Biomedical subjects

A Gottschau

Publications and source records attributed to A Gottschau.

At least 37 records · Page 2Linked to original sources

PubMed1995

Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli.

A recombinant Plasmodium falciparum glutamate-rich protein (GLURP) was produced in Escherichia coli as a nearly full-length protein. In order to map immunodominant regions on GLURP, the nonrepetitive amino-terminal region (R0) as well as the central repeat region (R1) and the carboxy-terminal repeat region (R2) were also produced as separate products. All four purified gene products reacted specifically with serum samples from adults living in an area of Liberia where malaria is holoendemic. It appears that the human immune response against GLURP is primarily directed against the R2 region because 94% of the serum samples reacted with this region in an immunoassay. Antibody reactivity against the R0 region was also observed in 75% of the serum samples, while the R1 region showed only weak antibody-binding activity. When the nearly full-length GLURP molecule was adsorbed to Al(OH)3 it was found to be immunogenic in mice. In these experiments, the antibody response was almost exclusively directed against the R2 region. When anti-GLURP sera were obtained from rabbits immunized with the three regions, R0, R1, and R2, respectively, they recognized in immunoprecipitation experiments authentic GLURP from P. falciparum grown in vitro. These results demonstrate that GLURP produced in E. coli can induce a humoral immune response against GLURP derived from blood-stage parasites.

Amino Acid Sequence↗

PubMed1995

Guinea pig cellular immune responses to proteins secreted by Mycobacterium tuberculosis.

To study the immunological activity of proteins secreted by Mycobacterium tuberculosis, we carried out comparative studies in guinea pigs infected intravenously with 2.5 x 10(3) CFU of this organism or with 2.5 x 10(4) CFU of Mycobacterium bovis BCG. Groups of infected guinea pigs were skin tested with fractions of secreted proteins covering well-defined narrow-molecular-mass regions, or such fractions were used for lymphocyte stimulation experiments. The lymphocyte stimulation experiments showed that the fraction containing proteins with molecular masses below 10 kDa had a superior stimulating capacity in tuberculous guinea pigs whereas the 24- to 30-kDa fraction gave significantly higher skin reactions in this group compared with BCG-vaccinated guinea pigs. A precise mapping within the region from 23 to 35 kDa by using a combination of narrow overlapping fractions and purified proteins enabled the identification of the 24-kDa antigen MPT64 as a molecule specific for tuberculous infection. Thus, MPT64 is a promising candidate for a specific diagnostic skin test reagent for human tuberculosis.

Animals↗

PubMed1995

Mortality rate and magnitude of Staphylococcus aureus bacteremia as assessed by a semiquantitative blood culture system.

A 4-year retrospective study ascertained the relation between the magnitude of Staphylococcus aureus bacteremia and mortality. 253 episodes of S. aureus bacteremia diagnosed in a Danish regional Department of Clinical Microbiology were included. Blood cultures were routinely done by inoculation of aseptically drawn blood into multiple tubes of bacteriological media. The rate of positive tubes was assumed to distinguish high- from low-grade bacteremia without providing an absolute count of colony forming units. The median number of tubes inoculated was 18 (range 6-48) with approximately 0.5-1 ml of blood per tube. The rate of positive tubes was related neither to the source of infection, i.e. whether the S. aureus infection was nosocomially or community-acquired, nor to the portal of entry. However, mortality increased with increasing rate: it was 18% for rates < 0.30, 23% for 0.30-0.69, 30% for 0.70-0.99, and 37% for a rate of 1.0. Thus, for S. aureus infections the magnitude of bacteremia seems to be a prognostic factor with possible bearings on clinical and therapeutic decisions.

Adolescent↗

PubMed1995

Bacteraemia due to Escherichia coli in a Danish university hospital, 1986-1990.

433 episodes of E. coli bactereaemia over a 5-year period in a Danish university hospital were studied with special emphasis on possible differences between nosocomial (NO) and community-acquired (CA) cases. Data from 186 males and 247 females with ages ranging from 9 days to 94 years were recorded. The average incidence of E. coli bacteraemia was 24.4 episodes/10,000 admissions/year. Older females accounted for the largest number of cases, which reflected the composition of the background population. The highest risk of infection was in males 80-89 years of age. The highest frequency of NO infections was in the departments of Intensive Care (90%) Orthopaedic Surgery (87%) and Haematology (80%). The most common focus was the urinary tract, with 72% of the episodes with a known focus, while the biliary tract was the focus in 14%. NO bacteraemia was independently related to immunosuppressive therapy, presence of predisposing factors, polymicrobial bacteraemia and presence of a non-urinary tract focus. A urinary tract focus was associated with CA bacteraemia, monomicrobial infection, female sex and a normal or elevated total white blood cell count. Patients with NO bacteraemia had predisposing factors more often than had CA patients, especially haematological malignancies and immunosuppressive therapy. Lack of a known bacterial focus was more common in NO than CA episodes, particularly among patients with haematologic malignancies. The overall mortality was 21%. Increased mortality was independently related to leukopenia (45%), immunosuppressive therapy and NO bacteraemia.

