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Mycetoma Caused by Madurella mycetomatis: A Completely Neglected Medico-social Dilemma

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Book cover Hot Topics in Infection and Immunity in Children IX

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 764))

Abstract

Mycetoma is a debilitating disease with a highly particular geographical distribution. The mycetoma belt circles the entire world just above the equator and defines the region with the highest prevalence and incidence. Although the disease is seen in Central America, India and all across Africa, Sudan seems to be the homeland of mycetoma. Mycetoma is an infectious disease caused either by bacteria (actinomycetoma) or true fungi (eumycetoma).

In Sudan most cases are caused by the fungal species Madurella mycetomatis. The precise natural habitat of this fungus is still an enigma, but its DNA can easily be found in soil and plant samples in endemic areas. Although the entire human population in these areas are in regular contact with the fungus, most individuals are unaffected. Thus mycetoma is an ideal clinical and experimental model system for the study of host-pathogen interactions. Also, given its relative importance locally, improvements in clinical and laboratory diagnostics and knowledge of the epidemiology of the disease are badly needed. This chapter describes the current state of affairs in the field of eumycetoma caused by M. mycetomatis. The value of laboratory research on this disease and future perspective for control and prevention of the infection are discussed.

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References

  1. Ahmed AO, van Leeuwen W, Fahal A, van de Sande W, Verbrugh H, van Belkum A (2004) Mycetoma caused by Madurella mycetomatis: a neglected infectious burden. Lancet Infect Dis 4(9):566–574

    Article  Google Scholar 

  2. McGinnis MR (1996) Mycetoma. Dermatol Clin 14(1):97–104

    Article  CAS  Google Scholar 

  3. Padhi S, Uppin SG, Uppin MS, Umabala P, Challa S, Laxmi V, Prasad VB (2010) Mycetoma in South India: retrospective analysis of 13 cases and description of two cases caused by unusual pathogens: Neoscytalidium dimidiatum and Aspergillus flavus. Int J Dermatol 49(11):1289–1296

    Article  Google Scholar 

  4. Afroz N, Khan N, Siddiqui FA, Rizvi M (2010) Eumycetoma versus actinomycetoma: diagnosis on cytology. J Cytol 27(4):133–135

    Article  Google Scholar 

  5. Wethered DB, Markey MA, Hay RJ, Mahgoub ES, Gumaa SA (1987) Ultrastructural and immunogenic changes in the formation of mycetoma grains. J Med Vet Mycol 25(1):39–46

    Article  CAS  Google Scholar 

  6. Ahmed A, Adelmann D, Fahal A, Verbrugh H, van Belkum A, de Hoog S (2002) Environmental occurrence of Madurella mycetomatis, the major agent of human eumycetoma in Sudan. J Clin Microbiol 40(3):1031–1036

    Article  Google Scholar 

  7. Ahmed AO, Abugroun E, Fahal AH, Zijlstra EE, van Belkum A, Verbrugh HA (1998) Unexpected high prevalence of secondary bacterial infection in patients with mycetoma. J Clin Microbiol 36:850–851

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Ameen M, Arenas R (2009) Developments in the management of mycetomas. Clin Exp Dermatol 34(1):1–7

    Article  CAS  Google Scholar 

  9. Ahmed AO, Desplaces N, Leonard P, Goldstein F, De Hoog S, Verbrugh H, van Belkum A (2003) Molecular detection and identification of agents of eumycetoma: detailed report of two cases. J Clin Microbiol 41(12):5813–5816

    Article  Google Scholar 

  10. Fahal AH, el Toum EA, el Hassan AM, Mahgoub ES, Gumaa SA (1995) The host tissue reaction to Madurella mycetomatis: new classification. J Med Vet Mycol 33(1):15–17

    Article  CAS  Google Scholar 

  11. Ameen M, Arenas R (2008) Emerging therapeutic regimes for the management of mycetomas. Expert Opin Pharmacother 9(12):2077–2085

    Article  CAS  Google Scholar 

  12. Mahgoub ES, Gumaa SA (1984) Ketoconazole in the treatment of eumycetoma due to Madurella mycetomii. Trans R Soc Trop Med Hyg 78:376–379

    Article  CAS  Google Scholar 

  13. Fahal AH, Rahman IA, El-Hassan AM, Rahman ME, Zijlstra EE (2011) The safety and efficacy of itraconazole for the treatment of patients with eumycetoma due to Madurella mycetomatis. Trans R Soc Trop Med Hyg 105(3):127–132

