Minimum infectious dose. The interaction of micro- and macroorganism can be built in various ways

© V. A. MARKIN, 2012

UDC 616.98:578.828.6]-092:612.017.1.064]-022.3-07

V. A. Markin

Estimation of the minimum infectious doses of HIV during the spread of infection

Branch of the Federal State Institution 48th Central Research Institute of the Ministry of Defense Russian Federation- Virological Center, Sergiev Posad

When predicting the spread of HIV infection, including bioterrorism, it is essential to determine the minimum infectious doses for humans. data on the epidemiology and pathogenesis of HIV infection, as well as the biological properties of the pathogen, can serve as the initial data for the theoretical determination of the approximate value of the infecting dose of HIV. The most common route of transmission of the virus is parenteral injection. The likelihood of HIV transmission with blood depends on the frequency of transfusions, the stage of HIV infection in the donor, and the amount of blood injected into the recipient. An analysis of literature data on the epidemiology, pathogenesis of the infection and the properties of the pathogen, on the risks of HIV infection in different groups was carried out, and information on infections among injection drug addicts was summarized, which made it possible to tentatively assess the level of human sensitivity as species to this virus.

Keywords: HIV, pathogenesis, infectious dose, distribution, prognosis

Estimation of the minimum infective doses of HIV in the prevalence of its infection

Branch, Central Research Institute Forty-Eight, Ministry of Defense of the Russian Federation - Virology Center,

Sergiyev Posad, Moscow Region

Estimation of the minimum human infective doses of HIV is essential to the prediction of its infection prevalence, including in bioterrorism. Information on the epidemiology and pathogenesis of HIV infection and on the biological properties of the pathogen may serve as reference data for the theoretical determination of a rough infectious dose of HIV. The most common route of virus infection is parenteral transmission. The likelihood of HIV transmission through blood depends on the frequency of transfusions, the stage of HIV infection in a donor and the amount of blood given to a recipient. The author has analyzed the data available in the literature on the epidemiology and pathogenesis of the infection, on the properties of the pathogen, and on the risks of HIV infection in different groups and summarized information on the infection among injecting drug users, which could roughly estimate the level of sensitivity in man as a biological species to this virus.

Key words: HIV, pathogenesis, infectious doseprevalence, prognosis

HIV infection is an unusual anthroponotic socially significant disease that threatens the existence of a person as a biological species. Probably, all human races are genetically susceptible to this pathogen, that is, it can be argued that the human immunodeficiency virus (HIV) is absolutely pathogenic for humans, and the identified CCR5 resistance gene provides protection for about 1% of people. Suffice it to say that only in 2006 in the sub-Saharan zone of Africa from acquired immunodeficiency syndrome (AIDS - the final stage of HIV infection) killed 2.1 million people, and in total about 42 million people became infected with HIV in the world, of which the pandemic claimed the lives of 24 million Every year, the pandemic covers from 2.7 to 3 million people. The actual prevalence of HIV infection is from 0.5 to 1% of the adult population of Russia; The emerging epidemiological situation can be qualified as critical, leading to significant human and economic losses, which undoubtedly makes this disease the most important global medical and social problem. The process of globalization dramatically increases the spread of HIV. Until now, the disease is incurable, leading to the death of all infected;

there are no specific means of prevention, etiotropic drugs do not cure the disease, but prolong the life of patients.

One of the most powerful factors in the spread of HIV is drug use - more than 90% of cases with an established mechanism of infection are associated with intravenous administration of psychoactive drugs, while in terms of the consumption of the most massive drugs - opium and cocaine - Russia ranks first and second in the world, respectively. There is a real danger of the spread of HIV with contaminated drugs, including for the deliberate introduction of the pathogen. It is important to note that some drugs increase the replication of HIV and related viruses.

When predicting the spread of HIV infection, for grading the degree of danger of materials contaminated with the pathogen (including illegal drugs distributed), it is important to estimate the minimum infectious doses for humans at different ways infections. For obvious reasons, these parameters cannot be determined experimentally. For the vast majority of viral diseases, the real value of the weighted average (normalized)

Contact Information:

Markin Vladimir Alexandrovich, dr honey. Sciences, art. scientific collaborator; e-mail: [email protected]

infectious doses for humans (ID50H) is still unknown and is usually estimated not quantitatively, but descriptively as "large" or "small" doses.

Several approaches are known in the literature for indirect assessment minimum and weighted average infectious human doses of especially dangerous pathogens of viral infections. Among them, the most accurate is the modeling on animals of several species (including monkeys) of the described intralaboratory cases of human infection. Another approach is interpolation per human (as a biological species) of values, doses that cause infection in laboratory animals; at the same time, the complexity of interpreting the obtained data lies in the uncertainty of the ratio of sensitivity to pathogens in humans and animals different types. A known approach is based on determining the ratio between immunizing doses of live vaccines and lethal doses of virulent strains of the same pathogens for animals and immunizing doses of vaccines for humans. Finally, another of the methods is associated with a quantitative assessment of the sensitivity to certain viruses of human cell cultures. This approach, in our opinion, is the least predictive, since it does not take into account either the barrier functions of tissues and organs, or the protective effect of the body's immune system, or the pathogenesis of the infection as a whole. It should be noted that all these methods of quantitative assessment of human sensitivity to viruses are hardly applicable in the case of HIV, since there are no appropriate vaccines, animal species (with the exception of chimpanzees) that adequately reproduce human infection are unknown, and there are features of the infection pathogenesis.

Target present work- summarizing the data of the available literature on the pathogenesis of HIV infection and the levels of risk of infection of people in different epidemiological situations for a probabilistic analytical assessment of the minimum infectious doses of the pathogen.

The initial data for a theoretical assessment of the approximate value of the infecting dose of HIV, apparently, can be information on the resistance of the pathogen, pathogenesis and epidemiology of the disease, which can be identified in the available literature.

Virus resistance to damaging environmental factors. Retroviruses are relatively stable in the external environment. HIV is quickly inactivated by many chemical disinfectants, ionizing radiation, during heat treatment, but 100% sterilization is ensured only by autoclaving with heating to 180 ° C for 1 hour. Saliva and sweat enzymes are detrimental to HIV. At the same time, in some substrates, especially in frozen blood and its preparations, semen, the virus remains viable for many years.

The results obtained in assessing the persistence of HIV in aqueous solutions of homemade opioids or ephedrine derivatives intentionally contaminated in the laboratory (initial concentration of the pathogen 107 TCID50 in 1 ml) show that at room temperature the pathogen in the opium-containing preparation "khanka" can remain infectious at least 14 days, and in the "screw" (obtained from ephedrine) - up to 30 minutes. AT aqueous solution heroin HIV remained infectious for at least 8 days, which, according to the authors of the work, is quite enough for the transportation, packaging and clandestine sale of a contaminated drug anywhere in Russia.

