Infant Botulism, Israel, 2007-2021.

Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007-2021. A total of 8 cases were reported during the study period. During 2019-2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March-July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.

Adaptive Resistance Mutations at Suprainhibitory Concentrations Independent of SOS Mutagenesis.

Emergence of resistant bacteria during antimicrobial treatment is one of the most critical and universal health threats. It is known that several stress-induced mutagenesis and heteroresistance mechanisms can enhance microbial adaptation to antibiotics. Here, we demonstrate that the pathogen Bartonella can undergo stress-induced mutagenesis despite the fact it lacks error-prone polymerases, the rpoS gene and functional UV-induced mutagenesis. We demonstrate that Bartonella acquire de novo single mutations during rifampicin exposure at suprainhibitory concentrations at a much higher rate than expected from spontaneous fluctuations. This is while exhibiting a minimal heteroresistance capacity. The emerged resistant mutants acquired a single rpoB mutation, whereas no other mutations were found in their whole genome. Interestingly, the emergence of resistance in Bartonella occurred only during gradual exposure to the antibiotic, indicating that Bartonella sense and react to the changing environment. Using a mathematical model, we demonstrated that, to reproduce the experimental results, mutation rates should be transiently increased over 1,000-folds, and a larger population size or greater heteroresistance capacity is required. RNA expression analysis suggests that the increased mutation rate is due to downregulation of key DNA repair genes (mutS, mutY, and recA), associated with DNA breaks caused by massive prophage inductions. These results provide new evidence of the hazard of antibiotic overuse in medicine and agriculture.

Botulinum Neurotoxin C Dual Detection through Immunological Recognition and Endopeptidase Activity Using Porous Silicon Interferometers.

Botulinum neurotoxins (BoNTs) are the most potent toxins known in nature produced by Clostridium botulinum strains, which can cause life-threatening diseases in both humans and animals. The latter is of serious environmental and economic concern, resulting in high mortality, production losses, and rejection of contaminated animal feed. The available in vivo mouse assay is inadequate for real-time and on-site assessment of outbreaks. Herein, we present a reflective-based approach for the detection of BoNT/C while estimating its activity. Two adjacent porous Si Fabry-Pérot interferometers are simultaneously utilized to quantify minute BoNT/C concentrations by a competitive immunoassay and to assess their endopeptidase activity. The reflectivity signals of each interferometer are amplified by biochemical reaction products infiltration into the scaffold or by peptide fragments detachment from the nanostructure. The optical assay is highly sensitive in compliance with the in vivo approach by presenting a detection limit of 4.24 pg mL-1. The specificity and selectivity of the designed platform are cross-validated against BoNT/B and BoNT/D, also relevant to animal health. Finally, the analytical performances of both interferometers for real-life scenarios are confirmed using actual toxins while depicting excellent compliance to complex media analysis. Overall, the presented sensing scheme offers an efficient, rapid, and label-free approach for potential biodiagnostic elucidation of botulism outbreaks.

Bartonella kosoyi sp. nov. and Bartonella krasnovii sp. nov., two novel species closely related to the zoonotic Bartonella elizabethae, isolated from black rats and wild desert rodent-fleas.

The genus Bartonella (Family: Bartonellaceae; Order: Rhizobiales; Class: Alphaproteobacteria) comprises facultative intracellular Gram-negative, haemotropic, slow-growing, vector-borne bacteria. Wild rodents and their fleas harbor a great diversity of species and strains of the genus Bartonella, including several zoonotic ones. This genetic diversity coupled with a fastidious nature of the organism results in a taxonomic challenge that has led to a massive collection of uncharacterized strains. Here, we report the genomic and phenotypic characterization of two strains, members of the genus Bartonella (namely Tel Aviv and OE 1-1), isolated from Rattus rattus rats and Synosternus cleopatrae fleas, respectively. Scanning electron microscopy revealed rod-shaped bacteria with polar pili, lengths ranging from 1.0 to 2.0 µm and widths ranging from 0.3 to 0.6 µm. OE 1-1 and Tel Aviv strains contained one single chromosome of 2.16 and 2.23 Mbp and one plasmid of 29.0 and 41.5 Kbp, with average DNA G+C contents of 38.16 and 38.47 mol%, respectively. These strains presented an average nucleotide identity (ANI) of 89.9 %. Bartonella elizabethae was found to be the closest phylogenetic relative of both strains (ANI=90.9-93.6 %). The major fatty acids identified in both strains were C18:1ω7c, C18 : 0 and C16 : 0. They differ from B. elizabethae in their C17 : 0 and C15 : 0 compositions. Both strains are strictly capnophilic and their biochemical profiles resembled those of species of the genus Bartonella with validly published names, whereas differences in arylamidase activities partially assisted in their speciation. Genomic and phenotypic differences demonstrate that OE 1-1 and Tel Aviv strains represent novel individual species, closely related to B. elizabethae, for which we propose the names Bartonella kosoyi sp. nov. and Bartonella krasnovii sp. nov.