Adolescent↗

PubMed1995

Staphylococcus aureus bacteremia: a 14-year nationwide study in hematological patients with malignant disease or agranulocytosis.

This retrospective nationwide study of 756 cases of S. aureus bacteremia in hematological patients, between 1977-1990, confirms that S. aureus bacteremia is disproportionately prevalent among, and a major cause of morbidity and mortality in, hematological patients. The case mortality rate attributable to S. aureus bacteremia (44%) was significantly higher than the rate (29%) found in patients without hematological disease. A decreasing mortality was, however, observed from the first to the last part of the study period (53 and 37% respectively). A logistic regression analysis showed that mortality was further dependent on age, the type of hematological disease and origin of infection/primary focus of infection. Analysis of clinical features confirmed that in comparison with other patients, S. aureus bacteremia in hematological patients more often was hospital-acquired, acquired without known portal of infection/primary focus of infection and much less frequently resulted in osteomyelitis or endocarditis. From phage typing and antibiotic susceptibility patterns no specific types of S. aureus were associated with hematological patients.

Adolescent↗

PubMed1994

Prolonged breast feeding, diarrhoeal disease, and survival of children in Guinea-Bissau.

OBJECTIVE: To analyse the impact of breast feeding on diarrhoeal disease and survival in children above 1 year of age in Guinea-Bissau, west Africa. DESIGN: A community study of an open cohort followed up weekly by interviews over 15 months. Data on feeding practices, anthropometry, and survival were recorded for three years. SETTING: 301 randomly selected houses in a semiurban area in the capital, Bissau. SUBJECTS: 849 children aged less than 3 years. MAIN OUTCOME MEASURES: Incidence and duration of diarrhoea, weight for age, and death of a child. RESULTS: The incidence of diarrhoea was higher in weaned children than in partially breast fed children, both in 1 year olds (relative risk 1.41; 95% confidence interval 1.23 to 1.62) and in 2 year olds (1.67; 1.29 to 2.15). The mean duration of an episode of diarrhoea was 5.3 days in breast fed children compared with 6.3 days in weaned children (P = 0.001). Independent of the age of weaning, a similar increase was found in an analysis comparing, for each child, the rate and duration of diarrhoea one month before and one month after weaning. Children with low weight for age were breast fed longer than the better nourished children (P = 0.02). Children aged 12-35 months who were not breast fed had a 3.5 times higher mortality (1.4 to 8.3) than breast fed children. CONCLUSIONS: The beneficial effects of breast feeding are not restricted to infancy. Though children who are partially breast fed after infancy may have a lower state of nutrition than the weaned ones, the benefit in terms of lower morbidity may be more important for child survival in places with a high morbidity from diarrhoea and with high mortality.

Age Factors↗

PubMed1994

The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique.

We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other receiving placebo every week from December 1989 to November 1990. The groups were then followed until November 1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were assessed by lymphocyte proliferation assays in vitro. Anti-GLURP and anti-Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum antibodies were measured by indirect fluorescent antibody test (IFAT). Immunological reactivities were evaluated every six months, at the end of the rainy season and at the end of the dry season, both during the period of chemoprophylaxis and during the follow-up. The antibody response rate to the GLURP was lower in the Maloprim group than in the placebo group during the intervention phase. The lymphoproliferative response rate to the malaria antigens was significantly lower at the end of the rainy season than at the end of the dry season, but the difference between the experimental group and the control group of schoolchildren was not statistically significant. These results suggest that the antibody responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly chemoprophylaxis successfully reduced the parasite rate during the rainy season from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may therefore have a useful role in combination with another partially effective malaria control measure such as insecticide-impregnated bed nets or a malaria vaccine.

Animals↗

PubMed1994

The etiology of early childhood diarrhea: a community study from Guinea-Bissau.

