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Sunday, September 1, 2024

Eradication of infectious diseases

A child with smallpox. In 1980, the World Health Organization announced the global eradication of smallpox. It is the only human disease to be eradicated worldwide.

The eradication of infectious diseases is the reduction of the prevalence of an infectious disease in the global host population to zero.

Two infectious diseases have successfully been eradicated: smallpox in humans, and rinderpest in ruminants. There are four ongoing programs, targeting the human diseases poliomyelitis (polio), yaws, dracunculiasis (Guinea worm), and malaria. 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 Eradicationmeasles, mumps, rubella, lymphatic filariasis (elephantiasis) and cysticercosis (pork tapeworm).

The concept of disease eradication is sometimes confused with disease elimination, which is 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.

The targeting of infectious diseases for eradication is based on narrow criteria, as both biological and technical features determine whether a pathogenic organism is (at least potentially) eradicable. The targeted pathogen must not have a significant non-human (or non-human-dependent) reservoir (or, in the case of animal diseases, the infection reservoir must be an easily identifiable species, as in the case of rinderpest). This requires sufficient understanding of the life cycle and transmission of the pathogen. An efficient and practical intervention (such as a vaccine or antibiotic) must be available to interrupt transmission. Studies of measles in the pre-vaccination era led to the concept of the critical community size, the minimal size of the population below which a pathogen ceases to circulate. The use of vaccination programs 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.

Eradicated diseases

So far, only two diseases have been successfully eradicated—one specifically affecting humans (smallpox) and one affecting cattle (rinderpest).

Smallpox

Boy with smallpox (1969). The last natural smallpox case was of Ali Maow Maalin, in Merca, Somalia, on 26 October 1977.

Smallpox is the first disease, and so far the only infectious disease of humans, to be eradicated by deliberate intervention. 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.

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 of less than one 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, in Ali Maow Maalin, in the Merca District, of Somalia. The source of this case was an outbreak in the nearby district of Kurtunwarey. All 211 contacts were traced, revaccinated, and kept under surveillance.

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 9 December 1979, and endorsed by the General Assembly of the World Health Organization on 8 May 1980. However, there is an ongoing debate 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 in people born since the late 1980s due to the cessation of vaccinations against the smallpox virus.

Rinderpest

During the twentieth century, there were a series of campaigns to eradicate rinderpest, a viral disease that infected cattle and other ruminants and belonged to the same family as measles, primarily through the use of a live attenuated vaccine. The final, successful campaign was led by the Food and Agriculture Organization of the United Nations. On 14 October 2010, with no diagnoses for nine years, the FAO announced that the disease had been completely eradicated, 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
2005 1,998
2010 1,352
2011 650
2012 222
2013 385
2014 359
2015 74
2016 37
2017 22
2018 33
2019 176
2020 140
2021 6
2022 30
2023 12

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 United States 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.

The following world regions have been declared polio-free:

The lowest annual wild polio prevalence seen so far was in 2017, with only 22 reported cases, although there were more total reported cases (including circulated vaccine-derived cases) than in 2016, mainly due to reporting of circulated vaccine-derived cases in Syria, where it likely had already been circulating, but gone unreported, presumably due to the civil war. Only two or three countries remain in which poliovirus transmission may never have been interrupted: Pakistan, Afghanistan, and maybe Nigeria. (There have been no cases caused by wild strains of poliovirus in Nigeria since August 2016, though cVDPV2 was detected in environmental samples in 2017.) Nigeria was removed from the WHO list of polio-endemic countries in September 2015 but added back in 2016, and India was removed in 2014 after no new cases were reported for one year.

On 20 September 2015, the World Health Organization announced that wild poliovirus type 2 had been eradicated worldwide, as it has not been seen since 1999. On 24 October 2019, the World Health Organization announced that wild poliovirus type 3 had also been eradicated worldwide. This leaves only wild poliovirus type 1 and vaccine-derived polio circulating in a few isolated pockets, with all wild polio cases after August 2016 in Afghanistan and Pakistan.

Dracunculiasis

International Guinea worm cases by year
Year Reported cases Countries
1989 892,055 16
1995 129,852 19
2000 75,223 16
2005 10,674 12
2010 1,797 6
2011 1,060 4
2012 542 4
2013 148 5
2014 126 4
2015 22 4
2016 25 3
2017 30 2
2018 28 3
2019 54 4
2020 27 6
2021 15 4
2022 12 3

Dracunculiasis, also called Guinea worm disease, is a painful and disabling parasitic disease caused by the nematode 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 dramatically from over 100,000 in 1995 to less than 100 cases since 2015. While 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 in 2020 six countries—South Sudan, Ethiopia, Mali, Angola, Cameroon and Chad—reported cases of guinea worm. 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. Nonetheless, the last 1% of the effort may be the hardest, with cases not substantially decreasing from 2015 (22) to 2020 (24). As a result of missing the 2020 target, the WHO has revised its target for eradication to 2030. The worm is now understood to be able to infect dogs, domestic cats and baboons as well as humans, providing a natural reservoir for the pathogen and thus complicating eradication efforts. In response, the eradication effort is now also targeting animals (especially wild dogs) for treatment and isolation since animal infections far outnumber human infections now (in 2020 Chad reported 1570 animal infections and 12 human infections).

