: March 25, 2013, When science is ahead of fantasy, volume 48, no. 6
Smallpox, often called the scourge of humanity, was completely eradicated 35 years ago through mass vaccination and strict epidemic control. This is the first and so far only example of the global elimination of a particularly dangerous infectious disease by the world community. But has smallpox disappeared forever, and will this or another dangerous smallpox-like infection return again? To answer this question, you need to know how and when the causative agent of this disease appeared, how it adapted to the human body and understand the mechanisms of mutual evolution of pathogens and their hosts
Smallpox, or smallpox (not to be confused with chickenpox), is a particularly dangerous infectious disease that has claimed more human lives than other infections or even wars.
The causative agent of this disease caused such characteristic clinical manifestations of infection and caused such large-scale epidemics with a high mortality rate that many historians and doctors left written evidence about this disease. And although the records that have survived to this day are fragmentary and scattered and do not always allow us to reliably establish the cause of a particular epidemic outbreak, it can be confidently stated that since ancient times this disease has been found in a large area limited in the west by Egypt and in the east by China.
In different languages, the name of this disease sounds different, but they all point to its most noticeable manifestation - skin lesions: Staroslav.
– smallpox (from showering, rash);
lat.
– variola vera (variegated, spotted);
English
– smallpox (small – small, pox – skin rash);
French
– la petite variole (small spotting)
Since the period of the Crusades, epidemics of this devastating disease regularly arose on the European continent as a result of the introduction of infection from the Middle East: in the VI-VII centuries. outbreaks of smallpox were recorded in France, Italy, Spain and other European countries. The first mentions of severe smallpox epidemics in Russia date back to the 15th century, and starting from the next century, smallpox became so common in Europe that the attention of chroniclers was attracted only to cases of its extremely widespread distribution.
And even in the 20th century, in those less than eighty years when mass anti-smallpox vaccination was carried out and an intensive fight against smallpox was carried out using strict quarantine measures, at least 300 million people in the world died from this infection!
Evolving together
Like other viruses, the smallpox virus is not able to exist on its own: in order to multiply, all viruses need to infect higher organisms that are sensitive to them. At the same time, in nature there are constant processes of changing genetic programs and selection (selection) of optimal variants, both in the viruses themselves and in their hosts. The only difference is that viruses multiply in an infected cell of the body in a short period of time (several hours) and produce numerous offspring (hundreds and thousands of daughter viral particles).
DIAGNOSIS – SMALLPOX!
In the 20th century Based on the severity of the clinical course and mortality rate, smallpox was divided into smallpox ( variola major
, mortality 5-40% of the number of cases) and smallpox (
variola minor
, mortality 0.1-2%).
In the countries of Asia and Africa at this time, smallpox was mainly widespread. The incubation period, from the moment of infection to the onset of fever, is usually 10-14 days. There are two main stages of the disease: prodromal (before the rash appears) and the rash stage. The first stage lasts 2-4 days and is characterized by high hyperthermia (up to 40.5 ° C), severe headache and characteristic pain in the sacrum. Tachycardia, increased breathing, nausea, often vomiting and delirium are noted. Then the body temperature decreases, and skin rashes appear in the form of small reddish nodules ( papules
), first on the face and hands, and then on other parts of the body.
Increasing in number and size, papules turn into vesicles with transparent contents and a characteristic depression in the center ( vesicles
).
By the 6-7th day, suppuration of the vesicles occurs ( pustule stage
), accompanied by a new rise in temperature.
On the 10-13th day of illness, the pustules reach their maximum size, after which they gradually flatten, dry out and turn into crusts, which fall off by the 30-40th day of illness, leaving reddish spots. Subsequently, in some areas (mainly on the face), characteristic recesses of the skin form in place of the spots - smallpox scars (the so-called pockmarked face
). People who have recovered from the disease acquire lifelong immunity to smallpox and are not chronic carriers of the virus.
