bluuebunny/crossref_metadata_2025 huggingface dataset:
Brucella
spp.—Brucellosis
Authors: Rowlinson Marie‐Claire , Lee Philip A.
Published: January 2025

Brucella
species are fastidious, aerobic, small, Gram‐negative coccobacilli that are nonmotile and non‐spore forming and are the causative agent of brucellosis, a reportable disease in most countries.
Brucella abortus
,
Brucella melitensis
, and
Brucella suis
are considered “overlap” select agents because they pose a serious threat to public health and safety as well as to animal health and animal products. To identify
Brucella
to the genus level, some biochemical testing is needed; however, automated systems and manual biochemical test kits cannot accurately identify the organism, due to its minimal reactivity. Brucellosis is the most common zoonotic disease worldwide, and although the epidemiology has changed with livestock vaccination and pasteurization of dairy products, it continues to be endemic in certain areas of Latin America, Asia, Africa, and the Middle East, causing an estimated 500,000 human cases of brucellosis annually.
Tularemia—
Francisella tularensis
Authors: Schaecher Kurt E.
Published: January 2025

Francisella tularensis
is a fastidious, tiny, Gram‐negative coccobacillus and the etiological agent of tularemia.
F. tularensis
is a known risk for laboratory‐acquired infection. The identification of
F. tularensis
should not be attempted with commercial identification systems because of the potential of generating aerosols and the high probability of misidentification.
F. tularensis
is widespread throughout the Northern Hemisphere and is responsible for recent tularemia outbreaks in several countries, including Norway and Turkey.
F. tularensis
is a zoonotic pathogen with an extremely wide host range that includes mammals, birds, and amphibians. The primary hosts for
F. tularensis
are believed to be small rodents (hares, voles, muskrats).
F. tularensis
was actively pursued as a biological warfare agent by both the United States and the former Soviet Union.
Novel Influenza Viruses and Highly Pathogenic Coronaviruses
Authors: Loeffelholz Mike J. , Relich Ryan F.
Published: January 2025

Three viruses in the family
Orthomyxoviridae
cause influenza in humans: influenza virus types A and B, and influenza virus C. Influenza viruses are enveloped and have a segmented, single‐stranded, negative‐sense RNA genome. There are seven known human‐pathogenic coronaviruses, including the human coronaviruses (HCoV229E, HCoV‐NL63, HCoV‐OC43, and HCoV‐HKU1), Middle East respiratory syndrome coronavirus (MERS‐CoV), severe acute respiratory syndrome coronavirus (SARSCoV or SARS‐CoV‐1) and SARSCoV‐2. In humans, coronaviruses primarily cause respiratory tract diseases that range from mild nasopharyngitis to severe, life‐threatening pneumonia; however, many of these viruses have been found to cause extrapulmonary diseases as well. The chapter covers safety considerations, specimen collection, and methods for preanalytical considerations. For analytical considerations, it provides specimen processing, incubation and examination of cultures, and culture identification. With postanalytical considerations, the chapter also provides attention to common test limitations, interpretive challenges, and results reporting.
Eastern Equine Encephalitis Virus
Authors: Vetter Sara M.
Published: January 2025

Eastern equine encephalitis virus (EEEV) is a member of the Alphavirus group in the family
Togaviridae
. It is an enveloped, positive‐sense RNA virus and is part of a group of other important arthropod‐borne viruses such as chikungunya virus and Ross River virus. EEEV is the etiological agent of eastern equine encephalitis (EEE) disease in humans and equines. The main mosquito vector is
Culiseta melanura
, which is found in the southeastern United States, Central America, and northern South America, but other “bridge vectors”, such as
Aedes
,
Culex
, and
Coquillettidia
, which feed on both birds and mammals, are responsible for infections in equines and humans. EEEV has been detected only in the Western Hemisphere, being found in eastern Canada and all U.S. states east of the Mississippi as well as several other states, including Arkansas, Minnesota, South Dakota, and Texas. Clinical manifestations of EEE infection vary from low‐grade fever to severe encephalitis, including death.
Immunoassays for the Diagnosis of Infectious Diseases
Authors: Theel Elitza S.
Published: January 2025

This chapter summarizes the common serologic testing methods used for detection of the humoral immune response to, or antigens released from, various infectious agents. It presents their application for the diagnosis of infectious diseases, including a discussion of the advantages and limitations of selected methods. An understanding of serologic immunoassays and their clinical utility requires an appreciation of the basic immunologic principles of humoral immunity. Serologic assays can be used for either screening or diagnostic purposes. Agglutination reactions utilize a particulate, insoluble antigen, in contrast to precipitation reactions, which are based on the interaction of soluble antigen and antibodies. The complement fixation assay is based on the interaction of immune complexes with components of the classical complement pathway. Another classic serologic technique is the neutralization assay. The term “enzyme immunoassay” is considered a general term that can be applied to any immunoassay which uses an enzyme label.
Investigation of Disease Outbreaks
Authors: Rolon Rebecca M. , Szymczak Wendy A.
Published: January 2025

