Agents for the therapy and prevention of malaria

Abstract

The invention relates to galactose-containing agents for the prophylaxis and / or alleviation and / or healing of infections with sporozoa of the genus Plasmodium and malaria disease caused thereby in a patient or potential patient.

Description

[0001] Funding for the treatment and prevention of malaria

[0002] Description

[0003] The invention relates to agents for the therapeutic treatment of infections with sporozoa of the genus Plasmodium and the resulting malaria disease in a patient or potential patient.

[0004] Malaria is one of the world's deadliest infectious diseases. According to WHO estimates, in 2021, almost half of the world's population was at risk from malaria, and more than 0.6 million deaths were attributed to malaria. Malaria is caused by parasites of the genus Plasmodium. The two species Plasmodium falciparum and Plasmodium vivax cause most malaria cases in humans. Children under 5 years of age and pregnant women in sub-Saharan Africa are most commonly affected. Every two minutes, a child dies from the effects of malaria. Rapid diagnostic tests and improved prevention through drug prophylaxis had led to a decline in the number of malaria cases starting in 2010. A number of factors have now brought this positive trend of declining case numbers to a halt. A key reason for this is the increasing resistance of Plasmodium to drugs that were previously very effective.Combination therapy with the active ingredient artemisinin is an essential pillar of therapy, especially in severe cases. However, resistance to artemisinin combination therapies is increasingly being identified, and in these cases, no effective treatment options are available for affected malaria patients.

[0005] The increasing global spread of resistance to malaria drugs is hampering the rapid and effective treatment of malaria. Furthermore, climate change could lead to the expansion of malaria-affected areas. The invasion of the Anopheles stephensi mosquito, which can adapt very easily to urban environmental conditions, into previously unaffected or largely unaffected regions poses a major risk. A new anti-malaria drug would be extremely important, but it would also be like looking for a needle in a haystack.

[0006] The current state of drug treatment for malaria is sobering and very worrying, because resistance has now developed against virtually all malaria drugs and there is still no vaccine available that provides satisfactory protection against malaria.

[0007] There is therefore an urgent need to establish new means of combating malaria. Of particular importance are agents with novel mechanisms of action.

[0008] Plasmodium falciparum transketolase (Pffk) plays a crucial role in the proliferation and survival of the parasite. For this reason, and because the amino acid sequence of Plasmodium falciparum transketolase differs significantly from that of human transketolase, Pffk was considered a suitable target in the early 2000s for the development and establishment of inhibitors that specifically inhibit Pffk but not human transketolase. The latter was a mandatory feature of the sought-after inhibitors because human transketolase plays a crucial role in the proliferation and survival of human cells and of humans as a whole, and is particularly crucial for the formation of new immune cells, which are important for the immunological control of Plasmodium.A suitable inhibitor must exclusively inhibit Plasmodium transketolase, but not human transketolase, so that humans do not suffer general disadvantages from the inhibition of their transketolase, and in particular from the inhibition of their immune system. To solve this problem, Joshi et al. expressed Pffk as a protein and studied it biochemically. Based on this, a structural model of Pffk was created and differences in its kinetic properties compared to human (i.e., the host) transketolase were demonstrated. This enabled the authors to significantly facilitate the design of new inhibitors with the potential of an antimalarial drug that only inhibits Plasmodium falciparum transketolase.

[0009] In the 2023 study by Kaushik et al., the focus of research was also on PfTk. This research group succeeded in producing PfTk as a recombinant protein. In their study, they investigated the antimalarial effect of extracts from the leaves of the plant Anacardium occidentale L., which are traditionally used to treat malaria, on the recombinant PfTk enzyme and on cultured P. falciparum blood-stage parasites. The extracts showed very pronounced inhibition of Plasmodium transketolase (75%) and outstanding inhibition of the growth of intraerythrocytic Plasmodium stages of over 99%. These results are strong evidence that inhibition of Plasmodium transketolase is a very promising approach for establishing a new antimalarial drug.

