114-772: COVID-19 Solidarity Response Fund was a global fund for supporting the work of the World Health Organization (WHO) in containing the COVID-19 pandemic . It was launched on 13 March 2020 by the United Nations Foundation and the Swiss Philanthropy Foundation in support of WHO, and was announced by the Director-General of WHO in Geneva, Switzerland. The fund ceased its active fundraising activities at
228-410: A marker gene . This gene, called GFP , or green fluorescent protein, would cause live samples of the virus to glow green under fluorescent light. The insertion of this gene, which would not influence the virulence of the virus, would be the only allowed modification of the genome. The committee stated the proposed modification would aid in research of treatments by making it easier to assess whether
342-491: A public health emergency of international concern, marking the second such declaration in the last two years due to the virus's transmission. The WHO's Constitution states that its objective "is the attainment by all people of the highest possible level of health". The WHO fulfils this objective through its functions as defined in its Constitution: As of 2012 , the WHO has defined its role in public health as follows: Since
456-443: A clinical case was observed, smallpox was confirmed using laboratory tests. Microscopically , poxviruses produce characteristic cytoplasmic inclusion bodies , the most important of which are known as Guarnieri bodies , and are the sites of viral replication . Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. They are found in virtually all poxvirus infections but
570-495: A convention concerning the bubonic plague was signed by sixteen of the nineteen states attending the Venice conference. While Denmark , Sweden-Norway , and the US did not sign this convention, it was unanimously agreed that the work of the prior conferences should be codified for implementation. Subsequent conferences, from 1902 until the final one in 1938, widened the diseases of concern for
684-415: A discrete rash, in which the pustules stood out on the skin separately. The distribution of the rash was most dense on the face, denser on the extremities than on the trunk, and denser on the distal parts of the extremities than on the proximal. The palms of the hands and soles of the feet were involved in most cases. Sometimes, the blisters merged into sheets, forming a confluent rash, which began to detach
798-513: A doctor in Berkeley, Gloucestershire , rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine from the root word vacca , which is Latin for cow. The procedure was much safer than variolation and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox
912-451: A fatality rate of around 30%, while variola minor’s mortality rate was about 1%. Throughout the 18th century, variola major was responsible for around 400,000 deaths annually in Europe alone. Survivors of the disease often faced lifelong consequences, such as blindness and severe scarring, which were nearly universal among those who recovered. In the first half of the 20th century, variola major
1026-614: A host cell varies across the poxviridae . Recombination of the genome occurs within actively infected cells. Following the onset of viral DNA replication, an intermediate set of genes codes for transcription factors of late gene expression. The products of the later genes include transcription factors necessary for transcribing the early genes for new virions, as well as viral RNA polymerase and other essential enzymes for new viral particles. These proteins are then packaged into new infectious virions capable of infecting other cells. Two live samples of variola major virus remain, one in
1140-523: A leading role in several public health achievements, most notably the eradication of smallpox , the near- eradication of polio , and the development of an Ebola vaccine . Its current priorities include communicable diseases , such as HIV/AIDS , Ebola , malaria and tuberculosis ; non-communicable diseases such as heart disease and cancer ; healthy diet , nutrition, and food security ; occupational health ; and substance abuse . The agency advocates for universal health care coverage, engagement with
1254-587: A potential treatment was effective in killing viral samples. The recommendation could only take effect if approved by the WHA . When the WHA discussed the proposal in 2005, it refrained from taking a formal vote on the proposal, stating that it would review individual research proposals one at a time. Addition of the GFP gene to the Vaccinia genome is routinely performed during research on
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#17328585326331368-423: A region of roughly 100 base pairs necessary for resolving concatomeric DNA (a stretch of DNA containing multiple copies of the same sequence), a few open reading frames , and short tandemly repeating sequences of varying number and length. The ITRs of poxviridae vary in length across strains and species. The coding sequence for most of the viral proteins in variola major virus have at least 90% similarity with
1482-528: A resolution on disability prevention and rehabilitation , with a focus on community-driven care. 1977 and 1978: The first list of essential medicines was drawn up, and a year later the ambitious goal of " Health For All " was declared. 1986: The WHO began its global programme on HIV/AIDS . Two years later preventing discrimination against patients was attended to and in 1996 the Joint United Nations Programme on HIV/AIDS (UNAIDS)
1596-429: A resolution passed on the subject, Alger Hiss , the secretary general of the conference, recommended using a declaration to establish such an organization. Sze and other delegates lobbied and a declaration passed calling for an international conference on health. The use of the word "world", rather than "international", emphasized the truly global nature of what the organization was seeking to achieve. The constitution of
