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Medical Mycology in India: past, present and future. by H.C. Gugnani, Ph.D. FRC. Path. Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi Delhi-110007 (formerly at Vallabhbhai Patel Chest Institute, University of Delhi). Dedication to Dr. Libero Ajello.

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Medical mycology in india past present and future

Medical Mycology in India: past, present and future

by

H.C. Gugnani, Ph.D. FRC. Path.

Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi

Delhi-110007 (formerly at Vallabhbhai Patel Chest Institute, University of Delhi)


Dedication to dr libero ajello

Dedication to Dr. Libero Ajello

  • Late Dr. Ajello was not only a pioneer medical mycologists but also an embodiment humility and kindness.

  • With his great qualities of head and heart, he helped numerous mycologists around the globe, particularly those in the developing countries in several ways.

  • Above all, he was a very humble and a kind person


Interaction with fungi

Interaction with fungi

  • The interaction of Indians with fungi started thousands of years ago.

  • There is scientific evidence that the mushroom, Amanita muscaria may have been the oldest of the hallucinogens used by the Aryans, about 3500 years ago, and may possibly be the most widely used cryptic symbolism in the Rig Veda


Interaction with fungi contd

Interaction with fungi-contd.

  • According to Wasson, Soma, the narcotic God of ancient India was believed to have originated from the Aryans, who invaded India, 3500 years ago, from the north which is now Afghanistan, into the Indus Valley, and with them, brought their cult of Soma.

  • Soma is one of the few enthnogens that is looked upon as a god rather than a sacred mediator.

  • After a detailed study of descriptions, Wasson concluded that Soma was a mushroom and specifically, Amanita muscara, the fly agaric. Interdisciplinary studies in 1967 also testified to this.


Early work on fungi in india

Early work on fungi in India

  • There are references to the use of mushrooms as foods and medicines in India in the ancient medical text, Charaka Samhita (3000+500 BC).

  • However, their scientific study is of recent origin. In the 18th century, Koening got his collecton from Tamil Nadu State identified as Podaxis pistillaris (L:Pers) Mosse by Linnaeus.

  • Subsequently Sir J.D. Hooker made a collection of fungi from hills that led to a series of papers by an English mycologist, Reverend M.J. Berkley. This first phase lasted up to 1899.

  • A significant feature of the second phase (1900-1960) was the involvement, besides European and American workers, of several Indian workers on larger as well as microfungi


Earliest records of fungal disease

Earliest records of fungal Disease

  • The earliest record of fungal disease in man is in Athara Veda (About 2000-100 BC), of mycetoma described under the name “Padavalmita”(Foot anthill) (Saran et al. 1972).

  • Gill, an English physician in South India first described a probable case of mycetoma in 1842 in his dispensary report in Madura (Madurai) in Tamil Nadu. Godfrey, a Garrison surgeon working in Bellary first described mycetoma (as “morbus “tuberculosis pedis”) in medical literature in 1946 (Lancet 1: 593-594).


Early research in medical mycology in india

Early research in medical mycology in India

  • In 1859, Eyere, one of Godfrey`s colleagues described 40 cases treated between 1844 and 1848.

  • It was Carter, who in 1861 first suggested the fungal etiology of the disease (Trans Med PhysSoc Bombay 7: 206-221) and introduced the term “mycetoma”

  • Later in 1874, Carter published a monograph ”On Mycetoma and Fungus Diseases of India” (J & Churchill Ltd.).


Early research in medical mycology in india continued

Early research in medical mycology in India-continued

  • Carter also described the pathological features of mycetoma, caused by the organism now known as Madurella mycetomatis.

  • Powell reported ringworm from Assam in 1904

  • Research in medical mycology in India started in 1920 under Lt. Col H. W. Acton (with C. McGuire, A. Maplestone, NC Dey, G. Panja, K.P. Banerjee and others) at Calcutta School of Tropical Medicine, Calcutta.

  • Acton described red-grained mycetoma from India Pioneering work was done on other mycoses.


