Herd immunity

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Herd_immunity 

The top box shows an outbreak in a community in which a few people are infected (shown in red) and the rest are healthy but unimmunized (shown in blue); the illness spreads freely through the population. The middle box shows a population where a small number have been immunized (shown in yellow); those not immunized become infected while those immunized do not. In the bottom box, a large proportion of the population have been immunized; this prevents the illness from spreading significantly, including to unimmunized people. In the first two examples, most healthy unimmunized people become infected, whereas in the bottom example only one fourth of the healthy unimmunized people become infected.

Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection from infectious disease that can occur with some diseases when a sufficient percentage of a population has become immune to an infection, whether through vaccination or previous infections, thereby reducing the likelihood of infection for individuals who lack immunity. Immune individuals are unlikely to contribute to disease transmission, disrupting chains of infection, which stops or slows the spread of disease. The greater the proportion of immune individuals in a community, the smaller the probability that non-immune individuals will come into contact with an infectious individual.

Individuals can become immune by recovering from an earlier infection or through vaccination. Some individuals cannot become immune because of medical conditions, such as an immunodeficiency or immunosuppression, and for this group herd immunity is a crucial method of protection. Once the herd immunity threshold has been reached, disease gradually disappears from a population. This elimination, if achieved worldwide, may result in the permanent reduction in the number of infections to zero, called eradication. Herd immunity created via vaccination contributed to the eventual eradication of smallpox in 1977 and has contributed to the reduction of other diseases. Herd immunity applies only to contagious disease, meaning that it is transmitted from one individual to another. Tetanus, for example, is infectious but not contagious, so herd immunity does not apply.

Herd immunity was recognized as a naturally occurring phenomenon in the 1930s when it was observed that after a significant number of children had become immune to measles, the number of new infections temporarily decreased. Mass vaccination to induce herd immunity has since become common and proved successful in preventing the spread of many infectious diseases. Opposition to vaccination has posed a challenge to herd immunity, allowing preventable diseases to persist in or return to populations with inadequate vaccination rates.

The exact herd immunity threshold (HIT) varies depending on the basic reproduction number of the disease. An example of a disease with a high threshold is the measles, with a HIT exceeding 95%.

Effects

Protection of those without immunity

Herd immunity protects vulnerable communities.

Some individuals either cannot develop immunity after vaccination or for medical reasons cannot be vaccinated. Newborn infants are too young to receive many vaccines, either for safety reasons or because passive immunity renders the vaccine ineffective. Individuals who are immunodeficient due to HIV/AIDS, lymphoma, leukemia, bone marrow cancer, an impaired spleen, chemotherapy, or radiotherapy may have lost any immunity that they previously had and vaccines may not be of any use for them because of their immunodeficiency.

A portion of those vaccinated may not develop long-term immunity. Vaccine contraindications may prevent certain individuals from being vaccinated. In addition to not being immune, individuals in one of these groups may be at a greater risk of developing complications from infection because of their medical status, but they may still be protected if a large enough percentage of the population is immune.

High levels of immunity in one age group can create herd immunity for other age groups. Vaccinating adults against pertussis reduces pertussis incidence in infants too young to be vaccinated, who are at the greatest risk of complications from the disease. This is especially important for close family members, who account for most of the transmissions to young infants. In the same manner, children receiving vaccines against pneumococcus reduces pneumococcal disease incidence among younger, unvaccinated siblings. Vaccinating children against pneumococcus and rotavirus has had the effect of reducing pneumococcus- and rotavirus-attributable hospitalizations for older children and adults, who do not normally receive these vaccines. Influenza (flu) is more severe in the elderly than in younger age groups, but influenza vaccines lack effectiveness in this demographic due to a waning of the immune system with age. The prioritization of school-age children for seasonal flu immunization, which is more effective than vaccinating the elderly, however, has been shown to create a certain degree of protection for the elderly.

For sexually transmitted infections (STIs), high levels of immunity in one sex induces herd immunity for both sexes. Vaccines against STIs that are targeted at one sex result in significant declines in STIs in both sexes if vaccine uptake in the target sex is high. Herd immunity from female vaccination does not, however, extend to homosexual males. If vaccine uptake among the target sex is low, then the other sex may need to be immunized so that the target sex can be sufficiently protected. High-risk behaviors make eliminating STIs difficult since even though most infections occur among individuals with moderate risk, the majority of transmissions occur because of individuals who engage in high-risk behaviors. For these reasons, in certain populations it may be necessary to immunize high-risk persons or individuals of both sexes to establish herd immunity.

Evolutionary pressure and serotype replacement

Herd immunity itself acts as an evolutionary pressure on pathogens, influencing viral evolution by encouraging the production of novel strains, referred to as escape mutants, that are able to evade herd immunity and infect previously immune individuals. The evolution of new strains is known as serotype replacement, or serotype shifting, as the prevalence of a specific serotype declines due to high levels of immunity, allowing other serotypes to replace it.

At the molecular level, viruses escape from herd immunity through antigenic drift, which is when mutations accumulate in the portion of the viral genome that encodes for the virus's surface antigen, typically a protein of the virus capsid, producing a change in the viral epitope. Alternatively, the reassortment of separate viral genome segments, or antigenic shift, which is more common when there are more strains in circulation, can also produce new serotypes. When either of these occur, memory T cells no longer recognize the virus, so people are not immune to the dominant circulating strain. For both influenza and norovirus, epidemics temporarily induce herd immunity until a new dominant strain emerges, causing successive waves of epidemics. As this evolution poses a challenge to herd immunity, broadly neutralizing antibodies and "universal" vaccines that can provide protection beyond a specific serotype are in development.

