Intracranial melioidosis: First report in a human immunodeficiency virus positive individual manifesting as cranial osteomyelitis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.217952
Source of Support: None, Conflict of Interest: None
Melioidosis is a disease caused by Burkholderia pseudomallei, a motile, gram-negative bacillus. It is a potentially fatal disease endemic to Southeast Asia and northern Australia, and is rarely encountered in the Indian subcontinent., It mostly affects adults with predisposing conditions, mainly those with diabetes mellitus., Seropositivity for human immunodeficiency virus (HIV) as a predisposing factor has not been reported earlier. The causative organism is intrinsically resistant to many antibiotics. Even with prolonged therapy, it is associated with significant mortality., Central nervous system (CNS) involvement is rare and most commonly manifests as meningitis or cerebral abscess. Only approximately 70 cases have been reported worldwide.,,, Cranial osteomyelitis is a rare manifestation. The authors describe a case of histologically proven cranial melioidosis presenting as osteomyelitis, the first one to be reported in a retroviral positive patient who was managed with debridement and prolonged antibiotic therapy. We emphasize the need for a strong clinical suspicion, especially in immunocompromised patients, an early diagnosis, and a prompt medical and surgical management.
A 41-year old male farmer working in paddy fields, hailing from the coastal region of Karnataka, with retroviral positive status for 15 years and not on antiretroviral treatment, presented with intermittent high-grade fever and septic shock 3 months back, for which a blood culture was found to be positive for melioidosis. He was put on intravenous ceftazidime for 2 weeks and later switched to doxycycline and amoxicillin-clavulanic acid. Two months later (still in his maintenance phase), he was referred to us with intermittent high-grade fever and a progressive fluctuant swelling over the left parietal scalp of 4-week duration.
On examination, he had a fever of 100°F, and his neurological and cardiorespiratory examinations were unremarkable. Local examination showed a soft, tender, fluctuant swelling in the left parietal region measuring approximately 6 × 7 cm with an underlying palpable bony defect.
On routine work-up, blood investigations showed leukocytosis and a raised erythrocyte sedimentation rate (ESR) of 35 mm/h. His CD4 (cluster of differentiation antigen 4) count was 350. His contrast-enhanced computed tomography (CT) of the brain [Figure 1]a and [Figure 1]b showed features of osteomyelitic erosion of the left parietal bone with a large subgaleal and a thin extradural collection. Tuberculosis and melioidosis (as he was a known case of the latter disease and on treatment for it) were considered as the most probable differential diagnoses.
An initial needle drainage of the purulent collection of the scalp was done under local anesthesia, and bacteriological culture isolated B. pseudomallei. It was followed by definitive surgery in the form of a parietal craniectomy and a thorough debridement of the subgaleal and extradural collections. Histopathological specimen revealed typical features of melioidosis [Figure 2]. He was given parenteral ceftazidime for 8 weeks in view of his low CD4 count and recurrence of Burkholderia infection. Later, he was put on maintenance phase of oral co-trimoxazole and amoxicillin-clavulanic acid for 8 months because the organism was resistant to doxycycline.
The patient has been doing well and is under regular follow-up; blood cultures have been sterile. At the last follow-up at 14 months, he was clinically disease-free and the CT scan showed no evidence of recurrent or fresh lesions [Figure 1]c.