1710-501: A series of conferences that took place until 1938, about 87 years. The first conference, in Paris, was almost solely concerned with cholera , which would remain the disease of major concern for the ISC for most of the 19th century. With the cause , origin, and communicability of many epidemic diseases still uncertain and a matter of scientific argument, international agreement on appropriate measures
1824-550: A significant infusion of financial and technical resources. The WHO's official mandate is to promote health and safety while helping the vulnerable worldwide. It provides technical assistance to countries, sets international health standards, collects data on global health issues, and serves as a forum for scientific or policy discussions related to health. Its official publication, the World Health Report , provides assessments of worldwide health topics. The WHO has played
1938-421: A source of infection”; noted that “Current recommendations for control of secondary smallpox infections emphasize transmission ‘by expelled droplets to close contacts (those within 6–7 feet)’”; but warned that the “emphasis on spread via large droplets may reduce the vigilance with which more difficult airborne precautions [i.e. against finer droplets capable of traveling longer distances and penetrating deeply into
2052-542: A year. The final known fatal case occurred in the United Kingdom in 1978 . Inoculation for smallpox appears to have started in China around the 1500s. Europe adopted this practice from Asia in the first half of the 18th century. In 1796, Edward Jenner introduced the modern smallpox vaccine. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated,
2166-510: Is a specialized agency of the United Nations responsible for global public health . It is headquartered in Geneva , Switzerland, and has six regional offices and 150 field offices worldwide. Only sovereign States can participate, and it is the largest intergovernmental health organization at the international level. The WHO's purpose is to achieve the highest possible level of health for all
2280-582: Is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and viscera . This form develops in approximately 2% of infections and occurs mostly in adults. Pustules do not typically form in hemorrhagic smallpox. Instead, bleeding occurs under the skin, making it look charred and black, hence this form of the disease is also referred to as variola nigra or "black pox". Hemorrhagic smallpox has very rarely been caused by variola minor virus. While bleeding may occur in mild cases and not affect outcomes, hemorrhagic smallpox
2394-420: Is also a later form of hemorrhagic smallpox (referred to late hemorrhagic smallpox, or variolosa pustula hemorrhagica ). The prodrome is severe and similar to that observed in early hemorrhagic smallpox, and the fever persists throughout the course of the disease. Bleeding appears in the early eruptive period (but later than that seen in purpura variolosa ), and the rash is often flat and does not progress beyond
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#17328585326332508-486: Is also under research as a viral vector for vaccines for unrelated diseases. The genome of variola major virus was first sequenced in its entirety in the 1990s. The complete coding sequence is publicly available online. The current reference sequence for variola major virus was sequenced from a strain that circulated in India in 1967. In addition, there are sequences for samples of other strains that were collected during
2622-541: Is believed to have had a mortality rate of less than 1%, as compared to variola major's 30%. Like variola major, variola minor was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with variola minor virus conferred immunity against the more dangerous variola major virus. Because variola minor was a less debilitating disease than smallpox, people were more frequently ambulant and thus able to infect others more rapidly. As such, variola minor swept through
2736-411: Is caused by infection with variola virus, which belongs to the family Poxviridae , subfamily Chordopoxvirinae , genus Orthopoxvirus . The date of the appearance of smallpox is not settled. It most probably evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago. The wide range of dates is due to the different records used to calibrate the molecular clock . One clade
2850-488: Is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among human DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus . To replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses , the most important of which is a viral-associated DNA-dependent RNA polymerase . Both enveloped and unenveloped virions are infectious. The viral envelope
2964-447: Is consistent with the other published estimates, it suggests that the archaeological and historical evidence is very incomplete. Better estimates of mutation rates in these viruses are needed. Examination of a strain that dates from c. 1650 found that this strain was basal to the other presently sequenced strains. The mutation rate of this virus is well modeled by a molecular clock. Diversification of strains only occurred in
3078-441: Is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox. Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. Earlier deaths included six European monarchs , including Louis XV of France in 1774. As recently as 1967, 15 million cases occurred
3192-415: Is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin . Infection with either variola major virus or variola minor virus confers immunity against the other. The more common, infectious form of the disease was caused by the variola major virus strain, known for its significantly higher mortality rate compared to its counterpart, variola minor. Variola major had