Initial vaccines against Streptococcus pneumoniae significantly reduced nasopharyngeal carriage of vaccine serotypes (VTs), including antibiotic-resistant types, only to be entirely offset by increased carriage of non-vaccine serotypes (NVTs). This did not result in a proportionate increase in disease incidence though, since NVTs were less invasive than VTs. Since then, pneumococcal vaccines that provide protection from the emerging serotypes have been introduced and have successfully countered their emergence. The possibility of future shifting remains, so further strategies to deal with this include expansion of VT coverage and the development of vaccines that use either killed whole-cells, which have more surface antigens, or proteins present in multiple serotypes.

Eradication of diseases

A cow with rinderpest in the "milk fever" position, 1982. The last confirmed case of rinderpest occurred in Kenya in 2001, and the disease was officially declared eradicated in 2011.

If herd immunity has been established and maintained in a population for a sufficient time, the disease is inevitably eliminated – no more endemic transmissions occur. If elimination is achieved worldwide and the number of cases is permanently reduced to zero, then a disease can be declared eradicated. Eradication can thus be considered the final effect or end-result of public health initiatives to control the spread of infectious disease.

The benefits of eradication include ending all morbidity and mortality caused by the disease, financial savings for individuals, health care providers, and governments, and enabling resources used to control the disease to be used elsewhere. To date, two diseases have been eradicated using herd immunity and vaccination: rinderpest and smallpox. Eradication efforts that rely on herd immunity are currently underway for poliomyelitis, though civil unrest and distrust of modern medicine have made this difficult. Mandatory vaccination may be beneficial to eradication efforts if not enough people choose to get vaccinated.

Free riding

Herd immunity is vulnerable to the free rider problem. Individuals who lack immunity, particularly those who choose not to vaccinate, free ride off the herd immunity created by those who are immune. As the number of free riders in a population increases, outbreaks of preventable diseases become more common and more severe due to loss of herd immunity. Individuals may choose to free ride for a variety of reasons, including the belief that vaccines are ineffective, or that the risks associated with vaccines are greater than those associated with infection, mistrust of vaccines or public health officials, bandwagoning or groupthinking, social norms or peer pressure, and religious beliefs. Certain individuals are more likely to choose not to receive vaccines if vaccination rates are high enough to convince a person that he or she may not need to be vaccinated, since a sufficient percentage of others are already immune.

Mechanism

Individuals who are immune to a disease act as a barrier in the spread of disease, slowing or preventing the transmission of disease to others. An individual's immunity can be acquired via a natural infection or through artificial means, such as vaccination. When a critical proportion of the population becomes immune, called the herd immunity threshold (HIT) or herd immunity level (HIL), the disease may no longer persist in the population, ceasing to be endemic.

The theoretical basis for herd immunity generally assumes that vaccines induce solid immunity, that populations mix at random, that the pathogen does not evolve to evade the immune response, and that there is no non-human vector for the disease.

Theoretical basis

Estimated R₀ and HITs (herd immunity threshold) of well-known infectious diseases

Disease	Transmission	R0	HIT
Measles	Airborne	12–18	92–95%
Pertussis	Airborne droplet	12–17	92–94%
Diphtheria	Saliva	6–7	83–86%
Rubella	Airborne droplet
Smallpox		5–7	80–86%
Polio	Fecal-oral route
Mumps	Airborne droplet	4–7	75–86%
COVID-19 (COVID-19 pandemic)		2.5–4	60–75%
SARS (2002–2004 SARS outbreak)		2–5	50–80%
Ebola (Ebola virus epidemic in West Africa)	Bodily fluids	1.5–2.5	33–60%
Influenza (influenza pandemics)	Airborne droplet	1.5–1.8	33–44%

Graph of herd immunity threshold vs basic reproduction number with selected diseases

The critical value, or threshold, in a given population, is the point where the disease reaches an endemic steady state, which means that the infection level is neither growing nor declining exponentially. This threshold can be calculated from the effective reproduction number R_e, which is obtained by taking the product of the basic reproduction number R₀, the average number of new infections caused by each case in an entirely susceptible population that is homogeneous, or well-mixed, meaning each individual can come into contact with every other susceptible individual in the population, and S, the proportion of the population who are susceptible to infection, and setting this product to be equal to 1:

${\displaystyle R_{0}\cdot S=1.}$

S can be rewritten as (1 − p), where p is the proportion of the population that is immune so that p + S equals one. Then, the equation can be rearranged to place p by itself as follows:

${\displaystyle R_{0}\cdot (1-p)=1,}$

${\displaystyle 1-p={\frac {1}{R_{0}}},}$

${\displaystyle p_{c}=1-{\frac {1}{R_{0}}}.}$

With p being by itself on the left side of the equation, it can be renamed as p_c, representing the critical proportion of the population needed to be immune to stop the transmission of disease, which is the same as the "herd immunity threshold" HIT. R₀ functions as a measure of contagiousness, so low R₀ values are associated with lower HITs, whereas higher R₀s result in higher HITs. For example, the HIT for a disease with an R₀ of 2 is theoretically only 50%, whereas a disease with an R₀ of 10 the theoretical HIT is 90%.

