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Nowadays, bortezomib, a proteasome inhibitor, is widely used in treatment of newly diagnosed or relapsed multiple myeloma. The aim of this study was to analyze efficiency of bortezomib retreatment in patients with relapsed or refractory multiple myeloma. From 2004 to 2016, 283 patients were retrospectively evaluated at all hematological centers in the Czech Republic. Bortezomib was administered at the standard dosing and in combined therapy with corticosteroids, chemotherapy or thalidomide. Before bortezomib retreatment, 61% of patients received previous lenalidomide treatment, 40.6% autologous transplantation, and median number of prior lines of therapy was three. In total, 21% of patients were refractory to the first bortezomib treatment. In bortezomib retreatment, overall response rate was 34.5%, median progression-free survival was 7.8 months (95% CI: 6.7–8.9), median duration of response was 10.5 months (95% CI: 8.0–13.0) and median overall survival was 20.3 months (95% CI: 17.9–22.7). Grade 3-4 adverse events included thrombocytopenia, neutropenia, anemia and infection. Neuropathy grade 2 or higher occurred in 19.4% of patients. We conclude that bortezomib retreatment is an effective and safe therapeutic alternative for relapsed or refractory multiple myeloma patients. [ABSTRACT FROM AUTHOR]

Lenalidomide (LEN) is an immunomodulator with clinical activity against myeloma cells. Based on the pivotal phase 3 trials MM-009 and MM-010, the combination of lenalidomide and dexamethasone(DEX) was approved for patients with multiple myeloma who received at least one prior therapy. Here, we evaluated LEN/DEX therapy in whole population and subsequently in selected sub-groups of patients with relapsed/refractory multiple myeloma followed in the Monoclonal Gammopathy Registry of the Czech Myeloma Group. 858 patients were treated with LEN/DEX in Czech Republic and Slovakia until end of 2017. The analyzed sub-groups were defined as patients with high-risk cytogenetic aberrations and patients with relapsed and refractory MM. The ORR (response better than PR) in whole group of patients was 46.3% for all lines of therapy, 26.4% for high-risk group and 32.1% for relapsed and refractory group. Overall survivals (OS) in the same sets were as follows: 25.6, 15.7 and 18.5 months respectively, progression free survival (PFS) was 11.2, 6.4 and 9.0 months, respectively. The most common adverse events were hematologic and infectious. In conclusion, we found our results correlated with those in other studies in terms of OS, PFS and also of treatment toxicity. [ABSTRACT FROM AUTHOR]

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Proteasome inhibitors are the backbone in the treatment of multiple myeloma with 3 of its representatives (bortezomib, carfilzomib, and ixazomib) having already been approved. There is a different situation altogether in the treatment of amyloid light chain (AL) amyloidosis where owing to the rarity of this entity neither of these drugs has currently gained approval. Amyloid light chain plasma cells are possibly more vulnerable to bortezomib than myeloma plasmocytes because of a slightly distinct mechanism of action, which is described in depth in this manuscript. Bortezomib is highly active and rapidly effective as a single agent and even more potent in combination with dexamethasone and alkylators. Bortezomib-based regimens have become a standard part of the initial treatment of AL amyloidosis in the majority of centers. We have reviewed all available data on bortezomib in various combinations and settings. Carfilzomib seems to be effective but also toxic in these fragile patients with a high rate of cardiac events. Oral ixazomib has shown a surprisingly high efficacy with manageable toxicity and has received the Food and Drug Administration Breakthrough Therapy designation in 2014 for relapsed AL amyloidosis patients. In this review we have comprehensively described the current available knowledge of these 3 proteasome inhibitors and their use in AL amyloidosis. [ABSTRACT FROM AUTHOR]

