Cardiac Safety of Modified Vaccinia Ankara for Vaccination against Smallpox in a Young, Healthy Study Population

Background Conventional smallpox vaccines based on replicating vaccinia virus (VV) strains (e.g. Lister Elstree, NYCBOH) are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. A new smallpox vaccine candidate based on a nonreplicating Modified Vaccinia Ankara (MVA) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial. Methods Cardiac safety of one and two doses of MVA compared to placebo was assessed in 745 healthy subjects. Vaccinia-naive subjects received either one dose of MVA and one dose of placebo, two doses of MVA, or two doses of placebo by subcutaneous injection four weeks apart;vaccinia-experienced subjects received a single dose of MVA. Solicited and unsolicited adverse events (AE) and cardiac safety parameters (recorded as Adverse Events of Special Interest, AESI) were monitored after each injection. Results A total of 5 possibly related AESI (3 cases of palpitations, 2 of tachycardia) were reported during the study. No case of myo- or pericarditis occurred. One possibly related serious AE (SAE) was reported during the 6-month follow-up period (sarcoidosis). The most frequently observed AEs were injection site reactions. Conclusions Vaccination with MVA was safe and well tolerated and did not increase the risk for development of myo-/pericarditis

Prevalence of Enteric Pathogens among International Travelers with Diarrhea Acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay)

Stools from tourists from Europe and North America who acquired diarrhea in Mombasa (Kenya), Goa (India), or Montego Bay (Jamaica) were examined for enteric pathogens. Enterotoxigenic Escherichia coli (ETEC) was the most common pathogen (25%) identified in the 3 locations. Isolation of Shigella species was more frequent in Goa and Mombasa than in Montego Bay (10%, 9%, and 0.3%, respectively; P < .005). Viruses (rotaviruses and enteric adenoviruses) were found in 9% of travelers to the 3 areas. Of 275 ETEC isolates in this study, 158 (57%) produced a defined colonization factor antigen (CFA). Coli surface 6 (CS6) was the most frequent and was found in 41%-52% of CFA/CS-positive ETEC isolates. The frequency of resistance among bacterial enteropathogens to traditional antimicrobial agents was particularly high throughout the study period in all 3 regions. Quinolones were active against the bacterial enteropathogens in the 3 site

Long-term kinetics of Zika virus RNA and antibodies in body fluids of a vasectomized traveller returning from Martinique: a case report

BACKGROUND: The magnitude of the current Zika virus (ZIKV) epidemic has led to a declaration of a Public Health Emergency of International Concern by the WHO. Findings of viable viral particles in semen for several weeks are corroborating reports of sexual transmission of ZIKV. Serious consequences of a positive diagnostic result particularly in the pregnant patient are calling for precise diagnostic tools also at later time points after infection. Currently, recommendations suggest a diagnostic period of direct viral detection of 5 to 7 days after onset of symptoms in serum or plasma, and up to 3 weeks in urine samples. CASE PRESENTATION: A vasectomized 41-year-old German returning from Martinique presented at the outpatient clinic of the Department for Infectious Diseases and Tropical Medicine, Munich, with subfebrile temperature, rash, malaise, severe retro-orbital pain and occipital lymphadenopathy. The main complaints resolved after ten days without specific treatment. We are reporting on clinical course and results of direct and indirect detection methods of ZIKV in different sample types including whole blood, ejaculate, urine, serum, plasma and saliva samples up to 119 days post symptom onset. Ejaculate samples remained PCR positive for ZIKV until day 77, whole blood samples until day 101. CONCLUSIONS: The case presentation adds to the still limited knowledge of kinetics of detection of ZIKV by direct as well as indirect methods. Here, a complete data set including results from PCR, serology and cell culture is provided allowing an improved evaluation of optimum diagnostic periods for testing a variety of sample types. Moreover, a high viral load of ZIKV RNA was detected in ejaculate of the vasectomized patient. This finding sheds new light on the possible localizations of ZIKV replication in the human male reproductive tract

