Rabies knowledge gaps and risk behaviour in Dutch travellers: An observational cohort study.

BACKGROUND: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers' knowledge and risk perception of rabies and risk behaviour during travel can help identify knowledge gaps and improve pre-travel risk education. METHODS: Cohort study in Dutch adult travellers, using two surveys: one before travel to assess knowledge and perception of rabies, and one after return to identify risk behaviour during travel. RESULTS: The pre-travel and post-travel survey were completed by 301 and 276 participants, respectively. 222 participants had travelled to a high-risk rabies-endemic country. 21.6 % of the participants scored their rabies knowledge as poor. Some participants were unaware cats or bats can transmit rabies (26.6 % and 13.6 %, respectively), or that post-exposure prophylaxis (PEP) is required for certain exposures such as skin abrasions without bleeding or licks on damaged skin (35.5 % and 18.9 %, respectively), while 27.9 % of participants did not know PEP needs to be administered within one day. 115 participants (51.8 %) reported any form of contact with any animal during travel. Two participants reported animal exposure, of which one took adequate PEP measures. Risk factors for animal contact abroad were regularly touching cats or dogs at home or abroad, longer travel duration, having pets during childhood and being an animal lover. CONCLUSIONS: Pre-travel rabies risk education currently does not meet travellers' needs, which is reflected in knowledge gaps and engagement in risk behaviour during travel. During pre-travel health advice, avoiding animal contact abroad should be emphasized, and additional education is required about indications for PEP.

Boostability after single-visit pre-exposure prophylaxis with rabies vaccine: a randomised controlled non-inferiority trial.

BACKGROUND: After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). However, PrEP is not sufficiently accessible as it is cost-intensive and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing some of these barriers. METHODS: In a block-randomised (2:2:2:1) controlled, multicentre non-inferiority trial, healthy adult travellers (aged 18-50 years and >50 years) were randomly assigned to (A) single-visit intramuscular (1·0 mL); (B) single-visit intradermal (0·2 mL); (C) standard two-visit intramuscular (1·0 mL; day 0 and 7) PrEP; or (D) no rabies vaccination. 6 months later, participants received simulated intramuscular rabies PEP (1·0 mL; day 0 and 3). Rabies virus neutralising antibody (RVNA) concentrations were measured repeatedly. The primary outcome was the fold increase in geometric mean RVNA concentrations between day 0 and 7 after simulated PEP for all participants. The two main comparisons of this primary outcome are between the standard two-visit schedule and the one-visit intramuscular schedule, and between the standard two-visit schedule and the one-visit intradermal schedule. The non-inferiority margin was 0·67. This study is registered with EudraCT, 2017-000089-31. FINDINGS: Between May 16, 2018, and March 26, 2020, 288 healthy adult travellers were randomly assigned and 214 participants were evaluated for the primary outcome. Single-visit intramuscular rabies PrEP induced an anamnestic antibody response non-inferior compared with the two-visit intramuscular schedule; single-visit intradermal PrEP did not. The fold increases in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43-3·77]) and 1·11 (0·66-1·87) times as high as the fold increase in the standard schedule, respectively. No vaccine-related serious adverse events were observed. Adverse events related to vaccination were mostly mild. INTERPRETATION: Single intramuscular rabies vaccination can effectively prime travellers (aged 18-50 years), and potentially other populations, and could replace current standard two-visit rabies vaccination as PrEP. FUNDING: ZonMW. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

Hospital-based care and/or death followed by repatriation in Dutch travelers: The HAZARD study.

