- Email: [email protected]
Response to the letter from Drs Hudnell and Shoemaker
Microbes and Infection 5 (2003) 349–350 www.elsevier.com/locate/micinf
Response to the letter Response to the letter from Drs Hudnell and Shoemaker >,>>
In “Human health effects of exposure to Pfiesteria piscicida: a review,” [1], an exhaustive compilation of every publication with respect to the basic biology of the organism was not attempted. Background information was provided as a foundation for the focus on human health effects. Articles were chosen without regard to such concerns as order of authors. In the area of human health, articles were selected based upon the quality of the work and relevance to the discussion. The work of Hudnell and Shoemaker [2,3] was not referenced due to concerns about their methodology and their advocacy of a measure (visual contrast sensitivity (VCS)), which has never been validated in a verified PEAS case or in affected laboratory workers, the two populations in which health effects and exposures have been documented [4,5]. They use VCS as both a diagnostic test and as an indicator for pharmacologic intervention. The current “gold standard” to verify a PEAS case [6] consists of documenting the combination of history of exposure plus relevant symptoms, not explainable by other clinical conditions after a complete medical evaluation as per the 1999 CDC guidelines [7]. This evaluation process would include a physical examination, metabolic screen and a complete battery of neuropsychological (NP) testing. The presence of the specific pattern of NP deficits, previously reported in the literature [4,5], would constitute a verified case. Hudnell and Shoemaker have chosen not to use this paradigm. They do not use an accepted and clinically validated test of cognitive function to assess the deficits in memory and concentration that are the most unique, significant and potentially disabling symptoms reported related to Pfiesteria exposure. Rather, they have chosen to use an indirect and nonspecific test of central nervous system function. VCS can be affected by a broad range of common conditions affecting the central nervous system and the visual pathways. Its sensitivity, specificity and predictive value in this application have not been systematically evaluated or compared to NP testing. The reports they cite, as discussed below, suggest that VCS is frequently abnormal in situations where subjects have no complaints and no neuropsychologic impairments. My reservations about their work have been expressed previously, both directly and in writing [8–10]. Other authors have expressed similar concerns [11,12].
In the Virginia study that was cited [13], no toxic events or fish kills had occurred. No cases of PEAS were verified using the accepted paradigm. No unusual patterns on the neurocognitive tests were seen, but VCS deficits were found in isolation. The authors conclude: “It is difficult to fully interpret and understand the VCS results”. A similar conclusion was stated in the continuation work [14], where age was found to be the most significant predictor of VCS abnormalities. Smoking and time on PLO-bearing water were noted to “also contribute to some of the variance”. The results of the work that we conducted in association with Dr. Hudnell and coworkers [15] are misrepresented in stating that “potentially confounding factors were not responsible for the VCS deficit seen in watermen”. All potentially confounding factors were not investigated in sufficient depth or detail to support such a sweeping statement. As coordinator of that investigation, the limits of the data collected are quite familiar and are noted in the article. In another joint work [16], the VCS performance of the controls was worse than that of the subjects. All the eleven subjects had exposure consistent with the 1999 PEAS case description, which is the current case description and the one used by Drs. Hudnell and Shoemaker in their work [2]. The selection process for the age- and sex-matched controls is described in the original article. As VCS testing had never previously been applied in any Pfiesteria-related work, controls were certainly not prescreened for potential confounders of that test. That such confounders are so prevalent represents a significant problem in the author’s support of VCS as a screening and diagnostic test. In both the studies [15,16], there was no pattern of specific NP abnormalities found in either the cases or the control groups, despite the VCS abnormalities observed. The state of Maryland has verified five PEAS cases in their ongoing surveillance process and has reported these to