Iatrogenic botulism. / Iatrogen botulisme.

This case study describes severe iatrogenic botulism following treatment with a botulinum toxin injection at a private clinic abroad.

Evaluation of the pilot wastewater surveillance for SARS-CoV-2 in Norway, June 2022 - March 2023.

BACKGROUND: During the COVID-19 pandemic, wastewater-based surveillance gained great international interest as an additional tool to monitor SARS-CoV-2. In autumn 2021, the Norwegian Institute of Public Health decided to pilot a national wastewater surveillance (WWS) system for SARS-CoV-2 and its variants between June 2022 and March 2023. We evaluated the system to assess if it met its objectives and its attribute-based performance. METHODS: We adapted the available guidelines for evaluation of surveillance systems. The evaluation was carried out as a descriptive analysis and consisted of the following three steps: (i) description of the WWS system, (ii) identification of users and stakeholders, and (iii) analysis of the system's attributes and performance including sensitivity, specificity, timeliness, usefulness, representativeness, simplicity, flexibility, stability, and communication. Cross-correlation analysis was performed to assess the system's ability to provide early warning signal of new wave of infections. RESULTS: The pilot WWS system was a national surveillance system using existing wastewater infrastructures from the largest Norwegian municipalities. We found that the system was sensitive, timely, useful, representative, simple, flexible, acceptable, and stable to follow the general trend of infection. Preliminary results indicate that the system could provide an early signal of changes in variant distribution. However, challenges may arise with: (i) specificity due to temporary fluctuations of RNA levels in wastewater, (ii) representativeness when downscaling, and (iii) flexibility and acceptability when upscaling the system due to limited resources and/or capacity. CONCLUSIONS: Our results showed that the pilot WWS system met most of its surveillance objectives. The system was able to provide an early warning signal of 1-2 weeks, and the system was useful to monitor infections at population level and complement routine surveillance when individual testing activity was low. However, temporary fluctuations of WWS values need to be carefully interpreted. To improve quality and efficiency, we recommend to standardise and validate methods for assessing trends of new waves of infection and variants, evaluate the WWS system using a longer operational period particularly for new variants, and conduct prevalence studies in the population to calibrate the system and improve data interpretation.

[Brucellosis with acute arthritis and positive blood culture] / Brucellose med akutt artritt og positiv blodkultur.

BACKGROUND: Brucellosis is transmitted from infected animals to humans mainly by unpasteurised dairy products. Typical symptoms include undulant fever and arthralgia, but the disease can affect all organ systems and cause chronic debilitating and disabling illness. The condition is likely severely underdiagnosed, especially in impoverished populations. CASE PRESENTATION: A young girl presented with a one-day history of ankle pain and low-grade fever. She was born in a refugee camp in the Middle East, but lived with a Norwegian foster family and was considered to be healthy before the symptoms emerged. Blood culture surprisingly revealed growth of Brucella melitensis. She was successfully treated with a combination of trimethoprim-sulfamethoxazole and rifampicin. INTERPRETATION: This girl was likely infected with Brucella through ingestion of goat's milk, which she was given in the refugee camp. The disease presented with arthritis nearly two years after exposure.

Increased household transmission and immune escape of the SARS-CoV-2 Omicron compared to Delta variants.

Understanding the epidemic growth of the novel SARS-CoV-2 Omicron variant is critical for public health. We compared the ten-day secondary attack rate (SAR) of the Omicron and Delta variants in households using Norwegian contact tracing data, December 2021 - January 2022. Omicron SAR was higher than Delta, with a relative risk (RR) of 1.41 (95% CI 1.27-1.56). We observed increased susceptibility to Omicron infection in household contacts compared to Delta, independent of contacts' vaccination status. Among three-dose vaccinated contacts, the mean SAR was lower for both variants. We found increased Omicron transmissibility from primary cases to contacts in all vaccination groups, except 1-dose vaccinated, compared to Delta. Omicron SAR of three-dose vaccinated primary cases was high, 46% vs 11 % for Delta. In conclusion, three-dose vaccinated primary cases with Omicron infection can efficiently spread in households, while three-dose vaccinated contacts have a lower risk of being infected by Delta and Omicron.