When the effective reproduction number R_e of a contagious disease is reduced to and sustained below 1 new individual per infection, the number of cases occurring in the population gradually decreases until the disease has been eliminated. If a population is immune to a disease in excess of that disease's HIT, the number of cases reduces at a faster rate, outbreaks are even less likely to happen, and outbreaks that occur are smaller than they would be otherwise. If the effective reproduction number increases to above 1, then the disease is neither in a steady state nor decreasing in incidence, but is actively spreading through the population and infecting a larger number of people than usual.

An assumption in these calculations is that populations are homogeneous, or well-mixed, meaning that every individual comes into contact with every other individual, when in reality populations are better described as social networks as individuals tend to cluster together, remaining in relatively close contact with a limited number of other individuals. In these networks, transmission only occurs between those who are geographically or physically close to one another. The shape and size of a network is likely to alter a disease's HIT, making incidence either more or less common.

In heterogeneous populations, R₀ is considered to be a measure of the number of cases generated by a "typical" infectious person, which depends on how individuals within a network interact with each other. Interactions within networks are more common than between networks, in which case the most highly connected networks transmit disease more easily, resulting in a higher R₀ and a higher HIT than would be required in a less connected network. In networks that either opt not to become immune or are not immunized sufficiently, diseases may persist despite not existing in better-immunized networks.

Overshoot

The cumulative proportion of individuals who get infected during the course of a disease outbreak can exceed the HIT. This is because the HIT does not represent the point at which the disease stops spreading, but rather the point at which each infected person infects fewer than one additional person on average. When the HIT is reached, the number of additional infections does not immediately drop to zero. The excess of the cumulative proportion of infected individuals over the theoretical HIT is known as the overshoot.

Boosts

Vaccination

The primary way to boost levels of immunity in a population is through vaccination. Vaccination is originally based on the observation that milkmaids exposed to cowpox were immune to smallpox, so the practice of inoculating people with the cowpox virus began as a way to prevent smallpox. Well-developed vaccines provide protection in a far safer way than natural infections, as vaccines generally do not cause the diseases they protect against and severe adverse effects are significantly less common than complications from natural infections.

The immune system does not distinguish between natural infections and vaccines, forming an active response to both, so immunity induced via vaccination is similar to what would have occurred from contracting and recovering from the disease. To achieve herd immunity through vaccination, vaccine manufacturers aim to produce vaccines with low failure rates, and policy makers aim to encourage their use. After the successful introduction and widespread use of a vaccine, sharp declines in the incidence of diseases it protects against can be observed, which decreases the number of hospitalizations and deaths caused by such diseases.

Assuming a vaccine is 100% effective, then the equation used for calculating the herd immunity threshold can be used for calculating the vaccination level needed to eliminate a disease, written as V_c. Vaccines are usually imperfect however, so the effectiveness, E, of a vaccine must be accounted for:

${\displaystyle V_{c}={\frac {1-{\frac {1}{R_{0}}}}{E}}.}$

From this equation, it can be observed that if E is less than (1 − 1/R₀), then it is impossible to eliminate a disease, even if the entire population is vaccinated. Similarly, waning vaccine-induced immunity, as occurs with acellular pertussis vaccines, requires higher levels of booster vaccination to sustain herd immunity. If a disease has ceased to be endemic to a population, then natural infections no longer contribute to a reduction in the fraction of the population that is susceptible. Only vaccination contributes to this reduction. The relation between vaccine coverage and effectiveness and disease incidence can be shown by subtracting the product of the effectiveness of a vaccine and the proportion of the population that is vaccinated, p_v, from the herd immunity threshold equation as follows:

Measles vaccine coverage and reported measles cases in Eastern Mediterranean countries. As coverage increased, the number of cases decreased.

${\displaystyle \left(1-{\frac {1}{R_{0}}}\right)-(E\times p_{v}).}$

It can be observed from this equation that, all other things being equal ("ceteris paribus"), any increase in either vaccine coverage or vaccine effectiveness, including any increase in excess of a disease's HIT, further reduces the number of cases of a disease. The rate of decline in cases depends on a disease's R₀, with diseases with lower R₀ values experiencing sharper declines.

Vaccines usually have at least one contraindication for a specific population for medical reasons, but if both effectiveness and coverage are high enough then herd immunity can protect these individuals. Vaccine effectiveness is often, but not always, adversely affected by passive immunity, so additional doses are recommended for some vaccines while others are not administered until after an individual has lost his or her passive immunity.

Passive immunity

Individual immunity can also be gained passively, when antibodies to a pathogen are transferred from one individual to another. This can occur naturally, whereby maternal antibodies, primarily immunoglobulin G antibodies, are transferred across the placenta and in colostrum to fetuses and newborns. Passive immunity can also be gained artificially, when a susceptible person is injected with antibodies from the serum or plasma of an immune person.

Protection generated from passive immunity is immediate, but wanes over the course of weeks to months, so any contribution to herd immunity is temporary. For diseases that are especially severe among fetuses and newborns, such as influenza and tetanus, pregnant women may be immunized in order to transfer antibodies to the child. In the same way, high-risk groups that are either more likely to experience infection, or are more likely to develop complications from infection, may receive antibody preparations to prevent these infections or to reduce the severity of symptoms.

