Eradication of infectious diseases

Eradication is the reduction of an infectious disease's prevalence in the global host population to zero.[1] It is sometimes confused with elimination, which describes either the reduction of an infectious disease's prevalence in a regional population to zero, or the reduction of the global prevalence to a negligible amount. Further confusion arises from the use of the term eradication to refer to the total removal of a given pathogen from an individual (also known as clearance of an infection), particularly in the context of HIV and certain other viruses where such cures are sought.

Selection of infectious diseases for eradication is based on rigorous criteria, as both biological and technical features determine whether a pathogenic organism is (at least potentially) eradicable. The targeted organism must not have a non-human reservoir (or, in the case of animal diseases, the infection reservoir must be an easily identifiable species, as in the case of rinderpest), and/or amplify in the environment. This implies that sufficient information on the life cycle and transmission dynamics is available at the time an eradication initiative is programmed. An efficient and practical intervention (e.g., a vaccine or antibiotic) must be available to interrupt transmission of the infective agent. Studies of measles in the pre-vaccination era led to the concept of the Critical community size, the size of the population below which a pathogen ceases to circulate.[2] Use of vaccination programmes before the introduction of an eradication campaign can reduce the susceptible population. The disease to be eradicated should be clearly identifiable, and an accurate diagnostic tool should exist. Economic considerations, as well as societal and political support and commitment, are other crucial factors that determine eradication feasibility.[3][4]

Eight attempts have been made to date to eradicate infectious diseases: two successful programs targeting smallpox and rinderpest; four ongoing programs targeting poliomyelitis, yaws, dracunculiasis and malaria; and two former programs targeting hookworm and yellow fever. Five more infectious diseases have been identified as of April 2008 as potentially eradicable with current technology by the Carter Center International Task Force for Disease Eradication—measles, mumps, rubella, lymphatic filariasis and cysticercosis.[5]

Eradicated

So far, two diseases have been successfully eradicated—one specifically affecting humans (smallpox), and one affecting a wide range of ruminants (rinderpest).

Smallpox

Main article: Smallpox

Smallpox was the first disease, and so far the only infectious disease of humans, to be eradicated by deliberate intervention.[6] It became the first disease for which there was an effective vaccine in 1798 when Edward Jenner showed the protective effect of inoculation (vaccination) of humans with material from cowpox lesions.[7]

Smallpox (variola) occurred in two clinical varieties: variola major, with a mortality rate of up to 40 percent and variola minor, also known as alastrim, with a mortality rate less than 1 percent. The last naturally occurring case of Variola major was diagnosed in October 1975 in Bangladesh. The last naturally occurring case of smallpox (Variola minor) was diagnosed on 26 October 1977, on Ali Maow Maalin, in the Merca District, of Somalia. The source of this case was a known outbreak in the nearby district of Kurtuware. All 211 contacts were traced, revaccinated, and kept under surveillance.[8]

Boy with smallpox.(1969). Last natural smallpox case was of Ali Maow Maalin, in, Merca, Somalia, on October 26:1977.[9][10]

After two years' detailed analysis of national records the global eradication of smallpox was certified by an international commission of smallpox clinicians and medical scientists on December 9, 1979, and endorsed by the General Assembly of the World Health Organization on May 8, 1980.[6] However, there is an ongoing controversy regarding the continued storage of the smallpox virus by labs in the US and Russia, as any accidental or deliberate release could create a new epidemic for persons born after or in the late 1980s due to the cessation of vaccinations against the smallpox virus.

Rinderpest

Main article: Rinderpest

During the 20th century, there were a series of campaigns to eradicate rinderpest, a viral disease which infected cattle and other ruminants and belonged to the same family as measles, primarily through the use of a live attenuated vaccine.[11] The final, successful campaign was led by the Food and Agriculture Organization (FAO) of the United Nations. On 14 October 2010, with no diagnoses for nine years, the FAO announced that the disease had been completely eradicated,[12] making this the first (and so far the only) disease of livestock to have been eradicated by human undertakings.