Melioidosis is a potentially fatal disease caused by a non-acid-fast, gram-negative bacillus, B. pseudomallei.,, The organism is an environmental saprophyte, found predominantly in the soil and surface water of paddy fields. Melioidosis is of major public health concern in endemic regions., Inhalation and inoculation are the major modes of transmission. Males are predominantly involved. In our case, because the patient was a farmer with no recent travel to endemic areas, the disease appeared to be acquired from soil inoculation while he had been working in paddy fields. The incidence of central nervous system (CNS) involvement in melioidosis ranges from 3% to 10%. The first Indian case of neurologic melioidosis was reported by Lath et al., and till date, only 15 cases of cranial melioidosis (including ours) have been reported from the subcontinent [Table 1].,,,,,,,,,, The mean age was 43.5 years and the male:female ratio was 3.6:1. This definitely appears more likely to be the tip of the iceberg. Factors such as lack of awareness among clinicians and a low index of suspicion, inability of rural population to access health services, and inadequate microbiological facilities probably contribute to the paucity of diagnosed cases from the the country. Osteomyelitis with/without scalp abscess is the most common CNS manifestation noted in the Indian scenario, which is quite different from the clinical presentation reported worldwide, wherein either meningoencephalitis (in Australia) or cerebral abscesses (in Thailand) were the most common features. The reason behind this difference is not known. Diabetes is the most common and most important predisposing factor for melioidosis. Other factors include chronic alcoholism, liver disease, malignant tumors, prolonged steroid use, chronic renal failure, and blood malignancies., In our analysis, diabetes mellitus (n = 5) and chronic alcoholism (n = 1) were common factors. Although the disease represents a manifestation of an immunocompromised state, HIV infection as a risk factor has rarely been reported in melioidosis. Ours is the first case of neurologic melioidosis to be reported in an HIV-positive individual. With factors such as high environmental suitability, presence of causative organism in soil, appropriate geographical location, and presence of more than 65 million diabetics, the Indian population is at a high risk to develop this disease. It will be no surprise if the disease becomes endemic in this region in the near future.,
Melioidosis is often considered to be a good mimicker; tuberculosis is the most important differential diagnosis because it mimics melioidosis in all aspects-clinical, radiological and pathological. In a recent Indian article, 22 suspected cases of tuberculosis were proven later to be melioidosis on microbiological culture. Hence, melioidosis needs to be considered in all potential cases, especially when the patient is not responding to antituberculous therapy., Melioidosis can also cause a false-positive Widal test. Other bacterial infections causing osteomyelitis can also produce a similar clinical picture. Further, in view of our report of this disease occurring in a HIV-positive individual, this infection needs to be considered in immunocompromised patients as well in the future.
The pathophysiology of neurologic melioidosis is yet not clear. A neurotropic exotoxin and direct invasion of the CNS have been suggested. The mortality rate of neurological melioidosis reaches approximately 25% despite prolonged antibiotic therapy.,, As noted in [Table 1], of those with available data, good outcomes were noted in 8 cases at a mean duration of 9.65 months (range: 2 weeks to 24 months). Two deaths were noted. Microbiological culture of the organism is the gold standard for the diagnosis of melioidosis; however, it takes at least 2–5 days to isolate the organism., Other rapid diagnostic tests have been deduced that include the indirect hemagglutination assay, enzyme immunoassay, rapid antigen detection using monoclonal antibody, immunochromatographic tests and others; however, none have attained consistent standards over time in relation to their specificity. Treatment of melioidosis is difficult because the organism is resistant to most of the common antibiotics and a prolonged antibiotic course is required. An initial intensive phase for a minimum of 2 weeks, followed by an eradication (or maintenance) phase for 3–6 months is the accepted standard therapeutic regimen practiced worldwide., Ceftazidime (doses up to 100 mg/kg/day) is the drug of choice in the intensive phase because of excellent CNS penetration and uniform susceptibility. We are of the opinion that in cases such as ours (HIV positive) with a disease recurring even on treatment, a longer intensive phase course of antibiotics shall prevent further recurrences. For the eradication phase, drugs commonly used are co-trimoxazole, doxycycline, and the uncommonly used ones are amoxicillin/clavulanate. Other adjunctive therapies currently under research include gamma-interferon, which may probably improve the effectiveness of the standard antimicrobial treatment.
The need of the hour, at least in developing countries, is a strong clinical suspicion, the performance of rapid low-cost diagnostic tests, the administration of a short duration of parenteral antibiotic regimen (keeping in mind the economic considerations), an adequate infection surveillance system, and development of fully protective vaccines. These might help in reducing the associated mortality and morbidity rates of this disease.
Cranial melioidosis is rare. A strong index of suspicion is necessary, especially in immunocompromised patients, for its early diagnosis and management. An intensive phase with parenteral antibiotics for a minimum of 2 weeks, followed by a maintenance phase of oral antibiotics for 3–6 months is the current standard treatment. Recurrences are frequent and need to be monitored.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]