This chapter reviews concepts associated with infectious diseases outbreaks, including disease surveillance, mechanisms used to detect outbreaks, and the epidemiological steps used to investigate an outbreak. It describes the role of the laboratory in outbreaks and includes examples where laboratory testing played a key role in the investigation of the outbreak. Outbreak investigations provide a unique opportunity for local authorities to provide enhanced education and awareness. Outbreak (or epidemic) intelligence is the process used to detect, verify, analyze, assess, and investigate signals that may represent a threat to public health. The chapter provides specific examples of how laboratories contributed to the SARS‐CoV‐2 outbreak response. In the recent SARS‐CoV‐2 pandemic, nucleic acid amplification and antigen detection assays have been used widely for virus identification from specimens, while WGS has been used for both the detection of and surveillance for emerging variants.
Molecular Epidemiology
Authors: MacCannell Duncan , Terry Fei Fan Ng , Chow Nancy , Jorba Jaume , Beck Andrew , Carleton Heather
Published: January 2025

The practice of infectious disease epidemiology has always been linked to advances in laboratory science, data analysis, and interpretation. This chapter is intended to serve as an introduction to molecular epidemiology and important terms and concepts associated with the field. It focuses on applications of these classical molecular epidemiologic techniques, and focuses on the increasing role and impact of genomic sequencing and bioinformatics in broad‐based pathogen identification, characterization, molecular surveillance, and outbreak response. The chapter discusses strategies for the development of molecular subtyping tools, including data analysis and interpretation, and comprehensive validation and quality control. All molecular subtyping methods show very high typeability with the organisms that they target. Data from ongoing molecular surveillance of viral and bacterial pathogens are used to decide on the most appropriate formulation for vaccines, and to assess for ongoing vaccine safety and effectiveness.
Disinfection and Sterilization
Authors: Arduino Matthew J. , McDonnell Gerald
Published: January 2025

The effective use of disinfection and sterilization procedures is important in patient care and laboratory settings. Inadequate disinfection and sterilization procedures may lead to health care‐associated and laboratory‐acquired infections. This chapter also discusses international consensus standards related to disinfection and sterilization in the health care environment. Cleaning is often an essential prerequisite to disinfection or sterilization to ensure the optimal activity of the antimicrobial effects of disinfectants or sterilization processes, as well as ensuring the lack of residual materials that may have other negative impacts. There are two major considerations in the use of any disinfection or sterilization product or process: antimicrobial expectations and safety. These safety practices include cleaning and disinfection of laboratory surfaces, sterilization, and hand hygiene. The chapter considers the most widely used sterilization method for clinical laboratory applications that is heat sterilization along with a brief explanation of alternative sterilization methods.
The Human Microbiome
Authors: Rao Meghana V. , Messina Julia A. , Surana Neeraj K.
Published: January 2025

Given the voluminous data regarding the microbiota and human health, this chapter focuses on exemplar data to highlight key findings that are often generalizable across body sites and disease states. The Human Microbiome Project, a landmark study that cataloged the microbiome in multiple anatomic sites in healthy adults, found that the composition of the microbiota differs by body site, there is tremendous interindividual variation, and the microbial gene content is relatively conserved irrespective of the body site or individual. The oropharyngeal microbiota translocates to the lower respiratory tract via normal microaspirations in healthy individuals. The ileal microbiota contains a number of
Streptococcus
spp. and other bacteria that are also found in the oral microbiota, a finding that suggests some continuity of microbes throughout the gastrointestinal tract. The skin microbiome is a diverse ecosystem with the greatest variation in microbial species over time and the greatest phylogenetic diversity of all anatomic sites.
Taxonomy of
Bacteria
and
Archaea
Authors: Lawson Paul A.
Published: January 2025

Taxonomy is more narrowly defined and can be considered to fall under the umbrella of systematics
per se
, consisting of classification, nomenclature, and identification. A reliable classification is a prerequisite for anyone dealing with microorganisms, whether in academia, industry, or health care. The establishment of orderly systems of classification is based on ranks, the highest of which is the domain; the domains of the prokaryotes are the
Archaea
and
Bacteria
. Even though phenotypic methods of numerical taxonomic identification were largely abandoned for the classification of new species, the determination of biochemical, nutritional, and physiological criteria remains a fundamental component of systematics and is routinely incorporated into the species description of published novel taxa. Genotypic information is derived from nucleic acids, whereas phenotypic information is derived from proteins and their functions, chemotaxonomic markers, and a wide range of other expressed features.
Specimen Collection, Transport, and Processing: Bacteriology
Authors: McElvania Erin , Singh Kamaljit
Published: January 2025

The clinical microbiology laboratory is responsible for providing guidance on how to select, collect, label, and transport specimens for processing in the laboratory. An improperly collected specimen can decrease the sensitivity of pathogen detection or introduce colonizing bacteria surrounding the site of infection, which complicates the laboratory workup of cultures and may result in unnecessary or inappropriate antimicrobial therapy. All specimen processing should be performed in a biosafety level 2 cabinet to prevent contamination of specimens, and staff should wear personal protective equipment, including a splash‐proof gown and gloves, to minimize accidental exposures. Superficial wound specimens are frequently submitted on swabs and often grow multiple organisms, including members of the commensal microbiota, which makes interpretation and treatment confusing for physicians. Detection of group A
Streptococcus
to diagnose pharyngitis is the most common test ordered for specimens from the upper respiratory tract.
Listeria
and
Erysipelothrix
Authors: Smith Kenneth P. , Harris Rebecca M.
Published: January 2025

