Asymptomatic arbovirus and campylobacter infections in German travelers to Asia.

The true risk for many travel diseases is unknown because most studies do not detect asymptomatic infections. In this study, we performed ELISA for dengue virus (DENV), chikungunya virus (CHIKV), Zika virus (ZIKV), hepatitis E virus (HEV), and Campylobacter jejuni on samples from 81 healthy Germans before and after they traveled to Asia. ELISA found five seroconversions for C. jejuni, two for DENV, one for ZIKV, and zero for HEV. For CHIKV, three subjects were positive before travel and negative afterwards. None had symptoms. These infections would have gone unnoticed by retrospective studies. Therefore, the risk for these infections may be higher than previously estimated.

Symptoms of illness during travel and risk factors for non-adherence to malaria prophylaxis-a cross-sectional study in travellers from Germany.

BACKGROUND: Perceived adverse effects of antimalarial chemoprophylaxis can be difficult to distinguish from travel-related illness and are often cited as important reasons for non-adherence or refusal of antimalarial chemoprophylaxis. We aimed to investigate the occurrence of symptoms of illness in travellers with and without chemoprophylaxis in a cross-sectional study after travel and to identify risk factors for non-adherence to prophylaxis. METHODS: We enrolled 458 travellers to Africa and South America during their pre-travel medical consultation at the travel clinic of the University Medical Centre Hamburg-Eppendorf and conducted post-travel interviews on symptoms of illness and intake of malaria prophylaxis. RESULTS: Eleven percent (49/437) of the participants reported symptoms of illness during travel. In total, 36% (160/448) of the participants reported prescription of chemoprophylaxis, the vast majority of these travelled to Africa (98%) and received atovaquone/proguanil (93%). Frequency of symptoms did not differ significantly between participants without prophylaxis and those taking atovaquone/proguanil. Non-adherence to prophylaxis was frequent (20%), but only 3% (4/149) of the participants stopped the medication early because of perceived side effects. Risk factors associated with non-adherence to prophylaxis included age under 30 years, travel to West or Central Africa and travel duration greater than 14 days. CONCLUSIONS: Symptoms of illness during travel occurred at similar frequencies irrespective of intake of chemoprophylaxis. Travellers should be informed about chemoprophylaxis in a balanced way, without raising fear of side effects, especially among groups at higher risk for incorrect use of prophylaxis.

Absence of Malaria-Associated Coagulopathy in Asymptomatic Plasmodium falciparum Infection: Results From a Cross-sectional Study in the Ashanti Region, Ghana.

Background: Coagulopathy is common in acute symptomatic Plasmodium falciparum malaria, and the degree of coagulation abnormality correlates with parasitemia and disease severity. Chronic asymptomatic malaria has been associated with increased morbidity. However, the role of coagulation activation in asymptomatic, semi-immune individuals remains unclear. This study investigates the potential effect of asymptomatic P falciparum infection on coagulation activation in semi-immune Ghanaian adults. Methods: Blood from asymptomatic Ghanaian adults with P falciparum blood stage infection detectable by polymerase chain reaction (PCR) or by both PCR and rapid diagnostic test and from noninfected individuals, was investigated. Markers of coagulation activation including global coagulation tests, D-dimer, antithrombin III, fibrinogen, and von Willebrand factor antigen were tested. Furthermore, blood count, inflammation markers, and liver and kidney function tests were assessed. Results: Acquired coagulopathy was not found in asymptomatic P falciparum infection. Asymptomatic malaria was associated with significantly lower platelet counts. Systemic inflammation markers and liver and kidney function tests were not altered compared to noninfected controls. Conclusions: There is no laboratory evidence for acquired coagulopathy in adults with asymptomatic P falciparum malaria in highly endemic regions. Lack of laboratory evidence for systemic inflammation and liver and kidney dysfunction indicates that asymptomatic malaria may not be associated with significant morbidity.

Impact of antibiotic intake on the incidence of extended-spectrum ß-lactamase-producing Enterobacterales in sub-Saharan Africa: results from a community-based longitudinal study.

