Christof D. Vinnemeier

Immunogenicity and safety of an inactivated 2012/2013 trivalent influenza vaccine produced in mammalian cell culture (Optaflu®): An open label, uncontrolled study

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.

Geographically weighted regression of land cover determinants of Plasmodium falciparum transmission in the Ashanti Region of Ghana

BackgroundMalaria is a mosquito-borne parasitic disease that causes severe mortality and morbidity, particularly in Sub-Saharan Africa. As the vectors predominantly bite between dusk and dawn, risk of infection is determined by the abundance of P. falciparum infected mosquitoes in the surroundings of the households. Remote sensing is commonly employed to detect associations between land use/land cover (LULC) and mosquito-borne diseases. Due to challenges in LULC identification and the fact that LULC merely functions as a proxy for mosquito abundance, assuming spatially homogenous relationships may lead to overgeneralized conclusions.MethodsData on incidence of P. falciparum parasitaemia were recorded by active and passive follow-up over two years. Nine LULC types were identified through remote sensing and ground-truthing. Spatial associations of LULC and P. falciparum parasitaemia rate were described in a semi-parametric geographically weighted Poisson regression model.ResultsComplete data were available for 878 individuals, with an annual P. falciparum rate of 3.2 infections per person-year at risk. The influences of built-up areas (median incidence rate ratio (IRR): 0.94, IQR: 0.46), forest (median IRR: 0.9, IQR: 0.51), swampy areas (median IRR: 1.15, IQR: 0.88), as well as banana (median IRR: 1.02, IQR: 0.25), cacao (median IRR: 1.33, IQR: 0.97) and orange plantations (median IRR: 1.11, IQR: 0.68) on P. falciparum rate show strong spatial variations within the study area. Incorporating spatial variability of LULC variables increased model performance compared to the spatially homogenous model.ConclusionsThe observed spatial variability of LULC influence in parasitaemia would have been masked by traditional Poisson regression analysis assuming a spatially constant influence of all variables. We conclude that the spatially varying effects of LULC on P. falciparum parasitaemia may in fact be associated with co-factors not captured by remote sensing, and suggest that future studies assess small-scale spatial variation of vegetation to circumvent generalised assumptions on ecological associations that may in fact be artificial.

Predictive value of fever and palmar pallor for P. falciparum parasitaemia in children from an endemic area.

Introduction Although the incidence of Plasmodium falciparum malaria in some parts of sub-Saharan Africa is reported to decline and other conditions, causing similar symptoms as clinical malaria are gaining in relevance, presumptive anti-malarial treatment is still common. This study traced for age-dependent signs and symptoms predictive for P. falciparum parasitaemia. Methods In total, 5447 visits of 3641 patients between 2–60 months of age who attended an outpatient department (OPD) of a rural hospital in the Ashanti Region, Ghana, were analysed. All Children were examined by a paediatrician and a full blood count and thick smear were done. A Classification and Regression Tree (CART) model was used to generate a clinical decision tree to predict malarial parasitaemia a7nd predictive values of all symptoms were calculated. Results Malarial parasitaemia was detected in children between 2–12 months and between 12–60 months of age with a prevalence of 13.8% and 30.6%, respectively. The CART-model revealed age-dependent differences in the ability of the variables to predict parasitaemia. While palmar pallor was the most important symptom in children between 2–12 months, a report of fever and an elevated body temperature of ≥37.5°C gained in relevance in children between 12–60 months. The variable palmar pallor was significantly (p<0.001) associated with lower haemoglobin levels in children of all ages. Compared to the Integrated Management of Childhood Illness (IMCI) algorithm the CART-model had much lower sensitivities, but higher specificities and positive predictive values for a malarial parasitaemia. Conclusions Use of age-derived algorithms increases the specificity of the prediction for P. falciparum parasitaemia. The predictive value of palmar pallor should be underlined in health worker training. Due to a lack of sensitivity neither the best algorithm nor palmar pallor as a single sign are eligible for decision-making and cannot replace presumptive treatment or laboratory diagnosis.

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers.

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.

Travelers to the FIFA world cup 2014 in Brazil: Health risks related to mass gatherings/sports events and implications for the Summer Olympic Games in Rio de Janeiro in 2016.