Yaws

"Yaws elimination in India – a step towards eradication"

Yaws is a rarely fatal but highly disfiguring disease caused by the spiral-shaped bacterium (spirochete) Treponema pallidum pertenue, a close relative of the syphilis bacterium 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 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. In 2012, the WHO targeted the disease for eradication by 2020, a goal that was missed.

As of 2020, there were 15 countries known to be endemic for yaws, with the recent discovery of endemic transmission in Liberia and the Philippines. In 2020, 82,564 cases of yaws were reported to the WHO and 153 cases were confirmed. The majority of the cases are reported from Papua New Guinea and with over 80% of all cases coming from one of three countries in the 2010-2013 period: Papua New Guinea, Solomon Islands, and Ghana. A WHO meeting report in 2018 estimated the total cost of elimination to be US$175 million (excluding Indonesia). In the South-East Asian Regional Office of the WHO, the eradication efforts are focused on the remaining endemic countries in this region (Indonesia and East Timor) after India was declared free of yaws in 2016.

The discovery that oral antibiotic azithromycin can be used instead of the previous standard, injected penicillin, was tested on Lihir Island from 2013 to 2014; a single oral dose of the macrolide antibiotic reduced disease prevalence from 2.4% to 0.3% at 12 months. The WHO now recommends both treatment courses (oral azithromycin and injected penicillin), with oral azithromycin being the preferred treatment.

Malaria

1962 Pakistani postage stamp promoting malaria eradication program
From 1962

Malaria has been eliminated from most of Europe, North America, Australia, North Africa and the Caribbean, and parts of South America, Asia and Southern Africa. The WHO defines "elimination" (or "malaria free") as having no domestic transmission (indigenous cases) for the past three years. They also define "pre-elimination" and "elimination" stages when a country has fewer than 5 or 1, respectively, cases per 1000 people at risk per year.

In 1955, WHO launched the Global Malaria Eradication Program. Support waned, and the program was suspended in 1969. Since 2000, support for eradication has increased, although some actors in the global health community (including voices within the WHO) thought that eradication as goal was premature and that setting strict deadlines for eradication may be counterproductive as they are likely to be missed.

According to the WHO's World Malaria Report 2015, the global mortality rate for malaria fell by 60% between 2000 and 2015. The WHO targeted a further 90% reduction between 2015 and 2030, with a 40% reduction and eradication in 10 countries by 2020. However, the 2020 goal was missed with a slight increase in cases compared to 2015.

While 31 out of 92 endemic countries were estimated to be on track with the WHO goals for 2020, 15 countries reported an increase of 40% or more between 2015 and 2020. Between 2000 and 30 June 2021, twelve countries were certified by the WHO as being malaria-free. Argentina and Algeria were declared free of malaria in 2019. El Salvador and China were declared malaria free in the first half of 2021.

Regional disparities were evident: Southeast Asia was on track to meet WHO's 2020 goals, while Africa, Americas, Eastern Mediterranean and West Pacific regions were off-track. The six Greater Mekong Subregion countries aim for elimination of P. falciparum transmitted malaria by 2025 and elimination of all malaria by 2030, having achieved a 97% and 90% reduction of cases respectively since 2000. Ahead of World Malaria Day, 25 April 2021, WHO named 25 countries in which it is working to eliminate malaria by 2025 as part of its E-2025 initiative.

A major challenge to malaria elimination is the persistence of malaria in border regions, making international cooperation crucial.

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. 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. In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world albendazole is used with diethylcarbamazine. Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis. In the Americas, 95% 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; both countries intend to eliminate the disease by 2020.

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.

Regional elimination established or underway

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. 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.

Other worm infections

Other than Dracunculiasis and lymphatic filariasis, there is no global commitment to eliminate helminthiasis (worm infections); however, the London Declaration on Neglected Tropical Diseases and the WHO aim to control worm infections, including schistosomiasis and soil-transmitted helminthiasis (which are caused by roundworms, whipworms and hookworms). It is estimated that between 576 and 740 million individuals are infected with hookworm. Of these infected individuals, about 80 million are severely affected.

Soil-transmitted helminthiasis

The current WHO goals are to control soil-transmitted helminthiasis (STH) by 2020 to a point where it does not pose a serious public health problem any more in children and 75% of children have received deworming interventions. By 2018, an average of 60% of school children were reached, however only 16 countries reached more than 75% coverage of pre-school children and 28 countries reached over 75% coverage of school-age children. In 2018, the number of countries with endemic STH was estimated to be 96 (down from 112 in 2010). Sizeable donations of a total of 3.3 billion deworming tablets by GlaxoSmithKline and Johnson & Johnson since 2010 to the WHO allowed progress on its goals. In 2019, the WHO targets were updated to eliminate morbidity of STH by 2030, with less than 2% of all children being infected by that date in all 98 currently endemic countries.

Schistosomiasis

The WHO set a goal to control morbidity of schistosomiasis by 2020 and eliminate the public health problems associated with it by 2025 (bringing infections down to less than 1% of the population). The effort is assisted by the Schistosomiasis Control Initiative. In 2018, a total of 63% of all school age children were treated.

