Prevalence and predictors of residual antibiotics in children's blood in community settings in Tanzania.

OBJECTIVE: Children account for a significant proportion of antibiotic consumption in low- and middle-income countries, with overuse occurring in formal and informal health sectors. This study assessed the prevalence and predictors of residual antibiotics in the blood of children in Mbeya and Morogoro regions of Tanzania. METHODS: The cross-sectional community-based survey used two-stage cluster sampling to include children aged under 15 years. For each child, information on recent illness, healthcare-seeking behavior, and use of antibiotics, as well as a dried blood spot sample, were collected. The samples underwent tandem mass spectrometry analysis to quantify the concentrations of 15 common antibiotics. Associations between survey variables and presence of residual antibiotics were assessed using mixed-effects logistic regression. RESULTS: In total, 1742 children were surveyed, and 1699 analyzed. The overall prevalence of residual antibiotics in the blood samples was 17.4% (296/1699), the highest among children under the age of five years. The most frequently detected antibiotics were trimethoprim (144/1699; 8.5%), sulfamethoxazole (102/1699; 6.0%), metronidazole (61/1699; 3.6%) and amoxicillin (43/1699; 2.5%). The strongest predictors of residual antibiotics in the blood were observed presence of antibiotics at home (aOR=2.9; 95% CI: 2.0-4.1) and reported consumption of antibiotics in the last two weeks (aOR=2.5; 95% CI: 1.6-3.9). However, half (145/296) of the children who had residual antibiotics in their blood, some with multiple antibiotics, had no reported history of illness or antibiotic consumption in the last two weeks, and antibiotics were not found at home. DISCUSSION: This study demonstrated a high prevalence of antibiotic exposure among children in Tanzanian communities, albeit likely underestimated, especially for compounds with short half-lives. A significant proportion of antibiotic exposure was unexplained and may have been due to unreported self-medication or environmental pathways. Incorporating biomonitoring into surveillance strategies can help better understand exposure patterns and design antibiotic stewardship interventions.

[Dengue vaccines, a time for cautious optimism?] / Vaccins contre la dengue, le temps de l'optimisme prudent ?

Vaccine could take a central role in the strategy to reduce the burden of dengue. The development of an effective and safe vaccine must address various immunological challenges. Several vaccines are currently in development. To date, two live-attenuated vaccines have been deployed. Both have an effectiveness that varies depending on the serotypes. The deployment of the Dengvaxia vaccine, which began in 2015, was marked by a major safety alert leading to its use being restricted to previously dengue-seropositive people over 9 years old. The Qdenga vaccine is currently being deployed. There is for now insufficient data to ensure its safety in seronegative people. Some travelers, who have previously been infected with dengue, are a group for whom a vaccination recommendation applies.

Les vaccins pourraient occuper une place centrale dans la stratégie de réduction du fardeau de la dengue. Le développement d'un vaccin efficace et sûr est complexe car il doit relever plusieurs défis immunologiques. Différents vaccins sont en développement. À ce jour, deux vaccins vivants atténués ont été déployés. Tous deux ont une efficacité qui varie selon les sérotypes. Le déploiement du vaccin Dengvaxia, débuté en 2015, a été marqué par une alerte de sécurité majeure conduisant à restreindre son usage aux personnes de plus de 9 ans, préalablement séropositives pour la dengue. Le vaccin Qdenga est en cours de déploiement. Le recul est insuffisant pour assurer son innocuité chez les séronégatifs. Certains voyageurs, ayant déjà été infectés par la dengue, constituent un groupe pour lequel une recommandation vaccinale s'applique.

[Malaria vaccines: a new tool for elimination?] / Vaccins contre le paludisme : un nouvel outil pour l'élimination ?

A malaria vaccine represents an essential complementary tool to curb the stagnation, or even increase, in malaria cases observed over the last decade due to the emergence of resistance to insecticides impregnated on mosquito nets, wars and internal conflicts, as well as global warming. In October 2021, WHO recommended the use of the RTS,S/ASO1 vaccine for children aged 5-17 months in areas of moderate to high transmission. In October 2023, a second vaccine received WHO approval for deployment in the same population, following demonstration of around 70 % efficacy in protecting young children against malaria for one year. Given their partial efficacy, however, these vaccines are not generally recommended for travelers to endemic countries.

