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Biomedical subjects

J Knobloch

Publications and source records attributed to J Knobloch.

At least 19 recordsLinked to original sources

Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. OBJECTIVES: To present epidemiological and clinical data on imported P. vivax malaria collected at European level. MATERIAL AND METHODS: Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. RESULTS: Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41-158) versus 31 days (inter-quartile range 4-133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. CONCLUSIONS: TropNetEurop data can contribute to the harmonization of European treatment policies.

Adult↗

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Age Factors↗

P19: a female and tissue specifically expressed gene in Schistosoma mansoni, regulated by pairing with the male.

A female-specific sequence was isolated from a cDNA library of Schistosoma mansoni and further characterized. Expression of the corresponding gene (p19) depends on pairing with a male. In situ hybridization and immunohistology experiments revealed exclusive expression of the gene in the cells of the vitellarium, suggesting a function in egg formation. In addition, experimental evidence for cross-linking of the protein under oxidative conditions supports the assumption that the p19 gene may code for an egg-shell precursor protein.

Amino Acid Sequence↗

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Adolescent↗

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Adolescent↗

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.

Adolescent↗

Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study.

Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers.

Adolescent↗

Reversal of multidrug resistance and increase in plasma membrane fluidity in CHO cells with R-verapamil and bile salts.

Studies with multidrug resistance modifiers indicate that perturbations of the cell membrane structure may influence P-glycoprotein (P-gp)-mediated drug transport. We describe studies of plasma membrane order using electron-paramagnetic resonance (EPR) in resistant (CH(R)C5) and sensitive (AUXB1) chinese hamster ovary cells treated with R-verapamil and bile salts. Cell growth rates were determined in presence of doxorubicin mitomycin and cisplatin. The plasma membrane order in untreated resistant cells was higher than in the sensitive cells. Both the bile salt taurochenodeoxycholate (TCDC; 0.2-1.6 mM) and R-verapamil (1-3 microM) lowered the membrane order in the CH(R)C5 cells to that in the sensitive cells and reversed the resistance to doxorubicin and mitomycin. The bile salt tauroursodeoxycholate (TUDC; 0.2-3 mM) did not lower membrane order and did not sensitise CH(R)C5 cells. Neither R-verapamil, TCDC nor TUDC reduced the membrane order of the sensitive cells AUXB1 cells. These results support the view that changes in multidrug resistance in Chinese hamster ovary cells and P-gp function are associated with alterations in the fluidity of the plasma membrane.

Animals↗

Diagnosis and monitoring of murine histoplasmosis by a nested PCR assay.

A newly developed nested PCR assay was applied to murine models of histoplasmosis. ICR and BALB/c mice were intravenously infected with Histoplasma capsulatum and sacrificed up to 29 days later. Samples of blood, spleen, and lung homogenates were cultured and examined by the PCR assay. In the ICR mouse model, 265 of 319 organ samples showed concordant results. With 7 samples, the culture was positive and the PCR assay was negative whereas a positive PCR but a negative culture were obtained with 47 samples (P < 0.0001 according to McNemar's test). Organ homogenates and blood samples of either spontaneously cured or treated BALB/c mice were PCR negative. The nested PCR assay performs excellently in the monitoring of spontaneously and treatment-cured murine histoplasmosis. It limits the infection risks of the laboratory staff and might be of diagnostic value for humans.

Animals↗

Case report: Nitazoxanide treatment failure in chronic isosporiasis.

We report a 60-year-old immunocompetent patient with chronic biliary isosporiasis who failed to respond to orally administered cotrimoxazole prophylaxis and orally administered treatment with nitazoxanide, a 5-nitrothiazole benzamide compound. Severe malabsorption was regarded as responsible for the subtherapeutic levels of nitazoxanide in plasma and bile, resulting in treatment failure. Intravenously administered cotrimoxazole stopped the shedding of Isospora belli oocysts in bile within 5 days, excluding initially suspected resistance to cotrimoxazole. Patients with malabsorption and cholangitis due to Coccidia such as Isospora belli and Cryptosporidium spp. or due to protozoa that cause microsporidiasis seem to be predisposed to fail to respond to otherwise effective treatment.

Administration, Oral↗

Schistosomiasis in German children.

UNLABELLED: Reports on schistosomiasis in children growing up in Europe are rare despite increased travel activity. We report on eight male and three female German children aged 50 months to 15 years with schistosomiasis. Six children were asymptomatic, whereas two presented with typical signs of Katayama fever. Persisting haematuria, headache with eosinophilia and pyelonephritis were observed in one child each. An exposure was reported for six of the children. Two were examined solely because schistosomiasis was diagnosed in a family member. All had antibodies against schistosomal antigens in at least two of three screening tests. However, schistosomal ova (Schistosoma haematobium) were detected in urine and faecal specimens from only three children. A tumour-like lesion of the bladder was found by ultrasound in only one of the children who also exhibited haematuria. Neither eosinophilia nor elevated IgE levels were constant findings. Six to 12 months after praziquantel treatment, parasitological and ultrasound checks were negative and levels of specific antibodies decreased. However, 2 years later, elevated antibody levels were detected in one girl without evidence of any new exposure. She became antibody-negative 1 year after a second course of treatment. CONCLUSION: In contrast to residents of endemic areas, parasitological and ultrasound examinations seem to be inferior to immunodiagnostics in children from non-endemic areas at temporary risk for schistosomiasis.

