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Biomedical subjects

T Jelinek

Publications and source records attributed to T Jelinek.

At least 37 records · Page 2Linked to original sources

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↗

Patterns of Plasmodium falciparum drug resistance in nonimmune travellers to Africa.

Falciparum malaria is a major cause of morbidity and mortality among tourists returning from endemic areas. Treatment of infected travellers is frequently standardised, and resistance tests are rarely done as they are difficult to perform and interpret. In vitro tests of resistance to chloroquine, mefloquine, quinine, halofantrine, tetracycline, and sulfadoxine/pyrimethamine were performed on Plasmodium falciparum isolates obtained from 52 German travellers returning from malarious areas in sub-Saharan Africa. All patients were treated successfully with a standard dose of mefloquine. No in vivo resistance was observed. Although 20 (38.5%) isolates showed no signs of in vitro resistance, the remaining 32 (61.5%) were resistant to at least one of the tested antimalarial agents. Of these 32 isolates, 11 were multiresistant. Resistance to chloroquine was most frequently observed (55.8%), followed by sulfadoxine/pyrimethamine (11.5%), mefloquine (9.6%), quinine (3.8%), and halofantrine (1.9%). In vitro resistance to tetracycline was not detected in this study group. Treatment of falciparum malaria without resistance testing appears to be effective in most cases, but possible therapeutic failure due to emerging drug resistance should be kept in mind.

Adolescent↗

Detection of Giardia lamblia and Entamoeba histolytica in stool samples by two enzyme immunoassays.

Two commercially produced enzyme immunoassays (EIAs) to detect antigens of Giardia lamblia and Entamoeba histolytica in stool specimens were evaluated. A total of 276 stool specimens were collected from patients who presented with various medical complaints in the outpatient clinic of the Department of Infectious Diseases and Tropical Medicine, University of Munich. Every specimen was examined by conventional microscopy and tested by both EIA kits. When microscopy was used as the reference standard, the EIA kit detecting Giardia lamblia showed a sensitivity of 100% and a specificity of 99.6%. The EIA kit detecting Entamoeba histolytica had a sensitivity of 81.8% and a specificity of 99.2%. Both tests showed no cross-reactivity with other intestinal protozoa. Antigen detection by EIA has the potential to become a valuable tool capable of making stool diagnostics more effective, although it should not be considered as a replacement for microscopic examination, since other potential pathogens could otherwise escape detection.

Animals↗

Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1beta after live yellow fever vaccination.

The inflammatory response in infectious and autoimmune diseases is regulated by the balance between pro- and anti-inflammatory cytokines. The IL-1 complex contains polymorphic genes coding for IL-1alpha, IL-1beta and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1beta and IL-1Ra after in vitro stimulation. Allele 2 of this polymorphism is associated with a number of inflammatory diseases. To determine the impact of the IL-1Ra polymorphism on in vivo human cytokine synthesis, we used a yellow fever vaccination model for the induction of cytokine synthesis in healthy volunteers. Two different yellow fever vaccines were used. After administration of the RKI vaccine (34 volunteers), plasma TNF-alpha concentration increased from 13.4 +/- 0.9 pg/ml to 23.3 +/- 1.1 pg/ml (P < 0.001), and plasma IL-1Ra concentration increased from 308 +/- 25 pg/ml to 1019 +/- 111 pg/ml (P < 0.001), on day 2. Using Stamaril vaccine, no increase in the plasma concentrations of either TNF-alpha or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-alpha synthesis after in vitro stimulation of MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline concentrations of IL-1Ra (350 +/- 32 pg/ml) compared with non-carriers (222 +/- 18 pg/ml, P < 0.001), and decreased concentrations of IL-1beta (0.9 +/- 0.2 pg/ml for carriers versus 2.8 +/- 0.7 pg/ml for non-carriers, P = 0.017). After yellow fever vaccination (RKI vaccine), no significant differences in the increase of IL-1Ra plasma levels were detected between carriers and non-carriers of allele 2 of the IL-1Ra gene polymorphism. This is the first study to examine the influence of this genetic polymorphism on in vivo-induced human IL-1beta and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1beta were significantly influenced by the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo-induced production of IL-1Ra and IL-1beta could be detected.

