Pandemic

The World Health Organization previously applied a six-stage classification to describe the process by which a novel influenza virus moves from the first few infections in humans through to a pandemic. It starts when mostly animals are infected with a virus and a few cases where animals infect people, then moves to the stage where the virus begins to be transmitted directly between people and ends with the stage when infections in humans from the virus have spread worldwide. In February 2020, a WHO spokesperson clarified that "there is no official category [for a pandemic]".[lower-alpha 1][17]

In a virtual press conference in May 2009 on the influenza pandemic, Dr. Keiji Fukuda, Assistant Director-General ad interim for Health Security and Environment, WHO said "An easy way to think about pandemic ... is to say: a pandemic is a global outbreak. Then you might ask yourself: 'What is a global outbreak?' Global outbreak means that we see both the spread of the agent ... and then we see disease activities in addition to the spread of the virus."[19]

In planning for a possible influenza pandemic, the WHO published a document on pandemic preparedness guidance in 1999, which was revised in 2005 and 2009. It defined phases and appropriate actions for each phase in an aide-mémoire titled WHO pandemic phase descriptions and main actions by phase. The 2009 revision, including descriptions of a pandemic and the phases leading to its declaration, was finalized in February 2009. The 2009 H1N1 virus pandemic was neither on the horizon at that time nor mentioned in the document.[20][21] All versions of this document refer to influenza. The phases are defined by the spread of the disease; virulence and mortality are not mentioned in the current WHO definition, although these factors have previously been included.[22]

Influenza intervals in the CDC's Pandemic Intervals Framework

In 2014, the United States Centers for Disease Control and Prevention introduced an analogous framework to the WHO's pandemic stages titled the Pandemic Intervals Framework.[23] It includes two pre-pandemic intervals,

• Investigation
• Recognition

and four pandemic intervals,

• Initiation
• Acceleration
• Deceleration
• Preparation

It also includes a table defining the intervals and mapping them to the WHO pandemic stages.

Estimates of hypothetical influenza deaths in the 2010 U.S. across varying values of case-fatality ratio and cumulative incidence of infection. Selected estimated numbers of deaths are indicated with a black line, across each relevant combination of case-fatality ratio and cumulative incidence. Case-fatality ratio is an example of a clinical severity measure, and cumulative incidence of infection is an example of a transmissibility measure in the Pandemic Severity Assessment Framework.[24]

Scaled examples of past influenza pandemics and past influenza seasons. Color scheme included to represent corresponding hypothetical estimates of influenza deaths in the 2010 US population, with the same color scale as the previous figure.[24]

In 2014, the United States Centers for Disease Control and Prevention adopted the Pandemic Severity Assessment Framework (PSAF) to assess the severity of pandemics.[23] The PSAF superseded the 2007 linear Pandemic Severity Index, which assumed 30% spread and measured case fatality rate (CFR) to assess the severity and evolution of the pandemic.[25]

Historically, measures of pandemic severity were based on the case fatality rate.[26] However, the case fatality rate might not be an adequate measure of pandemic severity during a pandemic response because:[24]

• Deaths may lag several weeks behind cases, making the case fatality rate an underestimate
• The total number of cases may not be known, making the case fatality rate an overestimate[27]
• A single case fatality rate for the entire population may obscure the effect on vulnerable sub-populations, such as children, the elderly, those with chronic conditions, and members of certain racial and ethnic minorities
• Fatalities alone may not account for the full effects of the pandemic, such as absenteeism or demand for healthcare services

To account for the limitations of measuring the case fatality rate alone, the PSAF rates the severity of a disease outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population.[24] Each dimension can be measured using more than one metric, which are scaled to allow comparison of the different metrics. Clinical severity can instead be measured, for example, as the ratio of deaths to hospitalizations or using genetic markers of virulence. Transmissibility can be measured, for example, as the basic reproduction number R₀ and serial interval or via underlying population immunity. The framework gives guidelines for scaling the various measures and examples of assessing past pandemics using the framework.

