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Biomedical subjects

A E Platonov

Publications and source records attributed to A E Platonov.

At least 19 recordsLinked to original sources
PubMed2006

[The influence of weather conditions on the epidemiology of vector-borne diseases by the example of West Nile fever in Russia].

Climate changes must influence the incidence of vector-borne infections, but their effects cannot be revealed due to lack of long-term observations. The impact of short-term weather changes may be used as a model. In Russia the biggest numbers of clinical cases of mosquito-borne West Nile infection were registered in 1999 in Volgograd and Astrakhan regions. The analysis of climatic dataset since 1900 shows that 1999 was the hottest year in Volgograd in the 20th century due to a very mild winter (December-March) and a rather hot summer (June-September). The author of the article puts forward a hypothesis that high winter temperatures favored the survival of over-wintering mosquito vectors, and high summer temperature facilitated the growth of the virus in the mosquitoes, as well as propagation of the mosquitoes themselves. The author assumes that conventional threshold temperatures for "beneficial for WNF conditions" in Russia are > or = 3 degrees C in winter, and > or = 22 degrees C in summer. These conditions coincided only in 1948 and 1999. In Astrakhan the "beneficial for WNF conditions" were registered in 30 out of 147 years of observation, and in 12 years between 1964 and 2003. This is not surprising that Astrakhan region is endemic for WNF in accordance with clinical and epidemiological data collected since the sixties. These findings give some hints on the WNF predisposing factors, as well as possibility of weather surveillance and prediction of WNF outbreaks in temperate climatic zones such as Southern Russia.

Animals↗
PubMed2005

Economic evaluation of Haemophilus influenzae type b vaccination in Moscow, Russian Federation.

OBJECTIVE: To estimate the cost-effectiveness of providing Haemophilus influenzae type b (Hib) vaccine to children in Moscow in routine immunization services. METHODS: The incidence of Hib meningitis among children aged <5 years in Moscow was obtained from a prospective surveillance study undertaken during October 1999-September 2001, with treatment cost data collected for all cases. Sequelae in surviving children were assessed in December 2002. The costs of Hib vaccination in Moscow were estimated assuming a vaccine price of US dollar 5 per dose and the same four-dose schedule and 97% coverage as for diphtheria-tetanus-pertussis vaccine. The most uncertain variables were varied in a sensitivity analysis. RESULTS: The annual incidence of Hib meningitis was 5.7 per 100,000 children <5 years. The average treatment cost for an acute Hib meningitis case was US dollar 1296. For a patient with sequelae, the average additional lifetime discounted treatment cost was US dollar 15,820. The total annual cost of Hib vaccination of infants in Moscow was estimated as US dollar 1.5 million per year. In the base case analysis, the cost-effectiveness ratios amount to US dollar 77,503 per Hib meningitis case averted and US dollar 10,842 per discounted disability adjusted life year averted. The break-even vaccine price, where the annual vaccination costs equal annual treatment costs averted, is only US dollar 0.04 per dose in the base case scenario. If discounted indirect costs are included, the break-even vaccine price is US dollar 0.5 per dose. CONCLUSION: In Moscow, the incidence of Hib meningitis is low and the costs of hospitalization and subsequent medical treatment are relatively inexpensive. Given these factors, Hib vaccine at US dollar 5 per dose would not be a cost-effective option in Moscow at the present time.

Bacterial Capsules↗
PubMed2005

[Polymorphism of mitochondrial DNA and infection with symbiotic cytoplasmic bacterium Wolbachia pipientis in mosquitoes of the Culex pipiens complex from Russia].

A total of 208 mosquitoes of the Culex pipiens complex from 15 basement and terrestrial populations collected in different regions of the European part of Russia and Siberia were examined by genetic methods. Among these, two major mitotypes, M and P, were identified. These mitotypes differed by six substitutions in the 246-bp mitochondrial DNA cytochrome oxidase I gene fragment examined. Urban basement mosquito ecotype C. pipiens (form molestus) were characterized by the presence of mitotype M and infection with the endosymbiotic bacteria of the genus Wolbachia. Mosquitoes of the C. pipiens complex inhabiting opened biotopes harbored mitotype P, or its variety, mitotype P1, and were not infected with Wolbachia. Thus, in natural conditions marked linkage disequilibrium between cytoplasmic elements, mitochondrial DNA and Wolbachia, can be observed. Similarity of mitotypes in form molestus mosquito from different geographical localities favors the hypothesis on the common ancestry of urban mosquitoes.

