Cerebral Malaria

Introduction to cerebral malaria Malaria is a very old disease. As far back as the "Yellow Emperor's Internal Classics" in 2000 BC, there are special articles such as "Malaria" and "Stab", which discuss the causes, symptoms and treatments of malaria. The law is divided into "day work", "day work" and "three days work". However, it was not until 1880 that the Frenchman Laveran found malaria parasites in the serum of malaria patients; in 1897, the British Ross found the relationship between mosquitoes and malaria transmission, and its true cause was clarified. Cerebral malaria is a common and serious central nervous system infection. In developing countries, cerebral malaria is an important cause of death and neurological diseases. In developed countries, it is also found to have an increasing influence on tourists in the tropical regions. . The early detection of cerebral malaria is as important as early treatment. Despite the use of uniform clinical standards, modern medicine has achieved some results in elucidating different pathogenesis, but the pathophysiology of malaria remains controversial. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: mosquito bites Complications: hypoglycemia, renal failure, jaundice, pulmonary edema

Cerebral malaria

(1) Causes of the disease

Malaria is a disease caused by Plasmodium, the most common and serious parasitic infectious disease in the human central nervous system.

Introduction to the life history of Plasmodium:

Asexual reproduction

(1) Extracellular phase of red blood cells: sporozoites enter the human body with the saliva of Anopheles mosquitoes, invade the liver cells through the connection between liver cells and their surface proteins, and invade the hepatocytes to spread the plaques. After about 6 days, the schizont ruptures. , releasing tens of thousands of merozoites into the bloodstream.

(2) erythrocyte internal phase: merozoites invade red blood cells, possibly through the sialic acid residue on the blood cell glycoprotein on the surface of red blood cells, after invading red blood cells, the circular merozoites (circular bodies, also known as small physalis) begin to phagocytose Red blood cell contents (mainly hemoglobin); the small larvae of Plasmodium falciparum look like a pair of insulated earmuffs, with a peripheral cytoplasm in the periphery and a deep-dyed dumbbell-shaped chromatin in the center.

The by-products of hemoglobin breakdown are hemoglobin and globin. Hemoglobin contains a heme polymer linked by hydroxy acid salt. Dark brown pigment crystals appear in the secondary lysosomes of small trophies, marking its trophozoites. During the 48 h of this stage, the adhesion of erythrocytes infected by Plasmodium is gradually enhanced, because the ligand of Plasmodium adheres to the protein on the surface of red blood cells, and some of the strongly adherent red blood cells adhere to the endothelial cells. It causes a net increase in intravascular blood volume; a part of it adheres to other uninfected red blood cells to form a rosette; and a part of it adheres to other red blood cells infected by Plasmodium, that is, self-agglutination.

The schizont further develops, matures, divides, releases a new generation of merozoites into the bloodstream and reinfects the new red blood cells. In a patient without the immunity of the malaria parasite, after 10 to 20 successful invasion of red blood cells, each fission The body can divide up to 32 merozoites, and the malaria parasite continues to multiply in a logarithmic manner, with fever occurring in about 13 days, which is also the average clinical incubation period of malaria.

2. Sexual reproduction period

(1) During the developmental stage of the host, through several asexual reproduction cycles in red blood cells, some merozoites differentiate into gametophytes, and the gametophytes have male and female points. The gametophytes can survive in the bloodstream for several weeks until they are sucked by human blood. Anopheles devours.

(2) In the developmental stage of the mosquito: in the mosquito, the male gametophyte divides, the flagella grows, swims in the mosquito stomach, and the female gametophyte forms an immobile circular body. The male and female gametophyte fuse and mature and divide to form a zygote. When the zygote grows and can move, it is called zygote. The outer layer of the stomach wall of the zygote is developed into a capsule. The capsule zygote rapidly expands when thousands of sporozoites develop, the capsule ruptures, and the sporozoite enters the mosquito. In the parotid gland, when the mosquito sucks blood, the sporozoites are injected into the next host. The whole process is called sporulation. It takes at least 8 days. The exact time depends on the temperature of the surrounding environment and the type of mosquitoes.

(two) pathogenesis

1. Pathophysiological mechanism of cerebral malaria

As an infection of the central nervous system, cerebral malaria has many interesting features.

First, the mechanism of coma is still unclear. The pathological feature of cerebral malaria is that red blood cells infected by Plasmodium adhere to endothelial cells in the deep microvascular of the brain, but how to cause coma is still controversial.

Second, if the patient is rescued, the coma is usually completely reversible, especially in those without acquired malaria immunity, and the probability of residual neurological sequelae in these patients is 1%.

