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Biomedical subjects

T Jelinek

Publications and source records attributed to T Jelinek.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1998

Effectiveness of chemoprophylaxis and other determinants of malaria in travellers to Kenya.

OBJECTIVE: To investigate the effectiveness of chemoprophylaxis and the determinants of malaria importation from Kenya. METHOD: In a population-based case-control study, 51 travellers from Bavaria diagnosed with falciparum malaria imported from Kenya (cases) and a sample of 383 healthy Bavarian travellers returning from Kenya (controls) were interviewed. Data were analysed by multiple logistic regression. RESULTS: Mefloquine (OR = 0.055; 95% CI 0.019-0.16) and chloroquine combined with proguanil (OR = 0.128; 95% CI 0.039-0.419) were highly protective against P. falciparum malaria, whereas other drugs were ineffective (OR = 1.225; 95% CI 0.536-2.803). Ineffective prophylaxis (10.4%) and non-prophylaxis (11.2%) were the main reasons for malaria importation. Travelling alone or with friends, male sex, and travel duration over 4 weeks could be identified as additional risk factors. The main reason for inadequate chemoprophylaxis was inappropriate medical advice (87.5%). Prophylaxis refusal occurred frequently despite correct advice (58.1%). Diagnosis was often delayed unnecessarily (27.5%). CONCLUSION: Malaria importation from Kenya could be reduced substantially (34%) by eliminating inappropriate medical advice.

Adult↗
PubMed1998

Polymorphisms in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes of Plasmodium falciparum and in vivo resistance to sulphadoxine/pyrimethamine in isolates from Tanzania.

The efficacy of sulphadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Africa is increasingly compromised by development of resistance. The occurrence of mutations associated with the active site sequence in the Plasmodium falciparum genes coding for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) is associated with in vitro resistance to pyrimethamine and sulphadoxine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results show that alleles of DHPS (436-alanine, 437-alanine and 540-lysine) were significantly reduced in prevalence on day 7 after S/P treatment. In this area, a DHPS with 436-serine, 437-glycine and 540-glutamate appears to play a major role in resistance to S/P in vivo. Evidence for the influence of mutations in the DHFR gene in this investigation is not clear, probably because of the high prevalence of 'resistance-related' mutations at day 0 in the local parasite population. For apparently the same reason, it was not possible to show a statistical association between S/P resistance and the presence of particular polymorphisms in the DHFR and DHPS genes before treatment.

Animals↗
PubMed1998

In vivo synthesis of tumor necrosis factor-alpha in healthy humans after live yellow fever vaccination.

Most knowledge about the synthesis of human tumor necrosis factor (TNF)-alpha and its regulation derives from in vitro studies. The hypothesis that the syndrome of malaise, myalgia, and low fever observed after a vaccination with live attenuated yellow fever virus could be associated with increased synthesis of TNF was investigated. Plasma samples of 15 healthy subjects taken before and until day 2 (until day 11 in 5 of these subjects) after yellow fever vaccination, showed a significant increase of plasma TNF concentration on day 2 after vaccination and a second peak on day 7. Interleukin-1 receptor antagonist (IL-1ra) concentration was significantly elevated in all subjects on day 2 after vaccination. In a control group receiving non-live vaccinations, TNF and IL-1ra concentrations were unchanged. Thus, yellow fever vaccination represents a routine medical intervention that results in a reproducible increase in the plasma concentration of TNF and secondary cytokines. This may serve as a unique model for the study of the regulation of TNF synthesis in vivo.

Adult↗
PubMed1998

Assessing the incidence of infection with Plasmodium falciparum among international travelers.

Circumsporozoite (CS) antibodies, indicating plasmodial infection but not necessarily development of disease, have been shown to be reliable indicators of transmission in endemic areas. To estimate the actual rate of plasmodial infection, the prevalence of CS antibodies was investigated by an ELISA test system in a selected population of 2,131 travelers returning from areas endemic for malaria who presented to an outpatient clinic without any apparent symptom or clinical sign of malaria. Serum specimens from 104 of the investigated 2,131 patients (4.9%) were found to be positive (titer > or = 6.25 international ELISA units [IEU]). The geometric mean titer of antibody concentrations (IEU) in seropositive patients was 18.64 IEU (95% confidence interval [CI] = 13.15-24.13), while it was 2.1 IEU (95% CI = 1.8-2.4) in seronegative patients. A significantly above average risk for plasmodial infection could be found among travelers to East Africa (risk ratio [RR] = 4.5, P < 0.001), West Africa (RR = 4.5, P < 0.001), and Southern Africa (RR = 3.2, P = 0.015), while areas with a comparatively low risk included Central America (RR = 0.86, P < 0.001), the Indian subcontinent (RR = 0.45, P = 0.015), South America (RR = 0.49, P = 0.091), East Asia (RR = 0.68, P = 0.441), West Asia (RR = 0.24, P = 0.099), and Southeast Asia (RR = 0.69, P = 0.094). The results of this study emphasize the importance of adequate malaria chemoprophylaxis in nonimmune travelers to endemic areas. By use of the described method, estimates of the true infection rate of malaria in travelers can be derived for certain areas and the value of prophylactic measures can be demonstrated.

