How much should we sequence? An analysis of the Swiss SARS-CoV-2 surveillance effort.

During the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent-something that is unknown at the time of sequencing-and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.IMPORTANCESwitzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses.

The Swiss Pathogen Surveillance Platform - towards a nation-wide One Health data exchange platform for bacterial, viral and fungal genomics and associated metadata.

The Swiss Pathogen Surveillance Platform (SPSP) is a shared secure surveillance platform between human and veterinary medicine, to also include environmental and foodborne isolates. It enables rapid and detailed transmission monitoring and outbreak surveillance of pathogens using whole genome sequencing data and associated metadata. It features controlled data access, complex dynamic queries, dedicated dashboards and automated data sharing with international repositories, providing actionable results for public health and the vision to improve societal well-being and health.

Vaccine-Preventable Infections Among Solid Organ Transplant Recipients in Switzerland.

Importance: Vaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear. Objectives: To assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population. Design, Setting, and Participants: This nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022. Exposures: Solid organ transplant. Main Outcomes and Measures: The main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed. Results: Of 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence. Conclusions and Relevance: In this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.

Assessing real-world vaccine effectiveness against severe forms of SARS-CoV-2 infection: an observational study from routine surveillance data in Switzerland.

BACKGROUND: In Switzerland, SARS-CoV-2 vaccination campaigns started in early 2021. Vaccine coverage reached 65% of the population in December 2021, mostly with mRNA vaccines from Moderna and Pfizer-BioNtech. Simultaneously, the proportion of vaccinated among COVID-19-related hospitalisations and deaths rose, creating some confusion in the general population. We aimed to assess vaccine effectiveness against severe forms of SARS-CoV-2 infection using routine surveillance data on the vaccination status of COVID-19-related hospitalisations and deaths, and data on vaccine coverage in Switzerland. METHODS: We considered all routine surveillance data on COVID-19-related hospitalisations and deaths received at the Swiss Federal Office of Public Health from 1 July to 1 December 2021. We estimated the relative risk of COVID-19-related hospitalisation or death for not fully vaccinated compared with fully vaccinated individuals, adjusted for the dynamics of vaccine coverage over time, by age and location. We stratified the analysis by age group and by calendar month. We assessed variations in the relative risk of hospitalisation associated with the time since vaccination. RESULTS: We included a total of 5948 COVID-19-related hospitalisations of which 1245 (21%) were fully vaccinated patients, and a total of 739 deaths of which 259 (35%) were fully vaccinated. We found that the relative risk of COVID-19 related hospitalisation was 12.5 (95% confidence interval [CI] 11.7-13.4) times higher for not fully vaccinated than for fully vaccinated individuals. This translates into a vaccine effectiveness against hospitalisation of 92.0% (95% CI 91.4-92.5%). Vaccine effectiveness against death was estimated to be 90.3% (95% CI 88.6-91.8%). Effectiveness appeared to be comparatively lower in age groups over 70 and during the months of October and November 2021. We also found evidence of a decrease in vaccine effectiveness against hospitalisation for individuals vaccinated for 25 weeks or more, but this decrease appeared only in age groups below 70. CONCLUSIONS: The observed proportions of vaccinated among COVD-19-related hospitalisations and deaths in Switzerland were compatible with a high effectiveness of mRNA vaccines from Moderna and Pfizer-BioNtech against hospitalisation and death in all age groups. Effectiveness appears comparatively lower in older age groups, suggesting the importance of booster vaccinations. We found inconclusive evidence that vaccine effectiveness wanes over time. Repeated analyses will be able to better assess waning and the effect of boosters.

Parental and provider vaccine hesitancy and non-timely childhood vaccination in Switzerland.

