Editorial: A farewell to polio vaccination? Not anytime soon
Paralytic poliomyelitis is quickly disappearing from the world. In June, the European Region of WHO was certified to be polio-free. This followed similar achievements in the Americas and the Western Pacific Region which had been certified polio-free in 1994 and 2000, respectively (WHO 2002a). Last year, less than 500 confirmed cases of polio were reported world-wide (WHO 2002b). Transmission of the polio wild virus has been restricted to 10 countries, among them India, Pakistan and Nigeria (Global Polio Eradication Initiative 2002).
This is an enormous accomplishment. Not long ago, paralytic polio was a dreaded affliction of young people everywhere. For example, 50 years ago, in the summer and autumn of 1952, Germany was hit by the most severe polio outbreak the country ever experienced. Almost 10 000 cases were recorded in a single year, of whom 800 resulted in death (Pöhn & Rasch 1993). Over the following 10 years, polio outbreaks in industrialized countries ceased, thanks to successful mass immunization campaigns. In developing countries, childhood immunization coverage improved markedly through the Expanded Programme on Immunization. Notwithstanding, there were still 350 000 people affected by poliomyelitis in 1988. In that year, the World Health Assembly resolved to eradicate polio from the world. This goal is today being pursued by the Global Polio Eradication Initiative, an alliance of WHO, Rotary International, CDC, UNICEF and others.
The WHO defines eradication as the achievement of a status whereby no further cases of a disease occur anywhere, and continued control measures are unnecessary (Last 1995). Technically, polio eradication appears to be feasible: an effective vaccine is available, and there exists no natural reservoir of polio virus outside humans. Recent developments, however, indicate that the eradication effort faces substantial problems. I shall discuss two of them in more detail. The first one relates to the attenuated live vaccine, the second one to the organization of immunization programmes.
First problem – the live vaccine
Sabin's attenuated live vaccine seems ideally suited for use in developing countries (Henderson 2002): it is cheap, it can be administered orally by helpers and it induces local immunity in the intestine shortly after vaccination, thus effectively protecting against faeco-oral transmission of polio virus. In addition, the vaccine virus is excreted via the intestine; under poor hygienic conditions it can infect non-immunized persons, thereby protecting them against poliomyelitis.
The live vaccine has disadvantages. In developing countries, at least 5–6 doses of the vaccine need to be given in order to convey a reliable immunity against all three serotypes of the polio virus. A rare but problematic side-effect are sporadic cases of paralytic poliomyelitis in vaccinated persons or their relatives – approximately one case per two million vaccinations (CDC 2000). Salk's inactivated vaccine does not have these disadvantages, but also lacks the advantages of the live vaccine listed above, and it is considerably more expensive.
The WHO had planned to eradicate polio through a massive use of the live vaccine, and then to stop polio vaccination completely. This strategy is based on two assumptions (Henderson 2002). First, that the live vaccine can cause sporadic cases, but no outbreaks, of paralytic poliomyelitis; and secondly, that vaccinated persons will not excrete the vaccine virus for more than 2–3 months.
If both assumptions were correct, polio vaccination could be discontinued soon after the transmission of wild virus has been interrupted globally. Some months later, the last vaccine recipients would have ceased to excrete the vaccine virus. Wild virus and vaccine virus would thus have been eradicated. From then on, newborn children would no longer have to be immunized against polio. Unfortunately, neither assumption is correct, as we now know.
Two years ago, an outbreak of paralytic polio occurred in Haiti and the Dominican Republic, with 21 cases, including two deaths. The two countries had previously been polio-free for more than 10 years. The genome of the virus isolates was sequenced, and the findings were sobering. The cases had not been caused by imported wild polio viruses, as had initially been suspected, but by vaccine viruses of the Sabin strain; these had back-mutated, recovering the neurovirulence and high contagiousness of the polio wild virus (Kew et al. 2002). The extent of genetic differences to the Sabin virus indicated that the mutated vaccine virus had been circulating in the population unnoticed for about 2 years. Under the prevailing poor hygienic conditions and low vaccination coverage, frequent infections and passages in humans occurred, each providing opportunities for mutations of the vaccine virus (Fine & Carneiro 1999).
The second assumption, that vaccine virus is excreted only for short time periods, does not hold either. People with (rare) B-cell-related immunodeficiency disorders may shed it for 10 or more years. Persistent infections in HIV-positive vaccine recipients cannot yet be ruled out completely. Hence, vaccine virus may still be circulating long after polio vaccination has been stopped (Fine & Carneiro 1999). If the vaccine virus would then revert to a neurovirulent form, the unprotected younger age cohorts would face the risk of massive outbreaks of paralytic polio.
Outbreaks of paralytic disease caused by mutated vaccine virus can be prevented if a high immunization coverage with the live vaccine is maintained, even after the transmission of wild virus has been interrupted globally. This is of particular importance in regions with a low hygienic standard. Thus a paradox situation arises: polio vaccination will no longer be directed against the wild virus, but against possible complications of the polio vaccination itself. The use of inactivated vaccine is unlikely to resolve the issue. It does not convey reliable intestinal immunity, hence it may not interrupt the transmission of already circulating vaccine virus. Besides, it is prohibitively expensive for general use in developing countries.
Second problem – the organization of immunization programmes
So how can the high immunization coverage required to prevent outbreaks due to mutated vaccine virus be achieved? This question leads to the second problem, the organization of immunization programmes. In many highly endemic regions, transmission of polio virus could not be interrupted by routine immunization alone. A sufficiently high vaccination coverage was achieved through additional National Immunization Days (NIDs). On such days, usually held two times a year, all children under 5 years of age receive an additional dose of the live vaccine, irrespective of their vaccination status.
The NIDs and supporting activities to eradicate polio require an enormous input of resources (Roberts 2001). In India, their implementation negatively affected the routine immunization programmes (Razum et al. 2001). For example, vaccines other than polio were no longer available at health centres on a regular basis, and measles immunization coverage declined substantially. This was seen as a temporary problem that would vanish as soon as polio had been eradicated. Now it becomes clear that vaccination against polio will have to be continued for many more years. A sustainable way to maintain a high polio coverage would be via the routine immunization programmes. These programmes, however, are no longer fully operational, because of the competition with the NIDs for scarce resources.
In summary, the control of poliomyelitis is an impressive accomplishment of preventive medicine. Many cases of disease, disability and death among young people have been prevented globally. According to WHO, the transmission of polio wild virus will be interrupted world-wide before the end of this year. New insights into the biological and epidemiological properties of the polio virus indicate that its complete eradication may have been an overly ambitious goal. Two veterans of smallpox eradication, Isao Arita and Donald A. Henderson, believe that polio vaccination will have to be continued for many years until the nature of poliovirus is better understood (Nomoto & Arita 2002), or, perhaps, for the indefinite future (Henderson 2002). Now the challenge is to keep up the motivation for a long-term continuation of control measures. In order to uphold the progress already made in polio control, the routine immunization programmes need to be reinvigorated.