The main elements of etiopathogenesis. The main natural route of HIV penetration into the human body is sexual. entrance gate for the virus, the mucous membranes of the genitals, rectum or oral cavity, where the main

target cells - CD+-lymphocytes and macrophages, in which the pathogen that has entered the body multiplies. From here, HIV spreads mainly lymphogenously to regional lymph nodes, in the cells of which it can also multiply. The level of accumulation in the lymph nodes can reach up to 106 (average 103) RNA copies per 106 cells. Further, having overcome the lymph nodes, HIV is carried by the bloodstream to organs and tissues.

In contrast to the natural ways of HIV infection, when the pathogen enters the bloodstream directly (with contaminated blood among drug addicts or iatrogenically), the virus bypasses the integumentary barrier systems of the body and gains the ability to directly enter cells that are sensitive to it.

Until now, a significant, in our opinion, aspect of infection remains unexplored - in what form of HIV is the most infectious (as a free virion or in infected cells (spermatozoa, lymphocytes, macrophages, etc.) containing immature virions or even a provirus). The physical state of the infection - a mature HIV particle or a provirus located in the genome of the host cell - undoubtedly determines the value of the minimum infecting dose, since intact virions are much more vulnerable to the action of enzymes and other barrier humoral factors of the macroorganism, which in fact inactivate part of the pathogen population that enters the body. Taking into account the peculiarities of the mechanism of HIV infection, it seems that even single viable cells that carry either a provirus or virions that have already matured and are ready for release are more dangerous to enter the macroorganism.

According to some reports, with sexual and vertical transmission, infection more often occurs directly by infected cells, in which the virus is inaccessible to antibodies. There is evidence that in breast milk the pathogen is in free form.

After HIV enters the cell, a double strand of DNA is formed that can integrate into the genome of the infected cell to form a provirus. 100,000 times more errors occur during reverse viral transcription than during normal viral replication, i.e. it generates an extremely high frequency of pathogen variability, leading to the formation a large number genovariants of the original strain or quasispecies, including recombinant ones, which is facilitated by the absence of special mechanisms for correcting genetic errors encoded in HIV. As a result, many variants of the pathogen appear in the body. The quantitatively dominant variant has an advantage in replication at the corresponding stage of pathogenesis.

In the process of ontogenesis, HIV captures many cell surface proteins, including histocompatibility proteins of the first and second classes, which provides the pathogen with antigenic mimicry - masking the virus from attacks by the host's immune system, in particular avoiding neutralization by antibodies.

In an unactivated cell, HIV can remain in the provirus stage indefinitely. Full life cycle the virus passes in 1-2 days; during the height of the infection, up to 109 viral particles can be formed in the body per day. At the same time, the concentration of viral nucleic acids in blood plasma can reach 103-105 RNA copies per 1 ml.

Thus, HIV can be present in a macroorganism in several forms - both a free virion and inside infected CD4+ cells - from a provirus to ready-to-release mature viral particles.

In infected people in the first weeks after

lesions in the absence of an antibody response, very small amounts of extracellular virions in blood plasma can be detected; at the same time, no more than 1% of circulating CD4+ lymphocytes are carriers of the provirus or express tRNA. Later, until the period clinical manifestations, the number of affected lymphocytes decreases to 0.001-0.0001% (1 per 10,000-100,000 cells). However, after some time, the concentration in the blood of the pathogen in one form or another sharply increases - up to 103-104 TCID50 in 1 ml or more.

AT different phases infection, the concentration of the virus in the blood can range from units to 104 TCID50 in 1 ml. In terms of the problem under consideration, the data presented in the work of D. D. Ho et al. are of interest. from 54 seropositive individuals: 16 asymptomatic, 20 with AIDS, and 18 with pre-AIDS. According to experimentally determined data, in the blood plasma of an asymptomatic carrier, the concentration of extracellular HIV is on average 30 TCID50 per 1 ml, and in the plasma of patients it is 90 times higher. The concentration of the virus in monocytes in the carrier is on average 20 TCID50 106, and in patients - 2200-2700 TCID50 106 per 1 cell. At the same time, according to M. Harper et al. , all mononuclear cells are infected, but 99.6% of them contain a latent virus, and 0.4% have an active one. In AIDS patients, 1 in 40 CD4+ mononuclear cells and 10% of other cells with the same receptor contain a provirus or virus. Accordingly, in an average virus carrier who does not have AIDS manifestations, 1 out of 50,000 mononuclear cells is infected, and in the later stages of the disease (when symptoms appear), the number of infected cells increases sharply and this is already 1 out of 400 mononuclear cells. Based on the fact that 10% of all mononuclear cells in AIDS patients are represented by CD4+-lymphocytes, it can be assumed that 1 out of 40 CD4+-lymphocytes in the blood of patients, respectively, will be carriers of HIV.

According to S. A. Jenison et al. , the concentration of HIV in the blood of those infected is determined by relatively close to the above values ​​- 1 ml of the blood of an AIDS patient contains from 10 to 1000 TCID50 of the pathogen. According to R. W. Coombs et al. , in the blood plasma of asymptomatic HIV carriers, the concentration of a free pathogen varies from 1 to 1043 (average 1014) TCID per 1 ml, in patients with AIDS - an average of 1025 TCID50 per 1 ml. In the work of H. A. Perkins, it was suggested that during HIV infection, the concentration of the virus in the blood ranges from 1 to 102 TCID50 per 1 ml.

With HIV infection in almost all biological fluids human body virus particles are present. According to the literature, in sweat, saliva, lacrimal fluid, breast milk and vaginal secretions, the concentration of the virus is about 1 TCID50 per 1 ml, in the seminal fluid the concentration of the pathogen reaches 10-50 TCID50 per 1 ml. The work reported that in breast milk with using PCR Pathogen RNA was detected in 39% of infected mothers. It is generally accepted that tears, saliva and sweat are very rare substrates for HIV transmission, and vaginal secretions, seminal fluid and especially blood are the main factors for transmission of the pathogen, although the virus concentration is low in the first five of these secretions.

Differences in the concentration of viral particles in secretions that can pass from an infected person to

healthy with contacts significant for infection, predetermine their unequal epidemic significance as factors in the transmission of the virus, i.e., the level of risk of infection by them.

Thus, the fundamental features of the etiopathogenesis of HIV infection are: antigenic mimicry, which allows the pathogen to escape from the immune surveillance of the macroorganism, including when overcoming barriers; the possibility of penetration of the pathogen into the body inside the CD4+ macrophages that captured it, bypassing the barriers of the mucous membranes; the formation during ontogenesis of a large number of quasi-species, which form more and more new ecological niches at different stages of infection development. In the aggregate implementation of all these and a number of other mechanisms, the pathogen manages to move from one macroorganism to another, apparently at very low infecting doses and for an extremely long time, which is very important for the spread of infection. In general, the features of the etiopathogenesis of HIV infection and its invariably fatal outcome indicate a very high virulence of the pathogen for humans. The epidemic potential of the pathogen can lead to the fact that the currently developing HIV pandemic can cause large-scale catastrophic consequences for individual countries or peoples in the distant future.

