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The Israeli public health response to wild poliovirus importation
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The Israeli public health response to wild poliovirus importation Ehud Kaliner*, Eran Kopel*, Emilia Anis, Ella Mendelson, Jacob Moran-Gilad, Lester M Shulman, Shepherd R Singer, Yossi Manor, Eli Somekh, Shmuel Rishpon, Alex Leventhal, Lisa Rubin, Diana Tasher, Mira Honovich, Larisa Moerman, Tamy Shohat, Ravit Bassal, Danit Sofer, Michael Gdalevich, Boaz Lev, Ronni Gamzu, Itamar Grotto
In 2013, a silent wild poliovirus type 1 importation and sustained transmission event occurred in southern Israel. With the aim of preventing clinical poliomyelitis and ensuring virus re-elimination, the public health response to the importation event included intensification of clinical and environmental surveillance activities, enhancement of vaccine coverage, and supplemental immunisation with a bivalent oral polio vaccine against wild poliovirus types 1 and 3. A national campaign launched in August, 2013, resulted in vaccination of 943 587 children younger than 10 years (79% of the eligible target population). Expanded environmental surveillance (roughly 80% population coverage) documented a gradual disappearance of wild poliovirus type 1 in the country from September, 2013, to April, 2014. No paralytic poliomyelitis case was detected. A prompt extensive and coordinated national public health response, implemented on the basis of evidence-based decision making, successfully contained this serious importation and sustained transmission event of wild poliovirus to Israel. On April 28, 2015, WHO officially declared Israel as a polio-free country.
Introduction Poliomyelitis, once a threat in every world region, was nearly eradicated in the 2000s. By the beginning of the new millennium, paralytic cases had declined by 99% worldwide.1–3 However, polioviruses have continued to circulate, especially in war-torn regions of the world where health-care infrastructure has been disrupted4,5 and opposition to polio vaccination exists (eg, Afghanistan and Pakistan).6 In Israel, poliomyelitis has been legally a notifiable disease since the early 1950s. Acute flaccid paralysis surveillance, the WHO gold standard for monitoring poliomyelitis,7 has been mandatory for children younger than 15 years since 1996. A routine childhood polio vaccine programme has been in place in Israel since 1957. It has included vaccination with inactivated polio vaccine (IPV; 1957–60), vaccination with trivalent oral polio vaccine (tOPV; 1961–89), a sequential IPV and tOPV programme (1992–2004), and vaccination exclusively with IPV since 2005,8 with national coverage averaging 95% over the past decade.9 Israel’s last poliomyelitis outbreak was in 1988, with 15 clinical cases of paralysis. The public health response consisted of one round of vaccination with tOPV for individuals younger than 40 years, three small supplemental immunisation activities (SIAs) at the epicentre, and a subsequent countrywide SIA (3·2 million vaccinated individuals, almost 100% coverage).8,10 In 1989, Israel established routine monthly environmental surveillance by sampling sewage sites across the country that regularly covered sewage samples from 30–40% of the population.10–13 This environmental surveillance identified importation and subsequent silent sustained transmission of a wild poliovirus type 1 strain in 2013.11–15 We summarise here the public health response measures and the evidence on which this response was based.
Establishment of an emergency response team Wild poliovirus type 1 was isolated on May 28, 2013, by the central virology laboratory from environmental
samples collected from Rahat, a Bedouin city in the South District. In response, the director general of the Ministry of Health along with the director of the Public Health Services appointed an emergency response team that consisted of members of the National Certification Committee for Polio Eradication, members of the National Vaccination Advisory Committee, virology experts, experts of infectious diseases, risk-communication specialists, and local health department officers. The emergency response team supervised the professional emergency response throughout the event and provided evidence-based recommendations through seven phases of epidemiological assessment and monitoring plans, laboratory studies, and communication strategies (appendix).
The response to the triggering event The national emergency response team managed all aspects of the isolation event identified in environmental surveillance samples collected on April 9, 2013, from sewage treatment facilities serving Rahat. We present the outcomes of the subsequent extensive epidemiological and laboratory investigation according to the seven phases of event management along a timeline and a corresponding timetable (figure 1; appendix).
Phase 1: population risk analysis Population immunity levels against wild poliovirus type 1 were rapidly established with a retrospective analysis of serum samples from 104 children aged 6–7 years (eg, those scheduled to receive an IPV booster) and, prospectively, from serum samples of 400 individuals representing all age groups in the Israeli population. A seroprotective concentration of neutralising antibodies against wild poliovirus type 1 was confirmed in 100·0% of the 104 children and 98·2% of the 400 prospectively sampled individuals. A review of computerised records of more than 1000 mother and child clinics of the Ministry of Health, a large health maintenance organisation, and several major municipalities did not
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Lancet Infect Dis 2015 Published Online July 24, 2015 http://dx.doi.org/10.1016/ S1473-3099(15)00064-X *Both authors contributed equally to this work Public Health Services, Ministry of Health, Jerusalem, Israel (E Kaliner MD, E Kopel MD, E Anis MD, Prof J Moran-Gilad MD, S R Singer MD, L Rubin MD, M Honovich MPH, L Moerman MD, Prof I Grotto PhD); The Division of Epidemiology, Public Health Services, Ministry of Health, Jerusalem, Israel (E Kopel, E Anis, S R Singer, L Moerman); Braun School of Public Health and Community Medicine, Hebrew University Hadassah Faculty of Medicine, Jerusalem, Israel (E Anis); Central Virology Laboratory, Public Health Services, Ministry of Health, The Chaim Sheba Medical Center, Tel Hashomer, Israel (Prof E Mendelson PhD, Prof L M Shulman PhD, Y Manor Mgr, D Sofer PhD); Faculty for Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel (Prof J Moran-Gilad, M Gdalevich MD, Prof I Grotto); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Prof E Mendelson, Prof L M Shulman, Prof E Somekh MD, D Tasher MD, Prof T Shohat MD, R Bassal PhD, Prof R Gamzu PhD); Pediatric Infectious Diseases Unit, Wolfson Medical Center, Holon, Israel (Prof E Somekh, D Tasher); Haifa District Health Office, Ministry of Health, Haifa, Israel (Prof S Rishpon MD); School of Public Health, Faculty of Health and Welfare Studies, University of Haifa, Haifa, Israel (Prof S Rishpon, L Rubin); Ministry of Health, Jerusalem, Israel (Prof A Leventhal MD, B Lev MD, Prof R Gamzu); Israel Center for Disease Control, Ministry of Health, Tel Hashomer, Israel
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(Prof T Shohat, R Bassal); and South District Health Office, Ministry of Health, Beer-Sheva, Israel (M Gdalevich) Correspondence to: Dr Eran Kopel, Public Health Services, Ministry of Health, Jerusalem 9101002, Israel [email protected]
See Online for appendix
Phase 1: population risk analysis
June to August, 2013
Phase 2: pathogen risk analysis
June to August, 2013
Phase 3: determining the viral transmission epicentre
June, 2013, to January, 2014
Phase 4: pinpointing reservoir of infected individuals for intervention planning
June, 2013, to January, 2014
Phase 5: emergency response and intervention
June, 2013, to January, 2014
Phase 6: intervention effectiveness evaluation
September, 2013, to July, 2014
Phase 7: verification of transmission interruption
January to September, 2014 Aug 5, 2013: South District first bOPV SIA
May May
Jul July
2013 May 28, 2013: first detection of silent WPV1 transmission
Sep Sept
Oct 7, 2013: South District second bOPV SIA Nov Nov
Aug 18, 2013: national bOPV SIA
Jan Jan
Jan 1, 2014: supplementary two-dose bOPV added to routine vaccine programme Mar March
May May
Jul July
April 28, 2015: recertification of Israel as polio free Sep Sept
2014 April 3, 2014: last WPV1-positive site became WPV1-negative
Figure 1: Timeline of key junctions, phases of evidence-based activities, and related public health decisions during the importation event of wild poliovirus type 1 to Israel, 2013–15 bOPV=bivalent oral polio vaccine. SIA=supplementary immunisation activity. WPV1=wild poliovirus type 1.
identify any pockets of undervaccinated or unvaccinated individuals (eg, IPV coverage <90%).
Phase 2: pathogen risk analysis—characterisation of wild poliovirus type 1 The routine sewage surveillance protocol16,17 was enhanced to increase throughput and shorten turnaround time so that the sustained transmission of wild poliovirus type 1 could be documented.12 Specific primers and probes, validated for quantitative RT-PCR using RNA extracted directly from concentrated sewage samples,18 provided real-time preliminary results for the weekly meetings of the emergency response team within 1 week of sample collection. Final confirmation by tissue cultures was achieved within 2–3 weeks of sample collection. Sequences of wild poliovirus type 1 were related to those of WPV1-SOAS-R3A from Pakistan that caused poliomyelitis in 2012 and that was isolated from sewage samples in Cairo, Egypt, in December, 2012.11 A Bayesian phylogenetic time-clock analysis, of complete (2643 nucleotides) capsid-coding regions with a 1·1% evolutionary rate, suggested that Israeli and Egyptian WPV1-SOAS-R3A lineages diverged in September, 2012, and that Israeli isolates split into two subbranches after January, 2013.11 A retrospective analysis revealed the presence of wild poliovirus type 1 in sewage samples collected from as early as February, 2013.11–13 Importantly, genotypic11 and phenotypic19 analyses did not identify unique characteristics that would allow easily sustained person-to-person transmission in a population vaccinated only with IPV, such as the 2
Israeli population. A slightly reduced neurovirulence might have contributed to the absence of paralytic cases in the background of high population immunity.19 However, epidemiological factors such as large families exposed over extended periods of time to high viral loads, rather than the virus itself, are likely to have contributed more substantially to sustained transmission.11–13,19
Phase 3: determining the viral transmission epicentre Routine monthly surveillance was expanded from eight to ten sites (30–40% nationally representative population coverage) to 62 sites (>80% population coverage) at the height of surveillance (ie, July, 2013), with increased numbers of samples taken per week from epidemiologically important sites, and remained steady at 62% national representative population coverage thereafter.12,15 The new sampling sites were geographically spread throughout the entire country.12,15 Five of ten environmental sites where positive sewage samples were obtained consecutively, defined as the silent wild poliovirus transmission geographical epicentre, were from inlets to sewage treatment facilities in southern Israel that served five Bedouin communities, and additional positive samples were obtained from a Beer-Sheva sewage treatment facility representing several small non-permanent Bedouin communities and from Beer-Sheva sewage lines (table 1). 14 sites representing mostly mixed ArabJewish populations in central Israel were either intermittently positive or positive only once. All sampling sites in northern Israel were consistently negative throughout the entire event period.
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Phase 4: pinpointing reservoir of infected individuals for intervention planning
Phase 5: emergency response and intervention The emergency response team devised a tailored contingency plan to protect the population from disease and to break the chain of transmission. Throughout the process, the emergency response team conferred with local and international experts of vaccine policy and infectious diseases, hosted two on-site visits for a team of experts from WHO and US Centres for Disease Control and Prevention, hosted an on-site visit to the central virology laboratory, and participated in many international video and telephone conferences. To protect the population from paralysis, especially children, the emergency response team recommended completion of a routine IPV childhood schedule of four doses for children up to age 6 years throughout Israel,
Date of last WPV1positive sample
Arara†
Continuous
April 3, 2014
Tel-Sheva†
Continuous
Feb 20, 2014
Shoket†
Continuous
Feb 13, 2014
Kseife†
Continuous
Feb 4, 2014
Tel Aviv metropolitan
Single measurement
Jan 30, 2014
Rahat†
Continuous
Jan 14, 2014
Lod
Intermittent
Oct 30, 2013
Beer-Sheva periphery†‡
Continuous
Oct 25, 2013
Jaljulia
Intermittent
Oct 21, 2013
Ramle
Intermittent
Oct 17, 2013
Kiryat Gat
Intermittent
Sept 2, 2013
Jerusalem
Single measurement
Aug 27, 2013
Bakk’a
Intermittent
Aug 14, 2013
Yiron
Single measurement
Aug 8, 2013
Taibe
Single measurement
July 1, 2013
WPV1=wild poliovirus type 1. *“Continuous” shows that poliovirus was found in sewage samples repeatedly by weekly or biweekly sampling; “intermittent” shows that poliovirus was found in sewage samples intermittently by weekly or biweekly sampling; and “single measurement” shows that poliovirus was found in sewage samples only once by weekly, biweekly, or monthly sampling. †Sampling sites located in the South District, which were consistently within the viral circulation epicentre. ‡Consists of several non-permanent small Bedouin communities.
Table 1: Chronology of 2013–14 laboratory findings at each sampling site by last WPV1-positive sewage sample
Incidence per 100 000 population aged <15 years
Since direct estimation of the number of infected individuals from environmental surveillance is not feasible,20 the environmental surveillance identified the geographical epicentre of excretors (ie, individuals who were shedding wild poliovirus type 1 in their faeces), and the point prevalence of infected individuals was further established with a stool-survey analysis of 2196 nonduplicate faecal samples collected from individuals residing within the identified epicentre (78% aged 0–10 years, 6% aged 10–22 years, and 16% older than 22 years). Wild poliovirus type 1 was detected in 61 faecal samples (2·8%), of which 55 (90·2%) were obtained from a Bedouin population and 59 (96·7%) were obtained from children aged 10 years or younger. The crude point prevalence for excretion of wild poliovirus type 1 was 5·4% in samples from Bedouin populations and 0·6% in samples from Jewish populations. 85% of these excretors had been vaccinated with at least three doses of IPV or IPV plus OPV in the past. Hospitals were scrutinised on a weekly basis for cases of acute flaccid paralysis in all age groups from June, 2013, to December, 2014. 32 acute flaccid paralysis cases in children younger than 15 years were reported (case incidence rate 1·44 cases per 100 000 population) and investigated in 2013 (figure 2). The surveillance index was 0·60 (calculated by multiplying the rate of non-polio acute flaccid paralysis cases up to 1·00 per 100 000 population with the percentage of acute flaccid paralysis cases with a WHO-defined adequate collection of two specimens within 14 days from onset of neurological symptoms). 44 additional cases of acute flaccid paralysis in individuals older than 15 years were reported in 2013. 157 individuals were admitted with aseptic meningitis and tested for poliovirus from July to August, 2013, to detect non-paralytic symptomatic poliovirus infections. All acute flaccid paralysis and aseptic meningitis cases reported were discarded as being poliomyelitis cases by WHO criteria.