Adolescent↗

Detection of Paracoccidioides brasiliensis in tissue samples by a nested PCR assay.

A nested PCR assay for the detection of Paracoccidioides brasiliensis DNA was evaluated, using a sequence of the immunogenic gp43 gene as a target. This gene encodes an outer membrane protein unique to this dimorphic fungus. DNA from six clinical isolates and the ATCC strain 60885 of P. brasiliensis, as well as DNA from closely related fungi, was examined to determine detection limits and cross-reactions. PCR was done on DNA extracts of lung homogenates from 23 experimentally P. brasiliensis-infected and two uninfected BALB/c mice and from 20 Histoplasma capsulatum-infected ICR mice. The results were compared to quantitative cultures. A detection limit of 0.5 fg of specific DNA was determined using cloned plasmid DNA. In all seven P. brasiliensis isolates, the expected 196-bp nested PCR product was found. Their sequences were 100% identical to the gp43 gene sequence in GenBank. DNA extracts of all other, related fungi were negative. The PCR assay was positive in 21 out of 23 culture-positive lung homogenates with concentrations of 1 x 10(3) to 1.3 x 10(7) CFU of P. brasiliensis per g of lung. Uninfected BALB/c mice and H. capsulatum-infected mice samples gave negative results. The high sensitivity and specificity of this new nested PCR assay for the detection of P. brasiliensis in tissue samples were demonstrated. The assay may be useful for diagnosis in human tissue samples.

Animals↗

Cytopathic effects of Blastocystis hominis on Chinese hamster ovary (CHO) and adeno carcinoma HT29 cell cultures.

Blastocystis hominis isolates from asymptomatic carriers and symptomatic patients were cultured in vitro, purified from the co-cultivated bacterial flora and tested for cytopathic effects on monolayers of Chinese Hamster Ovary (CHO) cells and Adeno Carcinoma HT29 cells. In the case of the CHO cells, living B. hominis cells and B. hominis cell lysates were able to cause significant cytopathic effects, which were dependent on the concentration of cells employed. Destruction of the cell monolayers was observed to the same extent with patient isolates derived from healthy or symptomatic B. hominis carriers. HT29 cells were less susceptible: B. hominis cells and cell lysates caused only minor effects which were not statistically significant. Culture filtrates of B. hominis exhibited cytopathic potential on CHO and HT29 cells; however, the control which consisted of filtrates from Robinson's cultures in which B. hominis failed to grow showed similar effects, too. Therefore the culture supernatants could not be proven to produce a specific cytopathic effect on CHO and HT29 cells.

Adenocarcinoma↗

Development of monoclonal antibodies specifically recognizing the cyst stage of Entamoeba histolytica.

Protozoan cysts were isolated according to a two-step sucrose gradient procedure. Pure cysts of Entamoeba histolytica, in fixed and native states, were injected into BALB/c mice intraperitoneally for immunization. The spleens of these animals were used for fusion with AG8 mouse myeloma cells. Hybridomas were obtained and tested for the recognition of E. histolytica, E. dispar, E. coli, E. hartmanni, Endolimax nana, Jodamoeba biitschlii, and Giardia lamblia. Three monoclonal antibodies were identified that reacted only with cysts and trophozoites of E. histolytica. These can be used for differentiation and identification of E. histolytica in feces.

Animals↗

Loss of in vitro cytotoxicity of cisplatin after storage as stock solution in cell culture medium at various temperatures.

BACKGROUND: Cisplatin (cis-dichlorodiammineplatinum [II]) is one of the most potent and widely used cytotoxic drugs in cancer therapy. However, in vitro cytotoxicity assays often yield diverging results. Therefore, it is believed by many investigators that cisplatin is not effective in vitro. The authors investigated whether the experimental conditions used could be responsible for the diverging results. METHODS: In vitro cytotoxicity assays were performed using the original cisplatin solution as distributed by the manufacturer or a 5-fold dilution of this in cell culture medium after storage for 2 weeks or 1 month at various temperatures (room temperature, 4 degrees C, and -20 degrees C). RESULTS: The original solution of cisplatin retained the full cytotoxic potency for at least 1 month under all storage conditions tested. The highest loss of cytotoxicity resulted from storage of cisplatin in cell culture medium in which a >7-fold increase in the concentration that inhibits 50% occurred after 2 weeks' storage at room temperature. Solutions stored in culture medium at -20 degrees C retained full cytotoxic potency. CONCLUSIONS: Cisplatin is a potent cytotoxic drug in vitro when stored under appropriate conditions. These findings are of relevance for in vitro studies with cisplatin.

Antineoplastic Agents↗