Field Epidemiology: Fit for the future.

In recent years, field epidemiologists have embraced rapidly evolving digital tools, data sources and technologies, and collaborated with an ever-growing field of scientific specialisms. The COVID-19 pandemic put field epidemiology under unprecedented demand and scrutiny. As the COVID-19 emergency recedes, it is timely to reflect on the core values of our profession and the unique challenges and opportunities that lie ahead. In November 2022, alumni of the European Programme for Intervention Epidemiology Training (EPIET) and the European Public Health Microbiology (EUPHEM) training programme celebrated 25 years of EPIET, and the present and future of field epidemiology was discussed. The output was recorded and qualitatively analysed. This Perspective reflects the authors' interpretation of the discussion. We should reaffirm our commitment to field epidemiology's core strengths: competence and rigour in epidemiology, surveillance, outbreak investigation and applied research, leading to timely and actionable evidence for public health. Our future success will be defined by an ability to adapt, collaborate, harness innovation, communicate and, ultimately, by our tangible impact on protecting and improving health.

Field Epidemiology and Public Health Microbiology training: capturing the alumni perspectives of the training's impact.

We present the findings from the European Programme for Intervention Epidemiology Training (EPIET) Alumni Network (EAN) Member Survey conducted in October to December 2021. The EAN consists of field epidemiologists (EPIET) and public health microbiologists (European Public Health Microbiology Training Programme (EUPHEM)) who stay connected after their 2-year fellowship. This active alumni network provides opportunities for career development, mentorship, knowledge exchange and sharing of best practices for community members, affiliated professionals and public health organisations in Europe. Overall, 281 of 732 members participated in the survey. Of the 192 European fellowship alumni respondents, 173 (90%) indicated that skills and competencies acquired during their fellowship improved performance in their role compared with their abilities before the fellowship. Reported skills and competencies that could be further strengthened included data management/analysis, communication, mathematical modelling and leadership/team management. The EAN Member Survey provides valuable feedback to the EAN, as well as the fellowship programme offices at the European Centre for Disease Prevention and Control (ECDC) and affiliated field epidemiology programmes. The COVID-19 pandemic was a stark reminder of how essential cross-border collaborations are for continued European health security. Maintaining and increasing the professional, well-trained workforce remains crucial for optimal response to infectious diseases and protection of public health.

Evaluation and optimization of the syndromic management of female genital tract infections in Nairobi, Kenya.

BACKGROUND: Genital tract infections pose a public health concern. In many low-middle-income countries, symptom-based algorithms guide treatment decisions. Advantages notwithstanding, this strategy has important limitations. We aimed to determine the infections causing lower genital tract symptoms in women, evaluated the Kenyan syndromic treatment algorithm for vaginal discharge, and proposed an improved algorithm. METHODS: This cross-sectional study included symptomatic non-pregnant adult women presenting with lower genital tract symptoms at seven outpatient health facilities in Nairobi. Clinical, socio-demographic information and vaginal swabs microbiological tests were obtained. Multivariate logistic regression analyses were performed to find predictive factors for the genital infections and used to develop an alternative vaginal discharge treatment algorithm (using 60% of the dataset). The other 40% of data was used to assess the performance of each algorithm compared to laboratory diagnosis. RESULTS: Of 813 women, 66% had an infection (vulvovaginal candidiasis 40%, bacterial vaginosis 17%, Neisseria gonorrhoea 14%, multiple infections 23%); 56% of women reported ≥ 3 lower genital tract symptoms episodes in the preceding 12 months. Vulvovaginal itch predicted vulvovaginal candidiasis (odds ratio (OR) 2.20, 95% CI 1.40-3.46); foul-smelling vaginal discharge predicted bacterial vaginosis (OR 3.63, 95% CI 2.17-6.07), and sexually transmitted infection (Neisseria gonorrhoea, Trichomonas vaginalis, Chlamydia trachomatis, Mycoplasma genitalium) (OR 1.64, 95% CI 1.06-2.55). Additionally, lower abdominal pain (OR 1.73, 95% CI 1.07-2.79) predicted sexually transmitted infection. Inappropriate treatment was 117% and 75% by the current and alternative algorithms respectively. Treatment specificity for bacterial vaginosis/Trichomonas vaginalis was 27% and 82% by the current and alternative algorithms, respectively. Performance by other parameters was poor to moderate and comparable between the two algorithms. CONCLUSION: Single and multiple genital infections are common among women presenting with lower genital tract symptoms at outpatient clinics in Nairobi. The conventional vaginal discharge treatment algorithm performed poorly, while the alternative algorithm achieved only modest improvement. For optimal care of vaginal discharge syndrome, we recommend the inclusion of point-of-care diagnostics in the flowcharts.

