Malaria case study

Mavandadi, S., Dimitrov, S., Feng, S., Yu, F., Sikora, U., Yaglidere, O., Padmanabhan, S., Nielsen, K., Ozcan, A., 2012. Distributed medical image analysis and diagnosis through crowd-sourced games a malaria case study. PLoS One 7, e37245. http //dx.doi.org/10.1371/ joumal.pone.0037245. 

In the first model, we sought to reveal subgraphs of a biological interaction network that show substantial adaptations when cells transcriptionally respond to a changing environment or treatment. As a case study, we investigated the response of the malaria parasite Plasmodium falciparum to chloroquine and tetracycline treatments. 

Guaianohdes have also been intensively examined toward protozoa like members of the genera Trypanosoma (sleeping sickness), Leishmania (leishmaniasis), and Plasmodium (malaria) only studies that also tested cytotoxic activity are considered here. In all cases, an antiprotozoal activity correlates positively with cytotoxicity, and the major determinants for activity are a,p-unsaturated carbonyl residues. Certain compounds are considerably more toxic against protozoa than against mammalian cells and vice versa. A comparative QSAR analysis has been undertaken, and both activities were found to depend mainly on the same structural elements and molecular properties. The observed variance in the biological data can maybe be explained by the positioning of the various molecules in the active site [63-65]. 

Within the malaria field, as mentioned, a few projects have delivered hits through target-based approaches (e.g., Pf (P. falciparum) DHODH). The DHODH project team, led by Prof. Margaret Phillips from the University of Texas South Western, ran a HTS of a compound collection against jy DHODH. They isolated several series of which one, a triazolopyrimidine, was selected for follow-up. This ultimately led to delivery of a preclinical candidate that, in 2014, delivered a positive proof of principle in a human challenge trial. This will be documented later as a specific case study. 

The inadequacy or nonexistence of health tools to combat tropical diseases is a key factor preventing effective control efforts. This was not always the case. During the first part of the twentieth century, tropical diseases were a concern of European colonial administrators because of their impact on territorial expansion diseases such as river blindness, sleeping sickness, and malaria incapacitated workers and limited exploitation of natural resources. This led to the establishment of the study of tropical medicine and the development of the European drug industry. But, as western interests withdrew, so did concern for tropical disease control (Janssens, Kivits, and Vuylsteke 1992). 

Clinical signs and symptoms of hypoglycemia are reported occasionally most cases are subclinical, but severe cases have been described (SEDA-13, 815). A study of the effect of quinidine on glucose homeostasis in Thai patients with malaria showed a near doubling of plasma insulin concentrations and a corresponding fall in serum glucose concentrations. An additional factor may have been impaired nutritional status and the effects of parenteral quinine in severely ill patients not taking food (SEDA-13, 815 SEDA-14, 240 SEDA-18, 288). 

Amopyroquine is a 4-aminoquinoline, structurally related to amodiaquine. It is not a new compound, but it is of renewed interest as a result of the extensive occurrence of resistance to chloroquine and the adverse effects of prophylactic amodiaquine. In a study in 152 patients with malaria, the efficacy of a 12 mg/kg, given as two intramuscular injections of 6 mg/kg 24 hours apart, was described as good (1). AU the patients became apyrexial and there was clearance of parasites on day 7 in 143 cases the nine who retained a low level of parasitemia were all children. In 50% of the cases, the parasite had been chloroquine-resistant. The drug was well tolerated, and there were no major adverse effects. 

In an open, uncontrolled study, fosmidomycin was administered for 3-5 days (1.2 g every 8 hours) to 27 adults with malaria, of whom 16 reported possibly drug-related adverse events (1). The most frequent adverse events were headache, weakness, myalgia, abdominal pain, and loose stools. There were two cases of raised alanine transaminase activity. 

Single-dose pyrimethamine + sulfadoxine (25 mg/kg n = 54) has been compared with mefloquine (15 mg/kg n = 48) in the treatment of uncomplicated P. falciparum malaria in an unblinded, randomized study in 102 Malawi children (10). Immediate vomiting was more common in those who took mefloquine (eight cases) than in those who took pyrimethamine + sulfadoxine (one case), with comparable parasite failure rates at 14 days (20 and 22% respectively). 

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