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A STATISTICAL MODEL OF THE INTERNATIONAL SPREAD OF WILD POLIOVIRUS IN AFRICA

Monday, 24th of October 2011

• A STATISTICAL MODEL OF THE INTERNATIONAL SPREAD OF WILD POLIOVIRUS IN AFRICA USED TO PREDICT AND PREVENT OUTBREAKS

Abstract and introduction below; full text, with equations and graphics, is at        

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001109

Using outbreak data from 2003–2010, Kathleen O'Reilly and colleagues develop a statistical model of the spread of wild polioviruses in Africa that can predict polio outbreaks six months in advance.

Kathleen M. O'Reilly1*, Claire Chauvin2, R. Bruce Aylward2, Chris Maher2, Sam Okiror3, Chris Wolff2, Deo Nshmirimana3, Christl A. Donnelly1, Nicholas C. Grassly1

1 Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom, 2 Global Polio Eradication Initiative, World Health Organization, Geneva, Switzerland, 3 Immunizations and Vaccine Development, World Health Organization, Brazzaville, Republic of the Congo

Abstract 

Background

Outbreaks of poliomyelitis in African countries that were previously free of wild-type poliovirus cost the Global Polio Eradication Initiative US$850 million during 2003–2009, and have limited the ability of the program to focus on endemic countries. A quantitative understanding of the factors that predict the distribution and timing of outbreaks will enable their prevention and facilitate the completion of global eradication.

Methods and Findings

Children with poliomyelitis in Africa from 1 January 2003 to 31 December 2010 were identified through routine surveillance of cases of acute flaccid paralysis, and separate outbreaks associated with importation of wild-type poliovirus were defined using the genetic relatedness of these viruses in the VP1/2A region. Potential explanatory variables were examined for their association with the number, size, and duration of poliomyelitis outbreaks in 6-mo periods using multivariable regression analysis. The predictive ability of 6-mo-ahead forecasts of poliomyelitis outbreaks in each country based on the regression model was assessed. A total of 142 genetically distinct outbreaks of poliomyelitis were recorded in 25 African countries, resulting in 1–228 cases (median of two cases). The estimated number of people arriving from infected countries and <5-y childhood mortality were independently associated with the number of outbreaks. Immunisation coverage based on the reported vaccination history of children with non-polio acute flaccid paralysis was associated with the duration and size of each outbreak, as well as the number of outbreaks. Six-month-ahead forecasts of the number of outbreaks in a country or region changed over time and had a predictive ability of 82%.

Conclusions

Outbreaks of poliomyelitis resulted primarily from continued transmission in Nigeria and the poor immunisation status of populations in neighbouring countries. From 1 January 2010 to 30 June 2011, reduced transmission in Nigeria and increased incidence in reinfected countries in west and central Africa have changed the geographical risk of polio outbreaks, and will require careful immunisation planning to limit onward spread.

Please see later in the article for the Editors' Summary

Citation: O'Reilly KM, Chauvin C, Aylward RB, Maher C, Okiror S, et al. (2011) A Statistical Model of the International Spread of Wild Poliovirus in Africa Used to Predict and Prevent Outbreaks. PLoS Med 8(10): e1001109. doi:10.1371/journal.pmed.1001109

Academic Editor: Mirjam Kretzschmar, The National Institute for Public Health and the Environment, Netherlands

Received: October 6, 2010; Accepted: September 7, 2011; Published: October 18, 2011

Copyright: © 2011 O'Reilly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was funded by the Poliovirus Research subcommittee of the WHO, a Royal Society University Research Fellowship to NCG. KMO, NCG, and CAD acknowledge the Medical Research Council for funding of the MRC Centre for Outbreak Analysis and Modelling at Imperial College. WHO is one of the spearheading partners of GPEI, and provides technical assistance and supports surveillance for acute flaccid paralysis. The Royal Society and the Medical Research Council had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: CM is a serving staff member of the World Health Organization. NG has received funding from the World Health Organization. All other authors have declared that no competing interests exist.

