白血病（ MDS を含む） 剖検例における内臓真菌症の疫学

1 Jpn. J. Med. Mycol. Vol. 47, 15 24, 2006. ISSN 0916 4804.. MDS . 1990, 1994, 1998, 2002 . 1 2 3. 4 1 1. 1 . 2 . 3 . 4 . 8 29 , 2005 . 11 9 , 2005 .. MDS , . , . , 435. /1,557 , 1989 , 319 /1,388 , 1993 , 246 /1,105 , 1997 , 260 /1,037. , 2001 , , , .. , MDS .. , , , , . GVHD 1989 , .. Candida Aspergillus , 1989 , . , 2001 , , . , GVHD . Key words: deep seated mycoses . , autopsy cases . , epidemiology . , leukemia . , myelodysplastic syndrome MDS , hematopoietic stem cell transplantation . , .. , . , Fig. 1 .. , , Fig. 1 , . , . Miyake 1948 1961 1 , Kanda , . 2 1958 1969 , Hotchi 5 . 1966 1975 3 , 1972 MDS, myelodysplastic syndrome . 1981 4 , , 1989 , 1993 , 1997 .. 2001 . , Yamazaki 5 Kume 6 . 1989 , 1990 , , .. 1994 , 1997 , . 2001 1989, 1993, 1997 2001 .. 7 . 1990 , , 32 1990 , 36 1994 8 , 9 10 . 40 1998 44 2002 .. 228-8555 1-15-1 . , .. 16 47 1 18.

2 5. Total mycoses Aspergillus Candida 4 Cryptococcus Zygomycetes Other % of mycoses 3. 2. 1. 0. 1969 1973 1977 1981 1985 1989 1993 1997 2001. year Fig. 1. Changes in rate of mycoses among total autopsy cases and of causative agents of mycoses from 1969 to 2001 in Japan Cases of stillborn babies were excluded from the annual autopsy cases. Visceral mycoses increased noticeably from in 1969 and peaked at in 1990, with incidences of candidosis and aspergillosis showed the greatest increase. Since 1990, however, the frequency of visceral mycoses has decreased gradually. Until 1989, the predominant causative agent was Candida followed in order by Aspergillus and Cryptococcus. Although the rate of candidosis has decreased by degrees from 1990, the rate of aspergillosis increased and surpassed that of candidosis in 1991. Aspergillosis increased conspicuously in 1997 Aspergillus , Candida and in 2001, the rate was even higher Aspergillus , Candida.

3 1 . , , , , , , , 1.. , . , , , 2.. , , , 3. , 4. , 5.. GVHD, The graft-versus-host , 6.. disease 2 , 3 . Filemaker Pro version , Claris . , , Co. , . , , 4 . , , , , . A , 59 , B , 89 5 . , No. , .. 35 No. , , , . , .. 10, , . , . , , , , GVHD . , , . , , T , Table 1 . 435 /1,557 , , , NK 1989 , 319 /1,388 , 1993 , . 11 . , 246 /1,105 , 1997 260 /1,037. , 2001 , . , . , , . Jpn. J. Med. Mycol. Vol. 47 No. 1 , 2006 17. Table 1. Annual frequencies of visceral mycoses and of mycoses without or with leukemia and myelodysplastic syndrome MDS , and mycoses rate in transplantation recipients and in GVHD with leukemia and MDS among the total autopsy cases for the years 1989, 1993, 1997 and 2001*. Total autopsy cases Year* 1989 1993 1997 2001. Autopsy cases Total no. of autopsies 37,557 31,027 26,681 25,459. Total with infection of total 1,673 1,136 1,143 1,165.

4 With monopathogen infection 1,587 1,096 1,106 1,125 . with complicated infection** 86 40 37 40 . Autopsy cases except leukemia and MDS. Year* 1989 1993 1997 2001. Total no. of autopsies 36,000 29,819 25,576 24,422. Total with infection s of total 1,238 817 897 905 . with monopathogen infection 1,186 799 872 877 . with complicated infection** 52 18 25 28 . Autopsy cases with leukemia and MDS. Year* 1989 1993 1997 2001. Total no. of autopsies 1,557 1,388 1,105 1,037. Total with infection s of total 435 319 246 260 . with monopathogen infection 400 297 235 248 . with complicated infection** 35 22 11 12 . Total no of cases with trasplantation 30 62 72 119. with total infection s of total 11 21 27 39 . Total no of cases with GVHD 7 16 22 30. with total infection s of total 1 7 8 13 . *, Annual of the Pathological Autopsy Cases in Japan references, 7, 8, 9 and 10.

5 Cases of stillborn babies were excluded from the annual autopsy cases. **, Mixed infection with more than two kinds of fungi in the infected organ. GVHD, graft-versus-host disease. Table 2 - 1. Annual frequencies of visceral mycoses in cases with leukemia and MDS by causative agents Number of cases* frequency rate . Agent 1989 1993 1997 2001. Aspergillus 145/435. 142/319. 125/246. 141/260.. Candida 146/435. 71/319. 56/246. 44/260.. Cryptococcus 12/435. 3/319 3/246 5/260 . Zygomycetes 25/435. 24/319. 17/246. 24/260.. Other 3/435 1/319 1/246 1/260 . Unknown** 69/435. 56/319. 33/246. 33/260.. Complicated** 35/435. 22/319. 11/246. 12/260.. Total 435/435. 100 319/319. 100 246/246. 100 260/260. 100 . * Cases of stillborn babies were excluded from the annual autopsy cases. ** An unidentified fungus was observed in the infected organ. ** Mixed infection with two or more kinds of fungi in the infected organ.