Low SARS-CoV-2 Cq values in healthcare workers with symptomatic COVID-19 infections, regardless of symptom severity, The Netherlands, January to August 2022.

We analysed SARS-CoV-2 PCR Cq values from 3,183 healthcare workers who tested positive between January and August 2022. Median Cq values were lower in symptomatic than in asymptomatic HCW. The difference in Cq values between HCW with mild vs moderate/severe symptoms was statistically significant but negligibly small. To prevent nosocomial infections, all symptomatic HCW should be tested irrespective of symptom severity. This information can support decisions on testing and isolation, in the context of ongoing pressure on healthcare systems.

The in situ efficacy of whole room disinfection devices: a literature review with practical recommendations for implementation.

BACKGROUND: Terminal cleaning and disinfection of hospital patient rooms must be performed after discharge of a patient with a multidrug resistant micro-organism to eliminate pathogens from the environment. Terminal disinfection is often performed manually, which is prone to human errors and therefore poses an increased infection risk for the next patients. Automated whole room disinfection (WRD) replaces or adds on to the manual process of disinfection and can contribute to the quality of terminal disinfection. While the in vitro efficacy of WRD devices has been extensively investigated and reviewed, little is known about the in situ efficacy in a real-life hospital setting. In this review, we summarize available literature on the in situ efficacy of WRD devices in a hospital setting and compare findings to the in vitro efficacy of WRD devices. Moreover, we offer practical recommendations for the implementation of WRD devices. METHODS: The in situ efficacy was summarized for four commonly used types of WRD devices: aerosolized hydrogen peroxide, H2O2 vapour, ultraviolet C and pulsed xenon ultraviolet. The in situ efficacy was based on environmental and clinical outcome measures. A systematic literature search was performed in PubMed in September 2021 to identify available literature. For each disinfection system, we summarized the available devices, practical information, in vitro efficacy and in situ efficacy. RESULTS: In total, 54 articles were included. Articles reporting environmental outcomes of WRD devices had large variation in methodology, reported outcome measures, preparation of the patient room prior to environmental sampling, the location of sampling within the room and the moment of sampling. For the clinical outcome measures, all included articles reported the infection rate. Overall, these studies consistently showed that automated disinfection using any of the four types of WRD is effective in reducing environmental and clinical outcomes. CONCLUSION: Despite the large variation in the included studies, the four automated WRD systems are effective in reducing the amount of pathogens present in a hospital environment, which was also in line with conclusions from in vitro studies. Therefore, the assessment of what WRD device would be most suitable in a specific healthcare setting mostly depends on practical considerations.

Success rates of MRSA decolonization and factors associated with failure.

BACKGROUND: We evaluated the success rate of MRSA decolonization directly after treatment and after one year in patients who were treated at the outpatient MRSA clinic of a large university medical centre to identify potential contributing factors to treatment success and failure. METHODS: Data from November 1, 2013 to August 1, 2020 were used. Only patients who had undergone complete MRSA decolonization were included. Risk factors for MRSA treatment failure were identified using a multivariable logistic regression model. RESULTS: In total, 127 MRSA carriers were included: 7 had uncomplicated carriage, 91 had complicated carriage, and 29 patients had complicated carriage in combination with an infection. In complicated carriers and complicated carriers with an infection final treatment was successful in 75.0%. Risk factors for initial treatment failure included having one or more comorbidities and not testing the household members. Risk factors for final treatment failure were living in a refugee centre, being of younger age (0-17 years), and having one or more comorbidities. CONCLUSIONS: The results of this study indicate that patients with a refugee status and children treated at the paediatric clinic have a higher risk of MRSA decolonisation treatment failure. For this reason, it might be useful to revise decolonization strategies for these subgroups and to refer these patients to specialized outpatient clinics in order to achieve higher treatment success rates.