[0010] The specificity and selectivity of the inhibitor or active ingredient of a new anti-malaria drug is considered key to the success of the drug during drug development. This applies not only to Plasmodium transketolase or other thiamine-dependent enzymes, as it is practically a dogma in pharmaceutical development and medicine that the selectivity and specificity of the inhibition with respect to the pathogen is the decisive criterion for the success of a drug.

[0011] Lokki et al. (2011) report on several studies in Burkina Faso that have shown that Fulani people are less parasitized, have fewer clinical malaria episodes, and have higher levels of anti-malaria antibodies compared to the sympatric Mossi and Rimabe ethnic groups, despite similar Plasmodium transmission intensity. In Mali, the Fulani have a lower parasite density and are less affected by the disease than the sympatric Dogon. The more susceptible Dogon population appears to respond to infection with pronounced splenomegaly, whereas the Fulani have a chronically enlarged spleen, which already provides protection. Lokki et al. cite a publication on a study in Nigeria that described Fulani people deriving 28–29% of their total energy intake from dairy products, which would correspond to approximately 700 grams of milk per day.This amount of milk would likely cause lactose intolerance symptoms in adults with lactase nonpersistence, i.e., those who no longer have lactase. Therefore, it is assumed that in Mali, Fulani with lactase persistence genotypes consume more milk than those with nonpersistence genotypes. In discussing their study results, Lokki et al. point out that the possible protective role of milk consumption in malaria infections has been debated for more than half a century. They cite studies from the 1950s that showed that a cow's milk diet had a suppressive effect on malaria infections in rats, mice, and monkeys, and that this was suggested to be primarily caused by a deficiency of p-aminobenzoic acid (PABA), because milk contains very little PABA.Lokki et al. also point out that infants under six months of age are less likely to develop severe malaria than older children, which is primarily explained by maternal antibodies acquired through breastfeeding, but could also be due to a PABA deficiency, particularly in exclusively breastfed children. Finally, the authors state that the potential protective effect of abundant milk consumption against malaria infection could have several explanations: First, milk might provide a generally improved nutritional status because it is rich in energy, protein, and fatty acids. Second, milk consists of a variety of immunomodulatory components. Furthermore, a diet dominated by dairy products could trigger a relative PABA deficiency, which then leads to a limitation of Plasmodium replication and thus protects against malaria.

[0012] Recently, Tatsinkou et al. (2023) published a study investigating the prophylactic effect of the probiotic bacterium Latilactobacillus sakei on malaria and inflammation in mice infected with Plasmodium berghei. The probiotic bacterium was isolated from the traditional fermented milk of the Fulani people. The results of this study showed that Latilactobacillus sakei has a protective effect in mice infected with Plasmodium berghei. The authors point out that the use of probiotic bacteria as a dietary supplement is a potential treatment regimen for malaria control. They also mention that the immunoprotective effect of probiotic bacteria from fermented milk against early malaria infection in mice has been previously investigated.

[0013] CN 112870206B discloses the use of mannose in the manufacture of a medicament for preventing cerebral malaria. This patent describes the effect of mannose in preventing cerebral malaria in malaria-affected mice. It reveals that the use of a 20% mannose solution instead of drinking water resulted in lower mortality and a reduced incidence of cerebral malaria in the affected mice.

[0014] Lv et al. (2022) also describe that feeding D-mannose to Plasmodium berghei-infected mice resulted in reduced parasitemia without any apparent side effects. Studies on the use of mannose in a model of experimental cerebral malaria (ECM) in mice provided results suggesting that mannose inhibits Plasmodium infection by regulating several host immune responses.

[0015] The present invention is based on the object of providing a novel agent for the palliative and / or prophylactic treatment of malaria diseases that can be produced and stored without any special effort. One solution to this problem lies in the provision of galactose for use in the prophylaxis and / or alleviation and / or cure of malaria diseases resulting from infection with sporozoa of the genus Plasmodium, wherein the agent can be a pharmaceutical product and / or a dietary food and / or dietary supplement.

[0016] In other words, one solution to this problem consists in providing galactose as the active ingredient of a product (medicinal product and / or dietary food and / or food supplement) for use in the prophylaxis and / or alleviation and / or cure of malaria diseases resulting from infection with sporozoa of the genus Plasmodium.