Estimation of human infecting doses of HIV. The probability of infection of a macroorganism, or the risk of infection, will be the resultant between the initial amount of the pathogen and the fractions of the population eliminated from the process that did not pass the barriers, did not meet the sensitive cell, did not find specific receptors on it during the time that the pathogen maintained its viability.

In experimental medicine, the sensitivity of animals as biological species to any pathogen is usually expressed as doses that cause damage to a certain proportion of the population (ID^, as a rule, 50% of the infected animals (ID50). For a prognostically significant assessment of the probabilistic value of the infectious dose We will use data from the available literature on the magnitude of the risks of infection for injecting drug users and accidentally infected medical personnel, expressed as a percentage or proportion of those infected after the introduction of the corresponding amount of infection.

In the literature, the likelihood of naturally occurring HIV infection is considered high, moderate, or low, depending on exposure to contaminated blood, semen, or other body fluids of infected people, respectively.

Of all the possible routes of transmission of the virus (sexual, parenteral, and from mother to fetus or newborn), the greatest danger is the injection of HIV infection, i.e., the parenteral route of transmission. Parenterally, the virus can be transmitted among drug addicts when using one syringe for intravenous drug administration, in medical institutions - with blood transfusions, accidental injections of medical personnel with used needles contaminated with fresh blood, cutting tools etc. The probability of contracting HIV in this case depends on the dose of the pathogen, determined by the concentration of the virus in the blood (associated with the stage of HIV infection in the virus carrier), the frequency of injections and the volume of the virus-containing substrate that has entered the body.

Blood infection. Let us estimate the approximate amount of a cell-bound pathogen that can be transmitted with blood on a contaminated syringe needle. 1 ml of blood contains 0.65 ml of plasma, and the average number of mononuclear cells is 2,106 cells; considering this-

th, as well as the above information on etiopathogenesis, the blood of an asymptomatic carrier may contain about 60 TCID per 1 ml, and a patient with pre-AIDS or AIDS - about 7000 TCID per 1 ml. In laboratory samples, when 1-10 ml of blood is taken from a patient, there may be from 7103 to 7104 TCID50 of the pathogen. In the case of the exchange of syringes between infected drug addicts, a needle containing about 10-100 µl of blood can contain from 0.6 to 6 TCID50 of the virus, respectively (if the infected person is an asymptomatic virus carrier). On a needle used by an AIDS patient, the amount of the pathogen is significantly larger and ranges from 70 to 700 TCID50 of the virus, which means that the risk of infection is higher. The parenteral route of infection of HIV by drug addicts who inject drugs in companies with shared syringes or needles leads to a relatively rapid spread of infection. This is explained, as can be seen from the above, with respect to high level viremia in drug addicts at the height of AIDS and, accordingly, high contamination of the needles they used from syringes with the pathogen in doses large enough for infection, as well as the resistance of the virus in the blood outside the macroorganism. This group of virus carriers poses a huge epidemiological danger for the yet uninfected drug addicts who come into contact with them.

The risk of acquiring HIV for drug addicts is determined primarily by the number of partners involved in group drug use, the frequency of injections and the degree of contamination of syringes. Thus, according to surveys, the frequency of infection among drug addicts who usually do not exchange syringes is 30%, among those who exchange rarely - 56% and among those who exchange regularly - 75%. These figures, obtained from surveys of drug addicts, do not indicate real levels of risk, but only trends and, accordingly, have little predictive value for assessing infectious doses.

It seems that it is more expedient to use foreign materials on investigations of infection of medical staff and descriptions of cases of infection during blood transfusion as reliable initial data. Accidental infection of medical personnel with HIV occurs, as a rule, as a result of a single accident associated with instruments infected with the blood of patients; all accidental damage skin medical staff abroad are registered, which allows us to estimate the proportion of infected people from the total number of victims. According to foreign literature, the proportion of HIV infection of medical staff from accidental injections with infected needles ranges from 0.3 to 0.5%. In a study of 19 cases of infection of medical staff, it was found that the amount of blood on the needles could average 1 μl. It is noted that a needle prick through a silicone glove reduces the initial volume of blood on the needle by 50%. Based on the etiopathogenesis data on the concentration of HIV in the blood of asymptomatic carriers and AIDS patients, and taking into account the possible volume of the inoculum, it is easy to determine that health workers were infected with a dose of the virus of the order of 0.001-0.01 TCID50. Taking into account the proportion of those infected with single injections (0.3-0.5%), it can be assumed that the value of ID0 5 for a person with injection infection will be from 0.001 to 0.01 TCID50 of the pathogen.

Information about the risks of HIV infection during blood transfusions can also be used in an approximate assessment of a person's sensitivity to this pathogen. In the United States, before the mandatory testing of donors for HIV, more than 10 thousand cases of infection with the virus after blood transfusion were detected, which was 0.04% of cases.

Effect (infection), N, %

The principle of graphical estimation of the approximate value of ID50 using an S-shaped dose-response curve.

The known values ​​of the infecting doses (A) and the corresponding levels of infection (N) - points A^ A2, N and N2 - determine the construction of an S-shaped curve in the dose-effect coordinate system. To determine the dose of ID50 from the central point of the rectilinear section of the curve, the perpendicular to the abscissa axis is restored.

recipients. Subsequently, in the United States, the frequency of infections from blood transfusions halved (to 0.02%). By the beginning of the 1990s, the number of recipients in the world who became infected through blood transfusions was 12 thousand among adults and three times more among children.

During a long-term follow-up of recipients who were accidentally injected with the blood of HIV-seropositive asymptomatic donors once, it was found that 90% of them turned out to be infected. These data suggest that a single transfusion dose (250 ml) of contaminated blood from asymptomatic donors has a risk of infection of at least 90%. Taking into account information on etiopathogenesis, it can be calculated that 250 ml of blood taken from an asymptomatic carrier of HIV contains 1.5 104 TCID50 of the virus, and taken from a clinically manifest patient - 1.75 106 TCID50. When calculating according to R. W. Coombs et al. a transfusion dose of blood from asymptomatic HIV carriers will contain 6.3 × 103 TCID50 of the virus. Accordingly, it can be assumed that the value of ID90 for intravenous infection of a person will be on average 1 104 TCID50 of the pathogen. This value is indicative, since outcomes with the introduction of smaller volumes of blood are unknown.

It is advisable to use the obtained estimated values ​​of ID05 and ID90 of HIV in case of injection infection of a person to calculate the approximate value of ID50 using a graphical method. Assuming as a starting point that the values ​​of infecting doses of HIV and the levels of infection of people by them in the aggregate correspond to a normal distribution, it is possible to construct the resulting curve in the coordinates “dose value - probability of infection” and determine the estimated value of ID50 (the evaluation principle is shown in the figure). As a result of this graphical determination, it was found that the HIV ID50 value for a person with injection infection is approximately 100-5000 (median value over a median of 500) TCID50 of the pathogen.

sexual infection. To estimate the magnitude of the infectious dose of HIV during sexual transmission of the pathogen, we will compare some data from the available literature, taking into account the low level of reliability of the information obtained from surveys. The risk of contracting HIV from one unprotected sexual contact with an infected man is about or less than 0.2% for women (ID0 2H). Based on the fact that the concentration of the pathogen in the seminal fluid ranges from 10 to 50 TCID50 per 1 ml, and the volume of the ejaculate is approximately 5 ml, it can be assumed that the value of ID0 2H during sexual intercourse

of HIV infection of women from men does not exceed 50-250 TCID50. Despite the fact that after 1-2 years of cohabitation, all female sexual partners become infected, the value of ID100Ch in the sexual method of HIV infection of women from men cannot be estimated, since single doses of the pathogen do not accumulate, and infection occurs due to a combination of any unfavorable circumstances ( the appearance of microtraumas, erosions, etc.).