Animals↗
PubMed2003

[Multilocus sequence-typing for characterization of Moscow strains of Haemophilus influenzae type b].

Haemophilius influenzae, type b (Hib) bacteria, were genotyped by multilocus sequence typing (MLST) using 5 loci (adk, fucK, mdh, pgi, recA). 42 Moscow Hib strains (including 38 isolates form cerebrospinal fluid of children, who had purulent meningitis in 1999-2001, and 4 strains isolated from healthy carriers of Hib), as well as 2 strains from Yekaterinburg were studied. In MLST a strain is characterized, by alleles and their combinations (an allele profile) referred to also as sequence-type (ST). 9 Sts were identified within the Russian Hib bacteria: ST-1 was found in 25 strains (57%), ST-12 was found in 8 strains (18%), ST-11 was found in 4 strains (9%) and ST-15 was found in 2 strains (4.5%); all other STs strains (13, 14, 16, 17, 51) were found in isolated cases (2.3%). A comparison of allelic profiles and of nucleotide sequences showed that 93% of Russian isolates, i.e. strain with ST-1, 11, 12, 13, 15 and 17, belong to one and the same clonal complex. 2 isolates from Norway and Sweden from among 7 foreign Hib strains studied up to now can be described as belonging to the same clonal complex; 5 Hib strains were different from the Russian ones.

Adenylate Kinase↗
PubMed2003

[Laboratory diagnostics of Crimean hemorrhagic fever by polymerase chain reaction].

Our group developed, within the present case study, two techniques' variations, i.e. a single-step RT-PCR and nested RT-PCR assays, for the purpose of detecting the Crimean-Congo hemorrhagic fever RNA virus in human samples. The above assays as well as those previously recommended by the Ministry of Health of the Russian Federation were simultaneously used in 14 clinical samples obtained from patients with Crimean hemorrhagic fever. After assessing the detection accuracy, it was found that the developed-by-us test system displayed the same or even better diagnostic values versus the previously recommended nested RT-PCR and a 1000-fold advantage over the previously recommended single-step RT-PCA. The single-step RT-PCR assay variation is always more preferable in sense of technical and economic motivations. Finally, the test system developed by us has every reason to become the method of choice in routine PCR diagnosis of Crimean hemorrhagic fever after all official trials and approvals are duly complied with.

DNA Primers↗
PubMed2001

Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis.

The genetic variability at six polymorphic loci was examined within a global collection of 502 isolates of subgroup III, serogroup A Neisseria meningitidis. Nine "genoclouds" were identified, consisting of genotypes that were isolated repeatedly plus 48 descendent genotypes that were isolated rarely. These genoclouds have caused three pandemic waves of disease since the mid-1960s, the most recent of which was imported from East Asia to Europe and Africa in the mid-1990s. Many of the genotypes are escape variants, resulting from positive selection that we attribute to herd immunity. Despite positive selection, most escape variants are less fit than their parents and are lost because of competition and bottlenecks during spread from country to country. Competition between fit genotypes results in dramatic changes in population composition over short time periods.

Alleles↗
PubMed2001

West Nile encephalitis in Russia 1999-2001: were we ready? Are we ready?

In 1963-1993, several strains of West Nile virus (WNV) were isolated from ticks, birds, and mosquitoes in the southern area of European Russia and western Siberia. In the same regions, anti-WNV antibody was found in 0.4-8% of healthy adult donors. Sporadic human clinical cases were observed in the delta of the Volga River. In spite of this, WNV infection was not considered by the health authorities as a potentially emerging infection, and the large WNV outbreak in southern Russia, started in late July 1999, was not recognized in a timely fashion. First evidence suggesting a WNV etiology of the outbreak was obtained by IgM ELISA on September 9. Two weeks later, the specific WNV RT-PCR was developed and WNV disease was confirmed in all 14 nonsurvivors from whom brain tissue samples were available. Retrospective studies of serum samples by IgM ELISA indicated WNV etiology in 326 of 463 survivors with aseptic meningitis or encephalitis. Moreover, 35 of 56 patients who contracted aseptic meningitis in 1998 had a high titer of WNV IgG antibody, so the WNV infection seems to have been introduced into the Volgograd region before 1999. A complete sequence (AF317203) of WN viral RNA, isolated from the brain of one Volgograd fatality, and partial sequences of an envelope E gene from other nonsurvivors showed that the Volgograd isolate had the greatest homology (99.6%) with WN-Romania-1996 mosquito strain RO97-50.

