Background Over 20 years, from October 1989, the Darwin prospective melioidosis study has documented 540 cases from tropical Australia, providing new insights into epidemiology and the clinical spectrum. Principal Findings The principal presentation was pneumonia in 278 (51%), genitourinary infection in 76 (14%), skin infection in 68 (13%), bacteremia without evident focus in 59 (11%), septic arthritis/osteomyelitis in 20 (4%) and neurological melioidosis in 14 (3%). 298 (55%) were bacteremic and 116 (21%) developed septic shock (58 fatal). Internal organ abscesses and secondary foci in lungs and/or joints were common. Prostatic abscesses occurred in 76 (20% of 372 males). 96 (18%) had occupational exposure to Burkholderia pseudomallei. 118 (22%) had a specific recreational or occupational incident considered the likely infecting event. 436 (81%) presented during the monsoonal wet season. The higher proportion with pneumonia in December to February supports the hypothesis of infection by inhalation during severe weather events. Recurrent melioidosis occurred in 29, mostly attributed to poor adherence to therapy. Mortality decreased from 30% in the first 5 years to 9% in the last five years (p<0.001). Risk factors for melioidosis included diabetes (39%), hazardous alcohol use (39%), chronic lung disease (26%) and chronic renal disease (12%). There was no identifiable risk factor in 20%. Of the 77 fatal cases (14%), 75 had at least one risk factor; the other 2 were elderly. On multivariate analysis of risk factors, age, location and season, the only independent predictors of mortality were the presence of at least one risk factor (OR 9.4; 95% CI 2.3–39) and age ≥50 years (OR 2.0; 95% CI 1.2–2.3). Conclusions Melioidosis should be seen as an opportunistic infection that is unlikely to kill a healthy person, provided infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care.
References
[1]
White NJ (2003) Melioidosis. Lancet 361: 1715–1722. doi: 10.1016/S0140-6736(03)13374-0
[2]
Chaowagul W, White NJ, Dance DA, Wattanagoon Y, Naigowit P, et al. (1989) Melioidosis: a major cause of community-acquired septicemia in northeastern Thailand. J Infect Dis 159: 890–899. doi: 10.1093/infdis/159.5.890
Ralph A, McBride J, Currie BJ (2004) Transmission of Burkholderia pseudomallei via breast milk in Northern Australia. Pediatr Infect Dis J 23: 1169–1171.
[5]
Dance DA (2000) Melioidosis as an emerging global problem. Acta Trop 74: 115–119. doi: 10.1016/S0001-706X(99)00059-5
[6]
Currie BJ, Dance DA, Cheng AC (2008) The global distribution of Burkholderia pseudomallei and melioidosis: an update. Trans R Soc Trop Med Hyg 102: Suppl 1S1–4. doi: 10.1016/S0035-9203(08)70002-6
[7]
Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, et al. (2000) Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 31: 981–986. doi: 10.1086/318116
[8]
American College of Chest Physicians/Society of Critical Care Medicine (1992) Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864–874. doi: 10.1097/00003246-199206000-00025
[9]
Cheng AC, Jacups SP, Gal D, Mayo M, Currie BJ (2006) Extreme weather events and environmental contamination are associated with case-clusters of melioidosis in the Northern Territory of Australia. Int J Epidemiol 35: 323–329. doi: 10.1093/ije/dyi271
[10]
Currie BJ, Mayo M, Anstey NM, Donohoe P, Haase A, et al. (2001) A cluster of melioidosis cases from an endemic region is clonal and is linked to the water supply using molecular typing of Burkholderia pseudomallei isolates. Am J Trop Med Hyg 65: 177–179.
[11]
Morse LP, Moller CC, Harvey E, Ward L, Cheng AC, et al. (2009) Prostatic abscess due to Burkholderia pseudomallei: 81 cases from a 19-year prospective melioidosis study. J Urol 182: 542–547; discussion 547. doi: 10.1016/j.juro.2009.04.010
[12]
Wuthiekanun V, Chierakul W, Langa S, Chaowagul W, Panpitpat C, et al. (2006) Development of antibodies to Burkholderia pseudomallei during childhood in melioidosis-endemic northeast Thailand. Am J Trop Med Hyg 74: 1074–1075.
