Studies about epidemic process. Antyepidemic measures in the focus of infectious diseases. Ant epidemic work of district doctors and doctors-infectionists.

Immune prophylaxis of infectious diseases. Schedule of prophylactic inoculations. Evaluation of immune prophylaxis efficiency. Urgent immune prophylaxis

 

General Epidemiology

The Subject Matter of Epidemiology

The word “epidemiology” has been used since the time when most of the infectious diseases were epidemic. Today, when infectious morbidity has considerably decreased, the concept of epidemiology includes the study of objective laws of aetiology, distribution and control of infectious diseases in a human community, and also elaboration of methods to prevent and control these diseases.

The following definition of the term “epidemiology” was formulated at the International Symposium of Epidemiologists in Prague (I960):

Epidemiology is an independent branch of medicine studying aetiology and spreading of infectious diseases in a human community and is aimed at prevention, control, and final eradication of these diseases”.

General and special epidemiologies are distinguished. General epidemiology studies the laws of distribution of infectious diseases among people (characteristics of sources of infection, the mechanism of transmission, susceptibility to infection, and the like) and the general principles of prevention and control of these diseases. Special epidemiology studies epidemiologic characteristics of each particular infectious disease and the methods to prevent and control it.

History of epidemiology. Ancient people had their own concept of contagiosity of some diseases and took first prophylactic measures; they rejected people with infectious diseases from their community, used variolation (deliberate inoculation with smallpox virus), disinfection, etc. All these measures were empirical and their efficacy was low. At those times it was impossible to prove instrumentally that infectious diseases might be evoked by living microorganisms, but numerous epidemics of black plague, smallpox and typhus, especially in the 14-15th centuries, aroused such suspicions in physicians. Fracastorius (Pic. 1), an Italian physician (1483-1553), produced a theory that proved contagiosity of these diseases.

Pic. 1. D. Fracastorius (1478-1553).

 

In Russia of the llth century, they isolated people with contagious diseases and burned the dead separately from the others. First quarantines were organized in the 16th century: patients were separated from their relatives, and funeral services over the dead were forbidden.

To prevent spread of plague epidemic into Moscow in 1552, posts were first organized in Russia to prevent penetration of people into the city from the outside. In the 17th century, quarantine piquets were organized during epidemics out at the entrance to the city and at the houses with the diseased. When a family died, the house with the dead and the utensils was bumed. According to the law, any case suspected for a contagious disease had to be reported to the officials.

In the 18th century, Edward Jenner (Pic. 2) an English physician, (1749-1823) devised a safe and effective method to prevent natural smallpox by inoculating people with cowpox vaccine.

At about the same time, the Russian epidemiologist D. Samoilovich (1744-1805) (Pic. 3) was among the first who attempted to discover microscopically the causative factor of plague in excrements and various tissues of the diseased. He was also actively involved in control of plague in Moscow in 1771-1772. Samoilovich organized quarantines at the Black Sea coastal area and became world famous for his work in epidemiology.

   Pic. 2. E. Jenner.                                   Pic. 3. D. Samoilovich

Development of industry and trade between different countries stimulated advances in medicine, including sanitary, quarantine, and anti-epidemic services.

The second half of the 19th century was marked by vigorous development of physics (optics), chemistry, biology and other sciences, which all provided conditions for developing a new science-microbiology.

The scientific discoveries made by Pasteur, Mechnikov, Koch, Ivanovsky and many others promoted the study of aetiology, pathogenesis, course of infectious disease and also their epidemiology. The study of epidemiology of some infectious diseases and working out of prophylactic measures revealed the important role of social factors in the spread of epidemics. Inadequate labour and living conditions, poverty, and poor sanitation promoted the spread of contagious diseases.

A great contribution to epidemiology was made by Minch 11 (1836-1896) and Mochutkovsky (1845-1903), who inoculated themselves with the blood of patients with recurrent fever (Minch) and typhoid fever (Mochutkovsky). They proved by their experiments that the diseases could be transmitted by blood-sucking insects.

Gabrichevsky (1860-1907) made an important contribution to the study of diphtheria (serotherapy), scarlet fever (study of aetiology, manufacture of vaccines and vaccination), epidemiology of malaria, etc.

Zabolotny (1866-1929) is the founder of Ukrainian epidemiology. He is the author of numerous papers on epidemiology of plague, cholera, epidemic typhus, etc. and also of the manual entitled “Fundamentals of Epidemiology”. Gromashevsky continued studies of their teacher.

Sysin (1879-1956), Semashko (1874-1949), Soloviev (1879-1928), Bashenin (1882-1978) and Martsinovsky (1874-1934) worked much to create anti-epidemic service in the Soviet state. Further development of the theory of epidemiology is associated with the names of Pavlovsky (1884-1965) and Gromashevsky (1887-1980) (Pic. 4). Pavlovsky’s works in the field of parasitology have won world repute. He developed also the theory of natural nidality of some infectious diseases.

Soviet epidemiologists Zabolotny, Vogralik, Bashenin, Gromashevsky, Pavlovsky and others have developed several theories in epidemiology. These are the first and second laws of sources of infection and the teaching of epidemic process. According to the law of infectious source, any infected person can be the source of infection; sometimes, this can be an animal. According to the second law, there exists agreement between location of the causative microorganism in a macroorganism and the mechanism of infection transmission. This law was used by Gromashevsky for classification of infectious diseases. The theory of epidemic process postulates that such a process develops and is maintained only through the interaction between the source of infection, the specific mechanism of transmission, and susceptibility of population with respect to a given disease. Teaching of natural nidality of infectious diseases and the effect of social factor on the course of an epidemic process are very important for a successful control of infectious diseases as well.

 

 

 

 

 

 

 

Pic. 4. Gromashevsky (1887-1980)

 

Advances in epidemiology are infeasible without improvement of labour and living conditions, adequate health care, and planned anti-epidemic measures.

 

The Concept of Infection

An infectious process is the interaction of a pathogenic microorganism with a macroorganism under certain environmental and social conditions. The concept “infectious disease” means the condition manifested by a disease state of a patient and the so-called carrier state.

The specific properties of infective agents, various pathogenicity and virulence of these agents, as well as the quantity of microorganisms that enter the macroorganism, resistance of the macroorganism and duration of specific immunity account for the multitude of clinical manifestations of infection.

Infection can be clinically pronounced or it may be asymptomatic, which is known as the carrier state (parasite, bacterium, virus carrier state). A clinically manifest infection can run a typical or atypical course. Patients with a typical form of infection demonstrate all symptoms specific for a given disease. One or several symptoms of a given disease are absent from the clinical picture of an atypical form, or the symptoms can be modified. A disease can be acute or run a protracted or even a chronic course.

A clinically manifest disease is usually classed as mild, moderate, and severe; according to the duration, the disease can be acute or chronic.

An acute infection (smallpox, measles, plague) is characterized by a short stay of the causative agent in the body and development of specific immunity in the patient toward the given infection.

A chronic infection (brucellosis, tuberculosis) can last for years.

Asymptomatic infections can be subclinical and latent.

A person with a subclinical infection (acute and chronic) looks in full health, and the disease can only be diagnosed by detecting the causative agents, specific antibodies, and functional and morphological changes in the organs and tissues that are specific for a given disease. Such patients (or carriers) are a special danger for the surrounding people since they are the source of infection. At the same time, a repeated subclinical infection in poliomyelitis, diphtheria, influenza, and some other acute infections promotes formation of an immune group of people (herd immunity). Acute and chronic subclinical forms (carrier state) are more common in typhoid fever, paratyphoid B, salmonellosis, viral hepatitis B, etc.

Latent or persistent forms of human and animal infections are a prolonged asymptomatic interaction of macroorganisms with the pathogenic agents which are present in modified (“defective”) forms. These are defective interfering particles in latent viral infections, and L forms, spheroplasts, etc. in bacterial infections. Being inside the host cell, these forms survive for long periods of time and are not released into the environment. Under the action of various provoking factors (such as thermal effects, injuries, psychic trauma, transplantation, blood transfusion, various disease states), persistent infection can be activated and become clinically manifest. The microbe regains its pathogenic properties.

Persistence of virus has been studied best of all, but at the present time, persistence of other pathogenic factors has been intensively studied as well, e. g. of the L forms of streptococci, staphylococci, meningococci, cholera vibrio, typhoid fever bacilli, microbes causing diphtheria, tetanus, etc.

