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Melioidosis: Epidemiology, clinical manifestations, and diagnosis

Melioidosis: Epidemiology, clinical manifestations, and diagnosis
Authors:
Bart Currie, MBBS, FRACP
Nicholas M Anstey, MBBS, FRACP, PhD
Section Editor:
Daniel J Sexton, MD
Deputy Editor:
Allyson Bloom, MD
Literature review current through: Dec 2022. | This topic last updated: Aug 30, 2022.

INTRODUCTION — Melioidosis is an infection caused by the facultative intracellular gram-negative bacterium Burkholderia pseudomallei [1-4]. This organism is a widely distributed environmental saprophyte in soil and fresh surface water in endemic regions [5].

The epidemiology, clinical manifestations, and diagnosis of melioidosis will be presented here. The treatment and prognosis of this disease are discussed separately. (See "Melioidosis: Treatment and prevention".)

EPIDEMIOLOGY

Geographic distribution

Historically endemic areas — Melioidosis occurs predominantly in Southeast Asia, northern Australia, South Asia (including India), and China (figure 1) [2,6-9]. The majority of diagnosed cases are from Thailand [10-13], Malaysia [14-17], Singapore [18-24], and northern Australia [25-27]. Cases are also reported from Papua New Guinea [28] and New Caledonia [29].

Northeastern Thailand and parts of northern Australia are "hyperendemic" for melioidosis [11,25], with seasonal peaks in the wet seasons. After 2010, there was an increase in incidence in northeastern Thailand, northern Australia, and South Asia [30-33].

Cases elsewhere globally — Melioidosis has been described outside the classic endemic regions. Many such cases are acquired by visitors to endemic areas, with symptoms arising after departure from the endemic area [34,35]. However, sporadic human or animal cases and occasional environmental isolates of B. pseudomallei have been increasingly described elsewhere, making the endemic boundaries of melioidosis less clear [8,9,36].

As an example, in the United States, melioidosis has been rare. Although most cases have been travel associated, several non-travel-associated cases have been reported, supporting the concept that B. pseudomallei is potentially endemic in the southern United States [37].

Endemicity in the Gulf Coast of the United States B. pseudomallei was identified in environmental samples (soil and water) from the Mississippi Gulf Coast region in July 2022 [38]. The environmental isolates were genetically linked to isolates cultured from two unrelated patients who lived in the area, had no history of travel, and presented with melioidosis in 2020 and 2022. This was the first confirmation that B. pseudomallei is endemic in the continental United States.

Bacterial genotyping of an earlier non-travel-associated case in Texas had supported the possibility that melioidosis may also be endemic there [39], as had a prediction model of the global presence of B. pseudomallei [40]. Nevertheless, environmental sampling from Texas has to date not recovered B. pseudomallei, so endemicity in that region of the Gulf Coast has yet to be confirmed.

Endemicity in Puerto Rico Although cases have rarely been reported from Puerto Rico, epidemiologic analysis and environmental sampling indicate that B. pseudomallei is endemic there [41]. Six cases of melioidosis were reported from eastern Puerto Rico between 1982 and 2012 [42]. During investigation of two of those cases, seropositivity to B. pseudomallei was identified in a subset of individuals who lived in proximity to the index patients, and B. pseudomallei was isolated from soil samples from a single site.

Sporadic non-travel-associated cases in the United States – Between March and July 2021, four non-travel-associated cases of melioidosis were described in patients from Georgia, Kansas, Texas, and Minnesota [43]. Genomic analysis suggested that an aromatherapy room spray product, which was manufactured in India and sold in the United States online and in stores between February and October, was the common source of exposure [44,45]. The B. pseudomallei isolates identified in this outbreak were most closely related to strains found in South Asia.

Previously, between 2008 and 2013, 34 cases of melioidosis were reported in the United States; only three did not have documented travel to an area endemic for melioidosis [46]. Despite extensive investigation, the source of the infection in these three cases could not be identified, but genomic analysis of B. pseudomallei from the patients suggested that the infecting bacteria were imported from Southeast Asia [47].

