High population immunity reduces poliovirus community transmission
Authors: Julie Garon, Roland W Sutter, Walter Orenstein
Journal: The Lancet Infectious Diseases (2017)

In April and May, 2016, the Global Polio Eradication Initiative (GPEI) withdrew the live attenuated Sabin type 2 poliovirus from trivalent oral poliovirus vaccine (tOPV) and replaced it with bivalent types 1 and 3 oral poliovirus vaccine (bOPV).1Hampton LM Farrell M Ramirez-Gonzalez A et al.Cessation of trivalent oral poliovirus vaccine and introduction of inactivated poliovirus vaccine: worldwide, 2016.MMWR Morb Mortal Wkly Rep. 2016; 65: 934-938Crossref PubMed Scopus (123) Google Scholar This switch was facilitated by certification of wild poliovirus type 2 eradication in September, 2015.2Global Polio Eradication InitiativeGlobal eradication of wild poliovirus type 2 declared.http://www.polioeradication.org/mediaroom/newsstories/Global-eradication-of-wild-poliovirus-type-2-declared/tabid/526/news/1289/Default.aspxDate: Sept 20, 2015Google Scholar The switch, as part of sequential withdrawal of Sabin strains,3Global Polio Eradication InitiativePolio eradication and endgame strategic plan 2013–2018.http://polioeradication.org/wp-content/uploads/2016/07/PEESP_EN_A4.pdfDate: 2013Google Scholar was necessary because continued use of oral poliovirus vaccine would invariably be followed by endemic and epidemic transmission of circulating vaccine-derived polioviruses with neurovirulence and transmissibility properties of wild polioviruses and, thus, not compatible with eradication. The GPEI recognised that type 2 population immunity, particularly intestinal immunity, would wane rapidly after the switch from tOPV to bOPV, that the emergence of vaccine-derived poliovirus type 2 must be expected, and that planning for outbreak response activities needed to be part of contingency measures. Furthermore, other risks would need to be addressed—eg, prolonged and chronic type 2 poliovirus excretion among individuals with primary immunodeficiency disorders, and containment breaches from laboratories and vaccine production facilities. However, no recent community-based study data were available at the time of the switch to quantify type 2 poliovirus community transmission risks. In The Lancet Infectious Diseases, Mami Taniuchi and colleagues report findings of a large-scale community transmission study undertaken in the Matlab area of Bangladesh.4Taniuchi M Famulare M Zaman K et al.Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling study.Lancet Infect Dis. 2017; (published online July 7.)http://dx.doi.org/10.1016/S1473-3099(17)30358-4PubMed Google Scholar They randomly assigned infants by village to three routine vaccination schedules: tOPV only (three doses), bOPV and one dose of inactivated polio vaccine (IPV; four doses), and bOPV and two doses of IPV (five doses). The authors also enrolled household contacts and assessed community contacts. The vaccine schedule was followed by a mass vaccination campaign with monovalent type 2 poliovirus vaccine (mOPV2) that was given to a random selection of roughly 40% of children younger than 5 years. A high proportion (76%) of children assigned bOPV and either one or two doses of IPV excreted type 2 poliovirus after challenge with mOPV2, compared with 39% of those treated with tOPV (odds ratio [OR] 0·201, 95% CI 0·102–0·389; p<0·0001). This finding was expected, since the bOPV groups had little intestinal immunity and should excrete virus after challenge. As other studies have shown, IPV per se does not induce sufficient intestinal immunity,5Hird TR Grassly NC Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.PLoS Pathog. 