Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2020  |  Volume : 18  |  Issue : 2  |  Page : 94-97

Melioidosis: An emerging infection in India

Department of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA

Date of Submission29-Dec-2019
Date of Decision20-Jan-2020
Date of Acceptance17-Feb-2020
Date of Web Publication17-Apr-2020

Correspondence Address:
Dr. Maria Koshy
Research Trainee, Department of Infectious Diseases, Mayo Clinic, Rochester, Minnesota
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmi.cmi_72_19

Rights and Permissions

Melioidosis, caused by Burkholderia pseudomallei, has been described as the great mimic, as disease manifestations are protean. It is present in the soil and surface water in endemic regions. Although initially thought to be endemic to Southeast Asia and Northern Australia, there has been an emergence of this infection in areas where it was previously absent. In recent years, environmental and clinical studies have shown a significant presence of melioidosis in India. The epidemic of diabetes, the most significant risk factor, could result in a surge of cases of melioidosis in India. Melioidosis can closely mimic tuberculosis. Increased awareness, a high index of suspicion and prompt diagnosis and initiation of therapy are essential to reduce the morbidity and mortality related to melioidosis.

Keywords: Burkholderia pseudomallei, emerging infection, India, melioidosis

How to cite this article:
Koshy M. Melioidosis: An emerging infection in India. Curr Med Issues 2020;18:94-7

How to cite this URL:
Koshy M. Melioidosis: An emerging infection in India. Curr Med Issues [serial online] 2020 [cited 2022 Aug 15];18:94-7. Available from: https://www.cmijournal.org/text.asp?2020/18/2/94/282788

  Introduction Top

Melioidosis is the infectious disease caused by the environmental bacterium, Burkholderia pseudomallei.[1] Infection is acquired by inhalation, ingestion, and inoculation. The incubation period for acute disease ranges from 1 to 21 days, with a latent period of up to 62 years having been described. The causative organism is inherently resistant to a range of antimicrobial agents, and ineffective therapy can result in high case fatality.[2]

B. pseudomallei has been described as the great mimic, as disease manifestations are protean.[3] The spectrum of disease ranges from acute septicemic disease, which is fulminant, to the chronic indolent form of the disease. Subclinical infection with delayed manifestation of the disease is also described.[4],[5]

Melioidosis is difficult to diagnose because of its wide spectrum of clinical manifestations and the inadequacy of conventional microbiological methods. This, along with a low index of suspicion, has led to this disease being underrecognized, even in the 45 endemic countries.[6],[7] Melioidosis remains a little known entity despite a recent modeling study predicting a surge of cases of melioidosis in India.[8] This review aims to delineate the epidemiology, pathophysiology, and diagnostics of melioidosis, in the context of the Indian subcontinent.

  Epidemiology and Global Burden of Melioidosis Top

B. pseudomallei is present in the soil and surface water in endemic regions. While the organism is most abundant in soil depths exceeding 10 cm from the surface, the rainy season can cause the organism to move closer to the surface and multiply.[9] This Gram-negative bacterium can survive extreme conditions; contamination of water and nosocomial infections have been frequently reported. Aerosolized bacteria have been rarely detected in air.[2] Although melioidosis was initially thought to be endemic to Southeast Asia and Northern Australia, there has been an emergence of this infection in areas where it was previously absent.[7]

  Melioidosis in India Top

While the true burden of melioidosis in India remains poorly understood, a 2016 modeling study has predicted a global incidence of ~165,000 cases worldwide with an estimated case fatality of 89,000 (54%). This study suggests melioidosis to be endemic to India with an annual incidence of ~52,500 cases.[7] The only serosurveillance study done in India in the Southwest coastal town of Udupi estimated seroprevalence of 29% (titer ≥1:20).[10] Studies attempting to identify B. pseudomallei from the environment have been limited.[11] Periods of heavy rainfall are known to be associated with an increase in number of cases, particularly acute septicemic and pneumonic presentations.[12] A linear correlation between monthly rainfall and case occurrence has also been documented in studies from India.[13],[14]

Both environmental and clinical studies have shown a significant presence of melioidosis in India.[13],[14],[15] A modeling study has predicted a surge in cases of melioidosis in India.[7] The diabetes epidemic in India, along with severe weather events related to global climate change, could further increase the incidence of melioidosis. There is an urgent need to improve laboratory facilities and increase awareness among health-care workers and public health officials, to tackle the surge.

