THE CHALLENGES THAT THE GLOBAL POLIO ERADICATION INITIATIVE FACES.

Posted by | May 08, 2008 | RESOURCES, TEXTBOOK | No Comments

In the last few decades, we have been able to curb the number of children affected by polio and the number of countries harbouring the virus with great success. This is made possible by the introduction of two very efficient vaccines and the establishment of a global mass-scale immunisation campaign that has already administered 10 billion doses of the vaccines[1]. This campaign was set up to eradicate the virus; however, recently, the campaign has been facing many challenges that have made it difficult to complete the mission.

The polio virus (PV) part of the Enterovirus genus of the Picornaviridae family is an RNA virus that is usually transmitted by the faecal-oral route and has probably been circulating for more than 3000 years. It did not, however, cause any major epidemics until the 19th century when hygiene standards increased. Paradoxically, the virus was able to thrive; children only started encountering the virus after the protective maternal antibodies had worn off and as such they were becoming infected at a later age when the virus is more damaging[2]. 95% of infections with PV are restricted to the gut and are asymptomatic. Nonetheless, the virus is shed in their stool and can be transmitted to others. In the remaining cases, the virus is able to spread into the blood and can either cause a minor illness which results in abortive poliomyelitis or can lead to severe symptoms and paralytic disease develops (acute flaccid paralysis, AFP). Abortive poliomyelitis cannot really be distinguished from other viral infections and is cleared within a week[3]. In 1% of total PV cases, AFP develops due to the death of muscle-innervating neurons. Muscles become weak and they eventually atrophy as they no longer receive any nerve stimulation[4]. If the lower spinal cord is invaded, paralysis of the legs occurs. However, if the infection spreads to the brain stem, the virus can cause paralysis of the diaphragm and in turn, severe breathing impairment. Permanent paralysis occurs in approximately 80% of cases with severe disease, death occurs in 10% and complete recovery is observed in the remaining 10%[5].

To combat this terrible disease, two vaccines were produced: the inactivated polio virus vaccine (IPV) by Jonas Salk in 1955 and the oral polio virus vaccine (OPV) by Albert Sabin in 1963. The IPV consists of “killed’’ polio virus vaccine of all three PV serotypes (trivalent vaccine). It is an injectable vaccine that is well tolerated. The OPV consists of a “live attenuated PV vaccine and is also trivalent. Most developing countries use the OPV because it is very convenient to administer and is cheap[6]. It has been shown to induce immunity in 95% of cases after three doses. It also provides excellent intestinal immunity, lifelong protection and helps prevent infection against the wild-type virus and is therefore is the vaccine of choice in places where the wild-type virus still circulates. Intestinal immunity is important because this is the main entry site the virus, of lesser importance is the acquisition of the virus through the respiratory route. The IPV, on the other hand, is mostly used in industrialised countries and confers 99% immunity after three doses but produces a weaker gastrointestinal immune response than the OPV. Therefore, it is not recommended in places where wild-type poliovirus is endemic because the likelihood of being infected through the oral-faecal route is much higher than through the respiratory route [3].

The Global Polio Eradication Initiative (GPEI) was established in 1988, after polio had been identified as being a candidate for this type of project. Humans are the virus’ only reservoir and the disease could be prevented by an effective and affordable vaccine. The successful results that were seen in the smallpox eradication were also an incentive. In 1979, smallpox was eradicated after a 10-year global effort. The GPEI was initially planned that by 2000, polio would be eradicated by a large-scale immunisation campaign. This was to be achieved by holding several immunisation days to reach a maximum number of children worldwide. The endeavour has not been entirely successful, but, nonetheless, wild-serotype 2 PV has been completely eradicated. The number of poliomyelitis cases dropped from 350,000 in 1988 to 2,917 in 2000 and out of 126 countries, only 4 remain endemic (Nigeria, India, Pakistan, Afghanistan)[4]. The program has had many challenges that prevented it from meeting its goal and the projected year of eradication has been pushed back several times. At the current stage, it has been set for 2010 but is unknown when the eradication will definitely take place[6]. There are several reasons why polio has been much more difficult to eradicate than smallpox (which occurred in 1979 after a 10 year global eradication effort) and these are mainly because of the high number of subclinical cases of polio, political instabilities in certain countries and the occurrence of vaccine-derived polio.

Unlike smallpox infections that show obvious clinical symptoms, there are 100 to 200 subclinical polio cases (who all excrete the virus) for every case of paralysis. This makes surveillance and control of polio extremely difficult. In contrast, since smallpox has easily identifiable signs of infection everyone surrounding the infection would be targeted for immunization and the virus would quickly be under control[7].

In 2003, three states in northern Nigeria boycotted the GPEI because political and religious leaders believed that the vaccine was a method used by Western countries to decrease the number of Muslims. They thought that the vaccine was laced with anti-fertility, cancerous agents and HIV. In an interview with the Baltimore Sun, a WHO doctor said: “If America is fighting people in the Middle East, the conclusion is that they are fighting Muslims”. The belief that the vaccine was contaminated is thought to stem from many factors. Firstly, some people thought that the population policy set in the 1980s by the Nigerian government that limited the number of children to four per woman was enforced by a vaccine. Also, the Nigerian people are suspicious of aggressive large-scale immunisation campaigns. As seen in John Murphy’s report in the Baltimore Sun this is understandable from a Nigerian’s perspective “…to be offered free medicine is about as unusual as a stranger’s going door to door in America and handing over $100 bills. It does not make any sense in a country where people struggle to obtain the most basic medicines and treatment at local clinics”. The consequence of the boycott was a 30% increase in polio cases in Nigeria in 2004 alone[8], and an even higher increase in subsequent years. It also led to the spread of the virus to several neighbouring countries where polio had not been observed in many years. Even more alarming was the spread to distant countries like Indonesia[6].