Hookworm

In North American countries, such as the United States, elimination of hookworm had been attained due to scientific advances. Despite the United States declaring that it had eliminated hookworm decades ago, a 2017 study showed it was present in Lowndes County, Alabama. 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.

Measles

Immunization coverage with measles-containing vaccines in infants, in 2007

As of 2018, all 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. The Americas set a goal in 1994 to eliminate measles and rubella transmission by 2000, and successfully achieved to reduce cases from over 250,000 in 1990 to only 105 cases in 2003. However, while eradication in the Americas was certified in 2015, the certification was lost in 2018 due to endemic measles transmission in Venezuela and subsequent spread to Brazil and Colombia; while additional limited outbreaks have occurred elsewhere as well. Europe had set a goal to eliminate measles transmission by 2010, which was missed due to 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. 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. In 2019, the WHO South-East Asian region has set a target to eliminate measles by 2023. As of September 2019, a total of 82 countries were certified to have eliminated endemic measle transmission.

In 2005, a global target was agreed for a 90% reduction in measles deaths by 2010 from the 757,000 deaths in 2000 (later updated to 95% by 2015). Estimates in 2008 showed a 78% decline to 164,000 deaths, further declining to 145,700 in 2013. however, progress has since stalled since and both the 2010 and 2015 target were missed: in 2018, still over 140,000 deaths were reported. As of 2018, global vaccination efforts have reached 86% coverage of the first dose of the measles vaccine and 68% coverage of the second dose.[]

The WHO region of the Americas declared on 27 September 2016 it had eliminated measles. The last confirmed endemic case of measles in the Americas was in Brazil in July 2015. May 2017 saw a return of measles to the US after an outbreak in Minnesota among unvaccinated children. Another outbreak occurred in the state of New York between 2018 and 2019, causing over 200 confirmed measles cases in mostly ultra-Orthodox Jewish communities. Subsequent outbreaks occurred in New Jersey and Washington state with over 30 cases reported in the Pacific Northwest.

The WHO European region missed its elimination target of 2010 as well as the new target of 2015 despite overall coverage of 90% of the first dose of the measles vaccine. In 2018, 84,000 cases were reported in the European region (an increase from 25,000 in 2017); with the majority of cases originating from Ukraine.

By the end of 2021, WHO's European regional office considered the endemic measles eliminated in 33 out of 53 member states, with the transmission interrupted in one more and re-established in five others.

Rubella

Four out of six WHO regions have goals to eliminate rubella, with the WHO recommending using existing measles programmes for vaccination with combined vaccines such as the MMR vaccine. The number of reported cases dropped from 670,000 in the year 2000 to below 15,000 in 2018, and the global coverage of rubella vaccination was estimated at 69% in 2018 by the WHO. The WHO region of the Americas declared on 29 April 2015 it had eliminated rubella and congenital rubella syndrome. The last confirmed endemic case of rubella in the Americas was in Argentina in February 2009. Australia achieved eradication in 2018. As of September 2019, 82 countries were certified to have eliminated rubella.

The WHO European region missed its elimination target of 2010 as well as the new target of 2015 due to undervaccination in Central and Western Europe. As of 2018, 39 countries out of 53 European countries have eliminated endemic Rubella and three additional ones that have interrupted transmission; a total of 850 confirmed rubella cases were reported in the European region in 2018 with 438 of these in Poland. European countries with endemic Rubella in 2018 were: Belgium, Bosnia and Herzegovina, Denmark, France, Germany, Italy, Poland, Romania, Serbia, Turkey and Ukraine. The disease remains problematic in other regions as well; the WHO regions of Africa and South-East Asia have the highest rates of congenital rubella syndrome and a 2013 outbreak of rubella in Japan resulted in 15,000 cases.

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. The current WHO goal is to increase the number of countries free of transmission from 4 (in 2020) to 12 in 2030. Elimination of this disease is under way in the region of the Americas, where this disease was 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. 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. Some African countries, such as Uganda, are also attempting elimination and successful elimination was reported in 2009 from two endemic foci in Mali and Senegal.

On 29 July 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. It has also been eliminated in Ecuador (2014), Mexico (2015), and Guatemala (2016). The only remaining countries in America in which the disease is endemic are Brazil and Venezuela as of 2021.

Prion diseases

Following an epidemic of variant Creutzfeldt–Jakob disease in the UK in the 1990s, there have been campaigns to eliminate bovine spongiform encephalopathy in cattle across the European Union and beyond which have achieved large reductions in the number of cattle with this disease. Cases of variant Creutzfeldt–Jakob disease have also fallen since then, from an annual peak of 29 cases in 2000 to five in 2008 and none in 2012. Two cases were reported in both 2013 and 2014: two in France; one in the United Kingdom and one in the United States.

Following the ongoing eradication effort, only seven cases of bovine spongiform encephalopathy were reported worldwide in 2013: three in the United Kingdom, two in France, one in Ireland and one in Poland. This is the lowest number of cases since at least 1988. In 2015, there were at least six reported cases (three of the atypical H-type). Four cases were reported globally in 2017, and the condition is considered to be nearly eradicated.

