Melioidosis: A Case of Pyrexia of Unknown Origin

INTRODUCTION Melioidosis was previously known to be endemic to Southeast Asia and Northern Australia. The reported cases are only the tip of the iceberg, as it is often misdiagnosed and treated as other infections. This is often due to lack of microbiological diagnostic facilities. According to the Centers for Disease Control and Prevention, from being non-endemic for melioidosis, India has now become endemic for the disease since 2012.[1] CASE REPORT A 58-year-old male, shopkeeper, hailing from a middle-class family from a coastal town in Kerala, was admitted with a history of fever for 3 weeks which was not subsiding despite evaluation and treatment at local hospital. He gave a history of high-grade intermittent fever for 3 weeks associated with chills and rigors. He had taken two courses of antibiotics from the local hospital, with no relief. There was no diurnal variation of fever or night sweats. There was generalised fatiguability, but no loss of appetite or loss of weight. He gave no history of cough, breathing difficulty or chest pain, abdominal pain, vomiting or bowel or urinary complaints. He did not give a history of joint pain, myalgia or skin rashes. None of his family members had fever or any other symptoms. He had contact with poultry and goats. He had a similar episode of fever 3 years back when he was evaluated for suspected pulmonary tuberculosis which was negative and was treated as pneumonia and his symptoms subsided with intravenous (IV) antibiotics. He had no history of diabetes mellitus, hypertension, dyslipidaemia, coronary artery disease, asthma, chronic obstructive pulmonary disease or any surgeries in the past. There was no significant family history of any illnesses. He was not on any chronic medications and had no drug allergies. He had no addictions. On examination, he was found to have a temperature of 102°F and a high blood pressure of 200/100 mmHg. Systemic examination was normal. Investigations showed normal complete blood count, C-reactive protein 153.7 mg/L, random blood sugar 316 mg/dL and thyroid-stimulating hormone 8.6 mIU/L. Renal and liver function tests (LFTs) were normal. Chest X-ray and electrocardiogram were normal. COVID-reverse transcription–polymerase chain reaction was negative. Provisional diagnosis Pyrexia under evaluation, newly detected Type II diabetes mellitus, newly detected essential hypertension, subclinical hypothyroidism. Treatment initiated IV Cefoperazone - Sulbactam, insulin, amlodipine, thyroxine and oral Paracetamol as needed (PRN). Serial investigations in view of persistent fever spikes, revealed thrombocytopenia and deranged liver function tests suggestive of obstructive jaundice. Malarial parasite, widal, dengue immunoglobulin (Ig) M, leptospirosis IgM, Brucella IgM, Prostate specific antigen (PSA), Human Immunodeficiency virus (HIV), venereal disease research laboratory test for syphilis (VDRL), Hepatitis B surface antigen (HbsAg), Hepatitis C Virus (HCV) and Anti-nuclear antibody (ANA) were negative. Ultrasound (USG) abdomen showed multiple splenic cysts and cholelithiasis. Echocardiogram was normal. Three blood cultures were performed, and all three samples became positive within 24 h. On subculture, these samples yielded growth of Gram-negative bacillus which showed bipolar staining on Gram staining. The isolate showed biochemical reactions such as oxidase positive, nitrate positive, gelation liquefaction positive and arginine dihydrolase positive and was identified as Burkholderia pseudomallei in the VITEK-2 system. Antibiotic sensitivity testing showed a typical resistance pattern to aminoglycosides and colistin and susceptibility to ceftazidime, meropenem and trimethoprim. Treatment was changed to IV ceftazidime and later IV meropenem was added on day 11 since the patient developed cough and had new chest findings with chest X-ray showing bilateral lower zone haziness. Computed tomography (CT) thorax and abdomen showed multiple nodular lesions in both lung fields pre-dominantly in the lower lobes, cholelithiasis, splenomegaly with multiple small hypoechoic lesions possibly multiple abscesses, minimal perisplenic and perihepatic ascites and minimal loculated right fissural pleural effusion. His general condition improved on day 18 and was discharged on day 20 with advice to continue IV meropenem at local hospital. Oral doxycycline 100 mg twice daily was given for 6 months to prevent relapse. Figures 1-5 show the investigation reports including USG abdomen, serial chest X-rays and blood culture.Figure 1: Ultrasound abdomen showing splenic microabscessesFigure 2: Chest X-ray day 1Figure 3: Chest X-ray day 10Figure 4: Chest