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Biomedical subjects

Herwig Kollaritsch

Publications and source records attributed to Herwig Kollaritsch.

At least 19 recordsLinked to original sources

Persistence of seroprotection 10 years after primary hepatitis A vaccination in an unselected study population.

Hepatitis A vaccines have been demonstrated to be highly immunogenic. Mathematical models have predicted antibodies to persist for at least 20-25 years. Most of these studies have been conducted in young and healthy study populations. We aimed to evaluate long-term immunity 10 years following complete primary immunization according to a 3-dose schedule (Havrix 720 El.U at months 0, 1, 6-12) in an adult and unselected study population. In total, 999 (98.3%) of 1016 vaccinees (mean age 54.7+/-S.D. 13.0), tested 10 years after primary vaccination, still had protective antibody levels (> or = 10 mIU/ml) as measured by ELISA. An anti-HAV titer cut off level of 11,400 mIU/ml was calculated to differentiate between vaccine-induced and infection-induced titer levels. The vaccine-induced geometric mean titer (GMT) was 406.1 mIU/ml (95% CI: 369.2-446.7 mIU/ml), showing an age-related trend, the 10-years seroprotection rate (SPR) was 97.9%. Females exhibited significantly higher GMTs than male vaccinees (p<0.001). The only parameter predicting a titer below 10 mIU/ml 10 years after vaccination was the body mass index (p=0.001). This study confirms that protection following primary hepatitis A vaccination persists for more than 10 years.

Adult↗

Hospital-based active surveillance of childhood pertussis in Austria from 1996 to 2003: estimates of incidence and vaccine effectiveness of whole-cell and acellular vaccine.

BACKGROUND: This study was undertaken to analyse the epidemiology of pertussis disease among hospitalised children during the transition period from whole-cell to acellular pertussis vaccine in order to compare the respective estimates of vaccine effectiveness. METHODS: Surveillance was conducted between 1 January 1996 and 31 December 2003. The data originated from a voluntary hospital-based surveillance network including all 44 nationwide paediatric departments. RESULTS: The mean annual hospitalisation incidence for children decreased over time, from 27.9 per 100,000 population in 1996 to 6.8 cases per 100,000 population in 2003. The mean age of reported hospitalised pertussis cases was 4.7 years (+/- 5.5 S.D.), increasing from 4.06 years (+/- 4.6 S.D.) in 1996 to 5.5 years (+/- 8.6 S.D.) in 2003. Estimated vaccine effectiveness (after three vaccine doses) was 79% for the whole-cell versus 92% for the acellular pertussis vaccine. A significantly higher proportion (19%) of fully immunised children among hospitalised patients was observed for the years where only acellular pertussis vaccine was used compared to whole-cell vaccine era (2%) which was, however, mainly due to children above 2 years of age. CONCLUSIONS: Our results imply that despite high vaccination coverage rate, pertussis is still a considerable cause of hospital admissions in children in Austria where it remains to be shown that the novel vaccination strategy of additional booster doses in adolescents and adults will control disease in the long term.

Adolescent↗

Persistence of antibodies after vaccination against tick-borne encephalitis.

Active vaccination against the tick-borne encephalitis (TBE) virus has successfully been implemented in endemic countries for many years. However, little was known about persistency of antibodies after completion of the primary vaccination and/or TBE booster immunization. Five recently performed serological follow-up studies in adults have now revealed that the persistence of protective immunity following at least one booster immunization was longer than expected. Notably, studies which analyzed different age groups indicate differences between younger adults aged 18-49 years and older adults aged > or = 50 years with respect to TBE antibody persistence and the immune response following a subsequent booster dose. To summarize, the serological studies included in this analysis generally support a reconsideration of current TBE booster recommendations and a prolongation of booster intervals at least in younger adults.

Adolescent↗

Comparative immunogenicity of a PreS/S hepatitis B vaccine in non- and low responders to conventional vaccine.

Conventional hepatitis B vaccines do not elicit adequate antibody production in 5-10% vaccinees. This trial tests the ability of a third-generation vaccine, containing PreS1 and PreS2 antigens in addition to the S antigen, to elicit seroprotective titres in documented non- and low-responders, compared with those to a conventional vaccine. In the primary population of non-responders (<10 IU/l anti-HBs antibodies after > or = 4 previous injections of conventional vaccine) an enhanced antibody response was seen to additional injections of the third-generation vaccine compared with a conventional vaccine (absolute difference 14.9%; P = 0.006). Enhanced antibody responses were also found in a population that included low responders.

