Leishmaniases as Re-emerging Diseases最新文献

Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing? 人类利什曼病疫苗:我们做了什么，还有什么缺失?

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75000

P. Cecílio, Fabiano Oliveira, Anabela Cordeiro da Silva

{"title":"Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?","authors":"P. Cecílio, Fabiano Oliveira, Anabela Cordeiro da Silva","doi":"10.5772/INTECHOPEN.75000","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75000","url":null,"abstract":"Responsible for up to 30,000 deaths annually, leishmaniasis is a complex spectrum of diseases endemic in 97 countries around the globe. Disease control relies heavily on the early diagnosis and treatment of the active cases (relevant for anthroponotic disease), although it is widely accepted that a prophylactic vaccine for human leishmaniasis is the way to achieve the successful elimination of human disease (taking in consideration the vast list of non-human reservoirs that enable the perpetuation of parasites all around the globe). The notion that infection leads to strong and long-lasting immunity against leishmaniasis supports vaccination as an achievable goal. However, and in spite of the different candidates tested along the years, till date, we still do not have an approved vaccine for humans. In this chapter, we will explore the last advances made in the field of vaccines against Leishmania without forgetting the historical perspective, essential to the understanding of the road already undergone. We will then discuss the correlates of disease and protection, still neither consensual nor definitive, as well as the issue of pre-clinical to clinical translation. The complete understanding of these issues will be essential for the approval of a successful vaccine for human leishmaniasis.","PeriodicalId":17975,"journal":{"name":"Leishmaniases as Re-emerging Diseases","volume":"49 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77772950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGR) Enzyme of the Sterol Biosynthetic Pathway: A Potential Target against Visceral Leishmaniasis 甾醇生物合成途径的3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR):对抗内脏利什曼病的潜在靶点

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75480

Sushma Singh, N. Babu

{"title":"3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGR) Enzyme of the Sterol Biosynthetic Pathway: A Potential Target against Visceral Leishmaniasis","authors":"Sushma Singh, N. Babu","doi":"10.5772/INTECHOPEN.75480","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75480","url":null,"abstract":"Sterol biosynthetic pathway is explored for its therapeutic potential for Visceral Leish maniasis. In Leishmania , this pathway produces ergosterol which is absent in host and there fore is a promising strategy to combat proliferation of both extracellular and intracellular forms of the parasite with minimal host toxicity. The present chapter focuses on 3hydroxy 3methylglutarylCoA reductase (HMGR) enzyme which is the ratelimiting enzyme of the ergosterol biosynthesis. HMGR gene of L. donovani was biochemically and biophysically characterized for the first time. HMGR over expressing transgenic parasites were generated to evaluate its role in parasite growth and infection ability. A series of statins like atorvas tatin, simvastatin and mevastatin were evaluated for its therapeutic efficacy and mode of action elucidated. Atorvastatin and mevastatin were found to be killing both the promas tigote and amastigote forms of the parasite without exhibiting host cytotoxicity. Besides, non-statin class of molecules like resveratrol and glycyrrhizic acid were also analyzed for antileishmanial potential. Two antidepressants, ketanserin and mianserin were found to kill both L. donovani promastigotes and intracellular amastigotes with no apparent toxicity to the host cells. Since targeting of the sterol biosynthetic pathway enzymes may be useful therapeutically, the present work may have implications in treatment of Leishmaniasis. The present review encompasses functional characterization of L. donovani HMGR enzyme and the evaluation of the effect of various HMGR inhibitors as potential candidates for treat ment of Leishmaniasis. Inhibitors which showed inhibition of both the extracellular and intra cellular forms of the parasites at low micromolar range with no cytotoxicity to host cells are promising antileishmanial candidates. They can be further explored in an experimental ani mal model of VL to evaluate its anti-VL efficacy.","PeriodicalId":17975,"journal":{"name":"Leishmaniases as Re-emerging Diseases","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89247910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Nanomedicines for Cutaneous Leishmaniasis 皮肤利什曼病的纳米药物

