In 2025, just 10 people worldwide were diagnosed with Guinea worm disease. Four decades earlier, the parasitic infection afflicted an estimated 3.5 million people every year across 21 countries in Africa and Asia. This decline has brought Guinea worm closer than ever to becoming the second human disease in history to be eradicated.
Despite centuries of medical progress, the world has eradicated just one human disease: smallpox, declared eradicated by the World Health Organization (WHO) in 1980 following a global vaccination campaign. Polio has remained close for decades, while diseases such as malaria and measles continue to circulate despite effective tools to control them.
So why do some diseases disappear while others persist? Whether a disease can be eradicated depends on a rare combination of biology, effective interventions, sustained political commitment, and decades of public health efforts.
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What does “disease eradication” actually mean?
With just 10 reported human cases worldwide in 2025, it would be easy to assume eradication is simply a formality. In public health, however, nuances such as control, elimination, and eradication have precise meanings, and this also explains why the final steps towards wiping out a disease are often the hardest.
At the first level is disease control, which seeks to reduce a disease to a level where it no longer represents a major public health burden. Influenza, human immunodeficiency virus (HIV), and tuberculosis all fall into this category. They continue to circulate globally, but vaccination, treatment, and public health measures limit their impact. Those interventions must continue indefinitely because if they stop, cases rise again.
A step further is elimination, which means reducing transmission to zero within a defined geographical area. The disease has not disappeared globally, and imported cases can still spark new outbreaks if surveillance or vaccination programs weaken. Measles is a good example. The United States declared endemic measles eliminated in 2000, yet outbreaks have continued as infected travelers reintroduced the virus into communities with insufficient vaccination coverage. Similarly, malaria has been eliminated from much of Europe and North America while remaining endemic across large parts of Africa, Asia, and Latin America.
Eradication sets the bar higher, as WHO defines it as the permanent reduction to zero of the worldwide incidence of infection, after which routine control measures are no longer needed. To date, only smallpox has met that definition.
The only eradicated disease: smallpox
Smallpox was among humanity’s deadliest diseases, killing an estimated 30% of those infected and leaving many survivors blind or scarred. Yet in 1980, following a global campaign led by WHO, it became the first human disease to be declared eradicated.
Epidemiologists often point out that smallpox had an unusually favorable combination of biological characteristics that made eradication possible in ways that few other infectious diseases can match.
Perhaps most importantly, humans were the virus’s only natural host. Unlike rabies, influenza, or malaria, smallpox did not circulate in animals. Once transmission was interrupted between people, there was no hidden reservoir capable of reintroducing the virus into the human population.
Cases were also difficult to miss as infected individuals developed a distinctive fever followed by a characteristic pustular rash, and people generally became infectious only after symptoms appeared. Health workers could identify cases, isolate patients, and vaccinate close contacts before the virus spread further.
The virus itself also worked in favor of its eradication because infection generally produced long-lasting immunity, while the smallpox vaccine offered strong and durable protection after a single vaccination in most people. The variola virus, which causes smallpox, was also genetically stable, meaning vaccines remained effective over time without needing frequent reformulation.
Finally, the crucial international effort made the rest of the job; WHO’s Intensified Smallpox Eradication Program, launched in 1967, coordinated surveillance, vaccine distribution and outbreak response across countries. The last naturally occurring case was recorded in Somalia in 1977, before the disease was officially declared eradicated three years later.
Few pathogens, a single human host, obvious symptoms, durable immunity, an effective vaccine and sustained global political commitment made smallpox the ideal candidate – a textbook case even. Looking at the diseases still awaiting eradication, removing just one of those ingredients can make the task much more difficult.
Guinea worm: eradicating a disease without medicine
If smallpox represents the textbook eradication campaign, Guinea worm is more singular as it does not rely on biomedical innovation. There is no vaccine, no drug, and no rapid diagnostic test for Guinea worm disease. Instead, the eradication program has relied on understanding the parasite’s life cycle and interrupting its transmission through relatively simple public health measures.
Guinea worm disease is caused by the parasitic nematode Dracunculus medinensis. People become infected after drinking stagnant water containing tiny freshwater crustaceans, copepods, that carry the parasite’s larvae. Around a year later, the adult female worm emerges through the skin, causing a painful blister. Seeking relief, infected people often immerse the affected limb in water, allowing the worm to release thousands of larvae and begin the cycle again.