Cost–benefit analysis

Herd immunity is often accounted for when conducting cost–benefit analyses of vaccination programs. It is regarded as a positive externality of high levels of immunity, producing an additional benefit of disease reduction that would not occur had no herd immunity been generated in the population. Therefore, herd immunity's inclusion in cost–benefit analyses results both in more favorable cost-effectiveness or cost–benefit ratios, and an increase in the number of disease cases averted by vaccination. Study designs done to estimate herd immunity's benefit include recording disease incidence in households with a vaccinated member, randomizing a population in a single geographic area to be vaccinated or not, and observing the incidence of disease before and after beginning a vaccination program. From these, it can be observed that disease incidence may decrease to a level beyond what can be predicted from direct protection alone, indicating that herd immunity contributed to the reduction. When serotype replacement is accounted for, it reduces the predicted benefits of vaccination.

History

Measles cases in the United States before and after mass vaccination against measles began.

The term "herd immunity" was coined in 1923. Herd immunity was first recognized as a naturally occurring phenomenon in the 1930s when A. W. Hedrich published research on the epidemiology of measles in Baltimore, and took notice that after many children had become immune to measles, the number of new infections temporarily decreased, including among susceptible children. In spite of this knowledge, efforts to control and eliminate measles were unsuccessful until mass vaccination using the measles vaccine began in the 1960s. Mass vaccination, discussions of disease eradication, and cost–benefit analyses of vaccination subsequently prompted more widespread use of the term herd immunity. In the 1970s, the theorem used to calculate a disease's herd immunity threshold was developed. During the smallpox eradication campaign in the 1960s and 1970s, the practice of ring vaccination, to which herd immunity is integral, began as a way to immunize every person in a "ring" around an infected individual to prevent outbreaks from spreading.

Since the adoption of mass and ring vaccination, complexities and challenges to herd immunity have arisen. Modeling of the spread of infectious disease originally made a number of assumptions, namely that entire populations are susceptible and well-mixed, which is not the case in reality, so more precise equations have been developed. In recent decades, it has been recognized that the dominant strain of a microorganism in circulation may change due to herd immunity, either because of herd immunity acting as an evolutionary pressure or because herd immunity against one strain allowed another already-existing strain to spread. Emerging or ongoing fears and controversies about vaccination have reduced or eliminated herd immunity in certain communities, allowing preventable diseases to persist in or return to these communities.

 

Polio vaccine

From Wikipedia, the free encyclopedia

 

Polio vaccine

Vaccine description
Target	Poliomyelitis
Vaccine type	OPV: attenuated; IPV: inactivated
Clinical data
Trade names	Ipol, Poliovax, others
AHFS/Drugs.com	Monograph
MedlinePlus	a601177
License data	US DailyMed: Ipol
Pregnancy category	AU: B2
Routes of administration	Parenteral (IPV), by mouth (OPV)
ATC code	J07BF01 (WHO) J07BF02 (WHO) J07BF03 (WHO) J07BF04 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
CAS Number	1008119-78-5
DrugBank	DB10796  DB10797
ChemSpider	None

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.

The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccines cause about three cases of vaccine-associated paralytic poliomyelitis per million doses given. This compares with 5,000 cases per million who are paralysed following a polio infection. Both are generally safe to give during pregnancy and in those who have HIV/AIDS but are otherwise well.

The first successful demonstration of a polio vaccine was by Hilary Koprowski in 1950, with a live attenuated virus which people drank. The vaccine was not approved for use in the United States, but was used successfully elsewhere. An inactivated polio vaccine, developed a few years later by Jonas Salk, came into use in 1955. Another attenuated live oral polio vaccine was developed by Albert Sabin and came into commercial use in 1961.

Polio vaccine is on the World Health Organization's List of Essential Medicines.

Medical uses

This 1963 poster featured CDC's national symbol of public health, the "Wellbee", encouraging the public to receive an oral polio vaccine.

Interruption of person-to-person transmission of the virus by vaccination is important in the global polio eradication, since no long-term carrier state exists for poliovirus in individuals with normal immune function, polio viruses have no nonprimate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote.

Inactivated

When the IPV (injection) is used, 90% or more of individuals develop protective antibodies to all three serotypes of polio virus after two doses of inactivated polio vaccine (IPV), and at least 99% are immune to polio virus following three doses. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to provide protection for many years.

Attenuated

Oral polio vaccines were easier to administer than IPV, as it eliminated the need for sterile syringes and therefore was more suitable for mass vaccination campaigns. OPV also provided longer-lasting immunity than the Salk vaccine, as it provides both humoral immunity and cell-mediated immunity.

One dose of OPV produces immunity to all three poliovirus serotypes in roughly 50% of recipients. Three doses of live-attenuated OPV produce protective antibodies to all three poliovirus types in more than 95% of recipients. OPV produces excellent immunity in the intestine, the primary site of wild poliovirus entry, which helps prevent infection with wild virus in areas where the virus is endemic. The live virus used in the vaccine can rarely shed in the stool and can rarely spread to others within a community. The live virus also has stringent requirements for transport and storage, which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is probably lifelong.

The trivalent (against wild types 1, 2, and 3) OPV has been used to nearly eradicate polio infection worldwide. Led by the Global Polio Eradication Initiative, 155 countries switched to use the bivalent (against wild types 1 and 3) between 17 April and 1 May 2016. The bivalent OPV is more effective against types 1 and 3, but does not cover type 2. The United States as of 2017 continues to recommend the use of a trivalent version, but a fully inactivated version.

