Lessons learned: use of WGS in real-time investigation of suspected intrahospital SARS-CoV-2 outbreaks.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a continuing source of hospital-acquired infection and outbreaks. At Akershus University Hospital in Norway, traditional contact tracing has been combined with whole-genome sequencing (WGS) surveillance in real-time to investigate potential hospital outbreaks. AIM: To describe the advantages and challenges encountered when using WGS as a real-time tool in hospital outbreak investigation and surveillance during the SARS-CoV-2 pandemic. METHODS: Routine contact tracing in the hospital was performed for all healthcare workers (HCWs) who tested positive for SARS-CoV-2. Viral RNA from all positive patient and HCW samples was sequenced in real-time using nanopore sequencing and the ARTIC Network protocol. Suspected outbreaks involving five or more individuals with viral sequences were described. FINDINGS: Nine outbreaks were suspected based on contact tracing, and one outbreak was suspected based on WGS results. Five outbreaks were confirmed; of these, two outbreaks were supported but could not be confirmed by WGS with high confidence, one outbreak was found to consist of two different lineages, and two outbreaks were refuted. CONCLUSIONS: WGS is a valuable tool in hospital outbreak investigations when combined with traditional contact tracing. Inclusion of WGS data improved outbreak demarcation, identified unknown transmission chains, and highlighted weaknesses in existing infection control measures.

Investigation of intra-hospital SARS-CoV-2 transmission using nanopore whole-genome sequencing.

BACKGROUND: During the SARS-CoV-2 pandemic, healthcare workers (HCWs) are being exposed to infection both at work and in their communities. Determining where HCWs might have been infected is challenging based on epidemiological data alone. At Akershus University Hospital, Norway, several clusters of possible intra-hospital SARS-CoV-2 transmission were identified based on routine contact tracing. AIM: To determine whether clusters of suspected intra-hospital SARS-CoV-2 transmission could be resolved by combining whole genome sequencing (WGS) of SARS-CoV-2 with contact tracing data. METHODS: Epidemiological data were collected during routine contact tracing of polymerase chain reaction-confirmed SARS-CoV-2-positive HCWs. Possible outbreaks were identified as wards with two or more infected HCWs defined as close contacts who tested positive for SARS-CoV-2 less than three weeks apart. Viral RNA from naso-/oropharyngeal samples underwent nanopore sequencing in direct compliance to the ARTIC Network protocol. FINDINGS: Five outbreaks were suspected from contact tracing. Viral consensus sequences from 24 HCWs, two patients, and seven anonymous samples were analysed. Two outbreaks were confirmed, one refuted, and two remained undetermined. One new potential outbreak was discovered. CONCLUSION: Combined with epidemiological data, nanopore WGS was a useful tool for investigating intra-hospital SARS-CoV-2 transmission. WGS helped to resolve questions about possible outbreaks and to guide local infection prevention and control measures.

High immunogenicity and good tolerability of a new hepatitis A vaccine candidate.

Immunogenicity and tolerability of a new formalin-inactivated, alum-adjuvanted whole virus vaccine against hepatitis A (VAQTA, MSD, West Point, USA) were evaluated by immunizing 52 healthy, anti-HAV negative volunteers with a 1 ml dose. A booster dose was given 6 months later. In these young adult vaccinees [27 males and 25 females, 19-34 (mean 26) years of age] VAQTA proved to be well tolerated and highly immunogenic. Two weeks after administration of one vaccine dose, all but one of the recipients (98%) had anti-HAV concentrations above the presumed minimum protective level of 10 IU l-1 with a geometric mean concentration (GMC) of 165 IU l-1. After 4 weeks, a 100% seroconversion rate could be demonstrated with a fourfold increase of the GMC to 728 IU l-1. Six months after vaccination, all but one of the 50 volunteers coming back for booster (98%) showed anti-HAV levels within the protective range. The antibody concentrations had decreased in the majority of vaccinees to a GMC of 362 IU l-1. The booster dose given at that time was shown to be very effective, leading to a pronounced rise of anti-HAV levels in all recipients with a 17-fold increase of the GMC to 6040 IU l-1. Six months after the booster, all vaccinees were still seropositive with a GMC of 3444 IU l-1. Higher antibody levels were found in females, the difference being significant 4 weeks and 6 months after vaccination and 4 weeks after booster. No serious local or systemic adverse reactions were observed.