Protozoa and rickettsia can also persist. For example, latent epidemic recrudescent typhus infection is manifested by relapses of epidemic recrudescent typhus (Brill’s disease).

 

The Concept of Epidemic Process

Microorganisms causing infectious diseases parasitize on host and persist due to continuous reproduction of new generations which change their properties in accordance with evolution of the environment conditions. Living inside its host, the microorganism persists for a definite period of time. Then the pathogenic microorganism can survive by changing its residence, i.e., by moving to another host via a corresponding transmission mechanism. This continuous chain of successive transmission of infection (patient-carrier), manifested by symptomatic or asymptomatic forms of the disease, is called an epidemic process.

According to Gromashevsky, the source of infectious microorganisms is an object which is the site of natural habitation and multiplication of the pathogenic microorganisms, and  in which the microorganisms are accumulared. Since pathogenic nucroorgansms are parasites, only living macroorganism can be such an object, i.e., a human or an animal.

An epidemic focus is the residence of infection source including the surrounding territory within the boundaries of which, the source can, under given conditions, transmit a given disease through the agency of the pathogenic microorganisms. The focus of infection remains active until the pathogenic microorganisms are completely eradicated, plus the maximal incubation period in persons that were in contact with the source of infection. The following three obligatory factors are necessary for the onset and continuous course of an epidemic process: the source of pathogenic microorganism, the mechanism of their transmission, and macroorganisms susceptible to infection (Pic. 5).

Pic. 5. Three obligatory factors are necessary for the onset and continuous course of an epidemic process: 1. the source of pathogenic microorganism, 2. the mechanism of their transmission, and 3. macroorganisms susceptible to infection

 

Infectious diseases are classed according to their source as anthroponoses (the source of infection is man), zoonoses (the source of infection is animal), and anthropozoonoses (both man and animal can be the source of infection).

An infected macroorganism (man or animal), being the sole source of infection, can have either clinically manifest or asymptomatic form of the disease.

A diseased person is the primary source from which the infection spreads. A patient is the most dangerous source of infection because he or she releases a great quantity of the pathogenic microorganisms.

The danger of infection spreading from the patient depends on the period of the disease. During the incubation period the role of the patient is not great because the pathogenic microorganism resides inside tissues and is seldom released from the infected organism. The pathogenic agents are released into environment during the late incubation period only in measles, cholera, dysentery, and some other diseases. The greatest quantity of microbes are released during the advanced stage of the disease which is associated with some clinical manifestations of the disease such as frequent stools (dysentery), frequent stools and vomiting (cholera), sneezing and cough (airway infections). The danger of infection spreading during the early period of the disease depends on pathogenesis of a particular infectious disease. For example, in typhoid fever or paratyphoid A and B, the patients are not dangerous to the surrounding people during the first week of the disease, while in respiratory infections, the patient is a danger to the surrounding people from the moment when the clinical symptoms of the disease become apparent.

Severity of the disease is of great epidemiologic importance for determining “the source of infection”. If the disease is severe, the patient remains in bed and can only infect his relatives. But it is difficult to diagnose the disease if it runs a mild course; besides, the patient often does not attend for medical aid and continues performing his routine duties (at the office, school, and the like) thus actively promoting the spread of infection.

Carrier of infection is another source of morbidity. According to modern views, carrier state is an infectious process that runs an asymptomatic course. But those who sustained an infectious disease, convalescents, and also healthy persons (transition) can also be carriers of infectious microorganisms. True, carriers release pathogenic agents into the environment in a smaller quantity than patients with clinically manifest diseases, but they are danger to community too since they actively associate with healthy people and spread the infection.

Recovery from some infectious diseases, e.g. dysentery, typhoid fever, paratyphoid, diphtheria, meningococcal infection, viral hepatitis B, is not always attended by complete destruction of the microbes in the patient. Carrier state can persist in persons who sustained diphtheria or meningococcal infection after their clinical recovery: acute carrier state can last from several days to several weeks. Persons who sustained typhoid fever or paratyphoid B can be the source of spread of the pathogenic microorganisms for months. Carrier state can persist for years or even for the rest of life (chronic carrier state) in 3-5 per cent of cases, which can be explained by defective immune system.

Various concurrent diseases can promote persistence of carrier state: diseases of the bile ducts and urinary system in typhoid fever and paratyphoid, chronic diseases of the nasopharynx in diphtheria, helminthiasis in dysentery, etc.

Healthy carriers are persons with asymptomatic infection. Transitory carrier state is characterized by rapid withdrawal of the pathogenic microorganisms from a subject; foci where these microorganisms might multiply are absent. From 30 to 100 carriers can be detected among people surrounding one patient with meningococcal infection of poliomyelitis. Healthy carriers are less dangerous for those who surround them because the pathogenic microorganisms are not usually detected in them during subsequent tests.

The danger of carrier state depends on hygiene and occupation of a carrier. If a carrier of typhoid fever, paratyphoid B, salmonellosis, or dysentery agents is employed at a food catering establishment or a children’s institution, he or she is especially dangerous for the surrounding people. Infected animals are the source of infectious diseases that are common for man and animal. Infection of a human with zoonosis by another person occurs in rare cases. Domestic animals and rodents are dangerous in the epidemiologic aspect. The degree of their danger as the source of infection depends on the character of relations between people and the animals, on the socioeconomic and living conditions. People can get infected during management of diseased animals, cooking and eating their meat (anthrax, brucellosis, Q fever, etc.). Rodents are the source of tularaemia, plague, leptospirosis, rickettsiosis, encephalitis, leishmaniasis and some other diseases.

Main and secondary sources of infection are distinguished in zoonosis. The main source are animals which are a harbour of pathogenic microorganisms and they create natural nidi of tularaemia, plague, and other diseases. Secondary sources of infection become involved periodically in epizootic.

Humans can be infected by wild animals when hunting, during stay in wild environment contaminated with excrements, when drinking water or eating food that may be contaminated with excrements of wild animals. Birds can also be transmitters of infection (omitosis, salmonellosis, etc.).

Pic. 6. Four mechanisms of infection transmission: (А) faecal-oral; (Б) air-bome; (В) transmissive; (Г) contact

 

Mechanism of transmission. For the epidemic to break out it is not sufficient to have a source of infection alone. The causative agent can survive only if it is transmitted from one host to another, because any given macroorganism destroys the pathogenic microorganisms by specific antibodies that are formed in it in response to the ingress of these microorganisms. Death of an individual host terminates the life of the parasitizing microorganisms. The only exception are spore-forming microbes (causative agents of anthrax, tetanus, botulism). The combination of routes by which the pathogenic microorganisms are transmitted from an infected macroorganism to a healthy one is called the mechanism of infection transmission.

Four mechanisms of infection transmission are distinguished according to the primary localization of pathogenic agents in macroorganisms: (1) faecal-oral (intestinal localization); (2) air-bome (airways localization); (3) transmissive (localization in the blood circulating system); (4) contact (transmission of infection through direct contact with another person or environmental objects) (Pic. 6).

Three phases are distinguished in the transmission of infection from one macroorganism to another: (1) excretion from an infected macroorganism; (2) presence in the environment; (3) ingress into a healthy macroorganism .

The method by which microbes are excreted from an infected macroorganism (the first phase) depends on the locus of infection in the infected individual or a carrier. If pathogenic microorganisms reside on respiratory mucosa (influenza, measles, pertussis) they can be released from the patient only with expired air or with droplets of nasopharyngeal mucus. If the infection is localized in the intestine, the pathogenic microorganisms can be excreted with faeces (dysentery). The pathogenic organisms in the blood infect blood-sucking arthropods.The presence of the causative agents outside a macroorganism (the second phase) is connected with various environmental objects. Pathogenic microorganisms excreted from the intestine get on soil, linen, household objects and water, while those liberated from the airways are borne in air. The environmental elements that transmit the pathogenic agent from one person to another are called transmission factors. The pathogenic agent can sometimes be transmitted by direct contact with an infected individual or a carrier (venereal diseases, rabies).

Microorganisms causing infectious diseases (viral hepatitis, rubella, toxoplasmosis, syphilis, etc.) infect the foetus through the placenta (transplacental transmission of infection).

