A compilation of published reports of mycoses in animals in India

The available published reports on animal mycoses in India and the fungal agents isolated from animal material are discussed.Among dermatophytes, the occurrence of Trichophyton verrucosum, T. mentagrophytes, T. rubrum, T. equinum, T. violaceum, T. simii, T. tonsurans, T. terrestre, T. ajelloi, Microsporum canis, M. gypseum and M. nanum has been reported. Cases of aspergillosis, candidiasis, phycomycosis, rhinosporidiosis, epizootic lymphangitis, mycotic abortions and mycotic mastitis have been recorded in animals in this country. However, there is no report of histoplasmosis, sporotrichosis, blastomycosis and coccidioidomycosis among animals from India.     

Invasive Pulmonary Fungal Infections in Cystic Fibrosis

Invasive pulmonary mycosis is after allergic bronchopulmonary aspergillosis (ABPA) a frequent and severe complication of CF lung disease. Among CF caregivers, there is an insecurity when and how to treat infections of the lung parenchyma caused by different fungi in patients with CF. This case series provides a multicenter experience on diagnostic, manifestation, and treatment of non-ABPA cases of pulmonary. Non-ABPA cases of pulmonary mycoses in patients with CF have been collected from the CF Centers in Berlin, Essen, Worms, Frankfurt (Germany), Leeds (UK), and Barcelona (Spain). Non-ABPA was defined as total serum IgE level <500 kU/L. Scedosporium and Lomentospora species seem to be more virulent in patients with CF and have been successfully treated with triple antifungal drug regimens in several cases. Rare fungi including yeasts can have pathogenic potential in CF. In this series, antibiotic treatment failure was the main indicator for the initiation of antifungal treatment. For an early and effective treatment of pulmonary mycoses in CF, the identification of biomarkers and of risk factors beyond antibiotic treatment failure is crucial and urgently needed. Furthermore, treatment efficacy studies are necessary for the different causative agents of these infections.     

Infecc Ón Humana PorNocardia Asteroides,En México

Summary Although the existence ofNocardia asteroides as a human pathogen in Mexico has been known for several years, up to now there are only few reports in our country concerning the isolation of this microorganism both as a saprophyte as well as human or animal pathogen. This fact is more interesting when compared with the high incidence ofN. brasiliensis, causal agent of actinomycotic mycetoma, the most frequently observed deep mycosis in Mexico.In this paper, the isolation of eigth strains ofN. asteroides from clinical specimens is reported. Five strains were isolated from sputa, one from a fistulous lesion of the scrotum, one from a brain abscess and one more from a foot mycetoma.One of the strains isolated from sputum was in a case of pulmonary nocardiasis; another of these strains was isolated from a patient with coexistent pulmonary tuberculosis and nocardiasis. With the last three strains isolated from sputa, it was not possible to establish any correlation between the isolations and the clinical and radiological findings of the patients; two of the patients had pulmonary tuberculosis and the isolation ofN. asteroides was achieved only in one occasion in each case, with scant growth, and observed in routine cultures made for tubercle bacilli. The last strain was isolated from the sputum of a patient with chronic bronchitis. Some comments are made to the possibility that these three last isolations merely represent a saprophytic phase of the fungus.Some clinical and other features are discussed concerning the other three cases of scrotal fistula, brain abscess and mycetoma produced byN. asteroides.     

Observations on paraffin baiting as a laboratory diagnostic procedure in nocardiosis

The efficacy of paraffin bait technique in the isolation ofNocardia asteroides from clinical specimens has been investigated. In a comparative study 1091 clinical specimens, mostly sputa and bronchial aspirates collected from 639 patients of bronchopulmonary diseases and 11 of meningitis, were examined by paraffin baiting and the conventional technique. Thirty-six clinical specimens originating from 12 of the patients yieldedN. asteroides by the paraffin bait technique but only 4 by the conventional technique. Approximately 95 % of 125 sputum samples inoculated withN. asteroides yielded the pathogen by paraffin baiting as against 49 % by the conventional technique. Paraffin baiting was more productive than the conventional technique in the isolation ofN. asteroides from mixed suspensions with a number of fungi and bacteria. It is concluded that paraffin baiting can be profitably adopted as a suitable technique for the isolation ofN. asteroides from clinical specimens, such as, sputum, gastric lavage, etc., which are often contaminated. The technique has no particular advantage with non-contaminated specimens.This work forms a part of the Ph. D. thesis of S.K.M. submitted in 1971 to the University of Delhi, and was presented at the Vth meeting of ISHAM held in Paris from 5th–10th July, 1971.     