Listeria
and
Erysipelothrix
are genera of small, non‐sporeforming, Gram‐positive bacilli that include the opportunistic human pathogens
Listeria monocytogenes
and
Erysipelothrix rhusiopathiae
. The clinical presentation of an individual exposed to
Listeria
varies from asymptomatic to mild gastroenteritis to life‐threatening illness, depending on a combination of factors that include bacterial virulence, inoculum size, and underlying host defenses. Isolation of
Listeria
can be achieved from clinical specimens from normally sterile sites, including blood and cerebrospinal fluid. Typing of
Erysipelothrix
is used for the analysis of outbreaks in farmed animals and other epidemiologic purposes but has little clinical relevance in humans. Historically, strain typing was performed by serologic testing based on somatic and flagellar antigens. Due to the lack of resistant strains, breakpoints exist for susceptible results only.
Mycobacterium
: Laboratory Characteristics of Slowly Growing Mycobacteria Other than
Mycobacterium tuberculosis
Authors: Caulfield Adam J. , Richter Elvira , Brown‐Elliott Barbara A. , Wengenack Nancy L.
Published: January 2025

This chapter describes the clinically significant, slowly growing nontuberculous mycobacteria (SGM). Pulsed‐Field Gel Electrophoresis has been a useful technique for strain typing of the SGM. It is important to recognize that an unidentified mycobacterial isolate should be treated as if it is
M. tuberculosis
and that appropriate safety measures, including biosafety level 3 practices and facilities, should be used until
M. tuberculosis
is ruled out. One of the first, easiest, and least expensive means of detecting the presence of mycobacteria in clinical samples is microscopic examination. Matrix‐assisted laser desorption ionization‐time‐of‐flight mass spectrometry has revolutionized the identification of microorganisms, including mycobacteria. Not all laboratories may have the necessary funds, facilities, or instrumentation to provide molecular testing in mycobacteriology. Antimicrobial susceptibility testing of clinically relevant mycobacteria is important for the treatment of infections caused by many mycobacterial species.
Neisseria
Authors: Lâm Thiên‐Trí , Vogel Ulrich , Claus Heike
Published: January 2025

Microaerobic growth by denitrification of nitrite via nitric oxide has also been shown for
Neisseria meningitidis
. The species
N. gonorrhoeae
and
N. meningitidis
are exclusively human pathogens. Identification of the serogroup of invasive
N. meningitidis
isolates is of interest with respect to vaccination of close contacts of the index case. A further level of differentiation to analyze local epidemiology is achieved by DNA sequence‐based typing schemes of hypervariable outer membrane proteins, which have been harmonized throughout Europe. Cultivation of
N. gonorrhoeae
is best performed on chocolate agar, which supports the growth of many other commensal bacteria. DNA‐based methods used for typing of
N. gonorrhoeae
include gel‐based methods such as
opa
typing and restriction fragment length polymorphism analysis by pulsed‐field gel electrophoresis. Serologic tests are used for the determination of protection against invasive meningococcal disease after vaccination or for seroepidemiological studies. First‐catch urine is recommended for the molecular detection of genitourinary
N. gonorrhoeae
infections in men.
Aeromonas*
Authors: Lamy Brigitte
Published: January 2025

Members of the genus
Aeromonas
are Gram‐negative facultative anaerobes that are straight, coccobacillary to bacillary cells with rounded ends.
Aeromonas
species are environmental opportunistic pathogens, involved in numerous types of diseases, including gastroenteritis and infections at a variety of extraintestinal sites, of which blood and wounds are the most common. Most clinical infections with aeromonads are related to an exposure to some type of aquatic source, whether the clinical specimen is feces or extraintestinal, and to a lesser extent to the ingestion of foods. Aeromonads survive well in specimens, and any of the widely used transport media are acceptable for transport, with Cary‐Blair generally considered to be the best for feces transportation. Whole‐genome sequencing is the reference method to identify aeromonads or to describe a novel species. Strains show a propensity to acquire resistance genes and to disseminate them to other bacteria. Antimicrobial susceptibility testing of local isolates is necessary because of emerging resistance.
Bacteroides
,
Porphyromonas
,
Prevotella
,
Fusobacterium
, and Other Anaerobic Gram‐Negative Rods
Authors: Conrads Georg , Nagy Elisabeth , Könönen Eija
Published: January 2025

With increasing use of sequencing techniques, obligate anaerobic Gram‐negative rods are increasingly detected in clinical infections, such as brain or liver abscesses with
Prevotella
and
Fusobacterium
species predominating. Production of pigment is visible characteristic valuable in presumptive identification; the pigmented Gram‐negative anaerobic rods are composed of saccharolytic and asaccharolytic species of the genera
Prevotella
and
Porphyromonas
and pigment‐producing
Alistipes
species.
Bacteroides
species can be involved in part in polymicrobial necrotizing soft tissue infections, and the
B. fragilis
group is, after Gram‐positive anaerobic cocci, one of the most common anaerobes found in infected moderate to severe diabetic foot wounds. Antimicrobial resistance among Gram‐negative anaerobes continues to rise. The chapter gives characteristics of anaerobic Gram‐negative genera that have grown from clinical specimens.
Algorithms for Identification of Curved and Spiral‐Shaped Gram‐Negative Rods
Authors: Nachamkin Irving
Published: January 2025