With the cessation of cannibalism among the Fore people, the last known victims of kuru died in 2005 or 2009, but the disease has a very long incubation period.

Syphilis

In 2007, the WHO launched a roadmap for the elimination of congenital syphilis (mother to child transmission). In 2015, Cuba became the first country in the world to eliminate mother-to-child syphilis. In 2017 the WHO declared that Antigua and Barbuda, Saint Kitts and Nevis and four British Overseas TerritoriesAnguilla, Bermuda, Cayman Islands, and Montserrat—have been certified that they have ended transmission of mother-to-child syphilis and HIV. In 2018, Malaysia also achieved certification. Nevertheless, eradication of syphilis by all transmission methods remains unresolved and many questions about the eradication effort remain to be answered.

African trypanosomiasis

Early planning by the WHO for the eradication of African trypanosomiasis, also known as sleeping sickness, is underway as the rate of reported cases continues to decline and passive treatment is continued. The WHO aims to eliminate transmission of the Trypanosoma brucei gambiense parasite by 2030, though it acknowledges that this goal "leaves no room for complacency." The eradication and control efforts have been progressing well, with the number of reported cases dropping below 10,000 in 2009 for the first time; with only 992 cases reported in 2019 and 565 cases in 2020. The vast majority of the 565 cases in 2020 (over 60%) were recorded in the Democratic Republic of the Congo. However, some researchers have argued that total elimination may not be achievable due to human asymptomatic carriers of T. b. gambiense and non-tsetse modes of transmission.

The Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) works to eradicate the vector (the tsetse fly) population levels and subsequently the protozoan disease, by use of insecticide-impregnated targets, fly traps, insecticide-treated cattle, ultra-low dose aerial/ground spraying (SAT) of tsetse resting sites and the sterile insect technique (SIT). The use of SIT in Zanzibar proved effective in eliminating the entire population of tsetse flies but was expensive and is relatively impractical to use in many of the endemic countries afflicted with African trypanosomiasis.

Rabies

Rabies-free countries and territories as of 2018

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 eliminate rabies during the twentieth century, and more recently much of continental Europe has been declared rabies-free.

Chagas disease

Chagas disease is caused by Trypanosoma cruzi and is mostly spread by Triatominae. It is endemic to 21 countries in Latin America. There are over 30,000 new cases per year and 12,000 deaths due to the disease. Eradication efforts focus on the elimination of vector-borne transmission and the elimination of the vectors themselves.

Leprosy

Since the introduction of multi-drug therapy in 1981, the prevalence of leprosy has been reduced by over 95%. The success of the treatment has prompted the WHO in 1991 to set a target of less than one case per 10,000 people (eliminate the disease as a public health risk) which was achieved in 2000. The elimination of transmission of leprosy is part of the WHO "Towards zero leprosy" strategy to be implemented until 2030.  It aims to reduce transmission to zero in 120 countries and reduce the number of new cases to about 60,000 per year (from ca. 200,000 cases in 2019). These goals are supported by the Global Partnership for Zero Leprosy (GPZL) and the London Declaration on Neglected Tropical Diseases. However, a lack of understanding of the disease and its transmission, and the long incubation period of the M. leprae pathogen have so far prevented the formulation of a full-scale eradication strategy.

Eradicable diseases in animals

Following rinderpest, many experts believe that ovine rinderpest, or peste des petits ruminants (PPR), is the next disease amenable to global eradication. PPR is a highly contagious viral disease of goats and sheep characterized by fever, painful sores in the mouth, tongue and feet, diarrhea, 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.

The World Organisation for Animal Health (WOAH) prioritises African swine fever, bovine tuberculosis, foot and mouth disease, and PPR.

Eradication difficulties

Public upheaval by means of war, famine, political means, and infrastructure destruction can disrupt or eliminate eradication efforts altogether.

Syndemic

From Wikipedia, the free encyclopedia

Syndemics is the evaluation of how social and health conditions arise, in what ways they interact, and what upstream drivers may produce their interactions. The word is a blend of "synergy" and "epidemics". The idea of syndemics is that no disease exists in isolation and that often population health can be understood through a confluence of factors (such as climate change or social inequality) that produces multiple health conditions that afflict some populations and not others. Syndemics are not like pandemics (where the same social forces produce clustered conditions equally around the world); instead, syndemics reflect population-level trends within certain states, regions, cities, or towns.

A syndemic or synergistic epidemic is generally understood to be the aggregation of two or more concurrent or sequential epidemics or disease clusters in a population with biological interactions, which exacerbate the prognosis and burden of disease. The term was developed by Merrill Singer in the early 1990s to call attention to the synergistic nature of the health and social problems facing the poor and underserved. Syndemics develop under health disparity, caused by poverty, stress, climate, or structural violence and are studied by epidemiologists and medical anthropologists concerned with public health, community health and the effects of social conditions on health. The concept was translated from anthropology to a larger audience in 2017, with the publication of a Series on Syndemics in The Lancet, led by Emily Mendenhall.

The syndemic approach departs from the biomedical approach to diseases to diagnostically isolate, study, and treat diseases as distinct entities separate from other diseases and independent of social contexts.