6 Table 2 - 2. Annual frequencies of visceral mycoses in transplantation recipients with leukemia and MDS by causative agents Number of cases* frequency rate . Agent 1989 1993 1997 2001. Aspergillus 3/11. 12/21. 12/27. 21/38.. Candida 3/11. 6/21 6/27 8/38 . Cryptococcus 0 0 0 0. Zygomycetes 0 1/21 2/27 3/38 . Other 0 0 1/27 0. Unknown** 5/11. 1/21 6/27 4/38 . Complicated** 0 1/21 0 2/38 . Total 11/11. 100 21/21. 100 27/27. 100 38/38. 100 . * Cases of stillborn babies were excluded from the annual autopsy cases. ** An unidentified fungus was observed in the infected organ. ** Mixed infection with two or more kinds of fungi in the infected organ. 18 47 1 18 . Table 2 - 3. Annual frequencies of visceral mycoses in cases with GVHD after transplantation in cases leukemia and MDS by causative agents Number of cases* frequency rate . Agent 1989 1993 1997 2001.

7 Aspergillus 1/1. 100 5/7. 7/8. 8/13.. Candida 0 1/7. 1/8. 2/13.. Cryptococcus 0 0 0 0. Zygomycetes 0 1/7. 0 0. Other 0 0 0 0. Unknown** 0 0 0 2/13.. Complicated** 0 0 0 1/13.. Total 1/1. 100 7/7. 100 8/8. 100 13/13. 100 . * Cases of stillborn babies were excluded from the annual autopsy cases. ** An unidentified fungus was observed in the infected organ. ** Mixed infection with two or more kinds of fungi in the infected organ.. , Table 3. Number of complicated mycoses cases with leukemia and MDS by causative agents*. , 30 /11. , 1989 , 21 /62 , 1993 , 27 Agents No. of cases . /72 , 1997 38 /119 , 2001 Aspergillus + Candida 53.. Candida + Zygomycetes 10.. Aspergillus + Zygomycetes 9.. , , GVHD Aspergillus + Cryptococcus 4.. , 1 / 7 , 1998 , 7 /16 Aspergillus + Trichosporon 2.. , 1993 , 8 /22 , 1997 , Trichosporon + unknown** 1.. Aspergillus + Zygomycetes + Cryptococcus 1.

8 13 /30 , 2001 , 1989 1997 . Total 80. 100 .. *, Data were compiled from Annual of the Pathological Autopsy Cases in Japan references, 7-10 . Cases of stillborn babies were excluded from the annual autopsy cases. Table 2 - 1, Table 2 - 2 Table 2 - 3 . **, An unidentified fungus was observed in the infected organ. Aspergillus . Candida 70 , . Zygomycetes , Cryptococcus Table 4 - 1. Proportion of severe infections for all mycoses with leukemia and MDS. , Trichosporon . No. of cases considered . Proportion Yr . , nonsevere severe*. Aspergillus 1989 179 256 256/435.. Candida , 1993 113 206 206/319.. 1997 60 186 186/246.. Zygomycetes 0 , 2001 92 168 168/260.. Trichosporon 0 , 3 . * Severe cases are defined in Materials and Methods the direct Aspergillus Candida 2 , Aspergillus Cryptococcus cause of death, infection involving both lobes of the lung, 1 Table 2 - 2.

9 , multiorgan systemic infection or fungemia etc . GVHD Aspergillus 100 , Candida 0 , Zygomycetes 0 Table , . 2 - 3 . Table 2 - 1 . , . , 1989 Table 2 - Aspergillus 145 /435 , Candida 2 , GVHD . 146 /435 , Table 2 - 3 . , . 1993 142 /319 , 2 . 71 /319 , 1997 125 Table 3 . /246 , 56 /246 , 2001 , 80 Aspergillus Candida . 141 /260 , 44 53 /80 , . /260 , Aspergillus Candida Candida Zygomycetes 10 /80 . , Aspergillus Jpn. J. Med. Mycol. Vol. 47 No. 1 , 2006 19. Zygomycetes 9 /80 , Aspergillus . Cryptococcus 4 /80 , Aspergillus Trichos- . poron 2 /80 , Trichosporon , Table 4 - 1 . 1 . , . 1989 256 /435 , 1993 . 80 3 Aspergillus, 206 /319 , 1997 186 /246 . Zygomycetes Cryptococcus 1 , 2001 . 168 /260 . Table 4 - 2. Proportion of severe infections in cases with , 1989 2001 . leukemia and MDS by causative agents in 1989 and 2001 . 1989 No. of cases considered Proportion Table 4 - 2.

10 1989 Aspergillus . Agent 82 /145 2001 96 /141 , nonsevere severe*. Zygomycetes 18 /25 . Aspergillus 63 82 82/145.. Candida 66 80 80/146. 19 /24 , 24 /35 . Cryptococcus 4 8 8/ 12. 10 /12 1989 2001 . Zygomycetes 7 18 18/ 25.. Other 1 2 2/ 3 . 11 15 . Unknown 27 42 42/ 69. , Candida 80 /146 19 . Complicated 11 24 24/ 35. /44 11 . Total 179 256 . 256/435 . No. of cases considered Table 5 . 2001 Proportion Agent . , . nonsevere severe*. 413 /768 , . Aspergillus 45 96 96/141.. , . Candida 25 19 19/ 44.. Cryptococcus 0 5 5/ 5 100 149 /614 , . Zygomycetes 5 19 19/ 24. 138 /614 , 84 /614 . Other 0 1 1/ 1 100 .. Unknown 15 18 18/ 33.. Complicated 2 10 10/ 12. 11 /47 7 . Total 92 168 . 168/260. /47 , 5 . /47 , . * Severe cases are defined in Materials and Methods the direct cause of death, infection involving both lobes of the lung, 68 /146 .. multiorgan systemic infection or fungemia etc.