Adaptation of Brucella melitensis Antimicrobial Susceptibility Testing to the ISO 20776 Standard and Validation of the Method.

Brucellosis, mainly caused by Brucella (B.) melitensis, is associated with a risk of chronification and relapses. Antimicrobial susceptibility testing (AST) standards for B. melitensis are not available, and the agent is not yet listed in the EUCAST breakpoint tables. CLSI recommendations for B. melitensis exist, but they do not fulfill the requirements of the ISO 20776 standard regarding the culture medium and the incubation conditions. Under the third EU Health Programme, laboratories specializing in the diagnostics of highly pathogenic bacteria in their respective countries formed a working group within a Joint Action aiming to develop a suitable method for the AST of B. melitensis. Under the supervision of EUCAST representatives, this working group adapted the CLSI M45 document to the ISO 20776 standard after testing and validation. These adaptations included the comparison of various culture media, culture conditions and AST methods. A Standard Operation Procedure was derived and an interlaboratory validation was performed in order to evaluate the method. The results showed pros and cons for both of the two methods but also indicate that it is not necessary to abandon Mueller-Hinton without additives for the AST of B. melitensis.

The First GAEN-Based COVID-19 Contact Tracing App in Norway Identifies 80% of Close Contacts in "Real Life" Scenarios.

The coronavirus disease 2019 (COVID-19) response in most countries has relied on testing, isolation, contact tracing, and quarantine (TITQ), which is labor- and time-consuming. Therefore, several countries worldwide launched Bluetooth-based apps as supplementary tools. The aim of using contact tracing apps is to rapidly notify people about their possible exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus make the process of TITQ more efficient, especially upon exposure in public places. We evaluated the Norwegian Google Apple exposure notification (GAEN)-based contact tracing app Smittestopp v2 under relevant "real-life" test scenarios. We used a total of 40 devices, representing six different brands, and compared two different exposure configurations, experimented with different time thresholds and weights of the Bluetooth attenuation levels (buckets), and calculated the true notification rates among close contacts (≤2 m and ≥15 min) and false notification of sporadic contacts. In addition, we assessed the impact of using different operating systems and locations of the phone (hand/pocket). The best configuration tested to trigger exposure notification resulted in the correct notification of 80% of the true close contacts and incorrect notification of 34% of the sporadic contacts. Among those who incorrectly received notifications, most (67%) were within 2 m but the duration of contact was <15 min and thus they were not, per se, considered as "close contacts." Lower sensitivity was observed when using the iOS operating systems or carrying the phone in the pocket instead of in the hand. The results of this study were used to improve and evaluate the performance of the Norwegian contact-tracing app Smittestopp.

Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021.

In late November 2021, an outbreak of Omicron SARS-CoV-2 following a Christmas party with 117 attendees was detected in Oslo, Norway. We observed an attack rate of 74% and most cases developed symptoms. As at 13 December, none have been hospitalised. Most participants were 30-50 years old. Ninety-six percent of them were fully vaccinated. These findings corroborate reports that the Omicron variant may be more transmissible, and that vaccination may be less effective in preventing infection compared with Delta.

Increased risk of hospitalisation and intensive care admission associated with reported cases of SARS-CoV-2 variants B.1.1.7 and B.1.351 in Norway, December 2020 -May 2021.

