Publications by authors named "François Chappuis"

195 Publications

Persistence of anti-sars-cov-2 antibodies: immunoassay heterogeneity and implications for serosurveillance.

Clin Microbiol Infect 2021 Jul 7. Epub 2021 Jul 7.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA; Unit of Population Epidemiology, Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland; Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address:

Objectives: Serologic studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-COV-2 infections as a function of time since infection for 3 commercially-available SARS-COV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence.

Methods: We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n=354) through 9 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays; Roche-N, Roche-RBD and EuroImmun S1. We developed a latent-class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates.

Results: Antibodies persisted at follow-up in 74% to 100% of participants, depending on immunoassays. Model estimates indicate that both Roche assays maintain high sensitivity with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates.

Conclusions: Antibodies persist after 9 months in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay-performance-adjustment are important for the interpretation of serologic studies in the case of decaying sensitivity after infection.
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http://dx.doi.org/10.1016/j.cmi.2021.06.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261139PMC
July 2021

Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting.

Ann Intern Med 2021 Jul 6. Epub 2021 Jul 6.

Geneva University Hospitals and University of Geneva, Geneva, Switzerland (F.C., I.G.).

Background: With millions of SARS-CoV-2 infections worldwide, increasing numbers of patients are coming forward with long-term clinical effects of the disease lasting several weeks to months.

Objective: To characterize symptoms 7 to 9 months after diagnosis of COVID-19.

Design: Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis.

Setting: From 18 March to 15 May 2020, symptomatic persons who tested positive for SARS-CoV-2 at the Geneva University Hospitals were followed by CoviCare, a virtual, clinical, outpatient follow-up program. Persons were contacted again at 30 to 45 days and 7 to 9 months from diagnosis.

Participants: Persons who were a part of the CoviCare program from 18 March to 15 May 2020.

Measurements: A standardized interview of symptoms consistent with COVID-19, with grading of intensity.

Results: Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), dyspnea (11.7%), and headache (10.0%).

Limitation: Limitations include generalizability and missing data for 34.8% of participants.

Conclusion: Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. These findings contribute to the recognition of long-term effects in a disease mostly counted by its death toll to date by promoting communication on postacute sequelae of SARS-CoV-2 and encouraging physicians to continue long-term monitoring of their patients.

Primary Funding Source: None.
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http://dx.doi.org/10.7326/M21-0878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280535PMC
July 2021

What is the impact of snakebite envenoming on domestic animals? A nation-wide community-based study in Nepal and Cameroon.

Toxicon X 2021 Jul 5;9-10:100068. Epub 2021 Jun 5.

Institute of Global Health, Department of Community Health and Medicine, Faculty of Medicine, University of Geneva, Chemin des mines 9, 1202, Geneva, Switzerland.

Snakebite envenoming is a life-threatening disease in humans and animals and a major public health issue in rural communities of South-East Asia and sub-Saharan Africa. Yet the impact of snakebite on domestic animals has been poorly studied. This study aimed to describe the context, clinical features, treatment, and outcomes of snakebite envenoming in domestic animals in Nepal and Cameroon. Primary data on snakebite in animals were recorded from a community-based nation-wide survey on human and animal snakebite in Nepal and Cameroon ( project). Mobile teams collected data on snakebite in humans and animals in 13,879 and 10,798 households in Nepal and Cameroon respectively from December 2018 to June 2019. This study included 405 snakebite cases (73 in Nepal and 332 in Cameroon) in multiple types of animals. An interview with a structured questionnaire collected specific information about the animal victims. Snake bites in animals took place predominantly inside and around the house or farm in Nepal (92%) and Cameroon (71%). Other frequent locations in Cameroon were field or pasture (12%). A large diversity of clinical features was reported in all types of envenomed animals. They showed either a few clinical signs (e.g., local swelling, bleeding) or a combination of multiple clinical signs. Only 9% of animal victims, mainly cattle and buffaloes and less frequently goats, sheep, and dogs, received treatment, predominantly with traditional medicine. The overall mortality of snakebite was 85% in Nepal and 87% in Cameroon. Results from this nationwide study show an important impact of snakebite on animal health in Nepal and Cameroon. There is a need for cost-effective prevention control strategies and affordable snakebite therapies in the veterinary field to save animal lives and farmer livelihood in the poorest countries of the world. The WHO global strategy to prevent and control snakebite envenoming supports a One Health approach, which may help develop integrated solutions to the snakebite problem taking into account human and animal health.
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http://dx.doi.org/10.1016/j.toxcx.2021.100068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214143PMC
July 2021