Un vaccin contre le paludisme représente une mesure complémentaire essentielle pour juguler la stagnation, voire l'augmentation des cas de paludisme observée durant cette dernière décade en raison de l'émergence de la résistance aux insecticides imprégnés sur les moustiquaires, des guerres et conflits internes ainsi que du réchauffement climatique. En octobre 2021, l'OMS a recommandé l'emploi du vaccin RTS,S/ASO1 pour les enfants de 5 à 17 mois dans les zones de transmission modérée à forte. En octobre 2023, un second vaccin a reçu l'aval de l'OMS pour son déploiement dans la même population, suite à la démonstration d'une efficacité d'environ 70 % pour protéger les jeunes enfants contre le paludisme pendant une année. Vu leur efficacité partielle, ces vaccins ne sont cependant généralement pas recommandés pour les voyageurs se rendant dans les pays d'endémie.

[Is mortality an objective indicator for measuring the impact of an epidemic?: The example of Covid-19 in Switzerland]. / La mortalité est-elle un indicateur objectif pour mesurer l'impact d'une épidémie ?. L'exemple du Covid-19 en Suisse.

Measuring the health impact of an epidemic using appropriate indicators is necessarily complex. Mortality does not sum up all the issues, but at least it seems to be an objective indicator. There are, however, a number of different mortality indicators, which do not all convey the same message. During the Covid-19 epidemic in Switzerland, the mortality rate rose by 10.2% in 2020, while life expectancy fell by "only" 0.8%, or 8.3 months, a decline described as "modest" or "complete freefall" depending on when it was published. In reality, the population living in Switzerland in 2020 lost an average of "only" 2.4 days, as the epidemic did not last their entire lives. The use of such an indicator, in comparison with losses due to other factors, would enable us to better estimate the real impact of an epidemic.

Mesurer l'impact sanitaire d'une épidémie à l'aide d'indicateurs appropriés est forcément complexe. La mortalité ne résume pas tous les enjeux mais semble au moins être un indicateur objectif. Il existe cependant différents indicateurs de mortalité ne donnant pas tous le même message. Lors de l'épidémie de Covid-19 en Suisse, le taux de mortalité a augmenté de 10,2 % en 2020, alors que l'espérance de vie n'a diminué « que ¼ de 0,8 %, ou 8,3 mois, recul par ailleurs qualifié de « modeste ¼ ou de « chute libre ¼ selon quand il a été publié. En réalité, la population vivant en Suisse en 2020 n'a perdu en moyenne « que ¼ 2,4 jours car l'épidémie n'a pas duré toute sa vie. L'utilisation d'un tel indicateur, en comparaison avec les pertes dues à d'autres facteurs, permettrait une meilleure estimation de l'impact réel d'une épidémie.

The Tools for Integrated Management of Childhood Illness (TIMCI) study protocol: a multi-country mixed-method evaluation of pulse oximetry and clinical decision support algorithms.

Effective and sustainable strategies are needed to address the burden of preventable deaths among children under-five in resource-constrained settings. The Tools for Integrated Management of Childhood Illness (TIMCI) project aims to support healthcare providers to identify and manage severe illness, whilst promoting resource stewardship, by introducing pulse oximetry and clinical decision support algorithms (CDSAs) to primary care facilities in India, Kenya, Senegal and Tanzania. Health impact is assessed through: a pragmatic parallel group, superiority cluster randomised controlled trial (RCT), with primary care facilities randomly allocated (1:1) in India to pulse oximetry or control, and (1:1:1) in Tanzania to pulse oximetry plus CDSA, pulse oximetry, or control; and through a quasi-experimental pre-post study in Kenya and Senegal. Devices are implemented with guidance and training, mentorship, and community engagement. Sociodemographic and clinical data are collected from caregivers and records of enrolled sick children aged 0-59 months at study facilities, with phone follow-up on Day 7 (and Day 28 in the RCT). The primary outcomes assessed for the RCT are severe complications (mortality and secondary hospitalisations) by Day 7 and primary hospitalisations (within 24 hours and with referral); and, for the pre-post study, referrals and antibiotic. Secondary outcomes on other aspects of health status, hypoxaemia, referral, follow-up and antimicrobial prescription are also evaluated. In all countries, embedded mixed-method studies further evaluate the effects of the intervention on care and care processes, implementation, cost and cost-effectiveness. Pilot and baseline studies started mid-2021, RCT and post-intervention mid-2022, with anticipated completion mid-2023 and first results late-2023. Study approval has been granted by all relevant institutional review boards, national and WHO ethical review committees. Findings will be shared with communities, healthcare providers, Ministries of Health and other local, national and international stakeholders to facilitate evidence-based decision-making on scale-up.Study registration: NCT04910750 and NCT05065320.