3306-557: Is now on the verge of extinction, thanks to a Global Vaccination Drive. The World Health Organization (WHO) stated the eradication programme has saved millions from deadly disease. Between 1990 and 2010, WHO's help has contributed to a 40% decline in the number of deaths from tuberculosis, and since 2005, over 46 million people have been treated and an estimated 7 million lives saved through practices advocated by WHO. These include engaging national governments and their financing, early diagnosis, standardising treatment, monitoring of
3420-493: Is rapidly followed by the development of petechiae and bleeding in the skin, conjunctiva and mucous membranes. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. Some people survive a few days longer, during which time the skin detaches and fluid accumulates under it, rupturing at the slightest injury. People are usually conscious until death or shortly before. Autopsy reveals petechiae and bleeding in
3534-453: Is typically fatal. Vaccination does not appear to provide any immunity to either form of hemorrhagic smallpox and some cases even occurred among people that were revaccinated shortly before. It has two forms. The early or fulminant form of hemorrhagic smallpox (referred to as purpura variolosa ) begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. The skin becomes dusky and erythematous, and this
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3648-674: The East India Company stationed in China and another by Clopton Havers . Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire , writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. According to Voltaire (1742), the Turks derived their use of inoculation from neighbouring Circassia . Voltaire does not speculate on where
3762-565: The US Centers for Disease Control and Prevention (CDC), the United Nations Children's Fund (UNICEF), and smaller organizations. As of 2011 , it has been working to immunize young children and prevent the re-emergence of cases in countries declared "polio-free". In 2017, a study was conducted as to why Polio Vaccines may not be enough to eradicate the Virus & conduct new technology. Polio
3876-766: The USSR , called on the World Health Assembly to undertake a global initiative to eradicate smallpox, resulting in Resolution WHA11.54. 1965: The first report on diabetes mellitus and the creation of the International Agency for Research on Cancer . 1966: The WHO moved its headquarters from the Ariana wing at the Palace of Nations to a newly constructed headquarters elsewhere in Geneva. 1967: The WHO intensified
3990-952: The United Nations Development Programme (UNDP), and the World Bank . 1975: The WHO launched the Special Programme for Research and Training in Tropical diseases (the TDR). Co-sponsored by UNICEF , UNDP, and the World Bank, it was established in response to a 1974 request from the WHA for an intensive effort to develop improved control of tropical diseases. The TDR's goals are, firstly, to support and coordinate international research into diagnosis, treatment and control of tropical diseases; and, secondly, to strengthen research capabilities within endemic countries. 1976: The WHA enacted
4104-572: The World Health Assembly finished on 24 July 1948, having secured a budget of US$ 5 million (then £1,250,000 ) for the 1949 year. G. Brock Chisholm was appointed director-general of the WHO, having served as executive secretary and a founding member during the planning stages, while Andrija Štampar was the assembly's first president. Its first priorities were to control the spread of malaria , tuberculosis and sexually transmitted infections , and to improve maternal and child health , nutrition and environmental hygiene. Its first legislative act
4218-422: The common cold : fever of at least 38.3 °C (101 °F), muscle pain , malaise , headache and fatigue. As the digestive tract was commonly involved, nausea, vomiting, and backache often occurred. The early prodromal stage usually lasted 2–4 days. By days 12–15, the first visible lesions – small reddish spots called enanthem – appeared on mucous membranes of the mouth, tongue, palate , and throat, and
4332-460: The global eradication of the disease in 1980, making smallpox the only human disease to have been eradicated to date. The initial symptoms of the disease included fever and vomiting. This was followed by formation of ulcers in the mouth and a skin rash . Over a number of days, the skin rash turned into the characteristic fluid-filled blisters with a dent in the center. The bumps then scabbed over and fell off, leaving scars. The disease
4446-470: The horsepox virus using publicly available sequence data for horsepox. The researchers argued that their work would be beneficial to creating a safer and more effective vaccine for smallpox, although an effective vaccine is already available. The horsepox virus had previously seemed to have gone extinct, raising concern about potential revival of variola major and causing other scientists to question their motives. Critics found it especially concerning that
4560-468: The replication of viral DNA. The first set of expressed genes are transcribed by pre-existing viral machinery packaged within the infecting virion. These genes encode the factors necessary for viral DNA synthesis and for transcription of the next set of expressed genes. Unlike most DNA viruses, DNA replication in variola virus and other poxviruses takes place within the cytoplasm of the infected cell. The exact timing of DNA replication after infection of
4674-624: The 18th and 19th centuries. Variola virus is large and brick-shaped and is approximately 302 to 350 nanometers by 244 to 270 nm, with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end. Four orthopoxviruses cause infection in humans: variola, vaccinia , cowpox , and monkeypox . Variola virus infects only humans in nature, although primates and other animals have been infected in an experimental setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. The life cycle of poxviruses
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4788-752: The Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. After publishing The present method of inoculating for the small-pox in 1767, Dr Thomas Dimsdale was invited to Russia to variolate the Empress Catherine the Great of Russia and her son, Grand Duke Paul , which he successfully did in 1768. In 1796, Edward Jenner ,
