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PubMed1993

Transient normalization of lymphocyte blastogenic and specific antibody responses following boosting of healthy elderly subjects with tetanus toxoid.

The diminished in vitro blastogenic response of lymphocytes from the elderly to mitogenic stimuli is cited as evidence of immunosenescence, but the response to specific microbial antigens has not been well characterized. We measured the response to tetanus toxoid before and after boosting in young and elderly subjects. Elderly subjects (age > or = 70) and young controls (age < 35) were subjected to clinical, laboratory, and nutritional evaluation to ensure a cohort of healthy subjects. Responses of lymphocytes from the elderly to the mitogens phytohemagglutinin and concanavalin A were markedly diminished compared to those from the young. For all subjects, the average in vitro blastogenic response to tetanus toxoid of lymphocytes from elderly subjects (n = 23) was significantly diminished compared to young controls (n = 23; 31,985 +/- 4502 vs 14,411 +/- 3714 cpm, p < .01). Following boosting with tetanus in those subjects in whom boosting with tetanus toxoid was indicated, blastogenesis was comparable between elderly (n = 17) and young subjects (n = 7; 38,078 +/- 11,451 vs 42,103 +/- 9247 cpm). The boosted response to tetanus apparently was not sustained, since in the subset of subjects with a history of tetanus immunization in the past 10 years, the response of the elderly was much less than that of the young. Thus, a cohort of healthy elderly with diminished blastogenic responses to mitogens was capable of at least a transiently normal response to tetanus post boosting.

Adult↗
PubMed1997

Neonatal tetanus in the United States: a sentinel event in the foreign-born.

BACKGROUND: Neonatal tetanus occurred in a 7-day-old infant born to Mexican immigrant parents in Tennessee in February, 1995. This was the first patient with neonatal tetanus reported in the United States since 1989. METHODS: We interviewed the infant's mother and physicians and reviewed the medical record. We conducted a telephone survey of 103 (17%) of the 609 licensed obstetrician/gynecologists practicing in Tennessee to assess vaccination history-taking practices during prenatal care. RESULTS: The mother was a 30-year-old gravida 4 para 3 woman who grew up in rural Mexico. After moving to the United States in 1987, she had delivered two children before this delivery. The hospital-based delivery and nursery stay in February, 1995, were uncomplicated. On the sixth day of life the infant became irritable and developed muscle stiffness. The next day he was examined by a pediatrician who diagnosed neonatal tetanus. The infant recovered fully after a 2-month hospitalization. The survey of obstetrical practices revealed that 61 (59%) of 103 respondents asked about the patient's vaccination status during prenatal care. However, of all respondents, only 14 (14%) confirmed that they specifically asked about prior tetanus vaccinations. Tetanus toxoid was available in 47% of offices on the day of the survey. CONCLUSIONS: Neonatal tetanus can still occur in the United States. This infant's immigrant mother had multiple missed opportunities to be vaccinated against tetanus during her three pregnancies in this country. Health care providers should ask patients about their vaccination status, particularly those patients who are foreign-born or who grew up outside the United States.

Emigration and Immigration↗
PubMed2006

Urinary catecholamine excretion in tetanus.

Imperfect understanding of the pathophysiology of tetanus has limited therapeutic advances. Autonomic disturbance is a major cause of mortality and is believed to be associated with catecholamine release, predominantly norepinephrine. We measured epinephrine and norepinephrine concentrations in 24-h urine collections from tetanus and critically ill patients suffering from other severe diseases. In patients with severe tetanus, mean (SD) epinephrine was 164.18 (129.37) nmol x day(-1) compared with 45.18 (37.74) nmol x day(-1) in mild-moderate disease (p = 0.008). In the severe group, mean (SD) norepinephrine was 411.64 (208.5), and 121.00 (81.81) nmol x day(-1) in moderately ill patients (p < 0.001). Compared with critically ill control patients, median epinephrine was 331.77 in tetanus patients and 89.70 nmol x day(-1) in controls (p < 0.001). Median norepinephrine concentration was 788.02 nmol x day(-1) in tetanus and 300.05 nmol x day(-1) in control patients, p = 0.006. The study finds a novel result of increased epinephrine excretion in tetanus and confirms that catecholamine excretion in tetanus exceeds that in other critically ill patients. These results should be considered in designing more effective therapeutic strategies.