Curved and spiral‐shaped bacteria have a common microscopic morphology but represent diverse bacterial pathogens. These organisms are curved, helical, or spiral‐shaped Gram‐negative rods. Most bacteria in this group of organisms are isolated from patients with gastrointestinal tract‐related infections, but may be isolated from blood cultures, wound cultures, or other less common specimen types. Increased hydrogen levels in the microaerobic environment are important for isolation of some
Campylobacter
and
Helicobacter
species. Many clinical laboratories use rapid identification systems such as matrix‐assisted laser desorption/ionization–time of flight mass spectrometry for quick identification of bacterial agents isolated in primary culture, or use multiplex molecular amplification systems for direct detection of common enteric pathogens in fecal samples. The chapter describes few laboratories perform conventional biochemical identification of the organisms.
Treponema
and
Brachyspira
Authors: Seña Arlene C. , Pillay Allan , Radolf Justin D.
Published: January 2025

Spirochetal phylotypes identified in the human mouth belong exclusively to the genus
Treponema
.
Brachyspira
spp. are oxygen‐tolerant anaerobes differentiated by phenotypic growth characteristics and degree of beta‐hemolysis. The epidemiologic importance of
Treponema denticola
and other oral treponemes arises to a great extent from their occurrence as members of the polymicrobial consortium that causes gingivitis and periodontitis. Two Brachyspira species,
Brachyspira aalborgi
and
Brachyspira pilosicoli
, have been associated definitively with human intestinal spirochetosis. The method used for direct detection of
Treponema pallidum
depends upon the stage of disease, the clinical presentation, and the type of specimen obtained.
T. pallidum
can be detected in lesion exudate by darkfield microscopy or nucleic acid amplification tests. Most infants with congenital syphilis are asymptomatic at birth. Serologic tests play an important role in syphilis diagnosis by supplementing direct detection methods for early syphilitic lesions, for diagnosing latent infection, and confirming suspected tertiary disease.
General Approaches to Identification of
Mycoplasma
,
Ureaplasma
, and Obligately Intracellular Bacteria
Authors: Bébéar Cécile , Dumler J. Stephen
Published: January 2025

This chapter focuses on
Mycoplasma
and
Ureaplasma
species, and provides characterization of
Coxiella burnetii
and
Tropheryma whipplei
, a requirement for intracellular growth. The most frequently used tests in clinical microbiology laboratories, Gram staining and culture on artificial media, are often unable to detect these organisms if they are present in clinical samples. Diagnosis of infections caused by these bacteria has traditionally been accomplished by Giemsa and Wright stains of clinical samples, by detection of antibody responses to infection using a variety of serologic tests, or by histopathologic analysis of biopsy samples. Molecular diagnostic tools and enhanced culture methods have significantly improved the ability to detect these agents and to diagnose the diseases they cause. The chapter summarizes the epidemiology of these infections and the diagnostic tests most often used for detection of the causative bacteria.
Rickettsia
and
Orientia
Authors: Blanton Lucas S. , Walker David H. , Bouyer Donald H.
Published: January 2025

The family
Rickettsiaceae
comprises two genera of small, obligately intracellular bacteria that reside free within the host cell's cytosol, namely,
Rickettsia
and
Orientia
. Pathogenic
Rickettsia
spp. reside in an arthropod host for at least a part of their life cycle, during which they are maintained by transovarian transmission and/or cycles involving horizontal transmission to vertebrate hosts. Nucleic acid amplification testing has been applied to the amplification of the DNA of spotted fever group and typhus group rickettsiae, usually from peripheral blood, buffy coat, or plasma and occasionally from fresh, frozen, or paraffin‐embedded tissue and from swabs of the ulcerated bases of eschars. The limited quantities of circulating rickettsial DNA during infection greatly hinder the clinical sensitivity of molecular detection from peripheral blood specimens. Species identification of rickettsial isolates was performed by microimmunofluorescence serotyping. Enzyme immunoassay has become an increasingly used method to detect antibodies reactive against
Orientia tsutsugamushi
.
Special Phenotypic Methods for Detecting Antibacterial Resistance
Authors: Simner Patricia J. , Humphries Romney M.
Published: January 2025

Special phenotypic tests may be performed as an adjunct or surrogate to standard antimicrobial susceptibility testing methods to help characterize an isolate's antimicrobial susceptibility to a drug or drug class or detect a particular resistance mechanism or phenotype. Special phenotypic susceptibility tests are categorized into supplemental tests, screening tests, surrogate agent tests, and equivalent agent tests. Phenotypic methods for the detection of resistance have been developed for use with both clinical specimens and cultured growth. Resistance to streptomycin is mediated by a different resistance mechanism, and consequently, streptomycin resistance must be determined separately from gentamicin resistance. Although erythromycin and clindamycin are in separate antimicrobial agent classes, i.e., macrolides and lincosamides, respectively, their mechanisms of action and mechanisms of resistance are similar. Antimicrobial resistance among Gram‐negative bacilli, and especially resistance to β‐lactam agents, is a serious public health concern worldwide.
Susceptibility Test Methods: Mycobacteria,
Nocardia
, and Other Actinomycetes
Authors: Brown‐Elliott Barbara A. , Cirillo Daniela‐Maria , Musser Kimberlee A. , Rowlinson Marie‐Claire
Published: January 2025

