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01Viral diseases are treated as bacterial diseases
Grass carp before the size of 750 g/tail is prone to hemorrhagic diseases caused by reovirus. It is characterized by four major characteristics: one is the redness of the dots on the palate of the oral cavity, the fins and gills; the second is muscle redness or punctate bleeding; the third is intestinal redness, or a bit of bleeding spots; the fourth is the redness of the fish swim bladder, or punctate bleeding.
When the above three characteristics are present, it is basically possible to highly suspect that it is a viral disease, and the treatment of drugs requires the use of drugs according to viral diseases. For example, instead of using harsh disinfectants, use mild sterilized iodine preparations. The second is to avoid the use of pesticides and irritating disinfectants through environmental improvement. At the same time, antiviral drugs are added to the feed, such as platen root plus a large dose of vitamin C, commercially available commodities such as five yellow essence, antiviral liquid and drugs that promote metabolism, etc., as a therapeutic drug in the early stage, and the use of immunoglycans plus fish intestine kang for a long time in the later stage is used for a complete cure.
It is worth emphasizing that once some people see a little yellow mucus in the intestines of grass carp, they immediately exclude the virus, in fact, this needs comprehensive analysis, and practice is the best way to test whether it is right or wrong. Another example is the herpes of carp, which is also a big mistake when many people see that the gill filament has ulceration and inflammation, and they are diagnosed as bacterial gills. For example, even if parasites are found on the gills of these fish, they can still not be used externally to kill insects.
Empirical judgment methods for viral diseases
We are all well aware that bacterial diseases are not a big problem when treated as viral diseases; but conversely, viral diseases, treated as bacterial diseases, may sometimes die more.
When diagnosing in the field, how to make a quick judgment becomes crucial. As we all know, once the fish become ill, farmers face losses every day, and they will not give us enough time to do PCR first, and then prescribe it after the results come out. At that time, even if the diagnosis is a virus, a few days have passed, and the fish may be dead for the most part, so the actual practice is still empirical judgment.
How is the diagnosis made?
Option 1: See if only one fish dies
For example, herpes virus disease of carp and crucian carp, the same pond fish, although there are grass carp, crucian carp, carp or silver carp at the same time, but only dead carp, or crucian carp. Sometimes there are more special, the same crucian carp, and only one species of crucian carp is dead, while other species of crucian carp are fine.
Option two Another factor in the outbreak of viral STDs in water temperature
For example, herpesvirus disease only occurs in the range of 13-29 degrees Celsius, and once it exceeds this water temperature range, it is rarely or non-pathogenic. Another example is The Lichun virus disease, which only occurs when the temperature is relatively low at the beginning of the year.
Option three, that is, the size of the fingerlings
As mentioned earlier, the type of fish is helpful in judging whether it is a viral disease, but the size of the fish can also be used to determine whether it is a viral disease, such as the reoccupational disease of grass carp, which occurs in grass carp with a size of less than 750 grams, which is prone to viral diseases, and beyond this weight, it is only the onset of the disease, and its impact is also very small.
In addition to the three items listed above that can help judge, specific to a certain kind of fish, there are actually specific ways to judge.
Still taking grass carp as an example, when reovirus occurs in the past, it has three major characteristics: one is redfin red gill cover, the other is red muscle type, and the third is intestinal bleeding type. Later, I found out in actual combat that in fact, many water bodies, fish maws are a bit congested, which can also be used as the basis for viral diseases.
Another example is the gill bleeding of crucian carp, which is the phenomenon of bleeding after one or two gills. There is also a herpes virus like carp, the eyes will be sunken, the upper edge of the mouth is uneven, and the gills are purple and swollen. They can all be used as a basis for judgment, and when these symptoms are more numerous, the easier it is to judge accurately.
Finally, the treatment of viral diseases can be released with five yellow essences plus compound iodine, mixed together and spilled. For internal use, you can use a viral buster, add immunogly polysaccharides and vitamin C sodium powder, and take it internally for four to five days.
