Symptoms of malaria in adults. Pathogenesis and clinical manifestations of malaria Signs of infection with malaria
Malaria causes about 350-500 million infections and about 1.3-3 million deaths in humans every year. Sub-Saharan Africa accounts for 85-90% of these cases, with the vast majority affecting children under 5 years of age. The death rate is expected to double over the next 20 years.
The first chronicle evidence of a fever caused by malaria was found in China. They date back to around 2700 BC. e., during the Xia Dynasty.
What provokes / Causes of Malaria:
The causative agents of malaria are the protozoa of the genus Plasmodium (Plasmodium). Four species of this genus are pathogenic for humans: P.vivax, P.ovale, P.malariae and P.falciparum In recent years, it has been established that a fifth species, Plasmodium knowlesi, also causes malaria in humans in Southeast Asia. A person becomes infected with them at the time of inoculation (injection) by a female malarial mosquito of one of the stages of the life cycle of the pathogen (the so-called sporozoites) into the blood or lymphatic system, which occurs during blood sucking.
After a short stay in the blood, the sporozoites of the malarial plasmodium penetrate into the hepatocytes of the liver, thereby giving rise to the preclinical hepatic (exoerythrocytic) stage of the disease. In a process of asexual reproduction called schizogony, from 2,000 to 40,000 hepatic merozoites, or schizonts, are eventually formed from one sporozoite. In most cases, these daughter merozoites re-enter the blood after 1-6 weeks. In infections caused by some North African strains of P. vivax, the primary release of merozoites from the liver into the blood occurs approximately 10 months after infection, coinciding with a short period of mass breeding of mosquitoes in the following year.
The erythrocyte, or clinical, stage of malaria begins with the attachment of merozoites that have entered the bloodstream to specific receptors on the surface of the erythrocyte membrane. These receptors, which serve as targets for infection, appear to be different for different species of malarial plasmodia.
Epidemiology of malaria
Under natural conditions, malaria is a naturally endemic, protozoal, anthroponotic, transmissible infection.
The causative agents of malaria find hosts in various representatives of the animal world (monkeys, rodents, etc.), but as a zoonotic infection, malaria is extremely rare.
There are three ways of contracting malaria: transmissible, parenteral (syringe, post-transfusion) and vertical (transplacental).
The main transmission route is transmissive. Human malaria vectors are female mosquitoes of the genus Anopheles. Males feed on the nectar of flowers.
The main vectors of malaria in Ukraine:
an. messae, An. maculipennis, An. atroparvus, An. Sacharovi, An. superpictus, An. pulcherrimus and others.
The life cycle of mosquitoes consists of a number of stages: egg - larva (I - IV age) - pupa - imago. Fertilized females attack a person in the evening or at night and feed on blood. In females that are not fed with blood, eggs do not develop. Blood-fed females remain in the dark corners of residential or utility rooms, thickets of vegetation until the end of the digestion of blood and the maturation of eggs. The higher the air temperature, the faster the development of eggs in the body of the female is completed - (gonotrophic cycle): at a temperature of + 30 ° C - up to 2 days, at + 15 ° C - up to 7 in P. vivax. Then they rush to the reservoir, where they lay their eggs. Such reservoirs are called anophelogenic.
The maturation of the aquatic stages of vector development also depends on temperature and lasts 2-4 weeks. At temperatures below +10°C, mosquitoes do not develop. During the warm season of the year, up to 3-4 generations of mosquitoes may appear in the middle latitudes, 6-8 in the south, and up to 10-12 in the tropics.
For sporogony, a temperature of at least + 16 ° C is required. Sporogony of P. vivax at +16°C is completed in 45 days, at +30°C - in 6.5 days. The minimum temperature for P. falciparum sporogony is +19 - 20°C, at which it is completed in 26 days, at +30°C - in 8 days.
The season for malaria transmission depends on this. In the tropics, the malaria transmission season reaches 8-10 months, in the countries of equatorial Africa it is year-round.
In temperate and subtropical climate zones, the malaria transmission season is limited to the summer-autumn months and lasts from 2 to 7 months.
In wintering mosquitoes, sporozoites die; therefore, females that hatch in the spring are not carriers of malarial plasmodia, and in each new season, mosquitoes are infected from malaria patients.
Perhaps intrauterine infection of the fetus through the placenta in the presence of infection in a pregnant mother, but more often this occurs during childbirth.
With these forms of infection, schizont malaria develops, in which there is no phase of tissue schizogony.
Susceptibility to malaria is universal. Only representatives of the Negroid race are immune to P. vivax.
The spread of malaria is determined by geographical, climatic and social factors. The boundaries of distribution are 60 - 64 ° north latitude and 30 ° south latitude. However, the species range of malaria is uneven. P. vivax, the causative agent of three-day malaria, has the widest range, the distribution of which is determined by geographic boundaries.
Tropical malaria has a smaller range because P. falciparum requires higher temperatures to develop. It is limited to 45° - 50° N. sh. and 20°S sh. Africa is the world's hotbed of tropical malaria.
The second place in distribution in Africa is occupied by four-day malaria, the range of which reaches 53 ° N. sh. and 29°S sh. and which has a focal, nesting character.
P. ovale is found mainly in the countries of West and Central Africa and on some islands of Oceania (New Guinea, Philippines, Thailand, etc.).
In Ukraine, malaria has been practically eliminated and mainly imported malaria and isolated cases of local infection are recorded - secondary from imported ones.
Malaria is imported to the territory of Ukraine from tropical countries and from neighboring countries - Azerbaijan and Tajikistan, where there are residual foci.
The largest part of imported cases is three-day malaria, which is the most dangerous due to possible transmission by mosquitoes sensitive to this type of pathogen. In second place is the importation of tropical malaria, the most severe clinically, but less dangerous epidemiologically, since Ukrainian mosquitoes are not sensitive to P. falciparum imported from Africa.
Cases of importation with an unidentified cause of infection are registered - “airport”, “baggage”, “accidental”, “transfusion” malaria.
The WHO European Office, due to the political and economic instability in the world, the growth of migration and the implementation of large-scale irrigation projects, highlights malaria as a priority problem due to the possibility of a return of the infection.
Under the influence of these factors, the formation of new foci of malaria, i.e., settlements with adjacent anophelogenic reservoirs, is possible.
In accordance with the WHO classification, 5 types of malaria foci are distinguished:
pseudo-focus - the presence of imported cases, but there are no conditions for the transmission of malaria;
potential - the presence of imported cases and there are conditions for the transmission of malaria;
active new - emergence of cases of local infection, transmission of malaria has occurred;
active persistent - the presence of cases of local infection for three years or more without interruption of transmission;
inactive - malaria transmission has ceased, there have been no cases of local infection during the last two years.
An indicator of the intensity of the risk of contracting malaria according to the WHO classification is the splenic index in children from 2 to 9 years old. According to this classification, 4 degrees of endemia are distinguished:
1. Hypoendemia - splenic index in children from 2 to 9 years old up to 10%.
2. Mesoendemia - splenic index in children from 2 to 9 years old is 11 - 50%.
3. Hyperendemia - the splenic index in children from 2 to 9 years old is above 50% and high in adults.
4. Holoendemia - the splenic index in children from 2 to 9 years old is constantly above 50%, the splenic index in adults is low (African type) or high (New Guinean type).
Pathogenesis (what happens?) during Malaria:
According to the method of infection, sporozoite and schizont malaria are distinguished. Sporozoite infection- This is a natural infection through a mosquito, with the saliva of which sporozoites enter the human body. In this case, the pathogen passes through the tissue (in hepatocytes), and then the erythrocyte phase of schizogony.
Schizont malaria due to the introduction of ready-made schizonts into the human blood (hemotherapy, syringe malaria), therefore, unlike sporozoite infection, there is no tissue phase here, which determines the features of the clinic and treatment of this form of the disease.
The immediate cause of attacks of malarial fever is the entry into the blood during the breakdown of morula merozoites, which are a foreign protein, malarial pigment, hemoglobin, potassium salts, erythrocyte residues, which change the specific reactivity of the body and, acting on the heat-regulating center, cause a temperature reaction. The development of a fever attack in each case depends not only on the dose of the pathogen (“pyrogenic threshold”), but also on the reactivity of the human body. The alternation of fever attacks characteristic of malaria is due to the duration and cyclicity of the erythrocyte schizogony of the leading generation of plasmodia of one species or another.
Alien substances circulating in the blood irritate the reticular cells of the spleen and liver, cause their hyperplasia, and with a long course - the growth of connective tissue. Increased blood supply to these organs leads to their increase and soreness.
Important in the pathogenesis of malaria is the sensitization of the body by a foreign protein and the development of autoimmunopathological reactions. The breakdown of erythrocytes in erythrocyte schizogony, hemolysis as a result of the formation of autoantibodies, increased phagocytosis of erythrocytes of the reticuloendothelial system of the spleen are the cause of anemia.
Relapses are typical for malaria. The reason for the near relapses in the first 3 months after the end of the primary acute symptoms is the preservation of a part of erythrocyte schizonts, which, due to a decrease in immunity, begin to actively multiply again. Late or distant relapses, characteristic of three-day and oval malaria (after 6-14 months), are associated with the completion of the development of bradysporozoites.
Symptoms of Malaria:
All clinical manifestations of malaria are associated only with erythrocyte schizogony.
There are 4 specific forms of malaria: three-day, oval-malaria, four-day and tropical.
