DILEMMA
Dilemma
Referenced from Jade Jordan
Genetic resistance and antimalarial drug action against P. vivax and P. falciparum.
Malaria is a tropical disease that, without immediate treatment, can be fatal. More than 40% of the world living in malaria-risk areas with around 90% of all malaria cases reported in Sub-Saharan Africa followed by Southeast Asia and South America. There are five species of Plasmodia known to cause malaria in humans and of these, Plasmodium vivax and Plasmodium falciparum are the most common and the ones that will be discussed here.
P. vivax mostly affects populations outside of Africa especially in South America and Southeast Asia, where it is the most prevalent species of Plasmodia. Whilst this malarial parasite is the most widespread in the world, infection with the species rarely results in death. On the other hand, P. falciparum is the deadliest and most pathogenic of the five human malarial parasites, as it multiplies more rapidly in the blood than the other species. Also the parasite can cause small clots in blood vessels for example, cerebral malaria is when this occurs in the brain. P. falciparum is the most common parasite affecting sub-Saharan Africa and this is where it is mainly found.
As malaria is prevalent only in particular parts of the world, population genetics plays an important role in malarial resistance: these areas often have unique gene pools, consisting of sometimes unexpectedly high numbers of some genes. This is due to natural selection for some traits such as sickle cell and duffy negative blood cells due to their role in resistance to malaria. Still, there is a great need for the development of new drugs in the fight against malaria, as resistance has developed to many commonly used therapies. In order to this, we need to understand the structures and life cycles of the parasites in question as will be discussed in this essay.
Plasmodium Life Cycle
P. vivax and P. falciparum have more or less the same complex life cycle involving a human and mosquito vector. The parasites carry out the asexual stage of the life cycle in the human host and reproduces sexually in the mosquito.
The first stage in its life cycle is the exo-erythrocytic cycle. When a malaria-infected female Anopheles mosquito feeds on a human host’s blood, the parasite enters the host in its sporozoite form, via the saliva of the mosquito. Once in the bloodstream, the sporozoites travel to the liver where they infect hepatocytes. The sporozoites do this through the specific binding of their surface proteins and the basolateral domain of hepatocytes and it is this binding that initiates the invasion into the liver cells.
Once the sporozoites have invfected the liver, the parasite usually becomes a schizont. However, P. vivax can also become hyponozoites. When in the hypnozoite state, the infection lies dormant for a few months or even years before it re-enters the cycle to form schizonts and causes relapse in the patient. Schizonts contain thousands of merozoites and one it is mature, the vessel ruptures, releasing the merozoites and entering the erythrocytic cycle.
In this stage of the life cycle, these merozoites infect erythrocytes (red blood cells) in the bloodstream and form trophozoites. It is at this point where malaria can be first detected and diagnosed in a patient. Ring stage trophozites are those that use energy acquired from the red blood cell, to become schizonts and release more merozoites to spread the infection. Other trophozoites mature and differentiate into male and female micro- and macrogametocytes respectively. The gametocytes of P. vivax and P. falciparum vary slightly in structure as can be
seen in Figure 1. It is these gametocytes that re-enter the mosquito to commence the sexual stage of the parasite’s life cycle: the sporogonic cycle. During a blood meal, the mosquito ingests the gametocytes and they fuse to form zygotes in the mosquito’s stomach. The zygotes elongate and develop into motile ookinetes. These penetrate the wall of the mosquito’s midgut where they mature into oocysts ,which grow and rupture to release sporozoites. In the mosquito, sporozoites travel to the salivary glands where they remain until the mosquito feeds on another human host so the whole cycle can repeat.