Vulnerable patients forgo health care during the first wave of the Covid-19 pandemic.

Prev Med 2021 09 23;150:106696. Epub 2021 Jun 23.

Division of Prison Health, Geneva University Hospitals, Chemin du Petit Bel Air 2, 1226 Thônex, Switzerland; Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Rue Gabriel-Perret-Gentil 4, 1205 Geneva, Switzerland.

During the first wave of the Covid-19 pandemic, access to health care was limited, and patients encountered important delays for scheduled appointments and care. Empirical data relying on patients' reports of forgoing health care are scarce. This study investigated Covid-19-related self-reports of forgoing health care in a sample of vulnerable outpatients in Geneva, Switzerland. We collected data from 1167 adult outpatients, including clinically vulnerable patients (with chronic diseases), geriatric patients (involved in a health care network for people aged 60 or older), and socially vulnerable patients (involved in a migrant health program or a mobile outpatient community care center) in June 2020. Data on sociodemographic factors, forgoing health care, and anti-SARS-CoV-2 antibodies were collected. Of the patients, 38.5% reported forgoing health care. Forgoing health care was more frequent for younger patients, women, patients with a low level of education, and patients with a chronic disease (p < .001). There was no significant association between the presence of anti-SARS-CoV-2 antibodies and forgoing health care (p = .983). As the decrease in routine management of patients might have important and unpredictable adverse health consequences, avoiding delayed health care is crucial.
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http://dx.doi.org/10.1016/j.ypmed.2021.106696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220858PMC
September 2021

Diagnostic accuracy of Panbio rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2.

PLoS One 2021 24;16(6):e0253321. Epub 2021 Jun 24.

Infectious Disease Division, Geneva University Hospitals, Geneva, Switzerland.

Background: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients.

Methods: We conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS during the second pandemic wave in Switzerland.

Results: 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT clinical sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a clinical specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS.

Interpretation: Based on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples, if taken by a trained person and high requirements regarding quality of the specimen, meet the criteria required by the WHO for Ag-RDTs (sensitivity ≥80% and specificity ≥97%) in a high incidence setting in symptomatic individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224876PMC
July 2021

Hepatic Alveolar Echinococcosis.

Semin Liver Dis 2021 Aug 23;41(3):393-408. Epub 2021 Jun 23.

Division of Tropical and Humanitarian Medicine, Faculty of Medicine, University Hospitals of Geneva, Faculty of Medicine, Switzerland.

Hepatic alveolar echinococcosis (HAE) is a rare but severe zoonosis caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm HAE is present only in the Northern Hemisphere, predominantly in China. Currently, there is a significant resurgence of cases in historically endemic areas associated with emergence of HAE in countries not previously concerned. Today, in European countries, HAE is often discovered by chance; however, clinicians should be made aware of opportunistic infections that progressively emerged recently as a result of therapeutic or pathological immunosuppression. Ultrasonography is the key first-line diagnostic procedure, with specific serology providing confirmation in 95% of the cases. Albendazole, only parasitostatic, is the mainstay for treatment. Surgical resection, if feasible, is the gold standard for treatment, and more patients are currently eligible for this option because of an earlier diagnosis. The prognosis has considerably improved but remains poor in countries where access to care is less favorable.
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http://dx.doi.org/10.1055/s-0041-1730925DOI Listing
August 2021

Development and validation of the OUTCoV score to predict the risk of hospitalisation among patients with SARS-CoV-2 infection in ambulatory settings: a prospective cohort study.

