Invasive aspergillosis

A 14 year review of autopsies in a German teaching hospital with a high autopsy rate (70%) and use of specific stains for invasive fungal infection, showed that 60% of those with invasive disease at autopsy were not diagnosed before death (Groll et al). In a prominent US cancer hospital, autopsy-proven invasive fungal infections from 1989 to 2003 showed that most (75%) were not diagnosed antemortem by using standard methods and criteria (Chamilos et al). Cultures for Aspergillus and similar moulds were negative in 60% of the cases.

Candidaemia and invasive candidiasis

The clearest demonstration of the underdiagnosis of invasive (tissue) candidiasis was demonstrated with the high volume blood culture system (Lysis centrifugation) in 1993 (Berenguer et al). In an autopsy study in which Candida was demonstrated histologically, the number of blood cultures collected prior to death was analysed. In those with single organ invasive candidiasis, only 5 of 18 (28%) patients had a positive blood culture, whereas 11 of 19 (58%) with disseminated candidiasis were positive. Others have echoed these conclusions (Yeo et al). Consequently, candidaemia represents a small fraction of the total number of patients with invasive tissue candidiasis. 

The issue is further complicated by antifungal treatment or prophylaxis which often obscures the diagnosis. This was recently shown in a large autopsy study from Japan in which only 20 of 94 (21%) patients with invasive candidiasis had a positive blood cultures and antifungal prophylaxis played a major part in underdiagnosis (p=0.018 in a multivariate analysis; Kami et al).

Underdiagnosis in the UK

Nationally candidaemia/invasive candidiasis cases have risen from 344 in the early 1990's to 1645 in 2004 (blood culture positive). There were 494 finished consultant episodes for aspergillosis nationally in 2003/4 with 45 deaths. However predicted caseload is substantially higher (click here to view data on invasive fungal infections in UK: select table 1).

The observed gap between actual reported cases and predicted cases is highly likely to be a problem of underdiagnosis or case ascertainment.

References

Berenguer J, Buck M, Witebsky F, Stock F, Pizzo PA, Walsh TJ. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis 1993;17:103-9.

Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, Safdar A, Raad II, Kontoyiannis DP. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). Haematologica 2006;91:986-9. 

Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G, Huebner K. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 1996;33:23-32.

Kami M, Machida U, Okuzumi K, Matsumura T, Mori Si S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y. Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Br J Haematol. 2002;117:40-6.

Yeo SF, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections. Clin Microbiol Rev 2000; 15: 465-484.