As smallpox , smallpox or variola ( Latin variolae ), also known as smallpox , is called a dangerous for humans and life-threatening infectious disease that of smallpox virus ( orthopoxvirus variolae ) is caused. Due to its high infectivity and lethality , the disease is one of the most dangerous for humans. The eponymous skin vesicle that is typical for the disease is known as pock or leaf .
There have been no new cases of smallpox since the last illness in Somalia in 1977 and from Janet Parker in 1978; the last case in Germany occurred in 1972. A consistent vaccination and control program by the WHO and other health organizations enabled the world to be declared smallpox-free by the WHO on May 8, 1980 or earlier, because the pathogen can only be passed on by humans.
The name “smallpox” appears for the first time in an Anglo-Saxon manuscript from the 9th century at the end of a prayer: … geskyldath me wih de lathan Poccas and with ealleyfeln. Amen. ("... protects me from the hideous smallpox and all evil. Amen.") The word pocke comes from Germanic and means "bag", "pocket", "bladder", " leaves " (Middle High German : pale ). It is related to the English pocket , pox , pocks and French poche . In English, to differentiate it from syphilis (“great pockes” or “great pox”), smallpox has been called “small pockes” (or “smallpox”) since the end of the 15th century; in French they are accordingly called petite vérole .
The name variola (from Latin varius , colorful, dappled, blotchy) was coined by Bishop Marius von Avenches (now Switzerland) around AD 571 and is said to have been used by the doctor and in the 11th century of the disease Translator Constantinus Africanus have been given.
Smallpox virus, TEM image
The causative agents of smallpox in humans are viruses of the genus Orthopoxvirus (species Variola virus alias Orthopoxvirus variolae ). Smallpox viruses are the largest known animal viruses at 200 to 400 nm. These viruses are also unusual in terms of their DNA replication in the cytoplasm compared to other DNA viruses . An infected with a poxvirus cell has a DNA synthesis in a " virus factory " outside the core on what else only in intracellular organelles such as mitochondria (and in plants, in chloroplasts ) or in the maturation of the hepatitis B virus within the capsid in Cytoplasm occurs. A second membrane structure within the virion is characteristic of smallpox viruses , which is located within the virus envelope and is synthesized de novo around the capsid during the assembly of the intracellular virus particle .
|Real smallpox||Variola vera,
Orthopoxvirus variolae alias
|10 ... 90% -
depending on the trunk
|White smallpox||Variola minor,
Orthopoxvirus variolae var. Alastrim
|1 ... 5%|
|East African Smallpox
In addition to smallpox in humans, there are also diseases caused by related viruses in a number of animals. Which also pass orthopox caused viruses animal pox - the so-called "mammal pox" as cowpox , monkeypox , cat , camel and mouse pox - are pathogenic, with the exception of the mice smallpox principle also for humans. So they are zoonoses and therefore notifiable animal diseases , but usually only cause mild diseases. The other caused by poxviruses animal diseases such as swine, sheep and goats , udder and avian pox , myxomatosis , Kaninchenfibromatose , stomatitis Papulosa of cattle, however, are strictly host-specific and not dangerous to humans.
Of particular importance is the cowpox pathogen, Orthopoxvirus vaccinia , which is closely related to the variola virus , but only causes a milder disease in humans. For this, the patient is immunized against real smallpox after being infected with cowpox. Therefore, variants of vaccinia were used for smallpox vaccination . The pathogen reservoir is probably rodents , and cats (→ catpox ) are an important vector for humans . In people with a weakened immune system (for example from AIDS or high-dose cortisone treatment ), cat-borne cowpox infections can also be fatal.
The vesicle disease in snakes is also incorrectly referred to as "smallpox" or "waterpox". However, it is not a viral disease, but a bacterial skin inflammation as a result of poor housing conditions.
Smallpox can be transmitted directly from person to person through droplet infection when coughing . In addition, the infection can also be a breath pass of dust, the z. B. when shaking out clothes or blankets of smallpox sufferers.
Course of disease
The incubation period is one to two and a half weeks, but mostly 12 to 14 days. At the onset of the disease there is a severe feeling of illness, headache and back pain with high fever (smallpox fever) and chills, and catarrh of the throat also occurs . At this point the patient is highly infectious. A biphasic fever is typical for smallpox: after 1–5 days the fever falls and rises again after a day. Now it comes to the typical skin symptoms.