APACHE↗
PubMed1979

Tetanus toxin and synaptic inhibition in the substantia nigra and striatum of the rat.

1. The effects of tetanus toxin were determined on GABA-mediated synaptic inhibition of substantia nigra neurones evoked by striatal stimulation and on the presumed dopamine- and 5-hydroxytryptamine-mediated synaptic inhibition of striatal neurones evoked by nigral and dorsal raphe nucleus stimulation, respectively, in the urethane-anaesthetized rat. 2. Following an intranigral injection of tetanus toxin, striatal-evoked inhibition of substantia nigra neurones, which is sensitive to bicuculline, was rapidly abolished. This effect was not accompanied by any significant change in the responses of nigral neurones to ionophoretically administered GABA or other putative neurotransmitters and thus indicates a presynaptic site of action of the toxin. 3. The rate of onset of action of the toxin in the substantia nigra was extremely rapid (1-4 min) and appeared to be related to the rate of activation of the inhibitory pathway. 4. Injections into the substantia nigra of tetanus toxin neutralized with antitoxin had no significant effect on striatal-evoked inhibition in the substantia nigra. 5. Injections of tetanus toxin into the striatum failed to influence the inhibition of striatal neurones evoked by stimulation of the ipsilateral substantia nigra or the dorsal raphe nucleus, suggesting that tetanus toxin does not impair monoamine-mediated inhibition in the central nervous system. 6. Synaptic excitation which preceded substantia-nigra-evoked inhibition in striatal neurones and which occasionally preceded striatal-evoked inhibition in nigral neurones was also unaffected by tetanus toxin. 7. It is suggested that tetanus toxin selectively abolishes GABA-mediated synaptic inhibition in the central nervous system and may be a useful tool in the identification of such synaptic inhibitory mechanisms.

Action Potentials↗
PubMed2006

Neurohumoral, immunoinflammatory and cardiovascular profile of patients with severe tetanus: a prospective study.

INTRODUCTION: Autonomic disturbances in tetanus are traditionally associated with adrenergic variations and/or cardiac dysfunction, based on case report data. The objective of this study was to measure catecholamines, (TNF)-alpha and troponin T relative to and left ventricular ejection fraction (LVEF) in patients with severe tetanus. METHODS: This prospective study was carried out at two general Intensive Care Units and included 21 patients consecutively admitted with severe tetanus. Catecholamines (dopamine, norepinephrine, epinephrine and total catecholamines), tumor necrosis factor (TNF)-alpha and LVEF were assessed during the first week of autonomic instability and following tetanus recovery. Troponin T was measured during autonomic instability only. RESULTS: Mean age of patients was 46 +/- 17 years, median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 8 (range 1-23). All patients had both blood pressure and heart rate instability. Two patients were recuperated from cardiac arrest. Intensive Care Unit mortality was 14% (3 cases). No increase in total catecholamines or in TNF-alpha levels was observed during autonomic instability or in the recovery period. Six patients had troponin T > 0.01 ng/ml and six had > 0.1 ng/ml. Mean LVEF was similar during autonomic instability and after tetanus recovery, 67 +/- 7% and 65 +/- 7%, respectively. Troponin T levels correlated with pressoric instability during autonomic instability. CONCLUSION: Our study demonstrated that in patients with severe tetanus no significant increased levels of catecholamines or TNF-alpha or evidence of cardiac systolic dysfunction was observed either during autonomic instability or in the recovery period. Elevated values of troponin T detected during autonomic instability were not associated with left ventricular dysfunction. Our data do not support the hypothesis that autonomic disturbances in tetanus are associated with adrenergic variations or cardiac dysfunction.

Adult↗
PubMed1986

IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization.