the CDC in the past year, after the original submission of my review [6]. In this publication [11], the authors comment on the difficulty of environmental exposure assessment, “...it remains difficult to conclude that the symptoms reported by those meeting the PEAS criteria are related to the presence of Pfiesteria”. I am grateful to Drs. Hudnell and Shoemaker for pointing out an error in the numbering of some references. The references to the predictive value of RAVLT on page 75, first column of the review should be attributed to Golub et al. Maryland Med. J. 47 (1998) 137–143. Finally, my statement that Pfiesteria toxin “...has not been isolated and chemically characterized” (emphasis is mine)
350
Response to the letter / Microbes and Infection 5 (2003) 349–350
remains the case today in spite of intense, continuing research on bioactive substances related to the organism and its culture media [17]. The 2001 article by Moeller et al. [18] documents work in progress. The pivotal role of characterization of the toxin is widely recognized. A Harmful Algal Blooms Conference is scheduled for October 21–15, 2002 in St. Petersburg, FL. Peter Moeller and John Ramsdell’s group has submitted an abstract describing their work on a water-soluble toxin P.D.R. Moeller et al., Proceedings of the 10th International Conference on Harmful Algae, St. Petersburg, FL. (2002) 201. Presentation of “partial structural data” is anticipated [19]. Several articles of particular interest have been published on this topic over the spring and summer [20–23]. In Pfiesteria-related research, the analogy of the blind men and the elephant is most apropos. Moreover, as individual laboratories contribute a piece of the puzzle, the puzzle seems to grow in complexity. Respectfully, Marian Swinker, MD, MPH
References [1]
M. Swinker, P. Tester, D.K. Attix, D. Schmechel, Human health effects of exposure to Pfiesteria piscicida: a review, Microb. Infect. 4 (2002) 751–761. [2] R.C. Shoemaker, H.K. Hudnell, Possible estuaryassociated syndrome: symptoms, vision and treatment, Environ. Health Perspect. 109 (Suppl) (2001) 529–545. [3] R.C. Shoemaker, Residential and recreational acquisition of possible estuary associated syndrome: a new approach to successful diagnosis and treatment, Environ. Health Perspect. 109 (Suppl. 5) (2001) 791–796. [4] L. Grattan, D. Oldach, T.M. Perl, M.H. Lowitt, D.L. Matuszak, C. Dickson, C. Parrott, R.C. Shoemaker, C.L. Kauffman, M.P. Wasserman, et al., Learning and memory difficulties after environmental exposure to waterways containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates, Lancet. 253 (1998) 532–539. [5] H. Glasgow, D. Schmechel, P. Tester, P. Rublee, Insidious effects of a toxic estuarine dinoflagellate on fish survival and human health, J. Toxicol. Environ. Health 46 (1995) 501–522. [6] L. Backer, A. Niskar, C. Rubin, K. Blindauer, D. Christianson, L. Naeher, H. Shurz Rogers, Environmental public health surveillance: possible estuary-associated syndrome, Environ. Health Perspect. 109 (Suppl. 5) (2001) 797–801. [7] US Center for Disease Control, Possible estuary-associated syndrome, M.M.W.R. 48 (1999) 381–388. [8] M. Swinker, W. Burke, Visual contrast sensitivityas a diagnostic tool (letter), Environ. Health Perspect. 110 (2002) A120–A121. [9] H.K. Hudnell, R.C. Shoemaker, Visual contrast sensitivity: response, Environ. Health Perspect. 110 (2002) A121–A123. [10] M. Swinker, Visual contrast sensitivity: response to the response, Environ. Health Perspect. 11 (2003) A17–A19. [11] J.G. Morris, Human health effects and Pfiesteria exposure: a synthesis of available clinical data, Environ. Health Perspect. 109 (2001) 787–790.
[12] C. Rubin, M. McGeehin, A. Holmes, L. Backer, G. Burrison, M. Earley, D. Griffith, R. Levine, W. Litaker, J. Mei, L. Naeher, L. Needham, E. Noga, M. Poli, H. Shurz Rogers, Emerging areas of research reported during the CDC national conference on Pfiesteria: from biology to public health, Environ. Health Perspect. 109 (2001) 633–637. [13] E. Turf, L. Ingsrisawang, M. Turf, J.D. Ball, M. Stutts, J. Taylor, S. Jenkins, A cohort study to determine the epidemiology of estuaryassociated syndrome, Virginia J. Sci. 50 (1999) 299–310. [14] L. Ingrisawang, M.E. Turf, M. Johnson, K. Hudnell, L.A. Perpins, E.E. Turf, A study of Virginia watermen to examine the relationship between Pfiesteria-like organisms and visual contrast sensitivity, Abstract, Proceedings CDC National Conference on Pfiesteria From Biology to Public Health, Stone Mountain, GA, October 18–20, 2000. [15] M. Swinker, D. Koltai, J. Wilkins, K. Hudnell, C. Hall, D. Darcey, K. Robertson, D. Schmechel, W. Stopford, S. Music, Estuaryassociated syndrome in North Carolina: an occupational prevalence study, Environ. Health Perspect. 