BACKGROUND: Travelers can experience health problems while abroad. This descriptive study aimed to quantify the disease burden leading to hospital-based care, repatriation or death in Dutch travelers during a stay in a foreign country, including Europe. METHODS: Retrospective study of demographic and clinical data from three medical assistance centers (MACs) and the Dutch Ministry of Foreign Affairs on Dutch travelers receiving hospital-based care or who died abroad in the years 2010-2014. Diagnoses were coded according to the International Classification of Diseases (ICD) and classified using the Global Burden of Disease tool. RESULTS: Data was available for 77,741 travelers' incidents: 75,385 medical consultations and 2,356 deaths. Four in five travelers received inpatient care, of which 36% concerned older travelers (65+) who had significantly longer hospital stays. Overall the top three diagnoses were: injuries (29%), infectious diseases (17%), and cardiovascular diseases (17%). Mental illness was reported in nearly 1.5% of the travelers. Incidence proportions were highest in South-Eastern Asia, with enteric infections as most common diagnosis. Injuries and communicable diseases occurred most often in South-Eastern Asia, while non-communicable diseases were mostly reported in South America. One in five travelers who consulted a physician was repatriated back home, mostly on a scheduled flight with or without medical escort. Cardiovascular diseases and injuries were the leading causes of death. CONCLUSIONS: Not only communicable diseases, but also injuries and chronic diseases (in particular cardiovascular diseases) frequently affected travelers' health while staying abroad and frequently necessitated hospital-based care. This should be addressed during the pre-travel counseling.

Measles seroprevalence among Dutch travelling families.

BACKGROUND: While measles vaccination is widely implemented in national immunisation programmes, measles incidence rates are increasing worldwide. Dutch inhabitants who were born between 1965-1975 may have fallen between two stools, lacking protection from a natural infection, and having missed the introduction of the measles vaccination schedule. With this study we aim to find the measles seroprevalence in travellers born between 1965 and 1975, compared to those born before 1965 and after 1975. METHODS: Families travelling to Eastern Europe or outside Europe during the preceding year were recruited via Dutch secondary schools between 2016 and 2018. Their vaccination status was assessed using questionnaires, vaccination records and measles serology in dried blood spot (DBS) eluates. Measles virus antibody concentrations were determined with an ELISA (EUROIMMUNE®) and a subset was retested with a focus reduction neutralization assay (FRNT). RESULTS: In 188 (79%) of the 239 available DBS eluates, the ELISA could detect sufficient measles virus-specific IgG antibodies. Of the negative samples that were retested with FRNT, 85% remained negative, resulting in an overall seroprevalence of 82% [95% CI 76-86]. Children had a lower seroprevalence (72%) than adults (87%). Travellers born between 1965 and 1975 were protected in 89%. CONCLUSIONS: In this study, we report a measles seroprevalence of 82% among Dutch travelling families. Remarkably, seroprevalence rates were lowest in children (12-18 years) instead of travellers born between 1965 and 1975. Although a fraction of people without detectable antibodies may be protected by other immune mechanisms, these data suggest that measles (re)vaccination should be considered for travellers to endemic regions.

A comparative study of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) blood levels and peripheral blood parasitemia as parameters of disease severity in individuals with imported falciparum malaria.

BACKGROUND: In falciparum malaria the total parasite biomass can be estimated by blood levels of histidine-rich protein 2 (PfHRP2), a Plasmodium falciparum-specific protein, which has been widely studied in malaria-endemic regions. This study investigates the usefulness of PfHRP2 as marker for disease severity in imported falciparum malaria. METHODS: A retrospective cohort analysis was done in 145 patients with imported falciparum malaria. Associations between PfHRP2, malaria disease severity and classic parameters of disease severity were examined by statistical analyses. Patients with different travel purposes were examined in two groups: visiting friends and relatives (VFRs) and other travel purposes (mainly tourists). RESULTS: High PfHRP2 levels were clearly associated with disease severity. VFRs status showed to be an independent determinant protecting against severe malaria. At similar PfHRP2 levels VFRs patients had significantly lower levels of peripheral blood parasitemia compared to other patients. CONCLUSION: Our study confirms the association between PfHRP2 and disease severity in patients with imported falciparum malaria, but for proper interpretation of PfHRP2 levels as disease severity marker in travellers, the possible presence of pre-existing acquired anti-malarial immunity should be taken into account as the correlation between PfHRP2 levels and disease severity differed significantly between VFRs patients and patients with other travel purposes.