Cases suggestive of endemic infection have also been reported from Africa, Indian Ocean countries (such as Mauritius), the Middle East, the Caribbean, and Central and South America [48-52].

Despite better recognition and increased surveillance of infection, the full extent of global distribution of B. pseudomallei remains unclear, especially the extent to which melioidosis has spread beyond historical locations and the timing and modes of global spread [53]. Phylogenetic analysis of autochthonous cases from Madagascar and other isolates from a global dataset suggests spread of B. pseudomallei from Asia to Africa, with subsequent spread from West Africa to the Americas that was potentially linked to the slave trade [54,55]. Statistical modelling of clinical cases and environmental studies globally estimated that, in 2015, there may have been 165,000 melioidosis cases globally, with 89,000 deaths [40]. That study predicted that melioidosis was likely to be endemic in 34 countries that so far have had no confirmed cases. Targeted surveillance together with support for improved regional microbiology facilities are needed to reveal the accuracy of these predictions [56].

Transmission — Transmission of infection can occur via percutaneous inoculation, inhalation, aspiration, and occasionally ingestion.

Primary routes of transmission – The predominant mode of transmission is likely percutaneous inoculation during exposure to wet season soils or contaminated water [6,25,57]. Cases of pneumonia following presumptive inoculating skin injuries are well documented, suggesting that the organism can reach the lungs via the hematogenous route [25]. Inhalation (as described among soldiers in Vietnam exposed to dust raised by helicopter rotor blades) had previously been thought to be the primary route of acquisition [58-60].

During severe weather events such as tropical storms and cyclones, the primary mode of transmission may shift from inoculation to inhalation [61-64]. This is supported by observations that rainfall in the two weeks prior to onset of symptoms may be an independent risk factor for a pneumonic presentation, septic shock, and death, which are thought to be more likely with inhalational exposure [61]. Cases of melioidosis pneumonia that occurred at the time of the December 2004 tsunami in the Indian Ocean were associated largely with aspiration events, although inoculation of the organism in the setting of lacerations may have also occurred [62-64].

Ingestion of water contaminated with B. pseudomallei may also be a relatively important route of transmission, especially in endemic regions with unchlorinated water supplies [25,65,66]. Such transmission could explain the much higher rate of parotid and liver abscesses observed in parts of Southeast Asia compared with northern Australia [5,53,67].

Uncommon routes of transmission – Person-to-person transmission is extremely unusual, despite the large bacterial load in severely ill patients with bacteremic pulmonary melioidosis [5,68]. Mother-to-infant transmission during breastfeeding has been described in the setting of B. pseudomallei mastitis [2,69]. Sexual transmission has also been postulated as an uncommon route of transmission [70,71]. Laboratory-acquired infections and iatrogenic infections from contaminated hospital or surgical equipment occasionally occur [5,72-77]. Transmission through blood transfusion or organ donation has not been reported.

Transmission related to animal exposure is very rare; three possible cases have been described in Australia [77,78].

Risk factors

Exposure risk — In endemic areas, individuals who have environmental exposure to soil and water have a higher risk of exposure to and infection with B. pseudomallei. As an example, in a study of 1148 individuals with culture-confirmed melioidosis identified over 30 years in the Northern Territory of Australia, occupational or recreational exposure to soil or surface water was documented for 16 and 78 percent, respectively [79]. Relevant activities included gardening and landscaping. In a study of 204 patients with melioidosis in Thailand, 85 percent were rice farmers [80].

The risk of exposure and infection also varies by season. The majority of endemic clinical cases of melioidosis occur in the monsoonal wet seasons: 75 percent of cases in northeast Thailand (May to October) [81] and 81 percent of cases in the Northern Territory of Australia (November to April) [32]. Severe weather events (eg, monsoons or tropical cyclones) have been associated with local clusters of infection [79].