OBJECTIVE: Although medical providers are a trusted vaccination information source for parents, they do not universally support vaccination. Complementary medicine (CM) providers are particularly likely to hold vaccine hesitant (VH) views, and VH parents often consult with them. Little research compares VH of parents and providers, and if and how each is associated with uptake of recommended childhood vaccines. METHODS: We defined non-timely receipt as recommended vaccines given > 1 month later than officially recommended, based on vaccination records. We administered versions of the Parent Attitudes about Childhood Vaccines (PACV) 5-item survey instrument to 1256 parents and their children's pediatricians (N = 112, 40 CM-oriented, 72 biomedical [not CM-oriented]) to identify moderately (PACV-score 5-6) and highly (PACV-score 7+) hesitant providers/parents. We obtained multivariable adjusted odds ratios to test relationships between parental VH and provider type/VH, and between non-timely receipt of selected childhood vaccines and parental VH and provider type/VH. RESULTS: No biomedical providers were VH, 9 CM providers were moderately VH, and 17 were highly VH. Parents seeing moderately and highly hesitant providers had adjusted odds ratio (AOR) for being VH = 6.6 (95% confidence interval (CI), 3.1-14.0) and AOR = 31.3 (95% CI 16.8-58.3), respectively. Across all vaccine uptake endpoints, children of moderately and highly hesitant parents had 1.9-3.8 and 7.1-12.3 higher odds of non-timely vaccination, and children seeing highly hesitant CM providers had 4.9-9.4 higher odds. Children seeing moderately hesitant CM providers had 3.3 higher odds of non-timely vaccination for the 1st dose of measles and 3.5 higher odds for 1st dose of polio/pertussis/tetanus. CONCLUSION: VH by both parents and providers each is associated with non-timely childhood vaccination. As VH parents are more likely to consult with VH providers, interventions aimed at increasing timely vaccination need to primarily target VH providers and their clients.

Listeriosis in infants: Prospective surveillance studies in Canada and Switzerland.

OBJECTIVES: International data on listeriosis during infancy from large populations are essential to guide evidence-based empiric antibiotic guidelines for sepsis in infancy. We aimed to determine the incidence, clinical manifestations, and outcome of listeriosis in infants <6 months of age in Canada and Switzerland. METHODS: Prospective, active surveillance of listeriosis in infants <6 months of age was conducted through the Canadian Paediatric Surveillance Program (May 2015 to April 2017) and the Swiss Paediatric Surveillance Unit (April 2017 to March 2018). Confirmed and probable cases were included. RESULTS: In Canada, eight sporadic listeriosis cases were reported (incidence, 1.1/100,000 live births/year). In Switzerland, four cases were reported (incidence, 4.5/100,000 live births/year) of which three were part of a confirmed outbreak with an unclear source. In the two countries, eight of the 12 cases (66.6%) presented as early-onset disease (within the first 7 days of life) and none presented after 28 days life. CONCLUSIONS: Neonatal listeriosis is rare. Infants presenting with sepsis, especially after 4 weeks of life, may not routinely require empiric antibiotic coverage for listeriosis. Outbreak-related cases still occur. Continued surveillance is important.

Approaching measles elimination in Switzerland: changing epidemiology 2007-2018.

Switzerland is aiming to eliminate measles, in line with the objectives of the World Health Organization (WHO). Physicians, laboratories and public health authorities have made great efforts to reach this goal. A continually increasing measles vaccination coverage and other preventive measures have made an impact: no major measles outbreak has been recorded since 2011. In order to evaluate progress towards elimination, measles epidemiology of a previous epidemic period (2007–2011) was compared with the current post-epidemic period (2012–July 2018) by analysis of data from the mandatory notification system. A decrease of 94% in the average annual incidence rate occurred between the two periods (from 133 to 9 cases per million inhabitants). This was accompanied by significant changes in the epidemiology that are expected and characteristic of countries with limited circulation of the measles virus. After analysing the performance of the Swiss surveillance system and the data provided, the WHO concluded that endemic measles transmission was interrupted in Switzerland in 2016 and 2017.

Health-seeking behaviour and treatment delay in patients with pulmonary tuberculosis in Switzerland: some slip through the net.