Pathogenic microorganisms can be transmitted mechanically during transfusion of blood or its components (plasma, erythrocytes, fibrinogen, etc.). Infection can be transmitted through inadequately sterilized medical tools (viral hepatitis, hepatitis B, AIDS).

The following main factors are involved in transmission of infection: air, water, foods, soil, utensils, arthropods (living agents).

Air is a factor of transmission of respiratory infections. Contamination occurs mostly in an enclosure where a patient is present. From the source of infection, microorganisms get into air together with droplets-of sputum. They are expelled in great quantities during sneezing, cough and conversation. Droplets of sputum containing the pathogenic microorganisms often remain suspended in the air for hours (smallpox, chickenpox, measles) and can sometimes be carried from one enclosure to another with air streams and precipitate on environmental objects. After drying, sputum droplets infect dust which is then inhaled by a healthy person. Dust infection is feasible only with those microorganisms that persist in the environment and can survive in the absence of water. Tuberculosis mycobacteria, for example, can survive in dust for weeks, and virus of smallpox for years. Agents causing Q fever, anthrax or tularaemia can be transmitted with dust.

Water is another very important medium by which infection can be transmitted. Pathogenic microorganisms can get into water by various routes: with effluents, sewage, with runoff water, due to improper maintenance of wells, laundry, animal watering, getting of dead rodents into water, etc. Spontaneous purification of water depends on ambient temperature, chemical composition, aeration degree, exposure to sun rays, the properties of the microorganisms, and other factors. Infection is transmitted by drinking contaminated water, using this water for domestic purposes, bathing, etc. Water can be the medium for transmission of cholera, typhoid fever, leptospirosis, dysentery, viral hepatitis A, tularaemia, and other diseases. If potable water gets contaminated with faecal sewage, water-borne infection can become epidemic with rapid spreading.

Transmission of infection with food is especially important since pathogenic microorganisms can multiply in foodstaffs. Food can be infected by contact with an infected person or a carrier, by insects or rodents. Food can be infected during improper transportation, storage, and cooking. The form in which a given food is taken is also epidemically important (uncooked natural foods, thermally processed foods, hot or cold foods). Consistency of foodstaff and its popularity are also important factors. Milk and meat are common transmission media. Dairy products (curds, sour cream), vegetables, fruits, berries, bread and other foods that are not cooked before use are important transmission factors as well. Milk, dairy products can transmit dysentery, typhoid fever, brucellosis, tuberculosis, etc. Meat and fish can be an important factor in development of salmonellosis. Intestinal diseases are often transmitted through vegetables, fruits and baked products.

Soil is contaminated by excrements of humans and animals, various wastes, dead humans and animals. Contamination of soil is an important epidemiologic factor because soil is the habitat and site of multiplication of flies, rodents, etc. Eggs of some helminths (ascarides, Trichuris trichiura, hookworms) are incubated in soil. The pathogenic microorganisms of soil can pass into water, vegetables, berries that are eaten by man uncooked.

It is especially dangerous to use faecal sewage to fertilize soil where cucumbers, tomatoes and other vegetables are grown. Tetanus, gangrene, and anthrax are transmitted through soil.

The role played by various environmental objects in transmission of diseases depends on contact with the source of infection, probability of transfer of a contaminated object to a healthy person, and also on the character of chemical and physical effect that a given object can produce on the pathogenic microorganism.

The objects at patient’s room can be the transmitting factor for influenza, tuberculosis, children’s infections, dysentery, typhoid fever, and other diseases. Domestic animals can be the source of infection, while arthropods can transmit infection.

Utensils and household objects such as dishes, cups, plates (in hospitals, canteens, etc.) can become a transmissing factor for tuberculosis, scarlet fever, typhoid fever, diphtheria. Soiled linen and underwear can promote the spread of infection such as scabies, intestinal or droplet infections.

Toys, pencils, and other objects in children’s use are important transmitting factors.

Living objects that transmit infection can be divided into two groups: specific and non-specific (mechanical). Specific carriers are lice, fleas, mosquitoes, ticks, etc. They transmit infection by sucking blood (inoculation) or contaminating human skin with their excrements. Inside specific transmitters of infection, the pathogenic microorganisms multiply, accumulate, and with time become dangerous to the surrounding. A louse, for example, sucks blood of a typhoid fever patient and excretes the pathogenic microorganisms with faeces only in 4-5 days. Non-specific carriers transmit the pathogenic microorganisms by purely mechanical method. Flies, for example, carry microbes of dysentery, typhoid fever, viral hepatitis and some other diseases that are found on their bodily surfaces, on the limbs, in the proboscis and the intestine. Gadflies transmit microbes causing anthrax and tularaemia by their stinging apparatus.

Transmitting factors determine also the third phase of transmission mechanism-inoculation of the successive biological object (host). The pathogenic factor is inhaled with air, ingested with food and water, or is transmitted into the blood by arthropods.

The forms of realization of the transmission mechanism, including the combination of factors involved in spreading of a corresponding disease, are known as the transmission routes of the infective agents.

The following transmission routes are distinguished: contact, air-bome (or dust-bome in some diseases), food- and water-borne, transmission by arthropods and soil, through the placenta, by medical parenteral and other manipulations.

Susceptibility and immunity. Susceptibility of people to a given infection is a very important factor in infection spreading. Susceptibility of an individual or of a community are distinguished. Susceptibility to a disease is a biological property of tissues of a human or an animal, characterized by optimum conditions for multiplication of pathogenic microorganisms. Susceptibility is a species property, that is transmitted by hereditary trait. Many infectious diseases can affect only a certain species of animals. Some anthroponoses, e.g. typhoid fever, scarlet fever, gonorrhoea do not affect animals even after artificial inoculation, because the animals are protected by hereditary (species) immunity.

But hereditary immunity is not an absolute property. Under some unfavourable conditions, immunity of a macroorganism can be altered. For example, overheating or cooling, avitaminosis, or some other unfavourable factors can promote the onset of a disease that would not, under normal conditions, affect man or animal. Pasteur, for example, exposed hens to cold to artificially provoke anthrax in them (the disease that does not affect hens under normal conditions).

The following kinds of immunity are distinguished: hereditary (species), acquired (natural: active, passive; artificial: active, passive).

Some features of epidemic process. An epidemic develops and is maintained only by the interaction between the source of infection, specific mechanism of its transmission, and susceptible population under giveatural and social conditions. The role of these motive forces during subsequent infection is different. The most active is the source of infection, the carrier of the infective factor, the pathogenic microorganisms multiply in it with subsequent release into the environment. The mechanism of infection transmission is decisive. It can be active ingress of the pathogenic factor into a healthy macroorganism through the agency of living carriers, inhalation with air, ingestion with food and water, or persistence of viable pathogenic microorganisms on various non-living objects before they enter another living organism. Susceptibility plays a passive role. In the presence of susceptibility, a person gets infected, while in the absence of such susceptibility a person is not afflicted.

The intensity of an epidemic process can also be different. Three stages of quantitative changes are usually distinguished in the epidemic course: sporadic incidence, epidemic, and pandemic.

Sporadic incidence is a normal (minimal) morbidity characteristic of a given infection for a given country or region. Many infectious diseases occur as single cases.

Group incidence of infectious diseases in a community is assessed in everyday medical practice as an epidemic outburst.

An epidemic is characterized by morbidity that 3-10 times exceeds the sporadic occurrence of a given disease in a given locality; it is also characterized by development of multiple epidemic foci.

Pandemic is characterized by widespread epidemic throughout large territories.

Endemic* characterizes an epidemic qualitatively. An endemic disease constantly occurs among population of a given area. Long existence of any infectious disease in a given country or area can be due to the presence of some natural factors.

Exotic disease is an opposite notion. It is used to designate an infectious disease that does not normally occur in a given country or area and can only be brought from a foreign country.

In veterinary the terms epidemic, pandemic, and endemic are replaced by epizootic, panzootic, and enzootic, respectively.

A focus of infection is a site or area where cases of an infectious disease can occur or has already occurred.

The quantitative and qualitative changes in the epidemic process depend on the natural and social conditions that can activate the source of infection, the transmission factor, or susceptibility of population, thus increasing their epidemiologic activity, or on the contrary, decreasing it.