[0017] The proportion of galactose in the total proportion of carbohydrates (i.e. carbohydrates including starch and sugar) in the product (of the product) is preferably at least 25% w / w. The product can therefore consist solely of galactose, and / or the active substance in the product can be exclusively galactose.

[0018] Galactose may be combined (in the product) with other sugars.

[0019] The product preferably also contains tagatose.

[0020] The agent preferably additionally contains medium-chain fatty acids (MCT), preferably C8 fatty acids.

[0021] The glycemic index of the product should be less than 25 (GI<25).

[0022] The agent according to the invention can be produced and stored without any particular effort. It is inexpensive compared to known medications and can therefore also be used by people with low incomes. This is particularly important because malaria is particularly prevalent in low-income regions. Furthermore, compared to existing malaria therapy and especially malaria prophylaxis, the present invention offers the significant advantage that the agent according to the invention can be used over a long period of time without significant side effects. This is particularly important for infants and children, who are particularly susceptible to side effects caused by medications.

[0023] For the therapeutic treatment of a patient suffering from malaria or plasmodia infestation, a treatment regimen is proposed which is characterized in that it provides for the administration of the agent in multiple doses (multiple doses), each single dose comprising 0.04 - 0.3 grams of galactose per 1 kg of the patient's body weight, and wherein the single doses are preferably administered daily and preferably 3 to 5 times a day (with an interval of several hours, in particular 2 to 5 hours, between two doses).

[0024] For the preventive treatment of a potential patient, i.e. a human at risk of plasmodia infection, a treatment regimen is proposed which is characterized in that it provides for the administration of the agent in multiple administrations (multiple administrations) of single doses, each single dose comprising 0.01 - 0.15 grams of galactose per 1 kg of human body weight, and wherein the single doses are preferably administered daily and preferably 3 to 5 times a day (with an interval of several hours, in particular 2 to 5 hours, between two doses).

[0025] The present invention is based on the following new and surprising findings of the inventor:

[0026] In their evolution, Plasmodia have developed a metabolic pathway independently of mammals that gives them enormous advantages in reproducing within the host. This evolution was also characterized by coevolution with the host, which has led to the metabolism of Plasmodium in humans being significantly different from that of Plasmodium in rodents. This difference was and is largely due to the different diets of humans (mixed diets) and rodents (high fiber content).

[0027] Plasmodium can multiply very rapidly in humans. This is especially true in the intraerythrocytic stage. Rapid multiplication requires an anabolic metabolism capable of rapidly generating large quantities of building blocks for new cell formation.

[0028] Intraerythrocytic proliferation of plasmodia is characterized by a plasmodia metabolism in which the production of ATP, the main energy carrier in cells, and the formation of building blocks for DNA and RNA synthesis, as well as lipid formation, occur comparatively little through the citric acid cycle and oxidative phosphorylation, but primarily through fermentation. In other words, intraerythrocytic plasmodia carry out a fermentation metabolism that requires the uptake of large amounts of glucose from the blood and in which, in addition to ribose and acetyl-CoA, lactic acid is also produced. In erythrocytes that harbor intracellular plasmodia, glucose uptake is 100 times higher than in non-infected erythrocytes.

[0029] Pyruvate dehydrogenase, normally present in mitochondria, is absent in the mitochondria of Plasmodium. Pyruvate dehydrogenase is present in the apicoplast of Plasmodium, which, like mitochondria, is the result of endosymbiosis with a previously free-living organism (in this case, an aegyptian organism). However, this enzyme is not used for the proliferation of Plasmodium in erythrocytes. The role of pyruvate dehydrogenase and its function of acetyl-CoA formation has been taken over by branched-chain amino acid ketodehydrogenase (BCKDE). This enzyme is normally involved in the breakdown of branched-chain amino acids and decarboxylates them like pyruvate dehydrogenase. With the help of BCKDE, the Plasmodium is able to convert glucose and thereby form acetyl-CoA.Acetyl-CoA is an essential building block for lipid synthesis, but also for amino acids and other important metabolites, and is therefore absolutely necessary for the formation of new plasmodia.