Early research in mycology and pl pathology in india

Early research in Mycology and Pl. Pathology in India

  • E.J. Butler, a British physician, started the work on fungal diseases of plants in India in 1903 with the publication of monograph on “Potato diseases of India” (Agr Ledger4: 112-119.).

  • He worked at the I.A.R.I from 1905-1921 in Pusa (Bihar) and established a strong school of mycology and plant pathology.

  • Butler is aptly called the father of “Indian Plant Pathology”. Before departing from India, he published in 1918 a book on “Fungi and Diseases in Plants”, which remains a classic till to-day.


Early research in mycology and pl pathology plan in india contd

Early research in Mycology and pl. pathology plan in India-contd.

  • Butler published an authoritative list of Indian fungi in collaboration with G.R. Bisby (Butler & Bisby 1930).

  • This publication has been continuously updated until the last edition by Sarabhoy et al (1993).


Establishment of separate med mycology departments sections

Establishment of separate Med. Mycology Departments/Sections

  • Calcutta (Kolkata) School of Tropical Medicine, Calcutta - A separate Department of Dermatology & Medical Mycology was established in 1931 with Dr A. Maplestone in –charge and Drs NC Dey, D Panja and LN Ghosh

  • An independent Medical Mycology Department was established in 1960 with Dr SR Bose as head.

  • Later Drs Maya Sanyal, N Basu, A Thammaya, and worked as a team for nearly three decades with other associates, mainly Drs PK Maiti, A Ray, PK Haldar and others in RG Kar Medical College and University College of Medicine, Kolkata.


Vallabhbhai patel chest institute university of delhi

Vallabhbhai Patel Chest Institute, University of Delhi

  • Mycological work started in the institute in 1957 with investigation of role of fungi in Bagassosis under an ICMR Project.

  • The Department of Medical Mycology was established in 1959 with appointment of Dr HS Randhawa as foundation staff; Dr RS Sandhu joined in the same year. Other Faculty staff who worked in the Department include Dr ZU Khan (1974-1992) and Dr HC Gugnani (1997-2004), Dr A Chowdhary (2001- to date). Dr Randhawa is continuing to work in the Dept. (after retirement in 1998) as Senior Emeritus Scientist of INSA.


All india institute of medical sciences new delhi

All India Institute of Medical Sciences, New Delhi

  • Medical Mycology section established under the leadership of Col. Prof SL Kalra, Head, Dept. of Microbiology in 1960 with Dr LN Mohapatra as Faculty staff in charge, later joined by HC Gugnani as ICMR project staff in 1962.

  • Later the Mycology section was headed by Dr R Kumar and more recently by Dr Uma Banerjee.


National institute of communicable diseases delhi

National Institute of Communicable Diseases, Delhi

  • Section of Medical Mycology was established in 1964 (under the Division of Microbiology) with HC Gugnani as the foundation staff (research office), later joined by SK Shome (Assistant Director) in 1967.

  • Later Drs ZU Khan, R Rajendran and K Chandrasekhar worked for varying periods.

  • Currently the Division of Med. Mycology is headed by Dr Chandrasekhar (Joint Director).


Madras medical college chennai govt gen hospital

Madras Medical College, Chennai & Govt. Gen. Hospital

  • The Mycology Section was started in 1960 under Dermatology Dept. as brain child of Prof. A. S. Thambiah with Dr PV Venugopal, and Dr A Kamalam.

  • Other faculty staff who worked were Dr G Sentamilselvi, VR Janaki and C Janaki as academic staff.

  • The section is presently headed by Dr C Janaki.


Post gradaute institute of medical education research chandigarh

Post-gradaute Institute of Medical Education & Research, Chandigarh

  • Mycology section was started under Dept. of Microbiology with the pioneering efforts of Dr P Talwar in 1964 . It was raised to the status of Division in 1979.

  • Dr A Chakrabarti joined as Faculty staff in 1988 and took over the reins of the Division in 1991 after retirement of Dr Talwar, and is currently supported by Dr Shiva Prakash.