OBJECTIVES: The global prevalence of intestinal extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) is approximately 17% in communities, with significant variations among regions. This longitudinal study aimed to assess the impact of antibiotic intake on the incidence of intestinal ESBL-PE in Ghanaian pharmacy customers outside of hospitals. METHODS: Screening for ESBL-PE was performed in four independent pharmacies in Kumasi, Ghana, using rectal swabs and an ESBL-PE-selective medium. Pharmacy customers purchasing antibiotics were recruited, and those buying non-antibiotic drugs served as controls. Participants who were negative for ESBL-PE provided follow-up swabs for up to 28 days. RESULTS: At baseline, 302 (75%) of 404 participants were colonized with ESBL-PE. Sixty-three participants who were negative for ESBL-PE at baseline received per-protocol follow-up, including 28 individuals who took antibiotics and 35 controls. The cumulative proportions of ESBL-PE in the antibiotics and control groups were 71% (20/28) and 54% (19/35) at the first follow-up (p 0.258), 86% (24/28) and 80% (28/35) at the second follow-up (p 0.741) and 86% (24/28) and 94% (33/35) at the third follow-up (p 0.393), respectively. DISCUSSION: The rate of intestinal ESBL-PE carriage among pharmacy customers outside of hospitals was higher than expected at baseline and further increased during the 28 days of follow-up, irrespective of antibiotic intake. This alarming finding needs to be considered in the antibiotic treatment of outpatients and emphasizes the urgent need for improved prevention strategies, development of new antibiotic drugs and potential future elimination strategies. Further longitudinal studies on ESBL-PE in African communities, also outside of pharmacy settings, are required.

Polymicrobial enteric infections in African infants with diarrhoea-results from a longitudinal prospective case-control study.

OBJECTIVES: This longitudinal case-control study aimed to determine the frequency of polymicrobial enteric detections in Ghanaian infants with and without diarrhoea. METHODS: Infants aged 1-12 months with and without diarrhoea attending the outpatient department of a peri-urban Ghanaian hospital were prospectively assessed and stool samples were collected on days 0, 6 and 28 and analysed for 18 enteric pathogens with PCR. RESULTS: At least one enteric pathogen was detected in 100 of 107 cases with diarrhoea (93%) and in 82 of 97 controls (85%). The number of pathogens was higher in cases than in controls (median three versus two pathogens, p 0.001). The adjusted attributable fraction (AF) for diarrhoea was highest for enterotoxigenic Escherichia coli (7.2%, 95% CI -2.0% to 16.3%), rotavirus (4.1%, 95% CI 0.6%-7.5%), Giardia lamblia (2.3%, 95% CI -0.7 to 5.3%) and astrovirus (2.3%, 95% CI -2.9 to 7.5%). In cases, a higher pathogen number was significantly associated with watery stool consistency (median 3, interquartile range (IQR) 2-5 versus median 2.5, IQR 1-4, p 0.014), stool frequency five or more per day (median 4, IQR 3-5 versus median 3, IQR 2-4, p 0.048) and vomiting (median 4, IQR 3-5 versus median 3, IQR 2-4, p 0.025). During follow-up, 94% (78/83) of cases and 85% (67/79) of controls had acquired at least one new pathogen without developing a new episode of diarrhoea. CONCLUSION: Enteric pathogens could be identified in the stool of the vast majority of Ghanaian infants, whereby pathogens were very frequently acquired without resulting in new episodes of diarrhoea during follow-up. A higher number of co-occurring pathogens may increase the risk of diarrhoea and disease severity.

High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018.

BACKGROUND: Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season. METHODS: Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed. RESULTS: Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum. CONCLUSIONS: Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri.

Risk factors for different intestinal pathogens among patients with traveler's diarrhea: A retrospective analysis at a German travel clinic (2009-2017).

BACKGROUND: Travelers' diarrhea (TD) is the most common illness experienced by travelers to developing regions of the world and may be caused by bacterial, parasitic or viral pathogens. The available diagnostic tests include stool microscopy for parasitic infections, culture-dependent methods for bacterial infections and molecular methods for bacterial, parasitic and viral infections. METHOD: We retrospectively evaluated demographic, clinical and microbiological data of patients presenting with TD at our travel clinic between 2009 and 2017. RESULTS: Among 676 patients with TD included in our study, at least one etiologic agent was found in 21% (n = 145) of cases. In total, 195 enteropathogens were detected of which 110 were bacteria, 70 protozoa and 15 helminths. Bacterial infections were significantly more common when symptoms were present less than 14 days and travel duration did not exceed 29 days. Protozoa and helminths were predominantly detected in patients with longer lasting complaints. After stool culture was replaced by a multiplex-PCR gastrointestinal pathogen panel (GPP) at our center, significantly more intestinal bacterial pathogens were detected. CONCLUSIONS: Our results support an individualized approach in the diagnostic workup of patients with TD taking host and travel characteristics into account to avoid unnecessary diagnostic testing. Molecular culture-independent diagnostic stool tests provide better coverage of the variety of etiological agents than traditional stool culture and have the benefit of rapid detection. However, the high sensitivity bears challenges differentiating colonization from infection.