[0030] Ribose is also essential for the formation of new plasmodia in erythrocytes as an essential building block for DNA and RNA. Ribose is formed by transketolase, the key enzyme of pentose phosphate metabolism. Like amino acid ketodehydrogenase (BCKDE) and pyruvate dehydrogenase, transketolase belongs to the family of thiamine-dependent enzymes. Unlike these dehydrogenases, however, transketolase does not degrade sugar through decarboxylation; rather, transketolases transfer a C2 unit of sugar from one sugar to another in a two-substrate reaction. This allows them to convert sugars, for example and in particular the production of the pentasaccharide ribose from hexasaccharides such as glucose and fructose. The latter represent the majority of the sugars in the human diet.

[0031] Since the formation of acetyl-CoA and ribose in plasmodia is carried out by thiamine-dependent enzymes, inhibitory thiamine analogues such as oxythiamine (OT) or benfo-oxythiamine (B-OT) can be used to inhibit this building block production. However, the cells of the plasmodia host organism also require these building blocks and also use thiamine-dependent enzymes for their synthesis. Therefore, experts believe that inhibitory thiamine analogues such as OT or B-OT are not suitable for inhibiting plasmodia proliferation in humans. Instead, researchers are trying to establish inhibitors that specifically inhibit the thiamine-dependent enzymes of plasmodia, but not, or only to a limited extent, the thiamine-dependent enzymes of humans. The specificity and selectivity of the inhibitors with regard to the plasmodia is considered to be the decisive criterion for the success of a drug and the key to the success of malaria therapy.

[0032] However, this ignores the fact that the selectivity and specificity of a therapy are determined not only by the selective and specific inhibition of a pathogen's target molecule, but also by the relationship between the pathogen's dependence on the process to be inhibited and the human's dependence on the process to be inhibited. The robustness and resulting resilience of the human organism, which means it can temporarily carry out certain processes only to a reduced extent, was a crucial factor in human survival and played an important role in evolution. In contrast to today, the food supply was very vulnerable in the past. Among hunter-gatherers, the dependence was very high. This was greatly reduced by agriculture because it became possible to grow sugar-rich foods such as grains and store them in dry conditions, thus ensuring a secure food supply.Even today, the human organism still carries within it the ancient survival programs from our hunter-gatherer times, which allow it to compensate for the lack of food over a certain period of time by switching its metabolism to what is known as ketogenic metabolism. The name is based on the formation of ketone bodies, which make it possible to replace some of the glucose needed in the brain with ketone bodies. Furthermore, ketone bodies also influence the psyche, enabling people to continue thinking positively and actively seek food despite fears of starvation. This ancient emergency program gives humans a resilience that plasmodia lack.

[0033] Plasmodia relies on a strategy for their intracellular proliferation in erythrocytes that relies on the availability of large amounts of glucose in the blood, which they require for their fermentation metabolism and the formation of the building blocks acetyl-CoA and ribose in order to proliferate rapidly. This is also evident in the extremely increased glucose uptake of erythrocytes that harbor plasmodia intracellularly. This is approximately 100 times higher than in normal, non-plasmodia-infected erythrocytes. These extreme differences between the metabolism of plasmodia and the metabolism of their human host cells with regard to the required amounts of glucose lead to a therapeutic approach based on the following findings and considerations:

[0034] Human cells can tolerate a severe restriction of glucose availability very well by switching to a ketogenic metabolism, in which ketone bodies and fatty acids released from fat deposits are broken down through oxidative phosphorylation in order to release energy for survival.

[0035] Intraerythrocytic plasmodia do not have this option, as they do not utilize the citric acid cycle and oxidative phosphorylation, but instead rely on glucose fermentation. This results in the extremely strong dependence of intraerythrocytic plasmodia on glucose.

