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A new variant of echovirus 4 associated with a large outbreak of aseptic meningitis
R Handsher1, L M Shulman, B Abramovitz
1Central Virology Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Background:
A large outbreak of aseptic meningitis which began in April 1997 involved hundreds of cases in all geographical regions of Israel and the Palestinian Authority, peaked between June and September, and lasted until December.
Objectives:
We have investigated the virus associated with the outbreak to determine its serotype and molecular type and to establish epidemiological links.
Design:
Virus strains isolated from 210 clinical samples were serotyped by neutralization using LBM and WHO antiserum pools and two echovirus 4 (EV4)-specific antisera, and by immunofluorescence using a monoclonal antibody. RNA was extracted and a 435 base long fragment derived from the 5'UTR of the genome was amplified by RT-PCR using common primers, and sequenced. Sequences were compared to echoviruses 4, 6 and 7 prototypes from ATCC, and to other echoviruses sequences from the EMBL/Genbank data base.
Results:
The outbreak isolates were identified by the EV4 type-specific antisera and the monoclonal antibody but not with the WHO pools. Very few isolates could be typed by the LBM pools. The EV4 isolates accounted for 68% of all enterovirus isolates in our laboratory in 1997. The age distribution of the patients was: 0-11 month, 11.2%; 1-4 years, 16.1%; 5-9 years, 31.8%; 10-14 years, 9.9%; 15-20 years, 9.5%; 21-44 years, 21.5%; and > 45 years, 0%. Males between 1 and 14 years of age were affected more frequently than females of the same age. The sequences of 25 of 28 EV4 isolates analyzed were closely related to each other (> 95% homology) and the remaining three isolates had < 95% homology to the others and to each other. Interestingly, the outbreak strains were less closely related to the EV4 prototype, than to several other echoviruses. Three closely related subgroups were identified which correlated with geographical distribution but the temporal distribution did not reveal links leading to the source of the outbreak.
Conclusion:
The outbreak was caused by a variant of EV4 which apparently did not circulate in the area before and thus was capable of causing a widespread infection.
Insights
A 1997 aseptic meningitis outbreak in Israel and the Palestinian Authority was caused by a novel echovirus 4 (EV4) variant. This EV4 strain, distinct from the prototype, led to widespread infection across all age groups.
Area of Science:
- Virology
- Epidemiology
- Molecular Biology
Background:
- A large-scale aseptic meningitis outbreak occurred in Israel and the Palestinian Authority in 1997.
- The outbreak involved hundreds of cases across all geographical regions, peaking between June and September.
Purpose of the Study:
- To investigate the virus responsible for the 1997 aseptic meningitis outbreak.
- To determine the serotype and molecular type of the causative virus.
- To establish epidemiological links related to the outbreak.
Main Methods:
- Virus strains from 210 clinical samples were serotyped using neutralization and immunofluorescence.
- Viral RNA was extracted, and a 5' untranslated region (UTR) fragment was amplified via RT-PCR.
- Sequencing and comparison of viral genetic material against known echovirus prototypes and database sequences.
Main Results:
- The outbreak isolates were identified as echovirus 4 (EV4) using specific antisera and monoclonal antibodies.
- EV4 accounted for 68% of all enterovirus isolates in the laboratory during 1997.
- Sequence analysis revealed high homology (>95%) among most outbreak strains, identifying three closely related subgroups correlated with geographical distribution.
Conclusions:
- The 1997 aseptic meningitis outbreak was caused by a variant of echovirus 4 (EV4).
- This EV4 variant was likely newly introduced into the region, explaining its capacity for widespread infection.