HIV incidence in the Estonian population in 2013 determined using the HIV-1 limiting antigen avidity assay.

OBJECTIVES: Estonia has one the highest number of new HIV diagnoses in the European Union, mainly among injecting drug users and heterosexuals. Little is known of HIV incidence, which is crucial for limiting the epidemic. Using a recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV incidence in 2013. METHODS: All individuals aged ≥18 years newly-diagnosed with HIV in Estonia January- December 2013, except blood donors and those undergoing antenatal screening, were included. Demographic and clinical data were obtained from the Estonian Health Board and the Estonian HIV-positive patient database. Serum samples were tested for recent infection using the LAg-avidity EIA assay. HIV incidence was estimated based on previously published methods. RESULTS: Of 69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age of 33 years (IQR: 28-42) and 65% male. Self-reported routes of HIV transmission were mostly heterosexual contact (n = 157, 53%) and injecting drug use (n = 62, 21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new infections in 2013 among the non-screened population. Incidence was highest (1.48%) among people who inject drugs. CONCLUSIONS: These high HIV incidence estimates in Estonia call for urgent action of renewed targeted public health promotion and HIV testing campaigns.

Antimicrobial susceptibility and serogroup/serotype distribution of nasopharyngeal isolates of Streptococcus pneumoniae in healthy Estonian children in 1999-2003.

This study determined nasopharyngeal (NP) carriage rates of Streptococcus pneumoniae among healthy Estonian children, aged 1-7 years, and characterised the serotype/serogroup distribution and antibiotic susceptibility rates. NP swabs were collected from 685 previously healthy children attending 29 day care centres during the winters of 1999-2000 and 2003. The NP carriage rate of S. pneumoniae was 44%. Rates of penicillin and erythromycin non-susceptibility were low (both 6%), but high (67%) rates of co-trimoxazole resistance were found. Among the pneumococcal serotypes identified, 64% were included in or cross-reacted with the licensed heptavalent pneumococcal vaccine.

Antibiotic usage and resistance - trends in Estonian University Hospitals.

The use of antibiotics, type of infections and resistance of prevalent bacteria was surveyed in Tartu University hospitals. The data from two ICUs (1995 and 1998), surgical and internal medicine departments (1998) were compared. Overall antibiotic usage in the ICUs and in the hospital as a whole had increased. There was a significant increase in Gram-positive bacterial infections and a decrease in Gram-negative infections in the ICUs. At the same time, susceptibility to several antibiotics decreased in most of the prevalent Gram-negative aerobes in the ICUs (Acinetobacter spp., Pseudomonas spp., Klebsiella spp.). Exceptions to this were the greater susceptibility of Pseudomonas spp. to gentamicin and Acinetobacter spp. to imipenem. Some changes in the predominant bacterial populations did not correlate to changes in antibiotic use.

Comparison of motor depressant effects of caerulein and N-propylnorapomorphine in mice.

The motor depressant effects of caerulein and N-propylnorapomorphine (NPA) were compared in male mice. Caerulein (1-50 micrograms/kg SC) in a dose dependent manner depressed the exploratory activity, whereas NPA in lower doses (0.5-10 micrograms/kg SC) decreased the motor activity, but in higher doses (over 50 micrograms/kg) had stimulating effect on the exploratory behavior. In mice selected according to their motor response after administration of 100 micrograms/kg NPA to weak and strong responders, the low dose of NPA (1 microgram/kg) similarly suppressed motor activity in both selected groups, while the effect of caerulein (2 micrograms/kg) was apparently higher in weak responders. Destruction of catecholaminergic terminals by 6-hydroxydopamine (60 micrograms ICV) reversed completely the motor depressant effect of NPA, whereas degeneration of serotoninergic terminals (5,7-dihydroxytryptamine 60 micrograms ICV or p-chloroamphetamine 2 X 15 mg/kg IP) enhanced the sedative effect of NPA. The motor depressant effect of caerulein remained unchanged after lesions of monoaminergic terminals in forebrain. Subchronic haloperidol (0.25 mg/kg IP, twice daily during 14 days) treatment, reducing significantly the density of high-affinity dopamine2- and serotonin2-receptors, decreased the motor depressant action of caerulein. It is possible that motor depressant effect of caerulein, differently from the action of NPA, is mediated through the high-affinity dopamine2-receptors and in lesser extent through the high-affinity serotonin2-receptors.

