Melioidosis, also known as Whitmore’s disease, is a potentially fatal infectious disease caused by the saprophytic environmental Gram-negative bacterium Burkholderia pseudomallei, resulting in about 89,000 deaths per year. Melioidosis is predominantly a tropical disease, with the Indian subcontinent bearing 44% of the global disease burden.¹ It is, however, classified as a rare disease because of its similarity to tuberculosis, diverse clinical symptoms, lack of awareness among clinicians, and dearth of proper testing facilities.²

The pathogen infects both humans and animals through direct contact with contaminated soil and water and can be naturally acquired through skin abrasion, ingestion, or inhalation.³ Environmental factors like tropical storms and rain, and specific occupations like rice farming, increases the chance of exposure.^4,5 Diabetes mellitus is the major risk factor along with chronic kidney, pulmonary, and coronary diseases.² The mean incubation period of B. pseudomallei in humans is nine days but can vary from days (acute) to years (chronic) depending on risk factors, inoculum size, route of entry, and the presence or absence of virulence factors.⁶ Acute melioidosis manifests as pneumonia, multiorgan abscesses, and fulminant septicemia, whereas the chronic infection presents as symptoms mimicking tuberculosis (TB) with or without bloody sputum and multiorgan abscesses with occasional neurological involvement.^2,7 However, unlike TB, scarring and calcification of the lungs are rarely observed in chronic melioidosis. The latent form of the disease may lie dormant for years, sometimes decades, and may reactivate in an immunocompromised state or with comorbidities including diabetes, renal failure, and alcoholism.⁸

B. pseudomallei can be detected in blood, throat and rectal swabs, sputum, and pus from abscesses but their presence in clinical samples is limited. Melioidosis can be confirmed by culturing biological specimens in selective media and antimicrobial activity assays. However, care must be taken not to misinterpret results as Pseudomonas, Burkholderia cepacia, or Bacillus species, infections.⁷ Under light microscopy, B. pseudomallei appear as safety-pin-shaped bacilli which can be confirmed by immunofluorescence microscopy. Although very specific, these methods are limited in sensitivity.⁹ Serological tests like hemagglutination and latex agglutination coupled with ELISA can be used to screen for suspected infection but one should be cautious to avoid false positives from B. thailandensis infection and take into account differences in antibody titers from geographic areas.¹⁰ Molecular diagnosis with PCR using 16S rRNA or B. pseudomallei-specific probes can be confirmatory. However, logistics and the availability of sophisticated instruments in rural areas limit the use of advanced molecular methods. Radiological imaging reveals multifocal nodular lesions in the lungs under X-ray and chronic infection may present lesions that resemble tuberculosis. Abscesses in organs, especially the liver and spleen, appear as a honeycomb pattern in computerized tomography (CT) scan. In neuronal involvement, magnetic resonance imaging (MRI) scan of the brain often shows ring-enhancing lesions and hyperintense changes but must be distinguished from cystic tumors by using diffusion-weighted imaging.¹¹

The treatment of melioidosis follows a two-step regimen – an intravenous intensive phase and an eradication phase. The intensive phase of therapy (10-14 days) employs antibiotics like ceftazidime and/or carbapenems. The eradication phase commences after clinical improvement from the intensive treatment and the choice of drugs is a combination of trimethoprim-sulfamethoxazole (TMP-SMX) or amoxicillin-clavulanic acid for 3-6 months.¹²

Individuals with open skin wounds, diabetes mellitus, and chronic kidney disease should avoid contact with soil and water, especially in endemic areas. Wearing boots can prevent infection of the lower limbs and feet. Patients presenting symptoms should be diagnosed with a high level of suspicion. Awareness among clinicians and healthcare workers can aid in the early diagnosis of melioidosis.

This case study underlines the recent increase in melioidosis in India and highlights the broad spectrum of clinical symptoms presented to better equip healthcare workers in diagnosing the disease in its earlier stages. The need for sustained treatment for better recovery and eradication of the pathogen is emphasized.

Case Presentation
Within a five-month period from October 2021 to February 2022, a tertiary healthcare center in Puducherry, South India, treated five cases of melioidosis, predominantly affecting men (Table 1). Three patients had a history of type II diabetes mellitus (T2DM), and one suffered from chronic kidney disease. Chief complaints included high-grade fever, abdominal pain, and vomiting. Case 1 presented with blurring of vision and ear pain, alongside complaints of giddiness and headache. Case 2 experienced recent trauma while playing kabaddi, and Case 4 underwent incision and drainage of an arm abscess. All patients tested negative for COVID-19. Routine blood analysis revealed elevated white blood cell counts in three patients (Case 1, 2 and 3), thrombocytopenia (Case 2 and 3) in two, and urinary tract infections in two (Case 1 and 4). Radiological tests indicated lung ground glass opacities and hepatosplenomegaly in three patients, with hypodense lesions in the liver and spleen in one patient. One patient exhibited a cyst in the urinary bladder with prostatomegaly (Case 4). Case 3’s brain MRI revealed an inflammatory granuloma with increased perilesional white matter edema, and a CT scan showed ill-defined hypodense lesions in various brain regions. A lumbar puncture of Case 3 indicated 430 cells/cu.mm (lymphocytes 80%, neutrophils 20%), suggesting CNS inflammation. Blood culture and antibiotic sensitivity tests (Table 2) confirmed B. pseudomallei infection in all five patients.

Table (1):
Underlying conditions, clinical manifestations, and outcomes of patients with melioidosis

Abbreviations: ARDS – acute respiratory distress syndrome, CKD – chronic kidney disease, CT- computed tomography, DAMA – discharged against medical advice, HRCT – high-resolution computed tomography, I&D – incision and drainage, LP – lumbar puncture, MER – meropenem, MRI – magnetic resonance imaging, RFT – renal function test, T2DM – type II diabetes mellitus, TMP-SMX – trimethoprim-sulfamethoxazole

Table (2):
Antibiotic susceptibility testing

Initially, broad-spectrum antibiotics were administered based on the initial diagnosis and symptoms. However, once B. pseudomallei infection was confirmed, all five patients were switched to intravenous meropenem (1-2 g) or ceftazidime (1 g) (i.v.) or a combination thereof within a week of their hospital admission. During the treatment course, Case 2, exhibiting asymptomatic and hemodynamically stable conditions, was discharged. Conversely, Cases 1 and 4, advised to continue medical treatment, opted for discharge against medical advice, citing logistical reasons. For Cases 3 and 5, the severity warranted intensive care, leading to admission to the intensive care unit (ICU). Unfortunately, Case 5 faced a fatal outcome during the intensive treatment phase.

Although, B. pseudomallei acute pulmonary infection was detected within 3 days of hospital admission and promptly started on i.v. meropenem, the patient developed sudden cardiac arrest on the 7th day preceded by bradycardia and could not be revived. This brings the mortality rate to 20% in the study, assuming the three patients who withdrew from treatment survived.