Vaccine-associated paralytic poliomyelitis and other diseases with acute flaccid paralysis syndrome in Belarus.

According to the WHO global polio eradication initiative acute flaccid paralysis (AFP) surveillance has been conducted in Belarus since 1996. For the period 1996-2002, 295AFP cases were reported. The main indices ofAFP surveillance in Belarus met the WHO criteria. A11 AFP cases, with the exception of one, were virologically examined. Polioviruses (PV) were isolated from 28 (9.5%) of them. Results of intratypic differentiation (a neutralization test with type-specific monoclonal antibodies and a restriction fragment length polymorphism assay) proved vaccine origin of all isolated PV. According to the final classification, 11 AFP cases were classified as vaccine-associated paralytic poliomyelitis (VAPP). Nine VAPP cases were recipient [six of them developed after the first, two--after the third and one--after the fourth oral poliovirus vaccine (OPV) dose] and two cases in non-vaccinated children were classified as contact VAPP cases. PV of all three serotypes were isolated with an equal frequency from the recipient cases and only PV2--from contact ones. Immunological investigations of children with VAPP showed that the majority of them had disorders in B-cell immunity. A risk of one VAPP case per 96,000 first OPV doses and per 745,000 distributed ones was estimated. The other 284 AFP cases were classified as AFP of non-polio etiology (non-polio AFP). Among them Guillain-Barré syndrome (118 cases, 41.5% of all non-polio AFP cases), traumatic neuritis (63 cases, 22.2%), transient monoparesis of limb (35 cases, 12.3%), myelitis (26 cases, 9.2%) were registered most frequently. Vaccine PV were isolated from 19 (6.7%) children with non-polio AFP, 28 (9.9%) children excreted non-polio enteric viruses. In contrast to VAPP, other AFP with PV isolation had no clinical picture typical of poliomyelitis, and had no any residual paralysis 60 days after the onset of paralysis. PV isolation from them seemed to be not related to the etiology of the disease, but was a mere coincidence of paralysis with the recent vaccination. Results of AFP surveillance supported the previous data on the absence of classical poliomyelitis cases caused by wild PV in Belarus for more than 35 years.

Enteroviruses identifications and differentiation on the basis of the selective group--specific inhibitory effect of chemical compounds.

Two new enteroviruses (EV) inhibitors with the selective group-specific effect were detected and studied representing the products of the original chemical synthesis. One of them--nifan (arylfuran derivative) inhibits poliomyelitis virus replication, the other one--belvtazide (synchonic acid derivative) blocks non-poliomyelitis EV (ECHO and Coxsackie B) replication. The study of the reference strains of poliomyelitis virus type 1-3, twenty-three ECHO virus types (from the 1st to the 33rd), Coxsackie B virus type 1-6 and 288 primary EV isolates did not reveal type or strain specific variability in the inhibitors effect. Nifan and belvtazide supress the replication of both EV monostrains and their mixtures. The isolates of mixed nature are inhibited by the mixture nifan + belvtazide. At the same time neither separate chemicals nor their blend affects viruses from other families (Adenoviridae, Orthomyxoviridae, Herpesviridae etc.). The mechanism of nifan and belvtazide action is intracellular EV replication inhibition (they do not affect the process of virus adsorption and penetration into the cell), suppression of de novo virus synthesis by 7.0-2.25 lg (tissue culture infective dose 50 per cent) TCID50/ml and of virus-induced RNA synthesis. The drugs feature is high selectivity (90-91%) regarding RNA polioviruses (nifan) and RNA non-poliomyelitis EV (belvtazide). Nifan and belvtazide antiviral effect selectivity allows unknown cytopathic agents (CPA) belonging to the EV to be established with the high degree (over 98%) of reproducibility at the stage of primary identification with the differentiation of poliomyelitis and non-poliomyelitis viruses.

The immunogenicity and reactogenicity of the trivalent vaccine, Trimovax, indicated for prevention of measles, mumps, and rubella, in 12-month-old children in Belarus.

In the Republic of Belarus, immunization of children against measles and mumps had been carried out using monovalent preparations according to the national schedule of measles vaccination at 12 months of age and mumps vaccination at 24 months of age. A rise of rubella incidence in the last few years (i.e., for the official registration period 1980 to 1998, there was an increase from 72.2 to 607.5 cases per 100,000 population) made it necessary to implement immunization against this infection, as well. Therefore, in 1996, combined vaccination against measles, mumps, and rubella of 12-month-old children was carried out for the first time in a clinical trial that used the vaccine Trimovax [Aventis Pasteur (formerly, Pasteur Mérieux Connaught), Lyon, France]. The reactogenicity of the vaccine was investigated in 372 children. Post-vaccination reactions were noted in 5.6% of children; in 1.3% of children the reactions were classified as severe [i.e. associated with body (axillary) temperature > or = 38.6 degrees C]. For the evaluation of immunogenicity, sera from 324 children were obtained 2 to 2.5 months after inoculation, and serum antibody levels were measured by enzyme immunoassays. Among the vaccines, protective antibody titers (expressed in inverse of dilution units) were observed to measles (> or = 1:50) in 97.8%, to mumps (> or = 1:50) in 93.8%, and to rubella (> or = 1:100) in 96.0% of children. Antibodies to all three components of the vaccine were mainly present in intermediate (1:200-1:800) or high (> or = 1:1600) titers: to measles in 96.3%; to mumps in 75.8%; and to rubella in 73.5% of vaccines. The results of these trials are evidence of the good safety and immunogenicity of this MMR vaccine, which provides an alternative to the currently used measles and mumps monovaccines, with the additional benefit of providing immunity against rubella, as well.