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Predictive period of incubation for Whipple's disease
Journal of Infection (2004) 49, 23–24
www.elsevierhealth.com/journals/jinf
Letter to the Editor Predictive period of incubation for Whipple’s disease Sir, We read with interest the publication of a cell free culture medium for Tropheryma whipplei recently published by Renesto et al. (2003).1 From the data in the article relating to the increase in the number of microbes (particles) during the third passage, we calculate the generation time as being 32.9 h using standard formulae based on the exponential growth phase.2 (See Addendum for calculation.) It is germane that an acute rise in temperature, often accompanied by an episode of hypotension within 12 h, following initial treatment of Whipple’s disease with penicillin, has been attributed to a Jarisch – Herxheimer reaction (JHr).3 – 6 On the basis that penicillin acts on the dividing cell, it will be expected that the maximum JHr will correspond to at least half its division time, if not earlier. This implies that the organisms are dividing at a similar rate in vivo as in vitro. If the analogy to syphilis is correct, where Treponema pallidum has a similar division time and if the rate of growth of T. whipplei, like T. pallidum during the early phase of the infection is not impeded by host defences,7 then we would predict a similar incubation period for Whipple’s disease of 3 – 4 weeks. This assumes that there will be a minimum infecting dose of 105 – 106 organisms/ml. Again if the analogy with syphilis is correct, there could be a spread of the incubation period from approximately 2 weeks to about 3 months. Discussion of the length of the incubation period has tended to be neglected as more attention has been paid to the manifestations of Whipple’s disease which may precede the clinical diagnosis by many years. For instance, George Whipple, who described the first case,8 noted that his patient had a 5-year history of an illness dominated by arthritis, fever, chronic cough, weight loss and diarrhoea before autopsy. An estimate of the incubation period may provide a useful start in the epidemiological search to find the sources of infection for Whipple’s
disease and the ecology and mode of acquisition of the causative bacterium.
Addendum Calculating the generation time If y ¼ number of organisms at the end of the time period x ¼ number of organisms at the beginning of the time period n ¼ number of generations where in the experiment x ¼ 2=43 £ 107 y ¼ 1:37 £ 1010 then in y ¼ x2n n¼
log y=x log10 2
Substituting log10 n¼
2:43 £ 107 1:3 £ 109 log10 2
! ¼
7:386 2 9:137 0:301
¼ T: 752 ¼ 5:82 generations Further if g ¼ the length of time it takes for the doubling of populations ¼ generation (division) time t ¼ the interval of time for which the above number of generations occurred where in the experiment t ¼ 8 days 172 h n ¼ 5:82 (see above) then g ¼ t=n substituting ¼
172 ¼ 32:99 h 5:82
Therefore, g ¼ 32:99 h
References 1. Renesto P, Crapoulet N, Ogata H, et al. Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet 2003;362:447—449. 2. Lamanna C, Mallette MF, Zimmerman LN. Basic bacteriology.
0163-4453/$30.00 Q 2004 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2004.02.002
24
3.
4.
5. 6. 7. 8.
Letter to the Editor
Its biological and chemical background, 4th ed. Baltimore: William Wilkins Company; 1973. pp. 377—378. Reed JI, Sipe JD, Wohlgethan JR, Doos WG, Canoso JJ. Response of the acute-phase reactants, C-reactive protein and serum amyloid A protein, to antibiotic treatment of Whipple’s disease. Arthritis Rheum 1985;28:352—355. Lopatin RN, Grossman ET, Horine J, Saeedi M, Sreenath B. Whipple’s disease in neighbors. J Clin Gastroenterol 1982;4: 223—226. Pastor BM, Geerken RG. Whipple’s disease presenting as pleuropericarditis. Am J Med 1973;55:827—831. Vellar ID, Niall JF, Davis NA, Hope R. Whipple’s disease: a report of two cases. Med J Aust 1974;1:661—663. Turner TB, Hollander DH. Biology of the treponematoses. Geneva: WHO; 1957. pp. 42—49. Whipple GH. A hitherto undescribed disease characterised
*Corresponding author.
anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Bull Johns Hopkins Hospital 1907;18:382—391.
