Ehud Kaliner

Insidious reintroduction of wild poliovirus into Israel, 2013.

Israel was certified as polio-free country in June 2002, along with the rest of the World Health Organization European Region. Some 11 years later, wild-type polio virus ₁ (WPV₁) was isolated initially from routine sewage samples collected between 7 and 13 April 2013 in two cities in the Southern district. WPV₁-specific analysis of samples indicated WPV₁ introduction into that area in early February 2013. National supplementary immunisation with oral polio vaccine has been ongoing since August 2013.

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.

Lessons from a Public Health Emergency — Importation of Wild Poliovirus to Israel

In 2013, samples from routine environmental surveillance at a sewage-treatment plant in Israel tested positive for wild-type poliovirus. In response, Israeli health policymakers ramped up environmental surveillance and launched supplementary immunization activities.

The Israeli public health response to wild poliovirus importation

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.

The Israeli national population program of genetic carrier screening for reproductive purposes

Purpose:The Israeli population genetic screening program for reproductive purposes, launched in January 2013, includes all known, nationally frequent severe diseases (carrier frequency 1:60 and/or disease frequency 1 in 15,000 live births). The carrier screening program is free of charge and offers testing for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy for nearly the entire population, according to disease frequency among the different groups within the population. We report the results of the first year of the program.Methods:Data on the tests performed over a 12-month period were collected from laboratories nationwide.Results:More than 62,000 individuals were examined. The carrier frequency was within the expected range for most of the diseases. The few exceptions included lower carrier rates for cystic fibrosis among Muslim Arabs (1:236) and Druze (1:1,021) and Niemann-Pick type A among Muslim Arabs in a delineated region of Israel (1:229).Conclusion:The national population genetic carrier screening is aimed toward providing couples with knowledge of the existing options for the prevention of serious genetic conditions when it is relevant for them. It is still too early to determine whether this aim has been achieved.Genet Med 18 2, 203–206.

Laboratory Challenges in Response to Silent Introduction and Sustained Transmission of Wild Poliovirus Type 1 in Israel During 2013

Wild poliovirus type 1 (WPV1) introduction into southern Israel in early 2013 was detected by routine environmental surveillance. The virus was identified genetically as related to the South Asian (SOAS) R3A lineage endemic to Pakistan in 2012. Intensified, high-throughput environmental surveillance using advanced molecular methods played a critical role in documenting and locating sustained transmission throughout 2013 and early 2014 in the absence of any acute flaccid paralysis. It guided the public health responses, including stool-based surveillance and serosurveys, to determine the point prevalence in silent excretors and measured the effect of vaccination campaigns with inactivated polio vaccine and bivalent oral polio vaccine on stopping transmission.

Field study of fecal excretion as a decision support tool in response to silent reintroduction of wild-type poliovirus 1 into Israel

BACKGROUND Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases. OBJECTIVES To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV. STUDY DESIGN A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping. RESULTS Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity. CONCLUSION The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.

Estimation of polio infection prevalence from environmental surveillance data

Close monitoring of virus shed into sewage systems allows quantitative surveillance of a polio outbreak. Keeping an eye on polio As the eyes are a mirror of the soul, a city’s sewage is a reflection of its people’s health. Berchenko et al. take advantage of a natural experiment in southern Israel to quantify this relationship for polio. By measuring virus shed into sewage waste in cities in which a known number of people received a live polio vaccine, the authors created tools that can be used to monitor polio incidence in other cities. Thus, virus levels in sewage waste can give an early warning of the reappearance of viral disease or verify its absence. A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unknown. We used two unique data sets collected during a natural experiment provided by the 2013 polio outbreak in Israel: ES data from different locations and records of supplemental immunization with the live vaccine. Data from the intersecting population between the two data sets (covering more than 63,000 people) yielded a dose-dependent relationship between the number of poliovirus shedders and the amount of poliovirus in sewage. Using a mixed-effects linear regression analysis of these data, we developed several quantitative tools, such as (i) ascertainment of the number of infected individuals from ES data for application during future epidemics elsewhere, (ii) evaluation of the sensitivity of ES, and (iii) determination of the confidence level of the termination of poliovirus circulation after an outbreak. These results will be valuable in monitoring future outbreaks with ES, and this approach could be used to certify poliovirus elimination or to validate the need for more containment efforts.

Estimated size of the population at risk of severe adverse events after smallpox vaccination in Israel

BACKGROUND The population at risk of adverse events after smallpox vaccination has increased in recent years. This has important implications for preparedness strategies against bioterrorism with the variola virus. The aim of the study was to estimate the size of this special population in Israel. METHODS The study was conducted in January 2010. Data on patients with contraindications to smallpox vaccination, as delineated by the Israel Ministry of Health for planning post-event strategies, were retrieved from the computerized records of the Department of AIDS and Tuberculosis and the Transplantation Center of the Israel Ministry of Health. In addition, the database of the main Health Maintenance Organization in Israel which insures 60% of the national population was searched using ICD-9 codes and specific medications issued in the last quarter of 2009. RESULTS Of the 7,563,800 persons residing in Israel in January 2010, 326,318 were at risk of an adverse event after smallpox vaccination. CONCLUSION Approximately 4.3% of the Israeli population should not be exposed to the currently used smallpox vaccine. This knowledge is important to ensure the effectiveness of mass vaccination programs in the event of a bioterror attack.