(1) Plasmodium cell adhesion and host "stacking" receptors: Red blood cells infected with Plasmodium falciparum can adhere to endothelial cells, which also exhibit other adhesion phenotypes, such as adhesion of uninfected red blood cells (formation of rose garlands) ), adhering to white blood cells and platelets, this adhesion is like self-aggregation between infected cells. Invitro studies show that cell adhesion is a specific receptor-mediated process, and a large variety of host molecules are recombinant proteins. Forms appear on the surface of endothelial cells, including: platelets (TSP), CD36, ICAM-1, VCAM-1, E-selectin, CD31, chondroitin sulfate A, and integrin 23BV, using immunohistochemistry Receptor studies have confirmed that this type of receptor is expressed in the brain of patients with cerebral malaria, and some receptors are upregulated. However, this receptor expression does not explain the specific brain receptor cohesion because of the same The body is also expressed in other vascular beds of the body. The up-regulation of accumulation receptors is due to systemic endothelial activation, not specifically occurring in cerebral malaria, when suffering from malaria. Other systemic vascular beds and other infectious diseases can emerge.

In cerebral malaria, whether or not the accumulation of malaria parasites can directly lead to coma is controversial. A study of 50 Vietnamese adults with severe malaria (with or without coma) confirmed survival time and duration of treatment. All taken into account, all CM patients showed brain accumulation, although many patients with brain PRBC accumulation did not appear coma until death, accumulation of coma for CM disease is necessary (essential), but not coma For all the reasons, some other scholars believe that stacking is only a side phenomenon. All symptoms of CM can be caused by soluble factors in the circulation, such as cell proliferation or oxides (Clark, 1991-1992). It is highly probable that After the accumulation of PRBC, a series of reactions are initiated, possibly including the release of soluble mediators from PRBC or host brain cells, which may directly lead to coma.

(2) Plasmodium adhesion ligands: Little is known about the adhesion of Plasmodium adhesion ligands to host endothelial cell accumulation receptors. In vitro experiments using micromanipulation to clone Plasmodium showed: for ICAM-1 and CD36 The adhesion is separate and independent, and the antigenic phenotype is compatible with the change of cell adhesion, indicating that the two phenotypes are composed of the same molecule. The bioadhesive study on the cell adhesion characteristics of laboratory isolates shows: Plasmodium falciparum erythrocytes Membrane protein-1 plays a role in the identification of a large gene family, the Var gene, in the P. falciparum gene pool, enabling the PFEMP-1 clone to be recently realized. A multi-gene family is randomly distributed in the P. falciparum gene pool, but Mainly concentrated in the granule expression region, they have several regions, including the Tamifi structural non-domains with similar structural sequences of Duffy's blood group antigen. The study of ligand structure sequences helps to elucidate the mechanism of cell adhesion phenotype differences. This cell adhesion phenotype differs depending on the species of the Plasmodium and their interaction with the host receptor.

(3) Endothelial activation of the blood-cerebrospinal fluid barrier: Whether from clinical or animal models, PRBC accumulation in brain microvessels is closely related to endothelial activation, and immunophenotypes are altered. Electron microscopy shows: endothelial cell culture It shows that these cells have obvious morphological changes, such as the phagocytosis of some red blood cells infected by Plasmodium. Although this phenomenon has not been found in humans, the more reasonable explanation is that the adhesion of PRBC to brain endothelial cells is like ICAM. The molecules of -1 and CD31 are likely to produce receptor-mediated cellular signals that cause changes in the structure and function of the blood-cerebrospinal fluid barrier. The adhesion of PRBC to brain endothelial cells may be of some significance, not only because of its impediment to blood flow. Role, and can lead to blood-cerebrospinal fluid barrier dysfunction, blood-cerebrospinal fluid barrier leakage and TNF- secretion associated with peripheral glial activation, can be seen in the mouse model of CM.

(4) Soluble neuroactive mediators: The rapid reversibility of malaria coma has led many authors to believe that the symptoms of CM may be caused by soluble, rapidly diffusing neurotransmitters, which may be the presence of malaria paratoxins, the release of host cell toxins caused by infection. , the release of local neural active mediators in the central nervous system, which can produce a fragmentary effect.

(5) TNF-: similar to severe sepsis, TNF-2 and other inflammatory procytotoxins are important hypothetical factors leading to multiple system organ failure in patients with severe malaria, hypotension, plasma of children in Africa Among them, the increase of TNF- level is closely related to the severity of the disease. Many other diseases, such as vivax malaria, plasma TNF- level is also high, but most of the clinically no coma, so simple systemic TNF - elevation is not the only cause of brain symptoms.

(6) Nitrogen oxides: Nitric oxide release from brain parenchyma has also been considered as a possible mechanism for cerebral malaria coma. However, studies on serum, cerebrospinal fluid nitric oxide metabolism have drawn conflicting conclusions, many The study found that plasma PNI (nitrogen intermediates) was positively correlated with the severity of the disease, while other studies found no association or even a negative correlation between the two, and the level in the cerebrospinal fluid did not have any useful value, if Nitric oxide plays a role in the etiology of cerebral malaria, which also acts locally, and is a relatively slow method for detecting cerebrospinal fluid and plasma with only nitric oxide metabolism levels.