Estimated HIV/AIDS prevalence among young adults (15-49) by country as of 2008

Although the WHO uses the term "global epidemic" to describe HIV ("WHO HIV/AIDS Data and Statistics". Retrieved 12 April 2020.), as HIV is no longer an uncontrollable outbreak outside of Africa, some authors use the term "pandemic".[38] HIV originated in Africa, and spread to the United States via Haiti between 1966 and 1972.[39] AIDS is currently a pandemic in Africa, with infection rates as high as 25% in some regions of southern and eastern Africa. In 2006, the HIV prevalence among pregnant women in South Africa was 29%.[40] Effective education about safer sexual practices and bloodborne infection precautions training have helped to slow down infection rates in several African countries sponsoring national education programs. There were an estimated 1.5 million new infections of HIV/AIDS in 2020. As of 2020 there have been about a total of 32.7 million deaths related to HIV/AIDS since the epidemic started.[41]

Total confirmed cases of COVID-19 per million people[42]

SARS-CoV-2, a new strain of coronavirus, was first detected in the city of Wuhan, Hubei Province, China, in December 2019.[43] It caused a pandemic of cases of an acute respiratory disease, which is referred to as coronavirus disease 2019 (COVID-19).[31] More than 200 countries and territories have been affected by COVID-19, with major outbreaks occurring in Brazil, Russia, India, Mexico, Peru, South Africa,[44][45] Western Europe, and the United States.[31] On 11 March 2020, the World Health Organization characterized the spread of COVID-19 as a pandemic, marking the first global pandemic since the 2009 swine flu pandemic.[31][46][47] As of 30 October 2022, the number of people infected with COVID-19 has reached more than 629 million worldwide. The current death toll is 6,588,602. [48] It is believed that these figures underestimate true totals as testing did not commence in the initial stages of the outbreak and many people infected by the virus have no or only mild symptoms so may not have been tested. Similarly, the number of deaths may also be understated as fatalities may have not been tested or are attributed to other conditions.[31] This was especially the case in large urban areas where a non-trivial number of patients died while in their private residences.[31]

Disposal of dead bodies during the cholera epidemic in Palermo in 1835

Since it became widespread in the 19th century, cholera has killed tens of millions of people.[104]

• 1817–1824 cholera pandemic. Previously restricted to the Indian subcontinent, the pandemic began in Bengal, then spread across India by 1820. 10,000 British troops and thousands of Indians died during this pandemic.[105] It extended as far as China, Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea before receding. Deaths in the Indian subcontinent between 1817 and 1860 are estimated to have exceeded 15 million. Another 23 million died between 1865 and 1917. Russian deaths during a similar period exceeded 2 million.[106]
• 1826–1837 cholera pandemic. Reached Russia (see Cholera Riots), Hungary (about 100,000 deaths) and Germany in 1831, London in 1832 (more than 55,000 persons died in the United Kingdom),[107] France, Canada (Ontario), and United States (New York City) in the same year,[108] and the Pacific coast of North America by 1834. It is believed that more than 150,000 Americans died of cholera between 1832 and 1849.[109]
• 1846–1860 cholera pandemic. Deeply affected Russia, with more than a million deaths. A two-year outbreak began in England and Wales in 1848 and claimed 52,000 lives.[110] Throughout Spain, cholera caused more than 236,000 deaths in 1854–55.[111] It claimed 200,000 lives in Mexico.[112]
• 1863–1875 cholera pandemic. Spread mostly in Europe and Africa. At least 30,000 of the 90,000 Mecca pilgrims were affected by the disease. Cholera killed 90,000 people in Russia in 1866.[113]
• In 1866, there was an outbreak in North America. It killed some 50,000 Americans.[109]
• 1881–1896 cholera pandemic. The 1883–1887 epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas.[114] Cholera claimed 267,890 lives in Russia (1892);[115] 120,000 in Spain;[116] 90,000 in Japan and 60,000 in Persia.
• In 1892, cholera contaminated the water supply of Hamburg, and caused 8,606 deaths.[117]
• 1899–1923 cholera pandemic. Had little effect in Europe because of advances in public health, but Russia was badly affected again (more than 500,000 people dying of cholera during the first quarter of the 20th century).[118] The sixth pandemic killed more than 800,000 in India. The 1902–1904 cholera epidemic claimed more than 200,000 lives in the Philippines.[119]
• Seventh cholera pandemic (1961–present). Began in Indonesia, called El Tor after the new biotype responsible for the pandemic, and reached Bangladesh in 1963, India in 1964, and the Soviet Union in 1966. The pandemic thereafter reached Africa in 1971 and the Americas in 1991. As of March 2022, the World Health Organization continues to define this outbreak as a current pandemic, noting that cholera has become endemic in many countries. In 2017, WHO announced a global strategy aimed at this pandemic with the goal of reducing cholera deaths by 90% by 2030.[120]