Fungi in sands of Mediterranean Sea beaches of Israel-Potential relevance to human health and well-being.

BACKGROUND: Sand of sea harbour bacteria that may cause enteric and other infections in humans, and are controlled by regulatory measures. Data on fungi in sea sand are scarce. Thus, an international group of mycologists was formed to explore fungal flora in sand of various waterbodies. OBJECTIVES: The aim was to explore fungal sand contamination in beaches of the Israeli Mediterranean Sea Coast, regarding possible impact on human health in three aspects: (a) faecal contamination, as judged by presence of the human enteric fungi; (b) contamination by fungi, causing dermal infections; (c) and the presence of moulds, causing respiratory allergies and pose a risk for infection in immunocompromised individuals. METHODS: The study included sand screen of six urban beaches from north to south of the Israeli Mediterranean Coast. Sand samples were extracted by water, and the water wash was cultured and quantitated. The fungi were identified phenotypically, by MALDI-TOF MS system and ITS sequencing. RESULTS: The screen revealed that about 80% of the isolates were moulds and about 20% yeasts. The mould species included opportunistic pathogens and potential allergens: Aspergillus fumigatus, Fusarium and Mucorales species. Yeast isolates included Candida, Cryptococcus and Rhodotorula species. CONCLUSIONS: (a) Fungi are contaminating Israeli Mediterranean sand beaches; (b) the contaminating fungi include various yeast and mould species; (c) some of the yeasts and mould species found in sand are known opportunistic pathogens, or respiratory allergens; (d) the data could serve as basis for initiating regulatory measures to control fungal contamination of sand for the benefit of public health.

From six to zero per cent Mycobacterium avium subsp. paratuberculosis milk ELISA positivity in three years - probably induced by Mycobacterium vaccae.

This research communication reports the results of a study aimed at investigating the effects of introducing Mycobacterium vaccae on paratuberculosis carriage in a dairy herd. M. vaccae is a non-pathogenic member of the Mycobacteriaceae, with immunomodulatory and immunotherapeutic capabilities, acting by stimulating the cellular immune system, important in protection against paratuberculosis. Starting in 2014 we administered, by gavage, 1010 live M. vaccae bacteria to all new-born heifers on a dairy farm, first within 24 h of birth and again 2 weeks later. Paratuberculosis carriage was monitored yearly by milk ELISA. Faecal samples of 50% of cows, aged 3 years, born 1, 2 or 3 years before the experiment's onset, were tested by qPCR for MAP shedding and compared to 100% treated cows of the same age. Within 3 years, milk ELISA positivity was reduced from 6 to 0% and remained unchanged for the subsequent 2 years. One qPCR positive control cow was found each year for a total of 3 animals (2.46%). One positive cow (1%) was found among the treated cows. Two of the 3 positive control animals, still present on the farm at the end of 2019, tested negative whereas the positive test cow continued shedding MAP. M. vaccae shedding heifers mixing with adult cows were the probable means of the microorganism's propagation. The results of this investigation indicate that the introduction of live M. vaccae may be an inexpensive and fast alternative to current paratuberculosis control practices, justifying further exploration of the topic.

Fungal infections in animals: a patchwork of different situations.