Thus, the analysis of literature data on cases of HIV infection in different risk groups for the first time made it possible to tentatively assess the level of sensitivity of a person as a biological species to the virus. The probabilistic values ​​of infecting doses of HIV for humans (IDCHI) are: for intravenous infection with IDCHI - within 0.001-0.01 TCID of the pathogen; IDFI - within 100-5000 (average 500) TCID50 of the pathogen; ID90CHI - approximately 10,000 TCID50 of the pathogen; in case of sexual infection of women from men, ID0 2H does not exceed 50-250 TCID50 of the pathogen, which generally indicates a high sensitivity of a person to the human immunodeficiency virus.

For the first time, the estimated infectious doses and the corresponding risks of human infection during intravenous administration of HIV are very significant for the epidemiological assessment of the real danger of the spread of infection among drug addicts and in case of accidental iatrogenic infections. To clarify the susceptibility of a person as a biological species to HIV, i.e., the ID50CHI parameter, it is advisable to continue such theoretical studies and search for other methodological approaches, which together will increase the reliability of this criterion and its prognostic significance.

LITERATURE

1. Briko N. I., Pokrovsky V. I. Globalization and the epidemic process // Epidem. and infectious Bol. - 2010. - No. 4. - S. 4-10.

2. HIV infection: clinic, diagnosis and treatment / Pokrovsky V. V., Ermak T. N., Belyaeva V. V. et al.; Ed. V. V. Pokrovsky. - M., 2003.

3. Lvov D.K. The importance of re-emerging infections in biosafety // Vopr. virusol. - 2002. - No. 5. - S. 4-7.

4. Lysenko A. Ya., Turyanov M. Kh., Lavdovskaya M. V., Podolsky V. M. HIV infection and AIDS-associated diseases. - M., 1996.

5. Netesov S. V. Infections: new threats in the 21st century // Molecul. honey. - 2004. - No. 4. - S. 41-49.

6. Onishchenko G. G. Pandemic of HIV infection: expert assessments, measures taken by the state // Zhurn. microbiol. - 2006. - No. 6. - S. 25-30.

7. Onishchenko G. G. Implementation of the decisions of the "Group of Eight" on the fight against infectious diseases, adopted at the summit in Saint Petersburg// Immunology. - 2010. - No. 4. - S. 172-176.

8. Pokrovsky VV Epidemic of HIV infection in Russia - where are you going? // Epid. and infectious Bol. - 2004. - No. 4. - S. 4-6.

9. V. A. Pokhodyaev, N. Gonchar. I., Pshenichnov V. A. Experimental study of the contact transmission of the Marburg virus // Vopr. vi-rusol. - 1991. - No. 6. - S. 506-508.

10. Selimova L. M., Khanina T. A., Kazennova E. V. et al. Effect of a drug containing heroin on the infectivity of human immunodeficiency virus type 1 in vitro // Vopr. virusol. - 2002. - No.

11. Selimova L. M., Khanina T. A., Zverev S. Ya. virusol. - 2003. - No.

12. Chermashentsev V. M., Zhukov V. A., Maryasov A. G. et al. Some theoretical approaches to evaluating the effectiveness of antiviral drugs // Vestn. RAMN. - 1993. - No. 9. - S. 3-7.

13. Busch M. P. Risk of HIV transmission by blood transfusion before the implementation of HIV-1 antibody screening // Transfusion. -1991. - Vol. 31. - P. 4-11.

14. Chiasson M. A. HIV transmission through artificial insemination // J. AIDS. - 1990. - Vol. 3, No. 1. - P. 69-71.

15. Coombs R. W., Collier A. C., Allain J.-P. et al. Plasma viremia in

human immunodeficiency virus infection // N. Engl. J. Med. - 1989.

Vol. 321, No. 24. - P. 1626-1631.

16. Current and future dimensions of the HIV. AIDS pandemic. - WHO, GPA, SFI, 1990. - Vol. 2, Rev. one.

17. DaneganE. Transfusion of HIV-I by component type and duration of shell storage before transfusion // Transfusion. - 1990. - Vol. 30.-P. 851-855.

18. Fauci A. S. The HIV: Infectivity and mechanism of pathogenesis // Science. - 1988. - Vol. 237.-P. 617-622.

19. Feinberg M., Green W. Molecular insights into HIV-1 pathogenesis // Curr. Opin. Immunol. - 1992. - Vol. 4. - P. 466-474.

20. Fortin J.-F, Cantin R., Tremblay M. J. Presence des proteins de la cellule hote sur les particules virales: Influence sur le cycle de vie du VIH-1 // Med. sci. - 2001. - Vol.17, No. 2. - P. 186-192.

21. GavrilinM. A., MathesL. E., PodellM. Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes // J. Neurovirol. - 2002. - Vol. 8. - P. 240-249.

22. Geissler E. Agreed measures and proposals to strengthen the convention // Strengthening the biological weapons, convention by confidence-building measures / Ed. E. Geissler. - Oxford, 1990. - P. 43-70.

23. Harper M. E., Marselle L. M., Gallo R. C. et al. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization // Proc. Natl. Acad. sci. USA. - 1986. - Vol. 83.-P. 772-776.

24. Ho D. D., Moudgh T., Alam M. Quantitation of HIV-1 in the blood of infected persons // N. Engl. J. Med. - 1989. - Vol. 321. - P. 16211625.

25. Hu D. J., Dondero T. J., Rayfield M. A. et al. The emerging genetic diversity of HIV // J. A. M. A. - 1996. - Vol. 275, No. 3. - P. 210216.

26 Jenison S. A. et al. Quantitative analysis of hepatitis B virus DNA in saliva and semen of chronically infected homosexual men // J. Infect. Dis. - 1987. - Vol. 156. - P. 299-307.

27. KalishM. L., RobbinsK. E., PieniazekD. et al. Recombinant viruses and early global HIV-1 epidemic // Emerg. Infect. Dis. - 2004. - Vol. 10, No. 7. - P. 1227-1234.

28. Lafeuillade A., Chollet L., Hittinger G. et al. Residual human immunodeficiency virus type 1 RNA in lymphoid tissue of patients with sustained plasma RNA of<200 copies/mL // J. Infect. Dis. -

1998. - Vol. 177. - P. 235-238.

