Thursday , October 6 2022

Why is malaria repeated? How are you filling the puzzle pieces slowly?


Why is malaria repeated? How are you filling the puzzle pieces slowly?

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Some people suffer from repeated malaria attacks. These may take weeks or months after contracting the disease. The phenomenon is too familiar for those bitten by mosquitoes that carry the type of malaria known as Plasmodium vivax. While the malaria agent in Africa is mainly Plasmodium falciparum, P. vivax is the most widespread of more than half a dozen species of malaria parasites that infect humans globally.

An unresolved problem is that people experience recurrent malaria of P. vivax despite having received treatment for the disease. There is still no absolute clarity about where – in which organs and tissues – the parasites that are responsible for persisting infections are hidden. Because we do not know this, we can not determine how to kill them. Without filling in these blank spaces, we can not achieve the goal of eradicating malaria parasites around the world.

During the last four decades, I've been considering intermittently what causes malaria to be repeated long after people have been infected by P. vivax and has made important conceptual advances. These, together with subsequent research from other scientists, have greatly improved our understanding of why malaria is being resorted to.

The latest breakthrough has been the definitive acceptance of the theory I proposed seven years ago. That is, the parasite is multiplied – not detected – in more organs and tissues of the body than only the liver and bloodstream (which is a conventional dogma).

One of the results of this new conclusion is the growing awareness that drugs could not eliminate malaria parasites with the same efficacy in all parts of the body they inhabit. This is a possible explanation (there are others too) why malaria may appear despite treatment.

We do not have all the answers yet. But new important ideas arise that have important implications for the treatment of malaria and, finally, their eradication.

The journey of discovery

For a long time, it has been assumed that there is only one source of malaria recurrence, that is, a sleepy liver stage of the P. vivax parasite called "hypnozoite." This term, which I invented 41 years ago, is derived from the Greek words Hipnos (dream) and Zoon (animals). Therefore, a "sleepy animal".

When a hypnozoic wakes up, it multiplies to the hepatic cell in which it lives, resulting in the formation of a large number of descendants, called merozoites. After leaving the hepatic cell, they invade red blood cells and they reproduce within them. When these cells explode, they release merozoites that then enter other red blood cells, in which the cycle repeats itself.

It is about the continued proliferation of merozootic stage parasites in the bloodstream that lead to a recurrent outbreak of symptomatic disease.

Until now, liver cells – and especially blood vessels – are generally considered the only human habitats in which malaria parasites live and multiply.

But biomedical knowledge has changed. Now it becomes clearer that recurrences are caused not only by merozoites inside the blood vessels but also by merozoites outside the blood vessels.

Seven years ago, I pointed out for the first time (based on some complicated initial tests) that P. vivax recurrences can also be explained if there is a reservoir of merozoitics out of the bloodstream.

The concept is simply that the non-sanguinary origin of P. vivax malaria recurrences can be both the merozoites that occur outside the blood vessels and hypnozoitic ones in the liver (not just hipnozoitic).

More recently, I discovered at the University of Witwatersrand that the bone marrow probably serves as a reservoir of merozoites for the P. vivax parasite. Other researchers had already suggested the possibility.

In addition, I have repeatedly rationalized that the same could be applied to the spleen, and perhaps also in other places. This was achieved by uniting the points (in other words, theoretically), partly through the analysis of the published literature, some of them relatively dark.

A change of paradigm

This improved understanding is an important development and has implications both for the treatment of malaria and for the elimination of parasites of malaria in human populations. This is because there are indications that a drug that kills merozoitics in one place in the body will not necessarily kill all the merozoites that occur elsewhere.

Therefore, not only the patient can not cure, but parasites can periodically enter the bloodstream and be eaten by mosquitoes when they are feeding. This can cause a further transmission of malaria when infected mosquitoes bite other people.

But scientific dogma is often firmly rooted. It took until last year the idea that there is a dual origin of non-sanguineal parasites in the recurrences of P. vivax (both merozoitics outside the bloodstream and hypnozoites) to obtain acceptance.

Disbelief – in addition to a certain demonization in the knee reactions to my nonconventional visions – is progressively metamorphosis. This is mainly due to new research at Harvard University, the University of Glasgow and elsewhere. Studies have yielded results that can be provided as additional support for my seven-year concept.

As a result, there is a dramatic and welcome change in attitude. Malwarists begin to reiterate my concept and repeat supporting evidence for this I have discovered and included in bits and pieces in my publications in recent years, as well as in international conferences.

That follows

More research is done to get an even deeper understanding of the malaria recurrence process. It is a question of studying parasites in cell culture, laboratory mice and non-human primates, using sophisticated images and other avant-garde techniques. In association with this work, they are conducting drug-related research to find out how best to treat patients with P. vivax malaria.

Kill the parasite of malaria with baculovirus in the liver: a drug discovery approach

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Why is malaria repeated? As they are filling the pieces of the puzzle (2019, January 14)
recovered on January 14, 2019

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