Dengue is spread by several species of female mosquitoes of the Aedes type, principally A. aegypti. The virus has five types; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. Several tests are available to confirm the diagnosis including detecting antibodies to the virus or its RNA.

• The Greek physician Hippocrates, the "Father of Medicine", first described influenza in 412 BC.[121]
• The first influenza pandemic to be pathologically described occurred in 1510. Since the pandemic of 1580, influenza pandemics have occurred every 10 to 30 years.[122][123][124]
• The 1889–1890 pandemic was attributed to influenza at the time but more recent research suggests it may have been caused by human coronavirus OC43. Also known as Russian Flu or Asiatic Flu, it was first reported in May 1889 in Bukhara, Uzbekistan. By October, it had reached Tomsk and the Caucasus. It rapidly spread west and hit North America in December 1889, South America in February–April 1890, India in February–March 1890, and Australia in March–April 1890. The H3N8 and H2N2 subtypes of the influenza A virus have each been identified as possible causes. It had a very high attack and mortality rate, causing around a million fatalities.[125]
• The "Spanish flu", 1918–1920. First identified early in March 1918 in U.S. troops training at Camp Funston, Kansas. By October 1918, it had spread to become a worldwide pandemic on all continents, and eventually infected about one-third of the world's population (or ≈500 million persons).[75] Unusually deadly and virulent, it persisted in pandemic form for at least two years before settling into more endemic patterns.[126] Within six months, some 50 million people were dead;[75] some estimates put the total number of fatalities worldwide at over twice that number.[127] About 17 million died in India, 675,000 in the United States,[128] and 200,000 in the United Kingdom. The virus that caused Spanish flu was also implicated as a cause of encephalitis lethargica in children.[129] The virus was recently reconstructed by scientists at the CDC studying remains preserved by the Alaskan permafrost. The 2009 pandemic H1N1 virus has a small but crucial structure that is similar to the Spanish flu.[130]
• The "Asian flu", 1957–58. An H2N2 virus was first identified in China in late February 1957 but not recognized globally until after an outbreak in Hong Kong in April.[131][132] From there, it spread throughout Southeast Asia and the greater continent during the spring and throughout the Southern Hemisphere during the middle months of the year, causing extensive outbreaks. By the end of September, nearly the entire inhabited world had been infected or at least seeded with the virus. The Northern Hemisphere experienced widespread outbreaks during the fall and winter, and some parts of the world saw a second wave during this time or in early 1958.[131] The pandemic caused about two million deaths globally.[133]
• The "Hong Kong flu", 1968–70. An H3N2 virus was first detected in Hong Kong in July 1968 and spread across the world, lasting until 1970. This pandemic exhibited a more "smoldering" pattern as compared with other influenza pandemics, with uneven impact in different places over time.[134] Its course at first resembled that of the 1957 pandemic, but after a couple of months its spread faltered; the virus did not immediately result in extensive outbreaks in some places, despite repeated introductions.[135] The United States notably experienced an intense epidemic during the 1968–1969 flu season, the first with the pandemic virus, while European and Asian countries were relatively less affected.[135][134] During the 1969–1970 season, however, the United States was much less affected, while Europe and Asia experienced extensive outbreaks of the pandemic virus. In the Southern Hemisphere, Australia experienced a pattern more akin to Europe and Asia, with a more severe second wave.[134] This pandemic killed approximately one million people worldwide.[136]
• The "1977 Russian flu", 1977–79. An H1N1 virus was first reported by the Soviet Union in 1977. The pandemic caused an estimated 700,000 deaths worldwide[137][138] and mostly affected the younger population.[139]
• The "Swine flu", 2009–10. An H1N1 virus first detected in Mexico in early 2009. Estimates for the mortality of this pandemic range from 150 to 500 thousand.[140][141]

