Back to Journals » Infection and Drug Resistance » Volume 11

Imported melioidosis in Japan: a review of cases

Authors Hadano Y

Received 20 October 2017

Accepted for publication 22 December 2017

Published 24 January 2018 Volume 2018:11 Pages 163—168

DOI https://doi.org/10.2147/IDR.S154696

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Joachim Wink

Download Article [PDF] 

Yoshiro Hadano

Department of Infectious Diseases, St. Mary’s Hospital, Kurume, Fukuoka, Japan

Abstract: Fourteen cases of reported melioidosis in Japan were reviewed. The mean age was 52.4 years (33–69 years), and all patients were male. All of the presumed exposures originated in Southeast Asia. The most common underlying disease was diabetes mellitus, including those patients with impaired glucose tolerance (n=8). As for mode of onset, 13 patients had acute infections and one had chronic infection. Of these 14 patients, the most common infection site on admission was lung (n=8), followed by bone (n=5), skin (n=4), gastrointestinal abscess formation (n=3), urinary tract (n=3), aorta (n=2), mediastinal lymph node swelling (n=1), and central nervous system (n=1). Bacteremia was observed in nine patients, and Burkholderia pseudomallei isolates were mostly susceptible to ceftazidime and carbapenem. Overall mortality was 14.3%. Melioidosis is a rare infection in Japan, with all known cases to date having been imported from Southeast Asia. Diabetes was a common risk factor.

Keywords: melioidosis, Burkholderia pseudomallei, Japan, Southeast Asia

 

Introduction

Melioidosis is a bacterial infection caused by the Gram-negative, facultative, environmental organism Burkholderia pseudomallei.1 Clinical manifestations include a diverse pattern that can be acute such as pneumonia with severe sepsis (defined as symptoms present for less than 2 months) or chronic infection (defined as symptoms present for over 2 months), similar to tuberculosis. Therefore, melioidosis is referred to as the “great mimicker”.2 With the expansion of commercial air traffic, international travel has become commonplace. As a result, travel-related infections are diagnosed in Japan. Therefore, cases of imported melioidosis from endemic regions have been reported recently. Because of the high fatality rate of melioidosis (14%–43%), it is essential that physicians are more aware of melioidosis. Currently, B. pseudomallei is considered to be absent in Japan, but Limmathurotsakul et al predict that Japan will have areas that would be suitable for B. pseudomallei, especially in the southern part of Japan, such as Okinawa and Kagoshima prefecture, due to similarity in the soil environment.3 Our goal was to review and clarify a series of cases and the epidemiology related to clinical manifestations of imported melioidosis in Japan.

Material and method

PubMed, Google, and Ichushi-Web (the Japanese Medical Database sponsored by the Japan Medical Abstracts Society) were searched for relevant articles from 1990 to 2017. The following keywords were used: melioidosis, Burkholderia pseudomallei, Japan, and case report. Case reports and reviews of case reports with full texts or abstracts available in English and Japanese were included. As a result, 14 cases were found. The data collected from medical articles are as follows: basic demographic characteristics (age, gender), underlying diseases, foreign travel history, mode of onset (acute or chronic with acute defined as symptoms lasting for less than 2 months before diagnosis and chronic defined as symptoms persisting for longer than 2 months), duration after exposure (<2 months, 2–6 months, >6 months, or unknown), chief complaints, clinical manifestations, septic shock status on admission, source of the B. pseudomallei isolates (blood, sputum, urine, skin/soft tissue, synovial fluid, cerebrospinal fluid, throat swab, and pus), bacteremia or not, key therapeutic regimen, susceptibility to antibiotics (ceftazidime, imipenem), and outcome (cure, recurrence, death, and unknown). Recurrence was defined as a clinical feature of melioidosis in association with one or more cultures positive for B. pseudomallei in a patient with a history of one or more previous episodes. This study was approved by the St. Mary’s Hospital Ethics Committee.