Sex and Gender Differences in Travel-Associated Disease

Background. No systematic studies exist on sex and gender differences across a broad range of travel-associated diseases. Methods. Travel and tropical medicine GeoSentinel clinics worldwide contributed prospective, standardized data on 58,908 patients with travel-associated illness to a central database from 1 March 1997 through 31 October 2007. We evaluated sex and gender differences in health outcomes and in demographic characteristics. Statistical significance for crude analysis of dichotomous variables was determined using hi; 2 tests with calculation of odds ratios (ORs) and 95% confidence intervals (CIs). The main outcome measure was proportionate morbidity of specific diagnoses in men and women. The analyses were adjusted for age, travel duration, pretravel encounter, reason for travel, and geographical region visited. Results. We found statistically significant (Pµ.001) differences in morbidity by sex. Women are proportionately more likely than men to present with acute diarrhea (OR, 1.13; 95% CI, 1.09-1.38), chronic diarrhea (OR, 1.28; 95% CI, 1.19-1.37), irritable bowel syndrome (OR, 1.39; 95% CI, 1.24-1.57), upper respiratory tract infection (OR, 1.23; 95% CI, 1.14-1.33); urinary tract infection (OR, 4.01; 95% CI, 3.34-4.71), psychological stressors (OR, 1.3; 95% CI, 1.14-1.48), oral and dental conditions, or adverse reactions to medication. Women are proportionately less likely to have febrile illnesses (OR, 0.15; 95% CI, 0.10-0.21); vector-borne diseases, such as malaria (OR, 0.46; 95% CI, 0.41-0.51), leishmaniasis, or rickettsioses (OR, 0.57; 95% CI, 0.43-0.74); sexually transmitted infections (OR, 0.68; 95% CI 0.58-0.81); viral hepatitis (OR, 0.34; 95% CI, 0.21-0.54); or noninfectious problems, including cardiovascular disease, acute mountain sickness, and frostbite. Women are statistically significantly more likely to obtain pretravel advice (OR, 1.28; 95% CI, 1.23-1.32), and ill female travelers are less likely than ill male travelers to be hospitalized (OR, 0.45; 95% CI, 0.42-0.49). Conclusions. Men and women present with different profiles of travel-related morbidity. Preventive travel medicine and future travel medicine research need to address gender-specific intervention strategies and differential susceptibility to diseas

Evidence for significant influence of host immunity on changes in differential blood count during malaria

Background: Malaria has been shown to change blood counts. Recently, a few studies have investigated the alteration of the peripheral blood monocyte-to-lymphocyte count ratio (MLCR) and the neutrophil-to-lymphocyte count ratio (NLCR) during infection with Plasmodium falciparum. Based on these findings this study investigates the predictive values of blood count alterations during malaria across different sub-populations. Methods: Cases and controls admitted to the Department of Infectious Diseases and Tropical Medicine from January 2000 through December 2010 were included in this comparative analysis. Blood count values and other variables at admission controlled for age, gender and immune status were statistically investigated. Results: The study population comprised 210 malaria patients, infected with P. falciparum (68%), Plasmodium vivax (21%), Plasmodium ovale (7%) and Plasmodium malariae (4%), and 210 controls. A positive correlation of parasite density with NLCR and neutrophil counts, and a negative correlation of parasite density with thrombocyte, leucocyte and lymphocyte counts were found. An interaction with semi-immunity was observed; ratios were significantly different in semi-immune compared to non-immune patients (P <0.001). The MLCR discriminated best between malaria cases and controls (AUC = 0.691; AUC = 0.741 in non-immune travellers), whereas the NLCR better predicted severe malaria, especially in semi-immune patients (AUC = 0.788). Conclusion: Malaria causes typical but non-specific alterations of the differential blood count. The predictive value of the ratios was fair but limited. However, these changes were less pronounced in patients with semi-immunity. The ratios might constitute easily applicable surrogate biomarkers for immunity

Travel and migration associated infectious diseases morbidity in Europe, 2008.

