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Table of Contents    
CASE REPORT
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 1100-1105

Melioidosis mimicking tuberculous vertebral osteitis: Case report and review of literature


1 Department of Neurosurgery, Institute of Neurosciences, Apollo Hospitals, Chennai, Tamil Nadu, India
2 Department of Infectious Diseases, Apollo Hospitals, Chennai, Tamil Nadu, India
3 Department of Radiology, Apollo Hospitals, Chennai, Tamil Nadu, India
4 Department of Microbiology, Apollo Hospitals, Chennai, Tamil Nadu, India

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. Anil Pande
Department of Neurosurgery, Institute of Neurosciences, Apollo Hospitals, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.236976

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 » Abstract 


Whitmore's disease or melioidosis is an infectious disease caused by Burkholderia pseudomallei. The reported cases are but the tip of the iceberg. This pathogenic saprophyte is commonly found in wet soil and water. An accidental or occupational exposure (in field workers, farmers, gardeners or villagers) to B. pseudomallei contaminated soil or pooled water is the primary source of infection. Neurosurgeons need to consider this as a possible rare cause of back pain and possible neurological deterioration. A diabetic type 2 rice farmer with severe lumbago and fever, misdiagnosed as vertebral tuberculous osteitis based on his radiological findings, was confirmed to harbour Burkholderia Pseudomallei, which was diagnosed using laboratory cultures. He made a remarkable recovery with antibiotic therapy. The empiric anti-tuberculous (ATT) drugs were stopped. The rare differential diagnosis of melioidosis should be thought of in diabetic patients with a psoas abscess and vertebral osteitis, especially in rice farmers from endemic regions that includes India.


Keywords: Burkholderia Pseudomallei, low back pain, melioidosis, psoas abscess, spinal infection, vertebral osteitis, Whitmore's disease
Key Message: Vertebral osteitis with paraspinal and psoas abscess can be caused by Burkholderia Pseudomallei. Reported cases of melioidosis or Whitmore′s disease are just the tip of the iceberg. Neurosurgeons need to consider this as a possible rare cause of lumbago often associated with neurological deterioration. Empiric anti-tuberculous (ATT) drugs should be used cautiously, especially in diabetic rice farmers. Reporting these rare cases is essential to assess the true burden of this serious, and occasionally, lethal illness.


How to cite this article:
Pande A, Nambi P S, Pandian S, Subramanian S, Ghosh S. Melioidosis mimicking tuberculous vertebral osteitis: Case report and review of literature. Neurol India 2018;66:1100-5

How to cite this URL:
Pande A, Nambi P S, Pandian S, Subramanian S, Ghosh S. Melioidosis mimicking tuberculous vertebral osteitis: Case report and review of literature. Neurol India [serial online] 2018 [cited 2018 Nov 18];66:1100-5. Available from: http://www.neurologyindia.com/text.asp?2018/66/4/1100/236976




Whitmore's disease or melioidosis is an infectious disease caused by Burkholderia pseudomallei, a pathogenic saprophyte commonly found in wet soil and water. An accidental or occupational exposure to B. pseudomallei present in the contaminated soil or pooled water is the primary source of infection. The manifestations of vertebral osteitis with paraspinal and psoas abscess, caused by Burkholderia Pseudomallei, in a diabetic rice farmer, who was misdiagnosed as having tuberculous affliction of the spine, is being reported. The patient was erroneously being administered empiric anti-tuberculous (ATT) medication


 » Case Report Top


A 40-year old, type 2 diabetic farmer from a village near Tirupati, Andhra Pradesh, India, presented with excruciating low back pain and intermittent high-grade fever of 45-days duration. The patient reported pain involving both the lower extremities with a high intensity specifically on the right side. However, no typical history of radiculopathy or myelopathy was found. There were no neurological deficits. His single leg raising test was positive bilaterally, but was nonconclusive due to the presence of severe pain. His past medical history revealed the presence of pulmonary tuberculosis infection 5 years ago for which he had been administered a 9-month course of essential anti-tuberculous (ATT) medications. His coronal magnetic resonance imaging (MRI) scan of the lumbar spine with contrast (done in another medical facility) revealed enhancing lytic areas in the L4 vertebral body and the right iliac bone, associated with peripherally enhancing, centrally necrotic, multi-loculated, right paraspinal abscess, with psoas and right gluteal soft tissue components [Figure 1]a and [Figure 1]b.
Figure 1: (a and b) Pretherapy: Coronal post-contrast T1 fat suppressed images show enhancing lytic lesions in the right half of L4 vertebral body and right iliac bone; peripherally enhancing centrally necrotic right paraspinal, right psoas and right gluteal soft tissue components are also noted

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Based on these radiological findings, a diagnosis of tuberculosis was made and ATT was started empirically.