Comorbidities — Severe or fatal melioidosis most commonly occurs in individuals with specific comorbidities [26,32,79,80,82]. The most important risk factors for melioidosis are [11,32,57,80-84]:

Diabetes mellitus

Hazardous alcohol use

Chronic kidney disease

Chronic lung disease

In a study of 1148 individuals with culture-confirmed melioidosis identified over 30 years in the Northern Territory of Australia, these were the most common underlying conditions, reported in 45, 40, 27, and 12 percent of patients, respectively [79]. Although no single risk factor was associated with mortality, absence of any risk factor was associated with survival. Only 3 of 186 patients with no identified risk factor died; those with at least one risk factor were at least eight times more likely to die.

Other less common risk factors include malignancy, immunosuppressive therapy or conditions, especially high-dose glucocorticoids, rheumatic heart disease, congestive cardiac failure, and kava consumption [25,79,80]. Pulmonary hemosiderosis, chronic granulomatous disease, tuberculosis, and thalassemia have also been proposed as potential risk factors [80,85,86].

In patients with cystic fibrosis, B. pseudomallei can cause both colonization and pulmonary infections [87-90]. Patients with cystic fibrosis traveling to melioidosis endemic areas should be counseled about the possibility of infection with B. pseudomallei and that it can cause problems analogous to Burkholderia cepacia [91].

Children with melioidosis are less likely than adults to have identifiable risk factors [92-95]. One study from Malaysia reported that the risk of melioidosis was substantially higher among children with thalassemia major until universal iron chelation therapy was introduced [96].

INCUBATION PERIOD — The incubation period for acute melioidosis following inoculating injury ranges from 1 to 21 days (mean 4 to 9 days) [76,79,97]. The incubation period is likely influenced by the inoculating dose, mode of transmission, host risk factors, and variable virulence properties of the isolate [60,98]. Rapid onset of melioidosis (within 24 hours of inoculation) has been seen in the setting of presumed aspiration following near-drowning [99,100], as well as in a small number of patients with heavy environmental exposure [97].

Melioidosis can also uncommonly present as reactivation of latent infection years after the initial exposure. (See 'Spectrum and time course of infection' below.)

CLINICAL FEATURES

Spectrum and time course of infection — Serologic studies suggest that most infections with B. pseudomallei are asymptomatic or subclinical [101]; severe clinical disease occurs mainly in those with certain comorbidities [32,102-106]. (See 'Comorbidities' above.)

Among symptomatic individuals, most present with acute infection (within two months of diagnosis). In a study of 1148 individuals with culture-confirmed melioidosis identified over 30 years in the Northern Territory of Australia, 88 percent presented with acute infection, 9 percent with chronic infection, and 3 percent with reactivation of latent infection [79]. The observation that most cases present during the wet seasons, when the risk of exposure is highest, also suggests that most infections in endemic areas are acute [7,11,25,32,83,104] (see 'Exposure risk' above). However, in occasional cohorts, chronic infection is more common than acute [107].

The clinical presentation varies by time course of infection, although pneumonia is overall the most common manifestation of melioidosis:

Acute infection – The most common clinical manifestation of acute infection is pneumonia; other sites of infection include skin and soft tissue and the genitourinary tract (figure 2). Bacteremic spread of the organism can result in clinical manifestations involving virtually any site. Over half of all patients are bacteremic and up to a quarter can present with septic shock; overall mortality from melioidosis ranges from less than 10 to over 40 percent [30,79]. (See 'Common manifestations' below.)

Chronic infection – Of those with chronic melioidosis (symptoms persisting for longer than two months), the majority present with chronic pulmonary symptoms and signs that may mimic tuberculosis or with a non-healing skin ulcer or abscess [79] (see 'Pneumonia' below and 'Skin infection' below). Chronic infection is more indolent than acute infection and has been associated with a 6.5 times lower mortality rate (2 percent) [79].

Latent infection with (re)activation – Infection with B. pseudomallei can uncommonly be latent and subsequently activate, analogous to tuberculosis. As above, only 3 percent of over 1000 cases of melioidosis in northern Australia were thought to be reactivation of latent infection [79]. The longest reported latent period between exposure in an endemic region and the development of melioidosis in a nonendemic region is 29 years [108-111]. Although one case had suggested a 62-year latency period, subsequent genotyping of the bacterial isolate indicated that ascertainment of the timing of initial infection was incorrect and that the patient was likely infected through more recent travel [51].

