葡萄糖酸锑钠长疗程治疗1例利什曼原虫与人类免疫缺陷病毒合并感染患者的追踪观察

Follow-up of a patient with Leishmania and human immunodeficiency virus co-infection who received prolonged sodium stibogluconate treatment

目的报道使用葡萄糖酸锑钠长疗程治疗1例利什曼原虫与人类免疫缺陷病毒(HIV)合并感染患者的疗效及预后。方法收集患者的临床资料,追踪观察患者的疗效及预后。结果患者1990年在四川省九寨沟县(内脏利什曼病流行区)工作。1992年末出现发热、肝脾肿大,被多家医院诊断为"肝硬化",对症治疗无效,脾脏持续肿大,并出现严重贫血、消瘦。1994年经骨髓穿刺涂片镜检发现利什曼原虫,诊断为内脏利什曼病,给予葡萄糖酸锑钠(五价锑600 mg/d×6 d,静脉滴注)治疗,病情缓解。2010年8月,患者发现左上腹有包块,伴腹胀,再次行骨髓穿刺涂片镜检,发现利什曼原虫,再次给予葡萄糖酸锑钠(五价锑600 mg/d×6 d,静脉滴注)治疗,病情缓解。住院期间初筛HIV抗体阳性,经蛋白质印迹(Western blotting)检测确认为HIV感染,CD4^+T淋巴细胞仅为42个/μl,诊断为艾滋病(AIDS)。2011年7月,患者开始接受抗HIV常规治疗[拉米夫定(3TC)300 mg/d+齐多夫定(AZT)600 mg/d+依非韦伦(EFV)600 mg/d],治疗2个月后出现严重贫血,将AZT更换为替诺福韦(TDF)300 mg/d,长期服用3TC+TDF+EFV。2012年7月25日患者因"腹胀2年"入住本院,入院时呈重度贫血貌,肝脏位于右锁骨中线肋缘下2 cm;脾脏下缘位于脐下7 cm,右缘位于前正中线右侧2 cm。骨髓涂片镜检查见利什曼原虫。继续给予抗HIV治疗(3TC+TDF+EFV),同时给予葡萄糖酸锑钠静脉滴注治疗内脏利什曼原虫感染[第1个疗程:先后给予葡萄糖酸锑钠(五价锑600 mg/d×4 d,1 200 mg/d×4 d)治疗,肝脾开始缩小后,改为隔天静脉滴注葡萄糖酸锑钠(五价锑600 mg/次×22次)]。在第1个疗程结束后1个月和3个月,分别给予1个疗程葡萄糖酸锑钠治疗(五价锑600 mg/次×18次)。3个疗程共计给予五价锑42 g治疗。2017年4月(抗利什曼原虫治疗结束后50个月)复诊,骨髓涂片检查未见利什曼原虫,CD4^+T淋巴细胞为249个/μl,HIV-RNA低于检测下限。结论对内脏利什曼原虫合并HIV感染的患者给予葡萄糖酸锑钠长疗程及抗HIV治疗,内脏利什曼感染获得治愈,患者预后较好。

Objective To observe the curative effect and prognosis of prolonged sodium stibogluconate treatment in a case of Leishmania and human immunodeficiency virus（HIV） co-infection. Methods Clinical information of the patient was collected. The curative effect and prognosis were followed-up. Results The patient was working in Jiuzhaigou County of Sichuan Province（an endemic area of visceral leishmaniasis） in 1990. At the end of 1992 he presented with fever, hepatomegaly and splenomegaly, and was diagnosed with liver cirrhosis by local hospitals. The symptoms were not improved after symptomatic treatment, with continued hapastosplenomegaly, accompanied by severe anemia and weight loss. He was later diagnosed with visceral leishmaniasis via bone marrow examination in1994, and given intravenous infusions of sodium stibogluconate（pentavalent antimony 600 mg/d for 6 days）. After 6 days of treatment, his condition got improved. In August 2010, an abdominal mass was found in the left upper quadrant,accompanied by abdominal distension. Leishmania amastigotes were found in the bone marrow smear. Again conventionaltreatment of pentavalent antimony was given for 6 days and his condition was improved. During hospitalization, the patient was screened for HIV antibody and found positive, which was further confirmed by Western blotting analysis. The CD4~＋T lymphocytes was as low as 42 cells/ml. He was diagnosed with acquired immunodeficiency syndrome（AIDS）. From July2011, he began to receive conventional treatment including lamivudine（3 TC, 300 mg/d） ＋ zidovudine（AZT, 600 mg/d） ＋efavirenz（EFV, 600 mg/d）. Two months later, AZT was replaced by tenofovir（TDF, 300 mg/d） due to severe anemia. On25 July 2012, he was admitted to our hospital for ＂abdominal distension for two years＂. Physical examination showed severe pallor and hepatosplenomegaly（the liver was 2 cm below the costal edge and the spleen was palpable 7 cm below the umbilical level）. Leishmania was found in the bone marrow aspirate. Therefore, anti-HIV treatment with 3 TC ＋ TDF ＋EFV was continued, combined with sodium stibogluconate（ pentavalent antimony 600 mg/day for 4 days, and 1 200 mg/day for an additional 4 days）. After the liver and spleen began to shrink, the usage of stibogluconate therapy（pentavalent antimony 600 mg per time for 22 times） was changed every other day. Another two phase treatment with stibogluconate（pentavalent antimony 600 mg for 18 times） was given at one month and three months after the end of first phase treatment, respectively. The patient was given pentavalent antimony therapy with a total dose of up to 42 g during the three phase treatment, while also receiving conventional treatment on AIDS. Fifty months after pentavalent antimony withdrawal in April 2017, Leishmania was not found in the bone marrow, the CD4~＋T lymphocytes was 225 cells/ml, and HIV-RNA was below detection limit. Conclusion Prolonged stibogluconate and conventional treatment can cure visceral leishmaniasis co-infected with HIV.