Bille, Jacques

Calandra, Thierry

Marchetti, Oscar

Senn, Laurence

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CORRESPONDENCE • CID 2008:47 (15 July) • 293given for approximately one-fifth of epi-sodes of febrile neutropenia. Interestingly,recovery of neutropenia occurred withina median of 11 days after fever onset, andpeak b-glucan levels for IC occurred aftera median of 12 days after fever onset. He-patosplenic candidosis caused the presen-tation of all but 1 case of IC. Because flu-conazole is not active against Aspergillusspecies, these data suggest that the use offluconazole might have influenced thesensitivity of b-glucan testing (only 1 caseof candidemia was detected) and the timefor the b-glucan test to reach its zenith.AcknowledgmentsPotential conflicts of interest. All authors: noconflicts.Alessandro C. Pasqualotto1,2and Teresa C. T. Sukiennik11Infection Control Department,Santa Casa Complexo Hospitalar, and 2UniversidadeFederal do Rio Grande do Sul, Porto Alegre, BrazilReferences1. Senn L, Robinson JO, Schmidt S, et al. 1,3-b-d-Glucan antigenemia for early diagnosis of in-vasive fungal infections in neutropenic patientswith acute leukemia. Clin Infect Dis 2008; 46:878–85.2. Herbrecht R, Berceanu A. b-Glucan detectiontest: a step toward preemptive therapy for fun-gal infections in leukemic patients? Clin InfectDis 2008; 46:886–9.3. Ostrosky-Zeichner L, Alexander BD, Kett DH,et al. Multicenter clinical evaluation of the(1r3) b-d-glucan assay as an aid to diagnosisof fungal infections in humans. Clin Infect Dis2005; 41:654–9.Reprints or correspondence: Dr. Alessandro C. Pasqualotto,Servic¸o de Controle de Infecc¸a˜o Hospitalar, Hospital DomVicente Scherer, 7 Andar, Santa Casa Complexo Hospitalar,Av. Independeˆncia 75, 90035-075, Porto Alegre, Brazil(pasqualotto@santacasa.tche.br).Clinical Infectious Diseases 2008; 47:292–3 2008 by the Infectious Diseases Society of America. Allrights reserved. 1058-4838/2008/4702-0026$15.00DOI: 10.1086/589571Reply to Pasqualottoand SukiennikTo the Editor—We thank Pasqualottoand Sukiennik [1] for their interestingcomments regarding our publicationabout 1,3-b-d-glucan (BG) antigenemiafor the early diagnosis of invasive asper-gillosis (IA) and candidiasis (IC) in neu-tropenic patients [2]. Because of the mor-bidity and mortality of these infections,early antifungal therapy is critical. A non-invasive monitoring tool that detects bothAspergillus and Candida species is an at-tractive approach. A positive result of thescreening test may trigger further inves-tigations and preemptive antifungal ther-apy. Our results suggest that BG may fulfillthis goal. Although BG does not differ-entiate IA from IC, combination of BGdata with imaging, culture, and histopath-ologic data allows an etiological diagnosisin most cases. Moreover, in patients withpositive screening results for BG, genus-specific fungal markers (i.e., galactoman-nan for Aspergilus species [3] and man-nan/antimannan for Candida species [4])may contribute to the differentiation of IAfrom IC. Because several treatment op-tions that are active against both fungi arenow available, therapeutic decisions areless dependent on an immediate etiolog-ical diagnosis [5]. A positive BG result maytrigger the initiation of antifungal therapy.The complementary investigations maythen allow its adjustment. The similaroverall survival rates for patients with IA(93%) and IC (89%) in our study supportthe efficacy of the initial empirical anti-fungal strategy.With regard to the diagnostic perfor-mance of BG, we observed similar sensi-tivities, specificities, and positive and neg-ative predictive values for IA (0.60, 0.96,0.64, and 0.95, respectively) and IC (0.59,0.96, 0.67, and 0.94, respectively). The me-dian time elapsed from fever onset to pos-itive BG result was also similar (mediantime, 0 days; range, 25 to 19 days forIA, median time, 2 days, range 1 to 16days for IC). These results support the ef-ficiency of BG for early detection of bothIA and IC. However, as pointed out byPasqualotto and Sukiennik [1], the me-dian time to the peak BG level in IA (me-dian time, 3 days; range, 25 to 25 days)was possibly shorter than for IC (mediantime, 12 