(7) intracranial pressure, cerebral blood supply and cerebral edema: intracranial pressure in patients with malaria can be estimated by cerebrospinal fluid pressure or intracranial pressure when lumbar puncture, cyanotic fluid pressure of Southeast Asian adults suffering from CM does not rise, but in Africa The elevated levels of ICP in children are closely related to poor prognosis. Increased intracranial pressure may lead to a decrease in cerebral perfusion pressure, which in turn causes cytotoxic edema, which can cause brain dryness in African children. However, autopsy suggests that The incidence of brain dryness in Vietnamese patients is quite low. Imaging studies of adult patients in Southeast Asia also indicate that most patients have no cerebral edema. Therefore, ICP may be different in different populations with CM.

(8) Genetic polymorphism of host susceptibility and resistance to cerebral malaria: The host has genetic polymorphisms in susceptibility and resistance to cerebral malaria. The earliest described and understood best is hereditary erythrocyte disease. In the population of malaria endemic areas, the genetic code for these diseases has a higher mutation rate, and homozygous is a potentially harmful phenotype. Heterozygotes have certain advantages against Plasmodium infection. These hereditary red blood cells The diseases include: sickle cell anemia, hereditary leukocytosis and alpha, beta thalassemia. This polymorphism enhances the host's resistance and is believed to be due to reduced malaria parasite invasion and The ability to survive in red blood cells, many HLA alleles, especially HLA-B53 in Gambian children, have a protective effect on severe malaria, but this is not always the case, their pathophysiological significance is still not clear, recently The promoter region of the D cell gene has been found to be closely related to malaria polymorphism. In theory, this polymorphism can be altered by altering individual cytotoxins. The response has affected the disease. In addition, a polymorphism that can increase the incidence of cerebral malaria in Kenyan children has recently been confirmed. This polymorphism is located in the accumulation of receptors. Research on the genetic susceptibility of the host has just begun, but It shows a good development prospect. In the next few decades, this research will definitely promote the understanding of the physical and physiological physiology of severe malaria.

2. Histopathological features of cerebral malaria

Italy's Marchiafava and his research team began the pathology study of cerebral malaria in the late 19th century. Since then, a large number of research results have been published, although these studies are related in scale, degree (depth), clinical and pathological. There are differences in sexuality. The heterogeneity between the internal and the project of these research projects is an important obstacle to confirm the rational characteristics of cerebral malaria. Many common pathological features have been recognized, although their significance and etiology still exist. Controversy, with the application of the World Health Organization diagnostic criteria and new test methods (such as electron microscopy, immunohistochemistry and molecular biology), a large number of recent clinical pathology research has turned to the pathology of cerebral malaria.

(1) Infected red blood cell agglutination: The first to explain this agglutination process is the Marchiafava group. Compared with normal red blood cells, these infected red blood cells greatly increase the blood circulation resistance, and they gather in the peripheral part of the large blood vessels. Some capillaries slow blood flow or even stagnate completely.

After the autopsy of dead cerebral malaria patients, histological electron microscopy of brain tissue showed that the microvascular vessels of the brain were dilated due to the presence of a large number of infected red blood cells, and these red blood cells adhered to the endothelial cells of the brain through the surface nodule proteins. The reason for this phenomenon is that the red blood cells infected by the late trophozoites and schizonts selectively disappear from the normal circulation and accumulate in the microvessels of vital organs, which is related to the clinical cell adhesion phenomenon. It is PRBC that is mediated by receptors and adheres to endothelial cells.

Some studies have shown that coma in severe malaria is closely related to erythrocyte agglutination in cerebral microvessels, while other studies suggest that coma is not associated with erythrocyte agglutination. These studies did not take into account factors such as the duration of treatment before death. These factors can affect the histological observation of red blood cell agglutination.

(2) Pigmentation and phagocytosis: When the Plasmodium is sporulated, the residual erythrocyte membrane shell adheres to the endothelial cells of the brain, which contain malaria parasite residues that are not needed by the human body, such as malaria and malaria. The protozoa digests the broken material left by hemoglobin during development. When the red blood cells newly infected by the immature Plasmodium falciparum re-enter the blood circulation, pigmentation can be seen along the cerebral blood vessels, and the circulating monocytes phagocytose the red blood cell outer shell. And malaria pigment, malaria pigment is toxic and stimulates monocytes in vitro (such as stimulating TNF-). The malaria pigment left after PRBC rupture also has direct pathological and physiological effects on brain endothelial cells.

(3) Bleeding: Bleeding is a common pathological feature of the brain. The naked eye can observe many small spots on the brain tissue. These hemorrhages are usually located at the edge of the subcortical white matter. Histological examination shows that there are 3 types of bleeding: The first type is simple hemorrhage, which can be seen in cases such as carbon monoxide poisoning and barotrauma. The second type is ring hemorrhage, which is characterized by a central necrotic blood vessel surrounded by uninfected red blood cells. Further to the outside is PRBC and white blood cells; the third is Dürck granuloma, the center is a blood vessel, surrounded by microglia and astrocytes.