Adult↗

Active hospital-based surveillance of rotavirus diarrhea in Austrian children, period 1997 to 2003.

BACKGROUND: Rotavirus is the most common pathogen causing severe dehydrating diarrhea in infants and young children worldwide. Any decision on implementation of rotavirus vaccination will be strongly influenced by the expected reduction in severe and therefore costly outcomes associated with rotavirus infection. The aim of this study was to provide data on hospitalization of young children with rotavirus infection in Austria. METHODS: The data were derived from active hospital-based sentinel surveillance for rotavirus during the period 1997 to 2003. RESULTS: During this period 25,600 children<15 years of age were hospitalized with acute laboratory-confirmed rotavirus gastroenteritis, the infection showing seasonal peaks between February and March. In 5 % of the cases first symptoms of diarrhea occurred at a minimum of 48 hours after hospital admission, indicating healthcare-associated origin of infection. The mean annual incidence of hospitalization per 100,000 population for the age group<5 years was 766 and for those<2 years 1742, the latter meaning that 1 in 60 Austrian children up to 2 years of age required hospitalization. An average peak incidence was observed between 8 and 14 months of age, with an average of 68% of the reported cases occurring in children aged<or=24 months. The mean length of hospital stay was 4.7 days, resulting in 17,200 rotavirus-associated hospital days per year. CONCLUSIONS: The observed incidence of hospitalization due to rotavirus in Austria is slightly higher than that reported in other industrialized countries. Our results reflect the considerable number of rotavirus-associated pediatric hospital in-patient days per year and the substantial annual direct costs of hospital care.

Adolescent↗

[Rabies: epidemiology, pre- and postexposure immunization].

In the mid-nineties rabies was eliminated from Austria by mass vaccination of foxes. This has eventually led to a decrease in knowledge about epidemiology, prophylaxis and post-exposure treatment of this deadly disease. In addition, there has been considerable scientific progress in the field of rabies vaccination during the last decade. International travel led to more then twice the amount of people from Austria travelling to rabies endemic countries than ten years ago. Frequent travelling to the new EU member states, amongst them rabies endemic countries, further increased the risk of being exposed to this disease. Formerly mainly emergency units in hospitals had to deal with post-exposure rabies prophylaxis. Now that mostly travellers are exposed, any family physician or travel medicine specialist should be able to provide adequate information and treatment. It seems therefore necessary to refresh actual recommendations and guidelines for rabies vaccination, epidemiology and pos-texposure treatment in order to facilitate the management of suspect cases by physicians in Austria.

Austria↗

Vaccines against traveler's diarrhoea and rotavirus disease - a review.

Diarrheal diseases constitute one of the most important health problems worldwide, preferentially in developing countries with a morbidity of estimated 5 billion and a mortality of 5 million cases per year. Children less than 5 years are particularly in danger with respect to the incidence and severity of the gastrointestinal symptoms. Travelers to developing countries are also at risk to develop diarrheal disorders; around 30-50% of them acquire so called "travelers's diarrhea" caused by bacteria, viruses or protozoa. It has been estimated that approximately 30-70% of diarrhea are due to bacteria, of which the most frequently detected enteric pathogens are non-invasive, enterotoxigenic Escherichia coli (ETEC). Their exotoxins, the heat stabile (ST) and the heat labile (LT) toxins are in large part responsible for the pathogenicity of the bacteria. About 20% of cases of traveler's diarrhea are caused by LT producing ETEC. This heat labile toxin exhibits a 80% sequence homology with cholera toxin. The presently available vaccine against cholera (Dukoral) contains inactivated Vibrio cholerae bacteria and the recombinant non-toxic B subunit of cholera toxin. Consequently, this vaccine displays also some efficacy against traveler's diarrhoea with up to 25% of travelers being protected against this disease. Rotaviruses are the leading recognized cause of diarrhoea-related illness and deaths among infants worldwide in developing and industrialized countries. Based on the high incidence of this disease two oral vaccines have been developed and will be available in Europe in 2006. Due to the impact of rotavirus diseases also in Austria vaccination against this disease has been already suggested in the Austrian vaccination schedules for infants from 6-24 weeks of age. One of the two vaccines, Rotarix, is an attenuated monovalent vaccine with a broad cross-reactivity against the most frequent serotypes. The second one, RotaTeq, is a pentavalent attenuated vaccine containing 5 human-bovine reassortants. Both vaccines display 85-98% efficacy against severe rotavirus disease and an excellent tolerability with no difference in side reactions to the placebo controls, particularly with respect to intussusceptions. With respect to increasing travel habits with infants and small children, particularly when visiting friends and relatives, vaccination against rotavirus infections will also be important in international travel.