[Role of serotonin2 receptors in regulating aggressive behavior]. / Rol' serotonin2-retseptorov v reguliatsii agressivnogo povedeniia.

Quipazine and pirenperone , the drugs interacting with serotonin2 -receptors, more readily displaced 3H-spiroperidol from its binding sites in the frontal cortex than in the striatum. Pirenperone (0,07-0,3 mg/kg), antagonist of serotonin2 -receptors, selectively decreased the intensity of apomorphine aggressiveness. The antiaggressive action of haloperidol (0,01-0,2 mg/kg) was in correlation with its antistereotypic activity. Long-term administration of naloxone (0,5; 15,0 mg/kg), together with apomorphine (0,5 mg/kg) reduced the number of head-twitches caused by quipazine (2,5 mg/kg). The administration of quipazine 48 hours after the last injection of naloxone and apomorphine caused spontaneous aggressiveness that did not differ from apomorphine aggressiveness. Intracerebroventricular injection of cholecystokinin tetrapeptide (CCK-4) markedly enhanced the foot-shock aggression. The same dose of CCK-4 also decreased the intensity of quipazine (2,5 mg/kg) head-twitches. Compared to haloperidol, pirenperone was a more selective antagonist of CCK-4. After long-term apomorphine treatment (0,5 mg/kg during 10 days, twice daily), the effect of CCK-4 on aggressive behaviour was markedly enhanced. It is possible that two subtypes of serotonin2 -receptors exist in the brain and have opposite action on the aggressive behaviour. CCK-4 may play the role of an endogenous modulator of sensitivity of serotonin2 -receptors involved in the control of aggressiveness.

Five-year prospective surveillance of nosocomial bloodstream infections in an Estonian paediatric intensive care unit.

BACKGROUND: Few studies provide rates of nosocomial bloodstream infections (BSIs) in mixed neonatal and paediatric intensive care units (PICUs). AIM: To determine the rate, pathogens and outcome of BSIs in an Estonian PICU. METHODS: Data were collected prospectively from 1st January 2004 to 31st December 2008 in the PICU of Tartu University Hospital. The definition criteria of the US Centers for Disease Control and Prevention were applied for the diagnosis of laboratory-confirmed BSI. FINDINGS: A total of 126 episodes of BSI were identified in 89 patients (74 neonates, eight infants, seven patients aged >1 year). Among neonates 42 (57%) had birth weight <1000 g. The overall incidence of BSI was 9.2 per 100 admissions, incidence density 12.8 per 1000 patient-days. Primary BSI was diagnosed in 92 episodes. Central line (CL)-associated BSI incidence density for neonates was 8.6 per 1000 CL-days with the highest incidence (27.4) among neonates with extremely low birth weight. The most common pathogens were coagulase-negative staphylococci (43%) and Serratia marcescens (14%). Resistance to meticillin was detected in four out of seven S. aureus isolates (all were part of an outbreak) and 23% of Enterobacteriaceae were extended spectrum beta-lactamase (ESBL)-producing strains. Overall case-fatality rate was 10%. CONCLUSION: We observed higher rates of BSIs in our mixed PICU than reported previously. High levels of antimicrobial resistance were detected. Future research should focus on the effects of infection control measures to prevent outbreaks and to decrease incidence of CL-associated BSI.

Epidemiology of nosocomial bloodstream infections in Estonia.

A prospective multicentre hospital-wide surveillance study was performed to investigate nosocomial bloodstream infections (BSIs) and to promote BSI surveillance in Estonia in 2004-2005. All patients from the acute care departments of two referral centres and one central hospital were included. A total of 549 episodes of BSI occurred in 507 patients (0.6 cases per 1000 patient-days). Of those, 55% occurred in intensive care units and 47% were catheter-associated infections. Of BSI cases, 24% occurred in patients with haematological malignancy. The in-hospital case-fatality rate was 31%. Of causative micro-organisms, 315 (53%) were Gram-positive aerobes, 232 (39%) were Gram-negative aerobes and 35 (6%) were fungi. Anaerobic bacteria accounted for 2%. The most common pathogens were coagulase-negative staphylococci (26%), Enterobacteriaceae (24%), enterococci (13%) and pseudomonas (10%). Eight percent of BSI were polymicrobial. Seven percent of Staphylococcus aureus isolates were meticillin resistant. Of pseudomonas isolates, 19%, 25%, 30% and 44% were resistant to ceftazidime, meropenem, piperacillin/tazobactam and imipenem, respectively. The incidence of BSI did not differ significantly from other reported studies. With the exception of relatively high antimicrobial resistance among pseudomonas, the overall resistance patterns of Estonian nosocomial bloodstream pathogens were similar to those seen in Nordic countries and lower than in Central and Southern Europe. This study contributes to the development and implementation of surveillance in Estonian hospitals.