29. LeBreton M., Yang O., Tamoufe U. et al. Exposure to wild primates among HIV-infected persons // Emerg. Infect. Dis. - 2007. - Vol. 13, No. 10. - P. 1579-1582.

30. Lewis P., Nduati R., Kreiss J. K. et al. Cell-free human immunodeficiency virus type 1 in breast milk // J. Infect. Dis. - 1998.

Vol. 177, No. 1. - P. 34-39.

31. McCutchan F E. Global epidemiology of HIV // J. Med. Virol. -2006. - Vol. 78 (suppl. 1). - P.S7-S12.

32. Padian N., Wiley J., Winkelstein W. Male-to-female transmission of HIV // J. A. M. A. - 1987. - Vol. 258.-P. 788-792.

33. Perkins H. A. Risk of AIDS for recipients of blood components from donors who subsequently developed AIDS // Blood. - 1987. - Vol. 70. - P. 1604-1610.

34. Piatac M. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR // Science. - 1993. - Vol. 259. - P. 1749-1754.

35. Reznick L., VerenK., SalahuddinS. Z. et al. Stability and inactivation of HTLV-III/LAV // J. A. M. A. - 1986. - Vol. 255. - P. 1887-1891.

36. RobbinsD. S. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes // J. Immunol. - 1989. - Vol. 139. - P. 25932597.

37. Robertson J. R. Epidemic of AIDS related virus infection among intravenous drug users. // Br. Med. J. - 1986. - Vol. 292. - P. 527529.

38. Schweitzer C., VellerF., SchmittM. P. et al. Morphine stimulates HIV replication in primary cultures of human Kupffer cells // Res. Virol. -1991. - Vol. 142. - P. 189-195.

39. Taeron C. Resistances: Faire face // J. Democr. Sanit. - 2002. - No. 143. - P. 5-9.

40. Tao Binli, Fultz Patricia N. Pathogenicity and comparative evolution in vivo of the transitional quasispecies SIVsmmPBjS // Virology. -

1999. - Vol. 259, No. 1. - P. 166-175.

41. Tremblay M. J. Un virus sournois qui ne cesse de se modifier, Sci. Vie. - 2002. - No. 1023. - P. 114-117.

42. Virus taxonomy: The classification and nomenclature of viruses. The seventh report of the International Committee on Taxonomy of viruses / Eds M. H. V. Regenmortel et al. - San Diego, 2000.

Doctrine of infection- this is the doctrine of the properties of microorganisms that allow them to exist in the macroorganism and exert a pathogenic effect on it, and about the protective and adaptive reactions of the macroorganism that prevent this effect.

Infection(from lat. inficio) - I bring in something harmful, I infect and late Latin "infectio" - I infect.

Infection- a set of processes arising from the interaction between micro- and macroorganism.

infectious process- a set of pathological, physiological, reparative and other reactions of a macroorganism in response to the introduction of a pathogenic microorganism.

infectious disease- a set of clinical and laboratory symptoms resulting from reactions to the introduction of a microorganism.

For a long time, microbiology dominated Henle-Koch triad and the leading role in the occurrence of infection was assigned to the microorganism. According to the Henle-Koch triad, a microorganism to be considered the causative agent of this infectious process:

should always occur in a given infectious process and not occur in healthy people and in patients with other diseases;

must be isolated from the patient in pure culture;

a pure culture of the microorganism should cause the same disease in experimental animals.

But over time, it became obvious that the development of infection depends not only on the properties of the pathogen, but is also largely determined by the state of the macroorganism. The microorganism causing the infection may also be present in a healthy host. Therefore, at present, the infectious process, its occurrence, development and outcome is considered from the point of view of a complex process of interaction between micro- and macroorganism under certain environmental conditions in which it occurs.

The interaction of micro- and macroorganism can be built in various ways:

I. Neutralism- objects do not affect each other.

II. Symbiosis- objects interact to varying degrees:

A) commensalism - only one partner benefits

B) Mutualism - mutually beneficial relationship

Opportunistic pathogens are found both in the environment and in the composition of normal microflora - for healthy individuals they are harmless, but with massive infection and a violation of the resistance of the macroorganism, they can cause an infectious process.

The occurrence, course and outcome of the infectious process is determined by three groups of factors:

quantitative and qualitative characteristics of the microbe - the causative agent of the infectious process;

the state of the macroorganism, the degree of its susceptibility to the microbe;

the action of physical, chemical, biological factors of the environment surrounding the microorganism and macroorganism.

Qualitative and quantitative characteristics of the microorganism - the causative agent of infection.

A pathogenic microorganism, in order to cause an infectious process, must have the following properties:

1) pathogenicity (virulence);

2) nosological specificity and organotropism;

nosological specificity - each type of pathogenic microbes is capable of causing an infectious process characteristic only for it, as well as a symptom complex of pathological reactions, no matter what susceptible macroorganism it gets into. Opportunistic microbes do not have such specificity.

organotropism - this is the defeat of cells, tissues and organs that are most suitable in their biochemical properties for the life of these microbes.

3) infectious dose - the pathogenic microorganism must penetrate in an amount that can cause infection. The infectious dose is individual for each species.

)

the smallest number of pathogenic microorganisms of a given strain and a certain virulence that can cause the development of an infectious process in a person or animal sensitive to this pathogen.

1. Small medical encyclopedia. - M.: Medical Encyclopedia. 1991-96 2. First aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic dictionary of medical terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what the "Infective dose" is in other dictionaries:

- (ID) the smallest number of pathogenic microorganisms of a given strain and a certain virulence, capable of causing the development of an infectious process in a human or animal susceptible to this pathogen ... Big Medical Dictionary

- (ID50) quantitative indicator of the virulence of the causative agent of an infectious disease, expressed by the value of the infectious dose, which, with a given route of infection, causes the development of the disease in 50% of experimental animals ... Big Medical Dictionary

Such an amount (dilution, density) issl. micro-organisms, which cause a clinically manifested local or generalized infection in 50% of individuals of the test system (animals, embryos, test tubes with cell edges). To determine ID 50 in ... Dictionary of microbiology

I see Infectious dose. II see Medium infectious dose ... Medical Encyclopedia

See Infectious Dose... Big Medical Dictionary

See Intermediate infectious dose... Big Medical Dictionary

I Infection (late Latin intectio infection) is a complex pathophysiological process of interaction between a macroorganism and a microorganism, which has a wide range of manifestations from asymptomatic carriage to severe forms of an infectious disease. The term "infection" ... ... Medical Encyclopedia

Infectious diseases characterized by predominant damage to the liver, occurring with intoxication and in some cases with jaundice. In accordance with the recommendation of the WHO Expert Committee on Hepatitis (1976) G. century. considered as several... Medical Encyclopedia

The doctrine of infectious diseases goes back centuries. The concept of the contagiousness of such diseases as plague, smallpox, cholera and many others originated among ancient peoples; long before our era, some simple precautions were already taken against contagious patients. However, these fragmentary observations and bold guesses were very far from truly scientific knowledge.