  Risk Factors Top

Diabetes mellitus is the most important risk factor for melioidosis. While studies estimate >50% of all worldwide cases of melioidosis to have diabetes, a study done in India reported diabetes to be present in 81.6% of cases.[14],[16] The impairment of host immunity caused by diabetes clearly plays a role in the pathogenesis of melioidosis. Other risk factors include age >45 years, excessive alcohol use, thalassemia, chronic kidney, and liver and lung disease. While prolonged steroid use and immunosuppression, predispose an individual to melioidosis, infection with human immunodeficiency virus has not been proven to be a significant risk factor.[5] Environmental risk factors are exposure to soil, water, and excessive rainfall. The male preponderance may correspond to the risk posed by environmental exposure.[17] A significant proportion of patients (~20%) have no recognized risk factors.[16]

  Pathophysiology Top


B. pseudomallei is a Gram-negative, intracellular, motile, facultative saprophyte. The organism exhibits great genetic diversity and capacity to rapidly evolve within the host.[1] An array of virulence factors makes B. pseudomallei intrinsically resistant to a wide range of antimicrobial agents. It first invades and replicates in the epithelial cells of the mucosa or broken skin, at its portal of entry. The organism has multiple secretion systems, the Type III secretion system (T3SS), T2SS, and T5SS. Multiple adhesins facilitate cell adhesion. The protease activator receptor 1 expressed on endothelial cells, platelets, monocytes, etc., promotes invasion, growth, and spread. Intracellular replication, survival, and spread occur in phagocytic and nonphagocytic cells. The following endocytosis into vesicles, it escapes into the cytoplasm for replication. Bacterial killing is mediated mainly by reactive oxygen species and reactive nitrogen intermediates. T3SS and its effector protein bop A are crucial for the evasion of autophagy, and macrophage lysis could represent an escape mechanism. The intercellular spread is facilitated by the formation of actin-based membranous protrusions of the host cell that extends into neighboring cells. This results in cell fusion and the formation of multinuclear giant cells, a hallmark of melioidosis. In addition, the organism can directly enter the bloodstream and infect antigen-presenting cells, causing bacteremia and sepsis syndrome. Entry into the lymphatic system contributes to spread to secondary sites.[5]

Host response

Most patients with melioidosis have atleast one risk factor, indicating that host immune response determines disease presentation and outcomes. Pattern recognition receptors, mainly the toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are the first to detect pathogen invasion and serve as the link between the innate and adaptive immune response. This leads to nuclear factor κB-induced immune activation through the release of pro-inflammatory cytokines. TLRs recognize pathogen-associated molecular proteins and activate the immune response through mediator proteins, specifically myeloid differentiation primary response protein MyD88. NLRs recognize bacterial virulence factors, leading to caspase 1-mediated release of interleukin 18 and interleukin 1β. Caspase also induces pyroptosis and caspase-dependent cell death. Interleukin 18 also activates interferon-gamma production, which is protective. Activation of complement and the coagulation cascade occurs along with recruitment of neutrophils. In response to interferon-gamma production, T-cell recruitment occurs and B-cells produce antibodies.[1],[5],[9]

  Clinical Spectrum of Disease Top

Melioidosis predominantly affects persons with regular contact with soil and water. Although pediatric melioidosis is a well-recognized entity, incidence peaks at 40–60 years.[17] Skin inoculation, inhalation, and ingestion are the most common routes of entry. However, the relative contributions of each method are poorly understood. Mother-to-child transmission through breastfeeding and vertical transmission has been reported to occur. The host factors and relative size of the inoculum are likely to determine the nature and severity of the clinical presentation.[5] The incubation period of 1–21 days (mean: 9 days) is likely dependent on factors such as strain virulence, inoculum size, route of entry, and host risk factors. These factors also determine the clinical presentation and outcomes.[18]

The clinical manifestations of melioidosis are protean and can range from an acute fulminant septicemic illness to chronic melioidosis, with a symptom duration of ≥2 months.[19] Bacteremia and pneumonia are considered as the hallmarks of acute melioidosis. Chronic melioidosis is characterized by the presence of deep-seated abscesses, often mimicking tuberculosis.[4] Abscesses tend to be multiple and commonly occur in the spleen, prostate, liver, and kidneys. The findings of “Swiss cheese” pattern on ultrasonography and “honeycomb” pattern on computed tomography are very suggestive of melioidosis.[18] Patients rarely report tenderness pertaining to the location of abscesses. Septic arthritis and osteomyelitis are frequently seen. Pustules and subcutaneous abscesses and pyomyositis often follow skin inoculation. Suppurative parotitis is more common in the pediatric population. Neurological involvement in the form of brain abscesses, myelitis, and brainstem encephalitis has been observed. Other sites of involvement include lymphadenitis, pericarditis, adrenal gland abscess, mycotic aneurysm, breast abscess, pancreatitis, orbital cellulitis, and sinusitis.

While acute septicemic melioidosis is thought to be more common than chronic melioidosis, a study done in a teaching hospital in India more frequently reported chronic melioidosis.[14] Genitourinary melioidosis is more frequently seen in Australia and suppurative parotitis in more frequently reported from Thailand. Genitourinary melioidosis has also been reported in 15% of male patients from India.[20] This suggests that geographic differences in the clinical presentation may exist.

