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Cholera, a devastating diarrheal disease that caused several global pandemics in the last centuries, may share some similarities with the new COVID-19. Cholera has affected many populations in history and still remains a significant burden in developing countries. The main transmission route was thought to be predominantly through contaminated drinking water. However, revisiting the historical data collected during the Copenhagen 1853 cholera outbreak allowed us to re-evaluate the role of drinking-water transmission in a city-wide outbreak and reconsider some critical transmission routes, which have been neglected since the time of John Snow. Recent empirical and cohort data from Bangladesh also strengthened the dynamic potentiality of other transmission routes (food, fomite, fish, flies) for transmitting cholera. Analyzing this particular nature of the cholera disease transmission, this paper will describe how the pattern of transmission routes are similar to COVID-19 and how the method of revisiting old data can be used for further exploration of new and known diseases.

BackgroundDuring the COVID-19 pandemic, decreasing rates of hospitalisations for cardiovascular disease raised concerns for undertreatment, particularly for vulnerable groups. We investigated how the initial COVID-19 public lockdown, impacted the risk of being hospitalised with a major cardiovascular event (MCE: myocardial infarction/stroke/heart failure) according to educational level.MethodsWe grouped all Danish residents according to educational attainment level (low, medium, high) and age (40–59, 60–69, ≥70 years). In each group, we calculated the age-standardised and sex standardised risk of MCE hospitalisation in the initial COVID-19 lockdown-period (13 March 2020–3 May 2020) and in the corresponding calendar period in 2019. We calculated age-standardised and sex-standardised risks to investigate whether the COVID-19 lockdown had a differential effect on MCE incidence according to educational level.ResultsIn the period in 2019, 2700 Danish residents were hospitalised with MCE, compared with only 2290 during the lockdown. During lockdown, the risk of hospitalisation for MCE decreased among residents aged ≥70 with low education (risk difference (RD) −46.2 (−73.2; −19.2) per 100,000) or medium education (RD −23.2 (−50.8; 4.3) per 100 000), but not among residents with high education (RD 5.1 (−32.3; 42.5), per 100 000). The risk of hospitalisation for MCE did not decrease significantly for the younger age groups.ConclusionsThe COVID-19 lockdown is associated with a reduced incidence for MCE, especially among low educated, elderly residents. This raises concern for undertreatment that without clinical awareness and action may widen the educational gap in cardiovascular morbidity and mortality.

Denmark implemented early widespread social distancing to reduce pressure on the healthcare system from the coronavirus disease 2019 (COVID-19) pandemic, with the aims to reduce mortality. Unintended consequences might be delays in treatment for other diseases and subsequent mortality. We examined national all-cause mortality comparing weeks 1–27 in 2020 and 2015–2019. This registry-based study used Danish national registry data until 5 July 2020. We examined all-cause mortality rates among all deaths recorded from 2015 to 2020 and among chronic conditions (cardiovascular (cardiac & circulatory), chronic pulmonary, chronic kidney disease, cancer, and diabetes), comparing each week in 2020 to weeks in 2015–2019. In 2020, there were 28,363 deaths in weeks 1–27 (30 December 2019–5 July 2020), the mean deaths in 2015–2019 were 28,630 deaths (standard deviation 784). Compared to previous years, the mortality rate in weeks 3–10 of 2020 was low, peaking in week 14 (17.6 per 100,000 persons in week 9, 19.9 per 100,000 in week 14). Comorbidity prevalence among deceased individuals was similar in 2020 and 2015–2019: 71.1% of all deceased had a prior cardiovascular diagnosis, 30.0% of all deceased had a prior cardiac diagnosis. There were 493 deaths with COVID-19 in weeks 11–27, (59.8% male), and 75.1% had a prior cardiovascular diagnosis. Weekly mortality rates for pre-existing chronic conditions peaked in week 14, and then declined. During the COVID-19 pandemic, due to timely lockdown measures, the mortality rate in Denmark has not increased compared to the mortality rates in the same period during 2015–2019. Electronic supplementary material The online version of this article (10.1007/s10654-020-00680-x) contains supplementary material, which is available to authorized users.