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75750

Ariane J. Sousa-Batista, B. Rossi-Bergmann

{"title":"Nanomedicines for Cutaneous Leishmaniasis","authors":"Ariane J. Sousa-Batista, B. Rossi-Bergmann","doi":"10.5772/INTECHOPEN.75750","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75750","url":null,"abstract":"Leishmaniasis is a vector-borne disease caused by Leishmania parasites, which cause a range of clinical manifestations in man. These are didactically classified into cutane - ous leishmaniasis (CL), the most common form of the disease, and visceral leishmaniasis (VL), the life-threatening form. There are so far no vaccines approved for humans. Conventional drugs pose limitations ranging from low efficacy and high cost to systemic toxicity. Low efficacy derives in part from difficult drug access to the parasites, which rides themselves inside macrophage phagosomes. This prompts to high dosage, with consequent increased toxicity. Difficult intracellular drug access can be overcome with nanomedicines such as biocompatible lipid and polymeric nanoparticles that can be phagocytosed by the infected macrophages. Besides cell membranes, appropriate drug nanostructuring may allow tissue barrier penetration and drug administration through higher compliance routes such as skin and intestine, in contrast to the usual intravenous and intramuscular routes. In general, CL and VL are both treated with toxic systemic injections, disregard of disease severity. This chapter will review and discuss studies with nanomedicines that have reached the market such as liposomal amphotericin B for intravenous administration, and innovative preclinical studies aiming at developing effective cutaneous and oral drugs with focus on CL .","PeriodicalId":17975,"journal":{"name":"Leishmaniases as Re-emerging Diseases","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82520373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Crossing Biological Barriers for Leishmaniasis Therapy: From Nanomedicinal Targeting Perspective 跨越生物屏障治疗利什曼病:从纳米药物靶向的角度

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75911

G. Shahnaz, H. S. Sarwar, M. Yasinzai

引用次数: 4

Vaccines for Visceral Leishmaniasis: Hopes and Hurdles 内脏利什曼病疫苗:希望与障碍

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75184

E. Khalil

{"title":"Vaccines for Visceral Leishmaniasis: Hopes and Hurdles","authors":"E. Khalil","doi":"10.5772/INTECHOPEN.75184","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75184","url":null,"abstract":"The leishmaniases are vector-borne parasitic diseases with multiple disease pheno- types that range from self-healing cutaneous ulcers to disfiguring post-kala-azar der mal leishmaniasis and fatal visceral leishmaniasis (VL). Infected individuals can develop subclinical infections or overt disease. Current treatments are toxic and expensive. The only successful control measure is case detection and drug treatment. Resistance to anti- leishmanial drugs are increasing with few drugs in the pipeline. The Leishmania parasites are good candidates for vaccine development, with no change in its antigenic coat and extensive cross-reactivity between species. First-generation vaccines are safe, immunogenic with inconclusive efficiency. These vaccines presented the leishmanin skin test (LST) as a potentially good surrogate marker of immunogenicity/protection that can help in future vaccine studies. First-generation vaccines are the only leishmaniasis vaccines that progressed to phase III. Second-generation vaccines are safe and immunogenic, but none progressed to phase III. Third-generation vaccines recently entered human testing. Alternative approaches include in silico prediction of immunogenic Leishmania epitopes with in vitro immunogenicity testing. New adjuvants can help in the quest to develop efficacious leishmaniasis vaccines. Failure of second- and third-generation vaccines to reach phase III, rising drug resistance and continued VL pandemics make it a necessity to revisit first-generation vaccines .","PeriodicalId":17975,"journal":{"name":"Leishmaniases as Re-emerging Diseases","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88098492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Leishmaniases in West Africa: Past and Current 西非的利什曼病:过去和现在

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.77009

A. Kone, M. Thera, B. Faye, O. Doumbo

引用次数: 1

The Polyamine Pathway as a Potential Target for Leishmaniases Chemotherapy 多胺途径作为利什曼病化疗的潜在靶点

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75867

J. I. Aoki, S. Muxel, Juliane Cristina RibeiroFernandes, L. Floeter-Winter

引用次数: 2

Alternative Treatment for Leishmaniasis 利什曼病的替代治疗

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.75895

R. M. Oliveira, S. A. Melo, Tatiane Aranha da Penha-Silva, Fernando Almeida-Souza, Ana LuciaAbreu-Silva

引用次数: 7

Visceral Leishmaniasis 内脏利什曼病

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/intechopen.75907

S. Bhattacharya, Ajanta Ghosal, S. Ganguly, S. Ganguly, Sabahat Azim, S. Dutta

引用次数: 0

Introductory Chapter: Leishmaniasis: An Emerging Clinical Syndrome 导论章:利什曼病:一种新兴的临床综合征

Leishmaniases as Re-emerging Diseases Pub Date : 2018-10-10 DOI: 10.5772/INTECHOPEN.79662

F. Afrin, H. Hemeg

引用次数: 0