Search

In 1984, a wild type 3 poliovirus (PV3/FIN84) spread all over Finland causing nine cases of paralytic poliomyelitis and one case of aseptic meningitis. The outbreak was ended in 1985 with an intensive vaccination campaign. By limited sequence comparison with previously isolated PV3 strains, closest relatives of PV3/FIN84 were found among strains circulating in the Mediterranean region. Now we wanted to reanalyse the relationships using approaches currently exploited in poliovirus surveillance. Cell lysates of 22 strains isolated during the outbreak and stored frozen were subjected to RT-PCR amplification in three genomic regions without prior subculture. Sequences of the entire VP1 coding region, 150 nucleotides in the VP1-2A junction, most of the 5' non-coding region, partial sequences of the 3D RNA polymerase coding region and partial 3' non-coding region were compared within the outbreak and with sequences available in data banks. In addition, complete nucleotide sequences were obtained for 2 strains isolated from two different cases of disease during the outbreak. The results confirmed the previously described wide intraepidemic variation of the strains, including amino acid substitutions in antigenic sites, as well as the likely Mediterranean region origin of the strains. Simplot and bootscanning analyses of the complete genomes indicated complicated evolutionary history of the non-capsid coding regions of the genome suggesting several recombinations with different HEV-C viruses in the past.

A nationwide programme to eliminate indigenous measles, mumps, and rubella, mainly by vaccinating children twice, was launched in Finland in 1982. Strong scientific methods to examine the immunological, clinical, and epidemiological variables have accompanied the programme. Measles was eliminated in 1996, and mumps and rubella in 1997. Now, 25 years from the start of this programme, Finland is facing new challenges. Since elimination, eight, 32, and six cases of measles, mumps, and rubella, respectively, have been reported. Of those, seven cases were failures of mumps vaccinations and one case was a rubella vaccination failure. Although outbreaks have been averted, the risks are increasing because the unvaccinated population is growing, epidemics occur in nearby countries, breakthrough cases arise, and declining antibodies suggest waning immunity. The chances for natural boosters are now at a minimum, and individuals are increasingly protected solely by vaccination. To maintain the absence of these diseases, the adopted policy should continue, but the country should also be prepared for prompt supplementary vaccinations in the case of epidemic outbreaks.

Background: Human rhinoviruses (HRVs) together with the closely related human enteroviruses (HEVs) cause most of the acute respiratory illnesses throughout the year. HRVs have been detected in most parts of the respiratory tract but not in pharyngeal tonsils., Objectives: We aimed to find out whether HRVs were detectable in tonsillar tissue and if their presence correlated to the tonsillar disease., Study Design: Thirty-three tonsillar samples collected in February-March 2003 from children with no acute respiratory symptoms were studied with HRV in situ hybridization (HRV-ISH). Ten tonsillar samples were further examined in a separate laboratory by two different reverse transcription polymerase chain reaction (RT-PCR) methods designed for detection of HRV/HEV RNA., Results: Twenty of the 33 samples (62%) were positive by HRV-ISH. Five positive and five negative HRV-ISH samples were investigated by two different PCR methods. HRV/HEV RNA was detected in 9 of the 10 specimens by a hanging drop-nested PCR. One HRV-ISH negative sample was positive by a conventional non-nested PCR. One of the samples studied by all three methods, from a patient with recurrent tonsillitis, had no detectable HRV/HEV RNA. Positive result in HRV-ISH did not correlate significantly with underlying tonsillar disease, history of respiratory infections or bronchial asthma. Altogether HRV/HEV RNA was detected in 75% of the tonsils with no correlation to patients' operation indication or history of respiratory diseases., Conclusions: In February-March, HRV/HEV RNA was frequently found in tonsillar tissue in children irrespective of the tonsillar pathology. Whether detection of the RNA is a marker of chronic infection or is merely remnant of past infection is not known.