The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be encountered in animals originating from environmental sources without transmission to humans. In addition, the endemic infections with indirect transmission from the environment, the zoophilic fungal pathogens with near-direct transmission, the zoonotic fungi that can be directly transmitted from animals to humans, mycotoxicoses and antifungal resistance in animals will also be discussed. Opportunistic mycoses are responsible for a wide range of diseases from localized infections to fatal disseminated diseases, such as aspergillosis, mucormycosis, candidiasis, cryptococcosis and infections caused by melanized fungi. The amphibian fungal disease chytridiomycosis and the Bat White-nose syndrome are due to obligatory fungal pathogens. Zoonotic agents are naturally transmitted from vertebrate animals to humans and vice versa. The list of zoonotic fungal agents is limited but some species, like Microsporum canis and Sporothrix brasiliensis from cats, have a strong public health impact. Mycotoxins are defined as the chemicals of fungal origin being toxic for warm-blooded vertebrates. Intoxications by aflatoxins and ochratoxins represent a threat for both human and animal health. Resistance to antifungals can occur in different animal species that receive these drugs, although the true epidemiology of resistance in animals is unknown, and options to treat infections caused by resistant infections are limited.

Prior antimicrobial use as a risk factor for resistance in selected Staphylococcus pseudintermedius isolates from the skin and ears of dogs.

BACKGROUND: Antimicrobial resistance within bacteria continues to present therapeutic challenges. One presumed risk factor for increased rates of resistance is prior exposure to antimicrobial drugs. OBJECTIVES: To examine the impact of time since most recent exposure, the number of prior antimicrobial exposures and duration of use on antimicrobial resistance rates in Staphylococcus pseudintermedius isolates. METHODS: Inclusion of a case in the study required laboratory isolation of S. pseudintermedius from a clinical specimen. Antibiograms and information regarding prior antimicrobial exposures were extracted from the medical records of dogs diagnosed with pyoderma or otitis externa. RESULTS: Meticillin resistance (MR) was identified in 48.1% of isolates. Recent use of beta-lactam antimicrobials was associated with increased odds of resistance to meticillin (P < 0.001) and fluoroquinolones (P < 0.001). Antimicrobial therapy within 1 month prior to sampling was also associated with MR (60.7%; P = 0.009) and multidrug resistance (61.9%; P = 0.029). The number of prior exposures to beta-lactams or fluoroquinolones were associated with resistance to these same classes (P = 0.001 and 0.02, respectively) and to other antimicrobial classes (P = 0.016 for resistance to fluoroquinolones following treatment with beta-lactams and P = 0.015 for MR following treatment with fluoroquinolones). Longer treatment duration with beta-lactam drugs was associated with higher proportion of MR (P = 0.004). CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment based upon culture and susceptibility testing is highly recommended for dogs that have received multiple antimicrobial drug exposures or that were treated within the preceding month. This may be especially important when the prior therapeutic regimen included a drug from the beta-lactam or fluoroquinolone classes.

Comparison between point-of-care dermatophyte test medium and mycology laboratory culture for diagnosis of dermatophytosis in dogs and cats.

BACKGROUND: Point-of-care Dermatophyte Test Medium (PoC-DTM) is a diagnostic procedure to rule in/rule out dermatophytosis in veterinary clinics. OBJECTIVE: To evaluate the performance of PoC-DTM in the clinic compared to DTM plate culture in a mycology laboratory and to compare results obtained by general practitioners and referral clinicians. ANIMALS: Hair samples were collected from 47 cats and 54 dogs with suspected dermatophytosis and from nine healthy controls (seven cats and two dogs). METHODS: This was a multicentre blinded study. In one group (65 suspected cases, 9 healthy controls), PoC-DTM results were evaluated by clinicians in a referral clinic (SP group) who examined the colony morphology macroscopically and microscopically. In the other group (36 suspected cases) PoC-DTM results were evaluated by clinicians from general practice for colour change only, with no macroscopic or microscopic examination (GP group). All hair samples were also cultured on DTM plates in a mycology laboratory. Laboratory culture was considered the gold standard for comparison. RESULTS: Agreements between tests were 97% (two false positive; κ = 0.839) and 80.6% (five false positives and two false negatives; κ = 0.466) in the SP and GP groups, respectively. This difference between groups was significant (P = 0.024). CONCLUSION AND CLINICAL IMPORTANCE: When applying macroscopic and microscopic evaluation of the colony, PoC-DTM is accurate for diagnosing dermatophytes with only a 3% chance of error. However, when macroscopic and microscopic examination is not included there is significant (19.4%) chance for an incorrect diagnosis.

