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Introduction: Eosinophilia in travelers returning from tropical countries is often caused by helminths. The high eosinophil counts arise particularly from tissue migration of invasive larvae.Methods: Review of literature selected by means of a Medline search using the MeSH terms 'eosinophilia' and 'helminth.'Results: The patient's geographic and alimentary history may suggest infection with particular parasitic worms. A targeted diagnostic approach is suggested. The physician should concentrate on the principal signs and be guided by the geographic and alimentary history. Elaborate diagnostic measures are seldom indicated.Discussion: Although eosinophilia alone has low positive predictive value for a worm infection, it points clearly to helminthosis if the patient has recently returned from the tropics and the eosinophilia is new. [ABSTRACT FROM AUTHOR]

Background. Malaria, anemia, and malnutrition contribute substantially to childhood morbidity in sub-Saharan Africa, but their respective roles and interactions in conferring disease are complex. We aimed to investigate these interactions. Methods. In 2002, we assessed plasmodial infection, anemia, and nutritional indices in 2 representative surveys comprising >4000 children in northern Ghana. Results. Infection with Plasmodium species was observed in 82% and 75% of children in the rainy and dry season, respectively. The fraction of fever attributable to malaria was 77% in the rainy season and 48% in the dry season and peaked in children of rural residence. Anemia (hemoglobin level, <11 g/dL) was seen in 64% of children and was, in multivariate analysis, associated with young age, season, residence, parasitemia, P. malariae coinfection, and malnutrition (odds ratio [OR], 1.68 [95% confidence interval {CI}, 1.38-2.04]). In addition, malnutrition was independently associated with fever (axillary temperature, >/=37.5 degrees C; OR, 1.59 [95% CI, 1.13-2.23]) and clinical malaria (OR, 1.67 [95% CI, 1.10-2.50]). Conclusions. Malnutrition is a fundamental factor contributing to malaria-associated morbidity and anemia, even if the latter exhibits multifactorial patterns. Our data demonstrate that malaria-control programs alone may not have the desired impact on childhood morbidity on a large scale without concomitant nutrition programs. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Diarrhoea is a frequent symptom associated with travelling to tropical regions, but the cause is often not found. Epidemiology was assessed including up-to-date real-time PCR approaches.We analysed datasets of 528 patients who presented at the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, between 2006 and 2010 for screening purposes or because of diarrhoea. Stool samples were obtained and investigated by microscopy, bacterial culture, two PCR assays targeting Entamoeba histolytica, Entamoeba dispar, Giardia duodenalis, and Cryptosporidium parvum, or Salmonella spp., Shigella/EIEC spp., Campylobacter jejuni, and Yersinia spp.Among patients with gastrointestinal symptoms, 51% tested positive for bacteria or parasites, of which 66% had a known enteropathogenic potential. In patients without diarrhoea, 53% (n = 80) were positive, and 33% of these cases harboured agents of pathogenic potential. Association with clinical symptoms was primarily found for bacterial infections. Blastocystis hominis, however, was more frequent in asymptomatic than in symptomatic travellers.In conclusion, the study stresses the etiological relevance of bacterial gastroenteritis in travellers returning from the tropics, the need for molecular approaches to increase diagnostic sensitivity and demonstrates that asymptomatic carriage of enteropathogens after prolonged stays in the tropics is similarly frequent compared with symptomatic infections in travellers.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings., Methods: In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39., Findings: Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild., Interpretation: Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks., Funding: Ixodes AG., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: IXIARO® is a Vero cell-derived, inactivated Japanese encephalitis (JE) vaccine licensed mainly in western countries for children and adults traveling to JE endemic areas. Limited immunogenicity and safety data in elderly travelers have been available., Objectives: To evaluate safety and immunogenicity of IXIARO in elderly subjects., Methods: Open-label, single arm, multi-centered study. Two-hundred subjects with good general health, including adequately controlled chronic conditions, received two doses of IXIARO®, 28days apart. Protective levels of antibodies were tested 42days after the second dose. Systemic and local adverse events (AEs) were solicited for 7days after each dose, unsolicited AEs were collected up to day 70 and in a phone call at month 7., Summary of Results: Subjects were aged 64-83years (median 69.0years). Nineteen percent of subjects had serious or medically attended AEs up to Day 70 (primary endpoint), none of them causally linked to IXIARO. Solicited local AEs were reported by 33.5% (most common: local tenderness) and solicited systemic AEs by 27% (most common: headache) of subjects. The seroprotection rate was 65% with a geometric mean titre (GMT) of 37. Subjects with tick borne encephalitis (TBE) vaccinations in the past 5years (N=29) had a SCR of 90% and GMT of 65., Conclusions: IXIARO is generally well tolerated in the elderly, and the safety profile is largely comparable with younger adults. SCR and GMT are lower compared to younger adults, but SCR is in the range reported in elderly for other vaccines e.g. against TBE, hepatitis-A virus (HAV)/hepatitis-B virus (HBV), influenza. The differences in SCR and GMT from younger to elderly adults were in the range of other vaccines. Duration of protection is uncertain in older persons, therefore a booster dose (third dose) should be considered before any further exposure to JE virus., (Copyright © 2016. Published by Elsevier Ltd.)