Multicellular organisms, such as humans, cannot be compared with viruses in terms of speed and efficiency of reproduction. When an epidemic develops in a real human population, which remains genetically unchanged in this short period of time, the spread of the virus between individuals occurs according to the principle of a chain reaction. This process can lead to the emergence of many mutant
(modified) variants of the original virus and the selection of one of them, which in given specific conditions has an advantage in distribution and reproduction. In cases where the infection is fatal, the individuals most sensitive to it die. Moreover, during any epidemic there are always individuals that are weakly sensitive or even completely resistant to a specific infectious agent.
Sensitivity to infection is determined by the genetic characteristics of individuals, therefore, during mass epidemics, not only new variants of viruses arise, but the host population is also enriched with individuals with genetically determined resistance to the virus. This is how interdependent joint evolution proceeds ( coevolution
) of the virus and its host, despite the fact that the rate of evolution in viruses is much higher compared to a similar process in animals and humans.
An important feature of smallpox is that it is a strictly anthroponotic infection
, i.e., it is transmitted only from person to person - today there are no other species of mammals that are sensitive to the causative agent of this disease.
Moreover, this infection is highly contagious
, i.e., the ability to be effectively transmitted from sick people to healthy people.
It is likely that the variola virus originated from a virus that affected a wide range of animal species sensitive to it, but which, in the process of evolution, lost this ability, adapting as much as possible to the human body (Shchelkunov et al.
, 2005).
Pathological changes
Photo of smallpox virus
Skin changes
On the skin of corpses who died from smallpox, there is a rash in varying degrees of maturity. Macroscopically, in the initial period, with the papular nature of the rash, inflammatory phenomena are detected in the papillary and subpapillary layers of the skin and swelling of the epidermis, and then, with the development of a macroscopically visible vesicle, serous exudate leaks into the thickness of the epithelium and the formation of cracks in the epidermis; due to significant inflammatory exudation in them, part of the partitions between them breaks through (the cellular structure of the developed pockmarks). At the edge of the necrotic lesion, a strong proliferation of epithelial cells occurs, surrounding the central necrotic lesion in the form of a roller and leading to the formation of a central depression (smallpox umbilical). Subsequently, suppuration and destruction of the affected area of the skin occurs and then gradual healing with the formation of a scar due to connective tissue proliferation of the destroyed corium or without the formation of a scar in the form of temporary pigmentation (with suppuration of only the epidermis).
Changes in mucous membranes
Rashes are also observed on the mucous membranes of the mouth, pharynx, esophagus, vagina, and colon. When a rash occurs on the mucous membranes, due to the absence of a dense layer of epithelium, the contents of the vesicles quickly break through to the surface with the formation of ulcers. The formation of extensive ulcers and necrosis may be due to the addition of an additional third-party infection.
Changes in parenchymal organs
The spleen appears significantly enlarged due to plethora and hyperplasia of pulp cells. Degenerative phenomena are observed in parenchymal organs (heart, liver, kidneys). Testicular damage presents with a picture of acute necrotizing orchitis with temporary stromal edema and disintegration of the tubular epithelium. In the bone marrow, mainly in the epiphyses, areas of serous-fibrinous impregnation with necrotization of the formed elements are found.
Changes in hemorrhagic form
In hemorrhagic forms of smallpox, hemorrhages are observed in places of specific smallpox changes, as well as in various parts of the body (in the serous cavities, renal pelvis, bladder, uterus, ovaries, mediastinum, muscles, etc.).
In a vicious circle
Variola virus is one of the largest and most complex mammalian viruses. Brick-shaped viral particles have relatively large sizes (250-300 × 200 × 250 nm), so after special staining they can be seen using a light microscope, which is impossible for other viruses. The variola virus genome is a linear double-stranded DNA molecule containing 187 thousand base pairs with covalently closed hairpin structures at both ends. The virus has about 200 genes in its genome, a huge number compared to most viruses of other families. Viral particles have several lipoprotein membranes and contain many structural proteins, as well as enzymes necessary for the reproduction of the virus in the host cell. The entire development cycle of the variola virus takes place in the cytoplasm of the cell in special structures called virosomes or viral factories.