Already in ancient Greece, some philosophers, for example Thucydides, expressed the idea of ​​living pathogens ("contagions") of infectious diseases, but these scientists were not able to confirm their assumptions with any reliable facts.

Outstanding Physician of the Ancient World Hippocrates(about 460-377 BC) explained the origin of epidemics by the action of "miasma" - contagious fumes, which supposedly can cause a number of diseases.

The progressive minds of mankind, even in the conditions of medieval scholasticism, rightly defended the idea of ​​the living nature of the causative agents of infectious diseases; like an Italian doctor fracastoro(1478-1553) developed a coherent doctrine of the contagions of diseases and the methods of their transmission in his classic work On Contagions and Contagious Diseases (1546).

Dutch naturalist Anthony van Leeuwenhoek(1632-1723) made a very important discovery at the end of the 17th century, discovering under a microscope (which he personally made and gave an increase of up to 160 times) various microorganisms in plaque, in stagnant water and infusion of plants. Leeuwenhoek described his observations in the book Secrets of Nature Discovered by Antony Leeuwenhoek. But even after this discovery, the idea of ​​microbes as causative agents of infectious diseases for a long time did not receive the necessary scientific justification, although devastating epidemics repeatedly developed in various countries of Europe, claiming thousands of human lives.

For many decades (in the 17th and 18th centuries), observations of epidemics of infectious diseases affecting large numbers of people convinced of the contagiousness of these diseases.

Of exceptional practical importance were the works of the English scientist Edward Jenner(1749-1823), who developed a highly effective method of inoculation against smallpox.

An outstanding domestic epidemiologist D.S. Samoilovich(1744-1805) proved the contagiousness of the plague in close contact with the patient and developed the simplest methods of disinfection for this disease.

The great discoveries of the French scientist Louis Pasteur (1822-1895) convincingly proved the role of microorganisms in the processes of fermentation and putrefaction, in the development of infectious diseases.

Pasteur's works explained the real origin of human infectious diseases, they were the experimental basis of asepsis and antiseptics, brilliantly developed in surgery by N.I. Pirogov, Lister, as well as their numerous followers and students.

Pasteur's great merit was the discovery of the principle of obtaining vaccines for protective vaccinations against infectious diseases: the weakening of the virulent properties of pathogens through a special selection of appropriate conditions for their cultivation. Pasteur obtained vaccines for anthrax and rabies.

German scientist Leffler proved in 1897 that the causative agent of foot-and-mouth disease belongs to the group of filterable viruses.

It should be noted that until the middle of the last century, many infectious diseases, called "fever" and "fever", did not differentiate at all. Only in 1813 did the French doctor Brittany suggested the independence of the disease of typhoid fever, and in 1829 Charles Louis gave a very detailed description of the clinic of this disease.

In 1856, typhoid and typhus were isolated from the group of "fever diseases" with a clear description of these completely independent diseases. Since 1865, they began to recognize a separate form of an infectious disease and relapsing fever.

World science appreciates the merits of the famous Russian clinician-pediatrist N.F. Filatov ( 1847-1902), who made a significant contribution to the study of childhood infectious diseases, as well as

D.K. Zabolotny(1866-1929), who made a number of important observations in the field of epidemiology of especially dangerous diseases (plague, cholera).

In the works of our compatriot N.F. Gamalei(1859-1949) reflected many issues of infection and immunity.

Thanks to the works of I.I. Mechnikov(1845-1916) and a number of other researchers since the 80s of the last century, the issues of immunity (immunity) in infectious diseases began to be resolved, the extremely important role of cellular (phagocytosis) and humoral (antibodies) defense of the body was shown.

In addition to the purely clinical study of infectious patients, laboratory methods began to be widely used to diagnose individual diseases from the end of the 19th century.

The work of a number of scientists ( I. I. Mechnikov, V. I. Isaev, F. Ya. Chistovich, Vidal, Ulengut) allowed at the end of the last century to use serological studies (agglutination, lysis, precipitation) for laboratory diagnosis of infectious diseases.

X. I. Gelman and O. Kalning the honor of developing a method for the allergic diagnosis of glanders (1892) is due. Recognition of malaria was greatly facilitated by the method of differential staining of the nucleus and protoplasm of the malarial plasmodium in blood smears, developed by D. L. Romanovsky (1892).

The meaning of the word "infection" is different. An infection is understood as a contagious beginning, i.e. pathogen in one case, and in another case, this word is used as a synonym for the concept of "infection, or contagious disease." Most often, the word "infection" is used to refer to an infectious disease. Infectious diseases have the following distinctive features:

1) the cause is a living pathogen;

2) the presence of an incubation period, which depends on the type of microbe, dose, etc. This is the period of time from the penetration of the pathogen into the host's body, its reproduction and accumulation to the limit that causes its pathogenic effect on the body (lasts from several hours to several months);

3) contagiousness, i.e. the ability of the pathogen to be transmitted from a sick animal to a healthy one (there are exceptions - tetanus, malignant edema);

4) specific reactions of the body;

5) immunity after recovery.

Infection(late Latin infektio - infection, from Latin inficio - I bring something harmful, infect) - the state of infection of the body; an evolutionary complex of biological reactions arising from the interaction of an animal organism and an infectious agent. The dynamics of this interaction is called the infectious process.

infectious process- this is a complex of mutual adaptive reactions to the introduction and reproduction of a pathogenic microorganism in a macroorganism, aimed at restoring disturbed homeostasis and biological balance with the environment.

The modern definition of an infectious process includes the interaction three main factors –

1) pathogen,

2) macroorganism

3) environment,

Each factor can have a significant impact on the outcome of the infectious process.

To cause disease, microorganisms must be pathogenic(pathogenic).

pathogenicity microorganisms is a genetically determined trait that is inherited. In order to cause an infectious disease, pathogenic microbes must enter the body in a certain infectious dose (ID). Under natural conditions, for the occurrence of infection, pathogenic microbes must penetrate certain tissues and organs of the body. The pathogenicity of microbes depends on many factors and is subject to large fluctuations in different conditions. The pathogenicity of microorganisms can decrease or, conversely, increase. Pathogenicity as a biological feature of bacteria is realized through their three properties:

infectiousness,

invasiveness and

Toxigenicity.

Under infectiousness(or infectivity) understand the ability of pathogens to enter the body and cause disease, as well as the ability of microbes to be transmitted using one of the transmission mechanisms, retaining their pathogenic properties in this phase and overcoming surface barriers (skin and mucous membranes). It is due to the presence in pathogens of factors that contribute to its attachment to the cells of the body and their colonization.

Under invasiveness understand the ability of pathogens to overcome the protective mechanisms of the body, multiply, penetrate into its cells and spread in it.

Toxigenicity bacteria due to their production of exotoxins. Toxicity due to the presence of endotoxins. Exotoxins and endotoxins have a peculiar effect and cause profound disturbances in the vital activity of the body.

