Intermittent chills

Introduction Intermittent chills are one of the symptoms of malaria. Malaria is an infectious disease caused by malaria parasites characterized by intermittent chills, high fever, sweating and splenomegaly, and anemia. Cut off the route of transmission, mainly to eliminate Anopheles mosquitoes and prevent bites by Anopheles mosquitoes. Remove Anopheles larvae breeding sites and use insecticides. Personal protection can be applied to repellents or mosquito nets to avoid being bitten by mosquitoes. Control the source of infection, improve the epidemic report, cure patients with malaria and patients with malaria parasites.

Cause

(1) Causes of the disease

Plasmodium belongs to the genus Hematopoi, Plasmodium, and Plasmodium in taxonomy. There are four malaria parasites in the human body, causing vivax malaria, falciparum malaria, three-day malaria and oval malaria. Although four species of Plasmodium exist in China, they are mainly Plasmodium vivax and Plasmodium falciparum. Plasmodium malaria is rare, and only a few cases are found in Plasmodium ovale.

1. Morphology: The discovery of Plasmodium in red blood cells is an important basis for the identification of malaria and species identification. The parasitic period of Plasmodium in red blood cells is called the red inner phase. This stage changes greatly with the growth, development and reproduction period of the worms. The morphological changes are very large (polymorphism), which can be generally divided into three main developmental stages. That is, trophozoite, schizont and gametophytic. When observing the morphology of Plasmodium by optical microscope, the thin film smear should be stained with Wright or Ji's solution. The stained Plasmodium nucleus is purple-red and the cytoplasm is blue. The malaria pigment is not affected by the dyeing. Brown.

1. Trophozoite: It is the earliest stage of feeding and growth of Plasmodium in cells. According to its development, there are early trophozoites and late trophozoites. The cytoplasm of the early trophozoites is less slender and has a vacuole in the middle. It is similar to the ring of the ring. The nucleus is small and is located on one side of the ring. It is similar to the gem on the ring, so it is also called the ring body. Signet ring). Later, the worms developed obviously, sometimes protruding from the pseudopod, and the nucleus also increased. The final product malarial pigments after digestion and decomposition of hemoglobin began to appear in the cytoplasm, and the morphology of the infected red blood cells changed again. Small spots of different forms can occur, which is called advanced trophozoites (also known as large trophozoites).

2. Schizont stage: After the mature trophozoites mature, the shape of the worm becomes round, the vacuoles in the cytoplasm disappear, and the nucleus begins to divide, which is called the pre-schizont or immature schizon. The nucleus of the schizont cytoplasm continued to divide, and the cytoplasm also split, and the malaria pigment gradually became concentrated. The last part of the cleavage of a small part of the nucleus surrounds a nucleus, forming many small individuals called merozoite. This merozoite-containing worm is called a schizon or mature schizon.

3, gametocyte (gametocyte): Plasmodium in the red blood cells after several generations of split body proliferation, part of the merozoites into the red blood cells no longer undergo split body proliferation, nuclear enlargement, cytoplasm increased, and finally developed into a circle, ellipse Individuals of the shape or crescent shape, called gametophytes. The gametophyte is divided into male and female (or size). The worm body is large, the cytoplasm is dense, the malaria pigment is large and coarse, the nucleus is dense, and the side of the worm body is the female gametophyte (large gametophyte); the loose and located at the center of the worm body It is a male gametophyte (small gametophyte). Parasitic in the human red blood cells, the four malaria parasites have smaller morphological worms, thin cytoplasm, and few malaria pigments.

2. Life history: The four malaria parasites parasitized in the human body have the same life history process. They need to pass through two generations of asexual reproduction and sexual reproduction. They are divided into three stages: red blood cell phase, red blood cell phase and spore proliferation phase. At the stage, both human and Anopheles are required. In the human body, he enters the development of hepatocytes (extra red blood cell phase), then proliferates in red blood cells and multiplies (intraerythrocytic phase), finally differentiates the gametophyte, completes asexual reproduction, and begins the initial development of sexual reproduction. Sexual reproductive development (spore proliferative phase) of gamete reproduction and spore propagation in Anopheles. Asexual reproduction is completed in the human body, sexual reproduction is completed in the mosquito, so the human is the intermediate host of the malaria parasite, and the mosquito is its terminal host.

