Trypanosomiasis: General Treatment

There are several different treatment schemes that are determined by the vertical control programme that is or was in place in many areas. Anaemia and any other infections should be treated first. The specific therapy is not simple. Drugs that do not penetrate into the cerebrospinal fluid and the brain are useful in the early stage (prior to invasion of the central nervous system). Drugs that do penetrate the blood-brain barrier must be used in the late stage. A number of drugs were developed many years ago. There is an urgent need for better, cheap drugs. There is also a need for clinical studies to compare different therapeutic regimens.

In May 2001, the pharmaceutical company Aventis signed an agreement with WHO to guarantee a gratis production of pentamidine, melarsoprol and eflornitine for at least 5 years. Médecins Sans Frontières (MSF) would be responsible for the logistical part of storage and transport of the drugs. Shortly afterwards, Bayer joined this partnership, providing suramin and reconsidering a decision to halt production of nifurtimox.

The blood-brain barrier is the boundary formed by the continuous “tight junctions” between the endothelial cells of the brain capillaries. There is a basal membrane between endothelial and neighbouring cells. Pericapillary astrocytes surround the whole complex. This barrier restricts the migration of polar substances from the blood to the brain. The barrier is important for maintaining the composition of the fluid surrounding the brain. There are special transport systems that allow certain aminoacids, glucose and specific macromolecules to enter the brain. In addition there is also passive diffusion of lipophilic low molecular weight substances. This high degree of access control provides substantial protection for the brain, but also has implications for drugs. However, the blood-brain barrier is not inert. Although fenestrated capillaries in the choroid plexus allow a more direct exchange between blood and cerebrospinal fluid, their area occupies only 1/5000th of the total exchange surface. There are also a few other small regions of the brain where there is no barrier, namely the area postrema, organum vasculosum of the lamina terminalis, the subfornical and subcommisural organs, the eminentia mediana of the hypothalamus and the neurohypophysis.

Category: Medicine Notes