The effect of natural conditions on the transmission mechanism of infection is especially marked when the pathogenic microorganisms are transmitted by living carriers. Absence of living transmitters (ticks, mosquitoes) during a certain season or reduction of their population reduces the human infection rate, and hence is important for the course of the epidemic process.

Pavlovsky has worked out a theory of natural nidality of transmissible diseases. He showed that many infectious diseases exist iature independently of man, in a certain combination of natural conditions in a given locality, in the presence of warm-blooded animals and arthropods that are depots of the pathogenic microorganisms. For example, ticks transmit encephalitis from diseased animals to healthy ones. Besides, ticks transmit the virus to their posterity.

According to Pavlovsky, natural nidality of transmissible diseases is characterized by indefinitely long existence of the pathogenic microorganisms, their specific transmitters and animals (reservoirs of the pathogenic microorganisms) during renewal of their generations independently of man in various biocenoses, both during the course of their evolution and at a given period of time.

Natural nidi of non-transmissible diseases can exist as well. For example, carriers of leptospirosis are not involved in circulation of the pathogenic microorganisms. Spread of this disease is confined within a certain geographic area where a particular rodent lives. Diseases with natural nidality are characterized by seasonal morbidity which is associated with biology of the carriers.

Many animals give posterity in spring; hence vernal rises in brucellosis morbidity. Plague exists in its latent form during hibernation of gophers and marmots. As rodents return to active life in spring, the infection activates and rapidly spreads among the young generation.

Natural processes have their effect oon-living transmission factors as well. Open water bodies get contaminated more easily with effluents and serve as the source of water-bome epidemic of typhoid fever during the cold season when spontaneous purification of water is slowed down and the microorganisms causing intestinal infections survive for longer periods of time.

Presence of people in enclosures promotes transmission of air-home infections, while wearing warm clothes without proper hygiene of individuals promotes multiplication of lice, carriers of louse-borne and recurrent fever. The effect of the natural factor on susceptibility is insignificant. It only increases or decreases nonspecific body resistance (barrier function of the skin, mucosa, blood, bile, etc.).

The social factor is more important epidemiologically. It includes the concept of living conditions of population: the quality of dwelling, density of population in residential buildings and areas, conveniences (water supply and sewage system), well-being of population, nutrition, cultural standards, sanitation, health-care system, social structure of a community, etc.

The course of an epidemic depends strongly on the living conditions, i.e., on population density, intensity of association between the source of infection and the surrounding people, the character of occupation, traffic, time of detection of carrier state or developing disease, and time of hospitalization or isolation in home conditions. Poor ventilation, overcrowded residence, inadequate insolation and ventilation of rooms and suboptimal sanitation promote spread of tuberculosis and other infectious diseases.

Domestic animals, poultry, and wild animals can be the source of infection. Man can be infected by a domestic animal due to inadequate veterinary control, untimely detection of diseased animals and their isolation, slaughter or treatment. Rodents and wild animals are regularly reduced in their number which decreases considerably their epidemiologic danger.

The condition of water supply and sewage systems, rational and timely cleaning of settlements are important for the spread of intestinal infections such as typhoid fever, paratyphoid, dysentery, cholera, poliomyelitis, viral hepatitis, etc.

Inadequate control and poor organization of food catering is responsible for spread of infectious diseases. Food can be infected by carriers among those who work in food catering, food shops, children’s and medical institutions. People can be infected by meat of diseased cattle and milk and dairy products manufactured from the milk of infected animals.

Labour conditions are often important for the development and spread of infectious diseases. Animal breeders, veterinary workers, those engaged in handling and processing animal materials (leather, wool, etc.), get infected by diseased animals (anthrax, brucellosis, etc.). These diseases can thus be occupational. Besides, factors decreasing resistance of people (hard labour, overcrowded dwellings, cooling and other debilitating factors) can also promote spread of infection.

Migration of population during social conflicts (famine, war), disasters, such as earthquake, flood, or fires, that are associated with destruction of dwellings and worsening of the living conditions and cause mass-scale migration of the victims, intensify the epidemic spread of infectious diseases, that previously occurred as single cases.

 

Classification of Infectious Diseases

In the 19th century, infectious diseases were classed as contagious (transmissible from person to person), miasmatic (transmitted through air), and contagious-miasmatic. Late in the 19th century, in view of advances made in bacteriology, the diseases were classified according to their aetiology. These classifications could not satisfy clinicians or epidemiologists since diseases with different pathogenesis, clinical course and epidemiologic characteristics were united in one group. Classifications based on clinical and epidemiologic signs proved ineffective too.

The classification proposed by Gromashevsky seems to be more reasonable than many others. It is based on the location of infection in the macroorganism. In accordance with the main sign, that determines the transmission mechanism, all infectious diseases are divided by the author into four groups: (1) intestinal infections; (2) respiratory infections; (3) blood infections; (4) skin infections. According to Gromashevsky, each group is subdivided into anthroponoses and zoonoses; their epidemiology and prevention differ substantially.

Intestinal infections. Intestinal infections are characterized by location of the causative agents in the intestine and their distribution in the environment with excrements. If the causative agent circulates in the blood (typhoid fever, paratyphoid A and B, leptospirosis, viral hepatitis, brucellosis, etc.), it can also be withdrawn through various organs of the body, e. g. the kidneys, lungs, the mammary glands.

As a microbe is released into the environment with faeces, urine, vomitus (cholera), it can cause disease in a healthy person only after ingestion with food or water. In other words, intestinal infections are characterized by the faecal-oral mechanism of transmission.

Maximum incidence of intestinal infections occurs usually during the warm seasons.

The anthroponoses include typhoid fever, paratyphoid, bacterial and amoebic dysentery, cholera, viral hepatitis A, poliomyelitis, helminthiasis (without the second host). The zoonoses include brucellosis, leptospirosis, salmonellosis, botulism, etc.

The main means of control of intestinal infection are sanitary measures that prevent possible transmission of the pathogenic microorganisms with food, water, insects, soiled hands, etc. Timely detection of the diseased and carriers, their removal from food catering and the like establishments is also very important.

Specific immunization is only of secondary importance in intestinal infections.

Respiratory infections. This group includes diseases whose causative agents parasitize on the respiratory mucosa and are liberated into the environment with droplets of sputum during sneezing, cough, loud talks, or noisy respiration.

People get infected when the microbes contained in sputum get on the mucosa of the upper airways. If the causative agent is unstable in the environment, a person can only be infected by lose contact with the sick or carrier (pertussis).

Pathogenic microorganisms causing some diseases can persist for a period of time in an enclosure where the sick is present. Infected particles of sputum or mucus can dry and be suspended in the air. Some diseases of this group can spread through contaminated linen, underwear, utensils, toys, etc.

Since susceptibility of people, and especially of children to respiratory infection is very high, and since the infection is easily transmitted from the diseased (or carriers) to healthy people, almost entire population of a given area usually gets infected, and some people can be infected several times. Some diseases of this group form a special subgroup of children’s infections (diphtheria, scarlet fever, measles, pertussis, epidemic parotitis, chickenpox, rubella). A durable immunity is usually induced in children who sustained these diseases. The main measure to control respiratory infections is to increase non-susceptibility of population, especially of children, by specific immunization.

It is important to timely reveal the sick and carriers, and also to break the mechanism of infection transmission: control of overcrowding, proper ventilation and isolation of enclosures, using UV-lamps, wearing masks, respirators, disinfection, and the like.

Blood infections. The diseases of this group are transmitted by blood-sucking insects, such as fleas, mosquitoes, ticks, etc., which bite people and introduce the pathogenic agent into the blood.

Tick-bome encephalitis, Japanese В encephalitis and some other infections are characterized by natural nidality which is due to specific geographic, climatic, soil and other conditions of infection transmission. The morbidity is the highest during the warm season which coincides with the maximum activity of the transmitters-ticks, mosquitoes, etc.

Control of blood infections includes altering natural conditions, improvement of soils, draining swamps, destroying sites where the insects multiply, disinsection measures against mosquitoes, ticks, etc., detoxication of sources of infection by their isolation and treatment, carrying out preventive measures.

If the source of infection are rodents, measures to control them are taken.

Active immunization is also effective.