Adult↗

In vitro interaction between artemisinin and chloroquine as well as desbutyl-benflumetol in Plasmodium vivax.

Malaria resulting from infection with Plasmodium vivax rarely causes death, however, patients usually suffer acute debilitating clinical symptoms and the recovery is slow. This study had the objective of assessing the pharmacodynamic interaction between artimisinin and chloroquine with a view of a potential acceleration of the clinicalparasitological response, and the investigation of therapeutic alternatives in the event of chloroquine resistance in Plasmodium vivax. Tests were based on the growth inhibition of Plasmodium vivax, determined by morphological differential counts of 200 asexual parasites. In total 45 isolates were evaluated successfully with parallel tests for artemisinin, chloroquine and desbutylbenflumetol (DBB) alone and combinations of artemisinin + chloroquine and artemisinin + DBB. Total inhibition was reached at a mean concentration of 1274.8 nM (95% CI 898.5 to 1808.7 nM), and 1852.2 nM (95% CI 1539.5 to 2228.6 nM) for artemisinin, and chloroquine respectively, whilst the 1:1 (m/m) combination of artemisinin and chloroquine was 1860.2 nM (95% CI 1454.4 to 2379.3 nM). EC(50) and EC(90) were 129.9 nM and 1058.5 nM for chloroquine, 32.6 nM and 735.5 nM for artemisinin, and 73.6 nM and 1103.0 nM for the 1:1 combination of both drugs. Interaction analysis according to Berenbaum yielded for the artemisinin + chloroquine combination at the EC(50) a mean SigmaFIC of 1.1126, at the EC(90) a mean SigmaFIC of 1.0331, and at the EC(99) a mean SigmaFIC of 1.1857. These results revealed marked additive interaction. For desbutylbenflumetol (DBB) the EC(50) and EC(90) were 1.5 nM and 28.8 nM, complete growth inhibition was observed at 90.4 nM (95% CI 75.1 to 108.7 nM). Interaction analysis indicated moderate antagonism at the lower concentration ranges, at the EC(90) additive interaction with a mean SigmaFIC of 1.0300, and synergism at the therapeutically most important EC(99) with a mean SigmaFIC of 0.5990.

Animals↗

Pharmacodynamic interaction between atovaquone and other antimalarial compounds against Plasmodium falciparum in vitro.

Atovaquone, a 2-hydroxy-1,4-naphthoquinone, was first introduced as a drug against opportunistic infections in immuno-compromised patients. Early clinical-parasitological experiences in the treatment of malaria were disappointing due to highly variable and poor absorption, a phenomenon typical for naphthoquinones. Proguanil was found to potentiate the activity of atovaquone and the combination of the two drugs was introduced as an antimalarial drug with blood schizontocidal and causal prophylactic activity. It is now widely used in therapy and prophylaxis. Despite the enhanced activity, the combination does not always overcome the problem of poor absorption of atovaquone, especially in the presence of gastro-intestinal disorders. Therefore, further combination with a fast-acting blood schizontocide, e.g. one of the artemisinins, could accelerate clinical improvement and normalization of absorption. The interaction between artemisinin and atovaquone and that of artemisinin and atovaquone + proguanil has been investigated in 37 fresh isolates of Plasmodium falciparum from northwestern Thailand, an area with high prevalence of multi-drug resistance. Interaction between atovaquone and artemisinin was synergistic above the EC(30), with mean SigmaFIC (Berenbaum) values of 0.9679 at the EC(50), 0.4014 at the EC(90) and 0.2214 at the EC(99). Synergism was more pronounced with the triple combination, i.e. atovaquone + proguanil and artemisinin, starting at the EC(10) level. The mean SigmaFIC values were 0.7626 at the EC(50), 0.2939 at the EC(90), and 0.1527 at the EC(99). The strong synergism at the therapeutically relevant effective concentrations suggests that the therapeutic efficacy of atovaquone-proguanil can be considerably enhanced by the additional administration of a suitable artemisinin derivative, e.g. artesunate.