(two) pathogenesis

The pathogenic stage of the life history of Plasmodium is mainly the intraerythrocytic phase. All clinical signs and symptoms of malaria, including the typical episodes of malaria, secondary anemia and splenomegaly, severe cases can also cause sinister malaria, malaria nephropathy, black urine fever, etc., all of which are proliferated by the red internal fissure Plasmodium and its pathophysiological changes. Although the extraerythrocytic stage has damage to liver cells, it has no obvious clinical symptoms, but it is associated with the incubation period and recurrence of malaria. From the whole process of malaria incidence, the sporozoites in the mosquito salivary glands invade the human body and go through a period of incubation before the clinical attack, followed by clinical episodes; if not thoroughly treated, the long or short latent period (latent period) re-ignition or recurrence.

1. Latency: It is the incubation period when the malaria parasite invades the human body until the onset of malaria. If the malaria mosquito is transmitted, the incubation period includes the development of the infrared phase and the proliferative period of the intraerythrocytic plague to reach a certain amount of time; if the intraerythrocytic parasite is directly injected into the human body due to blood transfusion, the incubation period is only The red endogenous Plasmodium proliferates to a certain amount of time.

2. A typical episode of malaria episodes, reburning and recurrent malaria is three consecutive stages of chills, fever, and sweating. The whole process is about 8 to 10 hours. After the episode, the patient's body temperature returned to normal and switched to intermittent. The episode of malaria is related to the proliferative cycle of the erythrocytic parasite, and also has a certain relationship with the number of erythrocytic parasites. The cause of the attack is that after the red blood cells are ruptured by the schizonts, merozoites, protozoal metabolites, residual and denatured hemoglobin, and red blood cell fragments enter the bloodstream together. Some of these substances are phagocytosed by macrophages, stimulating macrophages. An endogenous pyrogen is produced, which interacts with the malaria parasite metabolites in the hypothermia's thermoregulatory center, causing chills and fever through the regulation mechanism of the nervous system. After the blood stimuli are cleared, the body temperature begins to return to normal. . The typical seizure interval coincides with the Plasmodium red internal fission cycle. With the increase in the number of malaria episodes, the human body has immunity to the protozoa, or after incomplete treatment, most of the erythrocytic parasites are eliminated and no clinical symptoms appear.

However, after several weeks or months, in the absence of reinfection, the remaining Plasmodium may evade immunity for some reason (such as antigenic variation) and the general resistance and specific immunity of the body decline, re-breeding Causes a recurrence, called recrudescence. After the onset of malaria, the erythrocytic parasite has been completely eliminated by human immunity or sclerotherapy drugs, but due to the presence of late-onset sporozoites in the infrared phase, the end of the dormancy begins. The merozoites produced by the proliferation re-invade the red blood cells and multiply, which causes the protozoa to cause malaria, which is called relapse. When the recurrence is due to the body's certain immunity, the symptoms are generally lighter than the initial, and the number of episodes is also less.

3. Anemia and liver spleen

(1) Anemia: After repeated episodes of malaria, the number of red blood cells decreases rapidly, and hemoglobin decreases, causing different degrees of anemia. The anemia of falciparum malaria is more serious because Plasmodium falciparum invades various red blood cells, and the number of reproduction is large, and the destruction of red blood cells is more serious. The more episodes of malaria, the longer the course of the disease and the heavier the anemia.

(2) Liver and spleen: Patients with malaria may have large liver, especially in children with falciparum malaria. Splenomegaly is a sign of early appearance and significant features of malaria patients. The initial onset of splenomegaly begins 3 to 4 days after the onset of the disease, due to hyperemia and massive proliferation of macrophages.