INTRODUCTION: Since their emergence, SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.351 have spread worldwide. We estimated the risk of hospitalisation and admission to an intensive care unit (ICU) for infections with B.1.1.7 and B.1.351 in Norway, compared to infections with non-VOC. MATERIALS AND METHODS: Using linked individual-level data from national registries, we conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway diagnosed between 28 December 2020 and 2 May 2021. Variants were identified based on whole genome sequencing, partial sequencing by Sanger sequencing or PCR screening for selected targets. The outcome was hospitalisation or ICU admission. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression to examine the association between SARS-CoV-2 variants B.1.1.7 and B.1.351 with i) hospital admission and ii) ICU admission compared to non-VOC. RESULTS: We included 23,169 cases of B.1.1.7, 548 B.1.351 and 4,584 non-VOC. Overall, 1,017 cases were hospitalised (3.6%) and 206 admitted to ICU (0.7%). B.1.1.7 was associated with a 1.9-fold increased risk of hospitalisation (aRR 95%CI 1.6-2.3) and a 1.8-fold increased risk of ICU admission (aRR 95%CI 1.2-2.8) compared to non-VOC. Among hospitalised cases, no difference was found in the risk of ICU admission between B.1.1.7 and non-VOC. B.1.351 was associated with a 2.4-fold increased risk of hospitalisation (aRR 95%CI 1.7-3.3) and a 2.7-fold increased risk of ICU admission (aRR 95%CI 1.2-6.5) compared to non-VOC. DISCUSSION: Our findings add to the growing evidence of a higher risk of severe disease among persons infected with B.1.1.7 or B.1.351. This highlights the importance of prevention and control measures to reduce transmission of these VOC in society, particularly ongoing vaccination programmes, and preparedness plans for hospital surge capacity.

Prevention of human rabies: a challenge for the European Union and the European Economic Area.

Rabies is enzootic in over one hundred countries worldwide. In the European Union/European Economic Area (EU/EEA), the vast majority of human rabies cases are travellers bitten by dogs in rabies-enzootic countries, mostly in Asia and Africa. Thus, EU/EEA travellers visiting rabies enzootic countries should be aware of the risk of being infected with the rabies virus when having physical contact with mammals. They should consider pre-exposure vaccination following criteria recommended by the World Health Organization and if unvaccinated, immediately seek medical attention in case of bites or scratches from mammals. As the majority of the EU/EEA countries are free from rabies in mammals, elimination of the disease (no enzootic circulation of the virus and low number of imported cases) has been achieved by 2020. However, illegal import of potentially infected animals, mainly dogs, poses a risk to public health and might threaten the elimination goal. Additionally, newly recognised bat lyssaviruses represent a potential emerging threat as the rabies vaccine may not confer protective immunity. To support preparedness activities in EU/EEA countries, guidance for the assessment and the management of the public health risk related to rabies but also other lyssaviruses, should be developed.

Evaluation of the national surveillance of Legionnaires' disease in Norway, 2008-2017.

BACKGROUND: In Norway, Legionnaires' disease is reportable upon clinical suspicion to public health authorities and mandatorily notifiable through the Norwegian surveillance system for communicable diseases (MSIS) for both clinicians and laboratories. In the summer of 2017, several European countries reported high notification rates for Legionnaires' disease, which was not observed in Norway. We evaluated MSIS to assess if it meets its objectives of detecting cases and trends in incidence of Legionnaires' disease. METHODS: We retrieved MSIS data from 2008 to 2017 and calculated timeliness as days from sampling to notification, and internal completeness for key variables as the proportion of observations with a value. Where possible, we assessed internal validity on the presence of a plausible value. To estimate external completeness and validity we linked MSIS with hospital reimbursement claims in the Norwegian Patient Registry. To assess acceptability and representativeness, we surveyed doctors in 39 hospitals on their units' diagnostic and notification procedures, and their use of MSIS. RESULTS: There were 438 notified cases. Internal completeness and internal validity were high for key variables (≥95%). The median delay from sampling to notification was 4 days. There were 73 patients in MSIS only, 70 in the Norwegian Patient Registry only, and 351 in both registers. The external completeness of MSIS was 83% (95% CI 80-86%). For external validity, the positive predictive value of MSIS was 83% (95% CI 79-86%). Forty-seven respondents from 28 hospitals described testing procedures. These were inconsistent: 29 (62%) reported no systematic application of criteria for requesting legionella testing. Eighteen (38%) reported testing all patients with suspected pneumonia and a travel history. Thirty-one (66%) found the notification criteria clear. CONCLUSIONS: Our results suggest that the surveillance in MSIS can detect incidence changes for Legionnaires' disease over time, by place and person, but likely does not detect every case diagnosed in Norway. We recommend wider investigation of diagnostic procedures in order to improve representativeness and awareness of MSIS notification criteria among clinicians in order to improve acceptability of the surveillance. We also recommend a more comprehensive assessment of whether patients only registered in the Norwegian Patient Registry were true Legionnaires' disease cases.