Novel pseudo-staphylococcal cassette chromosome mec element (ψSCCmec57395) in methicillin-resistant Staphylococcus pseudintermedius CC45.

Genetic characterization of methicillin-resistant Staphylococcus pseudintermedius (MRSP) from Thailand and Israel revealed the presence of a predominant atypical clonal lineage which was not typeable by SmaI-PFGE and SCCmec typing. All the atypical isolates (n = 34) belonged to CC45 (30 ST45 and 2 ST179 isolates, 1 ST57 isolate, and 1 ST85 isolate). The isolates originated from healthy and diseased dogs and cats, as well as from the environment of one clinic. Cfr9I-pulsed-field gel electrophoresis (Cfr9I-PFGE) and dru typing permitted the further distinction of CC45 isolates from the two different countries. Microarray analysis identified genes that confer resistance to ß-lactams (mecA; blaZ), aminoglycosides [aac(6')-Ie-aph(2')-Ia; aph(3')-III; ant(6)-Ia], macrolides and lincosamides [erm(B)], tetracyclines [tet(M)], trimethoprim [dfr(G)], streptothricin (sat4), and chloramphenicol (catpC221). Fluoroquinolone resistance was attributed to specific amino acid substitutions, i.e., Ser84Leu in GyrA and Ser80Ile and Asp84Asn in GrlA. A novel pseudo-staphylococcal cassette chromosome (ΨSCCmec57395) element was identified in MRSP strain 57395 (sequence type ST45) by whole-genome sequencing. The 12,282-bp ΨSCCmec57395 element contained a class C1 mec gene complex but no ccr genes. In addition to the methicillin resistance gene mecA, ΨSCCmec57395 also carried determinants of resistance to heavy metals, such as arsenic, cadmium, and copper. Bsu36I restriction analysis of the ΨSCCmec57395 element amplified by long-range PCR revealed the presence of ΨSCCmec57395 in the 33 additional isolates of MRSP CC45. The ΨSCCmec57395 element represents a new class of SCCmec and has been identified in MRSP of CC45, which is a predominant clonal lineage in Israel and Thailand.

Pulmonary fungal infection caused by Neoscytalidium dimidiatum in a Risso's dolphin (Grampus griseus).

Neoscytalidium dimidiatum was isolated from two 12-18 cm abscesses in the lung and the mediastinal lymph nodes of a stranded Risso's dolphin (Grampus griseus). Histopathologic examination of samples of these organs revealed the presence of hyphae and sclerotic body-like fungal elements. Photobacterium damselae subsp. damselae was recovered from the dolphin's organs which also were found to contain numerous Monorygma grimaldii cysts. No histopathological signs of morbillivirus infection were seen. To the best of our knowledge, this is the first report of N. dimidiatum infection in a sea mammal.

Human and Zoonotic Dermatophytoses: Epidemiological Aspects.

INTRODUCTION: Dermatophytes are a group of molds characterized by the ability to produce keratinases, thereby carving out for themselves specific ecological niches. Their traditional division into three genera, Trichophyton, Microsporum, and Epidermophyton has been expanded to nine and the species in each genus were modified. Dermatophytes are among the most prevalent causes of human and animal mycoses. Their epidemiology is influenced by various factors. These factors may be evolutive such as the predilected environment of the fungus, namely, humans (anthropophilic), animals (zoophilic), or environment (geophilic), is evolutionary and thus may require centuries to develop. Many other factors, however, result from a variety of causes, affecting the epidemiology of dermatophytoses within a shorter time frame. OBJECTIVE: This review aims at summarizing the factors that have modified the epidemiology of dermatophytoses during the last decades. RESULTS: Geographic and climatic conditions, demography such as age and gender, migration, socio-economic conditions, lifestyle, and the environment have had an impact on changes in the epidemiology of dermatophytoses, as have changes in the pattern of human interaction with animals, including pets, farm, and wild animals. A typical example of such changes is the increased prevalence of Trichophyton tonsurans, which spread from Latin America to the United States and subsequently becoming a frequent etiological agent of tinea capitis in Africa, Middle East, and other areas. CONCLUSION: The comprehension of the epidemiology of dermatophytoses has a major bearing on their prevention and treatment. Since it is undergoing continuous changes, periodic assessments of the most recent developments of this topic are required. This article aims at providing such an overview.