109 (2001) 21–26. [16] M. Swinker, D. Koltai, J. Wilkins, W. Stopford, Is there estuary associated syndrome in North Carolina: findings in a series of hotline callers, North Carolina Med. J. 12 (2001) 126–132. [17] M. Rouhi, Where’s the Pfiesteria toxin? Chem. Eng. News 80 (9) (2002). [18] P.D.R. Moeller, S.L. Morton, B.A. Mitchell, S.K. Sivertsen, E.R. Fairey, T.M. Mikulski, H. Glasgow, M.J. Deamer-Melia, J.M. Burkholder, J.S. Ramsdell, Current progress in isolation and characterization of toxins isolated form Pfiesteria piscicida, Environ. Health Perspect. 109 (Suppl. 5) (2001) 739–743. [19] J. Kaiser, News focus: the science of Pfiesteria: elusive, subtle and toxic, Science 298 (2002) 346–349. [20] A.S. Gordon, B.J. Dyer, D. Seaborn, H.G. Marshall, Comparative toxicity of Pfiesteria spp., prolonging toxicity of P. piscicida in culture and evaluation of toxin(s) stability, Harmful Algae 1 (2002) 85–94. [21] R.W. Litaker, M.W. Vandersea, S.R. Kibler, V.J. Madden, E.J. Noga, P.A. Tester, Life cycle of the neurotrophic dinoflagellate Pfiesteria piscicida (dinophyceae), J. Phycol. 38 (2002) 442–463. [22] W.K. Vogelbein, V.J. Lovko, J.D. Shields, K.S. Reece, P.L. Mason, L.W. Haas, C.C. Walker, Pfiesteria shumwayae kills fish by micropredation not exotoxin secretion, Nature 418 (2002) 967–970. [23] J.P. Berry, K.S. Reece, K.S. Rein, D.G. Baden, L.W. Haas, W.L. Ribeiro, J.D. Shiels, R.V. Synder, W.K. Vogelbein, R.E. Gawley, Are Pfiesteria species toxigenic? Evidence against production of ichthyotoxins by Pfiesteria shumwayae, Proc. Natl. Acad. Sci. USA 99 (2002) 10970–10975.
Marian Swinker * Offıce of Prospective Health, East Carolina University School of Medicine, Room 188, Warron Building, 600 Moye Blvd., Greenville, NC 27858, USA E-mail address: [email protected] * Corresponding author. Tel.: +1-252-816-2070; fax: +1-252-816-2417. >
PII of original article S1286457903000364.
>>
doi of original article S1286457903000364.
© 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. PII: S 1 2 8 6 - 4 5 7 9 ( 0 3 ) 0 0 0 3 7 - 6
Response to the letter Response to the letter from Drs Hudnell and Shoemaker >,>>
In “Human health effects of exposure to Pfiesteria piscicida: a review,” [1], an exhaustive compilation of every publication with respect to the basic biology of the organism was not attempted. Background information was provided as a foundation for the focus on human health effects. Articles were chosen without regard to such concerns as order of authors. In the area of human health, articles were selected based upon the quality of the work and relevance to the discussion. The work of Hudnell and Shoemaker [2,3] was not referenced due to concerns about their methodology and their advocacy of a measure (visual contrast sensitivity (VCS)), which has never been validated in a verified PEAS case or in affected laboratory workers, the two populations in which health effects and exposures have been documented [4,5]. They use VCS as both a diagnostic test and as an indicator for pharmacologic intervention. The current “gold standard” to verify a PEAS case [6] consists of documenting the combination of history of exposure plus relevant symptoms, not explainable by other clinical conditions after a complete medical evaluation as per the 1999 CDC guidelines [7]. This evaluation process would include a physical examination, metabolic screen and a complete battery of neuropsychological (NP) testing. The presence of the specific pattern of NP deficits, previously reported in the literature [4,5], would constitute a verified case. Hudnell and Shoemaker have chosen not to use this paradigm. They do not use an accepted and clinically validated test of cognitive function to assess the deficits in memory and concentration that are the most unique, significant and potentially disabling symptoms reported related to Pfiesteria exposure. Rather, they have chosen to use an indirect and nonspecific test of central nervous system function. VCS can be affected by a broad range of common conditions affecting the central nervous system and the visual pathways. Its sensitivity, specificity and predictive value in this application have not been systematically evaluated or compared to NP testing. The reports they cite, as discussed below, suggest that VCS is frequently abnormal in situations where subjects have no complaints and no neuropsychologic impairments. My reservations about their work have been expressed previously, both directly and in writing [8–10]. Other authors have expressed similar concerns [11,12].