To evaluate immune responses to diphtheria and tetanus toxoids in infants we used enzyme-linked immunosorbent assays to detect total IgG and specific IgG-1, IgG-2, IgG-3, and IgG-4 antibody. One group of infants received a newborn dose and subsequently received the usual three doses of DTP. A second group of infants received only the routine dosage at 2, 4, and 6 months of age. In sera acquired at birth, 6, and 9 months of age, there were no statistically significant differences between the two vaccine groups in IgG antibody responses to diphtheria or tetanus, or in IgG subclass tetanus-specific antibody responses. In individual children, tetanus-specific subclass responses were similar in pattern to that for total IgG tetanus antibody, i.e. each IgG subclass response appeared to be regulated by similar mechanisms in that child, but the regulation differed between children. In contrast to a prior study of pertussis immunity, maternally acquired antibody did not significantly affect immune responses to diphtheria or tetanus toxoid by 9 months of age. There was no discernible tolerance due to early tetanus or diphtheria immunization or to high levels of maternally acquired antibody.

Antibodies, Bacterial↗
PubMed1978

Tetanus toxin interactions with the thyroid: decreased toxin binding to membranes from a thyroid tumor with a thyrotropin receptor defect and in vivo stimulation of thyroid function.

Normal rat thyroid membranes adsorb neurotoxicity when incubated with purified tetanus toxin. Membranes from a rat thyroid tumor with a thyrotropin receptor defect adsorb very little neurotoxicity when similarly evaluated. This inability of the tumor membranes to adsorb neurotoxicity is correlated with a defect in their ability to bind both 125I-labeled tetanus toxin and [125I]iodothyrotropin. The effect of tetanus toxin on the release of radioiodine from the thyroids of appropriately prepared mice has been measured by adapting methods used for the bioassay of thyrotropin. One minimum lethal dose of tetanus toxin given sc caused a significant release of radioiodine into the blood of mice 48 h after injection. In mice subjected to the stress of prior bleedings or anesthesia, the release of radioiodine from the thyroid by tetanus toxin was accelerated, i.e., the increase in blood radioiodine could be measured 24 h after injection. These results again suggest that tetanus toxin may interact with thyrotropin receptors on thyroid plasma membranes. The "sympathetic overactivity syndrome" seen in some patients with tetanus and the syndrome characterized as "thyroid storm" in patients with Graves' disease are discussed as they may relate to these observations.

Animals↗
PubMed2006

Economic analysis of prevaccination serotesting compared with presumptive immunization for polio, diphtheria, and tetanus in internationally adopted and immigrant infants.

BACKGROUND: No consensus exists about whether to conduct prevaccination serotesting or to presumptively vaccinate internationally adopted and immigrant infants with inactivated polio (IPV) and diphtheria-tetanus-acellular pertussis (DTaP) immunizations. OBJECTIVE: To study the clinical and economic outcomes from a societal perspective of prevaccination serotesting in a hypothetical 12-month-old internationally adopted or immigrant infant. DESIGN AND METHODS: A decision analysis model was developed comparing presumptive vaccination with IPV versus serotesting for poliovirus type 1, 2, and 3 antibodies followed by vaccination in unprotected patients. A similar decision analysis model was developed comparing presumptive vaccination with DTaP versus serotesting for diphtheria and tetanus toxoid antibodies. The main outcome measures were cost per patient protected from polio, diphtheria, and tetanus. RESULTS: Compared with presumptive immunization, prevaccination serotesting for polio increases the cost per patient from $57 to $62 and decreases the percentage of patients protected against polio from 95.3% to 94.0%. Serotesting for diphtheria and tetanus increases the cost per patient from $62 to $119 and increases the percentage of patients protected against both diphtheria and tetanus from 91.5% to 92.3%. Presumptive immunization with DTaP costs less and is more clinically effective than serotesting if >80% of patients do not complete the full vaccine series or if antibody seroprevalence to both diphtheria and tetanus is <51%. CONCLUSIONS: Presumptive immunization for polio improves outcomes and saves costs compared with prevaccination serotesting in internationally adopted and immigrant infants. The results for DTaP are less definitive, although immunization is the preferred strategy in populations with poor vaccine compliance or low seroprevalence of antibodies to diphtheria and tetanus.

Adoption↗
PubMedDate not supplied

Antibody response to a single tetanus toxoid booster in young women in rural south India.