Interventions to improve dispensing of antibiotics at the community level in low and middle income countries: a systematic review.

OBJECTIVES: Inappropriate antibiotic dispensing is one of the key drivers of antibiotic resistance. This review documents the effectiveness of interventions aimed at improving antibiotic dispensing practices at the community level by drug dispensers in low- and middle-income countries (LMIC). METHODS: We conducted a systematic search in PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science (11 November 2019). Studies were included if they reported data on the outcome measure: appropriate dispensing of medicine including antibiotics. The effectiveness of studies was assessed based on quantitative results reported in the studies included. RESULTS: A total of 1158 articles were screened. Thirteen studies from Asia (six), Africa (five) and South America (one) and one study from both Africa and Asia were included in this review. Nine (69.2%) studies reported significant effectiveness of interventions on all or more than 50% of antibiotic-related outcomes. Cochrane Effective Practice and Organization of Care interventions frequently applied were educational meetings (9/13), distribution of educational materials (7/13), educational outreach meetings (7/13), reminders (6/13), local consensus processes (6/13), distribution of supplies (6/14) and clinical practice guidelines (4/14), Nine studies reported on stakeholder involvement. CONCLUSION: This review shows that it is possible to improve antibiotic dispensing practices at the community level in LMIC. Stakeholders' involvement was key in the design and implementation of interventions.

SARS-CoV-2 whole-genome sequencing using reverse complement PCR: For easy, fast and accurate outbreak and variant analysis.

During the course of the SARS-CoV-2 pandemic reports of mutations with effects on spreading and vaccine effectiveness emerged. Large scale mutation analysis using rapid SARS-CoV-2 Whole Genome Sequencing (WGS) is often unavailable but could support public health organizations and hospitals in monitoring transmission and rising levels of mutant strains. Here we report a novel WGS technique for SARS-CoV-2, the EasySeq™ RC-PCR SARS-CoV-2 WGS kit. By applying a reverse complement polymerase chain reaction (RC-PCR), an Illumina library preparation is obtained in a single PCR, thereby saving time, resources and facilitating high-throughput screening. Using this WGS technique, we evaluated SARS-CoV-2 diversity and possible transmission within a group of 173 patients and healthcare workers (HCW) of the Radboud university medical center during 2020. Due to the emergence of variants of concern, we screened SARS-CoV-2 positive samples in 2021 for identification of mutations and lineages. With use of EasySeq™ RC-PCR SARS-CoV-2 WGS kit we were able to obtain reliable results to confirm outbreak clusters and additionally identify new previously unassociated links in a considerably easier workaround compared to current methods. Furthermore, various SARS-CoV-2 variants of interest were detected among samples and validated against an Oxford Nanopore sequencing amplicon strategy which illustrates this technique is suitable for surveillance and monitoring current circulating variants.

Disinfecting handheld electronic devices with UV-C in a healthcare setting.

Handheld Electronic Devices (HEDs) play a central role in the hospital environment. However, they can be a vehicle for transmitting (pathogenic) microorganisms. We studied whether disinfection with UV-C light is successful in disinfecting three different HEDs in a clinical setting. Disinfection with UV-C light was performed with the UV-Smart® D25. We took a total of 800 samples on two departments and counted colony forming units. More than half of the baseline measurements were moderately (>10CFU) or highly (>50 CFU) contaminated. Post-disinfection the CFU was 0 in 87% of measurements. We conclude that the UV-Smart® D25 can be used to disinfect non-critical HEDs in clinical healthcare.