2012; 8: e1002599Crossref PubMed Scopus (148) Google Scholar and no difference was noted in faecal excretion frequency between children who received one or two doses of IPV (77% vs 75%; OR 1·10, 95% CI 0·48–2·50; p=0·67). Among infants who did not receive the mOPV2 challenge, 6% excreted poliovirus, and among household contacts, 2% were found to be excreting. Furthermore, the household contacts excreted virus for a very short period only (about 1 week). Thus, under conditions favouring transmission, few household and community contacts in the study villages were infected. These findings suggest that countries such as Bangladesh would not be expected to have a high risk for emergence of vaccine-derived poliovirus type 2 events; moreover, should such viruses arise or be introduced now they would be unlikely to establish circulation. This outcome probably, in large part, reflects the high tOPV coverage in this population, resulting in substantial intestinal immunity to type 2 poliovirus in the community. In the pre-vaccine era, introduction of one infected individual with oral poliovirus vaccine would result in secondary exposure of greater than 90% of household contacts.6Gelfand HM Potash L Leblanc DR Fox JP Intrafamilial and interfamilial spread of living vaccine strains of polioviruses.JAMA. 1959; 170: 2039-2048Crossref PubMed Scopus (23) Google Scholar Findings of a study by Benyesh-Melnick and colleagues7Benyesh-Melnick M Melnick JL Rawls WE et al.Studies of the immunogenicity, communicability and genetic stability of oral poliovaccine administered during the winter.Am J Epidemiol. 1967; 86: 112-136Crossref PubMed Scopus (71) Google Scholar elucidated the community transmission of polio vaccine virus. The study by Taniuchi and colleagues has extended these findings to a tropical developing country setting, although to an area with excellent immunisation coverage. However, these study results cannot be generalised to other tropical developing countries, particularly those with suboptimum health systems. Since the switch from tOPV to bOPV in April and May, 2016, 38 vaccine-derived type 2 polioviruses have emerged globally.8Diop OM Asghar H Gavrilin E et al.Virologic monitoring of poliovirus type 2 after OPV2 withdrawal in April 2016: an important advance in eradicating poliomyelitis and eliminating live oral poliovirus vaccines worldwide, 2016–2017.Wkly Epidemiol Rec. 2017; 92: 293-300PubMed Google Scholar As expected, the countries at highest risk are Nigeria and Pakistan, where coverage with tOPV was suboptimum, suggesting substantial type 2 susceptibility before the switch to bOPV. 12 emergences required mOPV2 release from the global stockpile for outbreak control.8Diop OM Asghar H Gavrilin E et al.Virologic monitoring of poliovirus type 2 after OPV2 withdrawal in April 2016: an important advance in eradicating poliomyelitis and eliminating live oral poliovirus vaccines worldwide, 2016–2017.Wkly Epidemiol Rec. 2017; 92: 293-300PubMed Google Scholar More than 100 million doses of the mOPV2 vaccine have been distributed since the switch from tOPV to bOPV, in Nigeria, Pakistan, Mozambique, Syria, and the Democratic Republic of the Congo.8Diop OM Asghar H Gavrilin E et al.Virologic monitoring of poliovirus type 2 after OPV2 withdrawal in April 2016: an important advance in eradicating poliomyelitis and eliminating live oral poliovirus vaccines worldwide, 2016–2017.Wkly Epidemiol Rec. 2017; 92: 293-300PubMed Google Scholar In addition, as part of a ring vaccination effort around Borno State in Nigeria, the vaccine was also used in Niger, Chad, and Cameroon.8Diop OM Asghar H Gavrilin E et al.Virologic monitoring of poliovirus type 2 after OPV2 withdrawal in April 2016: an important advance in eradicating poliomyelitis and eliminating live oral poliovirus vaccines worldwide, 2016–2017.Wkly Epidemiol Rec. 2017; 92: 293-300PubMed Google Scholar Following these mass vaccination campaigns, new vaccine-derived type 2 polioviruses have emerged in some areas of Nigeria and Pakistan, probably because of insufficient campaign quality. Unless these countries can improve the quality of their outbreak control activities with mOPV2, vaccine-derived type 2 polioviruses will continue to emerge after each vaccination round, and efforts to successfully complete the polio endgame will prove elusive. Further, even in areas such as Matlab in Bangladesh, modelling shows that with increasing time, growing proportions of the population will have had no previous exposure to Sabin type 2 vaccine viruses, resulting in striking declines in population intestinal immunity, which will facilitate transmission of the virus should it be introduced in the coming years.9Thompson KM Tebbens