One of the major drawbacks with the OPV that is not a problem with the IPV is in very rare cases, it can cause vaccine associated paralytic polio (VAPP) in recipients of the vaccine or their contacts (one in 500,000 first-OPV doses)[4]. This has resulted in several outbreaks where the virus had been previously eradicated[5] and occurs when the attenuated virus regains phenotypes that resemble the wild-type virus. This does not come as a surprise since the vaccine virus contains only a few attenuating mutations and the virus’ polymerase makes a lot of mistakes that makes reversion easy[4].

In more recent years, it has become apparent that the OPV might not be working in certain areas of the world. In places like the states of Uttar Pradesh and Bihar in India, there are documented cases of children who developed AFP even after having been given ten doses of the vaccine. Some have speculated that this is not only due to the insufficient vaccine coverage but also due to extreme poverty and overcrowding. All these factors have rendered children chronically infected with enteric diseases and consequently, interferes with the vaccine efficacy and in turn causes vaccine failure[4]. However, these factors do not seem to explain why some places with similar or worse conditions have managed to eradicate the virus. Others believe that the people in these regions may have a genetic predisposition to the infection and increasing the amount of doses or trying to improve the OPV is not the way to proceed. The evidence to support this comes from the fact that in 2005, monovalent OPV1 and monovalent OPV3 were introduced and they still saw a 10-fold increase in polio incidence in 2006[9]. These monovalent vaccines are thought to be more efficient then the trivalent vaccine. Dr. Bruce Aylward, the director of the WHO polio eradication initiative, stated: “Part of the problem with the trivalent oral vaccine is that the viral strains compete with each other. Type 2 tends to be the strain that you get the best serological response to, and that compromises the response to type 1 and type 3” (infections from the type 2 strain were last recorded in 1999, type 1 was the cause of most infections between 2003-2006 and is the most transmittable, type 3 is found in the last 4 endemic countries but is less virulent than type 1)[10]. It has been suggested that switching to an improved version of the IPV would be the best. Perhaps this could be done by using novel adjuvants (a pharmacological agent to increase the vaccine’s efficacy) to induce intestinal immunity that is currently lacking in the IPV and is making it less effective than the OPV. Another hurdle to overcome would be to come up with a strategy that would enable easier administration of the vaccine like the OPV[4].

Furthermore, an added concern for the GPEI is the waning patience of donors to continue to fund a project that does not seem to end. Paula Dobriansky, US under secretary of state for democracy and global affairs stated “Donor fatigue is real. The WHO claimed we would have eradicated polio by a set date, not once, but twice before”[10]. To date, the program has cost US$ 4.5 billion and will require an additional US$ 575 million for the next 2 to 3 years. It was anticipated to only cost US$ 2 billion[1].

However, to cut back funding at this point would be nothing but disastrous and is definitely evident from the outbreaks of polio that occurred around the world following the boycott in Nigeria. And what needs to be emphasised here is that this interruption was just in one country. The GPEI has saved millions of people from suffering. If it does not make humanitarian sense to eradicate polio then we can look at it from an economic perspective. It is expected that the world would save US$ 1.5 billion a year once vaccination is no longer needed. This can be compared with smallpox eradication, where in 1967, smallpox killed 2 million people. The cost of the eradication program was approximately US$ 300 million (US$ 100 million from international assistance and US$ 200 million from recipient countries) but has subsequently saved the world roughly US$1.35 billion a year[7, 11] and millions of lives and livelihoods.

References

1. Lahariya C. Global eradication of polio: the case for “finishing the job”. Bull World Health Organ 2007;85:487-92

2. De Jesus NH. Epidemics to eradication: the modern history of poliomyelitis. Virol J 2007;4:70

3. Atkinson W, Hamborsky J, McIntyre L and Wolfe S. “Poliomyelitis”, Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). Washington DC: Public Health Foundation, 2007:101-114

4. Chumakov K, Ehrenfeld E, Wimmer E and Agol VI. Vaccination against polio should not be stopped. Nat Rev Microbiol 2007;5:952-8

5. Minor PD. Polio eradication, cessation of vaccination and re-emergence of disease. Nat Rev Microbiol 2004;2:473-82

6. Rey M, Girard MP. The global eradication of poliomyelitis: Progress and problems. Comp Immunol Microbiol Infect Dis 2008;31:317-25

7. Arita I, Nakane M and Fenner F. Public health. Is polio eradication realistic? Science 2006;312:852-4

8. Jegede AS. What led to the Nigerian boycott of the polio vaccination campaign? PLoS Med 2007;4:e73

9. Paul Y. OPV cannot eradicate polio from India: Do we need any further evidence? Vaccine 2008

10. Reynolds T. Polio: an end in sight? Bmj 2007;335:852-4

11. Barrett S. Eradication versus control: the economics of global infectious disease policies. Bull World Health Organ 2004;82:683-8

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