AIMS OF THE STUDY: To assess the health-seeking behaviour, the patient delay (onset of symptoms to first consultation) and the health system delay (first consultation to start of tuberculosis treatment) among patients with pulmonary tuberculosis (TB) diagnosed in Switzerland, and to assess the predictors of the various types of delay. METHODS: A survey among pulmonary TB patients was carried out in six cantons, covering 42% of all pulmonary adult TB cases notified in Switzerland. Data were collected by collaborators of the cantonal lung associations in charge of the follow-up of TB patients to investigate treatment seeking behaviour and to establish various delays and its predictors. Predictors of percentiles of delay (median and 75th percentile) were assessed using quantile regression. RESULTS: Among 252 eligible patients, 162 patients could be interviewed. Of these, 20.4% were born in Switzerland. Cough as a symptom was mentioned by 76% of the interviewed patients. Almost half of the 162 patients (46%) consulted first a general practitioner in an ambulatory care setting and 26% approached a hospital first. The median delay between symptom onset and first healthcare contact (patient delay) was 5.2 weeks, which is slightly longer than findings in other low prevalence countries. The interquartile range was 1.6 to 14.2 weeks. The median delay between first consultation in Switzerland and the start of TB treatment (health system delay) was 2 weeks. The interquartile range was 0.6 to 7.1 weeks. There were no clear predictors of patient delay. The main predictors of a longer median health system delay were the presence of fever (1.6 weeks, 95% confidence interval [CI] 0.5 to 2.6 weeks), having visited first a general practitioner or a paediatrician (1 week, 95% CI 0.1 to 1.9 weeks) and having seen three or four doctors before beginning TB treatment (2.9 weeks, 95% CI 0.7 to 5.1 weeks). A clear predictor of a shorter median health system delay was having undergone an X-ray at the first consultation (-2.9 weeks, 95% CI -4.8 to -0.9 weeks). Marginally significant for shorter delay was male sex (-2.6 weeks, 95% CI -5.4 to 0.1 weeks). CONCLUSIONS: No predictor of patient delay was found among the variables collected. For one fourth of the patients, the health system delay was longer than 7 weeks. General practitioners are commonly approached first, and they have to consider TB, also for patients not considered at high-risk for TB.

Serotypes and virulence profiles of Shiga toxin-producing Escherichia coli strains isolated during 2017 from human infections in Switzerland.

Since 2015, the Swiss Federal Office of Public Health registered an increase of notifications of STEC, probably due to the adoption of culture independent stx screening tests in diagnostic laboratories. This study aimed to identify the serotypes and virulence genes of 120 STEC isolated from human clinical stx positive specimens during 2017 in order to estimate any changes in serotype distribution and toxin profiles of STEC compared to the time span 2010-2014. Culturing of STEC from stool samples was achieved using the streak plate technique on MacConkey agar. We performed O and H serotyping by PCR and by micro array. Virulence genes were identified and subtyped using molecular methods, including stx1 and stx2 subtypes, and the intimin encoding gene, eae. STEC were recovered from 27.5% of the stx positive samples. STEC O157:H7 accounted for 7.5% of all isolates, and STEC O80:H2, O91:H10/H14/H21, O103:H2/H11, and O26:H11 accounted for 36.9% of the non-O157 strains. Forty-five isolates with stx1 variants, 47 with stx2 variants and 28 isolates with both stx1 and stx2 variants were identified. Forty (33.3% of all isolates) carried the subtypes associated with high pathogenic potential, stx2a, stx2c, or stx2d. The eae gene for intimin was detected in 54 strains (45% of all strains). Compared to 2010-2014, our data show that the proportion of the so called "top five" serogroups, STEC O26, O111, O103, and O157 declined from 53.7% to 28.3% in 2017. The proportion of isolates with stx2a, stx2c, or stx2d decreased from 50.5% to 33.3%. We also observed an increase of STEC harbouring the low pathogenic subtypes stx2b and stx2e from 12.6% to 29.2%, and of eae negative STEC from 29.5% in 2010-2014 to 55% in 2017. Simultaneously, there was a sharp increase of the patients' median age from 24 years to 46.5 years. Clinical manifestations in the patients included abdominal pain without diarrhea (22.3%), diarrhea (77.7%), and the haemolytic-uremic syndrome (HUS) (7.4%). Our data show that a greater number and a wider range of STEC serotypes are detected by culture-independent testing, with implications for public health services.

The epidemiology of hepatitis C in Switzerland: trends in notifications, 1988-2015.

With an estimated antibody prevalence of 0.7% in the low-risk population, hepatitis C virus (HCV) endemicity in Switzerland is low. We reviewed data from mandatory hepatitis C surveillance for 1988-2015 in order to describe the evolution of acute HCV infections and newly reported non-acute cases, and their epidemiological features. Crude and stratified annual incidence and notification rates and rate ratios were calculated using Poisson regression. Acute HCV incidence peaked in 2002 at 1.8 cases per 100,000 population, then declined sharply, levelling at around 0.7/100,000 from 2006. Notification rates for non-acute HCV cases peaked in 1999 (38.6/100,000), decreasing to 16.8/100,000 in 2015. Men constituted 65.5% of acute cases and 60.4% of non-acute cases. During the periods 1992-1995 and 2012-2015, the median age of acute cases increased from 28 to 37 and of non-acute cases from 32 to 48 years. The exposure leading to most acute (90.4%) and non-acute (71.9%) cases was presumably in Switzerland. Despite a sharp decrease since 2000, injecting drugs was the main reported exposure for both acute (63.8%) and non-acute (66.6%) cases, with a known exposure, followed by sexual contact with an infected person (18.9% and 10.3% respectively). Among all acute cases, the number of men who have sex with men increased sharply after the mid-2000s, totalling 41 during 2012-2015 (25.7%). Although the HCV epidemic peaked in 2000 - probably as a result of measures to control iatrogenic and percutaneous transmission - Switzerland must maintain prevention and surveillance.