    Article  CAS  Google Scholar 

  14. Ahmed AO, van de Sande WW, van Vianen W, van Belkum A, Fahal AH, Verbrugh HA, Bakker-Woudenberg IA (2004) In vitro susceptibilities of Madurella mycetomatis to itraconazole and amphotericin B assessed by a modified NCCLS method and a viability-base 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide (XTT) assay. Antimicrob Agents Chemother 48(7):2742–2746

    Article  CAS  Google Scholar 

  15. van de Sande WW, Luijendijk A, Ahmed AO, Bakker-Woudenberg IA, van Belkum A (2005) Testing of the in vitro susceptibilities of Madurella mycetomatis to six antifungal agents by using the Sensititre system in comparison with a viability-based 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5- ((phenylamino)carbonyl)-2H-tetrazolium hydroxide (XTT) assay and a modified NCCLS method. Antimicrob Agents Chemother 49(4):1364–1368

    Article  CAS  Google Scholar 

  16. de Hoog GS, Adelmann D, Ahmed AO, van Belkum A (2004) Phylogeny and typification of Madurella mycetomatis, with a comparison of other agents of eumycetoma. Mycoses 47(3–4):121–130

    Article  CAS  Google Scholar 

  17. Desnos-Ollivier M, Bretagne S, Dromer F, Lortholary O, Dannaoui E (2006) Molecular identification of black-grain mycetoma agents. J Clin Microbiol 44(10):3517–3523

    Article  CAS  Google Scholar 

  18. Padhye AA, Salkin IF (2011) Madurella pseudomycetomatis: an invalidly published name. J Clin Microbiol 49(4):1703

    Article  Google Scholar 

  19. Ahmed AO, Mukhtar MM, Kools-Sijmons M, Fahal AH, de Hoog S, van den Ende BG, Zijlstra EE, Verbrugh H, Abugroun ES, Elhassan AM, van Belkum A (1999) Development of a species-specific PCR-restriction fragment length polymorphism analysis procedure for identification of Madurella mycetomatis. J Clin Microbiol 37(10):3175–3178

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Ahmed A, van de Sande W, Verbrugh H, Fahal A, van Belkum A (2003) Madurella mycetomatis strains from mycetoma lesions in Sudanese patients are clonal. J Clin Microbiol 41(10):4537–4541

    Article  CAS  Google Scholar 

  21. Fahal AH, Abu S (2010) Mycetoma in children. Trans R Soc Trop Med Hyg 104:107–112

    Article  Google Scholar 

  22. Yousif MA, Hay RJ (1987) Leucocyte chemotaxis to mycetoma agents--the effect of the antifungal drugs griseofulvin and ketoconazole. Trans R Soc Trop Med Hyg 81(2):319–321

    Article  CAS  Google Scholar 

  23. van de Sande WW, Janse DJ, Hira V, Goedhart H, van der Zee R, Ahmed AO, Ott A, Verbrugh H, van Belkum A (2006) Translationally controlled tumor protein from Madurella mycetomatis, a marker for tumorous mycetoma progression. J Immunol 177(3):1997–2005

    Article  CAS  Google Scholar 

  24. Zaini F, Moore MK, Hathi D, Hay RJ, Noble WC (1991) The antigenic composition and protein profiles of eumycetoma agents. Mycoses 34(1–2):19–28

    CAS  PubMed  Google Scholar 

  25. Romero H, Mackenzie DW (1989) Studies on antigens from agents causing black grain eumycetoma. J Med Vet Mycol 27(5):303–311

    Article  CAS  Google Scholar 

  26. Jiang RS, Hsu CY (2004) Serum immunoglobulins and IgG subclass levels in sinus mycetoma. Otolaryngol Head Neck Surg 130(5):563–566

    Article  Google Scholar 

  27. Araujo MJ, Castañeda E (1997) Madurella mycetomatis antigen for the serodiagnosis of mycetoma. Rev Iberoam Micol 14(1):31–35

    CAS  PubMed  Google Scholar 

  28. de Klerk N, de Vogel C, Fahal A, van Belkum A, van de Sande WW (2011) Fructose-bisphosphate aldolase and pyruvate kinase, two novel immunogens in Madurella mycetomatis. Med Mycol (Epub ahead of print)

    Google Scholar 

  29. Rajendran C, Baby A, Kumari S, Verghese T (1991) An evaluation of straw-extract agar media for the growth and sporulation of Madurella mycetomatis. Mycopathologia 115(1):9–12

