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Eurosurveillance Monthly Release 2005: Volume 10/ Issue 3

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Eurosurveillance, Volume 10, Issue 3, 01 March 2005

Letter to the Editor

Bioterrorism, Glanders and melioidosis

Citation style for this article: Cheng AC, Dance DA, Currie BJ. Bioterrorism, Glanders and melioidosis. Euro Surveill. 2005;10(3):pii=528. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=528

Reply to letter

Letter to the Editor

We note with interest the recently published guidelines for management of melioidosis and glanders (1). We are clinicians with extensive experience with melioidosis in Australia and Thailand and would like to express our concern at a number of inaccuracies in these guidelines.

Although Burkholderia mallei and B. pseudomallei are closely related phylogenetically (2), they behave sufficiently differently epidemiologically and clinically to warrant separate descriptions. Their amalgamation has led to confusion; for example, ulceration and nodules in the nasal cavity are well described in human glanders, but less so in human melioidosis. Similarly, the unreferenced allusion to human-to-human transmission of glanders probably refers to melioidosis, which has been described rarely (3-5).

The bipolar staining characteristics of B. pseudomallei may be evident on Gram’s staining, but may also be confused with other gram negative bacilli, including Yersinia pestis. Microbiologists should also be aware that some biochemical test kits may potentially misidentify B. pseudomallei (6). The sniffing of plates is potentially dangerous; because of the potential for aerosolization, cultures should be handled in the laboratory at an appropriate level of containment (7,8).

In our experience, septicaemic illness is not characterized by photophobia, lacrimation or erythroderma, and rarely by a disseminated pustular reaction. Jaundice may occur but is more likely to indicate an alternative diagnosis such as leptospirosis; altered liver function is usually mild and is due to sepsis (9). Localized cutaneous infection is usually manifest as acute cellulitis or ulcers (10, 11). Parotid abscesses in children are only common in Thailand and have only been reported on one occasion in Australia (12, 13). Although the mortality of melioidosis in Thailand is between 40-50%, our experience suggests that aggressive intensive care results in a lower mortality of about 20% (11,14).

Where studies of natural infection have defined an incubation period of 1-21 days, infection with a high inoculum, such as following near-drowning or as might be expected following a bioterrorist attack, tends to result in shorter incubation periods, even as short as a few hours (15, 16). The incubation period of pulmonary disease is the same as for other manifestations of melioidosis. Apparent incubation periods as long as 62 years have also been reported in natural melioidosis (17,18). Chronic infection (defined as symptoms > 2 months) most commonly presents as pneumonia mimicking tuberculosis rather than that suggested (19).

The recommendations about treatment seem to imply that 6-12 months of intravenous antibiotics are required for pulmonary infections with these agents. Extensive published experience does not support this assertion. In Darwin, we have achieved low relapse rates and mortality using a minimum duration of 14 days of parenteral antibiotics, followed by oral cotrimoxazole alone for 12-20 weeks (11,19). Treatment of a similar duration is used in Thailand. Pneumonia is not known to be a risk factor for relapse (14,20). Prolonged intensive phase parenteral therapy is used generally only for deep-seated infections such as osteomyelitis, multiple undrained abscesses, or CNS infection.

Amoxicillin-clavulanate is not recommended as first-line eradication oral treatment for melioidosis unless cotrimoxazole and doxycycline are contraindicated, as it is associated with high relapse rates (21). Pharmacokinetic studies suggest that, if amoxicillin-clavulanate is to be used, dosing should be more frequent than standard regimens to ensure an appropriate level of clavulanate (22). Ciprofloxacin is neither active in vitro nor effective in vivo (23,24). There is limited experience with doxycyline in combination with ceftazidime in intensive phase therapy, and doxycyline monotherapy for eradication therapy is associated with a high rate of relapse (25).

We agree that there are few data on which to base recommendations regarding prophylaxis (26). We believe that cotrimoxazole offers the best hope of success on the basis of its therapeutic efficacy (27). We are unaware of experimental data supporting this recommendation.

Finally, the case definition of probable melioidosis as "severe unexplained febrile illness" and "severe respiratory illness" is unhelpful, and may include many other possible aetiological agents, including inhalational anthrax and pneumonic plague, as well as influenza and SARS. Caution should be exercised in using serological diagnosis; a rising titre is not likely to be useful in the acute situation, and background seropositivity is high in patients from endemic areas (28,29). No commercial serological test is available and serological test kits in development have not performed well in field evaluation studies (30,31).

Although we welcome the initiative taken to draft European guidelines, we would suggest that revision of the existing guidelines to correct these inaccuracies should be undertaken. Although the possibility of intentional release of B. pseudomallei is hopefully remote, cases of melioidosis in returned travellers from endemic areas occur sporadically (32) and these guidelines may well confuse clinicians caring for such patients.