The epidemiology of nontuberculous mycobacterial pulmonary disease in the Netherlands.

BACKGROUND: Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens of humans. Because NTM pulmonary disease (PD) is not a notifiable disease in Europe, the epidemiology of NTM-PD is not well known. However, the prevalence of NTM-PD is thought to be increasing, particularly in countries where tuberculosis rates have decreased. Here we aim to determine the prevalence of NTM-PD in the Netherlands. METHODS: Annual prevalence estimates of NTM-PD in the Netherlands (2012-2019) were derived from four separate databases, including two drug dispensing databases, an ICD-10 code database and a hospitalisation database. Databases covered a fraction of the Dutch population and were extrapolated. In addition, annual NTM-PD prevalence was also estimated by means of a pulmonologist survey. RESULTS: The estimated annual prevalence of NTM-PD using databases is between 2.3 and 5.9 patients per 100 000 inhabitants. Prevalence estimates derived from the drug dispensing databases, the hospitalisation database and the claims database were 2.3, 5.9, 3.5 and 4.5 per 100 000 inhabitants, respectively. The annual prevalence estimated in the pulmonologist survey was between 6.2 and 9.9 per 100 000 inhabitants. The annual prevalence remained stable over the included period. CONCLUSION: The estimated annual prevalence of NTM-PD using databases was between 2.3 and 5.9 patients per 100 000 inhabitants. Due to the possible presence of tuberculosis patients and low coverage in one dispensing database, we believe an annual prevalence of between 2.3 and 4.5 patients per 100 000 inhabitants is more probable, which still renders NTM-PD a serious health threat. This estimate is lower than the estimate from the pulmonologist survey, indicating physicians likely overestimate prevalence.

Outbreaks of healthcare-associated infections linked to water-containing hospital equipment: a literature review.

BACKGROUND: Healthcare-associated infections (HAIs) are a significant cause of morbidity and mortality in hospitalized patients. Water in the environment can be a source of infection linked to outbreaks and environmental transmission in hospitals. Water safety in hospitals remains a challenge. This article has summarized available scientific literature to obtain an overview of outbreaks linked to water-containing hospital equipment and strategies to prevent such outbreaks. METHODS: We made a list of water-containing hospital equipment and devices in which water is being used in a semi-closed circuit. A literature search was performed in PubMed with a search strategy containing the names of these medical devices and one or more of the following words: outbreak, environmental contamination, transmission, infection. For each medical device, we summarized the following information: the function of the medical device, causes of contamination, the described outbreaks and possible prevention strategies. RESULTS: The following water-containing medical equipment  or devices were identified: heater-cooler units, hemodialysis equipment, neonatal incubators, dental unit waterlines, fluid warmers, nebulizers, water traps, water baths, blanketrol, scalp cooling, and thermic stimulators. Of the latter three, no literature could be found. Of all other devices, one or more outbreaks associated with these devices were reported in the literature. CONCLUSIONS: The water reservoirs in water-containing medical devices can be a source of microbial growth and transmissions to patients, despite the semi-closed water circuit. Proper handling and proper cleaning and disinfection can help to reduce the microbial burden and, consequently, transmission to patients. However, these devices are often difficult to clean and disinfect because they cannot be adequately opened or disassembled, and the manufacturer's cleaning guidelines are often not feasible to execute. The development of equipment without water or fluid containers should be stimulated. Precise cleaning and disinfection guidelines and instructions are essential for instructing healthcare workers and hospital cleaning staff to prevent potential transmission to patients.

National point prevalence study on carriage of multidrug-resistant microorganisms in Dutch long-term care facilities in 2018.