Department of biological scienes r d university jabalpur

Department of Biological scienes, R.D University, Jabalpur

  • The work in medical mycology in this centre in MP (in Central India) was pioneered by Dr S M Singh in 1978 under the stewardship pf Prof GP Agarwal, the then Head of Dept.

  • The Laboratory has been has been providing mycological diagnostic services to the hospitals in and around Jabalpur for the past 20 years

  • His current team in the Department includes Dr Jayshree Naidu and Dr Nwage Rao.


Lokmanya tilak muncipal medicl college general hospital

Lokmanya Tilak Muncipal Medicl College & General Hospital

  • Mycology section established in the Department of Microbiology in 1979 by Dr Lina Deodhar, then Professor and Head of Dept. and Dr VB Ambekar.

  • With the expanding medical mycological work and research, Dr Uma Tendolkar, Associate Professor assumed the charge of the section in 1984 and is still with the Department.


Society for indian human and animal mycologists siham

Society for Indian Human and Animal Mycologists (SIHAM)

  • SIHAM was founded in 1995 in Jabalpur (M.P.) with the tenuous and laudable efforts of Prof. SM Singh and other colleagues with only 17 members.

  • Since then the society has steadily grown to its present strength of about 300 members;

  • The first annual Conference was organized by Prof. SM Singh at R.D. University, Jabalpur in February 1996. Subsequent Conferences were held in Jodhpur (organized by Prof. K.R Joshi), Chennai, Annamlai Nagar in Tamil Nadu (Prof. PV VenugopaL), and Chandigarh (Dr A Chakrabarty) in 1998, 2000, 2002 & 2004 respectively.


Siham continued

SIHAM -continued

  • It is because of these continued efforts that we are now attending the sixth Conference of SIHAM in Hyderabad today (Jan 2006), organized by Dr R Iyer and his colleagues.

  • SIHAM Mycoses Newsletter was started in 2002 with the laudable efforts of Dr A Chakrabarti (who is also it Editor), and with financial support of M/S Pfizer, India. It has continued to serve as a commendable source of valuable information and educational material on mycoses.

  • SIHAM is planning to publish its own journal.


Training workshops in medical mycology

Training workshops in Medical Mycology

  • Several training courses and workshops have been organized in medical mycology in different parts of the country. These included:

  • International workshop organized in PGI, Chandigarh in November with Faculty from USA UK, India with the financial support by British Council.

  • A National workshop was held very recently in Chennai in October 2005 as a part of the National Conference of Association of Medical Microbiologists of India (with resource persons as Drs A Chakrabarti, Dr Pankajlakshmi Venugopal & her colleagues, Dr Shiva Prakash.

  • These workshops have been attended by a large number of participants from several parts of India, and few from Nepal.


New species fungal pathogens

New species-fungal pathogens

  • Candida viswanathii, a new species recovered from CSF and sputum (Viswanathan & Randhawa, 1959 Sci & Cult25: 86-87; Sandhu & Randhawa Mycopath Mycol Appl 1962; 18: 181-18

  • Artrogrpahis kalrae (Tewari & Macpherson) Sigler & Carmichael) originally recovered from sputum, pathogenic for laboratory mice (Tewari & Macpherson. Mycologia 1971, 63: 602-611).

  • It was then named as Oidiodendron kalrai. The species is known to cause cutaneous and systemic infections.


New species fungal pathogens1

New species-fungal pathogens

  • Saksena discoveed in 1953 a new genus, Saksenaea with S. vasfiormis as the type species (also the only known species).

  • This fungus is world-wide saprobe in soil and has emerged as an important human pathogen, mostly associated with cutaneous and sub-cutaneous infections.


New novel fungal pathogens

New/Novel fungal pathogens

  • Misra, Srivastava & Latas (1979) discovered a new mucoraceous fungus, Aphanomyces with A. elegans as the type species (the only known species of the genus).

  • This has emerged as an important pathogen of immunocompetent and immuno-compromised host.