New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription.

BACKGROUND: Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis. METHODS: A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected. RESULTS: Two hundred and eighteen patients were included; 117 (54%) neonates (0-29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm3 and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without. CONCLUSIONS: A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.

Whole-genome sequencing and antimicrobial resistance in Brucella melitensis from a Norwegian perspective.

Brucellosis is a rarely encountered infection in Norway. The aim of this study was to explore all Brucella melitensis isolates collected in Norway from 1999 to 2016 in relation to origin of infection and antimicrobial resistance patterns. A total of 23 isolates were analysed by whole-genome sequencing and compared with selected sequences of B. melitensis available from NCBI. Additionally, SNP analysis in antibiotic resistance determining genes was performed. The majority belonged to the East Mediterranean clade (genotype II), while the remaining isolates belonged to the African clade (genotype III). These results indicate that human brucellosis in Norway is related to travels or migration from the Middle East, Asia or Africa, in accordance with results from Germany, Denmark and Sweden. Antibiotic susceptibility patterns were determined by broth microdilution method and/or gradient strip method. All isolates were susceptible for all tested antibiotics, except for rifampicin where phenotypical results indicated resistance or intermediate resistance in all isolates based on broth microdilution method, and in four isolates based on gradient strip testing. In contrast, screening of the rpoB gene did not reveal any mutations in the previously described rpoB "hot spot" regions related to rifampicin resistance, indicating overestimation of resistance based on phenotypical results.

Soluble markers of the Toll-like receptor 4 pathway differentiate between active and latent tuberculosis and are associated with treatment responses.

BACKGROUND: Biomarkers to differentiate between active tuberculosis (TB) and latent TB infection (LTBI) and to monitor treatment responses are requested to complement TB diagnostics and control, particularly in patients with multi-drug resistant TB. We have studied soluble markers of the Toll-like-receptor 4 (TLR-4) pathway in various stages of TB disease and during anti-TB treatment. METHODS: Plasma samples from patients with culture confirmed drug-sensitive TB (n = 19) were collected before and after 2, 8 and 24 weeks of efficient anti-TB treatment and in a LTBI group (n = 6). Soluble (s) CD14 and myeloid differentiation-2 (MD-2) were analyzed by the Enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) was analyzed by the Limulus Amebocyte Lysate colorimetric assay. Nonparametric statistics were applied. RESULTS: Plasma levels of sCD14 (p<0.001), MD-2 (p = 0.036) and LPS (p = 0.069) were elevated at baseline in patients with untreated active TB compared to the LTBI group. MD-2 concentrations decreased after 2 weeks of treatment (p = 0.011), while LPS levels decreased after 8 weeks (p = 0.005). In contrast, sCD14 levels increased after 2 weeks (p = 0.047) with a subsequent modest decrease throughout the treatment period. There was no significant difference in concentrations of any of these markers between patients with pulmonary and extrapulmonary TB or between patients with or without symptoms. CONCLUSION: Our data suggest that plasma levels of LPS, MD-2 and sCD14 can discriminate between active TB and LTBI. A decline in LPS and MD-2 concentrations was associated with response to anti-TB treatment. The clinical potential of these soluble TLR-4 pathway proteins needs to be further explored.

[Histoplasmosis among travellers to Central America]. / Histoplasmose blant reisende til Mellom-Amerika.

