A 66-year-old male school worker with a history of hypertension resided in Shandong Province, which is located in the Northern China. On April 2022, the patient was admitted to the local hospital because of a 30-day history of recurrent fever(Tm 39.0℃), chills, sore throat, fatigue, cough and weight loss. Laboratory results showed normal hemoglobin, platelet, renal function and electrolyte, but elevated leukocyte (13.53×109/L) with 83.40% neutrophils, C-reactive protein(CRP 71.88mg/L) and procalcitonin(PCT 0.723ng/ml), and slightly elevated alanine aminotransferase (133U/L) and aspartate aminotransferase(152U/L). Chest computed tomography(CT) revealed chronic bronchitis, multiple enlarged lymph nodes in bilateral hilum of lung, mediastinum and supraclavicular, suggesting lymphoma. The mediastinal lymph node obtained by bronchoscopy was sent for histological examination, and pathological examination indicated necrotic and inflammatory fibrous connective tissues, and several atypical cells. He was treated with cephalosporins and ibuprofen, but his fever persisted with a temperature fluctuating between 37.5 and 39.6°C. On May 10, laboratory results showed normal leukocyte (4.19×109/L), hemoglobin and platelet, but highly elevated CRP (73.72mg/L) and neutrophil ratio (91.60%). On May 16, the patient was admitted to our hospital for systematic diagnosis and treatment. Upon admission to the hospital, a physical examination revealed poor spirit and a body temperature of 38.9°C, and he still suffered cough, expectoration, chest distress. A dermatological examination revealed scattered red rashes on the back (Fig. 1A), and superficial lymph nodes couldn’t be touched. Laboratory results showed significantly decreased leukocyte(1.35×109/L) and platelets(29×109/L), but highly elevated CRP(178.77mg/L), PCT(32.03ng/ml), triglyceride (5.86mmol/L), ferritin(> 40000ng/ml), alanine aminotransferase (358U/L) and aspartate aminotransferase(1435U/L). Cytokines detection showed highly elevated IL-6(659.54pg/ml), IL-8 (6514.34pg/ml) and IL-10(333.92pg/ml). His hemoglobin, fibrinogen, renal function and electrolytes were within normal range. The fungus test showed normal 1-3-β-D-glucan but elevated galactomannan. Blood culture yielded Talaromyces marneffei and bone marrow culture also proved Talaromyces marneffei.
Talaromyces Marneffei infection has been rarely reported native in northern China.To verify the result of culture,we sequenced the peripheral blood sample to further confirm the infection. Sequencing results showed Talaromyces marneffei with 3965512 sequence reads and 96.55% genome coverage. The lymph node pathology specimen was restained and a suspected fungal structure was found (Fig. 1B). Disseminated Talaromyces marneffei infection was confirmed(3) and the patient was assessed to meet the 2004-HLH diagnostic criteria(6): recurrent fever, cytopenia (involving both peripheral blood lines), splenomegaly, ferritin > 40000ng/ml, elevated triglycerides. On the basis of the diagnosis of Talaromyces marneffei infection as well as secondary-HLH, the patient was given amphotericin B(7) and appropriate hormone (dexamethasone 7.5mg q12h). However, his clinical condition further deteriorated, and died of multiple organ failure despite antibiotic adjustment, blood filtration, ventilator assisted ventilation and other supportive treatments. Figure 1C showed the diagnosis and treatment of this patient in hospital.