Results

Table 1 shows the collected information on the 14 diagnosed melioidosis cases that have been reported in Japan.417 The mean age was 52.4 years (33–69 years), and all of the patients were male. All of the estimated exposures were in Southeast Asia, including Malaysia (n=2), Thailand (n=2), Vietnam (n=2), Cambodia (n=1), Indonesia (n=1), Myanmar (n=1), Philippines (n=1), Indonesia and Singapore (n=1), Malaysia, Thailand, and Vietnam (n=1), Malaysia, Singapore, and South China (n=1), and China, Malaysia, Singapore and Thailand (n=1). Depending on the category of travel, the subjects were classified as tourists (n=6), expatriates (n=3), business travelers (3), and immigrants (n=2). The most common underlying disease was diabetes mellitus, including those patients with impaired glucose tolerance (n=8), followed by alcoholism (n=1), gastric ulcer (n=2), alcoholic liver dysfunction (n=1), ureter cancer (n=1), none (n=1), and unknown (n=3). As for the mode of onset, 13 patients had acute infections, and one had chronic infection. Cases 13 and 14 were in septic shock on admission, but the other cases were stable. Of these 14 patients, eight patients had lung involvement (five patients with pneumonia, two patients with lung abscesses, and one patient with empyema), five patients had bone involvement (two patients with osteomyelitis, one patient with septic arthritis, one patient with osteomyelitis and septic arthritis), four patients had cutaneous involvement (three patients with a subcutaneous abscess, one patient with cellulitis), three patients presented with gastrointestinal abscess formations (two patients with a spleen abscess, one patient with liver and spleen abscesses), three patients had urinary tract abscesses (two patients with kidney and prostate abscesses, one patient with a kidney abscess), two patients had a mycotic aneurysm, one patient had mediastinal lymph node swelling, and one patient had a brain abscess. Bacteremia was observed in nine patients, and B. pseudomallei isolates were mostly susceptible to ceftazidime and carbapenems except for case seven (resistant to ceftazidime; MIC ≥16). This patient did not have a history of treatment with ceftazidime. The overall mortality in the melioidosis patients was 14.3% (n=2), and the recurrence rate was 14.3% (n=2) during the follow-up.

Table 1 Summary of imported melioidosis cases in Japan

Abbreviations: S, susceptible; R, resistant; N/A, not available; TMP-SMX, trimethoprim-sulfamethoxazole.

