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Biomedical subjects

U Bienzle

Publications and source records attributed to U Bienzle.

At least 37 records · Page 2Linked to original sources

Immunogenicity and safety of hepatitis A vaccine in liver and renal transplant recipients.

Organ transplant recipients with chronic hepatitis B or hepatitis C virus infection may be at increased risk of fulminant hepatitis A. Liver transplant (LTX) recipients, renal transplant (RTX) recipients, and healthy controls received 2 doses of hepatitis A vaccine 6 months apart. Anti-hepatitis A virus (anti-HAV) seroconversion after the primary dose occurred in 41% of the LTX patients, 24% of the RTX patients, and 90% of the controls. After the booster dose, the respective rates were 97%, 72%, and 100% (P<.001). RTX patients also had significantly lower geometric mean titers (GMTs) of anti-HAV than LTX patients and controls. In the RTX group, the seroconversion rate and GMT were inversely associated with the number of immunosuppressive drugs received by the patients. The vaccine was well tolerated. Hepatitis A vaccine can be recommended to LTX and RTX patients, but the patients should receive a full course of 2 doses before imminent exposure.

Adult↗

The role of red blood cell polymorphisms in resistance and susceptibility to malaria.

In regions highly endemic for Plasmodium falciparum malaria, red cell polymorphisms that confer resistance to severe disease are widespread. Sickle cell trait, alpha-thalassemia, glucose-6-phosphate dehydrogenase deficiency, and blood groups were determined in 100 children from Gabon with severe malaria who were matched with 100 children with mild malaria and followed up for evaluation of reinfections. The sickle cell trait was significantly associated with mild malaria and blood group A with severe malaria. During follow-up, the original severe cases had significantly higher rates of reinfection than the original mild cases, with higher parasitemia and lower hematocrit values. Incidence rates did not differ in the context of erythrocyte polymorphisms, but patients with sickle cell trait presented with markedly lower levels of parasitemia than those without. Thus, the severity of malaria is partly determined by the presence of blood group A and the sickle cell trait. The different presentation of reinfections in severe versus mild cases probably reflects different susceptibility to malaria.

ABO Blood-Group System↗

High rate of mixed and subpatent malarial infections in southwest Nigeria.

The rate of malarial parasitemia in children and adults was assessed by microscopy and the polymerase chain reaction in a holoendemic area in Nigeria. A high rate of subpatent Plasmodium falciparum parasitemia (19.6%) was found. Plasmodium malariae and P. ovale infections were common in a rural area (26.1% and 14.8%) but were observed sporadically in individuals from an urban area. Simultaneous infections with P. falciparum, P. malariae, and P. ovale were frequent in the rural area (11.7% triple infections). The rate of triple infections was higher than expected from the prevalences of each species (P < 0.00001). Spleen enlargement was associated with mixed infections of P. falciparum and P. malariae (odds ratio [OR] = 5.9, 95% confidence interval [CI] 3.0-11.7) and less frequently observed in individuals without detectable parasitemia (OR = 0.06, 95% CI = 0.01-0.3). Spleen enlargement and titers of antibodies to schizonts were positively correlated with parasite densities. The results also suggest that in some individuals a long-lasting subpatent parasitemia might occur.

Adolescent↗

Short report: high prevalence and imbalanced age distribution of the Plasmodium falciparum dihydrofolate reductase gene Asn108 mutation in an area of low pyrimethamine usage in Nigeria.

Resistance of Plasmodium falciparum to pyrimethamine is associated with a non-silent point mutation of the parasite dihydrofolate reductase (DHFR) gene (Ser108 --> Asn108). Wide-scale use of antimalarials is thought to contribute to the emergence of drug resistance. In 131 P. falciparum-infected children in rural Nigeria, the frequency of the resistant Asn108 genotype was assessed by enzymatic restriction digestion of polymerase chain reaction-amplified DHFR sequences and compared with residual pyrimethamine blood levels. The prevalence of the Asn108 variant was 41.2%. In 18.3% of the isolates, both the Asn108 and the wild-type alleles were present. In contrast to the high prevalence of resistant genotypes, residual pyrimethamine blood levels were detected in only 4%. Furthermore, age was found to be a determinant of the parasite genotype since the proportion of Asn108 variants decreased with age (P < 0.05). These findings indicate that additional, unidentified factors, rather than selection by residual drug levels alone, might be responsible for the emergence of pyrimethamine-resistant parasite genotypes.