Global eradication underway

Poliomyelitis (polio)

International Wild Poliovirus Cases by Year
Year Estimated Recorded
1975 49,293
1980 400,000 52,552
1985 38,637
1988 350,000 35,251
1990 23,484
1993 100,000 10,487
1995 7,035
2000 2,971[13]
2001 483
2002 1,922
2003 784
2004 1,258
2005 1,998
2006 1,985
2007 1,315
2008 1,651
2009 1,604
2010 1,352
2011 650
2012 222
2013 385
2014 359
2015 73
References:[14][15][16][17][18][19][20]

A dramatic reduction of the incidence of poliomyelitis in industrialized countries followed the development of a vaccine in the 1950s. In 1960, Czechoslovakia became the first country certified to have eliminated polio.

In 1988, the World Health Organization (WHO), Rotary International, the United Nations Children's Fund (UNICEF), and the U.S. Centers for Disease Control and Prevention (CDC) passed the Global Polio Eradication Initiative. Its goal was to eradicate polio by the year 2000. The updated strategic plan for 2004–2008 expects to achieve global eradication by interrupting poliovirus transmission, using the strategies of routine immunization, supplementary immunization campaigns, and surveillance of possible outbreaks. The WHO estimates that global savings from eradication, due to forgone treatment and disability costs, could exceed one billion U.S. dollars per year.[21]

The following world regions have been declared polio-free:

The lowest annual polio prevalence seen so far was in 2015, with 70 reported cases. Two further countries remain in which poliovirus transmission has never been interrupted (Pakistan, and Afghanistan).[23][24] Nigeria was removed from the WHO list of polio-endemic countries in September 2015, and India in 2014[25] after no new cases were reported for one year.[26]

On September 20, 2015, the World Health Organization announced that wild poliovirus type 2 had been eradicated worldwide.

Dracunculiasis

International Guinea Worm Cases by Year [27][28][29][30]
Year Reported Cases Countries
1989 892,055 16
1995 129,852 19
2000 75,223 16
2001 63,717 16
2002 54,638 14
2003 32,193 13
2004 16,026 13
2005 10,674 12
2006 25,217[31] 10
2007 9,585 9
2008 4,619 7
2009 3,190 5
2010 1,797 6
2011 1,060 4
2012 542 4
2013 148 5
2014 126 4 [32]
2015 22 4

Dracunculiasis, also called guinea worm disease, is a painful and disabling parasitic disease caused by a worm, Dracunculus medinensis. It is spread through consumption of drinking water infested with copepods hosting Dracunculus larvae. The Carter Center has led the effort to eradicate the disease, along with the CDC, the WHO, UNICEF, and the Bill and Melinda Gates Foundation.

Unlike diseases such as smallpox and polio, there is no vaccine or drug therapy for guinea worm. Eradication efforts have been based on making drinking water supplies safer (e.g. by provision of borehole wells, or through treating the water with larvicide), on containment of infection and on education for safe drinking water practices. These strategies have produced many successes: two decades of eradication efforts have reduced guinea worm's global incidence to 22 cases in 2015, down from an estimated 3.5 million in 1986. Success has been slower than was hoped—the original goal for eradication was 1995. The WHO has certified 180 countries free of the disease, and only four countries — South Sudan, Mali, Ethiopia, and Chad — reported cases of guinea worm in 2015. [28][33][34] As of 2010, the WHO predicted it would be "a few years yet" before eradication is achieved, on the basis that it took 6–12 years for the countries that have so far eliminated guinea worm transmission to do so after reporting a similar number of cases to that reported by Sudan in 2009.[35] Cases in 2015 are less than 1% of the number in 2009, so real progress has been made towards this prediction. Nonetheless, the last 1% may be the hardest.[33]