Each species form has its own characteristics. However, fever attacks, splenohepatomegaly and anemia are typical for all.
Malaria is a polycyclic infection, in its course there are 4 periods: the period of incubation (primary latent), primary acute manifestations, secondary latent and relapse period. The duration of the incubation period depends on the type and strain of the pathogen. At the end of the incubation period, symptoms appear - precursors, prodromes: weakness, muscle, headache, chilling, etc. The second period is characterized by recurring attacks of fever, for which a staging development is typical - a change in the stages of chills, heat and sweat. During the chill, which lasts from 30 minutes. up to 2 - 3 hours, the body temperature rises, the patient cannot warm up, the extremities are cyanotic and cold, the pulse is rapid, breathing is shallow, blood pressure is elevated. By the end of this period, the patient warms up, the temperature reaches 39 - 41 ° C, a period of fever sets in: the face turns red, the skin becomes hot and dry, the patient is excited, restless, headache, delirium, confusion, sometimes convulsions. At the end of this period, the temperature drops rapidly, which is accompanied by profuse sweating. The patient calms down, falls asleep, a period of apyrexia begins. However, then the attacks are repeated with a certain cyclicity, depending on the type of pathogen. In some cases, the initial (initial) fever is irregular or permanent.
Against the background of attacks, the spleen and liver increase, anemia develops, all body systems suffer: cardiovascular (myocardial dystrophic disorders), nervous (neuralgia, neuritis, sweating, chilliness, migraine), genitourinary (symptoms of nephritis), hematopoietic (hypochromic anemia, leukopenia, neutropenia, lymphomonocytosis, thrombocytopenia), etc. After 10-12 or more attacks, the infection gradually subsides, and a secondary latent period sets in. With incorrect or ineffective treatment, a few weeks or months later, short-term (3 months), late or distant (6-9 months) relapses occur.
Three day malaria. The duration of the incubation period: minimum - 10 - 20 days, in case of infection with bradysporozoites - 6 - 12 months or more.
Characterized by prodromal phenomena at the end of incubation. A few days before the onset of attacks, chilling, headache, back pain, fatigue, nausea appear. The disease begins acutely. The first 5-7 days of fever may be of an irregular nature (initial), then an intermittent type of fever is established with a typical alternation of attacks every other day. For an attack, a clear change in the stages of chills, heat and sweat is characteristic. The heat period lasts 2-6 hours, less often 12 hours and is replaced by a period of sweating. Attacks usually occur in the morning. The spleen and liver after 2-3 temperature paroxysms increase, are sensitive to palpation. On the 2nd - 3rd week moderate anemia develops. This species form is characterized by near and distant relapses. The total duration of the disease is 2-3 years.
Malaria oval. In many clinical and pathogenetic features, it is similar to three-day malaria, but differs in a milder course. The minimum incubation period is 11 days, there may be a long incubation, as with a three-day incubation - 6 - 12 - 18 months; from publications, the deadline for incubation is 52 months.
Attacks of fever occur every other day and, unlike 3-day malaria, occur mainly in the evening. Early and distant relapses are possible. The duration of the disease is 3-4 years (in some cases up to 8 years).
tropical malaria. The minimum duration of the incubation period is 7 days, fluctuations up to 10 - 16 days. Characterized by prodromal phenomena at the end of the incubation period: malaise, fatigue, headache, joint pain, nausea, loss of appetite, feeling chilly. Initial fever is constant or irregular, initial fever. Patients with tropical malaria often lack typical malaria symptoms of an attack: no or mild chills, feverish period lasts up to 30-40 hours, temperature drops without sudden sweating, muscle and joint pains are pronounced. Cerebral phenomena are noted - headache, confusion, insomnia, convulsions, hepatitis with cholemia often develops, there are signs of respiratory pathology (phenomena of bronchitis, bronchopneumonia); quite often expressed abdominal syndrome (abdominal pain, nausea, vomiting, diarrhea); impaired renal function.
Such a variety of organ symptoms makes diagnosis difficult and is the cause of erroneous diagnoses.
Duration of tropical malaria from 6 months. up to 1 year.
malarial coma- cerebral pathology in tropical malaria is characterized by rapid, rapid, sometimes lightning-fast development and a difficult prognosis. Three periods are distinguished in its course: somnolence, sopor and deep coma, the lethality in which is close to 100%.
Often, cerebral pathology is aggravated by acute renal failure.
No less severe course is characterized by hemoglobinuric fever, pathogenetically associated with intravascular hemolysis. Most often, it develops in individuals with genetically determined enzymopenia (deficiency of the G-b-PD enzyme) while taking antimalarial drugs. May result in the death of the patient from anuria due to the development of acute renal failure.
The algid form of tropical malaria is less common and is characterized by a cholera-like course.
Mixed malaria.
In malaria-endemic areas, simultaneous infection by several species of Plasmodium occurs. This leads to an atypical course of the disease, making it difficult to diagnose.
Malaria in children.
In malaria-endemic countries, malaria is one of the causes of high child mortality.
Babies under 6 months of age born to immune women in these areas acquire passive immunity and very rarely get malaria. Most severely, often with a fatal outcome, children aged 6 months and older are ill. up to 4 - 5 years. Clinical manifestations in children of this age differ in originality. Often there is no most striking symptom - malarial paroxysm. At the same time, symptoms such as convulsions, vomiting, diarrhea, abdominal pain are observed, there are no chills at the beginning of the paroxysm and sweating at the end.
On the skin - rashes in the form of hemorrhages, spotted elements. Anemia is on the rise.
In older children, malaria usually proceeds in the same way as in adults.
Malaria in pregnancy.
Malaria infection has a very adverse effect on the course and outcome of pregnancy. It can cause abortions, premature births, eclampsia of pregnancy and death.
Vaccinated (schizontal) malaria.
This malaria can be caused by any human malaria pathogen, but P. malariae is the predominant species.
In past years, for the treatment of patients with schizophrenia, neurosyphilis, the method of pyrotherapy was used, infecting them with malaria by injecting the blood of a malarial patient. This is the so-called therapeutic malaria.
Currently, depending on the conditions of infection with plasmodia-infected blood, blood transfusion and syringe malaria are isolated. The literature describes cases of accidental malaria - professional infection of medical and laboratory personnel, as well as cases of infection of recipients of transplanted organs.
The viability of Plasmodium in the blood of donors at 4°C reaches 7-10 days.
It should be noted that post-transfusion malaria can also be severe, and in the absence of timely treatment, give an unfavorable outcome. It is difficult to diagnose it, primarily because the doctor does not have an assumption about the possibility of nosocomial infection with malaria.
The increase in cases of schizont malaria is currently associated with the spread of drug addiction.
In the treatment of such patients, there is no need to prescribe tissue schizontocides. One form of schizont malaria is a congenital infection, i.e., infection of the fetus during fetal development (transplacental if the placenta is damaged) or during childbirth.
Immunity against malaria.
In the process of evolution, humans have developed different mechanisms of resistance to malaria:
1. innate immunity associated with genetic factors;
2. acquired active;
3. acquired passive immunity.
Acquired active immunity caused by infection. It is associated with humoral restructuring, the production of antibodies, an increase in the level of serum immunoglobulins. Only a small part of the antibodies plays a protective role; in addition, antibodies are produced only against erythrocyte stages (WHO, 1977). Immunity is unstable, quickly disappears after the release of the body from the pathogen, has a species- and strain-specific character. One of the essential factors of immunity is phagocytosis.
Attempts to create artificial acquired active immunity through the use of vaccines do not lose their value. The possibility of creating immunity as a result of vaccination with attenuated sporozoites has been proven. Thus, immunization of people with irradiated sporozoites protected them from infection for 3-6 months. (D. Clyde, V. McCarthy, R. Miller, W. Woodward, 1975).
Attempts have been made to create merozoite and gamete antimalarial vaccines, as well as a synthetic multispecies vaccine proposed by Colombian immunologists (1987).
Complications of malaria: malarial coma, rupture of the spleen, hemoglobinuric fever.
Diagnosis of Malaria:
Diagnosis of malaria is based on an analysis of the clinical manifestations of the disease, epidemiological and geographical history data and is confirmed by the results of a laboratory blood test.
The final diagnosis of the specific form of malaria infection is based on the results of a laboratory blood test.
With the study mode recommended by WHO for mass examinations, it is necessary to carefully examine 100 fields of view in a thick drop. Examination of two thick drops for 2.5 minutes. per each is more effective than examining one thick drop for 5 minutes. When Plasmodium malaria is detected in the very first fields of view, the viewing of preparations is not stopped until 100 fields of view are viewed so as not to miss a possible mixed infection.
If indirect signs of a malarial infection are detected in a patient (stay in the malarial zone, hypochromic anemia, the presence of pigmentophages in the blood - monocytes with clumps of almost black malarial pigment in the cytoplasm), it is necessary to examine a thick drop more carefully and not two, but a series of 4 - 6 at one prick. In addition, with a negative result in suspicious cases, it is recommended to take blood samples repeatedly (4-6 times a day) for 2-3 days.
The laboratory response indicates the Latin name of the pathogen, the generic name of Plasmodium is reduced to "P", the species name is not reduced, as well as the stage of development of the pathogen (required when P. falciparum is detected).
To control the effectiveness of treatment and identify possible resistance of the pathogen to the antimalarial drugs used, the number of Plasmodium is counted.
The detection of mature trophozoites and schizonts - morula in the peripheral blood in tropical malaria indicates a malignant course of the disease, which the laboratory must immediately inform the attending physician.