[13]
Cheng AC, Wuthiekanun V, Limmathurotsakul D, Chierakul W, Peacock SJ (2008) Intensity of exposure and incidence of melioidosis in Thai children. Trans R Soc Trop Med Hyg 102: Suppl 1S37–39. doi: 10.1016/S0035-9203(08)70010-5
[14]
Suputtamongkol Y, Hall AJ, Dance DA, Chaowagul W, Rajchanuvong A, et al. (1994) The epidemiology of melioidosis in Ubon Ratchatani, northeast Thailand. Int J Epidemiol 23: 1082–1090. doi: 10.1093/ije/23.5.1082
[15]
Ngauy V, Lemeshev Y, Sadkowski L, Crawford G (2005) Cutaneous melioidosis in a man who was taken as a Prisoner of War by the Japanese during World War II. J Clin Microbiol 43: 970–972. doi: 10.1128/JCM.43.2.970-972.2005
[16]
Clayton AJ, Lisella RS, Martin DG (1973) Melioidosis: a serological survey in military personnel. Mil Med 138: 24–26.
[17]
Currie BJ, Jacups SP, Cheng AC, Fisher DA, Anstey NM, et al. (2004) Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia. Trop Med Int Health 9: 1167–1174. doi: 10.1111/j.1365-3156.2004.01328.x
[18]
Limmathurotsakul D, Wongratanacheewin S, Teerawattanasook N, Wongsuvan G, Chaisuksant S, et al. (2010) Increasing incidence of human melioidosis in Northeast Thailand. Am J Trop Med Hyg 82: 1113–1117. doi: 10.4269/ajtmh.2010.10-0038
[19]
Lo TJ, Ang LW, James L, Goh KT (2009) Melioidosis in a tropical city state, Singapore. Emerg Infect Dis 15: 1645–1647. doi: 10.3201/eid1510.090246
[20]
Currie BJ, Fisher DA, Anstey NM, Jacups SP (2000) Melioidosis: acute and chronic disease, relapse and re-activation. Trans R Soc Trop Med Hyg 94: 301–304. doi: 10.1016/S0035-9203(00)90333-X
[21]
Currie BJ (2008) Advances and remaining uncertainties in the epidemiology of Burkholderia pseudomallei and melioidosis. Trans R Soc Trop Med Hyg 102: 225–227. doi: 10.1016/j.trstmh.2007.11.005
[22]
Currie BJ, Jacups SP (2003) Intensity of rainfall and severity of melioidosis, Australia. Emerg Infect Dis 9: 1538–1542. doi: 10.3201/eid0912.020750
[23]
Suputtamongkol Y, Chaowagul W, Chetchotisakd P, Lertpatanasuwun N, Intaranongpai S, et al. (1999) Risk factors for melioidosis and bacteremic melioidosis. Clin Infect Dis 29: 408–413. doi: 10.1086/520223
[24]
Limmathurotsakul D, Chaowagul W, Chierakul W, Stepniewska K, Maharjan B, et al. (2006) Risk factors for recurrent melioidosis in northeast Thailand. Clin Infect Dis 43: 979–986. doi: 10.1086/507632
[25]
Malczewski AB, Oman KM, Norton RE, Ketheesan N (2005) Clinical presentation of melioidosis in Queensland, Australia. Trans R Soc Trop Med Hyg 99: 856–860. doi: 10.1016/j.trstmh.2005.06.015
[26]
Shih HI, Chuang YC, Cheung BM, Yan JJ, Chang CM, et al. (2009) Sporadic and outbreak cases of melioidosis in southern Taiwan: clinical features and antimicrobial susceptibility. Infection 37: 9–15. doi: 10.1007/s15010-008-7324-8
[27]
Puthucheary SD, Parasakthi N, Lee MK (1992) Septicaemic melioidosis: a review of 50 cases from Malaysia. Trans R Soc Trop Med Hyg 86: 683–685. doi: 10.1016/0035-9203(92)90191-E
[28]
Chierakul W, Rajanuwong A, Wuthiekanun V, Teerawattanasook N, Gasiprong M, et al. (2004) The changing pattern of bloodstream infections associated with the rise in HIV prevalence in northeastern Thailand. Trans R Soc Trop Med Hyg 98: 678–686. doi: 10.1016/j.trstmh.2004.01.011
[29]
Chierakul W, Wuthiekanun V, Chaowagul W, Amornchai P, Cheng AC, et al. (2005) Short report: disease severity and outcome of melioidosis in HIV coinfected individuals. Am J Trop Med Hyg 73: 1165–1166.