Infectious, invasive (aggressive) and toxigenic (toxic) properties are relatively unrelated to each other, they manifest themselves differently in different microorganisms.

infectious dose- the minimum number of viable pathogens necessary for the development of an infectious disease. The severity of the course of the infectious process may depend on the size of the infectious dose of the microbe, and in the case of opportunistic bacteria, the possibility of its development.

The degree of pathogenicity or pathogenicity of microorganisms is called virulence.

The magnitude of the infectious dose largely depends on the virulent properties of the pathogen. There is an inverse relationship between these two characteristics: the higher the virulence, the lower the infectious dose, and vice versa. It is known that for such a highly virulent pathogen as the plague bacillus (Yersinia pestis), the infectious dose can vary from one to several microbial cells; for Shigella dysenteriae (Grigoriev-Shiga stick) - about 100 microbial cells.

In contrast, the infectious dose of low virulent strains can be equal to 10 5 -10 6 microbial cells.

The quantitative characteristics of virulence are:

1) DLM(minimum lethal dose) - the dose that causes the death of single, most sensitive experimental animals over a fixed period of time; taken as the lower limit

2) LD 50 is the amount of bacteria (dose) that causes the death of 50% of the animals in the experiment over a fixed period of time;

3) DCL(lethal dose) causes for a fixed period of time

100% death of animals in the experiment.

According to the degree of pathogenicity they are divided into:

Highly pathogenic (highly virulent);

Low pathogenic (low virulent).

High-virulence microorganisms cause disease in a normal organism, low-virulence - only in an immunosuppressed organism (opportunistic infections).

In pathogenic microorganisms virulence due to factors:

1) adhesion- the ability of bacteria to attach to epithelial cells. Adhesion factors are adhesion cilia, adhesive proteins, lipopolysaccharides in gram-negative bacteria, teichoic acids in gram-positive bacteria, in viruses - specific structures of a protein or polysaccharide nature; These structures responsible for adherence to host cells are called "adhesins". In the absence of adhesins, the infectious process does not develop;

2) colonization- the ability to multiply on the surface of cells, which leads to the accumulation of bacteria;

4) penetration- the ability to penetrate into cells;

5) invasion- the ability to penetrate into underlying tissues. This ability is associated with the production of enzymes such as

• neuraminidase is an enzyme that cleaves biopolymers that are part of the surface receptors of mucous membrane cells. This makes the shells available for exposure to microorganisms;

hyaluronidase - acts on the intercellular and interstitial space. This contributes to the penetration of microbes into the tissues of the body;

Deoxyribonuclease (DNase) - an enzyme that depolymerizes DNA, etc.

6) aggression- the ability to resist the factors of nonspecific and immune defense of the body.

To factors of aggression include:

Substances of various nature that make up the surface structures of the cell: capsules, surface proteins, etc. Many of them inhibit the migration of leukocytes, preventing phagocytosis; capsule formation- this is the ability of microorganisms to form a capsule on the surface that protects bacteria from phagocyte cells of the host organism (pneumococci, plague, streptococci). If there are no capsules, then other structures are formed: for example, in staphylococcus, protein A, with the help of this protein, staphylococcus interacts with immunoglobulins. Such complexes prevent phagocytosis. Or microorganisms produce certain enzymes: for example, plasmacoagulase leads to the folding of a protein that surrounds the microorganism and protects it from phagocytosis;

enzymes - proteases, coagulase, fibrinolysin, lecithinase;

Toxins, which are divided into exo- and endotoxins.

Exotoxins- These are substances of a protein nature released into the external environment by living pathogenic bacteria.

Exotoxins are highly toxic, have a pronounced specificity of action and immunogenicity (in response to their administration, specific neutralizing antibodies are formed).

By type of action exotoxins are divided into:

BUT. Cytotoxins- block protein synthesis in the cell (diphtheria, shigella);

B. Membranotoxins- act on cell membranes (staphylococcal leukocidin acts on the membranes of phagocyte cells or streptococcal hemolysin acts on the erythrocyte membrane). The most powerful exotoxins are produced by causative agents of tetanus, diphtheria, botulism. A characteristic feature of exotoxins is their ability to selectively affect certain organs and tissues of the body. For example, tetanus exotoxin affects the motor neurons of the spinal cord, and diphtheria exotoxin affects the heart muscle and adrenal glands.

For the prevention and treatment of toxin infections are used toxoids(neutralized exotoxins of microorganisms) and antitoxic serums.

Rice. 2. The mechanism of action of bacterial toxins. A. Damage to cell membranes by S. aureus alpha-toxin. C. Inhibition of cell protein synthesis by Shiga toxin. C. Examples of bacterial toxins that activate second messenger pathways (functional blockers).

Endotoxins- toxic substances that enter the structure of bacteria (usually the cell wall) and are released from them after the lysis of bacteria.

Endotoxins do not have such a pronounced specific effect as exotoxins, and are also less toxic. Do not turn into toxoids. Endotoxins are superantigens, they can activate phagocytosis, allergic reactions. These toxins cause general malaise of the body, their action is not specific.

Regardless of which microbe the endotoxin is derived from, the clinical picture is the same: it is, as a rule, fever and a severe general condition.

The release of endotoxins into the body can lead to the development of infectious-toxic shock. It is expressed in the loss of blood by capillaries, disruption of the circulatory centers and, as a rule, leads to collapse and death.

There are several forms of infection:

A severe form of infection is an infectious disease with a specific clinical picture (overt infection).

In the absence of clinical manifestations of infection, it is called latent (asymptomatic, latent, inapparent).

· Peculiar form of infection – microcarrier unrelated to previous illness.

The emergence and development of infection depends on the presence of a specific pathogen (pathogenic organism), the possibility of its penetration into the body of a susceptible animal, the conditions of the internal and external environment that determine the nature of the interaction of micro- and macroorganism.

Each type of pathogenic microbe causes a specific infection ( action specificity). The manifestation of infection depends on the degree pathogenicity a specific strain of the infectious agent, i.e. from its virulence, which is expressed by toxigenicity and invasiveness.

depending on the nature of the pathogen distinguish

bacterial,

viral,

fungal

other infections.

Entry gate of infection- the place of penetration of the pathogen into the human body through certain tissues, devoid of physiological protection against a particular type of pathogen.

They may be skin, conjunctiva, mucous membranes of the digestive tract, respiratory tract, urogenital apparatus. Some microbes exhibit a pathogenic effect only when they penetrate through strictly defined gates of infection. For example, the rabies virus causes disease only when introduced through lesions in the skin and mucous membranes. Many microbes have adapted to a variety of ways to enter the body.

Focus of infection(focal infection) - reproduction of the pathogen at the site of introduction

depending from the transmission mechanism pathogen distinguish

alimentary,

Respiratory (aerogenic, including dust and airborne),

wounded,

contact infections.

With the spread of microbes in the body develops generalized infection.

A condition in which microbes from the primary focus enter the bloodstream, but do not multiply in the blood, but are only transported to various organs, is called bacteremia. In a number of diseases (anthrax, pasteurellosis, etc.) develops septicemia: microbes multiply in the blood and penetrate into all organs and tissues, causing inflammatory and degenerative processes there.