Lactic acid fermentation in the development of a seaweed sauerkraut-style product: Microbiological, physicochemical, and sensory evaluation.

Consumption of nutrient-rich seaweeds and fermented nondairy foods represent fast growing trends among health-minded consumers. Assessment of lacto-fermented seaweed was performed to address these trends, and to offer shelf-life extension and product diversification for fresh kelps. The objectives were to evaluate the effects of kelp species and inclusion level on fermentation kinetics, physicochemical quality, safety, shelf-life, and consumer acceptability of a seaweed sauerkraut-style product. Six formulations with different inclusion levels (25, 50, and 75%) of shredded kelp (sugar kelp, SK or winged kelp, WK) were mixed with cabbage, 2% salt, and inoculated with Lactobacillus plantarum (approximately 106 CFU/g) and Leuconostoc mesenteroides (approximately 101 CFU/g). Products were processed in triplicate, fermented until a target pH of ≤4.6 was achieved, and sampled periodically for 60 days. Kelp species and inclusion level significantly affected most variables tested. The most rapid fermentation (3 days), as evidenced by pH decrease, lactic acid bacteria counts, and lactic acid levels, was noted in WK formulations. Some SK formulations took up to 14 days to achieve the target pH, and coliforms persisted to a greater extent in the SK formulations. Higher levels of kelp decreased the fermentation rate and concentration of fermentable sugars in the brine, but increased the total phenolic content and antioxidant activity of the sauerkrauts. Despite differences in instrumental color (L* a* b* ) and texture (shear force) among formulations, overall liking as rated by a consumer panel was not significantly affected by species or inclusion level. Results support the use of lacto-fermentation in the production of refrigeration-stable seaweed sauerkraut-style product. PRACTICAL APPLICATION: Health-conscious consumers are becoming increasingly interested in plant-based diets and fermented foods, and the development of novel seaweed sauerkraut-style products can help to meet these needs. This study demonstrated the successful production of a sauerkraut-style product formulated with up to 50% farm-raised kelp. Physical, chemical, microbiological, and consumer acceptability testing established lactic acid fermentation as a viable method for shelf life extension and value addition of fresh kelps. These results provide science-based information on an alternative processing method for cultivated seaweeds and can assist the industry in product diversification efforts.

Travel-related infections presenting in Europe: A 20-year analysis of EuroTravNet surveillance data.

BACKGROUND: Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. METHODS: We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. FINDINGS: 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. INTERPRETATION: Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. FUNDING: This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.

Travel-related hepatitis E: a two-decade GeoSentinel analysis.

BACKGROUND: Hepatitis E virus (HEV) is widely distributed worldwide and is endemic in developing countries. Travel-related HEV infection has been reported at national levels, but global data are missing. Moreover, the global availability of HEV diagnostic testing has not been explored so far. The aim of this study is to describe the epidemiology of HEV infections in returning travellers and availability of HEV diagnostic testing in the GeoSentinel surveillance network. METHODS: This was a multicentre retrospective cross-sectional study. All confirmed and probable HEV travel-related infections reported in the GeoSentinel Network between 1999 and 2018 were evaluated. GeoSentinel sites were asked to complete a survey in 2018 to assess the availability and accessibility of HEV diagnostic procedures (i.e. serology and molecular tests) throughout the study period. RESULTS: Overall, 165 travel-related HEV infections were reported, mainly since 2010 (60%) and in tourists (50%). Travellers were exposed to hepatitis E in 27 countries; most travellers (62%) were exposed to HEV in South Asia. One patient was pregnant at the time of HEV infection and 14 had a concomitant gastrointestinal infection. No deaths were reported. In the 51% of patients with information available, there was no pre-travel consultation. Among 44 GeoSentinel sites that responded to the survey, 73% have access to HEV serology at a local level, while 55% could perform (at a local or central level) molecular diagnostics. CONCLUSION: Reported access to HEV diagnostic testing is suboptimal among sites that responded to the survey; this could negatively affect diagnosing HEV. Pre-travel consultations before travel to South Asia and other low-income and high-prevalence areas with a focus on food and water precautions could be helpful in preventing hepatitis E infection. Improved HEV diagnostic capacity should be implemented to prevent and correctly diagnose travel-related HEV infection.