Pulse oximetry and clinical decision support algorithms show potential for supporting healthcare providers to identify and manage severe illness among children under-five attending primary care in resource-constrained settings, whilst promoting resource stewardship but scale-up has been hampered by evidence gaps.This study design article describes the largest scale evaluation of these interventions to date, the results of which will inform country- and global-level policy and planning .

A digital health algorithm to guide antibiotic prescription in pediatric outpatient care: a cluster randomized controlled trial.

Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities. Over 11 months, 23,593 consultations were included from 20 ePOCT+ health facilities and 20,713 from 20 usual care facilities. The use of ePOCT+ in intervention facilities resulted in a reduction in the coprimary outcome of antibiotic prescription compared to usual care (23.2% versus 70.1%, adjusted difference -46.4%, 95% confidence interval (CI) -57.6 to -35.2). The coprimary outcome of day 7 clinical failure was noninferior in ePOCT+ facilities compared to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). There was no difference in the secondary safety outcomes of death and nonreferred secondary hospitalizations by day 7. Using ePOCT+ could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing. Clinicaltrials.gov Identifier: NCT05144763.

Development of hybrid immunity during a period of high incidence of Omicron infections.

BACKGROUND: Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants. METHODS: We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n = 739) and north-eastern (n = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron). RESULTS: Seroprevalence remained stable from March 2022 (97.6%, n = 1894) to June/July 2022 (98.4%, n = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres [4518 World Health Organization units per millilitre (WHO U/mL)] compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%). CONCLUSIONS: This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population.

Factors Associated With COVID-19 Non-Vaccination in Switzerland: A Nationwide Study.

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness.

[Dengue fever is knocking on the doors of Europe]. / La dengue frappe aux portes de l'Europe.

Dengue is a subject of major concern in global health because its incidence is increasing, and its geographical area continues to expand. On a global scale, the projections available point in the direction of an extension of the geographical areas of the Aedes vectors, partly in connection with the increase in temperatures and the modification of precipitation cycles in the context of the climate change. This expansion is expected at the borders of the areas of current spread with, however, a possible contraction in certain areas that are now endemic. In Europe, the threat of a dengue epidemic outbreak now exists. It is on this continent that the number of new exposures in immunologically naïve people is likely to be the greatest in the near future.

La dengue est un sujet de préoccupation majeure en santé globale car son incidence augmente et son aire géographique ne cesse de s'étendre. À l'échelle globale, les projections dont on dispose vont dans le sens d'une extension des zones géographiques des vecteurs Aedes, en lien en partie avec l'augmentation des températures et la modification des cycles de précipitation dans le contexte du changement climatique. Cette expansion est attendue aux frontières des zones de diffusion actuelle avec toutefois une contraction possible dans certaines zones aujourd'hui endémiques. En Europe, la menace d'une flambée épidémique de dengue existe désormais. C'est sur ce continent que le nombre de nouvelles expositions chez des personnes immunologiquement naïves risque d'être le plus important dans un avenir proche.

Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case-control study.

INTRODUCTION: Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. METHODS: Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression. RESULTS: The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity. CONCLUSION: Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. REGISTRY: CORONA IMMUNITAS:: ISRCTN18181860.

Seroprevalence trends of anti-SARS-CoV-2 antibodies and associated risk factors: a population-based study.

