4.7 Review

Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2022.905278

Keywords

tuberculosis; malaria; host-directed therapy; immunity; intracellular development; pathogenesis; cell invasion

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2020/01043-9, 2020/10356-0, 2019/08445-8, 2019/25770-0]

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Tuberculosis and malaria are major causes of death due to infectious diseases worldwide. While both diseases can be treated with drugs, issues such as treatment compliance and drug resistance have hindered efforts to combat them. Recent research has shown that certain host biological processes play a role in the development of these diseases. Host-directed therapies, which can be administered alongside standard drug treatments, aim to speed up pathogen elimination and reduce harmful side effects caused by inflammation.
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, and malaria, caused by parasites from the Plasmodium genus, are two of the major causes of death due to infectious diseases in the world. Both diseases are treatable with drugs that have microbicidal properties against each of the etiologic agents. However, problems related to treatment compliance by patients and emergence of drug resistant microorganisms have been a major problem for combating TB and malaria. This factor is further complicated by the absence of highly effective vaccines that can prevent the infection with either M. tuberculosis or Plasmodium. However, certain host biological processes have been found to play a role in the promotion of infection or in the pathogenesis of each disease. These processes can be targeted by host-directed therapies (HDTs), which can be administered in conjunction with the standard drug treatments for each pathogen, aiming to accelerate their elimination or to minimize detrimental side effects resulting from exacerbated inflammation. In this review we discuss potential new targets for the development of HDTs revealed by recent advances in the knowledge of host-pathogen interaction biology, and present an overview of strategies that have been tested in vivo, either in experimental models or in patients.

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