(4) cerebral edema and brain swelling: radiological evidence and intracranial pressure tests have shown that there are brain swelling in many patients with severe malaria, however, there is a lack of pathological basis for cerebral edema, such as around the ventricles, brain parenchyma and cells Internal edema, autopsy of adult malaria patients in Vietnam showed no extensive cell edema, increased brain stem or brain weight, and other data from African children also showed no brain edema, an ongoing study on children in Malawi The study showed cerebral edema, so there are some differences between different populations. The incidence of brain swelling in children is significantly higher than that in adults. It may be that there is a difference in the regulation of cerebrovascular or the maintenance of blood-cerebrospinal fluid barrier. The question is: whether brain swelling and increased intracranial pressure mean cerebral edema, and accumulation of PRBC in the blood vessels may cause an increase in brain volume. However, one thing is certain, patients who die due to cerebral malaria can Brain edema was found.

(5) Inflammatory response of leukocytes and astrocytes: The observation of leukocytes in the vasculature of brains of patients with cerebral malaria varies, and many studies suggest that the appearance of white blood cells is a common pathological feature, and several scholars even believe that They elucidated the pathophysiological mechanisms of endothelial cell damage. Data from animal model mice indicate that mice with cerebral malaria do have intravascular leukocyte accumulation, followed by cell proliferation before the inflammatory response, possibly in the pathology of malaria. The main role, in addition to leukocyte extravasation around the bleeding area, white blood cells themselves migrate to the human brain is not a pathological feature of human brain malaria.

It has been suggested that the proliferative response of leukocytes or astrocytes in the circulation before the inflammatory response significantly contributes to the pathological process of murine malaria, which is similar to encephalitis. There is evidence that cerebral malaria is present in Vietnam. In patients, there is activation of brain endothelial cells, local destruction of blood-cerebrospinal fluid barrier protein, and associated peripheral blood macrophage activation. Activation of peripheral blood macrophages may reflect dysfunction of the blood-cerebrospinal fluid barrier. This change occurs in the murine malaria model. However, there is a big difference between murine malaria and human malaria, especially the agglutination of uninfected red blood cells in the brain. The animal model of mice provides a pathophysiological mechanism for studying human diseases. Convenient, but not fully accurate to reflect human disease.

(6) Neuronal toxicity and neuronal degeneration: There are few reports on neuronal degeneration in cerebral malaria, and despite PRBC agglutination, it is surprising that extensive neuronal ischemia or endothelial cell damage is not common, Marchuafava And Bignami has reported chromatin lysis in brain cells to explain clinically prominent cases of brainstem symptoms. Rigdon has reported a decrease in Purkin je cells and local degeneration of brain tissue in the cerebellum. Invitro's research also indicates In vivo, antibodies in circulating cerebral malaria can inhibit the growth of Purkinje cells in vitro. Recently, most of the studies have been the potential role of excitotoxic neurotransmitters from the Kynenrinime channel, which can cause coma in the mouse malaria model. Currently, neuronal death is mainly studied through reperfusion injury, release of excitotoxic neurotransmitters, and apoptosis. With the deepening of this study, the role of neuronal toxicity in the pathogenesis of human cerebral malaria will be more The more clear you are.

(7) Bone marrow, kidney, gastrointestinal, lung, heart, adrenal gland, etc. have different degrees of phagocytic proliferation, and can be seen phagocytic with red blood cells and malaria pigments containing Plasmodium, capillaries contain red blood cells containing Plasmodium, and even Microvascular obstruction, endothelial shedding, degeneration and necrosis.

Cerebral malaria prevention

To control and prevent malaria, we must conscientiously implement the prevention-oriented health work policy, and take comprehensive prevention measures against the three basic links of the malaria epidemic.

1. Manage the source of infection

Timely detection of malaria patients, registration, management and follow-up observation, as soon as possible to control and cure the disease; patients with worms for rest or anti-relapse treatment, usually in the spring or 1 month before the peak of the epidemic Anyone who has a history of malaria within two years and who has a Plasmodium or splenomegaly in the blood should be treated. In an infected area with a high incidence, consider treating children under 15 or all residents.

2. Cut off the route of transmission

In the mosquito season, the mosquito nets are used correctly, and the mosquitoes and anti-mosquito devices are used for outdoor duty. In addition to the large-scale application of mosquito killers, the most important thing is to eliminate stagnant water and eradicate mosquito breeding sites.

3. Protect susceptible people

(1) Medication prevention: entering the malaria area, especially in the epidemic season, it is necessary to take medication in high malaria areas. Generally, it takes 2 weeks before entering the malaria area and continues to leave the malaria area for 6-8 weeks. The following drugs can be used according to the conditions. Use.