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Copyright of Prävention und Gesundheitsförderung is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The erythrocyte binding antigen 175 kDa (EBA-175) gene is located on chromosome 7. It encodes protein that binds to specific receptor glycophorin A on the erythrocyte surface during invasion. It has a dimorphic nature (FCR3 and CAMP). This study was designed to determine the distribution of EBA-175 alleles of Plasmodium falciparum in the southeast of Iran Methods: We used the nested PCR method with specific primers, which improves the two fragments of the EBA-175 gene. Sixty eight microscopically positive blood samples were collected from the infected falciparum malaria subjects in the southeast of Iran. Results: In this study which marks the first one in Iran, CAMP strains (714 bp) and FCR-3 strains (795 bp) were found in 14 (37.8%) and 23 (62.2%) in the originally Iranian subjects and in 10 (32.3%) and 19 (61.3%) Pakistani infected migrants respectively. Two migrant cases (6.4%) had mix CAMP/FCR-3 infection. Conclusion: The two fragments of dimorphic EBA-175 gene were observed and the FCR-3 allele was more prevalent in Iran. There was no significant correlation between one of the EBA-175 alleles and the subject group in the mentioned region. This distributional pattern should be considered in designing to control P. falciparum malaria in the region. [ABSTRACT FROM AUTHOR]

Background: A survey was designed to assess travelers' willingness to take antibiotic chemoprophylaxis against travelers' diarrhea (TD) or to intervene with antibiotic or symptomatic treatments. Methods: A brief written questionnaire was administered to clients in North American (United States and Canadian) and European (UK and German) travel clinic waiting rooms to assess length, purpose, and destination of their upcoming trips; their perceived risk of developing TD at their destination; and their preferences for hypothetical treatment or chemoprophylaxis options, which included descriptions, but no mention of brand names, of a systemically absorbed antibiotic based on a fluoroquinolone, a nonabsorbed antibiotic based on rifaximin, and an over-the-counter antidiarrheal similar to loperamide. Results: The 209 UK and German travelers planned significantly longer travel than the 277 US and Canadian travelers (25 vs 15 d, p < 0.001) and correctly recognized high risk of TD more often than the North Americans (81% vs 61%, p < 0.001). More of the North Americans preferred any therapy options compared with the Europeans; only 14% of the North Americans preferred no treatment compared with 29% of the Europeans (p < 0.001). More of the North Americans and the Europeans preferred the nonabsorbed antibiotic than the systemically absorbed antibiotic, regardless of if combined with the antidiarrheal agent. Significantly more of the Europeans preferred not to take antibiotic chemoprophylaxis than North Americans (66% vs 37%, p < 0.001). Among the North Americans, significantly more travelers preferred chemoprophylaxis with the nonabsorbed than the systemic antibiotic (45% vs 33%, p= 0.003). Conclusions: Among the relatively small groups of travelers studied, the UK and German travelers were more cognizant of TD risk than US and Canadian travelers. The Europeans were less inclined to take chemoprophylaxis or treatment. Both groups preferred treatment or prophylaxis with the nonabsorbed antibiotic over the systemically absorbed antibiotic or the antidiarrheal agent. [ABSTRACT FROM AUTHOR]

Background. Japanese encephalitis (JE) is the most important mosquito-borne viral encephalitis and has a high case fatality rate. It is caused by Japanese encephalitis virus. Improved vaccines are urgently needed for residents in countries of endemicity, travelers, and the military. The aim of the present trial was to evaluate the safety and tolerability of IC51, Intercell's Vero cell- derived, purified, inactivated JE vaccine. Methods. This was a randomized (3:1), double-blind, placebo-controlled, multicenter phase 3 trial. Healthy subjects were randomized to receive 2 doses of IC51 (n = 2012) or placebo (n = 663) at a 4-week interval. Adverse events following immunization (AEFI) were documented over a period of 2 months. Results. The rate of severe AEFI was similar in the IC51 group (0.5%) and the placebo group (0.9%). The rate of medically attended AEFI and all AEFI was also similar in the IC51 group and the placebo group. The same applied for all adverse events, including local and systemic tolerability. Importantly, there were no signs of acute allergic reactions. Conclusion. The Intercell JE vaccine IC51 had a safety profile similar to that of placebo. These data, together with the immunogenicity data from a recent phase 3 trial, form the basis of application for licensure of this vaccine. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic features of tick typhus among German travelers has not been surveyed recently.Methods: Clinical features, travel and medical histories in 78 patients with tick typhus who presented to a German outpatient clinic for Infectious and Tropical Diseases were investigated, in order to identify common epidemiological factors and potential strategies of prevention. Diagnosis was confirmed by serological detection of IgG- and IgM-antibodies to Rickettsia conorii by indirect immunofluorescence.Results: The majority of patients (71.8%) had visited southern Africa prior to presentation. All patients presented with fever as the main symptom. An eschar was still present in 68 patients (87.2%) with regional lymphadenitis in 19.2%. However, only a minority of patients (17.9%) remembered a tick bite at the location of the eschar.Conclusion: Efforts to reduce the incidence of tick typhus in travelers should focus on preventive measures targeting behavioral changes. Avoiding tick bites during travel to endemic areas appears to be the single most important prophylactic action. Taking this into consideration, it should be possible to decrease the number of travelers returning with tick typhus significantly by adequate pretravel counseling. [ABSTRACT FROM AUTHOR]