02 There is no symptomatic treatment for fungal diseases
Fungal diseases, unlike bacterial diseases, are stubborn, like our athlete's foot, tend to have long treatment cycles and are also useful for specialized medications.
The root cause is that once the fish body is infected with fungi, when we find the outer hyphae on the surface of the body, in fact, the internal hyphae in the body have grown very long, and the condition is already very serious. Therefore, it increases the difficulty of treatment, especially difficult, a lot of fish infected with fungi, often face gill filament swelling, affecting the gill filament intake of dissolved oxygen, due to the lack of oxygen in the body, so the fish eat less, or do not eat, which further brings difficulty to the treatment. It can be taken internally, but it can only be used externally at this time, so the efficacy will be reduced.
Although the treatment is difficult, it is not incurable, in the front-line service found that in fact, the biggest loss to farmers is due to the examination, many people on the diagnosis of the disease caused by failure to detect the fungus, the fungal disease according to the general bacterial disease to treat.
All living things on Earth can be divided into five categories: the prokaryote world, the protists, the plant kingdom, the animal kingdom, and the other is the fungal realm. Because of the unique cell structure, lifestyle and reproductive mode of fungi, fungi are listed as a separate boundary. The cells of fungi are divided into three parts: nucleus, cell membrane and cell wall, and the fungal drugs that are now being developed are all developing drug targets for these three sites. Since the cell wall does not exist in the human cell structure, the ideal antifungal drug should be developed against the main components of the fungal cell wall, chitin, dextran and mannose, which is highly targeted and has fewer side effects. However, limited to human cognition of the synthetic pathways of fungal cell walls, there are only a small number of drugs such as polyoxymycin and fluorescent mycin, most of which are limited to the experimental stage, or I am lonely and unheard of, or consulted.
The other type is fungal drugs developed for the nucleus, but as far as I know, there are very few antifungal drugs developed for the nucleus, as if there is only one 5-flucytosine. Why so few? It is because fungi and animals have nuclei, the genetic information of the nucleus is transcribed and translated as a drug target, because the difference between the fungus and animal nuclei is very small, and the drug acts on the fungus will also act on the host cell, so the side effects will be very large. In this case, it is necessary to select both the inhibitory effect on the fungus and the small side effects on the host cells, and the probability of selecting the appropriate drug is very low.
Well, the two types of cases mentioned above, the antifungal drugs developed now are very few, and the most antifungal drugs on the market are still a little more for the development of fungal cell membranes, which is due to the unique structure of fungal cell membranes. What are the specific differences?
The cell membrane of the fungus is roughly similar to the structure of the cell membrane of animals, both contain glycoproteins and lipids; but the difference is that the lipids of fungi contain a unique component ergosterol, which plays an important role in maintaining the normal physiological function of the fungal cell membrane, while the cell membrane lipids of animals do not have this component. Because of this difference, most antifungal drugs are now developed based on this property. By inhibiting the enzyme preparation of the synthesis of ergosterol, the cell membrane of the fungus is destroyed, thus achieving the purpose of inhibiting the growth and reproduction of the fungus. For example, amphotericin B is produced by specific binding to ergosterol, while fluconazole, ketoconazole and terbinafine are produced by inhibiting enzyme preparations.
In addition to the particularity of ergosterol in fungi, sphingolipids are also structurally different from those found in animals and plants. The past has been overlooked, the latest research has many new discoveries, and perhaps there will be more new drug development in this area in the future.
In addition to some drugs that inhibit fungi developed according to the above theoretical research, there are also some antifungal drugs obtained through drug screening, although the test obtains effective data, but the drug target of drug action and the mechanism of antifungal need to be further studied.
Like usually I also like to take a variety of ingredients of medicine, personally think it may be effective for fungi, just by feeling, there is no effect, try to know, often try, try more, naturally there will be some experience. Like trichlorochloride, benzal bromide, potassium permanganate has limited effect on fungi, such as to inhibit or kill fungal spores, its concentration is very high.