Age Distribution↗
PubMed2000

[Multilocus sequencing--a new method of genotyping bacteria and first results of its use].

Comparative characterization (molecular typing) of isolates within a bacterial species is one of the major problems in microbiology and epidemiology. However, it is rather difficult to correlate data obtained in various laboratories, because traditional, including molecular, methods employed in typing pathogenic microorganisms cannot be standardized. In 1998, Maiden et al. proposed multilocus sequence typing (MLST); through which alleles of several housekeeping genes are directly assessed by nucleotide sequencing, each unique allele combination determining a sequence type of a strain. The advantages of this approach are that the culturing of pathogenic microorganisms is avoided, as their gene fragments are amplified directly from biological samples, and that the sequencing data are unambiguous, easy to standardize, and electronically portable. The latter makes it possible to generate an expandable global database for each species at an Internet site, in order to use it for the purposes of genotyping pathogenic bacteria (and other infectious agents). MLST protocols have been elaborated for Neisseria meningitidis, Streptococcus pneumoniae, and Helicobacter pylori; those for Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae are now being developed. Basic principles and the first results of MLST have been reviewed, including data on the distribution and microevolution of N. meningitidis clones causing epidemic meningococcal infection, the relative recombination and mutation rates in the N. meningitidis genome, the identification of antibiotic-resistant S. pneumoniae clones causing severe generalized infection, the grouping of H. pylori isolates from various geographic regions, etc.

Bacteria↗
PubMed1999

[Prognosis in meningococcal disease: methodology and practice].

78 patients with systemic meningococcal disease admitted to the Intensive Care Unit of the 2nd Moscow Hospital for Infectious Diseases were studied and the composite prognostic score was developed to estimate the risk of lethal outcome. The stepwise variable selection procedure for the multiple logistic regression was applied to 30 potential clinical and laboratory risk factors and markers. Five factors were selected for the score, namely the platelet count (< 150 x 10(6)/ml), the presence of hemorrhages into the eye or mucosal tissue, the interval from the last urination before admission (> 4 h), the respiration rate (> 170% of age-adjusted normal value) and age (< 2 or > 65 years) with regression coefficients 0.3, 0.2, 0.2 and 0.1, respectively. Both for the source clinical group and for the additional test group (64 patients), the scale was able to classify correctly 95% of cases using the data collected at admission. Ten prognostic scores proposed previously by foreign investigators were tested in the same patients and the best four scores were selected (GMSPS, Gedde-Dahl, Niklasson, Kahn); the scores classified correctly 85-90% of cases. This study is an example of methodological approaches to prognostic score construction in medicine.

Adolescent↗
PubMed1999

[The interconnection between the severity of meningococcal infection and the endotoxicity levels and patient's blood complement].

Seventy-eight patients with severe systemic meningococcal disease admitted to the Intensive Care Unit of the Second Moscow Hospital for Infectious Diseases were divided into four groups by complications of their disease: patients with refractory septic shock (RSS)--group 1; patients with early septic shock (ESS)--group 2; patients without shock but with severe mental disorders--group 3; patients without any of these complications--group 4. The LPS concentration in plasma was assessed by chromogenic method. Initial LPS levels in plasma of group 3 or group 4 patients (170 ng/l, median value and 360 ng/l, respectively) were greater than those of healthy donors (LPS < 15 ng/l). LPS concentration was significantly greater in group 2 (920 ng/l) or group 1 (12,400 ng/l). LPS levels declined exponentially in all the patients. The half-life was calculated to be 1.4 (+) -0.3 h. In group 2 and 1, respectively, the classical pathway complement activity in patients' serum was 50 and 10% of normal control values. To estimate significant prognostic factors for fatality in our patients, specificity and factor fatality difference of various clinical and laboratory factors were calculated. The cut-off LPS value for development of ESS was 600 ng/l and that for development of RSS and death was 8000 ng/l. For the prediction of fatality using the former cut-off value of LPS, sensitivity was 84% and specificity 100%. Using plasma complement activity (cut-off--15% of normal value) for prediction, sensitivity was 75% and specificity was 100%. Other factors (platelet and WBC count, blood pH, BP, etc.) had lower predictive power. Thus to date plasma endotoxin level and complement activity are the best prognostic factors in meningococcal disease.