[0036] In contrast, humans, as host organisms, have the ability to consciously and deliberately switch from glucose-based metabolism to a ketogenic metabolism by utilizing oxidative phosphorylation via the mitochondria. This flexibility in the metabolism of humans (as well as other mammalian hosts of Plasmodium) opens up the possibility of selectively and specifically inhibiting the growth of intraerythrocytic Plasmodium by altering the composition of the diet. A transition of the human metabolism to a ketogenic metabolism can be achieved by drastically reducing carbohydrates and protein and drastically increasing the fat content in the daily diet. This can be promoted using medium-chain fatty acids, which are particularly effective at triggering ketogenic metabolism. The sugar galactose also inhibits glucose-based fermentation and promotes oxidative metabolism via the mitochondria.The sugar galactose can therefore be used to inhibit fermentation and greatly increase the proportion of oxidative phosphorylation, making the mitochondria the decisive pillar of energy release. In other words, the metabolic shift from fermentation to oxidative energy release by the mitochondria can be achieved through the intake of the sugar galactose. This metabolic shift can be further supported with a ketogenic diet according to the currently known forms of, and in particular with, medium-chain fatty acids. An advantageous embodiment of the agent according to the invention therefore contains medium-chain saturated fatty acids ("medium-chain triglycerides", MCT), in particular and preferably C8 fatty acids. In this context, medium-chain saturated fatty acids are saturated fatty acids with a chain length of C8 to C10.The resulting metabolic state in humans, with a focus on energy release through mitochondria, results in the limitation of the substrate glucose in the blood, which leads to the inhibition of growth and proliferation of intraerythrocytic plasmodia.

[0037] Against this background, the invention proposes, for the purpose of combating Plasmodium infections and malaria, that the daily diet include a galactose-containing product (which can also consist of galactose alone), either as an alternative or as a supplement to a ketogenic diet. The extent of ketogenic metabolism can thus be moderated with the use of galactose, so that the negative aspects of ketosis are minimized or even completely prevented.

[0038] Consuming galactose may seem counterintuitive at first glance, but the natural sugar galactose, which in the form of lactose makes up a significant portion of the sugar in breast milk, is unsuitable for fermentation for energy production due to its basic biochemical structure and the biochemical metabolic pathways of humans. To ferment galactose, the human metabolism must convert it into glucose, which requires energy in the form of 2 ATP. The same amount of ATP is subsequently released during fermentation.

[0039] This means a net energy gain of zero. Therefore, the human body has no way to extract energy from galactose through fermentation.

[0040] In humans, the consumption of galactose therefore causes it to be utilized through the only possible pathway for meaningful use, namely oxidative metabolism in the mitochondria. One consequence of this is that the mobilization and combustion of fats is stimulated, leading to a significant increase in oxidative phosphorylation and a concomitant significant increase in oxygen consumption. The effect of galactose on this process is so potent that simply consuming galactose during a meal leads to the mobilization and combustion of fat.

[0041] These connections also explain for the first time the inhibitory effect of milk and the galactose it contains on the growth of plasmodia in humans.

[0042] The well-known observation that large milk consumption can provide protection against malaria has not previously been viewed in connection with the galactose contained in milk. Just as in humans and their cells, the lactic acid bacteria that thrive in milk are unable to ferment galactose. This applies both to the homofermentative lactic acid bacteria, which break down glucose into two molecules of lactic acid, and to the heterofermentative lactic acid bacteria, which specialize in breaking down pentoses and converting them into lactic acid and acetyl-CoA with the help of thiamine-dependent phosphoketolase. Therefore, only half of the milk sugar contained in milk, i.e. lactose, is fermented by the fermentative lactic acid bacteria. Lactose (milk sugar) is a disaccharide (double sugar) made up of the two monosaccharides glucose and galactose, and quantitatively determines the carbohydrate content of milk.When lactose is broken down by lactic acid bacteria, the disaccharide is first split into the two monosaccharides glucose and galactose. Glucose is then fermented into lactic acid. The galactose cannot be utilized and is left over. As a result, fermented dairy products are rich in galactose and low in glucose.

[0043] Consumption of fermented milk products is therefore more effective in terms of plasmodia-inhibiting effects than unfermented milk, because the lactose or its glucose content contained in unfermented milk is available as a substrate for the fermentation metabolism of the plasmodia.