In the Virginia study that was cited [13], no toxic events or fish kills had occurred. No cases of PEAS were verified using the accepted paradigm. No unusual patterns on the neurocognitive tests were seen, but VCS deficits were found in isolation. The authors conclude: “It is difficult to fully interpret and understand the VCS results”. A similar conclusion was stated in the continuation work [14], where age was found to be the most significant predictor of VCS abnormalities. Smoking and time on PLO-bearing water were noted to “also contribute to some of the variance”. The results of the work that we conducted in association with Dr. Hudnell and coworkers [15] are misrepresented in stating that “potentially confounding factors were not responsible for the VCS deficit seen in watermen”. All potentially confounding factors were not investigated in sufficient depth or detail to support such a sweeping statement. As coordinator of that investigation, the limits of the data collected are quite familiar and are noted in the article. In another joint work [16], the VCS performance of the controls was worse than that of the subjects. All the eleven subjects had exposure consistent with the 1999 PEAS case description, which is the current case description and the one used by Drs. Hudnell and Shoemaker in their work [2]. The selection process for the age- and sex-matched controls is described in the original article. As VCS testing had never previously been applied in any Pfiesteria-related work, controls were certainly not prescreened for potential confounders of that test. That such confounders are so prevalent represents a significant problem in the author’s support of VCS as a screening and diagnostic test. In both the studies [15,16], there was no pattern of specific NP abnormalities found in either the cases or the control groups, despite the VCS abnormalities observed. The state of Maryland has verified five PEAS cases in their ongoing surveillance process and has reported these to the CDC in the past year, after the original submission of my review [6]. In this publication [11], the authors comment on the difficulty of environmental exposure assessment, “...it remains difficult to conclude that the symptoms reported by those meeting the PEAS criteria are related to the presence of Pfiesteria”. I am grateful to Drs. Hudnell and Shoemaker for pointing out an error in the numbering of some references. The references to the predictive value of RAVLT on page 75, first column of the review should be attributed to Golub et al. Maryland Med. J. 47 (1998) 137–143. Finally, my statement that Pfiesteria toxin “...has not been isolated and chemically characterized” (emphasis is mine)
350
Response to the letter / Microbes and Infection 5 (2003) 349–350
remains the case today in spite of intense, continuing research on bioactive substances related to the organism and its culture media [17]. The 2001 article by Moeller et al. [18] documents work in progress. The pivotal role of characterization of the toxin is widely recognized. A Harmful Algal Blooms Conference is scheduled for October 21–15, 2002 in St. Petersburg, FL. Peter Moeller and John Ramsdell’s group has submitted an abstract describing their work on a water-soluble toxin P.D.R. Moeller et al., Proceedings of the 10th International Conference on Harmful Algae, St. Petersburg, FL. (2002) 201. Presentation of “partial structural data” is anticipated [19]. Several articles of particular interest have been published on this topic over the spring and summer [20–23]. In Pfiesteria-related research, the analogy of the blind men and the elephant is most apropos. Moreover, as individual laboratories contribute a piece of the puzzle, the puzzle seems to grow in complexity. Respectfully, Marian Swinker, MD, MPH
References [1]
M. Swinker, P. Tester, D.K. Attix, D. Schmechel, Human health effects of exposure to Pfiesteria piscicida: a review, Microb. Infect. 4 (2002) 751–761. [2] R.C. Shoemaker, H.K. Hudnell, Possible estuaryassociated syndrome: symptoms, vision and treatment, Environ. Health Perspect. 109 (Suppl) (2001) 529–545. [3] R.C. Shoemaker, Residential and recreational acquisition of possible estuary associated syndrome: a new approach to successful diagnosis and treatment, Environ. Health Perspect. 109 (Suppl. 5) (2001) 791–796. [4] L. Grattan, D. Oldach, T.M. Perl, M.H. Lowitt, D.L. Matuszak, C. Dickson, C. Parrott, R.C. Shoemaker, C.L. Kauffman, M.P. Wasserman, et al., Learning and memory difficulties after environmental exposure to waterways containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates, Lancet. 253 (1998) 532–539. [5] H. Glasgow, D. Schmechel, P. Tester, P. Rublee, Insidious effects of a toxic estuarine dinoflagellate on fish survival and human health, J. Toxicol. Environ. Health 46 (1995) 501–522. [6] L. Backer, A. Niskar, C. Rubin, K. Blindauer, D. Christianson, L. Naeher, H. Shurz Rogers, Environmental public health surveillance: possible estuary-associated syndrome, Environ. Health Perspect. 109 (Suppl. 5) (2001) 797–801. [7] US Center for Disease Control, Possible estuary-associated syndrome, M.M.W.R. 48 (1999) 381–388. [8] M. Swinker, W. Burke, Visual contrast sensitivityas a diagnostic tool (letter), Environ. Health Perspect. 110 (2002) A120–A121. [9] H.K. Hudnell, R.C. Shoemaker, Visual contrast sensitivity: response, Environ. Health Perspect. 110 (2002) A121–A123. [10] M. Swinker, Visual contrast sensitivity: response to the response, Environ. Health Perspect. 11 (2003) A17–A19. [11] J.G. Morris, Human health effects and Pfiesteria exposure: a synthesis of available clinical data, Environ. Health Perspect. 109 (2001) 787–790.