In practice, the former have found greater use. More often than other test systems, an indirect immunofluorescence reaction (IRIF) is used. As an antigen for the diagnosis of three-day and four-day malaria, smears and drops of blood with a large number of schizonts are used.
For the diagnosis of tropical malaria, the antigen is prepared from an in vitro culture of P. falciparum, since in most patients there are no schizonts in the peripheral blood. Therefore, for the diagnosis of tropical malaria, the French company BioMerieux produces a special commercial kit.
Difficulties in obtaining an antigen (a patient's blood product or from an in vitro culture), as well as insufficient sensitivity, make it difficult to introduce NRIF into practice.
New methods for diagnosing malaria have been developed on the basis of luminescent enzyme-linked immunosorbent sera, as well as using monoclonal antibodies.
Enzyme-linked immunosorbent assay using soluble antigens of Plasmodium malaria (REMA or ELISA), like RNIF, is mainly used for epidemiological studies.
Malaria Treatment:
Quinine is still the most commonly used drug for treating malaria. It was replaced for a while by chloroquine, but more recently quinine has regained popularity. The reason for this was the appearance in Asia and then spread to Africa and other parts of the world, Plasmodium falciparum with a mutation of resistance to chloroquine.
Extracts of the plant Artemisia annua (Artemisia annua), which contain the substance artemisinin and its synthetic analogues, are highly effective, but their production is expensive. Currently (2006), clinical effects and the possibility of producing new drugs based on artemisinin are being studied. Another work by a team of French and South African researchers has developed a group of new drugs known as G25 and TE3 that have been successfully tested in primates.
Although antimalarial drugs are on the market, the disease poses a threat to people who live in endemic areas where there is no adequate access to effective drugs. According to Médecins Sans Frontières, the average cost of treating a person infected with malaria in some African countries is as low as US$0.25 to US$2.40.
Malaria Prevention:
Methods that are used to prevent the spread of the disease or for protection in areas endemic for malaria include preventive medicines, mosquito extermination, and mosquito bite prevention products. At the moment there is no vaccine against malaria, but active research is underway to create one.
Preventive medicines
A number of drugs used to treat malaria can also be used for prevention. Usually, these drugs are taken daily or weekly at a lower dose than for treatment. Preventive medicines are commonly used by people visiting areas at risk of contracting malaria and are hardly used by the local population due to the high cost and side effects of these medicines.
Since the beginning of the 17th century, quinine has been used for prevention. The 20th century synthesis of more effective alternatives such as quinacrine (Acriquine), chloroquine, and primaquine reduced the use of quinine. With the advent of the chloroquine-resistant strain of Plasmodium falciparum, quinine has returned as a treatment, but not a preventive.
Mosquito extermination
Efforts to control malaria by killing mosquitoes have been successful in some areas. Malaria was once common in the United States and Southern Europe, but the draining of swamps and improved sanitation, along with the control and treatment of infected people, have made these areas unsafe. For example, in 2002, there were 1,059 cases of malaria in the United States, including 8 deaths. On the other hand, malaria has not been eradicated in many parts of the world, especially in developing countries - the problem is most prevalent in Africa.
DDT has proven to be an effective chemical against mosquitoes. It was developed during World War II as the first modern insecticide. At first it was used to fight against malaria, and then it spread to agriculture. Over time, pest control, rather than mosquito eradication, has come to dominate the use of DDT, especially in developing countries. Throughout the 1960s, evidence of the negative effects of its misuse increased, eventually leading to the banning of DDT in many countries in the 1970s. Until that time, its widespread use had already led to the emergence of DDT-resistant mosquito populations in many areas. But now there is the prospect of a possible return of DDT. The World Health Organization (WHO) today recommends the use of DDT against malaria in endemic areas. Along with this, it is proposed to apply alternative insecticides in areas where mosquitoes are resistant to DDT in order to control the evolution of resistance.
Mosquito nets and repellents
Mosquito nets help keep people away from mosquitoes and thereby significantly reduce infections and transmission of malaria. Nets are not a perfect barrier, so they are often used in conjunction with an insecticide that is sprayed to kill mosquitoes before they can find their way through the net. Therefore, nets impregnated with insecticides are much more effective.
For personal protection, closed clothing and repellents are also effective. Repellents fall into two categories: natural and synthetic. Common natural repellents are the essential oils of certain plants.
Examples of synthetic repellents:
DEET (active substance - diethyltoluamide) (eng. DEET, N, N-diethyl-m-toluamine)
IR3535®
Bayrepel®
Permethrin
transgenic mosquitoes
Several variants of possible genetic modifications of the mosquito genome are considered. One potential mosquito control method is the rearing of sterile mosquitoes. Significant progress has now been made towards the development of a transgenic or genetically modified malaria-resistant mosquito. In 2002, two groups of researchers have already announced the development of the first samples of such mosquitoes.
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Malaria
Malaria causes about 350-500 million infections and about 1.3-3 million deaths in humans every year. Sub-Saharan Africa accounts for 85-90% of these cases, with the vast majority affecting children under 5 years of age. The death rate is expected to double over the next 20 years.
The first chronicle evidence of a fever caused by malaria was found in China. They date back to around 2700 BC. e., during the Xia Dynasty.
What provokes / Causes of Malaria:
The causative agents of malaria are the protozoa of the genus Plasmodium (Plasmodium). Four species of this genus are pathogenic for humans: P.vivax, P.ovale, P.malariae and P.falciparum In recent years, it has been established that a fifth species, Plasmodium knowlesi, also causes malaria in humans in Southeast Asia. A person becomes infected with them at the time of inoculation (injection) by a female malarial mosquito of one of the stages of the life cycle of the pathogen (the so-called sporozoites) into the blood or lymphatic system, which occurs during blood sucking.
After a short stay in the blood, the sporozoites of the malarial plasmodium penetrate into the hepatocytes of the liver, thereby giving rise to the preclinical hepatic (exoerythrocytic) stage of the disease. In a process of asexual reproduction called schizogony, from 2,000 to 40,000 hepatic merozoites, or schizonts, are eventually formed from one sporozoite. In most cases, these daughter merozoites re-enter the blood after 1-6 weeks. In infections caused by some North African strains of P. vivax, the primary release of merozoites from the liver into the blood occurs approximately 10 months after infection, coinciding with a short period of mass breeding of mosquitoes in the following year.
The erythrocyte, or clinical, stage of malaria begins with the attachment of merozoites that have entered the bloodstream to specific receptors on the surface of the erythrocyte membrane. These receptors, which serve as targets for infection, appear to be different for different species of malarial plasmodia.
Epidemiology of malaria
Under natural conditions, malaria is a naturally endemic, protozoal, anthroponotic, transmissible infection.
The causative agents of malaria find hosts in various representatives of the animal world (monkeys, rodents, etc.), but as a zoonotic infection, malaria is extremely rare.
There are three ways of contracting malaria: transmissible, parenteral (syringe, post-transfusion) and vertical (transplacental).
The main transmission route is transmissive. Human malaria vectors are female mosquitoes of the genus Anopheles. Males feed on the nectar of flowers.
The main vectors of malaria in Ukraine:
an. messae, An. maculipennis, An. atroparvus, An. Sacharovi, An. superpictus, An. pulcherrimus and others.
The life cycle of mosquitoes consists of a number of stages: egg - larva (I - IV age) - pupa - imago. Fertilized females attack a person in the evening or at night and feed on blood. In females that are not fed with blood, eggs do not develop. Blood-fed females remain in the dark corners of residential or utility rooms, thickets of vegetation until the end of the digestion of blood and the maturation of eggs. The higher the air temperature, the faster the development of eggs in the body of the female is completed - (gonotrophic cycle): at a temperature of + 30 ° C - up to 2 days, at + 15 ° C - up to 7 in P. vivax. Then they rush to the reservoir, where they lay their eggs. Such reservoirs are called anophelogenic.
The maturation of the aquatic stages of vector development also depends on temperature and lasts 2-4 weeks. At temperatures below +10°C, mosquitoes do not develop. During the warm season of the year, up to 3-4 generations of mosquitoes may appear in the middle latitudes, 6-8 in the south, and up to 10-12 in the tropics.
For sporogony, a temperature of at least + 16 ° C is required. Sporogony of P. vivax at +16°C is completed in 45 days, at +30°C - in 6.5 days. The minimum temperature for P. falciparum sporogony is +19 - 20°C, at which it is completed in 26 days, at +30°C - in 8 days.
The season for malaria transmission depends on this. In the tropics, the malaria transmission season reaches 8-10 months, in the countries of equatorial Africa it is year-round.
In temperate and subtropical climate zones, the malaria transmission season is limited to the summer-autumn months and lasts from 2 to 7 months.
In wintering mosquitoes, sporozoites die; therefore, females that hatch in the spring are not carriers of malarial plasmodia, and in each new season, mosquitoes are infected from malaria patients.
Perhaps intrauterine infection of the fetus through the placenta in the presence of infection in a pregnant mother, but more often this occurs during childbirth.
With these forms of infection, schizont malaria develops, in which there is no phase of tissue schizogony.
Susceptibility to malaria is universal. Only representatives of the Negroid race are immune to P. vivax.
The spread of malaria is determined by geographical, climatic and social factors. The boundaries of distribution are 60 - 64 ° north latitude and 30 ° south latitude. However, the species range of malaria is uneven. P. vivax, the causative agent of three-day malaria, has the widest range, the distribution of which is determined by geographic boundaries.
