic meningitis in a patient with HIV with an extensive history of prior infections and exposures. Detailed Case Description: A 35-year-old man with a history of HIV, syphilis, and partially treated tuberculosis presented with headache, fever, and myalgias. He reported recent exposure to dust from a construction site and had sexual contact with a partner with active genital lesions. An initial workup revealed mildly elevated inflammatory markers, significant pulmonary scarring from tuberculosis with a classic "weeping willow sign", and lumbar puncture findings consistent with aseptic meningitis. An extensive evaluation was conducted to identify causes of bacterial and viral meningitis, including syphilis. Immune reconstitution inflammatory syndrome and isoniazid-induced aseptic meningitis were also considered based on his medications. EBV was ultimately isolated through PCR from the patient's peripheral blood. The patient's condition improved, and he was discharged on his home antiretroviral and anti-tuberculous treatment. CONCLUSION: Central nervous system infections represent unique challenges in patients with HIV. EBV reactivation can present with atypical symptoms and should be considered as a cause of aseptic meningitis in this population.

Tale of the Titers: Serologic Testing for SARS-CoV-2-Yes, No, and Maybe, With Clinical Examples From the IDSA Diagnostics Committee.

Diagnosis of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on detection of viral antigens or amplified viral nucleic acids. Serology, although invaluable for epidemiology, is not routinely needed clinically. However, in some settings, serologic data may have direct clinical utility: for example, in evaluation of persistent symptoms in patients without a prior diagnosis of acute infection. In contrast, SARS-CoV-2 serologic testing is sometimes used or requested in situations in which existing data do not support it, such as determination of need for vaccination. In this study, we describe available methods of serologic testing and provide cases supported by clinical vignettes of where such tests can be helpful, as well as examples where they are not. These examples may help clarify clinical decision making in this rapidly evolving area.

Gender, Age, and Regional Disparities in the Incidence and Mortality Trends of Infective Endocarditis in the United States Between 1990 and 2019.

The incidence of infective endocarditis (IE) has increased globally in the past decades, including in the United States. However, little is known about the differences in trends across states, gender, and age groups within the United States. Using the Global Burden of Disease database, we analyzed the incidence and mortality trends of IE in the United States between 1990 and 2019 using Joinpoint regression analyses, and compared between states, gender, and age groups. The age-standardized incidence rate (ASIR) of IE in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019. The increase in ASIR was greater among men than women (45.8% vs 34.1%). The incidence increase was driven by 55+ year-olds (112.7% increase), with rapid increases in the 1990s and early 2000s, followed by a plateau around the mid-2000s. In contrast, the incidence among 5-to-19-year-olds decreased by -36.6% over the 30-year period. The incidence increased among all age groups in the last 5 years of observation (2015 to 2019), with the largest increase in 5-to-19-year-olds (3.3% yearly). The 30-year increase in ASIR was greatest in Utah (66.2%) and smallest in California (30.2%). The overall age-standardized mortality attributable to IE increased in the United States by 126% between 1990 and 2019 versus 19.6% globally. In conclusion, although the overall incidence and mortality of IE increased over the past 30 years in the United States, there are significant differences between regions, gender, and age groups. These findings indicate unevenly distributed disease burden of IE across the nation.

Use of expert consensus to develop a shared list of procedures with potential for aerosol generation during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the lack of agreement regarding the definition of aerosol-generating procedures and potential risk to healthcare personnel. We convened a group of Massachusetts healthcare epidemiologists to develop consensus through expert opinion in an area where broader guidance was lacking at the time.

Fever and Ulcerative Skin Lesions in a Patient Referred for Altered Mental Status: Clinical and Microbiological Diagnosis of Ulceroglandular Tularemia.