Schedule

Share of one-year-olds vaccinated against polio in 2015

In countries with endemic polio or where the risk of imported cases is high, the WHO recommends OPV vaccine at birth followed by a primary series of three OPV and at least one IPV doses starting at 6 weeks of age, with a minimum of 4 weeks between OPV doses. In countries with >90% immunization coverage and low risk of importation, the WHO recommends one or two IPV doses starting at 2 months of age followed by at least two OPV doses, with the doses separated by 4–8 weeks depending on the risk of exposure. In countries with the highest levels of coverage and the lowest risks of importation and transmission, the WHO recommends a primary series of three IPV injections, with a booster dose after an interval of six months or more if the first dose was administered before 2 months of age.

Side effects

The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccine results in vaccine-associated paralytic poliomyelitis in about three per million doses. They are generally safe to give to those who are pregnant, and those who have HIV/AIDS, but who are otherwise well.

Vaccine-induced polio

cVDPV cases (red line) outnumbered wild polio cases (blue line) for the first time in 2017

A potential, adverse effect of the OPV is its known ability to recombine to a form that causes neurological infection and paralysis. This genetic reversal of the pathogen to a virulent form takes a considerable time (at least 12 months) and does not affect the person who was originally vaccinated. The vaccine-derived attenuated virus is normally excreted from vaccinated people for a limited period. Thus, in areas with poor sanitation and low vaccination coverage, the spontaneous reversal of the vaccine-derived virus to a virulent form and its spreading in the environment can lead to unvaccinated people becoming infected. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. Outbreaks of vaccine-associated paralytic poliomyelitis (VAPP), caused by a circulating vaccine-derived poliovirus (cVDPV), have been reported, and tend to occur in areas of low coverage by OPV, presumably because the OPV is itself protective against the related outbreak strain. With wild polio cases at record lows, 2017 was the first year where more cases of cVDPV were recorded than the wild poliovirus, a trend that is expected to continue.

To combat this, the WHO in 2016, decided to switch from the trivalent polio vaccine to the bivalent polio vaccine. This vaccine no longer contains the type 2 polio virus because it was eradicated in 1999.

Contamination concerns

In 1960, the rhesus monkey kidney cells used to prepare the poliovirus vaccines were determined to be infected with the simian virus-40 (SV40), which was also discovered in 1960 and is a naturally occurring virus that infects monkeys. In 1961, SV40 was found to cause tumors in rodents. More recently, the virus was found in certain forms of cancer in humans, for instance brain and bone tumors, pleural and peritoneal mesothelioma, and some types of non-Hodgkin lymphoma. However, SV40 has not been determined to cause these cancers.

SV40 was found to be present in stocks of the injected form of the IPV in use between 1955 and 1963. It is not found in the OPV form. Over 98 million Americans received one or more doses of polio vaccine between 1955 and 1963 when a proportion of vaccine was contaminated with SV40; an estimated 10–30 million Americans may have received a dose of vaccine contaminated with SV40. Later analysis suggested that vaccines produced by the former Soviet bloc countries until 1980, and used in the USSR, China, Japan, and several African countries, may have been contaminated, meaning hundreds of millions more may have been exposed to SV40.

In 1998, the National Cancer Institute undertook a large study, using cancer case information from the institute's SEER database. The published findings from the study revealed no increased incidence of cancer in persons who may have received vaccine containing SV40. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial, however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy.

Doses of oral polio vaccine are added to sugar cubes for use in a 1967 vaccination campaign in Bonn, West Germany

During the race to develop an oral polio vaccine, several large-scale human trials were undertaken. By 1958, the National Institutes of Health had determined that OPV produced using the Sabin strains were the safest. Between 1957 and 1960, however, Hilary Koprowski continued to administer his vaccine around the world. In Africa, the vaccines were administered to roughly one million people in the Belgian territories (now the Democratic Republic of the Congo, Rwanda, and Burundi). The results of these human trials have been controversial, and unfounded accusations in the 1990s arose that the vaccine had created the conditions necessary for transmission of simian immunodeficiency virus from chimpanzees to humans, causing HIV/AIDS. These hypotheses, however, have been conclusively refuted. By 2004, cases of poliomyelitis in Africa had been reduced to just a small number of isolated regions in the western portion of the continent, with sporadic cases elsewhere. Recent local opposition to vaccination campaigns have evolved due to lack of adequate information, often relating to fears that the vaccine might induce sterility. The disease has since resurged in Nigeria and in several other African nations without necessary information, which epidemiologists believe is due to refusals by certain local populations to allow their children to receive the polio vaccine.

Manufacture

Inactivated

The Salk vaccine, IPV, is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome.

In the United States, vaccine is administered along with the tetanus, diphtheria, and acellular pertussis vaccines (DTaP) and a pediatric dose of hepatitis B vaccine. In the UK, IPV is combined with tetanus, diphtheria, pertussis, and Haemophilus influenzae type b vaccines.

