Inferring the true number of SARS-CoV-2 infections in Japan.

INTRODUCTION: In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities. METHODS: We used reported COVID-19 deaths and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies and were adjusted to reflect the effects of pharmaceutical interventions, mass vaccination, and evolving variants. To account for the uncertainty in IFR, we sampled values from relevant distributions. RESULTS: We estimated that as of December 31, 2021, 3.07 million (CrI: 2.05-4.24 million) people had been infected in Japan, which is 1.77 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan. CONCLUSIONS: We have estimated that a substantial number of COVID-19 infections in Japan were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.

A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia.

As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint incubation and age at infection × 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia.

Systematic meta-analyses and field synopsis of genetic association studies in colorectal cancer.

BACKGROUND: Colorectal cancer is a major global public health problem, with approximately 950,000 patients newly diagnosed each year. We report the first comprehensive field synopsis and creation of a parallel publicly available and regularly updated database (CRCgene) that catalogs all genetic association studies on colorectal cancer (http://www.chs.med.ed.ac.uk/CRCgene/). METHODS: We performed two independent systematic reviews, reviewing 10 145 titles, then collated and extracted data from 635 publications reporting on 445 polymorphisms in 110 different genes. We carried out meta-analyses to derive summary effect estimates for 92 polymorphisms in 64 different genes. For assessing the credibility of associations, we applied the Venice criteria and the Bayesian False Discovery Probability (BFDP) test. RESULTS: We consider 16 independent variants at 13 loci (MUTYH, MTHFR, SMAD7, and common variants tagging the loci 8q24, 8q23.3, 11q23.1, 14q22.2, 1q41, 20p12.3, 20q13.33, 3q26.2, 16q22.1, and 19q13.1) to have the most highly credible associations with colorectal cancer, with all variants except those in MUTYH and 19q13.1 reaching genome-wide statistical significance in at least one meta-analysis model. We identified less-credible (higher heterogeneity, lower statistical power, BFDP >0.2) associations with 23 more variants at 22 loci. The meta-analyses of a further 20 variants for which associations have previously been reported found no evidence to support these as true associations. CONCLUSION: The CRCgene database provides the context for genetic association data to be interpreted appropriately and helps inform future research direction.