Age Distribution↗

Serum transferrin receptor levels are increased in asymptomatic and mild Plasmodium falciparum-infection.

BACKGROUND AND OBJECTIVE: The serum transferrin receptor (sTfR) concentration in an individual reflects the extent of erythropoietic activity and is considered a useful marker of iron deficiency independent of concurrent inflammation or infection. However, data on the impact of malaria on this parameter are ambiguous. We have examined potential associations of asymptomatic and mild Plasmodium falciparum-infections and of several erythrocyte variants with sTfR values in South West Nigeria. DESIGN AND METHODS: In a cross-sectional study among 161 non-hospitalized children, sTfR concentrations and P. falciparum parasitemia were assessed. In addition, hemoglobin (Hb) and serum ferritin values, Hb-types, glucose-6-phosphate dehydrogenase (G6PD)deficiency and a-globin genotypes were determined and the effects of these factors on sTfR levels were analyzed by univariate and multivariate statistical methods. RESULTS: P. falciparum-infection was present in 77% of the children. Mean sTfR levels were higher in infected than in non-infected children (geometric mean, 3.68, 95% confidence interval [3.5-3.9] vs. 2.99 [2.7-3.3] mg/L; p = 0.0009). There was a significant trend for higher sTfR values with increasing parasite density. sTfR values decreased continuously with age. Hb-types, G6PD-, and a-globin genotypes did not correlate with sTfR levels. In the multivariate analysis, age, Hb and log ferritin values, and parasite density of P. falciparum were independently associated with log sTfR values. INTERPRETATION AND CONCLUSIONS: sTfR concentrations are increased in asymptomatic and mild P. falciparum-infections suggesting adequate bone marrow response in this condition. The diagnostic value of sTfR levels for iron deficiency may be impaired in areas where stable malaria occurs.

Age Factors↗

HLA DPA1/DPB1 genotype and haplotype frequencies, and linkage disequilibria in Nigeria, Liberia, and Gabon.

The frequencies of DPA1 and DPB1 alleles and their occurrence in haplotypic linkage were assessed and compared in Nigerian, Liberian, and Gabonese individuals. Differences were seen in the distribution patterns; these differences were more pronounced between the Gabonese and the other two populations than between Liberians and Nigerians. Several haplotypic DPA1-DPB1 combinations could be verified by homozygosity. Linkage disequilibria of DPA1-DPB1 combinations, indicating further probable haplotypes, were estimated. Although different allele and haplotype frequencies were recognized in the three subgroups, the linkage disequilibria were mostly either positive or negative in all populations.

Ethnicity↗

HLA-DP control of human Schistosoma haematobium infection.

The DPA1 and DPB1 alleles of the major histocompatibility complex (MHC) class II were determined in 110 patients and 120 healthy controls of a Gabonese population from an area endemic for Schistosoma haematobium infection. The MHC-DP alleles of the variable second exons and their human leukocyte antigen (HLA) epitopes were correlated with egg excretion, interleukin-4 and interferon-gamma patterns, and bladder abnormalities, as detected by ultrasonography. A methionine at position 11 of the DP alpha molecule (Met-11) and DPA1*0301 were associated with schistosomiasis when compared with controls (phenotypic gene frequencies = 0.791 versus 0.583 and 0.555 versus 0.375, respectively). Met-11 homozygosity occurred more often in patients, whereas healthy controls were more frequently homozygous for an alanine at position 11 (Ala-11). The combination of the DPB1-epitope DEAV (positions 84-87 of the DP beta molecule) and Met-11 positive DPA1 alleles was more frequent in patients than in controls (0.573 versus 0.316). Two years after antischistosomal treatment, the rate of reinfection as examined in 55 of the 110 former patients was higher in DPA1*0301-positive individuals than in those not possessing this allele (P < 0.001). Ala-11 positive individuals showed less frequently ultrasonographic signs of bladder pathology than Ala-11 negative individuals (P < 0.05). Our results suggest a role of MHC-DP elements in the manifestation of disease in S. haematobium infection.

Adult↗

Hepatitis G virus RNA and hepatitis G virus antibodies in renal transplant recipients: prevalence and risk factors.