AimsTo investigate the admission rates of cardiovascular diseases, overall and according to subgroups, and subsequent mortality rates during the coronavirus disease 2019 societal lockdown (12 March 2020) and reopening phase (15 April 2020) in Denmark.Methods and resultsUsing Danish nationwide registries, we identified patients with a first-time acute cardiovascular admission in two periods: (i) 2 January–16 October 2019 and (ii) 2 January–15 October 2020. Weekly incidence rates of a first-time cardiovascular admission, overall and according to subtypes, in the two periods were calculated. The incidence rate of first-time cardiovascular admissions overall was significantly lower during the first weeks of lockdown in 2020 compared with a similar period in 2019 but increased after the gradual reopening of the Danish society. A similar trend was observed for all subgroups of cardiovascular diseases. The mortality rate among patients admitted after March 12 was not significantly different in 2020 compared with 2019 [mortality rate ratio 0.98; 95% confidence interval (CI) 0.91–1.06)].ConclusionIn Denmark, we observed a substantial decrease in the rate of acute cardiovascular admissions, overall and according to subtypes, during the first weeks of lockdown. However, after the gradual reopening of the Danish society, the admission rates for acute cardiovascular diseases increased and returned to rates similar to those observed in 2019. The mortality rate in patients admitted with cardiovascular diseases during lockdown was similar to that of patients during the same period in 2019.

Aims The aim of this study was to derive and validate a risk prediction model with nationwide coverage to predict the individual and population-level risk of cardiovascular disease (CVD). Methods and results All 2.98 million Danish residents aged 30–85 years free of CVD were included on 1 January 2014 and followed through 31 December 2018 using nationwide administrative healthcare registries. Model predictors and outcome were pre-specified. Predictors were age, sex, education, use of antithrombotic, blood pressure-lowering, glucose-lowering, or lipid-lowering drugs, and a smoking proxy of smoking-cessation drug use or chronic obstructive pulmonary disease. Outcome was 5-year risk of first CVD event, a combination of ischaemic heart disease, heart failure, peripheral artery disease, stroke, or cardiovascular death. Predictions were computed using cause-specific Cox regression models. The final model fitted in the full data was internally-externally validated in each Danish Region. The model was well-calibrated in all regions. Area under the receiver operating characteristic curve (AUC) and Brier scores ranged from 76.3% to 79.6% and 3.3 to 4.4. The model was superior to an age-sex benchmark model with differences in AUC and Brier scores ranging from 1.2% to 1.5% and −0.02 to −0.03. Average predicted risks in each Danish municipality ranged from 2.8% to 5.9%. Predicted risks for a 66-year old ranged from 2.6% to 25.3%. Personalized predicted risks across ages 30–85 were presented in an online calculator (https://hjerteforeningen.shinyapps.io/cvd-risk-manuscript/). Conclusion A CVD risk prediction model based solely on nationwide administrative registry data provided accurate prediction of personal and population-level 5-year first CVD event risk in the Danish population. This may inform clinical and public health primary prevention efforts.

Societal lockdowns during the first wave of the coronavirus disease 2019 pandemic were associated with decreased admission rates for acute cardiovascular conditions worldwide. In this nationwide Danish study of the first five weeks of a second pandemic lockdown, incidence of new-onset heart failure and atrial fibrillation remained stable, but there was a significant drop in new-onset ischemic heart disease and ischemic stroke during the fourth week of lockdown, which normalized promptly. The observed drops were lower compared to the first Danish lockdown in March 2020; thus, our data suggest that declines in acute cardiovascular disease admission rates during future lockdowns are avoidable.

Studies assessing the impact of total comorbidity burden on outcomes of COVID-19 in age- and sex-controlled analyses are lacking. Previous studies identified the following single comorbidities as risk factors for poor COVID-19 outcomes: coronary heart disease, congestive heart failure, cardiac arrhythmia, chronic obstructive pulmonary disease, cancer, and diabetes.1 In this nationwide study of Danish COVID-19 patients, we investigated if Charlson Comorbidity Index Score (CCIS) was associated with the risk of severe outcome and death.