The worm’s life cycle directed eradication efforts toward preventing the parasite from reaching the next person. Communities were supplied with cloth and pipe filters to remove infected copepods from drinking water, ponds were treated with the larvicide to kill the crustaceans, community volunteers were trained to identify cases quickly, and infected people were encouraged to avoid entering water sources until the worm had been fully removed. In many endemic areas, cash rewards were introduced for reporting suspected cases.
When eradication seemed close, researchers found out Guinea worm also affected animals. Since the early 2010s, large numbers of infections have been documented in dogs as well as, more occasionally, cats and baboons, creating transmission hypotheses that had not been taken into account when the eradication campaign began. One of the defining characteristics that made smallpox an ideal eradication candidate no longer applied to Guinea worm. But today, eradication seems close, and it could be a matter of time and sustained effort. There are other diseases that came close to eradication before encountering a setback.
Why polio is still not gone
Safe and effective polio vaccines have existed for more than 60 years, and more than 2.5 billion children have been immunized through the global campaign. Cases have fallen by more than 99%, and wild poliovirus types 2 and 3 have been declared eradicated. But wild poliovirus type 1 continues to circulate in Afghanistan and Pakistan.
Reaching every child has proved especially difficult in the remaining areas of transmission. Conflict, insecurity, population displacement and restrictions on access can prevent vaccination teams from visiting communities. In parts of Afghanistan and Pakistan, programs must also contend with vaccine refusals, misinformation and distrust of public institutions.
Polio is also much harder to track than smallpox. Only around one in 200 infections result in irreversible paralysis, meaning that a single confirmed case may signal far wider transmission. Eradication programs monitor cases of paralysis and test sewage water for signs of the virus, but gaps in surveillance can allow transmission to continue undetected.
Another difficulty comes from the polio vaccine itself, which contains a weakened live virus. After vaccination, that weakened virus can briefly replicate in the intestine and be shed into the environment. This can indirectly immunize other people in well-vaccinated communities, but if the virus circulates for a prolonged period in a population with low immunization coverage, it can accumulate genetic changes and regain the ability to cause paralysis.
In 2025, 40 cases of wild poliovirus type 1 were reported in Afghanistan and Pakistan, down from 99 in 2024. But wastewater surveillance continued to detect the virus more widely than case counts alone suggested.
What is stopping the next disease eradication?
Measles appears to be one of the strongest candidates biologically. Humans are its only natural reservoir, reliable diagnostic tests exist, and vaccination can provide long-lasting protection. A WHO feasibility assessment concluded that measles eradication is biologically and technically feasible, and sustained interruption of transmission has already been demonstrated across large geographical areas.
However, because the virus is extremely contagious, very high population immunity must be maintained everywhere. Eradication would require countries not to run occasional vaccination campaigns, but to maintain high and equitable coverage while rapidly identifying and containing imported cases.
Rabies presents almost the reverse problem. Effective vaccines can prevent the disease in humans both before and after exposure, and vaccinating dogs can stop most human transmission. WHO considers sustained vaccination of at least 70% of dogs in at-risk areas the most effective way to prevent human rabies deaths, and several countries have eliminated dog-mediated rabies through this approach.
Global eradication is harder because rabies is not confined to humans, or even to dogs. The virus circulates among domestic and wild mammals, creating reservoirs from which it can repeatedly return. Eliminating human deaths from dog rabies is a more realistic public health objective, but eradicating every form of rabies would require sustained control across animal populations, including wildlife.
Malaria is a different challenge: it is caused by parasites transmitted by Anopheles mosquitoes, so programs must target both human infections and the vectors that carry them. Insecticide-treated nets, indoor spraying, medicines, preventive treatment and, more recently, vaccines can all reduce disease and transmission. As of today, no tool provides the kind of simple, durable interruption achieved by the smallpox vaccine. Mosquitoes can evade indoor interventions, while mosquito resistance to insecticides and parasite resistance to antimalarial drugs reduce the effectiveness of existing measures.
A WHO advisory group concluded that there is no fundamental biological reason malaria could never be eradicated. However, its modeling found that even expanding existing interventions and adding tools then in development would not be sufficient to eliminate malaria from the hardest-hit parts of Africa. Disease eradication may be conceivable in the long term, but not achievable with the tools and coverage available today.
This is why we’ve only declared one disease eradicated so far. Some pathogens can hide in people who show no symptoms. Others circulate in animals, depend on insect vectors, or evolve around the interventions used against them. Even when biology is favorable and effective vaccines exist, eradication still depends on reaching almost every vulnerable population, maintaining surveillance after cases become rare, and sustaining efforts after the immediate crisis has ended. With Guinea worm, we’ve never been that close to eradication, but eliminating the last chains of transmission can be very challenging.