Definition

A syndemic is a synergistic epidemic. The term was developed by Merrill Singer in the mid-1990s, culminating in a 2009 textbook. Disease concentration, disease interaction, and their underlying social forces are the core concepts. Disease co-occurrence, with or without interactions, is known as comorbidity and coinfection. The difference between "comorbid" and "syndemic" is per Mustanski et al. "comorbidity research tends to focus on the nosological issues of boundaries and overlap of diagnoses, while syndemic research focuses on communities experiencing co-occurring epidemics that additively increase negative health consequences." It is possible for two afflictions to be comorbid, but not syndemic i.e., the disorders are not epidemic in the studied population, or their co-occurrence does not cause an interaction that then contributes to worsened health. Two or more diseases can be comorbid without interactions, or interaction occurs but it is beneficial, not deleterious. Syndemic theory seeks to draw attention to and provide a framework for the analysis of adverse disease interactions, including their causes and consequences for human life and well-being. Although the majority of this research has focused on HIV, an emerging body of work on syndemics has expanded to other co-occurring conditions.

Syndemic methods: from historical archives to mathematical models

Methods for evaluating syndemics have been a focus on scholarship for deepening the application of what has largely served as theory to understand why and how social and health conditions cluster together, interact, and are driven by shared forces, from climate (such as escalation of heat, rain, drought, and events) to poverty (such as food insecurity, poor housing, lack of safety, and limited work opportunities). In 2022, Alexander Tsai (an epidemiologist), Emily Mendenhall (a medical anthropologist), and Timothy Newfield (a historian) teamed up on a Special Issue in Social Science and Medicine to explore the various methodological ways in which syndemics can be understood, interpreted, and evaluated through history. For instance, historical syndemics may be evaluated using archival data that is incomplete but provides a novel way of thinking about disease biography. This is exemplified by Dylann Atcher Proctor's historical work on gastrointestinal distress in Gabon using historical archives that had never yet been evaluated on their own or synergistically.

Ethnographic data provides a deeper understanding of how and why larger social forces produce disease clusters and interactions and are crucial for understanding "why" syndemics occurr. Ethnographic insights have served as the bedrock of syndemic thinking since Merrill Singer's pioneering intellectual and practical work with the concept beginning in the 1990s. His first article based on ethnographic thinking about the SAVA Syndemic came from real time observations as the AIDS epidemic that unfolded in tandem with substance use amidst structural violence in urban America throughout the 1990s and early 2000s. Singer demonstrated how it was impossible to think about one condition without contextualizing the broader social, structural, and health contexts in which people lived. Discussion of ethnographic methods were detailed in Emily Mendenhall's books Syndemic Suffering and Rethinking Diabetes and is also exemplified in Mac Marshall's book Drinking Smoke.

The largest body of methodological scholarship has emerged around the utility of epidemiological data. Epidemiological data provides opportunities to investigate the synergistic ways in which diseases emerge and interact with social and health conditions. This latter method has been the focus of contention, particularly in dialogue between Alexander Tsai and Ronald Stall. Early epidemiological studies, for example, evaluated the ways in which social and health conditions co-occurred. Tsai argued that instead, there is a deeper need to interrogate how conditions syngistically interact to cause more adverse health conditions that the conditions would produce on their own. This has led to a slough of emergent research interrogating mathematical models that can take seriously how health conditions may cluster together and interact to affect the health and well being of populations residing in a specific nation, region, city, or town. A particularly useful model based on the Soweto Syndemics study was published in Nature Human Behavior. In particular, spatial models for thinking through syndemic clusters, such as using GIS, are an emerging area of interest in syndemics research.

Types of disease interaction

Diseases regularly interact and this interaction influences disease course, expression, severity, transmission, and diffusion. Interaction among diseases may be both indirect (changes caused by one disease that facilitate another through an intermediary) and direct (diseases act in direct tandem).

  • One disease can assist the physical transmission of the microbe causing another disease, for example, genital-tract ulceration caused by syphilis allowing sexual transmission of HIV.
  • One disease may enhance the virulence of another, as for example, herpes simplex virus co-infection exacerbates HIV infection with progression to AIDS, periodontal bacteria may enhance the virulence of herpesvirus, HIV-infected individuals are more susceptible to tuberculosis; As of 2011, the cause was not fully understood.
  • Changes in biochemistry or damage to organ systems, as for example diabetes weakening the immune system, promotes the progression of another disease, SARS.
  • A coinfection may open up multiple syndemic pathways. Lethal synergism between influenza virus and pneumococcus, causes excess mortality from secondary bacterial pneumonia during influenza epidemics. Influenza virus alters the lungs in ways that increase the adherence, invasion and induction of disease by pneumococcus, alters the immune response with weakened ability to clear pneumococcus or, alternately amplifying the inflammatory cascade.
  • Direct interaction of diseases occurs in the case of genetic recombination among different pathogens, for instance between Avian sarcoma leukosis virus and Marek's disease virus (MDV) in domestic fowl. Both cancer-causing viruses are known to infect the same poultry flock, the same chicken, and, even the same anatomic cell. In coinfected cells, the retroviral DNA of the avian leukosis virus can integrate into the MDV genome, producing altered biological properties compared to those of the parental MDV. The frequency of gene reassortment among human pathogens is less clear than it is the among plant or animal species but of concern as animal diseases adapt to human hosts and as man new diseases comes into contact.
  • When one disease diminishes or eradicates another it is a counter-syndemic disease interaction.
  • The linkage also may not be clear, despite apparent syndemic interactions among diseases, as for example in type 2 diabetes mellitus and hepatitis C virus infection.