BMJ Open 2021 06 18;11(6):e044242. Epub 2021 Jun 18.

Division of Primary Care, Geneva University Hospitals, Geneva, Switzerland.

Objectives: To develop and validate a rule-out prediction model for the risk of hospitalisation among patients with SARS-CoV-2 infection in the ambulatory setting to derive a simple score to determine outpatient follow-up.

Design: Prospective cohort study.

Setting: Swiss university hospital.

Participants: 1459 individuals with a positive result for SARS-CoV-2 infection between 2 March and 23 April 2020.

Methods: We applied the rule of 10 events per variable to construct our multivariable model and included a maximum of eight covariates. We assessed the model performance in terms of discrimination and calibration and performed internal validation to estimate the statistical optimism of the final model. The final prediction model included age, fever, dyspnoea, hypertension and chronic respiratory disease. To develop the OUTCoV score, we assigned points for each predictor that were proportional to the coefficients of the regression equation. Sensitivity, specificity, positive and negative likelihood ratios were estimated, including positive and negative predictive values in different thresholds.

Main Outcome Measure: The primary outcome was COVID-19-related hospitalisation.

Results: The OUTCoV score ranged from 0 to 7.5 points. The two threshold parameters with optimal rule-out and rule-in characteristics for the risk of hospitalisation were 3 and 5.5, respectively. Outpatients with a score <3 (997/1459; 68.3%) had no follow-up as at low risk of hospitalisation (1.8%; 95% CI 1.1 to 2.8). For a score ≥5.5 (20/1459; 1.4%), the hospitalisation risk was higher (30%; 95% CI 11.9 to 54.3).

Conclusions: The OUTCoV score allows to rule out two-thirds of outpatients with SARS-CoV-2 infection presenting a low hospitalisation risk and to identify those at high risk that require careful follow-up to assess the need for hospitalisation. The model provides a simple decision-making tool for an effective allocation of resources to maintain quality care for outpatient populations.
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http://dx.doi.org/10.1136/bmjopen-2020-044242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214986PMC
June 2021

Feasibility and safety of rVSV-ZEBOV vaccination of humanitarian health workers against Ebola virus disease: an observational study.

J Travel Med 2021 Jun 15. Epub 2021 Jun 15.

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 6, Geneva 1205, Switzerland.

Background And Rationale: Geneva University Hospitals were granted a temporary authorization to administer the recombinant live vesicular stomatitis virus rVSV-ZEBOV (Ervebo®) vaccine to expatriate humanitarian frontline workers (FLWs) prior to mission deployment.

Objectives: Our aims were to assess the feasibility of FLW vaccination before deployment and to report adverse events (AEs).

Methods: FLWs received a single injection of rVSV-ZEBOV (>7.2E7 plaque forming unit) during their pre-deployment medical check-up at the Travel Medicine Clinic of the Geneva University Hospitals (Day 0). A safety questionnaire regarding potential AEs was emailed to FLWs on Days 3 and 21. Early and delayed AEs were those starting within 3 or 21 days of vaccination, respectively.

Results: Between 1 August 2019 and 30 June 2020, 124 FLWs received the rVSV-ZEBOV vaccine. Eighty-six volunteers (86/124; 69%) received a concomitant vaccine. The response rate to the follow-up questionnaire was 88 and 55% at Days 3 and 21, respectively. Most respondents (105/109; 96.3%), experienced at least one AE, with a mean of three (±SD 1.75) AEs per person. The most common AE was injection site pain, followed by fever (53/109; 48.6%), fatigue (51/109; 46.7%) and myalgia (49/109; 44.9%). Most early AEs (360/377; 95.4%) resolved within 3 days, reflecting vaccine reactogenicity. Delayed AEs were reported by 6/69 (7.2%) subjects, the median time to symptom onset was 11 days (range: 5-14); half of them were joint-related AEs (3/6). Four serious adverse events (SAE) were observed: two cases of high grade fever, one rash and one case of arthritis. Two suspected unexpected serious adverse reactions were observed: one case of continuing recurrent transient dizziness and fatigue considered related to the vaccine; and one case of presbyopia that was deemed unrelated.

