Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal.
Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal.
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DOI：
10.1371/journal.pntd.0001691
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发表时间：
2012
影响因子：
3.8
通讯作者：
Bucheton B
中科院分区：
文献类型：
--
作者：
Jamonneau V;Ilboudo H;Kaboré J;Kaba D;Koffi M;Solano P;Garcia A;Courtin D;Laveissière C;Lingue K;Büscher P;Bucheton B
昏睡病的主要病原体布氏冈比亚锥虫感染的最终结果一直被认为是致命的。虽然很少有旧的报告提到未经治疗的患者自我治愈的病例，但这些研究当时缺乏准确的诊断工具。在这里，使用迄今为止最具体和敏感的工具，我们报告了一个长期随访（15年）的队列50人非洲锥虫病（HAT）患者从象牙海岸，其中11人拒绝治疗后，他们的初步诊断。在10/11例尽管多次就诊仍继续拒绝治疗的受试者中，使用显微镜和聚合酶链反应（PCR）观察到寄生虫清除。这些受试者中的大多数（7/10）也显示血清学应答降低，对锥虫可变抗原逐渐呈阴性（LiTat 1.3、1.5和1.6）。因此，除了HAT的“经典”致死性结局外，我们还发现HAT可能会发生其他自然进展：进展为明显的无寄生虫血症和无症状感染，并伴有强烈的长期血清学反应;进展为明显的感染自发消退（寄生虫学试验和PCR结果为阴性），并伴有治疗病例中观察到的抗体滴度逐渐下降。虽然这项研究没有精确估计这种感染的替代病程的频率，但值得注意的是，在该领域，国家控制计划遇到了显着比例的受试者显示阳性血清学检测结果，但寄生虫学检测结果为阴性。这些发现表明，这些受试者中的一些显示这样的感染过程。从我们的角度来看，认识到锥虫耐受性存在于人类中，就像现在广泛接受的动物一样，是HAT领域未来研究的重要一步。目前，大多数寄生虫病和传染病的感染结果多种多样，从自我治愈到无症状、严重或致命病例，这一点已得到广泛认可。然而，关于昏睡病的教条仍然是感染是100%致命的。在这里，我们描述了一个15年的随访病人诊断为人类非洲锥虫病（HAT）在象牙海岸，但谁拒绝治疗。我们的研究结果，基于临床，血清学，分子和寄生虫学的调查，结合诊断工具的领域和高度特异性和敏感的实验室检测，构成了最全面的研究自然进化的布氏冈比亚锥虫感染的人类宿主。确定了至少两种HAT自然进展为“经典”致死性疾病的替代性进展：进展为明显的无血性和无症状感染，以及进展为明显的感染自发消退。我们认为，认识到人类存在锥虫耐受性是未来研究的重要一步，旨在确定控制结核病的人类特异性防御和免疫机制。冈比亚病毒感染，因此是新的候选治疗或预防靶点。
The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years) of a cohort of 50 human African trypanosomiasis (HAT) patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR). Most of these subjects (7/10) also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6). Hence, in addition to the “classic” lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR) associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT. The existence of a diversity of infection outcomes – ranging from self-cure to asymptomatic, severe or fatal cases – is now widely recognised for most parasitic and infectious diseases. The dogma concerning sleeping sickness, however, is still that infection is 100% fatal. Here we describe a 15-year follow-up of patients diagnosed with human African trypanosomiasis (HAT) in the Ivory Coast but who refused treatment. Our results, based on clinical, serological, molecular, and parasitological investigations, combining diagnostic tools for the field and highly specific and sensitive laboratory tests, constitute the most comprehensive study on the natural evolution of Trypanosoma brucei gambiense infection in its human host. At least two alternative natural progressions of HAT to the “classic” fatal disease were identified: a progression to an apparently aparasitaemic and asymptomatic infection and a progression to an apparently spontaneous resolution of infection. We believe that recognising that trypanotolerance exists in humans is a major step forward for future research aimed at identifying human-specific defence and immune mechanisms involved in the control of T.b. gambiense infection and thus new candidate therapeutic or prophylactic targets.
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影响因子：
3.3
作者：
Jamonneau, V;Garcia, A;Truc, P
通讯作者：
Truc, P
影响因子：
3.3
作者：
Kaba, D;Dje, NN;Solano, P
通讯作者：
Solano, P
DOI：
10.1073/pnas.1232392100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Hanotte, O;Ronin, Y;Teale, A
通讯作者：
Teale, A
影响因子：
3.8
作者：
Deborggraeve, Stijn;Lejon, Veerle;Buscher, Philippe
通讯作者：
Buscher, Philippe
甘比坦锥虫疾病进展的小鼠模型--从静默感染到慢性感染和早期脑趋向性
影响因子：
3.8
作者：
Giroud, Christiane;Ottones, Florence;Baltz, Theo
通讯作者：
Baltz, Theo