PURPOSE: We aimed to assess the seroprevalence trends of SARS-CoV-2 antibodies in several Swiss cantons between May 2020 and September 2021 and investigate risk factors for seropositivity and their changes over time. METHODS: We conducted repeated population-based serological studies in different Swiss regions using a common methodology. We defined three study periods: May-October 2020 (period 1, prior to vaccination), November 2020-mid-May 2021 (period 2, first months of the vaccination campaign), and mid-May-September 2021 (period 3, a large share of the population vaccinated). We measured anti-spike IgG. Participants provided information on sociodemographic and socioeconomic characteristics, health status, and adherence to preventive measures. We estimated seroprevalence with a Bayesian logistic regression model and the association between risk factors and seropositivity with Poisson models. RESULTS: We included 13,291 participants aged 20 and older from 11 Swiss cantons. Seroprevalence was 3.7% (95% CI 2.1-4.9) in period 1, 16.2% (95% CI 14.4-17.5) in period 2, and 72.0% (95% CI 70.3-73.8) in period 3, with regional variations. In period 1, younger age (20-64) was the only factor associated with higher seropositivity. In period 3, being aged ≥ 65 years, with a high income, retired, overweight or obese or with other comorbidities, was associated with higher seropositivity. These associations disappeared after adjusting for vaccination status. Seropositivity was lower in participants with lower adherence to preventive measures, due to a lower vaccination uptake. CONCLUSIONS: Seroprevalence sharply increased over time, also thanks to vaccination, with some regional variations. After the vaccination campaign, no differences between subgroups were observed.

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs.

Prevalence of SARS-CoV-2 infection and associated risk factors among asylum seekers living in asylum centres: A cross-sectional serologic study in Canton of Vaud, Switzerland.

Background: Understanding the factors influencing SARS-CoV-2 transmission in asylum seekers and refugees living in centres is crucial to determine targeted public health policies protecting these populations fairly and efficiently. In response, this study was designed to explore the pandemic's spread into asylum centres during the first wave of the pandemic in Switzerland. Specifically, it aimed to identify the risk factors associated with a positive anti-SARS-CoV-2 seroprevalence test after the first semi-confinement period (16 March to 27 April 2020) amongst asylum seekers and refugees living in centres. Methods: This research is part of SérocoVID, a seroepidemiologic study of SARS-CoV-2 infection conducted in the canton of Vaud, Switzerland. Migrants living in two asylum centres, one known to have had an epidemic outbreak, were invited to participate in this study. Anti-SARS-CoV-2 IgG and IgA antibodies targeting the spike viral protein were measured in all participants using a Luminex immunoassay. Each participant also completed a questionnaire measuring socio-demographic characteristics, medical history (comorbidities, smoking status, BMI, flu-like symptoms), health literacy, public health recommendations (wearing a masque in a public area, social distancing and hands cleaning), behaviours and exposures (daily life activities, number of contacts weekly). The association of these independent variables with the serologic test result were estimated using a multivariable logistic regression model. Findings: A total of 124 participants from the two asylum centres took part in the study (Centre 1, n = 82; Centre 2, n = 42). The mean participation rate was 36.7%. The seroprevalence in Centres 1 and 2 were 13% [95% CI 0.03, 0.14] and 50% [0.34, 0.65], respectively. Next, 40.63% of SARS-CoV-2 positive people never developed symptoms (asymptomatic cases), and no one had severe forms of the Covid-19 disease requiring hospitalisation. Participants report high compliance with public health measures, especially hygiene rules (96.3% of positive answers) and social distancing (88.7%). However, only 11.3% said they always wore a masque in public. After adjusting for individual characteristics, infection risk was lower amongst people with high health literacy (aOR 0.16, p = 0.007 [0.04, 0.60]) and smokers (aOR 0.20, p = 0.013 [0.06, 0.69]). Conclusion: Despite the lack of severe complications of Covid-19 disease in this study, findings suggest that developing targeted public health measures, especially for the low health literacy population, would be necessary to limit the risk of outbreaks in asylum centres and improve this population's safety. Further investigations and qualitative approach are required to understand more finely how living conditions, risks and behaviours such as tobacco consumption, and the adoption of protective measures impact SARS-CoV-2 infection.

Clinical evaluation of BioFire® multiplex-PCR panel for acute undifferentiated febrile illnesses in travellers: a prospective multicentre study.