On examination, a paraspinal swelling and a left knee joint effusion were observed. Upon admission to our hospital, a computed tomographic (CT)/ultrasound (USG)-guided biopsy was planned. As the USG examination revealed a right paraspinal fluid collection with freely mobile internal echoes, an USG guided aspiration was performed under local anaesthesia. The aspirate revealed frank pus. Microscopy showed gram negative bacteria [Figure 2] and laboratory culture tests of the pus sample revealed the growth of Burkholderia pseudomallei in both blood [Figure 3] and MacConkey agar medium [Figure 4].
Figure 2: Microscopy showing Gram negative bacilli

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Figure 3: Growing colonies of  Burkholderia pseudomallei Scientific Name Search n blood agar

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Figure 4: Growing colonies of Burkholderia Pseudomallei on MacConkey agar

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On blood culture tests, the two aerobic test tubes also showed positive results and the same microorganism was identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The organism was found to be sensitive to antibiotics like ceftazidime, meropenem, and trimethoprim–sulfamethoxazole. No other mycobacterial and fungal growth were observed on the culture. Follow-up test cultures also revealed negative results for other microorganisms. The gene Xpert MTB (Mycobacterium tuberculosis) for tuberculosis was negative. The rheumatoid arthritis factor and human leucocytic antigen (HLA) B27 were also negative. Laboratory findings revealed significant neutrophilic leucocytosis with toxic granules and a white cell count of 18.35 × 103/mm 3, an erythrocytic sedimentation rate of 140 mm/hr in the first hour, and a haemoglobin level of 7.9 gm%. The glycosylated haemoglobin was 10.9%. The serum sodium, potassium and chloride levels were found to be 130, 4.2 and 90 mEq/l, respectively. The serum alkaline phosphatase level was 222 U/l. After treatment with antibiotics, regression of the primary psoas abscess was noted. He was managed conservatively, as has been the reported norm for the disease. Suggestions of the infectious disease specialist were also incorporated into the patient's treatment plan. Empiric ATT treatment started in the earlier hospital was aborted. The patient was started on intravenous ceftazidime (2 gm thrice daily) along with oral trimethoprim (TM)-sulfamethoxazole [SMX] (80 mg TMP with 400 mg SMX) and doxycycline (100 mg twice daily). Prolonged antibiotic therapy has been recommended in case of chronic infections. An intensive phase of therapy using intravenous ceftazidime for 6 weeks was given in view of the spinal involvement, followed by oral maintenance therapy with doxycycline and TM-SMX. He was advised to continue the antibiotic therapy for one year. His diabetic treatment was optimised. The glycosylated haemoglobin was reduced to 5.3% and white cell counts also came down to 11.3 × 103/mm 3. Other laboratory parameters were also found to normalise gradually. Finally, the patient was discharged on medication. His visual analogue scale (VAS) pain score reduced from 9 to 3 and he did not have any neurological deficits at the time of discharge. The follow-up MRI of the lumbar spine with contrast after 6 weeks of antibiotic therapy revealed significant resolution of the right paraspinal and gluteal soft tissue components, with residual right iliac bone disease persisting [Figure 5]a and [Figure 5]b.
Figure 5: (a and b) Posttherapy: Follow up MRI of the lumbar spine with contrast after 6 weeks of initiation of treatment reveals significant resolution of the right paraspinal and gluteal soft tissue components with residual right iliac bone disease

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 » Discussion Top


Melioidosis, also known as Whitmore's disease, is an infectious disease caused by a Gram-negative bacterium called Burkholderia Pseudomallei. B. Pseudomallei is an environmental saprophyte which is commonly found in wet soil and water. It was first described by Alfred Whitmore and C. S. Krishnaswami in 1911 as an undescribed infective disease occurring among the population of Rangoon, Burma.[1] Glanders caused by Burkholderia mallei is a disease of horses, but humans can also be infected.[2]

It is described as an emerging infectious disease with a mortality rate of 58%.[3] Majority of patients suffering from melioidosis are found to be diabetic (38-75%), and exposure to the contaminated water or soil is the root cause of affliction in 39-85% of patients. Commonly, rice farmers who have an increased exposure to contaminated soil and pooled water are prone to this infection.[4] The other predisposing factors cited are pre-existing renal disease, thalassemia, and an occupational exposure. An increase in the infectivity rate shows a strong correlation with rainfall.[5]