Existing methodologies to record diarrheal disease incidence in households have limitations due to a high-episode recall error outside a 48-hour window. Our objective was to use mobile phones for reporting diarrheal episodes in households to provide real-time incidence data with minimum resource consumption and low recall error. From June 2014 to June 2015, we enrolled 417 low-income households in Dhaka, Bangladesh, and asked them to report diarrheal episodes to a call center. A team of data collectors then visited persons reporting the episode to collect data. In addition, each month, the team conducted in-home surveys on diarrhea incidence for a preceding 48-hour period. The mobile phone surveillance reported an incidence of 0.16 cases per person-year (95% CI: 0.13–0.19), with 117 reported diarrhea cases, and the routine in-home survey detected an incidence of 0.33 cases per person-year (95% CI: 0.18–0.60), the incidence rate ratio was 2.11 (95% CI: 1.08–3.78). During focus group discussions, participants reported a lack in motivation to report diarrhea by phone because of the absence of provision of intervening treatment following reporting. Mobile phone technology can provide a unique tool for real-time disease reporting. The phone surveillance in this study reported a lower incidence of diarrhea than an in-home survey, possibly because of the absence of intervention and, therefore, a perceived lack of incentive to report. However, this study reports the untapped potential of mobile phones in monitoring infectious disease incidence in a low-income setting.

Aim To assess the risk of stroke and thromboembolism in patients with atrial fibrillation (AF) based on risk factor combinations of the CHA2DS2-VASc score. Methods and results Using nationwide Danish registries, patients with AF were included from 1997 to 2015 in this retrospective observational study. A multiple logistic regression, including interactions of history of stroke with age at AF, calendar year of AF, and the CHA2DS2-VASc score risk factors (congestive heart failure, hypertension, diabetes, vascular disease, and female sex) were used to predict the personalized risks of stroke within 1 year. A total of 147 842 patients with AF were included in the study cohort (median age 76 years, range 20–100 years, 51% females). Within the first year, 6% of the cohort were diagnosed with stroke. The predicted personalized 1-year absolute risk of stroke varied widely within each CHA2DS2-VASc score. To estimate the personalized risk of stroke an online calculator was created, the Calculator of Absolute Stroke Risk (CARS), which allows calculation of all the possible combinations of the CHA2DS2-VASc score (https://hjerteforeningen.shinyapps.io/riskvisrr/). Conclusion Calculation of the individual risk using a risk factor-based approach as opposed to using average risk for a particular CHA2DS2-VASc score can improve risk estimates. Furthermore, CARS can assist in the communication of the stroke risk for a more evidence-based shared decision-making of whether to initiate oral anticoagulation therapy.

Background Urgent recognition and treatment are needed in patients with acute coronary syndrome (ACS), however this may be difficult during the Coronavirus disease 2019 (COVID-19) pandemic with a national lock-down. We aimed to examine the incidence of ACS after national lock-down. Methods The Danish government announced national lock-down on March 11, 2020 and first phase of reopening was announced on April 6. Using Danish nationwide registries, we identified first-time ACS admissions in (1) January 1 to May 7, 2017-2019, and (2) January 1, 2020 to May 6, 2020. Incidence rates of ACS admissions per week for the 2017 to 2019 period and the 2020 period were computed and incidence rate ratios (IRR) were computed using Poisson regression analysis. Results The number of ACS admissions were 8,204 (34.6% female, median age 68.3 years) and 2,577 (34.0% female, median age 68.5 years) for the 2017 to 2019- and 2020 period, respectively. No significant differences in IRRs were identified for weeks 1 to 9 (January 1 to March 4) for 2020 compared with week 1 to 9 for 2017 to 2019. In 2020, significant lower IRRs were identified for week 10 (March 5 to 11) IRR = 0.71 (95% confidence intervals [CI]: 0.58 to 0.87), week 11 (12 to 18 March) IRR = 0.68 (0.56 to 0.84), and week 14 (April 2 to April 8) IRR = 0.79 (0.65 to 0.97). No significant differences in IRRs were identified for week 15 to 18 (April 9 to May 6). In subgroup analysis, we identified that the main result was driven by male patients, and patients ≥60 years. Conclusions During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.