BACKGROUND: Europeans represent the majority of international travellers and clinicians encountering returned patients have an essential role in recognizing, and communicating travel-associated public health risks. METHODS: To investigate the morbidity of travel associated infectious diseases in European travellers, we analysed diagnoses with demographic, clinical and travel-related predictors of disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet centres with a presumed travel associated condition. RESULTS: Gastro-intestinal (GI) diseases accounted for 33% of illnesses, followed by febrile systemic illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%). There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis, a dengue shock syndrome and a Plasmodium falciparum malaria.GI conditions included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis (2.3%). Among febrile systemic illnesses with identified pathogens, malaria (5.4%) accounted for most cases followed by dengue (1.9%) and others including chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological conditions were dominated by bacterial infections, arthropod bites, cutaneous larva migrans and animal bites requiring rabies post-exposure prophylaxis and also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory illness included 112 cases of tuberculosis including cases of multi-drug resistant or extensively drug resistant tuberculosis, 104 cases of influenza like illness, and 5 cases of Legionnaires disease. Sexually transmitted infections (STI) accounted for 0.6% of total diagnoses and included HIV infection and syphilis. A total of 165 cases of potentially vaccine preventable diseases were reported. Purpose of travel and destination specific risk factors was identified for several diagnoses such as Chagas disease in immigrant travellers from South America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel within Europe was also associated with health risks with distinctive profiles for Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied according to regions visited by ill travellers. The spectrum of travel associated morbidity also shows that there is a need to dispel the misconception that travel, close to home, in Europe, is without significant health risk.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Prevalence of Enteric Pathogens among International Travelers with Diarrhea Acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay)

Stools from tourists from Europe and North America who acquired diarrhea in Mombasa (Kenya), Goa (India), or Montego Bay (Jamaica) were examined for enteric pathogens. Enterotoxigenic Escherichia coli (ETEC) was the most common pathogen (25%) identified in the 3 locations. Isolation of Shigella species was more frequent in Goa and Mombasa than in Montego Bay (10%, 9%, and 0.3%, respectively; P < .005). Viruses (rotaviruses and enteric adenoviruses) were found in 9% of travelers to the 3 areas. Of 275 ETEC isolates in this study, 158 (57%) produced a defined colonization factor antigen (CFA). Coli surface 6 (CS6) was the most frequent and was found in 41%-52% of CFA/CS-positive ETEC isolates. The frequency of resistance among bacterial enteropathogens to traditional antimicrobial agents was particularly high throughout the study period in all 3 regions. Quinolones were active against the bacterial enteropathogens in the 3 site

Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe

BACKGROUND: Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide. RESULTS: 337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas. CONCLUSIONS: Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas

Retrospective clinical case series study in 2017 identifies Plasmodiumknowlesi as most frequent Plasmodium species in returning travellers from Thailand to Germany

Febrile illnesses are common in travellers returning from south-east Asia. However, malaria is a rare diagnosis in this population. A series of Plasmodium knowlesi infections was noted in German travellers returning from Thailand since 2012. Infectious disease and tropical medicine facilities registered by the German Society for Tropical Medicine and International Health were contacted in March 2017, and asked to report previous P. knowlesi cases. In addition, surveillance data from the Robert Koch-Institute were analysed. The facilities reported a total of six P. knowlesi-positive cases, all were returning travellers from Thailand. The P. knowlesi-positive cases made up 6/9 of all diagnosed malaria cases imported from Thailand in the time period 2012 to 2017. In 4/5 of cases where a malaria rapid diagnostic test had been applied it revealed a negative result. P. knowlesi is an important differential diagnosis in travellers returning from south-east Asia with itineraries that include Thailand. This study highlights the importance of this Plasmodium species in this patient subgroup. Whenever malaria is suspected in a returning traveller from Thailand, P. knowlesi should be taken into consideration and a differential PCR be executed as currently the unequivocal diagnosis of P. knowlesi is based on nuclear amplification techniques

Multicenter EuroTravNet/GeoSentinel Study of Travel-related Infectious Diseases in Europe

We analyzed prospective data on 17,228 European patients who sought treatment at GeoSentinel sites from 1997 to 2007. Gastrointestinal illness (particularly in tourists), fever (those visiting friends and relatives [VFRs]), and skin disorders (in tourists) were the most common reasons for seeking medical care. Diagnoses varied by country of origin, region visited, or categories of travelers. VFRs who returned from sub-Saharan Africa and Indian Ocean islands were more likely to experience falciparum malaria than any other group. Multiple correspondence analysis identified Italian, French, and Swiss VFRs and expatriate travelers to sub-Saharan Africa and Indian Ocean Islands as most likely to exhibit febrile illnesses. German tourists to Southeast and south-central Asia were most likely to seek treatment for acute diarrhea. Non-European travelers (12,663 patients from other industrialized countries) were less likely to acquire certain travel-associated infectious diseases. These results should be considered in the practice of travel medicine and development of health recommendations for European travelers