days; range, 1–46 days). The ki-netics of other fungal markers is influ-enced by the timing of antifungal therapy.Ongoing treatment or prophylaxis may re-sult in early and low peaks, whereas latestart is associated with delayed and higherpeaks [6]. In our study, the use of a Can-dida-specific prophylaxis (fluconazole inone-fourth of IA and IC cases) did notresult in a higher BG sensitivity in IA thanin IC. Moreover, the median time elapsedfrom fever onset to initiation of antifungaltherapy was similar for IA (median time,1 day; range,13 to 13 days) and IC (me-dian time, 3 days; range, 0–10 days). Onemight speculate that the early peak in IAand later peak in IC could reflect differentpathogeneses. The microbial load may in-deed differ: single pulmonary lesions weredocumented in IA, whereas multiple he-patosplenic lesions suggesting hematoge-nous dissemination were documented inIC. It remains to be determined whetherthe concomitance of late BG peak andneutrophil recovery in IC might reflect thereaction induced by the immune resto-ration typically associated with the radi-ological appearance of organ abscesses.Because of the small sample size, no firmconclusion can be drawn from our study[2] about the different kinetics of BG inIA and IC.AcknowledgmentsFinancial support. Wako Pure ChemicalIndustries.Potential conflicts of interest. All authors: noconflicts.Laurence Senn, Thierry Calandra,Jacques Bille, and Oscar MarchettiInfectious Diseases Service, Department ofMedicine and Institute of Microbiology,Centre Hospitalier Universitaire Vaudoisand University of Lausanne, SwitzerlandReferences1. Pasqualotto AC, Sukiennik TCT. b-Glucan inthe diagnosis of invasive fungal disease. ClinInfect Dis 2008; 47:292–3 (in this issue).2. Senn L, Robinson JO, Schmidt S, et al. 1,3-b-d-glucan antigenemia for early diagnosis of in-vasive fungal infections in neutropenic patientswith acute leukemia. Clin Infect Dis 2008; 46:878–85.3. Maertens J, Verhaegen J, Lagrou K, Van EJ,Boogaerts M. Screening for circulating galac-tomannan as a noninvasive diagnostic tool for294 • CID 2008:47 (15 July) • CORRESPONDENCEinvasive aspergillosis in prolonged neutropenicpatients and stem cell transplantation recipi-ents: a prospective validation. Blood 2001; 97:1604–10.4. Prella M, Bille J, Pugnale M, et al. Early diag-nosis of invasive candidiasis with mannan an-tigenemia and antimannan antibodies. DiagnMicrobiol Infect Dis 2005; 51:95–101.5. Marchetti O, Cordonnier C, Calandra T. Em-pirical antifungal therapy in neutropaenic can-cer patients with persistent fever. Eur J Cancer2007; 5(Suppl):32–42.6. Marr KA, Laverdiere M, Gugel A, LeisenringW. Antifungal therapy decreases sensitivity ofthe Aspergillus galactomannan enzyme immu-noassay. Clin Infect Dis 2005; 40:1762–9.Reprints or correspondence: Dr. Oscar Marchetti, InfectiousDiseases Service, Dept. of Medicine, Centre Hospitalier Univ-ersitaire Vaudois and University of Lausanne, Rue du Bugnon46, CH-1011 Lausanne, Switzerland (Oscar.Marchetti@chuv.ch).Clinical Infectious Diseases 2008; 47:293–4 2008 by the Infectious Diseases Society of America. Allrights reserved. 1058-4838/2008/4702-0027$15.00DOI: 10.1086/589572Dr. William H. Stewart:Mistaken or Maligned?To the Editor—Dr. William H. Stewartwas the US Surgeon General during 1965–1969 [1]. Despite his significant accom-plishments, Dr. Stewart is rememberedprimarily for his infamous statement: “Itis time to close the book on infectiousdiseases, and declare the war against pes-tilence won” [2]. Depending on thesource, the quote is dated to 1967 or 1969.Infectious diseases specialists, includingmyself [3, 4], have repeated this quote in-numerable times to underscore howwrong it was.I have spent the past 5 years seeking theprimary source for his often-malignedquote, with no success. And I am not theonly one. The US Public Health ServiceWeb site informs us that “Although thisremark has often been cited in the liter-ature, the Office of the PHS Historian hasnever been able to locate the source of thestatement, or to confirm that Dr. Stewartactually made such a comment. We haveasked Dr. Stewart about it, and he cannotrecall whether or not he made this state-ment” [2].Virtually every