Background.  Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Data on the efficacy of probiotics to prevent AAD and CDAD are unclear. We aimed to evaluate the efficacy of Saccharomyces boulardii to prevent AAD and CDAD in hospitalized adult patients. Methods.  We conducted a multicenter, phase III, double-masked, randomized, placebo-controlled trial in hospitalized patients who received systemic antibiotic treatment in 15 hospitals in Germany between July 2010 and October 2012. Participants received Perenterol forte 250 mg capsules or matching placebo twice per day within 24 hours of initiating antibiotic treatment, continued treatment for 7 days after antibiotic discontinuation, and were then observed for 6 weeks. Results.  Two thousand four hundred forty-four patients were screened. The trial was stopped early for futility after inclusion of 477 participants. Two hundred forty-six patients aged 60.1 ± 16.5 years and 231 patients aged 56.5 ± 17.8 were randomized to the S boulardii group and the placebo group, respectively, with 21 and 19 AADs in the respective groups (P = .87). The hazard ratio of AAD in the S boulardii group compared with the placebo group was 1.02 (95% confidence interval, .55-1.90; P = .94). Clostridium difficile-associated diarrhea occurred in 0.8% of participants (4 of 477). Nine serious adverse events were recorded in the S boulardii group, and 3 serious adverse events were recorded in the placebo group. None were related to study participation. Conclusions.  We found no evidence for an effect of S boulardii in preventing AAD or CDAD in a population of hospitalized patients without particular risk factors apart from systemic antibiotic treatment. ClinicalTrials.gov Identifier.  NCT01143272.

