The Elimination and Eradication theme focuses on how modelling and statistical analysis can support the elimination and eradication of infectious diseases. This could be, for example, through identifying immunity gaps, anticipating importation and outbreak risks, measuring the costs of control against the benefits of achieving elimination, and evaluating if and when transmission has been interrupted.  

The aims of this research theme are to:

• Share knowledge and experiences in developing mathematical models for the purpose of informing elimination and eradication.
• Develop and refine methodological approaches specific to elimination and eradication.
• Develop best practice in how modelling can be used by stakeholders and policy makers working in elimination and eradication.
• Improve how diagnostic tools and surveillance affects inference on elimination.

Introduction

In 1997 a workshop on the Eradication of Infectious Diseases was held to discuss and define the terms elimination and eradication, identify lessons that can be learned from previous and current programs and develop the science of eradication. Mathematical models were discussed at this meeting, and their inference has been informative from the beginning. At that time, only smallpox had been eradicated after decades of intensive control efforts through use of vaccination and surveillance for outbreaks of this deadly disease. Other eradication programmes have since failed; yellow fever, malaria, and yaws.  

Since this time world has changed; there is new enthusiasm for eradication. In the 1980s polio was successfully eliminated from the Americas and enormous efforts have been undertaken to eradicate. In veterinary medicine rinderpest has not been reported in animals since 2006 and an intense serological surveillance program has confirmed eradication. Guinea-worm disease is restricted only to 4 countries in sub-Saharan Africa. For some vector-borne diseases new control tools are becoming available and eradication is once again being discussed.

These exciting public health developments require an informed analysis to help support development of feasible elimination and eradication plans. Central to this is an understanding of the feasibility of eradication and mathematical modelling can have a role. Mathematical and statistical models can be used to inform:

• The feasibility of moving from control to elimination
• Whether an epidemic will die out within a period of time
• The probability that transmission has been eliminated

Especially when there are multiple options for an intervention, it is possible to compare the interventions by estimating the probability of each preferred outcome. Common to many of these themes is the use of data from outbreaks of infectious diseases to understand disease dynamics, and how they can be altered through control activities.

Crossness Sewage Treatment trip

On what was possibly the coldest day in 2019 we made a trip to Crossness Sewage Treatment works to see how the Victorians dealt with London’s sewage. This is related to elimination and eradication because cholera was a huge public health problem in London before the development of considerable engineering infrastructure to remove waste from contaminating the water supply in London, and sewage sampling is a critical form of surveillance for poliovirus and other pathogens. We were shown round the old treatment works at Crossness sewage by Petra Cox (Outreach Officer). Fascinating insights included the speed at which the project was planned and implemented by Joseph Bazalgette, and the beautiful details of the inside of the pumping station.

Elimination and Eradication CMMID seminar

In July 2019, we had a very interesting set of ‘turbo talks’ by researchers within LSHTM who are working on areas linked to elimination and eradication;

The meeting allowed us to ruminate over the common threads across these diseases. It was apparent that targets, even if they will not feasibly be met are useful to catalyse progress, but we wondered if this approach will erode with time (“crying wolf” with each new target). Across many diseases it was apparent that surveillance becomes critical as the disease reduces in incidence, and it is often at this time that stakeholders and funders of surveillance may lose interest. A few examples of the ‘freedom from infection’ framework were given, which provide a useful framework to understand the importance of surveillance in near-elimination settings.

• Kath O'Reilly - Polio
• Amy Pinsent – Trachoma
• Lindsay Wu – Malaria
• Lloyd Chapman – Leishmaniasis
• Tom Sumner – Tuberculosis

Please find a small sample of publications from the Elimination and Eradication theme below.

Robert A et al (2024). Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study

In a new mathematical modelling study using measles case data from England, Robert et al show that a rise in measles infections among people who have had two doses of MMR was in line with the effectiveness of the vaccine slowly decreasing by 0.04% each year after vaccination. 