Typhus is sometimes called "camp fever" because of its pattern of flaring up in times of strife. (It is also known as "gaol fever", "Aryotitus fever" and "ship fever", for its habits of spreading wildly in cramped quarters, such as jails and ships.) Emerging during the Crusades, it had its first impact in Europe in 1489, in Spain. During fighting between the Christian Spaniards and the Muslims in Granada, the Spanish lost 3,000 to war casualties, and 20,000 to typhus. In 1528, the French lost 18,000 troops in Italy, and lost supremacy in Italy to the Spanish. In 1542, 30,000 soldiers died of typhus while fighting the Ottomans in the Balkans.

During the Thirty Years' War (1618–1648), about eight million Germans were killed by bubonic plague and typhus.[142] The disease also played a major role in the destruction of Napoleon's Grande Armée in Russia in 1812. During the retreat from Moscow, more French military personnel died of typhus than were killed by the Russians.[143] Of the 450,000 soldiers who crossed the Neman on 25 June 1812, fewer than 40,000 returned. More military personnel were killed from 1500 to 1914 by typhus than from military action.[144] In early 1813, Napoleon raised a new army of 500,000 to replace his Russian losses. In the campaign of that year, more than 219,000 of Napoleon's soldiers died of typhus.[145] Typhus played a major factor in the Great Famine of Ireland. During World War I, typhus epidemics killed more than 150,000 in Serbia. There were about 25 million infections and 3 million deaths from epidemic typhus in Russia from 1918 to 1922.[145] Typhus also killed numerous prisoners in the Nazi concentration camps and Soviet prisoner of war camps during World War II. More than 3.5 million Soviet POWs died out of the 5.7 million in Nazi custody.[146]

Child with smallpox, c. 1908

Smallpox was a contagious disease caused by the variola virus. The disease killed an estimated 400,000 Europeans per year during the closing years of the 18th century.[147] During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths.[148][149] As recently as the early 1950s, an estimated 50 million cases of smallpox occurred in the world each year.[150] After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in December 1979. To this day, smallpox is the only human infectious disease to have been completely eradicated,[151] and one of two infectious viruses ever to be eradicated, along with rinderpest.[152]

Historically, measles was prevalent throughout the world, as it is highly contagious. According to the U.S. National Immunization Program, by 1962 90% of people were infected with measles by age 15.[153] Before the vaccine was introduced in 1963, there were an estimated three to four million cases in the U.S. each year.[154] Measles killed around 200 million people worldwide over the last 150 years.[155] In 2000 alone, measles killed some 777,000 worldwide out of 40 million cases globally.[156]

Measles is an endemic disease, meaning it has been continually present in a community, and many people develop resistance. In populations that have not been exposed to measles, exposure to a new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived smallpox.[157] The disease had ravaged Mexico, Central America, and the Inca civilization.[158]

In 2007, the prevalence of TB per 100,000 people was highest in Sub-Saharan Africa, and was also relatively high in Asian countries, e.g. India.

One-quarter of the world's current population has been infected with Mycobacterium tuberculosis, and new infections occur at a rate of one per second.[159] About 5–10% of these latent infections will eventually progress to active disease, which, if left untreated, kills more than half its victims. Annually, eight million people become ill with tuberculosis, and two million die from the disease worldwide.[160] In the 19th century, tuberculosis killed an estimated one-quarter of the adult population of Europe;[161] by 1918, one in six deaths in France were still caused by tuberculosis. During the 20th century, tuberculosis killed approximately 100 million people.[155] TB is still one of the most important health problems in the developing world.[162] In 2018, Tuberculosis became the leading cause of death from an infectious disease, with roughly 1.5 million deaths worldwide.[163]

Leprosy, also known as Hansen's disease, is caused by a bacillus, Mycobacterium leprae. It is a chronic disease with an incubation period of up to five years. Since 1985, 15 million people worldwide have been cured of leprosy.[164]

Historically, leprosy has affected people since at least 600 BC.[165] Leprosy outbreaks began to occur in Western Europe around 1000 AD.[166][167] Numerous leprosoria, or leper hospitals, sprang up in the Middle Ages; Matthew Paris estimated that in the early 13th century, there were 19,000 of them across Europe.[168]