Iatrogenic

The term iatrogenesis refers to adverse effects on health caused by medical treatment. This is possible if medical treatment or medical research creates conditions that increase the likelihood that two or more diseases come together in a population. For example, if gene splicing unites two pathogenic agents and the resulting novel organism infects a population. One study suggests the possibility of iatriogenic syndemics. During a randomized, double-blind clinical trial testing the efficacy of the prototype HIV vaccine called V520 there appeared to be an increased risk for HIV infection among the vaccinated participants. Notably, participants immune to the common cold virus adenovirus type 5 had a higher risk of HIV infection. The vaccine was created using a replication-defective version of Ad5 as a carrier, or delivery vector, for three synthetically produced HIV genes. On November 6, 2007, Merck & Co. announced that research had been stopped suspecting the higher rate of HIV infection among individuals in the vaccinated was because the vaccine lowered defenses against HIV.

Examples

Various syndemics though not always labeled as such have been described in the literature, including:

  • HIV/AIDS and food insecurity compromise an unrecognized syndemic axis in many resource-limited settings in sub-Saharan Africa
  • SAVA syndemic (substance abuse, violence and AIDS,
  • the VIDDA syndemic (violence, immigration/isolation, depression, diabetes, abuse)
  • the hookworm, malaria and HIV/AIDS syndemic,
  • the Chagas disease, rheumatic heart disease and congestive heart failure syndemic,
  • the possible asthma and infectious disease syndemic,
  • the malnutrition and depression syndemic,
  • the TB, HIV and violence syndemic,
  • the whooping cough, influenza, tuberculosis syndemic,
  • the HIV incidence, substance use, mental health, childhood sexual abuse, and intimate partner violence syndemics
  • the HIV and STD syndemic,
  • the stress and obesity syndemic,
  • the HIV infection, mental health and substance abuse syndemic.
  • the built environment, physical inactivity and obesity/diabetes syndemic, which Prince Charles pointed out in January 2006, in a speech at the Enhancing the Healing Environment conference hosted by The Prince's Foundation for the Built Environment and The King's Fund, St James's Palace, London.
  • HIV infection and opportunistic microbial infections and viral-caused malignancies like Kaposi's sarcoma 
  • periodontitis and herpes virus: bacteria of several different species (e.g., Porphyromonas gingivalis, Dialister pneumosintes, Prevotella intermedia) that adhere to and reproduce on tooth surfaces under the gum line multiply when bodily defenses are weakened by an HSV infection of the periodontium.
  • HIV being transiently suppressed during an acute measles infection. Several potential mechanisms could be responsible. Measles virus infection causes lymphopenia, a reduction in the number of CD4+ T lymphocytes circulating in the blood. The low point occurs just prior to the onset of the characteristic skin rash. Within a month of this nadir, the number of lymphocytes returns to normal levels. The drop in HIV virus levels may be due to a lack of target CD4+ T cells in which they replicate, or measles virus may stimulate the production of proteins suppressing HIV replication, including the β-chemokines, CD8+ cell noncytotoxic anti-HIV response, and the cytokines IL-10 and IL-16. median plasma levels of RANTES, a chemokine that attracts immune system components like eosinophils, monocytes, and lymphocytes were higher in HIV-infected children with measles than in those without measles (Moss and co-workers).
  • HIV suppression in tsutsugamuchi disease or scrub typhus, a mite-borne infection in Asia and Australia, but how this occurs is unclear.
  • COVID-19 is a syndemic of SARS‑CoV‑2 coronavirus infection combined with an epidemic of non-communicable diseases, both inter-acting on a social substrate of poverty and inequality, according to Richard Horton in the Lancet Global Burden of Disease study 2020 (GBD 2020).

19th century Native American

Contact between Native Americans and Europeans during the Columbian Exchange led to lethal syndemics within the Native American population due to diseases introduced which the Native Americans had not encountered before and had not built-up immunity to.