OBJECTIVES: Long-term care facilities (LTCFs) may act as a reservoir of ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) for hospitals and the general population. In this study, we estimated the prevalence and molecular epidemiology of rectal carriage with ESBL-E and CPE in residents of Dutch LTCFs between March 2018 and December 2018. METHODS: LTCFs were geographically selected across the country. For each LTCF, a random sample of residents were tested for ESBL-E and CPE in 2018. To identify risk factors for high carriage prevalence and/or individual carriage, characteristics of LTCFs and of a subset of the tested residents were collected. WGS was conducted on isolates from LTCFs with an ESBL-E prevalence of >10% and all CPE isolates to identify institutional clonal transmission. RESULTS: A total of 4420 residents of 159 LTCFs were included. The weighted mean ESBL-E prevalence was 8.3% (95% CI: 6.8-10.0) and no CPE were found. In 53 LTCFs (33%), where ESBL-E prevalence was >10%, MLST using WGS (wgMLST) was performed. This included 264 isolates, the majority being Escherichia coli (n = 224) followed by Klebsiella pneumoniae (n = 30). Genetic clusters were identified in more than half (30/53; 57%) of high ESBL-positive LTCFs. Among the E. coli isolates, blaCTX-M-15 (92/224; 41%) and blaCTX-M-27 (40/224; 18%) were the most prevalent ESBL-encoding genes. For K. pneumoniae isolates, the most common was blaCTX-M-15 (23/30; 80%). CONCLUSIONS: The estimated prevalence of ESBL-E rectal carriage in Dutch LTCFs is 8.3% and resistance is observed mainly in E. coli with predominance of blaCTX-M-15 and blaCTX-M-27. ESBL-E prevalence in LTCFs seems comparable to previously reported prevalence in hospitals and the general population.

Selective Decontamination of the Digestive Tract to Prevent Postoperative Pneumonia and Anastomotic Leakage after Esophagectomy: A Retrospective Cohort Study.

Infectious complications occur frequently after esophagectomy. Selective decontamination of the digestive tract (SDD) has been shown to reduce postoperative infections and anastomotic leakage in gastrointestinal surgery, but robust evidence for esophageal surgery is lacking. The aim was to evaluate the association between SDD and pneumonia, surgical-site infections (SSIs), anastomotic leakage, and 1-year mortality after esophagectomy. A retrospective cohort study was conducted in patients undergoing Ivor Lewis esophagectomy in four Dutch hospitals between 2012 and 2018. Two hospitals used SDD perioperatively and two did not. SDD consisted of an oral paste and suspension (containing amphotericin B, colistin, and tobramycin). The primary outcomes were 30-day postoperative pneumonia and SSIs. Secondary outcomes were anastomotic leakage and 1-year mortality. Logistic regression analyses were performed to determine the association between SDD and the relevant outcomes (odds ratio (OR)). A total of 496 patients were included, of whom 179 received SDD perioperatively and the other 317 patients did not receive SDD. Patients who received SDD were less likely to develop postoperative pneumonia (20.1% vs. 36.9%, p < 0.001) and anastomotic leakage (10.6% vs. 19.9%, p = 0.008). Multivariate analysis showed that SDD is an independent protective factor for postoperative pneumonia (OR 0.40, 95% CI 0.23-0.67, p < 0.001) and anastomotic leakage (OR 0.46, 95% CI 0.26-0.84, p = 0.011). Use of perioperative SDD seems to be associated with a lower risk of pneumonia and anastomotic leakage after esophagectomy.

Sexually transmitted infections in male heterosexual Dutch clients who visited German cross-border female sex workers; a 3 year retrospective study.

BACKGROUND: Some male heterosexual clients prefer to visit a cross-border Female Sex Worker (FSW) because of cheaper sex and unsafe sex practices, and may therefore be at risk for sexually transmitted infections (STI). The objective of this study was to assess whether having commercial cross-border sex is an independent risk factor for being diagnosed with a STI. METHODS: An observational retrospective study was performed using data of 8 Dutch STI clinics bordering Germany, between 2011 and 2013. All male heterosexual clients of FSWs were selected and data on country of FSW visit and occurrence of STI were used for multivariable regression analysis. RESULTS: The study population consisted of 2664 clients of FSW. Most clients visited the Netherlands (82.4%), followed by visits to another country (beyond cross-border) (9.9%) and cross-border visits (7.8%). Clients of FSW were less likely to be STI positive when they were younger than 25 years(OR = 0.6, 95%CI 0.4 to 0.8 25-44 years and OR = 0.5, 95%CI 0.4 to 0.7 older than 45 years), and more likely when they had 20 or more sex partners in the last 6 months (OR = 2.9, 95%CI 1.9 to 4.4), did not use a condom during last sexual contact (OR = 2.2, 95%CI 1.6 to 2.9) and made cross-border visits (OR = 1.7, 95%CI 1.1 to 2.6). CONCLUSIONS: As cross-border visits appears to be a novel independent risk factor for STI in clients of FSW, this group should therefore be advised on STI prevention.

Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020.

Healthcare workers (n = 803) with mild symptoms were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 90 positive) and asked to complete a symptom questionnaire. Anosmia, muscle ache, ocular pain, general malaise, headache, extreme tiredness and fever were associated with positivity. A predictive model based on these symptoms showed moderate discriminative value (sensitivity: 91.2%; specificity: 55.6%). While our models would not justify presumptive SARS-CoV-2 diagnosis without molecular confirmation, it can contribute to targeted screening strategies.

Determinants of Inappropriate Antibiotics Use in Rural Central Ghana Using a Mixed Methods Approach.

Background: The consequences of antibiotic resistance are projected to be most severe in low and middle income countries with high infectious disease burden. This study examined determinants of inappropriate antibiotic use at the community level in rural Ghana. Methods: An observational study involving qualitative and quantitative methods was conducted between July, 2016 and September, 2018 in Ghana. Two household surveys were conducted at two time points (2017 and 2018) among 1,100 randomly selected households over 1 year. The surveys focused on antibiotic use episodes in the past month. Four in-depth interviews and two focus group discussions were performed to further explain the survey results. Determinants of inappropriate antibiotic use were assessed using a mixed effect logistic regression analysis (multilevel analysis) to account for the clustered nature of data. We defined inappropriate antibiotic use as either use without prescription, not completing treatment course or non-adherence to instruction for use. Qualitative data were thematically analyzed. Results: A total of 1,100 households was enrolled in which antibiotics were used in 585 (53.2%) households in the month prior to the surveys. A total of 676 (21.2%) participants out of 3,193 members from the 585 reportedly used antibiotics for 761 episodes of illness. Out of the 761 antibiotic use episodes, 659 (86.6%) were used inappropriately. Paying for healthcare without health insurance (Odds Ratio (OR): 2.10, 95% CI: 1.1-7.4, p-value: 0.026), not seeking healthcare from health centers (OR: 2.4, 95% CI: 1.2-5.0, p-value: 0.018), or pharmacies (OR: 4.6, 95% CI: 1.7-13.0, p-value: 0.003) were significantly associated with inappropriate antibiotic use. Socio-demographic characteristics were not significantly associated with inappropriate antibiotic use. However, the qualitative study described the influence of cost of medicines on inappropriate antibiotic use. It also revealed that antibiotic users with low socioeconomic status purchased antibiotics in installments which, could facilitate inappropriate use. Conclusion: Inappropriate antibiotic use was high and influenced by out-of-pocket payment for healthcare, seeking healthcare outside health centers, pharmacies, and buying antibiotics in installments due to cost. To improve appropriate antibiotic use, there is the need for ministry of health and healthcare agencies in Ghana to enhance healthcare access and healthcare insurance, and to provide affordable antibiotics.

Risk factors for developing acute gastrointestinal, skin or respiratory infections following obstacle and mud run participation, the Netherlands, 2017.

BackgroundIn the Netherlands, obstacle, mud and survival runs are increasingly popular. Although outbreaks of gastroenteritis have been reported following these events, associated health risks have not been systematically assessed.AimTo investigate the incidence of acute gastrointestinal infections (AGI), skin infections (SI) and respiratory infections (RI) among obstacle run participants, as well as risk factors.MethodsBetween April and October 2017, we conducted a retrospective cohort study among 2,900 participants of 17 obstacle runs in the Netherlands. Demographic, symptomatic and behavioural data were collected from participants via an online questionnaire 1 week after participation in an obstacle run. Stool specimens were obtained from respondents for microbiological tests. Adjusted relative risks (aRR) and 95% confidence intervals (CI) using multilevel binomial regression analysis were calculated.ResultsOf 2,646 respondents (median age: 33 years; 53% male), 76 had AGI after the obstacle run; ingesting mud was associated with AGI (aRR: 1.7; 95% CI: 1.2-4.9) and 38 respondents had AGI during or in the week before the obstacle run. Overall, 103 respondents reported SI and 163 RI. Rinsing off in a hot tub was associated with SI (aRR: 2.2; 95% CI: 1.7-2.8). Of 111 stool specimens, 13 tested positive for six different pathogens. No clusters were found.ConclusionThe reported incidence of AGI, SI and RI was low. Risk of these infections could be decreased by informing participants on preventive measures, e.g. showering vs rinsing in the hot tub, avoiding ingesting mud and not participating with symptoms of AGI.

Effect of diabetes mellitus on TB drug concentrations in Tanzanian patients.

BACKGROUND: Diabetes mellitus (DM) is associated with poor TB treatment outcome. Previous studies examining the effect of DM on TB drug concentrations yielded conflicting results. No studies have been conducted to date in an African population. OBJECTIVES: To compare exposure to TB drugs in Tanzanian TB patients with and without DM. PATIENTS AND METHODS: A prospective pharmacokinetic study was performed among 20 diabetic and 20 non-diabetic Tanzanian TB patients during the intensive phase of TB treatment. Plasma pharmacokinetic parameters of isoniazid, rifampicin, pyrazinamide and ethambutol were compared using an independent-sample t-test on log-transformed data. Multiple linear regression analysis was performed to assess the effects of DM, gender, age, weight, HIV status and acetylator status on exposure to TB drugs. RESULTS: A trend was shown for 25% lower total exposure (AUC0-24) to rifampicin among diabetics versus non-diabetics (29.9 versus 39.9 mg·h/L, P=0.052). The AUC0-24 and peak concentration (Cmax) of isoniazid were also lower in diabetic TB patients (5.4 versus 10.6 mg·h/L, P=0.015 and 1.6 versus 2.8 mg/L, P=0.013). Pyrazinamide AUC0-24 and Cmax values were non-significantly lower among diabetics (P=0.08 and 0.09). In multivariate analyses, DM remained an independent predictor of exposure to isoniazid and rifampicin, next to acetylator status for isoniazid. CONCLUSIONS: There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM.

[Gastroenteritis at sporting events with water and mud: an example to illustrate outbreak investigation methods]. / Gastro-enteritis bij sportevenementen met water en modder.

OBJECTIVE To determine the size and causative pathogen of the outbreak and to identify risk factors for developing gastroenteritis among participants of the Survivalrun in Udenhout in September 2016. Design Retrospective cohort study. METHODS We sent an invitation to go to an online questionnaire to participants and volunteers of the Survivalrun by email. The link to the questionnaire was also shared on the Facebook page and website of the Survivalrun. We calculated attack rates (AR) and relative risks (RR) for several exposures to identify risk factors for developing diarrhoea and/or vomiting within 3 days after the run. In addition, stool samples of six participants were tested for common gastrointestinal pathogens. RESULTS A total of 444 people completed the questionnaire. Symptoms of gastroenteritis were reported by 163 study participants (37%). Five participants reported symptoms of gastroenteritis in the week before and three participants during the Survivalrun. Multivariate analysis identified the following risk factors for developing gastroenteritis: participation on the second day of the run(RR 2.4: 95% CI 1.1-5.3), ingesting water (RR 1.7: 95% CI 1.3-2.3) and ingesting mud (RR 1.3: 95% CI 1.1-1.6). Four out of six stool samples tested positive for norovirus (various types). CONCLUSION This outbreak investigation shows that pathogens, such as norovirus, can easily spread during sporting events where participants have to move through water and mud. Specific methods and knowledge of the circumstances are essential for a thorough outbreak investigation.