Contamination of non-chlorinated water supply has been found to be an underreported causative factor.[6] The rare transmission of the disease via breast feeding to neonates has been noted.[7] Even though neonatal infection is possible, clinical reports of neonatal cases suffering from melioidosis are rare.[8] The disease is reported to be endemic in the Indian subcontinent, where it is said to be an emerging disease with the few reported cases likened to be the tip of the iceberg.[9],[10] In recent years, melioidosis has also been reported globally in different countries like Australia, Malaysia, and Africa.[6],[11],[12] Melioidosis is commonly underdiagnosed and underreported in India.[13] In India, cases suffering from melioidosis have been largely reported from Tripura, Kerala, Orissa, Tamil Nadu, and Maharashtra.[14] The seroprevalance rates of 7% have been found from rice growing areas near Vellore.[9] Furthermore, travel history has to be taken into consideration, as melioidosis can be seen in distant non-endemic regions brought there by travellers or tourists.[15],[16]

Melioidosis is characterised by abscess formation in all parts of the body.[17] It is classified as acute or chronic (based on the duration of symptoms); bacteremic or non-bacteremic (based on the isolation of bacterium from blood culture); and, localized (or focal) or disseminated (or multifocal, based on the organ involvement) melioidosis. Although, melioidosis is found be to focal in 78.5% of cases, multifocal melioidosis is more frequently reported (28.5%).[6] The mortality rates are found be to be high (20-40%), and relapse can occur in 6-13% of patients.[6] Generally, all organ systems are found be involved in patients with melioidosis, including the head and neck.[18],[19] Neurological involvement is seen in approximately 7% of cases, and brain abscess, meningoencephalitis, and empyema, with both cranial and spinal involvement have been reported.[18],[19],[20],[21],[22],[23] A distinct neurological syndrome characterised by peripheral motor weakness, brain stem encephalitis, and respiratory failure is also seen.[22] In a recent study involving 95 confirmed cases of melioidosis from western coastal India, pneumonia was seen in 32.6% of cases, musculoskeletal involvement in 20%, melioidotic lymphadenopathy in 7.4%, and dental abscess in 6.3% of the patients.[24] Rarely, in about 1-2% of cases, it can cause mycotic aneurysms.[25] Another larger study from Australia found that 81% of infections occurred commonly during the monsoon season.[11]

As melioidosis is probably not rare, it is underreported in India.[24] Involvement of the musculoskeletal system is infrequent and this low rate of involvement is attributed to the relatively low blood supply of the musculoskeletal system.[6] Spinal infection is classically defined as an infectious disease affecting the vertebral body, intervertebral disc and/or adjacent paraspinal tissue, although in melioidosis, involvement of the vertebral column is rare.[26],[27] Melioidotic psoas abscess has also been reported.[28] Vertebrae, predominantly in the lumbar region, are the most commonly affected locations in haematogenous osteomyelitis. Generally, the infection spreads to the proximate vertebral bodies and the intervening disc by the ascending and descending branches of posterior spinal arteries, while the isolated involvement of distant vertebral bodies is infrequent.[29] In recent years, the incidence rate of vertebral osteomyelitis has significantly increased.[30],[31],[32]

Even though patients may present a year after the bacteraemia episode, the pathogen isolated from cultures can guide the required antibiotic therapy.[30] Clinically, pyogenic spinal infections present as excruciating back pain, which is more severe at night.[30] Spinal involvement is rare in pyogenic osteomyelitis, whereas the most common differential diagnosis is tuberculosis.[33] The most frequent causative microorganisms for pyogenic infections are Gram positive bacteria like Staphylococcus aureus.[34] In India, lumbago is often treated with empiric ATT in patients with vertebral osteitis, that is confirmed using imaging and clinical findings. Furthermore, 60-90% of these patients may not have lesions anywhere else in the body. In the clinical presentation of melioidosis, most patients are found to be diabetic; and excruciating low back pain and high temperature are the frequent symptoms.