Skin infections. The diseases of this group occur as a result of contamination of the skin or mucosa with the pathogenic microorganisms. They can remain at the portal of infection (tetanus, dermatomycoses), or affect the skin, enter the body and be carried to various organs and tissues with the circulating blood (erysipelas, anthrax). The transmitting factors can include bed linen, clothes, plates and dishes and other utensils, that can be contaminated with mucus, pus or scales. Pathogenic microorganisms causing venereal diseases, rabies, AIDS, and some other diseases are transmitted without the agency of the environmental objects. Wound infections are characterized by damage to the skin as a result of injury (tetanus, erysipelas).

The main measures to control skin infections include isolation and treatment of the source of infection, killing diseased animals, homeless dogs and cats, improving sanitation and living conditions of population, personal hygiene, control of traumatism, and specific prophylaxis.

 

SCHEDULED IMMUNOPROPHYLAXIS AND URGENT PREVENTION. THEIR ORGANIZATION, WAYS OF REALIZATION

 

Susceptibility and immunity.

Susceptibility of people to a given infection is a very important factor in infection spreading. Susceptibility of an individual or of a community are distinguished. Susceptibility to a disease is a biological property of tissues of a human or an animal, characterized by optimum conditions for multiplication of pathogenic microorganisms. Susceptibility is a species property, that is transmitted by hereditary trait. Many infectious diseases can affect only a certain species of animals. Some anthroponoses, e.g. typhoid fever, scarlet fever, gonorrhoea do not affect animals even after artificial inoculation, because the animals are protected by hereditary (species) immunity.

But hereditary immunity is not an absolute property. Under some unfavourable conditions, immunity of a macroorganism can be altered. For example, overheating or cooling, avitaminosis, or some other unfavourable factors can promote the onset of a disease that would not, under normal conditions, affect man or animal. Pasteur, for example, exposed hens to cold to artificially provoke anthrax in them (the disease that does not affect hens under normal conditions).

The following kinds of immunity are distinguished: hereditary (species), acquired (natural: active, passive; artificial: active, passive).

Acquired immunity, both natural and artificial, is specific because specific antibodies are produced in an infected macroorganism in response to the ingress of foreign antigens.

Natural active immunity is formed in a macroorganism as a result of a sustained disease (postinfection or acquired immunity). Duration of such immunity varies from several years (measles, chickenpox, plague, tularaemia) to a year (brucellosis, dysentery). Natural active immunity can sometimes develop without apparent illness. It is formed as a result of an asymptomatic disease or multiple ingress of the pathogenic microorganisms that are unable to provoke a clinically manifest disease. (For example, only 0.2-0.5 per cent of the infected, develop meningococcal infection; the percentage is even lower in poliomyelitis.)

Natural passive immunity is acquired by a foetus from bis mother through the placenta (intrauterine immunity). A newbom acquires it with mother’s milk. This immunity is not stable and persists only for 6-8 months to protect the nursling from some infectious diseases (measles, rubella, etc.).

Artificial active (postvaccinal) immunity is created by inoculation with bacteria, their toxins, or virus (antigen) attenuated or inactuated by various techniques. After administration into a macroorganism, they undergo active re-organization which is aimed at production of substances that destroy the pathogenic microorganisms or their toxins (antibodies, antitoxins). Artificial active immunity develops during 3-4 weeks and persists from 6 months to 5 years. The effect of postvaccinal immunity on the course of an epidemic process depends on the scale of vaccination of population, especially of children (against tuberculosis, diphtheria, pertussis, measles, poliomyelitis, and other infections). Vaccination is considered successful if at least 80 per cent of the vaccinated develop adequate immunity (according to WHO experts).

Artificial passive immunity is created by administration of antibodies (sera, immunoglobulins). It persists for 3-4 weeks and then the antibodies are destroyed and excreted from the body. Passive immunization is necessary in situations where the danger of infection exists or if the macroorganism is already infected (in foci of measles, pertussis, etc.).

Depending on a particular antigen, the following types of immunity are distinguished: antimicrobial, antitoxic, and antiviral.

Depending on the period within which the infectious microorganisms are removed from the body, immunity can be sterile (the macroorganism is freed from the pathogenic agent after cure) and non-sterile (immunity persists until the pathogenic microorganism remains in the macroorganism).

Apart from individual immunity there also exists community (herd) immunity.

Community immunity is non-susceptibility of a community to a given infection. This type of immunity is created by specific prophylactic and other measures that are taken by health-care services, and also by improvement of well-being of population. Susceptibility to a disease, the course of infection, and duration of immunity depend on diet (that must be rich in proteins and vitamins), ambient temperature, physiological condition of an individual, pre-existing or attending diseases.

Non-susceptibility to smallpox, for example, was formerly attained by compulsory mass-scale immunization. After eradication of smallpox in the world, smallpox vaccination is no longer necessary.

The immunologic structure of population is the ratio of the number of people susceptible to a given infection to the number of those non-susceptible to the disease. This ratio is determined by various immunologic, serologic, and allergic reactions. If the number of susceptible people is not great, they are surrounded by the majority of non-susceptible persons and the disease is thus not spread.

 

Measures to increase non-susceptibility of population.

Non-susceptibility of population is increased by improving general non-specific resistance of population by improving the living and labour conditions, nutrition, physical training, health envigorating measures and by creating specific immunity through preventive vaccination. The ancients noted that people who had sustained many infectious diseases became non-susceptible to repeated infection with the same disease. In the Orient (China, India) they believed that if a person could sustain a mild form of an infection, it could protect him from dangerous diseases during epidemic outbursts. They protected themselves from smallpox by rubbing the content of smallpox lesions into the skin or ingested crusts (variolation), or put contaminated underwear of smallpox patients on healthy children, etc.

In Europe, first attempts to create artificial non-susceptibility to infectious diseases were made in the 18th century. Variolation was practiced in England, Germany, Italy, France, Russia and some other countries. Samoilovich, for example, suggested that population could be immunized by the bubonic contents of plague patients.

The discovery of the English physician Edward Jenner has become a turn point in the teaching of artificial immunity. In 1796, Jenner developed a process of producing immunity to smallpox by inoculation with cowpox vaccine.

Louis Pasteur produced a live vaccine against anthrax by attenuating the causative agents at high temperature. His principle was used successfully by other investigators who also manufactured live vaccines. Virulence of tuberculosis bacteria has thus been decreased by multiple cultivation of the starting culture on bile-potato media.

Most effective proved the method of controlled variability of microbes and selection of low-virulence and highly immunogenic strains. Artificial active immunity is now induced by vaccines (from Latin vacca, cow and vaccina, cowpox); the method is known as vaccination.

 

The following preparations are used to prevent infectious diseases:

live vaccines prepared from attenuated non-pathogenic microorganisms or viruses; inactivated vaccines prepared from inactive cultures of pathogenic microorganisms causing infectious diseases; chemical vaccines (antigens), isolated from microorganisms by various chemical methods; toxoids, prepared by treating toxins (the poisons produced by microorganisms causing infectious diseases) with formaldehyde.

Vaccines can produce immunity against a given infectious disease or can be polyvalent, i. e., effective against several infectious diseases. Adsorbed vaccines are popular. Aluminium hydroxide is used as an adsorbent. Adsorbed vaccines induce active durable immunity in the vaccinated macroorganism by creating a depot at the site of administration of the antigen, which is slowly absorbed.

Live vaccines are used to create specific immunity against poliomyelitis, measles, influenza, tuberculosis, brucellosis, plague, tularaemia, anthrax, Q fever, skin leishmaniasis, epidemic parotitis, and some other diseases.

Live vaccines prepared from attenuated vaccine strains of microorganisms are more effective than inactivated chemical vaccines. Immunity induced by live vaccines is about the same as produced by normal infection. Live vaccines are given in a single dose intra-cutaneously, subcutaneously, per os, into the nose or by scarification. The disadvantage of live vaccines is that they should be stored and transported at a temperature not exceeding 4-8 °С.

http://www.pbs.org/wgbh/nova/bioterror/vacc_smallpox.html

Inactivated vaccines are prepared from highly virulent strains with adequate antigen properties. They are used to prevent typhoid fever, paratyphoid, cholera, influenza, pertussis, tick-borne encephalitis, and some other diseases. Depending on the microorganism species, various methods are used to inactivate them. The microorganisms can be treated with formaldehyde, acetone, alcohol, merthiolate, or at high temperature. Efficacy of inactivated vaccines is lower than that of live vaccines although there are some highly effective inactivated vaccines as well. Inactivated vaccines are injected subcutaneously. Adsorbed vaccines are given intramuscularly. Inactivated vaccines are more stable in storage. They can be kept at temperatures from 2 to 10 °С.

http://www.pbs.org/wgbh/nova/bioterror/vacc_measles.html

Chemical vaccines are more active immunologically. These are specific antigens extracted chemically from microbial cells. Adsorbed chemical vaccines are used for active immunization against typhoid fever, paratyphoid and other diseases.

