The 2010 outbreak of poliomyelitis in Tajikistan: epidemiology and lessons learnt.

A large outbreak of poliomyelitis, with 463 laboratory-confirmed and 47 polio-compatible cases, took place in 2010 in Tajikistan. Phylogenetic analysis of the viral VP1 gene suggested a single importation of wild poliovirus type 1 from India in late 2009, its further circulation in Tajikistan and expansion into neighbouring countries, namely Kazakhstan, Russia, Turkmenistan and Uzbekistan. Whole-genome sequencing of 14 isolates revealed recombination events with enterovirus C with cross-overs within the P2 region. Viruses with one class of recombinant genomes co-circulated with the parental virus, and representatives of both caused paralytic poliomyelitis. Serological analysis of 327 sera from acute flaccid paralysis cases as well as from patients with other diagnoses and from healthy people demonstrated inadequate immunity against polio in the years preceding the outbreak. Evidence was obtained suggesting that vaccination against poliomyelitis, in rare cases, may not prevent the disease. Factors contributing to the peculiarities of this outbreak are discussed. The outbreak emphasises the necessity of continued vaccination against polio and the need, at least in risk areas, of quality control of this vaccination through well planned serological surveillance.

Genetic variability of wild-type measles viruses, circulating in the Russian Federation during the implementation of the National Measles Elimination Program, 2003-2007.

Genetic characterization of wild-type measles viruses (MVs) is an important component of laboratory surveillance of measles. In this study, a phylogenetic analysis was performed of the nucleoprotein gene sequences of 228 MVs isolated in the Russian Federation between 2003 and 2007. Five genotypes, D4, D5, D6, D8, and H1, were detected. From 1999 through the first 6 months of 2003, the most prevalent genotype in the European part of Russia was D4. All genotype D4-type viruses were closely related to each other (with overall sequence diversity of

Poliomyelitis in Russia in 1998-1999.

After introducing surveillance for poliomyelitis and AFP cases in the Russian Federation in 1998, 740 AFP cases have been registered in 1998-1999, and 18 of that number were considered as vaccine-associated paralytic poliomyelitis (VAPP). Of 18 cases 11 were classified as VAPP of vaccine recipients and confirmed by virus isolation; from two of the vaccine recipients virus was not isolated, and five were poliomyelitis cases in contact non-vaccinated children. In all the cases the disease was characterised with the typical clinical picture with residual pareses and paralyses. One case was fatal. Vaccine virus type 3 has been isolated from all the vaccine recipients. The MAPREC test has shown that the quality of monovaccine type 3 bulks used for vaccinating these children did not differ from the quality of other bulk vaccines produced by the Chumakov Institute of Poliomyelitis. Patients surveyed for gammaglobulin were positive. Polioviruses type 1 isolated from two of the contact cases had changed antigenic properties and were recombinants of types 1 and 2.

Outbreak of paralytic poliomyelitis in the Chechen Republic in 1995.

An outbreak of poliomyelitis with 146 cases among children of whom six died occurred in the Chechen Republic in 1995. Sporadic cases of poliomyelitis have been reported in the neighbouring Ingush Republic. The outbreak lasted for five months (from May to September) and the maximum number of cases was registered in July. The age of the patients did not exceed 11 years, and more than 90% of the patients were children aged from one month to four years. The overwhelming majority of the patients had not been vaccinated in the routine OPV immunization programme. The outbreak was due to wild poliovirus type 1 belonging to genotype T previously known to circulate in the territory of the former Soviet Union (FSU). Chechen and Ingush isolates were very closely related to each other and to isolates from Central Asia, Tajikistan, 1994. Only a very distant relatedness of the Chechen and Ingush isolates was found with the strains isolated at about the same time outside the FSU (China 1994, Pakistan 1995). The presence of high numbers of non-vaccinated/poorly vaccinated persons and the poor sanitary and hygienic conditions for civilians due to the military conflict were factors that had a role in the outbreak.

Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an immunodeficient patient: a unifying model.

We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodeficient patient. Different regions of the viral RNA were found to evolve nonsynchronously, and the rate of evolution of the 2AB region in the vaccine-derived population was not constant throughout its history. Synonymous replacements occurred not completely randomly, suggesting the need for conservation of certain rare codons (possibly to control translation elongation) and the existence of unidentified constraints in the viral RNA structure. Nevertheless the major contribution to the evolution of the two lineages came from linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of the mutations in both lineages were fixed as a result of successive sampling, from the heterogeneous populations, of random portions containing predominantly neutral and possibly adverse mutations. As a result of such a mode of evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generated. The proposed unifying model of natural poliovirus evolution has important implications for the epidemiology of poliomyelitis.

Molecular epidemiology of wild poliovirus type 1 in Europe, the Middle East, and the Indian subcontinent.

The genomic relationships of wild poliovirus type 1 strains recently isolated in Europe, the Middle East, and the Indian subcontinent was analyzed by automated amplicon sequencing of the VP1/2A junction region of the genome. Four major genotypes of poliovirus type 1 were found to circulate. Two genotypes were found predominantly in Eastern Europe, one of these in the Caucasian Region and the other in countries bordering the Black Sea. A third genotype circulated mainly in Egypt. The fourth and largest genotype circulated in the largest geographic area. Strains belonging to this genotype could be found in countries as far apart as Malaysia and Ukraine. Considerable genetic variation was observed among strains isolated in Egypt, Pakistan, and India, where poliovirus is endemic. Strains belonging to all four genotypes circulated in Pakistan. Data confirm the extent of poliovirus circulation in certain regions, stressing the need for intensification of vaccination in these regions.

Frequent isolation of intertypic poliovirus recombinants with serotype 2 specificity from vaccine-associated polio cases.

Five representatives from a collection of 21 Sabin type 2-like poliovirus strains isolated from paralytic poliomyelitis cases in two regions of the USSR have been subjected to limited nucleotide sequencing. All proved to be intertypic recombinants having the genes encoding capsid proteins of Sabin 2 origin and a 3'-end portion of the genome derived from either type 1 (3 isolates) or type 3 (2 isolates) Sabin strains. The crossover points in all the 5 genomes have been mapped to different loci of the P3 region. At least 6 additional isolates from the same collection (and 2 isolates from healthy contacts), appeared to have a type 2/type 1 recombinant genome, as judged by oligonucleotide mapping. The biological significance of frequent occurrence of recombinants among field isolates of vaccine-related strains is discussed.

The osmotic pressure of the maintenance medium and reproduction of poliovirus.

When the osmotic pressure of the maintenance medium is decreased, poliovirus reproduction is inhibited. Poliovirus strains may vary in their sensitivity to the effect of hypotonic solutions. Mutants have been selected (designated as osm mutants) the reproduction of which is characterized by particularly high resistance to media with reduced osmotic pressure. Initial stages of the virus-cell interaction proceed at similar rates in physiologic and hypotonic solutions. Reactions sensitive to hypotonic solutions take place in the second half of the latent period and during the stage of virus maturation. The multiplication of viruses in moderately hypotonic solutions exhibits a marked dependence upon the temperature and the presence of cystine in the medium, even though these factors have relatively small influence upon the reproduction of the viruses in isotonic solutions. Despite complete cessation of the production of infectious virus in certain hypotonic media, there is a considerable synthesis of virus-induced RNA. At least some of the RNA produced under these conditions is infectious. With a further decrease of the osmotic pressure of the medium the synthesis of the viral RNA is inhibited. Some possible explanations of the observed facts are briefly discussed.