Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Cardiovascular risk factors in adolescents with prediabetes.

AIMS: Adolescents with Type 2 diabetes are more likely to have cardiovascular disease (CVD) risk factors but there are few data available among adolescents with prediabetes. We characterized CVD risk factors among adolescents with prediabetes in the USA and compared levels of those risk factors with adolescents with normal glucose. METHODS: The 2005-2014 National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey, included 2843 adolescents aged 12-19 years after excluding those with diabetes. Prediabetes was based on an HbA1c , a fasting plasma glucose or a 2-h plasma glucose. We determined cardiometabolic risk factors in adolescents using age-appropriate cut-off points. We calculated odds ratios (OR) and 95% confidence intervals (CI) of these outcomes associated with having prediabetes compared with normal glucose levels. RESULTS: The weighted prevalence of prediabetes was 17.4%. After adjustment, prediabetes (vs. normal glucose) was associated with obesity (OR 1.86, 95% CI 1.35-2.55), low HDL-cholesterol (OR 1.62, 95% CI 1.08-2.44), high triglycerides (OR 1.61, 95% CI 1.12-2.30) and elevated liver transaminase (OR 2.09, 95% CI 1.19-3.67), but not with hypertension (OR 1.77, 95% CI 0.88-3.54), elevated total cholesterol (OR 1.30, 95% CI 0.82-2.06), elevated LDL-cholesterol (OR 1.59, 95% CI 0.88-2.88) or albuminuria (OR 1.24, 95% CI 0.76-2.02). CONCLUSIONS: US adolescents with prediabetes are more likely to have obesity, low HDL-cholesterol, high triglycerides and elevated liver transaminase than adolescents with normal glucose. Addressing prediabetes in youth is important for the prevention of Type 2 diabetes and long-term comorbidity.

Trends in dietary intake among adults with type 2 diabetes: NHANES 1988-2012.

BACKGROUND: Dietary recommendations for adults with diabetes are to follow a healthy diet in appropriate portion sizes. We determined recent trends in energy and nutrient intakes among a nationally representative sample of US adults with and without type 2 diabetes. METHODS: Participants were adults aged ≥20 years from the cross-sectional National Health and Nutrition Examination Surveys, 1988-2012 (N = 49 770). Diabetes was determined by self-report of a physician's diagnosis (n = 4885). Intake of energy and nutrients were determined from a 24-h recall by participants of all food consumed. Linear regression was used to test for trends in mean intake over time for all participants and by demographic characteristics. RESULTS: Among adults with diabetes, overall total energy intake increased between 1988-1994 and 2011-2012 (1689 kcal versus 1895 kcal; Ptrend < 0.001) with evidence of a plateau between 2003-2006 and 2011-2012. In 2007-2012, energy intake was greater for younger than older adults, for men than women, and for non-Hispanic whites versus non-Hispanic blacks. There was no change in the percentage of calories from carbohydrate, total fat or protein. Percentage of calories from saturated fat was similar across study periods but remained above recommendations (11.2% in 2011-2012). Fibre intake significantly decreased and remained below recommendations (Ptrend = 0.002). Sodium, cholesterol and calcium intakes increased. There was no change in energy intake among adults without diabetes and dietary trends were similar to those with diabetes. CONCLUSIONS: Future data are needed to confirm a plateau in energy intake among adults with diabetes, although the opportunity exists to increase fibre and reduce saturated fat.

Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone.

We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary follicle-stimulating hormone (FSH), but normal luteinizing hormone (LH) secretion. Ovulation was induced by administration of exogenous FSH and resulted in a successful pregnancy. Sequence analysis of the FSH beta-subunit gene indicated that she is homozygous for a two nucleotide frameshift deletion in the coding sequence. Her mother and son are heterozygous for this mutation. This deletion results in an alteration of amino acid codons 61-86 followed by a premature termination codon. The predicted truncated beta-subunit peptide lacks regions which are important for association with the alpha subunit and for binding to and activation of the FSH receptor. Abnormalities of FSH structure or function might be an under recognised but treatable cause of infertility.

Variation of a carotenoid-based trait in relation to oxidative stress and endocrine status during the breeding season in the Eurasian kestrel: a multi-factorial study.

