Renal disease caused by malaria

　　1. Etiology

　　Humans are generally susceptible to several species of human malaria. Malarial infection is the only etiological factor for the disease. It has been found that the incidence of kidney disease in malarious areas is much higher than that in non-epidemic areas during the same period. In recent years, clinical and tissue studies have confirmed that malarial antigens are present in the immune complexes in the glomeruli of patients, further confirming that malaria is an important etiological factor for the occurrence of kidney disease.

　　2. Pathogenesis

　　Renal damage caused by malaria can be divided into three types: acute renal failure, acute reversible renal damage, and chronic progressive renal damage. Acute renal failure is one of the serious complications of malignant malaria, with an incidence rate of about 0.45%. Its onset is related to factors such as acute intravascular hemolysis, reduced blood volume, increased blood viscosity, and disseminated intravascular coagulation. The latter two are closely related to immune reactions.

　　1. Acute renal failure:Acute renal failure caused by malaria is mainly characterized by tubular degeneration and necrosis of the distal renal tubules, with hemoglobin casts and granular casts in the lumen, and interstitial edema. Acute renal failure in malignant malaria is often non-oliguric, making it easily overlooked in clinical practice. Common causes include acute intravascular hemolysis (blackwater fever), which is common in malignant malaria, and congenital glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is an important factor. The release of malarial toxins and the use of antimalarial drugs (such as quinine and primaquine), antipyretics and analgesics, etc., are all predisposing factors. In severe cases, patients may develop acute renal failure.

　　2. Acute reversible renal damage:Under immunofluorescence, IgM (mainly), IgG, and C3 are deposited beneath the basement membrane and in the mesangial area. Under the electron microscope, electron-dense deposits are visible, and some malaria parasites can be found. Some people have found that after the implantation of malignant malaria antigens, circulating antibodies bind to them and form immune complexes in situ. This indicates that renal damage in humans and experimental animals is caused by immune complexes. Most patients with this type of renal damage (such as proteinuria, glomerulonephritis, and nephrotic syndrome, etc.) respond well to antimalarial treatment.

　　Renal biopsy shows thickening of the glomerular mesangium, proliferation and hypertrophy of endothelial cells, and irregular thickening of the basement membrane.

　　3. Chronic progressive renal damage:Chronic progressive renal damage caused by malaria can also detect malaria parasites in renal tissue. It was confirmed in the 1960s that the renal damage was due to an immune abnormal reaction induced by malaria infection, leading to immune complex nephritis. In recent years, it is believed that nephropathy caused by tertian malaria may be an autoimmune reaction, with the early stage involving the formation of immune complexes from circulating tertian malaria antigens or due to antigen implantation in the renal tubule capillary wall, combining with antibodies to form immune complexes in situ, causing initial renal damage. Subsequently, the protein in the destroyed renal tissue can act as an autoantigen, promoting the generation of autoantibodies, and then causing immune complex nephritis. There is a cross-reactive immune response between serum antinuclear antibodies in residents of endemic areas of tertian malaria and antinuclear antibodies of the tertian malaria parasite.

　　1. Blackwater fever is a severe complication of malignant malaria characterized by acute hemolysis, hemoglobinuria, and high fever, which is more common in cases of recurrent attacks and irregular quinine intake.

　　2. Nephropathy caused by malaria is mainly manifested by hypertension, proteinuria, hematuria, and edema. All four types of malaria can complicate this condition, but it is more common in tertian malaria.

　　3. Splenomegaly, hepatomegaly, changes in blood cells, and pseudo-peritonitis are also common complications.

　　1. The main clinical manifestations of nephropathy caused by malaria are hypertension, proteinuria, hematuria, and edema. All four types of malaria can complicate this condition, but it is more common in tertian malaria.

　　2. Acute renal failure caused by malaria may present with high fever, excessive sweating, and insufficient water intake leading to decreased effective blood volume, followed by increased compensatory sympathetic nervous activity, increased catecholamine secretion, and strong vasoconstriction of renal vessels, resulting in a significant decrease in renal blood flow, which can cause or worsen renal insufficiency.