Aims Pre-existing cardiovascular diseases (CVDs) have been proposed to identify patients at higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes, but existing evidence is conflicting. Thus, it is unclear whether pre-existing CVDs are independently important predictors for severe COVID-19.Methods and results In a nationwide Danish cohort of hospital-screened COVID-19 patients aged ≥40, we investigated if pre-existing CVDs predict the 30-day risk of (i) composite outcome of severe COVID-19 and (ii) all-cause mortality. We estimated 30-day risks using a Cox regression model including age, sex, each CVD comorbidity, chronic obstructive pulmonary disease-asthma, diabetes, and chronic kidney disease. To illustrate CVD comorbidities’ importance, we evaluated the predicted risks of death and severe infection, for each sex, along ages 40–85. In total, 4090 COVID-19 hospital-screened patients were observed as of 26 August 2020; 22.1% had ≥1 CVD, 23.7% had severe infection within 30 days and 12.6% died. Predicted risks of both outcomes at age 75 among men with single CVD comorbidities did not differ in clinically meaningful amounts compared with men with no comorbidities risks for the composite outcome of severe infection; women with heart failure (28.2%; 95% CI 21.1–37.0%) or atrial fibrillation (30.0%; 95% CI: 24.2–36.9%) showed modest increases compared with women with no comorbidities (24.0%; 95% CI: 21.4–26.9%).Conclusions The results showing only modest effects of CVDs on increased risks of poor COVID-19 outcomes are important in allowing public health authorities and clinicians to provide more tailored guidance to cardiovascular patients, who have heretofore been grouped together as high risk due to their disease status.

ObjectiveTo investigate the association between recent statin exposure and risk of severe COVID-19 infection and all-cause mortality in patients with COVID-19 in Denmark.Design and settingObservational cohort study using data from Danish nationwide registries.ParticipantsPatients diagnosed with COVID-19 from 22 February 2020 to 17 May 2020 were followed from date of diagnosis until outcome of interest, death or 17 May 2020.InterventionsUse of statins, defined as a redeemed drug prescription in the 6 months prior to COVID-19 diagnosis.Primary and secondary outcome measuresAll-cause mortality, severe COVID-19 infection and the composite.ResultsThe study population comprised 4842 patients with COVID-19 (median age 54 years (25th–75th percentile, 40–72), 47.1% men), of whom 843 (17.4%) redeemed a prescription of statins. Patients with statin exposure were more often men and had a greater prevalence of comorbidities. The median follow-up was 44 days. After adjustment for age, sex, ethnicity, socioeconomic status and comorbidities, statin exposure was not associated with a significantly different risk of mortality (HR 0.96 (95% CI 0.78 to 1.18); 30-day standardised absolute risk (SAR), 9.8% (8.7% to 11.0%) vs 9.5% (8.2% to 10.8%); SAR difference, −0.4% (−1.9% to 1.2%)), severe COVID-19 infection (HR 1.16 (95% CI 0.95 to 1.41); 30-day SAR, 13.0% (11.8% to 14.2%) vs 14.9% (12.8% to 17.1%); SAR difference, 1.9% (−0.7% to 4.5%)), and the composite outcome of all-cause mortality or severe COVID-19 infection (HR 1.05 (95% CI 0.89 to 1.23); 30-day SAR, 17.6% (16.4% to 18.8%) vs 18.2% (16.4% to 20.1%); SAR difference, 0.6% (−1.6% to 2.9%)). The results were consistent across subgroups of age, sex and presumed indication for statin therapy. Among patients with statin exposure, there was no difference between statin drug or treatment intensity with respect to outcomes.ConclusionsRecent statin exposure in patients with COVID-19 infection was not associated with an increased or decreased risk of all-cause mortality or severe infection.