Analysis of malaria imported into eight European countries from the Indian sub-continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus statement on the use of chemoprophylaxis within TropNetEurop. The proportion of cases from the ISC in 2004 ranged from 1.4%-4.6% of total imported cases. Plasmodium falciparum cases reported from the eight countries was only 23 (13% of all cases from the region). Total malaria reports between 1999-2004 fell from 317 to 180. The risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed. The group recommended non-selective prescribing of chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should be dropped. [ABSTRACT FROM AUTHOR]

Background: Traveling to tropical regions is related to increased health risks. Travelers' diarrhea is the most frequent health problem, but the range of travel-related diseases also includes potential life-threatening diseases such as malaria. The actual risk of European travelers acquiring specific infectious diseases and other hazards in the tropics is to a large extent unknown and is therefore often adopted from that of the indigenous population. The objective of this study was to elucidate the risk for travel-related diseases, symptoms, and accidents in a population of Europeans who travel to popular tourist destinations.Methods: From July 2003 to June 2004, 794 travelers consulting the travel clinic of the Berlin Institute of Tropical Medicine were recruited for a questionnaire-based observational study before traveling to Kenya, Tanzania, Senegal, the Gambia, India, Nepal, Thailand, or Brazil.Results: Overall, illness was reported by 42.9% of travelers, with 10.2% reporting more than one adverse health event. Most frequently gastrointestinal symptoms were noted (34.6%), followed by respiratory symptoms (13.7%). More than 5% experienced an accident. Travel to the Indian subcontinent nearly doubled the risk of becoming ill; travel to Thailand significantly decreased the risk. Additional risk factors were a long duration of staying abroad, young age, and traveling under basic conditions. Of all travelers, 80% did not follow the traditionally recommended dietary restrictions. Among travelers visiting malaria-endemic areas, 20% did not carry any antimalarial drugs with them, not continuous chemoprophylaxis or standby medication.Conclusions: Because of the rising travel activity, especially to tropical countries, the importance of qualified pretravel advice consultation is increasing. To improve the travelers' health, attention needs to be paid to individual risk factors, the prevention and therapy of travelers' diarrhea, malaria prophylaxis, management of respiratory illness, and personal safety. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a rare, non-notifiable disease in Germany. Epidemiological and clinical data, therefore, are scarce. Most infections seen in Germany are contracted outside the country. The German surveillance network for imported infectious diseases (Surveillance Importierter Infektionen in Deutschland, or SIPMID) recorded 42 cases of imported leishmaniasis (16 visceral, 23 cutaneous, and 3 mucocutaneous) from January 2001 to June 2004. Although most infections were acquired in European Mediterranean countries, the risk of infection was highest for travelers to Latin America. HIV coinfection was observed significantly more often in patients with visceral leishmaniasis than in patients with cutaneous/mucocutaneous leishmaniasis (31 vs. 4%, p=0.02). The median time to a definitive diagnosis was 85 days in cases of visceral leishmaniasis and 61 days in cases of cutaneous/mucocutaneous leishmaniasis, reflecting the unfamiliarity of German physicians with leishmanial infections. Visceral leishmaniasis was treated most frequently with amphotericin B, whereas cutaneous/mucocutaneous leishmaniasis was treated with a variety of local and systemic therapies. The findings presented here should serve to increase awareness as well as improve clinical management of leishmaniasis in Germany. [ABSTRACT FROM AUTHOR]