  Diagnosis Top

Melioidosis should be considered by the clinician in the setting of residence in or travel to a melioidosis-endemic region. The diagnosis should be considered for community-acquired pneumonia, sepsis, and superficial and deep-seated abscesses, in the presence of host risk factors such as diabetes and the presence of environmental and occupational risk to acquiring infection. A high index of suspicion is key, in view of the diverse clinical manifestations.[18]

Culture is the gold standard for the diagnosis of melioidosis. It is 100% specific, but sensitivity may be as low as 60%. Appropriate specimens including blood and urine cultures, throat swabs, and pus, whenever present, need to be obtained.[21] The isolation of B. pseudomallei from any site, including throat swabs, respiratory secretions, wound surface swabs, and urine should be viewed as representative of infection, as it is not considered a colonizer in humans. Laboratories should be notified when melioidosis is suspected, both in endemic and nonendemic settings, as the organism is considered a hazard group 3 tier 1 biological agent, and appropriate measures for safe handling need to be undertaken. In addition, the organism can be misidentified as a culture contaminant. For specimens from nonsterile sites, the use of selective media such as Ashdown agar and Burkholderia cepacia agar is critical. The organism is a nonlactose fermenter, aerobic, oxidase positive and motile and is typically resistant to aminoglycosides, polymyxin, and colistin and sensitive to amoxicillin/clavulanic acid.

Antimicrobial susceptibility testing for trimethoprim -sulfamethoxazole (TMP-SMX) using the disk diffusion method can be inaccurate, and the E-test should be used alternatively.[18] Serological tests, most commonly indirect hemagglutination assay, are of poor value in an endemic setting in view of high background seroprevalence rates. When used in a nonendemic setting, paired sera demonstrating a rising titer supports a diagnosis of melioidosis. The polymerase chain reaction has been evaluated, but not in routine use.[21]

Imaging of the patient to delineate the extent of infection, can aid both diagnosis and management. A delay in diagnosis of melioidosis can be fatal, as most empiric antibiotics used in suspected sepsis, do not adequately cover B. pseudomallei.[1]

  Management Top

In view of the protracted course of the disease, a prolonged course of appropriate antibiotics is essential to achieve cure. Early diagnosis and initiation of therapy can greatly reduce mortality in melioidosis.[5] The treatment includes an initial intensive phase of intravenous therapy followed by an eradicative phase of oral antimicrobial therapy.

Intensive therapy

The parenteral intravenous therapy is for 10–14 days or until clinical response is seen, whichever occurs later. Ceftazidime is the agent of choice, and carbapenems are used as an alternative, in the event of treatment failure, positive blood cultures at 7 days, and the development of a new focus of infection while on ceftazidime. A longer course of intensive therapy (>4 weeks) may be considered for deep-seated infections, bone and joint involvement, neuromelioidosis, and extensive disease.[1]

Eradicative therapy

Patients can be switched to oral eradicative therapy once they show clear signs of clinical improvement, remain afebrile, and blood cultures remain sterile. The antimicrobial agent of choice is TMP-SMX given for 3–6 months. Although previously given in conjunction with doxycycline, the MERTH trial has demonstrated noninferiority and better tolerance of single-agent TMP-SMX.[22] Amoxicillin-clavulanic acid has been used as an alternative agent for eradication therapy in pregnant women and children. Monitoring patients for adherence during the eradicative phase is critical in preventing recurrence.[5]

Adjuvant treatment and surgical intervention

Adjunctive measures include surgical or guided drainage of single large abscesses of the liver, muscle, and prostatic abscesses, when feasible. Debridement and washout in osteomyelitis and septic arthritis are usually necessary. In the setting of multiple small abscesses, serial imaging can help assess response to therapy.[5] Early recognition of sepsis, adequate fluid resuscitation, and management of seriously ill patients in intensive care units reduces the mortality. Immunomodulating therapy such as granulocyte-macrophage colony-stimulating factor, Interleukin-7, and anti-programmed cell death protein 1 are under investigation.[5]

  Recurrence Top

Melioidosis is notoriously difficult to eliminate. Recurrence is the second most dreaded complication, after death and can be due to relapse (failure to eradicate infecting strain) or re-infection with a new bacterial strain. It can occur in 5%–25% of cases, and risk factors include choice and duration of antimicrobial therapy, patient compliance, bacteremia, and multifocal disease.[23]

  Prevention Top

Melioidosis is potentially preventable. Although research investigating live attenuated, subunit, plasmid-based DNA, and killed whole-cell vaccine candidates is underway, at present, there is no licensed vaccine for human use.[5] Guidelines need to be developed for persons with risk factors traveling to melioidosis-endemic areas, as well as for farmers with occupational exposure to soil and water.[18]

