The patient was a 31-year-old female admitted to the hospital with fever. More than 20 days prior to admission, she developed a fever with no apparent cause, with a maximum temperature of 39.8  C. The fever was accompanied by chills but no sore throat or cough. She received anti-infective treatment, such as imipenem/cilastatin sodium, at other hospitals, but her fever symptoms did not improve significantly; therefore, she was transferred to our hospital for further treatment. She was previously diagnosed with chronic hepatitis B for more than 10 years and took oral tenofovir antiviral therapy regularly. She had been diagnosed with polycystic ovary syndrome 5 years previously and had been treated with prednisone in the past. In addition, she denied recent travel, surgery or trauma, and she reported no history of infectious diseases, diabetes mellitus or use of alcohol or drugs.
On admission, she had a high body temperature (38.5  C), an increased respiratory rate (23 breaths/min), normal blood pressure (117/61 mmHg), increased heart rate (124 beats/min), and normal oxygen saturation in ambient air (97%). Physical examination showed slightly harsh breath sounds in both lungs, and no rales were heard. The liver and spleen could be palpated by one finger under the rib.
Laboratory investigations showed decreased haemoglobin 97 g/L, platelets [68x109/L; normal range, (100-300)x109/L], CD4 cell count [135 cell/microL; normal range, 471-1220 cell/microL], and albumin (34 g/L; normal range, 40-55 g/L). The patient's procalcitonin level (0.45 g/L; normal range, <0.046 ng/L), C-reactive protein (28.20 normal range, <5.00 ng/L), and interleukin-2 receptor (4450 mug/L; normal range, 223-710 mug/L) levels were elevated. The patient's red blood cells [3.92x1012/L; normal range, (3.8-5.1)x1012/L], white blood cells [5.46x109/L; normal range, (3.5-9.5)x109/L], globulin (32.0 g/L; normal 20-35 g/L), triacylglycerol (triglycerides: 1.82 mmol/L), fibrinogen (2.75 g/L; normal 2-4 g/L), ferritin (217 ng/L; normal 24-336 ng/L) and aspergillus-antigen test for serum galactomannan (0.27 mug/L; normal 0-0.85 mug/L) were in the normal ranges. Tests for HBV-DNA, HCV-RNA, CMV-DNA, EB-DNA, anti-dsDNA, ANA profile, HIV-1 antibody, anti-tuberculosis antibody, and 1,3-beta-D-glucan were negative. Peripheral blood cultures drawn during repeated fever episodes and SARS-CoV-2 based on PCR testing of a nasopharyngeal swab were both negative. Abdominal CT examination showed enlargement of the liver and spleen and multiple cystic lesions in the bilateral adnexa. (Figure 1A) We also performed head CT, chest CT, urological ultrasonography, thyroid ultrasonography, routine echocardiography and other related tests, all of which yielded negative results. (Figure 1B) After admission, we continued to administer anti-infective treatment with imipenem/cilastatin sodium (500 mg every 8 h), but the patient still had recurrent fevers. Due to the patient's low CD4 cell count, we still considered the cause of her fever as infection rather than tumour or immunogenic. The patient remained hyperthermic and did not respond to multiple medications, and we encountered difficulties in the diagnosis and treatment of the disease. Then, we performed a bone marrow smear and found some phagosomes in the cytoplasm that were suspected to be Histoplasma capsulatum. (Figure 2) The bone marrow fluid was subjected to mNGS analysis on Day 4 of hospitalization. mNGS was performed according to the standard protocol of Illumina sequencing on the NextSeq550 platform. A total of 363 sequence readings of histoplasmosis were detected in bone marrow within 24 h, accounting for 2.614% of the genome coverage. The clinical diagnosis was disseminated Histoplasma capsulatum infection. On the fifth day of hospitalization, we changed imipenem/cilastatin sodium to amphotericin B deoxycholate (40 mg once a day) intravenous infusion and fluorouracil tablet (1 g once a day) oral anti-infection therapy after searching for evidence of the pathogen. Considering the side effects of amphotericin B deoxycholate, the patient received an acid suppressant for gastric protection, reduced glutathione (GSH) for liver protection, and oral potassium chloride for potassium supplementation. During the course of treatment, the patient's creatinine level was found to be elevated, and amphotericin B deoxycholate was gradually adjusted to 25 mg once a day intravenously. After active treatment, the patient's general condition improved, and her body temperature gradually returned to normal. (Figure 3) Prior to discharge, the patient's interleukin 2 receptor and procalcitonin returned to normal levels. (Table 1) A bone marrow smear did not reveal Histoplasma capsulatum. The patient was discharged from the hospital on oral itraconazole 200 mg twice daily antifungal therapy, and the bone marrow smear was normal after 6 months of follow-up. 
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