If an acute infectious disease can quickly spread in the host population and lead to rapid death or recovery with the acquisition of immunity, then its outbreak should lead to a rapid depletion of the “reserve” of individuals sensitive to it. And if at the same time the causative agent of such a human infection loses the ability to reproduce in a pre-existing natural reservoir, i.e., in wild animals, then in a relatively small and sparse human population the epidemic will quickly fade.
In a large population of people with a high population density, the infection can be transmitted from one area to another, returning to the starting point years later, when a new generation sensitive to the pathogen has already been born and grown up. In this case, the anthroponotic infection will be maintained in a certain area for many years, turning into the so-called endemic state
.
The oldest surviving descriptions of smallpox date back to the 4th century.
(China) and 7th century. (India and the Mediterranean), define this disease primarily as a childhood infection, with the highest mortality rate among children. This indicates that the disease was already endemic at that time in these densely populated geographic areas. In India, despite the centuries-old endemicity of the disease and the long-term co-evolution of the smallpox virus and the population of this region, the mortality rate among unvaccinated children under 5 years of age during smallpox epidemics that periodically occurred there even in the 20th century. could reach 50% (Fenner et al.
, 1988). This is due to the fact that the variola virus has a multifactorial system for effectively overcoming numerous protective reactions of the human body directed against infectious agents (Shchelkunov, 2011; Shchelkunov, 2012). Therefore, the likelihood of genetic adaptation of the human population to this virus, which would significantly reduce the degree of its pathogenicity for humans, is extremely low.
Over the past centuries, evolution has largely affected the virus itself. At the same time, in the most densely populated and vast territories (the Indian subcontinent), smallpox epidemics occurred with the highest mortality rate, and in regions with low population density - with a lower one.
Prevention
In the fight against smallpox, vaccination undoubtedly plays a leading role.
Nevertheless, sanitary and hygienic measures must be fully carried out both at the patient’s bedside and in his environment. If a patient with smallpox is discovered, he must be immediately isolated. A case of illness is urgently reported to higher health authorities, up to and including the Minister of Health. Isolation of the patient continues until the crusts completely fall off, but not less than 40 days from the date of illness. Persons who have been in contact with a smallpox patient are immediately vaccinated, including newborns from two weeks of age. Monitoring of those in contact with the patient continues for 14 days from the moment of isolation of the infected person and final disinfection. Final disinfection after isolation of the patient is carried out in the room in which the patient was before hospitalization, and in the rooms that the infected person visited in the last 2 days before the disease and since the moment of the disease.
It is impossible to overcome smallpox with sanitary and hygienic measures alone. During periods of outbreaks of epidemics, there are constantly abortive and erased forms that cannot be counted or processed and continue to disseminate the infectious principle among others. In the fight against smallpox, there is a powerful achievement of medicine - vaccination and revaccination, that is, active immunization of the weakened due to the passage of the live smallpox virus through the animal body.
From animals to humans
It is known that most human pathogens originate from zoonotic
(i.e., characteristic of wild animals) infectious agents. Moreover, many viruses may not cause significant disease in their natural host, but can be highly pathogenic when transferred to another species, including humans. Some of the most striking such examples are the Marburg and Ebola viruses, whose natural hosts are African bats. They do not cause disease in these animals even when laboratory infected with large doses, but in humans they cause severe hemorrhagic fevers with a mortality rate of up to 80%.
The persistence of smallpox is only possible in a large and dense human population. In the process of human evolution, populations of such large sizes began to arise during the transition of people to a sedentary lifestyle and the development of agriculture
The formation of large populations of domestic animals was important for the infectious “history” of man. It is these animals with which people often come into close contact that usually serve as effective intermediate reservoirs for the transmission of the pathogen from wild animals to humans.
Moreover, at the first stages of this process, most zoonotic pathogens are not able to be transmitted from a sick person to a healthy person. However, as the frequency of infection of a new host increases, as a result of natural evolution the virus may acquire the ability to be transmitted effectively between people and thus cause epidemics. The period of complete adaptation of the virus to a new host and its transformation into an epidemically dangerous pathogen can sometimes take many years (Shchelkunov, 2011).
