Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells.
Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells.
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DOI：
10.3390/tropicalmed8100478
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发表时间：
2023-10-20
影响因子：
2.9
通讯作者：
Stowell SR
中科院分区：
文献类型：
--
作者：
Jajosky RP;Wu SC;Jajosky PG;Stowell SR
诺氏疟原虫（Plasmodium knowlesi，Pk）是人畜共患疟疾的病原菌，被称为“第五种人类疟疾寄生虫”。Pk疟疾是一种新出现的威胁，因为感染正在增加，可能是致命的。虽然大多数感染发生在东南亚（SEA），特别是马来西亚，但旅行者经常访问该地区，并可能在世界各地出现Pk疟疾。因此，临床医生需要知道（1）最近前往SEA后出现发热的患者可能感染了Pk，（2）Pk经常被误诊为三日疟原虫（通常导致不太严重的疟疾）。本文就Pk疟疾的历史、病理生理、临床特点、诊断和治疗作一综述。严重的疾病在成年人中最常见。体征和症状可包括发热、腹痛、黄疸、急性肾损伤、急性呼吸窘迫综合征、低钠血症、寄生虫血症和血小板减少症。登革热是鉴别诊断中要考虑的疾病之一。关于病理生理机制，当Pk寄生虫侵入成熟红细胞（RBC，即，在红细胞（RBC）（正常细胞）和网织红细胞中，红细胞（RBC）表面的变化可导致危及生命的细胞粘附、隔离和RBC变形性降低。由于涉及红细胞阶段的分子机制是导致严重疾病和致死性结果的原因，因此人工交换输血（ET）或自动RBC交换（RBCX）通过用未感染的、可变形的健康供体RBC替换“粘性”寄生RBC可能非常有益，这在生物学上是合理的。在这里，我们建议使用特殊的抗PK供体RBC来优化疟疾的连续手动ET/RBCX。提出了“治疗合理的交换输血”（T-REX），其中输注PK抗性RBC（而不是促进疾病的RBC）。由于Duffy抗原在人RBC表面的表达对于寄生虫入侵是必不可少的，Duffy阴性RBC（也称为Fy（a-b-）RBC）的T-REX可以用抗Pk入侵的RBC取代患者的大部分循环正常细胞（在持续约2小时的单个过程中）。当隔离或非隔离的iRBC破裂时-在24 h Pk无性生命周期中-释放的裂殖子不能侵入Fy（a-b-）RBC。当Fy（a-b-）RBC单位稀缺时（例如，在马来西亚），临床医生可以考虑重复使用PK耐药RBC的风险和益处，如葡萄糖-6-磷酸脱氢酶缺陷（G6 PDd）RBC和东南亚卵母细胞（SAO）。患者通常需要非常短的恢复时间（<1小时）。Fy（a-b-）RBC应该具有正常的寿命，而SAO和G6 PDd RBC可能具有轻度减少的半衰期。由于SAO和G6 PDd红细胞来自健康且不贫血的筛查献血者，因此这些红细胞溶血风险低，并且在患者从疟疾中恢复后不需要去除。如果（1）抗疟药物不容易获得，（2）患者可能进展为严重疾病，或（3）出现耐药菌株，T-REX可能特别有用。总之，T-REX是手动ET/RBCX的拟议优化，尚未使用，但医生可以考虑治疗Pk疟疾患者。
Plasmodium knowlesi (Pk) causes zoonotic malaria and is known as the “fifth human malaria parasite”. Pk malaria is an emerging threat because infections are increasing and can be fatal. While most infections are in Southeast Asia (SEA), especially Malaysia, travelers frequently visit this region and can present with Pk malaria around the world. So, clinicians need to know (1) patients who present with fever after recent travel to SEA might be infected with Pk and (2) Pk is often misdiagnosed as P. malariae (which typically causes less severe malaria). Here we review the history, pathophysiology, clinical features, diagnosis, and treatment of Pk malaria. Severe disease is most common in adults. Signs and symptoms can include fever, abdominal pain, jaundice, acute kidney injury, acute respiratory distress syndrome, hyponatremia, hyperparasitemia, and thrombocytopenia. Dengue is one of the diseases to be considered in the differential. Regarding pathophysiologic mechanisms, when Pk parasites invade mature red blood cells (RBCs, i.e., normocytes) and reticulocytes, changes in the red blood cell (RBC) surface can result in life-threatening cytoadherence, sequestration, and reduced RBC deformability. Since molecular mechanisms involving the erythrocytic stage are responsible for onset of severe disease and lethal outcomes, it is biologically plausible that manual exchange transfusion (ET) or automated RBC exchange (RBCX) could be highly beneficial by replacing “sticky” parasitized RBCs with uninfected, deformable, healthy donor RBCs. Here we suggest use of special Pk-resistant donor RBCs to optimize adjunctive manual ET/RBCX for malaria. “Therapeutically-rational exchange transfusion” (T-REX) is proposed in which Pk-resistant RBCs are transfused (instead of disease-promoting RBCs). Because expression of the Duffy antigen on the surface of human RBCs is essential for parasite invasion, T-REX of Duffy-negative RBCs—also known as Fy(a-b-) RBCs—could replace the majority of the patient’s circulating normocytes with Pk invasion-resistant RBCs (in a single procedure lasting about 2 h). When sequestered or non-sequestered iRBCs rupture—in a 24 h Pk asexual life cycle—the released merozoites cannot invade Fy(a-b-) RBCs. When Fy(a-b-) RBC units are scarce (e.g., in Malaysia), clinicians can consider the risks and benefits of transfusing plausibly Pk-resistant RBCs, such as glucose-6-phosphate dehydrogenase deficient (G6PDd) RBCs and Southeast Asian ovalocytes (SAO). Patients typically require a very short recovery time (<1 h) after the procedure. Fy(a-b-) RBCs should have a normal lifespan, while SAO and G6PDd RBCs may have mildly reduced half-lives. Because SAO and G6PDd RBCs come from screened blood donors who are healthy and not anemic, these RBCs have a low-risk for hemolysis and do not need to be removed after the patient recovers from malaria. T-REX could be especially useful if (1) antimalarial medications are not readily available, (2) patients are likely to progress to severe disease, or (3) drug-resistant strains emerge. In conclusion, T-REX is a proposed optimization of manual ET/RBCX that has not yet been utilized but can be considered by physicians to treat Pk malaria patients.
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影响因子：
3
作者：
Auer-Hackenberg L;Staudinger T;Bojic A;Locker G;Leitner GC;Graninger W;Winkler S;Ramharter M;Worel N
通讯作者：
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影响因子：
5.7
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Knowlesi疟疾：人类风险因素，临床谱和病理生理学。
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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Manning, Jessica E.
影响因子：
3.7
作者：
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通讯作者：
Dodoo D