Adolescent↗
PubMed1999

[Human resistance to generalized bacterial infections (exemplified by meningococcal infection)].

The hierarchical organization of human host defense systems against systemic bacterial infections is considered by using meningococcal disease as a model. The bactericidal action of the complement system is the most potent defense mechanism against meningococci. The antibody-independent alternative pathway of complement activation is more important in infancy. When the specific antibody level increases by natural immunization or vaccination, the antibody-dependent classical pathway of complement activation provides an additional protection. The bactericidal effect of human phagocytes, primarily neutrophils, is mediated partly by the receptors of complement components and immunoglobulins and serves as an additional mechanism of resistance. The relative risk of meningococcal disease may be approximately estimated as 1,000 for the individuals without blood complement bacteriolytic activity, as 80 for those without specific bactericidal antibodies, and as 3 for individuals with ineffective phagocytosis as compared to those with the normal complement system, high levels of bactericidal antibodies, and effective phagocytosis by neutrophils.

Antibodies, Bacterial↗
PubMed1999

[Clinical features of meningococcal infection in subjects with deficient terminal components of complement].

AIM: To evaluate clinical characteristics of meningococcal disease (MD) in individuals with terminal complement component deficiency (TCCD) who are thousands times more susceptible to MD than complement-sufficient persons. MATERIALS AND METHODS: 61 cases of MD in TCCD patients and 200 randomly selected cases of MD in complement-sufficient patients were analyzed. RESULTS: Meningitis without meningococcemia accounted for 17% of the MD episodes in the control group of complement-sufficient patients but none in individuals with TCCD who had meningococcemia (10%) or meningococcemia with meningitis (90%). Moderate disease predominated in patients with TCCD (70%) and no episodes of fatal disease were noted, whereas severe disease was more common in the control group which had an 8% case fatality rate and frequent complications such as endotoxic shock (15% of episodes) and brain edema (26%). The severity of the disease in TCCD patients did not differ between the first and subsequent episodes, between males and females, between episodes caused by serogroup A and B meningococci, etc. CONCLUSION: In comparison to complement-sufficient persons, the course of the disease in patients with TCCD is statistically less severe.

Adolescent↗
PubMed1998

Meningococcal disease and polymorphism of FcgammaRIIa (CD32) in late complement component-deficient individuals.

Late complement component-deficient (LCCD) individuals lack plasma bactericidal activity and are highly susceptible to meningococcal disease. Phagocytosis plays a significant role in immune defence against meningococci and involves FcgammaRIIa (CD32) on leucocytes. Two allotypic forms are currently recognized: FcgammaRIIa-R131 and RIIa-H131. Neutrophils with the IIa-H/H131 allotype are more effective in phagocytosis than IIa-R/R131. We studied the distributions of IIa-R131 and IIa-H131 allotypes among 29 Russian LCCD patients who had suffered from recurrent episodes of meningococcal disease. The distribution of IIa-R/R131 to heterozygous IIa-R/H131 to homozygous IIa-H/H131 genotypes was 0.14:0.29:0.57 for LCCD patients who developed the first episode of disease before 10 years of age. The distribution was 0.21:0.64:0.14 for patients who experienced meningococcal disease above the age of 10 years (chi2 = 6, P < 0.05, odds ratio for IIa H/H131 versus R/R131 = 8). Meningococcal disease had a 'grave' course in 14 of 31 disease episodes in patients with IIa-R/R131 and IIa-R/H131 allotypes, in contrast to 1 of 18 episodes in patients with IIa-H/H131 allotype (chi2 = 7, P < 0.01, odds ratio = 14). We conclude that IIa-H/H131 individuals appear to have a higher acquired antibody-mediated phagocytosis-dependent resistance to meningococcal disease above the age of 10 years. Additionally, effective CD32-mediated phagocytosis may restrict the severity of meningococcal disease in LCCD patients with IIa-H/H131 phenotype.

Adolescent↗
PubMed1998

Association of human Fc gamma RIIa (CD32) polymorphism with susceptibility to and severity of meningococcal disease.