Laboratory finding*
3·0
2013 2014
2·5 2·0 1·5 1·0 0·5 0
Jan
Feb
March
April
May
June
July
Aug
Sept
Oct
Nov
Dec
Month
Figure 2: Monthly incidence of acute flaccid paralysis per 100 000 population younger than 15 years in 2013 and 2014
and for children up to age 18 years and adults in Rahat and the surrounding area, the initially identified epicentre of silent transmission. In this area, routine IPV coverage (at least three doses of IPV) was completed mostly in June, 2013, and reached 98% (n=10 124) of about 10 300 eligible children aged 10–18 years (catch-up immunisation activity). An IPV booster was given to 12 419 eligible adults (31%; older than 18 years) of about 40 000 who were previously vaccinated. The routine IPV coverage in this area just before the importation event was 90% in the roughly 9000 children aged between 6 months and 5 years. This coverage was
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rapidly raised during June, 2013, to 97%, which was similar to the overall IPV coverage in the South District for this age group. A 95% routine IPV coverage of the roughly 4800 children aged between 6 and 9 years was also reached at that time and area. To break the chain of viral transmission, the emergency response team, supported by WHO on-site team experts, recommended an OPV SIA with a bivalent OPV (bOPV) containing Sabin 1 and Sabin 3 polio vaccine strains for all children younger than 10 years, who had no previous exposure to OPV since it had been taken out of the routine vaccine programme in 2005. This decision posed risk-communication challenges because the emergency use of an OPV SIA in an IPV-only country with almost all individuals protected against paralytic disease, and with no clinical poliomyelitis cases identified (ie, silent transmission), was unprecedented. Thus, the urgent need was to reach a consensus within the professional medical community to support this decision— especially since an anti-vaccine campaign was anticipated— to convey an effective risk-communication message to the public to convince them of the necessity for vaccination of the designated cohort of children, and to minimise nonadherence by use of traditional and new media sources.14,21 A bOPV SIA was initiated on Aug 5, 2013, in the South District and was expanded on Aug 18, 2013, to the rest of the country (figure 3). Most of the estimated 1·2 million target cohort was rapidly vaccinated during the first 2 weeks of the operation. At the end of the bOPV SIA, the national bOPV coverage (table 2) reached 79% (943 587 children younger than 10 years), and bOPV coverage was 90% for the entire target age group in the South District. The highest coverage, almost 100% for 100 90
Bivalent oral polio vaccine coverage (%)
80 70
District Ashkelon South Haifa Jerusalem Central North Tel Aviv
60
Phase 6: intervention effectiveness evaluation Semiquantitative results for Sabin strain RNA in sewage were used as a surrogate for monitoring adherence and effectiveness of vaccination with bOPV.15 Intensified environmental surveillance documented a gradual decline in the number of positive sites and a decrease in the amount of virus at each site until the last documented positive site, the Bedouin village of Arara, has remained negative since April 3, 2014 (table 1). A second stool survey done to assess intervention effectiveness sampled the population of the entire identified epicentre in the South District. The samples of this second stool survey were collected at a rate of about 100 samples per week between Sept 1, 2013, and June 29, 2014, from the population of children with the highest point prevalence in the first stool survey—namely, Bedouin children younger than 10 years. 2477 nonduplicate faecal stool samples were obtained, of which 22 (<1%) samples were positive for wild poliovirus type 1. The two last positive samples were collected on Oct 13, 2013, and Feb 16, 2014. Stool samples were also collected from family members and friends of these children, and all of these subsequent samples tested negative. The findings of these weekly stool samples supported the
50
bOPV coverage 40 30 20 10
7
No v3
Oc t2
Oc t1 3 Oc t2 0
9
Oc t6
22
pt 2 Se
5 pt 1
pt Se
Se
pt 8 Se
Au g2 5 Se pt 1
Au g1 1 Au g1 8
Au g5
0
North
92%
South
90%
Haifa
79%
Ashkelon
77%
Jerusalem
73%
Centre
69%
Tel Aviv
65%
Total
79%
bOPV=bivalent oral polio vaccine.
Week
Figure 3: Vaccination coverage with bivalent oral polio vaccine during the supplementary immunisation activity in 2013, by district
4
the eligible target age group, was reached in the southern Bedouin communities at the epicentre. On Oct 7, 2013, a second, regional bOPV SIA in the South District epicentre covered 52% of the target population. Finally, the Ministry of Health accepted the emergency response team’s recommendation to reduce the risk for re-emergence of wild poliovirus type 1 by vaccinating, from 2014 onwards, all children born after July 1, 2013, with a dose of bOPV at age 6 months and a second dose at age 18 months, in addition to the routine IPV-only schedule. All potential adverse reactions to bOPV were thoroughly investigated and reported to the public, and the emergency response team had proactive discussions with community leaders of specific target populations (eg, urban and rural communities of high socioeconomic status and antivaccination ideologies, Bedouin communities).
Table 2: bOPV coverage achieved by the supplementary immunisation activity in Israel between Aug 5 and end of November, 2013, by district
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overall evidence for gradual containment, interruption, and finally cessation of transmission of wild poliovirus type 1 in the South District.
Phase 7: verification of transmission interruption In accordance with the recommendation of the European Regional Certification Commission for Polio Eradication, the same sensitive methods used to detect wild poliovirus type 1 have been used to document its absence. Samples were taken from sewage treatment facilities in several locations: the geographical epicentre sites at the South District, sampled weekly until July 1, 2014, and bimonthly since then; sites that were previously intermittently positive; and consistently negative sites. Since July, 2014, all sites in the original 2013 epicentre have been sampled bimonthly and all other sites sampled monthly. Since April 3, 2014, all environmental surveillance samples have been negative. Acute flaccid paralysis surveillance, in 2014, had registered 27 cases in children younger than 15 years; each case was reported and investigated (case incidence rate 1·30 cases per 100 000 population, surveillance index 0·85). Both of these indicators are above the standard global WHO-recommended thresholds for adequate surveillance performance. No poliomyelitis case was detected by any of the surveillance measures during this period of viral importation and silent transmission in 2013–14.
Public health policy and debate The described public health policy was guided by evidence-based epidemiological characterisation of the event and was assisted by enhanced environmental surveillance in the form of shorter resampling intervals, increased numbers of sites, use of specific molecular assays to quantify wild poliovirus type 1, expanded clinical surveillance, active countrywide investigation of aseptic meningitis cases, and the conduction of two large stool surveys in the South District. The major group of individuals excreting wild poliovirus type 1—ie, children younger than 10 years— was identified by these combined epidemiological and laboratory-based studies. This identification allowed the evidence-based scientific targeting of this cohort by a national OPV SIA intervention using the longstanding safe bOPV22,23 and thus also minimised vaccine-associated paralytic poliomyelitis risk and a potential emergence of type 2 vaccine-derived poliovirus, as previously occurred in Nigeria and elsewhere.24–26 The generally high IPV coverage in the country also contributed to the overall low risk. Wild poliovirus type 1 disappeared from most environmental sites except those in the epicentre within 6–7 weeks after the nationwide bOPV SIA had begun, which is within the expected timeframe for development of gut immunity.27 This disappearance was used to justify a geographically restricted second bOPV SIA within the
more persistent epicentre. Public adherence was generally satisfactory but was higher in peripheral areas than in central urban regions. In the first round of bOPV SIA, 80% coverage of the target population at the epicentre of silent transmission had already been reached within 2 weeks and peaked at 90%, whereas the second round, at the southern epicentre, received less public support. Evidence-based policy could have a major disadvantage—namely, time consumption. As a result, a delay in response could be expected. However, one of the major advantages of environmental surveillance is the delivery of a substantial window of opportunity from the time of poliovirus importation until the (undesired) appearance of clinical poliomyelitis cases, thus allowing precious time for an orderly and calculated risk assessment and data gathering process. Facing an argumentative, so-called post-modern, public opinion atmosphere, including an anti-vaccination movement’s appeal to the Supreme Court (which was fortunately rejected unanimously), this decision pathway should and could only be proceeded along carefully (but promptly) to ensure sufficient public adherence with the further deployed public health measures.