This chapter includes a description of the main laboratory tools for the detection of antimicrobial resistance (drug resistance) in tuberculosis (TB), other mycobacterial infections, and aerobic actinomycetes. Nontuberculous mycobacteria (NTM) and aerobic actinomycetes can also cause substantial disease in humans. The incidence of NTM infection continues to increase, particularly in certain patient populations, and AST for NTM and aerobic actinomycetes is an important component of optimal patient care. The chapter discusses the antimicrobial agents that are used in treating mycobacterial infections. It discusses antimicrobial agents in alphabetical order. For TB, first‐line drugs are less toxic, can be given orally using short‐course therapy, and are used to treat pulmonary TB disease susceptible to those agents.
Nocardia
spp. and other aerobic actinomycetes can cause serious disease in immunocompromised and occasionally even healthy hosts. In vitro susceptibility testing should be performed on all clinically significant isolates to serve as a guide for therapy and to monitor for resistance.
Influenza Viruses
Authors: Atmar Robert L.
Published: January 2025

The influenza viruses are members of the family
Orthomyxoviridae
. The transmission of influenza viruses to people from avian and swine species highlights the need for vigilant surveillance for such events. Antigen detection assays are used in a variety of formats to rapidly detect influenza viruses in clinical specimens and to confirm the identity of isolates grown in culture. Influenza viruses have been detected in clinical specimens by direct and indirect visualization of their typical morphological appearance by electron microscopy. Influenza virus isolation procedures should be performed under biosafety level 2 conditions. Influenza virus infections are also identified by serologic methods. The pandemic strain may develop because of genetic reassortment following coinfection of a susceptible host with human and animal influenza viruses or through gradual adaptation of an avian strain to mammalian hosts.
Rhinoviruses
Authors: Landry Marie Louise , Lu Xiaoyan
Published: January 2025

Human rhinoviruses (RVs) are members of the family
Picornaviridae
. RVs derive their name from the predominant site of their replication and symptomatology, the nose. The wider use of molecular methods in viral diagnostics has led to the discovery of a novel group of RVs identified in patients with lower respiratory tract disease. Symptoms of RV infection parallel the rise and fall of chemical mediators of inflammation. Psychological stress and inadequate sleep appear to increase susceptibility and the development of clinical symptoms. A presumptive diagnosis of RV isolates in cell culture is made by the appearance and progression of characteristic cytopathic effects in the appropriate cell lines. Serotyping of RV isolates by neutralization with type‐specific antisera used to be the gold standard for RV identification. Molecular typing based on reverse transcription polymerase chain reaction and amplicon sequencing has essentially replaced serotyping for type‐specific identification of RVs.
Hepatitis A and E Viruses
Authors: Izopet Jacques , Kamar Nassim
Published: January 2025

Hepatitis A virus (HAV) is a species of the genus
Hepatovirus
within the family
Picornaviridae
. HAV has a primitive capsid related to picorna‐like viruses, which infect insects. Hepatitis E virus (HEV) belongs to the
Hepeviridae
family. HAV is a small RNA virus with an icosahedral capsid. Close contact between infected and susceptible people is the most common mode of HAV transmission in developing and developed countries. HAV can be transmitted by transfusion of blood or blood products on rare occasions. HAV and HEV are both transmitted mainly by the fecal‐oral route. Occurrence of clinical manifestations of hepatitis E in immunocompetent individuals is associated with high viral load. Enzyme or chemiluminescent immunoassays for anti‐HAV IgM and IgG are commercially available in microplate and multiparametric automated formats. Regarding HEV infection, the availability of high‐performance serologic and molecular tools allowed a significant change in the understanding of global epidemiology and pathology.
Aspergillus
,
Talaromyces
, and
Penicillium
Authors: Chen Sharon C.‐A. , Meyer Wieland , Sorrell Tania C. , Halliday Catriona L.
Published: January 2025

The genus
Aspergillus
is classified in the family Trichocomaceae of the Ascomycota. The majority of human infections due to known
Aspergillus
species are caused by
A. fumigatus
, followed by
A. flavus
,
A. terreus
, and
A. niger
, with recognition that these designations represent complexes of closely related species.
Aspergillus
species are environmental saprophytes that thrive in decaying vegetation and are readily cultured from soil, water, certain foods, and air.
Aspergillus
DNA can be detected in clinical specimens either by nucleic acid amplification methods specifically targeting
Aspergillus
or by panfungal PCR assays followed by DNA sequencing for species identification.
Penicillium sensu lato
is associated with two teleomorphic genera:
Eupenicillium
and
Talaromyces
. Assays have been developed to detect antibodies to
Talaromyces marneffei
,
Talaromyces marneffei
antigen, or both in serum and other body fluids in various test formats, including immunodiffusion, indirect immunofluorescence, and enzyme‐linked immunosorbent assay.
Fusarium
and Other Opportunistic Hyaline Fungi
Authors: Zhang Sean X. , O'Donnell Kerry , Wiederhold Nathan P. , Cañete‐Gibas Connie F.
Published: January 2025

The opportunistic hyaline or lightly colored molds constitute a phylogenetically diverse group of common to rare fungi, some of which are only known to reproduce asexually while others possess sexual and asexual life cycles. Serologic procedures currently have little clinical utility in the diagnosis of uncommon hyaline opportunistic fungi. Identification of uncommon hyaline molds should always be evaluated considering the patient's immune status as well as the anatomic site of recovery and frequency of isolation. This chapter describes the salient colony and microscopic features of medically important species in the genus
Fusarium
and other select hyaline opportunists. As for
Aspergillus
and
Candida
, multilocus DNA typing systems have been developed to identify clinically and veterinary important isolates of
Fusarium
. The typical antifungal susceptibility profiles of
Fusarium
species are of relative resistance to most antifungal agents.
Curvularia, Exophiala, Scedosporium, Sporothrix,
and Other Melanized Fungi
Authors: Guarro Josep , Madrid Hugo , de Hoog Sybren
Published: January 2025