A potential enteropathogen was found in 50% of 1219 diarrheal episodes and 48% of 511 asymptomatic controls in a 1-year community study of childhood diarrhea. Rotavirus (3% of episodes), Cryptosporidium species (6%), and enteropathogenic Escherichia coli (EPEC) with EPEC adherence factor (4%) were more prevalent in cases than controls. Giardia lamblia (19%) was the most prevalent organism but was not associated with diarrhea. Enterotoxigenic E. coli (12%), Strongyloides stercoralis (5%), Shigella species (2%), Entamoeba histolytica trophozoites (2%), and Vibrio cholerae (1%) were found at nonsignificantly higher rates. Salmonella and Campylobacter species were more prevalent among control infants. Cryptosporidium species and sequential infections from other pathogens caused persistent diarrhea.

Child↗

PubMed1994

Impact of the agar medium and disc type on disc diffusion susceptibility testing against teicoplanin and vancomycin.

Susceptibility to teicoplanin and vancomycin was assessed by three disc types: two commercially available discs (NeoSensitabs and PDM disc (30 micrograms)) and one locally prepared 30 micrograms disc (SS disc) on four different medium types: Mueller-Hinton agar (MH medium), MH medium and PDM agar II supplemented with 5% horse blood (HMB medium and PDM medium, respectively), and Danish blood agar (DBA medium). Two previously studied groups of Gram-positive bacteria were tested: group B (N = 75) comprised miscellaneous cocci, and group C (N = 59) mostly rods. With NeoSensitabs, mean zone diameters were larger than with PDM and SS discs on all medium types, and mean zone diameters were larger on DBA medium than on MHB and PDM medium with all disc types. The impact of the medium type on the zone diameter was evaluated for 121 strains growing on MHB medium, PDM medium, and DBA medium. Bacterial groups B and C each divided into three MIC groups were analysed separately. We compared mean zone diameters for each specific group with the average zone diameter, i.e. the mean value for all zone diameters obtained. The smallest deviations from the average zone diameters were observed on PDM medium for both teicoplanin and vancomycin. Thirty-seven percent of strains failed to grow on MH medium, but supplementation of MH medium with horse blood significantly reduced the zone diameter for group B strains both for teicoplanin and vancomycin. Poor predictability of MIC from the zone diameter was found especially for strains with MICs < or = 1 microgram/ml. The medium type hardly affected the results of regression analysis. In contrast, the medium type markedly affected the results of error-rate bounded analysis. No errors were recorded with the SS disc on MHB medium for either teicoplanin or vancomycin, but no strains with MICs of vancomycin within the intermediate group could be correctly classified on DBA medium.

Agar↗

PubMed1994

Immune responses to band 3 neoantigens on Plasmodium falciparum-infected erythrocytes in subjects living in an area of intense malaria transmission are associated with low parasite density and high hematocrit value.

During the intracellular development of the human malarial parasite, Plasmodium falciparum, cryptic regions of the erythrocyte band 3 protein are exposed. Antibodies against these band 3-related neoantigens block cytoadherence, and peptides based on amino acid sequences of putative exofacial loops of band 3 protein block the in vitro and in vivo adherence of P. falciparum-infected erythrocytes. At present, it is not known whether reactivity to these antigens is related to exposure to the malaria parasite or is correlated with protective immunity. The reactivities of plasma to peptides containing amino acid sequences of putative exofacial loops 3 and 7 of human band 3 protein were determined for children and adults living in an area of perennial malaria transmission (Liberia) and for donors who had never been exposed to malaria (Denmark). Plasma samples from children and adults living in an area of intense malaria transmission showed a much higher reactivity with the band 3 peptides than did those from nonimmune individuals. High reactivity to the loop 3 peptide (amino acids 546 to 555) was correlated with lower mean parasite density in children in the 5- to 9-year-old age group. The presence of antibodies against loop 3 and 7 peptides was not associated with a low packed erythrocyte volume (hematocrit); in fact, higher-than-average reactivities to both peptides were positively correlated with high hematocrit values, indicating that antibodies which specifically recognize the band 3-related neoantigens are not involved in hemolysis (autoimmunity).

Adolescent↗

PubMed1994

Evaluation of the E-test for susceptibility testing of the Bacteroides fragilis group. Danish study group.

The susceptibilities of 100 clinical isolates belonging to the Bacteroides fragilis group to 9 antibiotics, i.e. ampicillin, piperacillin, ceftriaxone, cefotaxime, cefoxitin, imipenem, erythromycin, clindamycin, and metronidazole, were tested using a standard agar dilution method and the E-test. Overall, 81% of the E-test MICs were within one log2 dilution step of the agar dilution MICs and 95% were within two log2 dilution steps. The E-test showed significantly lower MIC values than the agar dilution method for ampicillin, cefotaxime, and imipenem, and significantly higher MIC values for piperacillin, ceftriaxone, erythromycin, clindamycin, and metronidazole. However, this only resulted in minor discrepancies that did not change the susceptibility status. The E-test is easy to perform and read, and the MIC values correlated well with the MICs obtained by the agar dilution method when testing susceptibility of the Bacteroides fragilis group.