reference to the state-ment is a secondary citation, and many ofthese secondary citations are circular (i.e.,they reference one another rather than aprimary source). The only primary ref-erence to this statement, listed in a bookabout emerging infections [5], regards aspeech given by Dr. Stewart at the 65thAnnual Meeting of the Association of Stateand Territorial Health Officers in 1967 [6].However, the speech contains nothingeven remotely resembling the allegedquote. Quite to the contrary, Dr. Stewartactually said, “Warning flags are still flyingin the communicable disease field….While we are engaged in taking on newduties…we cannot and must not lose sightof our traditional program responsibili-ties” (p. 4).It is difficult to believe that a SurgeonGeneral who was concerned about the tra-ditional public health responsibility to de-fend against communicable diseaseswould declare that the era of infectiousdiseases had come to a close. It appearsthat Dr. Stewart’s now-legendary quotemay be a medical “urban legend.”Nevertheless, Dr. Anthony Fauci has as-sured us that the belief that infectious dis-eases had been conquered was widespreadin the 1960s and 1970s [7]. Furthermore,in 1978, one of the world’s leaders in in-fectious diseases, Dr. Robert Petersdorf,commented that, “Even with my greatpersonal loyalty to Infectious Disease, Icannot conceive of the need for 309 more[graduating trainees in] infectious dis-ease…unless they spend their time cul-turing each other” [8, p. 630]. As late as1985, Dr. Petersdorf had not changed hismind; at the Infectious Diseases Society ofAmerica’s annual meeting that year, hestated that “the millennium where fellowsin infectious disease will culture one an-other is almost here” [9].If anyone is aware of a real primarycitation to Dr. Stewart’s quote, I and oth-ers would be extremely interested in hear-ing from you. Failing that, perhaps it istime to replace Dr. Stewart’s possiblyapocryphal quotation with citations fromverifiable sources, such as Dr. Fauci [7] orDr. Petersdorf [8, 9].AcknowledgmentsPotential conflicts of interest. B.S.: noconflicts.Brad Spellberg1,21Division of Infectious Diseases and 2David GeffenSchool of Medicine, Harbor–University of CaliforniaLos Angeles, Torrance, CaliforniaReferences1. US Department of Health & Human Services.Office of the Surgeon General: William H.Stewart (1965–1969). 4 January 2007. Availableat:http://www.surgeongeneral.gov/library/history/biostewart.htm. Accessed 4 January 2007.2. The Office of the Public Health Service His-torian. Frequently asked questions. 7 December2004. Available at: http://lhncbc.nlm.nih.gov/apdb/phsHistory/faqs.html.3. Spellberg B, Guidos R, Gilbert D, et al. Theepidemic of antibiotic-resistant infections: a callto action for the medical community from theInfectious Diseases Society of America. Clin In-fect Dis 2008; 46:155–64.4. Spellberg B, Powers JH, Brass EP, Miller LG,Edwards JE. Trends in antimicrobial drug de-velopment: implications for the future. Clin In-fect Dis 2004; 38:1279–86.5. Garrett L. The coming plague: newly emergingdiseases in a world out of balance. New York:Penguin, 1995.6. Stewart WH. A mandate for state action. In:Proceedings of the 65th Annual Meeting of theAssociation of State and Territorial Health Of-ficers (Washington, DC). Association of State& Territorial Health Officers, 1967.7. Fauci AS. Infectious diseases: considerationsforthe 21st century. Clin Infect Dis 2001; 32:675–85.8. Petersdorf RG. The doctors’ dilemma. N EnglJ Med 1978; 299:628–34.9. Petersdorf RG. Whither infectious diseases?Memories, manpower, and money. J Infect Dis1986; 153:189–95.Reprints or correspondence: Dr. Brad Spellberg, 1124 W.Carson St., RB2, Torrance, CA 90502 (bspellberg@labiomed.org).Clinical Infectious Diseases 2008; 47:294 2008 by the Infectious Diseases Society of America. Allrights reserved. 1058-4838/2008/4702-0028$15.00DOI: 10.1086/589579Confounding May Leadto Overestimation ofPneumococcalPolysaccharide VaccineEffectiveness amongHIV-Infected IndividualsTo the Editor—In a recently publishedobservational study, Rodriguez-Barradaset al. [1] found that vaccination of HIV-

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