This chapter covers most of the agents of phaeohyphomycosis, chromoblastomycosis, and sporotrichosis, as well as a number of agents of superficial and cutaneous disease. Pleoanamorphism is particularly striking in members of the black yeasts and in the genera
Scedosporium
and
Triadelphia
. Members of the genus
Curvularia
usually produce elongated conidia that are inconspicuously distoseptate and often possess an intermediate, asymmetrically swollen cell that gives the conidia a typically curved appearance.
Exophiala
is the main genus of clinically relevant black yeasts.
Sporothrix brasiliensis
is highly virulent and has caused large epidemics in Brazil; transmission occurs particularly through stray cats. Dematiaceous fungi are able to cause superficial infections, such as those of the skin and nails. Some melanized phialidic fungi were segregated from
Phialophora
on molecular and morphological grounds; these fungi now constitute small islands of clinical significance in the order Calosphaeriales, which otherwise contains plant‐associated moulds.
Microsporidia
Authors: Weiss Louis M.
Published: January 2025

Microsporidia are found in invertebrates and vertebrates, infecting every major animal group. Microsporidia produce distinctive, environmentally resistant spores, and the shape and size of these spores vary depending on the species. This chapter summarizes microsporidia associated with human infection and related clinical manifestations. Encephalitozoon species including
E. intestinalis
,
E. hellem
,and
E. cuniculi
are widely distributed in mammals and have been identified in both immune‐competent and immune‐compromised humans. The successful sequencing of various microsporidia genomes has led to the application of molecular‐based techniques for the diagnosis of microsporidia infections in humans. Serologic assays such as carbon immunoassay, indirect immunofluorescence test, enzyme‐linked immunosorbent assay, and immunoblot assays have been used to demonstrate microsporidian‐specific antibodies in several species of animals.
Antifungal Agents
Authors: Lockhart Shawn R. , Berkow Elizabeth L.
Published: January 2025

This chapter summarizes the comparative activities of the major systemic antifungal agents against important groups of fungi. It discusses the characteristics of the several other agents that can be used for the oral or parenteral treatment of superficial, subcutaneous, or systemic fungal infections. The allylamines are a group of synthetic antifungal compounds effective in the topical and oral treatment of dermatophytoses. Terbinafine is a lipophilic drug that is available for oral or topical administration. With the exception of fluconazole and isavuconazole, food has a significant effect on the absorption of azole antifungals. Itraconazole is a lipophilic triazole drug available for oral or parenteral administration. Ketoconazole is a lipophilic drug formulated for oral or topical use. The echinocandins are semisynthetic lipopeptide antifungal agents that target the fungal cell wall. Micafungin is a water‐soluble antifungal agent, derived from a fermentation product of
Coleophoma empetri
.
Susceptibility Test Methods: Yeasts and Filamentous Fungi
Authors: Johnson Elizabeth M. , Arendrup Maiken Cavling
Published: January 2025

Accurate and predictive antifungal susceptibility testing has become imperative and is widely accepted as a useful tool for informing decision making during the management of patients with invasive fungal infections that recommendations for testing appear in management guidelines. Clinical and Laboratory Standards Institute and European Committee for Antimicrobial Susceptibility Testing have both set clinical breakpoints for a number of antifungal agents and fungal species. Breakpoints are species specific, which makes accurate species identification a vital part of breakpoint interpretation. Quality control of minimal inhibitory concentration tests is essential to good laboratory practice. Standardized broth macrodilution and microdilution methods are available for testing molds and yeasts, as are standardized disk diffusion methods for systemically active antifungal drugs. The application of molecular methods to the detection of resistance in isolates of filamentous fungi has proved to be easier in
Aspergillus
isolates than in
Candida
because resistance mechanisms appear to be fewer.
Antiparasitic Agents
Authors: LEDER KARIN , McGUINNESS SARAH L.
Published: January 2025

A number of effective antiparasitic drugs are currently available. These agents are important both for therapy of infected individual patients and for control of parasitic infections at the community level. This chapter focuses on the mechanisms of action, pharmacology, clinical utility, and adverse effects of common first‐line antiparasitic therapies and newer drug alternatives. Major anthelmintic drugs, namely, albendazole, mebendazole, praziquantel, ivermectin, and diethylcarbamazine, are reviewed in detail, as is the newly approved moxidectin. Nitazoxanide, an agent with both anthelmintic and antiprotozoal activity, is also discussed. Major antiprotozoal drugs, including those used for malaria, infections with gastrointestinal protozoa, leishmaniasis, and trypanosomiasis, are also reviewed. Nitazoxanide is a 5‐nitrothiazole derivative with broad‐spectrum activity against numerous intestinal protozoa, helminths, and anaerobic bacteria. Major indications for its use are also shown. It was initially developed as a veterinary anthelmintic with activity against intestinal nematodes, cestodes, and liver trematodes.
Susceptibility Test Methods: Parasites
Authors: CLAIN JÉRÔME , COJEAN SANDRINE , HOUZÉ SANDRINE
Published: January 2025