Conclusion: AEs to rVSV-ZEBOV were common but in general transient and were well tolerated, pre-deployment rVSV-ZEBOV vaccination in FLW is feasible and can be included with pre-mission check-up.
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http://dx.doi.org/10.1093/jtm/taab086DOI Listing
June 2021

Large variation in anti-SARS-CoV-2 antibody prevalence among essential workers in Geneva, Switzerland.

Nat Commun 2021 06 8;12(1):3455. Epub 2021 Jun 8.

Department of Health and Community Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Limited data exist on SARS-CoV-2 infection rates across sectors and occupations, hindering our ability to make rational policy, including vaccination prioritization, to protect workers and limit SARS-CoV-2 spread. Here, we present results from our SEROCoV-WORK + study, a serosurvey of workers recruited after the first wave of the COVID-19 pandemic in Geneva, Switzerland. We tested workers (May 18-September 18, 2020) from 16 sectors and 32 occupations for anti-SARS-CoV-2 IgG antibodies. Of 10,513 participants, 1026 (9.8%) tested positive. The seropositivity rate ranged from 4.2% in the media sector to 14.3% in the nursing home sector. We found considerable within-sector variability: nursing home (0%-31.4%), homecare (3.9%-12.6%), healthcare (0%-23.5%), public administration (2.6%-24.6%), and public security (0%-16.7%). Seropositivity rates also varied across occupations, from 15.0% among kitchen staff and 14.4% among nurses, to 5.4% among domestic care workers and 2.8% among journalists. Our findings show that seropositivity rates varied widely across sectors, between facilities within sectors, and across occupations, reflecting a higher exposure in certain sectors and occupations.
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http://dx.doi.org/10.1038/s41467-021-23796-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187639PMC
June 2021

[Traveler's consultations in time of pandemic COVID-19: changing practices and sentinel role ?]

Rev Med Suisse 2021 May;17(737):872-876

Service de médecine tropicale et humanitaire, Département de médecine de premier recours, HUG, 1211 Genève 14.

What is the status of travel medicine in the context of the COVID-19 pandemic? This article describes the evolution of travel medicine consultations at the University Hospital of Geneva with the introduction of pre-travel screening for the SARS-CoV-2 virus. 9141 travelers were screened between August 2020 and January 2021 for various destinations, one third of which were intra-European. The various international restrictions led to the creation of thirteen separate medical certificates and a list of requirements for 150 countries updated weekly. A significant increase in positivity (up to 5%) in the asymptomatic traveler was associated with the months of October and November 2020 and with certain destinations. This rate of positivity in the asymptomatic traveler population could be a sentinel indicator of viral transmission in the community.
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May 2021

[SARS-CoV-2 screening in travelers: what approach to assess transmission risk ?]

Rev Med Suisse 2021 May;17(737):866-870

Service de médecine tropicale et humanitaire, Département de médecine de premier recours, HUG, 1211 Genève 14.

Before a trip, a screening for SARS-CoV-2 infection by RT-PCR is often required and raises the problem of detection of residual viral RNA at distance from the acute infection (post-Covid). At the University Hospital of Geneva, we developed an expertise to distinguish acute from post-Covid infections. Between October and December 2020, 30% of the people tested positive were able to travel because the result corresponded to post-Covid and 65% were put in isolation because of an acute infection with a risk of transmission. To overcome the detection of residual viral RNA by RT-PCR, a rapid antigenic test would be an interesting and less expensive alternative. It could also be performed a few hours before departure.
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May 2021

Recommandations sanitaires en temps de crise, aussi lentement que nécessaire….