Background: Dengue fever (DF) is one of the most relevant human arboviral infections worldwide and has become a frequent cause of fever in the returning traveller. This retrospective study aimed to characterize epidemiological and clinical features and laboratory findings of dengue fever in German travellers., Methods: This descriptive study analyzed medical records of patients diagnosed with DF presenting at the Section of Tropical Medicine of the University Medical Centre Hamburg-Eppendorf from 2007 to 2011. Data were collected and analyzed retrospectively., Results: In total, data of 119 DF patients (52 female, 67 male) were included in this study. The median age of the patients was 35 (range 15-75 years). DF was most frequently acquired in South-East Asia (n = 65; 54.7%), and in particular in Thailand (n = 23; 19.7%). A considerable percentage of DF infections (n = 14; 11.8%) was imported from Africa. Patients predominantly presented with fever, headache, rash, myalgia and arthralgia but also with gastrointestinal symptoms, i.e. diarrhoea. Nine patients showed signs of minor haemorrhagic manifestations. Neurological complications occurred in 13 patients. Low platelet count, leukopenia and elevated liver enzymes were the most relevant laboratory findings. Twenty patients (17.8%) had to be hospitalized. Overall, the clinical course was mostly mild to moderate, 13 patients (10.9%) showed DF warnings signs, no fatalities occurred., Conclusions: DF presented as a mostly mild to moderate disease in this study cohort. Outpatient treatment was adequate for the majority of patients. Still, detailed knowledge of clinical symptoms and laboratory features is essential for appropriate triage., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Helicobacter pylori coinfection in human immunodeficiency virus (HIV) patients has been associated with higher CD4+ cell counts and lower HIV-1 viral loads, with the underlying mechanisms being unknown. The objective of this study was to investigate the impact of H. pylori infection on markers of T-cell activation in HIV-positive and HIV-negative individuals., Methods: In a cross-sectional, observational study, HIV patients (n = 457) and HIV-negative blood donors (n = 79) presenting to an HIV clinic in Ghana were enrolled. Data on clinical and sociodemographic parameters, CD4+/CD8+ T-cell counts, and HIV-1 viral load were recorded. Helicobacter pylori status was tested using a stool antigen test. Cell surface and intracellular markers related to T-cell immune activation and turnover were quantified by flow cytometry and compared according to HIV and H. pylori status., Results: Helicobacter pylori infection was associated with decreased markers of CD4+ T-cell activation (HLA-DR+CD38+CD4+; 22.55% vs 32.70%; P = .002), cell proliferation (Ki67; 15.10% vs 26.80%; P = .016), and immune exhaustion (PD-1; 32.45% vs 40.00%; P = .005) in 243 antiretroviral therapy (ART)-naive patients, but not in 214 patients on ART. In HIV-negative individuals, H. pylori infection was associated with decreased frequencies of activated CD4+ and CD8+ T cells (6.31% vs 10.40%; P = .014 and 18.70% vs 34.85%, P = .006, respectively)., Conclusions: Our findings suggest that H. pylori coinfection effectuates a systemic immune modulatory effect with decreased T-cell activation in HIV-positive, ART-naive patients but also in HIV-negative individuals. This finding might, in part, explain the observed association of H. pylori infection with favorable parameters of HIV disease progression., Clinical Trials Registration: Clinicaltrials.gov NCT01897909., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Internists should expect to be the first contact for patients with rare, but highly contagious, life-threatening illnesses. Although certainly not encountered often, it is associated with significant consequences. Thus, physicians should be familiar with viral hemorrhagic fevers: filoviruses cause Ebola and Marburg fever, arenaviruses cause Lassa fever and South American hemorrhagic fevers, and the bunyaviruses cause among others Crimean-Congo hemorrhagic fever. Furthermore, physicians should be familiar with highly contagious respiratory infections, such as hantavirus pulmonary syndrome, pneumonic plague, and Middle East respiratory syndrome (MERS).

An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines. In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix(®) (GlaxoSmithKline), Typhim Vi(®) (Sanofi Pasteur MSD) or Hepatyrix(®) (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (-1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA. Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 μg/ml versus 6.13 μg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 μg/ml versus 14.58 μg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0. In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study., Methods: Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57., Results: Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine., Conclusions: This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated regimen, if licensed, could potentially be a valid alternative for individuals requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis on short notice., (© 2015 International Society of Travel Medicine.)