　　3. Chronic progressive renal damage caused by malaria is mainly manifested as nephrotic syndrome, with most patients dying within one year, resulting in a high mortality rate (about 13%). It usually occurs in conjunction with nephrotic syndrome and is more common in children. Typical renal edema appears within 3 weeks after the control of the disease, and even pleural effusion and ascites may occur. It is accompanied by splenomegaly, hepatomegaly, anemia, and after the edema subsides, persistent proteinuria and renal dysfunction and hypertension may occur, with a few cases of rapidly progressive renal failure.

　　1. Controlling the source of infection, improving epidemic reporting, and curing patients with malaria and carriers of plasmodium.

　　2. Interrupting the transmission route mainly involves the destruction of Anopheles mosquitoes, preventing them from being bitten. Clearing the breeding places of Anopheles larvae and using insecticides. Personal protection can use repellents or mosquito nets, etc., to avoid being bitten by mosquitoes.

　　3. Enhancing the disease resistance of the population Malaria vaccination may reduce the incidence and mortality rate of the disease, but due to the diversity of plasmodium antigens, it brings great difficulties to vaccine development. Currently, the main research is on sporozoite protein and gene vaccines, which have not yet been able to be used on the scene.

　　Malaria vaccine, AIDS vaccine, and tuberculosis vaccine have become the three vaccines prioritized for global development. China's independently developed 'recombinant malaria vaccine' has been approved by the National Drug Administration and the World Health Organization and has entered clinical trials. Chemical drug prevention is currently a commonly used measure. Health populations and immigrants in high malaria areas can be selected appropriately. With the effective prevention and treatment of various types of malaria, the renal damage caused by malaria will be controlled accordingly.

　　1. Examination of pathogenic organisms in blood

　　Among the four types of human plasmodium, only malignant malaria is present in the peripheral blood in the form of ring forms and gametocytes, and there are more opportunities to detect them during the attack period. Most of the parasites enter the visceral capillaries during the intercritical period. If the gametocytes have not appeared at that time, the blood examination may temporarily show negative results. Therefore, it is most appropriate to check blood during the attack period of malignant malaria; the blood examination of the other three types of malaria is not time-limited, and the parasites can be seen in both the attack and intercritical periods. Therefore, for patients with clinical symptoms similar to malaria but negative for blood examination, it is necessary to persist in checking for several days, checking blood twice a day, and carefully examining the thick blood film according to the regulations. Its power is many times higher than that of the thin blood film. Ultimately, plasmodium can be detected in the peripheral blood in all cases of malaria. Taking a blood smear from the patient's earlobe or finger tip, staining, and microscopic examination is still the most reliable method for diagnosing malaria. If intraerythrocytic plasmodium is found, it can be diagnosed immediately.

　　Considering the accuracy of the microscopic method is affected by factors such as the density of blood parasites,制片 and staining techniques, deformation or density reduction of parasites after medication, and microscopic experience, there have been some improvements in traditional blood examination methods in recent years. One of them is to use capillaries containing anticoagulant and acridine orange to collect 60μl of blood from the patient, add a floatation tube, centrifuge it, and concentrate the plasmodium on the upper layer of red blood cells and the lower layer of white blood cells. Due to the presence of the floatation tube in the center of the tube, the above two layers of cells and the plasmodium are pushed to the tube wall, and the plasmodium with fluorescence can be directly detected under a fluorescence microscope. This method has a concentration effect, which can improve sensitivity. The other is to replace ordinary water with 0.5% to 1.0% saponin solution for hemolysis, and then stain with Giemsa's solution before microscopic examination. The advantage is that the bottom plate of the thick blood film treated with saponin is clear, without red blood cell remnants and platelet interference, which is helpful for the detection of plasmodium.

