Measles cases in highly vaccinated population of Novosibirsk, Russia, 2000-2005.

While the proportion of measles cases in vaccinees is expected to increase as vaccine coverage increases, such cases must be carefully investigated. The present study was conducted to examine possible contributions to vaccine failures (VFs) and to genetically characterize measles virus (MV) strains circulating in Novosibirsk, Russia during 2000-2005. Totally, 27 adult measles patients admitted to a regional hospital were prospectively enrolled in our study. Genetic characterization of the MV strains revealed circulation of genotypes A, D4 and D6 between 2000 and 2003 years; a genotype D6 MV was associated with the 2005 measles outbreak. Based on IgG avidity testing, half of the vaccinated patients demonstrated evidence of secondary vaccine failure (SVF). Patients, representing both levels of vaccine failure in our study were characterized by the lack of protective titers of neutralizing antibodies against circulating MVs, despite high IgG levels in many cases and high IgG avidity in SVF cases.

Mumps vaccine failure investigation in Novosibirsk, Russia, 2002-2004.

The aims of this study were to estimate the importance of vaccine failure (VF) in cases of mumps during 2002-2004 in the city of Novosibirsk, Western Siberia, Russia, and to genotype the responsible virus strain. Mumps virus-specific RT-PCR testing of saliva was performed for 18 cases of mumps. Sera were tested for IgM and IgG, IgG avidity, and the ability to neutralise a panel of mumps viruses, including the Leningrad-3 mumps vaccine virus. Of the 12 patients for whom vaccination status was positively determined, 11 showed serological evidence of primary VF. Sequence analysis of virus RNA amplified from saliva revealed a genotype C2 virus in 2002, a genotype H2 virus in 2003, and both genotypes in 2004. Although several vaccinated patients were positive for mumps virus IgG at the time of first sampling, only nominal levels of neutralising antibody were detected, and these were effective in neutralising the vaccine strain, but not genotype C and H mumps virus strains. These results suggest that the majority of cases of mumps in vaccinees are caused by primary VF, defined as either a lack of seroconversion or a lack of IgG maturity, as based on avidity testing. The results also support the hypothesis that sera of low neutralising antibody titre have a limited ability to neutralise heterologous mumps virus strains, suggesting that antigenic differences between circulating and mumps vaccine virus strains may play a role in cases of breakthrough infection. Consistent with previous reports, mumps virus genotypes C and H continue to circulate in Novosibirsk.

Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus.

Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.

Measles in Minsk, Belarus, 2001-2003: clinical, virological and serological parameters.

BACKGROUND: A number of cases of measles have been reported in the Republic of Belarus despite vaccine coverage of 98%. The absence of information on measles virus genotypes circulating in the Republic of Belarus has made it difficult to asses the situation. OBJECTIVES: The purpose of this study was to isolate and sequence measles virus strains from clinical cases in Minsk, Belarus, and to estimate the role of vaccine failure in those cases. STUDY DESIGN: Between 2001 and 2003 years, 14 measles cases admitted to the Hospital of Infectious Diseases of Minsk were enrolled in our study. Clinical, routine laboratory, as well as serological and virological examinations were carried out. Detection of measles antibodies and IgG avidity testing was performed using commercial test kits. All measles cases were confirmed by RT-PCR and phylogenetically characterized. RESULTS: Only 42.9% of the cases met the WHO laboratory criteria for measles, however, all cases were confirmed by RT-PCR. Most of the measles cases were attributed to secondary vaccine failure (SVF). Phylogenetic analysis revealed the presence of genotype A virus strains in 2001 and 2002 with D6 and D7 genotypes in 2003. CONCLUSIONS: For the first time, MVs were genetically characterized in Belarus. Our results suggest that in a highly vaccinated population, most of measles cases represent vaccine failures and are vaccine-modified. Our results also indicate that confirmation of a clinical diagnosis of vaccine-modified measles requires a combination of serological and virological tests.

Acute infectious mononucleosis and coincidental measles virus infection.