Primary subcutaneous Nocardia asteroides infection in a renal allograft recipient

Nocardia asteroides is an important opportunistic pathogen in immunocompromised hosts. The primary infection is usually in the lungs and is followed by dissemination to other parts of the body. Primary subcutaneous infection with Nocardia asteroides has been reported rarely (three reports) and no such case has been reported in a renal transplant recipient. We describe here a case of renal transplant recipient who developed primary subcutaneous infection with Nocardia asteroides within one and half years of the transplantation. This revised version was published online in June 2006 with corrections to the Cover Date.     

Review of animal mycoses in Australia

This review covers the available literature on the mycoses of animals in Australia since the last review published in 1967. Of the cutaneous infections, dermatophytoses have been recorded in a wide range of animals: cattle, horses, goats, pigs, sheep, cats, dogs, mice, guinea-pigs, rabbits, a lion, kangaroos, a camel, koalas and wallabies. These infections were caused by several species and varieties of the genera,Microsporum andTrichophyton. Eight agents of ringworms have been recorded in the horse. Two subcutaneous mycoses, phaeohyphomycosis and sporotrichosis have been reported. Phaeohyphomycosis is becoming more common but sporotrichosis is rare having been recorded only once in a cat.The following systemic mycoses have been recorded: adiaspiromycosis, aspergillosis, candidiasis, cryptococcosis, dactylariosis, fusariomycosis, histoplasmosis, miscellaneous mycoses, mycotic abortion and related conditions, zygomycosis, pythiosis, protothecosis and green algal infections. Cryptococcosis has affected 11 different animal species. Mycotic abortion is a serious disease in Victoria. Pythiosis of horses has been extensively studied in northern Australia.     

Cloning vector system forNocardia spp.

An electro-transformation system has been developed forNocardia asteroides andNocardia corallina by using aNocardia-Escherichia coli shuttle vector. The shuttle vector, named pCY104, was constructed by joining a 2.5-kb crypticN. asteroides plasmid pCY101 with theE. coli plasmid pIJ4625. The resistance genes for kanamycin, chloramphenicol, and thiostrepton on plasmid pCY104 were expressed inN. asteroides andN. corallina. The transformation method was optimized forN. asteroides, and transformation efficiency of 8×10⁴ transformants per g plasmid DNA was achieved routinely.     

Pathogenicity of Nocardia caviae,N. asteroides and N. brasiliensis

The pathogenicity ofNocardia caviae, N. asteroides andN. brasiliensis has been tested for white mice, guinea pigs and rabbits and chorio-allantoic membrane of the developing chick embryo. Altogether, 14 strains belonging to the 3Nocardia species originating from soil, human and animal sources in India or abroad were tested. All of them proved pathogenic though the degree of virulence varied from strain to strain. Incorporation of hog gastric mucin in the inoculum enhanced the virulence of all the 3Nocardia species for white mice.N. caviae strains were uniformly more virulent than those ofN. asteroides andN. brasiliensis.In the white mice inoculated intraperitoneally, a greater dissemination of the disease was apparent withN. caviae than withN. asteroides. Of the 6 strains ofN. caviae tested, 5 disseminated to the lung, 3 to the heart and 2 to the brain. InN. asteroides dissemination of the disease to the brain was observed with 2 of its 3 strains.N. brasiliensis showed no dissemination.N. caviae was found to be equally virulent for white mice, guinea pigs and rabbits. On the other hand,N. asteroides andN. brasiliensis were more virulent for white mice than for guinea pigs and rabbits. The lesions caused byN. caviae in mice, guinea pigs and rabbits persisted up to 4 weeks. In strong contrast to this the lesions due toN. asteroides andN. brasiliensis found in the guinea pigs and rabbits showed a strong tendency towards spontaneous clearance.Histologically, the lesions caused byN. caviae, N. asteroides andN. brasiliensis in mice, guinea pigs and rabbits were in the form of abscesses which showed an acute or chronic reaction. In the case ofN. caviae these abscesses showed both granules and freely dispersed cocco-bacillary bodies or filaments. As forN. asteroides it occurred in the form of cocco-bacillary bodies or filaments whereasN. brasiliensis consistently produced granules in the lesions.The lesions caused by the 3Nocardia species on the chorio-allantoic membrane of the developing chick embryo were in the form of abscesses which contained cocco-bacillary bodies and branching filaments but no granules.This forms a part of the thesis submitted by P.V.K. for Ph. D. degree, of the University of Delhi.     

Fungal co-infection in COVID-19 patients: Should we be concerned?

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD₄ interferon-gamma expression, and fewer CD₄ and CD₈ cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy.     