The order in which the skin symptoms ( efflorescences ) occur is typical: macula (spot) → papule → vesicle (vesicles) → pustules ( pus vesicles ) → crust . In contrast to the efflorescences in chickenpox , the differently localized skin lesions are all at the same stage one after the other. They occur almost all over the body, with the head, hands and feet most severely affected, and the chest, abdomen and thighs only weakly affected. The armpits and hollows of the knees are excluded. The purulent fluid in the pustules gives off a very unpleasant odor. If the course of the disease is less severe, the pustules gradually dry up about two weeks after the onset of the disease and leave clearly visible scars. In more severe cases, blindness , deafness , paralysis , brain damage and pneumonia can occur. The disease is often fatal. The estimated lethality of untreated smallpox is around 30 percent.
There is no known cure for smallpox, only a preventive vaccination is possible; it can still develop its protective effect if it is carried out up to about five days after infection. The smallpox vaccination is a live vaccination and is burdened by a number of vaccination complications, so that vaccination should only be given in the case of clear outbreaks of smallpox. Mass vaccination is e.g. B. not provided in the USA - the emergency plans there only provide for a vaccination of the people at risk. In contrast, quarantine measures (isolation of sick and sick areas) have proven effective to contain the disease .
On April 18, 1801, Johann Friedrich Küttlinger had successfully carried out a smallpox vaccination for the son of the headmaster Degen in Neustadt an der Aisch in Middle Franconia . On August 26, 1807, Bavaria became the first country in the world to introduce compulsory vaccinations. Baden followed in 1809, Prussia in 1815, Württemberg in 1818, Sweden in 1816, England in 1867 and the German Empire in 1874. In Lutheran Sweden, the Protestant clergy played a pioneering role in voluntary smallpox vaccination as early as 1800. The first vaccination in Liechtenstein was carried out in 1801, and from 1812 it was mandatory to have vaccinations.
The compulsory vaccination against smallpox, prescribed worldwide by the World Health Organization from 1967 on, ended in West Germany in 1976. In Austria, the compulsory vaccination ended in 1981. The vaccination was typically carried out with a vaccination gun or lancet, mostly on the upper arm, where the resulting, intentional infection in the Usually a pustule and ultimately a rounded, deepened vaccination scar that can be seen in many vaccinated people to this day. In some countries it was necessary to show the vaccination scar when entering the country during periods of mandatory vaccination.
Vaccination by variola virus
Simple forms of vaccination have long been known. The preventive infection with small amounts of variola viruses, now known as variolation , has been known from China for at least 3000 years, where ground scabs of pustules were sniffed. In India, however, this material was scratched into the skin. In Europe, Lady Montagu (1689–1762), the wife of a British diplomat in Istanbul, introduced variolation by scratching some liquid from the smallpox vesicles into the skin. In 1767 the physician Franz Heinrich Meinolf Wilhelm (1725–1794) carried out a smallpox vaccination (probably a variolation) at the Würzburg Juliusspital .
Vaccination with vaccinia viruses
The second, safer vaccination method is based on the observation, which has been documented since 1765 at the latest, that people who have had a suspected cowpox infection are protected from infections with real smallpox.
Sutton smallpox inoculation
When Edward Jenner worked as an assistant to the country doctors Daniel and Edward Ludlow during his training in Thornbury in Gloucestershire in 1768 , he first heard of cowpox. Since 1766, fellow country doctors Hugh Grove and Daniel Sutton began a series of inoculations of smallpox, which triggered a weak smallpox infection, but then led to immunity. This was known as the "Sutton Method". Another country doctor colleague, John Fewster, made the discovery during these years that some patients did not even develop a mild smallpox infection if they had previously had cowpox. He reported this to the local medical association in 1765, and so Fewster was considered the discoverer of the benefits of cowpox. The Göttingen Jobst Böse also reported on the phenomenon in 1769. It was only the cowpox inoculation as a logical step that Jenner discovered. The infected cows were not infected with real cowpox, but with vaccinia viruses , the infections of which are much more harmless.
His biographer John Baron, 13 years after Jenner's death, circulated the myth that Jenner had heard of the benefits of a previous cowpox infection via "rumors in the cow stalls" and withheld Fewster's finding. This was known as the “milkmaid myth”. Jenner himself had never claimed to have been the discoverer or first person to describe the benefits of cowpox infection.