The effective concentration of formaldehyde, glutaraldehyde, polyvitascopal iodine, and pentaploids is relatively slightly lower, and its safety is slightly better, and some have certain feasibility in production, but the dosage is also very large, mainly for soaking drugs.
Taking formaldehyde as an example, when the soaking concentration reaches 20ppm to have a significant inhibitory effect on fungal spores, if it wants to have a killing effect, the concentration should be increased accordingly, and the soaking time should be extended at the same time, at 25ppm, it is necessary to soak for a whole day to have a significant killing effect.
In addition, the combination of two or more kinds of compounds, such as pentaplus plus glutaraldehyde, the efficacy will increase. This kind of trial, as long as I have time this year, I will continue to do it, hoping to find a drug that is effective, low cost, and feasible in production.
About fungi
In our country, the research of fishing drugs is far behind the research of human medicine, and many of the fishing drugs in use now are mostly drawing on the research results of veterinary drugs or human drugs. Therefore, in the development or application, especially the understanding of pharmacology, it is the same as veterinary drugs or human drugs. In aquatic products, more antifungal drugs are used now: salicylic acid, iodine, sulfur puzzlefloxacin, pentaploids and other ingredients, everyone is using, but it seems to be much worse than the banned malachite green effect, these two years there are many people in this area of exploration.
There is a professor of a college and university, once launched a product, I deliberately took it to test, according to the instructions to use, but there is no effect, I called the professor again, and then according to its requirements to increase the amount of use, if the effect is very good, it is to increase the amount and then increase the amount, the cost is not low. The cost of using a flow pond or a fry is acceptable, but it is indeed very limited to use on large waters. In order to try out effective antifungal drugs, I had to comb through some of the more common antifungal drugs that are now used.
The first category: imidazoles. The main component of the Dakonin, which we are familiar with for the treatment of athlete's foot, is ketoconazole, which belongs to the class of imidazoles. Some fishing ponds for fishing sturgeon, a sturgeon weighs tens of hundreds of pounds, often strained during fishing, in the winter it is easy to get water mold, in the case of last resort, you can only use the Method of Daknin to treat the place with water mold.
Its mechanism of action is to inhibit the synthesis of ergot solid enzymes by inhibiting the fungal cytochrome P450, destroying the integrity of fungal cells, and causing the substances in the cells to leak out, so as to achieve the purpose of inhibiting or killing fungi. Similar drugs include clotrimazole, econazole, miconazole and bibenzalazole.
In imidazole drugs, there is also a component of the drug, although the external effect is not so prominent, but internal administration, but because of the low binding rate with plasma proteins, low metabolism in the body, high oral absorption rate and fast, but also not affected by food and gastric acid and other characteristics, for fungal diseases deep into the muscle, can be used as the preferred drug, it is fluconazole.
The second category: polyenes. It is represented by amphotericin B and mycin, which are of equal nature, but the toxicity of mycin is stronger.
The principle of action is that by combining with ergosterol on the fungal cell membrane, micropores appear in the cell membrane, causing extravasation of material within the cell, by changing the permeability of the cell membrane, thereby inhibiting or killing the fungus.
Because the cell membranes of mammalian red blood cells and renal tubular epithelial cells also contain steroids, polyenes have side effects on mammals, and there are risks of hemolysis and kidney damage.
Thankfully, the affinity of polyenes for ergosterol on fungal cell membranes is greater than on mammalian cell membranes, so even though there is a risk of side effects, it is still within the controllable range. In addition, polyene drugs are not taken internally because of oral and intramuscular malabsorption and instability, which further reduces the harm of their side effects. It should be noted in the administration that ketoconazole and amphotericin B have a mutual interference effect, so ketoconazole and amphotericin can not be mixed.
The third category: aperrylamine antifungal drugs. The characteristics of this type of drug are somewhat similar to the first type of imidazole, which is also an enzyme that acts on fungi, but the enzyme of this type of drug is to inhibit squalene cyclooxidase, so that squalene accumulates, and the synthesis of ergosterol is blocked, thereby inhibiting or killing fungal cells.