Describes three of the 17 malaria cases in Dominican Republic resort areas in 2004, and summarizes the overall investigation, which led to expansion of U.S. Centers for Disease Control and Prevention recommendations for chloroquine prophylaxis to include all of La Altagracia and Duarte provinces. Epidemiologic investigations conducted; Prevention and control measures taken; Recommendations for travellers to prevent mosquito bites.

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. [ABSTRACT FROM AUTHOR]

The article presents data from the first 3 years of sentinel surveillance for imported schistosomiasis in Europe from the European Network on Imported Infectious Diseases Surveillance (TropNetEurop). An analysis of reports for epidemiologic and clinical features to generate valid data on imported infectious diseases is tackled. It reveals the difference of the pattern of regions where immigrants contracted schistosomiasis from the spatial distribution of schistosomiasis foci in endemic areas.

Background: Schistosomiasis is a major parasitic disease, increasingly imported into temperate climates by immigrants from and travelers to endemic areas.Method: To generate valid data on imported infectious diseases to Europe and to recognize trends over time, the European Network on Imported Infectious Diseases Surveillance (TropNetEurop) was founded in 1999. Three hundred and thirty-three reports of schistosomiasis were analyzed for epidemiologic and clinical features.Results: Male patients accounted for 64% of all cases. The average age of all patients was 29.5 years. The majority of patients were of European origin (53%). Europeans traveled predominantly for tourism (52%). Main reasons for travel for people from endemic areas were immigration and refuge (51%) and visits to relatives and friends (28%). The majority of infections were acquired in Africa; 92 infections were clearly attributable to Schistosoma haematobium, 130 to Schistosoma mansoni, and 4 to Schistosoma intercalatum. Praziquantel was the only treatment used. No deaths were recorded.Conclusion: TropNetEurop sentinel provides valuable epidemiologic and clinical data on imported schistosomiasis to Europe. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a major parasitic disease, increasingly imported into temperate climates by immigrants from and travelers to endemic areas. Method: To generate valid data on imported infectious diseases to Europe and to recognize trends over time, the European Network on Imported Infectious Diseases Surveillance (TropNetEurop) was founded in 1999. Three hundred and thirty three reports of schistosomiasis were analyzed for epidemiology and clinical features. Results: Male patients accounted for 64% of all cases. The average age of all patients was 29.5 years. The majority of patients were of European origin (53%). Europeans traveled predominantly for tourism (52%). Main reasons for travel for people from endemic areas were immigration and refuge (51%) and visits to relatives and friends (28%). The majority of infections were acquired in Africa; 92 infections were clearly attributable to Schist soma haematobium, 130 to Schist soma mansoni ,and 4 to Schistosoma intercalatum. Praziquantel was the only treatment used. No deaths were recorded. Conclusion: TropNetEurop sentinel provides valuable epidemiologic and clinical data on imported schistosomiasis to Europe. [ABSTRACT FROM AUTHOR]

Reevaluates previous findings indicating that age is a risk factor for severe falciparum malaria in nonimmune patients. Association of antimalarial chemoprophylaxis with a lower-case-fatality rate and a lower frequency of cerebral complications; Evidence that falciparum malaria is more serious in older patients.