Jenner's cowpox inoculation
It was not until 1796 that “cowpox” inoculation was introduced with a certain broad impact in England. To test his thesis of protection against smallpox through inoculation with cowpox, Jenner first infected eight-year-old James Phipps with material obtained from the smallpox of the infected cows and, after the disease had subsided, with real smallpox. The boy survived. When Jenner's article was rejected by the Royal Society , he made further attempts - including with his 11-month-old son Robert. In 1798 he published his results and had to experience that people tried to ridicule him. Nevertheless, the method he propagated prevailed. This procedure is called vaccination . Since the vaccine came from cows, Jenner called his vaccine Vaccine (from Latin vacca , dt. 'Cow') and the technique of artificial immunization 'Vaccination' (from Latin vaccinus , dt. 'From cows'). The word vaccination today means in English vaccination in general, also in German a vaccine is called vaccine , in the plural vaccines.
Further researchers and first descriptors
After the Englishman Edward Jenner, Wilhelm Bernhard Nebel from the University of Heidelberg was one of the first doctors in Germany who had dealt with the inoculation of smallpox from 1729 and published about it. The artificial smallpox infection with less pathogenic types of smallpox to protect against “real smallpox” was also described and tested elsewhere in individual cases from around 1771 onwards. a. by Sevel, Jensen, Benjamin Jesty (1774), Rendall and Peter Plett (1791). It was even tried out in the country in 1787. The doctor Calmeyer vaccinated 57 children in Gehrde (Lower Saxony) so successfully that none of them died.
In 1799, the doctor Jean de Carro , who worked at the University of Vienna , was the first on the European continent to introduce the smallpox vaccination in Vienna as a result of the preparatory work by Jenner . Just a decade later, compulsory vaccinations were made in many countries.
The modified vaccinia Ankara virus used for the smallpox vaccination was developed by Anton Mayr in the 1970s . In many countries, vaccination of young children and re-vaccination after about 12 years have become a legal requirement.
In July 2018, the American Food and Drug Administration (FDA) approved Tecovirimate (trade name: TPOXX, manufacturer: Siga Technologies ). The antiviral agent was approved for the treatment of smallpox, although according to the World Health Organization, smallpox has been eradicated since 1980. The background is the fear that the highly contagious and dangerous pathogen could occur as a bio-warfare agent.
Similar to coronaviruses , the smallpox virus Variola vera was probably transmitted from animals to humans, probably from rodents. When this change took place is being investigated.
Antiquity and the Middle Ages
Smallpox has probably been known for thousands of years, and it is believed that it occurred 12,000 years ago in the first settlements in northeastern Africa. From there they may have been brought to India by Egyptian traders. In several places in the Old Testament (including 2 Kings 20.7 EU ; Lev 13.18 EU and the suffering of Job ) in Hebrew as shekhin (pustule, ulcer), medical historians associated the disease with smallpox. In particular, the sixth Egyptian plague ( Ex 9.2–11 EU ) is considered by many experts to describe a smallpox epidemic. In the Vita Mosis , Philo of Alexandria describes this plague with all the symptoms of smallpox. This epidemic, also known as the “Egyptian ulcer” ( schechin mizraim. Dtn 28.27 EU ), was also identified with Uhedu disease, which is mentioned several times in the Ebers papyrus . The ancient Egyptian word uhedu or uhet stands for a peculiar, deadly skin rash that is accompanied by ulcers. The mummy of Pharaoh Ramses V of Egypt shows lesions that could histologically correspond to pockmarks. The faces of older mummies from the 18th to 20th dynasties also show traces of smallpox.
At the time of Hippocrates (4th century BC) smallpox probably also appeared in Greece.
In China, the smallpox described by the alchemist Ge Hong was believed to have been around 250 BC. Brought in by the Huns over the still unfinished Great Wall of China . Hence the name hunnenpox used there .
Smallpox came to Europe probably in AD 165 with the entry of the victorious Roman legions after the capture of the Parthian city of Seleukia-Ctesiphon in what is now Iraq . The smallpox spread rapidly to the Danube and the Rhine . The result was a mass extinction over 24 years that went down in history as the Antonine Plague . The Baghdad doctor Muhammad ibn Zakarīyā ar-Rāzī described the difference between smallpox and measles around 910 and knew that no second smallpox infestation can occur in a person. The crusaders of the 11th – 13th centuries Century contributed significantly to the spread of smallpox.