Pulmonary Aspergillus Overlap Syndromes

Background

Broadly, there are three main categories in pulmonary aspergillosis: chronic forms of aspergillosis; allergic bronchopulmonary aspergillosis; and invasive aspergillosis (IPA). IPA has been further subdivided into angioinvasive and airway-invasive aspergillosis. Aspergillus overlap syndromes is defined as the occurrence of more than one form aspergillus disease in a single individual.

Objectives

To help clinicians correctly deal with AOS.

Methods

Retrospectively study the clinical findings of nine patients presenting with AOS.

Results

Four cases were diagnosed as angioinvasive aspergillosis complicated with ABPA, three cases as IPA overlap aspergilloma, and two cases as ABPA with AWIA. All the patients presented with cough and expectoration. In three patients with IPA overlap aspergilloma, two had hemoptysis, two had wheezing and fever. All of patients with IPA overlap ABPA had wheezing, dyspnea, and fever, three had sputum plugs, two had hemoptysis, and five patients had mucopurulent discharge and rhonchi in auscultation. Their total IgE ranged from 129 to 2124 IU/ml (676.5 ± 557.33 IU/ml). Fungal culture in sputum showed A. Fumigatus in three patients. All the six patients with IPA overlap ABPA applied steroid therapy and antifungal therapy. Three of them received two or more antifungal drugs successively, and three received combinational therapy. All the patients improved except one diagnosed ABPA overlap IPA.

Conclusions

Clinical manifestation of AOS is not typical. Poor first-line therapeutic effects and complicated diagnosis criteria require clinicians to be aware of AOS when facing patients with aspergillosis.

     

Morphological changes of trichophyton mentagrophytes under the influence of increased carbon dioxide tension

Summary Growth pigment production as well as macroconidia and arthrospore formation ofTrichophyton mentagrophytes are stimulated under the influence of increased carbon dioxide tension. Macroconidia with spirals and pistol forms of macroconidia are observed.The granular form ofT. mentagrophytes displays an asteroid growth (Dextrose agar of Sabouraud) with an ingrowth and elongation of the ray branches in the agar and a decrease of the air-mycelium. The culture completely resembles to those ofT. mentagrophytes varasteroides. The macroconidia appear elongated and they acquire an asteroid arrangement. The less granular strains ofT. mentagrophytes take the appearance ofT. interdigitale type.An analogy is made between these morphogenetic changes under the effect of increased CO₂ tension in vitro and the influence of the animal organism in the evolution of the growth forms of dermatophytes in vivo in the process of their parasitic adaptation.     

Cytokines in the treatment of fungal infections

The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon- has been very effective as a modulator of resistance against a variety of fungal infectionsin vitro. The effect of interferon- against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon- enhances the elimination ofCandida, and consequently the agent is not effective in severly granulocytopenic animals. Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed.Abbreviations CGD chronic granulomatous disease - G-CSF granulocyte colony-stimulating factor - M-CSF monocyte colony-stimulating factor - GM-CSF granulocyte-monocyte colony-stimulating factor - IFN- interferon-gamma - IL interleukin - LAK lymphokine-activated killer - LPS lipopolysaccharide - MDP muramyl dipeptide - NK natural killer - PMN polymorphonuclear leukocytes - rh recombinant human - ROI reactive oxygen intermediates - TNF tumor necrosis factor     

Use of paraffin bait technique in the isolation of Nocardia asteroides from sputum

Summary The use of paraffin bait technique in the isolation ofNocardia asteroides has been tested in 241 samples of sputa obtained from 235 cases of respiratory diseases.N. asteroides was recovered on 6 occasions from sputum of a patient using the paraffin bait technique. On the other hand cultures of sputa from the same patient on routine agar media such as Sabouraud's agar and Lowenstein Jensen medium yielded only one isolated of the pathogen.This work forms a part of the Ph. D. thesis of P.V.K. submitted to the University of Delhi.     