4902-544: The Health Organization of the League of Nations. After World War II , the United Nations absorbed all the other health organizations, to form the WHO. During the 1945 United Nations Conference on International Organization, Szeming Sze , a delegate from China, conferred with Norwegian and Brazilian delegates on creating an international health organization under the auspices of the new United Nations. After failing to get
5016-655: The ISC, and included discussions of responses to yellow fever , brucellosis , leprosy , tuberculosis , and typhoid . In part as a result of the successes of the Conferences, the Pan-American Sanitary Bureau (1902), and the Office International d'Hygiène Publique or " International office of Public Hygiene " in english(1907) were soon founded. When the League of Nations was formed in 1920, it established
5130-555: The Near East). According to WHO's estimations, 78.3% of people think this figure is too high, and the requirement to respond to the COVID-19 pandemic until the end of 2020 was US$ 1.7 billion. As of 7 December 2020, 87.6% (US$ 1.52 b) of required amount had been collected. The fund received donations from a variety of notable corporations, non-profit organizations and individuals between March 2020 and December 2021. World Health Organization The World Health Organization ( WHO )
5244-788: The Solidarity Response Fund, in addition to several hundred thousand private individuals. In the following months, several additional beneficiaries of the fund were added in order to work together with WHO on the COVID-19 pandemic response. This includes UNICEF , CEPI (the Coalition for Epidemic Preparedness Innovations), WFP (the World Food Programme), UNHCR (the UN Refugee Agency), and UNRWA (the United Nations Relief and Works Agency for Palestine Refugees in
5358-635: The United Nations together with the exchange of letters related thereto, and taking into account the respective co-ordinating responsibilities of both organizations, it is recognized by the World Health Organization that the International Atomic Energy Agency has the primary responsibility for encouraging, assisting and co-ordinating research and development and practical application of atomic energy for peaceful uses throughout
5472-730: The United States at the CDC in Atlanta, and one at the Vector Institute in Koltsovo, Russia. Research with the remaining virus samples is tightly controlled, and each research proposal must be approved by the WHO and the World Health Assembly (WHA). Most research on poxviruses is performed using the closely related Vaccinia virus as a model organism. Vaccinia virus, which is used to vaccinate for smallpox,
5586-557: The United States, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates. Along with variola major, the minor form has now been totally eradicated from the globe. The last case of indigenous variola minor was reported in a Somali cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980. Variola minor
5700-517: The WHO eradication campaign. A genome browser for a complete database of annotated sequences of variola virus and other poxviruses is publicly available through the Viral Bioinformatics Resource Center . The WHO currently bans genetic engineering of the variola virus. However, in 2004, a committee advisory to the WHO voted in favor of allowing editing of the genome of the two remaining samples of variola major virus to add
5814-480: The WHO over the organization's unwillingness to share the penicillin recipe. They would not return until 1956. 1950: A mass tuberculosis inoculation drive using the BCG vaccine gets under way. 1955: The malaria eradication programme was launched, although objectives were later modified. (In most areas, the programme goals became control instead of eradication.) 1958: Viktor Zhdanov , Deputy Minister of Health for
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#17328585326335928-590: The WHO was to report as to whether RTS,S /AS01, were a viable malaria vaccine . For the time being, insecticide -treated mosquito nets and insecticide sprays are used to prevent the spread of malaria, as are antimalarial drugs – particularly to vulnerable people such as pregnant women and young children. In 1988, WHO launched the Global Polio Eradication Initiative to eradicate polio . It has also been successful in helping to reduce cases by 99% since WHO partnered with Rotary International ,
6042-425: The WHO's role and priorities in public health, ranging from narrowing its mandate to strengthening its independence and authority. During the 1970s, WHO had dropped its commitment to a global malaria eradication campaign as too ambitious, it retained a strong commitment to malaria control. WHO's Global Malaria Programme works to keep track of malaria cases, and future problems in malaria control schemes. As of 2012,
6156-498: The World Health Organization was signed by all 51 countries of the United Nations, and by 10 other countries, on 22 July 1946. It thus became the first specialized agency of the United Nations to which every member subscribed. Its constitution formally came into force on the first World Health Day on 7 April 1948, when it was ratified by the 26th member state. The WHO formally began its work in September 1, 1948. The first meeting of
6270-507: The absence of Guarnieri bodies could not be used to rule out smallpox. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. If particles with the characteristic morphology of herpesviruses are seen this will eliminate smallpox and other orthopoxvirus infections. Definitive laboratory identification of variola virus involved growing
6384-565: The basis for global prevention, treatment, and support the plan to fight the AIDS pandemic . 2006: The WHO launches the Global action plan for influenza vaccines 2016: The Global action plan for influenza vaccines ends with a report which concludes that while substantial progress has been made over the 10 years of the Plan, the world is still not ready to respond to an influenza pandemic. 2016: Following
