Trypanosomal infection

Probably also contributing to the lack of an acquired immunity is the fact that the antibody produced to trypanosome infection is chiefly IgM, which is known to have a relatively short half-life. 

Different parasites elicit different humoral and/or cellular immune responses. In malaria and trypanosome infections, antibody appears to play a... 

The major trypanosomes infecting domestic animals are Trypanosoma vizmx and T. congolense (cattle and horses), T. brucei and T. evansi (horses), and T. suis (pigs). All these parasites invade the blood cells in the early stage. Later the trypano-... 

The period of systematic development of arsenic drugs commenced at the end of the nineteenth century, and brought about some remarkable improvements in medicine. Arsenic compounds, administered as Fowler s solution (potassium arsenite), Donovan s solution (arsenic iodide) or de Valagin s solution (arsenic trichloride), were employed to treat rheumatism, arthritis, asthma, malaria, trypanosome infections, tuberculosis, and diabetes. N-Acetylar-sanilic acid (C8H10ASNO4), and primarily Sal-varsan (arsphenamine, C12H14AS2CI2N2O2) were discovered by Ehrlich in 1909, and remained in use to treat syphilis until the advent of antibiotics in the 1940s (Baumler... 

Because of it highly ionic nature, suramin will not cross the blood-brain barrier and, therefore, is ineffective for the treatment of trypanosomal infections that reach the CNS. In addition, suramin is tightly bound to serum albumin. Despite this binding, the drug is preferentially absorbed by trypanosomes through a receptor-mediated endocytosis of serum protein. Because the drug remains in the bloodstream for an extended period of time, suramin has value as a prophylactic drug. 

Table 6.2 Therapeutic interference Injections into trypanosome-infected mice...

Fig. 13.1 The parasiticidal effect in trypanosome-infected rats of (A) arsphenaniine ( Salvarsan ), (B) oxophenarsine ( Mapharside ), and (C) oxophenarsine plus reduced glutathione. (Redrawn from Voegtlin, 1925.)...

Most preparations of Au have no curative effect on trypanosome infections of mice, but when the infected mice are given the Au compounds either before or during the injection of arsenicals the activity of the latter is markedly increased. That the seat of action of the Au compounds is probably the trypanosomes is indicated by the fact that normal mice... 

It is of interest to mention briefly a rational explanation for the mechanism of action of the arsenicals used in the treatment of trypanosome infections. Chemically three types of arsenicals are employed the trivalent, pentavalent, and arsenobenzene. In general the trivalent arsenicals are effective both in vitro and in vivo, whereas the pentavalent and arsenobenzene types are effective only imder in vivo conditions. It is known that the host reduces the pentavalent arsenicals to the trivalent state and that the arsenobenzenes are oxidized by the trypanosomes to the trivalent state before they become effective. Furthermore, there is substantial evidence to indicate that the trypanosomes have a remarkable affinity for these arsenicals, the fixation taking place in the matter of only a few minutes. In its initial stages the parasiticidal reaction is a reversible process, but in the later stages it passes into an irreversible phase, probably owing to secondary biochemical reactions. 

Leishmaniasis. This important human parasite has the widest distribution of the trypanosomal infections, affecting an estimated 10 million people. Its many forms and varied clinical picture make it difficult to characterize. Visceral forms mimic malaria symptoms (i.e. enlarged liver and spleen) and can be highly fatal. Large outbreaks have occurred in recent years, especially in northern and eastern Africa, central Asia and Brazil. Sand fly vectors are difficult to control and no serious vector control campaigns have been mounted as a way of managing this still emerging parasitic disease. 

N. K. Parnell, L. Gupthill and L Solaano-Gallego, Use in small animal trypanosome infections, in Handbook of Small Animal Practice, ed. R. V. Morgan, 5th ed., Saunders, London, 2008, pp. 1132-1146. 

Ehrlich s first chemotherapeutic experiments were performed with dyes. Three series gave good results in the chemotherapy of trypanosomiasis in the mouse, namely the acridines, the triphenylmethanes, and the azo dyes, but none was outstanding. True, in 1904 Ehrlich cured trypanosome-infected mice with trypan red (a polyazo dye), which thereby became the first man-made chemotherapeutic agent. This aroused interest, but unfortunately the drug was inactive in man, and his thoughts turned to organic arsenical compounds. 

THERAPEUTIC INTERFERENCE INJECTIONS INTO TRYPANOSOME-INFECTED MICE... 

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