Rev Med Suisse 2021 05;17(737):859-860

Service de médecine tropicale et humanitaire, Département de médecine de premier recours, HUG, Genève.

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May 2021

SARS-CoV-2 testing strategy: A comparison of restricted and extended strategies in a Swiss outpatient cohort from the community and hospital employees.

PLoS One 2021 22;16(4):e0250021. Epub 2021 Apr 22.

Division of Primary Care, Geneva University Hospitals, Geneva, Switzerland.

Background: Testing is a key measure to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we empirically compared two SARS-CoV-2 testing strategies.

Methods: We used data from a Swiss single-centre, outpatient cohort study (n = 6,331 test results). A "restricted" strategy was applied to individuals with respiratory symptoms and/or fever and selected risk factors, or an epidemiological link and an "extended" strategy included any clinical symptoms without restriction, irrespective of risk factors and exposure. Data on infection, symptoms, viral load were collected during the first wave (March 11-April 21, 2020) and patients were followed up for clinical complications and hospitalisations until August 31, 2020.

Findings: Infection, clinical complications, and hospitalisation rates were lower for those in the extended strategy compared with the restricted strategy (17.2% vs. 25.0%, 12.3% vs. 20.8%, and 0.7% vs. 2.3%). In the whole cohort, participants included in the extended strategy had a lower number of symptoms (3.51 vs. 4.57; p < .001) and visits occurred earlier after symptom onset (0-3 days: 59.2% vs. 44.2%; p < .001). Among positive cases, the viral load was higher for the extended strategy (p < .001).

Conclusions: These findings highlighted the crucial importance to implement a widespread testing strategy to achieve a better understanding of the infection, to mount an effective control response, by capturing people when their viral load is highest. A widespread test strategy should be available without barriers to help break the chains of transmission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250021PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061911PMC
May 2021

High frequency of Taenia solium antigen positivity in patients admitted for neurological disorders in the Rural Hospital of Mosango, Democratic Republic of Congo.

BMC Infect Dis 2021 Apr 17;21(1):359. Epub 2021 Apr 17.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium ("Better Diagnosis for Neglected Infections") and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses.

Methods: We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay.

Results: For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3-16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9-9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort.

Conclusions: T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region.
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http://dx.doi.org/10.1186/s12879-021-06032-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052782PMC
April 2021

Diagnostic accuracy of two commercial SARS-CoV-2 antigen-detecting rapid tests at the point of care in community-based testing centers.

PLoS One 2021 31;16(3):e0248921. Epub 2021 Mar 31.

Division of Infectious Disease, Geneva University Hospitals, Geneva, Switzerland.

Objectives: Determine the diagnostic accuracy of two antigen-detecting rapid diagnostic tests (Ag-RDT) for SARS-CoV-2 at the point of care and define individuals' characteristics providing best performance.

Methods: We performed a prospective, single-center, point of care validation of two Ag-RDT in comparison to RT-PCR on nasopharyngeal swabs.

Results: Between October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioTM Covid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. Lower sensitivity of 88.2% was seen on the same day of symptom development (day 0).

Conclusions: We provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248921PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011749PMC
April 2021

Novel transdisciplinary methodology for cross-sectional analysis of snakebite epidemiology at national scale.

PLoS Negl Trop Dis 2021 02 12;15(2):e0009023. Epub 2021 Feb 12.

Institute of Global Health (IGH), Department of Community Health and Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Background: Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.

Methodology/principal Findings: We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.

Conclusions/significance: This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
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http://dx.doi.org/10.1371/journal.pntd.0009023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906452PMC
February 2021

A Systematic Literature Review of Microscopy Methods Reported in Malaria Clinical Trials.

Am J Trop Med Hyg 2020 Dec 21. Epub 2020 Dec 21.

Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.

Microscopy of stained blood films is essential for the diagnosis of malaria, differentiation of parasite species, and estimation of parasite density performed for assessments of antimalarial drug efficacy. The accuracy and comparability of these measures over time and space are vital to discern the emergence or spread of antimalarial drug resistance. Although evidence-based guidelines for malaria microscopy methods exist, the age-old microscopy techniques for parasitological assessments are subject to considerable methodological variations. The purpose of this review was to explore critically how microscopy methods were reported in published malarial studies between 2013 and 2017 with the focus on outlining the methodological differences and improving reporting standards in practice.
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http://dx.doi.org/10.4269/ajtmh.20-1219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941839PMC
December 2020

Antibiotic use prior to seeking medical care in patients with persistent fever: a cross-sectional study in four low- and middle-income countries.

Clin Microbiol Infect 2020 Nov 11. Epub 2020 Nov 11.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Objectives: Community-level antibiotic use contributes to antimicrobial resistance, but is rarely monitored as part of efforts to optimize antibiotic use in low- and middle-income countries (LMICs). We investigated antibiotic use in the 4 weeks before study inclusion for persistent fever.

Methods: The NIDIAG-Fever (Neglected Infectious diseases DIAGnosis-Fever) study investigated aetiologies of infections in patients ≥5 years old with fever ≥1 week in six healthcare facilities in Cambodia, the Democratic Republic of the Congo (DRC), Nepal, and Sudan. In the present nested cross-sectional study, we describe prevalence and choice of antibiotics before and at study inclusion, applying the Access/Watch/Reserve (AWaRe) classification of the WHO List of Essential Medicines. Factors associated with prior antibiotic use were analysed.

Results: Of 1939 participants, 428 (22.1%) reported the prior use of one or more antibiotics, ranging from 6.3% (24/382, Cambodia) to 35.5% (207/583, Nepal). Of 545 reported antibiotics, the most frequent were Watch group antibiotics (351/545, 64.4%), ranging from 23.6% (DRC) to 82.1% (Nepal). Parenteral administration ranged from 5.9% to 69.6% between study sites. Antibiotic use was most frequent among young patients (5-17 years of age; risk ratio 1.42, 95%CI 1.19-1.71) and men (RR 1.29; 95%CI 1.09-1.53). No association was found with specific symptoms. Of 555 antibiotics started before study inclusion, 275 (49.5%) were discontinued at study inclusion.

Conclusions: Watch antibiotics were frequently used, and discontinued upon study inclusion. The antibiotic use frequency and choice varied importantly between LMICs. Data on local antibiotic use are essential to guide efforts to optimize antibiotic use in LMICs, should not be restricted to hospitals, and need to take local healthcare utilization into account.
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http://dx.doi.org/10.1016/j.cmi.2020.11.003DOI Listing
November 2020

Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial.

BMJ Open 2020 11 12;10(11):e040110. Epub 2020 Nov 12.

HIV Unit, Geneva University Hospitals, Geneva, Switzerland.

Introduction: Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.

Methods And Analysis: COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.

Ethics And Dissemination: Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.

Trial Registration Number: Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).

Registered Report Identifier: CCER 2020-0864.
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http://dx.doi.org/10.1136/bmjopen-2020-040110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662450PMC
November 2020

A Case report of atovaquone/proguanil induced esophageal ulcers.

J Travel Med 2020 Nov;27(7)

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 6, 1205 Geneva, Switzerland.

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http://dx.doi.org/10.1093/jtm/taaa198DOI Listing
November 2020

Snakebite epidemiology and health-seeking behavior in Akonolinga health district, Cameroon: Cross-sectional study.

PLoS Negl Trop Dis 2020 06 25;14(6):e0008334. Epub 2020 Jun 25.

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland.

Background: Snakebite envenoming causes 81,000-138,000 annual human deaths and pain, terror, or disability in 4.5-5.4 million victims. Accurate community-based epidemiological data is scarce. Our objective was to assess snakebite incidence, mortality, and health-seeking behavior, in an affected health district of Cameroon.