Discussion

In this study, all Japanese melioidosis cases were attributed to travel to Southeast Asia, with no evidence of B. pseudomallei acquisition within Japan, including southern regions with environmental suitability for this pathogen. The distribution of melioidosis is in the tropical region, mainly between the latitudes 20 degrees north and south, including Southeast Asia. Northeast Thailand, northern Australia, Singapore, and parts of Malaysia are currently recognized as highly endemic areas.18 According to the reports for travel-related health problems in those returning to Japan, 65%~77.5% of the patients were returning after having traveled to melioidosis-endemic countries, especially Southeast Asia.19,20 Although melioidosis is a rare disease in Japan, with no known autochthonous cases reported to date, it is essential for physicians in Japan to be aware of possible infection in travelers returning from melioidosis-endemic countries, especially from Southeast Asia. This study found that the most common underlying disease was diabetes mellitus and impaired glucose tolerance. According to a previous report, the main risk factors for melioidosis are mainly diabetes mellitus, excessive alcohol use, thalassemia, chronic renal diseases, chronic lung diseases, and high soil and water exposure.2123 A previous report showed that the most common presenting feature of melioidosis was pneumonia (51%), followed by genitourinary infection (14%), skin infection (13%), bacteremia without any proven focus (11%), septic arthritis and/or osteomyelitis (4%), and neurological melioidosis (3%).24 Similarly, 8/11 patients in our study had lung involvement and 5/11 patients had bone involvement. As for the mode of infection, 13 cases were acute, and one case was chronic. The incubation period from defined inoculating events was 1–21 days with an average of 9 days.25 Physicians in non-endemic regions should be alert to a diagnosis of melioidosis for all patients who have a history of travel and residence in endemic areas including immigrants. In this study, carbapenem was the main therapeutic regimen. For intensive therapy, ceftazidime and carbapenem are the treatments of choice. A previous randomized comparative study in northeast Thailand showed that there was no difference between imipenem and ceftazidime in terms of survival advantage for patients with severe melioidosis but ceftazidime was significantly associated with treatment failure, relative to imipenem (ceftazidime group: 41%, imipenem group: 20%, p=0.025).26 An additional study suggested that meropenem may result in better outcomes, especially in severe cases of melioidosis. Meropenem is used rather than imipenem in Australia due to fewer neurogenic side effects.27 Japanese doctors may choose carbapenem due to a lack of experience in management of patients with melioidosis. The fatality rate of human melioidosis is high: 43% in northeast Thailand and 14% in Australia.21,24 In this study, the mortality rate was 14.3%. This result was similar to the outcome in Australia. In general, patients in developed countries have easier access to a hospital, and can receive a high level of intensive care in terms of modern equipment and adequate human resources, when compared to that of developing countries. Since treatment antibiotics were almost all the same, this may also explain the geographical difference in mortality. There are some limitations to this study. First, the data were extracted from the records of published articles on each patient. This study did not state the estimated assumed mode of transmission or the molecular analysis of the isolated strain that confirms the actual source. So far, B. pseudomallei is considered to be absent in Japan. But there is the possibility that the causative bacteria may have been acquired in Japan. Another limitation was the inadequate follow-up duration. The actual recurrence rate may be higher than that in our results. Finally, this review is based on case reports with full texts or abstracts available in English and Japanese languages only.

Conclusion

In conclusion, the epidemiological and clinical features of imported melioidosis cases in Japan were reviewed. It is important to keep in mind that melioidosis is a rare cause of imported infection, but can occur, especially in cases of bacteremia or lung involvement in patients with diabetes who are returning from Southeast Asia.

Acknowledgments

The author thanks Mr Kaoru Hatakeyama (Tokyo Metropolitan Institute of Public Health) and Mr Motoki Sugasaki (Tokushima University Hospital).

Disclosure

The author reports no conflicts of interest in this work.

References

1.

Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med. 2012;367(11):1035–1044.

2.

Yee KC, Lee MK, Chua CT, Puthucheary SD. Melioidosis, the great mimicker: a report of 10 cases from Malaysia. J Trop Med Hyg. 1988;91(5):249–254.

3.

Limmathurotsakul D, Golding N, Dance DA, et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol. 2016;1:15008.

4.

Arakawa M, Mitsui T, Miki R, Yabuuchi E. Chronic melioidosis: a report of the first case in Japan. Kansenshogaku Zasshi. 1993;67(2):154–162.

5.

Akitani I, Muraoka Y, Ochiai E, et al. [A case of melioidosis returning from Malaysia]. Journal of Japanese Society for Clinical Microbiology. 1995;5:43–47. Japanese.

6.

Sugimura H, Watanabe K, Sugimura S, et al. [A surgically treated case of abdominal aortic aneurysm associated with melioidosis]. Japanese Journal of Cardiovascular Surgery. 1998;27(4):237–240. Japanese.

7.

Kunishima H, Seki R, Iwabuchi T, Nakamura T, Ishida N, Takagi T, Shimada J. [Case of melioidosis associated with acute empyema and cellulitis of the leg]. Nihon Naika Gakkai Zasshi. 1999;88(6):1101–1103. Japanese.

8.

Yamamoto K, Kurose K, Yamamoto E, et al. [A case of systemic melioidosis (Burkholderia pseudomalleri infection)]. Kyosai Med J. 2000;49S:256. Japanese.

9.