2-deoxy-D-(14C)-glucose study of the interaction of caerulein and apomorphine.

The interaction of ceruletide (CER) and apomorphine (APO) was studied in mice. APO and CER were injected subcutaneously. In wheelcage experiments, lower doses (50 to 100 micrograms/kg) of APO depressed dose-dependently the locomotor activity in mice, but a higher dose (1 mg/kg) of APO produced a smaller effect than 100 micrograms/kg of APO. CER (20 micrograms/kg) slightly depressed the locomotor activity in mice. The coadministration of APO and CER caused stronger inhibition in the locomotor activity than the single administration of these drugs. The effects of APO and CER on the neuronal uptake of 2-deoxy-D-(14C)-glucose (2-DG) were also examined. APO (50 and 1000 micrograms/kg) inhibited the 2-DG uptake in most regions of the brain, although the inhibitory effect was larger at lower doses. CER inhibited the 2-DG uptake in some regions, but enhanced it in others. The combination of APO and CER markedly enhanced the 2-DG uptake. Thus, it was difficult to correlate the effects of the combination of APO and CER on locomotor activity with 2-DG uptake.

Antibiotic use in 3 European university hospitals.

The use of antibiotic drugs was studied in university teaching hospitals in Tartu, Estonia, Huddinge, Sweden and Badajoz, Spain. Data on drug deliveries to hospital wards during 1992 are presented in defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days). In addition, the time trends of antibiotic use in Tartu University Hospital from 1992 to 1995 are shown. The total amount of antibiotic drugs used for systemic treatment in 1992 was similar in the 3 hospitals, 41 DDD/100 bed-days in Tartu vs. 51 DDD/100 bed-days in Badajoz and 47 DDD/100 bed-days in Huddinge. The antibiotics used most frequently were tetracyclines and aminoglycosides in Tartu, broad-spectrum penicillins and cephalosporins in Badajoz and narrow-spectrum penicillins and cephalosporins in Huddinge. Injectable preparations accounted for one-half of the antibiotics used. Among the medical departments, the total use of antibiotics varied up to 3-fold (from 19 to 61 DDD/100 bed-days), less than among the surgical departments (18-94 DDD/100 bed-days). The frequency of antibiotic use was very similar in departments of similar profile in the 3 hospitals (i.e. in departments of neurology, urology, etc.). The use of antibiotic drugs in intensive care units was twice as high in Huddinge (243 DDD/100 bed-days) as in Badajoz (106 DDD/100 bed-days) and Tartu (135 DDD/100 bed-days) in 1992. In conclusion, the international differences in the use of antibiotics in hospital were not in the frequency of use, but in the predominant prescription preferences in the hospital.

[Role of serotonin and dopamine receptors in the mechanism of action of haloperidol and pirenperone]. / Rol' serotoninovykh i dofaminovykh retseptorov v mekhanizme deistviia galoperidola i pirenperona.

The effects of haloperidol, a typical neuroleptic, and pirenperone, a selective blocker of serotonin-2-receptors, were studied and compared. Acute administration of haloperidol had effects mainly in dopaminergic models, whereas pirenperone was active only in serotoninergic models. Chronic administration of both drugs made the systems indicated hypersensitive. This effect may be important in the mechanism of action of neuroleptic drugs.

[Stimulation by cerulein--an analog of the octapeptide cholecystokinin--of 3H-spiroperidol binding after the long-term administration of neuroleptics]. / Stimuliatsiia tseruleinom--analogom oktapeptida kholetsistokinina--sviazyvaniia 3H-spiroperidola posle dlitel'nogo vvedeniia neiroleptikov.

It has been established in experiments on white male rats that prolonged administration (twice a day for 14 days) of haloperidol (0.25 mg/kg) and pyreneperone (0.25 mg/kg) resulted in the reduced interaction between 3H-spiroperidol and low affinity binding sites for apomorphine in subcortical structures, whereas 3H-spiroperidol binding with high affinity binding sites for apomorphine increased both in the frontal cortex and subcortical structures of the forebrain. After prolonged administration of neuroleptics the displacing effect of cerulein, an analog of cholecystokinin octapeptide, was replaced by the stimulant action on 3H-spiroperidol binding. It is assumed that increased interaction between 3H-spiroperidol and high affinity binding sites for apomorphine on dopamine2- and serotonin2-receptors underlies the antipsychotic action of neuroleptics after their prolonged administration. Cholecystokinin octapeptide is a necessary factor for realization of this action of neuroleptics.

