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Tuesday, 16th of August 2011 Print


During a recent visit to South Africa, I learned that the national immunization program had already incorporated IPV (in a five antigen combination vaccine) into its infant vaccination schedule, while retaining OPV for mass campaigns, the birth dose and at six weeks of age.

In its July 2011 report, the Independent Monitoring Board of GPEI said

  • Selective use of combined IPV/OPV is being talked about; why not take a serious look at it?

‘We hear murmurings about the idea of giving IPV and OPV in combination. Proponents highlight the  particular value of this idea in areas where access to children is severely limited by conflict. In such  settings, each opportunity to access a child is valuable. Repeated vaccination forays cannot be made so  the value of each must be captured by using the most effective intervention that there is. Some evidence   suggests that a combined approach reduces the risk of vaccine failure compared to giving either IPV or   OPV alone. (figure 7). Others are opposed to the idea, believing that it adds unnecessary complexity  and cost, and could be dangerous. We do not take a particular view on the answer to this question. But  we observe that the question is floating in the ether rather than being grasped. This does have the  potential to be a useful innovation, so the debate needs to be properly aired. We make a  recommendation to stimulate this.’ (see full report at www.polioeradication.org).


After consulting the IMB report,  I checked the WHO homepage and found that 83 countries and territories are currently using IPV, either as part of the regular schedule or, in some countries, for special groups. This included 18 developing countries of the Americas (plus the US and Canada), one African country, and 13 Asian countries. From Andorra to Uruguay, I don’t see a single country using IPV or combined IPV/OPV schedules with recent WPV, VAPP, or cVDPV cases. That is quite an accomplishment.

This 83 is not a majority of the 193 countries of the world, but it is quite a record for a vaccine which lacks several advantages of OPV: it cannot be administered by lay personnel in mass campaigns, it does not provoke  gut immunity like that produced by OPV, and it is more expensive than OPV, both alone and, especially in combination vaccines. IPV has two overwhelming advantages as we move towards the polio endgame: it does not provoke the VAPP and the cVDPV associated with the oral vaccine.

Some people believe that IPV should be used in the post-eradication era to prevent the reappearance of polio, others, that it should be used now, to speed the process of eradication.

Here are a few of the published articles on OPV/IPV combinations in developing areas. Note in particular the discussion from Gaza and Israel, a rare case of public health policy from a developing area influencing that in a developed country.

Good reading.




Best viewed at http://www.ncbi.nlm.nih.gov/pubmed/9203722


 WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines*

World Health Organization, Geneva, Switzerland                    

 To assess an immunization schedule combining oral (OPV) and inactivated poliovirus vaccines

(lPV), a clinical trial was conducted in The Gambia, Oman, and Thailand. Children were randomized to receive OPV at birth and at 6, 10, and 14 weeks of age; OPV at birth followed by both OPV and IPV at 6, 10, and 14 weeks of age; or placebo at birth followed by IPV at 6, 10, and 14 weeks of age. Serum specimens were available at 24 weeks for 1291 (77%) of 1685 enrolled infants. In the combined-schedule group, the proportion of children seropositive at 24 weeks was 95%-99% for type 1,99%-100% for type 2, and 97%-100% for type 3. In The Gambia and Oman, the combinedschedule performed significantly better than OPV for type 1 (95%-97% vs. 88%-90%) and type 3 (97%-99% vs. 72%-73%). Across the study sites, IPV given at 6, 10, and 14 weeks of age provided inadequate protection against poliovirus. The combined schedule provided the highest levels of serum antibody response, with mucosal immunity equivalent to that produced by OPV alone.

Abstract above; full text and figures at http://jid.oxfordjournals.org/content/175/Supplement_1/S215.long

In 1988, the World Health Assembly established the target of global eradication of poliomyelitis by the year 2000 [1]. Since then, remarkable progress has occurred in freeing many countries from poliomyelitis [2, 3]. Extensive use of trivalent oral poliovirus vaccine (OPV) has been associated with the interruption of wild poliovirus circulation in the Americas, where the last case of paralytic disease associated with wild poliovirus isolation occurred in August 1991 [4].