[30]
Ketheesan N, Barnes JL, Ulett GC, VanGessel HJ, Norton RE, et al. (2002) Demonstration of a cell-mediated immune response in melioidosis. J Infect Dis 186: 286–289. doi: 10.1086/341222
[31]
Barnes JL, Warner J, Melrose W, Durrheim D, Speare R, et al. (2004) Adaptive immunity in melioidosis: a possible role for T cells in determining outcome of infection with Burkholderia pseudomallei. Clin Immunol 113: 22–28. doi: 10.1016/j.clim.2004.06.006
[32]
Cheng AC, Stephens DP, Anstey NM, Currie BJ (2004) Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis. Clin Infect Dis 38: 32–37. doi: 10.1086/380456
[33]
Cheng AC, Limmathurotsakul D, Chierakul W, Getchalarat N, Wuthiekanun V, et al. (2007) A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clin Infect Dis 45: 308–314. doi: 10.1086/519261
[34]
Easton A, Haque A, Chu K, Lukaszewski R, Bancroft GJ (2007) A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. J Infect Dis 195: 99–107. doi: 10.1086/509810
[35]
Chanchamroen S, Kewcharoenwong C, Susaengrat W, Ato M, Lertmemongkolchai G (2009) Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects. Infect Immun 77: 456–463. doi: 10.1128/IAI.00503-08
[36]
Dorman SE, Gill VJ, Gallin JI, Holland SM (1998) Burkholderia pseudomallei infection in a Puerto Rican patient with chronic granulomatous disease: case report and review of occurrences in the Americas. Clin Infect Dis 26: 889–894. doi: 10.1086/513928
[37]
MacGregor R, Gluckman S (1979) Effect of alcohol intoxication on granulocyte mobilization and kinetics. Blood 52: 551–559.
[38]
Zhang P, Bagby GJ, Stoltz DA, Summer WR, Nelson S (1999) Granulocyte colony-stimulating factor modulates the pulmonary host response to endotoxin in the absence and presence of acute ethanol intoxication. J Infect Dis 179: 1441–1448. doi: 10.1086/314763
[39]
Camarena L, Bruno V, Euskirchen G, Poggio S, Snyder M (2010) Molecular mechanisms of ethanol-induced pathogenesis revealed by RNA-sequencing. PLoS Pathog 6: e1000834. doi: 10.1371/journal.ppat.1000834
[40]
Happel KI, Nelson S (2005) Alcohol, immunosuppression, and the lung. Proc Am Thorac Soc 2: 428–432. doi: 10.1513/pats.200507-065JS
[41]
Davies PD, Yew WW, Ganguly D, Davidow AL, Reichman LB, et al. (2006) Smoking and tuberculosis: the epidemiological association and immunopathogenesis. Trans R Soc Trop Med Hyg 100: 291–298. doi: 10.1016/j.trstmh.2005.06.034
[42]
Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart 90: 464–470. doi: 10.1136/hrt.2002.007005
[43]
O'Carroll MR, Kidd TJ, Coulter C, Smith HV, Rose BR, et al. (2003) Burkholderia pseudomallei: another emerging pathogen in cystic fibrosis. Thorax 58: 1087–1091. doi: 10.1136/thorax.58.12.1087
[44]
Visca P, Cazzola G, Petrucca A, Braggion C (2001) Travel-associated Burkholderia pseudomallei infection (Melioidosis) in a patient with cystic fibrosis: a case report. Clin Infect Dis 32: e15–16. doi: 10.1086/317528
[45]
Schulin T, Steinmetz I (2001) Chronic melioidosis in a patient with cystic fibrosis. J Clin Microbiol 39: 1676–1677. doi: 10.1128/JCM.39.4.1676-1677.2001
[46]
Holland DJ, Wesley A, Drinkovic D, Currie BJ (2002) Cystic Fibrosis and Burkholderia pseudomallei Infection: An Emerging Problem? Clin Infect Dis 35: e138–140. doi: 10.1086/344447
[47]
Currie BJ (2003) Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions. Eur Respir J 22: 542–550. doi: 10.1183/09031936.03.00006203
[48]
Flemma RJ, DiVincenti FC, Dotin LN, Pruitt BAJ (1969) Pulmonary melioidosis; a diagnostic dilemma and increasing threat. Ann Thorac Surg 7: 491–499. doi: 10.1016/S0003-4975(10)66386-2
[49]
Gibney KB, Cheng AC, Currie BJ (2008) Cutaneous melioidosis in the tropical top end of Australia: a prospective study and review of the literature. Clin Infect Dis 47: 603–609. doi: 10.1086/590931
[50]
Woods ML, Currie BJ, Howard DM, Tierney A, Watson A, et al. (1992) Neurological melioidosis: seven cases from the Northern Territory of Australia. Clin Infect Dis 15: 163–169. doi: 10.1093/clinids/15.1.163
[51]
Currie BJ, Fisher DA, Howard DM, Burrow JN (2000) Neurological melioidosis. Acta Trop 74: 145–151. doi: 10.1016/S0001-706X(99)00064-9
[52]
Koszyca B, Currie BJ, Blumbergs PC (2004) The neuropathology of melioidosis: two cases and a review of the literature. Clin Neuropathol 23: 195–203.