Novel fungal pathogens

Novel fungal pathogens

  • Ustilago maydis, a plant pathogen causal agent of maize smut, was identified as a etiological agent of a unique case of brain mycosis, manifesting as brain tumour with symptoms of blindness and raised intracranial tension (Randhawa, HS, Tandon HD & Smetana HF. Bull Cal Sch Trop Med 1959; 7: 45-46.

  • Association of Candida tropicalis with maize stalk rot (Lalaramani et al. 1974 Experientia59:109-11.

  • Systemic mycosis (cerebral phaeohyphomycosis) caused by Chaetomium globosum. (Anandi et al. 2001) J Clin Microbiol 1989; 27: 2226-2229).


Novel fungal pathogens contd

Novel fungal pathogens-contd.

  • Nodulisporium sp as an etiological agent of human infection (cerebral phaeo-hyphomycosis) (Umabala et al. J Clin Microbiol 2001, 39: 4213-4318)

  • Maxillary sinusitis caused by Ascotrihca chartarum (Singh et al. 1990 J Med Vet Mycol 28 275-278.)

  • Rhizoctonia sp. as etiological agent of mycotic keratitis (Srivastava et al. 1968; Sabouraudia15: 125-131.


Novel fungal pathogens contd1

Novel fungal pathogens-contd.

  • Acremonium recifei as a as a causal agent of myctoma (Koshi et al Am J trop Med Hyg 1979; 28: 692-696).

  • Cutaneous phaeohyphomycosis due to Alternaria chlamydospora (Singh et al. 1990 J Med Vet Mycol 28 275-278).

  • Aspergillus versicolor as the causal agent of cerebral abscess (Venugopal et al Sabouraudia 1978, 13)


Novel fungal pathogens contd2

Novel fungal pathogens-contd.

  • Cylindrocarpon sp. as an etiological agent of mycetoma (Hemashettar et al. 2000 JCM 38:4288-91)

  • Emericella quadrilineata (anamorph Aspergillus tetrazonus) as an etiological agent of onychomycosis (Gugnani et al. 2004; JCM 42: 914-916.).


Development of rapid novel diagnostic techniques

Development of rapid/novel diagnostic techniques

  • Application of paraffin bait for better recovery of Nocardia asteroides from clinical specimens (Mishra & Randhawa 1969 Appl Microbiol 18: 686-687.)

  • Modified inositol assimilation by Cryptoooccus neoformans, yielding results within 48 hrs as against 14 days by Adams-Cooper technique (Paliwal et al., 1979 Canad J Microbiol 25: 346-348.)


Novel techniques continued

Novel techniques - continued

  • Use of Berthiolate color reaction for rapid detection of urea hydrolysis (within 30-50 minutes) by C. neoformans and other yeasts (Paliwal et al. 1977 Environ Microbiol 33:219-220) as against 8-72 hrs usually required with Christensen urea agar

  • Use of L-DOPA pigmentation test for development of mouse-grey violaeous black pigment 15-30 min., diagnostic of C. neoformans in inoculated in phosphate-buffered liquid medium incubated at 37 0C, as compared with over 5 hrs using the test described by Hopfer & Groschel (1975) (Paliwal & Randhawa, 1978 Antonie van Leeuwenhoek 44:261-264).


Rapid novel diagnostic techniques

Rapid/novel diagnostic techniques

  • Simplified Staib (birdseed/nigerseed) agar for pigment production by C. neoformans (Paliwal et al. J Clin Microbiol 1978; 7: 346-346.)

  • A new medium, tobacco agar, for pigment production of Cryptoooccus neoformans (Tendolkar et al.Indian J Med Microbiol 2003; 21: 277-279.This has led to a new use of the medium i.e. differentiating Candida dubliniensis from Candida albicans (Khan et al., 2004 J. Clin Microbial 42: 4796-4798.).


Novel diagnostic techniques continued

Novel diagnostic techniques-continued

  • Cotton seed agar (7% aqueous seed extract of Gossipium hirsutum or G. arboreum) as an inexpensive but efficacious mediumfor in vitro conversion of Blastomyces dermatitidis to yeast form (Chaturvedi et al. 1990 J Med Vet Mycol 28: 139-145.