[0044] Galactose does not allow for any net energy gain (ie, no net ATP gain) via the plasmodia's fermentation metabolism and is therefore practically useless for the plasmodia's strategy of rapid growth via fermentation.

[0045] The human organism possesses the so-called Leloir pathway, through which it can convert galactose into glucose using energy and thus supply cells with glucose. Galactose is therefore a sugar that cannot be used by plasmodia for their fermentation metabolism and rapid growth. However, it enables the human organism. Important cells, such as nerve cells, can produce glucose from galactose, which they then metabolize via the pentose phosphate pathway, thus protecting the cell from cell death. The glucose produced in these important cells via Leloir metabolism is not available to the plasmodia and therefore does not promote their growth, but is available for important processes in humans, for example and particularly in the brain.

[0046] With the help of this glucose, programmed cell death in cells, especially nerve cells, can be prevented, so that galactose protects host cells without promoting the growth of plasmodia. Mannose also helps avoid the negative effects of a ketogenic diet, as mannose also inhibits fermentation, but mannose can be converted into fructose and glucose. Mannose is phosphorylated within a cell by hexokinase to mannose-6-phosphate, which prevents it from leaving the cell. If the cell does not need mannose-6-phosphate for the construction of glycoproteins, it can be converted into fructose-6-phosphate under the catalytic influence of the enzyme mannose-6-phosphate isomerase, which can be utilized by glycolysis.Compared to galactose, however, the consumption of mannose has the disadvantage that it is relatively frequently associated with intolerance symptoms, particularly digestive problems such as flatulence or diarrhea. Experience has shown that galactose is easily tolerated by the human body. One possible reason for this is that the human body, and in particular the human digestive system, is usually accustomed to lactose and thus galactose from birth through the diet of milk and dairy products. Mannose, on the other hand, occurs naturally primarily as a building block of numerous plant polysaccharides.

[0047] A key biochemical difference between galactose and fatty acids is that fatty acids cannot be converted into glucose, whereas galactose can be used to produce glucose. However, energy must be invested in this conversion process. The plasmodia's strategy of rapidly growing and evading the immune system of their human host is based on large amounts of glucose, which is then converted into the key building blocks acetyl-CoA and ribose, with another portion being excreted as lactic acid. Although galactose, like glucose, is a six-carbon sugar, its molecular structure makes it unsuitable for the metabolic pathways chosen by the plasmodia and therefore inhibits the metabolism of the intraerythrocytic plasmodia.

[0048] Due to the lack of understanding of the significance of these biochemical differences, no diets, dietary foods or food supplements have been developed to date that inhibit the growth of galactose-based Plasmodium.

[0049] Since many to most people in malaria areas are lactose intolerant, the use of lactose-containing milk is not useful or only makes limited sense there.

[0050] The galactose-based agent according to the invention, ie with a galactose content of at least 25% w / w based on the total carbohydrate content (ie the total carbohydrate content of the agent including starch and sugar), enables in principle all people, even those who are lactose intolerant, to protect themselves against malaria by consuming this agent as part of their diet.

[0051] In this way, they inhibit the fermentation metabolism of the Plasmodium and thus their proliferation in their bodies. By inhibiting the fermentation metabolism of the Plasmodium, the formation of lactic acid, the end product of this fermentation metabolism, is simultaneously inhibited. This counteracts the immunosuppression caused by the Plasmodium and triggered by lactic acid, and the immune system's attack on the Plasmodium is no longer inhibited. Furthermore, immunological response mechanisms are promoted that enable the formation of a protective immune response following future Plasmodium infections.

[0052] The agent according to the invention preferably contains other sugars that stabilize blood sugar and support ketogenic metabolism, particularly by promoting the formation of butyrate. One such sugar is, for example and in particular, tagatose. Intestinal bacteria use tagatose for energy production, thereby forming butyrate. Butyrate also has an inhibitory effect on the fermentation metabolism of plasmodia, since butyrate is a fatty acid and cannot be used for fermentation. Furthermore, tagatose, with the butyrate released from it, inhibits inflammation in the body and thus supports the human immune system.