Yaws

Yaws is a rarely fatal but highly disfiguring disease caused by the spiral-shaped bacterium (spirochete) Treponema pallidum pertenue, a relative of the syphilis bacteria Treponema pallidum pallidum, spread through skin to skin contact with infectious lesions. The global prevalence of this disease and the other endemic treponematoses, bejel and pinta, was reduced by the Global Control of Treponematoses (TCP) programme between 1952 and 1964 from about 50 million cases to about 2.5 million (a 95% reduction). However, following the cessation of this program these diseases remained at a low prevalence in parts of Asia, Africa and the Americas with sporadic outbreaks. According to the new official WHO roadmap, the elimination should be achieved by 2020.[36][37] Yaws is currently targeted by the South-East Asian Regional Office of the WHO for elimination from the remaining endemic countries in this region (India, Indonesia and East Timor) by 2010, and so far, this appears to have met with some success, since no cases have been seen in India since 2004.[38][39] The discovery that oral antibiotic azithromycin can be used instead of the previous standard, injected penicillin, was tested on Lihir Island from 2013-2014;[40] a single oral dose of the macrolide antibiotic reduced disease prevalance from 2.4% to 0.3% at 12 months.[41] The campaign was in an early stage in 2013, still gathering data on disease incidence and planning initial large-scale treatment campaigns in Cameroon, Ghana, Indonesia, Papua New Guinea, the Solomon Islands, and Vanuatu.[42]

Malaria

Malaria elimination has already been achieved in most of Europe, North America, Australia, North Africa and the Caribbean, and parts of South America, Asia and Southern Africa, according to the Malaria Elimination Group at UCSF.[43] The WHO defines elimination as having no domestic transmission for the past three years. They also define an "elimination stage" when a country is on the verge of eliminating malaria, as being <1 case per 1000 people at risk per year. According to the 2011 WHO World Malaria Report,[44] 28 countries are certified as having eliminated malaria. Eight countries appear to be malaria free but steps still need to be taken to ensure they do not re-establish transmission. Nine countries are in the elimination stage and eight the pre-elimination stage (<5 cases per 1000 people at risk per year).[44]

At the Gates Foundation Malaria Forum in October 2007, Bill and Melinda Gates called for a new plan for malaria eradication, by going as far as possible with existing tools while also investing in new ones.[45][46] Nearly a year later, on September 25, 2008, the Roll Back Malaria (RBM) Partnership unveiled the Global Malaria Action Plan (GMAP), in which a series of measures were proposed to eliminate malaria as a global public health concern by 2015, eliminate all malaria transmission within 8–10 countries by the same deadline, and build towards its eventual global eradication.[47] The Malaria Policy Advisory Committee (MPAC) of the World Health Organization (WHO) was formed in 2012, "to provide strategic advice and technical input to WHO on all aspects of malaria control and elimination".[48] In November 2013, WHO and the malaria vaccine funders group set a goal to develop vaccines designed to interrupt malaria transmission with the long-term goal of malaria eradication.[49]

Regional elimination established or under way

Some diseases have already been eliminated from large regions of the world, and/or are currently being targeted for regional elimination. This is sometimes described as "eradication", although technically the term only applies when this is achieved on a global scale.[50] Even after regional elimination is successful, interventions often need to continue to prevent a disease becoming re-established. Three of the diseases here listed (lymphatic filariasis, measles, and rubella) are among the diseases believed to be potentially eradicable by the International Task Force for Disease Eradication, and if successful, regional elimination programs may yet prove a stepping stone to later global eradication programs.

This section does not cover elimination where it is used to mean control programs sufficiently tight to reduce the burden of an infectious disease or other health problem to a level where they may be deemed to have little impact on public health, such as the leprosy, neonatal tetanus, or obstetric fistula campaigns.