Possible recurrent pandemic (H1N1) 2009 infection, Israel.

To the Editor: We report 2 cases of possible recurrent laboratory-confirmed infection with pandemic (H1N1) 2009 virus in Israel. Patient 1, a 24-year-old man, had Noonan syndrome (1,2). He was hospitalized on August 10, 2009, because of high-grade fever and cough. At admission, a nasopharyngeal specimen was collected for pandemic (H1N1) 2009 virus real-time reverse transcription–PCR (RT-PCR) (ABI 7500; Applied Biosystems, Foster City, CA, USA) for the pandemic hemagglutinin gene; a validated in-house protocol developed at Israel Central Virology Laboratory was used, as previously described (3). Briefly, the in-house assay was validated against the assay for pandemic (H1N1) 2009 virus developed by the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA). The in-house assay was as sensitive as the CDC assay; however, the in-house primers and probes were more specific for detecting pandemic (H1N1) 2009 virus with 105% amplification efficiency of viral RNA that was logarithmically serially diluted. In addition, of 100 samples tested side by side with the in-house and CDC assays, 75 samples were positive by both assays, and 25 were negative by both assays; thus, the sensitivity and specificity of the in-house assay were 100%. The patient was not treated with neuraminidase inhibitors and did not require supportive treatment; after 1 day of hospitalization, he was discharged with a diagnosis of upper respiratory tract infection. The laboratory subsequently reported the RT-PCR as positive for pandemic (H1N1) 2009 virus. On November 22, the man was hospitalized again for dyspnea and fever. The RT-PCR result from a nasopharyngeal sample collected at admission was positive. Hemagglutination-inhibition assay demonstrated a high titer (320) of serum antibody against pandemic (H1N1) 2009 virus in a blood sample taken at admission. The patient took oseltamivir for 5 days, and his condition markedly improved. Result of a repeat RT-PCR at discharge was negative. An identical neuraminidase gene sequence was detected during both illness episodes (August and November). The specimens were also tested with an experimental RT-PCR assay for rapid detection of the oseltamivir resistance mutation H275Y on the pandemic neuraminidase gene (4). For specimens collected during both episodes, the virus was oseltamivir sensitive. Patient 2, a 13.5-year-old boy, had severe cerebral palsy. On July 27, 2009, high-grade fever with dyspnea developed. He was treated as an outpatient for 5 days with oseltamivir and clinically improved. However, on August 11, he had fever with respiratory distress and was hospitalized. RT-PCR for pandemic (H1N1) 2009 virus was positive on August 14. A second course of oseltamivir was administered for 10 days with the dosage adjusted for age and doubled from that of the previous regimen. Further testing with the experimental rapid RT-PCR indicated the viral strain had the oseltamivir resistance mutation. On September 14, RT-PCR was negative. On December 11, the boy was again hospitalized because of respiratory distress and high-grade fever. On December 14, RT-PCR was positive for pandemic (H1N1) 2009 virus, and a 5-day regimen of oseltamivir was started. Another specimen taken the same day was negative. A high serum antibody titer (320) to pandemic (H1N1) 2009 virus was measured by hemagglutination-inhibition assay on December 16; no oseltamivir resistance mutation was found. Additional laboratory testing included a complete panel for respiratory viruses, which was negative for human metapneumovirus; respiratory syncytial virus; adenovirus; seasonal influenza virus types A and B; and parainfluenza virus types 1, 2, and 3. These 2 cases of possible recurrent pandemic (H1N1) 2009 infection demonstrated a wide interval between illness episodes. Neither patient had accompanying immunodeficiency, and both had antibody titers far beyond the accepted seroprotective threshold for influenza (5), albeit ineffective. These titers probably resulted from primary infection rather than from subclinical exposure, which manifests itself as a lower titer by order of magnitude (6,7). Virus clearance was not laboratory confirmed for patient 1 after the first episode because no samples were taken after hospital discharge. Patient 2 had both positive and negative RT-PCRs for pandemic (H1N1) 2009 virus (Table) from samples collected the same day during the second hospitalization, which also may disprove reinfection. The positive result could be explained by laboratory contamination during the RT-PCR processing that indicated a false-positive result. However, contamination is unlikely because each run of the RT-PCR was routinely accompanied by runs of negative controls (that contain water) to rule out such contamination. Nonanalytic factors such as specimen misidentification also are unlikely because the central virology laboratory, which is the national reference center, has an ISO-9000 qualification from the Standards Institution of Israel (www.sii.org.il/20-en/SII_EN.aspx). Furthermore, no other respiratory virus was found by laboratory testing at that time. The patient was infected with an oseltamivir-resistant pandemic (H1N1) 2009 virus during the first illness episode and with an oseltamivir-sensitive virus during the second episode and had 2 RT-PCRs with negative results between the episodes. Table Real-time RT-PCR for pandemic (H1N1) 2009 virus and results of experimental assay* for oseltamivir resistance mutation H275Y, Israel, 2009† The novel pandemic influenza virus may be able to reinfect certain chronically ill persons. Caregivers should be aware of this trait when considering the differential diagnosis of influenza-like illness in a patient with a documented, and even treated, pandemic (H1N1) 2009 infection.