Methods: We conducted a cross-sectional multicluster household survey in Akonolinga health district, Centre Region, Cameroon, from October to December 2016. Using probability-proportional-to-size, 20 villages were randomly selected, then, all inhabited households were systematically selected. Annual incidence and adjusted odds-ratio for predictors were estimated.

Findings: Among the 9,924 participants, 66 suffered a snakebite during the past year: the resulting incidence is 665 (95%CI: 519-841) per 100,000 inhabitants per year. Victims were aged 5-75y (median: 34y), 53% were male and 57% farmer-cultivators. Two children died (case-fatality rate: 3%); 39 (59%) presented severity signs, including 2 (3%) neurotoxic syndromes, 20 (30%) systemic digestive syndromes, and 17 (26%) severe cytotoxic syndromes. Non-severe cases included 20 (30%) mild cytotoxic syndromes and 7 (11%) dry bites. Only two victims (3%) received antivenom. 59 (89%) used family traditional practices, 25 (38%) traditional healers, and 31 (47%) consulted health facilities. Median delays to these three care-options were 5, 45, and 60 minutes, respectively. Traditional treatments included incisions (n = 57; 86%), tourniquets (n = 51; 77%) and black-stones (n = 44; 67%). The two last procedures were also used in health facilities (n = 18). Consulting traditional healers was associated with severity (adjusted-OR: 19.6 (2.5-156), p = 0.005) and complications (aOR: 17.3, 2.4-123, p = 0.004). Long-term disabilities were subjective psychological trauma (n = 47; 71%), finger amputation (n = 1; 2%), ankylosis (n = 1; 2%) and chronic pain (n = 1; 2%).

Conclusions: We observed alarming levels of snakebite incidence, mortality, antivenom scarcity, and use of traditional medicine. It could represent several thousands of victims at national level. We suggested conducting a country-wide study, and improving antivenom supply, first-aid training, for traditional healers and health professionals.
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http://dx.doi.org/10.1371/journal.pntd.0008334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343182PMC
June 2020

Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19.

Prim Care Diabetes 2021 02 30;15(1):16-17. Epub 2020 May 30.

Division of Endocrinology, Diabetology, Hypertension and Nutrition, Switzerland.

The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient-provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.
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http://dx.doi.org/10.1016/j.pcd.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260491PMC
February 2021

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.

Lancet 2020 08 11;396(10247):313-319. Epub 2020 Jun 11.

Division of Primary Care, Geneva University Hospitals, Geneva, Switzerland; Department of Health and Community Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Background: Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic.

Methods: The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Here we present results from the first 5 weeks of the study.

Findings: Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4-8·0, n=341). The estimate increased to 8·5% (5·9-11·4, n=469) in the second week, to 10·9% (7·9-14·4, n=577) in the third week, 6·6% (4·3-9·4, n=604) in the fourth week, and 10·8% (8·2-13·9, n=775) in the fifth week. Individuals aged 5-9 years (relative risk [RR] 0·32 [95% CI 0·11-0·63]) and those older than 65 years (RR 0·50 [0·28-0·78]) had a significantly lower risk of being seropositive than those aged 20-49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community.

Interpretation: These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over <2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5-9 years and adults older than 65 years, compared with those aged 10-64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission.

Funding: Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases.
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http://dx.doi.org/10.1016/S0140-6736(20)31304-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289564PMC
August 2020

Lessons learned about co-creation: developing a complex intervention in rural Peru.

Glob Health Action 2020 12;13(1):1754016

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals & University of Geneva, Switzerland.