Following the Vietnam War, approximately 225,000 returning military personnel were estimated to be at potential risk of reactivation of melioidosis [112]. Although occasional cases of B. pseudomallei (re)activation had been documented in Vietnam veterans, they were rare relative to the number of individuals exposed [59,108].

Impact of age on clinical presentation — Most cases of melioidosis occur in adults [113]. As an example, in a study of 1148 individuals with culture-confirmed melioidosis identified over 30 years in the Northern Territory of Australia, the median age was 50 years, and only 48 individuals (4 percent) were younger than 15 years of age [79].

The most common clinical presentations of B. pseudomallei infection are also distinct and generally less severe in children compared with adults [93,95]. In the study described above, children were more likely than adults to present with localized skin infection (58 versus 11 percent) and less likely to have bacteremia (15 versus 58 percent) [79]. Pneumonia occurs infrequently in children. In Southeast Asia, suppurative parotitis is a common presentation in childhood [92,93]. (See 'Parotitis' below.)

Although reported mortality rates in children are lower than in adults, mortality in neonates is exceptionally high (75 percent in one systematic review [114]).

Common manifestations

Pneumonia — Pneumonia is the most common clinical presentation of melioidosis in adults in almost all studies [2,15,22,113] and was reported in over half of the cases that occurred in the Northern Territory of Australia from 1989 to 2019 (figure 2) [79]. Patients with both acute and chronic infection present with pneumonia:

Acute presentation – Melioidosis can present similarly to acute community-acquired pneumonia, with high fever, cough, sputum, chills, rigors, and respiratory distress with or without shock [115]. Chest radiographic findings vary widely and may include discrete diffuse or patchy consolidation that is lobar or multilobar, necrotizing lesions, and pleural effusions (image 1 and image 2) [115-117]. Cavitation and abscesses with fluid levels can occur (picture 1). However, on initial chest radiograph, the infiltrates may be smaller and less extensive than would be expected in severely ill bacteremic patients. Mediastinal lymphadenopathy can occur, potentially linked to inhalational melioidosis, although melioidosis does not usually cause calcification.

Subacute or chronic presentation – Melioidosis can present similarly to tuberculosis, with chronic cough, purulent sputum production, hemoptysis, and night sweats. Imaging findings can also mimic tuberculosis with cavitating, nodular, or streaky infiltrates with fibrotic changes (image 3). Upper lobe consolidation is especially common in chronic melioidosis but can also often be seen in acute presentations. Some patients present with pleural effusion alone.

Skin infection — Skin infections are a relatively common site of localized infection (figure 2) [118]. Cutaneous melioidosis includes skin ulcers (picture 2) and abscesses, as well as pustules and furuncles, crusted erythematous lesions, and macular lesions (picture 3) [32,119]. Often, individuals are diagnosed after having failed to respond to other antibiotics targeted to typical skin pathogens.

Diffuse cellulitis is rare in studies from Australia [119], although it is more frequently reported in Asia [120]. Secondary skin infection characterized by multiple pustules due to systemic spread from a distant site has also been described, as has the uncommon spread of infection to subcutaneous tissues.

In an Australian series, cutaneous melioidosis is less likely to be associated with bacteremia than other forms and is more likely associated with a chronic presentation [79,119].

Genitourinary — Genitourinary melioidosis includes prostatic infection or abscess (image 4), kidney abscess, and urinary tract infection (figure 2). It presents with fever in association with suprapubic pain, dysuria, difficulty passing urine, or acute urinary retention requiring catheterization [121-123]. Diarrhea is a frequent additional complaint. On rectal exam, the prostate may be tender and boggy [123]. Prostatic abscess can also occur as a secondary manifestation in individuals who initially presented with a different site of involvement (eg, pneumonia).

Bacteremia — Bacteremia with B. pseudomallei can be primary (in the absence of a localized site of infection) or secondary (figure 2). In a study of 1148 individuals with culture-confirmed melioidosis identified over 30 years in the Northern Territory of Australia, bacteremia occurred in 633 (56 percent); 129 of those were cases of primary bacteremia without an evident focus of infection [79]. Such patients with primary bacteremia were commonly immunocompromised patients who presented with an acute febrile illness.