BACKGROUND: Tetanus toxoid immunization is an integral part of the maternal and child health programme in developing countries. It is likely that many women may have had childhood immunization and so already have antitetanus antibodies at the time of their first antenatal visit. A single dose of tetanus toxoid injection can boost the levels of antitetanus antibodies in these women. This study was undertaken to assess the previous immunization status by verbal history and assess the effect of a single tetanus toxoid injection in young women. METHODS: Ninety-nine unmarried women between 18 and 22 years of age were enrolled for the study. The history of childhood immunization was obtained from their mothers. Blood samples were collected to measure IgG antibody levels to tetanus using ELISA. Antibody levels were also measured on day 14 after a dose of tetanus toxoid injection. RESULTS: Of the 99 women studied, 81 had a history of childhood immunization while 18 did not. Overall, 92% of the women had protective levels of antibodies at the time of first testing and 99% of the women were protected with a single dose of tetanus toxoid. CONCLUSION: In areas with good maternal and child health services, a single booster dose of tetanus toxoid can be considered adequate for primigravidae with a history of childhood immunization.

Adolescent↗
PubMed2001

Exposure risks and tetanus immunization in women of family owned farms. Implications for occupational and environmental health nursing.

A sampling pool of 4,808 farms in 10 parishes across southeast Louisiana was used to examine the risk factors of farm women who engage in activities putting them at risk for tetanus and to examine the circumstances related to vaccination. Data were collected, via stratified random sampling, in summer 1998 resulting in 657 completed interviews. Only 53.6% of women were current with a tetanus booster, having received their immunization within the past 10 years. Just as many women received tetanus vaccination following an injury or accident as for prevention. As women aged, they were less likely to be compliant. In the South, a number of environmental factors contribute to the risk for tetanus exposure and infection. These risk factors were examined in light of compliance with tetanus booster compliance. Increasing awareness of risk is essential because although tetanus is uncommon, the death rate from tetanus is greater than 30%.

Adult↗
PubMed2005

Impaired immunity against tetanus in type 2 diabetes.

BACKGROUND: The aim of this study was to compare serum levels of tetanus antibody in diabetic patients over 50 years of age with those of age- and sex-matched non-diabetic controls. MATERIAL/METHODS: The study population consisted of 115 type 2 diabetic patients and 115 age- and sex-matched non-diabetic patients. Serum levels of tetanus IgG were measured by a commercial ELISA kit, and levels over 0.1 IU/ml were considered protective. RESULTS: Mean serum levels of tetanus antibody in the diabetic and control groups were 0.164+/-0.140 IU/ml vs. 0.374+/-0.534 IU/ml, respectively (p<0.001). Mean serum levels of tetanus antibody in the diabetics vs. controls aged 50-64 years were 0.172+/-0.141 IU/ml vs. 0.568+/-0.653 IU/ml and in those p<0.001, p=1.000). Among patients aged 50-64 years, 38 (55.9%) cases in the diabetic and 45 (73.8%) in the control group demonstrated protective levels of tetanus antibodies (p=0.034). Of patients p=0.298). CONCLUSIONS: Serum levels of tetanus antibody decreased in diabetic patients older than 50 years of age, whereas this period of time is prolonged to 65 years in healthy individuals. All individuals over 65 years should be vaccinated against tetanus; however, vaccination over 50 years of age might be considered for diabetic patients.

Aged↗
PubMed2006

Tetanus in adults--a continuing problem: an analysis of 217 patients over 3 years from Delhi, India, with special emphasis on predictors of mortality.

Tetanus is still widely prevalent in many parts of the world especially in the developing countries. This study was conducted to assess the demographic and clinical features, treatment and outcome of tetanus in adults with a special emphasis on identification of predictors of mortality. This was a retrospective study of all adult patients admitted with tetanus over a three-year period from 1998 to 2000 at Lok Nayak Hospital, New Delhi, India. The demography, clinical features, treatment and complications of the patients were assessed and were evaluated against two possible outcomes- survival or death, to identify the predictors of mortality. There were 217 adults (148 males, 69 females) admitted with generalized tetanus during the study period. The mean age of the patients was 36.08 +/- 18.84 years. In most instances (63.5%), wounds / injuries served as the source of infection. Overall 31.8% had mild, 21.7% had moderate and 46.5% had severe disease at presentation. Respiratory failure and dysautonomia were the frequently observed complications. Of the 217 patients, 82 died - a mortality rate of 37.78%. Parameters that were significantly associated with increased mortality were: age (especially > 60 years); shorter duration of symptoms - trismus, rigidity and dysphagia; severe disease at presentation and shorter period of onset. Tetanus is a preventable disease associated with a high fatality rate. Universal coverage of immunization programme and appropriate wound prophylaxis is the corner stone of tetanus eradication. The treatment of tetanus is difficult and requires specialized and intensive care. The presence of parameters indicating an adverse outcome at the beginning in the patients will help identify the subset of patients that need more intensive management especially in resource poor nations.