Implication for polio eradication end-game strategies The events described here are also relevant for the endgame strategy of global poliovirus eradication. First, poliovirus can silently circulate in countries immunising exclusively with IPV and presumably without mucosal gut immunity in the population,28,29 even when IPV coverage is very high, substantiating previous outbreak reports.30–32 The 2013 importation event in Israel is an important reminder that under specific circumstances and conditions, any country could be at risk. Each country has its own vulnerabilities: population movement from polio-endemic areas, suboptimal living conditions of specific populations, ideological or religious communities refusing to vaccinate and thus creating undervaccinated population pockets, environmental conditions, and, importantly, sanitation infrastructure. Second, an SIA vaccine of choice should be bOPV or monovalent OPV to reduce the risk of serotype-2 vaccineassociated paralytic poliomyelitis and circulation of neurovirulent vaccine-derived polioviruses, and also in anticipation of the worldwide ban of Sabin 2 vaccines by early 2016.33 Third, surveillance of acute flaccid paralysis is not sufficiently sensitive in highly IPV-vaccinated populations, since the risk of clinical disease is very low. Instead, environmental surveillance, with its ability to quantitatively recover the virus,12,18,34,35 might become a preferable method for substantial early warning and real-time event monitoring, under the condition of reasonable implementation of valid and acceptable standards for such surveillance. Efforts to standardise
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procedures and reduce the labour-intensive steps and high costs should be encouraged.36 Fourth, much of the population in many countries will expect a transparent evidence-based decision-making process, particularly in times of emergency. Therefore, countries should have a predefined risk-communication contingency plan that includes massive resource allocation for a prompt and continuous media response.
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Conclusions Israel has maintained routine IPV coverage of the full series at an average of 95% for decades. The pre-event proportion of the population with immunological protection was confirmed to be greater than 98% by serological surveys. Nevertheless, hypersensitive routine environmental surveillance detected the importation of wild poliovirus type 1 into Israel in 2013 and documented unexpected22 sustained transmission throughout the summer in the South District. The reasons for sustained transmission remain unknown. One hypothesis is that exclusive immunisation of all children born in Israel since 2005 with a routine IPVonly regimen, combined with distinct environmental conditions and sanitation infrastructure in several communities with large families, contributed to sustained transmission at the southern epicentre during the summer of 2013. The complete absence of paralytic poliomyelitis clinical cases is probably attributable to the high routine IPV vaccination coverage of children younger than 10 years at the epicentre and to the overall consistently high national routine childhood IPV coverage over the years. On April 28, 2015, WHO officially declared Israel as a polio-free country.37
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Contributors EKa and EKo wrote the first draft and managed all subsequent revisions. All authors provided critical comments on the draft. Declaration of interests LMS has received a WHO grant for environmental surveillance of poliovirus to his institution and support from WHO for travel to WHO meetings and from the US Food and Drug Administration for travel to a workshop at the US National Institutes of Health. All other authors declare no competing interests. Acknowledgments We thank the many medical teams and individual medical professionals who participated and supported the national public health emergency response, and especially all the public health nurses who worked long shifts continuously for days to vaccinate almost 1 million children over a short time period. References 1 Global Polio Eradication Initiative. Global Polio Eradication Initiative: 10th meeting of the Independent Monitoring Board. Wkly Epidemiol Rec 2014; 89: 361–67. 2 Nathanson N, Kew OM. From emergence to eradication: the epidemiology of poliomyelitis deconstructed. Am J Epidemiol 2010; 172: 1213–29. 3 Kimman TG, Boot H. The polio eradication effort has been a great success—let’s finish it and replace it with something even better. Lancet Infect Dis 2006; 6: 675–78. 4 Bhutta ZA. Conflict and polio: winning the polio wars. JAMA 2013; 310: 905–06.
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Tangermann RH, Hull HF, Jafari H, Nkowane B, Everts H, Aylward RB. Eradication of poliomyelitis in countries affected by conflict. Bull World Health Organ 2000; 78: 330–38. Wassilak SG, Oberste MS, Tangermann RH, Diop OM, Jafari HS, Armstrong GL. Progress toward global interruption of wild poliovirus transmission, 2010–2013, and tackling the challenges to complete eradication. J Infect Dis 2014; 210 (suppl 1): S5–15. Acute flaccid paralysis surveillance: a global platform for detecting and responding to priority infectious diseases. Wkly Epidemiol Rec 2004; 79: 425–32. Swartz TA. The epidemiology of polio in Israel. An historical perspective. Publication 317. Tel Aviv: Israel Center for Disease Control (ICDC), Ministry of Health, 2008. http://www.health.gov.il/ PublicationsFiles/ICDC_317.pdf (accessed May 26, 2015). WHO. WHO vaccine-preventable diseases: monitoring system. 2014 global summary. Geneva: World Health Organization. http://apps.who.int/immunization_monitoring/globalsummary/ coverages?c=ISR (accessed Aug 24, 2014). Slater PE, Orenstein WA, Morag A, et al. Poliomyelitis outbreak in Israel in 1988: a report with two commentaries. Lancet 1990; 335: 1192–95. Shulman LM, Gavrilin E, Jorba J, et al. Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013. Euro Surveill 2014; 19: 20709. Manor Y, Shulman LM, Kaliner E, et al. Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013. Euro Surveill 2014; 19: 20708. Anis E, Kopel E, Singer SR, et al. Insidious reintroduction of wild poliovirus into Israel, 2013. Euro Surveill 2013; 18: 20586. Kaliner E, Moran-Gilad J, Grotto I, et al. Silent reintroduction of wild-type poliovirus to Israel, 2013—risk communication challenges in an argumentative atmosphere. Euro Surveill 2014; 19: 20703. Shulman LM, Mendelson E, Anis E, et al. Laboratory challenges in response to silent introduction and sustained transmission of wild poliovirus type 1 in Israel during 2013. J Infect Dis 2014; 210 (suppl 1): S304–14. WHO. Polio laboratory manual. 4th edn. Geneva: World Health Organization, 2004. http://whqlibdoc.who.int/hq/2004/WHO_ IVB_04.10.pdf (accessed May 26, 2015). Manor Y, Blomqvist S, Sofer D, et al. Advanced environmental surveillance and molecular analyses indicate separate importations rather than endemic circulation of wild type 1 poliovirus in Gaza district in 2002. Appl Environ Microbiol 2007; 73: 5954–58. Hindiyeh MY, Moran-Gilad J, Manor Y, et al. Development and validation of a real time quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) assay for investigation of wild poliovirus type 1-South Asian (SOAS) strain reintroduced into Israel, 2013 to 2014. Euro Surveill 2014; 19: 20710. Shulman LM, Martin J, Sofer D, et al. Genetic analysis and characterization of wild poliovirus type 1 during sustained transmission in a population with >95% vaccine coverage, Israel 2013. Clin Infect Dis 2015; 60: 1057–64. Hovi T, Shulman LM, van der Avoort H, Deshpande J, Roivainen M, de Gourville EM. Role of environmental poliovirus surveillance in global polio eradication and beyond. Epidemiol Infect 2012; 140: 1–13. State of Israel Ministry of Health. Supplemental polio vaccination campaign. http://www.health.gov.il/English/Topics/Vaccination/ two_drops/Pages/default.aspx (accessed Aug 24, 2014). WHO. Report of the 26th Meeting of the European Regional Certification Commission for Poliomyelitis Eradication. Copenhagen, Denmark, June 18–20, 2012. Copenhagen: World Health Organization Regional Office for Europe, 2012. http://www. euro.who.int/__data/assets/pdf_file/0005/184739/e96806.pdf (accessed May 26, 2015). WHO. Scientific evidence in support of: Note for the record: 5th meeting of the SAGE Working Group, World Health Organization, Geneva, September 3–4, 2012. Geneva: World Health Organization, 2012. http://www.who.int/immunization/sage/meetings/2012/ november/3__SAGE_WG_Scientific_Evidence22Oct2012.pdf (accessed May 26, 2015). Jenkins HE, Aylward RB, Gasasira A, et al. Implications of a circulating vaccine-derived poliovirus in Nigeria. N Engl J Med 2010; 362: 2360–69.
