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.

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.

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.

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.

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.

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.

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.

Risk factors for persisting measles susceptibility: a case-control study among unvaccinated orthodox Protestants.

Background: Measles is an infectious disease providing lifelong immunity. Epidemics periodically occur among unvaccinated orthodox Protestants in the Netherlands. During the 2013/2014 epidemic, 17% of the reported patients was over 14 years old. Apparently, they did not catch measles during the previous 1999/2000 epidemic and remained susceptible. We wanted to identify risk factors for this so-called persisting measles susceptibility, and thus risk factors for acquiring measles at older age with increased risk of complications. Methods: A case-control study was performed among unvaccinated orthodox Protestants born between 1988 and 1998; cases had measles in 2013/2014, controls during or before 1999/2000. Associations between demographic, geographical and religion-related determinants and persisting measles susceptibility were determined using univariate and multivariable logistic regression. Analyses were stratified in two age-groups: infants/toddlers and primary school-aged children during the 1999/2000 measles epidemic. Results: In total, 204 cases and 563 controls were included. Risk factors for persisting measles susceptibility for infants/toddlers in 1999/2000 were belonging to a moderately conservative church, absence of older siblings and residency outside low vaccination coverage (LVC)-municipalities. Risk factors for primary school-aged children were residency outside LVC-municipalities and attendance of non-orthodox Protestant primary school. Conclusion: Unvaccinated orthodox Protestant adolescents and adults who resided outside the LVC-municipalities, did not attend an orthodox Protestant primary school, had no older siblings and belonged to a moderately conservative church were at risk for persisting measles susceptibility and, thus, for acquiring measles at older age with increased risk of complications. For this subgroup of orthodox Protestants targeted information on vaccination is recommended.

Integrating hepatitis B, hepatitis C and HIV screening into tuberculosis entry screening for migrants in the Netherlands, 2013 to 2015.

We evaluated uptake and diagnostic outcomes of voluntary hepatitis B (HBV) and C virus (HCV) screening offered during routine tuberculosis entry screening to migrants in Gelderland and Amsterdam, the Netherlands, between 2013 and 2015. In Amsterdam, HIV screening was also offered. Overall, 54% (461/859) accepted screening. Prevalence of chronic HBV infection (HBsAg-positive) and HCV exposure (anti-HCV-positive) in Gelderland was 4.48% (9/201; 95% confidence interval (CI): 2.37-8.29) and 0.99% (2/203; 95% CI: 0.27-3.52), respectively, all infections were newly diagnosed. Prevalence of chronic HBV infection, HCV exposure and chronic HCV infection (HCV RNA-positive) in Amsterdam was 0.39% (1/256; 95% CI: 0.07-2.18), 1.17% (3/256; 95% CI: 0.40-3.39) and 0.39% (1/256; 95% CI: 0.07-2.18), respectively, with all chronic HBV/HCV infections previously diagnosed. No HIV infections were found. In univariate analyses, newly diagnosed chronic HBV infection was more likely in participants migrating for reasons other than work or study (4.35% vs 0.83%; odds ratio (OR) = 5.45; 95% CI: 1.12-26.60) and was less likely in participants in Amsterdam than Gelderland (0.00% vs 4.48%; OR = 0.04; 95% CI: 0.00-0.69). Regional differences in HBV prevalence might be explained by differences in the populations entering compulsory tuberculosis screening. Prescreening selection of migrants based on risk factors merits further exploration.

Increase in vaccination coverage between subsequent generations of orthodox Protestants in The Netherlands.

Background: The Netherlands experienced several outbreaks of vaccine preventable diseases, largely confined to an orthodox Protestant minority group. Based on religious arguments some orthodox Protestants accept vaccination, while others refuse. Their acceptance of vaccination, however, seems to be changing over time. We estimated vaccination coverage in subsequent generations of orthodox Protestants and identified determinants of the intention to vaccinate their (future) children. In 2013 orthodox Protestants in the age of 18-40 years were invited to fill out an online questionnaire on their own vaccination status, vaccination status of their parents, the vaccination status or vaccination intention for their (future) children, and possible determinants of the intention to vaccinate (future) children. Vaccination coverage of respondents' parents and respondents was compared using chi-square tests. Logistic regression was used to identify determinants associated with vaccination of (future) children. In total, 981 orthodox Protestant respondents were included in the study. Vaccination coverage among the parents of respondents was 40.1% (95% CI 37.8-42.5%), among respondents 55.3% (95% CI 52.2-58.4%). This means an increase of 15.2% in one generation ( P < 0.001). About 65% of respondents vaccinated or intends to vaccinate their (future) children. Multivariate logistic regression showed that strongest predictors for vaccinating (future) children were low or moderate level of religious conservatism (OR 10.4 [95% CI 5.7-18.9] and 4.6 [95% CI 2.9-7.4], respectively), being vaccinated themselves (OR 6.0 [95% CI 4.3-8.5]) and high educational level (OR 2.5 [95% CI 1.6-4.0]). Vaccination coverage among Dutch orthodox Protestants is increasing over time.

Negative attitude and low intention to vaccinate universally against varicella among public health professionals and parents in the Netherlands: two internet surveys.

BACKGROUND: Prior to introduction of universal varicella vaccination, it is crucial to gain insight into the willingness to vaccinate among the population. This is because suboptimal national vaccination coverage might increase the age of infection in children, which will lead to higher complication rates. We studied the attitude and intention to vaccinate against varicella among Dutch public health professionals who execute the National Immunisation Programme (NIP), and parents. METHODS: Medical doctors and nurses of regional public health services (RPHS) and child health clinics (CHC), and a random sample of parents received an internet survey on varicella vaccination. Separate logistic regression models were used to identify determinants for a positive attitude (professionals) or a positive intention (parents) to vaccinate against varicella within the NIP (free of charge). RESULTS: The questionnaire was completed by 181 RPHS professionals (67%), 260 CHC professionals (46%), and 491 parents (33%). Of professionals, 21% had a positive attitude towards universal varicella vaccination, while 72% preferred to limit vaccination to high-risk groups only. Of parents, 28% had a positive intention to vaccinate their child against varicella within the NIP. The strongest determinant for a positive attitude or intention to vaccinate against varicella among professionals and parents was the belief that varicella is a disease serious enough to vaccinate against. CONCLUSIONS: We showed that a majority of the Dutch public health professionals and parents in this study have a negative attitude or low intention to vaccinate universally against varicella, as a result of the perceived low severity of the disease. Most participating professionals support selective vaccination to prevent varicella among high-risk groups.

Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients.

East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC0-24) and peak plasma concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC0-24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. The Cmax was below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were the Cmaxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampin Cmax below the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies.

Investigation of outbreaks complicated by universal exposure.

Outbreaks in which most or all persons were exposed to the same suspected source of infection, so-called universal exposure, are common. They represent a challenge for public health specialists because conducting analytical studies in such investigations is complicated by the absence of a nonexposed group. We describe different strategies that can support investigations of outbreaks with universal exposure. The value of descriptive epidemiology, extensive environmental investigation, and the hypothesis-generation phase cannot be overemphasized. An exposure that seems universal may in fact not be universal when additional aspects of the exposure are taken into account. Each exposure has unique characteristics that may not be captured when investigators rely on the tools readily at hand, such as standard questionnaires. We therefore encourage field epidemiologists to be creative and consider the use of alternative data sources or original techniques in their investigations of outbreaks with universal exposure.

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.

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.