1 pyrimethamine: 4 tablets once a week, or 8 tablets once every two weeks, long-term use can cause giant cell anemia, can also produce tolerance, (ethylpyrimidine each 6.25mg).

2 piperaquine or piperaquine phosphate: 0.6 g of the substrate, once every 20 to 30 days, can also be used in the chloroquine-resistant area.

3 compound antimalarial drugs: antimalarial tablets No. 1, containing ampicillin 20mg, dapsone 100mg, 1 tablet per day for the first and second days, 1 tablet per week, antimalarial tablets 2, each containing pyrimethamine 17.5mg, sulfadoxine (perfume sulfonamide) 250mg, 2 tablets per day for the first and second days, 2 tablets every 10 days thereafter, anti-malaria tablets No. 3, containing piperaquine phosphate 250mg, sulfadoxine 50mg, once a month 4 tablets at a time.

2 tablets of chloroquine, once every 10 days, those who receive blood transfusion can take chloroquine daily (1 tablet) matrix 0.15g, and even served for 3 to 5 days.

Taking preventive drugs may cause some side effects, such as dizziness, dizziness, nausea, vomiting, etc., so severe liver, heart, kidney disease and pregnant women should be used with caution or hanged, in order to prevent the emergence of drug-resistant strains, change once every 3 months drug.

(2) Autoimmune: The vaccine is being researched and tested.

Cerebral malaria complications Complications hypoglycemia renal failure jaundice pulmonary edema

Hypoglycemia

Patients with falciparum malaria often have hypoglycemia, and the prognosis is poor. Hypoglycemia may be caused by the disease itself. It may also be a side effect of anti-malarial treatment with quinine or quinidine. The clinical manifestations of hypoglycemia are sometimes atypical, and they are mistaken. The clinical features of falciparum malaria, such as sweating, anxiety, confusion, coma, if clinically suspected hypoglycemia, and can not immediately get blood glucose measurements, should immediately give 50% glucose for experimental treatment, if hypoglycemia does exist Then, this experimental treatment will significantly improve the symptoms.

2. Acidosis

The pathophysiology and prognosis of metabolic acidosis in patients with falciparum malaria have only recently received attention. The respiratory distress syndrome in children with falciparum malaria in Africa has not been recognized before or is incorrectly attributed to severe anemia ( Followed by heart failure), it is now believed that it is mainly caused by lactic acid accumulation in the body and renal reabsorption of bicarbonate barrier.

Renal reabsorption of bicarbonate is common in patients with severe malaria. In addition, blood volume reduction and anemia are also associated with lactic acidosis. Previously, patients with cerebral malaria with elevated cerebrospinal fluid lactate have a poor prognosis, but clinical This is not the case, because metabolic acidosis can involve the brain or not.

3. Severe anemia

Anemia is a common symptom of falciparum malaria. Malaria is a infection of red blood cells by malaria parasites. Anemia is an inevitable result. If anemia is particularly significant, anemia itself can also be regarded as a diagnostic criterion for severe malaria, which is included in Kenya hospital for malaria. Among the 2,433 children, the incidence of severe anemia (Hb < 5 g / dl) was 29%, and the mortality rate was 18%, which was higher than the overall mortality rate of 8%.

Severe anemia, such as respiratory distress, will be particularly severe. Among Vietnamese adults hospitalized for severe malaria, the incidence of severe anemia is 16%, and 90% of patients with severe anemia are associated with at least one type of severe malaria. Other symptoms, and severe anemia itself can not be used as a effective indicator of poor prognosis.

4. Renal failure

There are many forms of kidney damage in malaria patients, the most important of which is "acute tubular necrosis syndrome", which is similar to kidney damage in sepsis. Renal failure is most common in patients without malaria immunity. Occasionally, black urine is hot.

Among patients without malaria immunity, the incidence of acute renal failure (ARF) is high. Of the 560 severely infected adult malaria patients hospitalized, 158 (28%) had renal failure at admission, 41%. Patients with renal failure at different stages of the disease, and finally 14% of patients need dialysis treatment, patients with renal failure at admission, the mortality rate is higher (29% of patients with renal failure, no renal failure The patient was 9.2%), which is significantly different from African children with severe malaria, whose renal dysfunction is usually subclinical and the vast majority do not require dialysis.

The initial manifestations of patients with renal failure are oliguria or anuria, often accompanied by jaundice and lactic acidosis, often requiring immediate or early dialysis. When the acute stage of malaria occurs, such as renal failure, mostly non-urinary renal failure, There is little need for dialysis treatment. For example, this group of patients needs dialysis. The indications are often not hyperkalemia or water retention, but uremia or non-lactic acidosis.