Animals↗

[Travel vaccination recommendations for Central and Eastern European countries based on country-specific risk profiles].

Within the last years, an increasing trend of voyages to Central and Eastern European destinations could be observed. However, Europeans travelling within their own continent do not consider themselves as travellers exposed to possibly travel-associated infections since problem awareness among tourists as well as consulting doctors is rather scanty. The objective of this expert statement is to outline country-specific risk profiles as well as guidelines with regard to relevant travel immunizations for this region. These recommendations are mainly based on risk estimates according to national incidences and prevalences of vaccine-preventable diseases such as hepatitis A, hepatitis B, typhoid fever, meningococcal meningitis, rabies, and tick-borne encephalitis.

Communicable Disease Control↗

Drug sensitivity of Plasmodium falciparum along the Thai-Myanmar border using the new field-deployable HRP2 in vitro assay.

Drug resistance in Plasmodium falciparum has turned into a major problem throughout the malaria endemic regions of the world. Surveillance of antimalarial drug resistance is therefore essential for early changes in drug policies. In the course of this first major application of the new field-deployable histidine-rich protein 2 (HRP2) in vitro drug sensitivity assay, we investigated the current status of drug sensitivity to the standard antimalarial drugs dihydroartemisinin, mefloquine, quinine, and chloroquine in an area with an exceptionally high level of multidrug resistance in Thailand. The geometric mean of 50 and 90% inhibitory concentrations determined for 44 successfully tested samples by the HRP2 assay were comparable to earlier published results from the same area suggesting relatively little change in the local drug resistance pattern during the past years. The HRP2 field test was found to be highly sensitive and simple enough to be entirely performed in the field.

Animals↗

Synergism of desbutyl-benflumetol and retinol against Plasmodium falciparum in vitro.

This in vitro study was conducted to assess the blood schizontocidal activity of desbutyl-benflumetol (DBB), a new benzindene derivative, retinol and a combination of both compounds. The tests were carried out according to the methodology of the WHO standard test Mark II, measuring the drug-dependent inhibition of schizont maturation, and using 43 fresh isolates of Plasmodium falciparum from northwestern Thailand, an area with established multidrug-resistance. DBB and retinol showed a mean 50% effective concentration (EC-50) of 3.73 nM and 466.86 nM and 90% effective concentration (EC-90) of 19.83 nM and 5531.69 nM respectively. The combination of DBB and 3.50 muM retinol showed strong inhibition of schizont maturation, with an EC-90 for DBB of 0.67 nM. At the therapeutically relevant EC-99, the combination was about 10 times more effective than expected, suggesting that retinol potentiated the effect of DBB. A concentration of 3.50 muM retinol corresponds to the 95th percentile of the physiological serum levels. It is well known that retinol levels are significantly decreased in acute falciparum malaria. Supplementation with retinol during malaria treatment may improve the therapeutic results of blood schizontocides of the fluorene class.

Animals↗

In vitro activity of artemisinin alone and in combination with retinol against Plasmodium falciparum.

Increasing resistance of Plasmodium falciparum to antimalarial drugs is an important public health problem, demanding novel therapeutic approaches. This study had the objective of assessing the in vitro activity of artemisinin and its combination with retinol in fresh isolates of P. falciparum in an area with a high proportion of multidrug-resistant strains. The tests were based on the inhibition of schizont maturation. In 45 successfully tested isolates, the mean effective concentrations (ECs) of artemisinin were 10.29 nM for the EC-50 and 34.86 nM for the EC-90. The EC50 and EC90 for artemisinin in the artemisinin-retinol mixture were 2.71 nM and 13.37 nM, respectively. The combination showed synergistic activity. Retinol appears to be a promising partner for the antimalarial therapy with artemisinins.

Adolescent↗

Simple histidine-rich protein 2 double-site sandwich enzyme-linked immunosorbent assay for use in malaria drug sensitivity testing.

A simple double-site sandwich enzyme-linked immunosorbent assay (ELISA) for Plasmodium falciparum in vitro drug sensitivity tests based on measuring histidine-rich protein 2 (HRP2) is presented. The ELISA uses two commercial monoclonal antibodies and provides a drastically cheaper alternative to the test kits previously used in the HRP2 drug sensitivity test. The assay is simple to establish and perform. The sensitivity is comparable and the drug sensitivity results very closely match those obtained with the commercial ELISA kits (R(2) = 0.979; P < 0.001; mean log difference at the 50% inhibitory concentration = 0.07).

