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Biomedical subjects

L P Titov

Publications and source records attributed to L P Titov.

At least 19 recordsLinked to original sources
PubMed2003

Serotype-specific mucosal immune response and subsequent poliovirus replication in vaccinated children.

A total of 32 unimmunized children (median age 5 months) living in an orphanage in Minsk, Belarus, were vaccinated with three doses of oral poliovirus vaccine (OPV) with a 60-day interval between the doses. Blood samples were drawn before the immunizations and 45-50 days after each vaccine dose. Excretion of the vaccine viruses was followed by examining fecal specimens collected weekly after each vaccine dose. All children seroconverted by the second dose of OPV at the latest to all three serotypes of poliovirus but differences were seen regarding the intestinal responses. The strongest responses in both neutralizing antibodies and virus-binding IgA in fecal suspensions were seen toward poliovirus Type 2. Consistent with this, relatively little poliovirus Type 2 excretion was seen after the second and third doses of OPV as compared to that of poliovirus Type 1 or Type 3. The delayed development of functional intestinal immunity against the latter serotypes was associated with relatively weaker intestinal antibody responses compared to poliovirus Type 2. In the case of poliovirus Type 3, about 10% of children were still excreting the vaccine virus 9 weeks after administering the third dose. These results are consistent with epidemiological observations of the serotype-specific efficacy of OPV immunizations. The proportion of specimens showing nonpolio enteric viruses gradually increased through the 6-month study period. This may reflect the possibility that after the first dose of OPV, intensive replication of the vaccine viruses may out compete the nonpolio viruses in the intestines of the vaccinees or, alternatively, mask nonpolio viruses during the cell culture isolation procedure.

Antibodies, Viral↗
PubMed2003

Virologic and serologic investigations of West Nile virus circulation in Belarus.

In 1985-1994 virologic and serologic investigations were performed for the purposes of West Nile (WN) virus circulation establishment on the territory of Belarus. Blood-sucking mosquitoes, midges, wild small mammals, birds as well as blood and cerebrospinal samples from patients with nondifferentiated fevers and from healthy individuals were under studies. Four virus strains were isolated in Belarus for the first time, namely: 1--from birds (48-WN Tremlya); 2--from Aedes mosquitoes (319 and 2438); 1--from a febrile patient (Win). Their antigenic and biological properties were examined in cell cultures and laboratory animals. The isolates turned to be identical with each other and closely related to reference Egypt strain Eg 101, that is a topotype for the African virus group. One more WN virus strain (8891) was isolated from Anopheles mosquitoes in 1999. Specific antibodies to the virus in human blood sera were identified by immunological and serologic assays in 1.7% of Belarusian population. In Gomel and Brest Regions the percentage of seropositive individuals reached 5.8 and 15.4, respectively. WN virus antibodies prevailed in 0.6-5.8% of cattle, in 2.9-6.8% of wild small mammals and in 6.5-16.7% of birds. Thus, the conclusion was made on the existence of favourable conditions for the virus spread throughout the whole country and in the south in particular. Blood-sucking mosquitoes and birds are principle vectors in WN virus circulation in Belarus. 16 serologically confirmed cases of WN encephalitis were revealed in patients with fever of obscure etiology. In the view of the given data, reports on the reemergence of the pathogen in different countries and the tendency in global warming WN virus monitoring should become a subject of concern for Belarusian public medical care services.

Adolescent↗
PubMed2003

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.

Adolescent↗
PubMed2002

Immunochromatographic strip test for rapid detection of diphtheria toxin: description and multicenter evaluation in areas of low and high prevalence of diphtheria.

An immunochromatographic strip (ICS) test was developed for the detection of diphtheria toxin by using an equine polyclonal antibody as the capture antibody and colloidal gold-labeled monoclonal antibodies specific for fragment A of the diphtheria toxin molecule as the detection antibody. The ICS test has been fully optimized for the detection of toxin from bacterial cultures; the limit of detection was approximately 0.5 ng of diphtheria toxin per ml within 10 min. In a comparative study with 915 pure clinical isolates of Corynebacterium spp., the results of the ICS test were in complete agreement with those of the conventional Elek test. The ICS test was also evaluated for its ability to detect toxigenicity from clinical specimens (throat swabs) in two field studies conducted within areas of the former USSR where diphtheria is epidemic. Eight hundred fifty throat swabs were examined by conventional culture and by use of directly inoculated broth cultures for the ICS test. The results showed 99% concordance (848 of 850 specimens), and the sensitivity and specificity of the ICS test were 98% (95% confidence interval, 91 to 99%) and 99% (95% confidence interval, 99 to 100%), respectively.

Antibodies, Bacterial↗
PubMed2002

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.

Antiviral Agents↗
PubMed2001

Viral water contamination as the cause of aseptic meningitis outbreak in Belarus.

In the recent years Echovirus-30 associated outbreaks have taken place in different European countries. Aseptic meningitis caused by Echovirus-30 was the main diagnosis of a large outbreak in Belarus in Summer-Autumn, 1997, involving 460 patients. Echovirus-30 was detected in cerebrospinal fluid of the patients with aseptic meningitis. This serotype played the dominant role in the outbreak. Minor serotypes and mixtures of enteroviruses were detected in faeces and nasopharyngeal lavages. Investigation of environmental samples gave evidence of expressed viral contamination of drinking water and water sources (river and ground sources). River water sources were considerably contaminated with viruses. The incidence of virus isolation was 50%. After cleaning procedures, the incidence became two times lower, proving imperfect water purification and disinfection procedures. Sequence analysis of isolates from Belarus (isolates from water and patient's cerebrospinal fluid) showed the difference of 0.2%. The outbreak peculiarities such as high attack rate and wide-spread of the disease incidences, clinical form variability, isolation of outbreak strain from water and a good agreement between minor serotypes isolated from faeces and water samples as well as correlation in the dynamics of acute intestine infections, aseptic meningitis morbidity and bacterial water contamination can be considered as evidence of its water-borne. Echovirus-30 isolates from Belarus were very closely related to each other and to several European isolates. Sequence difference between isolates of 1994-1998 from European countries was found to be 4.3%. The data can point to the common primary source of enterovirus infection, connected to water and to the possibility of epidemic strain transmission from neighbouring states to the Republic of Belarus.

Disease Outbreaks↗
PubMed2000

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.

Antibodies, Viral↗
PubMed1999

[Use of rapid methods in detection of enteroviruses].

Indirect immunofluorescence (IIF) and RT-PCR were used for rapid diagnosis of enterovirus infection during an outbreak of aseptic meningitis in Gomel. IgM to enterovirus were detected in 93.6% sera by IIF and in 71.4% cerebrospinal fluid specimens by RT-PCR. IIF takes only 1.5-2 h and RT-PCR 6-7 h. The methods are recommended for rapid diagnosis of enterovirus infection.

Antibodies, Viral↗
PubMed1993

[New test for detection of hypersensitivity to mycobacterial tuberculosis].

A new test for abnormal sensitization of the body with M. tuberculosis proposed by the authors implies conduction of leukocyte migration inhibition test under theophylline-induced block of T-suppressor function. Examination of 82 tuberculous patients and 30 healthy subjects proved high accuracy of the test able to identify the sensitization significantly, irrespective of the activity of T-cell suppressive population. The method is applicable also in latent tuberculosis, the detection of which permits earlier introduction of adequate therapy.

Adult↗