BACKGROUND: Both Epstein-Barr and measles viruses (MV) cause immune suppression, and the association of the two viruses is evaluated as life threatening. The cell immune impairment caused by simultaneous Epstein-Barr and measles viral infections was responsible for the complicated course of the disease in all described previously reports and for unfavorable outcomes in most of the cases. Timely diagnosis of coincidental viral infections could be a useful predictor for the clinical course and complications. Diagnosis must be based on an accurate assessment of clinical, hematologic, serologic manifestations and supported by appropriate laboratory methods. Recognizing the infectious etiology of concomitant infections is important for both clinicians and epidemiologists. OBJECTIVE: To describe a case report of a 20-year-old woman previously vaccinated against measles infected with acute mononucleosis and coincidental measles virus infection. STUDY DESIGN: The clinical, routine laboratory, as well as serological and virologic findings of this patient were scrutinized. Special emphasis was placed on the use of RT-PCR/PCR for confirming the involvement of both measles virus and Epstein-Barr virus (EBV) in this patient's illness. RESULTS: Infectious mononucleosis was not suspected at admission to the hospital. The final diagnosis of a concomitant measles virus infection and acute infectious mononucleosis was facilitated using viral serology to detect virus-specific IgG and IgM antibodies and by RT-PCR for the detection of measles virus RNA and EBV DNA from peripheral blood monocyte cells (PBMC). CONCLUSION: The present report highlights the difficulty of diagnosing two coincidental virus infections on clinical grounds. Serological and molecular laboratory methods, specifically the PCR (RT-PCR) analysis, are found to be useful for confirming the concomitant viral infections and proper identification of the infecting pathogens.

Protective effect of exogenous recombinant mouse interferon-gamma and tumour necrosis factor-alpha on ectromelia virus infection in susceptible BALB/c mice.

The resistance to mousepox is correlated with the production of type I cytokines: interleukin (IL)-2, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. We intend to describe the modulation of generalized ectromelia virus (EV) infection with exogenous administration of mrIFN-gamma and mrTNF-alpha separately and in combination using susceptible BALB/c mice. The treatment schemes presented resulted in the localization of the generalized EV infection and its development into non-fatal sloughing of the infected limb. This was accompanied by low virus titres in the treated mice due to control of systemic virus replication and virus clearance. The balance of type I versus type II cytokines was dominated by a type I response in the treated groups. The group treated with the combination of IFN-gamma and TNF-alpha exhibited the best survival with Th1-dominant (IFN-gamma and IL-12) cytokine profiles, whereas the TNF-alpha-treated group of mice was less successful in clearance of virus and demonstrated the lowest survival rate. The successful cytokine treatment schemes in this orthopoxvirus model system may have important implications in the treatment of viral diseases in humans and, in particular, of variola virus infection.

Changes in immune parameters and their correction in human cases of tick-borne encephalitis.

Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system diseases in humans. General infection leads to the development of meningitis or encephalitis, which is characterized by swelling of the brain due to inflammation. Tetracyclines may act locally to moderate inflammation in the CNS. In this study, we investigated the potential clinical benefits of administering tetracycline hydrochloride to patients hospitalized due to suspected TBEV infection presenting with fever and evidence of a recent tick bite. We also characterized an acute immune response to TBEV by profiling certain cytokines and soluble receptors in Tetracycline-treated and untreated patients. Increased serum levels of TNF-alpha, IL-1 alpha and IL-6 were found in all patients at admission. Soluble receptors presented in the serum of patients in a magnitude higher levels than the corresponding cytokines and were increasing during first weak of hospitalization. Levels of IL-10 were also rising during that period. In our study tetracycline hydrochloride acted as an immunomodulator, which was able to reduce manifestations of inflammation response during TBE course; this action led to quicker improvement of symptoms and, consequently, to a faster clinical recovery. The positive result of tetracycline hydrochloride treatment was accompanied by certain particularities in the dynamics of studied cytokines and receptors: the concentrations of IL-6, IL-1 beta, TNF-alpha dropped quicker and reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased faster and reached higher maximum levels in the tetracycline-treated groups. Children had the highest levels of IL-6, which were not neurotoxic.

Experimental study on the possibility of treatment of some hemorrhagic fevers.

After intracerebral challenge with 100 PFU of Lassa virus (strain Josiah), all infected mice (CBA/calac) died (control group). Production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) significantly increased in the blood of these mice during the infection. For neutralization of increasing concentrations of these cytokines recombinant IL-1RA was used intraperitonealy at a dose 100 microg kg(-1), everyday, within 5 days from the third day after the challenge. Injections of IL-1RA decreased the concentration of IL-1beta and TNF-alpha and resulted in survival of all infected mice (treatment group). Marburg fever (strain Popp) caused in guinea pigs by 5 LD(50) of virus lead to the significant increase of TNF-alpha in the animal's blood and caused a lethal outcome (control group). Treatment of infected guinea pigs by IL-1RA or anti-TNF serum decreased the concentration of TNF-alpha and resulted in survival of half of the animals (treatment group). For the treatment recombinant IL-1RA was used at a dose 100 microg kg(-1), intramuscularly, everyday, within 6 days from the third day after the challenge or anti-TNF serum, intramuscularly 0.5 ml (2000 U ml(-1); 1 U of the antiserum neutralises 0.03 ng of TNF-alpha), everyday, within 6 days from the third day after the challenge.