Based on data from deciphering viral genomes, it was possible to estimate the time of speciation and independent evolution of various orthopoxviruses, which include the variola virus (Babkin, Shchelkunov, 2008). It turned out that the “related” variola and camelpox viruses originated from a single ancestor orthopoxvirus (apparently a rodent virus) about 3.4 ± 0.8 thousand years ago, and then evolved independently.
Probably, about 4 thousand years ago, this orthopoxvirus, which had a wide range of hosts, acquired the ability to infect humans. At the same time, it caused only skin lesions in both people and domestic animals without serious consequences. Along the trade routes of ancient civilizations, the virus could have spread over a vast area from the Indian subcontinent to the river valley. Nile, causing sporadic outbreaks of relatively mild infection in these areas. However, as the virus adapted to the human body, increasingly widespread outbreaks could occur, which, in turn, led to the emergence of new variants of the virus (Shchelkunov, 2009).
Complications
Complications from smallpox are numerous. They can lead to the death of the patient, as well as to blindness, deafness, etc.
Leather
Skin complications:
- abscesses,
- phlegmon,
- erysipelas,
- bedsores,
- gangrene followed by general purulent infection.
Respiratory system
From the respiratory tract:
- necrotic perichondritis, sometimes leading to laryngeal stenosis,
- acute swelling of the pharynx,
- pneumonia (bronchopneumonia),
- purulent pleurisy,
- lung abscesses.
Heart and blood vessels
From the heart and blood vessels the following are observed:
- endocarditis,
- pericarditis,
- myocarditis,
- thrombophlebitis.
Kidneys
Kidney complications:
- albuminuria,
- jades.
Hearing organs
Complications from the organ of hearing - purulent otitis.
Eyes
On the part of the eyes, complications are expressed in the form of:
- blepharitis,
- ulcerative keratitis with iritis and panophthalmitis, leading to blindness.
Nervous system
From the nervous system, although not often, encephalitis and myelitis are observed, leading to paralysis.
First Comings
It is believed that smallpox originated in the region of Egypt (Middle East), however, in the numerous regional written sources that have reached us from that time, there is no mention of epidemics of this disease. Therefore, it is worth considering an alternative option related to the history of the ancient highly developed Indus (Harappan) civilization, which was discovered by archaeologists only in the 1920s. (Albedil, 1991).
"COOL" GODDESS
Shitala, the Hindu goddess of smallpox, occupies a very special place among the countless personifications of Devi, the variety of which is so rich in Hinduism. Her cult is widespread throughout almost the entire territory of Northern and Central India, from Sindh and Gujarat in the west of the country to Bengal, Assam and Orissa in the east, as well as outside the country - in Bangladesh and Nepal. Despite some variability in iconography, Sheetala is easily recognizable: she is depicted riding a donkey, naked or dressed as a married woman, often as an elderly Brahmin woman. She had a fan on her head, a broom and a vessel with water in her hands. The cult of this goddess obviously developed quite late - the first mentions of her appear in medical treatises of the 16th century, although descriptions of the disease itself are found in texts created long before the beginning of our era. Judging by many signs, the cult of Shitala is folk in origin and was not immediately included in Hindu religious ideas. Thus, there is no mention of Shitala in the early Brahminical texts, and its priests to this day are for the most part not Brahmins, but representatives of the low caste Malakars. In some places, blood sacrifices are still made to the goddess, although in general she prefers bloodless offerings - coconuts, cold rice, sweets and other “cooling” foods. The goddess, born from the cooled ashes of a sacrificial fire, hates heat and always seeks coolness, rewarding those who can appease her and punishing careless adherents with the heat of smallpox. It is not surprising that within these ideas, smallpox was seen not as a dangerous disease, but rather as the result of the manifestation of the presence of an angry deity. Therefore, treatment of a patient with smallpox primarily included procedures aimed at cooling the body of the unfortunate victim of divine rage: cold drink, fanning, wiping the body with ice water or wet leaves of the neem tree - the favorite plant of the goddess, truly known for its effectiveness against many skin diseases. All these actions were accompanied by chants addressed to Sheetala. The highest mortality rate from smallpox was recorded in India during the hot, dry months of the year, from February to April, decreasing sharply towards the beginning of the rainy season. Therefore, smallpox in India was often called a spring disease, and Shitala, accordingly, a spring goddess (the main holiday dedicated to her falls in mid-March). And today, during the holiday, in order to avoid the wrath of the “cool” goddess, any “warming” actions are prohibited - cooking hot food, eating spices, lighting fires in houses, as well as marital relations. Although the name of this goddess is primarily associated with smallpox, her character is very multifaceted. For example, Sheetala is also considered the protector of children and the giver of good fortune. But although the features of the cult may vary from place to place, the main characteristic of the goddess remains unchanged - she is always “cool” (this is how her name is literally translated from Sanskrit). Today, "cool" Shitala is more than a local deity protecting against smallpox: she serves as a symbol and constant living reminder of the need to maintain the correct balance of heat and cold in the human body. Violation of this balance, causing the wrath of the goddess, can lead to the emergence of a dangerous disease.