Background: Due to time constraints imposed by pending departure dates of travelers, the application of multiple vaccinations is commonly practiced in pretravel counseling. However, data regarding the tolerability of schedules with simultaneous vaccinations with different products are sparse.Method: In order to investigate effects of this practice, a prospective study was conducted with 1,183 healthy travelers who presented prior to their departure. Standardized questionnaires covering possible side effects were collected during and after vaccination.Results: Results showed an increase of the overall frequency of side effects with an increasing number of simultaneously applied vaccines. In travelers with two or more vaccinations, side effects occurred less frequently than previously published. In double vaccinations, side effects occurred in 36.7% of vaccinees, triple vaccinations in 40.3%, in more than three vaccinations in 50.0%. Subjective rating by the vaccinees showed an excellent tolerability of multiple vaccinations.Conclusion: Multiple vaccines can be given at the same time with limited subjective side effects. These findings may increase the acceptability of vaccinations given in combination to travelers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Circumsporozoite (CS) antibodies are a reliable serological marker for the infection of Plasmodium falciparum. The purpose of this investigation was to construct and evaluate an enzyme-linked immunosorbent assay test for the detection of CS antibodies. While the sensitivity of the newly developed test reached 78%, the specificity was 99%. In addition, the optimized kit was used to test for infection with P. falciparum in 1903 travellers that were recruited from a prospective study for malaria chemoprophylaxis. Sixty-six of the 1903 patients (3.5%) showed elevated CS antigen antibody titres. However, seroconversion could only be demonstrated in 18 (0.95%) patients. Among those seroconverting, there was a significantly higher percentage of male travellers (1.28%) than female travellers (0.56%). Positive reactions were more frequent among returnees from West and East Africa (1.49 and 1.14%, respectively) than among those from other endemic areas, e.g. South America (n=0). Despite its limited sensitivity, this newly developed kit for CS antibody testing may be a valuable tool for the estimation of the risk for travellers in malarious regions to acquire an infection with P. falciparum. It may also be useful for the determination of the efficacy of malaria chemoprophylaxis for inhibiting outbreak of disease. [ABSTRACT FROM AUTHOR]

Summarizes the results from the first two years of sentinel surveillance for imported malaria by the European Network on Imported Infectious Disease Surveillance which was founded in February 1999. Number of patients reported with falciparum malaria; Factors that determine the incidence of imported cases of malaria; Signs and symptoms in European travelers and immigrants with falciparum malaria.

This study was conducted to investigate the predictive value of blood eosinophilia (total white blood cell count with 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 like-lihood of the presence of helminth infections increases con-siderably with the extent of eosinophilia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1α, IL-1β and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1β 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-α 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-α or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-α 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-1β (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-1β and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1β were significantly... [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The symptoms, medical history, and treatment of 98 patients with cutaneous larva migrans (creeping eruption) who attended a travel-related-disease clinic during a period of 4 years are reviewed. This condition is caused by skin-penetrating larvae of nematodes, mainly of the hookworm Ancylostoma braziliense and other nematodes of the family Ancylostomidae. Despite the ubiquitous distribution of these nematodes, in the investigated group only travelers to tropical and subtropical countries were affected; 28.9% of the patients had symptoms for >1 month, and for 24.5% the probable incubation period was >2 weeks. The efflorescences typically were on the lower extremities (73.4% of all locations). The buttocks and anogenital region were affected in 12.6% of all locations, and the trunk and upper extremities each were affected in 7.1%. Only a minority of patients presented with eosinophilia or an elevated serum level of IgE. No other laboratory data appeared to be related to the disease. Therapy with topical thiabendazole was successful for 98% of the patients. Systemic antihelmintic therapy was necessary in two cases because of disseminated, extensive infection. [ABSTRACT FROM PUBLISHER]

In order to identify the prevalence of Entamoeba histolytica in tourists with diarrhoea returning from countries of the developing world, sensitivity and specificity of a commercially available enzyme immunoassay (EIA) kit for the detection of Entamoeba histolytica coproantigen in stool were evaluated. Five hundred seventy-seven specimens from 469 patients were examined by microscopy and EIA. Sixty-two specimens from 49 patients were considered positive for Entamoeba histolytica. Compared with microscopic examination of stool samples, the EIA was found to be slightly more sensitive (90.3% vs. 87.1%) and was 97.7% specific for Entamoeba histolytica. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]