　　2. Immunological detection

　　The main methods for detecting plasmodium antigens and antibodies include agarose gel diffusion test, immunoelectrophoresis, enzyme-linked immunosorbent assay, direct fluorescence or enzyme immunostaining, etc. It can detect patients with plasmodium parasitemia and can be used for clinical diagnosis, epidemiological investigation, tracing the source of infection, evaluating efficacy, and inferring the trend of malaria outbreaks by determining the levels of antibodies in the population of epidemic areas. It can also screen blood donors to prevent malaria transmission through blood transfusion and evaluate the effectiveness of antimalarial measures. In addition, for those who have had repeated attacks without a known cause, detecting malaria antibodies can help with diagnosis. The methods for detecting antibodies commonly used include indirect fluorescence antibody test, indirect hemagglutination test, enzyme-linked immunosorbent assay, etc.

　　3. Nucleic acid probe detection

　　There are several different nucleic acid probes used for the detection of plasmodium in China outside. Due to their unique high specificity, their sensitivity can be higher than that of microscopy, and it is considered that nucleic acid probe technology has great hope of replacing conventional microscopic examination. It can process a large number of samples in batches in a short time and is considered to be a powerful diagnostic tool for malaria epidemiological investigation and evaluation of antimalarial measures, as it can quantitatively and estimate the level of plasmodium parasitemia.

　　4. PCR detection

　　Among various methods for detecting malaria, PCR has the highest sensitivity and specificity. To further improve the sensitivity and specificity of PCR technology and facilitate its promotion in practical work, research has been conducted on nested PCR (nested PCR) and PCR-ELISA methods. In addition to being able to directly detect plasmodium in anticoagulated samples, the technology for detecting plasmodium on filter paper dried blood spots has also matured, making it convenient to monitor malaria in remote areas using PCR technology. Due to its high requirements for experimental technology and conditions, it is limited in its application on-site. Under the conditions of most malaria-endemic areas, it is necessary to return to a laboratory with better conditions for further analysis and processing after on-site blood collection.

　　5. Dipstick method

　　The sensitivity (84.2％～93.9％) and specificity (81.1％～99.5％) of this method for diagnosing malaria are both high; it also has the characteristics of simple operation, rapid stability, and ease of learning. However, there are also certain limitations to the application of the Dipstick method, as it is difficult to detect the plasmodium that is still in the incubation period or only contains mature sporozoites in the blood.

　　6. Acute renal injury

　　Due to the atrophy and necrosis of the distal renal tubules, examination shows the lumen contains hemoglobin casts and granular casts, interstitial edema of the kidneys, and patients may have a large amount of proteinuria, red and white blood cell urine, and cast urine, most of which are non-selective proteinuria. The serum albumin level is reduced, α2 globulin is increased, cholesterol is increased, C3 is decreased, and other manifestations of glomerulonephritis and nephrotic syndrome; patients may also have symptoms of increased blood viscosity, which is due to fibrin deposition on the surface of erythrocytes containing plasmodium, causing them to stick together in clumps, leading to microcirculatory disorders, and ultimately resulting in renal failure and disseminated intravascular coagulation (DIC).

　　In acute reversible renal injury, renal biopsy shows thickening of the glomerular mesangium, proliferation and hypertrophy of endothelial cells, irregular thickening of the basement membrane, and under immunofluorescence, IgM (predominant), IgG, and C3 are observed to be deposited beneath the basement membrane and in the mesangial area. Under the electron microscope, electron-dense deposits are seen, and some malaria parasites can be found.

　　The pathological changes of the kidney in three-day malaria are mainly focal (about 30%) or diffuse thickening of the glomerular capillary wall, segmental sclerosis around the capillary loops and in the mesangial cells (30% to 75%), basement membrane thickening, with a small amount of crescent formation in some cases. The lesions progress to complete glomerulosclerosis (about 75%) in the entire kidney, and secondary renal tubular atrophy follows, characterized by thickening of the capillary wall, narrowing and occlusion of the lumen, atrophy of the renal tubules, and significant interstitial infiltration.

　　Immunofluorescence microscopy mainly shows IgM deposits in the mesangial area, with a small amount of IgG, C3, and occasionally IgA. Immunoglobulins usually appear within one week of onset and last for up to half a year. In recent years, it is believed that the size of the deposits is related to IgG subtypes, with coarse particles often containing IgG3 and fine particles often containing IgG2. Under the electron microscope, subendothelial basement membrane-like substances are observed in the glomerular basement membrane, and electron-dense deposits are present within the basement membrane.