Human rhinoviruses (HRV) have been shown to be the major causative agent for mild respiratory infections, but also associated with more serious diseases, such as acute otitis media and pneumonia in children, and asthma. Despite the economical and medical importance of HRV, little is known about the circulation and genetic diversity of HRV during a given season. The aim of this study was to genetically characterize HRV strains causing acute respiratory infections in a cohort of small children during a 2 years follow-up time. Genetic relationships between 61 HRV field isolates were studied using partial genomic sequencing in the VP4/VP2 region (420 nt) and phylogenetic analysis of these sequences. Sequences from the clinical isolates clustered in the two previously known phylogenetic clades, the designated genetic group 2 (including HRV 14) being more predominant. The maximum genetic variation within group 1 was 32.3% and within group 2 it was 32.7%. Several distinct clusters could be observed, some of which were strictly seasonal, whereas some other variants were detected during several seasons. The results of this study show striking genetic diversity of the HRV strains circulating in a given community during a short time.

The use of the inactivated poliovirus vaccine (IPV) will increase before and probably also after the global eradication of the wild type poliovirus. Before eradication, the switch from the use of oral poliovirus vaccine (OPV) to IPV has been due to the better safety record of IPV. Introduction of IPV in the regular immunisation schedules is made easier by the development of several combination vaccines, including IPV. Maternal antibodies and young age, often considered problematic for early initiation of IPV schedules, did not compromise optimal maintenance of seropositivity during infancy or long-term persisting antibody levels in our studies. OPV-derived, potentially pathogenic and transmissible poliovirus strains, excreted by some individuals for years, may present a problem for a blunt stopping of all polio immunisations after eradication. Our recent results suggest that locally excreted IgA might have a role in the elimination of poliovirus infection in the intestinal tissues.

Objective: To study the correlation between the yield of virus-induced interferon (IFN) production in leukocyte cultures and the risk of recurrent respiratory infections., Methods: A sample of 71 consecutive children enrolled in the Finnish Otitis Media Cohort Study were selected. Children suffering from frequently recurring respiratory infections (FRRIs) were defined as the highest quintile of the entire cohort of 329 children, as regards the number of upper respiratory infections (URIs) and/or episodes of acute otitis media (AOM) during the follow-up period from 2 to 24 months., Results: In the sample of 71 children, there were 18 children with FRRI (> or = 9 URI and/or > or = 4 AOM). Leukocyte cultures, prepared from blood drawn from these 18 children at 6 months of age, produced lower yields of IFN than those of the remaining 53 children, when stimulated with adenovirus (P <0.001), coronavirus (P<0.001) or rhinovirus (P=0.002). The difference in IFN yields was even greater (P<0.001 with all three viruses) if the comparison was made between children with FRRI and those with no or maximally one URI during the follow-up period. When the IFN production capacity induced by rhinovirus was measured at the age of 24 months, a statistically significant difference between the children with FRRI and the others was also seen (P=0.002). Influenza A virus-induced IFN production capacity did not differ between the groups at either age (P=0.209)., Conclusions: Lowered IFN responses in children suffering from recurrent URIs and/or AOM may, in a subgroup of the children, be due to a genetic property of the child. However, because of the great interindividual variations, we cannot use the IFN production capacity as such for prediction of forthcoming respiratory infections and/or otitis media.

Background: We have previously developed a mu-capture-based radioimmunoassay (RIA) for detecting virus-specific IgM for the diagnosis of poliomyelitis. To probe captured IgM we used radiolabelled, purified preparations of representatives of each poliovirus serotype (Roivainen M, Agboatwalla M, Stenvik M, Rysa T, Akram DS, Hovi T. J Clin Microbiol 1993;31:2427-32). However, this assay is not directly applicable for wider use because preparation and handling of radioactive reagents is cumbersome and potentially hazardous., Objectives: To develop a non-radioactive modification of the assay retaining the number of steps and reagents to a minimum., Study Design: Replacement of radioactive labelling by in vitro biotinylation of purified virions, and detection of bound virions with horseradish peroxidase-conjugated streptavidin. To study sensitivity and poliovirus serotype-specificity, 129 sera and 115 CSF specimens from children with acute poliomyelitis were used in comparative tests with the in-house RIA. In addition, sera from 40 healthy adults and 11 paired sera from patients with non-polio enterovirus infection were used to assess specificity., Results: While results with the new test on specimens from clinically confirmed polio patients revealed some correlation with those obtained in the in-house RIA, studies on sera from healthy adults indicated, that non-specific binding of biotinylated virions is difficult to control. Moreover, examination of sera from patients with non-polio enterovirus infection suggested frequently occurring cross-reactivity between immune responses induced by polio- and other enterovirus infections. The latter were also seen in the RIA., Conclusion: Cross-reactive epitopes between poliovirus serotypes and between polioviruses and other enteroviruses may compromise the use of an assay for virus-specific IgM for poliovirus diagnosis. Biotinylation of the virions seemed to aggravate these problems.

