Plasmodium Species and Drug Resistance [Working Title]最新文献

Stable Artesunate Resistance in A Humanized Mouse Model of Plasmodium falciparum 恶性疟原虫人源化小鼠模型青蒿琥酯稳定耐药性的研究

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-10-12 DOI: 10.5772/intechopen.100381

S. Saini, Rajinder Kumar, R. Tyagi

{"title":"Stable Artesunate Resistance in A Humanized Mouse Model of Plasmodium falciparum","authors":"S. Saini, Rajinder Kumar, R. Tyagi","doi":"10.5772/intechopen.100381","DOIUrl":"https://doi.org/10.5772/intechopen.100381","url":null,"abstract":"Plasmodium falciparum, the most devastating human malaria parasite, confers higher morbidity and mortality. Although efforts have been made to develop an effective malaria vaccine, stage- and species-specific short-lived immunity crippled these efforts. Hence, antimalarial drug treatment becomes a mainstay for the treatment of malaria infection in the wake of the unavailability of an effective vaccine. Further, there has been a wide array of antimalarial drugs effective against various developmental stages of P. falciparum due to their different structures, modes of action, and pharmacodynamics as well as pharmacokinetics. The development of resistance against almost all frontline drugs by P. falciparum indicates the need for combination therapy (artemisinin-based combination therapy; ACT) to treat patients with P. falciparum. A higher pool of parasitemia under discontinuous in vivo artemisinin drug pressure in a developed humanized mouse allows the selection of artesunate resistant (ART-R) P. falciparum. Intravenously administered artesunate, using either single flash doses or a 2-day regimen, to the P. falciparum-infected human blood chimeric NOD/SCID.IL-2Rγ−/− immunocompromised (NSG) mice, with progressive dose increments upon parasite recovery, was the strategy deployed to select resistant parasites. Parasite susceptibility to artemisinins and other antimalarial compounds was characterized in vitro and in vivo. P. falciparum has shown to evolve extreme artemisinin resistance as well as co-resistance to antimalarial drugs. Overall, the present information shall be very useful in devising newer therapeutic strategies to treat human malaria infection.","PeriodicalId":231860,"journal":{"name":"Plasmodium Species and Drug Resistance [Working Title]","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130202361","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: 0

Molecular Approaches for Malaria Therapy 疟疾治疗的分子方法

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-07-28 DOI: 10.5772/intechopen.98396

Mitali Mishra, V. Mishra, Varsha Kashaw, S. Kashaw

引用次数: 1

P. falciparum and Its Molecular Markers of Resistance to Antimalarial Drugs 恶性疟原虫及其抗疟药物耐药分子标记

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-07-08 DOI: 10.5772/INTECHOPEN.98372

Peter Hodoameda

{"title":"P. falciparum and Its Molecular Markers of Resistance to Antimalarial Drugs","authors":"Peter Hodoameda","doi":"10.5772/INTECHOPEN.98372","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.98372","url":null,"abstract":"The use of molecular markers of resistance to monitor the emergence, and the spread of parasite resistance to antimalarial drugs is a very effective way of monitoring antimalarial drug resistance. The identification and validation of molecular markers have boosted our confidence in using these tools to monitor resistance. For example, P. falciparum chloroquine resistance transporter (PfCRT), P. falciparum multidrug resistance protein 1 (PfMDR1), P. falciparum multidrug kelch 13 (pfk13), have been identified as molecular markers of resistance to chloroquine, lumefantrine, and artemisinin respectively. The mechanism of resistance to antimalarial drugs is mostly by; (1) undergoing mutations in the parasite genome, leading to expelling the drug from the digestive vacuole, or (2) loss of binding affinity between the drug and its target. Increased copy number in the pfmdr1 gene also leads to resistance to antimalarial drugs. The major cause of the widespread chloroquine and sulfadoxine-pyrimethamine resistance globally is the spread of parasites resistant to these drugs from Southeast Asia to Africa, the Pacific, and South America. Only a few mutations in the parasite genome lead to resistance to chloroquine and sulfadoxine-pyrimethamine arising from indigenous parasites in Africa, Pacific, and South America.","PeriodicalId":231860,"journal":{"name":"Plasmodium Species and Drug Resistance [Working Title]","volume":"141 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128995375","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: 1

Drug Design for Malaria with Artificial Intelligence (AI) 基于人工智能(AI)的疟疾药物设计

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-07-07 DOI: 10.5772/INTECHOPEN.98695

B. Ghosh, Soham Choudhuri

引用次数: 2

Malaria: Introductory Concepts, Resistance Issues and Current Medicines 疟疾:介绍概念、耐药性问题和当前药物

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-07-04 DOI: 10.5772/INTECHOPEN.98725

Dejen Nureye

{"title":"Malaria: Introductory Concepts, Resistance Issues and Current Medicines","authors":"Dejen Nureye","doi":"10.5772/INTECHOPEN.98725","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.98725","url":null,"abstract":"Malaria continues to be the main community health problem in numerous nations. Six species of Plasmodium are documented as the cause of human malaria infection. Among others, Plasmodium falciparum and Plasmodium vivax parasites produce an immense challenge in the public health. Anopheles funestus and Anopheles gambiae are the major transimmiter of the disease (malaria) from one person to another. The disease parasite has a complicated cycle of life that occurs in human and mosquitoes. In general, malaria diagnosis is divided into parasitological and clinical diagnosis. Internationally, the death rate of malaria becomes reduced although few records from Ethiopia describe the presence of raised prevalence of malaria in certain areas. Apart from reduction in incidence and prevalence, transmission of malaria is continued throughout the globe. Hence, its control needs a combined approach comprising treatment with effective antimalarial agents. A lot of novel compounds are under pre-clinical and clinical studies that are triggered by the occurrence of resistance among commonly used antimalarial drugs. In addition to the already known new compounds and targets for drug discovery, scientists from all corner of the world are in search of novel targets and chemical entities.","PeriodicalId":231860,"journal":{"name":"Plasmodium Species and Drug Resistance [Working Title]","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130978781","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: 2