Allen C. Cheng^a,b, David A.B. Dance^c, Bart J. Currie^a,d

^a Menzies School of Health Research, Charles Darwin University, Darwin, Australia,
^b Geelong Hospital, Barwon Health, Geelong, Australia,
^c Health Protection Agency, Plymouth, United Kingdom,
^d Northern Territory Clinical School, Flinders University, Darwin, Australia

Address for correspondence: Allen Cheng, email: allenc@menzies.edu.au

References

1. Bossi P, Tegnell A, Baka A, van Loock F, Hendriks J, Werner A, et al. Bichat guidelines for the clinical management of glanders and melioidosis and bioterrorism-related glanders and melioidosis. Euro Surveill 2004;9(12).

2. Godoy D, Randle G, Simpson AJ, Aanensen DM, Pitt TL, Kinoshita R, et al. Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. J Clin Microbiol 2003;41(5):2068-79.

3. Ralph A, McBride J, Currie BJ. Transmission of Burkholderia pseudomallei via breast milk in northern Australia. Pediatr Infect Dis J 2004;23(12):1169-71.

4. McCormick JB, Sexton DJ, McMurray JG, Carey E, Hayes P, Feldman RA. Human-to-human transmission of Pseudomonas pseudomallei. Ann.Intern.Med 1975;83:512-513.

5. Holland DJ, Wesley A, Drinkovic D, Currie BJ. Cystic fibrosis and Burkholderia pseudomallei: An emerging problem? Clin Infect Dis 2002;35:e138-40.

6. Inglis TJ, Chiang D, Lee GS, Chor-Kiang L. Potential misidentification of Burkholderia pseudomallei by API 20NE. Pathology 1998;30(1):62-4.

7. Ashdown LR. Melioidosis and safety in the clinical laboratory. J Hosp Infect 1992;21:301-306.

8. Dance DA, Smith MD, Wuthiekanun V, Walsh M, White NJ. Melioidosis and laboratory safety. J.Hosp.Infect. 1992;22:333-334.

9. Cheng AC, Jacups SP, Anstey NM, Currie BJ. A proposed scoring system for predicting mortality in melioidosis. Trans R Soc Trop Med Hyg 2003;97(5):577-81.

10. Currie BJ, Carapetis JR. Skin infections and infestations in Aboriginal communities in northern Australia. Australas J Dermatol 2000;41(3):139-43; quiz 144-5.

11. Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, et al. Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 2000;31(4):981-6.

12. Dance DA, Davis TM, Wattanagoon Y, Chaowagul W, Saiphan P, Looareesuwan S, et al. Acute suppurative parotitis caused by Pseudomonas pseudomallei in children. J Infect Dis 1989;159:654-660.

13. Faa AG, Holt PJ. Melioidosis in the Torres Strait Islands of Far North Queensland. Commun Dis Intell 2002;26(2):279-283.

14. White NJ. Melioidosis. Lancet 2003;361(9370):1715-22.

15. Currie BJ, Fisher DA, Howard DM, Burrow JN, Selvanayagam S, Snelling PL, et al. The epidemiology of melioidosis in Australia and Papua New Guinea. Acta Trop 2000;74(2-3):121-7.

16. Lee N, Wu JL, Lee CH, Tsai WC. Pseudomonas pseudomallei infection from drowning: the first reported case in Taiwan. J Clin Microbiol 1985;22:352-354.

17. Chodimella U, Hoppes WL, Whalen S, Ognibene AJ, Rutecki GW. Septicemia and suppuration in a Vietnam veteran. Hosp Pract 1997;32(5):219-21.

18. Ngauy V, Lemeshev Y, Sadkowski L, Crawford G. Cutaneous melioidosis in a man who was taken as a prisoner of war by the Japanese during World War II. J Clin Microbiol 2005;43(2):970-2.

19. Currie BJ, Fisher DA, Anstey NM, Jacups SP. Melioidosis: acute and chronic disease, relapse and re-activation. Trans R Soc Trop Med Hyg 2000;94:301-4.

20. Chaowagul W, Suputtamongkol Y, Dance DA, Rajchanuvong A, Pattara-arechachai J, White NJ. Relapse in melioidosis: incidence and risk factors. J Infect Dis 1993;168(5):1181-1185.

21. Rajchanuvong A, Chaowagul W, Suputtamongkol Y, Smith MD, Dance DAB, White NJ. A prospective comparison of co-amoxiclav and the combination of chloramphenicol, doxycycline, and co-trimoxazole for the oral maintenance treatment of melioidosis. Trans R Soc Trop Med Hyg 1995;89:546-549.

22. Dance DA, Wuthiekanun V, Chaowagul W, White NJ. The activity of amoxycillin/clavulanic acid against Pseudomonas pseudomallei. J Antimicrob Chemother 1989;24(6):1012-4.