Toxoids are formaldehyde-treated exotoxins of the microorganisms causing diphtheria, tetanus, cholera, botulism, and other diseases. Diphtheria and tetanus toxoid is used in the adsorbed form. Toxoids are highly efficacious. When administered into a macroorganism, the vaccine induces an active immunity against a particular infection. Live vaccines produce an immunity that lasts from 6 months to 5 years. Duration of immunity produced by inactivated vaccines is from a few months to a year.

http://www.pbs.org/wgbh/nova/bioterror/vacc_tetanus.html

Immune sera and their active fractions (mainly immunoglobulins) induce passive immunity. Immune sera and immunoglobulins are prepared from blood of hyperimmune animals and from people who have sustained a particular disease or have been immunized otherwise. Passive immunization is used for urgent prophylaxis of people who are infected or supposed to be infected, and also for treatment of the corresponding infectious disease. The effect of immune sera and immunoglobulins lasts from 3 to 4 weeks. They are given intramuscularly.

Bacteriophages are used to prevent and treat some infectious diseases. Bacteriophages are strictly specific toward separate species and even types of.bacteria.

The preparations can be given parenterally (percutaneously, intracutaneously, subcutaneously, intramuscularly, intravenously) or enterally (per os), intranasally or by inhalation (aerosols).

When giving vaccines parenterally, it is necessary to observe sterile conditions and to adhere to the rules specified for injection of a particular vaccine. Jet injections are widely used now: the preparations are administered into the skin, subcutaneously and intramuscularly using various syringes.

When given in the liquid state or in tablets, the vaccine should be taken together with water.

Vaccination should be performed by a physician or secondary medical personnel after thorough examination of persons to be vaccinated in order to reveal possible contraindications, the presence of allergic reactions to medicines, food, etc.

The main contraindications to prophylactic vaccination are as follows: (1) acute fever; concurrent diseases attended by fever; (2) recently sustained infections; (3) chronic diseases such as tuberculosis, heart diseases, severe diseases of the kidneys, liver, stomach or other internal organs; (4) second half of pregnancy; (5) first nursing period; (6) allergic diseases and states (bronchial asthma, hypersensitivity to some foods, and the like).

Vaccination can induce various reactions. These can be malaise, fever, nausea, vomiting, headache and other general symptoms; a local reaction can develop: inflammation at the site of injection (hyperaemia, oedema, infiltration, regional lymphadenitis). Pathology can also develop in response to vaccination; such pathologies are regarded as postvaccination complications. They are divided into the following groups: (1) complications developing secondary to vaccination; (2) complications due to aseptic conditions of vaccination; (3) exacerbation of a pre-existing disease.

Prevention of postvaccination complications includes: strict observation of aseptic vaccination conditions, adherence to the schedule of vaccination, timely treatment of pathological states (anaemia, rickets, skin diseases, etc.), timely revealing of contraindications to vaccination, and screening out the sick or asthenic persons. All cases with severe reactions to vaccination should be reported to higher authorities. If vaccination is performed by scarification, the results are not always positive, and the vaccine must therefore be tested. The results of vaccination should be assessed at various terms, depending on a particular disease against which a person is vaccinated. The result of vaccination against, e. g. anthrax, should be assessed in 2-3 days.

Vaccination should be performed according to a predetermined plan, or for special epidemiologic indications. Planned vaccination is performed against tuberculosis, diphtheria, tetanus, pertussis, poliomyelitis, measles, epidemic parotitis, and against some other infections within the confinement of separate districts or population groups, regardless of the presence or absence of a given disease. Vaccination for special epidemiologic indications are performed in the presence of direct danger of spreading of a particular infection. Vaccination reports must be compiled and special entries made in histories.

 

 

Making Vaccines

Today there is mounting concern about the threat of a bioterrorist attack using smallpox — so much concern that in October 2001 the American government decided to order enough vaccine to protect every U.S. citizen.

Smallpox has a fearsome reputation, having killed more people in history than any other infectious disease. It was quite a victory, then, when English physician Edward Jenner developed an inoculation against smallpox in 1796. Armed with the knowledge that milkmaids who had been exposed to cowpox, a relatively mild affliction, didn’t come down with smallpox, Jenner intentionally infected an eight-year-old boy with cowpox. Two months later he infected the boy again, this time with smallpox. As Jenner expected, the child didn’t come down with the disease — he was immune. Although Jenner’s experiment was highly unethical, especially by today’s standards, it did lead to widespread inoculations against the feared disease. He called his new procedure vaccination, after vacca, which is Latin for cow.

A vaccine works by generating an immune response in the body against some kind of pathogen — a virus or bacteria or some other agent that causes disease. Normally when a pathogen invades the body, the immune system works to get rid of the pathogen. Often, though, the immune system gets a slow start, which gives the pathogen time to multiply and wreak havoc. What a vaccine does is expose the immune system to a less-threatening version of a pathogen and, in effect, prime it to recognize and quickly eliminate the pathogen’s harmful counterpart, should it ever invade the body.

This feature lets you create six vaccines in your own virtual laboratory, using a different technique to produce each one.

·        Making Vaccines

 

Here are the instructions you need to create six different types of vaccines. To find out how a vaccine is made, select a pathogen below.

Live vaccines contain living pathogens. These pathogens invade cells within the body and use those cells to produce many copies of themselves, just as their more harmful counterparts would. The “similar pathogen” and “attenuated” vaccines discussed in this feature are examples of live vaccines. Although these vaccines trigger a full immune response, there is a small risk of the viruses within evolving into more-virulent strains. Non-live vaccines contain agents that do not reproduce in the body. “Killed,” “subunit,” and “toxoid” are examples of non-live vaccines. These vaccines trigger a partial immune response. Genetic vaccines are non-live vaccines that trigger a full immune response.

The procedures outlined in this feature have been greatly simplified. Also, some steps are meant to show what is done but not how. For example, a gene cannot be plucked out of DNA using tweezers, and there’s no box-like device called a purifier that can extract toxins from bacteria as well as viruses from pus.

 

Similar-pathogen vaccine: smallpox virus

Step 1 Use the sterile petri dish to collect fluid from pustules on the cow’s udder.

 

To create a vaccine that will protect you against a pathogen, you usually begin with that pathogen and alter it in some way. Not so with smallpox. To create this vaccine, you begin with another virus that is similar to the smallpox virus, yet different enough not to bring on the smallpox disease once it enters your body. This similar virus is cowpox.

The cow to the left has been intentionally infected with cowpox virus. The fluid that you collect from virus-caused pustules on the cow’s udder contains many copies of the virus.

Step 2 Use the purifier to isolate the viruses.

 

Smallpox vaccines contains cowpox viruses but not the bacteria and other impurities found in the fluid collected from such pustules.

To make the vaccine, therefore, you’ll need to separate the cowpox viruses from the rest of the fluid.

Step 3 Fill the syringe with the purified cowpox viruses.

 

The smallpox vaccine is a live vaccine; the cowpox viruses it contains will invade cells in your body, multiply, and spread to other cells in your body, just as the smallpox viruses would. And as with smallpox, the body’s immune system will mount an attack against the cowpox and subsequently always “remember” what it looks like. Then, if cowpox or the similar smallpox ever enters the body, the immune system will quickly get rid of the invaders.

Done The smallpox vaccine is complete.

 

At one time, cows were used to create the smallpox vaccine. In fact, the decades-old stockpile in the U.S. today was made using live calves through a process similar to the one outlined here. Advancements in biotechnology, however, have led to more efficient procedures that make use of bioreactors.

Attenuated vaccine: measles virus

Step 1 Use the tissue culture to grow new viruses.

 

You are about to create a live-attenuated vaccine, which means that you need to alter a pathogen — in this case a measles virus — so that it will still invade cells in the body and use those cells to make many copies of itself, just as would any other live virus. The altered virus must be similar enough to the original measles virus to stimulate an immune response, but not so similar that it brings on the disease itself.