Plasmodium Species and Drug Resistance 疟原虫种类与耐药性

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-06-23 DOI: 10.5772/intechopen.98344

Sintayehu Tsegaye Tseha

{"title":"Plasmodium Species and Drug Resistance","authors":"Sintayehu Tsegaye Tseha","doi":"10.5772/intechopen.98344","DOIUrl":"https://doi.org/10.5772/intechopen.98344","url":null,"abstract":"Malaria is a leading public health problem in tropical and subtropical countries of the world. In 2019, there were an estimated 229 million malaria cases and 409, 000 deaths due malaria in the world. The objective of this chapter is to discuss about the different Plasmodium parasites that cause human malaria. In addition, the chapter discusses about antimalarial drugs resistance. Human malaria is caused by five Plasmodium species, namely P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. In addition to these parasites, malaria in humans may also arise from zoonotic malaria parasites, which includes P. inui and P. cynomolgi. The plasmodium life cycle involves vertebrate host and a mosquito vector. The malaria parasites differ in their epidemiology, virulence and drug resistance pattern. P. falciparum is the deadliest malaria parasite that causes human malaria. P. falciparum accounted for nearly all malarial deaths in 2018. One of the major challenges to control malaria is the emergence and spread of antimalarial drug-resistant Plasmodium parasites. The P. vivax and P. falciparum have already developed resistance against convectional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and atovaquone. Chloroquine-resistance is connected with mutations in pfcr. Resistance to Sulfadoxine and pyrimethamine is associated with multiple mutations in pfdhps and pfdhfr genes. In response to the evolution of drug resistance Plasmodium parasites, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated falciparum malaria since the beginning of 21th century. However, artemisinin resistant P. falciparum strains have been recently observed in different parts of the world, which indicates the possibility of the spread of artemisinin resistance to all over the world. Therefore, novel antimalarial drugs have to be searched so as to replace the ACTs if Plasmodium parasites develop resistance to ACTs in the future.","PeriodicalId":231860,"journal":{"name":"Plasmodium Species and Drug Resistance [Working Title]","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132793227","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: 7

Regulation of T-reg/Th-17 Balance: One Step Closer Towards Immunotherapy Against Malaria Infection T-reg/Th-17平衡调节:向疟疾感染免疫治疗迈进了一步

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-06-21 DOI: 10.5772/intechopen.97045

S. Mukherjee, Soubhik Ghosh, A. Bhattacharyya

{"title":"Regulation of T-reg/Th-17 Balance: One Step Closer Towards Immunotherapy Against Malaria Infection","authors":"S. Mukherjee, Soubhik Ghosh, A. Bhattacharyya","doi":"10.5772/intechopen.97045","DOIUrl":"https://doi.org/10.5772/intechopen.97045","url":null,"abstract":"According to World Malaria Report 2020, the rate of decline in malaria case incidence and deaths caused by malaria has ceased in latter half of the past decade. Though Artemisinin Combination Therapy (ACT) is still the major therapeutic approach globally to treat malaria patients, increased resistance of Plasmodium sp. to artemisinin can be looked upon as a major factor responsible for the rate of decline. In the present world, immunotherapeutic approaches are in the limelight to treat several infections, autoimmune disorders, cancers but application of such therapeutic measures in case of malaria are yet not available. Among different immune cells, T-regulatory cells (T-reg) and Th-17 cells and the balance between them, helps in determining the outcome of the immune response in host during both lethal and non-lethal malaria. TGFβ and IL-6 are two major cytokines that play important role in fine tuning the Treg/Th-17 balance by modulating dendritic cell responses, specially by regulating the ratio between myeloid DC and plasmacytoid DC (mDC/pDC). Studies in rodent malaria models have revealed that neutralization of IL-6 by using anti IL-6 monoclonal antibodies in-vivo has been found effective in declining the parasitemia, malaria induced deaths and also in reverting back the altered T-reg/Th-17 balance to normal levels. Apart from these, autophagy is one of the major factors which also contributes to regulate the T-reg/Th-17 balance. In malaria infected mice, autophagy induction has been found to normalise the dysregulated T-reg/Th-17 ratio and promote anti-inflammatory Th-2 pathway by supressing pro-inflammatory Th-1 pathway. So, Treg/Th-17 balance and its associated regulators can be important immunotherapeutic targets for malaria prevention in near future.","PeriodicalId":231860,"journal":{"name":"Plasmodium Species and Drug Resistance [Working Title]","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122848526","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: 1

Recent Advances in Antimalarial Drug Discovery: Challenges and Opportunities 抗疟药物发现的最新进展:挑战与机遇

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-06-21 DOI: 10.5772/intechopen.97401

Imrat, A. Verma, P. R. Mina

引用次数: 4

Adaptive Drug Resistance in Malaria Parasite: A Threat to Malaria Elimination Agenda? 疟原虫的适应性耐药性:对消除疟疾议程的威胁?

Plasmodium Species and Drug Resistance [Working Title] Pub Date : 2021-06-04 DOI: 10.5772/INTECHOPEN.98323

M. Okpeku

引用次数: 0