Past and current malaria prevalence in 2009

Malaria is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria.[169] Drug resistance poses a growing problem in the treatment of malaria in the 21st century, since resistance is now common against all classes of antimalarial drugs, except for the artemisinins.[170]

Malaria was once common in most of Europe and North America, where it is now for all purposes non-existent.[171] Malaria may have contributed to the decline of the Roman Empire.[172] The disease became known as "Roman fever".[173] Plasmodium falciparum became a real threat to colonists and indigenous people alike when it was introduced into the Americas along with the slave trade. Malaria devastated the Jamestown colony and regularly ravaged the South and Midwest of the United States. By 1830, it had reached the Pacific Northwest.[174] During the American Civil War, there were more than 1.2 million cases of malaria among soldiers of both sides.[175] The southern U.S. continued to be affected by millions of cases of malaria into the 1930s.[176]

Yellow fever has been a source of several devastating epidemics.[177] Cities as far north as New York, Philadelphia, and Boston were hit with epidemics. In 1793, one of the largest yellow fever epidemics in U.S. history killed as many as 5,000 people in Philadelphia—roughly 10% of the population. About half of the residents had fled the city, including President George Washington.[178] Another major outbreak of the disease struck the Mississippi River Valley in 1878, with deaths estimated at 20,000. Among the hardest-hit places was Memphis, Tennessee, where 5,000 people were killed and over 20,000 fled, then representing over half the city's population, many of whom never returned. In colonial times, West Africa became known as "the white man's grave" because of malaria and yellow fever.[179]

Antibiotic-resistant microorganisms, which sometimes are referred to as "superbugs", may contribute to the re-emergence of diseases that are currently well controlled.[186] For example, cases of tuberculosis that are resistant to traditionally effective treatments remain a cause of great concern to health professionals. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.[187] China and India have the highest rate of multidrug-resistant TB.[188] The World Health Organization (WHO) reports that approximately 50 million people worldwide are infected with MDR TB, with 79 percent of those cases resistant to three or more antibiotics. In 2005, 124 cases of MDR TB were reported in the United States. Extensively drug-resistant tuberculosis (XDR TB) was identified in Africa in 2006 and subsequently discovered to exist in 49 countries, including the United States. There are about 40,000 new cases of XDR-TB per year, the WHO estimates.[189]

In the past 20 years, common bacteria including Staphylococcus aureus, Serratia marcescens and Enterococcus, have developed resistance to various antibiotics such as vancomycin, as well as whole classes of antibiotics, such as the aminoglycosides and cephalosporins. Antibiotic-resistant organisms have become an important cause of healthcare-associated (nosocomial) infections (HAI). In addition, infections caused by community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA) in otherwise healthy individuals have become more frequent in recent years.

Early development of vaccines may be one way to prepare for future pandemics that couldn't get prevented. In 2021, scientists called for accelerated efforts in the development of broadly protective vaccines, especially a universal coronavirus vaccine that durably protects not just against all SARS-CoV-2 variants but also other coronaviruses, including already identified animal coronaviruses with pandemic potential.[190] Other components may include measures related to disease surveillance for detecting pathogens (including early warning systems), data collection and modelling to enable tracing and explaining the spread of pathogens, improvements to public-health guidance and communication, and the development of relevant therapies, including therapies beyond vaccines.[191]

Viral hemorrhagic fevers such as Ebola virus disease, Lassa fever, Rift Valley fever, Marburg virus disease, Severe fever with thrombocytopenia as well as Argentine, Bolivian, Brazilian, Crimean-Congo and Venezuelan hemorrhagic fevers[192] are highly contagious and deadly diseases, with the theoretical potential to become pandemics.[193][194] Their ability to spread efficiently enough to cause a pandemic is limited, however, as transmission of these viruses requires close contact with the infected vector, and the vector has only a short time before death or serious illness. Furthermore, the short time between a vector becoming infectious and the onset of symptoms allows medical professionals to quickly quarantine vectors, and prevent them from carrying the pathogen elsewhere. Genetic mutations could occur, which could elevate their potential for causing widespread harm; thus close observation by contagious disease specialists is merited.

