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Biomedical subjects

F von Sonnenburg

Publications and source records attributed to F von Sonnenburg.

At least 19 recordsLinked to original sources
PubMed2006

[33 year old Libanese woman with recurrent haemoptysis and cystic lesion of the lung].

A 33 year old woman from Lebanon presented with recurrent hemoptysis, subfebrile temperature, dyspnoe in stress, fatigue, weight loss, and pruritus. Serological tests and results from chest X-ray and computer tomography revealed cystic echinococcosis with pulmonary involvement. After refusal of surgical therapy a medical treatment with albendazole was implemented. Two months after the start of the therapy only a small fibrotic residuum in the lung was seen. A spontaneous healing success seems unlikely because of the duration of the pulmonary cyst and the progressive symptoms before treatment.

Adult↗
PubMed2005

In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months postinfection.

Human immunodeficiency virus type 1 (HIV-1) superinfection refers to the acquisition of another strain by an already infected individual. Here we report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multi-region genotyping assay. The subject was identified in the window period and was first infected with a complex ACD recombinant strain, became superinfected 6 to 9 months later with an AC recombinant, and was monitored for >2.5 years. The plasma viral load exceeded 400,000 copies/ml during the first 9 months of infection but resolved to the set point of 67,000 copies/ml by 3 months after superinfection; the CD4 cell count was 377 cells/mul at 30 months. Viral diversity was evaluated with techniques designed to fully sample the quasi-species, permitting direct observation of the evolution, temporal fluctuation, and intercompartment dynamics of the initial and superinfecting strains and recombinants derived from them. Within 3 months of superinfection, seven different molecular forms were detected in gag and six were detected in env. The proportions of forms fluctuated widely over time in plasma and peripheral blood mononuclear cells, illustrating how challenging the detection of dually infected individuals can be. Strain-specific nested PCR confirmed that the superinfecting strain was not present until the 9 month follow-up. This study further defines the parameters and dynamics of superinfection and will foster appropriate studies and approaches to gain a more complete understanding of risk factors for superinfection and its impact on clinical progression, epidemiology, and vaccine design.

Evolution, Molecular↗
PubMed2004

Methodological lessons from a cohort study of high risk women in Tanzania.

OBJECTIVES: To describe the development, characteristics, and follow up of a high risk cohort of women in Tanzania. Differences in social background and sexual behaviour of women working in traditional and modern alcohol selling workplaces are shown. METHODS: Data from questionnaires four months before the enrollment of the cohort, at enrollment, and at 32 months were compared. Key informant interviews, social mapping exercises, and focus group discussions were held before the start of the cohort. RESULTS: In the absence of organised prostitution, two different groups of women with high risk exposure were identified during the baseline survey: female workers in modern alcohol selling places such as bars, guesthouses, and restaurants (barmaids) and in traditional places (local brew sellers). Overall, the population had a mean age of 27.7 years with barmaids tending to be younger (24.3 years) than local brew sellers (34.2 years). The main duration of stay in the current workplace was 2.1 years (barmaids 0.9 years; local brew sellers 4.1 years). Barmaids were more likely to have paying casual sex partners than local brew sellers and used condoms more regularly. Local brew sellers tend to be more stable with only 10% lost to follow up after 32 months compared with 24.4% of the bar workers. CONCLUSIONS: Preliminary work revealed major differences in characteristics and behaviour between women working in modern and traditional alcohol selling outlets. Thorough preparation of the study, close monitoring of the cohort, and provision of selected benefits resulted in high retention rates over a 32 month project in a highly mobile population.

Adult↗
PubMed2002

Diagnostic value of molecular markers in chloroquine-resistant falciparum malaria in Southern Mauritania.

Despite its diminishing efficacy because of increased resistance, chloroquine remains the primary antimalarial agent in many endemic areas. Evidence is mounting that point mutations on the Pfcrt and possibly the Pfmdr1 genes are conferring plasmodial resistance to chloroquine. In 1998, atypically strong rainfalls led to an increased activity of falciparum malaria in Mauritania that affected non-endemic regions bordering the Saharan desert. An in vivo study on chloroqine resistance was combined with studies for molecular markers of drug resistance. Detection of Pfmdr1-76-tyrosine showed an increased odds ratio (2.91) for resistance (P = 0.0195). However, by use of this codon alone, sensitivity for detection of resistance was 60.6%, and specificity was 65.3%. In comparison, detection of the K76T mutation at Pfcrt showed a very high sensitivity (100%) while specificity remained relatively low (65.4%). For the combination of mutations on both genes, the odds ratio for detection of resistance increased to 5.31 (P = 0.0005). Here, sensitivity was again decreased to 60.6% while specificity increased to 76.9%. The results of this study suggest that detection of Pfcrt T76 can be applied for predicting chloroquine resistance in epidemiologic settings with sufficiently high sensitivity to make it an attractive alternative to time- and labor-consuming in vivo trials. Additional testing for Pfmdr Y76 provides increased specificity to this approach.