  Conclusion Top

Melioidosis is an emerging infection in India, with diabetes being a significant risk factor. Chronic melioidosis can closely mimic tuberculosis. A better understanding of the geographical distribution of the organism and improved awareness among health-care workers is crucial to tackle the disease. A high index of suspicion and prompt diagnosis and initiation of therapy can reduce the mortality.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med 2012;367:1035-44.  Back to cited text no. 1
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:e900.  Back to cited text no. 2
John TJ. Melioidosis, the mimicker of maladies. Indian J Med Res 2004;119:vi-viii.  Back to cited text no. 3
Dance DA. Melioidosis. Curr Opin Infect Dis 2002;15:127-32.  Back to cited text no. 4
Wiersinga WJ, Virk HS, Torres AG, Currie BJ, Peacock SJ, Dance DA, et al. Melioidosis. Nat Rev Dis Primers 2018;4:17107. Doi: 10.1038/nrdp.2017.107.  Back to cited text no. 5
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.  Back to cited text no. 6
Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 2016;1:15008. Doi:10.1038/nmicrobiol.2015.8.  Back to cited text no. 7
Cousins S. India is at high risk from surge in cases of melioidosis, warn researchers. BMJ 2016;352:i275.  Back to cited text no. 8
Cheng AC, Currie BJ. Melioidosis: Epidemiology, pathophysiology, and management. Clin Microbiol Rev 2005;18:383-416.  Back to cited text no. 9
Vandana KE, Mukhopadhyay C, Tellapragada C, Kamath A, Tipre M, Bhat V, et al. Seroprevalence of Burkholderia pseudomallei among adults in coastal areas in Southwestern India. PLoS Negl Trop Dis 2016;10:e0004610.  Back to cited text no. 10
Prakash A, Thavaselvam D, Kumar A, Kumar A, Arora S, Tiwari S, et al. Isolation, identification and characterization of Burkholderia pseudomallei from soil of coastal region of India. Springerplus 2014;3:438.  Back to cited text no. 11
Currie BJ, Jacups SP. Intensity of rainfall and severity of melioidosis, Australia. Emerg Infect Dis 2003;9:1538-42.  Back to cited text no. 12
Vidyalakshmi K, Lipika S, Vishal S, Damodar S, Chakrapani M. Emerging clinico-epidemiological trends in melioidosis: Analysis of 95 cases from western coastal India. Int J Infect Dis 2012;16:e491-7.  Back to cited text no. 13
Koshy M, Jagannati M, Ralph R, Victor P, David T, Sathyendra S, et al. Clinical manifestations, antimicrobial drug susceptibility patterns, and outcomes in melioidosis cases, India. Emerg Infect Dis 2019;25:316-20.  Back to cited text no. 14
Chrispal A, Rajan SJ, Sathyendra S. The clinical profile and predictors of mortality in patients with melioidosis in South India. Trop Doct 2010;40:36-8.  Back to cited text no. 15
Currie BJ, Jacups SP, Cheng AC, Fisher DA, Anstey NM, Huffam SE, et al. Melioidosis epidemiology and risk factors from a prospective whole-population study in Northern Australia. Trop Med Int Health 2004;9:1167-74.  Back to cited text no. 16
Suputtamongkol Y, Chaowagul W, Chetchotisakd P, Lertpatanasuwun N, Intaranongpai S, Ruchutrakool T, et al. Risk factors for melioidosis and bacteremic melioidosis. Clin Infect Dis 1999;29:408-13.  Back to cited text no. 17
Limmathurotsakul D, Peacock SJ. Melioidosis: A clinical overview. Br Med Bull 2011;99:125-39.  Back to cited text no. 18
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.  Back to cited text no. 19
Koshy M, Sadanshiv P, Sathyendra S. Genitourinary melioidosis: A descriptive study. Trop Doct 2019;49:104-7.  Back to cited text no. 20
Hoffmaster AR, AuCoin D, Baccam P, Baggett HC, Baird R, Bhengsri S, et al. Melioidosis diagnostic workshop, 2013. Emerg Infect Dis 2015;21:e141045. doi:10.3201/eid2102.141045.  Back to cited text no. 21
Chetchotisakd P, Chierakul W, Chaowagul W, Anunnatsiri S, Phimda K, Mootsikapun P, et al. Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): A multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet 2014;383:807-14.  Back to cited text no. 22
Limmathurotsakul D, Chaowagul W, Chierakul W, Stepniewska K, Maharjan B, Wuthiekanun V, et al. Risk factors for recurrent melioidosis in northeast Thailand. Clin Infect Dis 2006;43:979-86.  Back to cited text no. 23


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Epidemiology and...
Melioidosis in India
Risk Factors
Clinical Spectru...

 Article Access Statistics
    PDF Downloaded334    
    Comments [Add]    

Recommend this journal