Less common sites of infection — Additional manifestations include bone and joint involvement, neurologic involvement, parenchymal abscesses, and parotitis. Rare foci of infection described in case reports or case series include mycotic aneurysms [32,124-129], mediastinal masses [32], pericardial collections (image 5) [10,26,130], and adrenal abscesses [26,131-133].

Septic arthritis or osteomyelitis — Bone and joint involvement is a relatively uncommon initial presentation of melioidosis (picture 4) [10,32,57,134,135]. Septic arthritis and osteomyelitis can also occur as a secondary manifestation in individuals who initially presented with a different site of involvement (eg, pneumonia).

In a retrospective review of 50 patients with B. pseudomallei septic arthritis or osteomyelitis in Australia, the lower limbs were the most commonly affected site, although cases occurred in the upper limbs, vertebra, and pelvis as well [136]. Twenty-eight percent of lower limb septic arthritis cases had accompanying osteomyelitis.

Neurologic involvement — Melioidosis can rarely cause encephalomyelitis (ie, meningoencephalitis) and meningitis, cerebral abscesses, myelitis, and epidural abscess. The type of neurologic manifestation may vary geographically. Encephalomyelitis due to melioidosis accounts for approximately 4 percent of melioidosis cases in northern Australia but is rarely described elsewhere; in Southeast Asia, cerebral abscess secondary to bacteremic seeding is the more common neurologic manifestation [53,137].

Encephalomyelitis associated with melioidosis primarily involves the brainstem; brainstem abscesses can also occur. Patients can present with unilateral upper motor neuron limb weakness, cerebellar signs, cranial nerve palsies (particularly VI, VII nerve palsy and bulbar palsy), or flaccid paraparesis [138,139]. Most have normal or near-normal consciousness on initial presentation. Cerebrospinal fluid (CSF) analysis demonstrates a predominantly monocytic pleocytosis (with white blood cell counts ranging from 30 to 775), elevated protein, and normal or slightly decreased glucose [138,139]. Culture of CSF is often negative. (See 'Culture' below.)

Computed tomography (CT) of the brain is typically normal in patients with encephalomyelitis associated with melioidosis; however, magnetic resonance imaging (MRI) usually reveals dramatic changes with extensive increased T2-weighted signal intensity in the brainstem (image 6). In the setting of flaccid paraparesis, similar changes may be observed in the spinal cord [139].

That melioidosis encephalomyelitis appears mostly restricted to cases in Australia may reflect regional genotypic differences between B. pseudomallei strains [140]. Animal studies suggest that brainstem infection can result from direct nerve root translocation of the bacteria from the nasal passages [141]. Similar nerve root translocation from skin sources has also been posited [95].

Abscesses within organs — Abscesses in internal organs are well recognized, especially in the spleen (where they are often multifocal), kidney, prostate (image 4), and liver (image 7) [10,26,57]. Fevers, chills, and rigors with and without hypotension are common, but localizing symptoms are often absent.

Parotitis — Suppurative parotitis is a common presentation of melioidosis in children in Thailand and Cambodia, accounting for up to 40 percent of cases among Thai children [92,93,142]. Children present with parotid pain accompanied by swelling and tenderness. Parotitis is far less common in Australia. Ingestion of water contaminated with B. pseudomallei may at least in part explain the higher rates of parotitis seen in parts of Southeast Asia [53,67].

True colonization is very uncommon — Patients with chronic lung disease and infection with B. pseudomallei who are not adequately treated may have residual respiratory infection following resolution of overt signs of disease. The majority of such cases manifest at least low-grade lung infection or disease elsewhere, and there is a significant risk of subsequent invasive disease [91,97,143]. With appropriate treatment, persisting infection is exceptionally uncommon, but true colonization with avirulent B. pseudomallei resulting from gene reduction has been described [144,145]. Therefore, isolation of B. pseudomallei from any clinical specimen generally warrants treatment.