Diferenciacion bioquimica de algunas especies de actinomycetes patogenos

Resumen Se realizó un estudio de diversas propiedades deN. asteroides, N. brasiliensis y algunosStreptomyces patógenos.Se investigaron los siguientes puntos: a) morfología microscópica, b) descomposición de diversas substancias tales como caseína y tirosina, c) hidrólisis de gelatina y — coagulación de leche, d) producción de ácido a partir de diferentes carbohidratos.De los resultados se deduce que existen dos grandes grupos dentro el géneroNocardia:Grupo 1. Caracterizado por utilizar la caseína y tirosina, hidrolizar la gelatina, coagular la leche y producir generalmente ácido a partir de inositol, galactosa, glucosa y fructosa; a este grupo pertenece exclusivamenteNocardia brasiliensis.Grupo 2. Microorganismos caracterizados por su baja actividad, no descomponen la caseína ni la tirosina, excepcionalmente hidrolizan la gelatina y coagulan la leche, producen ácido a partir de glucosa. En este grupo incluímos todas las cepas recibidas comoN. asteroides y otras tales como —N. leishmanii, N. gypsoides, N. transvalensis, N. convoluta, N. polychromogenes, N. globerula, N. blackwellii, N. minima, N. pasteuroides, N. phenotolerans, N. corneus yN. melanosporus.Por otra parteN. pretoriana, N. rhodnii yN. corallina, tienen en común conN. asteroides la incapacidad de utilizar la caseína y coagular la leche pero estas cepas descomponen la tirosina, característica que no presentó ninguna de las cepas clasificadas comoN. asteroides, por lo que se considera necesario hacer estudios adicionales para decidir la posición taxonómica de estas especies.Las propiedades bioquímicas deStreptomyces fueron similares a las deN. brasiliensis por lo que la separación del géneroStreptomyces deN. brasiliensis no es posible basarla en estas pruebas, siendo la ausencia de fragmentación y ácido resistencia, además de la producción de esporas, las únicas características diferenciales observables.

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Summary In this paper a study is presented of the various properties ofN. asteroides, N. brasiliensis and some pathogenicStreptomyces.The following aspects were studied: a) microscopic morphology, b) descomposition of several substances such as casein and tyrosine, c) gelatin hydrolysis and milk coagulation, d) acid production using different carbohydrate.From the results obtained it is deduced that two main groups exist within the genusNocardia:Group 1. Characterized by their ability to utilize casein and tyrosine, hydrolyse gelatin, coagulate milk and usually producing acid from inositol, galactose, glucose and fructose: onlyNocardia brasiliensis belongs to this group.Group II. Microorganisms characterized by their low activity, inability to decompose casein and tyrosine, exceptionally they hydrolyse gelatin or coagulate milk. In this group we include all the strains received asN. asteroides and others such asN. leishmanii, N. gypsoides, N. transvalensis, N. convoluta, N. polychromogenes, N. globerula, N. blackwellii, N. minima, N. pasteuroides, N. phenotole rans, N. corneus andN. melanosporus.On the other handN. pretoriana, N. rhodnii andN. corallina, have in common withN. asteroides the inability to utilize casein or coagulate milk, however, these strains decompose tyrosine, a characteristic which is not present in any other strains classified asN. asteroides, therefore it is necessary to carry out additional studies so that the taxonomic position of these species may be decided.The biochemical properties ofStreptomyces were similar to those ofN. brasiliensis, therefore it is not possible through these methods, to make the separation of the genusStreptomyces fromN. brasiliensis, the absence of fragmentation, the acid fastness and production of spores are the only differential characteristics that could be observed.

     

An ultrastructural comparison of the cell envelopes of selected strains of Nocardia asteroides and Nocardia brasiliensis

Growth curves were determined for three strains each ofNocardia asteroides andNocardia brasiliensis. Two strains ofN. brasiliensis and one strain ofN. asteroides had longer lag periods of growth than the remaining three strains. All strains had generation times of approximately 5.5 hours.The ultrastructure of the cell envelope of eachNocardia strain in early stationary phase growth was also examined. All the strains had typical trilaminar cell walls and cell membranes. The thickness of the cell wall layers, especially the inner peptidoglycan layer, varied from strain to strain. The inner layer of two strains ofN. brasiliensis and one strain ofN. asteroides was 12 nm or more in thickness, while that of the remaining three strains was 7 nm thick. These observed differences in growth patterns and/or thickness of the cell wall layers could be correlated to the varying degress of virulence as well as the divergent pathologies exhibited by these organisms.     

Pathogenesis of Invasive Pulmonary Aspergillosis in Transplant Recipients

Purpose of Review

Transplant patients are at high risk for invasive pulmonary aspergillosis, and the associated mortality is high. The purpose of this study is to review the pathogenesis of invasive pulmonary aspergillosis (IPA) in transplant patients.

Recent Findings

The pathogenesis of aspergillosis is multifactorial and results from a complex interplay between the pathogen and host. It is well recognized that Aspergillus causes IPA in immunocompromised patients. Recent studies have shown that Aspergillus might also cause diseases likely attributed to an unmodulated immune response in certain transplant recipients such as bronchopulmonary aspergillosis or bronchiolitis obliterans syndrome in lung transplant recipients.