Tropical malaria has a smaller range because P. falciparum requires higher temperatures to develop. It is limited to 45° - 50° N. sh. and 20°S sh. Africa is the world's hotbed of tropical malaria.
The second place in distribution in Africa is occupied by four-day malaria, the range of which reaches 53 ° N. sh. and 29°S sh. and which has a focal, nesting character.
P. ovale is found mainly in the countries of West and Central Africa and on some islands of Oceania (New Guinea, Philippines, Thailand, etc.).
In Ukraine, malaria has been practically eliminated and mainly imported malaria and isolated cases of local infection are recorded - secondary from imported ones.
Malaria is imported to the territory of Ukraine from tropical countries and from neighboring countries - Azerbaijan and Tajikistan, where there are residual foci.
The largest part of imported cases is three-day malaria, which is the most dangerous due to possible transmission by mosquitoes sensitive to this type of pathogen. In second place is the importation of tropical malaria, the most severe clinically, but less dangerous epidemiologically, since Ukrainian mosquitoes are not sensitive to P. falciparum imported from Africa.
Cases of importation with an unidentified cause of infection are registered - “airport”, “baggage”, “accidental”, “transfusion” malaria.
The WHO European Office, due to the political and economic instability in the world, the growth of migration and the implementation of large-scale irrigation projects, highlights malaria as a priority problem due to the possibility of a return of the infection.
Under the influence of these factors, the formation of new foci of malaria, i.e., settlements with adjacent anophelogenic reservoirs, is possible.
In accordance with the WHO classification, 5 types of malaria foci are distinguished:
pseudo-focus - the presence of imported cases, but there are no conditions for the transmission of malaria;
potential - the presence of imported cases and there are conditions for the transmission of malaria;
active new - emergence of cases of local infection, transmission of malaria has occurred;
active persistent - the presence of cases of local infection for three years or more without interruption of transmission;
inactive - malaria transmission has ceased, there have been no cases of local infection during the last two years.
An indicator of the intensity of the risk of contracting malaria according to the WHO classification is the splenic index in children from 2 to 9 years old. According to this classification, 4 degrees of endemia are distinguished:
1. Hypoendemia - splenic index in children from 2 to 9 years old up to 10%.
2. Mesoendemia - splenic index in children from 2 to 9 years old is 11 - 50%.
3. Hyperendemia - the splenic index in children from 2 to 9 years old is above 50% and high in adults.
4. Holoendemia - the splenic index in children from 2 to 9 years old is constantly above 50%, the splenic index in adults is low (African type) or high (New Guinean type).
Pathogenesis (what happens?) during Malaria:
According to the method of infection, sporozoite and schizont malaria are distinguished. Sporozoite infection- This is a natural infection through a mosquito, with the saliva of which sporozoites enter the human body. In this case, the pathogen passes through the tissue (in hepatocytes), and then the erythrocyte phase of schizogony.
Schizont malaria due to the introduction of ready-made schizonts into the human blood (hemotherapy, syringe malaria), therefore, unlike sporozoite infection, there is no tissue phase here, which determines the features of the clinic and treatment of this form of the disease.
The immediate cause of attacks of malarial fever is the entry into the blood during the breakdown of morula merozoites, which are a foreign protein, malarial pigment, hemoglobin, potassium salts, erythrocyte residues, which change the specific reactivity of the body and, acting on the heat-regulating center, cause a temperature reaction. The development of a fever attack in each case depends not only on the dose of the pathogen (“pyrogenic threshold”), but also on the reactivity of the human body. The alternation of fever attacks characteristic of malaria is due to the duration and cyclicity of the erythrocyte schizogony of the leading generation of plasmodia of one species or another.
Alien substances circulating in the blood irritate the reticular cells of the spleen and liver, cause their hyperplasia, and with a long course - the growth of connective tissue. Increased blood supply to these organs leads to their increase and soreness.
Important in the pathogenesis of malaria is the sensitization of the body by a foreign protein and the development of autoimmunopathological reactions. The breakdown of erythrocytes in erythrocyte schizogony, hemolysis as a result of the formation of autoantibodies, increased phagocytosis of erythrocytes of the reticuloendothelial system of the spleen are the cause of anemia.
Relapses are typical for malaria. The reason for the near relapses in the first 3 months after the end of the primary acute symptoms is the preservation of a part of erythrocyte schizonts, which, due to a decrease in immunity, begin to actively multiply again. Late or distant relapses, characteristic of three-day and oval malaria (after 6-14 months), are associated with the completion of the development of bradysporozoites.
Symptoms of Malaria:
All clinical manifestations of malaria are associated only with erythrocyte schizogony.
There are 4 specific forms of malaria: three-day, oval-malaria, four-day and tropical.
Each species form has its own characteristics. However, fever attacks, splenohepatomegaly and anemia are typical for all.
Malaria is a polycyclic infection, in its course there are 4 periods: the period of incubation (primary latent), primary acute manifestations, secondary latent and relapse period. The duration of the incubation period depends on the type and strain of the pathogen. At the end of the incubation period, symptoms appear - precursors, prodromes: weakness, muscle, headache, chilling, etc. The second period is characterized by recurring attacks of fever, for which a staging development is typical - a change in the stages of chills, heat and sweat. During the chill, which lasts from 30 minutes. up to 2 - 3 hours, the body temperature rises, the patient cannot warm up, the extremities are cyanotic and cold, the pulse is rapid, breathing is shallow, blood pressure is elevated. By the end of this period, the patient warms up, the temperature reaches 39 - 41 ° C, a period of fever sets in: the face turns red, the skin becomes hot and dry, the patient is excited, restless, headache, delirium, confusion, sometimes convulsions. At the end of this period, the temperature drops rapidly, which is accompanied by profuse sweating. The patient calms down, falls asleep, a period of apyrexia begins. However, then the attacks are repeated with a certain cyclicity, depending on the type of pathogen. In some cases, the initial (initial) fever is irregular or permanent.
Against the background of attacks, the spleen and liver increase, anemia develops, all body systems suffer: cardiovascular (myocardial dystrophic disorders), nervous (neuralgia, neuritis, sweating, chilliness, migraine), genitourinary (symptoms of nephritis), hematopoietic (hypochromic anemia, leukopenia, neutropenia, lymphomonocytosis, thrombocytopenia), etc. After 10-12 or more attacks, the infection gradually subsides, and a secondary latent period sets in. With incorrect or ineffective treatment, a few weeks or months later, short-term (3 months), late or distant (6-9 months) relapses occur.
Three day malaria. The duration of the incubation period: minimum - 10 - 20 days, in case of infection with bradysporozoites - 6 - 12 months or more.
Characterized by prodromal phenomena at the end of incubation. A few days before the onset of attacks, chilling, headache, back pain, fatigue, nausea appear. The disease begins acutely. The first 5-7 days of fever may be of an irregular nature (initial), then an intermittent type of fever is established with a typical alternation of attacks every other day. For an attack, a clear change in the stages of chills, heat and sweat is characteristic. The heat period lasts 2-6 hours, less often 12 hours and is replaced by a period of sweating. Attacks usually occur in the morning. The spleen and liver after 2-3 temperature paroxysms increase, are sensitive to palpation. On the 2nd - 3rd week moderate anemia develops. This species form is characterized by near and distant relapses. The total duration of the disease is 2-3 years.
Malaria oval. In many clinical and pathogenetic features, it is similar to three-day malaria, but differs in a milder course. The minimum incubation period is 11 days, there may be a long incubation, as with a three-day incubation - 6 - 12 - 18 months; from publications, the deadline for incubation is 52 months.
Attacks of fever occur every other day and, unlike 3-day malaria, occur mainly in the evening. Early and distant relapses are possible. The duration of the disease is 3-4 years (in some cases up to 8 years).
tropical malaria. The minimum duration of the incubation period is 7 days, fluctuations up to 10 - 16 days. Characterized by prodromal phenomena at the end of the incubation period: malaise, fatigue, headache, joint pain, nausea, loss of appetite, feeling chilly. Initial fever is constant or irregular, initial fever. Patients with tropical malaria often lack typical malaria symptoms of an attack: no or mild chills, feverish period lasts up to 30-40 hours, temperature drops without sudden sweating, muscle and joint pains are pronounced. Cerebral phenomena are noted - headache, confusion, insomnia, convulsions, hepatitis with cholemia often develops, there are signs of respiratory pathology (phenomena of bronchitis, bronchopneumonia); quite often expressed abdominal syndrome (abdominal pain, nausea, vomiting, diarrhea); impaired renal function.
Such a variety of organ symptoms makes diagnosis difficult and is the cause of erroneous diagnoses.
Duration of tropical malaria from 6 months. up to 1 year.
malarial coma- cerebral pathology in tropical malaria is characterized by rapid, rapid, sometimes lightning-fast development and a difficult prognosis. Three periods are distinguished in its course: somnolence, sopor and deep coma, the lethality in which is close to 100%.
Often, cerebral pathology is aggravated by acute renal failure.
No less severe course is characterized by hemoglobinuric fever, pathogenetically associated with intravascular hemolysis. Most often, it develops in individuals with genetically determined enzymopenia (deficiency of the G-b-PD enzyme) while taking antimalarial drugs. May result in the death of the patient from anuria due to the development of acute renal failure.
The algid form of tropical malaria is less common and is characterized by a cholera-like course.
Mixed malaria.