Differential diagnosis — The differential diagnosis of melioidosis is broad and depends on the presenting features. As examples, acute pneumonia due to melioidosis could present similarly to other causes of community-acquired pneumonia (both bacterial and viral), chronic pulmonary infection often mimics tuberculosis, and skin involvement could be mistaken for staphylococcal or streptococcal skin and soft tissue infections. Multiple distinct sites of infection (eg, abscesses in multiple organs) should raise the possibility of Staphylococcus aureus or causes of other bacterial sepsis and disseminated infection.

The microbiologic differential diagnoses of clinical syndromes that have been associated with melioidosis are discussed elsewhere:

(See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology'.)

(See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Microbiology' and "Skin lesions in the returning traveler".)

(See "Acute bacterial prostatitis", section on 'Microbiology'.)

(See "Gram-negative bacillary bacteremia in adults", section on 'Microbiology'.)

(See "Clinical manifestations and complications of pulmonary tuberculosis", section on 'Differential diagnosis'.)

DIAGNOSIS

Clinical suspicion and diagnostic evaluation — The approach to diagnosis of melioidosis demonstrates the importance of the residence and travel history in the workup of infectious syndromes:

In endemic regions, melioidosis should be routinely considered part of the differential diagnosis of acute or chronic pneumonia, ulcerated or purulent skin lesions, undifferentiated sepsis, and prostatic abscesses; it should also be suspected as a potential cause of bone or joint infection, encephalomyelitis involving the brainstem and/or spinal cord, and cerebral or visceral abscesses. (See 'Historically endemic areas' above and 'Common manifestations' above.)

Outside of endemic regions, melioidosis should be suspected in individuals who present with one of these syndromes and have a history of travel to an endemic area or are from areas where cases are being increasingly reported, particularly if evaluation or treatment for other causes has not been informative. (See 'Cases elsewhere globally' above.)

The possibility of chronic melioidosis or, more rarely, (re)activation of latent melioidosis should also be considered in individuals with exposure to endemic areas who are being evaluated for suspected pulmonary tuberculosis.

For all such presentations, suspicion for melioidosis should be heightened in individuals with comorbidities that increase the likelihood of symptomatic infection, such as diabetes mellitus, hazardous alcohol use, and chronic kidney or lung disease. (See 'Comorbidities' above.)

When the possibility of melioidosis is suspected, we collect specimens from the following sites for microscopy and culture, the latter of which is the primary method of diagnosis [146] (see 'Culture' below):

Blood

Sputum (or other deep respiratory specimen)

Urine

Throat swab

Rectal swab

Swab from any ulcer or skin lesion

Pus/fluid from any drainable abscess or collection

Cerebrospinal fluid (CSF) from individuals with evidence of encephalitis or meningitis (although culture yield of CSF is low)

The likelihood of diagnosing melioidosis is maximized if appropriate clinical samples are obtained from symptomatic at-risk patients from a variety of sites and are sent to the microbiology laboratory for microscopy and culture. In the Northern Territory of Australia, a hyperendemic region, all cultures from blood, sputum, urine, and purulent drainage collected in both primary care clinics and hospitals during the wet season, when melioidosis cases peak, are routinely processed for B. pseudomallei detection [79].

B. pseudomallei grows readily in standard blood cultures, but in cultures from nonsterile sites, it can be overgrown by other organisms, including normal flora. Thus, use of selective media can be helpful to enhance organism recovery from those sites. Timely transport of specimens is important as organism viability decreases with low temperatures and desiccation [146]. If possible, sputum and swabs from skin lesions, throat, and rectum should be plated or inoculated directly onto selective media. The clinical laboratory should be made aware of the suspicion for melioidosis when specimens are submitted, particularly in nonendemic areas.

Serology is not generally useful in the diagnosis of melioidosis because of poor performance and lack of clear thresholds for diagnosis. (See 'Limited role of serology' below.)

Additional imaging to evaluate for other sites of infection — Most patients with suspected melioidosis who presented with pulmonary symptoms or sepsis will have already had chest imaging; we also perform chest radiograph in all other patients with suspected melioidosis. We also routinely perform computed tomographic (CT) scan of the abdomen and pelvis in all adult patients with confirmed or suspected melioidosis, if not already done, to evaluate for asymptomatic abscesses in the prostate (image 4), spleen, liver (image 7), and kidneys [25,116,123]. In children and adult females who are not systemically ill, abdominal ultrasound is a reasonable alternative to CT scan to avoid radiation exposure.