To create a new strain of the virus, you’ll need to let it grow in a tissue culture.

Step 2 Fill the syringe with a strain of the virus that has desirable characteristics.

 

The tissue culture is an artificial growth medium for the virus. You will intentionally make the environment of the culture different than that of the natural human environment. For this vaccine, you’ll keep the culture at a lower temperature.

Over time, the virus will evolve into strains that grow better in the lower temperature. Strains that grow especially well in this cooler environment are selected and allowed to evolve into new strains. These strains are more likely to have a difficult time growing in the warmer environment of the human body. After many generations, a strain is selected that grows slow enough in humans to allow the immune system to eliminate it before it spreads.

Done The measles vaccine is complete.

 

Like the smallpox vaccine, the virus within the vaccine will invade body cells, multiply within the cells, then spread to other body cells. The virus used in the measles vaccine today took almost ten years to create. The starting stock for the virus originated from a virus living in a child in 1954.

Live-attenuated vaccines are also used to protect the body against mumps, rubella, polio, and yellow fever.

 

Killed vaccine: polio virus

 

Step 1 Use the tissue culture to grow new viruses.

 

The goal in creating a killed vaccine is to disable a pathogen’s replicating ability (its ability to enter cells and multiply) while keeping intact its shape and other characteristics that will generate an immune response against the actual pathogen. When the body is exposed to the killed polio vaccine, its immune system will set up a defense that will attack any live polio viruses that it may encounter later.

To produce this vaccine, you first need many copies of the polio virus. You can grow these in a tissue culture.

Step 2 Use the purifier to isolate the polio viruses.

 

The polio virus uses the cells within the tissue culture to produce many copies of itself.

These copies of the virus need to be separated from the tissue culture.

Step 3 Use formaldehyde to kill the viruses.

 

There are several ways to inactivate a virus or bacteria for use in a vaccine. One way is to expose the pathogen to heat. This is how the bacteria in the typhoid vaccine is inactivated. Another way is to use radiation.

For the polio vaccine developed by Jonas Salk in 1954, formaldehyde was used. You’ll use formaldehyde in creating your polio vaccine, too.

Step 4 Fill the syringe with the killed polio virus.

 

The dead viruses in your polio vaccine will not produce a full immune response when injected in a body. This is true for all vaccines that are not live. For this reason, these vaccines usually require booster shots.

Done The polio vaccine is complete.

 

There are two polio vaccines widely used today. One is Salk’s killed vaccine; the other is a live-attenuated vaccine first developed by Albert Sabin.

In addition to polio and typhus, killed vaccines are used to prevent influenza, typhoid, and rabies.

 

Toxoid vaccine: tetanus

Step 1 Use the growth medium to grow new copies of the Clostridium tetani bacteria.

 

With a toxoid vaccine, the goal is to condition the immune system to combat not an invading virus or bacteria but rather a toxin produced by that invading virus or bacteria. The tetanus shot is such a vaccine. Tetanus is a disease caused by toxins created by the bacteria Clostridium tetani. The vaccine conditions the body’s immune system to eliminate these toxins.

To produce the vaccine, you first need to grow many copies of the Clostridium tetani bacteria.

Step 2 Isolate the toxins with the purifier.

 

While in the growth medium, the bacterial cells produce the toxin, which are toxic molecules that are often released by the cells.

To produce the vaccine, you’ll need to separate these molecules from the bacteria and the growth medium.

Step 3 Add aluminum salts to the purified toxins.

 

In this state, the toxin would be harmful to the human body. To make the vaccine, it needs to be neutralized.

Sometimes formaldehyde is used to neutralize toxins. For your vaccine, you’ll use aluminum salts to decrease its harmful effects.

Step 4 Fill the syringe with the treated toxins.

 

The toxin would work as a vaccine now, but it wouldn’t stimulate a strong immune response. To increase the response, an “adjuvant” is added to the vaccine.

For the tetanus vaccine, another vaccine acts as the adjuvant. This other vaccine inoculates against pertussis. The vaccine for diphtheria — also a toxoid vaccine — is also often added to the tetanus/pertussis combo, making for the DPT vaccine.

Done The tetanus vaccine is complete.

 

As with other inactivated vaccines, there are disadvantages with toxoid vaccines. Even with the adjuvant, these vaccines do not produce a full immune response. Booster shots are needed to maintain the immunity.

 

 

Subunit vaccine: hepatitis B

Step 1 Use the tweezers to pull out a segment of DNA from the hepatitis B virus.

 

A subunit vaccine makes use of just a small portion of a pathogen. For a virus, the vaccine can contain just a piece of the protein coat that surrounds the virus’s DNA (or RNA). Even small portion of a virus is sometimes enough to stimulate an immune response in the body.

There are several ways to produce a vaccine for hepatitis B vaccine. For your vaccine, you’ll use genetic engineering techniques.

 

Step 2 Add the segment of DNA to the DNA of a yeast cell (which is in the yeast culture).

 

A segment of the virus’s DNA is responsible for the production of the virus’s protein coat. You will add this segment to the DNA within a yeast cell.

The yeast cell, as it grows, will “read” the viral DNA incorporated in its own DNA and produce the protein that makes up the protein coat of hepatitis B.

Step 3 Use the purifier to isolate the hepatitis B antigen produced by the yeast cells.

 

The vaccine, once administered, will stimulate the immune system to attack the antigen (i.e., the protein coat). Then, if the inoculated person is later exposed to the virus, the immune system will quickly respond to the invader and eliminate it before it has a chance to spread widely.

To finish making the vaccine, you need to separate the proteins from the yeast cells.

Step 4 Fill the syringe with the purified hepatitis B antigen.

 

The isolated hepatitis B protein, produced by the yeast cells, contains none of the viral DNA that makes hepatitis B harmful. Therefore, there is no possibility of it causing the disease.

Done The hepatitis B vaccine is complete.

Another example in the subunit category is the anthrax vaccine approved in the U.S. (The countries of the former Soviet Union have an attenuated version of the vaccine.) The U.S. vaccine is currently administered to military personnel.

 

Naked-DNA vaccine: HIV

Step 1 Use the growth medium, which includes PCR primers, to make billions of copies of a single gene.

 

Genetic vaccines, sometimes called naked-DNA vaccines, are currently being developed to fight diseases such as AIDS. The goal of these vaccines is to use a gene from a pathogen to generate an immune response. A gene contains the instructions to create a protein. With a genetic vaccine, small loops of DNA in the vaccine invade body cells and incorporate themselves into the cells’ nuclei. Once there, the cells read the instructions and produce the gene’s protein.

Using a technique called PCR, which stands for polymerase chain reaction, you’ll make many copies of a specific gene. The work of finding the gene and copying sequences of its DNA is done by “primers.”

Step 2 Combine the virus genes with vectors.

 

To make your genetic vaccine, you’ll use vectors. Vectors are agents that are able to enter and instruct cells to create proteins based on the vector’s DNA code. In this case, the vectors are loops of double-stranded DNA. You can exploit the vector’s ability to create proteins by splicing a gene from the virus into a vector. The cell that the vector later invades will then produce proteins created by the virus.

The vectors and copied genes have been treated with restriction enzymes, which are agents that cut DNA sequences at known locations. The enzymes have cut open the round vectors and trimmed the ends of the copied genes.

Step 3 Add bacteria to the vectors to allow the altered vectors to replicate.

 

The ends of the vectors have again come together, but now with a gene spliced into the loop. You’ll need many copies of the vector/gene loop for your genetic vaccine. These copies can be produced with the help of bacteria.

Vectors are capable of self-replicating when within a bacterial host, as long as that host is in an environment conducive to growing. After you combine the vectors and bacteria, the vectors will be shocked into the bacteria.

Step 4 Use the purifier to separate the altered vectors from the bacteria.

 

The final vaccine should include only the vectors, so you’ll need to separate them from the bacteria after enough copies have been produced. This can be done with a detergent, which ruptures the cell walls of the bacteria and frees the DNA within.

The relatively large bacterial DNA can then be separated from the smaller DNA loop that makes up the vector.

Step 5 Fill the syringe with the altered vectors.

 

Upon inoculation, billions of copies of the altered vector will enter the body. Of these, only 1 percent will work their way into the nuclei of body cells. But that’s enough.