Attenuated

Sabin immunization certificate

 

Example of OPV in dragee candy

OPV is an attenuated vaccine, produced by the passage of the virus through nonhuman cells at a subphysiological temperature, which produces spontaneous mutations in the viral genome. Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin. Other groups, led by Hilary Koprowski and H.R. Cox, developed their own attenuated vaccine strains. In 1958, the National Institutes of Health created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio, while retaining a low incidence of neuropathogenicity in monkeys. Large-scale clinical trials performed in the Soviet Union in late 1950s to early 1960s by Mikhail Chumakov and his colleagues demonstrated safety and high efficacy of the vaccine. Based on these results, the Sabin strains were chosen for worldwide distribution. Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. The primary attenuating factor common to all three Sabin vaccines is a mutation located in the virus's internal ribosome entry site, which alters stem-loop structures and reduces the ability of poliovirus to translate its RNA template within the host cell. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV (TOPV) was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. A second wave of mass immunizations led to a further dramatic decline in the number of polio cases. Between 1962 and 1965, about 100 million Americans (roughly 56% of the population at that time) received the Sabin vaccine. The result was a substantial reduction in the number of poliomyelitis cases, even from the much-reduced levels following the introduction of the Salk vaccine.

OPV is usually provided in vials containing 10–20 doses of vaccine. A single dose of oral polio vaccine (usually two drops) contains 1,000,000 infectious units of Sabin 1 (effective against PV1), 100,000 infectious units of the Sabin 2 strain, and 600,000 infectious units of Sabin 3. The vaccine contains small traces of antibiotics—neomycin and streptomycin—but does not contain preservatives.

History

In a generic sense, vaccination works by priming the immune system with an 'immunogen'. Stimulating immune response, by use of an infectious agent, is known as immunization. The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community.

The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest states.

1935

Two separate teams, led by John Kolmer and Maurice Brodie respectively, developed polio vaccines and reported their results at the annual meeting of the American Public Health Association in November 1935. Despite promising results, both were cancelled as a result of the angry reaction from other researchers, as vaccinated children had died in both studies. It would be another 20 years before a successful polio vaccine achieved government licensure.

John Kolmer (1886–1962), of Temple University, presented his findings first. He had developed an attenuated poliovirus vaccine, which he tested in about 10,000 children across much of the United States and Canada. Five of these children died of polio and 10 more were paralyzed, usually in the arm where the vaccine was injected, and frequently affecting children in towns where no polio outbreak had occurred. He had no control group, but asserted that many more children would have gotten sick. The response from other researchers was uncharacteristically blunt; one of them directly called Kolmer a murderer.

Maurice Brodie, a young researcher at New York University and the New York City Health Department, presented his results afterwards, but the feelings of the researchers were already unfavorable before he started because of Kolmer's report. Brodie and his team had prepared a formaldehyde-killed poliovirus vaccine, testing it first on himself and five co-workers, and eventually on 7,500 children and adults, with another 4,500 people serving as a control group. In the control group, Brodie reported that one out of 900 developed polio; in the group receiving the vaccine, only one out of 7,500 developed polio, making the vaccine 88% effective during the first year. However, other researchers believed that the one case was likely caused by the vaccine, and two more possible cases were reported later.

After this meeting, Brodie, whose polio vaccine was at least partially effective and reasonably safe, and who developed several ground-breaking ideas about vaccination whose validity was confirmed two decades later with the development of the Salk vaccine, was immediately fired and had trouble finding employment again. Brodie died three and a half years later. Kolmer, an established researcher whose vaccine was unsafe and probably ineffective, kept his job, was given a second appointment as professor of medicine at the Temple University School of Dentistry the next year, continued to publish research papers, and received multiple awards throughout his academic career.

1948

A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948, Thomas H. Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that there were a few unused tubes. He retrieved a sample of mouse brain infected with polio virus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow, but the polio cultures were successful. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized in 1954 for their labors with a Nobel Prize in Physiology or Medicine. Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotypes (Poliovirus type 1 – PV1, or Mahoney; PV2, Lansing; and PV3, Leon); the finding that prior to paralysis, the virus must be present in the blood; and the demonstration that administration of antibodies in the form of gamma globulin protects against paralytic polio.

1950–1955

1955 newspaper headlines on the development of an effective polio vaccine

During the early 1950s, polio rates in the U.S. were above 25,000 annually; in 1952 and 1953, the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, respectively, up from a typical number of some 20,000 a year, with deaths in those years numbering 3,200 and 1,400. Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox. Also working at Lederle was Polish-born virologist and immunologist Hilary Koprowski of the Wistar Institute in Philadelphia, who tested the first successful polio vaccine, in 1950. His vaccine, however, being a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salk's polio vaccine (a dead-virus injectable vaccine) had reached the market. Koprowski's attenuated vaccine was prepared by successive passages through the brains of Swiss albino mice. By the seventh passage, the vaccine strains could no longer infect nervous tissue or cause paralysis. After one to three further passages on rats, the vaccine was deemed safe for human use. On 27 February 1950, Koprowski's live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village, an institution for the physically and mentally disabled located in New York. After the child suffered no side effects, Koprowski enlarged his experiment to include 19 other children.

Jonas Salk

Administration of the polio inoculation, including by Salk himself, in 1957 at the University of Pittsburgh, where his team had developed the vaccine

 

Mass polio vaccination in Columbus, Georgia circa 1961 for the National Polio Immunization Program

The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, which required years of subsequent testing. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later, the results were published in JAMA. Leone N. Farrell invented a key laboratory technique that enabled the mass production of the vaccine by a team she led in Toronto. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania.

Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis, the largest medical experiment in history at that time. The test began with about 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and eventually involved 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio. The results of the field trial were announced 12 April 1955 (the tenth anniversary of the death of President Franklin D. Roosevelt, whose paralytic illness was generally believed to have been caused by polio). The Salk vaccine had been 60–70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. Soon after Salk's vaccine was licensed in 1955, children's vaccination campaigns were launched. In the U.S, following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States.