Adult↗
PubMed2001

Diagnostic significance of blood eosinophilia in returning travelers.

This study was conducted to investigate the predictive value of blood eosinophilia (total white blood cell count with > or =8% eosinophils) for the diagnosis of travel-related infections in 14,298 patients who returned from developing countries. The data show that blood eosinophilia in travelers returning from developing countries has only limited predictive value for the presence of travel-related infections. However, the likelihood of the presence of helminth infections increases considerably with the extent of eosinophilia.

Adolescent↗
PubMed2001

High proportion of unrelated HIV-1 intersubtype recombinants in the Mbeya region of southwest Tanzania.

BACKGROUND: In Mbeya, a rural region of southwest Tanzania, HIV-1 subtypes A, C and D have been co-circulating since the early 1990s. OBJECTIVE: To define to what extent the co-existence of subtypes has led to recombinant HIV-1 strains and whether there is evidence for epidemic spread of any circulating recombinant form. METHODS: Nine HIV-1-seropositive young adults from Mbeya Town with no evident high-risk behaviour contributed peripheral blood mononuclear cells for this study. Nine virtually full-length-genome-sequences were amplified from this DNA and phylogenetically analysed. RESULTS: Out of the nine samples, two were subtype A (22%), two were subtype C (22%) and five were recombinants (56%): four A/C recombinants and one C/D recombinant. None of the recombinants were related to each other; all of them had different mosaic structures. Most of the genome in the recombinants was subtype C. CONCLUSION: A high proportion of unrelated intersubtype recombinants, none of them apparently spreading in the population, may be present in southwest Tanzania.

Adolescent↗
PubMed2001

Genetic diversity of Plasmodium falciparum and its relationship to parasite density in an area with different malaria endemicities in West Uganda.

Field populations of Plasmodium falciparum can be effectively genotyped by PCR-amplification of selected fragments of the Merozoite Surface Proteins 1 and 2 (MSP1 and MSP2). Genetic diversity of P. falciparum populations in areas with different transmission levels (holo- vs. mesoendemic) was investigated in Kabarole District, West Uganda. 225 samples positive for P. falciparum were analysed by amplification of polymorphic regions and classified according to prevalence of allelic families. A large number of alleles was detected for each locus: 22 for MSP1 block 2 and 24 for MSP2 and, 175 (78%) of MSP1 alleles and 143 (64%) of MSP2 showed multiple infections within a range of 2-8 clones. Significant differences between holoendemic and mesoendemic areas in regards of population structure and number of multiclonal infections of P. falciparum were not apparent. However, a significant correlation between parasite density, selected MSP2 loci and differences between parasite density in monoclonal vs. multiclonal infections occurred. Multiplicity of infection was age-dependent.

Adult↗
PubMed2000

Risk and aetiology of diarrhoea at various tourist destinations.

Almost two of three tourists developed traveller's diarrhoea during 2-week stays at high-risk destinations. Large differences in infection rates between hotels were seen. Patients with milder forms of diarrhoea show a similar chronology to those more severely affected. Although enterotoxigenic Escherichia coil was the most frequent cause, viral pathogens were detected more often than in other studies.

Brazil↗
PubMed2000

Reliability of malaria microscopy in epidemiological studies: results of quality control.

To assess the interrater reproducibility of malaria microscopy in epidemiological studies, 711 thick blood films from population-based surveys were randomly selected and reread by 4 experienced microscopists. Sample estimates of the prevalence of P. falciparum infection, geometric mean parasite density and the proportion of samples above various parasite density cut-off levels were almost identical in the routine and quality control readings. Differences were, however, encountered in the sample estimates for gametocyte ratio, proportion of mixed infection and average density index. In all three cases the quality control result was significantly higher than the routine evaluation. On the level of the individual slide there was good interrater agreement for the presence of P. falciparum infections (Kappa index kappa = 0.79) which was even better when parasite densities between 4 and 100/microl were excluded (kappa = 0.94). With respect to the assessment of parasite density, a high level of disagreement was found. While the mean difference between the two readings was not different from 0, the second reading was between 0.12 and 10 times that of the first. However, the level of disagreement significantly fell with increasing parasite densities. Thus malaria microscopy is very reliable for the estimation of parasite ratios and geometric mean parasite densities within and between studies as long as the same methodology is used, but tends to underestimate the gametocyte ratio and proportion of mixed infections. Care must be taken, however, when individual parasite density is related to other explanatory variables, due to the high degree of variability in the parasite enumeration.