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Burns CC, Shaw J, Jorba J, et al. Multiple independent emergences of type 2 vaccine-derived polioviruses during a large outbreak in northern Nigeria. J Virol 2013; 87: 4907–22. Adu F, Iber J, Bukbuk D, et al. Isolation of recombinant type 2 vaccine-derived poliovirus (VDPV) from a Nigerian child. Virus Res 2007; 127: 17–25. Alexander JP Jr, Gary HE Jr, Pallansch MA. Duration of poliovirus excretion and its implications for acute flaccid paralysis surveillance: a review of the literature. J Infect Dis 1997; 175 (suppl 1): S176–82. Hird 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: e1002599. Swartz TA, Green MS, Handscher R, et al. Intestinal immunity following a combined enhanced inactivated polio vaccine/oral polio vaccine programme in Israel. Vaccine 2008; 26: 1083–90. Shulman LM, Handsher R, Yang CF, et al. Resolution of the pathways of poliovirus type 1 transmission during an outbreak. J Clin Microbiol 2000; 38: 945–52. Oostvogel PM, van Wijngaarden JK, van der Avoort HG, et al. Poliomyelitis outbreak in an unvaccinated community in the Netherlands, 1992–93. Lancet 1994; 344: 665–70. Hovi T, Cantell K, Huovilainen A, et al. Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population. Lancet 1986; 1: 1427–32.
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GAPIII 2014 (April 29, 2015 revision). WHO global action plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses and sequential cessation of OPV use. Geneva: World Health Organization. http://www. polioeradication.org/Portals/0/Document/Resources/ PostEradication/GAPIII_2014.pdf (accessed May 26, 2015). Hovi T, Stenvik M, Partanen H, Kangas A. Poliovirus surveillance by examining sewage specimens. Quantitative recovery of virus after introduction into sewerage at remote upstream location. Epidemiol Infect 2001; 127: 101–06. Lodder WJ, Buisman AM, Rutjes SA, Heijne JC, Teunis PF, de Roda Husman AM. Feasibility of quantitative environmental surveillance in poliovirus eradication strategies. Appl Environ Microbiol 2012; 78: 3800–05. Kopel E, Kaliner E, Grotto I. Lessons from a public health emergency—importation of wild poliovirus to Israel. N Engl J Med 2014; 371: 981–83. Siegel-Itzkovich J. The Jerusalem Post (Jerusalem), April 29, 2015. http://www.jpost.com/Breaking-News/WHO-declares-Israel-poliofree-400572 (accessed May 26, 2015).
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The Israeli public health response to wild poliovirus importation Ehud Kaliner*, Eran Kopel*, Emilia Anis, Ella Mendelson, Jacob Moran-Gilad, Lester M Shulman, Shepherd R Singer, Yossi Manor, Eli Somekh, Shmuel Rishpon, Alex Leventhal, Lisa Rubin, Diana Tasher, Mira Honovich, Larisa Moerman, Tamy Shohat, Ravit Bassal, Danit Sofer, Michael Gdalevich, Boaz Lev, Ronni Gamzu, Itamar Grotto
In 2013, a silent wild poliovirus type 1 importation and sustained transmission event occurred in southern Israel. With the aim of preventing clinical poliomyelitis and ensuring virus re-elimination, the public health response to the importation event included intensification of clinical and environmental surveillance activities, enhancement of vaccine coverage, and supplemental immunisation with a bivalent oral polio vaccine against wild poliovirus types 1 and 3. A national campaign launched in August, 2013, resulted in vaccination of 943 587 children younger than 10 years (79% of the eligible target population). Expanded environmental surveillance (roughly 80% population coverage) documented a gradual disappearance of wild poliovirus type 1 in the country from September, 2013, to April, 2014. No paralytic poliomyelitis case was detected. A prompt extensive and coordinated national public health response, implemented on the basis of evidence-based decision making, successfully contained this serious importation and sustained transmission event of wild poliovirus to Israel. On April 28, 2015, WHO officially declared Israel as a polio-free country.
Introduction Poliomyelitis, once a threat in every world region, was nearly eradicated in the 2000s. By the beginning of the new millennium, paralytic cases had declined by 99% worldwide.1–3 However, polioviruses have continued to circulate, especially in war-torn regions of the world where health-care infrastructure has been disrupted4,5 and opposition to polio vaccination exists (eg, Afghanistan and Pakistan).6 In Israel, poliomyelitis has been legally a notifiable disease since the early 1950s. Acute flaccid paralysis surveillance, the WHO gold standard for monitoring poliomyelitis,7 has been mandatory for children younger than 15 years since 1996. A routine childhood polio vaccine programme has been in place in Israel since 1957. It has included vaccination with inactivated polio vaccine (IPV; 1957–60), vaccination with trivalent oral polio vaccine (tOPV; 1961–89), a sequential IPV and tOPV programme (1992–2004), and vaccination exclusively with IPV since 2005,8 with national coverage averaging 95% over the past decade.9 Israel’s last poliomyelitis outbreak was in 1988, with 15 clinical cases of paralysis. The public health response consisted of one round of vaccination with tOPV for individuals younger than 40 years, three small supplemental immunisation activities (SIAs) at the epicentre, and a subsequent countrywide SIA (3·2 million vaccinated individuals, almost 100% coverage).8,10 In 1989, Israel established routine monthly environmental surveillance by sampling sewage sites across the country that regularly covered sewage samples from 30–40% of the population.10–13 This environmental surveillance identified importation and subsequent silent sustained transmission of a wild poliovirus type 1 strain in 2013.11–15 We summarise here the public health response measures and the evidence on which this response was based.
Establishment of an emergency response team Wild poliovirus type 1 was isolated on May 28, 2013, by the central virology laboratory from environmental
samples collected from Rahat, a Bedouin city in the South District. In response, the director general of the Ministry of Health along with the director of the Public Health Services appointed an emergency response team that consisted of members of the National Certification Committee for Polio Eradication, members of the National Vaccination Advisory Committee, virology experts, experts of infectious diseases, risk-communication specialists, and local health department officers. The emergency response team supervised the professional emergency response throughout the event and provided evidence-based recommendations through seven phases of epidemiological assessment and monitoring plans, laboratory studies, and communication strategies (appendix).
The response to the triggering event The national emergency response team managed all aspects of the isolation event identified in environmental surveillance samples collected on April 9, 2013, from sewage treatment facilities serving Rahat. We present the outcomes of the subsequent extensive epidemiological and laboratory investigation according to the seven phases of event management along a timeline and a corresponding timetable (figure 1; appendix).