An example of a syndemic from the 19th century can be found on the reservations on which Native Americans were confined with the closing of the U.S. frontier. It is estimated that in 1860 there were well over 10 million bison living on the American Plains. By the early 1880s, the last of the great herds of bison upon which Plains Indian peoples like the Sioux were dependent as a food source were gone. At the same time, after the U.S. military's defeat at the Battle of the Little Bighorn in 1876, there was a concerted effort to beat the Sioux into total submission. Thus, in 1872, Secretary of the Interior Columbus Delano stated: "as they become convinced that they can no longer rely upon the supply of game for their support, they will return to the more reliable source of subsistence [i.e., farming]." As a result, they were forced to give up their struggle for an independent existence on their own lands and take up reservation life at the mercy of government authority. Treaties that were signed with the Sioux in 1868 and 1876 stipulated that they would be provided with government annuities and provisions in payment for sections of their land and with the expectation among federal representatives that the Sioux would become farmers on individually held plots of land. The Sioux found themselves confined on a series of small reservations where they were treated as a conquered people. Moreover, the government reneged on its promises, food was insufficient and of low quality. Black Elk, a noted Sioux folk healer, told his biographer: "There was hunger among my people before I went across the big water [to Europe in 1886], because the Wasichus [whites] did not give us all the food they promised in the Black Hills treaty... But it was worse when I came back [1889]. My people looked pitiful... We could not eat lies and there was nothing we could do." Under extremely stressful conditions, with inadequate diets, and as victims of overt racism on the part of the registration agents appointed to oversee Indian reserves, the Sioux confronted infectious disease from contact with whites. knowledge about the epidemiology of the Sioux from this period is limited, James Mooney, an anthropologist and representative of the Bureau of Indian Affairs sent to investigate a possible Sioux rebellion, described the health situation on the reservation in 1896: "In 1888 their cattle had been diminished by disease. In 1889, their crops were a failure ... Thus followed epidemics of measles, grippe [influenza], and whooping cough Pertussis, in rapid succession and with terrible fatal results..." Similarly, the Handbook of American Indians notes, "The least hopeful conditions in this respect prevail among the Dakota [Sioux] and other tribes of the colder northern regions, where pulmonary tuberculosis and scrofula are very common... Other more common diseases, are various forms of, bronchitis ...pneumonia, pleurisy, and measles in the young. Whooping cough is also met with." Indian children were removed to white boarding schools and diagnosed with a wide range of diseases, including tuberculosis, trachoma, measles, smallpox, whooping cough, influenza, and pneumonia.

The Sioux were victims of a syndemic of interacting infectious diseases including the 1889–1890 flu pandemic, inadequate diet, and stressful and extremely disheartening life conditions, including outright brutalization with events like the massacre at Wounded Knee in 1890 and the murder of their leader Sitting Bull. While the official mortality rate on the reservation was between one and two percent, the death rate was probably closer to 10 percent.

Influenza

There were three influenza pandemics during the 20th century that caused widespread illness, mortality, social disruption, and significant economic losses. These occurred in 1918, 1957, and 1968. In each case, mortality rates were determined primarily by five factors: the number of people who became infected, the virulence of the virus causing the pandemic, the speed of global spread, the underlying features and vulnerabilities of the most affected populations, and the effectiveness and timeliness of the prevention and treatment measures that were implemented.

The 1957 pandemic was caused by the Asian influenza virus (known as the H2N2 strain), a novel influenza variety to which humans had not yet developed immunities. The death toll of the 1957 pandemic is estimated to have been around two million globally, with approximately 70,000 deaths in the United States. A little over a decade later, the comparatively mild Hong Kong influenza pandemic erupted due to the spread of a virus strain (H3N2) that genetically was related to the more deadly form seen in 1957. The pandemic was responsible for about one million deaths around the world, almost 34,000 of which were in the United States. In both of these pandemics, death may not have been due only to the primary viral infection, but also to secondary bacterial infections among influenza patients; in short, they were caused by a viral/bacterial syndemic (but see Chatterjee 2007).

The worst of the 20th-century influenza pandemics was the 1918 pandemic, where between 20 and 40 percent of the world's population became ill and between 40 and 100 million people died. More people died of the so-called Spanish flu (caused by the H1N1 viral strain) pandemic in the single year of 1918 than during all four-years of the Black Death. The pandemic had devastating effects as disease spread along trade and shipping routes and other corridors of human movement until it had circled the globe. In India, the mortality rate reached 50 per 1,000 population. Arriving during the closing phase of World War I, the pandemic impacted mobilized national armies. Half of U.S. soldiers who died in the "Great War," for example, were victims of influenza. It is estimated that almost 34 of a million Americans died during the pandemic. In part, the death toll during the pandemic was caused by viral pneumonia characterized by extensive bleeding in the lungs resulting in suffocation. Many victims died within 48 hours of the appearance of the first symptom. It was not uncommon for people who appeared to be quite healthy in the morning to have died by sunset. Among those who survived the first several days, however, many died of secondary bacterial pneumonia. It has been argued that countless numbers of those who expired quickly from the disease were co-infected with tuberculosis, which would explain the notable plummet in TB cases after 1918.

Climate change

As a result of the floral changes produced by global warming, an escalation is occurring in global rates of allergies and asthma. Allergic diseases constitute the sixth leading cause of chronic illness in the United States, impacting 17 percent of the population. Asthma affects about 8 percent of the U.S. population, with rising tendency, especially in low income, ethnic minority neighborhoods in cities. In 1980 asthma affected only about three percent of the U.S. population according to the U.S. CDC. Asthma among children has been increasing at an even faster pace than among adults, with the percentage of children with asthma going up from 3.6 percent in 1980 to 9 percent in 2005. Among ethnic minority populations, like Puerto Ricans the rate of asthma is 125 percent higher than non-Hispanic white people and 80 percent higher than non-Hispanic black people. The asthma prevalence among American Indians, Alaska Natives and black people is 25 percent higher than in white people.