RJD Modeling the dynamics of oral poliovirus vaccine cessation.J Infect Dis. 2014; 210: S475-S484Crossref PubMed Scopus (67) Google Scholar Thus, rapid containment of existing type 2 outbreaks is vital to achieving eradication. A major question raised by the study of Taniuchi and colleagues is whether IPV will provide any benefits to the community in preventing transmission of type 2 viruses. Clearly, it is inferior to tOPV; however, no control group of people unvaccinated against type 2 virus (eg, a bOPV only group) was included in the trial, to determine if IPV provides any reduction compared with no type 2 vaccine at all. Ecological data from Israel suggest IPV might be more effective in limiting transmission of vaccine viruses than of wild viruses. After 8 years of IPV use, Israel suffered almost a year of sustained wild poliovirus type 1 transmission without any cases of paralysis.10Anis E Kopel E Singer S et al.Insidious reintroduction of wild poliovirus into Israel, 2013.Euro Surveill. 2013; 18: 20586Crossref PubMed Scopus (124) Google Scholar It is likely that vaccine viruses were introduced into Israel yet no circulating vaccine-derived polioviruses were detected. However, unlike Bangladesh, Israel is an industrialised country with high socioeconomic status, and the low force of infection and diminished contact might have played a part. In Yogyakarta, Indonesia, after a switch to IPV from tOPV, no vaccine-derived polioviruses were detected despite detection of type 2 Sabin viruses, indicating introductions into the population.11Wahjuhono G Revolusiana Widhiastuti D et al.Switch from oral to inactivated poliovirus vaccine in Yogyakarta Province, Indonesia: summary of coverage, immunity, and environmental surveillance.J Infect Dis. 2014; 210: S347-S352Crossref PubMed Scopus (21) Google Scholar Whether this represents an effect of IPV on transmission or simply a statistical phenomenon (ie, not enough introductions to yield a circulating vaccine-derived poliovirus) is unclear. Some studies have shown that two doses of IPV—when the second dose is given at older ages than in the study by Taniuchi and colleagues—at a time when maternal antibody is likely to have waned does confer some protection against shedding superior to one IPV dose.12Asturias EJ Bandyopadhyay AS Self S et al.the Latin American IPV001BMG Study GroupHumoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial.Lancet. 2016; 388: 158-169Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar In April, 2017, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended that countries should include at least two doses of IPV in routine immunisation schedules after global withdrawal of trivalent, bivalent, and monovalent oral poliovirus vaccines.13WHOMeeting of the Strategic Advisory Group of Experts on immunization, April 2017: conclusions and recommendations.Wkly Epidemiol Rec. 2017; 92: 301-320PubMed Google Scholar What are the implications for policy implementation? It is clear IPV provides protection against paralytic disease, and to a lesser degree against emergence from leftover tOPV or against community transmission. Therefore, until the risk of reintroduction is either eliminated or reduced to virtually zero, IPV should continue to be used. Surveillance, including environmental surveillance in high-risk populations, is important to determine with IPV use whether viruses are re-introduced and circulate. Of course, for any vaccine policy to have most effect in securing complete polio eradication, achieving and maintaining high immunisation coverage is essential. JG and WO receive funding from the Bill & Melinda Gates Foundation. RWS declares no competing interests. Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling studyIn this study, simulating 1 year of tOPV cessation, Sabin 2 transmission was higher in household contacts of mOPV2 recipients in villages receiving bOPV and either one or two doses of IPV, but transmission was not increased in the community as a whole as shown by the non-significant difference in incidence among infants. Dynamical modelling indicates that transmission risk will be higher with more time since cessation. Full-Text PDF Open Access