Eumycetoma caused by Madurella mycetomatis in a mare.

A case of equine eumycotic mycetoma caused by Madurella mycetomatis is described. This is the first report of M. mycetomatis as the etiologic agent of human or animal infections in Israel. The definitive identification of the isolate was established by molecular methods. In addition the mold was cultured on various media through which we found that its growth rate was significantly augmented on incubation on trypticase soy agar, more so if horse serum was added to this medium. Sixteen previously published cases defined by the authors as mycetoma in horses are briefly reviewed. Among these, only one indicated that the infection was caused by M. mycetomatis.

Bovine subclinical mastitis caused by Mannheimia granulomatis.

Mannheimia granulomatis was isolated for 10 months from the milk of a cow with elevated somatic cell counts. The infection was self-limiting. Phenotypic and molecular characteristics of the isolate were determined.

Disseminated canine mold infections.

Disseminated canine mold infections are reviewed. Case inclusion criteria were dogs as hosts, two or more non-adjacent organs affected and identification of the etiological agent at least to the genus level. Of the 157 cases identified, 59.3% were caused by Aspergillus spp. of which 36.3% belonged to the section Terrei. German Shepherd breed dogs constituted 67.8% of the cases, 89.7% of which were caused by fungi of the section Terrei. Female dogs constituted 72.7% of the cases. The average age was 4.3years (range 1-13years). Pathogenesis, especially virulence factors facilitating the hematogenous dissemination, are discussed. Clinical signs reported most frequently included weight loss, lethargy, discospondylitis, osteomyelitis, urinary tract infections, ophthalmitis, head tilt and gait difficulties. Of 50 dogs with data on temperature, 25 had a fever of 40°C (104°F) or above. The most common hematologic and biochemical test result aberrations included increased neutrophil counts and serum protein concentration, azotemia and decreased urine specific gravity. The diagnostic value of fungal antigen detection, antibody titers and imaging are discussed. An attempt to treat was made in 59 (37.6%). Failure and relapses (sometimes after years) were common, but there was some success observed in eight cases. Identification of the gene/s predisposing dogs to disseminated mycoses, increased awareness, improved diagnostic methods and less expensive drugs should contribute to the reduction of disseminated mold infections in dogs in the future.

Receiver operating characteristic-based assessment of a serological test used to detect Johne's disease in Israeli dairy herds.

The overall accuracy of an enzyme-linked immunosorbent assay (ELISA) used to detect Johne's disease at herd level was explored in relation to an imperfect test (fecal culture) in 57 Israeli dairy herds. Receiver-operating characteristic (ROC) analysis indicated an area under the curve (AUC) that corresponded to a test accuracy of 82.0% (69.5% to 90.9%; 95% confidence), with optimized herd sensitivity and herd specificity of 70.4% and 83.3%, respectively; and predictive values of 79.2 (+) and 75.8% (-). The optimal ELISA cutoff was 3.16% (> 3.16% seropositive cows in a herd), which was associated with likelihood ratios (LR) of 4.22 (+LR) and 0.36 (-LR), and post-test probabilities of 0.79 (+) and 0.17 (-). For herds with < or = 200 cows (n = 19 herds), the 95% confidence interval (CI) for the AUC was 0.62-0.97 and the optimal cutoff was 3.33% (HSe = 87.5, HSp = 81.8); for herds with > 200 but < or = 270 cows (n = 19 herds), the 95% AUC CI was 0.62-0.97 and the optimal cutoff was 1.13% (HSe = 90.0, HSp = 77.78); and for herds with > 270 cows (n = 19 herds), the 95% AUC CI was 0.69-0.99 and the optimal cutoff was 0.7% (HSe = 100.0, HSp = 70.0). The AUC was not influenced by across-herd prevalence [R2 (adjusted) = 0.0, P > 0.05]. Findings may be applied to facilitate targeted sampling of herds similar to those evaluated. For instance, a test cutoff of 0.76% could be considered for "ruling disease in," while a cutoff of 3.7% could be used for "ruling disease out." Caveats that may influence this analysis are discussed.