[53]
Dance DA, Davis TM, Wattanagoon Y, Chaowagul W, Saiphan P, et al. (1989) Acute suppurative parotitis caused by Pseudomonas pseudomallei in children. J Infect Dis 159: 654–660. doi: 10.1093/infdis/159.4.654
[54]
Owen SJ, Batzloff M, Chehrehasa F, Meedeniya A, Casart Y, et al. (2009) Nasal-associated lymphoid tissue and olfactory epithelium as portals of entry for Burkholderia pseudomallei in murine melioidosis. J Infect Dis 199: 1761–1770. doi: 10.1086/599210
[55]
Pearson T, Giffard P, Beckstrom-Sternberg S, Auerbach R, Hornstra H, et al. (2009) Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer. BMC Biol 7: 78. doi: 10.1186/1741-7007-7-78
[56]
Sitthidet C, Stevens JM, Chantratita N, Currie BJ, Peacock SJ, et al. (2008) Prevalence and sequence diversity of a factor required for actin-based motility in natural populations of Burkholderia species. J Clin Microbiol 46: 2418–2422. doi: 10.1128/JCM.00368-08
[57]
Low JG, Quek AM, Sin YK, Ang BS (2005) Mycotic aneurysm due to Burkholderia pseudomallei infection: case reports and literature review. Clin Infect Dis 40: 193–198. doi: 10.1086/426590
[58]
Demar M, Ferroni A, Dupont B, Eliaszewicz M, Bouree P (2005) Suppurative epididymo-orchitis and chronic prostatitis caused by Burkholderia pseudomallei: a case report and review. J Travel Med 12: 108–112. doi: 10.2310/7060.2005.12208
[59]
Chung HC, Lee CT, Lai CH, Huang CK, Lin JN, et al. (2008) Non-septicemic melioidosis presenting as cardiac tamponade. Am J Trop Med Hyg 79: 455–457.
[60]
Wibulpolprasert B, Dhiensiri T (1999) Visceral organ abscesses in melioidosis: sonographic findings. J Clin Ultrasound 27: 29–34. doi: 10.1002/(SICI)1097-0096(199901)27:1<29::AID-JCU5>3.0.CO;2-C
Low Choy J, Mayo M, Janmaat A, Currie BJ (2000) Animal melioidosis in Australia. Acta Trop 74: 153–158. doi: 10.1016/S0001-706X(99)00065-0
[63]
Chaowagul W (2000) Recent advances in the treatment of severe melioidosis. Acta Trop 74: 133–137. doi: 10.1016/S0001-706X(99)00062-5
[64]
Vadivelu J, Puthucheary SD, Drasar BS, Dance DA, Pitt TL (1998) Stability of strain genotypes of Burkholderia pseudomallei from patients with single and recurrent episodes of melioidosis. Trop Med Int Health 3: 518–521. doi: 10.1046/j.1365-3156.1998.00262.x
[65]
Limmathurotsakul D, Wuthiekanun V, Chantratita N, Wongsuvan G, Thanwisai A, et al. (2007) Simultaneous infection with more than one strain of Burkholderia pseudomallei is uncommon in human melioidosis. J Clin Microbiol 45: 3830–3832. doi: 10.1128/JCM.01297-07
[66]
Limmathurotsakul D, Wuthiekanun V, Chierakul W, Cheng AC, Maharjan B, et al. (2005) Role and significance of quantitative urine cultures in diagnosis of melioidosis. J Clin Microbiol 43: 2274–2276. doi: 10.1128/JCM.43.5.2274-2276.2005
[67]
Cheng AC, Fisher DA, Anstey NM, Stephens DP, Jacups SP, et al. (2004) Outcomes of patients with melioidosis treated with meropenem. Antimicrob Agents Chemother 48: 1763–1765. doi: 10.1128/AAC.48.5.1763-1765.2004
[68]
Cheng AC, West TE, Limmathurotsakul D, Peacock SJ (2008) Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med 5: e175. doi: 10.1371/journal.pmed.0050175
[69]
Liu Y, Loh JP, Aw LT, Yap EP, Lee MA, et al. (2006) Rapid molecular typing of Burkholderia pseudomallei, isolated in an outbreak of melioidosis in Singapore in 2004, based on variable-number tandem repeats. Trans R Soc Trop Med Hyg 100: 687–692. doi: 10.1016/j.trstmh.2005.08.017
[70]
Wiersinga WJ, van der Poll T (2009) Immunity to Burkholderia pseudomallei. Curr Opin Infect Dis 22: 102–108. doi: 10.1097/QCO.0b013e328322e727
[71]
Nuntayanuwat S, Dharakul T, Chaowagul W, Songsivilai S (1999) Polymorphism in the promoter region of tumor necrosis factor-alpha gene is associated with severe meliodosis. Hum Immunol 60: 979–983. doi: 10.1016/S0198-8859(99)00073-7