An open-label phase 1/2a trial of a genetically modified rodent malaria parasite for immunization against Plasmodium falciparum malaria.

For some diseases, successful vaccines have been developed using a nonpathogenic counterpart of the causative microorganism of choice. The nonpathogenicity of the rodent Plasmodium berghei (Pb) parasite in humans prompted us to evaluate its potential as a platform for vaccination against human infection by Plasmodium falciparum (Pf), a causative agent of malaria. We hypothesized that the genetic insertion of a leading protein target for clinical development of a malaria vaccine, Pf circumsporozoite protein (CSP), in its natural pre-erythrocytic environment, would enhance Pb's capacity to induce protective immunity against Pf infection. Hence, we recently generated a transgenic Pb sporozoite immunization platform expressing PfCSP (PbVac), and we now report the clinical evaluation of its biological activity against controlled human malaria infection (CHMI). This first-in-human trial shows that PbVac is safe and well tolerated, when administered by a total of ~300 PbVac-infected mosquitoes per volunteer. Although protective efficacy evaluated by CHMI showed no sterile protection at the tested dose, significant delays in patency (2.2 days, P = 0.03) and decreased parasite density were observed after immunization, corresponding to an estimated 95% reduction in Pf liver parasite burden (confidence interval, 56 to 99%; P = 0.010). PbVac elicits dose-dependent cross-species cellular immune responses and functional PfCSP-dependent antibody responses that efficiently block Pf sporozoite invasion of liver cells in vitro. This study demonstrates that PbVac immunization elicits a marked biological effect, inhibiting a subsequent infection by the human Pf parasite, and establishes the clinical validation of a new paradigm in malaria vaccination.

In vitro screening of technical lignins to determine their potential as hay preservatives.

Our objectives were to evaluate technical lignins for their antifungal properties against 3 molds and 1 yeast causing hay spoilage, and their ability to preserve ground high-moisture alfalfa hay nutritive value in vitro. In experiment 1, 8 technical lignins and propionic acid (PRP; positive control) were tested at a dose of 40 mg/mL. The experiment had a randomized complete block design (RCBD, 4 runs) and a factorial arrangement of 3 molds × 10 additives (ADV). The effects of the ADV on yeast were evaluated separately with a RCBD. Sodium lignosulfonate (NaL) and PRP were the only treatments with 100 ± 2.8% inhibition of fungi. In experiment 2, the minimum inhibitory concentration (MIC) for selected lignins and PRP were determined. At pH 4, NaL had the lowest MIC across the molds (20-33.3 mg/mL) and magnesium lignosulfonate (MgL) for the yeast (26.7) among the lignins. However, PRP had MIC values that were several-fold lower across all fungi (1.25-3.33). In experiment 3, a RCBD (5 blocks) with a 3 (ADV; NaL, MgL, and PRP) × 4 (doses: 0, 0.5, 1, and 3% wt/wt fresh basis) factorial arrangement of treatments was used to evaluate the preservative effects of ADV in ground high-moisture alfalfa hay inoculated with a mixture of the fungi previously tested and incubated under aerobic conditions in vitro. After 15 d, relative to untreated hay (14.9), dry matter (DM) losses were lessened by doses as low as 1% for NaL (3.39) and 0.5% for PRP (0.81 ± 0.77%). The mold count was reduced in both NaL at 3% (3.92) and PRP as low as 0.5% (3.94) relative to untreated hay (7.76 ± 0.55 log cfu/fresh g). Consequently, sugars were best preserved by NaL at 3% (10.1) and PRP as low as 0.5% (10.5) versus untreated (7.99 ± 0.283% DM), while keeping neutral detergent fiber values lower in NaL (45.9) and PRP-treated (45.1) hays at the same doses, respectively, relative to untreated (49.7 ± 0.66% DM). Hay DM digestibility was increased by doses as low as 3% for NaL (67.5), 1% MgL (67.0), and 0.5% PRP (68.5) versus untreated hay (61.8 ± 0.77%). The lowest doses increasing neutral detergent fiber digestibility relative to untreated hay (23.3) were 0.5% for MgL and PRP (30.5 and 30.1, respectively) and 1% for NaL (30.7 ± 1.09% DM). Across technical lignins, NaL showed the most promise as a potential hay preservative. However, its effects were limited compared with PRP at equivalent doses. Despite not having an effect on preservation, MgL improved DM digestibility by stimulating neutral detergent fiber digestibility. This study warrants further development of NaL under field conditions.