6498-448: The bloodstream in large numbers, a condition known as viremia . This resulted in the second wave of multiplication in the spleen , bone marrow , and lymph nodes. The clinical definition of ordinary smallpox is an illness with acute onset of fever equal to or greater than 38.3 °C (101 °F) followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development without other apparent cause. When
6612-424: The budget and activities. The WHO is funded primarily by contributions from member states (both assessed and voluntary), followed by private donors. Its total approved budget for 2020–2021 is over $ 7.2 billion, while the approved budget for 2022–2023 is over $ 6.2 billion. The budget is $ 6.83 billion for 2024–2025. The International Sanitary Conferences (ISC), the first of which was held on 23 June 1851, were
6726-477: The central region of the genome is highly consistent across orthopoxviruses , and the arrangement of genes is consistent across chordopoxviruses. The center of the variola virus genome contains the majority of the essential viral genes, including the genes for structural proteins , DNA replication , transcription , and mRNA synthesis. The ends of the genome vary more across strains and species of orthopoxviruses . These regions contain proteins that modulate
6840-503: The closely related Vaccinia virus . The public availability of the variola virus complete sequence has raised concerns about the possibility of illicit synthesis of infectious virus. Vaccinia , a cousin of the variola virus, was artificially synthesized in 2002 by NIH scientists. They used a previously established method that involved using a recombinant viral genome to create a self-replicating bacterial plasmid that produced viral particles. In 2016, another group synthesized
6954-611: The continuing effects of nuclear disasters in Chernobyl and Fukushima . They believe WHO must regain what they see as independence. Independent WHO held a weekly vigil from 2007 to 2017 in front of WHO headquarters. However, as pointed out by Foreman in clause 2 it states: In particular, and in accordance with the Constitution of the World Health Organization and the Statute of the International Atomic Energy Agency and its agreement with
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#17328585326337068-621: The course of the illness, but this happened most frequently during the first week of the rash when most of the skin lesions were intact. Infectivity waned in 7 to 10 days when scabs formed over the lesions, but the infected person was contagious until the last smallpox scab fell off. Concern about possible use of smallpox for biological warfare led in 2002 to Donald K. Milton's detailed review of existing research on its transmission and of then-current recommendations for controlling its spread. He agreed, citing Rao, Fenner and others, that “careful epidemiologic investigation rarely implicated fomites as
7182-403: The diagnosis of infection. Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox could be distinguished by several methods. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly
7296-545: The end of 2021, with further donations to be directed to the WHO Foundation . The purpose of the response fund was to "support WHO's work, including with partners, to track and understand the spread of the virus; to ensure patients get the care they need and frontline workers get essential supplies and information; and to accelerate research and development of a vaccine and treatments for all who need them." Major companies, including Facebook , H&M , and Google donated to
7410-589: The establishment of international standards for biological products. The WHO was established on April 7, 1948, and formally began its work on September 1, 1948. It incorporated the assets, personnel, and duties of the League of Nations ' Health Organization and the Paris-based Office International d'Hygiène Publique , including the International Classification of Diseases (ICD). The agency's work began in earnest in 1951 after
7524-586: The fiftieth anniversary of WHO's founding. He, did, however, accept that more had to be done to assist maternal health and that progress in this area had been slow. 2000: The Stop TB Partnership was created along with the UN's formulation of the Millennium Development Goals . 2001: The measles initiative was formed, and credited with reducing global deaths from the disease by 68% by 2007. 2002: The Global Fund to Fight AIDS, Tuberculosis and Malaria
7638-408: The genome of vaccinia , a related virus used for vaccination against smallpox. Gene expression of variola virus occurs entirely within the cytoplasm of the host cell , and follows a distinct progression during infection. After entry of an infectious virion into a host cell, synthesis of viral mRNA can be detected within 20 minutes. About half of the viral genome is transcribed prior to
7752-449: The global smallpox eradication campaign by contributing $ 2.4 million annually to the effort and adopted a new disease surveillance method, at a time when 2 million people were dying from smallpox per year. The initial problem the WHO team faced was inadequate reporting of smallpox cases. WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. The WHO also helped contain
7866-429: The group was able to recreate viable virus in a short time frame with relatively little cost or effort. Although the WHO bans individual laboratories from synthesizing more than 20% of the genome at a time, and purchases of smallpox genome fragments are monitored and regulated, a group with malicious intentions could compile, from multiple sources, the full synthetic genome necessary to produce viable virus. Smallpox