In malaria-endemic areas, simultaneous infection by several species of Plasmodium occurs. This leads to an atypical course of the disease, making it difficult to diagnose.
Malaria in children.
In malaria-endemic countries, malaria is one of the causes of high child mortality.
Babies under 6 months of age born to immune women in these areas acquire passive immunity and very rarely get malaria. Most severely, often with a fatal outcome, children aged 6 months and older are ill. up to 4 - 5 years. Clinical manifestations in children of this age differ in originality. Often there is no most striking symptom - malarial paroxysm. At the same time, symptoms such as convulsions, vomiting, diarrhea, abdominal pain are observed, there are no chills at the beginning of the paroxysm and sweating at the end.
On the skin - rashes in the form of hemorrhages, spotted elements. Anemia is on the rise.
In older children, malaria usually proceeds in the same way as in adults.
Malaria in pregnancy.
Malaria infection has a very adverse effect on the course and outcome of pregnancy. It can cause abortions, premature births, eclampsia of pregnancy and death.
Vaccinated (schizontal) malaria.
This malaria can be caused by any human malaria pathogen, but P. malariae is the predominant species.
In past years, for the treatment of patients with schizophrenia, neurosyphilis, the method of pyrotherapy was used, infecting them with malaria by injecting the blood of a malarial patient. This is the so-called therapeutic malaria.
Currently, depending on the conditions of infection with plasmodia-infected blood, blood transfusion and syringe malaria are isolated. The literature describes cases of accidental malaria - professional infection of medical and laboratory personnel, as well as cases of infection of recipients of transplanted organs.
The viability of Plasmodium in the blood of donors at 4°C reaches 7-10 days.
It should be noted that post-transfusion malaria can also be severe, and in the absence of timely treatment, give an unfavorable outcome. It is difficult to diagnose it, primarily because the doctor does not have an assumption about the possibility of nosocomial infection with malaria.
The increase in cases of schizont malaria is currently associated with the spread of drug addiction.
In the treatment of such patients, there is no need to prescribe tissue schizontocides. One form of schizont malaria is a congenital infection, i.e., infection of the fetus during fetal development (transplacental if the placenta is damaged) or during childbirth.
Immunity against malaria.
In the process of evolution, humans have developed different mechanisms of resistance to malaria:
1. innate immunity associated with genetic factors;
2. acquired active;
3. acquired passive immunity.
Acquired active immunity caused by infection. It is associated with humoral restructuring, the production of antibodies, an increase in the level of serum immunoglobulins. Only a small part of the antibodies plays a protective role; in addition, antibodies are produced only against erythrocyte stages (WHO, 1977). Immunity is unstable, quickly disappears after the release of the body from the pathogen, has a species- and strain-specific character. One of the essential factors of immunity is phagocytosis.
Attempts to create artificial acquired active immunity through the use of vaccines do not lose their value. The possibility of creating immunity as a result of vaccination with attenuated sporozoites has been proven. Thus, immunization of people with irradiated sporozoites protected them from infection for 3-6 months. (D. Clyde, V. McCarthy, R. Miller, W. Woodward, 1975).
Attempts have been made to create merozoite and gamete antimalarial vaccines, as well as a synthetic multispecies vaccine proposed by Colombian immunologists (1987).
Complications of malaria: malarial coma, rupture of the spleen, hemoglobinuric fever.
Diagnosis of Malaria:
Diagnosis of malaria is based on an analysis of the clinical manifestations of the disease, epidemiological and geographical history data and is confirmed by the results of a laboratory blood test.
The final diagnosis of the specific form of malaria infection is based on the results of a laboratory blood test.
With the study mode recommended by WHO for mass examinations, it is necessary to carefully examine 100 fields of view in a thick drop. Examination of two thick drops for 2.5 minutes. per each is more effective than examining one thick drop for 5 minutes. When Plasmodium malaria is detected in the very first fields of view, the viewing of preparations is not stopped until 100 fields of view are viewed so as not to miss a possible mixed infection.
If indirect signs of a malarial infection are detected in a patient (stay in the malarial zone, hypochromic anemia, the presence of pigmentophages in the blood - monocytes with clumps of almost black malarial pigment in the cytoplasm), it is necessary to examine a thick drop more carefully and not two, but a series of 4 - 6 at one prick. In addition, with a negative result in suspicious cases, it is recommended to take blood samples repeatedly (4-6 times a day) for 2-3 days.
The laboratory response indicates the Latin name of the pathogen, the generic name of Plasmodium is reduced to "P", the species name is not reduced, as well as the stage of development of the pathogen (required when P. falciparum is detected).
To control the effectiveness of treatment and identify possible resistance of the pathogen to the antimalarial drugs used, the number of Plasmodium is counted.
The detection of mature trophozoites and schizonts - morula in the peripheral blood in tropical malaria indicates a malignant course of the disease, which the laboratory must immediately inform the attending physician.
In practice, the former have found greater use. More often than other test systems, an indirect immunofluorescence reaction (IRIF) is used. As an antigen for the diagnosis of three-day and four-day malaria, smears and drops of blood with a large number of schizonts are used.
For the diagnosis of tropical malaria, the antigen is prepared from an in vitro culture of P. falciparum, since in most patients there are no schizonts in the peripheral blood. Therefore, for the diagnosis of tropical malaria, the French company BioMerieux produces a special commercial kit.
Difficulties in obtaining an antigen (a patient's blood product or from an in vitro culture), as well as insufficient sensitivity, make it difficult to introduce NRIF into practice.
New methods for diagnosing malaria have been developed on the basis of luminescent enzyme-linked immunosorbent sera, as well as using monoclonal antibodies.
Enzyme-linked immunosorbent assay using soluble antigens of Plasmodium malaria (REMA or ELISA), like RNIF, is mainly used for epidemiological studies.
Malaria Treatment:
Quinine is still the most commonly used drug for treating malaria. It was replaced for a while by chloroquine, but more recently quinine has regained popularity. The reason for this was the appearance in Asia and then spread to Africa and other parts of the world, Plasmodium falciparum with a mutation of resistance to chloroquine.
Extracts of the plant Artemisia annua (Artemisia annua), which contain the substance artemisinin and its synthetic analogues, are highly effective, but their production is expensive. Currently (2006), clinical effects and the possibility of producing new drugs based on artemisinin are being studied. Another work by a team of French and South African researchers has developed a group of new drugs known as G25 and TE3 that have been successfully tested in primates.
Although antimalarial drugs are on the market, the disease poses a threat to people who live in endemic areas where there is no adequate access to effective drugs. According to Médecins Sans Frontières, the average cost of treating a person infected with malaria in some African countries is as low as US$0.25 to US$2.40.
Malaria Prevention:
Methods that are used to prevent the spread of the disease or for protection in areas endemic for malaria include preventive medicines, mosquito extermination, and mosquito bite prevention products. At the moment there is no vaccine against malaria, but active research is underway to create one.
Preventive medicines
A number of drugs used to treat malaria can also be used for prevention. Usually, these drugs are taken daily or weekly at a lower dose than for treatment. Preventive medicines are commonly used by people visiting areas at risk of contracting malaria and are hardly used by the local population due to the high cost and side effects of these medicines.
Since the beginning of the 17th century, quinine has been used for prevention. The 20th century synthesis of more effective alternatives such as quinacrine (Acriquine), chloroquine, and primaquine reduced the use of quinine. With the advent of the chloroquine-resistant strain of Plasmodium falciparum, quinine has returned as a treatment, but not a preventive.
Mosquito extermination
Efforts to control malaria by killing mosquitoes have been successful in some areas. Malaria was once common in the United States and Southern Europe, but the draining of swamps and improved sanitation, along with the control and treatment of infected people, have made these areas unsafe. For example, in 2002, there were 1,059 cases of malaria in the United States, including 8 deaths. On the other hand, malaria has not been eradicated in many parts of the world, especially in developing countries - the problem is most prevalent in Africa.
DDT has proven to be an effective chemical against mosquitoes. It was developed during World War II as the first modern insecticide. At first it was used to fight against malaria, and then it spread to agriculture. Over time, pest control, rather than mosquito eradication, has come to dominate the use of DDT, especially in developing countries. Throughout the 1960s, evidence of the negative effects of its misuse increased, eventually leading to the banning of DDT in many countries in the 1970s. Until that time, its widespread use had already led to the emergence of DDT-resistant mosquito populations in many areas. But now there is the prospect of a possible return of DDT. The World Health Organization (WHO) today recommends the use of DDT against malaria in endemic areas. Along with this, it is proposed to apply alternative insecticides in areas where mosquitoes are resistant to DDT in order to control the evolution of resistance.
Mosquito nets and repellents
Mosquito nets help keep people away from mosquitoes and thereby significantly reduce infections and transmission of malaria. Nets are not a perfect barrier, so they are often used in conjunction with an insecticide that is sprayed to kill mosquitoes before they can find their way through the net. Therefore, nets impregnated with insecticides are much more effective.
For personal protection, closed clothing and repellents are also effective. Repellents fall into two categories: natural and synthetic. Common natural repellents are the essential oils of certain plants.
Examples of synthetic repellents:
DEET (active substance - diethyltoluamide) (eng. DEET, N, N-diethyl-m-toluamine)
IR3535®
Bayrepel®
Permethrin
transgenic mosquitoes
Several variants of possible genetic modifications of the mosquito genome are considered. One potential mosquito control method is the rearing of sterile mosquitoes. Significant progress has now been made towards the development of a transgenic or genetically modified malaria-resistant mosquito. In 2002, two groups of researchers have already announced the development of the first samples of such mosquitoes.