[12] C. Rubin, M. McGeehin, A. Holmes, L. Backer, G. Burrison, M. Earley, D. Griffith, R. Levine, W. Litaker, J. Mei, L. Naeher, L. Needham, E. Noga, M. Poli, H. Shurz Rogers, Emerging areas of research reported during the CDC national conference on Pfiesteria: from biology to public health, Environ. Health Perspect. 109 (2001) 633–637. [13] E. Turf, L. Ingsrisawang, M. Turf, J.D. Ball, M. Stutts, J. Taylor, S. Jenkins, A cohort study to determine the epidemiology of estuaryassociated syndrome, Virginia J. Sci. 50 (1999) 299–310. [14] L. Ingrisawang, M.E. Turf, M. Johnson, K. Hudnell, L.A. Perpins, E.E. Turf, A study of Virginia watermen to examine the relationship between Pfiesteria-like organisms and visual contrast sensitivity, Abstract, Proceedings CDC National Conference on Pfiesteria From Biology to Public Health, Stone Mountain, GA, October 18–20, 2000. [15] M. Swinker, D. Koltai, J. Wilkins, K. Hudnell, C. Hall, D. Darcey, K. Robertson, D. Schmechel, W. Stopford, S. Music, Estuaryassociated syndrome in North Carolina: an occupational prevalence study, Environ. Health Perspect. 109 (2001) 21–26. [16] M. Swinker, D. Koltai, J. Wilkins, W. Stopford, Is there estuary associated syndrome in North Carolina: findings in a series of hotline callers, North Carolina Med. J. 12 (2001) 126–132. [17] M. Rouhi, Where’s the Pfiesteria toxin? Chem. Eng. News 80 (9) (2002). [18] P.D.R. Moeller, S.L. Morton, B.A. Mitchell, S.K. Sivertsen, E.R. Fairey, T.M. Mikulski, H. Glasgow, M.J. Deamer-Melia, J.M. Burkholder, J.S. Ramsdell, Current progress in isolation and characterization of toxins isolated form Pfiesteria piscicida, Environ. Health Perspect. 109 (Suppl. 5) (2001) 739–743. [19] J. Kaiser, News focus: the science of Pfiesteria: elusive, subtle and toxic, Science 298 (2002) 346–349. [20] A.S. Gordon, B.J. Dyer, D. Seaborn, H.G. Marshall, Comparative toxicity of Pfiesteria spp., prolonging toxicity of P. piscicida in culture and evaluation of toxin(s) stability, Harmful Algae 1 (2002) 85–94. [21] R.W. Litaker, M.W. Vandersea, S.R. Kibler, V.J. Madden, E.J. Noga, P.A. Tester, Life cycle of the neurotrophic dinoflagellate Pfiesteria piscicida (dinophyceae), J. Phycol. 38 (2002) 442–463. [22] W.K. Vogelbein, V.J. Lovko, J.D. Shields, K.S. Reece, P.L. Mason, L.W. Haas, C.C. Walker, Pfiesteria shumwayae kills fish by micropredation not exotoxin secretion, Nature 418 (2002) 967–970. [23] J.P. Berry, K.S. Reece, K.S. Rein, D.G. Baden, L.W. Haas, W.L. Ribeiro, J.D. Shiels, R.V. Synder, W.K. Vogelbein, R.E. Gawley, Are Pfiesteria species toxigenic? Evidence against production of ichthyotoxins by Pfiesteria shumwayae, Proc. Natl. Acad. Sci. USA 99 (2002) 10970–10975.
Marian Swinker * Offıce of Prospective Health, East Carolina University School of Medicine, Room 188, Warron Building, 600 Moye Blvd., Greenville, NC 27858, USA E-mail address: [email protected] * Corresponding author. Tel.: +1-252-816-2070; fax: +1-252-816-2417. >
PII of original article S1286457903000364.
>>
doi of original article S1286457903000364.
© 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. PII: S 1 2 8 6 - 4 5 7 9 ( 0 3 ) 0 0 0 3 7 - 6