Current poliomyelitis eradication strategies recommended by the World Health Organization (WHO) focus on the early and intensive use ofOPV with routine delivery of doses at birth and 6, 10, and 14 weeks of age. Also recommended for countries in which polio is endemic are supplemental OPV delivery strategies, including national immunization days and house-to-house immunization in high-risk areas, strategies that were successful in the elimination effort in the Americas and are being adopted in other parts of the world.

Nonetheless, in developing countries there is wide variation in the serologic response ofchildren to OPV, with overall levels of seroresponse below those seen in industrialized countries. A review of 32 studies in developing countries found that after three doses of OPV, the mean proportion of infants with detectable levels of serum neutralizing antibody was only 73% (range, 36%-99%) for type 1,90% (range, 71%-100%) for type 2, and 70% (range, 40%-99%) for type 3 [5]. A recent large-scale randomized trial in Brazil and The Gambia has confirmed these findings [6]. Even after eight OPV doses delivered in mass campaigns, gaps in immunity, as defined by serum antibody levels, persist in some countries, especially for type 3 [7]. There is also evidence that OPV may not always succeed in preventing transmission of wild poliovirus, even when vaccine coverage is excellent. Outbreaks of poliomyelitis have occurred in some countries where coverage with three or more doses of OPV has been high, notably in Brazil [8], Bulgaria [9], The Gambia [10], Jordan [11], Israel [12], Malaysia [13, 14], Namibia [15], Oman [16, 17], and Saudi Arabia [18]. In these settings, vaccine efficacy has appeared to correlate with seroconversion rates, and some children with well-documented immunization histories have contracted paralytic disease.

 Some industrialized countries have become polio-free using inactivated poliovirus vaccine (IPV), but this vaccine has not been recommended by WHO for polio eradication in developing countries. When given to children in developing countries at intervals of 2 months, starting at 8 weeks of age, IPV has evoked excellent serologic response, but it is not known how long this protection lasts [19]. Because IPV does not produce the high levels of intestinal mucosal immunity seen with OPV, a person who is protected from paralytic disease by serum antibody may still excrete and transmit poliovirus to others. Moreover, unlike OPV, IPV is a killed vaccine, and it cannot, spread secondarily to contacts.

 A few countries or areas have become polio-free using a combination of OPV and IPV, notably Denmark [20] and the Palestine Self-Rule Areas of Gaza and West Bank [21]. However,these countries or areas use relatively complex schedules that are not completed until the first birthday or older (table 1). In 1988, the World Health Assembly requested research to develop additional polio immunization strategies that could speed the success of polio eradication [1]. Subsequently, the Global Advisory Group of the WHO Expanded Programme on Immunization specifically requested the assessment of a combined polio immunization schedule that would be practical to implement in developing countries, because it was anticipated that such a schedule could provide infants with the beneficial effects of both poliovirus vaccines at an early age [22].

In response to these recommendations, the WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines was formed. Here we report the results of a randomized clinical trial of a combined polio immunization schedule in The Gambia, Oman, and Thailand. To provide findings broadly applicable to future policy recommendations, the combined schedule was studied in different regions of the world. The study group thought it was important to study a simple schedule with simultaneous delivery of OPV and IPV at ages routinely recommended by WHO for immunization in developing countries, with polio immunization completed before 4 months of age (table 1). The trial assessed both the serum immune response and the mucosal immune response (as judged by protection on challenge with monovalent type 1 OPV at 6 months of age).




American Journal of Public Health | May 2011, Vol 101, No. 5


Blum et al. in November 2010 described the pioneering work of Natan Goldblum, a great Israeli virologist and innovator in polio immunization.1 Another important facet of his work was as a key contributor to development of the combined or sequential oral polio vaccine (OPV) and inactivated polio vaccine (IPV) programs used in the West Bank and Gaza since the late 1970s. 