Air pollution

Increases in asthma rates have occurred despite improvements in air quality produced by the passage and enforcement of clean air legislation, such as the U.S. Clean Air Act of 1963 and the Clean Air Act of 1990. Existing legislation and regulation have not kept pace with changing climatic conditions and their health consequences. Compounding the problem of air quality is the fact that air-borne pollens have been found to attach themselves to diesel particles from truck or other vehicular exhaust floating in the air, resulting in heightened rates of asthma in areas where busy roads bisect densely populated areas, most notably in poorer inner-city areas.

For every elevation of 10 μg/m3 in particulate matter concentration in the air a six percent increase in cardiopulmonary deaths occurs according to research by the American Cancer Society. Exhaust from the burning of diesel fuel is a complex mixture of vapors, gases, and fine particles, including over 40 known pollutants like nitrogen oxide and known or suspected carcinogenic substances such as benzene, arsenic, and formaldehyde. Exposure to diesel exhaust irritates the eyes, nose, throat and lungs, causing coughs, headaches, light-headedness and nausea, while causing people with allergies to be more susceptible allergy triggers like dust or pollen. Many particles in disease fuel are so tiny they are able to penetrate deep into the lungs when inhaled. Importantly, diesel fuel particles appear to have even greater immunologic effects in the presence of environmental allergens than they do alone. "This immunologic evidence may help explain the epidemiologic studies indicating that children living along major trucking thoroughfares are at increased risk for asthmatic and allergic symptoms and are more likely to have respiratory dysfunction." according to Robert Pandya and co-workers.

The damaging effects of diesel fuel pollution go beyond a synergistic role in asthma development. Exposure to a combination of microscopic diesel fuel particles among people with high blood cholesterol (i.e., low-density lipoprotein, LDL or "bad cholesterol") increases the risk for both heart attack and stroke above levels found among those exposed to only one of these health risks. According to André Nel, Chief of Nanomedicine at the David Geffen School of Medicine at UCLA, "When you add one plus one, it normally totals two... But we found that adding diesel particles to cholesterol fats equals three. Their combination creates a dangerous synergy that wreaks cardiovascular havoc far beyond what's caused by the diesel or cholesterol alone." Experimentation revealed that the two mechanisms worked in tandem to stimulate genes that promote cell inflammation, a primary risk for hardening and blockage of blood vessels (atherosclerosis ) and, as narrowed arteries collect cholesterol deposits and trigger blood clots, for heart attacks and strokes as well.


A Note on Mathematical Models

A mathematical model is a simplified representation using mathematical language to describe natural, mechanical or social system dynamics. Epidemiological modelers unite several types of information and analytic capacity, including: 1) mathematical equations and computational algorithms; 2) computer technology; 3) epidemiological knowledge about infectious disease dynamics, including information about specific pathogens and disease vectors; and 4) research data on social conditions and human behavior. Mathematical modelling in epidemiology is now being applied to syndemics.

For example, modelling to quantify the syndemic effects of malaria and HIV in sub-Saharan Africa based on research in Kisumu, Kenya researchers found that 5% of HIV infections (or 8,500 cases of HIV since 1980) in Kisumu are the result of the higher HIV infectiousness of malaria-infected HIV patients. Additionally, their model attributed 10% of adult malaria episodes (or almost one million excess malaria infections since 1980) to the greater susceptibility of HIV infected individuals to malaria. Their model also suggests that HIV has contributed to the wider geographic spread of malaria in Africa, a process previously thought to be the consequence primarily of global warming. Modelling offers an enormously useful tool for anticipating future syndemics, including eco-syndemic, based on information about the spread of various diseases across the planet and the consequent co-infections and disease interactions that will result.

PopMod is a longitudinal population tool developed in 2003 that models distinct and possibly interacting diseases. Unlike other life-table population models, PopMod is designed to not assume the statistical independence of the diseases of interest. The PopMod has several intended purposes, including describing the time evolution of population health for standard demographic purposes (such as estimating healthy life expectancy in a population), and providing a standard measure of effectiveness for health interventions and cost-effectiveness analysis. PopMod is used as one of the standard tools of the World Health Organization's (WHO) CHOICE (Choosing Interventions that are Cost-Effective) program, an initiative designed to provide national health policymakers in the WHO's 14 epidemiological sub-regions around the world with findings on a range of health intervention costs and effects.

Future research

First, there is a need for studies that examine the processes by which syndemics emerge, the specific sets of health and social conditions that foster multiple epidemics in a population and how syndemics function to produce specific kinds of health outcomes in populations. Second, there is a need to better understand processes of interaction between specific diseases with each other and with health-related factors like malnutrition, structural violence, discrimination, stigmatization, and toxic environmental exposure that reflect oppressive social relationships. There is a need to identify all of the ways, directly and indirectly, that diseases can interact and have, as a result, enhanced impact on human health. Third there is a need for the development of an eco-syndemic understanding of the ways in which global warming contributes to the spread of diseases and new disease interactions. There is a need for a better understanding of how public health systems and communities can best respond to and limit the health consequences of syndemics. Systems are needed to monitor the emergence of syndemics and to allow early medical and public health responses to lessen their impact. Systematic ethno-epidemiological surveillance with populations subject to multiple social stressors must be one component of such a monitoring system.

Lie point symmetry

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