23. Chetchotisakd P, Chaowagul W, Mootsikapun P, Budhsarawong D, Thinkamrop B. Maintenance therapy of melioidosis with ciprofloxacin plus azithromycin compared with cotrimoxazole plus doxycycline. Am J Trop Med Hyg 2001;64(1-2):24-7.

24. Chaowagul W, Suputtamongkol Y, Smith MD, White NJ. Oral fluoroquinolones in the maintenance treatment of melioidosis. Trans R Soc Trop Med Hyg 1997;91:599-601.

25. Chaowagul W, Simpson AJ, Suputtamongkol Y, Smith MD, Angus BJ, White NJ. A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis. Clin Infect Dis 1999;29(2):375-80.

26. Russell P, Eley SM, Ellis J, Green M, Bell DL, Kenny DJ, et al. Comparison of efficacy of ciprofloxacin and doxycycline against experimental melioidosis and glanders. J Antimicrob Chemother 2000;45(6):813-8.

27. Laboratory exposure to Burkholderia pseudomallei--Los Angeles, California, 2003. MMWR Morb Mortal Wkly Rep 2004;53(42):988-90.

28. Kanaphun P, Thirawattanasuk N, Suputtamongkol Y, Naigowit P, Dance DA, Smith MD, et al. Serology and carriage of Pseudomonas pseudomallei: a prospective study in 1000 hospitalized children in northeast Thailand. J Infect Dis 1993;167:230-233.

29. Ashdown LR. Indirect haemagglutination test for melioidosis. Med J Aust 1987;147:364-365.

30. O'Brien M, Freeman K, Lum G, Cheng AC, Jacups SP, Currie BJ. Further evaluation of a rapid diagnostic test for melioidosis in an area of endemicity. J Clin Microbiol 2004;42(5):2239-40.

31. Wuthiekanun V, Amornchai P, Chierakul W, Cheng AC, White NJ, Peacock SJ, et al. Evaluation of immunoglobulin M (IgM) and IgG rapid cassette test kits for diagnosis of melioidosis in an area of endemicity. J Clin Microbiol 2004;42(8):3435-7.

32. Currie BJ. Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions. Eur Respir J 2003;22(3):542-50.

Reply to letter

Bioterrorism, glanders and melioidosis

We have read with great interest the letter from Cheng et al. relating to the publication of the Bichat guidelines for the clinical management of glanders and melioidosis and bioterrorism-related glanders and melioidosis.
As mentioned in the article title, the main objective of those clinical guidelines was to describe, as exhaustively as possible, the clinical features of patients infected by agents due to deliberate release of biological agents, based on published descriptions.
An aerosolised form of an infectious agent would be the most effective dissemination mode in a bioterrorist attack, and in the absence of reliable data on this mode (a few laboratory contaminations, GIs’ infected during the Vietnam war), we have good reason to take pulmonary infections as the main initial indication of bioterrorism-related infections.
The aim of the guidelines was to make a clinical diagnosis tool available to all clinicians in Europe who are not familiar with this type of infection. It was not our intention to replace or contradict national guidelines, already developed specifically for this occurrence.

We are convinced that Burkholderia mallei and B pseudomallei are extremely close phylogenetically, even if there is some variation at epidemiological, clinical and diagnostic levels.Glanders cases are reported very rarely in the literature, it seemed to us difficult to dissociate them from meliodiosis. The descriptions that we made on those pathologies concerned data unanimously described in literature reviews on this theme. However, we sincerely thank Cheng et al. for informing us of their clinical experience, and for improving the completeness of the clinical description in those guidelines.

We welcome information on therapeutic experience. The therapeutic recommendations made in the guidelines are those issued by a panel of scientists from the European Medicines Evaluation Agency (EMEA). Cheng et al.’s comments are completely relevant, and are in agreement with our summaries of the clinical guidelines. As was pointed out, little data exist for B. mallei. As for B pseudomallei, it was never stated that this was sensitive to ciprofloxacin, and Cheng et al. were right to to reiterate its resistance in vitro and in vivo.

We also agree that amoxicillin-clavulanic acid should not be first-line treatment but secondary to imipenem or ceftazidime. The initial duration of injecting antibiotic treatments is of course 2 to 3 weeks for the pulmonary and septic forms of melioidosis, followed by an oral treatment over a total period of 6 to 12 months according to the literature data.

We all hope that those guidelines will serve as a clinical diagnosis basis for clinicians who may be confronted with an exceptional situation of bioterrorist attack. This occurrence, as we all hope, remains very unlikely with the infectious agents mentioned. Therefore it seems important to read those guidelines with a ‘bioterrorist’ vision in mind.

Philippe Bossi
Department of Infectious Diseases, Pitié-Salpêtrière Hospital, Paris, France

Georgios Gouvras
Task Force on Biological and Chemical Agent Threats, Public Health Directorate, European Commission, Luxembourg

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