There are also similarities between the characteristics of propylene antifungals and polyene drugs, that is, the absorption in the body is not good, when the drug enters the body, through gastrointestinal absorption and liver metabolism, the concentration of the drug into the blood will be greatly reduced, so the first elimination effect is obvious, more suitable for external use. When used topically on the skin, the effect of topical use is better than ketoconazole and amphotericin, if the effect of dakonin and other substances is not obvious, such drugs can be used as the preferred medication for recurrence, such as terbinafine, which we now commonly use in human medicine.
The fourth category: pyrimidine drugs. For example, 5-flucytosine is a drug that acts on the nucleus of fungi. When the drug enters the fungal cell, it is converted to fluorouracil under the action of cytosine deaminase, because fluorouracil replaces the normal metabolite uracil, so the protein synthesis of the fungus is disturbed, thus achieving the effect of bacteriostatic or bactericidal.
5-fluorocytosine has low toxicity and good oral absorption, and the drug has a very low plasma protein binding rate in the body, which is not catabolized in the body and is mainly cleared by the kidneys.
For example, after oral administration, 90% of the drug is excreted from the urine in its original form within 24 hours of 5-flucytosine. On the downside, the antimicrobial profile of 5-fluorocytosine is narrow and prone to drug resistance. In order to avoid drug resistance during use, the dose will be increased in the early stage, or used in combination with amphotericin B or ketoconazole with synergistic effects.
The fifth category: drugs that act on the cell wall of the fungus. As we all know, the cell wall of fungi is mainly composed of dextran, chitin and mannan protein complexes, while mammals do not have a cell wall, so as long as the drug acts on these components on the fungal cell wall, then these drugs can selectively act on the fungus and have no harm to the host.
Drugs developed for the cell wall of fungi include dextran synthase inhibitors such as caspofungin, chitin synthase inhibitors such as polyoxymycin, nicomycin, and acting on mannan and mannan protein complexes such as purnamecin and caspofungin.
Finally, there is the gray flavin that inhibits the mitosis of fungi, which acts on the principle of binding to tubulin and acts, which is well absorbed orally and can be distributed to various parts of the body after absorption. When mixing medicines, vegetable oils, such as vegetable oil (also called clear oil in some places), can reduce drug loss and increase drug absorption rate.
For systemic fungal diseases, oral administration of griseofulvin can be effective in the treatment of fungal diseases in the case of feeding. Under the existing circumstances, through years of breeding front-line practice, I have screened out some drugs that do have a certain effect on fungi, such as thiomafloxacin, salicylic acid, hydrogen peroxide, peracetic acid, iodine, formaldehyde, glutaraldehyde, etc.
03 Rotten gills are not treated internally
During this time, the water temperature in many places is more than 20 degrees Celsius, when the water temperature falls from high temperature to less than 30 degrees Celsius, in addition to the high incidence of viral diseases, in fact, there is still a high incidence period of bacterial diseases.
Taking columnar flavivius as an example, in fish species such as forktail catfish, grass carp, crucian carp, etc., columnar xanthobacterium is a common bacterium that causes bacterial gills. According to the Hubei Institute of Water Science Chen Xia et al. in 2017 on grass carp to do the test on columnar flavix infection, from 30 ° C this water temperature section, down to 25 ° C mortality rate is the highest, when the water temperature dropped to 15 degrees Celsius, the mortality rate is only 5%; when the water temperature exceeds 35 ° C, the mortality rate of fish is also decreasing.
This conclusion is very consistent with the actual production. In September, in the white dew stage, there is a high period of disease on the rise of dead fish in many places, on the one hand, at this time of year, before this rain, it will bring a lot of exogenous pathogens to the pond; at the same time, the water temperature gradually drops to the optimal water temperature suitable for the propagation of columnar yellow bacillus, and the pathogenicity and toxicity are enhanced. Considering that there is a time process from infection to onset and death, there is a time process, so in September, when the water temperature is maintained at more than 20 degrees Celsius, there is a wave of high incidence of disease.
