Challenges and recent progress in drug discovery for tropical diseases

De Rycker, Manu; Baragaña, Beatriz; Duce, Suzanne L.; Gilbert, Ian H.

doi:10.1038/s41586-018-0327-4

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Challenges and recent progress in drug discovery for tropical diseases

review-article

Author(s): Manu De Rycker ¹ , Beatriz Baragaña ¹ , Suzanne L. Duce ² , Ian H. Gilbert ¹ ^,

Publication date (Electronic): 25 July 2018

Journal: Nature

Publisher: Nature Publishing Group UK

Keywords: Target identification, Parasitic infection, Infectious diseases

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Abstract

Infectious tropical diseases have a huge effect in terms of mortality and morbidity, and impose a heavy economic burden on affected countries. These diseases predominantly affect the world’s poorest people. Currently available drugs are inadequate for the majority of these diseases, and there is an urgent need for new treatments. This Review discusses some of the challenges involved in developing new drugs to treat these diseases and highlights recent progress. While there have been notable successes, there is still a long way to go.

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A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium.

William Checkley, A. White, Devan Jaganath … (2015)

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances. Copyright © 2015 Elsevier Ltd. All rights reserved.

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Is Open Access

Determinants of relapse periodicity in Plasmodium vivax malaria

Nicholas J. White (2011)

Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important implications for the assessment of radical treatment efficacy and for malaria control and elimination.

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Record: found
Abstract: found
Article: not found

Human African trypanosomiasis.

Gerardo Priotto, Vincent Jamonneau, Giuliano Cecchi … (2017)

Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent successes, the disease is still endemic in parts of sub-Saharan Africa, where it is a considerable burden on rural communities, most notably in central Africa. Since patients are also reported from non-endemic countries, human African trypanosomiasis should be considered in differential diagnosis for travellers, tourists, migrants, and expatriates who have visited or lived in endemic areas. In the absence of a vaccine, disease control relies on case detection and treatment, and vector control. Available drugs are suboptimal, but ongoing clinical trials provide hope for safer and simpler treatments.

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Author and article information

Contributors

Ian H. Gilbert: i.h.gilbert@dundee.ac.uk

Journal

Journal ID (nlm-ta): Nature

Journal ID (iso-abbrev): Nature

Title: Nature

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 0028-0836

ISSN (Electronic): 1476-4687

Publication date (Electronic): 25 July 2018

Publication date (Print): 2018

Volume: 559

Issue: 7715

Pages: 498-506

Affiliations

[1 ]ISNI 0000 0004 0397 2876, GRID grid.8241.f, Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, , Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, ; Dundee, UK

[2 ]ISNI 0000 0004 0397 2876, GRID grid.8241.f, Medicines Monitoring Unit (MEMO), , Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, ; Dundee, UK

Article

Publisher ID: 327

DOI: 10.1038/s41586-018-0327-4

PMC ID: 6129172

PubMed ID: 30046073

SO-VID: 330ed561-914e-4658-8dc2-b2fe97037d38

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.