    Article  CAS  Google Scholar 

  30. van de Sande WW, Gorkink R, Simons G, Ott A, Ahmed AO, Verbrugh H, van Belkum A (2005) Genotyping of Madurella mycetomatis by selective amplification of restriction fragments (amplified fragment length polymorphism) and subtype correlation with geographical origin and lesion size. J Clin Microbiol 43(9):4349–4356

    Article  CAS  Google Scholar 

  31. Vos P, Hogers R, Bleeker M, Reijans M, van de Lee T, Hornes M, Frijters A, Pot J, Peleman J, Kuiper M et al (1995) AFLP: a new technique for DNA fingerprinting. Nucleic Acids Res 23(21):4407–4414

    Article  CAS  Google Scholar 

  32. van Belkum A, Fahal AH, van de Sande WW (2011) In vitro susceptibility of Madurella mycetomatis to posaconazole and terbinafine. Antimicrob Agents Chemother 55(4):1771–1773

    Article  CAS  Google Scholar 

  33. N’diaye B, Dieng MT, Perez A, Stockmeyer M, Bakshi R (2006) Clinical efficacy and safety of oral terbinafine in fungal mycetoma. Int J Dermatol 45(2):154–157

    Article  Google Scholar 

  34. van de Sande WW, Fahal AH, Bakker-Woudenberg IA, van Belkum A (2010) Madurella mycetomatis is not susceptible to the echinocandin class of antifungal agents. Antimicrob Agents Chemother 54(6):2738–2740

    Article  CAS  Google Scholar 

  35. Mahgoub ES, Gumaa SA (1984) Ketoconazole in the treatment of eumycetoma due to Madurella mycetomii. Trans R Soc Trop Med Hyg 78(3):376–379

    Article  CAS  Google Scholar 

  36. Negroni R, Tobón A, Bustamante B, Shikanai-Yasuda MA, Patino H, Restrepo A (2005) Posaconazole treatment of refractory eumycetoma and chromoblastomycosis. Rev Inst Med Trop Sao Paulo 47(6):339–346

    Article  Google Scholar 

  37. van de Sande WW, Fahal AH, Riley TV, Verbrugh H, van Belkum A (2007) In vitro susceptibility of Madurella mycetomatis, prime agent of Madura foot, to tea tree oil and artemisinin. J Antimicrob Chemother 59(3):553–555

    Article  CAS  Google Scholar 

  38. Wassenaar TM, Gaastra W (2001) Bacterial virulence: can we draw the line? FEMS Microbiol Lett 201(1):1–7

    Article  CAS  Google Scholar 

  39. Findlay GH, Vismer HF (1974) Black grain mycetoma. A study of the chemistry, formation and significance of the tissue grain in Madurella mycetomi infection. Br J Dermatol 91(3):297–303

    Article  CAS  Google Scholar 

  40. Revankar SG, Sutton DA (2010) Melanized fungi in human disease. Clin Microbiol Rev 23(4):884–928

    Article  Google Scholar 

  41. van de Sande WW, de Kat J, Coppens J, Ahmed AO, Fahal A, Verbrugh H, van Belkum A (2007) Melanin biosynthesis in Madurella mycetomatis and its effect on susceptibility to itraconazole and ketoconazole. Microbes Infect 9(9):1114–1123

    Article  CAS  Google Scholar 

  42. Martinez LR, Ntiamoah P, Gácser A, Casadevall A, Nosanchuk JD (2007) Voriconazole inhibits melanization in Cryptococcus neoformans. Antimicrob Agents Chemother 51(12):4396–4400

    Article  CAS  Google Scholar 

  43. Rid R, Simon-Nobbe B, Langdon J, Holler C, Wally V, Pöll V, Ebner C, Hemmer W, Hawranek T, Lang R, Richter K, MacDonald S, Rinnerthaler M, Laun P, Mari A, Breitenbach M (2008) Cladosporium herbarum translationally controlled tumor protein (TCTP) is an IgE-binding antigen and is associated with disease severity. Mol Immunol 45(2):406–418

    Article  CAS  Google Scholar 

  44. van de Sande WW, Fahal A, Verbrugh H, van Belkum A (2007) Polymorphisms in genes involved in innate immunity predispose toward mycetoma susceptibility. J Immunol 179(5):3065–3074

    Article  CAS  Google Scholar 

  45. Mahgoub ES, Gumaa SA, El Hassan AM (1977) Immunological status of mycetoma patients. Bull Soc Pathol Exot Filiales 70(1):48–54