Goldblum and Joseph Melnick from Baylor University were asked to consult in 1978 with the Israel Ministry of Health and the Gaza and West Bank public health services. During this time, I was the Coordinator for Health in the West Bank and Gaza for the Israeli Ministry of Health (from 1978-1994), with oversight responsibility for health in the West Bank and Gaza including immunization policy and other aspects of health services and training of Palestinian health providers.

 At that time, we faced continuing polio epidemics, mostly in Gaza where sanitary conditions were poor, despite high levels of OPV coverage. As an outcome of the discussions with Goldblum and Melnick, a new approach they recommended was jointly agreed to by the Israeli and Palestinian health officials.

This accord expanded the routine immunization program from four doses of OPV by adding three doses of IPV given in a mixed sequence during the first year of life. This method was later dubbed the Gaza system.Coverage was soon greater than 85%, and catch-up campaigns were conducted for persons aged up to 18 years. Polio disappeared during the next two years and was effectively eradicated from these previously endemic areas.2

 During the 1980s, Israel maintained an OPV-only policy, but with a trial IPV program in 2 districts of the country. In 1988, an outbreak of paralytic poliomyelitis occurred mainly among adolescents and young adults in one of these trial districts where the IPV-only policy was in effect (15 cases and one death). As a result of this episode, Israel adopted the Gaza system, and total eradication of polio was rapidly achieved.3,4


After eradication of polio in Gaza, the West Bank, and subsequently in Israel, the Gaza system was adopted and continues in other parts of the Middle East. A combined or sequential OPV and IPV program is an important policy option for polio control.5,6 In light of challenges in countries in which the virus is still endemic (Nigeria, India, Afghanistan, and Pakistan), with recent spread to other countries, the combination of OPV and IPV should again be considered for the endstage of polio eradication in remaining high risk areas.7,8

Ted Tulchinsky, MD, MPH

About the Author

Ted Tulchinsky is with the Braun School of Public Health, Hebrew University-Hadassah, Hadassah, Ein Karem, Jerusalem, Israel.


Correspondence may be sent to T.H. Tulchinsky, MD, MPH, Braun School of Public Health, Hebrew University-Hadassah, Ein Karem, Jerusalem, Israel 91120 (e-mail: tedt@hadassah.org.il). Reprints can be ordered at http://www.ajph.org by clicking the ‘‘Reprints/Eprints’’ link.

This letter was accepted December 19, 2010.


1. Blum N, Katz E, Fee E. Professor Natan Goldblum: the pioneer producer of the inactivated poliomyelitis vaccine in Israel. Am J Public Health. 2010;100(11):2074–2075.


1. Tulchinsky T, Abed Y, Shaheen S, et al. A ten-year experience in control of poliomyelitis through a combination of live and killed vaccines in two developing areas. Am J Public Health. 1989;79(12):1648–1652.


1. . Slater PE, Orenstein WA, Morag A, et al. Poliomyelitis outbreak in Israel in 1988: a report with two commentaries. Lancet. 1990;335(8699):1192– 1195. discussion 1196–8.


1. Goldblum N, Gerichter CB, Tulchinsky TH, Melnick JL. Poliomyelitis control in Israel, 1948-1993: changing strategies with the goal of eradication in an endemic area. Bull World Health Organ. 1994;72(5):783–796.


1. Parent du Chaˆtelet I, Merchant AT, Fisher-Hoch S, et al. Serological response and  poliovirus excretion following different combined oral and inactivated poliovirus vaccines immunization schedules. Vaccine. 2003; 21(15):1710–1718.


1. Asturias EJ, Dueger EL, Omer SB, et al. Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants. J Infect Dis. 2007;196(5):692–698.


1. Centers for Disease Control and Prevention. Outbreaks following wild poliovirus  importations—Europe, Africa, and Asia, January 2009-September 2010. MMWR Morb Mort Wkly Rep. 2009;59(43):1393–1399.