Phase 1: population risk analysis Population immunity levels against wild poliovirus type 1 were rapidly established with a retrospective analysis of serum samples from 104 children aged 6–7 years (eg, those scheduled to receive an IPV booster) and, prospectively, from serum samples of 400 individuals representing all age groups in the Israeli population. A seroprotective concentration of neutralising antibodies against wild poliovirus type 1 was confirmed in 100·0% of the 104 children and 98·2% of the 400 prospectively sampled individuals. A review of computerised records of more than 1000 mother and child clinics of the Ministry of Health, a large health maintenance organisation, and several major municipalities did not
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Lancet Infect Dis 2015 Published Online July 24, 2015 http://dx.doi.org/10.1016/ S1473-3099(15)00064-X *Both authors contributed equally to this work Public Health Services, Ministry of Health, Jerusalem, Israel (E Kaliner MD, E Kopel MD, E Anis MD, Prof J Moran-Gilad MD, S R Singer MD, L Rubin MD, M Honovich MPH, L Moerman MD, Prof I Grotto PhD); The Division of Epidemiology, Public Health Services, Ministry of Health, Jerusalem, Israel (E Kopel, E Anis, S R Singer, L Moerman); Braun School of Public Health and Community Medicine, Hebrew University Hadassah Faculty of Medicine, Jerusalem, Israel (E Anis); Central Virology Laboratory, Public Health Services, Ministry of Health, The Chaim Sheba Medical Center, Tel Hashomer, Israel (Prof E Mendelson PhD, Prof L M Shulman PhD, Y Manor Mgr, D Sofer PhD); Faculty for Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel (Prof J Moran-Gilad, M Gdalevich MD, Prof I Grotto); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Prof E Mendelson, Prof L M Shulman, Prof E Somekh MD, D Tasher MD, Prof T Shohat MD, R Bassal PhD, Prof R Gamzu PhD); Pediatric Infectious Diseases Unit, Wolfson Medical Center, Holon, Israel (Prof E Somekh, D Tasher); Haifa District Health Office, Ministry of Health, Haifa, Israel (Prof S Rishpon MD); School of Public Health, Faculty of Health and Welfare Studies, University of Haifa, Haifa, Israel (Prof S Rishpon, L Rubin); Ministry of Health, Jerusalem, Israel (Prof A Leventhal MD, B Lev MD, Prof R Gamzu); Israel Center for Disease Control, Ministry of Health, Tel Hashomer, Israel
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(Prof T Shohat, R Bassal); and South District Health Office, Ministry of Health, Beer-Sheva, Israel (M Gdalevich) Correspondence to: Dr Eran Kopel, Public Health Services, Ministry of Health, Jerusalem 9101002, Israel [email protected]
See Online for appendix
Phase 1: population risk analysis
June to August, 2013
Phase 2: pathogen risk analysis
June to August, 2013
Phase 3: determining the viral transmission epicentre
June, 2013, to January, 2014
Phase 4: pinpointing reservoir of infected individuals for intervention planning
June, 2013, to January, 2014
Phase 5: emergency response and intervention
June, 2013, to January, 2014
Phase 6: intervention effectiveness evaluation
September, 2013, to July, 2014
Phase 7: verification of transmission interruption
January to September, 2014 Aug 5, 2013: South District first bOPV SIA
May May
Jul July
2013 May 28, 2013: first detection of silent WPV1 transmission
Sep Sept
Oct 7, 2013: South District second bOPV SIA Nov Nov
Aug 18, 2013: national bOPV SIA
Jan Jan
Jan 1, 2014: supplementary two-dose bOPV added to routine vaccine programme Mar March
May May
Jul July
April 28, 2015: recertification of Israel as polio free Sep Sept
2014 April 3, 2014: last WPV1-positive site became WPV1-negative
Figure 1: Timeline of key junctions, phases of evidence-based activities, and related public health decisions during the importation event of wild poliovirus type 1 to Israel, 2013–15 bOPV=bivalent oral polio vaccine. SIA=supplementary immunisation activity. WPV1=wild poliovirus type 1.
identify any pockets of undervaccinated or unvaccinated individuals (eg, IPV coverage <90%).
Phase 2: pathogen risk analysis—characterisation of wild poliovirus type 1 The routine sewage surveillance protocol16,17 was enhanced to increase throughput and shorten turnaround time so that the sustained transmission of wild poliovirus type 1 could be documented.12 Specific primers and probes, validated for quantitative RT-PCR using RNA extracted directly from concentrated sewage samples,18 provided real-time preliminary results for the weekly meetings of the emergency response team within 1 week of sample collection. Final confirmation by tissue cultures was achieved within 2–3 weeks of sample collection. Sequences of wild poliovirus type 1 were related to those of WPV1-SOAS-R3A from Pakistan that caused poliomyelitis in 2012 and that was isolated from sewage samples in Cairo, Egypt, in December, 2012.11 A Bayesian phylogenetic time-clock analysis, of complete (2643 nucleotides) capsid-coding regions with a 1·1% evolutionary rate, suggested that Israeli and Egyptian WPV1-SOAS-R3A lineages diverged in September, 2012, and that Israeli isolates split into two subbranches after January, 2013.11 A retrospective analysis revealed the presence of wild poliovirus type 1 in sewage samples collected from as early as February, 2013.11–13 Importantly, genotypic11 and phenotypic19 analyses did not identify unique characteristics that would allow easily sustained person-to-person transmission in a population vaccinated only with IPV, such as the 2
Israeli population. A slightly reduced neurovirulence might have contributed to the absence of paralytic cases in the background of high population immunity.19 However, epidemiological factors such as large families exposed over extended periods of time to high viral loads, rather than the virus itself, are likely to have contributed more substantially to sustained transmission.11–13,19
Phase 3: determining the viral transmission epicentre Routine monthly surveillance was expanded from eight to ten sites (30–40% nationally representative population coverage) to 62 sites (>80% population coverage) at the height of surveillance (ie, July, 2013), with increased numbers of samples taken per week from epidemiologically important sites, and remained steady at 62% national representative population coverage thereafter.12,15 The new sampling sites were geographically spread throughout the entire country.12,15 Five of ten environmental sites where positive sewage samples were obtained consecutively, defined as the silent wild poliovirus transmission geographical epicentre, were from inlets to sewage treatment facilities in southern Israel that served five Bedouin communities, and additional positive samples were obtained from a Beer-Sheva sewage treatment facility representing several small non-permanent Bedouin communities and from Beer-Sheva sewage lines (table 1). 14 sites representing mostly mixed ArabJewish populations in central Israel were either intermittently positive or positive only once. All sampling sites in northern Israel were consistently negative throughout the entire event period.