Accurate methods for ascertaining responses of parasites to antiparasitic drugs can prove useful at several levels. Drug susceptibility tests can be separated into four broad categories:
in vivo
tests,
in vitro
tests, tests with experimental animals, and molecular tests. Most drug resistance tests in malaria focus on
Plasmodium falciparum
, the most prevalent and virulent species.
Trichomonas vaginalis
is one of the most common nonviral sexually transmitted infections in the United States and throughout the world; however, metronidazole and tinidazole are the only drugs currently approved by the U.S. Food and Drug Administration to treat trichomoniasis. Treatment failure in leishmaniasis may result from either true drug resistance, innate differences in the
Leishmania
sp. sensitivity to drugs, or patient factors, such as immunodeficiencies, that preclude effective chemotherapeutic action. Drug resistance testing of schistosomes differs greatly from that of protozoan parasites in both purpose and methods.
Blended phenotype of TECPR2‐associated hereditary sensory‐autonomic neuropathy and Temple syndrome
Authors: Zubair Umar , Yang Kathryn , Schierbaum Luca , Tam Amy , Battaglia Nicole , Rong Joshua , Quiroz Vicente , Ebrahimi‐Fakhari Darius
Published: January 2025

Uniparental isodisomy (UPiD) can cause mixed phenotypes of imprinting disorders and autosomal‐recessive diseases. We present the case of a 3‐year‐old male with a blended phenotype of TECPR2‐related hereditary sensory and autonomic neuropathy (HSAN9) and Temple syndrome (TS14) due to maternal UPiD of chromosome 14, which includes a loss‐of‐function founder variant in the TECPR2 gene [NM_014844.5: c.1319del, p.Leu440Argfs*19]. This case illustrates challenges associated with a mixed phenotype of ultra‐rare disorders and underscores the importance of investigating recessive conditions in homozygosity regions when atypical clinical features occur in patients with well‐characterized imprinting disorders.
Fatigue Strength Plateau Induced by Primary Alpha Phase Size in TC11 Alloy
Authors: Shao Ze , Zhang ZhenJun , Liu Rui , Qu Zhan , Zhao ZhenKai , Liu HanZhong , Pang JianChao , Zhang ZheFeng
Published: January 2025

Enhancing the fatigue strength of materials by increasing their tensile strength is generally considered as an effective strategy. This study observed a fatigue strength plateau in TC11 alloy: despite significant variations in tensile strength, the fatigue strength of TC11 alloy demonstrates remarkable stability. It is determined that this anomalous behavior is governed by a unique fatigue cracking mechanism associated with the primary α phase (αp) in dual‐phase titanium alloys due to the pilling‐up of dislocations and consequent cleavage (pillingup‐cleavage). Under this mechanism, the critical cracking stress is predominantly influenced by the pilling‐up distance of dislocations (reflected in the size of αp phase) and is relatively independent of the lattice frictional resistance (expressed in the nanoindentation hardness of αp phase). This leads to the occurrence of fatigue strength plateau in TC11 alloy in this study.
Multielement Filament Memristor Enabling Multifunctional Neuromorphic Device
Authors: Jang Mingu , Song Hanchan , Kim Hae Jin , Yoon Jung Ho , Kim Kyung Min
Published: January 2025

Memristors exhibit changes in internal resistance in response to external voltage, introducing new functionalities to electronic devices. This enables diverse applications in non‐volatile memory, neuromorphic devices, sensors, and computing systems, highlighting their growing importance in electronics. These applications leverage various mechanisms underlying memristors. Therefore, understanding these mechanisms and discovering new memristive mechanisms are essential for overcoming implementation challenges and developing emerging applications. Here, a new type of memristor is introduced comprising an Ag/Ag:Cu‐islands/HfO2/Pt structure, characterized by a hybrid mechanism and its potential for multifunctional applications. The memristor combines the metallic filament (Ag/Cu alloy) of the electrochemical metallization (ECM) mechanism with the oxygen vacancy filament of the valence change memory (VCM) mechanism, achieving both the high on/off ratio of ECM and the analog characteristics of VCM with enhanced reliability. Both resistive and threshold switching characteristics are shown by controlling the compliance current, making the device applicable to artificial synapses and neurons. Notably, this device exhibits heat‐responsive nociceptor characteristics, positioning it as a promising candidate for next‐generation neuromorphic devices.
Copper‐Loaded Nitrogen‐Rich Mesoporous C3N6 Based Nanozymes for Calorimetric Detection of Glutathione and Glucose
Authors: Britto Jolitta Sheri John , Wong Sharon L. , Patel Vaishwik , Tran Thi Kim Anh , Perumalsamy Vibin , Morey Mukul , Ta Xuan Minh Chau , Tricoli Antonio , Bahadur Rohan , Singh Gurwinder , Kumar Prashant , Vinu Ajayan
Published: January 2025