BACKGROUND: Hepatitis G virus (HGV/GBV-C) RNA indicating current infection has been frequently isolated from the sera of transplant recipients and other multitransfused individuals. Lifetime exposure to the virus, however, is unknown. We carried out a study to determine the prevalence and risk factors of HGV antibodies and of HGV RNA among renal transplant recipients, and to investigate possible associations between HGV RNA and immunosuppressive treatment. METHODS: HGV RNA was detected by reverse transcriptase-polymerase chain reaction, and HGV antibodies (anti-E2) by a newly developed immunoassay. To assess risk factors for HGV exposure, univariate and multivariate analysis was performed. RESULTS: Of the 221 patients, 14% were HGV RNA positive and 40% had HGV antibodies. Both HGV RNA and anti-HGV were present in only two individuals. Thus, the overall HGV exposure prevalence was 53%. It increased significantly with the number of blood transfusions. In logistic regression, the adjusted HGV exposure prevalence odds ratio was 5.7 (95% confidence interval [CI]: 2.2-15) among patients with > or =10 transfusions (baseline: no transfusions). Other independent risk factors were a longer duration of hemodialysis and a longer time interval since transplantation. HGV viremia was not associated with the type of immunosuppressive treatment. Alanine aminotransferase levels were not significantly increased among HGV RNA-positive patients. CONCLUSIONS: Much higher proportions of renal transplant recipients were exposed to HGV than is suggested by HGV RNA detection alone. The majority of infected individuals apparently eliminate the virus over time. Contaminated blood transfusions have to be regarded as a main risk factor for HGV infection.

Adolescent↗

Routine immunizations in adult renal transplant recipients.

BACKGROUND: Vaccination guidelines for transplant recipients include regular boosters of tetanus, diphtheria, and inactivated polio vaccine, but there are few published data on the efficacy of these vaccines in patients receiving immunosuppressive therapy. METHODS: Serum antibody values were evaluated before and 4 weeks after tetanus, diphtheria, and inactivated polio vaccination in 164 renal transplant recipients compared with healthy controls. Twelve months later, antibody levels were evaluated in 55 patients. RESULTS: Prebooster tetanus antitoxin values were lower in transplant recipients than in controls. All patients developed protective tetanus antibody levels (> or = 0.01 IU/ml) after vaccination. After 12 months, serum antibodies had decreased, but all patients maintained protective values. Diphtheria antitoxin titers before and after booster vaccination were lower in patients than in controls: 88.5% of patients and 96.2% of controls developed protective diphtheria antibody values. Twelve months after vaccination, diphtheria antitoxin values were below the protective level (0.1 IU/ml) in 38% of patients. Prebooster antibody values to poliovirus types 1 and 3 were comparable in patients and controls, whereas antibodies to poliovirus type 2 were lower in transplant recipients. Seroprotection rates and geometric mean antibody titers after vaccination were equivalent between the two groups for all three poliovirus types. No difference was observed in antibody levels between patients on different immunosuppressive drug regimens. Adverse reactions were significantly less often reported by transplant recipients. CONCLUSIONS: In transplant recipients, tetanus and inactivated polio vaccinations are well tolerated and induce protective antibody levels; diphtheria vaccination as currently recommended is less effective and protective antitoxin values decrease rapidly in these patients within 1 year after vaccination.

Adolescent↗

Intravenous or intramuscular anti-HBs immunoglobulin for the prevention of hepatitis B reinfection after orthotopic liver transplantation.

To prevent reinfection with hepatitis B virus after orthotopic liver transplantation, patients receive long-term intravenous anti-HBs immunoprophylaxis. We compared the pharmacokinetics of intravenously and intramuscularly administered commercially available hepatitis B virus immunoglobulins. The study group consisted of 12 patients on immunoprophylaxis after orthotopic liver transplantation, who were Hbs antigen negative; 11 were anti-HBe positive and one was HBe positive. The patients first received intravenous immunoglobulin, and six of them were then transferred to intramuscular immunoglobulin. Our findings show that with fortnightly intramuscular application of 1000 IU of anti-HBs, reproducible and stable antibody titers above 100 IU of anti-HBs can be achieved. Side effects of intramuscular immunoprophylaxis are minimal and the method is safe. The switch from intravenous (1500 IU of anti-HBs) to intramuscular (1000 IU of anti-HBs) reduced the cost of immunoprophylaxis by more than 50%.

Adult↗

History of syringe sharing in prison and risk of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection among injecting drug users in Berlin.