K. M. Vozdigan, senior specialist of the exhibition department of the Museum of Anthropology and Ethnography (Kunstkamera) RAS, St. Petersburg
About 2.5 thousand years BC. e. in a long river valley The largest cities of that time appeared on the Indus River, the population of which by the beginning of the 2nd millennium BC. e. was about 5 million people. However, for an unknown reason, 1.8-1.6 thousand years BC. e. these cities were depopulated. There is no evidence that they died as a result of wars or natural disasters; Moreover, during excavations of the largest city of Mohenjo-Daro, numerous human remains were found on the streets without visible wounds or damage, despite the fact that, as archaeologists have established, cremation of the dead was typical for this culture.
The most obvious explanation for the collapse of the Indus civilization, one of the three most ancient civilizations of mankind, along with the ancient Egyptian and Sumerian, may be an epidemic of a fatal disease. Since the time of occurrence of the smallpox virus (3.4 ± 0.8 thousand years ago) corresponds well to the period of a sharp decline in the population of the Indus Valley (3.8-3.6 thousand years ago), it can be assumed that it was smallpox in As a new deadly infection, it became the cause of mass epidemics among the local population, which had no immunity to it, which led to a sharp decrease in its population (Shchelkunov, 2009). The size of this human population appears to have prevented the infection from becoming endemic, and this highly virulent human infectious agent has disappeared.
However, its zoonotic progenitor (or a low-virulent variant of variola virus with a wide host range) apparently continued to circulate in a natural reservoir (rodents) over a large area. This situation is typical for any new highly lethal human infection: the most famous example is the Spanish flu epidemic in 1918-1919.
Researchers of ancient manuscripts, including the Talmud and the Bible, did not find in them descriptions of epidemics of a strictly anthroponotic infection with skin rashes resembling smallpox. However, if we use the assumption put forward above that the causative agent of smallpox originated from an orthopoxvirus with a wide range of hosts, which in the first stages of adaptation to humans of smallpox retained the properties of a zoonotic infection with little pathogenicity for humans, then in the text of the Bible we find the description we need, relating to the time of the exodus Jewish people from Egypt (14th century BC): “... and there was inflammation with boils on people and on livestock throughout the whole land of Egypt” (Exodus, the sixth plague of Egypt).
This indicates that in Egypt and the Middle East, already in ancient times, epidemics of zoonotic infection of people and domestic animals with skin rashes on the body, not accompanied by death, apparently occurred (Shchelkunov, 2011).
In modern times, smallpox showed its deadly power after the discovery of America by Europeans. During the XVI-XVII centuries. it was repeatedly brought to the New World from Europe and West Africa along with slaves. The indigenous population of America never encountered this infection, so smallpox became a terrible disaster for them - some tribes died out almost completely. It is known that in Mexico alone in 1520, smallpox claimed about 3.5 million lives! Only after powerful smallpox epidemics passed through both American continents did the disease become endemic with a low (less than 1%) mortality rate. The population of South and North America at the time of Columbus’s landing was about 70 million people, but as a result of similar epidemics and, to a much lesser extent, wars, by 1800 it had decreased to 600 thousand people
It is possible that the mysterious “catastrophe” of the Bronze Age in the Middle East and Eastern Mediterranean, dating back to 1.2-1.1 thousand years BC, is also connected with the smallpox epidemic, but with a high mortality rate. e. This period is characterized by a sharp decline in the human population of this vast region, the destruction of cities and catastrophic changes in social structure (Robbins and Manuel, 2001). And it was from this time that two of the three Egyptian mummies found with skin lesions characteristic of smallpox date back to this time (Fenner et al.
