Reducing contacts to stop SARS-CoV-2 transmission during the second pandemic wave in Brussels, Belgium, August to November 2020.

To evaluate the effect of physical distancing and school reopening in Brussels between August and November 2020, we monitored changes in the number of reported contacts per SARS-CoV-2 case and associated SARS-CoV-2 transmission. The second COVID-19 pandemic wave in Brussels was the result of increased social contact across all ages following school reopening. Physical distancing measures including closure of bars and restaurants, and limiting close contacts, while primary and secondary schools remained open, reduced social mixing and controlled SARS-CoV-2 transmission.

Factors Influencing the Incubation of an Infectious Form of Creutzfeldt-Jakob Disease.

The French epidemics of iatrogenic Creutzfeldt-Jakob disease after growth hormone (GH) treatment provide an opportunity to understand factors governing the inter-human transmission of prions. The present analysis relying on truncated Weibull distribution supports a relationship between host genetics, dose of the at-risk GH, age at treatment onset, and duration of the incubation period.

Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology.

Abeta deposits and tau pathology were investigated in 24 French patients that died from iatrogenic Creutzfeldt-Jakob disease after exposure to cadaver-derived human growth hormone (c-hGH) in the 1980s. Abeta deposits were found only in one case that had experienced one of the longest incubation periods. Three cases had also intracellular tau accumulation. The analysis of 24 batches of c-hGH, produced between 1974 and 1988, demonstrated for the first time the presence of Abeta and tau contaminants in c-hGH (in 17 and 6 batches, respectively). The incubation of prion disease was shorter in the French patients than the incubation times reported in two previously published British series. We interpreted the low incidence of Abeta in this French series as a consequence of the shorter incubation period observed in France, as compared to that observed in the United Kingdom. This concept suggested that a mean incubation period for the development of detectable Abeta deposits would be longer than 18 years after the first exposure. Moreover, we hypothesized that tau pathology might also be transmissible in humans.

Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009.

Diagnostic criteria of Creutzfeldt-Jakob disease (CJD), a rare and fatal transmissible nervous system disease with public health implications, are determined by clinical data, electroencephalogram (EEG), detection of 14-3-3 protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion protein gene examination. The specificity of protein 14-3-3 has been questioned. We reviewed data from 1,572 autopsied patients collected over an 18-year period (1992-2009) and assessed whether and how 14-3-3 detection impacted the diagnosis of sporadic CJD in France, and whether this led to the misdiagnosis of treatable disorders. 14-3-3 detection was introduced into diagnostic criteria for CJD in 1998. Diagnostic accuracy decreased from 92% for the 1992-1997 period to 85% for the 1998-2009 period. This was associated with positive detections of 14-3-3 in cases with negative EEG and alternative diagnosis at autopsy. Potentially treatable diseases were found in 163 patients (10.5%). This study confirms the usefulness of the recent modification of diagnosis criteria by the addition of the results of CSF real-time quaking-induced conversion, a method based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate that has proven to be a highly specific test for diagnosis of sporadic CJD.

Short report: The potential of PCR on skin flakes from bed linens for diagnosis of scabies in an outbreak.

BACKGROUND: Scabies outbreaks are common in nursing homes in the Netherlands. In October 2018, a local public health service (PHS) in The Hague was notified of a new scabies outbreak in a nursing home in that region. The PHS initiated an outbreak investigation. Cases were defined as: possible (reported symptoms), probable (scabies-like lesions) and confirmed (PCR or microscopy in skin flakes). Head-to-toe examinations were performed of all residents and those staff members who reported symptoms suggestive of scabies. Skin scrapings of lesions were tested either with microscopy or by PCR. Experimentally for case finding, skin flakes from bed linens of residents who reported symptoms of itchiness but did not have primary lesions were sent for PCR testing. PRINCIPAL FINDINGS: All residents (41) and 37/44 staff were included in this outbreak investigation. We identified 30 possible, four probable and six confirmed cases. The overall attack rate for probable/confirmed cases was 10/78 (13%). Of the six confirmed cases, two were confirmed by PCR, three by microscopy, and one showed positive findings with both techniques. Two out of the three bed-linen specimens were PCR-positive. CONCLUSIONS: In this outbreak of scabies in a nursing home, PCR was used on skin flakes from bed linens, which led to the detection of two additional cases. This illustrates the potential of PCR during the investigation of scabies outbreaks.

Susceptibility to Creutzfeldt-Jakob disease after human growth hormone treatment in France.

OBJECTIVE: To identify, among the available data concerning host characteristics and exposure, risk factors influencing the susceptibility for developing iatrogenic Creutzfeldt-Jakob disease (iCJD) in a cohort of patients treated with human cadaver-sourced growth hormone (hGH) in France. METHODS: This study included all 1,443 individuals treated in France with hGH from January 1982 to December 1985, out of which 119 cases of hGH-iCJD have been identified so far. We applied a 3 sequential step Cox analysis involving univariable, stepwise, and nonstepwise multivariable procedures. The variables studied were sex, age at hGH treatment initiation, and treatment characteristics (batches and doses). RESULTS: While no effect of age at treatment initiation was observed, a significant effect of sex on disease susceptibility was unexpectedly evidenced with a 2-fold increase of disease occurrence in male patients. This effect did not depend on differences of exposure between male and female patients. We identified 4 categories of hormone batches from high risk to no association with susceptibility. A relationship between the dose received from at-risk hormone batches and the attack rate (number of patients developing the disease among exposed individuals) was demonstrated. CONCLUSIONS: Studying the hGH-exposed patients in France provides epidemiologic evidence of a relationship between dose of inoculum and disease occurrence in humans and suggests an unexpected effect of sex on individual susceptibility.

Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD. METHODS: We recruited patients older than 18 years old who had a diagnosis of definite or probable sporadic CJD or genetic forms of the disease via Italian reference centres and the French national referral system. Patients were randomly assigned (ratio 1:1) to receive oral doxycycline (100 mg daily) or placebo under double-blind conditions from the day of randomisation to death. Centralised randomisation was done independently of enrolment or evaluation of patients using a minimisation method in Italy and a simple randomisation in France. Participants, caregivers, and clinicians were masked to group assignment. The primary efficacy variable was the survival time from randomisation. Interim analyses were planned to detect a significant effect of treatment as early as possible. This trial is registered with EudraCT, 2006-001858-27 for the Italian study and 2007-005553-34 for the French study. FINDINGS: From April 12, 2007, to Aug 19, 2010, in Italy, and from Jan 30, 2009, to Jan 10, 2012, in France, 121 patients with CJD were enrolled in the study, 62 of whom were randomly assigned to the treatment group and 59 to the placebo group. The first interim analysis showed absence of superiority of doxycycline compared with placebo, and the trial was stopped for futility. Efficacy analyses did not show significant differences between patients treated with doxycycline and placebo with regard to survival times (HR 1.1, 95% CI 0.8-1.7, p=0.50). Serious adverse events were judged not to be related to treatment, whereas a relation was deemed probable or possible for five non-serious adverse events that occurred in each treatment group. INTERPRETATION: Doxycycline at a dose of 100 mg per day was well tolerated but did not significantly affect the course of CJD, at variance with the results of previous observational studies. Our experience could be useful in the design of large multinational controlled trials of potential anti-prion molecules in this rare disease. FUNDING: Agenzia Italiana Farmaco, Italian Ministry of Health, AIEnP, and French Ministry of Health.