Carotenoid-based skin colorations vary seasonally in many bird species and are thought to be honest sexually selected signals. In order to provide more insight in the potential signal function and underlying mechanisms of such colorations we here quantified patterns of variation of leg coloration in adult male and female Eurasian kestrels (Falco tinnunculus tinnunculus) over the breeding season, and evaluated the relationship between coloration and levels of carotenoids, androgens and estrogens, oxidative damage and plasma non-enzymatic antioxidant capacity. We studied both reproducing wild and non-reproducing captive birds to test for the effect of diet and breeding effort. Males were more colored than females only during mating, and independently of diet, suggesting that leg-color is a sexually selected trait. Seasonal variation in leg color was associated with circulating carotenoids, but concentrations of these molecules were not related to antioxidant capacity, body condition or oxidative damage. These results indicate that carotenoid-based colorations may not be an honest signal of health status in this species. Production of carotenoid rich eggs coincided with low levels of circulating carotenoids in females, indicating that carotenoids might be a limited resource for laying female kestrels. Finally, young rearing males had higher levels of oxidative damage than females, and wild birds of both sexes had higher levels of these parameters than captive birds. These results may indicate that parental effort and physical activity are costly, independently from hormonal status. Since androgens did not explain carotenoid variation we suggest that multiple interacting factors can regulate carotenoid levels along the season.

Only high concentrations of ethanol affect GABAA receptors of rat cerebellum granule cells in culture.

In the experiments described in the present report, we evaluated the effects of ethanol on the activity of GABAA receptors of cerebellar granule cells in culture. Only very high ethanol concentrations (100-300 mM) showed a clear and significant stimulatory effect on the activity of such receptors. This result was unexpected. In fact, previous reports from other groups would have suggested high ethanol sensitivity of at least one population of GABAA receptors expressed by granule cells.

[Customer satisfaction in home care: methodological issues based on a survey carried out in Lazio]. / La qualità percepita in Assistenza domiciliare: considerazioni metodologiche alla luce di un'esperienza nel Lazio.

Home care customer satisfaction has been, until now, rarely evaluated. After illustrating the main italian regional surveys on this issue, the article presents a customer satisfaction survey carried out in the district of Civitavecchia (Local Health Unit 'Rome F'), Lazio, regarding 30 home care beneficiaries. Methodological aspects emerging from the survey are basically focused on: advantages and disadvantages of quantitative and qualitative approaches (possibly associated each other); main criteria of eligibility of people selected for interviewing, both patients or caregivers; conditions that maximize answers reliability, including training on interviewers. Authors highlight opportunity of using such kind of survey, integrated with other different tools, into a systemic vision, for promoting management changes coming from suggested problems, aimed at total quality management.

Serotypes of carriage and invasive isolates of Streptococcus pneumoniae in Brazilian children in the era of pneumococcal vaccines.

Nasopharyngeal carriage of Streptococcus pneumoniae is a key factor in the development of invasive disease and the spread of resistant strains within the community. A single nasopharyngeal swab was obtained from 648 unvaccinated children aged <5 years, either healthy or with acute respiratory tract infection or meningitis, during the winters of 2000 and 2001. The overall pneumococcal carriage rate was 35.8% (95% CI 32.1-39.6). The pneumococcal serotypes found most frequently in the nasopharynx were 14, 6B, 6A, 19F, 10A, 23F and 18C, which included five of the seven serotypes in the currently licensed seven-valent conjugate vaccine (PCV7); serotypes 4 and 9V were less common. Serotypes 1 and 5 were isolated rarely from the nasopharynx. A comparison of 222 nasopharyngeal isolates with 125 invasive isolates, matched for age and time to the carrier isolates, showed a similar prevalence of penicillin non-susceptible pneumococci (PNSp) (19.8% and 19.2%, respectively). PNSp serotypes were similar (6B, 14, 19F, 19 A, 23B and 23F) for carriage and invasive disease isolates. The coverage of PCV7 for carriage isolates (52.2%) and invasive isolates (62.4%) did not differ significantly (p 0.06); similarly, there was no significant difference in PCV7 coverage for carriage isolates (34.5%) and invasive isolates (28.2%) of PNSp. These data suggest that PCV7 has the potential to reduce pneumococcal carriage and the number of carriers of PNSp belonging to vaccine serotypes.

Geographic distribution of penicillin resistance of Streptococcus pneumoniae in Brazil: genetic relatedness.