The clinical features of acute renal failure in malaria patients are very similar to the "acute tubular necrosis" syndrome caused by bacterial sepsis or hypovolemia, indicating that the pathological processes may be the same, from several malaria patients with renal failure. Renal biopsy taken on the body showed that the pathological changes of the renal tubules were consistent with ATN and also supported the above inference, while glomerulonephritis was rarely reported.

5. Black urine heat

The clinical features of black urine fever are fever, massive intravascular hemolysis and hemoglobinuria, which can lead to acute renal failure in severe cases. Its exact cause is unclear. No single cause can explain all cases of black urine fever. It is known that black urine fever occurs only in tropical malaria endemic areas and is associated with malaria parasite infection, quinine and glucose-phosphate dehydrogenase deficiency, but how these factors lead to hemolysis is still unclear. Previously, black urine fever It was the leading cause of kidney failure and death in malaria patients and is now rarely seen.

6. Huang Wei

Astragalus is also very common with ARF. Astragalus is associated with renal failure, cerebral malaria, and severe parasiticemia. It is caused by a combination of hemolysis and mild liver function abnormalities. Patients do not have flutter-like tremors. Severe liver dysfunction and hepatic encephalopathy, serum transaminase may increase, liver function decline may lead to lactic acidosis.

7. Pulmonary edema

Pulmonary edema is a serious complication of severe malaria. It is common in pregnant women. If there is no mechanical ventilation device, pulmonary edema often causes death. From a clinical point of view, it is similar to adult respiratory distress syndrome, although fluid excess can promote pulmonary edema, but the patient's Central venous pressure and pulmonary artery pressure are usually normal.

8. Hemodynamic shock (cold malaria)

Hemodynamic shock is a serious complication of severe malaria.

Like bacterial sepsis, it is characterized by decreased systemic vascular tone and increased or normal cardiac output. Shock is usually caused by other serious malaria complications, often accompanied by elevated plasma lactate levels and metabolic acidosis. The prognosis is poor, occasionally accompanied by bacterial sepsis, but blood cultures are usually sterile.

9. Hemostatic function is abnormal

The risk of bleeding in patients with severe malaria increases, especially when multiple systemic dysfunction occurs, nosebleeds, bleeding gums and even more severe upper gastrointestinal bleeding can occur, but life-threatening bleeding is rare.

Platelet reduction is common in malaria patients, but platelets are rarely less than 25,000/l, and laboratory tests for disseminated intravascular coagulation are usually normal unless they are associated with particularly severe disease.

Symptoms of cerebral malaria Common symptoms Abdominal discomfort Diarrhea Irritability Low blood pressure Deep coma Anorexia Fatigue High heat consciousness disorder Cold and hot alternation

Uncomplicated malaria

The clinical manifestations of uncomplicated falciparum malaria are very similar to those of the other three benign human malaria. At first, the symptoms may even be milder than that of vivax malaria. The symptoms are headache, myalgia, fatigue, irritability, after 24 to 48 hours. Fever, fever is usually accompanied by chills, chills, occasionally accompanied by chills and stiffness, headache, myalgia will increase, and anorexia, rarely seen in the typical Plasmodium falciparum infection, occasionally the highest body temperature Can be more than 39%, although there is no obvious abnormality in lung function tests, but respiratory symptoms such as cough, shortness of breath, etc., liver, splenomegaly, mild abdominal discomfort, nausea, vomiting, diarrhea, constipation are also common, malaria infection The complex clinical symptoms are not specific and are not very helpful for diagnosis. Any patient who lives in or has been in an epidemic area and has a fever alone should be highly suspected of malaria until clinically confirmed as other diseases.

In different regions and populations, the proportion of acute malaria infections that develop into severe malaria is different. This proportion is seriously affected by antimalarial treatment. It is estimated that among malaria children, the proportion of acute malaria infections that develop severe malaria is about 1%. Among adults in Thailand, the mortality rate of malaria is 1%.

2. Comparison of adults and children

Severe malaria studies have been reported in two groups of African children and non-malaria-immune Southeast Asian adults, with significant clinical differences between the two groups.

3. Brain malaria

Causes of conscious damage caused by severe malaria include: forms of seizures, hypoglycemia, severe acidosis, and hypotension (shock). Non-brain causes of coma can worsen cerebral malaria. In clinical work, any patient is confirmed to have Plasmodium falciparum infection and damage to consciousness or other brain dysfunction should be considered as critically ill patients, and immediate antimalarial treatment should be performed with special supervision.