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Phase 4: pinpointing reservoir of infected individuals for intervention planning
Phase 5: emergency response and intervention The emergency response team devised a tailored contingency plan to protect the population from disease and to break the chain of transmission. Throughout the process, the emergency response team conferred with local and international experts of vaccine policy and infectious diseases, hosted two on-site visits for a team of experts from WHO and US Centres for Disease Control and Prevention, hosted an on-site visit to the central virology laboratory, and participated in many international video and telephone conferences. To protect the population from paralysis, especially children, the emergency response team recommended completion of a routine IPV childhood schedule of four doses for children up to age 6 years throughout Israel,
Date of last WPV1positive sample
Arara†
Continuous
April 3, 2014
Tel-Sheva†
Continuous
Feb 20, 2014
Shoket†
Continuous
Feb 13, 2014
Kseife†
Continuous
Feb 4, 2014
Tel Aviv metropolitan
Single measurement
Jan 30, 2014
Rahat†
Continuous
Jan 14, 2014
Lod
Intermittent
Oct 30, 2013
Beer-Sheva periphery†‡
Continuous
Oct 25, 2013
Jaljulia
Intermittent
Oct 21, 2013
Ramle
Intermittent
Oct 17, 2013
Kiryat Gat
Intermittent
Sept 2, 2013
Jerusalem
Single measurement
Aug 27, 2013
Bakk’a
Intermittent
Aug 14, 2013
Yiron
Single measurement
Aug 8, 2013
Taibe
Single measurement
July 1, 2013
WPV1=wild poliovirus type 1. *“Continuous” shows that poliovirus was found in sewage samples repeatedly by weekly or biweekly sampling; “intermittent” shows that poliovirus was found in sewage samples intermittently by weekly or biweekly sampling; and “single measurement” shows that poliovirus was found in sewage samples only once by weekly, biweekly, or monthly sampling. †Sampling sites located in the South District, which were consistently within the viral circulation epicentre. ‡Consists of several non-permanent small Bedouin communities.
Table 1: Chronology of 2013–14 laboratory findings at each sampling site by last WPV1-positive sewage sample
Incidence per 100 000 population aged <15 years
Since direct estimation of the number of infected individuals from environmental surveillance is not feasible,20 the environmental surveillance identified the geographical epicentre of excretors (ie, individuals who were shedding wild poliovirus type 1 in their faeces), and the point prevalence of infected individuals was further established with a stool-survey analysis of 2196 nonduplicate faecal samples collected from individuals residing within the identified epicentre (78% aged 0–10 years, 6% aged 10–22 years, and 16% older than 22 years). Wild poliovirus type 1 was detected in 61 faecal samples (2·8%), of which 55 (90·2%) were obtained from a Bedouin population and 59 (96·7%) were obtained from children aged 10 years or younger. The crude point prevalence for excretion of wild poliovirus type 1 was 5·4% in samples from Bedouin populations and 0·6% in samples from Jewish populations. 85% of these excretors had been vaccinated with at least three doses of IPV or IPV plus OPV in the past. Hospitals were scrutinised on a weekly basis for cases of acute flaccid paralysis in all age groups from June, 2013, to December, 2014. 32 acute flaccid paralysis cases in children younger than 15 years were reported (case incidence rate 1·44 cases per 100 000 population) and investigated in 2013 (figure 2). The surveillance index was 0·60 (calculated by multiplying the rate of non-polio acute flaccid paralysis cases up to 1·00 per 100 000 population with the percentage of acute flaccid paralysis cases with a WHO-defined adequate collection of two specimens within 14 days from onset of neurological symptoms). 44 additional cases of acute flaccid paralysis in individuals older than 15 years were reported in 2013. 157 individuals were admitted with aseptic meningitis and tested for poliovirus from July to August, 2013, to detect non-paralytic symptomatic poliovirus infections. All acute flaccid paralysis and aseptic meningitis cases reported were discarded as being poliomyelitis cases by WHO criteria.
Laboratory finding*
3·0
2013 2014
2·5 2·0 1·5 1·0 0·5 0
Jan
Feb
March
April
May
June
July
Aug
Sept
Oct
Nov
Dec
Month
Figure 2: Monthly incidence of acute flaccid paralysis per 100 000 population younger than 15 years in 2013 and 2014
and for children up to age 18 years and adults in Rahat and the surrounding area, the initially identified epicentre of silent transmission. In this area, routine IPV coverage (at least three doses of IPV) was completed mostly in June, 2013, and reached 98% (n=10 124) of about 10 300 eligible children aged 10–18 years (catch-up immunisation activity). An IPV booster was given to 12 419 eligible adults (31%; older than 18 years) of about 40 000 who were previously vaccinated. The routine IPV coverage in this area just before the importation event was 90% in the roughly 9000 children aged between 6 months and 5 years. This coverage was
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rapidly raised during June, 2013, to 97%, which was similar to the overall IPV coverage in the South District for this age group. A 95% routine IPV coverage of the roughly 4800 children aged between 6 and 9 years was also reached at that time and area. To break the chain of viral transmission, the emergency response team, supported by WHO on-site team experts, recommended an OPV SIA with a bivalent OPV (bOPV) containing Sabin 1 and Sabin 3 polio vaccine strains for all children younger than 10 years, who had no previous exposure to OPV since it had been taken out of the routine vaccine programme in 2005. This decision posed risk-communication challenges because the emergency use of an OPV SIA in an IPV-only country with almost all individuals protected against paralytic disease, and with no clinical poliomyelitis cases identified (ie, silent transmission), was unprecedented. Thus, the urgent need was to reach a consensus within the professional medical community to support this decision— especially since an anti-vaccine campaign was anticipated— to convey an effective risk-communication message to the public to convince them of the necessity for vaccination of the designated cohort of children, and to minimise nonadherence by use of traditional and new media sources.14,21 A bOPV SIA was initiated on Aug 5, 2013, in the South District and was expanded on Aug 18, 2013, to the rest of the country (figure 3). Most of the estimated 1·2 million target cohort was rapidly vaccinated during the first 2 weeks of the operation. At the end of the bOPV SIA, the national bOPV coverage (table 2) reached 79% (943 587 children younger than 10 years), and bOPV coverage was 90% for the entire target age group in the South District. The highest coverage, almost 100% for 100 90
Bivalent oral polio vaccine coverage (%)
80 70
District Ashkelon South Haifa Jerusalem Central North Tel Aviv
60
Phase 6: intervention effectiveness evaluation Semiquantitative results for Sabin strain RNA in sewage were used as a surrogate for monitoring adherence and effectiveness of vaccination with bOPV.15 Intensified environmental surveillance documented a gradual decline in the number of positive sites and a decrease in the amount of virus at each site until the last documented positive site, the Bedouin village of Arara, has remained negative since April 3, 2014 (table 1). A second stool survey done to assess intervention effectiveness sampled the population of the entire identified epicentre in the South District. The samples of this second stool survey were collected at a rate of about 100 samples per week between Sept 1, 2013, and June 29, 2014, from the population of children with the highest point prevalence in the first stool survey—namely, Bedouin children younger than 10 years. 2477 nonduplicate faecal stool samples were obtained, of which 22 (<1%) samples were positive for wild poliovirus type 1. The two last positive samples were collected on Oct 13, 2013, and Feb 16, 2014. Stool samples were also collected from family members and friends of these children, and all of these subsequent samples tested negative. The findings of these weekly stool samples supported the
50
bOPV coverage 40 30 20 10
7
No v3
Oc t2
Oc t1 3 Oc t2 0
9
Oc t6
22
pt 2 Se
5 pt 1
pt Se
Se
pt 8 Se
Au g2 5 Se pt 1
Au g1 1 Au g1 8
Au g5
0
North
92%
South
90%
Haifa
79%
Ashkelon
77%
Jerusalem
73%
Centre
69%
Tel Aviv
65%
Total
79%
bOPV=bivalent oral polio vaccine.