Highlights • The incidence of IE during lockdown was 11.1 IE cases per 100,000 PY. • No reduction in the incidence of IE during the lockdown compared to preceding years. • No difference in the incidence of IE pre- versus post-lockdown in 2020., Background The incidence of infective endocarditis (IE) has increased in recent decades. Societal lockdown including reorganization of the healthcare system during the COVID-19 pandemic may influence the incidence of IE. This study sets out to investigate the incidence of IE during the Danish national lockdown. Methods In this nationwide cohort study, patients admitted with IE in either one of two periods A) A combined period of 1 January to 7 May for 2018 and 2019, or B) 1 January to 6 May 2020, were identified using Danish nationwide registries. Weekly incidence rates of IE admissions for the 2018/2019-period and 2020-period were computed and incidence rate ratios (IRR) for 2020-incidence vs 2018/2019-incidence were calculated using Poisson regression analysis. Results In total, 208 (67.3% men, median age 74.1 years) and 429 (64.1% men, median age 72.7 years) patients were admitted with IE in 2020 and 2018/2019, respectively. No significant difference in incidence rates were found comparing the 2020-period and 2018/2019-period (IRR: 0.96 (95% CI: 0.82–1.14). The overall incidence rate pre-lockdown (week 1–10: 1 January to 11 March 2020) was 14.2 IE cases per 100,000 person years (95% CI: 12.0–16.9) as compared with 11.4 IE cases per 100,000 person years (95% CI: 9.1–14.1) during lockdown (week 11–18: 12 March to 6 May 2020) corresponding to an IRR of 0.80 (95% CI: 0.60–1.06) and thus no significant difference pre- versus post-lockdown. Conclusion In this nationwide cohort study, no significant difference in the incidence of IE admissions during the national lockdown due to the COVID-19 pandemic was found.

Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting. We examined the risk of severe COVID-19 between ibuprofen-prescribed and non-ibuprofen patients with COVID-19 in a nationwide register-based study of patients with COVID-19 in Denmark between the end of February 2020 and May 16, 2020. Patients with heart failure (n = 208), 14 days before COVID-19 vs. ≤ 14 days of COVID-19 were 17.1% (95% CI 12.3–22.0) vs. 14.3% (95% CI 7.1–23.1). In conclusion, in this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID-19.

Background and Objectives Male sex has been associated with severe coronavirus disease 2019 (COVID-19) infection. We examined the association between male sex and severe COVID-19 infection and if an increased risk remains after adjustment for age and comorbidities. Methods Nationwide register-based follow-up study of COVID-19 patients in Denmark until 16 May 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe COVID-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver, rheumatic, and chronic kidney disease (CKD). Results Of 4842 COVID-19 patients, 2281 (47.1%) were men. Median age was 57 [25%–75% 43–73] for men versus 52 [38–71] for women (P < .001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P < .001) as well as AF, stroke, and HF (all P = .01) were more often seen in men, and so was CKD (P = .03). Obesity diagnosis (P < .001) were more often seen in women. Other comorbidity differences were insignificant (P > .05). The fully adjusted average risk ratio was 1.63 [95% CI, 1.44–1.84]. Conclusions Men with COVID-19 infection have >50% higher risk of all-cause death, severe COVID-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.

Background: Initially, the World Health Organization (WHO) and national health boards issued a warning against NSAID use in corona virus disease 2019 (COVID-19) patients and recommended that paracetamol or acetaminophen instead should be administered. However, later and current WHO and European Medicine Agency recommendations do not call for avoidance of ibuprofen in COVID-19 patients. Given the current uncertainty of drug safety for NSAID use in patients with COVID-19, we performed a nationwide register-based study on the association of recent ibuprofen exposure and COVID-19 severity. Methods: Using national administrative databases, we identified COVID-19 patients in Denmark between end of February 2020 and April 2, 2020. Patients Results: Among 1,872 patients, 46 (2.5%) were exposed to ibuprofen prior to COVID-19 infection. Patients with recent ibuprofen exposure tended to be older and more likely to have hypertension, diabetes, myocardial infarction, chronic obstructive pulmonary disease, and cancer, though all insignificant (P>0.05). When adjusting for these covariates, odds ratio was 1.57 [95% CI 0.72-3.38], with 12 ibuprofen-exposed patients meeting the endpoint (26.1% [95% CI 13.4-38.8%]) versus 272 unexposed patients (14.9% [95% CI 13.4-16.4%]), P=0.15. Conclusion: The association between ibuprofen and severe COVID-19 was insignificant, although with a trend towards increased disease severity risk.