Determinants of post-malarial anemia in African children treated with parenteral artesunate.

The pathophysiology of malarial anemia is multifactorial and incompletely understood. We assessed mechanistic and risk factors for post-malarial anemia in Ghanaian and Gabonese children with severe P. falciparum malaria treated with parenteral artesunate followed by an oral artemisinin-combination therapy. We analyzed data from two independent studies in which children were followed on Days 7,14, and 28 after treatment with artesunate. Specific hematological parameters included the presence of hemoglobinopathies and erythropoietin. Presence of once-infected erythrocytes was assessed by flow cytometry in a sub-population. Of 143 children with a geometric mean parasitemia of 116,294/µL (95% CI: 95,574-141,505), 91 (88%) had anemia (Hb < 10 g/dL) at presentation. Hemoglobin increased after Day 7 correlating with increased erythropoiesis through adequate erythropoietin stimulation. 22 children (24%) remained anemic until Day 28. Post-artesunate delayed hemolysis was detected in 7 children (5%) with only minor differences in the dynamics of once-infected erythrocytes. Hyperparasitemia and hemoglobin at presentation were associated with anemia on Day 14. On Day 28 only lower hemoglobin at presentation was associated with anemia. Most children showed an adequate erythropoiesis and recovered from anemia within one month. Post-artesunate delayed hemolysis (PADH) and hyperparasitemia are associated with early malarial anemia and pre-existing anemia is the main determinant for prolonged anemia.

Brain magnetic resonance imaging in imported malaria.

BACKGROUND: Previous studies have documented a spectrum of brain magnetic resonance imaging (MRI) abnormalities in patients with cerebral malaria, but little is known about the prevalence of such abnormalities in patients with non-cerebral malaria. The aim of this study was to assess the frequency of brain MRI findings in returning travellers with non-cerebral malaria. METHODS: A total of 17 inpatients with microscopically confirmed Plasmodium falciparum non-cerebral malaria underwent structural brain MRI at 3.0 Tesla, including susceptibility-weighted imaging (SWI). Presence of imaging findings was recorded and correlated with clinical findings and parasitaemia. RESULTS: Structural brain abnormalities included a hyperintense lesion of the splenium on T2-weighted imaging (n = 3) accompanied by visible diffusion restriction (n = 2). Isolated brain microhaemorrhage was detected in 3 patients. T2-hyperintense signal abnormalities of the white matter ranged from absent to diffuse (n = 10 had 0-5 lesions, n = 5 had 5-20 lesions and 2 patients had more than 50 lesions). Imaging findings were not associated with parasitaemia or HRP2 levels. CONCLUSION: Brain MRI reveals a considerable frequency of T2-hyperintense splenial lesions in returning travellers with non-cerebral malaria, which appears to be independent of parasitaemia.

[Prophylaxis and Therapy of Malaria: Current Recommendations]. / Prophylaxe und Therapie der Malaria: aktuelle Empfehlungen.

Malaria incidence is decreasing on a global scale, while the number of imported cases has remained at a high level in Germany. To decrease this number, counselling of travellers to malaria-endemic regions is important. Patients to high risk countries need regular chemoprophylaxis. The alternative of stand-by emergency treatment for travellers to regions with low or medium risk has been met with growing criticism. For the treatment of all malaria cases, artemisinins are a mainstay of treatment. Regular follow-up is warranted to prevent relapses. After treatment with intravenous artesunate for complicated malaria, delayed haemolysis must be kept in mind. A special situation has risen in Germany since 2014 with a growing number of Eritrean migrants presenting with Plasmodium vivax malaria. These patients need an additional course of primaquine to prevent relapses.

Helminthic infections in returning travelers and migrants with eosinophilia: Diagnostic value of medical history, eosinophil count and IgE.