Ampicillin↗

PubMed1993

Cryptosporidiosis in infancy and childhood mortality in Guinea Bissau, west Africa.

OBJECTIVE: To investigate the epidemiology of and mortality from cryptosporidiosis in young children in Guinea Bissau, West Africa. DESIGN: Three year community study of an open cohort followed up weekly. SETTING: 301 randomly selected houses in a semi-urban area in the capital, Bissau. SUBJECTS: 1315 children aged less than 4 years. MAIN OUTCOME MEASURES: Cryptosporidium infection detected by examination of stools during episode of diarrhoea and death of a child. RESULTS: Cryptosporidium spp were found in 239 (7.4%) out of 3215 episodes of diarrhoea. The parasite was most common in younger children (median age 12 months) and at the beginning of the rainy seasons. The prevalence of cryptosporidiosis was 15% (77/513) in cases of persistent diarrhoea compared with 6.1% (148/2428) in diarrhoea lasting less than two weeks (p < 0.0001). Cryptosporidiosis was associated with excess mortality in children who had the infection in infancy, and this excess mortality persisted into the second year of life (relative mortality 2.9 (95% confidence interval 1.7 to 4.9)). The excess mortality could not be explained by malnutrition, or by socioeconomic factors, hygienic conditions, or breast feeding. CONCLUSIONS: Cryptosporidiosis is an important cause of death in otherwise healthy children in developing countries.

Child, Preschool↗

PubMed1993

Classification of clinical falciparum malaria and its use for the evaluation of chemosuppression in children under six years of age in Liberia, west Africa.

The possible role of malaria as cause of morbidity was assessed during one year in 262 children aged 6 months to 6 years living in two villages in a rural area of Liberia. The study population was followed by weekly clinics and three-monthly surveys and the children were randomly allocated to receive either chloroquine or placebo every 3 weeks. The morbidity of the children was evaluated by criteria based on the history and the clinical condition into four different stages, in order to describe the probability that an observed clinical event could be attributed to malaria infection, based on the presence of detectable parasites in the blood, the history the previous week, and the clinical status of the child. The level of anaemia, splenomegaly and measured body temperature supported that malaria was the major contributor to the overall morbidity observed. Based on the stage classification of clinical illness, children were classified as having 'possible clinical malaria' or 'probable clinical malaria'. Malaria appeared to be an important cause of febrile episodes during both dry and rainy seasons. During the rainy season more than 60% of the children experienced at least one clinical malaria episode, and during the dry season more than 50% of the children experienced at least one clinical attack of malaria. Children receiving chemosuppression had overall fewer clinical malaria attacks, and the effect of the chemosuppression was most pronounced in the dry season, the odds ratio comparing children receiving regular chemosuppression with children receiving presumptive treatment only was estimated to 0.39 (0.25-0.62).

Anemia↗

PubMed1993

Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children.

The aims of the present study were to describe the age-related immunoglobulin M (IgM) and IgG response to part of a 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum and to determine possible correlations of possession of these antibodies with malaria morbidity. IgM and IgG levels were measured with a recombinant fusion protein consisting of the carboxy-terminal 783 amino acids of the GLURP. Samples for the study were obtained during a longitudinal malaria morbidity survey performed in The Gambia; cross-sectional surveys were performed at the beginning of the transmission season in May and in October. Seropositivity rates increased with age to a maximum of 77% for IgM and 95% for IgG in adults. High prevalences of seropositivity were associated with certain human leukocyte antigen class II alleles (DRw8, DR9, DR7, DR4, DQw7, and DQw2) or haplotypes. The relationship between anti-GLURP489-1271 antibodies and clinical immunity is not clear; asymptomatically infected children aged 5 to 8 years had significantly higher levels of IgG than clinically ill children of the same age, suggesting that antibodies to the carboxy-terminal part of the GLURP may contribute to immunity to P. falciparum. However, this was not significant for younger children.

Adolescent↗

PubMed1993

Risk factors for hepatitis B virus infection in heterosexuals attending a venereal disease clinic in Copenhagen.