Biomolecular sensing is routinely implemented in healthcare industries for disease diagnostics. Copper nanoparticles efficiently mimic peroxidase, which is needed for efficient glucose and glutathione sensing. However, bare copper nanoparticles are toxic to humans, therefore, anchoring materials are needed to prevent health hazards. Among the carbon‐based anchoring materials, graphene and its derivatives have already been implemented. However, due to poor C–Cu interaction, copper incorporation is inefficient in those systems, which necessitates the exploration of new suitable anchoring platforms. Nitrogen‐rich carbon nitride C3N6 with edge nitrogen atoms and plenty of in‐built vacancy sites in its lattice, apart from its facile synthesis, low cost, scalable production, and non‐toxic nature; offers excellent candidature for this purpose. Cu‐loaded mC3N6 (Cu‐mC3N6) nanozyme is synthesized employing hard silica template SBA‐15 and aminoguanidine hydrochloride and hydrated copper nitrate. First, peroxidase‐like activity is investigated for Cu‐mC3N6 nanozyme with chromogenic 3,3′,5,5′‐ tetramethylbenzidine (TMB) dye, followed by calorimetric detection of glutathione and glucose. Edge nitrogen active sites in the mC3N6 accommodate higher copper loading, resulting in enhanced peroxidase‐like activity and glutathione biosensing performance with a low detection limit of 0.42 ppm. It is believed that the present research will inspire the development of future‐generation nanozymes.
A Multicellular In Vitro Model of the Human Intestine with Immunocompetent Features Highlights Host‐Pathogen Interactions During Early Salmonella Typhimurium Infection
Authors: Damigos Spyridon , Caliskan Aylin , Wajant Gisela , Giddins Sara , Moldovan Adriana , Kuhn Sabine , Putz Evelyn , Dandekar Thomas , Rudel Thomas , Westermann Alexander J. , Zdzieblo Daniela
Published: January 2025

Studying the molecular basis of intestinal infections caused by enteric pathogens at the tissue level is challenging, because most human intestinal infection models have limitations, and results obtained from animals may not reflect the human situation. Infections with Salmonella enterica serovar Typhimurium (STm) have different outcomes between organisms. 3D tissue modeling of primary human material provides alternatives to animal experimentation, but epithelial co‐culture with immune cells remains difficult. Macrophages, for instance, contribute to the immunocompetence of native tissue, yet their incorporation into human epithelial tissue models is challenging. A 3D immunocompetent tissue model of the human small intestine based on decellularized submucosa enriched with monocyte‐derived macrophages (MDM) is established. The multicellular model recapitulated in vivo‐like cellular diversity, especially the induction of GP2 positive microfold (M) cells. Infection studies with STm reveal that the pathogen physically interacts with these M‐like cells. MDMs show trans‐epithelial migration and phagocytosed STm within the model and the levels of inflammatory cytokines are induced upon STm infection. Infected epithelial cells are shed into the supernatant, potentially reflecting an intracellular reservoir of invasion‐primed STm. Together, the 3D model of the human intestinal epithelium bears potential as an alternative to animals to identify human‐specific processes underlying enteric bacterial infections.
Ultramicroporous Tröger's Base Framework Membranes With Ionized Sub‐nanochannels for Efficient Acid/Alkali Recovery
Authors: Sun Haopan , Gan Ning , Lin Yuqing , Wu Baolong , Qiu Yulong , Su Jingwen , Zhou Ziding , Zou Fengyin , Yu Jianguo , Matsuyama Hideto
Published: January 2025

Membrane technology holds significant potential for the recovery of acids and alkalis from industrial wastewater systems, with ion exchange membranes (IEMs) playing a crucial role in these applications. However, conventional IEMs are limited to separating only monovalent cations or anions, presenting a significant challenge in achieving concomitant H⁺/OH⁻ permselectivity for simultaneous acid and alkali recovery. To address this issue, the charged microporous polymer framework membranes are developed, featuring rigid Tröger's Base network chains constructed through a facile sol‐gel process. The intrinsic ultramicropore confinement and quaternary ammonium‐charged functional groups provide ultrahigh size‐sieving capability and enhanced Donnan exclusion for H⁺/OH⁻ selectivity; meanwhile, the internal protoplasmic channels of the polymer frameworks serve as highways for rapid ion transfer. The resulting membrane achieves high H⁺/Fe2⁺ and OH⁻/WO₄2⁻ selectivities of 694.4 and 181.0, respectively, for concurrent acid and alkali separation in diffusion dialysis and electrodialysis processes over extended operational periods (exceeding 1600 and 600 h, respectively), while maintaining remarkable transport rates. These results outperform most literature‐reported and nearly all commercially available membranes. This study validates the novel applicability of polymer framework materials with ionized angstrom‐scale channels and versatile functionalities in high‐performance IEMs for acid/alkali resource recovery.
Neuron‐Inspired Biomolecular Memcapacitors Formed Using Droplet Interface Bilayer Networks
Authors: Segars Braydon , Rosenberg Kyle , Shrestha Sarita , Maraj Joshua J. , Sarles Stephen A. , Freeman Eric
Published: January 2025

Brain‐inspired (or neuromorphic) computing circumvents costly bottlenecks in conventional Von Neumann architectures by collocating memory and processing. This is accomplished through dynamic material architectures, strengthening or weakening internal conduction pathways similar to synaptic connections within the brain. A new class of neuromorphic materials approximates synaptic interfaces using lipid membranes assembled via the droplet interface bilayer (DIB) technique. These DIB membranes have been studied as novel memristors or memcapacitors owing to the soft, reconfigurable nature of both the lipid membrane geometry and the embedded ion‐conducting channels. In this work, a biomolecular approach to neuromorphic materials is expanded from model synapses to a charge‐integrating model neuron. In these serial membrane networks, it is possible to create distributions of voltage‐sensitive gates capable of trapping ionic charge. This trapped charge creates transmembrane potential differences that drive changes in the system's net capacitance through electrowetting, providing a synaptic weight that changes in response to the history and timing of input signals. This fundamental change from interfacial memory (dimensions of the membrane) to internal memory (charge trapped within the droplets) provides a functional plasticity capable of multiple weights, longer‐term retention roughly an order of magnitude greater than memory stored in the membranes alone, and programming‐erasure.