OBJECTIVES: Eosinophilia in travelers and migrants returning from the tropics is often associated with invasive helminthic infections. Total IgE is considered a useful additional diagnostic parameter; however, both parameters are also increased in various other non-helminthic diseases. METHODS: We retrospectively evaluated travelers and migrants seen at our department between September 2007 and May 2014. Patients with an absolute eosinophil count ≥500 cells/µl were considered for further analyses. RESULTS: Among 6618 returned travelers and migrants, 154 (2.3%) had a total eosinophil count ≥500 cells/µL. Of these, 71 patients (46%) were diagnosed with helminthic infection. In an additional 62 patients (40%) with eosinophilia a final diagnosis was found, including non-helminthic infections in 34 patients and non-infectious causes in 28 patients, while in 21 patients (14%) no diagnosis was made. Patients with helminthic infections had higher eosinophil counts than travelers and migrants with other diagnoses (median 981 vs. 710 cells/µl; p = 0.001), while total IgE levels (n = 70; 172 vs. 152 kU/l; p = 0.731) were similar in both groups. CONCLUSION: Eosinophil count but not total IgE levels are associated with helminthic infections in returning travelers and migrants with eosinophilia. Our results do not support the use of total IgE to differentiate helminthic infections from other causes of eosinophilia in this population.

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.

Current meningitis outbreak in Ghana: Historical perspectives and the importance of diagnostics.

Bacterial meningitis continues to be one of the most dreaded infections in sub-Saharan Africa and other countries that fall in the "meningitis belt" due to recurrent nature of the infection and the sequel of deliberating effects among survivors even after treatment. Ghana has had recurrent epidemics in the past but has been free from high mortality levels. Whereas reasons for the low reported number of deaths in the past are unclear, we hypothesize that it may be due to increased vaccination from expanded program on immunization (EPI) and consequent herd immunity of the general population. As at the end of February, 2016, 100 individuals were reported to have died out of 500 recorded cases. The infection may cause severe brain damage and kills at least 1 out of 10 individuals if quick interventions are not provided. The Ghana Health Service (GHS) and the Ministry of Health (MoH), together with other local and international stakeholders are working intensely to control the spread of the infection in affected communities with treatment and other health management programmes. This review presents a quick overview of meningitis in Ghana with emphasis on S. pneumoniae (responsible for about 70% of cases in the recent epidemic) together with some recommendations aimed at ensuring a "meningitis-free Ghana".

Response to fever and utilization of standby emergency treatment (SBET) for malaria in travellers to Southeast Asia: a questionnaire-based cohort study.

BACKGROUND: Guidelines in several European countries recommend standby emergency treatment (SBET) for travellers to regions with low or medium malaria transmission instead of continuous chemoprophylaxis: travellers are advised to seek medical assistance within 24 h in case of fever and to self-administer SBET only if they are not able to consult a doctor within the time period specified. Data on healthcare-seeking behaviour of febrile travellers and utilization of SBET is however scarce as only two studies were performed in the mid-1990s. Since tourism is constantly increasing and malaria epidemiology has dramatically changed in the meantime more knowledge is urgently needed. METHODS: Some 876 travellers to destinations in South and Southeast Asia with low or medium malaria transmission were recruited in the travel clinic of the University Medical Center Hamburg-Eppendorf. Demographic and travel-related data were collected by using questionnaires. Pre-travel advice was carried out and SBET was prescribed in accordance to national guidelines. Post-travel phone interviews were performed to assess health incidents during travel and individual responses of travellers to febrile illness. RESULTS: Out of 714 patients who were monitored, 130 (18%) reported onset of fever during travel or 14 days after return. Of those travellers who reported fever, 100 (80%) carried SBET during travel. The vast majority of 79 (79%) febrile travellers who carried SBET did not seek medical assistance. Overall, 14 (14%) febrile patients who carried SBET and six (20%) patients who did not carry SBET took the correct measure (doctor visit or timely SBET administration) as a response to febrile illness, respectively. Only two travellers self-administered SBET, but both of them applied the wrong regimen. CONCLUSIONS: In view of declining malaria transmission and improving medical infrastructure in most countries of Southeast Asia and obvious obstacles concerning SBET as shown in this study the current strategy should be re-evaluated. Pre-travel advice concerning malaria in SEA should focus on appropriate mosquito bite protection and clearly emphasize the need to see a doctor within 24 h after onset of fever.

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.

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 patient's 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.

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.

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 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.

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

BACKGROUND: Malaria 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. METHODS: Data 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. RESULTS: Complete 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. CONCLUSIONS: The 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.