The infection may be

Spontaneous (natural) and

experimental (artificial).

Spontaneous infection occurs in natural conditions when the transmission mechanism inherent in this pathogenic microbe is realized, or when opportunistic microorganisms living in the animal's body are activated ( endogenous infection or autoinfection). If a specific pathogen enters the body from the environment, they speak of exogenous infection.

If, after the transfer of the infection and the release of the macroorganism from its pathogen, a re-disease occurs due to infection by the same pathogenic microbe, they speak of reinfection and.

Celebrate and superinfection- a consequence of a new (repeated) infection that occurred against the background of an already developing disease caused by the same pathogenic microbe.

The return of the disease, the reappearance of its symptoms after the onset of clinical recovery is called relapse. It occurs when the animal's resistance is weakened and the pathogens of the disease that have survived in the body are activated. Relapses are characteristic of diseases in which insufficiently strong immunity is formed.

Mixed infections (mixed infections, mixed) develop as a result of infection with several types of microorganisms; such conditions are characterized by a qualitatively different course (usually more severe) in comparison with monoinfection, and the pathogenic effect of pathogens does not have a simple total character. Microbial relationships in mixed (or mixed) infections are variable:

If microorganisms activate or aggravate the course of the disease, they are defined as activators, or synergists (for example, influenza viruses and group B streptococci);

If microorganisms mutually inhibit the pathogenic action, they are designated as antagonists (for example, E. coli inhibits the activity of pathogenic Salmonella, Shigella, Streptococcus and Staphylococcus);

Indifferent microorganisms do not affect the activity of other pathogens.

Manifest infections may be typical, atypical or chronic.

Typical infection. After entering the body, the infectious agent multiplies and causes the development of characteristic pathological processes and clinical manifestations.

Atypical infection. The causative agent multiplies in the body, but does not cause the development of typical pathological processes, and the clinical manifestations are unexpressed, erased. The atypicality of the infectious process can be caused by a reduced virulence of the pathogen, active opposition of protective factors to its pathogenic potencies, the influence of ongoing antimicrobial therapy, and a combination of these factors.

chronic infection usually develops after infection with microorganisms capable of long-term persistence. In some cases, under the influence of antimicrobial therapy or under the action of protective mechanisms, bacteria are converted into L-forms. At the same time, they lose the cell wall, and with it the structures recognized by AT and serving as targets for many antibiotics. Other bacteria are able to circulate in the body for a long time, “avoiding” the action of these factors due to antigenic mimicry or changes in the antigenic structure. Such situations are also known as persistent infections [from Lat. persisto, persistens, survive, withstand]. At the end of chemotherapy, L-forms can return to their original (virulent) type, and species capable of long-term persistence begin to multiply, which causes a secondary exacerbation, a relapse of the disease.

Slow infections. The name itself reflects the slow (over many months and years) dynamics of an infectious disease. The pathogen (usually a virus) enters the body and is latently present in the cells. Under the influence of various factors, the infectious agent begins to multiply (while the rate of reproduction remains low), the disease takes a clinically pronounced form, the severity of which gradually increases, leading to the death of the patient.

In the overwhelming majority of cases, pathogenic microorganisms enter unfavorable conditions in various areas of the body, where they die or are exposed to protective mechanisms or are eliminated purely mechanically. In some cases, the pathogen lingers in the body, but is subjected to such "containment" pressure that it does not show pathogenic properties and does not cause the development of clinical manifestations ( abortive, latent, dormant infections).

Abortive infection[from lat. aborto, not to bear, in this context - not to realize the pathogenic potential] is one of the most common forms of asymptomatic lesions. Such processes can occur with species or intraspecific, natural or artificial immunity (therefore, a person does not suffer from many animal diseases). The mechanisms of immunity effectively block the vital activity of microorganisms, the pathogen does not multiply in the body, the infectious cycle of the pathogen is interrupted, it dies and is removed from the macroorganism.

Latent or hidden, infection [from lat. latentis, hidden] - a limited process with a long and cyclic circulation of the pathogen, similar to that observed in overt forms of the infectious process. The pathogen multiplies in the body; causes the development of protective reactions, is excreted from the body, but no clinical manifestations are observed. Such conditions are also known as inapparent infections (from the English inapparent, implicit, indistinguishable). So, viral hepatitis, poliomyelitis, herpetic infections, etc. often occur in a latent form. Persons with latent infectious lesions pose an epidemic danger to others.

Dormant Infections may be a type of latent infections or conditions after a clinically significant illness. Usually, this establishes a clinically unmanifested balance between the pathogenic potencies of the pathogen and the body's defense systems. However, under the influence of various factors that reduce resistance (stress, hypothermia, malnutrition, etc.), microorganisms acquire the ability to exert a pathogenic effect. Thus, individuals carrying dormant infections are the reservoir and source of the pathogen.

microbearing. As a result of a latent infection or after a past illness, the pathogen "lingers" in the body, but is subjected to such "containment pressure" that it does not show pathogenic properties and does not cause the development of clinical manifestations. This condition is called microcarrying. Such subjects release pathogenic microorganisms into the environment and pose a great danger to those around them. There are acute (up to 3 months), protracted (up to 6 months) and chronic (more than 6 months) microcarriage. Carriers play an important role in the epidemiology of many intestinal infections - typhoid fever, dysentery, cholera, etc.

pathogenicity- a visual attribute. Thus, intraspecific variations are always possible. This means that pathogenicity can be expressed differently in different strains. The probability of developing an infectious disease is largely determined by the species properties of the pathogen, the amount of the pathogen, the ways and place of penetration into the body, and the rate of reproduction.

infectious dose

When a small number of pathogenic microorganisms enter the body (which happens most often), they are usually effectively eliminated by the protective factors of the body. For the development of the disease, it is necessary that the pathogen has sufficient virulence, and its quantity (infective dose) exceeds a certain threshold, determined in each case by the virulence of the pathogen and the state of resistance of the organism. In the context of pathogenic properties infectious dose can be considered as a certain number of microorganisms, providing the possibility of adhesion, colonization and invasion into tissues.

Reproduction rate

The likelihood of developing an infectious process and its severity is significantly affected pathogen multiplication rate. For example, the plague bacillus multiplies so quickly in the body that the immune system practically does not have time to respond to its penetration by forming protective reactions.

Entrance gate of an infection. Tropism. Panthropism.

No less important pathogen penetration. Many pathogens are distinguished tropism[from Greek. trope, direction] to certain tissues. For example, gonococcus causes typical lesions after contact with the mucous membranes of the genital organs or eyes, and dysenteric amoeba - on the intestinal mucosa. On the other hand, tuberculosis or plague bacilli are capable of causing disease regardless of the route of entry, leading to the development of polymorphic lesions that vary depending on the site of entry. These pathogens are characterized pantropism. Having penetrated into the body, the pathogen begins to multiply at the site of introduction, forming the primary lesion (primary affect), or spreads (disseminates) to other organs and tissues.