What is Malaria?
Malaria (Italian mala aria – “bad air”, formerly known as “swamp fever”) is a group of vector-borne infectious diseases transmitted to humans by mosquito bites of the genus Anopheles (“malaria mosquitoes”) and accompanied by fever, chills, splenomegaly (enlarged spleen ), hepatomegaly (an increase in liver size), anemia. It is characterized by a chronic relapsing course. Caused by parasitic protists of the genus Plasmodium (80-90% of cases – Plasmodium falciparum).
Malaria causes about 350-500 million infections each year and about 1.3-3 million deaths in humans. Sub-Saharan Africa accounts for 85-90% of these cases, the vast majority of children being infected under the age of 5 years. Mortality is expected to double in the next 20 years.
History of Malaria
It has been suggested that people have had malaria for over 50,000 years. The birthplace of malaria is believed to be West Africa (P. falciparum) and Central Africa (P. vivax). Molecular genetic data indicate that the pre-parasitic ancestor of plasmodium was a free-living protozoan capable of photosynthesis, which adapted to live in the intestines of aquatic invertebrates. He could also live in the larvae of the first bloodsucking insects of the Diptera order, which appeared 150-200 million years ago, quickly acquiring the opportunity to have two hosts. With the advent of humans, malaria parasites developed, capable of changing hosts between humans and mosquitoes of the genus Anopheles. The oldest mosquito fossils found with the remains of malaria parasites are 30 million years old.
The first chronic records of malaria fever were discovered in China. They date from about 2700 BC. e., during the reign of the Xia Dynasty.
Causes of Malaria
The causative agents of malaria are the simplest 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 the fifth species, Plasmodium knowlesi, also causes malaria in humans in Southeast Asia. A person becomes infected with them at the moment of inoculation (injection) by a female malaria 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 bloodsucking.
After a short stay in the blood, sporozoites of malarial plasmodium penetrate the hepatocytes of the liver, thereby giving rise to a preclinical hepatic (exoerythrocyte) stage of the disease. In the process of asexual reproduction, called schizogony, from one sporozoite as a result, from 2,000 to 40,000 hepatic merozoites, or schizonts, are formed. In most cases, these daughter merozoites again enter the bloodstream after 1-6 weeks. In infections caused by some North African P.vivax strains, the primary release of merozoites from the liver into the blood occurs approximately 10 months after the infection, at a time coinciding with the short-term period of mass mosquitoes in the next year.
In infections caused by P. falciparum and P. malariae, the hepatic stage of development of parasites at this end. In infections caused by other types of malarial plasmodium, the “sleeping” hepatic stages (the so-called hypnosis) remain and persist for a long time in the liver, they can cause new relapses of the disease and new episodes of the release of parasites into the blood (parasitemia) months and years after infection.
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, are apparently different for different types of malarial plasmodia.
Epidemiology of Malaria
In vivo, malaria is a naturally endemic, protozoal, anthroponous, vector-borne infection.
The source of infection is a patient or parasitic carrier in the blood of which there are gametocytes. A more effective source is a patient, as a rule, with higher parasitemia and low immunity. Parasitic carriers are less important, because they have more formed antiparasitic immunity and the antibodies circulating in the blood block the development of gametocytes in the carrier organism.
The most effective source of infection is children who are more accessible for mosquito bites, because their body surface is more exposed, and they do not use incense that repels mosquitoes. In addition, the lack of immunity in children is accompanied by a higher parasitemia.
A patient or parasitic carrier is contagious to a mosquito during the entire period of the presence of gametocytes in its blood. In three-day, oval and four-day malaria, gametocytes appear from the first days of the disease and disappear from the blood simultaneously with schizonts. In tropical malaria, gametocytes enter the patient’s blood on the 7-10th day after the onset of attacks and remain in the blood long enough – 1.5-2 months after the disappearance of schizonts, that is, patients with tropical malaria later become a source of infection, but remain longer him after the disappearance of clinical symptoms.
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, posthemotransfusion) and vertical (transplacental).
The main transmission path is transmission. The carriers of human malaria are female mosquitoes of the genus Anopheles. Males feed on nectar of flowers.
The main carriers of malaria in Ukraine:
An. messae, An. maculipennis, An. atroparvus, An. sacharovi, An. superpictus, An. pulcherrimus et al.
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 saturated with blood, eggs do not develop. Blood-fed females remain in the dark corners of residential or utility rooms, vegetation thickets until the end of blood digestion and egg maturation. The higher the air temperature, the faster the development of eggs in the female body ends (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 pond, where they lay their eggs. Such reservoirs are called anofelogenic.
The maturation of the water stages of carrier 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 mosquito generations can appear in the middle latitudes, 6–8 in the south, and up to 10–12 in the tropics.
The development of plasmodia of malaria in the mosquito organism is also affected by air temperature and the degree of parasite adaptation to this type of carrier.
For sporogony, a temperature of at least + 16 ° C is required. Sporogonia P. vivax at + 16 ° C is completed in 45 days, at + 30 ° C – in 6.5 days. The minimum temperature for sporogony P. falciparum is +19 – 20 ° С, at which it ends in 26 days, at + 30 ° С – in 8 days.
The season for the transmission of malaria depends on this. In the tropics, the malaria transmission season reaches 8-10 months, in equatorial Africa – year-round.
In temperate and subtropical climatic 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 flying out in the spring are not carriers of plasmodium malaria, and mosquitoes come from malaria patients every new season.