Adolescent↗
PubMed1998

Evidence of dengue virus infection in a german couple returning from hawaii

Dengue is an acute, mosquito-transmitted viral disease characterized by fever, arthralgia, myalgia, rash, nausea, and vomiting and caused by any of four different serotypes of the virus (DEN-1, DEN-2, DEN-3, and DEN-4).1 The disease is endemic in most tropical areas of the world and has been reported in international travelers returning from such areas.2 The incidence of epidemic and endemic dengue has increased substantially in the Americas since 1977, and various epidemics have occurred.1-4

Journal Article↗
PubMed1997

Prevalence of infection with dengue virus among international travelers.

BACKGROUND: Dengue has been recognized as a potential hazard to tourists. A prospective, controlled study in the outpatient clinic of a German infectious disease clinic was conducted to assess the prevalence of dengue virus infection among international travelers. METHODS: Serum samples from 130 patients with signs or recent history clinically compatible with dengue (fever, headache, muscle and joint pain, or rash), 95 matched controls with diarrhea, and 26 patients who never visited a country endemic for dengue were investigated. RESULTS: Nine (6.9%) of the 130 patients with compatible symptoms and 1 (1%) of the 95 controls with diarrhea developed rising antibody titers against dengue virus. Of these 10 patients with probable dengue infection, 6 had been to Thailand, 2 to Malaysia, and 1 each to Indonesia and Brazil. CONCLUSIONS: Infection with dengue virus appears to be a realistic threat to travelers to Southeast Asia. Symptoms commonly associated with dengue, such as fever, myalgia, arthralgia, and vomiting, can be helpful for diagnosis when present, but the absence of typical symptoms does not exclude infection.

Acute Disease↗
PubMed1997

[Endocrinologic and metabolic complications of Alagille syndrome].

BACKGROUND: Patients with gastrointestinal and hepatobiliary disorders, either congenital or acquired early in childhood, are at high risk for various endocrine and metabolic abnormalities. CASE REPORT: A 27-year-old woman with Alagille's syndrome presented with progressive jaundice and gait disturbances following surgery and ingestion of oral contraceptives. On physical examination, short stature, facial dysmorphism and neuromuscular symptoms such as polyneuropathy and spinocerebellar ataxia were noted. Serum concentrations of total bilirubin (54 mg/dl) and alkaline phosphatase were markedly increased, whereas serum levels of haptoglobin, zinc, vitamin D and E were decreased. Although prehepatic or intrahepatic etiologies of jaundice were more likely in this patient, posthepatic etiologies were ruled out by abdominal ultrasound and endoscopic retrograde cholangio-pancreaticography. Based on a working diagnosis of acute drug-induced cholestasis, treatment with high doses of lipid-soluble vitamins and ursodeoxycholic acid was initiated. In response to therapy, her abnormal laboratory results normalized and her neurologic symptoms markedly improved. CONCLUSION: This clinicopathological conference of a patient with Alagille's syndrome illustrates the clinical presentation and therapy of metabolic and endocrine complications in chronic cholestasis.

Adult↗
PubMed1997

[Epidemiology and clinical aspects of imported schistosomiasis].