BACKGROUND: In April 2004, the Norwegian Institute of Public Health was notified about an outbreak of a respiratory illness among participants on a cultural-historical theme tour to Central America. One patient was examined in a Swedish hospital where the clinician suspected histoplasmosis, which later was verified by serology and by culture of Histoplasma capsulatum. In order to describe the outbreak and identify the possible source of infection, a clinical and epidemiological study was conducted. MATERIAL AND METHODS: A questionnaire on symptoms, treatment and participation in various activities was sent to all the tour participants. Reminders were sent by e-mail. In addition, some participants underwent a more detailed clinical examination. RESULTS: 19 of the 21 travellers completed the questionnaire. All travellers had visited several caves inhabited by bats in El Salvador and Guatemala. During the last 10 days of the journey, 16 of the respondents (84%) acquired a respiratory illness that lasted for more than 3 weeks. The diagnosis was confirmed by serology in 8 of the 14 tested cases. Antibacterial therapy was given to 11 patients and antifungal therapy to 3 patients. Only one patient was hospitalised. INTERPRETATION: The described outbreak of histoplasmosis was probably caused by exposure to Histoplasma capsulatum during a visit in bat-infested caves. Due to the increasing popularity of adventure and theme travels, this disease may become more frequent in our population. The condition should be considered in travellers with prolonged respiratory illness after visits to caves or other closed environments with little circulation of air that are potentially contaminated with bat or bird droppings. Persons with immunosuppression may develop severe illness, and should consider avoiding places with increased risk.

[Local and global environmental medicine--assessment by Norwegian physicians]. / Lokal og global miljømedisin--norske legers vurderinger.

BACKGROUND: Local and global environmental problems are challenges to our societies and affect human health. This study examines how Norwegian physicians see these problems. MATERIAL AND METHODS: 1,260 physicians were sent a questionnaire on their knowledge, attitudes and practice related to this subject. The response rate was 88%. RESULTS: Four out of five physicians believe that the global environmental situation is a big threat to human health. Three out of five believe that physicians have a particular responsibility to contribute to a sustainable environment and development and should set an example by a sustainable lifestyle. Half of them believe that the health service has a greater responsibility for sustainability than other institutions. Only one out of three report that environmentally acceptable conditions have been focused in their workplace. Half of the general practitioners and one third of the specialists are faced with environmental health problems every week. More than every third doctor experience patients with "environmental hypochondria". Physicians feel that they need to know more about environmental medicine; mass media is their most important source of information. INTERPRETATION: The study indicates that Norwegian physicians understand the significance of the environmental situation and recognise the responsibility of the profession. However, this knowledge is to a lesser extent translated into practice.

[Severe falciparum malaria treated with exchange transfusion]. / Alvorlig falciparummalaria behandlet med utskiftingstransfusjon.

BACKGROUND: Acute severe malaria can be seen at any Norwegian hospital. The prognosis of this serious disease depends on rapid and effective treatment. MATERIAL AND METHODS: Two case reports of patients treated with exchange transfusions are presented. RESULTS: Two young Norwegian women travelled without adequate prophylaxis against malaria in South-East Asia and Central and Southern Africa respectively. A few days after leaving the endemic areas they got high fever, joint and muscular pain, and headache. In one of the patients the symptoms were interpreted as flu symptoms; one week later the patient was admitted to hospital suffering from severe malaria. The other patient was admitted to hospital on the day she returned to Norway, six days after getting febrile. Thin blood films showed Plasmodium falciparum, with 30% and 40-50% parasitaemia respectively. Both patients were icteric with thrombocytopenia and increased creatinine. The first patient had severe renal failure and signs of cerebral affection. She was treated with haemodialysis and exchange transfusions. The other patient was treated with exchange transfusions because of her high parasitaemia. Both patients made a complete recovery and were discharged after three and two weeks. INTERPRETATION: Severe falciparum malaria is a condition with high case-fatality if diagnostics and treatment is not optimal. In especially severe cases, exchange transfusion may be lifesaving.