The formation and environmental release of highly toxic organohalogen compounds associated with informal recycling of waste electric and electronic equipment (e-waste) is a growing problem at e-waste dumps/recycling sites (EWRSs) in many developing countries worldwide. We chose a cross-sectional study design to measure the internal exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) as well as polychlorinated biphenyls (PCBs) of individuals working on one of the largest EWRSs of Africa, located at Agbogbloshie, Accra, Ghana, and in controls from a suburb of Accra without direct exposure to EWRS activities. In whole blood samples of 21 age matched male exposed individuals (mean age: 24.7 years, SD 6.0) and 21 male controls (mean age: 24.4 years, SD 5.7) 17 PCDD/F congeners were determined. Moreover three indicator PCB congeners (#138, #153 and #180) were measured in blood of 39 exposed (mean age: 27.5 years, SD 11.7) and 19 non-exposed (mean age: 26.8 years, SD 9.7) patients. Besides a health examination, biometric and demographic data, residential and occupational history, occupational exposures and working conditions were recorded using a standardized questionnaire. In the exposed group, median PCDD/F-concentrations were 6.18 pg/g lipid base WHO2005-TEq (range: 2.1-42.7) and significantly higher compared to the control group with 4.60 pg/g lipid base WHO2005-TEq (range: 1.6-11.6). Concentrations were different for 2,3,7,8-TetraCDD, three HexaCDD and all 10 PCDF congeners, indicating a combustion pattern. Using a multivariate regression analysis exposure to EWRS activities was the most important determinant for PCDD/F exposure. Median PCB levels for the indicator congeners #138, #153 and #180 were 0.011, 0.019 and 0.008 μg/l whole blood (ranges: 0.002-0.18, 0.003-0.16, 0.002-0.078) in the exposed group and, surprisingly, significantly higher in the controls (0.037, 0.062 and 0.022; ranges: 0.005-0.46, 0.010-0.46, 0.004-0.21). In a multivariate regression approach e-waste related activities had no positive influence on internal PCB exposure, but rather the time living in Accra. The internal PCB exposure is in particular notable for a country where PCBs have historically never been produced or used. The impact of EWRS activities on organohalogen compound exposure of individuals working at and living in the surroundings of the Agbogbloshie EWRS, and the surprisingly high PCB exposure of people living in Accra not involved in e-waste activities require further investigation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon., Methods: In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls., Results: At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence., Conclusions: Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The present study evaluated the safety and immunogenicity of the 2013/2014 trivalent surface antigen inactivated subunit seasonal influenza virus vaccine Fluvirin® in healthy adults (18 - ≤ 60 years) and elderly (>60 years). The vaccine contained 15 µg haemagglutinin protein from each of influenza A/California/7/2009 (H1N1)pdm09-like strain, A/Victoria/361/2011 (H3N2)-like strain and B/Massachusetts/2/2012-like strain (B/Yamagata) as recommended by the WHO in the 2013/2014 Northern Hemisphere season. Antibody response to each influenza antigen after vaccination was measured prior to vaccination and 21 d after by single radial hemolysis (SRH) assay or hemagglutination inhibition (HI) assay in accordance with Guidance CPMP/BWP/214/96. 125 subjects (61 adults and 64 elderly) were enrolled in the study. Pre-vaccination protective antibody levels (SRH area ≥ 25 mm(2)) against A(H1N1), A(H3N2) and the B strain were detected in 17%, 20% and 57% of adults and in 36%, 20% and 55% of elderly, respectively, Post-vaccination, SRH area ≥ 25 mm(2) was detectable in 95%, 82% and 92% in adult and in 80%, 84% and 92% of the elderly subjects for A(H1N1), A(H3N2) and the B strain, respectively. Geometric mean ratio (GMR) was higher in adult subjects (2.62-7.62) than in elderly subjects (2.33-3.42). All three CHMP licensure criteria were met for all strains contained in the vaccine for both age groups. The most frequently reported solicited local and systemic reactions were pain at the injection side, headache and fatigue. In conclusion, the vaccine demonstrated a good immunogenicity and an acceptable safety profile in both adults and elderly.

Introduction: Facing the rapid scale-up of antiretroviral treatment (ART) programs in resource-limited settings, monitoring of treatment outcome is essential in order to timely detect and tackle drawbacks [1]., Methods: In a prospective cohort study, 300 consecutive patients starting first-line ART were enrolled between 2009 and2010 in a large HIV treatment centre in rural Cameroon. Patients were followed up for 12 months. Virologic failure was defined as a VL >1000 cop/mL at month 12. Besides CD4 and viral load (VL) analysis, HIV-1 drug resistance testing was performed in patients with VL>1000 copies (c)/mL plasma. In those patients and controls, minority HIV-1 drug resistance mutations at baseline, and plasma drug levels were analyzed in order to identify the risk factors for virologic failure., Results: Most enrolled patients (71%) were female. At baseline median CD4 cell count was 162/µL (IQR 59-259), median log10 VL was 5.4 (IQR 5.0-5.8) c/mL, and one-third of patients had World Health Organisation (WHO) stage 3 or 4; 30 patients died during follow-up. Among all patients who completed follow-up 38/238 had virologic failure. These patients were younger, had lower CD4 cell counts and more often had WHO stage 3 or 4 at baseline compared to patients with VL<1000c/mL. Sixty-three percent of failing patients (24/38) had at least one mutation associated with high-level drug resistance. The M184V mutation was the most frequently detected nucleoside reverse transcriptase inhibitor (NRTI) mutation (n=18) followed by TAMs (n=5) and multi-NRTI resistance mutations (n=4). The most commonly observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance mutations were K103N (n=10), Y181C (n=7), and G190A (n=6). Drug resistance mutations at baseline were detected in 12/65 (18%) patients, in 6 patients with and 6 patients without virological failure (p=0.77). Subtherapeutic NNRTI levels (OR 6.67, 95% CI 1.98-22.43, p<0.002) and poorer adherence (OR 1.54, 95% CI 1.00-2.39, p=0.05) were each associated with higher risk of virologic failure in the matched pair analysis. Unavailability of ART at the treatment centre was the single most common cause (37%) for incomplete adherence in these patients., Conclusions: Virologic failure after one year of first-line ART in rural Cameroon was not associated with transmitted drug resistance, but with reduced drug plasma levels and incomplete adherence. Strategies to assure adherence and uninterrupted drug supply are important factors for therapy success.

Most imported diseases can be well treated-provided the diagnosis is made in due time. For example, only the rapid and correctly performed treatment of falciparum malaria can impede severe complications and save the patient's life. Effective treatments for amebiasis, giardiasis, leishmaniasis and worm diseases are available. However, it has to be mentioned that evidence from clinical trials is often insufficient. Accordingly only few international guidelines for imported diseases exist.

Background: Parenteral artesunate is recommended as first-line therapy for severe malaria. While its efficacy is firmly established, data on safety are still incomplete. Delayed hemolysis has been described in hyperparasitemic nonimmune travelers, but it is unknown if African children are equally at risk., Methods: Children aged 6 to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambaréné, Gabon, and Kumasi, Ghana. The primary outcome was incidence of delayed hemolysis on day 14., Results: In total, 72 children contributed complete data sets necessary for primary outcome assessment. Delayed hemolysis was detected in 5 children (7%), with 1 child reaching a nadir in hemoglobin of 2.8 g/dL. Patients with delayed hemolysis had higher parasite counts on admission (geometric mean parasite densities (GMPD) 306 968/µL vs 92 642/µL, P = .028) and were younger (median age: 24 months vs 43 months, P = .046) than the rest of the cohort. No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed., Conclusions: Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria. Physicians should be aware of this complication and consider prolonged follow-up., Clinical Trials Registration: Pan-African Clinical Trials Registry: PACTR201102000277177 (www.pactr.org)., (© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: While several anti-malarials are known to affect the electric conduction system of the heart, less is known on the direct effects of Plasmodium falciparum infection. Some earlier studies point to a direct impact of Plasmodium falciparum infection on the electric conduction system of the heart. The aim of this study was to analyse infection- and drug-induced effects on the electric conduction system., Methods: Children aged 12 months to 108 months with severe malaria were included in Kumasi, Ghana. In addition to basic demographic, clinical, biochemical and parasitological, biochemical data were measured data upon hospitalization (day 0) and 12-lead electrocardiograms were recorded before (day 0) and after (day 1) initiation of quinine therapy as well as after 42 (±3) days., Results: A total of 180 children were included. Most children were tachycardic on day 0 but heart rate declined on day 1 and during follow up. The corrected QT intervals were longest on day 1 and shortest on day 0. Comparison of QT intervals with day 42 (healthy status) after stratification for age demonstrated that in the youngest (<24 months) this was mainly due to a QT shortage on day 0 while a QT prolongation on day 1 was most pronounced in the oldest (≥48 months). Nearly one third of the participating children had measurable 4-aminoquinoline levels upon admission, but no direct effect on the corrected QT intervals could be shown., Conclusion: Severe P. falciparum infection itself can provoke changes in the electrophysiology of the heart, independent of anti-malarial therapy. Especially in young - thus non immune - children the effect of acute disease associated pre-treatment QT-shortage is more pronounced than quinine associated QT-prolongation after therapy. Nevertheless, neither malaria nor anti-malarial induced effects on the electrophysiology of the heart were associated with clinically relevant arrhythmias in the present study population.