Cross-border outbreak of Salmonella enterica ssp. enterica serovar Bovismorbificans: multiple approaches for an outbreak investigation in Germany and Switzerland.

QUESTION UNDER STUDY: In July 2014, an outbreak of Salmonella enterica ssp. enterica serovar Bovismorbificans was detected in Switzerland. The goal of the outbreak investigation was to rapidly identify and eliminate the contamination source in order to prevent new cases. METHODS: A case-case study design was applied comprising reported cases of S. Bovismorbificans and cases of other serovars. A trawling questionnaire was administered by telephone interview. Data were collected for 34 cases (20 S. Bovismorbificans and 14 Salmonella spp.) pertaining to food consumption during the 72 hours prior to symptom onset. RESULTS: A statistically significant association between an S. Bovismorbificans infection and the consumption of 'salads' (odds ratio [OR] 14.3, 95% confidence interval [CI] 1.47-138.27) as well as the consumption of 'sprouts' (OR 10.6, 95% CI 1.16-97.59) was found. Principal places of consumption of 'salads' and 'sprouts' in outbreak cases were restaurants in southern Germany (80.0%, 95% CI 56.3%-94.3%). Microbiological analysis in Germany identified S. Bovismorbificans on sprouts, and genotype analysis confirmed that Swiss and German cases shared the same outbreak strain. The contaminated products were removed from the market in Germany, preventing an on-going outbreak. CONCLUSION: The combination of the applied methods and the collaboration between the two countries proved to be crucial elements of this investigation. A series of sprouts-associated salmonellosis outbreaks underpin the importance of this vegetable as a potential food-borne pathogen carrier.

A 5-year comparison of performance of sentinel and mandatory notification surveillance systems for measles in Switzerland.

A sensitive, specific and timely surveillance is necessary to monitor progress towards measles elimination. We evaluated the performance of sentinel and mandatory-based surveillance systems for measles in Switzerland during a 5-year period by comparing 145 sentinel and 740 mandatory notified cases. The higher proportion of physicians who reported at least one case per year in the sentinel system suggests underreporting in the recently introduced mandatory surveillance for measles. Accordingly, the latter reported 2-36-fold lower estimates for incidence rates than the sentinel surveillance. However, these estimates were only 0.6-12-fold lower when we considered confirmed cases alone, which indicates a higher specificity of the mandatory surveillance system. In contrast, the sentinel network, which covers 3.5% of all outpatient consultations, detected only weakly and late a major national measles epidemic in 2003 and completely missed 2 of 10 cantonal outbreaks. Despite its better timeliness and greater sensitivity in case detection, the sentinel system, in the current situation of low incidence, is insufficient to perform measles control and to monitor progress towards elimination.

Surveillance systems for sexually transmitted diseases in Switzerland.

BACKGROUND: In Switzerland (population 7.4 million), 3 different systems contribute to surveillance for sexually transmitted infections. GOAL: The goal of this study was to compare time trends from surveillance systems for chlamydia, gonorrhea, and syphilis. STUDY DESIGN: We studied surveillance data (1997-2003) from laboratory reports in women and men, men attending dermatology clinics, and women attending gynecologists. RESULTS: Laboratory reports of episodes of Chlamydia trachomatis and Neisseria gonorrhoeae increased by 31% (from 2573 to 3449 cases) and 104% (from 259 to 528 cases), respectively. Over the same period, chlamydia reports from men attending dermatology clinics and women attending gynecologists did not change and dermatology clinic-based reports of gonorrhea in men increased only slightly. Syphilis reports from dermatology clinics increased by 127% (from 22 to 50 cases). CONCLUSIONS: Increases in laboratory reports of chlamydia and gonorrhea were not consistently detected in sentinel populations. Numbers of cases reported to all 3 systems were low. The performance of surveillance systems for sexually transmitted infections should be evaluated regularly.