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Malaria - symptoms and treatment
What is malaria? We will analyze the causes of occurrence, diagnosis and treatment methods in the article of Dr. Alexandrov P.A., an infectious disease specialist with an experience of 12 years.
Definition of illness. Causes of the disease
Malaria (febris intermittens, marsh fever) - a group of protozoal human transmissible diseases caused by pathogens of the genus transmitted by mosquitoes of the genus Anopheles and damaging elements of the reticulohistiocytic system and erythrocytes.
It is clinically characterized by a syndrome of general infectious intoxication in the form of febrile paroxysms, enlargement of the liver and spleen, and anemia. In the absence of urgent highly effective treatment, serious complications and death are possible.
Etiology
Type - the simplest ( Protozoa)
Class - sporozoans ( Sporozoa)
Detachment - hemosporidium ( Haemosporidia)
Family - Plasmodidae
Genus -
- P.malariae(quartan);
- P. falciparum(tropical malaria) - the most dangerous;
- P. vivax(three-day malaria);
- P.ovale(oval-malaria);
- P. knowlesi(zoonotic malaria of Southeast Asia).
Duration of exoerythrocytic schizogony (tissue reproduction):
- P. falciparum- 6 days, P.malariae- 15 days (tachysporozoites - development after a short incubation);
- P.ovale- 9 days, P. Vivax- 8 days (bradysporozoites - the development of the disease after a long incubation);
The duration of erythrocyte schizogony (reproduction in erythrocytes, that is, in the blood):
Epidemiology
Specific carrier - mosquito of the genus Anopheles(more than 400 species), which is the final host of the infectious agent. Man is only an intermediate host. Mosquitoes are active in the evening and at night. The presence of water plays a large role, so the greatest spread of infection occurs in humid places or during the rainy season.
Transmission mechanism:
- transmissive (inoculation - bite);
- vertical (transplacental from mother to fetus, during childbirth);
- parenteral route (blood transfusion, organ transplant).
The spread of malaria is possible in the presence of:
- source of infection;
- carrier;
- favorable climatic conditions: the ambient air temperature must be constantly not lower than 16 ° C and continuous for 30 days - this condition is dominant in the geographical area of the possible spread of malaria (for example, in the middle zone of the Russian Federation, such climatic conditions are practically impossible).
If you experience similar symptoms, consult your doctor. Do not self-medicate - it is dangerous for your health!
It starts off sharp.
The incubation period depends on the type of pathogen:
- three-day - 10-21 days (sometimes 6-13 months);
- four-day - 21-40 days;
- tropical - 8-16 days (sometimes a month with intravenous infection, for example, with blood transfusion);
- oval malaria - 2-16 days (rarely up to 2 years).
The main syndrome of the disease is a specific general infectious intoxication, which occurs in the form malaria attack. It begins more often in the first half of the day with a change in the phases of chills, heat and sweat. Sometimes preceded by a prodrome (malaise). The attack begins with chills, the patient cannot warm up, the skin becomes pale, cold to the touch and rough (duration - 20-60 minutes). During this time, a person loses up to 6000 kcal. Then the fever begins (body temperature rises to 40 ° C within 2-4 hours). Then comes a period of increased sweating (body temperature decreases, general well-being improves). In the interictal period, a person’s well-being can be described as a state “after the banquet”. Then everything repeats again.
On examination, various degrees of depression of consciousness can be detected (based on the severity of the disease). The position of the patient also corresponds to the severity of the disease. Soreness of the muscles and joints is manifested, during the attack there is some variability in the type of skin, depending on the type of pathogen:
- in three-day malaria, pallor with chill and red, hot skin with heat;
- with tropical malaria - pale dry skin;
- with a four-day illness - the gradual development of pallor.
Peripheral lymph nodes are not enlarged. On the part of the cardiovascular system, tachycardia, a decrease in blood pressure are characteristic; with four-day malaria, there is a "top" noise, muffled tones. Dry rales, tachypnea (rapid shallow breathing), increased respiratory rate, dry cough are heard in the lungs. With a severe degree, pathological types of breathing appear. On the part of the gastrointestinal tract, there is a decrease in appetite, nausea, vomiting, bloating and enteritis syndrome (inflammation of the small intestine), hepatolienal syndrome (enlargement of the liver and spleen). Often dark urine.
Clinical criteria for malaria:
Malaria pathogenesis
Mosquitoes of various species of the genus Anopheles, drinking the blood of a sick person (with the exception of zoonotic malaria), they give access to the patient's blood into their own stomach, where the sexual forms of plasmodia enter - male and female gametocytes. The progress of sporogony (sexual development) is crowned with the formation of many thousands of sporozoites, which, in turn, accumulate in significant quantities in the salivary glands of the mosquito. Thus, a blood-sucking mosquito becomes a source of danger to humans and remains infectious for up to 1-1.5 months. A susceptible person is infected by the bite of an infected (and contagious) mosquito.
Further, sporozoites through the blood and lymph flow (are in the blood for about 40 minutes) penetrate into the liver cells, where their tissue schizogony (asexual reproduction) occurs and merozoites are formed. During this period, clinical well-being is observed. In the future, with tropical and four-day malaria, merozoites completely leave the liver, and with three-day and oval malaria, they can lodge in hepatocytes for a long time.
Development of hemoglobinuric fever (black water fever) is associated with massive intravascular hemolysis (destruction of red blood cells with the release of hemoglobin) and deficiency of glucose-6-phosphate dehydrogenase in red blood cells (shock kidney).
Malarial encephalitis develops when erythrocytes stick together in the capillaries of the brain and kidneys with the formation of erythrocyte thrombi, which, together with the general process, leads to an increase in the permeability of the walls of blood vessels, the release of plasma into the extravascular bed and cerebral edema.
Malaria in pregnancy proceeds very hard, with frequent development of complications, the syndrome of malignant malaria is characteristic. Mortality, compared with non-pregnant women, is 10 times higher. When the mother is ill in the first trimester, a significant increase in the risk of abortion and fetal death is characteristic. Perhaps intrauterine infection, leading to developmental delays and clinical and laboratory signs of malaria in the newborn.
Differential Diagnosis:
Classification and stages of development of malaria
By severity:
- light;
- medium heavy;
- heavy.
By form:
- typical;
- atypical.
For complications:
Complications of malaria
Diagnosis of malaria
The basis of the laboratory diagnosis of malaria is blood microscopy using a thick drop method (detection of malarial plasmodium) and a thin smear (more accurate determination of the type of plasmodium). If malaria is suspected, the study should be repeated up to three times, regardless of the presence of fever or apyrexia.
The following studies are being carried out:
Malaria treatment
The place is the infectious diseases department of the hospital.
It is necessary to use antimalarial drugs based on the availability of data on the possibility of malaria (if the method of etiological confirmation is unavailable and the likelihood of malaria is high, treatment must be prescribed), determination of the type of plasmodium.
Based on the patient's condition and the manifestations of the disease, a complex of pathogenetic and symptomatic therapy is prescribed.
At the slightest sign of malaria (fever, chills after visiting southern countries), you should immediately visit a doctor or call an ambulance. Self-medication is life-threatening.
Forecast. Prevention
With timely treatment and the absence of complications, most often there is a complete recovery. With delayed treatment (especially in Europeans) and the development of complications, the prognosis is unfavorable.
Prevention is based on vector control. This includes the use of protective insecticide-impregnated mosquito nets, the use of indoor insecticides in the form of repellant sprays, and the chemoprophylaxis of malaria. It is also quite effective to drain swamps, lowlands and deprive mosquitoes of their natural environment. Travelers should not be outside sheltered residential areas at night, especially outside cities.
A number of antimalarial vaccines have been used, such as RTS,S/AS01 (Mosquirix™), but their use has so far been limited as they provide only partial protection in children (may be used in children in high-risk areas of Africa).
Anemia, hepatomegaly and splenomegaly.
Malaria is transmitted through the bites of female malarial mosquitoes (Anopheles).
Other names of the disease- swamp fever, intermittent fever.
Plasmodium malaria (most often Plasmodium falciparum), when it enters the body, attaches to erythrocytes and tissue macrophages (protective immunity cells), after spreading throughout the body, it causes a number of pathologies in various organs. The end result of malaria can be death of the infected person.
The largest number of reported cases of malaria infection is in Africa (closer to the equator, i.e. below the Sahara), Southeast Asia, Central and South America, Oceania.
The peak incidence of malaria falls on the time of the greatest activity of mosquitoes - summer-autumn.
Pathogenesis (disease development)
The pathogenesis of malaria largely depends on the mode of infection.
So, with a direct bite of a malarial mosquito, the sporozoites of Plasmodium with its saliva, with the blood flow, enter the liver cells, where they settle, develop, turning into tissue schizonts, then grow and divide many times (the process of reproduction, or schizogony). Further, the cytoplasm is distributed around the new nuclei and many thousands of “armies” of tissue merozoites (mobile spores of plasmodia) are formed. The whole cycle of development of plasmodium in liver cells is called tissue schizogony. After that, the causative agent of malaria partially remains in the liver, and partially, it penetrates into erythrocytes, spreading with the blood flow to other organs and systems, where the process of development and reproduction also begins.
With direct infection with malarial plasmodium - through injections, blood transfusions, etc., the pathogen immediately invades the erythrocytes and spreads throughout the body (erythrocyte phase of schizogony).