Week
Figure 3: Vaccination coverage with bivalent oral polio vaccine during the supplementary immunisation activity in 2013, by district
4
the eligible target age group, was reached in the southern Bedouin communities at the epicentre. On Oct 7, 2013, a second, regional bOPV SIA in the South District epicentre covered 52% of the target population. Finally, the Ministry of Health accepted the emergency response team’s recommendation to reduce the risk for re-emergence of wild poliovirus type 1 by vaccinating, from 2014 onwards, all children born after July 1, 2013, with a dose of bOPV at age 6 months and a second dose at age 18 months, in addition to the routine IPV-only schedule. All potential adverse reactions to bOPV were thoroughly investigated and reported to the public, and the emergency response team had proactive discussions with community leaders of specific target populations (eg, urban and rural communities of high socioeconomic status and antivaccination ideologies, Bedouin communities).
Table 2: bOPV coverage achieved by the supplementary immunisation activity in Israel between Aug 5 and end of November, 2013, by district
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overall evidence for gradual containment, interruption, and finally cessation of transmission of wild poliovirus type 1 in the South District.
Phase 7: verification of transmission interruption In accordance with the recommendation of the European Regional Certification Commission for Polio Eradication, the same sensitive methods used to detect wild poliovirus type 1 have been used to document its absence. Samples were taken from sewage treatment facilities in several locations: the geographical epicentre sites at the South District, sampled weekly until July 1, 2014, and bimonthly since then; sites that were previously intermittently positive; and consistently negative sites. Since July, 2014, all sites in the original 2013 epicentre have been sampled bimonthly and all other sites sampled monthly. Since April 3, 2014, all environmental surveillance samples have been negative. Acute flaccid paralysis surveillance, in 2014, had registered 27 cases in children younger than 15 years; each case was reported and investigated (case incidence rate 1·30 cases per 100 000 population, surveillance index 0·85). Both of these indicators are above the standard global WHO-recommended thresholds for adequate surveillance performance. No poliomyelitis case was detected by any of the surveillance measures during this period of viral importation and silent transmission in 2013–14.
Public health policy and debate The described public health policy was guided by evidence-based epidemiological characterisation of the event and was assisted by enhanced environmental surveillance in the form of shorter resampling intervals, increased numbers of sites, use of specific molecular assays to quantify wild poliovirus type 1, expanded clinical surveillance, active countrywide investigation of aseptic meningitis cases, and the conduction of two large stool surveys in the South District. The major group of individuals excreting wild poliovirus type 1—ie, children younger than 10 years— was identified by these combined epidemiological and laboratory-based studies. This identification allowed the evidence-based scientific targeting of this cohort by a national OPV SIA intervention using the longstanding safe bOPV22,23 and thus also minimised vaccine-associated paralytic poliomyelitis risk and a potential emergence of type 2 vaccine-derived poliovirus, as previously occurred in Nigeria and elsewhere.24–26 The generally high IPV coverage in the country also contributed to the overall low risk. Wild poliovirus type 1 disappeared from most environmental sites except those in the epicentre within 6–7 weeks after the nationwide bOPV SIA had begun, which is within the expected timeframe for development of gut immunity.27 This disappearance was used to justify a geographically restricted second bOPV SIA within the
more persistent epicentre. Public adherence was generally satisfactory but was higher in peripheral areas than in central urban regions. In the first round of bOPV SIA, 80% coverage of the target population at the epicentre of silent transmission had already been reached within 2 weeks and peaked at 90%, whereas the second round, at the southern epicentre, received less public support. Evidence-based policy could have a major disadvantage—namely, time consumption. As a result, a delay in response could be expected. However, one of the major advantages of environmental surveillance is the delivery of a substantial window of opportunity from the time of poliovirus importation until the (undesired) appearance of clinical poliomyelitis cases, thus allowing precious time for an orderly and calculated risk assessment and data gathering process. Facing an argumentative, so-called post-modern, public opinion atmosphere, including an anti-vaccination movement’s appeal to the Supreme Court (which was fortunately rejected unanimously), this decision pathway should and could only be proceeded along carefully (but promptly) to ensure sufficient public adherence with the further deployed public health measures.
Implication for polio eradication end-game strategies The events described here are also relevant for the endgame strategy of global poliovirus eradication. First, poliovirus can silently circulate in countries immunising exclusively with IPV and presumably without mucosal gut immunity in the population,28,29 even when IPV coverage is very high, substantiating previous outbreak reports.30–32 The 2013 importation event in Israel is an important reminder that under specific circumstances and conditions, any country could be at risk. Each country has its own vulnerabilities: population movement from polio-endemic areas, suboptimal living conditions of specific populations, ideological or religious communities refusing to vaccinate and thus creating undervaccinated population pockets, environmental conditions, and, importantly, sanitation infrastructure. Second, an SIA vaccine of choice should be bOPV or monovalent OPV to reduce the risk of serotype-2 vaccineassociated paralytic poliomyelitis and circulation of neurovirulent vaccine-derived polioviruses, and also in anticipation of the worldwide ban of Sabin 2 vaccines by early 2016.33 Third, surveillance of acute flaccid paralysis is not sufficiently sensitive in highly IPV-vaccinated populations, since the risk of clinical disease is very low. Instead, environmental surveillance, with its ability to quantitatively recover the virus,12,18,34,35 might become a preferable method for substantial early warning and real-time event monitoring, under the condition of reasonable implementation of valid and acceptable standards for such surveillance. Efforts to standardise
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procedures and reduce the labour-intensive steps and high costs should be encouraged.36 Fourth, much of the population in many countries will expect a transparent evidence-based decision-making process, particularly in times of emergency. Therefore, countries should have a predefined risk-communication contingency plan that includes massive resource allocation for a prompt and continuous media response.
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Conclusions Israel has maintained routine IPV coverage of the full series at an average of 95% for decades. The pre-event proportion of the population with immunological protection was confirmed to be greater than 98% by serological surveys. Nevertheless, hypersensitive routine environmental surveillance detected the importation of wild poliovirus type 1 into Israel in 2013 and documented unexpected22 sustained transmission throughout the summer in the South District. The reasons for sustained transmission remain unknown. One hypothesis is that exclusive immunisation of all children born in Israel since 2005 with a routine IPVonly regimen, combined with distinct environmental conditions and sanitation infrastructure in several communities with large families, contributed to sustained transmission at the southern epicentre during the summer of 2013. The complete absence of paralytic poliomyelitis clinical cases is probably attributable to the high routine IPV vaccination coverage of children younger than 10 years at the epicentre and to the overall consistently high national routine childhood IPV coverage over the years. On April 28, 2015, WHO officially declared Israel as a polio-free country.37
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Contributors EKa and EKo wrote the first draft and managed all subsequent revisions. All authors provided critical comments on the draft. Declaration of interests LMS has received a WHO grant for environmental surveillance of poliovirus to his institution and support from WHO for travel to WHO meetings and from the US Food and Drug Administration for travel to a workshop at the US National Institutes of Health. All other authors declare no competing interests. Acknowledgments We thank the many medical teams and individual medical professionals who participated and supported the national public health emergency response, and especially all the public health nurses who worked long shifts continuously for days to vaccinate almost 1 million children over a short time period. References 1 Global Polio Eradication Initiative. Global Polio Eradication Initiative: 10th meeting of the Independent Monitoring Board. Wkly Epidemiol Rec 2014; 89: 361–67. 2 Nathanson N, Kew OM. From emergence to eradication: the epidemiology of poliomyelitis deconstructed. Am J Epidemiol 2010; 172: 1213–29. 3 Kimman TG, Boot H. The polio eradication effort has been a great success—let’s finish it and replace it with something even better. Lancet Infect Dis 2006; 6: 675–78. 4 Bhutta ZA. Conflict and polio: winning the polio wars. JAMA 2013; 310: 905–06.
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