Man dies covered in necrotic lesions after amoebas eat him alive
Man dies covered in necrotic lesions after amoebas eat him alive
男子遭阿米巴原虫“活吞”，全身布满坏死性病灶后不幸离世
Over the course of six months, black lesions and deep ulcers formed over the body of a 78-year-old man, puzzling doctors. His face was covered in dark scabs. A lesion had destroyed his left eyelid, and one had created a hole between the roof of his mouth and his nasal cavity. It wasn’t until he was transferred to a Yale School of Medicine hospital for higher-level care that doctors finally identified the cause of his ghastly affliction: a common free-living amoeba that can be found almost anywhere, including tap water. But by then, it was too late. The man’s case is reported in the journal Emerging Infectious Diseases.
在长达六个月的时间里，一名78岁男子的身体上长出了黑色病灶和深层溃疡，令医生们困惑不已。他的脸上布满了黑色的结痂。一处病灶摧毁了他的左眼睑，另一处则在他的口腔顶部和鼻腔之间穿出了一个洞。直到他被转院至耶鲁大学医学院接受更高级别的护理后，医生们才终于查明了他这种可怕病症的病因：一种在包括自来水在内的几乎任何地方都能找到的常见自由生活阿米巴原虫。但那时，一切都太晚了。该病例已发表在《新发传染病》（Emerging Infectious Diseases）杂志上。
Unicellular terror
单细胞恐怖
The amoeba the doctors found was Acanthamoeba, which is known to cause such horrifying infections. But it’s rare, and when it explodes into a full-body, often deadly malady, it tends to be in patients who have compromised immune systems or are otherwise debilitated. As such, the opportunistic pathogen is most often found in people with HIV/AIDS, cancers, and diabetes, as well as those on powerful immunosuppressive drugs, like transplant patients. The man didn’t fit into any of these categories.
医生发现的阿米巴原虫是棘阿米巴（Acanthamoeba），这种原虫以引发此类恐怖感染而闻名。但这种情况非常罕见，当它演变成全身性且通常致命的疾病时，往往发生在免疫系统受损或身体虚弱的患者身上。因此，这种机会性病原体最常见于艾滋病患者、癌症患者、糖尿病患者，以及服用强效免疫抑制药物的患者（如器官移植受者）。而这名男子并不属于上述任何一类。
Besides widespread infections, Acanthamoeba is known to cause localized ones, most notably eye infections—aka Acanthamoeba keratitis. It’s rare, but often linked to contact wearers who don’t clean their lenses properly. If not identified and treated early, it can easily lead to permanent vision loss. The unicellular terror can also cause a rare brain infection (granulomatous amebic encephalitis), again, mostly in immunocompromised patients. And it can infect wounds or the sinuses, particularly in people who rinse their sinuses with tap water that hasn’t been boiled. Acanthamoeba and other amoeba species have been found in more than 50 percent of US tap water samples.
除了广泛感染外，棘阿米巴还已知会引起局部感染，最显著的是眼部感染，即棘阿米巴角膜炎。这种情况虽罕见，但通常与隐形眼镜佩戴者未正确清洁镜片有关。如果不能及早发现和治疗，很容易导致永久性视力丧失。这种单细胞恐怖生物还可能引起一种罕见的脑部感染（肉芽肿性阿米巴脑炎），同样多见于免疫功能低下的患者。它还可以感染伤口或鼻窦，特别是对于那些使用未经煮沸的自来水冲洗鼻窦的人来说。在美国超过50%的自来水样本中都发现了棘阿米巴及其他阿米巴原虫。
Of all the known ways to get an Acanthamoeba infection, nasal rinsing was the most likely one in the man’s case. The man had nasal polyps and used sinus rinses to alleviate his symptoms. However, his symptoms didn’t start in his nasal passages—they started on his legs. There, red nodules formed and progressed to develop dark centers. Some became deep ulcers, while others became necrotic, turning to black scabs. Then began erupting on his trunk, arms, and neck.
在所有已知的棘阿米巴感染途径中，鼻腔冲洗是该男子最可能的感染方式。他患有鼻息肉，并使用鼻窦冲洗来缓解症状。然而，他的症状并非始于鼻腔，而是始于腿部。在那里，红色结节形成并逐渐发展出黑色中心。一些结节变成了深层溃疡，另一些则发生坏死，变成了黑色结痂。随后，病灶开始在他的躯干、手臂和颈部爆发。
Catching a killer
捕捉杀手
Before his transfer to Yale, doctors elsewhere tried to identify the mysterious cause, doing multiple biopsies of his diseased skin. Tests were negative for bacterial or fungal pathogens. But they showed his blood vessels were inflamed and full of clumps of immune cells. Doctors worried that his immune system was attacking his blood vessels, causing the necrotic lesions. So, they put him on immunosuppressant drugs. But his condition only worsened, and the lesions only progressed.