Investigations of the bones and teeth of buried skeletons in Scandinavia, England and Russia from the period 600 to 1050 AD (area of the Vikings ) have shown that the genome of the smallpox virus that occurred at that time is clearly different from the recent smallpox virus that appeared in the 20th century differs. It has been shown that the virus from the Viking Age has greater genetic similarities to the camelpox virus and the taterapox virus. This supports the assumption that the smallpox virus originally came from animals ( zoonotic pathogen). Because of the differences, it is believed that the Vikings were infected with a sideline of Variola vera , which later became extinct. In addition, the genetic studies suggest that the smallpox virus has lost some of its genes over time, on the one hand genes that were necessary for transmission to other species. After specializing in humans, these had become obsolete. On the other hand, it concerned genes with which the virus evaded the attack of the immune system. This caused a stronger immune reaction and was associated with a higher mortality (pathogenicity).
16th to 19th century
The European conquerors brought smallpox with them to America, where from 1518 it triggered devastating epidemics among the Indians that killed millions. It is assumed that a quarter to half, according to Guenter Lewy even up to 90% of the indigenous population of America fell victim to smallpox after the arrival of the Europeans. The smallpox epidemic on the Pacific coast of North America from 1775 onwards has been well studied . The Europeans, on the other hand, were heavily contaminated by numerous previous smallpox epidemics and therefore relatively little endangered. Whether the smallpox was used as a biological weapon against the Indians is controversial despite all research. There is an exchange of letters and a receipt from June 1763, according to which two blankets and a handkerchief from the hospital of the besieged Fort Pitt - where the smallpox broke out - were presented to a delegation of the Lenni Lenape Indians. But the attempt was unsuccessful; the epidemic that broke out later is attributed to other causes. The various allegations made regarding a smallpox outbreak in 1837 among the Mandan on the Missouri River were exposed as scientific falsifications . The person in charge, Ward Churchill , lost his chair as a result of the academic scandal. In the case of the smallpox epidemic on the Pacific coast of North America in 1862, it can be shown that decision-makers with very different motives promoted the spread as a result of their actions and that there were happy reactions from the population about the subsequent mass death. After vaccination of most whites and many Indians in Victoria , an undesirable spread of smallpox among the white settlers could almost be ruled out in this case.
The smallpox probably came to Australia with seafarers from Makassar in Indonesia, who began collecting sea cucumbers in Arnhem Land every year from around 1700 onwards . The first smallpox epidemic to be documented was that of 1789 by members of the First Fleet in what is now the Sydney area .
In Europe, smallpox was sometimes seen as a childhood disease, and the disease, from which up to 10% of all small children died by the end of the 18th century, was also known as “child blatation”. From the 18th century onwards, cases of smallpox increased and replaced the plague as the worst disease. It is estimated that 400,000 people died of smallpox each year, and a third of those who survived went blind. Often children did not become part of the family until they had overcome smallpox. Famous personalities like Mozart , Haydn , Beethoven and the young Goethe were not spared from the disease, Ludwig XV. of France and Tsar Peter II died from it. The Habsburgs' marriage policy was also repeatedly confused by smallpox. The Empress Maria Theresa , who was pursuing an alliance policy by marrying her daughters to other mansions, had to change her plans several times because two of her daughters died of smallpox and a third ( Marie Elisabeth ) was completely disfigured by them.
The last major smallpox epidemics occurred in Germany in 1870 (as a war epidemic in the Franco-German War 1870/71 ) and in 1873 before the introduction of the Reich Vaccination Act in 1874, during which around 181,000 people died.
The first, still vague, morphological evidence of the smallpox virus is attributed to the Mexican-born Hamburg vaccination doctor Enrique Paschen (1860–1936), who already in 1906 used a light microscope to find the particles in the lymph, which he named "elementary bodies" and "Paschen's bodies" after him Variola major saw children with disease.
Smallpox epidemics still existed in Europe in the 1950s and 1960s. B. 1950 in Glasgow , 1958 in Heidelberg (18 cases of illness, two of them fatal), 1963 in Breslau (99 cases of illness, seven of them fatal) and 1967 in Czechoslovakia . In contrast, a single case in Hamburg in early summer 1957 was isolated. From 1967 onwards, the World Health Organization (WHO) decided that vaccination against smallpox became mandatory worldwide. A worldwide campaign to eradicate smallpox was started with large-scale vaccination campaigns. Under the leadership of Donald Henderson , “ring vaccination” was successfully used as a suitable strategy: important checkpoints where people come together, such as markets or rest areas, were closely monitored. In the event of an outbreak, the first carrier was then isolated and all contact persons vaccinated.
In 1962 there was a smallpox epidemic in the Eifel .