Confirming the diagnosis

Culture — Growth of B. pseudomallei from culture of any site is diagnostic of melioidosis [146]. Although prolonged “colonization” of the airways can occur in occasional situations, it is still likely reflective of a low-grade infection. (See 'True colonization is very uncommon' above.)

Blood cultures are positive for B. pseudomallei in 40 to 70 percent of individuals with melioidosis [118]. The organism grows in a wide range of commercially available blood culture media. With automated blood culture systems, almost all B. pseudomallei-positive specimens are detected within 48 hours [147]. However, such systems are less sensitive than conventional broth cultures; in one study, sensitivity for B. pseudomallei in blood culture was 74 percent for the automated system versus 90 percent with conventional culture, in which bacterial growth was detected by visualization [148].

B. pseudomallei grows well on MacConkey, blood, and chocolate agars. Using Ashdown agar, which contains gentamicin, or Ashdown liquid transport broth, which contains colistin, allows selective growth of B. pseudomallei and thus enhances recovery from sites where normal flora would have otherwise grown [149]. Alternative selective culture media have also been evaluated [150], but Ashdown remains the most commonly used in endemic areas.

Once an organism grows, identification of B. pseudomallei can be made by combining the commercial API 20NE or 20E biochemical kit with a simple screening system. This screening system includes Gram stain, the oxidase reaction, typical growth characteristics, and resistance to certain antibiotics [151,152]. B. pseudomallei is an oxidase-positive, non-lactose-fermenting, Gram-negative bacillus. Concerns have been raised about the low sensitivity of some biochemical tests and the potential for some commercial automated biochemical identification systems to misidentify the organism as other species, such as Burkholderia cepaciaBacillus spp, and Pseudomonas spp [6,153-157]. However, polymerase chain reaction (PCR) is being increasingly used for confirmation of bacterial isolates cultured from clinical samples [154], as is matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) [158]. Nevertheless, misidentification (eg, as Burkholderia thailandensis) has also been reported with MALDI-TOF MS [45]. With larger database profiles, B. pseudomallei is less frequently incorrectly identified as other Burkholderia species [159].

In patients with encephalomyelitis, culture of CSF is often negative; in such cases, the diagnosis is made by culture of B. pseudomallei from other sites in an individual with CSF leukocytosis and consistent findings on imaging. (See 'Neurologic involvement' above.)

When there is high suspicion for melioidosis but cultures are negative for B. pseudomallei, we recommend repeating cultures from potential foci of infection in addition to further imaging as clinically indicated based on presentation, and serial serology (see 'Limited role of serology' below). In rare circumstances, such as some cases of possible neurologic melioidosis, we make a presumptive diagnosis based on clinical suspicion despite negative cultures and treat as melioidosis, while acknowledging that isolation of B. pseudomallei on culture is required for a confirmed diagnosis.

Microscopy — Gram stain of sputum or purulent drainage from abscesses may demonstrate gram-negative bacilli. B. pseudomallei often has a characteristic bipolar staining with a "safety pin" appearance, particularly when the stain is performed from cultured isolates rather than directly from a clinical specimen (picture 5). However, the Gram stain appearance alone is not sufficient for diagnosis [118].

Limited role of serology — Serologic testing is not a reliable method of diagnosis. The indirect hemagglutination test (IHAT) and other serologic tests are available, but their utility remains limited, particularly in endemic areas [160,161].

Both sensitivity and specificity of IHAT are suboptimal [118,146]. In one study of patients with culture-confirmed melioidosis, serology was only positive at the time of presentation in approximately half, and approximately a quarter of those with longitudinal serologic testing did not seroconvert [162]. Conversely, significant background rates of antibodies to B. pseudomallei occur in healthy individuals in endemic areas, and there is no standardized threshold for titers suggestive of active infection [1,106,163]. Accuracy varies widely across different assays.

