A Traveller in Time: Phylogenetic Analysis to Identify a Disseminated Infection Acquired 30 Years Earlier

A 79-year-old East Indian man and retired office manager, originally from Tanzania (Africa) presented with hypotension and respiratory distress requiring intensive care unit admission. His background included a medical history of type 2 diabetes, hypertension, hypercholesterolemia and chronic obstructive pulmonary disease (40 packs/year smoker). A reticulonodular chest radiograph pattern (Figure 1A) had been identified three months earlier because of new constitutional symptoms (fatigue, weight loss, anorexia and fever) and dyspnea. He had not travelled since immigrating to Canada 30 years prior. His vital signs included an oral temperature of 35.3°C, blood pressure of 73/49 mmHg, heart rate of 113 beats/min, respiratory rate of 33 breaths/min and an oxygen saturation of 99% (inspired mixture of 31% oxygen). Pertinent physical examination findings showed a cachectic individual with splenomegaly and expiratory wheezes but no rash, clubbing or palpable lymphadenopathy. Tazobactam-piperacillin, intravenous hydrocortisone and noradrenaline infusions were commenced. His blood test results were as follows: white blood count 4.0×109/L; hemoglobin level 109 g/L (normocytic); platelet count 139×109/L; hyponatremia with a sodium level of 125 mmol/L; normal potassium, bicarbonate and creatinine levels; and glucose level 7.5 mmol/L. Liver function and enzyme testing showed cholestasis (alkaline phosphatase 339 U/L, gamma-glutamyl transferase 647 U/L, alanine amino-transferase 14 U/L, total bilirubin 33 μmol/L, conjugated bilirubin 19 μmol/L and albumin 27 g/L). Computed tomography scan identified bilateral emphysematous lung changes, multiple precarinal/paratracheal lymph nodes (smaller than 1 cm), bilateral adrenal masses, hepatosplenomegaly, colitis, a splenic lesion and mild ascites (Figure 1B). Functional testing of the adrenal glands (1 μg and 250 μg adrenocorticotropic hormone stimulation test) indicated adrenal insufficiency. Figure 1 Chest x-ray and computed tomography scan of patient at presentation to the intensive care unit. A Reticulonodular pattern. B Splenomegaly with polar lesion (white arrow) and bilateral adrenal hyperplasia (white arrowheads) Review of the patient’s records from three months previously revealed similar computed tomography abnormalities. His nuclear bone scan was normal, and upper endoscopy revealed two small antral ulcers. The T cell subset ratio was normal (CD4/CD8 ratio 2.4, CD4 0.31×109/L and CD8 0.13×109/L), and serology for HIV by enzyme immunoassay was negative. Tumour markers (carcinoembryonic antigen, alpha-fetoprotein and prostate-specific antigen) and serum protein electrophoresis were within normal ranges. Bronchoscopy and standard microbiological analyses were performed. What is the diagnosis?