From January 1993 through December 1996, 1,252 Streptococcus pneumoniae strains from different geographic regions of Brazil were studied for penicillin (Pen) susceptibility. All pneumococci were isolated from normally sterile fluids from patients, newborns to 88 years old. Pen resistance (R) had a mean rate of 15.1%, with 14.5% of strains showing intermediate level Pen-R and 0.6% showing high-level Pen-R. Similar Pen-R rates were observed in different regions of the country, in the range of 9.5% to 17.1%. A Pen-R increase was noted from 9.6% in 1993 to 20.6% in 1996. Pen-R was mostly associated to serotypes 6B, 14, 19A, and 23F (89%). Chromosomal DNA relatedness of Pen-R strains was determined by pulsed field gel electrophoresis (PFGE). High genetic diversity was identified, being represented by 27 patterns among the 92 strains. Two important features were observed: the predominance of relatively low-level Pen MIC (range 0.1-0.5 mg/L) in 86 of the 92 strains, and the presence of 60.8% as four major PFGE clusters unique to Brazil. Another feature was the geographic spread of these clusters over large distances in the country. The city of São Paulo seems to be a Pen-R focus (18.4%) in Brazil. Only two strains representing the international clone B widely spread in France, Portugal, and Spain, belonging to serotype 14, were found.

Antibiotic resistance in Streptococcus pneumoniae in six Latin American countries: 1993-1999 surveillance.

The impact of invasive pneumococcal invasive disease is increased by the emergence of antibiotic resistance. We report regional and temporal variations in antibiotic resistance for 4,105 invasive Streptococcus pneumoniae isolates collected from Latin American children <5 years, between 1993 and 1999. Reduced susceptibility to penicillin was detected in 1,182 isolates (28.8%); 36% of these were resistant (> or = 2 microg/ml), including 12.6% with MIC > or = 4 microg/ml, occurring primarily in serotypes 14 and 23F. Reduced susceptibility to third-generation cephalosporins was detected in 12.1% of the collection. Mexico had the highest proportion of reduced susceptibility to penicillin (51.6%) and to third-generation cephalosporins (22%), whereas Brazil had the lowest at 20.9% and 0.7%, respectively. Isolates cultured from patients with pneumonia were more likely to have reduced susceptibility to third-generation cephalosporins than isolates from patients with meningitis (p < 0.0001). Susceptibility to trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, and vancomycin was tested by disk diffusion for 2.899 isolates. Reduced susceptibility was observed for 45.6%, 11.5%, 6.9%, and 0%, respectively. Thirty-one percent of the strains were resistant to > or = 2 drugs. High levels of antibiotic resistance in Latin America emphasize the need for the development of and adherence to rational antibiotic use guidelines. On-going surveillance will monitor the impact of these programs.

Prevalence of serotypes and antimicrobial resistance of streptococcus pneumoniae strains isolated from Brazilian children with invasive infections. Pneumococcal Study Group in Brazil for the SIREVA Project. Regional System for Vaccines in Latin America.

A laboratory surveillance study was developed in Brazil in 1993 to determine capsular types and antimicrobial susceptibility of Streptococcus pneumoniae strains. By studying 360 strains isolated from children with invasive infections in three different cities, 8 out of 34 types were identified as being the most prevalent and considered as the reference group for further analyses. This group comprised 77.7% of all strains studied, and includes the types 1, 5, 6A/B, 9V, 14, 19F, 19A, and 23F. The prevalence of this reference group was significantly higher among strains isolated from children with pneumonia than meningitis. Similarly, this group was more prevalent among strains isolated from children 3 to 6 years of age than from children under 2 years of age. Most strains (78.6%) were found to be susceptible to penicillin and only 1.4% showed high resistance to this antibiotic. However, intermediate resistance to penicillin was detected in 20% of the strains. This laboratory surveillance will be maintained and extended to other cities of Brazil to better define and monitor the trends of pneumococcal infections for proper control and prevention.

Antimicrobial resistance patterns of Haemophilus influenzae isolated from patients with meningitis in São Paulo, Brazil.

From 1989 to 1995, a total of 391 Haemophilus influenzae isolates were recovered from the cerebrospinal fluid (CSF) of hospitalized patients in São Paulo, Brazil. The majority of strains were isolated from infants aged less than 5 years. Strains belonging to biotype I (64.7%), biotype II (34.5%) and biotype IV (0.76%) were detected. Ninety-nine percent of these strains were serotype b. Minimal inhibitory concentration (MIC) was determined for ampicillin, chloramphenicol and ceftriaxone. The ss-lactamase assay was performed for all strains. The rate of ss-lactamase producer strains ranged from 10 to 21.4% during a period of 7 years, with an overall rate of 13.8%. Of the 391 strains analyzed, none was ss-lactamase negative ampicillin resistant (BLNAR). A total of 9.7% of strains showed resistance to both ampicillin and chloramphenicol; however, 4% of them were resistant to ampicillin only and 2% to chloramphenicol. All strains were susceptible to ceftriaxone and the MIC90 was 0.007 microg/ml, suggesting that ceftriaxone could be an option for the treatment of bacterial meningitis in pediatric patients who have not been screened for drug sensitivity.