Animals↗
PubMed1999

Application of the ParaSight-F dipstick test for malaria diagnosis in a district control program.

A rapid test for the diagnosis of Plasmodium falciparum infections based on the detection of histidine-rich-protein II, the ParaSight-F test, was evaluated after introduction in a district malaria control program in Uganda. Suspected treatment failures, pregnant women and infants with clinical malaria and general fever cases were tested at health facilities in malaria hypo-, meso- and holoendemic areas. A total of 1326 tests were carried out by health unit staff, cross read by experienced laboratory staff and results compared with thick film microscopy as the standard. Rater agreement in reading the dipstick result between health unit staff and laboratory staff was high, kappa index 0.94 (0.88-0.99). Sensitivity was 99.6% (99.0-100) for parasite densities above 500/microl, 98.6% (97.7-99.6) for densities above 50/microl and 22.2% (8.6-42.3) for densities below 10/microl. With the applied testing strategies no differences were found between endemicity levels or patient categories. Specificity was 86.2% (83.3-88.8) overall, but significantly higher in general fever cases (92.7%) compared to the other patient groups (84.3%, P=0.009). At the given prevalences positive predictive values (ppv) were above 80% and negative predictive values (npv) above 90% in all cases except in pregnant women (ppv: 77.8%). We conclude that in certain situations this test is an alternative to microscopy to improve diagnostic facilities for case management in malaria control programs in endemic African countries.

Adolescent↗
PubMed1999

Epidemiology, etiology, and impact of traveler's diarrhea in Jamaica.

CONTEXT: Traveler's diarrhea (TD) can incapacitate travelers. Characteristics of TD could be helpful in identifying individuals who might benefit from a vaccine against TD. OBJECTIVE: To determine epidemiology, etiology, and impact of TD in Jamaica. Design Two-armed, cross-sectional survey conducted between March 1996 and May 1997. SETTING: Sangster International Airport and 10 hotels in Montego Bay area, Jamaica. SUBJECTS: To investigate epidemiology and impact, 30369 short-term visitors completed a questionnaire just before boarding their homebound aircrafts. To investigate etiology, 322 patients (hotel guests) with TD provided stool samples. MAIN OUTCOME MEASURES: Attack and incidence rates of reported diarrhea and of classically defined TD (> or =3 unformed stool samples in 24 hours and > or =1 accompanying symptom), incapacity, risk factors, and etiology. RESULTS: The attack rate for diarrhea was 23.6% overall, with 11.7% having classically defined TD. For a mean duration of stay of 4 to 7 days, the incidence rate was 20.9% (all TD) and 10.0% (classic TD). Among airport respondents, the incapacity lasted a mean of 11.6 hours. Less than 3% of all travelers avoided potentially high-risk food and beverages. The most frequently detected pathogens were enterotoxigenic Escherichia coli, Rotavirus, and Salmonella species. CONCLUSIONS: A realistic plan for reducing TD is needed. Preventive measures such as the improvement of hygienic conditions at the destination, and/or the development of vaccines against the most frequent pathogens associated with TD may contribute toward achieving this goal.

Adolescent↗
PubMed1999

Reductions in risk behaviour provide the most consistent explanation for declining HIV-1 prevalence in Uganda.

OBJECTIVE: To monitor the HIV-1 epidemic in Western Uganda and the possible impact of interventions. DESIGN: Results from sentinel surveillance of HIV-1 seroprevalence were compared with cross-sectional serosurvey data and model simulations. METHODS: Age-specific trends in HIV-1 prevalence between 1991 and 1997 amongst antenatal clinic (ANC) attenders in the town of Fort Portal, where a comprehensive AIDS control programme has been implemented since 1991, were analysed. Results were compared with outputs from a mathematical model simulating the HIV-1 epidemic in Uganda. Two scenarios were modelled: one without and one with behaviour change. Sentinel surveillance data were compared with data from a population-based HIV-1 serosurvey at the study site, which was carried out in early 1995. RESULTS: Data from 3271 ANC attenders identified greater education and being single as risk factors for HIV-1 infection. A significant decrease of risk for women with secondary school education over time was observed, whereas the risk for illiterate women remained high. Among women aged 15-19 years (n = 1045) education and marital status-adjusted HIV-1 prevalence declined steadily from 32.2% in 1991 to 10.3% in 1997. For 20-24-year-old women (n = 1010) HIV-1 prevalence increased until 1993 from 19.9% to 31.7% and decreased thereafter (21.7% in 1997). These trends closely follow the prediction of the model simulation assuming behaviour change, and for 1995-1997, confidence intervals of the HIV-1 prevalence estimate exclude the model output for an uninfluenced epidemic. No clear trends of HIV-1 prevalence were found in older women (n = 1216) and comparisons with the model were ambiguous. Sentinel surveillance data at the time of the population survey closely reflected results for the female general population sample for the two younger age-groups (15-19 and 20-24 years). In contrast, pregnant women aged 25-29 years showed significantly lower rates than the population sample (20.8% versus 45.1%). CONCLUSION: HIV-1 prevalence amongst ANC attenders aged 15-24 years can be used to monitor the HIV-1 epidemic in the given setting. Declining trends of HIV-1 prevalence in women aged 15-19 and 20-24 years most likely correspond to a reduced HIV-1 incidence attributable to changes in behaviour. Our data also show that sentinel surveillance data need to be age-stratified to give useful information.