[Decreased sensitivity of cholecystokinin receptors in the brain as affected by the prolonged administration of haloperidol]. / Ponizhenie chuvstvitel'nosti kholetsistokininovykh retseptorov v mozge pod vliianiem dlitel'nogo vvedeniia galoperidola.

The authors have used behavioural and radioreceptor methods of investigation, that helped to find correlates of the behavioural phenomena on the receptor level.

[Modulating effect of cerulein on benzodiazepine receptors]. / Moduliruiushchee vliianie tseruleina na benzodiazepinovye retseptory.

Subcutaneous administration of caerulein (100-500 micrograms/kg) significantly reduced the development of picrotoxin (8 mg/kg) seizures in male mice. The same doses of caerulein inhibited 3H-flunitrazepam binding in in vivo experiments. Proglumide, an antagonist of cholecystokinin receptors, in low dose (5 mg/kg) potentiated the effects of caerulein (100 micrograms/kg), whereas the administration of proglumide in high dose (25 mg/kg) reduced the action of caerulein on 3H-flunitrazepam binding and picrotoxin seizures. Caerulein (5-1000 nM) decreased 3H-flunitrazepam binding in in vitro experiments only after supplementation of the binding medium with 120 mM NaCl and 5mM KCl. The results suggest the possible interaction of caerulein with chloride ionophor. It seems probable that the direct interaction of caerulein with chloride ionophor in involved in the inhibitory effect of caerulein on picrotoxin seizures and 3H-flunitrazepam binding.

[Effect of an imidazobenzodiazepine (RO 15-1788) on aggressive behavior in mice]. / Vliianie imidazobenzodiazepina (RO 15-1788) na agressivnoe povedenie myshei.

Imidazobenzodiazepine (Ro 15-1788, 5 mg/kg) similarly to a lose dose of apomorphine (0.1 mg/kg) decreased the intensity of footshock aggression in male rats. Ro 15-1788 significantly potentiated the antiaggressive action of apomorphine. Pirenperone (0.01 mg/kg) potentiated the effect of both drugs, whereas haloperidol (0.01 mg/kg) had an opposite action. After long-term treatment with apomorphine and Ro 15-1788 the tolerance to their antiaggressive action developed. This change was in agreement with increased serotonin metabolism in the forebrain. Unlike the action on aggressive behavior, Ro 15-1788 similarly to haloperidol (0.05 mg/kg) decreased the motor depressant effect of apomorphine (0.01 mg/kg) in mice. This effect correlated with the lowered serotonin metabolism after Ro 15-1788 administration. Unlike apomorphine, Ro 15-1788 reversed catalepsy induced by haloperidol (0.25 mg/kg). Administration of pirenperone (0.03 mg/kg) and destruction of serotoninergic terminals by p-chloroamphetamine (2 X 15 mg/kg) significantly potentiated the sedative action of apomorphine. It appears that different action of Ro 15-1788 on behavioral effects of apomorphine is related to different influence of Ro-1788 on serotoninergic processes in the striatum and limbic structures.

[Nonuniform effect of prolonged haloperidol administration on the GABA(A) and benzodiazepine receptors in different parts of the brain]. / Neodinakovoe vliianie dlitel'nogo vvedeniia galoperidola na GAMK(A)- i benzodiazepinovye retseptory v raznykh otdelakh mozga.

The experiments on male mice and rats have revealed reversed behavioral effects of muscimol and Ro 15-1788 after 15 days of haloperidol (0.25 mg/kg, twice daily) treatment. Muscimol (0.75 mg/kg), which depressed motor activity in saline-pretreated mice, stimulated it after discontinuation of long-term haloperidol administration. Ro 15-1788 stimulating effect in saline-pretreated rats gave way to sedative effect following haloperidol withdrawal. Simultaneously, the number of 3H-muscimol and 3H-flunitrazepam binding sites was decreased in forebrain, but increased in hindbrain. It was suggested that GABAA and benzodiazepine receptors in forebrain and hindbrain play opposite (inhibiting and stimulating, respectively) functional roles in the regulation of behaviour.