Infection with malaria is also possible with blood transfusion, as well as with the use of blood-contaminated needles and syringes. When storing blood at + 4 ° C, parasites persist for up to 2 weeks.
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.
The susceptibility to malaria is universal. Only P. vivax is immune to the Negroid race.
The prevalence of malaria is due to geographical, climatic and social factors. The distribution limits 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, the distribution of which is determined by the geographical boundaries, has the widest range.
The range of tropical malaria is less, because the development of P. falciparum requires a higher temperature. It is limited to 45 ° – 50 ° s. w. and 20 ° s. w. Africa is the global hotbed of tropical malaria.
Four-day malaria, the area of which reaches 53 ° C, is the second most common in Africa. w. and 29 ° s w. 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 is practically eliminated and mainly imported malaria is recorded and isolated cases of local infection – secondary from imported ones.
Malaria is imported into Ukraine from tropical countries and from neighboring countries – Azerbaijan and Tajikistan, where residual foci exist.
The largest part of imported cases is three-day malaria, which is most dangerous due to the possible transmission of mosquitoes that are sensitive to this type of pathogen. In second place is the import of tropical malaria, the most clinically difficult, but less dangerous epidemiologically, as the mosquitoes of Ukraine are not sensitive to P. falciparum imported from Africa.
Cases of delivery with an unknown cause of infection are recorded – “airport”, “luggage”, “random”, “transfusion” malaria.
In view of the political and economic instability in the world, the growth of migration and the implementation of large-scale irrigation projects, the WHO European Bureau has identified malaria as a priority problem in connection with the possibility of returning the infection.
Under the influence of these factors, the formation of new foci of malaria, i.e., settlements with adjacent anophelogenic water bodies, is possible.
In accordance with the WHO classification, 5 types of foci of malaria 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 – the occurrence of local infections, transmission of malaria;
- active persistent – the presence of cases of local infection for three years or more without interruption of transmission;
- inactive – the transmission of malaria has ceased; there have been no cases of local infection in the last two years.
To assess the incidence of malaria in a certain area, malariometric indices are used: parasitic (percentage of people with blood parasites among the examined), splenic (percentage of people with an enlarged spleen among the examined), endemic (percentage of people with blood parasites and an enlarged spleen), etc.
An indicator of the intensity of the risk of infection with malaria according to the WHO classification is the splenic index in children from 2 to 9 years. According to this classification, 4 degrees of endemicity are distinguished:
- Hypoendemia – splenic index in children from 2 to 9 years to 10%.
- Mesoendemic – splenic index in children from 2 to 9 years old is 11 – 50%.
- Hyperendemia – splenic index in children from 2 to 9 years old is above 50% and high in adults.
- 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 during Malaria
According to the method of infection, sporozoite and schizont malaria are distinguished. Sporozoite infection is a natural infection through a mosquito, with which sporozoites penetrate the human body with saliva. In this case, the pathogen passes through tissue (in hepatocytes), and then the erythrocyte phase of schizogony.
Schizont malaria is caused by the introduction of ready-made schizonts into the human blood (hemotherapy, syringe malaria), therefore, unlike sporozoite infection, the tissue phase is absent here, which determines the clinical features and treatment of this form of the disease.
With tissue schizogony, there are no obvious manifestations of malaria, the clinical manifestation of infection is associated only with the erythrocytic development of the parasite.
The immediate cause of malaria fever attacks is the release of merozoites, a foreign protein, malaria pigment, hemoglobin, potassium salts, red blood cell residues, which change the specific reactivity of the body and, when acting on a 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 episodes characteristic of malaria is due to the duration and cyclicity of the erythrocytic schizogony of the leading generation of plasmodia of one kind or another.
Foreign substances circulating in the blood irritate the reticular cells of the spleen, liver, cause their hyperplasia, and with a prolonged course – the growth of connective tissue. The increased blood supply to these organs leads to their increase and soreness.
Of great importance in the pathogenesis of malaria is the sensitization of the body to a foreign protein and the development of autoimmunopathological reactions. The breakdown of red blood cells with erythrocyte schizogony, hemolysis due to the formation of autoantibodies, increased phagocytosis of red blood cells of the reticuloendothelial system of the spleen are the cause of anemia.
The pathogenesis of malignant forms (N. N. Ozeretskovskaya, 1980) is based on systemic lesions of microvessels with thrombohemorrhagic syndrome: increased capillary permeability, hemodynamic disturbances, shifts in the blood coagulation system, vasculitis, hemorrhages, which are found mainly in tropical malaria. Often observed in this form of malaria, brain damage is associated with the fact that the erythrocyte schizogony of P. falciparum occurs mainly in the capillaries of the internal organs, especially the brain, where a large number of parasites accumulate rapidly. As a result of a violation of the permeability of the vascular wall, perivascular edema occurs, blood viscosity increases, blood flow slows down, which leads to the formation of parasitic thrombi. Of no small importance in the development of malignant forms of tropical malaria are the manifestations of toxic toxic shock and allergies.
Relapses are typical of malaria. The reason for the near relapses in the first 3 months after the end of the primary acute symptoms is the preservation of part of the erythrocyte schizonts, which, due to a decrease in immunity, begin to actively multiply again. Late or long-term relapses characteristic of three-day and oval malaria (after 6-14 months) are associated with the completion of the development of bradysporozoites.