Adolescent↗
PubMed1991

Tetanus toxin and neuronal membranes: the relationship between binding and toxicity.

Tetanus toxin labeled by the Bolton-Hunter technique possesses high specific activity and retains substantial biological activity. This material can be used to characterize tetanus toxin binding to receptors in brain membrane preparations. In experiments aimed at measuring the absorption of labeled toxin, the displacement of labeled toxin by unlabeled toxin and the on-rate and off-rate constants, the data revealed two binding sites. The high affinity site had a Kd of 0.033 to 0.070 nM and a Bmax of 0.26 to 0.4 pmol/mg of protein; the low affinity site had a Kd of 0.89 to 6.9 nM and a Bmax of 1.55 to 3.0 pmol/mg of protein. The binding of tetanus toxin to brain membranes was enhanced greatly by low pH and ionic strength. Similarly to tetanus toxin, botulinum neurotoxin could be labeled by the Bolton-Hunter technique, and its binding to brain membranes was also enhanced by low pH and ionic strength. In studies with a neutralizing monoclonal antibody against tetanus toxin, the antigen-antibody interaction was not significantly altered by media with low ionic strength and pH. On the other hand, the ability of the antibody to block toxin binding to brain membranes was reduced substantially in nonphysiologic media. In a bioassay aimed at determining the effect of pH and tonicity on tissue association by toxin, low pH and ionic strength did not enhance toxicity. The biological activity of tetanus toxin was unaffected and that of botulinum neurotoxin was greatly diminished. The present findings confirm the widely reported observation that low pH and ionic strength promote tissue association by tetanus toxin, but they challenge the premise that this binding is relevant to the normal process of cell poisoning.

Animals↗
PubMed1989

A role for cGMP during tetanus toxin blockade of acetylcholine release in the rat pheochromocytoma (PC12) cell line.

In order to identify the specific molecular mechanisms involved in neurosecretion, we investigated the mechanism of action of tetanus toxin, a potent presynaptic neurotoxin, in the rat adrenal pheochromocytoma PC12 cell line. It has recently been reported that tetanus toxin is a potent inhibitor of the release of depolarization-evoked 3H-acetylcholine (ACh) from nerve growth factor-differentiated PC12 cells (Sandberg et al., 1989a). In PC12 cells, as in many neural tissue preparations, cGMP accumulation in intact cells increased 6- to 17-fold when stimulated with veratridine (200 microM), carbachol (1 mM), Ba2+ (2 mM), or K+ (30 mM). Preincubation of the cells with tetanus toxin inhibits this accumulation by greater than 95%. The toxin dose-inhibition curves for 3H-ACh release and cGMP accumulation are similar, with half-maximal doses of tetanus toxin seen at approximately 5 nM. The time courses for the development of the effects of tetanus on 3H-ACh release and on cGMP accumulation were also similar. Protocols which elevated intracellular cGMP levels reversed the action of the toxin. For example, evoked ACh release was restored in intoxicated PC12 cells by a 15 min exposure to 100 microM 8-bromo-cGMP. The half-maximal dose was observed at 50 microM nucleotide. Examination of the nucleotide specificity revealed that only cyclic guanine analogs were effective in reversing the effects of tetanus toxin. These results suggested that the inhibition of depolarization-evoked cGMP accumulation is causally related to the action of tetanus toxin on neurosecretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Delayed cutaneous hypersensitivity response in tetanus toxoid sensitized rhesus monkeys: predictor of anergy and value in tuberculin skin testing.