Sani H. Aliyu, Hugo Ludlam, David J.M. Wright* Clinical Microbiology and Public Health Laboratory, Health Protection Agency, Addenbrooke’s Hospital, Cambridge CB2 2QW, UK E-mail address: [email protected] Accepted 18 February 2004 Available online 9 April 2004
www.elsevierhealth.com/journals/jinf
Letter to the Editor Predictive period of incubation for Whipple’s disease Sir, We read with interest the publication of a cell free culture medium for Tropheryma whipplei recently published by Renesto et al. (2003).1 From the data in the article relating to the increase in the number of microbes (particles) during the third passage, we calculate the generation time as being 32.9 h using standard formulae based on the exponential growth phase.2 (See Addendum for calculation.) It is germane that an acute rise in temperature, often accompanied by an episode of hypotension within 12 h, following initial treatment of Whipple’s disease with penicillin, has been attributed to a Jarisch – Herxheimer reaction (JHr).3 – 6 On the basis that penicillin acts on the dividing cell, it will be expected that the maximum JHr will correspond to at least half its division time, if not earlier. This implies that the organisms are dividing at a similar rate in vivo as in vitro. If the analogy to syphilis is correct, where Treponema pallidum has a similar division time and if the rate of growth of T. whipplei, like T. pallidum during the early phase of the infection is not impeded by host defences,7 then we would predict a similar incubation period for Whipple’s disease of 3 – 4 weeks. This assumes that there will be a minimum infecting dose of 105 – 106 organisms/ml. Again if the analogy with syphilis is correct, there could be a spread of the incubation period from approximately 2 weeks to about 3 months. Discussion of the length of the incubation period has tended to be neglected as more attention has been paid to the manifestations of Whipple’s disease which may precede the clinical diagnosis by many years. For instance, George Whipple, who described the first case,8 noted that his patient had a 5-year history of an illness dominated by arthritis, fever, chronic cough, weight loss and diarrhoea before autopsy. An estimate of the incubation period may provide a useful start in the epidemiological search to find the sources of infection for Whipple’s
disease and the ecology and mode of acquisition of the causative bacterium.
Addendum Calculating the generation time If y ¼ number of organisms at the end of the time period x ¼ number of organisms at the beginning of the time period n ¼ number of generations where in the experiment x ¼ 2=43 £ 107 y ¼ 1:37 £ 1010 then in y ¼ x2n n¼
log y=x log10 2
Substituting log10 n¼
2:43 £ 107 1:3 £ 109 log10 2
! ¼
7:386 2 9:137 0:301
¼ T: 752 ¼ 5:82 generations Further if g ¼ the length of time it takes for the doubling of populations ¼ generation (division) time t ¼ the interval of time for which the above number of generations occurred where in the experiment t ¼ 8 days 172 h n ¼ 5:82 (see above) then g ¼ t=n substituting ¼
172 ¼ 32:99 h 5:82
Therefore, g ¼ 32:99 h
References 1. Renesto P, Crapoulet N, Ogata H, et al. Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet 2003;362:447—449. 2. Lamanna C, Mallette MF, Zimmerman LN. Basic bacteriology.
0163-4453/$30.00 Q 2004 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2004.02.002
24
3.
4.
5. 6. 7. 8.
Letter to the Editor
Its biological and chemical background, 4th ed. Baltimore: William Wilkins Company; 1973. pp. 377—378. Reed JI, Sipe JD, Wohlgethan JR, Doos WG, Canoso JJ. Response of the acute-phase reactants, C-reactive protein and serum amyloid A protein, to antibiotic treatment of Whipple’s disease. Arthritis Rheum 1985;28:352—355. Lopatin RN, Grossman ET, Horine J, Saeedi M, Sreenath B. Whipple’s disease in neighbors. J Clin Gastroenterol 1982;4: 223—226. Pastor BM, Geerken RG. Whipple’s disease presenting as pleuropericarditis. Am J Med 1973;55:827—831. Vellar ID, Niall JF, Davis NA, Hope R. Whipple’s disease: a report of two cases. Med J Aust 1974;1:661—663. Turner TB, Hollander DH. Biology of the treponematoses. Geneva: WHO; 1957. pp. 42—49. Whipple GH. A hitherto undescribed disease characterised
*Corresponding author.
anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Bull Johns Hopkins Hospital 1907;18:382—391.
Sani H. Aliyu, Hugo Ludlam, David J.M. Wright* Clinical Microbiology and Public Health Laboratory, Health Protection Agency, Addenbrooke’s Hospital, Cambridge CB2 2QW, UK E-mail address: [email protected] Accepted 18 February 2004 Available online 9 April 2004