Adolescent↗
PubMed1999

Population structure of recrudescent Plasmodium falciparum isolates from western Uganda.

It has been proposed that polymorphisms of the Merozoite Surface Protein 1 and 2 (MSP1 and MSP2) and the Glutamate Rich Protein (GLURP) genes can be considered as genetic markers for the genotyping of field populations of Plasmodium falciparum. During a field study on in vivo drug resistance against chloroquine, sulphadoxine/pyrimethamine (S/P) and cotrimoxazole in West Uganda, sensitive and resistant isolates were collected from patients by fingerprick for genotyping. 59 (72.8%) of the 81 P. falciparum samples isolated at day 0 showed multiclonal infection with 2-7 clones. Among the isolates we investigated, presence of the allelic family MAD20 of MSP1 at day 0 was significantly (P = 0.0041) associated with decreased resistance to antimalarials. Use of this method in a field study on in vivo drug resistance demonstrates another potential application of genotyping as a tool for epidemiological investigations.

Adolescent↗
PubMed1999

Seroconversion to circumsporozoite antigen of Plasmodium falciparum demonstrates a high risk of malaria transmission in travelers to East Africa.

Circumsporozoite (CS) antibodies have been shown to be reliable indicators of malaria transmission in endemic areas. Their prevalence in travelers can indicate the degree of exposure to plasmodial infection. Two hundred sixty-two short-term travelers to Kenya were recruited to a prospective study to determine the incidence of CS antibody conversion. All travelers were receiving malaria chemoprophylaxis. Serum samples were drawn before departure and 4-6 weeks after their return to Germany. Sera from 310 volunteers who did not leave Germany served as controls. Serum specimens from 13 (4.96%) of the 262 travelers were found to be positive after return. None of the travelers developed symptoms of clinical malaria or antibodies against the blood stages of Plasmodium falciparum. All 310 control samples tested negative. These data demonstrate a considerable risk of malaria transmission for short-term travelers to East Africa.

Adolescent↗
PubMed1999

Sensitivity and specificity of dipstick tests for rapid diagnosis of malaria in nonimmune travelers.

Swift diagnosis of Plasmodium falciparum malaria in areas where the disease is not endemic is frequently complicated by the lack of experience on the side of involved laboratory personal. Diagnostic tools based on the dipstick principle for the detection of plasmodial histidine-rich protein 2 (HRP-2) and parasite-specific lactate dehydrogenase (pLDH), respectively, have become available for the qualitative detection of P. falciparum malaria. In order to evaluate two of the currently available assays, specimens from 231 patients were screened during a prospective multicenter study. Among the screened specimens, samples from 53 patients (22.9%) were positive for P. falciparum malaria by microscopy and/or PCR. While the test kit based on the detection of HRP-2 performed with a sensitivity of 92.5% and a specificity of 98.3%, the kit for the detection of pLDH showed a sensitivity of 88.5% and a specificity of 99.4%. Dipstick tests have the potential of enhancing speed and accuracy of the diagnosis of P. falciparum malaria, especially if nonspecialized laboratories are involved.

Biomarkers↗
PubMed1999

Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children.

In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.

Alleles↗
PubMed1999

Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in Uganda: correlation with polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes.

The efficacy of sulfadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Africa is increasingly compromised by development of resistance. The occurrence of active site mutations in the Plasmodium falciparum gene sequences coding for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) is known to confer resistance to pyrimethamine and sulfadoxine. This study investigated the occurrence of these mutations in infected blood samples taken from Ugandan children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results confirm the occurrence of mutations in DHFR and DHPS that were significantly selected under S/P pressure at day 7: a combination of alleles 51-isoleucine and 108-asparagine in DHFR, and 436-serine, 437-alanine, 540-lysine and 581-alanine in DHPS, appears to play a major role in the development of in vivo resistance in P. falciparum strains against S/P. Therefore, earlier results derived from isolates from hyperendemic areas in Tanzania were confirmed by this investigation.

Animals↗