Towards a global research network for the molecular pathological stratification of leishmaniasis.

建立利什曼病分子病理分层的全球研究网络。

• 批准号: MR/P024661/1
• 负责人: Paul Kaye
• 金额: $ 76.49万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP024661%2F1
• 关键词: Towards; global; research; network; molecular

The leishmaniasis are parasitic diseases caused by one of several species of single cell parasites (Leishmania) that are transmitted to humans by the bite of infected phlebotamine sand flies. These diseases affect over 150 million people across 98 countries worldwide, including many low and middle income countries (LMICs). Some forms of leishmaniasis are fatal, whereas other are very stigmatising and affect quality of life, particularly in children and women. Few drugs are available for patients leishmaniasis and no vaccines are currently registered for use in preventing or treating these diseases. Importantly, the drugs that we do have are not universally effective and often have significant side effects. Sometimes patients even in the same geographical area will respond quite differently to therapy, and for some drugs effectiveness may vary widely between different countries. In order to make the best use of current and future drugs for the leishmaniasis, we need to understand more about why this is the case, and use that information to select appropriate drugs or drug combination for use in different settings. Using the appropriate treatment would save costs in health care, minimise the patient suffering that results from administering ineffective treatments, and reduce the economic burden of disease on patients, their families and communities. In this proposal, we are aiming to lay the foundation blocks that will drive a new way of managing patients with leishmaniasis and conducting research into these diseases. We will use new molecular approaches to extract as much information as possible from small tissue samples that are collected from patients to diagnose their leishmaniasis, and use this information to start to develop new tests that can help clinicians decide on the best course of treatment. We will use the internet to ensure that the information obtained from these tissue samples is used most effectively for research, clinical decision making and for education and training. We will conduct an analysis of the added value of these changes in approach, in order to provide a case for their adoption by health systems in LMICs and by the funders of research. Ultimately, by adopting these practices we will seek to deliver improvements in health and economic prosperity in LMICs. The research we propose over the next two years will not provide all the answers, but will provide necessary proof of concept data to support applications for future funding that may allow us to realise this longer term ambition.

利什曼病是由几种单细胞寄生虫(利什曼原虫)中的一种引起的寄生虫病，这些单细胞寄生虫通过受感染的苯妥拉明沙蝇的叮咬传播给人类。这些疾病影响全球98个国家的1.5亿多人，其中包括许多低收入和中等收入国家。一些形式的利什曼病是致命的，而其他形式的利什曼病非常令人羞辱，并影响生活质量，特别是在儿童和妇女中。对利什曼病患者可用的药物很少，目前还没有登记用于预防或治疗这些疾病的疫苗。重要的是，我们拥有的药物并不是普遍有效的，而且往往有显著的副作用。有时，即使在同一地区的患者对治疗的反应也会有很大的不同，对于某些药物，不同国家的疗效可能会有很大差异。为了最大限度地利用当前和未来的药物治疗利什曼病，我们需要更多地了解为什么会出现这种情况，并利用这些信息来选择适当的药物或药物组合用于不同的环境。使用适当的治疗将节省医疗保健成本，最大限度地减少患者因实施无效治疗而遭受的痛苦，并减轻疾病对患者、其家人和社区的经济负担。在这项提案中，我们的目标是奠定基础，推动一种管理利什曼病患者的新方法，并对这些疾病进行研究。我们将使用新的分子方法从从患者那里收集的小组织样本中提取尽可能多的信息来诊断他们的利什曼病，并利用这些信息开始开发新的测试，以帮助临床医生决定最佳治疗方案。我们将利用互联网确保从这些组织样本中获得的信息最有效地用于研究、临床决策以及教育和培训。我们将对这些方法变化的附加值进行分析，以便为低收入中等收入国家的卫生系统和研究资助者提供采用这些方法的案例。最终，通过采用这些做法，我们将寻求改善低收入中等收入国家的健康状况和经济繁荣。我们在未来两年提出的研究不会提供所有答案，但将提供必要的概念数据，以支持未来可能使我们实现这一长期抱负的资金申请。

项目成果

IL-32 producing CD8 + memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions

产生 IL-32 的 CD8 记忆 T 细胞和 Tregs 定义了人皮肤利什曼病皮肤病变中的 IDO1 / PD-L1 生态位

• DOI: 10.1101/2024.01.02.23300281
• 发表时间: 2024
• 作者: Dey N

Immune dysregulation and inflammation causing hypopigmentation in post kala-azar dermal leishmaniasis: partners in crime?

• DOI: 10.1016/j.pt.2023.07.005
• 发表时间: 2023-09-13
• 期刊: TRENDS IN PARASITOLOGY
• 影响因子: 9.6
• 作者: Sengupta，Ritika;Roy，Madhurima;Chatterjee，Mitali
• 通讯作者: Chatterjee，Mitali

Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis.

• DOI: 10.1172/jci142765
• 发表时间: 2021-11-15
• 期刊: The Journal of clinical investigation
• 作者: Dey NS;Senaratne S;Somaratne V;Madarasinghe NP;Seneviratne B;Forrester S;Montes de Oca M;Reis LC;Moulik S;Walrad PB;Chatterjee M;Goto H;Wickremasinghe R;Lagos D;Kaye PM;Ranasinghe S
• 通讯作者: Ranasinghe S

VALIDATE: Exploiting the synergy between complex intracellular pathogens to expedite vaccine research and development for tuberculosis, leishmaniasis, melioidosis and leprosy.

• DOI: 10.12688/f1000research.14386.1
• 发表时间: 2018
• 期刊: F1000Research
• 作者: Fletcher HA;Chatterjee M;Cooper A;Hussell T;Kaye PM;Prior J;Reljic R;Vermaak S;Vordermeier M;Williams A;McShane H
• 通讯作者: McShane H

Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases.

• DOI: 10.1155/2021/6614475
• 发表时间: 2021
• 期刊: Journal of immunology research
• 影响因子: 4.1
• 作者: Reis LC;Ramos-Sanchez EM;Araujo FN;Leal AF;Ozaki CY;Sevillano OR;Uscata BA;Goto H
• 通讯作者: Goto H