The global eradication of poliomyelitis, believed to be achievable around the year 2000, relies on strategies which include high routine immunization coverage and mass vaccination campaigns, along with continuous monitoring of wild-type virus circulation by using the laboratory-based acute flaccid paralysis (AFP) surveillance. Israel and the Palestinian Authority are located in a geographical region in which poliovirus is still endemic but have been free of poliomyelitis since 1988 as a result of intensive immunization programs and mass vaccination campaigns. To monitor the wild-type virus circulation, environmental surveillance of sewage samples collected monthly from 25 to 30 sites across the country was implemented in 1989 and AFP surveillance began in 1994. The sewage samples were processed in the laboratory with a double-selective tissue culture system, which enabled economical processing of large number of samples. Between 1989 and 1997, 2,294 samples were processed, and wild-type poliovirus was isolated from 17 of them in four clusters, termed “silent outbreaks,” in September 1990 (type 3), between May and September 1991 (type 1), between October 1994 and June 1995 (type 1), and in December 1996 (type 1). Fifteen of the 17 positive samples were collected in the Gaza Strip, 1 was collected in the West Bank, and 1 was collected in the Israeli city of Ashdod, located close to the Gaza Strip. The AFP surveillance system failed to detect the circulating wild-type viruses. These findings further emphasize the important role that environmental surveillance can play in monitoring the eradication of polioviruses.

BackgroundVaccine-derived polioviruses (VDPVs) have caused poliomyelitis outbreaks in communities with sub-optimal vaccination. Israeli environmental surveillance of sewage from populations with high (>95%) documented vaccine coverage of confirmed efficacy identified two separate evolutionary clusters of VDPVs: Group 1 (1998–2005, one system, population 1.6×106) and Group 2 (2006, 2 systems, populations 0.7×106 and 5×104).Principal FindingsMolecular analyses support evolution of nine Group 1 VDPVs along five different lineages, starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1 recombinant strain, and independent evolution of three Group 2 VDPVs along one lineage starting from a different recombinant strain. The primary evidence for two independent origins was based on comparison of unique recombination fingerprints, the number and distribution of identical substitutions, and evolutionary rates. Geometric mean titers of neutralizing antibodies against Group 1 VDPVs were significantly lower than against vaccine strains in all age-group cohorts tested. All individuals had neutralizing titers >1∶8 against these VDPVs except 7% of the 20–50 year cohort. Group 1 VDPVs were highly neurovirulent in a transgenic mouse model. Intermediate levels of protective immunity against Group 2 VDPVs correlated with fewer (5.0+1.0) amino acid substitutions in neutralizing antigenic sites than in Group 1 VDPV's (12.1±1.5).SignificanceVDPVs that revert from live oral attenuated vaccines and reacquire characteristics of wild-type polioviruses not only threaten populations with poor immune coverage, but are also a potential source for re-introduction of poliomyelitis into highly immune populations through older individuals with waning immunity. The presence of two independently evolved groups of VDPVs in Israel and the growing number of reports of environmental VDPV elsewhere make it imperative to determine the global frequency of environmental VDPV. Our study underscores the importance of the environmental surveillance and the need to reconsider the global strategies for polio eradication and the proposed cessation of vaccination.

An echovirus type 22 outbreak involving 19 neonatal intensive care unit (NICU) patients during the months of October and November 1992 is reported. Twelve infants presented with diarrhea, 7 of whom had bloody stools and x-ray findings compatible with early stages of necrotizing enterocolitis, while one infant demonstrated characteristic pneumatosis intestinalis. Outbreaks of echovirus type 22 infection in premature infants have rarely been reported. The possibility of Echovirus 22 infection should be considered in neonatal gastrointestinal disease associated with features of necrotizing enterocolitis.

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Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3-3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

Aim-To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. Method-The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the diVerences between the term and preterm groups was determined using Student's t test. Results-A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p=NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p<0.03). Conclusion-Hepatitis B vaccine is eVective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12-24 months of age to booster the non-responders.

An outbreak of poliomyelitis with 20 cases occurred in Israel, Gaza, and the West Bank from October 1987 to October 1988. The wild type 1 poliovirus associated with the outbreak was most closely related to viruses found in the Nile Delta. The epidemiologic links among patients involved in the outbreak and patients with community-acquired infections during the outbreak were inferred from the evolutionary relationships among isolates of the outbreak virus. Complete VP1 sequences (906 nucleotides) were determined for 12 clinical and 4 sewage isolates. A total of 58 nucleotide differences were found among the 16 isolates; 74% of all substitutions were synonymous third-position transitions. An evolutionary tree, representing both the pathways of VP1 sequence evolution and the inferred chains of virus transmission during the outbreak, was constructed under the assumption that each substitution had occurred only once. The combined epidemiologic and molecular data suggest that a single founder strain was introduced into Israel from the vicinity of Gaza in the fall of 1987. Poliovirus circulation was apparently localized to southern communities during the winter and spread north by the following summer into the Hadera subdistrict of Israel, where it radiated via multiple chains of transmission into other communities in northern Israel and the West Bank. The close sequence matches (>99%) between clinical and sewage isolates from the same communities confirm the utility of environmental sampling as a tool for monitoring wild poliovirus circulation.

An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40°C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A 481 to G in the 5 untranslated region and the VP1 amino acid I 143 to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for ϳ6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication.