Long-term safety of replication-defective smallpox vaccine (MVA-BN) in atopic eczema and allergic rhinitis.

BACKGROUND: Availability of a safe smallpox vaccine may be necessary under certain circumstances. Use of the old life virus vaccine was associated with serious adverse events, particularly in the setting of atopic eczema (AE) and immunodeficiency. Modified virus Ankara (MVA)-BN, a highly attenuated strain of vaccinia virus, was developed for vaccination with improved safety profile. METHODS: A phase 1 study was conducted in 60 subjects without history of smallpox vaccination to gain experience with smallpox vaccination using this strain in healthy and atopic subjects. Healthy subjects, subjects with a history of AE, subjects with mild active AE and subjects with mild allergic rhinitis without AE were equally allocated into four groups. MVA-BN was injected s.c. in a dose of 108 TCID50 twice in a 4-week interval. RESULTS: No serious or unexpected adverse reactions were reported. All subjects experienced mild to moderate pain and redness at the injection site. Dermatologic examinations did not reveal any unfavourable reactions to the study medication, particularly no sign or exacerbation of eczema for as long as 196 days. All subjects seroconverted after two vaccinations and no significant difference in antibody titres between the four different groups was observed. CONCLUSIONS: A good safety profile of the MVA-BN vaccine was shown. The absence of adverse events in subjects with atopic disorders appears promising for the development of a safe smallpox vaccine for patients with AE or other atopic diseases.

Suspected new wave of muscular sarcocystosis in travellers returning from Tioman Island, Malaysia, May 2014.

In May 2014, six patients presented in Germany with a Sarcocystis-associated febrile myositis syndrome after returning from Tioman Island, Malaysia. During two earlier waves of infections, in 2011 and 2012, about 100 travellers returning to various European countries from the island were affected. While the first two waves were associated with travel to Tioman Island mostly during the summer months, this current series of infections is associated with travel in early spring, possibly indicating an upcoming new epidemic.

Infection-induced anaemia: a cross-sectional study of 14,636 German travellers aged 20-49 years.

BACKGROUND: Anaemia is a frequently diagnosed condition which can develop as a consequence of numerous factors, including infectious diseases (IDs). Travelling, especially in sub-/tropical regions, leads to an elevated risk of contracting IDs. The aim of our study was to assess the epidemiological significance of IDs in inducing anaemia among a large cohort of returned travellers. METHODS: This was a cross-sectional study in which data on 17,009 returned travellers aged 20-49 years who consulted the travel medicine clinic of the University of Munich between 1999 and 2011 were retrieved and analysed. RESULTS: Of the returned travellers, 8.3 % (6.0 % of males/10.4 % of females) were diagnosed with anaemia. The prevalence of anaemia was significantly elevated among patients of African (21.4/28.3 %) and Asian (11.6/15.7 %) origin. When the study population was restricted to the 14,636 travellers of German origin, 7.1 % of the returned travellers (4.6/9.6 %) were diagnosed with anaemia. The prevalence was significantly elevated among patients who travelled for >30 days (5.7 of males/10.6 % of females) and for male travellers visiting friends and relatives (7.7 %). However, these correlations were confounded by malaria. The prevalence of anaemia was significantly elevated only among returned travellers diagnosed with malaria (36.1 of males/26.9 % of females) and with symptomatic intestinal Entamoeba histolytica infections (30.0/33.3 %). CONCLUSION: Following the exclusion of confounding by malaria from the statistical analysis, the prevalence of anaemia was found to be significantly elevated among patients of African and Asian origin, and among patients of German origin who had travelled for >30 days, it could be mainly attributable to chronic, long-lasting causes. Although more than 550 travel-associated IDs were assessed in our study, only symptomatic intestinal Entamoeba histolytica infections and, to an even larger extent, malaria were determined to be of epidemiological significance for inducing anaemia among travellers.

Infectious diseases among travellers and migrants in Europe, EuroTravNet 2010.

To investigate trends in travel-associated morbidity with particular emphasis on emerging infections with the potential for introduction into Europe, diagnoses of 7,408 returning travellers presenting to 16 EuroTravNet sites in 2010 were compared with 2008 and 2009. A significant increase in reported Plasmodium falciparum malaria (n=361 (6% of all travel-related morbidity) vs. n=254 (4%) and 260 (5%); p<0.001), P. vivax malaria (n=51 (1%) vs. n=31 (0.5%) and 38 (1%); p=0.027) and dengue fever (n=299 (5%) vs. n=127 (2%) and 127 (2%); p<0.001) was observed. Giardia lamblia was identified in 16% of patients with acute diarrhoea, with no significant annual variation. The proportion of acute diarrhoea due to Campylobacter increased from 7% in 2008 to 12% in 2010 (p=0.001). We recorded 121 patients with pulmonary tuberculosis in 2010, a threefold increase in the proportionate morbidity from 2008 to 2010. In 2010, 60 (0.8%) cases of chronic Chagas disease, 151 (2%) cases of schistosomiasis and 112 (2%) cases of cutaneous larva migrans were reported. Illness patterns in sentinel travellers, captured by EuroTravnet, continue to highlight the potential role of travellers in the emergence of infectious diseases of public health concern in Europe and the relevance of offering medical travel advice and enforcing specific and adequate prophylaxis.

Comparative study on infection-induced thrombocytopenia among returned travellers.

BACKGROUND: Thrombocytopenia is a frequent finding among ill returned travellers and may be caused by a large number of different conditions, including infectious diseases specific or typical for tropical and subtropical regions. In order to assess the diagnostic significance of thrombocytopenia we investigated a large cohort of returned travellers. METHODS: This was a comparative study in which data collected on 19,473 returned travellers who consulted the outpatient travel clinic of the the University of Munich Hospital between 1999 and 2009 were analysed. Of these, 732 (3.8%) travellers were diagnosed with thrombocytopenia, and their data were compared with those of the remaining 18,741 travellers with normal platelet counts. RESULTS: Thrombocytopenia was significantly more frequent among patients with malaria (63%), acute human immunodeficiency virus infection (48%), dengue fever/dengue haemorrhagic fever (DF/DHF; 47%), Epstein-Barr virus infectious mononucleosis (23%), paratyphoid/typhoid fever (14%), and rickettsiosis (12%). Malaria and DF/DHF caused 25% of all cases of thrombocytopenia (platelet count <140,000/µl) and 75% of all cases of severe thrombocytopenia (platelet count <30,000/µl). Sex, age, country of origin, duration and type of travel were not significantly correlated with thrombocytopenia. The most frequent travel destinations were Asia (42%), Africa (33%), and Latin America (14%). Travellers to Sub-Saharan Africa (high risk for malaria) and to South/South-east Asia (high risk for DF/DHF) had the highest relative risk for thrombocytopenia. CONCLUSION: Platelet count among returned travellers is an essential screening parameter, as thrombocytopenia is highly correlated with important infectious diseases, particularly with malaria and DF/DHF.

Travel-related imported infections in Europe, EuroTravNet 2009.

The aim of this study was to investigate travel-associated morbidity in European travellers in 2009 in comparison with 2008, with a particular emphasis on emerging infectious diseases with the potential for introduction into Europe. Diagnoses with demographic, clinical and travel-related predictors of disease from ill returning travelers presenting to 12 core EuroTravNet sites from January to December 2009 were analysed. A total of 6392 patients were seen at EuroTravNet core sites in 2009, as compared with 6957 in 2008. As compared with 2008, there was a marked increase in the number of travellers exposed in North America and western Europe. Respiratory illnesses, in particular pandemic A(H1N1) influenza, influenza-like syndromes, and tuberculosis, were also observed more frequently. A significant increase in reported dengue cases in 2009 as compared with 2008 was observed (n = 172, 2.7% vs. n = 131, 1.90%) (p 0.002). The numbers of malaria and chikungunya cases were also increasing, although not significantly. Two deaths were recorded: visceral leishmaniasis and sepsis in a Sudanese migrant, and Acinetobacter sp. pneumonia in a patient who had visited Spain. This is the most comprehensive study of travel-related illness in Europe in 2009 as compared with 2008. A significant increase in travel-related respiratory and vector-borne infections was observed, highlighting the potential risk for introduction of these diseases into Europe, where competent vectors are present. The number of traveller deaths is probably underestimated. The possible role of the travellers in the emergence of infectious diseases of public health concern is highlighted.

Skin disorders among travellers returning from tropical and non-tropical countries consulting a travel medicine clinic.

OBJECTIVE: To evaluate the causes and risks for imported skin disorders among travellers. METHODS: Data of 34,162 travellers returning from tropical and non-tropical countries and presenting at the outpatient travel medicine clinic of the University of Munich, Germany, between 1999 and 2009 were analyzed for this study. Of these, 12.2% were diagnosed with skin disorders. RESULTS: Main destinations visited were Asia (40%), Africa (27%) and Latin America (21%). Tourism in the form of adventure travel/backpacking (47%) and package holidays (23%) was the most common purpose of travel. The leading causes of skin disorders were arthropodal (23%), bacterial (22%), helminthic (11%), protozoan (6%), viral (6%), allergic (5%) and fungal (4%). The 10 most frequently diagnosed specific skin diseases associated with specific destinations were insect bites (17%, Southern Europe), cutaneous larva migrans (8%, Asia and Latin America), cutaneous leishmaniasis (2.4%, Mediterranean Region/Middle East), dengue fever (1.5%, Asia), rickettsioses (1.3%, Southern Africa), myiasis (0.8%, Central America), filarioses (0.7%, Africa), tick bites (0.6%, Central/Eastern Europe), schistosomiasis (0.6%, Africa) and tungiasis (0.6%, Africa). Travellers in sub-Saharan Africa had the highest relative risk of acquiring skin disorders. CONCLUSION: As more than 20% of all skin disorders among returned travellers were caused by arthropods and about 50% by infectious pathogens, pre-travel consultations should include specific prophylaxis and consider the most important risk factor for the travel destination.

Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese Encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX1440 in healthy subjects: A single-blind, randomized, controlled Phase 3 study.

In travellers often several pre-departure immunizations are indicated, thus data are needed about possible interactions between vaccines. This Phase 3 study investigated the immunogenicity and safety of IC51 (JE vaccine) and HAVRIX1440 (hepatitis A vaccine) when administered alone or concomitantly to healthy subjects. The immune response was compared between single and concomitant vaccination in terms of geometric mean titre (GMT) and seroconversion rate (SCR) on Days 28 and 56. Immunogenicity was comparable for the 2 vaccines whether given together or separately which suggests that travellers to such regions could receive the vaccinations concomitantly.

Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine.

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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00605058.

[33 year old Libanese woman with recurrent haemoptysis and cystic lesion of the lung]. / 33-jährige Libanesin mit rezidivierenden Hämoptysen und zystischer Raumforderung in der Lunge.

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.

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.

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.

Hepatitis A booster vaccination: is there a need?

Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. Effective vaccines against hepatitis A have been available since 1992, and they provide long-term immunity against the infection. However, there is no worldwide consensus on how long protection will last or whether there will be a need for hepatitis A virus (HAV) booster vaccinations in the future. In most countries, booster-vaccination policy is guided by manufacturers' recommendations, national authorities, or both. In June, 2002, a panel of international experts met to review the long-term immunogenicity and protection conferred by HAV vaccine in different population groups. Data have shown that after a full primary vaccination course, protective antibody amounts persist beyond 10 years in healthy individuals, and underlying immune memory provides protection far beyond the duration of anti-HAV antibodies. The group concluded that there is no evidence to lend support to HAV booster vaccination after a full primary vaccination course in a healthy individual. However, further investigations are needed before deciding if boosters can be omitted in special patient-groups.

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.

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.

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.

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.