Background: Enterovirus outbreaks are known to occur in neonatal wards and enteroviruses may cause community-acquired sepsis-like disease in the neonatal period. Less well is known their possible role in suspected systemic infections during the perinatal period., Objectives: To investigate the occurrence of enterovirus infections in neonatal patients suspected of systemic infection., Study Design: A population-based prospective survey was organized in the hospitals of the Greater Helsinki Region during 13 months in 1993-94. Criteria for enrollment included onset of symptoms before the age of 29 days and a decision, on clinical grounds, to take a blood culture for bacteria. Acute phase samples of blood, feces, nasopharyngeal swab, and cerebrospinal fluid, if available, were inoculated in monolayer cultures of four different cell lines. In addition, enterovirus infections were searched for using an enterovirus group-reacting IgM test., Results: One hundred and thirty-seven patients had a sufficient number of specimens examined, and were thus evaluable. Most of the infants had the onset of the symptoms within a few days after birth. An enterovirus was isolated from four newborn infants (3%), while seven children (5%) were found to excrete adenovirus. Enteroviral antigen was detected in cell cultures inoculated with specimens from two additional infants. Virus-positive infants had no evidence of bacterial infection and did not show specific clinical signs or symptoms differentiating them from the rest of the study group. All enrolled infants recovered without sequelae., Conclusion: We conclude that sporadic viral infections may be common in neonatal patients with suspected systemic infection, and this should be taken into account when judging the etiology.

The enhanced potency inactivated poliovirus vaccine (E-IPV) was modified to contain trypsin-treated type 3 poliovirus (PV3), strain Saukett, as the type 3 component (TryIPV). This pilot vaccine was previously shown to redistribute the vaccine-induced antibody specificities in mice to mimic those seen in man after poliovirus infection. Groups of infants were then immunised with three doses of TryIPV or E-IPV in a randomised, double-blind trial. Six months after the third dose, at the age of 18 months, the children were challenged with one dose of oral monovalent type 3 poliovirus vaccine. Intestinal immunity was evaluated by assessing the length and extent of PV3 excretion through determination of PV3 titres in 9 successive faecal specimens (2-42 days after challenge). No significant difference in the length or extent of virus excretion was seen between the groups. The results indicate that TryIPV, under the conditions used, was no more potent than the regular E-IPV in inducing resistance to intestinal poliovirus infection.

A modified trivalent enhanced potency IPV (E-IPV) containing trypsin-treated PV3/Saukett as the type 3-component (TryIPV) was evaluated in preclinical and Phase I and Phase II clinical trials with the regular E-IPV as a control. In Balb/c mice, TryIPV-induced antibodies targeted outside the trypsin-sensitive antigenic site, as expected. Immunogenicity of TryIPV in man, as judged by a booster response in neutralizing antibodies to type 1, 2 or 3 poliovirus, was as good as that of the regular E-IPV in both adults and children. In children the preimmunization titres of antibodies neutralizing the trypsin-treated PV3/Saukett were significantly lower than those for the untreated virus. Both vaccines induced a striking increase of antibody titres to both virus preparations. No significant harmful effects were observed. We conclude that the pilot vaccine is suitable for further evaluation.

Antibody responses in Balb/c mice immunized with different preparations of type 3 poliovirus/Saukett were compared. Live and formalin-inactivated virus preparations, either as such or after selective cleavage by trypsin, were used. The latter treatment is known to yield surface-modified virus particles similar to those generated during natural infection in man. We have previously shown that these modified viruses are poorly neutralized by sera from persons immunized solely with inactivated poliovirus vaccine. Trypsin-cleaved virus-immunized mice produced antibodies capable of neutralizing both virus preparations. Surprisingly, a major part of these neutralizing antibodies 5 months after the third dose were still of the IgM class. In contrast, antibodies from mice immunized with untreated, intact virus were mainly of the IgG class and they readily neutralized the immunogen itself but were not usually able to neutralize the trypsin-cleaved virus. These results indicate that neutralizing antibodies induced in Balb/c mice by trypsin-modified type 3 poliovirus show an 'improved' distribution of antigenic site specificities resembling that seen in man after poliovirus infection.