Adolescent↗

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↗

Prevalence of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum isolates from southern Mauritania.

The increasing resistance of Plasmodium falciparum in the treatment of uncomplicated malaria with pyrimethamine/sulphadoxine has been associated in several studies with the occurrence of point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). In this study, the prevalence of these mutations was examined in samples from south-east Mauritania, where atypically strong rainfalls in 1998 and 1999 led to a severe outbreak of falciparum malaria. We analysed 386 samples by polymerase chain reaction (PCR) for infection with P. falciparum, of which 162 (41.97%) were positive. These isolates were examined for point mutations in the genes of DHFR (codons 16, 51, 59, 108 and 164) and DHPS (codons 436, 437, 540, 581 and 613) by nested PCR and subsequent mutation-specific restriction enzyme digest. We found a low overall prevalence of DHFR gene mutations (up to 18.6% of isolates), but a high overall prevalence of DHPS gene mutations (up to 49.1% of isolates). Thus, emerging resistance to antifolate drugs may be expected to develop soon in the investigated area. This study demonstrates the utility of simple, relatively rapid and inexpensive molecular methods and their application in surveillance programmes. Testing for prevalence of point mutations conferring antifolate resistance might help to identify the developing of drug resistance at a very early stage.

Adolescent↗

Population structure of Plasmodium falciparum isolates during an epidemic in southern Mauritania.

While the population structure of Plasmodium falciparum is well analysed in selected areas with high malaria endemicity in East and West Africa, only limited data are available for low endemicity regions bordering the Saharan desert. This is one of the first studies for the Sahel, where atypically strong rainfalls in 1998 and 1999 led to a severe outbreak of falciparum malaria in south-east Mauritania. During a study on in vivo-drug resistance against chloroquine we collected blood samples of patients with fever in two medical centres located in non-endemic and hypoendemic areas. We analysed 386 samples by polymerase chain reaction for infection with P. falciparum, and 173 (45%) tested positive. The isolates were genotyped for three polymorphic genetic markers: merozoite surface protein 1 (MSP1), MSP2 and glutamate-rich protein (GLURP). Differences between the two regions could be shown in either number of clones per infection or in their distribution on the different allelic groups. While the mean minimal number of clones in the non-endemic region around Aioun was 1.57, blood samples collected in the hypoendemic region around Kobeni showed multiple infections with an average of 2.34 clones (P < 0.001). In addition, clear differences between endemic regions were apparent in three of the investigated allelic groups: RO33 of the MSP1 gene and FC and Indochina of the MSP2 gene.

Adolescent↗

Evaluation of a dipstick test for the rapid diagnosis of imported malaria among patients presenting within the network TropNetEurop.

Lack of experience on the part of involved laboratory personnel frequently complicates swift diagnosis of imported falciparum malaria in non-endemic areas. Diagnostic tools based on the dipstick principle for the detection of plasmodial histidine-rich protein 2 have been marketed for several years and have been extensively evaluated. Recently, a test kit capable of detecting antigen of Plasmodium falciparum and P. vivax has been introduced. In order to evaluate this newly available tool, specimens from 664 patients were screened during the course of a prospective multicentre study within the European Network on Imported Infectious Disease Surveillance (TropNetEurop). Among the screened specimens, samples from 82 patients (12.3%) were positive for falciparum malaria using expert microscopy. A further 17 samples were positive for vivax malaria. The evaluated test kit performed with a sensitivity of 87.8% and a specificity of 99% for detection of falciparum malaria. Respective values for vivax malaria were 76.5% and 100%. Dipstick tests have the potential of improving the speed and accuracy of the diagnosis of falciparum malaria, especially if non-specialized laboratories are involved. However, decreased values of sensitivity and specificity, in comparison with expert microscopy, still impose a clear limit on the usefulness of the currently available kits.