Abbreviations: AIC, Akaike's information criteria; AFP, acute flaccid paralysis; AUC, area under the curve; CI, confidence interval; DRC, the Democratic Republic of the Congo; GPEI, Global Polio Eradication Initiative; OPV, oral poliovirus vaccine; SE, standard error; SIA, supplementary immunisation activity; WHO, World Health Organization

* E-mail: k.oreilly@imperial.ac.uk

Editors' Summary 

Background

During the first half of the 20th century, polio (poliomyelitis) was one of the most feared infectious diseases in industrialized countries, paralyzing thousands of young children every year. The virus that causes polio enters the human body through ingestion of contaminated water or food, multiplies in the gut, and is shed through the feces (stool) into the environment, where it spreads rapidly if sanitation or personal hygiene is poor. Most people infected with poliovirus have no symptoms, but about one in 200 infected people develop paralytic polio, in which poliovirus invades and destroys the nerve cells that control the arm and leg muscles, leading to acute flaccid paralysis (AFP; limb paralysis). In the worst cases, poliovirus paralyzes the muscles involved in breathing, which can be fatal unless patients are helped to breathe with an “iron lung” or ventilator. There is no cure for paralytic polio, and although AFP usually lasts less than two weeks, some patients never regain full use of their limbs.

Why Was This Study Done?

From 1955 onwards, routine polio vaccination rapidly reduced or eliminated wild polio (polio occurring through natural infection) in developed countries, but the disease remained common in developing countries. Consequently, in 1988, the Global Polio Eradication Initiative was launched. Between 1988 and 2009, routine vaccination and supplementary immunization activities (additional doses of polio vaccine given to all young children on national immunization days) reduced the annual number of children paralyzed by polio from 350,000 to about 1,600 and the number of countries where polio is endemic (always present) from 125 to four. Unfortunately, continued circulation of wild polioviruses in Nigeria and India resulted in reinfection of 19 African countries in 2009 and re-establishment of polio transmission in four countries. A better understanding of the factors that affect the distribution and timing of wild polio outbreaks might help experts prevent such outbreaks and could facilitate global polio eradication. Here, the researchers develop a statistical model of the spread of wild polioviruses in Africa and assess its ability to predict polio outbreaks in individual African countries.

What Did the Researchers Do and Find?

The researchers used routine AFP surveillance to identify children who developed polio in Africa between 2003 and 2010. They determined whether each case was associated with the importation of wild poliovirus based on genetic analysis the polioviruses and then used “multivariable regression analysis” to identify factors associated with the number, size, and duration of polio outbreaks. During the study period, 142 genetically distinct polio outbreaks (involving one to 228 cases) were recorded in 25 African countries, with the average number of outbreaks in each country declining with reduced population movements from each infected country. The estimated number of people migrating into a country from an infected country was associated with the number of outbreaks in that country. Thus, countries with a high rate of immigration from Nigeria and other countries where polio is still endemic had more polio outbreaks than countries with less immigration from these countries. A country's mortality rate for children under 5 years of age (an indicator of sanitary conditions and access to health care) was also associated with the number of outbreaks, and immunization coverage was associated with the size, duration, and number of outbreaks. Finally, in 82% of instances, for a randomly selected country where an outbreak was observed, the statistical model predicted six months ahead of time more outbreaks for that country than for any randomly selected country where there were no outbreaks. That is, the model's predictive ability was 82%.

What Do These Findings Mean?

These findings indicate that outbreaks of polio in Africa over the study period resulted mainly from continued transmission in Nigeria and other countries that reported polio cases and from poor immunization status. They also highlight how the geographical risk of polio is changing over time in Africa. Importantly, the risk factors included by the researchers in their statistical model are sufficient to describe the scale and geographical distribution of polio outbreaks in Africa six months in advance with a high predictive ability. Although the accuracy of the predictions made by the model is limited by the structure of the model and by the data fed into it, the information provided by this and other predictive models should help the Global Polio Eradication Initiative plan its future immunization and surveillance campaigns and should facilitate the elimination of polio from Africa.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1​001109.

The Global Polio Eradication Initiative provides information about polio and about global efforts to eradicate the disease; its website includes links to videos about global polio elimination efforts

The World Health Organization provides information about polio and attempts to eradicate the disease (in several languages)

The US Centers for Disease Control and Prevention provides information about polio vaccination

The UK National Health Service Choices website has information on polio

MedlinePlus provides links to more resources on polio (in English and Spanish)

Personal stories about polio are available through the British Polio Fellowship Heritage Project; the National Museum of American History Whatever happened to polio? website includes an archive of polio-related pictures