(3) malaria nephrotic syndrome: malaria can be complicated by glomerulonephritis acute renal failure or nephrotic syndrome during the attack. It is generally considered to be an immunopathological phenomenon and is a type III allergic reaction. Kidney disease caused by acute malaria is a temporary reversible disease that can be cured by antimalarial treatment. Nephrotic syndrome can occur in some patients who have not been cured for a long time. Malaria nephropathy is more common in patients with falciparum malaria and three-day malaria.

(4) Dangerous malaria: refers to the possibility of finding Plasmodium falciparum in the blood and eliminating other diseases. It has one of the following manifestations: super-pelletiasis (infection rate of Plasmodium falciparum in the peripheral blood>5 %); coma or other disturbances of consciousness for more than 6 hours; severe anemia (hemoglobin jaundice; water, electrolyte or acid-base balance disorders; renal failure (24h urine volume less than 400ml); high fever or other inclusions. Malaria usually occurs during the epidemic of falciparum malaria or in people without immunity.

The onset of this type of patient is no different from the general case, but after one or two episodes, the condition suddenly becomes heavier, the symptoms are complicated, the changes are impermanent, the disease develops quickly and sinister, and the mortality rate is high. More than 80% of the clinical manifestations of sinister malaria are seen in patients with falciparum malaria. According to the clinical symptoms, it is divided into brain type, super high heat type, cold type, gastrointestinal type, etc., among which brain type malaria is mostly.

an examination

Related inspection

blood test

1. Examination of pathogens in the blood: The four malaria parasites in the human body are only falciparum malaria. Only the ring body and gametophyte are seen in the surrounding blood, and there are more chances to be detected during the attack period. Most of the protozoa enter the visceral capillaries during the intermittent period. If the gametophyte has not yet appeared, the blood test may be temporarily negative, so it is most appropriate to check the blood during the onset of falciparum malaria; the blood test of the other three malaria is not limited by time, and the protozoa can be seen in both the attack and the intermittent period. Clinically similar to malaria, blood test protozoa negative, should insist on a blood test 2 times a day, for several days. Carefully check the thick blood membrane according to the regulations, its power is many times higher than the thin blood film. Any malaria will eventually find the malaria parasite in the surrounding blood. Blood smears, staining, and microscopic examinations are taken from the earlobe or fingertips of patients, and it is still the most reliable method for the diagnosis of malaria. If the intraerythrocytic parasite is found, it can be diagnosed.

In view of the fact that the accuracy of the microscopy method is affected by factors such as the density of protozoa in the blood, the production and dyeing techniques, the deformation or density of protozoa after taking the drug, and the experience of microscopic examination, the traditional blood test method has been improved in recent years. One is Becton Dickinson's quantitative buffy coat. Using a capillary containing an anticoagulant and acridine orange, take 60 l of blood from the patient, add a floater, and after centrifugation, the Plasmodium is concentrated in the upper layer of red blood cells and the lower layer of white blood cells. Due to the presence of a pontoon in the middle of the tube, the above two layers of cells are The Plasmodium is pushed towards the wall of the tube and the fluorescing Plasmodium can be examined directly under a fluorescence microscope. This method has a concentrated effect, which improves sensitivity and does not require dyeing, saving time. The second is 0.5% to 1.0% saponin solution instead of ordinary water hemolysis, and then microscopically stained with Gibber's solution. The advantage is that the saponin-treated thick blood membrane bottom plate is clear, free of red blood cell debris and platelet interference, and helps the malaria parasite to be detected.

2. Immunological testing

1. Detection of Plasmodium antigen: It can detect protozoa, so it can be used for clinical diagnosis of patients with current disease and investigation of infection source and examination effect. The main methods are agarose diffusion test, convective immunoelectrophoresis, enzyme-linked immunosorbent assay, direct fluorescence or enzyme immunostaining.