Hookworm

In North American countries, such as the United States, elimination of hookworm had been attained due to scientific advances. The Rockefeller Foundation's hookworm campaign in the 1920s was supposed to focus on the eradication of hookworm infections for those living in Mexico and other rural areas. However, the campaign was politically influenced, causing it to be less successful, and regions such as Mexico still deal with these infections from parasitic worms. This use of health campaigns by political leaders for political and economic advantages has been termed the science-politics paradox.[51]

Lymphatic filariasis

Lymphatic filariasis is an infection of the lymph system by mosquito-borne microfilarial worms which can cause elephantiasis. Studies have demonstrated that transmission of the infection can be broken when a single dose of combined oral medicines is consistently maintained annually for approximately seven years.[52] The strategy for eliminating transmission of lymphatic filariasis is mass distribution of medicines that kill the microfilariae and stop transmission of the parasite by mosquitoes in endemic communities.[52] In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world albendazole is used with diethylcarbamazine.[53] Using a combination of treatments better reduces the number of microfilariae in blood.[52] Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.[52][54] In the Americas, >90% of the burden of lymphatic filariasis is on the island of Hispaniola (comprising Haiti and the Dominican Republic). An elimination effort to address this is currently under way alongside the malaria effort described above; the Dominican Republic expects to eliminate its seven remaining foci by 2010, but lymphatic filariasis is still endemic to 110 of 140 communes in Haiti.[55]

As of October 2008, the efforts of the Global Programme to Eliminate LF are estimated to have already prevented 6.6 million new filariasis cases from developing in children, and to have stopped the progression of the disease in another 9.5 million people who have already contracted it. Overall, of 83 endemic countries, mass treatment has been rolled out in 48, and elimination of transmission reportedly achieved in 21.[56]

Measles

Five out of six WHO regions have goals to eliminate measles, and at the 63rd World Health Assembly in May 2010, delegates agreed to move towards eventual eradication, although no specific global target date has yet been agreed.[57][58][59] The Americas set a goal in 1994 to eliminate measles and rubella transmission by 2000, and successfully achieved regional measles elimination in 2002, although there have been occasional small outbreaks from imported cases since then.[60] Europe had set a goal to eliminate measles transmission by 2010, but were hindered by the MMR vaccine controversy and by low uptake in certain groups, and despite achieving low levels by 2008, European countries have since experienced a small resurgence in cases. They have set a new target of 2015.[61] The Eastern Mediterranean also had goals to eliminate measles by 2010 (later revised to 2015), the Western Pacific aims to eliminate the disease by 2012, and in 2009 the regional committee for Africa agreed a goal of measles elimination by 2020. As of May 2010, only the South-East Asian region has yet to set a target date for elimination of measles transmission.[57]

In 2005, a global target was agreed for a 90% reduction in measles deaths by 2010 from the 757,000 deaths in 2000; estimates for 2008 show a 78% decline so far to 164,000 deaths.[62] However, some have been pushing to attempt global eradication.[63] This was updated at the 2010 World Health Assembly to a targeted 95% reduction in mortality by 2015, alongside specific vaccination and structural targets,[57][58] and in a meeting in November 2010, the Strategic Advisory Group of Experts on Immunization "concluded that measles can and should be eradicated".[64] A study of the costs of eradicating measles compared to the costs of maintaining indefinite control was commissioned in 2009 by the WHO and the Bill and Melinda Gates Foundation.[65] In 2013, measles deaths globally were down to 145,700.[66]

As of mid 2013, measles elimination in many areas is stalling. "This year, measles and rubella outbreaks are occurring in many areas of the world where people have no immunity to these viruses. The reasons people are unvaccinated range from lack of access to vaccines in areas of insecurity, to poor performing health systems, to vaccine refusals. We need to address each of these challenges if we’re going to meet global measles and rubella elimination goals," said Dr. Myrna Charles of the American Red Cross, as reported in a post in the Measles and Rubella Initiative's blog.[67] A look at the WHO’s epidemiological graph of measles over time from 2008-2013 show that, with little more of two years to go to 2015, measles cases in 2013 are moving in the wrong direction, with more cases this year than at the same point in 2012 or 2011.[68]