Antigen-based diagnosis of Schistosoma infection in travellers: a prospective study.

BACKGROUND: Travellers infected with Schistosoma spp. might be pauci- or even asymptomatic on first presentation. Therefore, schistosomiasis may remain undiagnosed in this population. Active infection, as evidenced by the presence of the tissue-dwelling worm, can be demonstrated via the detection of adult worm-derived circulating anodic antigen (CAA) utilising a robust well-described lateral flow-(LF) based test applying background-free up-converting reporter particles (UCP). In this prospective study, we assessed the diagnostic value of serum and urine UCP-LF CAA test in comparison with two Schistosoma-specific serological assays detecting antibodies against adult worm antigen-immuno fluorescence assay (AWA-IFA) and against soluble egg antigen-enzyme-linked immunosorbent assay (SEA-ELISA) antigens in travellers. METHODS: Samples were collected from 106 Dutch travellers who reported freshwater contact in sub-Saharan Africa and who were recruited up to 2 years after return. Subjects were asked to complete a detailed questionnaire on travel history, water contact, signs and symptoms compatible with schistosomiasis. RESULTS: Two travellers were positive by serum CAA and an additional one by urine CAA. A total of 22/106 (21%) samples were antibody positive by AWA-IFA and 9/106 (9%) by SEA-ELISA. At follow-up 6 weeks and 6 months after praziquantel treatment, all seropositives remained antibody positive whereas CAA was cleared. Seropositivity could not be predicted by the type of fresh water-related activity, country visited or symptoms reported. CONCLUSION: The low number of UCP-LF CAA positives suggests that in travellers, active infections often do not establish or have very low worm burden. Based on our high seroconversion rates, we conclude that the AWA-IFA assay is the most sensitive test to detect schistosome exposure. Given the lack of predictive symptoms or risk factors, we recommend schistosomiasis screening at least by serology in all travellers with reported freshwater contact in high-endemic areas.

Prevalence and risk factors for carriage of ESBL-producing Enterobacteriaceae in a population of Dutch travellers: A cross-sectional study.

BACKGROUND: We investigated prevalence and predictive factors for ESBL-E carriage in a population of mostly travellers prior to their travel (n = 2216). In addition, we examined ESBL genotype before travel and compared these to returning travellers. METHOD: A questionnaire and faecal sample were collected before travel, and a second faecal sample was collected immediately after travel. Faecal samples were analysed for ESBL-E, with genotypic characterization by PCR and sequencing. Risk factors for ESBL-E carriage prior to travel were identified by logistic regression analyses. RESULTS: Before travel, 136 participants (6.1%) were colonized with ESBL-E. Antibiotic use in the past three months (ORadjusted 2.57; 95% CI 1.59-4.16) and travel outside of Europe in the past year (1.92, 1.28-2.87) were risk factors for ESBL-E colonisation prior to travel. Travel outside of Europe carried the largest attributable risk (39.8%). Prior to travel 31.3% (40/128) of participants carried blaCTX-M 15 and 21.9% (28/128) blaCTX-M 14/18. In returning travellers 633 acquired ESBL-E of who 53.4% (338/633) acquired blaCTX-M 15 and 17.7% (112/633) blaCTX-M 14/18. CONCLUSION: In our population of Dutch travellers we found a pre-travel ESBL-E prevalence of 6.1%. Prior to travel, previous antibiotic use and travel outside of Europe were the strongest independent predictors for ESBL-E carriage, with travel outside of Europe carrying the largest attributable risk. Our molecular results suggest ESBL genes found in our study population prior to travel were in large part travel related.