Antimicrobial resistance among invasive Haemophilus influenzae strains: results of a Brazilian study carried out from 1996 through 2000.

A total of 1712 strains of Haemophilus influenzae isolated from patients with invasive diseases were obtained from ten Brazilian states from 1996 to 2000. beta-Lactamase production was assessed and the minimum inhibitory concentrations (MIC) of ampicillin, chloramphenicol, ceftriaxone and rifampin were determined using a method for broth microdilution of Haemophilus test medium. The prevalence of strains producing beta-lactamase ranged from 6.6 to 57.7%, with an overall prevalence of 18.4%. High frequency of beta-lactamase-mediated ampicillin resistance was observed in Distrito Federal (25%), São Paulo (21.7%) and Paraná (18.5%). Of the 1712 strains analyzed, none was beta-lactamase negative, ampicillin resistant. A total of 16.8% of the strains were resistant to chloramphenicol, and 13.8% of these also presented resistance to ampicillin, and only 3.0% were resistant to chloramphenicol alone. All strains were susceptible to ceftriaxone and rifampin and the MIC90 were 0.015 micro g/ml and 0.25 micro g/ml, respectively. Ceftriaxone is the drug of choice for empirical treatment of bacterial meningitis in pediatric patients who have not been screened for drug susceptibility. The emergence of drug resistance is a serious challenge for the management of invasive H. influenzae disease, which emphasizes the fundamental role of laboratory-based surveillance for antimicrobial resistance.

Fibromuscular dysplasia. A case report with multivessel vascular involvement.

A case of multivessel fibromuscular dysplasia involving the cervico-cephalic arteries, the right renal artery and the iliac arteries is reported. It was associated with reversible bilateral internal carotid arteries and vertebral arteries dissection, left thalamic infarct, right hemorrhagic cerebellar infarct, renovascular hypertension and intermittent claudication of the right lower limb. This report indicates that fibromuscular dysplasia is a systemic angiopathy. Renovascular hypertension may foster the appearance of complication such as dissection of the arteries affected by fibromuscular dysplasia. In the case investigated the dissection of cervico-cephalic arteries was followed by spontaneous healing and a favourable neurological outcome whereas at the iliac arteries a rapid deterioration was observed.

Dot-enzyme-linked immunosorbent assay (Dot-ELISA) for detection of pneumococcal polysaccharide antigens in pleural fluid effusion samples. Comparison with bacterial culture, counterimmunoelectrophoresis and latex agglutination.

A dot-enzyme-linked immunosorbent assay (Dot-ELISA) for pneumococcal antigen detection was standardized in view of the need for a rapid and accurate immunodiagnosis of acute pneumococcal pneumonia. A total of 442 pleural fluid effusion samples (PFES) from children with clinical and laboratory diagnoses of acute bacterial pneumonia, plus 38 control PFES from tuberculosis patients and 20 negative control serum samples from healthy children were evaluated by Dot-ELISA. The samples were previously treated with 0.1M EDTA pH 7.5 at 90 degrees C for 10 min and dotted on nitrocellulose membrane. Pneumococcal omniserum diluted at 1:200 was employed in this assay for antigen detection. When compared with standard bacterial culture, counterimmunoelectrophoresis and latex agglutination techniques, the Dot-ELISA results showed relative indices of 0.940 to sensitivity, 0.830 to specificity and 0.760 to agreement. Pneumococcal omniserum proved to be an optimal polyvalent antiserum for the detection of pneumococcal antigen by Dot-ELISA. Dot-ELISA proved to be a practical alternative technique for the diagnosis of pneumococcal pneumonia.

Genetic relationships of Corynebacterium diphtheriae strains isolated from a diphtheria case and carriers by restriction fragment length polymorphism of rRNA genes.

In the present study we report the results of an analysis, based on ribotyping of Corynebacterium diphtheriae intermedius strains isolated from a 9 years old child with clinical diphtheria and his 5 contacts. Quantitative analysis of RFLPs of rRNA was used to determine relatedness of these 7 C.diphtheriae strains providing support data in the diphtheria epidemiology. We have also tested those strains for toxigenicity in vitro by using the Elek's gel diffusion method and in vivo by using cell culture method on cultured monkey kidney cell (VERO cells). The hybridization results revealed that the 5 C.diphtheriae strains isolated from contacts and one isolated from the clinical case (nose case strain) had identical RFLP patterns with all 4 restriction endonucleases used, ribotype B. The genetic distance from this ribotype and ribotype A (throat case strain), that we initially assumed to be responsible for the illness of the patient, was of 0.450 showing poor genetic correlation among these two ribotypes. We found no significant differences concerned to the toxin production by using the cell culture method. In conclusion, the use of RFLPs of rRNA gene was successful in detecting minor differences in closely related toxigenic C.diphtheriae intermedius strains and providing information about genetic relationships among them.