The primary problem in using the tuberculin skin test in nonhuman primates is the clinical uncertainty concerning the animal's ability to elicit a delayed cutaneous hypersensitivity response. A negative tuberculin skin test can only be meaningful if the animal can produce a delayed cutaneous hypersensitivity reaction. Veterinarians deliberately sensitize animals to antigens in the form of prophylactic vaccination. Therefore, if nonhuman primates were deliberately sensitized to an antigen capable of producing a hypersensitivity response, that antigen should serve as a positive control for delayed cutaneous hypersensitivity reactions. Tetanus toxoid was chosen because repeated immunizations with this antigen is recommended routine medical practice for nonhuman primates housed outdoors. Twenty juvenile, male rhesus (Macaca mulatta) monkeys were selected for this study. The monkeys were assigned randomly to one of two groups of ten animals. The test group was vaccinated with tetanus toxoid intramuscularly at 1 month intervals for a total of three vaccinations. The control group was treated the same except saline was administered rather than tetanus toxoid. Following sensitization, the two groups of animals were challenged with tetanus toxoid intradermally. Eight of the ten monkeys in the test group responded to the tetanus toxoid while none of the control groups responded to the tetanus toxoid. Elicitation of a delayed cutaneous response in animals sensitized to tetanus antigen before challenge may serve as a positive control for delayed cutaneous hypersensitivity. This simple test may serve as a useful adjunct in making objective clinical decisions concerning anergy-suspect animals.

Animals↗
PubMed1986

Tetanus in Japan: trends of mortality, case fatality and causes of death.

The rapid decline of tetanus mortality in recent years, from 2.84 to 0.02 per 10(5) population during the period of 1947-1982 was largely due to the decrease in neonatal tetanus mortality which declined from 36.1 to 0 per 10(5) live birth during the same period (1947-1979). The incidence of neonatal tetanus was inversely related to the percent of babies born in medical institutions. Vaccination against tetanus contributed to the rapid decline of tetanus mortality in the 0 to 9 years old group excluding the neonates, but not necessarily in the other age groups. There was a conspicuous decline in case fatality from about 50-40% during 1940-1970 to 20% and 10% in the periods from 1971-1980 and 1981-1982, respectively. This is attributed to the recent trend of treating tetanus patients in intensive care units where even the most extremely moribund patients have come to be successfully treated in the past few decades. The causes of death of tetanus patients changed from about 1975. Respiratory insufficiency with or without pulmonary infection was predominant in the period from 1961-1974. Unexpected complications, i.e. perforation of esophageal fistula, bleeding from gastrointestinal ulcers, myocardial infarction, respiratory insufficiency due to hyalinosis of alveolar septae associated with prolonged artificial respiration etc. were the major causes of death in the years 1975-1985.

Adult↗
PubMed1980

[Prevention of tetanus in emergency and first aid services. Technical and organizational criteria].

The Authors emphasize the measures to be taken for tetanus prevention in an individually wounded patient. They have to be decided on the basis of: 1) A knowledge and understanding of the pathological process of tetanus; 2) The mode of action and limitations of the various preventive measures available; 3) The nature of the patient's wound; 4) The patient's history of tetanus immunization. The recommendations should therefore be regarded not as a set of hard and fast rules but as guidelines since, as with any scheme of general guidance on medical practice, they will not invariably cover the circumstances of all individual patients. In tetanus prevention it is of basic importance to establish and maintain active immunity by means of combined vaccines. Nevertheless, with availability of human tetanus immunoglobulins severe immunological reactions as anaphylactic shock are extremely unlike to occur. So that their use can be recommended in patients with tetanus prone wounds, who have not previously been given tetanus toxoid.

Emergency Medical Services↗
PubMedDate not supplied

[Zoonoses in Vojvodina. I. Epidemiologic characteristics of tetanus in Vojvodina].

Epidemiologic characteristics of tetanus in Voivodina were analyzed on the basis of reported cases of sickness or death, during the period from 1962 to 1991, and epidemiologic investigation on 35 sick persons suffering from tetanus during the last 5 years. By compulsory immunization against tetanus this disease is practically eliminated at the age when one is protected by immunity vaccine. Abandoning domiciliary childbirth neonatorum tetanus has been eliminated. Today tetanus occurs sporadically as a result of small, naive injuries, mostly in nonimmunized elderly people. Considering number of the sick, in 6.1% it happens to persons older than 60 years of age. Tetanus remains a health problem because of its high lethality, which is statistically significantly higher in older patients. On the basis of gathered results it is realistic to expect that applying compulsory immunization against tetanus to older people in 10 year intervals will not eliminate this disease, but it will significantly reduce lethality which is still about 25% in Voivodina.

Adult↗