Antibodies, Protozoan↗

Dengue fever in international travelers.

Dengue virus infection is becoming increasingly recognized as one of the world's major emerging infectious diseases. Although only a few systematic studies have been conducted to assess the incidence and clinical course of dengue fever in travelers, it is now possible to estimate risk factors for travelers to areas of endemicity. Dengue virus and its vector, Aedes mosquitoes, benefit from human habitation and travel-related aspects of human behavior. Thus, travelers serve an important double role as potential victims of the disease and as vehicles for further spread of dengue.

Animals↗

Influence of rheumatoid factor on the specificity of a rapid immunochromatographic test for diagnosing dengue infection.

In order to determine the influence of rheumatoid factor in serum specimens on the specificity of an immunochromatographic test for the detection of antibodies against dengue virus, 50 clinical specimens containing rheumatoid factor were evaluated for cross reactivity with a commercially available assay. While specificity for the detection of immunoglobulin (Ig) G antibodies was 100%, the IgM component of the test showed false-positive results in 26% of cases. Thus, it is important to consider interference by rheumatoid factor when using immunochromatographic assays for the detection of specific IgM produced during dengue infection.

Antibodies, Viral↗

Correlation of in vivo-resistance to chloroquine and allelic polymorphisms in Plasmodium falciparum isolates from Uganda.

The efficacy of chloroquine in the treatment of uncomplicated falciparum malaria in Africa is heavily compromised by high levels of drug resistance. The occurrence of active site mutations in the Plasmodium falciparum multi drug resistance-gene 1 (pfmdr1) has been associated with development of resistance to chloroquine. This study investigates the occurrence of several mutations at codons 86, 1042 and 1246 of the pfmdr1-gene in infected blood samples taken from Ugandan children before treatment with chloroquine and their relationship to clinical and parasitological resistance. Even though a clear association of CQR to one certain pfmdr1 single point mutation could not be substantiated, the frequency of resistance was consistently higher for samples revealing any of the mutations than among wild type samples, and 90% of the clinically resistant samples did present a mutation. Thus detection of these allelic pfmdr1 polymorphisms is not a decisive factor for prediction of clinical chloroquine resistance, but an interplay of the different mutations with unknown cofactors is to be assumed and the possible role of other genetic alterations remains to be investigated.

ATP-Binding Cassette Transporters↗

Self-use of rapid tests for malaria diagnosis by tourists.

In a survey among febrile European tourists in Kenya, only 68% were able to carry out immunochromatographic dipstick tests for detection of Plasmodium falciparum antigen correctly, and ten of 11 with malaria failed to diagnose themselves correctly. Rapid tests for self-diagnosis by tourists cannot be recommended without appropriate training before departure.

Female↗

Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display.

The 14-3-3 proteins interact with diverse cellular molecules involved in various signal transduction pathways controlling cell proliferation, transformation, and apoptosis. To aid our investigation of the biological function of 14-3-3 proteins, we have set out to identify high-affinity antagonists. By screening phage display libraries, we have identified a set of peptides which bind 14-3-3 proteins. One of these peptides, termed R18, exhibited a high affinity for different isoforms of 14-3-3 with estimated K(D) values of 7-9 x 10(-)(8) M. Recognition of multiple isoforms of 14-3-3 suggests the targeting of R18 to a structure that is common among 14-3-3 proteins, such as the conserved ligand-binding groove. Indeed, mutations that alter critical residues in the ligand-binding site of 14-3-3 drastically decreased the level of 14-3-3-R18 association. R18 efficiently blocked the binding of 14-3-3 to the kinase Raf-1, a physiological ligand of 14-3-3, and effectively abolished the protective role of 14-3-3 against phosphatase-induced inactivation of Raf-1. The cocrystal structure of R18 in complex with 14-3-3zeta revealed the occupancy of the general binding groove of 14-3-3zeta by R18, explaining the potent inhibitory effect of R18 on 14-3-3-ligand interactions. Such a well-defined peptide will be an effective tool for probing the role of 14-3-3 in various signaling pathways, and may lead to the development of 14-3-3 antagonists with pharmacological applications.