The proportion of measles cases in adults who had previously received two doses of the MMR vaccine in England increased from 1.9% (20/1064) to 7.2% (57/790) between 2011 and 2019. Robert et al implemented a compartmental model to examine whether the rise could be explained by the small proportion of people who do not gain protection from MMR after two doses, or whether waning protection from the vaccine might also be a factor. A mathematical model with very gradual waning in protection from MMR (approximately 0.04% per year of age) could best reproduce the real number and age distribution of recent measles cases in double-vaccinated people in England.  

This finding shows that the MMR vaccine remains highly protective against measles for life, protecting over 95% of vaccinated individuals after each dose, and maintaining a high effectiveness for decades. As measles is highly infectious, the slow waning of immunity is enough to contribute to measles outbreaks, impacting the size and duration of outbreaks. These findings emphasize the need to increase vaccination coverage in the population to mitigate the risks of outbreaks and achieve. 

Robert A, Suffel A, Kucharski A. Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study. The Lancet Public Health, 2024.

Fu H et al (2023). Impact and cost-effectiveness of measles vaccination through microarray patches in 70 low-income and middle-income countries: mathematical modelling and early-stage economic evaluation

Microarray patches are a promising technology being developed to reduce barriers to vaccine delivery based on needles and syringes. A recent analysis by Fu et al show that the introduction of microarray patches could substantially reduce measles burden in low- and middle-income countries: the model showed that the introduction of measles-rubella microarray patches could prevent between 27% and 37% of measles burden between 2030 and 2040 compared with the needles and syringe-only immunisation strategy. 

The analysis included 70 low- and middle-income countries, and indicates that the largest health impact of introducing microarray patches would be achieved under lower coverage projection (i.e. vaccine coverage stagnating at the 2019 level) and accelerated introduction of microarray patches (i.e. prioritising countries with high burden and low vaccine coverage), with 39 million measles cases averted.

The findings highlight the cost-effectiveness of introducing microarray patches, as they would lead to savings on the cost of measles treatment. The cost-effectiveness analysis of microarray patches was carried out across a range of assumptions on coverage trend and vaccine procurement prices. The authors conclude that introducing microarray patches in most low- and middle-income countries will be a cost-effective strategy to revitalise measles immunisation programmes with stagnant uptake and reach undervaccinated children. Sustainable introduction and uptake of measles-rubella microarray patches has the potential to improve vaccine equity within and between countries and accelerate progress towards measles elimination. 

Fu H, Abbas K, Malvolti S, Gregory C, Ko M, Amorij J-P, Jit M. Impact and cost-effectiveness of measles vaccination through microarray patches in 70 low-income and middle-income countries: mathematical modelling and early-stage economic evaluation. BMJ Global Health, 2023.

Nightingale E et al. Sub-national estimation of surveillance sensitivity to inform declaration of disease elimination: A retrospective validation against the elimination of wild poliovirus in Nigeria

A fundamental question in the global commitment to polio eradication is how long a period of absence would be consistent with regional elimination, and the safe withdrawal of the oral polio vaccine is contingent on the answer. A recent analysis by Nightingale et al presents a statistical framework to estimate time-varying sensitivity of two key components of polio surveillance - environmental sampling and clinical cases of acute flaccid paralysis - for detecting infection at the local government authority level. 

We estimate the probability of freedom from infection (FFI) at a critical prevalence level that is consistent with interruption of transmission, given the absence of virus in collected samples. We validated this framework against two periods of poliovirus absence in Nigeria (2014-2016 and 2016-2020).  

We observed substantial heterogeneity in surveillance sensitivity over time and space and, given this, concluded an 85% probability (95% uncertainty interval: 77.1-90.2%) of the country being free from WPV1 infection after 23 months without detection from 2014. Detection of WPV1 in July 2016 demonstrated that circulation had indeed persisted during this time. In contrast, we conclude a probability of 98% (97.9-98.7%) by the time elimination of the serotype was officially declared in 2020.

The inferred probability of FFI during both time periods was found to be consistent with the retrospectively known status of regional elimination. This supports the validity of applying this framework prospectively to inform the certification of wild poliovirus elimination from remaining endemic regions, and to determine the resolution of cVDPV2 outbreaks.