Ecology epidemiology of mycoses histoplasmosis

Ecology & Epidemiology of Mycoses: Histoplasmosis

  • Isolation of Histoplasma capsulatum, the etiological agent of histoplasmosis from one of the three samples of soil admixed with bat guano in Serampore (Sanyal M & Thammaya Indian J Med Res 1975 63: 1020-1028,)

  • The samples were collected from an abandoned room of a 350-year old palatial building building infested with insectivorous bat, Scotophilus heathi.


Blastomycosis

Blastomycosis

  • Recovery of Blastomyces dermatitidis, from the visceral organs of a bat (Rhinopoma hardwickei hardwickei), thus implicating these flying mammals as an additional host or a vector of this dimorphic pathogen. (Khan et al.1982 Sabouraudia 20: 137-144, Randhawa et al.1985 Sabouraudia 23: 78-86.)

  • These findings and the report of the first autochthonous case of blastomycosis in India (Randhawa et al 1983 Sabouraudia21: 215-221.) established the endemicity of this disease in India.


Other systemic mycoses

Other systemic mycoses

  • Coccidioidomycosis - First authentic case of this disease (originating from Arizona in USA) reported from India (Baruch et al. 1996 Lancet; 348: 1313) followed by another such case (Verghese et al.2002 Med Mycol 40:307-9.)

  • Rhinosporidiosis - Asian water buffalo (Babalus bubalis) as a host for Rhinosporidium seeberi (Rao et al, 1975)


Aspergillosis

Aspergillosis

  • Series of studies demonstrating the frequent occurrence of ABPA in India (Khan et al Scand J RespDis 1976; 57: 73-87; Shah A. Indian J. Chest Dis. Allied Sci 1994;36: 273-289.

  • Association of a virulence with p-aminobenzoic acid deficiency in Aspergillus fumigatus (Sandhu et al 1976 Infect Immun 13: 527-532)


Aspergillosis contd

Aspergillosis-contd.

  • Identification, cloning, and expression of a 44 Kda novel allergen/antigen of A. fumigatus with sequence homology to L3 ribosomal protein with a probable role in resistance of the fungus to antifugnal drugs (Saxena et al. 2003 Clin Exp Immunol134: 86-91.

  • Role of surfactant proteins SPA-A, SP-D and MBL in the host defense against allergic and invasive aspergillosis by in vitro and in vivo studies (Madan et al.2005, Med Mycol 43, Supplement 1: S155-163).


Infection due to cryptococcus neoformans and its ecology

Infection due to Cryptococcus neoformans and its ecology

  • First report of cutaneous infection due to Cryptococcus laurentii (Kamalam & Thambiah 1977 Brit J Dermatol97: 221-223.) 

  • Isolation of C. neoformans var. gattii from flowers of Euclayptus camaldulensis, from the bark of E. terreticornis and C. n. var. neoformans (var. grubii) from decayed wood inside trunk hollows of Syzygium cumini and of C. n. var. neoformans from Ficus religiosa trees in Chandiagrh, Delhi/New Delhi (Padhye et al. 1993, Randhawa et al.,2001; 2003; Gugnani et al. 2005).


C n eoformans ecology contd

C. neoformans - ecology contd.

  • Recovery of C.n. var. grubii from the flowers of Eucalyptus camaldulensis. The two isolates were clonal (Gugnani et al 2005 Med Mycology 43: 565-569,)

  • These studies evidence that natural habitat of C. neoformans is not confined to any particular tree

  • First study of molecular characterization of clinical and environmental isolates of C. neoformans from India (Kidd et al 2001, )


Infections to other yeasts and yeast like fungi

Infections to other yeasts and yeast-like fungi

  • An nosocomial outbreak due to an unusual yeast, Pichia anomala involving 379 neonates and children (Chakrabarti et al. 2001 JCM 39: 1702-1706. Molecular studies of 40 isolates multilocus enzyme electrophoresis suggested the clonal naure of the isolates

  • First report of nosocomial outbreak of candidemia due to Candida tropicalis in neonates documenting clonal origin of isolates. (Chowdhary et al. Mycoses2003, 46: 287-292).


