Shadow Disease chronic active Toxoplasmosis (eBook)

5. Toxoplasma gondii – a master of disguise

Toxoplasma gondii is a single-celled parasite and only slightly bigger than bacteria. Several hundred of it fit inside single muscle cells or neurons, and there are almost no restrictions for them. As far as known, it can infect all warm-blooded creatures, and Toxoplasma have even been found in fishes and sea mammals. According to recent knowledge, about 30%-60% of the world’s population carry Toxoplasma gondii (64). This is about 2 to 4 billion people, but even in 2019, 110 years after the discovery of Toxoplasma, the effects and consequences of this infestation have not fully been understood.

In comparison, “only” little more than 1 billion people worldwide are infected with malaria, a related parasitic tropical disease (Bundesgesundheitsblatt 2008 / 51: 236-249). Malaria relies on the Anopheles mosquito as “key factor” and is therefore restricted more to the tropics and sub-tropics. By using cats as a means of reproduction and distribution, Toxoplasma gondii is less climate-sensitive, and toxoplasma are found all over the world. From this point of view, Toxoplasma gondii is even “more successful” than malaria.

Today we are looking back on 110 years of research on toxoplasmosis, which have given us thorough and detailed insights. Those doctors and scientists who have gifted us with this recent standard of knowledge deserve our thanks and respect. However, toxoplasma are masters of disguise and have been blinding doctors and researchers about their dangerous potential by means of their sophisticated mechanisms of camouflage and deception until today. Findings, which could correct this, have been known for some years, but have hardly affected the field outside a small group of scientists.

We now have to amalgamate this knowledge urgently and make use of it for the benefit of our patients, because Toxoplasma activity results in many more cases than we have assumed (31) see also p. →.

The reproduction of Toxoplasma gondii works like this. Toxoplasma survive the passage through stomach and gut in oocysts (eggs) or also in bradyzoites (in infected meat). Inside the host, they quickly transform into “tachyzoites”. This initially occurring, “fast” form of Toxoplasma can trigger severe, acute pictures of disease and have thus been the focus of research for many years.

They can move very effectively and are able to invade quickly, within a few seconds, nearly any cell. There they create temporary caverns (pseudocysts) and reproduce with a specific type of cell-division until they number several hundred per cell. These cells burst and release new tachyzoites. Speed is absolutely of the essence then, since the host's immune system has already identified the attacker and starts to produce antibodies in great quantities. These antibodies are specifically tailored towards attacking viruses, bacteria or parasites, and are destined to dock with their surface structures and thus mark them as prey for huge white immune cells, called “macrophages”.

The available antibody tests only record those antibodies specific to tachyzoites.

A first catch is that research findings as early as 1964 presented at the First International Congress for Parasitology showed that not all laboratory animals infected with Toxoplasma developed detectable antibodies (48), and this was confirmed later (24, 53).

It is still unknown today how many people do not develop detectable antibodies after an infection with Toxoplasma. A test for antibodies in these people would not show the presence of Toxoplasma.

Our immune system´s preparations for defence take about one week and during that time Toxoplasma reproduces and try to spread as far as possible. The parasite prefers neural and muscular tissue, but can also invade other organs. Apart from solid bones there is nothing that they cannot reach.

So, the week is over ….and now they will be taken under fire, right…?

No, not really, since it has been common knowledge since 1976 that the antibodies we produce, offer only very little protection against Toxoplasma (32). The reason why this is the case was found a lot later. It had been known that Toxoplasma change into a different form, bradyzoites, due to the immune system´s increasing pressure. But it was only discovered in 1996 that in doing so they change the surface structure of their outer membrane to a great extent (76, 77). This is a brilliant biological camouflage, which gives toxoplasma a crucial advantage, because it is highly probable that antibodies cannot dock to the bradyzoites due to this structural change.

To make sure that Toxoplasma, now in the form of bradyzoites, is really safe from the immune system and that this won't start a production of bradyzoite specific antibodies, the parasites now invade the host cell deeply.

They take over parts of the “interior” of their host cells, from which they create solid, durable cysts. These cysts will be their home for many years to come. Here, they are protected and can power down their metabolism. In this form, they induce nearly no bradyzoite specific antibody production (95), so their hiding place is very effective.

The lab tests currently in use do not detect bradyzoites themselves or bradyzoite antibodies.

On the other hand, bradyzoites can still reproduce, especially if the host´s immune system is not attentive enough, weakened (6, 42) or over-burdened by other disease factors. It has been known for a long time that inside these cysts, Toxoplasma can survive and remain infectious within a host for a lifetime, but it was assumed that in this form they would be “passive” and “inactive” and thus no threat to the host-organism.

However, it is now known that even after their transformation from tachyzoites to bradyzoites, Toxoplasma are significantly more active than assumed earlier. First hints reach back to 1989 (26). In 2008 an extensive study was published which focused on the long-term effect of an active toxoplasmosis (42). In neuronal tissue of infected mice there were found signs of inflammation, structural damage of the tissue and a lot of bradyzoite cysts, which together resulted in a seriously impaired health and altered behaviour of the mice.

The researchers could also show that bradyzoites are able to evoke this disease on their own, without the “support” of tachyzoites.

It is also known that bradyzoite - activity as well as tachyzoite - activity can induce increased cytokines in atrocytes and microglial cells (specialized immune cells of the brain (27)), and cytokines are known to induce inflammation and depression (see literature reference on page →). In 2015 another proof of activity of bradyzoites was found by a team of researchers at the University of Kentucky (84). Researchers could establish in animal testing that new bradyzoite cysts can be formed in the course of a chronic toxoplasmosis and concluded that bradyzoites can cause chronic diseases. Particularly cells of the muscular and nerve tissue can be filled with several hundreds of bradyzoites after a number of years.

All this considered, bradyzoites are surely not “harmless”.

The antibodies, which are produced by our immune system with great effort are tailored exclusively to the “fast” form of Toxoplasma, the tachyzoites, and are only effective against them. They cannot reach the “slow” types, i.e. the bradyzoites in their cysts, and they most likely couldn´t “dock” to them anyhow, because of their changed surface structure.

After their change to bradyzoites, Toxoplasma can therefore only be kept in check by our immune system with great difficulty. At that point, the Toxoplasma have retreated effectively and the immune system’s hunt is temporarily ended. But in the form of bradyzoites, Toxoplasma have by no means entered a “cul-de-sac”, as medicine has assumed for many years, because this life form only represents a clever change in tactics – and they are also not inactive, but rather hustle along the progression of the disease.

The knowledge that bradyzoites can be very active and a threat to health (26, 42, 84) has unfortunately not been adapted from scientific research to clinical medicine. Here, standard thinking still persists that bradyzoites are “harmless” and that our laboratory findings represent the disease process correctly.

According to basic research both assumptions are outdated, but they persist, and the result is that Toxoplasma related diseases are being excluded from diagnosis when lab tests show negative results. The ingenuity of Toxoplasma goes even further. They possess astounding skills, which help them to overcome another line of defence of our immune system, as will be described in the following. Our immune system does not master Toxoplasma. It can at best achieve a stalemate.

It has been known since 1989 that Bradyzoites can re-transform to their attacking form, i.e. the fast tachyzoites (26). Both shapes live together in the cysts, but under pressure of a healthy immune system there is a clear weighting towards bradyzoites. Several studies (6, 35, 78, 79) have proven that continuous activity of certain white blood cells is necessary to prevent Toxoplasma from becoming more active and to prevent them to break free from their cysts.

To achieve this, the white blood cells,...