BACKGROUND: Injecting drug users (IDU) are at risk of parenterally transmitted diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. We investigated whether a history of syringe sharing in prison is a risk factor for these infections. In the longitudinal part of the study, HBV, HCV, and HIV seroincidence rates were determined. METHODS: The participants were recruited by multisite-sampling at different agencies for IDU. Data on risk behaviour were obtained by a standardized questionnaire. Serological markers for HBV, HCV, and HIV were determined. Logistic regression analysis was performed to adjust for confounding effects. RESULTS: A history of syringe sharing in prison was significantly associated with HBV (adjusted prevalence odds ratio [POR] = 3.9, 95% confidence interval [CI]: 2-10), HCV (POR = 9.7, 95% CI: 3-33), and HIV infection (POR = 10.4, 95% CI: 4-29). The HIV seroincidence rate was 5.9 per 100 person-years. None of the IDU receiving methadone maintenance treatment (MMT) seroconverted whereas the HIV incidence was 8.5 among IDU not in MMT (P = 0.01). CONCLUSIONS: The increased risk of HBV, HCV, and HIV infection among IDU who had shared syringes in prison warrants specific preventive action. The longitudinal data suggest that IDU in MMT have a lower risk of HIV infection.

Adult↗

HLA DRB1-DQA1-DQB1 haplotype diversity in two African populations.

HLA class II DRB1-DQA1-DQB1 haplotypic polymorphism was determined in 120 Liberian and 230 Gabonese individuals. In our study groups, the number of allelic variants observed for each locus was similar to that found in non-African populations. However, 39 novel haplotypes and several yet unrecognized DRB1-DQA1 and DQA1-DQB1 combinations were identified. The extent of HLA-haplotypic variability in Africans appears to result from the high degree of allele combinations rather than from allelic polymorphism.

Africa↗

Malaria Chemoprophylaxis in German Tourists: A Prospective Study on Compliance and Adverse Reactions.

Background: The number of tourists visiting malaria endemic regions is continuously increasing. The risk of aquiring malaria infection can largely be prevented by the regular use of chemoprophylactic drugs combined with using protective measures against mosquito bites. In a prospective study we wished to determine the tolerability of chemoprophylactic drugs and the factors that influence compliance with malaria chemoprophylaxis and antimosquito measures. Method: German travelers (n = 6504) who attended the Berlin Institute of Tropical Medicine in Berlin for pretravel medical advice were interviewed by phone 4 weeks after their journeys about compliance with the recommended malaria chemoprophylaxis and the incidence of side effects. Results: Compliance was better with mefloquine (94.5%) than with chloroquine (85.9%) (p<.001) or chloroquine plus proguanil (79.8%) (p<.001). Compliance was influenced by the purpose of travel, duration of stay, places of stay, and adverse reactions. Side effects occurred in 20.6% of the travelers who took chemoprophylactic drugs. There was no significant difference in the incidence of side effects between the three drug regimens, but people who took mefloquine more often reported neuropsychiatric reactions (6.5% versus 3.9% with chloroquine and 3.6% with chloroquine and proguanil; p<.001)). Side effects were usually mild to moderate and in no instance required hospitalization. People who took their drugs with meals less often reported side effects (15.2%) (p<.01). Conclusion: The knowledge of user profiles (and particular factors that presage side effects and noncompliance) may help us to improve pretravel counseling, thereby reducing the risk that travelers may acquire malaria infection.

Journal Article↗

Determinants of current HIV risk behaviour among injecting drug users in Warsaw, Poland.

Of the injecting drug users (IDUs), 24% had borrowed, and 37% had passed on syringes in the previous 6 months. In logistic regression analysis, current borrowing of syringes was significantly associated with a shorter duration of injecting drug use, a higher number of drug-injecting sex partners in the previous 6 months, and with current lending of syringes. A majority of the IDUs have modified previous HIV risk behaviour but these modifications are insufficient and not sustained over time. Intensified AIDS prevention measures for IDUs in Poland are needed.

Adult↗

Immunogenicity of an inactivated hepatitis A vaccine administered according to two different schedules and the interference of other "travellers" vaccines with the immune response.

A total of 2036 persons consulting vaccination centers in Germany were vaccinated with an inactivated hepatitis A vaccine (containing 720 ELISA units of antigen) either according to the standard schedule (two vaccinations given 4 weeks apart) or to an abbreviated schedule (two vaccinations given 2 weeks apart) in a controlled clinical study. The abbreviated schedule induced a similar rate of seroconversion and geometric mean antibody titre as compared to the standard schedule. The incidence of reactions reported after vaccination was similar in both groups. When other "travellers" vaccines were given simultaneously neither the immunogenicity nor the reactogenicity of the hepatitis A vaccine were influenced. These findings have considerable practical importance in the prevention of hepatitis A in travellers.

Adolescent↗