The body’s immune system responds to these proteins once they leave the cell. But more importantly, it also reacts to proteins that are incorporated into the cells’ walls. So in addition to mounting an attack against the free-floating proteins, the immune system attacks and eliminates cells that have been colonized by a pathogen. The vaccine, then, works like a live vaccine, but without the risk. (With a live vaccine, the pathogen can continue to replicate and destroy cells as it does so.)

Done The naked-DNA vaccine is complete.

Trials for a genetic vaccine that may protect against AIDS began in 1995. These vaccines, which contained HIV genes, were given to patients who already were infected with HIV. A year later, the trials were expanded to test people without HIV. These trials are still being conducted and have not yet produced conclusive results.

Human trials for genetic vaccines against herpes, influenza, malaria, and hepatitis B are also underway.

Note: Although the genetic material of HIV is RNA, the procedure for making the vaccine is similar.

Addition 1

Order MPH of Ukraine № 276 from 31.10.2000.

CALENDAR of PREVENTIVE INOCULATIONS in UKRAINE

Section 1. Inoculation on age

Century			Inoculation against
1 day		Hepatitis В2
3 days	Tuberculosis1
1 month
3 months		Hepatitis В2	Diphtheria, wooping cough, tetanus3	Poliomyelitis4
4 months			Diphtheria, wooping cough, tetanus3	Poliomyelitis4
5 months		Hepatitis В2	Diphtheria, wooping cough, tetanus 3	Poliomyelitis4
6 months
12-15 months					Measles, rubeola, parotitis 5
18 months			Diphtheria, wooping cough, tetanus3	Poliomyelitis 4
3 years				Poliomyelitis4
6 years			Diphtheria, tetanus 3	Poliomyelitis4	Measles, rubeola, parotitis 5
7 years	Tuberculosis1
11 years			Diphtheria, tetanus 3		Measles, rubeola, parotities 5 (at absence of vaccination in 6 years)
14 years	Tuberculosis1		Diphtheria, tetanus 3	Poliomyelitis 4
15 years					Rubeola (girls), parotitis (boys)5
18 years			Diphtheria, tetanus 3
Have grown		To hepatitis В2	Diphtheria, tetanus 3

1 Revaccination in 7 and 14 years children with negative reaction to the Mantu test are subject. Association in one day of inoculation against a tuberculosis with others parenteral manipulations is inadmissible.

For vaccination of prematures with weight of a body that is more than 2000 g, and also children, not inoculated in the patrimonial house through presence of medical contra-indications, it is necessary to apply a vaccine in BCG-M.

Children who were not vaccinated in the patrimonial house through medical contra-indications, are subject to obligatory vaccination in children’s polyclinics after removal of contra-indications. After execution the child of bi-monthly age before performance of inoculation BCG should lead Mantu test and to carry out inoculation in case of negative result of test.

Children with negative reaction to Mantu test about 2 IN at absence of aftervaccinal (BCG) scar should carry out additional inoculation in 2 years after vaccination or in 2 years after revaccination BCG.

2 For vaccination against a hepatites B the alternative scheme can be used – 0, 1, 6 months of life of the child.

Newborn which were born from mothers – carriers HBsAg, are vaccinated under the circuit – 0 (the first 12 hours of life), 1,6,12 months of life of the child.

At infringement of term of the beginning of vaccination against a hepatites B intervals between introductions of this vaccine are kept. Association with inoculation against a diphtheria, wooping cough, a tetanus and a poliomyelitis is allowed at presence of the combined vaccine, inoculation will be carried out under the circuit – 3, 4, 5 months from birth of the child.

Adults are also subject to vaccination also: medical workers (students of average and supreme medical educational establishments) who professionally have contact to blood, its preparations and carry out parenteral manipulations.

3 – an interval between the first and second, second and third inoculation is equal 30 days. The interval between the third and fourth inoculation should represent not less than 12 months and no more than 2 years.

Inoculation of children till 4 years outside of terms of the Calendar intend from such calculation that the child can receive quadruple vaccination till 3 years of 11 months and 29 days.

Second third and the fourth revaccination will carry out in 11, 14 and 18 years ADT-М-anatoxin. To children, who were inoculated against a tetanus concerning a trauma during last two years revaccination in 11 years will carry out – М-anatoxin.

Children till 6 years of 11 months of 29 days which have contra-indication to introduction APDT vaccine or had been ill on wooping cough, inoculates with ADT-anatoxin. Vaccination will be carried out three times (an initial vaccine complex) with intervals between the first and second inoculation of 30 days, between the second and the third – 9-12 months.

Inoculation of children after 6 years outside of terms of the Calendar will be carried out with ADT-М-anatoxin quadruple (an initial vaccine complex): an interval between the first and the second, second and third inoculations equally З0 days. The fourth inoculation will be carried out in 6-9 months after the third immunization.

The first scheduled revaccination of adults on age to epidindications which were inoculated earlier, it is necessary to carry out – М-anatoxin 5 years after last inoculation. The further scheduled of revaccination to adults will be carried out with an interval of 10 years with ADT-М-anatoxin.

Teenagers also adults, which were not inoculated earlier or have no data according to immunization, inoculates with ADT-М-anatoxin three times (the interval between the first and second inoculation has to represent 30-45 days, between the second and the third – 6-12 months).

Revaccination is carried out not earlier than in 3 years after last inoculation against a diphtheria and a tetanus.

For active immunization against a tetanus of persons over 60 years, inoculated last 10 years use the reduced circuit of vaccination (disposable inoculation with АП-anatoxin in a double doze – 20 odes./ml with obligatory revaccination in 12 months a doze of 10 од./ml) and further each 10 years without restriction of age.

4 – for immunization oral poliomyelitis vaccine (OPV) is applied. Inactivated vaccine (IV) can be used for first two inoculations and at contra-indications to OPV – for any inoculation. The child who was inoculated against a poliomyelitis without infringements of the Calendar of inoculations also has received in general 4 dozes of OPV immunization against a poliomyelitis is subject to the further only for epidindications.

After inoculation of OPV it is offered to restrain injections, parenteral interventions, scheduled operations during 2 week.

5 – vaccination against measles, epidemic of parotitis and rubeola will be carried out by monovaccines or threvaccine in the age of 12-15 months. To children who were not vaccinated against measles, a parotitis or rubeola, inoculation can be begun in any age.

The second doze of a vaccine against measles, a parotitis and rubeola is recommended to enter to children in the age of 6 years. Persons who have not received in due time the second doze, should be revaccinated in 11 years. Persons who were not earlier vaccinated or have not received revaccination, can be inoculated for epidindications in any age till 30 years.

The transferred disease on measles, an epidemic parotitis or rubeola is not contra-indication to inoculation by threvaccine. If in the anamnesis transferred two the named illnesses, inoculatioeeds to be carried out only monovaccine against that infection, on what the child was not sick. At presence of monovaccine against rubeola first of all it is necessary to inoculate girls 15-years age. Women of mature age who were not sick on rubeola and were not inoculated against it, can receive individual inoculations at own will according to the instruction to a vaccine.

The scheme of vaccination of HIV – infected patients and children with AIDS

Inoculation against a poliomyelitis carried out by inactivated – poliomy­elitis vaccine.

1. 1-2 weeks before of vaccination it is desirable to appoint multi-vitamins, which contains vitamin A.

2. Vaccination is carry out under supervision of the doctor – pediatrist or children’s doctor-infectionst in out – polyclinic or stationary conditions.

3. In postvactional period home nursing of the child by the medical worker on 3-4th and 10-11s day is carried out.

4. Alive oral polyvaccine does not intend to members of HIV – infected family also to persons who have close contact with HIV – infected, in connection with a great risk of occurrence vaccineasociated poliomyelitis at HIV infected person.

5. Inoculation of the child, born from HIV – infected mother, against a tuberculosis and a poliomyelitis (alive oral vaccine) it will be carried out after removal of the diagnosis of the HIV-infection at the child. Vaccination against a poliomyelitis will be carried out if the child was not inoculated earlier inactivated poliomyelitis vaccine.

6. Passive immunoprophylactic of HIV-infected also ill on AIDS child it will be carried out (behind epidemic indications) during the first 98 hours after contact irrespective of carried out before inoculations.

7. Before seasonal rise of a level of disease on a flu HIV infected children are subject to prime vaccineprophylactic against a flu.