Education, Epidemiology, Infectious Diseases, Vaccines, Viruses

Successful Mass Vaccination Programs: From Smallpox to COVID-19

Author Chandana Balasubramanian , 04-Oct-2023

On October 2nd, 2023, the World Health Organization (WHO) approved a second vaccine to prevent malaria, an important milestone in the fight against this highly contagious disease. An effective mass vaccination campaign is desperately needed, since there is no effective treatment for this disease.


According to WHO, there were 247 million cases of malaria in 2021 with the African region home to 95% of all cases and 96% of all malaria-related deaths. Tragically, children under 5 are the most vulnerable and account for 80% of all deaths in the region. The new vaccine brings hope to many in need.


And there is more danger on the horizon. With climate change, mosquito-borne illnesses like malaria are in danger of affecting non-endemic regions, spreading the disease far and wide.


R21, the new malaria vaccine has shown to have high efficacy when the shot is given just before the season when high transmission begins. It has an efficacy of 66% for 12 months after the first 3 doses and a booster dose a year later strengthens its effect.


Mass vaccination programs helped us eradicate smallpox, significantly reduce polio cases through the oral polio vaccine (OPV), and lower the number of deaths, severe diseases, and hospitalizations from diphtheria, cholera, tetanus, influenza, rubella, measles, and more.


In light of the R21 malaria vaccine approval and rollout, let’s take a look at three notable mass immunization campaigns through the years, starting with the recent COVID-19 vaccines.



The COVID-19 mass vaccine program

The COVID-19 pandemic caused unprecedented global devastation. WHO reports that there have been over 770 million confirmed cases of COVID-19 with almost 7 million deaths reported (as of September 13, 2023).

The development and distribution of COVID-19 vaccines were instrumental in lowering the risk of severe hospitalizations and deaths from COVID-19.

COVID-19 vaccines: the mRNA vaccine milestone


During the pandemic, several types of COVID-19 vaccines were developed. Some vaccines had inactivated coronaviruses or isolated proteins from the virus to stimulate an immune response. This technique of making vaccines has been used for decades.

However, the biggest breakthrough in vaccine technology, in recent times, was the approval of mRNA-based vaccines for public use.

This condensed timeline for the COVID-19 vaccine approval was unprecedented. In the past, it could take decades for vaccines to go from research to commercial distribution. However, to deal with the rising body count from the SARS-CoV-2 virus and its strains, mRNA-based COVID-19 vaccines were authorized within a year of when the pandemic broke.

Once approved, the vaccine rollout took collaboration between countries, public health agencies, scientists, doctors, and many more for millions of global citizens to receive COVID-19 vaccinations.


The mass vaccination programs had a profound impact on reducing the severity of COVID-19 illness. While breakthrough infections can occur in vaccinated individuals, the vaccines significantly reduced the risk of severe disease, hospitalization, and death.

The scientists responsible for the research that paved the way for mRNA vaccines were recognized for their groundbreaking work. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their work on mRNA vaccines.

By vaccinating a large proportion of the population, mass vaccination programs minimize the burden on healthcare systems, so that resources can be directed to other critical medical needs.


  • Over 13 billion COVID-19 vaccine doses were administered worldwide, as of September 9, 2023. While this sounds like a high number, one-third of the global population unfortunately remains unvaccinated.
  • There remains a level of distrust and vaccine hesitancy in pockets worldwide, which may need to be addressed.
  • The level of vaccine misinformation during the pandemic has far-reaching consequences, beyond the COVID-19 vaccines. In April 2023, the United Nations Children’s Fund (UNICEF) reported that almost 67 million children were deprived of routine childhood vaccines during the pandemic and one of the reasons was mistrust in vaccines.



Apart from saving lives during the COVID-19 pandemic and after, the approval of mRNA-based vaccines has incredible potential for other diseases. mRNA vaccines are being studied for use against other SARS viruses, hepatitis C, malaria, tuberculosis, other communicable diseases, and even some cancers.