PATIENTS AND METHODS: Travel and medical histories as well as clinical features of 62 German and 21 native patients with schistosomiasis who were presented to a German outpatient clinic for infectious and tropical diseases were investigated in order to identify the risk factor leading to infection in travellers and expatriates. RESULTS: All patients were able to remember the incidents which led to a likely exposure to cercariae of schistosoma spp. Fifty-nine German patients (95%) acquired infection in Africa, 2 (3%) in South America and one each (2% each) in the Euphrat and the Mekong River, respectively. All but 1 native patients acquired infection in Africa. The highest proportion of infection (45% in Germans and 37% in native patients) was imported from West Africa. Patients returning from this area had had either contact with tributaries of the Niger or with waters of the Volta River, notably the Lake Volta and/or its delta. The most sensitive method for detection of schistosomiasis appeared to be a combination of thorough travel history and serological testing (IHA, IFAT and ELISA) of all patients with possible infection. CONCLUSIONS: In the investigated group, most infections were acquired by travellers on a lengthy and adventurous journey or by expatriates venturing outside their normal areas of activity. Most patients knew that they travelled in an area endemic for schistosomiasis but were uninformed about the risks they took with their behaviour in a specific setting. Others simply could not avoid skin exposure to freshwater like backpacking tourists travelling in boats on the Niger or Congo River and native patients. Travellers to the tropics should therefore be informed thoroughly about the dangers of water-related diseases such as schistosomiasis.

Adult↗
PubMed1997

The role of Blastocystis hominis as a possible intestinal pathogen in travellers.

The role of Blastocystis hominis as a pathogen for man has been controversially discussed, while travel history has been implicated as a risk factor of infection. Few controlled studies of the association between B. hominis and symptomatic diseases have been performed. Therefore, a case-control study among 795 German tourists returning from tropical countries was conducted. The prevalence of the organism among patients with and without symptoms was assessed. Blastocystis hominis was detected in 69 of 469 (14.7%) patients with diarrhoea and in 21 of 326 (5.7%) controls. However, other organisms causing diarrhoea were detected in 18 of the 69 (26.1%) symptomatic patients with B. hominis. Thus, 51 of 469 (10.8%) symptomatic patients had B. hominis in the absence of other pathogens in their stool, significantly more than in the asymptomatic group (5.2%; P = 0.005). Irrespective of the development of symptoms, the organism was most frequently acquired during journeys to the Indian subcontinent. The results of this study suggest that B. hominis is associated with development of diarrhoea in travellers to tropical destinations and that frequently concurrent infections with other organisms occur.

Animals↗
PubMed1997

High prevalence of mutations in the dihydrofolate reductase gene of Plasmodium falciparum in isolates from Tanzania without evidence of an association to clinical sulfadoxine/pyrimethamine resistance.

Recently the efficacy of sulfadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Tanzania has been seriously compromised by the development of resistance. The occurrence of active site mutations in the Plasmodium falciparum gene sequence coding for dihydrofolate reductase (DHFR) is known to confer resistance to pyrimethamine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results confirm the occurrence of one or more DHFR mutations in all the samples, but no relationship was found with the presence of parasites in the blood at day 7. The results suggest that alterations in the coding region for dihydropteroate synthetase (DHPS), the enzyme target for sulfadoxine, should be studied in order to predict resistance to the S/P combination. It has been proposed earlier that sulfadoxine could itself act on DHFR, because of a false dihydrofolate produced by drug metabolism through DHPS and dihydrofolate synthase. The results of this treatment study suggest that such a possibility is unlikely.

Animals↗
PubMed1997

Prevalence of infection with Cryptosporidium parvum and Cyclospora cayetanensis among international travellers.

BACKGROUND: Cryptosporidium parvum and Cyclospora cayetanensis are recognised as possible pathogens of traveller's diarrhoea. AIMS: To identify the prevalence of C parvum and Cyc cayetanensis in travellers returning from developing countries. PATIENTS: Nine hundred and seventy eight stool samples wer taken from 795 patients returning from developing countries. METHODS: Microscopy (iron-haematoxylin stain, SAF concentration, modified acid fast stain) and a commercially available enzyme linked immunosorbent assay (ELISA) kit for the detection of Cryptosporidium antigen in stool. RESULTS: Of the 795 patients in the study, 469 suffered from diarrhoea. Infection with Cyc cayetanensis could be detected in five subjects (1.1%) by acid fast stain, and 13 patients (2.8%) were infected with C parvum. On evaluation, the antigen capture ELISA turned out to be clearly less sensitive for detection of C parvum than microscopy. All patients with either C parvum or Cyc cayetanensis infection suffered from watery diarrhoea. CONCLUSIONS: C parvum and Cyc cayetanensis are not major causes of diarrhoea in international travellers. In cases of persistent watery diarrhoea, however, these pathogens should be taken into account in the differential diagnosis.

Animals↗