BACKGROUND: Identifying the causes of Acute Undifferentiated Febrile Illness (AUFI) is key to improve the management of returning travellers with fever. We evaluated a BioFire®FilmArray® prototype panel of multiplex nucleic acid amplification tests (NAAT) targeting different relevant pathogens in travellers returning with fever. METHODS: Prospective, multicentre study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November 2017-November 2019). We evaluated 15 target analytes: Plasmodium spp., Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp. and Salmonella spp. Results were compared with composite reference standards (CRSs) for each target infection, including direct methods [smear microscopy, rapid diagnostic test (RDT), reference NAAT and blood cultures] and indirect methods (paired serology). FINDINGS: Among 455 travellers with AUFI, 229 target infections were diagnosed; the prototype panel detected 143 (overall sensitivity and specificity of 62.5 and 99.8%, respectively). The panel identified all Plasmodium infections (n = 82). Sensitivity for dengue (n = 71) was 92.9, 80.8 and 68.5% compared with RDT, NAAT and CRS, respectively. Compared with direct methods and CRS, respectively, the prototype panel detected 4/4 and 4/6 chikungunya, 2/2 and 4/29 Leptospira spp., 1/1 and 1/6 O. tsutsugamushi and 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A. phagocytophylum and 0/3 Borrelia spp. diagnosed by serology and only 1/7 Salmonella spp. diagnosed by blood cultures. 77/86 (89.5%) infections not detected by the panel were diagnosed by serology. INTERPRETATION: The prototype panel allowed rapid and reliable diagnosis for malaria, dengue and chikungunya. Further improvements are needed to improve its sensitivity for Zika and important travel-related bacterial infections.

Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

BACKGROUND: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. AIM: To explore the factors associated with the overruling of initial procalcitonin guidance. DESIGN AND SETTING: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. METHOD: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. RESULTS: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03-3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32-9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34-23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18-4.37); and the GP's number of years of experience (aOR per year 1.05, 1.01-1.09). CONCLUSIONS: Overruling of procalcitonin guidance was associated with GPs' socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.

Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: A prospective comparative clinical trial.

BACKGROUND: Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. METHODS: In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. RESULTS: Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. CONCLUSIONS: RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

ePOCT+ and the medAL-suite: Development of an electronic clinical decision support algorithm and digital platform for pediatric outpatients in low- and middle-income countries.

Electronic clinical decision support algorithms (CDSAs) have been developed to address high childhood mortality and inappropriate antibiotic prescription by helping clinicians adhere to guidelines. Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content. To address these challenges we developed ePOCT+, a CDSA for the care of pediatric outpatients in low- and middle-income settings, and the medical algorithm suite (medAL-suite), a software for the creation and execution of CDSAs. Following the principles of digital development, we aim to describe the process and lessons learnt from the development of ePOCT+ and the medAL-suite. In particular, this work outlines the systematic integrative development process in the design and implementation of these tools required to meet the needs of clinicians to improve uptake and quality of care. We considered the feasibility, acceptability and reliability of clinical signs and symptoms, as well as the diagnostic and prognostic performance of predictors. To assure clinical validity, and appropriateness for the country of implementation the algorithm underwent numerous reviews by clinical experts and health authorities from the implementing countries. The digitalization process involved the creation of medAL-creator, a digital platform which allows clinicians without IT programming skills to easily create the algorithms, and medAL-reader the mobile health (mHealth) application used by clinicians during the consultation. Extensive feasibility tests were done with feedback from end-users of multiple countries to improve the clinical algorithm and medAL-reader software. We hope that the development framework used for developing ePOCT+ will help support the development of other CDSAs, and that the open-source medAL-suite will enable others to easily and independently implement them. Further clinical validation studies are underway in Tanzania, Rwanda, Kenya, Senegal, and India.

SARS-CoV-2 Seroprevalence in Employees of Four Essential Non-Health Care Sectors at Moderate/High Risk of Exposure to Coronavirus Infection: Data From the "First Wave".

OBJECTIVE: The aim of this study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in Swiss non-health care employees at a moderate to high risk of exposure: bus drivers and supermarket, laundry service, and mail-sorting center employees. METHODS: Data on 455 essential workers included demographics, SARS-CoV-2 exposure and use of protective measures. Anti-SARS-CoV-2 immunoglobulins G and A targeting the spike protein were measured between May and July 2020. RESULTS: The overall crude seroprevalence estimate (15.9%; 95% confidence interval [CI], 12.6% to 19.7%) among essential workers was not significantly higher than that of the general working-age population (11.2%; 95% CI, 7.1% to 15.2%). Seroprevalence ranged from 11.9% (95% CI, 6.3% to 19.8%) among bus drivers to 22.0% (95% CI, 12.6% to 19.7%) among food supermarket employees. CONCLUSIONS: We found no significant difference in seroprevalence between our sample of essential workers and local working-age population during the first lockdown phase of the COVID-19 pandemic. Having a seropositive housemate was the strongest predictor of SARS-CoV-2 seropositivity.