(1) adult cerebral malaria: usually manifested as diffuse, symmetrical encephalopathy, can be induced by epileptic seizures, can also gradually develop within a few hours, a strict definition of cerebral malaria requirements: in the peripheral blood Plasmodium falciparum found in the asexual reproduction stage, the coma after seizure lasted for at least 30 minutes, and excluded other causes of encephalopathy (such as bacterial meningitis, viral encephalopathy), hypoglycemia should also be excluded, can not be The awakening coma has the following two requirements: one is the GCS (Glasgow's coma scale) score in the exercise score 3 (misorientation), the second is the language score 2 (the meaning of the sound is completely incomprehensible), and the blink score in the GCS It is of little significance, because in patients with cerebral malaria, although the patient is in a deep coma, the eyes are open, and the signs of the focal nervous system are common. Despite the mild neck stiffness, the significant falsehood caused by bacterial meningitis. Characteristics of meningitis: photophobia, high neck stiffness, pupil reflex to light, corneal reflex, eye-head, eye-vestibular reflex, and convergent reflex often Primitive reflexes such as pout reflexes may occur, mandibular reflexes are usually active, and overall muscle tension may increase, sputum sputum is easily induced, symmetry sputum reflexes are active, hypotonia is occasionally seen, abdominal wall reflexes usually disappear In critically ill patients, go to the brain tonic (extremity of the extremities), cortical rigidity (upper limb flexion, lower extremity straightening) can occur spontaneously (in the case of concurrent hypoglycemia), can also be induced by noxious stimulation.

In adults without malaria immunity, the incidence of convulsions is less than that of children, about 20% of cerebral malaria is convulsed, and patients with unconscious disorders rarely have convulsions, and convulsions are not associated with hypoglycemia.

In adult patients, coma usually lasts 1 to 5 days (average 2 days), but occasionally it lasts for 2 weeks. Most adults with cerebral malaria do not have significant neurological abnormalities after waking up from a coma.

(2) Children's cerebral malaria: Children's cerebral malaria is strictly defined as: the ability to lose the ability to locate pain stimuli. This test is not suitable for children of very young age, although the Blantyre coma score is not accurate, but clinically Commonly used, strictly defined cerebral malaria score 2/5, longer children can be assessed with adult GSC, for children, other causes of disturbance of consciousness should also be considered, such as convulsions (compared to general benign convulsions) There is a longer period of attack), hypoglycemia (in the early stage, good response to intravenous glucose) and taking sedatives. For scientific research, the definition of exact cerebral malaria is important, but in actual clinical work, any Children with malaria who are prone to collapse (with or without disturbance of consciousness) should be treated according to severe malaria. The so-called collapse is that you can't sit still without help, while the normal peers can sit still and collapse in the clinic. Easy to identify, requiring urgent treatment, for cerebral malaria, from fever to coma, African children are generally 48h, which is shorter than adults without malaria immunity They should wake up faster, usually 2 to 3 days. In patients with deep coma, abnormal parasitic reflexes, increased or decreased whole body muscle tone, cortical or denervation and angular arch reversal may occur. The brain is dry, followed by brain stem signs, and the patient may die.

In African children with malaria, convulsions are the most common clinical manifestation of the nervous system. More than 70% of children with cerebral malaria have convulsions. Convulsions can occur as part of cerebral malaria, or they can appear alone. Crawley is in The study pointed out that children with cerebral malaria developed epilepsy and then received hospitalization. Among them, 25% of children had an electroencephalogram showing a recessive status epilepticus. These children have various clinical manifestations of seizures, such as no Regular breathing patterns, nystagmus, slight twitching of fingers and mouth, seizures in these children are quickly terminated after taking anticonvulsant drugs, and epilepsy is common in children with unconscious disturbances of falciparum malaria, especially under 3 years of age. The crowd, some of which are seizures, are febrile seizures.

(3) Nervous system sequelae: Although some children with cerebral malaria survived, they have residual neurological sequelae, such as ataxia, cortical blindness and hemiplegia, which have become a huge burden on human society. These sequelae are often deep coma with long-term coma. The recurrent episodes of convulsions are associated with hypoglycemia. The incidence of neurological complications may be above 20%, but the rate drops to <5% after 6 months of illness. Does the mild neuropsychiatric sequela persist? Different claims are still unclear whether cerebral malaria has a long-term impact on children's psychosocial and intellectual development.

(4) Other nervous system manifestations: The nervous system manifestations of falciparum malaria are not only coma, seizures, neurological sequelae, but also a self-limiting post-malaria neurological syndrome in adults in Vietnam. For acute disturbance of consciousness, insanity, seizures or tremors, a study showed that from the clearance of Plasmodium to the onset of neurological symptoms, the average duration of 96h (6h ~ 60 days), this syndrome in all patients with falciparum malaria The incidence rate is 0.12%, which is usually 300 times more likely to cause severe illness than uncomplicated malaria. A randomized trial has shown that this syndrome is more likely to occur in patients treated with metformin for antimalarial therapy. Patients treated with quinine and sulfadoxine/pyrimethamine are not common.

Examination of cerebral malaria

Blood picture

Red blood cells and hemoglobin decreased after multiple episodes, and falciparum malaria was particularly heavy; the total number of white blood cells increased slightly after initial onset, and then normal or slightly lower, leukocyte-classified monocytes often increased, and phagocytosis of malaria pigment particles.

