Welcome to this lecture on Malaria. A few words: to some people Malaria is the most important disease in the tropics. To other people, HIV/AIDS is the most important disease in the world. For us parasitologists, we think malaria is important. More important, less important, these are relative terms, but malaria is certainly important, it kills mostly children under five years. Malaria is a disease, complex is long, so we have divided this presentation into three parts. Part one will deal with the parasites in the human blood. My name is Mramba Nyindo, my colleague is Jovin Kitau. We are at the Kilimanjaro Christian Medical University College in Moshi, Tanzania, welcome. Distribution of Malaria is almost all over, there are areas with very high prevalence, all in the here, on the African continent. Here, go to Bengal, India, there are areas where malaria is just kind of high. There are areas were malaria is more than that, there are areas where malaria is low, and there are areas where malaria does not occur at all, it's a wide distribution. The component of the life cycle of malaria parasites will be discussed now. The definitive host of malaria parasite is the mosquito, that is where syngamy occurs, it occurs in the mosquito. It is in the mosquito that has syngamy occurs to generate the gametocytes, there are three components of the life cycle here, sporogony, that means Gametogenesis in the mosquito, Merogony in the human blood, Schizogony in the human blood and Gametogony in the human blood, actually gametocytes arise in the affected human blood cells. What happens is that humans become infected with sporozoites that are injected by the female Anopheles mosquito. Where? Into the subcutaneous tissue or directly into the blood stream. These sporozoites will travel to the liver, Sporozoites may pass several hepatocytes before they are settled, and when they are settled they will invade and start to develop in the hepatocytes of the liver. Liver invasion co-receptors on sporozoites must be mentioned. There are two malaria parasite co-receptors we know, which facilitate invasion of sporozoites into the hepatocyte, there is thrombospondin domains on the circumsporozoite protein, this second one is thrombosporin-related adhesive protein trap. In the liver we have heparin sulphate proteoglycans, Hepatocytes and these are actually the concept as for what we've already mentioned. That these thrombospondin domains and the thrombosporin related adhesive protein, TRAP, where they on sprorozoites, will bind specifically to heparin sulphate proteoglycans on the hepatocytes, and when that happens, they are the sporozoite invasion of hepatocytes, inside hepatocytes, each sporozoite develops a schizont, and these schizont contains thousands of merozoites. These terminologies will come up very often so take note of them. Invasion of hepatocytes does not lead to disease, not only invasion but also settling there we don't, like malaria sporozoites for example may stay there for a very, very long time, even a year, but there is no disease, so liver infection per se does not constitute a disease situation. Exoerythrocytic development in the liver is the terminology given, Malaria parasite developed in the liver, or development in the liver, we call it exoerythrocytic schizogony, it is initiated by sporozoites which will become schizonts, we have already said that. Then there must be a progressive development to schizogony. Let's start with the infected hepatocytes will rupture, the schizont also rupture, it will release merozoites, these merozoites are released from the schizonts, the merozoites will invade red blood cell. Now, we are moving to red blood cells, we are now, forgetting about the liver, the parasites must vacate the hepatocytes and invade red blood cells, and here they will initiate today every erythrocytic cycle termed in the erythrocytic schizognony cycle. Let's look at merozoites, asexual stages, they will invade red blood cells when released from hepatocytes. What happens in the red blood cells? They develop to trophozoites, these are hair-like bodies, and you will see as we move on. In Plasmodium falciparum there may be one, two, or three trophozoites in one red blood cell, and I will show you that as we move on. Let's look at the development of trophozoites in the red blood. They will become schizonts, which rupture and release another set of merozoites which will then also invade red blood cells, therefore, the erythrocytic cycle is repeated in the course of malaria infection, and this repetition over time gives you the malaria fever. Let's look at the formation of the gametocytes. At a certain stage of malaria, parasites in the red blood cells trophozoites must arise, which will initiate gametocytes, because if gametocytes are not formed, there is no malaria transmission cycle because these are the ones, gametocytes, these are the ones which will grow for different stages in the mosquito vector. Here is a picture, the life cycle here is demonstrated, this is a probably a normal red blood cell, this is a this will, as I said earlier, there could be one or two, there are two in a red blood cell, these will grow, will grow, will grow, will grow, grow, and become shizonts. This is alistoid shizonts, and fully developed shizonts are here, what is in these shizonts? HLMN ozoids. These are gametocytes, which will arise from very early stage of the development. So you have, what I've drawn here, schizogony, merogony, schizogony cycle in the red blood cell, it is responsible for characteristic malaria disease, this is a situation which repeats itself, and it's very uncomfortable for people infected with malaria parasites, Schizogony, merogony, schizogony cycle. Erythrocytic merogony becomes synchronized in the early stages of malaria infection. Formation of merozoites is haphazard. Now, as the infection proceeds with the time, the formation of merozoites becomes highly synchronized, it happens at one point, yes? Sorry about these arrows, I think the computer didn't feel very comfortable to look at it, but what we are trying to is, this merogony becomes highly synchronized, if it is a three hour, or three day malaria cycle, four day, whatever, that is what is known as synchronization. Plasmodium vivax and the Plasmodium falciparum have a 48 hour development cycle in the red blood cell. To repeat ourselves, the erythrocytic cycle, will cause clinical disease manifestation this, it will be explained in detail by Doctor John Bartlett, he will talk about the disease. Each mature schizont, also called a rosette, will contain many merozoites, something up to 20 or more, synchronization of shizogony repeat myself is extremely important, so, it gives you high temperature, shivering and sweating, and equally, even when it is so hot, you feel cold and, look for a woolen blanket. I would like to end here, at this part of the malarial parasites in the human body, and we shall go back to later.