　　1, Foods to eat

　　Choose light, refreshing, and easily digestible high-protein foods, which are rich in various nutrients and have sufficient water content, such as milk, liver soup, egg soup, fruit juice, and vegetable soup.

　　During the period of high fever, it is advisable to eat light, plain, semi-liquid foods such as rice porridge, noodles, vegetable soup, fruit juice, milk, and egg soup.

　　For those with severe fever and dry mouth and throat, it is advisable to eat fresh fruits and vegetables such as watermelons, pears, water chestnuts, and sugarcane.

　　1, Malva Herb Juice: Squeeze the juice of fresh Malva herb, take it two hours before the onset of malaria, and take it for several days in a row; or crush seven garlic bulbs and add a little hot wine, take it two hours before the onset of malaria, and take it for two days. Or roast the garlic head until it turns yellow, drink wine and eat garlic two hours before the onset of malaria, and take it all at once.

　　2, Vinegar Fried Eggs: Boil three eggs without shells with 200g of rice vinegar in a pot, and take it warm in one dose.

　　3, Garlic and Pepper Leaf Soup: 100g of pepper leaves and one garlic clove, boil 500ml of soup, and drink it. Suitable for those with more cold symptoms than fever in malaria.

　　4, White Pepper Powder: Crush 20 grains of white pepper, boil it with 100g of wine, and drink it.

　　5, Red Bean Carp Soup: 150g of red beans, one carp, one red date, a piece of dried tangerine peel, and 50g of ginger. Boil until soft, season with oil and salt, once a day. Alternatively, you can use 250g of dog meat, 150g of black beans, 100g of ginger, a piece of dried tangerine peel, and 10 red dates, boiled in water. Eat the meat and drink the soup. Suitable for intermittent malaria, three-day malaria, or long-standing malaria that does not heal.

　　6, Black Rice Bean Soup: Two black rats, 150g of black beans, 10 red dates, and a piece of dried tangerine peel. Remove the fur and internal organs of the rats, wash, and boil in water. Eat the meat and drink the soup, once a day.

　　7, Catfish Soup: Boil 200g of胡子鲇 (i.e.,塘虱鱼 or 塘角鱼), 50g of black beans, 10 red dates, and 3g of dried tangerine peel in water. Eat the fish and the mixture together.

　　8, Goat Horn Soup: Grind 300g of goat horn into powder, add 1000ml of water, and boil to 500ml. Take it three hours before the onset of malaria.

　　9, Turtle Soup: Boil a turtle weighing about 500g with an appropriate amount of water, season with salt, and eat the meat and drink the soup. Take once a day until cured. This recipe is suitable for three-day malaria or recurrence of malaria after labor.

　　10, Ginger Tea: Grind ginger to a pulp and wrap it around both knees four hours before the onset of malaria, which can prevent malaria for several days. If the skin itches, remove it.

　　11, Wild Duck and Jujube Soup: One wild duck, 10g of ginger, 15g of jujube, appropriate amounts of wine, salt, and oil. After killing the wild duck, remove the feathers, slice the meat and ginger, add jujube, a small amount of oil, salt, and wine, and cook together. Eat in several servings, and eat one every few days. This recipe is suitable for those with persistent malaria that does not heal.

　　Two, Foods to Avoid

　　Eat less of the products that generate dampness, such as mango.

　　1, For those with warm-type malaria, high fever, thirst, red urine, and constipation, avoid spicy, warm, and irritant foods such as cigarettes, alcohol, garlic, chili, pepper, and chives.

　　2, For those with cold-type malaria, chest tightness, lack of appetite, nausea, and thick and greasy fur, avoid eating greasy and sweet foods such as fried foods, fatty meat, sweet potatoes, molasses, and glutinous rice sweets.

　　3, For those who suffer from recurrent malaria, avoid eating seafood and pickled foods such as rubber fish, yellow croaker, mackerel, shrimp, pickled fish, spicy and sour vegetables, and pumpkin.