Summary

This review focuses on two crucial axes of the damage response framework applicable to aspergillosis: (1) Aspergillus virulence attributes that enable it to survive and proliferate in the host (thermotolerance, stress and hypoxic response, secretion of secondary metabolites) and (2) host response with specific focus on innate immunity and angiogenesis.

     

Extended serotyping scheme forVibrio cholerae

Fifty-seven new O serogroups have been added to the existing serotyping scheme ofVibrio cholerae to extend the scheme from O84 to O140. Prominent new additions were serogroups O139 and O140. The reference strain of O139 was isolated from a patient from an epidemic of cholera-like diarrhea in Madras, Southern India. Serogroup O140 was assigned to a group ofV. cholerae strains which were tentatively named as the Hakata serogroup and which possessed the C (Inaba) factor but not the B (Ogawa) nor the A (major specific antigen of O1 serogroup ofV. cholerae). As all antisera against reference strains ofV. cholerae contained some amount of antibody to the rough (R) antigen, all diagnostic O antisera must be absorbed with the reference rough strain, CA385.     

Estimation of the Burden of Chronic and Allergic Pulmonary Aspergillosis in India

Background and Objectives

It would be of considerable interest to clinicians if the burden of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) in India were known. Herein, we estimate the burden of CPA following pulmonary tuberculosis (PTB), and ABPA (and severe asthma with fungal sensitization [SAFS]) complicating asthma.

Methods

We used the population estimates for India from the 2011 census data. The burden of asthma was estimated using three different methods (Global Initiative against Asthma [GINA] report statement, World Health Survey [WHS] estimates, Indian study on the epidemiology of asthma and chronic bronchitis [INSEARCH]). Global and India-specific figures were used for calculating the prevalence of ABPA and SAFS. The World Health Organization estimates were used for calculating PTB rates while the frequency of CPA was assessed from a previously published scoping review. Sensitivity analysis was performed to determine the burden in various scenarios.

Results

The total Indian population in 2011 was 1.2 billion. The asthma prevalence in adults was estimated at about 27.6 (range, 17–30) million. The burden of ABPA ranged from 0.12–6.09 million with different assumptions (best estimate, 1.38 [range, 0.86–1.52] million). The prevalence of SAFS was approximated at about 0.52–1.21 million (best estimate, 0.96 [range, 0.6–1.06] million). The incident TB cases were about 2.1 million while the annual incidence of CPA varied 27,000-0.17 million cases, with different estimates. If the mortality of CPA is estimated as 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000.

Conclusion

There is a significant burden of ABPA, SAFS and CPA in India. Prospective community-based studies are required to accurately determine the prevalence of these disorders.     

Conformation of an immunoreactive undecapeptide fragment (10–20) of Asp f 1 by NMR and molecular modeling

Allergic bronchopulmonary aspergillosis (ABPA), caused by Aspergillus fumigatus, is a complication of allergic asthma. Asp f 1 secreted by A. fumigatus is reported to be a major allergen/antigen involved in pathogenesis of aspergillosis. A 11-mer immunodominant epitope (Leu-Asn-Pro-Lys-Thr⁵-Asn-Lys-Trp-Glu-Asp¹⁰-Lys) of Asp f 1 has shown immunoreactivity with specific IgG and IgE antibodies in the sera of patients with ABPA in ELISA inhibitionassay. Various studies have suggested that the peptide has a potential use in the development of ELISA based diagnostic kit for early diagnosis of infections caused by A. fumigatus.In view of these interesting properties of the undecapeptide wehave embarked on an investigation of its conformation to understand the relationship between structure and immunoreactivity. NMR and molecular modeling studies of the peptide suggest a structure with a -turn spanning residuesAsn⁶ – Glu⁹ in water at pH 4.0, a -pleated sheet in DMSO and a -helix in 40% HFA.     

Role of Serological Tests in the Diagnosis of Mold Infections

Purpose of Review

To understand the role of antibody detection in the diagnosis of infections caused by filamentous fungi (molds). Rapid and accurate profiling of infection-causing fungal pathogens remains a significant challenge in modern health care. Classical fungal culture and serology continue to be relevant even though over the past few decades, antigen (biomarker) assays such as ELISA and lateral flow devices have been developed and validated.

Recent Findings

This article reviews the current antibody detection systems (serological tests) for the diagnosis of mold infections associated with pulmonary disease and introduces new developments. Classic and more recently developed serological techniques and their performance characteristics, including immunodiffusion, complement fixation, and ELISA.

Summary

The diseases covered are allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, invasive aspergillosis, mucormycosis, diseases caused by filamentous basidiomycetes, infection caused by Talaromyces marneffei and pythiosis. Serology remains a cornerstone for fungal diagnostic testing.