[New knowledge about viral hepatitis]. / Ny kunnskap om viral hepatitt.

Epidemics caused by a faecaloral transmitted hepatitis virus other than the hepatitis A virus are reported from developing countries. This type of hepatitis is called hepatitis E and is caused by a calicivirus termed hepatitis E virus. Many characteristics of this disease are similar to those of hepatitis A. The groups usually infected are older children and young adults in developing countries with poor sanitary facilities. Faecal contamination of the drinking water is assumed to be the main path of transmission. Large epidemics with thousands of icteric cases have been described. Neither hepatitis A nor hepatitis E develops into chronicity. In pregnant women there is an unexplained high case fatality rate of nearly 20%. The available diagnostic tools are based upon demonstration of nucleic acids in the virus genome extracted from faecal and blood specimens and upon immunological tests founded on synthetic peptides or antigens developed by means of gene technology. Hepatitis E is an important kind of epidemic hepatitis in the countries of the third world. Up to now the source of the virus remains unknown, but it has been possible to inoculate and cause replication of the virus in primates and even pigs. The possibility that this kind of hepatitis is a zoonosis has to be further documented.

Postoperative wound infection: relation to different types of operation and wound contamination categories in orthopaedic surgery.

During one year, 1,407 operations were performed on inpatients in an orthopaedic department. The presence or absence of postoperative wound infection was recorded during the hospital stay, at discharge and at follow up. Wound infections were linked to operations of different contamination categories and to the different types of operation performed. Better information about the risk for postoperative wound infection and the need for antibiotic prophylaxis was provided by considering the different operation types.

Diagnostic significance of pleural fluid lactate concentration in pleural and pulmonary diseases.

Pleural fluid samples from 198 patients were analysed in order to evaluate the usefulness of lactate concentration as a diagnostic test for separating infectious from non-infectious processes in the pleural cavity. Pleural fluid lactate was quantified by means of a gas chromatographic method. The highest lactate levels were found in patients with septic pleuritis. Significantly lower values were observed in cases with malignancies. With a cut off value of 10 mmol/l, the predictive value of a positive test was 0.94 and of a negative test 1.0. Because of the high predictive values of the test, measurement of lactate concentration in pleural fluid offers a rapid and useful information in the differentiation between infectious and non-infectious pleural disease.

Case of Legionnaires' disease with deep venous thrombosis.

During the last three years many cases of Legionnaires' disease have been reported. Several cases reported had underlying disorders such as immunity deficiencies, or were undergoing immunosuppressive therapy. In this report we describe a previously healthy young man who acquired Legionnaires' disease and recovered after ampicillin-gentamicin treatment. During recovery he developed a lower leg thrombosis followed by pulmonary embolism.

A clinical study of co-trimazine in comparison with co-trimoxazole and sulphalene in urinary tract infections.

Co-trimoxazole, co-trimazine and sulphalene were tested in a controlled clinical trial of the treatment of urinary tract infections. Forty-three patients were treated with co-trimoxazole, 41 with co-trimazine, and 21 with sulphalene. During the study, sulphalene was found to be inferior to the other drugs and was excluded from further trials. The clinical efficacy of co-trimoxazole and co-trimazine was equal although the doses of trimethoprim and sulphonamide in co-trimoxazole were much higher than that in co-trimazine. In the latter sulphadiazine was used instead of sulphamethoxazole, the intention being to increase the concentration of active sulphonamide in the urine. Side effects tended to be less frequent in the patients treated with co-trimazine, although not significantly.

Co-trimoxazole and nitrofurantoin in urinary-tract infections: a controlled clinical study.

The clinical efficacies of co-trimoxazole and nitrofurantoin were compared in patients with urinary-tract infections associated with significant bacteriuria with coliform bacteria tested and found to be sensitive to both drugs. Of 27 patients treated with co-trimoxazole, 23 were cured after 10 days' treatment with 320 mg trimethoprim and 1600 mg sulphamethoxazole daily (85%). Of 18 patients treated with nitrofurantoin (200 mg/day for 10 days), 7 were cured (39%). Thus, cotrimoxazole was significantly superior (p less than 0.01) in this study. A significant (p less than 0.001) but temporary and modest rise of the serum-creatinine levels was noted after 5 days' treatment with co-trimoxazole. Such a rise was not observed in the nitrofurantoin group. Only a few minor side effects were noted in both groups.