RE: Review of revised manuscript MYCO871

This is a re-review of this revised manuscript regarding a large case series of blastomycosis from Manitoba and northwestern Ontario. I will, therefore, not repeat my prior general comments.

The authors have addressed all of my previous concerns, either by manuscript revision or justification of sections of concern that were not changed.

Regarding the second reviewer’s point concerning changes in treatment over time effecting mortality, in the authors’ absence of treatment data, they could consider comparing the mortality rate for a more recent portion of the time period of their case series with that of the previous years.

Mortality for patients diagnosed with blastomycosis (1987-2004) Year Number of Cases Number (%) deaths 1987 3 0 1988 7 0 1989 11 0 1990 20 0 1991 7 2 (28.6) 1992 13 0 1993 14 0 1994 14 0 1995 15 4 (26.7) 1996 19 0 1997 15 1 (6.7) 1998 20 4 (20.0) 1999 38 0 2000 27 2 (7.4) 2001 37 6 (16.2) 2002 30 3 (10.0) 2003 20 2 (10.0) 2004 8 0

As the reviewer noted, data pertaining to the different types of therapy and patient outcomes are not available. It was suggested in the most recent review that mortality data be provided to determine if we could infer a survival improvement over the period of study. In the table above, we provide the percentage of deaths of patients for whom the diagnosis of blastomycosis was known, and who presented to the facilities from where data were collected. Although it may appear that the number of deaths from blastomycosis has diminished over time, it is important to note that bias may exist in the data that has been collected, as these cases are only those who presented to the health care facilities under study; we do not have a true appreciation of the denominator, because there are persons who develop blastomycosis who are not sufficiently ill to require admission to hospital, and there are those persons who may have had mild, self-limited infections who never presented to medical attention. It is therefore that we would prefer to not provide this information as part of the final manuscript.

One very minor point: new reference 41 was suggested regarding discussion of length of time from symptom onset until diagnosis. Thus, it is more appropriately cited six lines earlier (perhaps with reference 12) in addition to, or instead of, its present location.

As suggested, ref 41 also was cited 6 lines above the previous citation.

Overall, this paper is one of the largest case series yet reported and it should add to the literature regarding this enigmatic disease which is often associated with diagnostic delay.

Thank you.