X-ray on 1-month follow-upFigure 5: Blood culture showing growth of Bulkholderia pseudomalleiDuring the course in hospital, we could elicit a retrospective history of swimming through flood waters in September 2018 which would have been the cause for melioidosis. The episode of respiratory infection in November 2018 would have been caused by the same agent and the current episode is a relapse seen in chronic melioidosis. The patient was followed up every week for 1 month and later monthly. Over the course of 1st month, his chest X-ray became normal, USG abdomen showed resolving splenic abscesses, CT showed resolution of pleural effusion and ascites and LFT returned to normal. Review of literature There have been isolated case reports of melioidosis from a few states across the country for the past few years. Most of the time, B. pseudomallei may be misreported as Pseudomonas species, especially in resource-poor laboratories. Due to its varied clinical presentation, the specific clinical diagnosis can be difficult, thereby making laboratory diagnosis mandatory. This could have a huge impact on patient care as this organism has a different treatment protocol as well as virulence determinants which influence the course of management.[1] A strong clinical and microbiological suspicion for melioidosis should be considered in the differential diagnosis of acute pyrexia of unknown origin, acute respiratory distress syndrome and acute onset of sepsis, especially in the tropics.[2] Melioidosis is endemic to tropical regions of the world.[3] The causative organism is the Gram-negative bacillus, B. pseudomallei. The mode of spread is through inhalation or inoculation from contaminated soil or water. Higher incidence is seen in those with diabetes,[4] chronic kidney disease, chronic lung diseases, thalassemia, immunosuppression, excessive alcohol consumption and occupational exposure to surface water. Environmental factors aiding melioidosis include monsoon, heavy rainfall and humidity.[5] Melioidosis may be acute or chronic. There may be relapse or reactivation of latent infection.[6] It may mimic other infections such as tuberculosis.[7] Common clinical presentations include pneumonia, septicaemia and pneumonia with septicaemia.[8] Rarely it presents with soft-tissue infection, bone and joint involvement,[1] visceral abscesses including hepatic abscess, splenic abscess[9] or prostatic abscess and central nervous system infection.[10] Facial involvement including suppurative parotitis[11] and ocular involvement. The time between exposure to bacteria and the emergence of symptoms may range from 1 day to many years though generally it is 2 to 4 weeks. Diagnosis is by isolating B. pseudomallei from blood, urine, sputum, skin lesions or abscesses or detecting an antibody response to the bacteria. Although B. pseudomallei grows on blood agar and MacConkey agar, it is often dismissed as a culture contaminant or misidentified as Pseudomonas species when non-sterile clinical or environmental specimens are cultured.[12] Chest X-ray may show multiple small pulmonary nodules and multilobar infiltrates which may later become cavitatory lesions or pulmonary abscesses and pleural effusion. USG abdomen may reveal microabscesses in liver and spleen.[13] Treatment of melioidosis combines treating fatal septicaemia with the eradication of long-term persistent disease in pulmonary, soft tissue, skeletal and other organ systems.[14] IV antibiotics for 2 to 8 weeks, followed by 3 to 6 months of oral antibiotics are recommended. IV antibiotics of choice are ceftazidime 1 g Q8H/Q6H or meropenem 1 g Q8H. Oral antibiotics to prevent relapse include cotrimoxazole or amoxycillin-clavulanate or doxycycline. DISCUSSION Here, we present the case of a 58-year-old male who was admitted with fever of 3-week duration. On day 5, a diagnosis of melioidosis was confirmed following the growth of B. pseudomallei in blood cultures. CT thorax and abdomen showed lung and splenic findings which were similar to previous literature reports.[13] Aggressive antibiotic therapy and concurrent management of his comorbidities helped in his recovery. He was followed up with oral antimicrobial therapy for 6 months as suggested in various literature reports.[14] A retrospective history suggested probable infection 3 years back which relapsed.[2] This case highlights the importance of high index of suspicion of melioidosis in pyrexia of unknown origin in our country and the need for strong microbiological support in identifying the pathogen. 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 his/her/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. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.