: Co-creation is the process of involving stakeholders in the development of interventions. Although co-creation is becoming more widespread, reports of the process and lessons learned are scarce.: To describe the process and lessons learned from using the COHESION manual, a co-creation methodology to develop interventions aimed at the improvement of diagnosis and/or management of chronic diseases at the primary healthcare level in a low-resource setting in Peru.: Observational study to describe the use of the COHESION manual 'Moving from Research to Interventions: The COHESION Model' developed for a multi-country project in low- and middle-income countries for co-creation and the adaptations needed to customize it to the local context of rural communities in northern Peru.: The actual process of co-creation in Peru included co-creation-related questions in the formative research; an initial consultation with stakeholders at the micro, meso, and macro levels (e.g. community members, health workers, and policy-makers); the analysis of the collected data; a second consultation with each stakeholder group; the prioritization of intervention options; and finally the design of a theory of change for all activities included in the complex intervention. The complex intervention included: 1) offer training in specific diseases and soft skills to health workers, 2) create radio programs that promote chronic disease prevention and management plus empower patients to ask questions during their visits to primary health care (PHC) facilities, and 3) provide a small grant to the PHC for infrastructure improvement. Small adaptations to the COHESION manual were necessary for this co-creation process.: This study provides a practical example of the process of co-creating complex interventions to increase access and quality of health care in a low-resource setting. The process, components, challenges and opportunities identified could be useful for other researchers who want to co-create interventions with beneficiaries in similar settings.
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http://dx.doi.org/10.1080/16549716.2020.1754016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269078PMC
December 2020

[Mental health and stress in humanitarian expatriates].

Rev Med Suisse 2020 May;16(693):993-997

Service de médecine tropicale et humanitaire, HUG, 1211 Genève 14.

Humanitarian work is stressful and can have an impact on the mental health of humanitarian expatriates. In order to reduce stress and its consequences, humanitarian organizations are implementing various measures to keep their staff healthy. Humanitarian workers, on the other hand, must take care of themselves and apply self-protection mechanisms. Most humanitarian workers are doing well. The treating doctor plays a key role in detecting people and behavior at risk. He/she encourages the expatriate to use his/her resources and provide the adequate support and medical follow-up if necessary. Collaboration with the staff health units of humanitarian organizations allows for optimal care of humanitarian workers' medical conditions.
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May 2020

Covid-19 : et notre monde se referma comme une huître….

Rev Med Suisse 2020 May;16(693):975-976

Policlinique de médecine tropicale, voyages et vaccinations, Unisanté, Centre de médecine générale et santé publique, Lausanne.

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May 2020

Spotlight on experiences of medicine unavailability: access to medicines challenges for NCDs and NTDs - the contrasting cases of insulin and praziquantel.

Expert Rev Clin Pharmacol 2020 Apr 21;13(4):341-353. Epub 2020 Mar 21.

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals , Geneva, Switzerland.

Introduction: Effective medicines exist to address global health challenges including Neglected Tropical Diseases (NTD) and Noncommunicable Diseases (NCD) however these are often unavailable and unaffordable. To date, little literature exists comparing medicine unavailability across broad disease areas.

Areas Covered: Using insulin and praziquantel as tracer medicines this review aims to demonstrate that separating global health governance agendas for NCDs and NTDs ultimately impacts the effectiveness of coalitions for access for the poorest populations. Electronic literature searches were performed through Science Direct, PubMed, and Google Scholar (March-May2017 and updated in September-December2019) using keywords from Shiffman's framework; NCDs; NTDs; and for each medicine. Best practice from each area was analyzed.

Expert Opinion: Many actors responded to the London Declaration which reinforced praziquantel's central role in control and elimination of schistosomiasis whereas access to affordable insulin emerged secondary to framing around prevention and management of diabetes. For insulin key stakeholders are not aligned around access. The position taken by pharmaceutical companies as donors versus commercial actors was critical to sustainable affordable access to these medicines. Integrated access models for low resource populations need shared pathways given the increasing need for essential medicines in the context of Universal Health Coverage.
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http://dx.doi.org/10.1080/17512433.2020.1740589DOI Listing
April 2020
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