Pott's spine has been wrongly and empirically diagnosed in cases which could eventually turn out actually to be any of the following entities: malignant primary spine tumours, metastatic spine tumours, nocardosis, actinomycosis, candidiasis, cryptococcosis, histoplasmosis, paracoccidioidomycosis, septic arthritis, tuberculosis caused by Mycobacterium kansasii, and spinal cord abscess. Granulomatous diseases like  Brucellosis More Details and rarely, atypical tuberculosis, Mycobacterium avium Scientific Name Search  complex (MAC) and Mycobacterium avium intracellulare (MAI) can rarely mimic or be mimicked by melioidosis.[35],[36],[37] The most common predisposing factors for the occurrence of melioidosis are spinal sepsis and reduced neutrophil function secondary to type 2 diabetes mellitus, obesity, alcoholism, thalassemia, chronic renal and lung disease, steroid use, immunosuppression in transplant patients and occupational exposure to pooled water and wet soil.[5],[14],[38] Before their clinical manifestations start, most of the patients remain clinically asymptomatic for 2-6 weeks.[34] An impaired or reduced neutrophil function is the central factor for increased susceptibility to infection, as it leads to co-infection or concurrent infection with tuberculosis. Along with B. pseudomallei, intracellular pathogens like Mycobacterium tuberculosis, non-typhoid  Salmonella More Details, and leptospirosis have been reported together, co-infecting a single lesion.[39],[40],[41] A high index of suspicion has been advocated in pulmonary and extra-pulmonary tuberculosis-like presentation in diabetic and immunocompromised subjects where melioidosis has been likened to be a great mimic.[28]

The biochemistry and microbiology of melioidosis has been studied extensively and reported. Biomarkers like complete blood count, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin are utilised to investigate and monitor the treatment response.[42] On radiological examination, multiple abscesses exhibit a Swiss cheese or honeycomb appearance. Nontuberculous pyogenic vertebral osteitis most commonly involves the lumbar vertebrae (58%), followed by the thoracic (30%) and cervical (11%) vertebrae.[43] In contrast, tuberculous vertebral osteitis frequently involves the dorsal spinal vertebrae. Plain radiographs may be normal, as was seen in the present case. The sensitivity of plain radiographs in diagnosing this disorder is only 59%, and reduction in the disc height and end plate abnormalities are noted in the advanced stages of the ailment.[44] MRI has a sensitivity of 96%, which is better than the sensitivity of technetium 99m-hydroxydiphosphonate (HDP) bone scanning and Gallium 67 scanning.[44] An MRI assessment of the disc height and signal intensity changes clearly define the presence of nuclear clefts, vertebral signal intensity alterations, end plate erosions on T1 weighted images, and the presence of paraspinal and epidural inflammation.[45] Iliopsoas abscess can have a varied aetiology and should not always be generalized to be seen as a part of the tuberculous pathology. In fact, 21.5% of the patients harbouring an iliopsoas abscess are found to be having a polymicrobial aetiology, and an abscess is found to be having a spinal origin in a majority of these patients.[46],[47],[48] The follow-up MRI scans show a reduction in the soft tissue involvement, but persisting tissue and bony findings may be seen in patients who have responded well to treatment.[49] CT or ultrasound or both have been used to guide the aspiration of the iliopsoas abscess with good results.[50],[51] A controlled treatment study reported that antibiotic therapy for at least 6 weeks or longer is highly recommended comparable to 12 weeks of therapy.[52]

Although management protocols for spinal infections are standardised, spinal melioidosis still remains an unchartered terrain and requires validation of the guidelines, mainly for the type of antibiotics to be administered and their duration of therapy. Surprisingly, repeated environmental exposure does not result in the development of cellular or humoral immunity.[5],[53] The exact diagnosis of clinical cases of meliodosis along with the reporting and recording of these cases is an important need of the hour, as a missed or mistaken diagnosis and an erroneous treatment can result in a fatality.[36] Vaccines are being developed and may be useful in high risk patients (for example, in diabetic rice farmers) and in endemic regions.[2],[4]


 » Conclusion Top


Melioidosis is an emerging infectious condition and is underreported. It is a great mimic and can be a life-threatening condition. As a tropical saprophyte, Burkholderia pseudomallei lives in wet soil and water. Endemic exposures are frequent in villagers, farmers, and field workers. ATT in vertebral osteitis should be used cautiously. As the treatment required for melioidosis is radically different, waiting for a response to empiric ATT therapy can be lethal. Isolation of the pathogen from the lesion using CT and/or ultrasound guided biopsy and further laboratory analysis can guide therapy in these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgement

We would like to acknowledge the help provided by Ms Rathi Priya Annan, MS (Neuroscience), in the preparation of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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