7980-495: The hosts' immune systems, and are primarily responsible for the variability in virulence across the orthopoxvirus family. These terminal regions in poxviruses are inverted terminal repetitions (ITR) sequences. These sequences are identical but oppositely oriented on either end of the genome, leading to the genome being a continuous loop of DNA. Components of the ITR sequences include an incompletely base paired A/T rich hairpin loop ,
8094-526: The last European outbreak in Yugoslavia in 1972 . After over two decades of fighting smallpox, a Global Commission declared in 1979 that the disease had been eradicated – the first disease in history to be eliminated by human effort. 1974: The Expanded Programme on Immunization and the control programme of onchocerciasis was started, an important partnership between the Food and Agriculture Organization (FAO),
8208-449: The late 20th century, the rise of new actors engaged in global health—such as the World Bank , the Bill & Melinda Gates Foundation, the U.S. President's Emergency Plan for AIDS Relief ( PEPFAR ) and dozens of public-private partnerships for global health—have weakened the WHO's role as a coordinator and policy leader in the field; subsequently, there are various proposals to reform or reorient
8322-436: The lesions remained almost flush with the skin at the time when raised vesicles would have formed in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10% of cases, and most (72%) were children. Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of viremia . The prodromal symptoms continued even after
8436-406: The lower respiratory tract] are maintained”. Once inhaled, the variola virus invaded the mucous membranes of the mouth, throat, and respiratory tract. From there, it migrated to regional lymph nodes and began to multiply. In the initial growth phase, the virus seemed to move from cell to cell, but by around the 12th day, widespread lysis of infected cells occurred and the virus could be found in
8550-408: The malignant and hemorrhagic forms were usually fatal. The modified form was almost never fatal. In early hemorrhagic cases, hemorrhages occurred before any skin lesions developed. The incubation period between contraction and the first obvious symptoms of the disease was 7–14 days. At least 90% of smallpox cases among unvaccinated persons were of the ordinary type. In this form of the disease, by
8664-477: The monitoring of public health risks, coordinating responses to health emergencies, and promoting health and well-being generally. The WHO is governed by the World Health Assembly (WHA), which is composed of its 194 member states. The WHA elects and advises an executive board made up of 34 health specialists; selects the WHO's chief administrator, the director-general (currently Tedros Adhanom Ghebreyesus of Ethiopia ); sets goals and priorities; and approves
8778-404: The onset of the rash. The rash on the mucous membranes ( enanthem ) was extensive. Skin lesions matured slowly, were typically confluent or semi-confluent, and by the seventh or eighth day, they were flat and appeared to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant smallpox
8892-429: The oral, nasal, or pharyngeal mucosa of an infected person. It was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person. Some infections of laundry workers with smallpox after handling contaminated bedding suggested that smallpox could be spread through direct contact with contaminated objects ( fomites ), but this was found to be rare. Also rarely, smallpox
9006-464: The other being rinderpest (a disease of even-toed ungulates ) in 2011. The term "smallpox" was first used in England in the 16th century to distinguish the disease from syphilis , which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague. The United States and Russia retain samples of variola virus in laboratories, which has sparked debates over safety . There are two forms of
9120-421: The other organization has or may have a substantial interest, the first party shall consult the other with a view to adjusting the matter by mutual agreement. The nature of this statement has led some groups and activists including Women in Europe for a Common Future to claim that the WHO is restricted in its ability to investigate the effects on human health of radiation caused by the use of nuclear power and
9234-523: The outer layers of skin from the underlying flesh. Patients with confluent smallpox often remained ill even after scabs had formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62%. Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. It was rare in unvaccinated people, with one case study showing 1–2% of modified cases compared to around 25% in vaccinated people. In this form,
9348-546: The perceived failure of the response to the West Africa Ebola outbreak , the World Health Emergencies programme was formed, changing the WHO from just being a "normative" agency to one that responds operationally to health emergencies. 2020: the World Health Organization announced that it had classified the novel coronavirus outbreak as a public health emergency of international concern. The novel coronavirus
9462-573: The person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of smallpox. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of
9576-493: The practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming dynasty . If successful, inoculation produced lasting immunity to smallpox. Because
9690-491: The prodromal illness still occurred but may have been less severe than in the ordinary type. There was usually no fever during the evolution of the rash. The skin lesions tended to be fewer and evolved more quickly, were more superficial, and may not have shown the uniform characteristic of more typical smallpox. Modified smallpox was rarely, if ever, fatal. This form of variola major was more easily confused with chickenpox . In malignant-type smallpox (also called flat smallpox)
9804-454: The same size since the viral effect progresses more uniformly. A variety of laboratory methods were available for detecting chickenpox in the evaluation of suspected smallpox cases. The earliest procedure used to prevent smallpox was inoculation with variola minor virus (a method later known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before