A week before the announcement of the Francis Field Trial results in April 1955, Pierre Lépine at the Pasteur Institute in Paris had also announced an effective polio vaccine.

Safety incidents

In April 1955, soon after mass polio vaccination began in the US, the Surgeon General began to receive reports of patients who contracted paralytic polio about a week after being vaccinated with Salk polio vaccine from Cutter pharmaceutical company, with the paralysis limited to the limb the vaccine was injected into. The Cutter vaccine had been used in vaccinating 200,000 children in the western and midwestern United States. Later investigations showed that the Cutter vaccine had caused 40,000 cases of polio, killing 10. In response the Surgeon General pulled all polio vaccine made by Cutter Laboratories from the market, but not before 250 cases of paralytic illness had occurred. Wyeth polio vaccine was also reported to have paralyzed and killed several children. It was soon discovered that some lots of Salk polio vaccine made by Cutter and Wyeth had not been properly inactivated, allowing live poliovirus into more than 100,000 doses of vaccine. In May 1955, the National Institutes of Health and Public Health Services established a Technical Committee on Poliomyelitis Vaccine to test and review all polio vaccine lots and advise the Public Health Service as to which lots should be released for public use. These incidents reduced public confidence in polio vaccine, leading to a drop in vaccination rates.

1961

Albert Sabin (right) with Robert Gallo, circa 1985

At the same time that Salk was testing his vaccine, both Albert Sabin and Hilary Koprowski continued working on developing a vaccine using live virus. During a meeting in Stockholm to discuss polio vaccines in November 1955, Sabin presented results obtained on a group of 80 volunteers, while Koprowski read a paper detailing the findings of a trial enrolling 150 people. Sabin and Koprowski both eventually succeeded in developing vaccines. Because of the commitment to the Salk vaccine in America, Sabin and Koprowski both did their testing outside the United States, Sabin in Mexico and the Soviet Union, Koprowski in the Congo and Poland. In 1957, Sabin developed a trivalent vaccine containing attenuated strains of all three types of poliovirus. In 1959, ten million children in the Soviet Union received the Sabin oral vaccine. For this work, Sabin was given the medal of the Order of Friendship Among Peoples, described as the Soviets' highest civilian honor, Sabin's oral vaccine using live virus came into commercial use in 1961.

Once Sabin's oral vaccine became widely available, it supplanted Salk's injected vaccine, which had been tarnished in the public's opinion by the Cutter incident of 1955, in which Salk vaccines improperly prepared by one company resulted in several children dying or becoming paralyzed.

1987

An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice there. The first dose of polio vaccine is given shortly after birth, usually between 1 and 2 months of age, and a second dose is given at 4 months of age. The timing of the third dose depends on the vaccine formulation, but should be given between 6 and 18 months of age. A booster vaccination is given at 4 to 6 years of age, for a total of four doses at or before school entry. In some countries, a fifth vaccination is given during adolescence. Routine vaccination of adults (18 years of age and older) in developed countries is neither necessary nor recommended because most adults are already immune and have a very small risk of exposure to wild poliovirus in their home countries. In 2002, a pentavalent (five-component) combination vaccine (called Pediarix) containing IPV was approved for use in the United States.

1988

A Somali boy is injected with inactivated poliovirus vaccine (Mogadishu, 1993)

A global effort to eradicate polio, led by the World Health Organization (WHO), UNICEF, and the Rotary Foundation, began in 1988, and has relied largely on the oral polio vaccine developed by Albert Sabin and Mikhail Chumakov (Sabin-Chumakov vaccine).

After 1990

Polio was eliminated in the Americas by 1994. The disease was officially eliminated in 36 Western Pacific countries, including China and Australia, in 2000. Europe was declared polio-free in 2002. Since January 2011, no cases of the disease have been reported in India, hence in February 2012, the country was taken off the WHO list of polio-endemic countries. In March 2014, India was declared a polio-free country.

Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occur, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained. In November 2013, the WHO announced a polio outbreak in Syria. In response, the Armenian government put out a notice asking Syrian Armenians under age 15 to get the polio vaccine. As of 2014, polio virus had spread to 10 countries, mainly in Africa, Asia, and the Middle East, with Pakistan, Syria, and Cameroon advising vaccinations to outbound travelers.

Polio vaccination programs have received resistance from some people in Pakistan, Afghanistan, and Nigeria (the three countries as of 2017 with remaining polio cases). Some Muslim religious leaders believe that the vaccines are secretly being used for sterilization of Muslims. The fact that the CIA organized a fake vaccination program in 2011 to help find Osama Bin Laden is an additional cause of distrust. In 2015, the WHO announced a deal with the Taliban to encourage them to distribute the vaccine in areas they control. However, the Pakistani Taliban was not supportive. On 11 September 2016, two unidentified gunmen associated with the Pakistani Taliban, Jamaat-ul-Ahrar, shot Zakaullah Khan, a doctor who was administering polio vaccines in Pakistan. The leader of the Jamaat-ul-Ahrar claimed responsibility for the shooting and stated that the group would continue this type of attack. Such resistance to and skepticism of vaccinations has consequently slowed down the polio eradication process within the three remaining endemic countries.

Travel requirements

Polio vaccination is required for travellers...