The smallpox eradication program

Smallpox is one of the oldest and deadliest infections, having killed a significant number of people in history. It is caused by the variola virus which killed millions of people before it was eradicated.

WHO estimates that the case fatality rate of smallpox is as high as 30%. In just the 20th century alone, smallpox was responsible for almost 500 million deaths. In the 18th century, the death rate from smallpox ranged as high as 60%.

The discovery of the smallpox vaccine changed everything. Over the decades, billions of lives have been saved from the deadly virus.

Smallpox vaccine

Crowd at a smallpox vaccination center


The smallpox vaccine was developed by Edward Jenner in the late 18th century. The doctor discovered that milkmaids who were infected by cowpox were immune to smallpox.

Being the world’s first vaccine, the discovery proved to be a giant leap forward in fighting infectious diseases. As a result, Dr. Jenner is known as the ‘Father of Immunology.’

While his contribution was significant, an effective smallpox vaccine was only developed and available for distribution in the 1950s.


The World Health Assembly began its first smallpox eradication campaign in the late 1950s, resulting in the eradication of the disease worldwide. Smallpox was declared eradicated in 1980 by the World Health Organization.

While the vaccine itself was a historic achievement, another innovation bolstered eradication efforts. When the smallpox vaccine was being rolled out, a bifurcated needle was invented.

The bifurcated needle could hold the required vaccine dose between its prongs. This meant that vaccine manufacturers could optimize distribution to more people without wastage. Also, because the needles were inexpensive and could be easily sterilized, the vaccine could be shared wi a wider number of countries.  

Reasons why smallpox eradication efforts were successful include:

  • The smallpox vaccine stimulated long-term protection against the smallpox virus.
  • Global smallpox vaccination programs targeted high-risk and remote areas.
  • The campaign involved various international organizations, governments, and healthcare professionals collaborating together against the deadly disease.
  • Strict surveillance and containment measures were put in place, which helped prevent the spread of the disease.



  • The Cold War between the United States and the then-USSR posed a challenge—would the two sides work together against a common enemy? Fortunately, through diplomacy, the two countries aligned well to protect their people from the scourge of smallpox.
  • Inadequate vaccine supply in Nigeria made it hard to inoculate 80% of the population, as originally planned. Instead, this shortage led to a new way to inoculate populations of people – surveillance containment or ring vaccinations. Here, people who were infected were first identified and isolated, and a ring of their close contacts were vaccinated.
  • Eradicating smallpox in India proved to be a logistical challenge. A dearth of refrigeration facilities and a large amount of population in rural areas challenged mass immunization efforts.



The smallpox eradication campaign was a resounding success; there has been no case of smallpox since the late seventies. In 1977, a 23-year-old Somali man in Merca, Somalia, received the vaccine and became the last known endemic case of smallpox.

Measles mass vaccination campaigns

Measles is highly contagious and spreads from person to person quite rapidly through respiratory droplets.

Like COVID-19, this makes it hard to control the spread of the disease, particularly in crowded places. The disease can also lead to severe complications like pneumonia, encephalitis, and even death in vulnerable populations.

In the past, because there was no effective treatment for measles, it was hard to manage symptoms, prevent spread, and provide care. As a result, the disease had a high mortality rate, causing significant suffering and loss of life before the vaccine was developed.

The measles mass vaccination program was successful in reducing deaths and hospitalizations from the measles virus.

The Measles vaccine and the MMR

2020 global measles vaccine coverage chart for 1 year olds

Image courtesy of GIDEON Informatics: Worldwide Measles vaccine coverage in 2020


Although measles has been around and documented since the 9th century, it became more widespread in later centuries through globalization. Unfortunately, the virus killed millions before a successful vaccine was discovered.

The first milestone in the history of the measles vaccine arrived in 1954 during a measles outbreak outside Boston, MA in the United States. At the time, Dr. Thomas Peebles, under the supervision of Dr. John Franklin Enders, isolated the measles virus for the first time, setting the stage for a vaccine.