9918-479: The second day of the rash the macules had become raised papules . By the third or fourth day, the papules had filled with an opalescent fluid to become vesicles . This fluid became opaque and turbid within 24–48 hours, resulting in pustules . By the sixth or seventh day, all the skin lesions had become pustules. Between seven and ten days the pustules had matured and reached their maximum size. The pustules were sharply raised, typically round, tense, and firm to
10032-491: The separation of variola virus from Taterapox (an Orthopoxvirus of some African rodents including gerbils ) at 3,000 to 4,000 years ago. This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. If the mutation rate is assumed to be similar to that of the herpesviruses , the divergence date of variola virus from Taterapox has been estimated to be 50,000 years ago. While this
10146-427: The smallpox. Variola major is the severe and most common form, with a more extensive rash and higher fever. Variola minor is a less common presentation, causing less severe disease, typically discrete smallpox, with historical death rates of 1% or less. Subclinical ( asymptomatic ) infections with variola virus were noted but were not common. In addition, a form called variola sine eruptione (smallpox without rash)
10260-520: The spleen, kidney, serous membranes , skeletal muscles, pericardium , liver, gonads and bladder. Historically, this condition was frequently misdiagnosed, with the correct diagnosis made only at autopsy. This form is more likely to occur in pregnant women than in the general population (approximately 16% of cases in unvaccinated pregnant women were early hemorrhagic smallpox, versus roughly 1% in nonpregnant women and adult males). The case fatality rate of early hemorrhagic smallpox approaches 100%. There
10374-438: The spread and effect of tuberculosis, and stabilising the drug supply. It has also recognized the vulnerability of victims of HIV/AIDS to tuberculosis. Smallpox Smallpox was an infectious disease caused by variola virus (often called smallpox virus), which belongs to the genus Orthopoxvirus . The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified
10488-425: The temperature fell to near-normal. These lesions rapidly enlarged and ruptured, releasing large amounts of virus into the saliva. Variola virus tended to attack skin cells, causing the characteristic pimples, or macules , associated with the disease. A rash developed on the skin 24 to 48 hours after lesions on the mucous membranes appeared. Typically the macules first appeared on the forehead, then rapidly spread to
10602-411: The touch. The pustules were deeply embedded in the dermis, giving them the feel of a small bead in the skin. Fluid slowly leaked from the pustules, and by the end of the second week, the pustules had deflated and began to dry up, forming crusts or scabs. By day 16–20 scabs had formed over all of the lesions, which had started to flake off, leaving depigmented scars. Ordinary smallpox generally produced
10716-475: The vesicular stage. Hemorrhages in the mucous membranes appear to occur less often than in the early hemorrhagic form. Sometimes the rash forms pustules which bleed at the base and then undergo the same process as in ordinary smallpox. This form of the disease is characterized by a decrease in all of the elements of the coagulation cascade and an increase in circulating antithrombin . This form of smallpox occurs anywhere from 3% to 25% of fatal cases, depending on
10830-439: The virulence of the smallpox strain. Most people with the late-stage form die within eight to 10 days of illness. Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. The case fatality rate for late hemorrhagic smallpox is around 90–95%. Pregnant women are slightly more likely to experience this form of the disease, though not as much as early hemorrhagic smallpox. Smallpox
10944-442: The virus on chorioallantoic membrane (part of a chicken embryo ) and examining the resulting pock lesions under defined temperature conditions. Strains were characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic tests and enzyme linked immunosorbent assays (ELISA), which measured variola virus-specific immunoglobulin and antigen were also developed to assist in
11058-551: The whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process took no more than 24 to 36 hours, after which no new lesions appeared. At this point, variola major disease could take several very different courses, which resulted in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic smallpox. Historically, ordinary smallpox had an overall fatality rate of about 30%, and
11172-488: The world without prejudice to the right of the World Health Organization to concern itself with promoting, developing, assisting and co-ordinating international health work, including research, in all its aspects. The key text is highlighted in bold, the agreement in clause 2 states that the WHO is free to perform any health-related work. 1947: The WHO established an epidemiological information service via telex . 1949: The Soviet Union and its constituent republics quit
11286-407: The world's people, defining health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." The main functions of the World Health Organization include: to promote the control of epidemic and endemic diseases; to provide and improve the teaching and training in public health, the medical treatment of disease and related matters; and to promote
11400-500: Was a new strain of coronavirus that had never been detected in humans before. The WHO named this new coronavirus " COVID-19 " or "2019-nCov". 2022: The WHO suggests formation of a Global Health Emergency Council, with a new global health emergency workforce, and recommends revision of the International Health Regulations. 2024: WHO has declared the spread of mpox (formerly monkeypox) in several African countries