Background: Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. Clinical manifestations of leishmaniasis include cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). About 90% of cases occur in the tropics or subtropics but the disease is also endemic in the Mediterranean area. No systematic analysis on leishmaniasis in travellers visiting endemic areas in Europe is available., Methods: Within the European travel medicine network EuroTravNet, we performed a retrospective analysis in travellers who acquired leishmaniasis within Europe diagnosed between 2000 and 2012., Results: Forty cases of leishmaniasis (30 CL and 10 VL) were identified; the majority were acquired in Spain (n = 20, 50%), Malta and Italy (each n = 7, 18%). Median age was 48 years (range 1-79). Three of eight (37.5%) of the VL patients were on immunosuppressive therapy. The most frequent reason for travel was tourism (83%). Median duration of travel for patients with CL and VL was 2 weeks with ranges of 1-21 weeks in CL and 1-67 weeks in VL, respectively (P = 0.03)., Conclusions: Health professionals should include leishmaniasis in the differential diagnosis in patients returning from southern Europe - including short-term travellers - with typical skin lesions or systemic alterations like fever, hepatosplenomegaly and pancytopenia., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Malaria is the most important infectious disease imported by travelers and migrants from tropical and subtropical areas. It is imported quite frequently. It is a life-threatening disease. Symptoms are nonspecific and cannot easily be distinguished from a wide range of other febrile conditions. Therefore, travel history must be taken in all patients with fever of unknown origin and malaria diagnostics must be performed immediately on suspicion of malaria. Uncomplicated falciparum malaria should be treated in the hospital with either atovaquone-proguanil or with an artemisinin-based combination preparation. If there is evidence of severe malaria, the patient must be moved to an intensive care unit. The antiparasitic agent of choice is then artesunate.

Background: The present study aimed to evaluate immunogenicity and safety of the 2012/2013 seasonal influenza vaccine (Optaflu(®)) after the World Health Organization recommended two new strains for the composition., Results: Twenty-one days post-vaccination geometric mean titers (GMTs) against A(H1N1), A(H3N2) and the B strain were 528, 935, and 201 for adults and 272, 681, and 101 for elderly subjects, respectively. The proportion of subjects with a HI titer of ≥ 40 against the three strains A(H1N1), A(H3N2) and B was 98%, 100%, and 98% in adults and 100%, 100%, and 85% in elderly subjects, respectively. Optaflu(®) met the CHMP criteria of the Committee for Medicinal Products for Human Use (CPMP/BWP/214/96). Pre-vaccination titers indicated seroprotection against the A(H1N1), the A(H3N2) and the B strain in 56%, 86%, and 54% of the adults and in 61%, 85%, and 40% of the elderly with highest titers against the A(H3N2) strain. In the safety analysis injection site pain (37%) and myalgia (31%) were the most common local and systemic reactions. No serious adverse events were recorded., Conclusion: The 2012/2013 seasonal influenza vaccine Optaflu(®) showed good immunogenicity and an acceptable safety profile in both adults and elderly., Methods: In this trial, 126 subjects (63 adults ≥18 to ≤60 y, 63 elderly ≥61 y) were vaccinated with a single dose Optaflu(®) containing each of the three virus strains recommended for the 2012/2013 season (A/California/7/2009(H1N1)-like strain, A/Victoria/361/2011(H3N2)-like strain, and B/Wisconsin/1/2010-like strain). Immunogenicity was assessed by hemagglutinin inhibition (HI) and single radial hemolysis (SRH) assays on day 22, the safety profile was investigated throughout the whole study period.