Sources of food contamination in a closed hydroponic system.

This study investigated potential contamination sources in a commercial, closed hydroponic system. Water, substrate and lettuce (Lactuca sativa) samples were evaluated for microbiological indicator populations, including aerobic plate count (APC), coliform bacteria (CB) and yeast and mould (YM). Listeria spp. detection via cultural enrichment and agglutination was negative for all samples. Peat moss substrate (postharvest) had the highest counts for APC (6·8 log CFU per g), CB (4·5 log MPN per g) and YM (5·1 and 4·8 log CFU per g respectively). Roots embedded in plugs demonstrated counts for all populations nearly as high as the substrate. Among water samples, a seedling water reservoir housing germinated plants yielded the highest count for APC (5·1 log CFU per g) and CB (2·4 log MPN per g) likely due to the large numbers of plugs and their close proximity in the reservoir. Harvested lettuce leaves demonstrated higher APC (4·1 log CFU per g) than preharvest leaves (1·7 log CFU per g) due to the transfer of microbes from the root ball. These data suggest that substrates are a significant potential source of contamination in hydroponic systems and likely facilitate microbial transfer to harvested leaves. There is, therefore, the need to further investigate mitigation of potential contamination events. SIGNIFICANCE AND IMPACT OF THE STUDY: Hydroponic production is known to provide safe, clean produce. This study, however, suggests that the hydroponic substrate (peat moss plug) is a possible source of contamination in the hydroponic system. This finding is important as most harvested hydroponic lettuces are packaged and sold with substrate and root ball intact. This implies a high probability of microbial transfer from the root ball to edible harvested lettuce leaves.

Transforming growth factor-beta profiles correlate with clinical symptoms and parameters of haemostasis and inflammation in a controlled human malaria infection.

BACKGROUND: After a controlled human malaria infection (CHMI), presentation of clinical signs and symptoms and host responses is heterogeneous. Transforming growth factor-beta (TGF-ß) is the first serum cytokine that changes in malaria-naïve volunteers after CHMI. We studied a possible relation between TGF-ß changes, pro-inflammatory cytokines, activation of haemostasis and endothelial cells and clinical symptoms. METHODS: A panel of cytokines including TGF-ß, and markers of activation of haemostasis and endothelial cells were measured in blood samples of 15 volunteers at baseline before CHMI and during CHMI at day of treatment. The change of the parameters on the day of treatment was examined for a significant alteration during infection. RESULTS: Nine of 15 volunteers showed a significant decrease in TGF-ß compared to baseline, with concomitant increased concentrations of D-dimer (p = 0.012), Von Willebrand factor (p = 0.017), IL-6 (p = 0.012) and IFN-γ (0.028) and a significantly decreased platelet count (p = 0.011). In contrast, 6 of 15 volunteers showed sustained or increased TGF-ß concentrations without change in the aforementioned parameters. The sustained responders presented with less moderate and severe clinical symptoms than the negative responders (p = 0.036) and had a higher baseline lymphocyte count (p = 0.026). TGF-ß concentrations did not correlate with the parasitaemia on day of treatment. CONCLUSION: Early decreases of serum TGF-ß might function a marker for a pro-inflammatory host response and downstream clinical symptoms and pathology during CHMI.