Phagocytosis of bacteria constitutes an important defense mechanism against invasive bacterial diseases. Efficacy of phagocytosis by polymorphonuclear neutrophils is known to vary between allotypes of Fc gamma RIIa (a class of Fc receptors for immunoglobulins that is constitutively expressed on neutrophils). We compared the distribution of Fc gamma RIIa-R131 and Fc gamma RIIa-H131 allotypes in 98 Slavic complement-sufficient patients with meningococcal disease with that of the allotypes in 107 healthy controls. A strong association was found between the IIa-R/R131 allotype and the development of meningococcal disease after the age of 5 years, compared with IIa-R/H131 and IIa-H/H131 allotypes (P < .03; odds ratio [OR], 2.9). A severe course of meningococcal disease was observed in 21 (68%) of 31 episodes in patients with IIa-R/R131 genotype and in 22 (54%) of 41 episodes in patients with IIa-R/H131 genotype, in contrast to eight (31%) of 26 episodes in patients with IIa-H/H131 genotype (P < .02; OR, 4.7). Our data show that individuals older than 5 years of age who have the IIa-H/H131 allotype are less susceptible to severe meningococcal disease than are individuals with the IIa-R/R131 or IIa-R/H131 genotype.

Adolescent↗
PubMed1997

Heterozygous C8beta complement deficiency does not predispose to meningococcal disease.

We have identified 42 Russian patients with homozygous C8beta complement component deficiency, all of whom had experienced at least one episode of systemic meningococcal disease. About 90% of these individuals have a C --> T exchange in exon 9, leading to a premature stop codon. If, like the homozygous-deficient state, heterozygous C8beta deficiency constitutes a risk factor for meningococcal disease, it would be expected to be detected with increased frequency among individuals suffering from this disease. Using allele-specific polymerase chain reaction (PCR), we studied 153 consecutive patients with meningococcal disease admitted to the Moscow Hospital for Infectious Diseases to determine the frequency of C8 null allele. No individuals with heterozygous C --> T exchange were identified among these 153 patients, despite the fact that seven persons were detected who had homozygous C8beta deficiency, caused by the same C --> T exchange in exon 9, and one patient who had C7 component deficiency. Thus, heterozygous deficiency, although more frequent than homozygous deficiency in the general population, does not result in a substantial increase in susceptibility to meningococcal disease.

Complement C8↗
PubMed1997

DNA haplotypes of the complement C6 and C7 genes associated with deficiencies of the seventh component; and a new DNA polymorphism in C7 exon 13.

Eight common DNA polymorphisms have been described for the linked C6 and C7 genes. We now describe a ninth polymorphism in C7 exon 13 which is located in a tight cluster with two previously reported markers. We have used all these markers to investigate the heterogeneity of C7 deficiency. Five of the nine C7 deficient probands (resident in Ireland, South Africa, Russia and Israel) are heterozygous for C6/C7 haplotypes. Seven different C7 deficient haplotypes were found for C7 markers alone, but all the four Israelis share one and three out of four Irish haplotypes share another. The markers appear to be a good guide to the heterogeneity of C7 deficiency and have been useful in choosing homozygous subjects for the investigation of molecular defects.

Child↗
PubMed1996

Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies.

Combined subtotal deficiency of C6 and C7, in which both proteins are expressed at very low levels, has been observed in homozygous form in two families. A defect at the 5' splice donor site of intron 15 of the C6 gene explains the low molecular weight of the C6 protein and is probably responsible for its low expressed concentration. The C7 defect is more enigmatic: the protein is of normal molecular weight, low circulating concentration, and altered isoelectric point. An Arg > Ser codon substitution in exon 11 is the only molecular alteration within the mature C7 protein. These defects are associated with a characteristic set of polymorphic DNA markers in the C6/C7 region, forming a distinct haplotype. The haplotype has been found in combination with a number of other haplotypes containing defective genes that lead either to C6 or C7 deficiency, but with different consequences. Where it is combined with a C6-deficient gene, the serum C7 levels can be surprisingly high, possibly because there is no C6 generating C56 to consume the C7. In contrast, where the C7 genes are both defective (but still partially functional), there may be a profound deficit of circulating C7 because there is ample C6 to produce C56 and consume the already small amount of C7. Each molecular defect has also been found in isolation and has the expected effect.

Amino Acid Sequence↗