Guideline Objectives: These guidelines aim to enhance patient care by optimizing the diagnosis and treatment of infections due to creeping disease (cutaneous larva migrans) and to raise awareness among doctors of current treatment options., Methods: S1 guideline, non-systematic literature search, consensus process using a circular letter., (© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Travelers diarrhea affects millions of tourists each year. Most cases are caused by a variety of bacterial enteropathogens: toxigenic Escherichia coli, Campylobacter, Shigella, Salmonella, Aeromonas, Plesiomonas and non-cholera vibrios. Treatment may include antibacterial therapy with either ciprofloxacin, or azitrhomycin, or rifaximin. Viral pathogens such as norovirus usually cause short-term illness that typically resolves before travelers seek medical attention. Chronic gastrointestinal disease in returning travelers often is caused by parasitic pathogens like Giardia lamblia. The impact of prevention of travelers diarrhea is limited, therefore travelers should be informed about early self-treatment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: For rapid initiation of anti-malarial treatment and prevention of complications, early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria. Routine laboratory values do not correlate well with disease severity. The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation; endothelial and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum malaria., Methods: In a prospective case-control study, 79 adult travellers with both uncomplicated and complicated P. falciparum malaria were included between 2007 and 2011. Forty-one healthy subjects were included as controls. Blood samples were obtained within 24 hours after first consultation to assess routine laboratory values as well as markers related to inflammation (PAPP-A, copeptin, CRP), endothelial activation (MPO, elastase-2, endothelin-1, sICAM-1, sVCAM-1), cardiac function (NT-proBNP, MR-proANP), coagulation (fibrinogen, D-dimers, platelet count), and haemolysis (LDH). Prognostic performance was assessed using the receiver operating characteristic curve (area under the curve = AUROC)., Results: Twelve (15.2%) patients had severe P. falciparum malaria. In the patient group, significant thrombocytopaenia was found, all other markers but PAPP-A were significantly elevated. Diagnostic performance was best for CRP with an AUROC of 1.00, followed by MPO (0.99), D-dimers (0.98), elastase-2 (0.98), and sICAM-1 (0.98). Biomarker levels did not correlate well with disease severity., Conclusion: The combination of travel history, fever prior to blood sampling, and CRP serum levels above or below 10.8 mg/l upon hospital admission, best discriminated between malaria patients and control persons. None of the biomarkers studied predicted the presence or the development of malaria complications, neither at the time of admission, nor during hospitalization.

Background: Severe malaria is a potentially life-threatening infectious disease. It has been conclusively shown that artesunate compared to quinine is superior in antiparasitic efficacy and in lowering mortality showing a better short-term safety profile. Regarding longer-term effects, reports of delayed haemolysis after parenteral artesunate for severe malaria in returning travellers have been published recently. So far, delayed haemolysis has not been described after the use of parenteral quinine., Methods: In this retrospective study, all patients treated for severe malaria at the University Medical Centre Hamburg-Eppendorf were included between 2006 and 2012. The primary endpoint was the proportion of delayed haemolysis in patients treated with quinine versus those who received artesunate. As secondary endpoint, the proportion of any adverse event was assessed., Results: A total of 36 patients with severe malaria were included in the analysis. Of these, 16 patients contributed sufficient data to assess the endpoint delayed haemolysis. Twelve were treated primarily with intravenous quinine - with four patients having received intrarectal artesunate as an adjunct treatment - and five patients were treated primarily with artesunate. Five cases of delayed haemolysis could be detected - two in patients treated with quinine and intrarectal artesunate and three in patients treated with artesunate. No case of delayed haemolysis was detected in patients treated with quinine alone.While adverse events observed in patients treated with artesunate were limited to delayed haemolysis (three patients, 60%) and temporary deterioration in renal function (three patients, 60%), patients treated with quinine showed a more diverse picture of side effects with 22 patients (71%) experiencing at least one adverse event. The most common adverse events after quinine were hearing disturbances (12 patients, 37%), hypoglycaemia (10 patients, 32%) and cardiotoxicity (three patients, 14%)., Conclusions: This study provides further evidence on delayed haemolysis after artesunate and underlines the importance of a standardized follow-up of patients treated with artesunate for severe malaria.