During 2014 there were 23 outbreaks of measles in the USA and over 600 individual cases, which is the highest seen in decades. In 2015 the US has had one major outbreak of measles originating from an amusement park in California of a variant of the virus circulating in the Philippines in 2014. From this there have been 113 individual measles cases and one death (out of the total of 189 cases in the U.S. in 2015).[69][70]

Rubella

Main article: Rubella

The WHO region of the Americas declared on 29 April 2015 it had eliminated rubella and congenital rubella syndrome.[71] The last confirmed endemic case of rubella in the Americas was in Argentina in February 2009.[72][71]

The WHO European region missed its elimination target of 2010 due to undervaccination in Central and Western Europe; it has set a new goal of 2015.[73]

The disease remains problematic in other regions; in Japan, there were 15,000 cases in 2013.[71]

Onchocerciasis

Onchocerciasis (river blindness) is the world's second leading cause of infectious blindness. It is caused by the nematode Onchocerca volvulus, which is transmitted to people via the bite of a black fly. Elimination of this disease is under way in the region of the Americas, where this disease is endemic to Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela. The principal tool being used is mass ivermectin treatment. If successful, the only remaining endemic locations would be in Africa and Yemen.[74] In Africa, it is estimated that greater than 102 million people in 19 countries are at high risk of onchocerciasis infection, and in 2008, 56.7 million people in 15 of these countries received community-directed treatment with ivermectin. Since adopting such treatment measures in 1997, the African Programme for Onchocerciasis Control reports a reduction in the prevalence of onchocerciasis in the countries under its mandate from a pre-intervention level of 46.5% in 1995 to 28.5% in 2008.[75] Some African countries, such as Uganda,[76] are also attempting elimination and successful elimination was reported in 2009 from two endemic foci in Mali and Senegal.[77]

On July 29, 2013, the Pan American Health Organization (PAHO) announced that after 16 years of efforts, Colombia had become the first country in the world to eliminate the parasitic disease onchocerciasis.[78]

Bovine spongiform encephalopathy (BSE) and new variant Creutzfeldt–Jakob disease (vCJD)

Following an epidemic of vCJD in the UK in the 1990s, there have been campaigns to eliminate BSE in cattle across the EU and beyond which appear to have achieved large reductions in the number of cattle with this disease.[79] Cases of vCJD have also fallen since then, for instance from an annual peak of 29 cases in 2000 to 5 cases in 2008 and zero in 2012. However, since then 2 cases have been reported in both 2013 and 2014: 2 in France; 1 in the United Kingdom; and 1 in the United States.[80][81]

Following the ongoing eradication effort, only 7 cases of BSE were reported worldwide in 2013: 3 in the United Kingdom; 2 in France; 1 in Ireland; and 1 in Poland. This is the lowest number of cases since at least 1988.[82][83] In 2015 there were at least 6 reported cases (3 were of the atypical H-type).[84]

Syphilis

In 2015, Cuba became the first country in the world to eradicate mother-to-child syphilis.[85]

Rabies

Main article: Prevalence of rabies
Rabies-free countries as of 2010

Because the rabies virus is almost always caught from animals, rabies eradication has focused on reducing the population of wild and stray animals, controls and compulsory quarantine on animals entering the country, and vaccination of pets and wild animals. Many island nations, including Iceland, Ireland, Japan, Malta and the United Kingdom managed to eradicate rabies during the twentieth century,[86] and more recently much of continental Europe has been declared rabies-free.[87]

Other eradicable diseases

As far as animal diseases are concerned, now that rinderpest has been stamped out, many experts believe peste des petits ruminants (PPR) is the next disease amenable to global eradication. Also known as goat plague or ovine rinderpest, PPR is a highly contagious viral disease of goats and sheep characterized by fever, painful sores in the mouth, tongue and feet, diarrhoea, pneumonia and death, especially in young animals. It is caused by a virus of the genus Morbillivirus that is related to rinderpest, measles and canine distemper.[88]

See also

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