在转院至耶鲁之前，其他地方的医生曾试图查明这一神秘病因，并对他患病的皮肤进行了多次活检。细菌或真菌病原体的检测结果均为阴性。但检查显示他的血管发炎，且充满了免疫细胞团。医生担心他的免疫系统正在攻击血管，从而导致了坏死性病灶。因此，他们让他服用了免疫抑制药物。但他的病情反而恶化，病灶进一步扩散。
When he arrived at Yale, he had a fever and high heart rate, and appeared frail. He had lost 16 pounds and was drowsy and confused. He was blanketed in lesions. The Yale doctors noted that the lesions began after he returned from Florida, where he spent the winters. While there, he was exposed to a red tide (caused by algae) while cleaning up after a hurricane. Otherwise, he had a medical history of just the nasal polyps and asthma, which he treated with a monoclonal antibody drug, dupilumab.
当他到达耶鲁时，他伴有发烧和心率过快，看起来非常虚弱。他体重减轻了16磅，且昏昏欲睡、神志不清。他全身布满了病灶。耶鲁的医生注意到，这些病灶是在他从佛罗里达过冬回来后开始出现的。在佛罗里达期间，他在飓风过后的清理工作中接触过赤潮（由藻类引起）。除此以外，他的病史仅有鼻息肉和哮喘，并一直在使用单克隆抗体药物度普利尤单抗（dupilumab）进行治疗。
Given that his lesions progressed, they redid a skin biopsy, this time finding cells that looked like amoebas. DNA testing confirmed Acanthamoeba. The doctors quickly put him on a five-drug regimen recommended for such infections by the Centers for Disease Control and Prevention, but he continued to deteriorate. They then sought and got approval from the Food and Drug Administration for a single-patient experimental trial of an antibiotic (nitroxoline) that had shown success in treating a different amoeba in another patient.
鉴于他的病灶持续恶化，医生重新进行了皮肤活检，这次发现了看起来像阿米巴原虫的细胞。DNA检测证实了是棘阿米巴感染。医生迅速为他采用了美国疾病控制与预防中心（CDC）推荐的五药联合治疗方案，但他的病情仍在恶化。随后，他们向美国食品药品监督管理局（FDA）申请并获得了批准，对该患者进行了一种抗生素（硝羟喹啉）的单人实验性治疗，该药物此前在治疗另一名患者的不同阿米巴感染时曾取得成功。
Once the doctors started it in the man, it appeared to work. His fever broke briefly, some of his lesions improved, and no new ones formed. But the improvements were short-lived. His kidney function worsened, and doctors took him off the drugs to prevent further damage. His lesions showed signs of secondary infections and multiorgan failure developed. He died six weeks after the amoeba infection was identified.
医生开始为该男子用药后，药物似乎起效了。他的发烧短暂消退，部分病灶有所好转，也没有出现新的病灶。但这种改善是短暂的。他的肾功能恶化，医生不得不停药以防止进一步损害。他的病灶出现了继发感染的迹象，并发展为多器官衰竭。在确诊阿米巴感染六周后，他不幸离世。
Speculation on multifactor infection
关于多因素感染的推测
The doctors were left to speculate on how he met such a gruesome end. The nasal rinses were the most obvious route of exposure. His old age and declining immune responses may have played a role, too, they speculate. But they also looked at the one medication he was on: dupilumab. It’s a monoclonal antibody that inhibits certain immune signals, namely interleukin-4 and interleukin-13 cytokines, which play a role in overactive (T2) inflammatory responses.
医生们只能推测他是如何遭遇如此惨烈结局的。鼻腔冲洗是最明显的暴露途径。他们推测，他的高龄和免疫反应下降可能也起了一定作用。但他们也关注了他正在服用的一种药物：度普利尤单抗。这是一种单克隆抗体，能抑制特定的免疫信号，即白细胞介素-4和白细胞介素-13细胞因子，这些因子在过度活跃的（T2）炎症反应中起作用。
The doctors noted that other drugs targeting T2 inflammatory responses have been linked—in rare cases—to parasitic infections. A trial of dupilumab that included over 400 children reported that six children given the drug developed parasitic worm infections, while there were no such cases in the control group. The researchers leading the trial concluded at the time that the worm infections weren’t related to dupilumab. But the Yale doctors wondered if maybe they had been. “Although dupilumab is not classically considered an immunosuppressive agent, it possibly increases the risk for parasitic infections,” they wrote.
医生指出，其他针对T2炎症反应的药物在极少数情况下也与寄生虫感染有关。一项包含400多名儿童的度普利尤单抗试验报告称，有6名服用该药物的儿童出现了寄生虫感染，而对照组中没有此类病例。当时领导该试验的研究人员得出结论，认为寄生虫感染与度普利尤单抗无关。但耶鲁的医生们怀疑，或许两者之间存在关联。“虽然度普利尤单抗在传统上不被视为免疫抑制剂，但它可能增加了寄生虫感染的风险，”他们写道。
Overall, they speculate that the drug may have been one factor among several—including nasal rinsing and age—that led to the man’s amoeba infection. While further data will be needed to firm up any link, the researchers highlight that physicians shouldn’t overlook potential signs of free-living amoebas.
总的来说，他们推测该药物可能是导致该男子感染阿米巴原虫的多个因素之一，其他因素还包括鼻腔冲洗和年龄。虽然需要更多数据来证实这种联系，但研究人员强调，医生不应忽视自由生活阿米巴原虫的潜在迹象。