Approach

Melioidosis follows exposure to, and infection with, the soil and water bacterium Burkholderia pseudomallei.[43][58] Hot spots for infection are northeast Thailand and northern Australia, but melioidosis is endemic in most countries of Southeast Asia and South Asia and is increasingly being documented from countries in Africa and Central and South America.[24][25][59][60][61] Local resources are available in many endemic areas, such as:

Infection can occur in travellers from those locations, and has also been reported in non-endemic countries including France, the US, Saudi Arabia, and China.[26][27][28][29][30] The vast majority of cases of melioidosis are from recent infection, but latency and subsequent activation years after infection is well recognised although rare.[7][40][42]

Glanders is a disease of horses and other equines caused by a closely related bacterium, Burkholderia mallei, that can sometimes be transmitted to humans, although human glanders is extremely rare nowadays.[3][4][41]

Both conditions have a similar clinical presentation and have been considered together throughout this topic.

History

Melioidosis

  • Exposure to B pseudomallei can be occupational, recreational, or following severe weather events where bacteria may be aerosolised, so a history of soil or water contact or outdoor activities is the norm.[8][26][43][45][62]

  • A high percentage of patients with confirmed disease are diabetic. Both type 1 and type 2 diabetes and poor diabetic control increase the risk.[7][8][50][51] Other risk factors include hazardous alcohol use, chronic renal disease, malignancy and immunosuppressive therapy, thalassaemia, and cystic fibrosis and other chronic lung diseases.[7][50][51][52][53][54]

  • Between 20% and 40% of people with melioidosis in endemic regions have no identified risk factor, but this is not usually associated with severe disease.[7][51]

Glanders

  • Patients with glanders usually have a history of contact with horses or laboratory work with B mallei.[3][4][41]

Physical examination

Disease onset occurs 1 day to 3 weeks after infection and is acute in presentation, but 10% of cases present with chronic melioidosis (symptomatic >2 months). Activation from a latent focus can occur decades after an initial asymptomatic infection in <5% of cases.[7][63]

Over 50% of cases present as community-acquired pneumonia,[37][64] and almost one quarter of all cases have septic shock on presentation.[65]

Patients usually have fever, sweats, cough (with or without sputum production), and symptoms (e.g., swelling and pain, dyspnoea, urinary retention) that relate to the localised foci of infection.

Skin ulcers/abscesses,[9] lymphadenitis, parotitis (usually unilateral), and infection in internal organs without evident sepsis can be the major findings in some cases. Internal organ abscesses may be present (e.g., prostate, muscle, liver, spleen, lung).

Septic arthritis and/or osteomyelitis can rarely be the primary presentation of melioidosis, but are more common as secondary manifestations that appear clinically a week or more into therapy for melioidosis, presenting as pneumonia or other sepsis.[13] A case of a patient presenting with spondylodiscitis has been reported.[14]

CNS melioidosis, while rare, may present as osteomyelitis or scalp/extra-axial abscess.[15] A case of a spinal epidural abscess has also been reported.[16] Melioidosis encephalomyelitis is rare and mostly restricted to infection in northern Australia and seen relatively more commonly in children.[10][17][18] Presentation is with fevers, often headaches with/without altered conscious state, and cranial nerve palsies (e.g., lower motor neuron VII and VIII nerve), usually with some peripheral motor weakness.[19] Occasionally flaccid paralysis with/without urinary retention occurs from myelitis without the features of brainstem encephalitis.[10] Bacteraemic spread can result in brain abscesses and this is not restricted to Australia.[20] 

Mycotic pseudo-aneurysms of usually atherosclerotic major arteries (most commonly the abdominal aorta) are a rare but life-threatening primary or secondary clinical manifestation of melioidosis that requires urgent referral to a vascular surgeon.[21]

Initial investigations

Culture of B pseudomallei (or B mallei) is the gold standard and the only way to confirm melioidiosis or glanders. Blood cultures are positive in >50% of cases. Sputum, urine, and pus/swab cultures are usually positive where reflecting the site of clinical disease. In patients strongly suspected of having melioidosis in whom other cultures are negative, culture of a throat swab and the centrifuged deposit of urine on selective media may be helpful.[66][67][68][69][70] Any isolation of B pseudomallei from a clinical sample is considered confirmatory of a diagnosis of melioidosis. Melioidosis cannot be diagnosed with certainty without a positive culture, although in some patients cultures will be repeatedly negative because of difficulty identifying and sampling the focus of infection. In such cases, cultures should be repeated if necessary.

Chest x-ray and computed tomography (CT) scan or ultrasound of abdomen and pelvis should be ordered for all cases to confirm the extent of disease.[7][71][72][73] If CT is not available, and to avoid CT radiation dose in children and younger women, ultrasound of abdomen and pelvis is an alternative.

Serology, while available in some endemic regions, has poor specificity for melioidosis because of background seropositivity in those living in endemic areas.[38][74]

Other investigations

Exposure to B pseudomallei, and its near neighbours, is very common in endemic areas, resulting in high background seropositivity.[74] Some healthy people have very high titres in tests like the indirect haemagglutination test; therefore, a single titre is not a reliable test to make a diagnosis. The demonstration of 4-fold rising titres may be more useful, especially in people from non-endemic areas. However, some patients with culture-confirmed melioidosis never mount an antibody response.[38]

Cerebrospinal fluid (CSF) culture is often negative in cases of encephalomyelitis. In these patients, CSF analysis shows increased protein and white cells (often lymphocytes predominate).[18]

Several polymerase chain reaction (PCR) tests for melioidosis and glanders have been developed, the most useful of which targets TTS-1.[75] Whilst the positive predictive value is high they lack sensitivity, especially on blood, and so cannot be used to rule out infection.

Emerging investigations

Rapid antigen detection tests are currently under evaluation.[76][77][78] As with PCR, the specificity and positive predictive value are high, but negative tests cannot rule out infection.

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