Use of a sustained release preparation of clotrimazole to treat dermatophytosis in a siamang (Hylobates syndactylus).

In November 2004, an adult male siamang (Hylobates syndactylus) from The Tisch Family Zoological Gardens-Jerusalem Biblical Zoo (Israel) presented with skin lesions on various body parts. Lesions consisted of alopecia and dry, crusty areas of hyperkeratosis. A diagnosis of dermatophytosis due to Microsporum canis was determined by fungal culture of skin scraping taken from the edge of several lesions. Treatment with various oral and topical antifungal agents such as griseofluvin, itraconozole, and lufenuron resulted in the resolution of most lesions and a decrease in size of the single remaining lesion, which continued to be culture positive for M. canis. The animal was anesthetized and an experimental sustained-release clotrimazole varnish was painted directly on the lesion. Initially there was no change in the lesion, and 2 months later a slightly altered formula was applied under anesthesia. One month later, the lesion began to reduce in size; 3 months after the start of treatment, although 2 years after the onset of clinical signs, the lesion resolved. Minimizing the number of treatments is always an advantage when dealing with exotic animals or zoological collections.

Therapy of Non-Dermatophytic Mycoses in Animals.

This review focuses on aspects of antimycotic therapy specific to veterinary medicine. In the first part, drug availability, limited mostly by economic consideration but also by clinical applicability and specific adverse effects, is described for polyenes, 5 fluorocytosine, azoles, echinocandins and terbinafine. In the second part, current knowledge and experience in the treatment of selected fungal infections are overviewed. These mycoses include disseminated mold infections in small animals (dogs and cats) and avian species, upper respiratory tract infections of small animals (sino-nasal and sino-orbital aspergillosis) and horses (guttural pouch mycosis), eumycetoma, infections caused by dimorphic fungi, (blastomycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis and sporothrichosis) and by yeasts and yeast-like microorganism (Cryptococcus spp. and Malassezia pachydermatis).

Diagnostic Aspects of Veterinary and Human Aspergillosis.

The genus Aspergillus is composed of more than 300 species, a fraction of which are involved in animal or human infections mostly following environmental exposure. Various risk factors (i.e., immunosuppression, tuberculosis) have been recognized for human whereas for veterinary infections, unhygienic management, trauma, anatomical conformation of the skull, or suspected immunological deficiencies have been suggested. In animals, aspergillosis is mostly sporadic but in some circumstance such as infections on poultry farms may involve the whole flock. Since the high prevalence of immunosuppression in human patients has not been mirrored in veterinary medicine, and although to the best of our knowledge, no comprehensive data on the prevalence of aspergillosis in animals has been published, their epidemiology has not changed during the last decades. The impact of these infections may be economic or if they are incurable, sentimental. The objective of the first part is to describe the diagnosis of the main clinical entities caused by Aspergillus spp. in animals. It includes disseminated canine aspergillosis, canine and feline sino-nasal and sino-orbital aspergillosis, guttural pouch mycosis in horses, mycotic abortion in cattle, mycotic keratitis in horses, and avian aspergillosis. When pathogenesis and clinical aspects are relevant for diagnosis-they will be addressed as well. The second part deals with human aspergillosis, which is a multifaceted disease, manifested in a spectrum of clinical entities affecting one or more organs. Diagnosis is based on the clinical manifestation, supported and confirmed by laboratory means, involving the classical approach of demonstrating the etiological agent in the clinical specimens and in culture. Noncultural methods, such as antigen detection and/or molecular assays to detect fungal nucleic acids or protein profiles, are used as well. The isolation and identification of the fungus allows the determination of its susceptibility to antifungal drugs. Thus, antifungal susceptibility testing maybe considered as part of the diagnostic process, which is of relevance for management of the infection. In this review article, the part dealing with diagnostic aspects of aspergillosis in humans concentrates on susceptibility testing of Aspergillus spp. to antifungal drugs and drug combinations. The technologies and methods of susceptibility testing are described and evaluated.