[0053] These "other sugars" generally include, in particular, those that inhibit the fermentation metabolism of the Plasmodium and also the pentose phosphate pathway and thus the lactic acid formation of the Plasmodium, thus causing the positive effects on the human immune system described above with regard to the elimination of the Plasmodium.

[0054] The agent according to the invention may also contain sugars such as allulose and the sugar substitute erythritol (erythritol), which are practically not metabolised by the host organism (human organism) but are excreted, and which are also not used for the fermentation metabolism in the plasmodia and therefore do not promote their growth.

[0055] Stevia can be used to sweeten the product according to the invention, particularly in the form of a dietary food or dietary supplement. The product according to the invention preferably also contains an addition of medium-chain saturated fatty acids (MCTs), particularly C8 fatty acids, to promote a ketogenic metabolic state and stable blood sugar levels.

[0056] The intake or administration of the galactose-containing agent according to the invention can and should be combined with a ketogenic diet to keep the patient's blood glucose level as low and stable as possible. In addition, so-called exogenous ketones, which cannot be used by Plasmodium for fermentation, should and can be consumed.

[0057] For malaria prevention, the product according to the invention should be consumed daily. Furthermore, foods that have a low impact on blood sugar levels (low glycemic index) and a low glycemic load should be consumed.

[0058] Hospitalized malaria patients should never be treated with glucose-containing intravenous fluids, as is currently the case. The amount of vitamin B1 or thiamine administered to the patient should also be kept to a minimum to avoid triggering the activation of thiamine-dependent enzymes in the plasmodia.

[0059] The following are examples of embodiments of the agent according to the invention in the form of a beverage, a chocolate mass, a powder mixture for mixing a beverage and a sugar mixture:

[0060] Example 1: Drink with composition (I)

[0061] Ingredients per 1 liter:

[0062] 10 g galactose

[0063] 15 g tagatose

[0064] 15 g Erythritol -Stevia 400 (4 times sweeter than household sugar)

[0065] 20 ml glycerin

[0066] 15 ml gluconic acid (50%)

[0067] 20 g resistant dextrin

[0068] 3 ml cola base

[0069] 370 mg choline

[0070] 300 mg taurine

[0071] 3 g magnesium lactate 2-hydrate 6 g polyphenol mixture (green tea, grape, assai, rooibos, baobab pulp, goji extract) Drink with the composition (A)

[0072] Ingredients per 1 liter:

[0073] 19 g galactose

[0074] 6 g tagatose

[0075] 15 g Erythritol -Stevia 400 (4 times sweeter than household sugar)

[0076] 10 ml glycerin

[0077] 15 ml gluconic acid (50%)

[0078] 20 g resistant dextrin

[0079] 2 g MCT coated on gum arabic

[0080] 3 ml cola base

[0081] 3 g magnesium lactate dihydrate

[0082] 3 g polyphenol mixture (green tea, grape, assai, rooibos, baobab pulp, goji extract) Drink with the composition (B)

[0083] Ingredients per 1 liter: 100 g galactose

[0084] 13 g tagatose

[0085] 17 ml gluconic acid (50%)

[0086] 20 g resistant dextrin

[0087] 2 g MCT coated on gum arabic

[0088] 100 ml lemon flavor

[0089] 3 g magnesium lactate dihydrate

[0090] 5 ml citric acid Chocolate with the composition (A)

[0091] Ingredients per 100 grams:

[0092] 40.5 g cocoa mass Ecuador

[0093] 25 g tagatose

[0094] 18 g galactose

[0095] 12 g cocoa butter 4 g resistant starch 0.5 g soy lecithin Chocolate with the composition (B)

[0096] Ingredients per 100 grams: 38 g cocoa mass Ecuador

[0097] 14 g tagatose

[0098] 29.5 g galactose

[0099] 2 g MCT (C8) coated on gum arabic

[0100] 12 g cocoa butter

[0101] 4 g resistant starch

[0102] 0.5 g soy lecithin

[0103] Powder mixture (A) for mixing a beverage

[0104] Ingredients per 100 grams:

[0105] 24 g MCT fat coated on gum arabic

[0106] 11 g resistant dextrin

[0107] 13 g lupine flour (e.g. sweet lupine)