With tissue schizogony, clinical manifestations are practically absent, while with erythrocyte schizogony, the patient almost immediately shows signs of blood damage - fever and others.
Fever in malaria develops as a result of the reaction of the immune system and the heat-regulating center to the appearance in the body of substances, the appearance of which is due to the breakdown of morula merozoites. These are malarial pigment, hemoglobin, erythrocyte residues, etc. The severity of fever depends on the degree of infection and the reactivity of the body's defenses.
The frequency of fever attacks is due to periods of erythrocyte schizogony (the cycle of development and division of malarial plasmodia).
The presence of foreign substances circulating in the blood causes irritation of the reticular cells of the liver, spleen, kidneys and other organs, which leads to hyperplasia of these organs, resulting in proliferation of connective tissue, an increase in the size of the affected organs and their pain.
Anemia in malaria is caused by the breakdown of erythrocytes against the background of erythrocyte schizogony, hemolysis during the formation of autoantibodies, as well as increased phagocytosis of erythrocytes of the reticuloendothelial system of the spleen.
Relapses of malaria are due to a decrease in the reactivity of immunity in the presence of remnants of erythrocyte schizonts, due to which the causative agent of the disease begins to multiply again. Relapses may be present even 6-14 months after the end of the clinical manifestations of malaria.
An interesting point that scientists came to in experiments on mice is that when the body is infected with malarial plasmodium, the body odor of the “victim” of the mosquito changes, which in turn attracts even more mosquitoes.
Statistics
According to WHO statistics, as of 2016, 216,000,000 cases of malaria were registered in the world, and this figure is 5,000,000 more than in 2015. The number of deaths from this disease in 2016 was 445,000. However, the percentage mortality from the beginning of the 21st century has decreased by 47-54%, depending on the region.
If we talk about the regions, then 90% of all cases of malaria falls on the countries of Africa, especially below the Sahara desert.
Most affected are children under 5 years of age.
Malaria - ICD
ICD-10: B50 - B54;
ICD-9: 084.
Symptoms of malaria depend on the method of infection, the reactivity of the body's defenses and the degree of damage.
Other types of malaria infection are - transplacental (during pregnancy - from mother to baby), parenteral (during transfusions of donor infected blood) and contact-household (with injections, cuts - an extremely rare occurrence).
In total, about 400 species of Anopheles mosquitoes are known, of which only about 30 are carriers of malaria infection.
Malaria mosquitoes live almost all over the world except in cold or dry areas. Especially a large number of them live in areas with a warm and humid climate - Central and South Africa (about 90% of all cases of malaria), Central and South America, Southeast Asia, Oceania.
On the territory of Russia, the European part of the country - the South-Eastern regions can be attributed to malaria zones.
Types of malaria
The classification of malaria is as follows:
Depending on the pathogen:
oval malaria- characterized by a paroxysmal cyclic course with an increase and decrease in the clinical manifestations of the disease, the period of the full cycle of which is 2 days. The causative agent is Plasmodium ovale.
Three day malaria- characterized by a paroxysmal cyclic course with an increase and decrease in the clinical manifestations of the disease, the period of the full cycle of which is 3 days. The causative agent is Plasmodium vivax.
Quartan- characterized by a paroxysmal cyclic course with an increase and decrease in the clinical manifestations of the disease, the period of the full cycle of which is 4 days. The causative agent is Plasmodium malariae.
tropical malaria- the most severe form of malaria, the causative agent of which is Plasmodium falciparum. A similar course of malaria can be provoked by another Plasmodium pathogenic for humans - Plasmodium knowlesi. It is characterized by the absence of tissue schizogony, i.e. accumulation and reproduction of plasmodium in the liver - development occurs in the blood (erythrocyte schizogony).
According to the mode of infection:
Schizont malaria- infection of the body occurs when the blood is infected with ready-made (formed) schizonts. It is characterized by an early clinical manifestation of malaria.
Diagnosis of malaria
Diagnosis of malaria includes the following examination methods:
Malaria treatment
How to treat malaria? Treatment of malaria is aimed at stopping the infection, maintaining the body and minimizing the clinical manifestations of the disease. The main method of therapy is medication, with the use of antimicrobial drugs.
1. Antimicrobial therapy (essential malaria drugs)
The main drugs for the relief of malaria are produced on the basis of quinine (an alkaloid that is part of the bark of the cinchona tree), chloroquinone (a derivative of 4-aminoquinoline), artemisinin (an extract of the annual wormwood plant - Artemisia annua) and its synthetic analogues.
The difficulty in treatment lies in the ability of malarial plasmodium to mutate and acquire resistance to one or another antimalarial drug, so the choice of drug is made on the basis of diagnosis, and in case of mutation, the drug is changed. It is also worth noting that many antimalarial drugs are not registered in the Russian Federation.
Essential medicines for malaria- quinine ("Quinine hydrochloride", "Quinine sulfate"), chloroquine ("Delagil"), cotrifazid, mefloquine ("Mefloquine", "Lariam"), proguanil ("Savarin"), doxycycline ("Doxycycline", "Doxylan" ), as well as combination drugs - atovaquone / proguanil (Malaron, Malanil), artemether / lumefantrine (Coartem, Riamet), sulfadoxine / pyrimethamine (Fansidar).
Separation of antimalarial drugs depending on the phase of the disease (localization of plasmodia):
Histoschizotropic - affect mainly tissue forms of infection (in the presence of plasmodium in liver cells, active substances): quinopide, primaquine.
Hematoschizotropic - affect mainly erythrocyte forms of infection (active substances): quinine, chloroquine, amodiaquine, halofantrine, pyrimethamine, mefloquine, lumefantrine, sulfadoxine, clindamycin, doxycycline, artemisinin.
Gametotropic - affect mainly gametes: quinocide, quinine, hydroxychloroquine, primaquine, pyrimethamine. This group of drugs is mainly used for tropical malaria.
2. Symptomatic therapy
If the patient is in a coma, he is turned on his side to avoid suffocation when vomiting vomit.
At a persistent high temperature of 38.5 ° C and above, compresses and - "", "", "" are used. Acetylsalicylic acid is contraindicated.
In case of violations of the water balance, rehydration therapy is carried out with caution.
With a decrease in hematocrit below 20%, a transfusion of blood products is prescribed.
To maintain the health of the liver, including due to the use of antimicrobials, the doctor may prescribe hepatoprotectors - Phosphogliv, "", "Liv 52".
The choice of other drugs depends on the complications and syndromes associated with malaria.
Treatment of malaria with folk remedies
Treatment of malaria at home is not recommended, due to the high mortality from this disease in the absence of timely antimicrobial therapy.
Malaria prevention includes:
- Destruction of mosquitoes in places of residence, the use of insecticides (for example, DDT -ethane).
- Installing mosquito protection in homes - nets, mosquito traps and others, especially increases efficiency when the mosquito net is treated with insecticide.
- Application of mosquito repellents.
- Refusal to travel to malaria endemic countries - Central and South Africa, Central and South America, Southwest Asia, Oceania.
- The use of certain antimicrobial drugs that may be included in the course of treatment for infection with malarial plasmodium - primaquine, quinacrine, mefloquine (Lariam), artesunate / amodiaquine. However, if a person still becomes ill with malaria, the remedy used for prevention can no longer be used. In addition, these drugs have a number of side effects. The prophylactic is started 1 week before the trip to the endemic area and up to 1 month after the trip.
- Experimental (as of 2017) vaccinations are PfSPZ (which is applicable to Plasmodium falciparum) as well as Mosquirix™ (RTS,S/AS01).
- Some scientists are currently developing genetic modifications of mosquitoes that are resistant to malaria.
- Immunity against malaria infection develops slowly and, according to doctors, provides little or no protection against re-infection with malaria.
Which doctor will contact?
- Immunologist
Video
The fear of contracting an infectious disease is familiar to many travelers to tropical countries. It is in the warm regions that most of the pathogens of severe pathologies in the human body live. One such disease is tropical malaria.
What kind of disease is this, what are the causes and sequence of its occurrence, what are the symptoms and treatment, and how to help the body quickly get rid of a terrible disease - read in our publication.
Description of the infection
At the moment, science has established five types of plasmodia - the causative agents of this pathology.
The disease got its name from the Italian word malaria. In translation, malaria means bad, spoiled air. Another name for this disease is also known - swamp fever. This is because, along with hepatolienal syndrome (enlargement of the liver and spleen) and anemia (anemia), paroxysm of fever is considered the main symptom of malaria.
"Malarial fever causes 3 million deaths each year, of which one million are young children."
The main source of infection in malaria is the bite of a female malarial mosquito, since anopheles males feed on the nectar of flowers. Infection occurs when the causative agent strain of malaria enters the blood of a person:
- After being bitten by an Anophele mosquito.
- From mother to child during pregnancy and childbirth.
- Through the use of non-sterile medical instruments with remnants of infected blood cells.
People have been suffering from malaria since ancient times. The intermittent fever inherent in the disease is described in a Chinese chronicle dated to 2700 BC. e. The search for the root cause of malaria lasted for thousands of years, but the first success came to physicians in 1880, when the French physician Charles Laveran was able to detect plasmodia in the blood of an infected patient.
Malaria has been known since ancient times
Among women: pain and inflammation of the ovaries. Fibroma, myoma, fibrocystic mastopathy, inflammation of the adrenal glands, bladder and kidneys develop.