2, detection of Plasmodium antibodies: can be used in epidemiological investigations, trace the source of infection; to determine the prevalence of malaria by measuring the level of antibodies in the epidemic population; screening blood donors to prevent malaria transfusion infection, and assessing antimalarial measures The effect and so on. In addition, for multiple episodes and no cause identified, detection of malaria antibodies is helpful for diagnosis. Indirect fluorescent antibody test, indirect hemagglutination test, enzyme-linked immunosorbent assay, etc. are commonly used for detecting antibodies.

3. Nucleic acid probe detection: Several different nucleic acid probes have been used at home and abroad for the detection of Plasmodium. Due to its unique high specificity, sensitivity is higher than microscopic examination. It is considered that nucleic acid probe technology is very promising to replace conventional microscopy, and a large number of samples can be processed in batches in a short time. It has been considered to quantify and estimate malaria. The level of protozoa is a potential diagnostic tool for the investigation of malaria epidemiology and for evaluating the effectiveness of antimalarial measures. There are still some technical problems to be solved in the current mass production of nucleic acid probes and large-scale field use.

4. PCR detection: It is currently recognized that among various malaria detection methods, the sensitivity and specificity of the PCR method are the highest. In order to further improve the sensitivity and specificity of PCR technology, and to facilitate the promotion in practical work, on the basis of this, nested PCR (nested PCR), PCR-ELISA and other methods were studied. In addition to being able to directly detect Plasmodium in anticoagulant samples, PCR has also matured the detection of Plasmodium on filter paper dry blood droplets, which facilitates the use of PCR technology to monitor malaria in remote areas. Due to its high requirements on experimental techniques and conditions, it limits its application in the field. As for the current conditions of most malaria areas, after blood collection on site, it is necessary to return to a laboratory with better conditions for further analysis and treatment.

5. Dipstick method: At present, the World Health Organization recommends the application of the Dipstick method, which is based on the principle that Plasmodium falciparum can synthesize and secrete a stable water-soluble antigen, histidine rich protein II (HRPII), for its preparation. The monoclonal antibody was dropped on the immunochromatographic strip, and the presence of histone-rich protein II in the blood was detected by adsorption, washing and color development. According to foreign reports comparing Dipstick and several other methods, the sensitivity of Dipstick method for diagnosis of malaria (84.2% to 93.9%) and specificity (81.1% to 99.5%) are high; and it is easy to operate, fast, stable and easy to learn. Features, suitable for areas where microscopy or laboratory technology quality is difficult to guarantee, and the extent to which malaria is to be determined, malaria is low-spread, and drug abuse is needed to reduce resistance development. It must be pointed out that the application of the Dipstick method also has certain limitations. It is difficult to detect Plasmodium falciparum that is still in the latent period or contains only mature gametophytes in the blood.

Differential diagnosis

1, fever with chills: fever with chills refers to the pathological body temperature caused by the disease and accompanied by symptoms of chills.

2, high fever chills: most of the chills occurred before acute febrile illness. The pathogen of infectious diseases, when the body causes fever, the patient's body chills, goose bumps and tremors, that is, muscle involuntary activities, this is called aversion to cold, referred to as chills. The chill is the first sound of high fever. During the chill, the body temperature has risen. In the early stage when the fever is not too high, sometimes the patient has only a sense of chills in the body, and there is no shudder, which is called chills.

3, aversion to cold: aversion to cold, that is, fear of cold, chills. Symptoms of aversion to cold can appear in external evidence or yang deficiency. Exogenous aversion to cold, is due to the cold in the table, must have fever, headache, pulse floating and other evidence; yang deficiency and aversion to cold, visceral deficiency, yang deficiency, must see cold, pulse Shen and other cold syndrome. In addition, there are still hot and cold outside, although there are symptoms of aversion to cold, cold hands and feet, but the patient is thirsty, breathing, constipation, redness, and smoothness.

4, tremor: tremor is a regular and repeated involuntary body shake, can occur throughout the body, but with more limbs, the amplitude can be large or small, the speed can be fast or slow, generally between 1 per second Up to 10 times.

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