    CAS  PubMed  Google Scholar 

  46. Mahgoub ES (1978) Experimental infection of athymic nude New Zealand mice, nu nu strain with mycetoma agents. Sabouraudia 16(3):211–216

    Article  CAS  Google Scholar 

  47. Gumaa SA, Abu-Samra MT (1981) Experimental mycetoma infection in the goat. J Comp Pathol 91(3):341–346

    Article  CAS  Google Scholar 

  48. Nishimura K, Miyaji M (1985) Pathogenicity of Exophiala jeanselmei for ddY mice. Mycopathologia 91(1):29–33

    Article  CAS  Google Scholar 

  49. Ahmed AO, van Vianen W, ten Kate MT, van de Sande WW, van Belkum A, Fahal AH, Verbrugh HA, Bakker-Woudenberg IA (2003) A murine model of Madurella mycetomatis eumycetoma. FEMS Immunol Med Microbiol 37(1):29–36

    Article  CAS  Google Scholar 

  50. Greenberg AK, Knapp J, Rom WN, Addrizzo-Harris DJ (2002) Clinical presentation of pulmonary mycetoma in HIV-infected patients. Chest 122(3):886–892

    Article  Google Scholar 

  51. van de Sande WW, Fahal A, Tavakol M, van Belkum A (2010) Polymorphisms in catechol-O-methyltransferase and cytochrome p450 subfamily 19 genes predispose towards Madurella mycetomatis-induced mycetoma susceptibility. Med Mycol 48(7):959–968

    Article  CAS  Google Scholar 

  52. Kuijpers TW (2002) Clinical symptoms and neutropenia: the balance of neutrophil development, functional activity, and cell death. Eur J Pediatr 161(Suppl 1):S75–82

    Article  CAS  Google Scholar 

  53. Newport MJ, Finan C (2011) Genome-wide association studies and susceptibility to infectious diseases. Brief Funct Genomics 10(2):98–107

    Article  CAS  Google Scholar 

  54. Shugart YY, Wang Y, Jia WH, Zeng YX (2011) GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases. Chin J Cancer 30(4):226–230

    Article  CAS  Google Scholar 

  55. Zhang J, Chiodini R, Badr A, Zhang G (2011) The impact of next-generation sequencing on genomics. J Genet Genomics 38(3):95–109

    Article  Google Scholar 

  56. Ostergaard P, Simpson MA, Jeffery S (2011) Massively parallel sequencing and identification of genes for primary lymphoedema: a perfect fit. Clin Genet 80(2):110–116

    Article  CAS  Google Scholar 

  57. Morelli G, Song Y, Mazzoni CJ, Eppinger M, Roumagnac P, Wagner DM, Feldkamp M, Kusecek B, Vogler AJ, Li Y, Cui Y, Thomson NR, Jombart T, Leblois R, Lichtner P, Rahalison L, Petersen JM, Balloux F, Keim P, Wirth T, Ravel J, Yang R, Carniel E, Achtman M (2010) Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat Genet 42(12):1140–1143

    Article  CAS  Google Scholar 

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Acknowledgements

Mycetoma research in Wendy van de Sande’s laboratory was facilitated by a grant in the VENI program provided by the Netherlands Organisation for Scientific Research (NWO).

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Authors and Affiliations

  1. bioMérieux, Microbiology Unit, La Balme-Les-Grottes, France

    Alex Van Belkum

  2. Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan

    Ahmed Fahal

  3. Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands

    Wendy W.J. van de Sande

Authors
  1. Alex Van Belkum
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  2. Ahmed Fahal
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  3. Wendy W.J. van de Sande
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Corresponding author

Correspondence to Alex Van Belkum .

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Editors and Affiliations

  1. Royal Children's Hospital, Dept. Pediatrics, University of Melbourne, Flemington Road, Parkville, 3052, Victoria, Australia

    Nigel Curtis

  2. Institute of Child Life and Health, UBHT Education Centre, University of Bristol, Upper Maudlin Street, Bristol, BS28AE, UK

    Adam Finn

  3. University of Oxford, Level 4,John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Andrew J. Pollard

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Van Belkum, A., Fahal, A., van de Sande, W. (2013). Mycetoma Caused by Madurella mycetomatis: A Completely Neglected Medico-social Dilemma. In: Curtis, N., Finn, A., Pollard, A. (eds) Hot Topics in Infection and Immunity in Children IX. Advances in Experimental Medicine and Biology, vol 764. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4726-9_15

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