BACKGROUND Health threats during mass gatherings, such as the FIFA world cup 2014 differ from traditional health risks. The influence of event type, demographics of attendees and environmental conditions are still not fully understood. METHODS An observational, prospective case-control survey conducted at the Frankfurt international airport in Germany on 544 travelers to the FIFA world cup 2014 and 432 regular travelers to Brazil departing after the end of the world cup. RESULTS Travelers to the FIFA world cup 2014 were predominantly male whereas the gender distribution in the control group was more balanced. The majority in both groups obtained insect bites and sunburns as environmental risk factors. Every third traveler suffered from diarrheal complaints in both groups, whereas the proportion of travelers with flu-like symptoms was higher in the case group. Travelers to the FIFA world cup 2014 indicated alcohol intake and sexual contacts outside of a relationship more frequently than travelers in the control group. CONCLUSIONS The additional health risks of travelers to sporting events as the FIFA world cup 2014 should be addressed in addition to traditional health threats in pre-travel counseling for the Summer Olympic Games 2016 in Brazil.

Pre-travel advice at a crossroad: Medical preparedness of travellers to South and Southeast-Asia - The Hamburg Airport Survey

BACKGROUND Specific travel-related recommendations exist for the prevention or self-treatment of infectious diseases contracted by travellers to the tropics. In the current study, we assessed the medical preparedness per these recommendations, focusing on whether travellers carried antidiarrheal and antimalarial medication with them stratified by type of pre-travel advice. METHODS We surveyed travellers departing from Hamburg International Airport to South or Southeast Asia, using a questionnaire on demographic, medical and travel characteristics. RESULTS 975 travellers were analysed - the majority (817, 83%) being tourists. A large proportion packed any antidiarrheal medication (612, 63%) - most frequently loperamide (440, 72%). Only 176 of 928 (19%) travellers to destinations with low-to medium risk for malaria packed a recommended antimalarial medication. The majority (162, 17%) of them carried antimalarials as stand-by emergency treatment (SBET). 468 (48%) travellers had a pre-travel medical consultation. This lead to higher odds of carrying SBET- with the highest odds associated with a consultation at a travel medicine specialist (OR 7.83 compared to no consultation). CONCLUSIONS Attending a travel medicine specialist was associated with better adherence to current recommendations concerning the carriage of stand-by emergency treatment of malaria. However, the proportion of travellers seeking pre-travel health advice was overall low in our population. Promoting pre-travel consultations may, therefore, lead to higher adherence to the current recommendations in travel medicine.

Group B Streptococci serotype distribution in pregnant women in Ghana: assessment of potential coverage through future vaccines

Group B streptococcal (GBS) colonization of pregnant women can lead to subsequent infection of the new‐born and potentially fatal invasive disease. Data on GBS colonization prevalence and serotype distribution from Africa are scarce, although GBS‐related infections are estimated to contribute substantially to infant mortality. In recent years, GBS vaccine candidates provided promising results in phase I and II clinical trials. We aimed to assess the prevalence and serotype distribution of GBS in Ghana since this knowledge is a prerequisite for future evaluation of vaccine trials.

A 2013/2014 northern hemisphere season surface antigen inactivated trivalent influenza vaccine--Assessing the immunogenicity and safety in an open label, uncontrolled study.

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 mm2) 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 mm2 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.

Diagnosing Salmonella enterica Serovar Typhi Infections by Polymerase Chain Reaction Using EDTA Blood Samples of Febrile Patients From Burkina Faso

BACKGROUND Globally, there are an estimated 22 million cases of Salmonella enterica serovar Typhi infection each year. However, this figure is likely to be an underestimate due to the low sensitivity of blood culture in S. Typhi diagnosis. The aim of this study was to diagnose S. Typhi by conventional polymerase chain reaction (PCR) using patients blood preserved with ethylenediamine tetraacetic acid (EDTA). METHODS From April 2012 to September 2013, typhoid fever surveillance was conducted in Polesgo and Nioko, 2 dry slum areas in Ouagadougou, Burkina Faso. Blood culture was performed for febrile patients using an automated blood culture system. Additional blood was collected in EDTA tubes from those patients and preserved at -80°C. DNA was extracted from EDTA blood and PCR was performed to identify presence of S. Typhi. Randomly selected PCR products were further sequenced to identify S. Typhi-specific amplicons. RESULTS Of 1674 patients, S. Typhi was isolated from 18 (1.1%) individuals by blood culture. EDTA blood was collected from 1578 patients, of which 298 EDTA samples were tested by PCR. Salmonella Typhi-specific DNA was identified in 44 (14.8%) samples. The sensitivity of S. Typhi-specific PCR from EDTA blood was 89% (74%-100%) among the blood culture-positive cases. Sixteen S. Typhi-positive PCR products were sequenced, and 13 retrieved the sequence of a S. Typhi-specific amplicon. CONCLUSIONS These findings suggest that blood culture-based diagnoses of S. Typhi underestimate the burden of typhoid fever in Burkina Faso. PCR could be considered as an alternative method for the identification and diagnosis of S. Typhi in blood samples.