Markers of hepatitis B virus (HBV) infection were measured in 465 non-drug-abusing heterosexually transmitted disease (STD) patients. HBV markers were found in altogether 70 persons, of whom 7 were HBsAg carriers. Those chronically infected were all born in HBV intermediate/high endemic areas. Gonorrhoea was the only STD that was correlated to an increased risk of HBV markers. Number of sexual partners, sex and age was not correlated with HBV infection, irrespective of country of origin. The risk of having HBV markers in an STD clientele in Copenhagen was highly dependent on the country of birth, as the prevalences were 7% (21/307) in persons born in Denmark, 19% (9/47) in those born in other low endemic areas and 36% (40/111) in those born in intermediate/high endemic areas. Falling incidence of gonorrhoea and other STD may render it difficult to point out risk factors indicative of HBV immunization in heterosexual STD patients. In low-risk countries, screening for HBV markers should however be offered to all immigrants and refugees as a part of an HBV immunization program.

Adolescent↗

PubMed1993

Antibiotic sensitivity of the Bacteroides fragilis group in Denmark. Danish Study Group.

Resistance rates to 9 antibiotics were determined for 370 isolates of the Bacteroides fragilis group submitted during a 5-month period in 1990-91 from 6 laboratories in Denmark. There was no resistance to imipenem (MIC > 8 mg/l) or metronidazole (MIC > 16 mg/l), while resistance to ampicillin was the rule (97% at > 4 mg/l) and to ceftriaxone rather common (19% at > 32 mg/l). Resistance was uncommon to cefoxitin (0.5% at > 32 mg/l), cefotaxime (6% at > 32 mg/l), piperacillin (7% at > 64 mg/l), ampicillin/sulbactam (1% at > 16 mg/l), and clindamycin (3% at > 4 mg/l). Two hundred and thirty-nine strains were Bacteroides fragilis. The 131 other strains were generally more resistant than the Bacteroides fragilis strains. For 5 antibiotics the Bacteroides fragilis had a significantly lower MIC in western than in eastern laboratories. For the group with other strains there was no significant difference.

Anti-Bacterial Agents↗

PubMed1993

HIV-2 infection in Bissau, West Africa, 1987-1989: incidence, prevalences, and routes of transmission.

In a community study, the HIV-1 and HIV-2 antibody status of the inhabitants of 100 randomly chosen houses in Bissau, West Africa, were followed from 1987 to 1989. There was no HIV-1 infection alone, while the HIV-2 seroprevalence in adults was 8.9% (58 of 652) in 1987 and 10.1% (61 of 603) in 1989. HIV-2 seroprevalence in 15- to 39-year-olds was 6.1% in 1987 and 11.3% in newcomers in 1989 [the Mantel-Haentzel weighted relative risk (RRMH) = 1.86; 95% confidence interval (CI): 1.07-3.24]. Three hundred thirty adults who were HIV-2 seronegative in 1987 were reexamined in 1989; seven had seroconverted. Follow-up time was 700 person years, giving an incidence of HIV-2 infection of 1 per 100 person years. With a history of sexually transmitted disease (STD), the RR of seroconverting was 9.95 (2.31-42.80). Blood transfusions received since 1987 did not result in seroconversions. No case of vertical transmission of HIV-2 was seen. There was an excess mortality in those who were HIV-2 seropositive; however, it was statistically significant only for children (RR = 22.27; 95% CI: 6.92-71.70; p < 0.0001), not for adults (RR = 2.16; 95% CI: 0.81-5.76; p = 0.23), when considering death from disease only.

Adolescent↗

PubMed1993

Doctor and patient characteristics as modifiers of the effect of a changing remuneration system in general practice.

The objectives of the study was to investigate the effects on general practitioners' activities of a change in their remuneration system from a capitation-based system to a mixed fee-per-item and capitation-based system. It was our hypothesis that the effect of the change in remuneration varied between subgroups of doctors and patients as a result of the modifying effect of the doctors' age, sex, practice facilities, assistance, side jobs, and size of practice as well as patients' age, sex, and diagnostic group. The study was carried out as a follow-up with data collected from contact sheets completed by general practitioners in one period before a change in remuneration and two periods after. These data were supplemented by a questionnaire on doctors' characteristics as well as by health insurance data on population characteristics. The general increases in diagnostic and curative activities and reductions in referrals by general practitioners as a result of the change were found to be quite similar across subgroups of doctors and patients. While, total contact rates changed little, the sex of doctors showed a modifying effect: male doctors tended to increase their contact rates compared to female doctors. This tendency was most prominent among female patients with non-infectious diseases.

Age Factors↗