[Comprehensive assessment in public health]. / La Valutazione multidimensionale in Sanità Pubblica.

The Italian health system has been completely public for 25 years; it is now adopting a federal structure conferring to the single regions a leading role in public health management. Therefore clear evaluation methods and tools need to be adopted in order to guarantee equity-based decision making. Multidimensional evaluation, a method first developed in the geriatric setting, represents an extremely useful tool both to establish the best profile of assistance and to guide the management of different services. It is mainly used to evaluate health status and needs for assistance within non self-sufficient populations, largely composed of the elderly. Currently available assessment tools reveal different approaches, goals and level of accuracy. The authors have examined and compared 21 different multidimensional assessment tools adopted in Italy with a standardized method based on pre-established data collection and evaluation criteria. Both quantitative (number of items used for every single dimension or sub-dimension) and quali-quantitative aspects (level of detail for every single dimension or sub-dimension) are included in the analysis. Tools were also evaluated according to the degree of fulfilment of certain fixed requirements. In the authors' opinion, given a specific assistance setting and its users, once the goals and requirements of the evaluation instrument are clearly defined, adopting this methodology--defined as "Progressive exclusion method for easier visualization of criteria correspondence and quali-quantitative aspects", would help to identify the most suitable assessment tools to be used. The authors hope that, on a regional level, the public health system will make a greater use of homogeneous multidimensional comprehensive assessment tools in order to foster both a uniform approach towards the needs for assistance and transparent criteria of resources allocation in public health services.

Microbiological epidemiological history of meningococcal disease in Rio de Janeiro, Brazil.

The main objectives of the present study were to investigate the clinical and laboratory features of meningococcal disease in the city of Rio de Janeiro, Brazil, during the overlap of 2 epidemics in the 1990s. We conducted a study of a series of cases of meningococcal disease admitted in a Meningitis Reference Hospital. All clinical isolates available were analyzed by means of microbiological epidemiological markers. In 1990, Neisseria meningitidis serogroup B:4,7:P1.19,15, 1.7,1 sulfadiazine-resistant of the ET-5 complex emerged causing epidemic disease. Despite mass vaccination campaign (VaMengoc B+C®), the ET-5 clone remained hyperendemic after the epidemic peaked. In 1993 to 1995, an epidemic of serogroup C belonged to the cluster A4 overlapped, with a significant shift in the age distribution toward older age groups and an increase of sepsis. Serogroup C epidemics are a recurrent problem in Rio de Janeiro, which can be hindered with the introduction of a conjugate vaccine. We hope the data presented here brings useful information to discuss vaccines strategies and early management of suspected cases.

Prevalence of diphtheria and tetanus antibodies and circulation of Corynebacterium diphtheriae in São Paulo, Brazil.

The introduction of routine vaccination against tetanus and diphtheria in Brazil has decreased the incidence and changed the epidemiology of both diseases. We then investigated the prevalence of Corynebacterium diphtheriae carrier status and diphtheria and tetanus immunity in São Paulo, Brazil. From November 2001 to March 2003, 374 individuals were tested for the presence of C. diphtheriae in the naso-oropharynx and of serum diphtheria and tetanus antibodies. Participants were all healthy individuals without acute or chronic pathologies and they were stratified by age as follows: 0-12 months and 1-4, 5-9, 10-14, 15-24, 25-39, 40-59, and > or =60 years. Antibodies were assessed using a double-antigen ELISA. C. diphtheriae species were identified by biochemical analysis and toxigenicity was assessed by the Elek test. For diphtheria, full protection (antibodies > or =0.1 IU/mL) was present in 84% of the individuals, 15% had basic protection (antibodies > or =0.01 and <0.1 IU/mL) and 1% were susceptible (antibodies <0.01 IU/mL). Full tetanus protection (antibodies > or =0.1 IU/mL) was present in 79% of the participants, 18% had basic protection (antibodies > or =0.01 and <0.1 IU/mL) and 3% were susceptible (antibodies <0.01 IU/mL). The geometric mean of diphtheria and tetanus antibodies reached the highest values at 5-9 years and decreased until the 40-59-year age range, increasing again in individuals over 60 years. Three participants (0.8%) were carriers of C. diphtheriae, all non-toxigenic strains. The present results demonstrate the clear need of periodic booster for tetanus and diphtheria vaccine in adolescents and adults after primary immunization in childhood.