14-3-3 Proteins↗

[Typhus abdominalis in travelers. Headaches originating in the abdomen].

The incidence of typhoid fever in emerging countries remains high, being estimated to be 500 per 100,000 head of population. Tourists from the industrialized countries can contract the infection in particular when travelling under conditions of poor hygiene in endemic regions. The risk of contracting typhoid appears to be highest on lengthy travels on the Indian subcontinent, while short visits to Latin America or Africa appreciably less often result in an infection. Currently, two vaccines are approved for use in Germany: a live oral vaccine containing the defective S. typhi mutant Ty 21a, and a parenteral inactivated vaccine prepared from the Vi capsid antigen of S. typhi. Both vaccines are well tolerated and provide similar levels of protection. The reported protection rate for the live vaccine varies in various studies between 33 and 67%; that of the inactivated vaccine between 55 and 75%. Medical advice prior to travel should weigh up such risk factors as age, duration of the journey, destination and the nature of the journey. While vaccination is particularly recommended for travelers with one or more risk factors, it should always be pointed out that an infection is nevertheless possible. In view of the fact that immunization against hepatitis A and typhoid fever are often indicated simultaneously, the development of a combination vaccine would be desirable.

Cross-Cultural Comparison↗

[Persistent arthralgias in Ross-River-Virus disease after travel to the South Pacific].

HISTORY AND CLINICAL FINDINGS: A 57-year-old patient presented with malaise and severe persistent arthralgia of the left shoulder. He reported an acute illness with fever, generalized myalgia and arthralgias of the large joints which had started one month earlier during his flight back to Germany after a two weeks trip to the South Pacific. Physical examination showed extensive pain on palpation of the glenohumeral and acromioclavicular joints with impairment of active and passive mobility. Investigation of the cervical spine was normal. INVESTIGATIONS: Apart from elevated C-reactive protein and erythrocyte sedimentation rate levels, routine laboratory investigations were normal including negative immunodiagnostic tests for autoantibodies and various global infections that may be associated with arthritis. Immunofluorescence tests showed significant levels of specific IgM- and IgG-antibodies against Ross River virus (RRV) but not against other arboviruses endemic in the South Pacific and Australia (Dengue, West Nile, Chikungunya, Sindbis, Barmah Forest). This was confirmed by a positive RRV neutralisation test. Attempts at virus isolation and detection of viral RNA by PCR were not successful. TREATMENT AND COURSE: Symptomatic treatment with high doses of diclofenac quickly led to pain relief, and arthralgias receded within 10 days after begin of treatment. However, several bouts of arthralgia of the left shoulder and left knee occurred during a period of 4 months. CONCLUSIONS: Because of the current epidemiological situation in the South Pacific and Australia, infections by arboviruses like RRV should be considered in travellers returning from these areas with severe and persistent arthralgia of unknown origin, even in the absence of fever and other symptoms of acute infection.

Alphavirus Infections↗

Sensitivity and specificity of a rapid immunochromatographic test for diagnosis of visceral leishmaniasis.

A rapid immunochromatographic dipstick test has become available for the qualitative detection of total anti-Leishmania immunoglobulins using the recombinant K39 antigen. To evaluate the test, 96 serum specimens from patients with a variety of tropical infections were tested. Fourteen of the specimens derived from patients with parasitologically confirmed kala-azar, and all were strongly positive for antibodies to Leishmania donovani complex using the immunofluorescence test. Although all 82 samples negative by the immunofluorescence test were confirmed as negative by the dipstick assay, only 10 (71.4%) of the 14 positive samples were reactive. These results indicate that the test in its current form lacks sufficient sensitivity to be recommended as a screening tool, but it might be useful for indicating further diagnostic procedures in a clinical setting.

Animals↗