Malaria, therapy

In an attempt to increase efficacy in therapy, the production of bivalent or multivalent species by linking subunits (non-covalently, covalently, or by disulfide bonds) has been proposed. For example, a bispecific single-chain antibody fragment has been investigated for malaria therapy. This is a combination of two scFv, one directed against the CD3 molecule on human T lymphocytes, and the other against an epitope of a surface protein of Plasmodium falciparum, the parasite which causes malaria [8]. 

Other somatic therapies were developed in the first half of the twentieth century, with variable results. Malaria therapy was conceived in 1917, insulin shock in 1927, psychosutgery in 1936, and electroconvulsive treatment (ECT) in 1938. All of these methods, as originally conceived, carried serious risks, and most demonstrated marginal effectiveness. Psychosurgeries were carried out by the thousands in the 1940s, resulting in rather effective behavioral control over agitated psychotic patients... 

The use of these artemisinin derivatives in combination with an antimalarial drug with a longer half-life, as recommended by WHO, can not only delay emergence of resistance but also partially overcome the problem of short plasma half-life [19]. Nevertheless, chemically and metabolically more stable artemisinins would bring improvement in malaria therapy and bitherapy (or combination therapy) [20],... 

I Early Nobel prizes awarded in the field of psychiatry (Wagner-Jauregg in 1927 for malaria therapy and Moniz in 1949 for the prefrontal leucotomy) have proven to be ineffective and abused respectively. 

Cinchona alkaloids have been used since the sixteenth century to treat malaria. It is well established that quinine, quinidine, cinchonidine, cinchonine, and their dihydro derivatives exhibit similar antimalarial activity (50, 51). Quinine owes its favored position in malaria therapy to its earlier isolation. Its use is becoming increasingly important in treating infections caused by strains of Plasmodium falciparum which are resistant to all other antimalarial drugs (52). However, some of the... 

Tetracyclines, like doxycycline, are broad-spectrum antibiotics with extended use as cheap and effective antibacterials. They act at the level of protein synthesis, and impair, in case of Plasmodium fakiparum, the formation of mero-zoites. Due to a slow onset of activity, doxycycline is used in combination with faster acting drugs for malaria therapy as a single compound it is today applied in prophylaxis, frequently in regions with known chloroquine resistance. 

Among four major Cinchona alkaloids, quinidine and cinchonine were most active in the malaria therapy followed by quinine and cinchonidine. For example, quinidine is two- to threefold more active than quinine in both chloroquine-sensitive and chloroquine-resistant strains of P. falciparum [224]. Due to its cardiac... 

Finally, the same approach has also been effective in malaria therapy (data not shown) indicative of the broad therapeutic potential of this macrolide conjugation strategy. Various anti-malarial drugs can be conjugated to the macrolide desosamine ring that in turn mediates their uptake into the parasite vacuole leading to improved overall efficacy in vivo. Examples using this approach include certain kinase inhibitors, and antimicrobial compounds as the small molecule payloads. 

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