A 68-year-old man from a mountainous area in Hebei Province, China, presented to the Rheumatology and Immunization Department of The 980th Hospital in Shijiazhuang, Hebei Province on February 16, 2022 with fever, sweating, and fatigue. He had previously been hospitalized in Jingxing County Hospital of Traditional Chinese Medicine (TCM) in Shijiazhuang City, Hebei Province on February 1, 2022. On admission to Jingxing County Hospital of TCM, his temperature was 39.0 C. He had chills, but no cough, sputum, abdominal pain, diarrhea, or urinary symptoms. His blood test results showed pancytopenia, rapid erythrocyte sedimentation rate, elevated C-reactive protein and ferritin, hyponatremia, hypokalemia, hypoproteinemia, and elevated serum enzyme levels ( Table 1 ). Bone marrow aspiration smear showed granulocytopenia with megakaryocyte maturation disorder. Abdominal ultrasound examination showed splenomegaly, a widened common bile duct, with no space-occupying lesions in liver, gallbladder, and kidney; brain computed tomography (CT) showed bilateral basal ganglia lacunar cerebral infarction; and lung CT showed bilateral lung fiber cord shadows, and bilateral increased lung branch air tube bundles. No definitive diagnosis was made during the previous hospitalization. After 11 days of antibiotic and symptomatic treatment, including administration of fluid and electrolytes, his symptoms persisted, he continued to have fever, fatigue, and a maximum temperature of >39 C.
He presented to our hospital for further diagnostic evaluation and treatment on February 16, 2022. Outpatient laboratory testing showed a negative SARS-CoV-2 polymerase chain reaction (PCR) test result, and chest CT showed signs of mild chronic inflammation in both lungs, slightly enlarged mediastinal lymph nodes, calcification of aorta and coronary arteries, a pericardial effusion, calcification under the capsule of the right lobe of the liver, and splenomegaly. After excluding SARS-CoV-2 infection, he was admitted to the Rheumatology and Immunology Department.
The patient had had no history of oral ulcers, rashes, joint swelling, or pain. He reported a decrease in body weight of approximately 10 kg in the past 6 months. His medical history included a resection of benign prostatic hyperplasia in July 2020, and a laparoscopic right hernia repair 3 months prior to admission. The patient did not have any history of infectious diseases such as hepatitis and tuberculosis. He had been vaccinated against COVID-19; however, his other vaccination history was unknown. Additionally, he was a non-smoker, did not drink alcohol, and had no family history of heritable diseases.
Physical examination on admission showed a temperature of 38.2 C, poor nutritional status, and an inability to walk. Additionally, his muscle strength in both legs was grade 3, and he had pitting edema on the anterior of both tibias and the dorsa of the feet.
He underwent a series of laboratory tests after admission ( Table 1 ). These tests revealed pancytopenia, increased ESR, CRP, and ferritin, and elevated liver enzymes. mNGS of blood samples showed a total of 6,120 reads identified as microbial genome sequences, of which 5,946 (97.16%) reads belonged to Leishmania donovani ( Figure 1 ). Bone marrow smear revealed an increase in the number of hemophagocytes, and amastigotes could been observed ( Figures 2A-E ). Based on these results, he was diagnosed with VL and hemophagocytic lymphohistiocytosis (HLH), 5 days after admission. A timeline depicting the patient's condition, diagnosis, and treatment is presented in  Figure 3 . After confirming the diagnosis of VL, anti-leishmania treatment should be administered as soon as possible. Antimony agent or amphotericin B is the commonly used drug, but only amphotericin B was available in the hospital pharmacy. To avoid further aggravation of the patient's condition, amphotericin B 5mg/day was administered intravenously (gradually increased to 0.5mg/kg per day according to the patient's tolerance), and dexamethasone sodium phosphate injection (10mg/day intravenous injection) was given for HLH induction treatment. Meanwhile, we considered the side effects of amphotericin B, which include fever, nausea, vomiting, and hypokalemia. With these side effects, the patient could not adhere to treatment, and it would not be conducive for efficacy evaluation. Therefore, after consultation with the patient and his family, we requested the hospital pharmacy to contact the antimony agent manufacturer for emergency drug delivery. The antimony agent was delivered two days later and replaced the amphotericin B immediately. A "six day plan" was adopted for antimony sodium gluconate (6ml 1/day intramuscular injection) for six consecutive days. The patient's condition improved rapidly after treatment. The results of bone marrow puncture on March 1, 2022, showed no abnormalities in the morphology of bone marrow cells, and no hemophagocytic cells nor amastigotes were observed ( Figure 2F ). The changes in the patient's laboratory indicators are shown in  Figure 4 . The patient was discharged from the hospital on March 4, 2022. After discharge, he underwent regular follow-up and remained in a stable condition for the following 8 months.