Adult↗

[Immunization recommendations for travel in the Mediterranean area].

The Mediterranean region is a popular destination for tourists during the summer. However, European tourists, who are travelers within their own continent, do not consider themselves exposed to possible, travel-associated infections, since problem awareness among tourists as well as doctors is rather weak. The objective of this consensus paper is to outline guidelines with regard to relevant travel immunizations for Mediterranean destinations. These recommendations are mainly based on risk calculations according to country-specific incidences and prevalences of vaccine-preventable diseases such as hepatitis A, hepatitis B, typhoid fever, meningococcal meningitis, rabies, and tick-borne encephalitis.

Animals↗

Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe.

BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

Adolescent↗

Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria.

OBJECTIVES: This study was undertaken to analyse incidence rates, serotype distribution and antimicrobial resistance patterns of invasive Streptococcus pneumoniae isolates from hospitalized children up to 5 years of age with invasive pneumococcal disease (IPD), including meningitis, in Austria. METHODS: From February 2001-January 2003, nationwide prospective surveillance was conducted that included all paediatric hospitals and clinical microbiological laboratories. All invasive pneumococci isolated were serotyped and tested for antimicrobial susceptibility. RESULTS: The mean annual incidence rates of IPD per 10 000 population for the age groups <24 months and <60 months were 14.5 (7.7 for meningitis) and 13.7 (6.0 for meningitis), respectively. The case fatality rate was 6% for IPD and 12% for meningitis. Of all IPD cases, 69.6% (73.1% for meningitis) were covered by serotypes and 83.9% (88.5% for meningitis) by cross-protection of vaccine-related serotypes. Intermediate penicillin G susceptibility (MIC 0.12-1 mg/L) was found in 12/56 strains. No penicillin G-resistant strains were found. A total of 19/56 isolates showed decreased susceptibility to macrolide agents (MIC >/= 1 mg/L). CONCLUSIONS: The IPD incidence rate was similar, and serotype coverage of the 7-valent conjugated vaccine marginally superior, to Germany. The surprisingly high level of antimicrobial resistance among invasive isolates considerably amplifies the potential impact of a childhood pneumococcal vaccination programme in Austria.

Anti-Infective Agents↗

A randomized, open-label study of the immunogenicity and reactogenicity of three lots of a combined typhoid fever/hepatitis A vaccine in healthy adults.

BACKGROUND: Travelers are often advised to receive both the typhoid fever and hepatitis A virus (HAV) vaccines, particularly when going to areas where the 2 diseases are endemic. Thus, combined administration of these vaccines could make immunization more acceptable by reducing the number of injections needed. OBJECTIVE: This study compared the safety profiles and immunogenicity of 3 batches of a combined typhoid fever/HAV vaccine administered using a dual-chamber bypass syringe. METHODS: This randomized, open-label study was conducted at 2 university-based travel clinics in Germany and Austria. Subjects received a single IM injection from 1 of 3 batches of the combined vaccine. Blood samples were drawn immediately before and 28 days after vaccination to evaluate the response to the 2 antigens by assessing geometric mean titers (GMTs) and rates of seroconversion and seroprotection. Subjects recorded all adverse events (AEs) occurring during the study period in a diary. RESULTS: Six hundred ten healthy adults were enrolled in the study. Twenty-eight days after vaccination, 90.6% of the study population had protective typhoid Vi antibody titers (> or = 1 microg/mL) and 100% had protective HAV antibody titers (> or = 20 mIU/mL). Seroconversion rates and GMTs were not significantly different between the 3 batches. There were no differences with regard to local or systemic AEs between the 3 batches of vaccine. There were no immediate adverse reactions (within 30 minutes of vaccination) and no serious AEs related to vaccination. Of 609 evaluable subjects (1 was lost to follow-up after the first visit), 555 (91.1%) experienced > or = 1 local reaction within the first 7 days after vaccination, mainly pain at the injection site (550 [90.3%]), but only 26 (4.3%) described this pain as severe. Vaccine-related headache and mild to moderate asthenia were each reported by 54 subjects (8.9%). Symptoms resolved spontaneously in all cases. CONCLUSIONS: The 3 batches of the combined typhoid fever/HAV vaccine administered by dual-chamber bypass syringe were equally well tolerated and effective in healthy adults, and did not differ significantly in terms of GMTs or seroconversion rates.

Adult↗