Want to know what to do? For starters, we recommend
Features of human infection
Anopheles, to which the malarial mosquito belongs, live on almost all continents, with the exception of territories whose climate is too harsh - Antarctica, the Far North and Eastern Siberia.
However, only those members of the Anopheles genus that live in southern latitudes cause malaria, since the Plasmodium they carry can only survive in warm climates.
With the help of the image you will learn what a malaria mosquito looks like.
Mosquitoes are the main carrier of the disease.
"According to the WHO, 90% of infections have been reported in Africa."
Anopheles are blood-sucking insects. Therefore, malaria is considered a disease of transmissible etiology, that is, an infection that is transmitted by blood-sucking arthropods.
The life cycle of anopheles takes place near water bodies, where the mosquito lays eggs and larvae appear. For this reason, malaria is common in waterlogged and swampy areas. An increase in the incidence can be observed during periods of heavy rains that have replaced drought, as well as as a result of population migration from epidemiologically disadvantaged regions.
The degree of infection is determined by the number of bites of infectious mosquitoes per year. In the countries of Southeast Asia, this figure rarely reaches one, while residents of tropical Africa can be attacked by insect vectors more than 300 times a year.
The main distribution area of the disease is tropical latitudes.
Like many infectious diseases, epidemics and acute outbreaks of malaria most often occur in endemic areas or in remote areas where people do not have access to essential medicines.
To reduce the incidence rate, modern epidemiology recommends vaccinating people living in swampy areas where the disease is usually common.
Varieties of pathology
The development of various forms of malaria is provoked by different types of plasmodia.
The most common and one of the most dangerous types of the disease is tropical malaria. It is distinguished by lightning-fast damage to internal organs, the rapid course of the disease, and a large number of severe complications. Often leads to death. Treatment of the infection is hampered by the resistance of the strain to most antimalarials. The causative agent is Plasmodium falciparum.
This type of infection is characterized by relapsing fever with significant daily temperature fluctuations, including a critical decrease in its indicators. Attacks are repeated at short intervals. The infection lasts for a year.
As a rule, with tropical malaria, cerebral, septic, algidic and renal forms of pathologies develop, as well as malarial coma, increased tendon reflexes and a coma.
Three-day malaria is the result of infection with a strain of Plasmodium vivax. Downstream, the three-day form of the pathology is similar to oval malaria caused by a strain of Plasmodium ovale, which is much less common. If malaria attacks are similar in symptoms, then the methods of its treatment are usually the same.
The incubation of strains that cause a three-day form of infection is short and long, depending on the variety of Plasmodium. The first signs of malaria of the three-day type can appear both after 14 days and after 14 months.
Its course is characterized by multiple relapses and the appearance of complications in the form of hepatitis or nephritis. Pathology responds well to treatment. The total duration of infection is 2 years.
The disease is characterized by the development of complications.
"Negroids have antimalarial immunity and are resistant to the Plasmodium vivax strain."
Four-day malaria (quartana) is a form of infection with a strain of Plasmodium malariae.
Malaria of the four-day type is characterized by a benign course, without enlargement of the spleen and liver and other pathological conditions that usually develop against the background of the disease. The main symptoms of quartana are quickly eliminated with medication, but it is difficult to completely get rid of malaria.
"Bouts of four-day malaria can recur even 10 to 20 years after its symptoms have been eliminated."
There are known cases of infection of people as a result of blood transfusions from donors who had previously had a four-day form of infection.
Another pathogen, a strain of Plasmodium knowlesi, has recently been discovered. It is known that this strain of Plasmodium causes the spread of malaria in Southeast Asia. So far, epidemiology does not have complete information about the features of this form of the disease.
All types of malaria differ in symptoms, course and prognosis of the disease.
The specifics of the development of infectious pathology
"Several thousand daughter cells can develop from a single sporozoite, enhancing the progress of the disease."
The subsequent stages in the development of the pathogen determine all the pathological processes that characterize the clinical picture of malaria.
- tissue schizogony.
The disease has several stages of development.
Moving along with the blood flow, Plasmodium penetrate into the hepatocytes of the liver and are divided into forms of rapid and slow development. Subsequently, chronic malaria arises from a slowly developing form, causing numerous relapses. After the liver cells are destroyed, the plasmodia enter the blood vessels and attack the red blood cells. At this stage, the clinical symptoms of malaria do not appear.
- Erythrocyte schizogony.
Having penetrated into erythrocytes, schizonts absorb hemoglobin and increase in size, which causes rupture of the erythrocyte and the release of malarial toxins and newly formed cells - merozoites into the blood. Each merozoite is again introduced into the erythrocyte, starting a repeated cycle of damage. At this stage of malaria, a characteristic clinical picture is manifested - fever, enlargement of the spleen and liver.
- Gametocytogonia.
The final stage of erythrocyte schizogony, which is characterized by the formation of plasmodium germ cells in the blood vessels of the internal organs of a person. The process is completed in the stomach of the mosquito, where the gametocytes enter with the blood after the bite.
The life cycle of Plasmodium, which causes the development of malaria, is presented in the video below.
The duration of the life cycle of plasmodia influences the incubation period of malaria.
Manifestations of symptoms
From the moment an infectious agent enters the human body to the stage when the pathological anatomy of malaria appears, a lot of time can pass.
Four-day malaria can appear within 25-42 days.
The pathogenesis of tropical malaria occurs relatively quickly - in 10-20 days.
Three-day malaria has an incubation period of 10 to 21 days. Infection, transmitted by slowly developing forms, becomes acute within 6-12 months.
Oval-malaria manifests itself in 11-16 days, when infected with slowly developing forms - from 6 to 18 months.
Depending on the period of development of the disease, the symptoms of malaria differ in the intensity and nature of the manifestations.
- prodromal period.
The first signs of the disease are nonspecific and look more like a viral infection than a serious illness like malaria. The malaise is accompanied by headaches, deterioration of health, weakness and fatigue, periodically manifested by pain in the muscles and a feeling of discomfort in the abdomen. The average duration of the period is 3-4 days.
- period of primary symptoms.
Occurs when a fever occurs. The paroxysm characteristic of the acute period appears in the form of successive stages - chills with an increase in temperature from 39 ° C and a duration of up to 4 hours, fever with an increase in temperature to 41 ° C and a duration of up to 12 hours, increased sweating, lowering the temperature to 35 ° C.
- Intercritical period.
During it, the body temperature normalizes and the well-being improves.
Symptoms of the disease depend on the stage.
In addition, there are such consequences of malaria as yellowness of the skin, confusion, drowsiness or insomnia, anemia.
Features of pathological changes
Depending on the type of disease, malarial paroxysm is determined by specific characteristics. The definition of three-day malaria involves a short morning attack that appears every other day. The duration of the attack is up to 8 hours.
The four-day form is characterized by a recurrence of attacks every two days.
During the tropical form of the disease, short interictal periods (3-4 hours) are observed, and the temperature curve is characterized by the predominance of heat for 40 hours. Often the body of patients can not withstand such a load, which leads to death.
With a long course of the disease, the plasmoid pigment is absorbed by the internal organs.
It is possible to detect complications of malaria in the form of an increase in organs in children a few days after the onset of the disease with the help of palpation. Children, unlike adults, are not protected by immunity that can resist infection.
In the tropical form of infection, pathological anatomy is observed in the brain, pancreatic and intestinal mucosa, heart and subcutaneous tissue, in the tissues of which stasis is formed. If a patient has been in a malarial coma for more than a day, petechial hemorrhage and necrobiosis in certain parts of the brain are possible.
The pathomorphology of three-day and four-day malaria is practically the same.
Elimination of the consequences of infection
To diagnose an infectious lesion in medicine, a complete blood count, urinalysis, biochemical analysis, as well as clinical, epidemic, anamnestic criteria and laboratory results are used.
Differential diagnostic testing of patients' blood smears for malaria and possible complications is indicated for all patients with febrile symptoms. The procedure is prescribed before the start of treatment.
Often, donors - carriers of pathogens transmitted through the blood - become the source of infection.
As soon as the diagnosis is confirmed, the patient is hospitalized in an infectious diseases hospital and treatment is prescribed.
The aims and objectives of treatment measures are summarized in the form of a short guide:
Treatment has a number of main directions.
- The vital activity of the causative agent of the disease in the patient's body must be interrupted.
- The development of complications should be prevented.
- Do everything to save the life of the patient.
- To ensure the prevention of the development of a chronic form of pathology and the appearance of relapses.
- Prevent the spread of the infectious agent.
- Prevent Plasmodium from developing resistance to antimalarial drugs.
The basis of medical care for the patient is preparations of hematoschizotropic (Hingamin, Delagil, Chloridine) and gametocidal action (Delagil). In the acute course of the disease, the patient is provided with complete rest, plenty of fluids, and protection from hypothermia. In addition, a diet is recommended, aimed at increasing immunity and general strengthening of the patient's body, and folk remedies for malaria.
Even a strong and healthy man finds it difficult to cope with the infection on his own. Without the help of professional doctors, the disease can cause such severe complications as malarial coma, the development of hemorrhagic and convulsive syndrome, malarial algid, cerebral edema, renal failure, urinary retention, the appearance of a hemorrhagic rash, DIC, etc.
The fight against malaria involves measures to prevent the disease - protection from mosquito bites, vaccination and antimalarial drugs.
The disease is very insidious. It must be treated under constant medical supervision. At home, it is impossible to achieve the desired effect; at best, it will be possible to remove the symptoms of the disease. However, this is not enough - to avoid relapse, you need long-term adequate treatment.