Background: Acute schistosomiasis constitutes a rare but serious condition in individuals experiencing their first prepatent Schistosoma infection. To circumvent costly and time-consuming diagnostics, an early and rapid diagnosis is required. So far, classic diagnostic tools such as parasite microscopy or serology lack considerable sensitivity at this early stage of Schistosoma infection. To validate the use of a blood based real-time polymerase chain reaction (PCR) test for the detection of Schistosoma DNA in patients with acute schistosomiasis who acquired their infection in various endemic regions we conducted a European-wide prospective study in 11 centres specialized in travel medicine and tropical medicine., Methods: Patients with a history of recent travelling to schistosomiasis endemic regions and freshwater contacts, an episode of fever (body temperature ≥38.5°C) and an absolute or relative eosinophil count of ≥700/μl or 10%, were eligible for participation. PCR testing with DNA extracted from serum was compared with results from serology and microscopy., Results: Of the 38 patients with acute schistosomiasis included into the study, PCR detected Schistosoma DNA in 35 patients at initial presentation (sensitivity 92%). In contrast, sensitivity of serology (enzyme immunoassay and/or immunofluorescence assay) or parasite microscopy was only 70% and 24%, respectively., Conclusion: For the early diagnosis of acute schistosomiasis, real-time PCR for the detection of schistosoma DNA in serum is more sensitive than classic diagnostic tools such as serology or microscopy, irrespective of the region of infection. Generalization of the results to all Schistosoma species may be difficult as in the study presented here only eggs of S. mansoni were detected by microscopy. A minimum amount of two millilitre of serum is required for sufficient diagnostic accuracy.

Background: In Africa, success of antiretroviral treatment (ART) seems to lag behind in children compared with adults, and high therapeutic failure rates have been reported. We aimed to identify prevalence and determinants of virological failure in HIV-infected children treated under programmatic conditions., Methods: All patients <18 years on ART presenting to the HIV clinic at the Bamenda Regional Hospital, a secondary referral hospital in rural Cameroon, from September 2010 to August 2011, were enrolled in this cross-sectional study. Clinical data, self-reported adherence, CD4(+) T-cell counts and viral load were recorded. Therapeutic drug monitoring was performed on stored plasma samples. Determinants of virological failure were identified using descriptive statistics and logistic regression., Results: A total of 230 children with a mean age of 8.9 years (sd 3.7) were included. At the time of analysis, the mean duration of HAART was 3.5 years (sd 1.7) and 12% had a CD4(+) T-cell count <200 cells/µl. In total, 53% of children experienced virological failure (>200 copies/ml). Among children on nevirapine (NVP), plasma levels were subtherapeutic in 14.2% and supratherapeutic in 42.2%. Determinants of virological failure included male sex, lower CD4(+) T-cell counts, subtherapeutic drug levels, longer time on ART and a deceased mother. Poor adherence was associated with subtherapeutic NVP plasma levels and advanced disease stages (WHO stage 3/4)., Conclusions: This study demonstrates high virological failure rates and a high variability of NVP plasma levels among HIV-infected children in a routine ART programme in rural Cameroon. Strategies to improve adherence to ART in HIV-infected children are urgently needed.

Purpose: The aim was to assess whether impaired cardiac function contributes to symptoms of severe malaria in general or to metabolic acidosis in particular in children living in endemic regions., Methods: In a prospective observational investigation, 183 children with severe malaria were investigated for hemodynamic status and cardiac function upon admission (day 0) and after recovery (day 42). Cardiac function parameters were assessed by cardiac ultrasonography. Blood gas analyses and cardiac enzymes were measured at hospitalization and follow-up. Differences in subgroups with and without metabolic acidosis as well as other severe malaria-defining symptoms and conditions were assessed., Results: Cardiac index (CI) was significantly increased on day 0 compared to day 42 (5.8 ml/m(2), SD ± 1.8 ml/m(2), versus 4.7 ml/m(2), SD ± 1.4 ml/m(2); P < 0.001). CI correlated negatively with hemoglobin levels but not with parameters indicating impaired tissue perfusion or metabolic acidosis. Parasite levels had a significant influence on metabolic acidosis but not on CI. Alterations related to cardiac function, hemoglobin levels and metabolic acidosis were most prominent in children younger than 2 years., Conclusion: Increased CI reflecting high output status is associated with low hemoglobin levels while metabolic acidosis is linked to parasite levels.