In production, we often see diseases caused by Xanthobacterium columnarum. Columnar xanthobacterium exists in the cultured water, the surface of the fish and the gills can often be isolated, but usually not necessarily pathogenic, on the one hand, and the physique of the fish, on the other hand, more related to the number of bacteria in the water body and pathogenicity. When the concentration of bacteria is high and the water temperature is in the range of 20-30 degrees Celsius, the virulence is the strongest, and it is also the most susceptible to infection at this time
For gills that have become ill, due to the rotten gills caused by bacteria, they have colonized in the gills, and the bacteria pass through the blood tubules of the gills, either constantly releasing toxins into the blood, causing sepsis; or multiplying in the blood and causing bacterial blood; or spreading through blood vessels to organs and tissues in the fish, colonizing them, causing tissue ulceration, causing pus and blood.
This is the case when grass carp tend to fester from within after wintering every year. As long as the bacteria enter the blood, do not let the antibacterial drugs enter the blood, just blind external use of killing, obviously a bit of a bull's head is not the feeling of the horse's mouth, which is some farmers in the treatment of bacterial rotten gills on the effect is not good, the biggest mistake made.
04 Neglect of immune function enhancement after long-term use of antibiotics in large doses
In the aquaculture water body, the species and number of bacteria are very large. Through experiments, we found that we can take a pond of water, dilute the distilled water more than ten times, and then inoculate the bacteria on the plate, and countless bacteria can still grow on the plate, which shows that the number of bacteria in the cultured water body is very large.
The number is large, to what extent, people may not have much clear concept. Let's talk about a case around us, take us as an example, the number of bacteria in the air is far lower than that of the farmed water body, but from the perspective of human medicine, from the mouth to the anus, there are hundreds of bacteria that can be inoculated and cultured, and it is predicted that this is only one-tenth of the total number of bacteria. Compared with the fish living in the water body, the number and type of bacteria in the body are estimated to be only more.
So many bacteria, some are pathogenic bacteria, some are conditional pathogenic bacteria, some are beneficial bacteria, some may also be friends and foes, such as E. coli in the human body, when the number of bacteria is too large, it is possible to cause enteritis, because the reproduction of E. coli requires iron ions, so the human body can control E. coli through iron ions.
In addition to bacteria and hosts, bacteria also have symbiotic, alternate, competitive, and hunting relationships with each other. Over the course of hundreds of millions of years of evolution, bacteria have helped fish digest food and provided energy for fish, and it is precisely because of the role of this fish body microbiome that the survival advantage of fish has been improved. Therefore, in the process of treating diseases, it is not as simple as killing the bacteria in the water body and the bacteria in the fish, and at present, it is impossible to kill the bacteria of the farmed water body and the fish body.
The correct understanding should be that all disinfectants and antibacterial drugs are only adjusting the structural composition of bacteria in the fish, whether this bacteria are a little more, or another bacterium is a little more; or artificially let a certain bacterium be a little more, through it to inhibit other pathogenic bacteria.
If there is Bacillus subtilis in the fish, it is difficult for Staphylococcus aureus in the environment to colonize in the fish, and it is naturally difficult to cause harm.
In this way, when the pathogenic bacteria cause diseases, through the internal administration of antibacterial and external disinfectants, the pathogenic bacteria are killed to a certain extent, and the next step to be done is to cultivate beneficial bacteria and enhance the immunity of the fish body. In May of this year, I went to the same reservoir to do three drug susceptibility tests, the first time, after doing it, the sensitive medicine was used, effective, the number of fish deaths was greatly reduced, but it could not break the roots, when the farmers used the drug continuously for a week, when the drug was reused, the number of dead fish appeared repeatedly. The second time I did it, I didn't get the bacteria in the kidneys. A few days later, I went to do it for the third time, and the sensitive medicine I got this time was different from the previous one.