Several new enzyme-linked immunosorbent assays (ELISAs) targeting specific antigens, such as hemolysin co-regulated protein 1 (Hcp1) and O-polysaccharide (OPS), are being evaluated [164].

Other techniques — A variety of other antigen- and DNA-detection techniques have been used to increase the diagnostic yield, the rapidity of establishing a diagnosis, or to confirm isolate identity. However, most of these techniques are not yet commercially available [152,163,165-171].

Rapid immunofluorescence microscopy of pus, sputum, and urine has been useful in Thailand [172].

PCR has been evaluated but has historically not been sufficiently sensitive or specific for direct detection from clinical samples (eg, blood) [168,173,174]. It is being used more frequently to identify isolates that have grown on culture. (See 'Culture' above.)

A lateral flow immunoassay targeting capsular polysaccharide antigen shows promise for the rapid diagnosis of melioidosis directly from clinical samples and is also useful for confirming culture isolate identity [175-177].

SUMMARY AND RECOMMENDATIONS

Bacterial cause – Melioidosis is an infection caused by the facultative intracellular gram-negative bacterium Burkholderia pseudomallei. (See 'Introduction' above and 'Culture' above and 'Microscopy' above.)

Geographic distribution – Melioidosis occurs predominantly in the historically endemic regions: Southeast Asia, northern Australia, South Asia (including India), and China. Northeastern Thailand and parts of northern Australia are "hyperendemic," with seasonal peaks in the wet seasons. It has also occurred in non-travelers in other tropical and subtropical locations, such as Africa and the Americas (including Puerto Rico and the Gulf Coast of the United States), where the organism has been found in environmental samples. Elsewhere, infections primarily occur in travelers to endemic areas. (See 'Geographic distribution' above.)

TransmissionB. pseudomallei is transmitted predominantly through percutaneous exposure to wet season soils or contaminated water. During severe weather events, inhalation may be the primary mode of transmission. Ingestion of unchlorinated water supplies is another potential route. Person-to-person transmission is highly unusual. (See 'Transmission' above and 'Exposure risk' above.)

Spectrum of illness – Most B. pseudomallei infections are likely asymptomatic or subclinical. Most symptomatic infections present acutely and are associated with significant morbidity (figure 2). Severe clinical disease occurs mainly in adults with certain comorbidities (diabetes mellitus, hazardous alcohol use, chronic kidney and lung disease). (See 'Spectrum and time course of infection' above and 'Comorbidities' above and 'Impact of age on clinical presentation' above.)

Clinical features – Pneumonia is the most common clinical presentation of both acute (image 1 and image 2) and chronic (image 3) melioidosis in adults (figure 2). Skin infections, including ulcers (picture 2), abscesses, and macular lesions (picture 3), are also common. Genitourinary infection consists mainly of prostatic abscesses. Overall, bacteremia occurs in around half of cases, and septic shock in up to a quarter. (See 'Common manifestations' above.)

Less commonly, melioidosis can also present with a variety of clinical manifestations, including bone and joint infection, neurologic infection, and abscesses in visceral organs, generally due to bacteremic spread (figure 2). (See 'Less common sites of infection' above.)

Diagnostic evaluation – When melioidosis is suspected (consistent clinical syndromes in residents of or travelers from endemic areas), we suggest sending blood, sputum, urine, and throat and rectal swabs for microscopy and culture. We also send pus or swabs from any ulcer or skin lesions, drainable abscesses, and, in individuals with central nervous system abnormalities, cerebrospinal fluid (CSF). The laboratory should be notified of the clinical suspicion for melioidosis. We also obtain abdominal imaging to identify additional sites of infection. (See 'Clinical suspicion and diagnostic evaluation' above and 'Additional imaging to evaluate for other sites of infection' above.)

Microbiologic diagnosis – Growth of B. pseudomallei from culture of any site is diagnostic of melioidosis. On microscopy, the gram-negative bacillus often has a characteristic bipolar staining with a "safety pin" appearance. Serologic testing is not a reliable method of diagnosis, and other techniques are not widely available. (See 'Confirming the diagnosis' above.)

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