BACKGROUND: Tularemia is a devastating disease that affects multiple organ systems and can have several different presentations. In its most frequent form-that of ulceroglandular tularemia-a detailed history and physical examination can enable a physician to make the diagnosis clinically, leading to the prompt initiation of the appropriate antibiotic treatment. Detailed Case Description: A 63-year-old man was brought by ambulance to the emergency department for an evaluation of an altered mental status noted by his psychiatrist at a telehealth appointment. A physical examination revealed a fever and two ulcerative lesions with a central eschar on his left leg (of which the patient was unaware) with ipsilateral tender inguinal lymphadenopathy. When asked, the patient recalled visiting Martha's Vineyard and having removed ticks from his legs. Gentamicin was administered on the clinical suspicion of ulceroglandular tularemia. Blood and skin lesion cultures grew Gram-negative rods, which were confirmed to be Francisella tularensis on hospital day eight, and the patient fully recovered. CONCLUSION: This case highlights the importance of clinician perception of altered mental status as a key alarm sign, the necessity of a thorough physical exam independent of the chief compliant in the emergency department, and the essential role of pattern recognition by front-line providers for the appropriate management of uncommon but serious infections such as tularemia.

West Nile virus: another emerging arboviral risk for travelers?

Purpose of Review: West Nile virus (WNV) is an arbovirus transmitted by mosquitos of the genus Culex. Manifestations of WNV infection range from asymptomatic to devastating neuroinvasive disease leading to flaccid paralysis and death. This review examines WNV epidemiology and ecology, with an emphasis on travel-associated infection. Recent Findings: WNV is widespread, including North America and Europe, where its range has expanded in the past decade. Rising temperatures in temperate regions are predicted to lead to an increased abundance of Culex mosquitoes and an increase in their ability to transmit WNV. Although the epidemiologic patterns of WNV appear variable, its geographic distribution most certainly will continue to increase. Travelers are at risk for WNV infection and its complications. Literature review identified 39 cases of documented travel-related WNV disease, the majority of which resulted in adverse outcomes, such as neuroinvasive disease, prolonged recovery period, or death. Summary: The prediction of WNV risk is challenging due to the complex interactions of vector, pathogen, host, and environment. Travelers planning to visit endemic areas should be advised regarding WNV risk and mosquito bite prevention. Evaluation of ill travelers with compatible symptoms should consider the diagnosis of WNV for those visiting in endemic areas as well as for those returning from destinations with known WNV circulation.

SARS-CoV-2 prevalence at eight urban health clinics in Nicaragua: possible implications for the COVID-19 pandemic.

Objective: To assess the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in selected health clinics in the three largest urban areas in Nicaragua, where data regarding coronavirus disease 2019 (COVID-19) testing, morbidity and mortality is severely limited. Methods: In this cross-sectional study, participants were tested for SARS-CoV-2 RNA by loop-mediated isothermal amplification (LAMP), and were tested for antibodies using immunoassays. A questionnaire recorded subjects' COVID-19-associated symptoms and risk factors. Data were collected from 22 February to 19 March 2021, 1 year after the first confirmed cases of SARS-CoV-2 in Nicaragua. Study participants were enrolled while attending routine check-ups or seeking care unrelated to COVID-19. Study participation was random and voluntary. All patients were eligible to participate. Symptom history was not part of the eligibility criteria. Results: The prevalence of current SARS-CoV-2 infection was high (14%, LAMP-positive/seronegative). Antibody testing showed higher overall seroprevalence (38%). Cough was the symptom most strongly associated with being LAMP-positive (odds ratio 3.57, 95% confidence interval 2.65-4.81). Loss of smell had the highest positive predictive value, and was significantly associated with being LAMP-positive. Conclusion: The prevalence of current SARS-CoV-2 infection and seropositivity were fairly high. More than half of the sample population had evidence of current or past infection. Knowledge of this previously unknown elevated level of infection is crucial for healthcare providers and policy makers.

To Test, Perchance to Diagnose: Practical Strategies for Severe Acute Respiratory Syndrome Coronavirus 2 Testing.

Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in symptomatic and asymptomatic patients is an important component of the multifaceted approach of managing the coronavirus disease 2019 pandemic. Determining how to best define testing strategies for different populations and incorporating these into broader infection prevention programs can be complex. Many circumstances are not addressed by federal, local, or professional guidelines. This commentary describes various scenarios in which testing of symptomatic or asymptomatic individuals for SARS-CoV-2 virus (antigen or ribonucleic acid) can be of potential benefit. Consideration to pretest probability, risks of testing (impact of false-positive or false-negative results), testing strategy, as well as action based on test results are explored. Testing, regardless of setting, must be incorporated into overarching infection control plans, which include use of personal protective equipment (eg, masks), physically distancing, and isolation when exposure is suspected.