Suzuki T, Yamada Y, Kunishima H, et al. [A case of melioidosis with diabetes mellitus]. St. Marianna Medical Journal. 2002;30(1):189–194. Japanese.

10.

Shibuya H, Taniguchi Y, Tashiro N, Hara K, Hisada T. [A Japanese case of melioidosis presenting as multiple organ lesions accompanied by sepsis and disseminated intravascular coagulation, after a visit to Thailand]. Kansenshogaku Zasshi. 2007;81(3):297–301. Japanese.

11.

Satake Y, Kato M, Numahata K, et al. [A case of melioidosis mimicking renal tumor]. Hinyoukigeka. 2007;20(5):720. Japanese.

12.

Kurata K, Nukui Y, Shimada H, Inoue Y, Yoshimura N, Horino A. [A case of melioidosis occurring after a long-term stay in Vietnam that developed pulmonary cavitation and relapsed with multiple pulmonary nodules]. Nihon Kokyuki Gakkai Zasshi. 2011;49(6):443–448. Japanese.

13.

Sogawa M, Fukuda T, Moro H, et al. [Successful treatment of a rare cause of mycotic aneurysm: A case report]. Niigata Medical Journal. 2012;126(5):273. Japanese.

14.

Sugasaki T, Sato M, Okamoto T. [A case of Burkholderia pseudomallei bacteremia]. Japanese Journal of Medical Technology. 2014;63:352. Japanese.

15.

Ito Y, Otsuka M, Aoki K, et al. [A case of isolated from no underlying diseases of Burkholderia pseudomallei infection]. Journal of Japanese Society for Clinical Microbiology. 2015;25(4):65–70. Japanese.

16.

Nakai S, Inagaki M, Inoue M, et al. [A fatal Case of Melioidosis with Septic Shock and Multiple Organ Dysfunction Syndrome]. Chuubu Journal of Acute Medicine. 2015;11:33–37. Japanese.

17.

Katanami Y, Kutsuna S, Horino A, et al. A fatal case of melioidosis with pancytopenia in a traveler from Indonesia. J Infect Chemother. 2017;23(4):241–244.

18.

Currie BJ, Dance DA, Cheng AC. The global distribution of Burkholderia pseudomallei and melioidosis: an update. Trans R Soc Trop Med Hyg. 2008;102 Suppl 1:S1–4.

19.

Mizuno Y, Kudo K. Travel-related health problems in Japanese travelers. Travel Med Infect Dis. 2009;7(5):296–300.

20.

Hadano Y, Shirano M, Goto T. Travel-related illness at a tertiary care hospital in Osaka, Japan. Int J Gen Med. 2016;9:355–359.

21.

Limmathurotsakul D, Wongratanacheewin S, Teerawattanasook N, et al. Increasing incidence of human melioidosis in Northeast Thailand. Am J Trop Med Hyg. 2010;82(6):1113–1117.

22.

Suputtamongkol Y, Chaowagul W, Chetchotisakd P, et al. Risk factors for melioidosis and bacteremic melioidosis. Clin Infect Dis. 1999;29(2):408–413.

23.

Currie BJ, Jacups SP, Cheng AC, Fisher DA, Anstey NM, Huffam SE, Krause VL. Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia. Trop Med Int Health. 2004;9(11):1167–1174.

24.

Currie BJ, Ward L, Cheng AC. The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. PLoS Negl Trop Dis. 2010;4(11):e900.

25.

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(3):301–304.

26.

Simpson AJ, Suputtamongkol Y, Smith MD, et al. Comparison of imipenem and ceftazidime as therapy for severe melioidosis. Clin Infect Dis. 1999;29(2):381–387.

27.

Cheng AC, Fisher DA, Anstey NM, Stephens DP, Jacups SP, Currie BJ. Outcomes of patients with melioidosis treated with meropenem. Antimicrob Agents Chemother. 2004;48(5):1763–1765.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]