　　One, Treatment

　　Most nephropathy caused by malaria is preventable, and treatment should focus on the primary disease.

　　1, Chloroquine: The application of chloroquine can control the onset of malaria. The initial oral dose is 1.0g, 0.75g each on the second to third day, the total dose is 2.5g. For those who need long-term treatment, it is recommended to maintain a dose of ≤0.25/d. The initial intravenous dose is 1.5g, and 0.5g each on the second to third day. For patients with malignant malaria accompanied by acute renal failure, low molecular weight dextran, dipyridamole (Panshengding) or a small amount of heparin should be used at the same time as antimalarial treatment to reduce blood viscosity and prevent thrombosis. For those who have developed acute renal failure, early peritoneal dialysis is recommended.

　　2, Artemisinin: It is an anti-malarial drug independently developed in China, extracted from the traditional Chinese medicine Qinghao (Artemisia annua, a plant of the Compositae family) as a sesquiterpene lactone drug, which belongs to a highly effective and rapid-acting antimalarial drug. It has a rapid and powerful killing effect on the asexual schizonts of the malarial parasites in the erythrocytic stage. It has no cross-resistance with chloroquine. Its action is related to the interference with the function of the plasma membrane-mitochondria of the parasites. The drug has low toxicity and is safe, mainly used for patients with chloroquine-resistant malignant malaria. Its biggest shortcoming is that the recurrence rate is relatively high. The initial dose can be taken orally as 1.0g, and 0.5g is taken again 6-8 hours later, 0.5g each on the second and third day, or derivatives such as蒿甲醚 can be used, intramuscular injection, the initial dose is 0.2g, half of the second to fourth day, the total amount is 0.6g, or Qinghao suan ( Qinghao ester), the initial dose is 0.2g, intravenous infusion, 0.1g each on the second to third day.

　　Three, Primaquine can prevent the recurrence and transmission of malaria. Oral administration of 26.4mg/d (equivalent to 15mg of base), taken for 14 days, or oral administration of 39.6mg/d (equivalent to 22.5mg of base), taken for 8 days. Chloroquine should be used first for 3 days before taking the drug. Patients with a deficiency in G-6-PD should avoid Primaquine and other drugs to prevent blackwater fever, which can lead to severe renal damage. If blackwater fever occurs, chloroquine or artemisinin, or artemether should be used instead.

　　Four, Acute renal damage caused by malaria, although it belongs to proliferative glomerulonephritis, has a good response to antimalarial treatment. Generally, glomerulonephritis regresses and urine returns to normal about a month after antimalarial treatment.

　　However, antimalarial treatment can never completely eliminate renal damage. Corticosteroids are effective for patients with highly selective proteinuria, so corticosteroid treatment can be used for patients with selective proteinuria, and some patients' conditions can be alleviated; some patients have also been relieved by cyclophosphamide or azathioprine. Non-selective proteinuria patients have little effect on corticosteroids.

　　Two, Prognosis

　　The prognosis of general cases (simple acute infection) can vary greatly due to the type of malaria parasite, the patient's immune status, and the presence or absence of complications. However, in simple acute infections without severe complications, whether it is an intermittent fever or malignant malaria case, it can generally be safely and rapidly controlled after treatment with antimalarial drugs.

　　The prognosis of severe cases of malaria is mainly seen in cases of malignant malaria with no immunity, commonly in immigrants entering the epidemic area and children in high malaria areas. During outbreaks of malignant malaria, residents of all ages in the local area can be affected. These cases often worsen due to delays in diagnosis and treatment. With the development of medicine and the continuous improvement of understanding and treatment levels of severe malaria, some clinical manifestations originally belonging to the scope of severe malaria are actually not severe. For example, gastrointestinal malaria is the most common type of severe malaria, but the prognosis is generally good. Cerebral malaria is the most common clinical manifestation of severe malaria, with a mortality rate of 22% reported in treated patients abroad. Acute renal damage caused by malaria can have different outcomes depending on the changes in the primary disease.