For his various achievements in the field of infectious diseases, Dr. Enders, the doctor who led the research efforts, is known as the ‘Father of Modern Vaccines.’ He was later awarded the Nobel Prize in Physiology or Medicine for cultivating the poliomyelitis virus.

In 1961, after small-scale testing, the measles live attenuated vaccine (called the Edmonston strain) was declared 100% effective against measles and approved for commercial use.

As mass vaccination efforts continued, in 1968, another pioneer in vaccine technology, Dr. Maurice Hilleman, created a weaker version of the live attenuated vaccine to reduce the intensity of side effects. This strain, known as the Edmonston-Enders strain, was then distributed across the world.


The first measles mass vaccination program began in Africa in 1966. In 1967, The Gambia became the first country where transmission was interrupted. Vaccination efforts continued but were slower until there was a big breakthrough.

In 1971, Dr. Hilleman combined the measles vaccine with the ones against mumps and rubella, creating the MMR vaccine. The MMR was a gamechanger since it accelerated mass vaccination efforts. Children only needed one vaccine to protect against three diseases, and it became easier for healthcare workers to convince parents to give their babies one shot instead of many.

In 2005, the varicella vaccine was added to the MMR making it the MMRV vaccine. The MMR was 96% effective in preventing measles.


  • Since measles is highly contagious, any community needs a 95% vaccination rate to consider themselves free of the virus.
  •  The measles vaccine was heat-sensitive, so it was hard to maintain the vaccines at the right temperature as they were shipped and delivered across the globe, even in rural areas where refrigeration and urban infrastructure were a challenge.
  • The measles vaccination program coincided with the smallpox eradication campaign, and some public health departments and governments prioritized smallpox eradication over measles.
  • In 1998, a research article tied the MMR vaccine to autism, spreading suspicion and misinformation. Although the study was highly flawed, fraudulent, and later retracted, it caused fear and negatively impacted vaccine rates.



Even though the measles vaccine is affordable and widely available, in 2021, there were 128,000 measles deaths affecting mostly children under five.

Measles is the leading vaccine-preventable disease in the world, and efforts to improve vaccination efforts must continue. Another reason why vaccination is most important is because there is no specific treatment for measles; prevention is key.

Learning from mass vaccination efforts in the past

Mass vaccination programs are beneficial because they:

1. Prevent Outbreaks: Mass vaccination programs significantly contribute to controlling the spread of infectious diseases, especially in densely populated areas like cities. When there is a high level of vaccine coverage, these campaigns create a protective barrier, known as herd immunity.

Herd immunity is the level to which a population of people becomes immune to a contagious disease. A community is said to have achieved herd immunity when a sufficient percentage of people are immune to the disease-causing pathogen, which reduces the disease’s ability to spread and infect more people.

2. Minimize the healthcare burden: Mass vaccination programs help alleviate the strain on healthcare systems during an emergency. They can help reduce the number of severely ill individuals, which can prevent or reduce the spread of infectious disease outbreaks, and help healthcare providers better manage their resources.

3. Protect vulnerable and at-risk populations: Mass vaccination programs help safeguard vulnerable populations like infants, the elderly, and people with compromised immune systems. When a significant portion of a population gets immunized, those who cannot receive vaccinations due to medical reasons or age restrictions can be shielded.


We have a lot to learn from the mass vaccination programs of the past to boost the fight against future contagious diseases.

Public outreach, better communication channels, drug delivery innovations, and greater collaboration between public health officials can help us achieve vaccine equity. Only then can we bridge vaccine coverage gaps, counter vaccine hesitancy, and fight against common infectious diseases that continue to harm our global community.


The GIDEON difference

GIDEON is one of the most well-known and comprehensive global databases for infectious diseases. Data is refreshed daily, and the GIDEON API allows medical professionals and researchers access to a continuous stream of data. Whether your research involves quantifying data, learning about specific microbes, or testing out differential diagnosis tools, GIDEON has you covered with a program that has met standards for excellence.

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Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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