The last smallpox epidemic in Germany took place in early 1970 when a 20-year-old brought smallpox to the northern Sauerland and infected a total of 20 people. The sick were isolated in the Marienhospital in Wimbern . The last case of smallpox in the Federal Republic of Germany was found in Hanover in 1972 in a Yugoslav guest worker who was returning from Kosovo , where a smallpox epidemic had broken out. The last case of real smallpox was documented in Bangladesh in 1975, the last case of white smallpox in 1977 in Merka , Somalia , the last person to fall ill was Ali Maow Maalin, then 23. The last death worldwide from smallpox occurred in 1978 in Birmingham , England, from a laboratory infection. On May 8, 1980, the WHO determined that smallpox had been eradicated. The global elimination program gave 2.4 billion doses of vaccine and spent $ 300 million, and required more than 200,000 volunteers.
However, other smallpox infections cannot be completely ruled out. Officially, the virus still exists in two laboratories around the world; however, it is unclear whether some states hold unpublished virus stocks.
Most states lifted the compulsory smallpox vaccination again from the 1970s (in parts of Germany the first vaccination was suspended in 1975, later the re-vaccination). Based on experience from the 1950s and 1960s, the CDC reckons with 15 life-threatening complications and two deaths per million people vaccinated.
Risk of smallpox after eradication
Since 1980 there have been officially only two places where smallpox viruses are stored, namely the research center of the US disease control agency CDC ( Centers for Disease Control and Prevention ) in Atlanta and its Russian counterpart VECTOR in Kolzowo, southeast of Novosibirsk . Some thought was given to destroying the last holdings, but these ideas were discarded. The stocks would be the last chance to test smallpox vaccines for effectiveness.
After the “natural” spread of smallpox was eliminated with vaccination campaigns, the virus returned to public attention as a possible method of a bio-weapons attack . Iris Hunger, the head of the Bioweapons Control Research Center at the Carl Friedrich von Weizsäcker Center for Science and Peace Research, criticized as early as 2003 that an accident or terrorist attack could release the frozen pathogens.
After the terrorist attacks on September 11, 2001 , the industrialized countries stocked up extensively with smallpox vaccine for their populations (including the USA with 100 million vaccine doses) so that they could react immediately. In the wake of the impending war in Iraq , the Federal Republic of Germany commissioned Bavarian Nordic around the turn of the year 2002/2003 to produce a little more than one dose of vaccine for every German resident. In addition to the USA and Germany, South Africa , the UK and Israel also had large stocks of vaccines in 2003 . The developing countries, on the other hand, were unable to afford the expensive doses of vaccines for their entire population. The WHO also has 64 million vaccine doses in stock, but this number of vaccine doses will not be sufficient for the population in developing countries and smallpox could spread again with catastrophic consequences.
In order to eliminate the residual risk from the stored smallpox viruses, the representatives of the member states of the World Health Organization (WHO) wanted to reach an agreement by 2014 on when the two remaining collections of the deadly pathogen would be rendered harmless. At the meeting in May 2014, the majority voted in favor of annihilation, but did not reach the necessary consensus. In particular, "Russian research institutions" and the US Department of Defense wanted to receive the virus. This was justified by the fact that it was needed for further research and development. However, the virus itself is no longer needed to manufacture a vaccine and a cure. A new date for the discussion has not been decided, so the viruses will remain in the two laboratories indefinitely.
In 2014, sealed ampoules containing freeze-dried smallpox virus were discovered in a storeroom at the National Institutes of Health , which has been part of the Food and Drug Administration since 1972 . According to initial investigations, the samples date from the 1950s.
The Canadian microbiologist David Evans from Edmonton was able to show in 2016 that it only takes a small team, around six months of work and less than 100,000 euros to recreate smallpox viruses in the laboratory, which he succeeded in doing with the horse pox viruses, which are very similar to human smallpox viruses and are the same in the reconstruction process.
In Austria, cases of suspected disease and death from smallpox are still notifiable in accordance with (1) number 1 of the 1950 Epidemic Act . Doctors and laboratories, among others, would be obliged to report ( Epidemic Act).
In Switzerland, smallpox also a notifiable disease and that after the Epidemics Act (EpG) in connection with the epidemic Regulation and of the Regulation of EDI on the reporting of observations of communicable diseases of man . In addition, positive and negative laboratory results for smallpox viruses (variola virus / vaccinia virus) must be reported in accordance with the standards mentioned and of the EDI ordinance mentioned.
- Janet Parker , the last known smallpox death
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