Illustration created at the Centers for Disease Control and Prevention (CDC), reveals xultrastructural morphology exhibited by coronaviruses; note the spikes that adorn the outer surface, which impart the look of a corona surrounding the virion.[195]

Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1).[31] A new strain of coronavirus (SARS-CoV-2) causes Coronavirus disease 2019, or COVID-19,[196] which was declared as a pandemic by the WHO on 11 March 2020.[31]

Some coronaviruses are zoonotic, meaning they are transmitted between animals and people. Detailed investigations found that SARS-CoV-1 was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans. Several known coronaviruses are circulating in animals that have not yet infected humans. Common signs of infection include respiratory symptoms, fever, cough, shortness of breath, and breathing difficulties. In more severe cases, an infection can cause pneumonia, acute respiratory distress syndrome, kidney failure, and even death. Standard recommendations to prevent the spread of infection include regular hand washing, wearing a face mask, going outdoors when meeting people, and avoiding close contact with people who have tested positive regardless of whether they have symptoms or not. It is recommended that people stay two meters or six feet away from others, commonly called social distancing.

After the SARS outbreak, in 2003 the Italian physician Carlo Urbani (1956–2003) was the first to identify severe acute respiratory syndrome (SARS) as a new and dangerously contagious disease, although he became infected and died. It is caused by a coronavirus dubbed SARS-CoV-1. Rapid action by national and international health authorities such as the World Health Organization helped to slow transmission and eventually broke the chain of transmission, which ended the localized epidemics before they could become a pandemic. However, the disease has not been eradicated and could re-emerge. This warrants monitoring and reporting of suspicious cases of atypical pneumonia.[197]

President Barack Obama is briefed in the Situation Room about the 2009 flu pandemic, which killed as many as 17,000 Americans.[198]

Wild aquatic birds are the natural hosts for a range of influenza A viruses. Occasionally, viruses are transmitted from these species to other species, and may then cause outbreaks in domestic poultry or, rarely, in humans.[199][200]

In February 2004, avian influenza virus was detected in birds in Vietnam, increasing fears of the emergence of new variant strains. It is feared that if the avian influenza virus combines with a human influenza virus (in a bird or a human), the new subtype created could be both highly contagious and highly lethal in humans. Such a subtype could cause a global influenza pandemic, similar to the Spanish flu or the lower mortality pandemics such as the Asian flu and the Hong Kong flu.

From October 2004 to February 2005, some 3,700 test kits of the 1957 pandemic influenza virus, H2N2, were accidentally spread around the world from a lab in the U.S.[201]

In May 2005, scientists urgently called upon nations to prepare for a global influenza pandemic that could strike as much as 20% of the world's population.[202]

In October 2005, cases of the avian flu (the deadly strain H5N1) were identified in Turkey. EU Health Commissioner Markos Kyprianou said: "We have received now confirmation that the virus found in Turkey is an avian flu H5N1 virus. There is a direct relationship with viruses found in Russia, Mongolia, and China." Cases of bird flu were also identified shortly thereafter in Romania, and then Greece. Possible cases of the virus have also been found in Croatia, Bulgaria, and the United Kingdom.[203]

By November 2007, numerous confirmed cases of the H5N1 strain had been identified across Europe.[204] However, by the end of October, only 59 people had died as a result of H5N1, which was atypical of previous influenza pandemics.

Avian flu cannot be categorized as a "pandemic" because the virus cannot yet cause sustained and efficient human-to-human transmission. Cases so far are recognized to have been transmitted from bird to human, but as of December 2006 there had been few (if any) cases of proven human-to-human transmission.[205] Regular influenza viruses establish infection by attaching to receptors in the throat and lungs, but the avian influenza virus can attach only to receptors located deep in the lungs of humans, requiring close, prolonged contact with infected patients, and thus limiting person-to-person transmission.

An outbreak of Zika virus began in 2015 and strongly intensified throughout the start of 2016, with more than 1.5 million cases across more than a dozen countries in the Americas. The World Health Organization warned that Zika had the potential to become an explosive global pandemic if the outbreak was not controlled.[206][207]