[0108] 19 g butter powder

[0109] 18 g cream powder

[0110] 6 g galactose

[0111] 2 g tagatose

[0112] 3 g Erythritol -Stevia 200 (twice as sweet as household sugar)

[0113] 0.93 g polyphenols (e.g. quercetin, resveratrol, ECGC from green tea)

[0114] 0.07 g vitamin E in the form of tocotrienols

[0115] 1 g calcium propionate

[0116] 2 g L-citrulline DL-malate

[0117] Sugar mixture (A), suitable for mixing or adding to other

[0118] Food

[0119] Ingredients per 100 grams:

[0120] 85 g galactose

[0121] 15 g Tagatose Cited non-patent literature:

[0122] Kaushik M, Hoti SL, Saxena JK, Hingamire T, Shanmugam D, Joshi RK, Metgud SC, Ungar B, Singh I, Hegde HV : Antimalarial Activity of Anacardium occidentale Leaf Extracts Against Plasmodium falciparum Transketolase (PfTK). Acta Parasitol. 2023 Dec; 68(4):832-841. doi: 10.1007 / sl 1686-023-00718-6. Epub 2023 Oct 13. PMID: 37831282.

[0123] Lokki A.I., Järvelä I., Israelsson E., Maiga B.; Troye-Blomberg M., Dolo, A., Doumbo O.K., Meri S., Holmber V.: Lactase persistence genotypes and malaria susceptibility in Fulani of Mali. Malaria Journal 2011 10:9; doi: 10.1186 / 1475-2875-10-9

[0124] Lv L., Xu Z., Zhao M., Gao J., Jiang R., Wang Q., Shi X. (2022): Mannose inhibits Plasmodium parasite growth and cerebral malaria development via regulation of host immune responses. In: Front. Immunol. 13:859228. doi: 10.3389 / fimmu.2022.859228

[0125] Tatsinkou L.L.T., Fossi B.T., Sotoing G.T., Mambou H.M.A.Y., Ivo P.E.A., Achidi E.A.: Prophylactic effects of probiotic bacterium Latilactobacillus sakei on haematological parameters and cytokine profile of mice infected with Plasmodium berghei ANKA during early malaria infection. Life Science 2023 Oct 15; 331 : 122056. doi: 10.1016 / j .lfs.2023.122056. Epub 2023 Aug 29. PMID: 37652156

Claims

Claims 1. Galactose for use in a method for the therapeutic treatment of infections with sporozoa of the genus Plasmodium and resulting malaria disease in a patient or potential patient.

2. Galactose according to claim 1, characterized in that it is used as a medicament.

3. Galactose according to claim 1, characterized in that it is used as a dietary food or food supplement.

4. Galactose according to one of claims 1 to 3, characterized in that it is used in combination with tagatose.

5. Galactose according to one of claims 1 to 4, characterized in that it is used in combination with allulose.

6. Galactose according to one of claims 1 to 5, characterized in that the application takes place in combination with medium-chain saturated fatty acids (MTC), in particular and preferably C8 fatty acids.

7. Galactose according to one of claims 2 to 6, characterized in that the proportion of galactose based on the total carbohydrate content of the agent is at least 25% w / w.

8. Galactose according to one of claims 2 to 7, characterized in that the agent has a total glycemic index of less than 25 (GI<25).

9. Galactose according to any one of claims 1 to 8, characterized in that the therapeutic treatment is carried out according to a treatment regimen which provides for the administration of multiple single doses, each single dose comprising 0.04 - 0.3 grams of galactose per 1 kg of body weight of the patient, and wherein the single doses are preferably administered daily and preferably 3 to 5 times a day (with an interval of several hours between two doses).

10. Galactose according to any one of claims 1 to 9, characterized in that the therapeutic treatment is a preventive treatment of a potential patient and is carried out according to a treatment scheme which is suitable for the administration provides for multiple administrations of single doses, each single dose comprising 0.01 - 0.15 grams of galactose per 1 kg of the patient's body weight, and wherein the single doses are preferably administered daily and preferably 3 to 5 times a day (with an interval of several hours between two doses).