When the sensitive medicine was used this time, the number of dead fish was finally controlled, and I thought of one thing, that is, through the long-term use of antibacterial drugs, the bacteria of the fish may alternate, or most of the bacteria in their bodies have been killed, but the symptoms are still there. So at this time, if you continue to take it internally, in fact, the significance is not great, at this time, the key is not to kill the bacteria again, but to enhance the body's immunity, so later I put Yu Kang Bao and Yu Kang immune polysaccharides to use, the results verified my judgment, the facts proved that this method is effective. If I look at it today, I will also add Yukang intestine, so that the effect will be better, by speeding up the repair of the intestinal mucosa, shortening the course of treatment. Finally, to sum up in one sentence, that is, to make the fish healthy, not to let the fish live in an environment without bacteria, but to let the fish live in an environment with various bacteria, and it can still stay healthy!
05 Metabolic diseases have failed to regulate metabolism
For the concept of hepatobiliary disease of fish, in fact, it is only in fish, in people and livestock and poultry, liver disease is liver disease, biliary disease is biliary disease, metabolism is metabolic disease, inflammation is inflammatory disease, the distinction is very clear. Perhaps the research on fish diseases is relatively backward, so there is the saying of hepatobiliary disease.
For now, many people are through the color of the liver to judge whether hepatobiliary disease occurs, and this concept many years ago, soochow University of the older generation of aquatic experts put forward the liver colorless understanding, the amount of blood in the liver affects the change of liver color, and the amount of blood in the fish body is not related to liver disease, more is more closely related to bacterial sepsis, viral bleeding, mechanical trauma, so it is indeed a bit far-fetched to judge liver disease by color.
Earlier we have shared diseases caused by bacteria and fungi, such as inflammation of the liver, the liver of fish will exceed the normal proportion of size, swelling, or diffuse hepatitis in the abdominal cavity, attached to the mesentery.
When such a liver is removed and placed in a container for about ten minutes, it can be found that there is fluid oozing. This is the hepatitis caused by inflammation, if you want to diagnose the diagnosis, you can see through the liver tissue slice, you will find that the liver cells are larger than normal liver cells, and the section will appear bulge, the intracellular structure is blurred, the edges of the cells are turned outward, and a large number of fine particles appear in the cytoplasm.
Liver enlargement, everyone is very good to judge, but the liver has metabolic disorders, it is easy to be ignored by farmers, such as liver atrophy. If it is found that the edges of the liver are thin and the texture becomes hard, it will be accompanied by a smaller liver volume, a decrease in weight, and when sliced, it will be found that the hepatocyte volume is reduced, the cytoplasm is dense, the nucleus is concentrated, the color is darker when staining, the intestinal wall becomes thinner during the infusion examination, and the intestine shrinks, that is, metabolic disorders can be diagnosed.
For example, we often find that some grass carp have black body color, loose scales, easy to descale, and the fish still rely on transportation, and accompanied by a decline in food intake, an increase in the bait coefficient, a slowdown in growth and other phenomena.
When the liver is sliced, a large number of vacuoles can be found in the liver cells, and the nucleus is squeezed into a corner by the oil, and lipid lesions appear. This phenomenon is actually caused by metabolic disorders, the fish body ingests excess fat, needs a lot of bile to deemulsify fat, promote metabolism, if the long-term overload of secretion of bile, eventually fish is prone to fatty liver.
For fish that have developed metabolic disorders, when taking drugs at this time, the first thing to think about is not to use antibiotics to anti-inflammatory, but to supplement fish kangbao, vitamins to promote metabolism, and then consider using other drugs for symptoms. However, in the actual use of drugs, many people have not done so, one is antibiotics, because the liver of the fish is obstructed, due to the lack of liver metabolism, in fact, the utilization rate of the drug effect is very poor, which is also a misunderstanding that many people in the drug are prone to occur.
(Source: Fish Farming Classic, Author: Xiao Jianchun Xiao Jiancong)
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