Nightingale E, Pham-Minh L, Bello I, Okrior S, Erbeto T, Baba M, Adeneji A, Auzenbergs M, Edmunds J, O'Reilly K. Sub-national estimation of surveillance sensitivity to inform declaration of disease elimination: A retrospective validation against the elimination of wild poliovirus in Nigeria. Preprint, 2025.

Robert A et al (2021). The impact of local vaccine coverage and recent incidence on measles transmission in France between 2009 and 2018

We show from French surveillance data that high vaccine coverage protects against outbreaks from imported cases. Importantly, the WHO criteria for measles elimination (low recent incidence) was associated with a higher probably of observing cases, presumably due to a build up of susceptibility. 

Robert A, Kucharski A, Funk S. The impact of local vaccine coverage and recent incidence on measles transmission in France between 2009 and 2018. Preprint, 2021.

Macklin G et al (2020). Evolving epidemiology of poliovirus serotype 2 following withdrawal of the serotype 2 oral poliovirus vaccine

Using a statistical model, we discovered that most outbreaks of polio across Asia and sub-Saharan Africa are likely associated with the serotype 2 vaccine strain. To block transmission when poliovirus outbreaks occur requires deployment of the only tool in the box: the existing live attenuated serotype 2 oral vaccine, which increases the risk of vaccine-derived disease.

 

Macklin G, O'Reilly K, Grassly N, Edmunds W, Mach O, Santhana Gopala Krishnan R, Voorman A, Vertefeuille J, Abdelwahab J, Gumede N, Goel A, Sosler S, Bandyopadhyay A, Pallansch M , Nandy R, Mkanda P, Diop O, Sutter R. Evolving epidemiology of poliovirus serotype 2 following withdrawal of the serotype 2 oral poliovirus vaccine. Science, 2020.

Polio Eradication: A public health catch-22

In March 2020, several researchers within the Elimination and Eradication theme published a paper in Science, describing the epidemiology and challenges of eradicating poliomyelitis. In 2016, the serotype 2 component of the oral poliovirus vaccine given to children was withdrawn. This measure was taken to prevent vaccine-associated disease outbreaks caused by mutation in the live attenuated vaccine. At the time, children around the world had lowered immunity to serotype 2 poliovirus because the inactivated vaccine is far less effective and a new oral vaccine was not yet ready. 

Using a statistical model, Macklin et al. discovered that most outbreaks of polio across Asia and sub-Saharan Africa are likely associated with the serotype 2 vaccine strain. To block transmission when poliovirus outbreaks occur requires deployment of the only tool in the box: the existing live attenuated serotype 2 oral vaccine, which increases the risk of vaccine-derived disease.

In late 2020 the new oral vaccine, the nOPV2, received emergency use licensure and the first use of nOPV2 in field conditions is expected to be completed in early 2021. The nOPV2 has been shown in Phase I and II trials to be considerably more genetically stable, and has the potential to be an important tool in preventing further cases of vaccine-derived disease. Research is continuing within the theme to support polio eradication through epidemiological analysis and modelling, such as that reported in a follow on paper in Vaccine and discussed in this expert opinion piece. 

Measles elimination in Europe

In a recent commentary in the Lancet, several members of CMMID suggest that measles elimination in Europe is in crisis . In 2018 within the 53 countries of the EURO region more than 80,000 confirmed cases were reported. Measles is well understood to be an acute and highly transmissible infectious disease, but also an infection with a highly immunogenic vaccine that is available through routine immunisation. There are many challenges of measles elimination, including vaccine hesitancy and issues with access to vaccines, especially in vulnerable and highly mobile populations.

In a recent analysis of data from France, Alexis Robert has illustrated that vaccine coverage is highly protective against imported cases and localised outbreaks, and regions reporting recent incidence had a lower risk of local transmission, a finding consistent with acquisition of local immunity. Importantly, the WHO criteria for measles elimination (ie. low recent incidence) was associated with a higher probably of observing cases, presumably due to a build up of susceptibility. This finding has implications for elimination assessments for measles as the criteria are inconsistent with the epidemiology of measles, and should consider important factors such as local vaccination coverage.