  From all countries, to all countries

  From some countries, to all countries

  From some countries, to all countries

  From some countries, to some countries

  To some countries

  From some countries

Travellers who wish to enter or leave certain countries must be vaccinated against polio, usually at most 12 months and at least 4 weeks before crossing the border, and be able to present a vaccination record/certificate at the border checks. Most requirements apply only to travel to or from so-called 'polio-endemic', 'polio-affected', 'polio-exporting', 'polio-transmission', or 'high-risk' countries. As of August 2020, Afghanistan and Pakistan are the only polio-endemic countries in the world (where wild polio has not yet been eradicated). Several countries have additional precautionary polio vaccination travel requirements, for example to and from 'key at-risk countries', which as of December 2020 include China, Indonesia, Mozambique, Myanmar, and Papua New Guinea.

Polio vaccination requirements for international travel

Country	Details
Afghanistan	Travellers from polio-endemic countries (Pakistan) need Carte Jaune proof of polio vaccination (received between 4 weeks and 12 months before departure) upon arrival. Residents and ALL travellers staying in Afghanistan longer than 4 weeks need proof of polio vaccination (received between 4 weeks and 12 months before departure) when departing from Afghanistan.
Belize	Travellers from Afghanistan and Pakistan need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival. Belize residents travelling countries with confirmed polio cases also need proof of vaccination.
Brunei	Travellers from polio-exporting countries need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Egypt	Travellers from Afghanistan, Angola, Benin, Cameroon, the Central African Republic, China, Congo-Kinshasa, Ethiopia, Ghana, Indonesia, Kenya, Mozambique, Myanmar, Niger, Nigeria, Pakistan, Papua New Guinea, Philippines, and Somalia need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Georgia	Travellers from at-risk countries need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival. Travellers without proof are offered OPV vaccination upon arrival.
India	Travellers from Afghanistan, Congo-Kinshasa, Ethiopia, Kenya, Nigeria, Pakistan, Somalia, and Syria need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Iran	Travellers from Afghanistan, Pakistan, and Nigeria need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival. Travellers without proof will be vaccinated upon arrival.
Iraq	Travellers aged 15+ from Afghanistan and Pakistan need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival; children under age 15 must have received three doses of polio vaccine prior to travel. Travellers without proof will be vaccinated upon arrival. Travellers departing Iraq to Afghanistan and Pakistan must also provide proof of vaccination upon departure.
Jordan	Travellers from Afghanistan and Pakistan need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Lebanon	Travellers from and to polio-affected countries need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Libya	Travellers from Afghanistan and Pakistan need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Maldives	Travellers from and to polio-exporting countries, as well as Hajj and Umrah pilgrims, need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Morocco	Travellers from polio-affected countries need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Nepal	Travellers from Afghanistan, Kenya, Nigeria, Pakistan, and Papua New Guinea need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Oman	Travellers from polio-exporting countries need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Pakistan	Travellers from ALL countries planning to stay in Pakistan for more than 4 weeks need Carte Jaune proof of OPV vaccination upon arrival. Residents and ALL travellers staying in Pakistan longer than 4 weeks need proof of OPV vaccination when departing from Pakistan.
Philippines	Travellers from or to high-risk countries need Carte Jaune proof of polio vaccination upon arrival or before departure, respectively.[97] Due to an ongoing local VDPV2 outbreak, the government recommends all others travellers to consider getting a polio vaccine or booster dose, depending on their situation.
Qatar	Travellers from polio-exporting countries (identified by Qatar as: Afghanistan, Nigeria, Pakistan and Philippines) need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Saint Kitts and Nevis	Travellers from polio-endemic countries as identified by WHO (Afghanistan and Pakistan) need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Saudi Arabia	Travellers from active-transmission (including wild or vaccine-derived poliovirus) and at-risk countries, as well as all travellers from Afghanistan, Congo-Kinshasa, Mozambique, Myanmar, Niger, Nigeria, Pakistan, Papua New Guinea, Somalia, Syria, and Yemen need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival. Regardless of immunisation status, all travellers from Afghanistan, Myanmar, Nigeria, Pakistan, Papua New Guinea, Somalia, Syria, and Yemen will be given an Oral Polio Vaccine dose upon arrival.
Seychelles	Travellers from countries with polio outbreaks need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival.
Syria	Travellers from Cameroon, Equatorial Guinea, and Pakistan need Carte Jaune proof of OPV or IPV vaccination (received between 4 weeks and 12 months before departure) upon arrival. ALL Syria residents departing Syria to any country also need proof of vaccination.
Ukraine	Long-term visitors departing to states with wild or circulating vaccine-derived poliovirus transmission should present Carte Jaune proof of vaccination with at least one dose of bivalent OPV or IPV (received between 4 weeks and 12 months before departure). Persons obliged to undertake urgent international travel must be immunised with a single dose of polio vaccine prior to their departure. There is also risk of polio virus transmission inside Ukraine itself, and travellers to Ukraine are recommended to be up to date with their polio vaccination before entry.

Society and culture

Cost

The Global Alliance for Vaccines and Immunization supplies the inactivated vaccine to developing countries for as little as €0.75 (about US$0.86) per dose in 10-dose vials, in 2015.

Misconceptions

A misconception has been present in Pakistan that polio vaccine contained haram ingredients and could cause impotence and infertility in male children, leading some parents not to have their children vaccinated. This belief is most common in the Khyber Pakhtunkhwa province and the FATA region. Attacks on polio vaccination teams have also occurred, thereby hampering international efforts to eradicate polio in Pakistan and globally.