Dermatomycoses

Dermatomycoses

  • Demonstration of soil as a natural source and rodents (mainly Meriones hurrine, Suncus murinus ) as animal reservoirs of Trichophyton simii Pahye et al, 1966 Hindustan Antibiotic Bull ; Gugnani et al. 1967, 1975 Sabouraudia6: 77-80., Mykosen 18: 529-536.)

  • First report of an epizootic of dermatophtytosis in poultry due to Trichophyton simii (Gugnani & Randhawa, 1973, Sabouradia 11: 1-3. )


Dermatomycoses contd

Dermatomycoses-contd.

  • A focus of Trichophyton schoenleini infection of scalp in children (favus) in the Kashmir valley, possibly originating from Middle east (Hajni et al, 1987) and of T, yaoundei in Karnataka (Hemishettyar et al 1990 J Med. Vet Mycol)

  • Association of Trichophyton mentagrophytes with the bark of Eucalyptus tree (E. camaldulensis) (Musa et al 2000 . J Mycol Medicale 2000; 10: 136-139 )


Dermatomycoses contd phaeohyphomycoses

Dermatomycoses contd. & phaeohyphomycoses

  • Studies from Jabalpur highlighted for the first time the etiological role of non-dermatophytic filamentous fungi including dematiaceous fuingi in causing cutaneous infections in India.

  • The species included Nattrassia mangiferae, Curvularia lunata, C.pallescens, Alternaria chlamydospora, Exserohilum rostratum (Singh SM & Barde AK Indian J Dermatol Venerol Lepr 1980; 46: 350-355; Barde AK & Singh SM. Mycoses 1983; 26: 365-370; Agarwal A, Singh SM. Mycoses 1995; 38: 301-303, Mycopathologia 1995; 131


Dermatomycoses contd phaeohyphomycoses contd

Dermatomycoses contd. & phaeohyphomycoses contd.

  • Further studies by other workers. viz. Mathews, Verghese, Ranjan and their associates have highlighted the role of dematiaceous fungi in causing subcutaneous phaeohyphomycosis


Mycetoma

Mycetoma

  • Several investigators from different parts of India have made significant contributions on the prevalence and etiology of mycetoma in the country. Some of the studies are by Klokke et al. 1968; Desai et al. 1970; Koshi et al. 1972; Dasgupta et al . 1974; Taralakshmi /& Pankajlaksmi, 1977; Kamalam & Thambiah, 1987; Joshi et al. 1987; Venugopal & Venugopal 1995; Sanyal et al. 1976; Sentamilselvi et al. 1997.


Mycetoma contd

Mycetoma- contd.

  • Some of the notable contributins on the etiology of myctoma include first isolations of Leptosphaeria senegalensis and L. tompkinsii from outside of Africa(Pankajlkshmi &Taralakshmi. Int J Dermatol 1990)


Molecular diagnosis of fungal infections in india

Molecular diagnosis of fungal infections in India

  • Use of PCR in the diagnosis of fungal endophthalmitis from Sankar Netralaya, ChennaI (Anand et al. Ophthalmology 108: 326-330.. Indian J Med Res 200, 114: 133-140.)

  • Demonstration of usefulness of PCR in laboratory diagnosis of systemic fungal infections in a study from Mumbai (Iyer et al. Indian J Med Microbiol 2002, 20: 132-136.)


Molecular diagnosis of fungal infections in india contd

Molecular diagnosis of fungal infections in India-contd.

  • Use of PCR in diagnosis of cryptococcal meningitis (Iyer Revathi S, Banker (Indian J Med Sci 2002; 56. 593-597.

  • We need to evaluate PCR in greater number of laboratories before confirming the usefulness of this technique.


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