, 1988).
It can be assumed that during this period, in the region of the Middle East and Eastern Mediterranean, where several million people lived, a virus dangerous to humans re-emerged, but the insufficiently high human population again did not allow the new anthroponotic infection to become endemic and persist.
The next “coming” of smallpox occurred in the middle of 1 thousand years BC. e. on the Indian subcontinent. Here, in the Ganges Valley, by that time the largest (about 25 million people) and dense human population had formed. Obviously, this population size was already sufficient for the newly formed highly pathogenic strain of the virus to become endemic.
At this time, among the European countries, the most populous was Greece, whose population by 400 BC. e. was approximately 3 million people. In both Greece and the Middle East, smallpox apparently was not observed at that time: at least, there were no epidemics in the army of Alexander the Great on the way from the Mediterranean Sea to India. But during the stay of this army on the territory of the Indian subcontinent in 327 BC. e. There was an outbreak of the disease with skin lesions characteristic of smallpox.
The transition of smallpox to an endemic state in the Indian subcontinent ensured the persistence of this highly pathogenic agent for humans for many centuries, until the 20th century. From here, this disease gradually spread throughout the world, and it was possible to eliminate it on a global scale only in the second half of the last century with the help of special preventive vaccinations.
Chance of getting sick
The contagiousness of the chickenpox virus is truly unique - it is 100%. All age groups are susceptible to chickenpox. However, this infection most often affects children. About half of the diseases in childhood occur between the ages of 5 and 9 years; children aged 1–4 and 10–14 years are less likely to get sick. About 10% of the cases are people 14 years of age and older. Among this age group, over the past 5 years, the incidence of chickenpox has increased from 28 to 58 per 100 thousand population. Children in the first months of life are most often resistant to this infection. However, babies born prematurely and weakened by other diseases can become seriously ill with chickenpox.
The maximum incidence of chickenpox is observed in the autumn-winter months. Epidemic outbreaks are observed mainly in organized groups among preschool children. Children attending kindergartens and nurseries get chickenpox 7 times more often than unorganized children.
The risk group also includes patients with immunodeficiencies, including HIV infection. Severe cases of chickenpox have been described in children receiving hormonal therapy with steroid drugs. Cases of congenital chickenpox have also been described in children whose mothers had chickenpox in the first half of pregnancy; perinatal infection occurs in children whose mothers became ill 5 days before and 48 hours after the birth of the child.
In persons with severe immunodeficiency of various etiologies (in rare cases with HIV infection and in patients after organ transplantation; often with acclimatization, decreased immunity caused by severe stress), the disease may recur.
Treatment
Treatment of chickenpox mainly involves preventing bacterial complications. To prevent the spread of the virus, careful hygiene must be observed, including showering daily and trimming young children's nails (to prevent scratching and breaking up the rash blisters).
The use of antiviral agents during treatment, such as acyclovir, is only justified for premature infants, patients with compromised immune systems and adults (due to the greater severity of the infection). The traditional means of “treating” chickenpox – “brilliant” – is not any effective remedy; baths and trays with a small addition of soda, antihistamines and pain-relieving ointments to relieve itching are much more effective.
Historical information and interesting facts
Chickenpox was first described in the mid-16th century in Italy by doctors Vidus-Vidius and Ingranus. For a long time, chickenpox was not recognized as an independent disease and was considered a type of smallpox. After the causative agent of chickenpox was discovered in the contents of chickenpox vesicles in 1911, the disease began to be considered a separate nosological form. The virus itself was isolated only in 1958. The chickenpox virus infects only humans, and the only reservoir of infection is also humans.