2. Plasmodium inspection

(1) Blood smear: Peripheral blood smear is the most sensitive and specific test method. This method is to count the infected red blood cells on the peripheral blood smear with a microscope. The peripheral blood smear is improved. Treated by Musa staining or reversed Fide staining, if the smear is fixed with alcohol prior to staining, Plasmodium is found in intact red blood cells, and the percentage of infected red blood cells is used to indicate the smear count, as described above. For the grinding method, the thicker blood smear can be directly stained, the red blood cells are dissolved, leaving only the visible Plasmodium and white blood cell nucleus. This is the so-called slab method, using Plasmodium associated with every 200 or 400 white blood cells. The number is used to indicate its count, the sheet method is easy to read and the slab method is more sensitive.

If the patient has been treated for antimalarial treatment before or during the infection with Plasmodium, his blood smear may begin to be negative. If the clinical suspected malaria infection, the blood smear should be repeated, with no symptoms and signs of severe malaria. Patients with acquired immunity should be diagnosed with severe falciparum malaria if they develop a fragment of Plasmodium pigment in their circulating white cytoplasm at low magnification.

(2) Myeloid smear staining for Plasmodium, the positive rate is higher than that of blood.

3. Serological examination

Antimalarial antibodies usually appear 2 to 3 weeks after infection, peak at 4 to 8 weeks, and then gradually decline. Indirect immunofluorescence, indirect hemagglutination and enzyme-linked immunosorbent assays have been applied, and the positive rate is up to 90%. It is generally used for epidemiological examinations.

Recently, there have been many methods for rapid diagnosis of Plasmodium infection. The first one is based on acridine orange fluorescence technology, which is improved and applied to clinical quantitative naked clothing (OBC) technology. The latest is the infiltration tablet method. The method is to determine the malaria parasite lactate dehydrogenase, the latter method can detect the malaria parasite and distinguish its species, and the former method is specific to Plasmodium falciparum, neither of which is sensitive to the thick slice method, but undoubtedly these two The methods will play a role in the laboratories of European and American countries where malaria is not common.

4. The role of lumbar puncture in cerebral malaria

Due to the pathophysiological consequences of increased intracranial pressure in patients with cerebral malaria (especially in children), it is controversial whether to perform lumbar puncture in the early stages of malaria patients.

For any patient with a conscious disorder (or seizures in children under the age of one), lumbar puncture is critical for the exclusion of bacterial meningitis. Some people worry that for children with brain swelling, lumbar puncture can induce cerebral palsy, which is a theory. Concerns, but not confirmed, and imaging studies show that most children and adults with cerebral malaria do not have cerebral edema, there is no evidence that elevated intracranial pressure in adult patients plays a major role in disease development Waist wear is often considered a safe means of examination. It is very important that all patients' antimalarial treatment should not be delayed by the waist.

CT, MRI examination helps to differentiate the diagnosis.

Diagnosis and diagnosis of cerebral malaria

diagnosis

1. Epidemiology: There is a history of living or traveling in a malaria endemic area, a history of malaria episodes in recent years, or a fever patient who has recently received a blood transfusion.

2. Cerebral malaria: occurs more frequently in the epidemic period, more acute, high fever, chills, convulsions, convulsions, etc., infants and young children in the epidemic area suddenly have high fever, chills, coma, should also consider this disease.

3. Laboratory examination: mainly to find malaria parasites, usually found to be diagnosed, blood tablets to find malaria parasites should be collected in the cold war, the number of protozoa at this time, easy to find, should be repeated multiple times when needed, and must Look for thick blood tablets.

If the clinical high degree of suspicion and the blood film is negative, the bone marrow puncture smear can be used to find the malaria parasite.

4. Therapeutic diagnosis:

The clinical manifestations are very similar to malaria, but after several examinations, no Plasmodium was found. Try to kill the red endogenous protozoa (such as chloroquine), and treat the 48h fever control, which may be malaria.

Patients with conscious disturbances or seizures who have lived in malaria-endemic areas should be suspected of having cerebral malaria, regardless of whether they have taken anti-malarial drugs prophylactically, malaria can also be transmitted by means other than tattoo bites. Such as blood transfusion, contaminated needles or organ transplants, etc., without considering this, may delay the diagnosis, this delay is very dangerous.

If a critically ill patient is highly suspected of having malaria and the first smear is negative, diagnostic treatment for antimalarial disease must be performed empirically.

Differential diagnosis

Malaria is high fever, heat-type retention or relaxation, similar to sepsis, but severe symptoms of sepsis systemic poisoning; focal inflammation or metastatic suppurative lesions; total white blood cells and neutrophils; blood culture can have pathogen growth.

Cerebral malaria is easily confused with epidemic encephalitis, toxic dysentery, and heatstroke. It is usually necessary to carefully search for malaria parasites. Toxic dysentery should also be done in the form of feces, culture, and sometimes unclear treatment with antimalarial drugs. To wait for the result.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.