11514-606: Was about 30%, with higher rates among babies. Often, those who survived had extensive scarring of their skin, and some were left blind. The earliest evidence of the disease dates to around 1500 BC in Egyptian mummies . The disease historically occurred in outbreaks . It was one of several diseases introduced by the Columbian exchange to the New World , resulting in large swathes of Native Americans dying . In 18th-century Europe, it
11628-431: Was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola. The genome of variola major virus is about 186,000 base pairs in length. It is made from linear double stranded DNA and contains the coding sequence for about 200 genes . The genes are usually not overlapping and typically occur in blocks that point towards the closer terminal region of the genome. The coding sequence of
11742-526: Was concerning the compilation of accurate statistics on the spread and morbidity of disease. The logo of the World Health Organization features the Rod of Asclepius as a symbol for healing. In 1959, the WHO signed Agreement WHA 12–40 with the International Atomic Energy Agency (IAEA), which says: whenever either organization proposes to initiate a programme or activity on a subject in which
11856-469: Was difficult to reach. Seven of these international conferences, spanning 41 years, were convened before any resulted in a multi-state international agreement. The seventh conference, in Venice in 1892, finally resulted in a convention. It was concerned only with the sanitary control of shipping traversing the Suez Canal , and was an effort to guard against importation of cholera. Five years later, in 1897,
11970-416: Was drawn up to improve the resources available. 2005: The WHO revises International Health Regulations (IHR) in light of emerging health threats and the experience of the 2002/3 SARS epidemic , authorizing WHO, among other things, to declare a health threat a Public Health Emergency of International Concern . 2006: The WHO endorsed the world's first official HIV/AIDS Toolkit for Zimbabwe, which formed
12084-698: Was formed. 1988: The Global Polio Eradication Initiative was established. 1995: The WHO established an independent International Commission for the Certification of Dracunculiasis Eradication (Guinea worm disease eradication; ICCDE). The ICCDE recommends to the WHO which countries fulfil requirements for certification. It also has role in advising on progress made towards elimination of transmission and processes for verification. 1998: The WHO's director-general highlighted gains in child survival, reduced infant mortality , increased life expectancy and reduced rates of "scourges" such as smallpox and polio on
12198-428: Was highly contagious, but generally spread more slowly and less widely than some other viral diseases, perhaps because transmission required close contact and occurred after the onset of the rash. The overall rate of infection was also affected by the short duration of the infectious stage. In temperate areas, the number of smallpox infections was highest during the winter and spring. In tropical areas, seasonal variation
12312-442: Was less evident and the disease was present throughout the year. Age distribution of smallpox infections depended on acquired immunity . Vaccination immunity declined over time and was probably lost within thirty years. Smallpox was not known to be transmitted by insects or animals and there was no asymptomatic carrier state. Transmission occurred through inhalation of airborne variola virus, usually droplets expressed from
12426-421: Was nearly always fatal and death usually occurred between the 8th and 12th day of illness. Often, a day or two before death, the lesions turned ashen gray, which, along with abdominal distension, was a bad prognostic sign. This form is thought to be caused by deficient cell-mediated immunity to smallpox. If the person recovered, the lesions gradually faded and did not form scars or scabs. Hemorrhagic smallpox
12540-456: Was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by viral culture . In addition, there were two very rare and fulminating types of smallpox, the malignant (flat) and hemorrhagic forms, which were usually fatal. The initial symptoms were similar to other viral diseases that are still extant, such as influenza and
12654-440: Was spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. The virus can cross the placenta , but the incidence of congenital smallpox was relatively low. Smallpox was not notably infectious in the prodromal period and viral shedding was usually delayed until the appearance of the rash, which was often accompanied by lesions in the mouth and pharynx. The virus can be transmitted throughout
12768-404: Was the primary cause of smallpox outbreaks across Asia and most of Africa. Meanwhile, variola minor was more commonly found in regions of Europe, North America, South America, and certain parts of Africa. Variola minor virus, also called alastrim, was a less common form of the virus, and much less deadly. Although variola minor had the same incubation period and pathogenetic stages as smallpox, it
12882-511: Was the variola major strains (the more clinically severe form of smallpox) which spread from Asia between 400 and 1,600 years ago. A second clade included both alastrim (a phenotypically mild smallpox) described from the American continents and isolates from West Africa which diverged from an ancestral strain between 1,400 and 6,300 years before present. This clade further diverged into two subclades at least 800 years ago. A second estimate has placed
12996-420: Was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person or rarely via contaminated objects . Prevention was achieved mainly through the smallpox vaccine . Once the disease had developed, certain antiviral medications could potentially have helped, but such medications did not become available until after the disease was eradicated. The risk of death
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