Aim To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown. Methods and results Using nationwide Danish registries, we included all patients, aged 18–90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12–1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56–0.78), 0.53 (0.45–0.64), and 0.41 (0.34–0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93–2.12). Conclusions Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic., Graphical Abstract Graphical Abstract

To investigate the transmission of faecal bacteria by flies to food under natural settings.Over a period of 2 months, paired (exposed and non-exposed) containers with cooked rice were placed on the ground in kitchen areas in an urban slum area in Dhaka, Bangladesh, and the numbers of flies landing on the exposed rice were counted. Following exposure, the surface of the rice was microbiologically and molecularly analysed for the presence of Escherichia coli and genes of diarrhoeagenic E. coli and Shigella strains.Rice was at greater risk (P0·001) of being contaminated with E. coli if flies landed on the rice than if no flies landed on the rice (odds ratio 5·4 (P0·001, 95% CI: 2·5-11·7). Mean contamination in exposed rice samples (n = 60) was 3·1 × 103 CFU/g (95% CI: 2·2 × 103-4·0 × 103). Furthermore, for approximately half of the observed fly landings, the average CFU per fly landing was0·6 × 103 CFU. Genes of diarrhoeagenic E. coli and Shigella species were detected in 39 of 60 (65%) of exposed rice samples. Two fly species were identified: the common housefly (Musca domestica) and the oriental latrine fly (Chrysomya megacephala).Flies may transmit large quantities of E. coli to food under field settings. The findings highlight the importance of implementing control measures to minimise exposure of food to flies to ensure food safety. Fly control measures should be considered for the prevention of diarrhoeal diseases caused by E. coli.

Uncertainty persists regarding cholera transmission routes. We conducted a structured review of case-control studies on cholera transmission and provide a qualitative summary of reported exposures in order to inform public health efforts and future cholera research.We searched two electronic databases for published case-control studies that investigated risk factors for cholera and included any publications that did not match our exclusion criteria. From the included studies, we grouped exposures using two parameters, whether transmission domain was public or domestic, and also on the vehicle of transmission. We extracted data on study location, method of case and control inclusion, type of statistical analysis performed and which exposures were included. Additionally, two parallel subgroup analyses were performed. The first included the subgroup of all studies that used culture-confirmed cholera cases, and the second included the subgroup of all studies employing a multivariate analysis. In the second analysis, we calculated the population attributable risk (PAR).Our search yielded 2347 peer-reviewed publications, of which 65 did not match our exclusion criteria, comprising 69 individual studies. Water-based exposures were investigated in 97% of these studies, of which 70% found a significant association with cholera infection. Food-based exposures were investigated in 75% of studies, of which 63% found a significant association with risk of cholera infection. Close personal contact with cholera cases was investigated in 30% of studies, of which 52% found a significant association with risk of cholera infection. Hygiene-related exposures were investigated in 51% of studies, of which 63% found a significant association with cholera transmission. Among studies that examined at least one exposure related to the domestic domain, 76% found a significant association with cholera infection vs. 71% of studies investigating at least one public domain exposure. The subgroup analyses produced similar results.Despite strong evidence for cholera transmission via foodborne-, hygiene-, waterborne- and close personal contact-related pathways in both domestic and public domains, we found that non-waterborne-related factors are understudied. Future cholera case-control studies would benefit from investigating all transmission vehicles and transmission domains.L'incertitude persiste quant aux voies de transmission du choléra. Nous avons mené une analyse structurée d’études cas-témoins sur la transmission du choléra et fourni un résumé qualitatif des expositions rapportées afin d’éclairer les efforts de santé publique et les recherches futures sur le choléra. MÉTHODES: Nous avons recherché dans deux bases de données électroniques, des études cas-témoins publiées, portant sur les facteurs de risque du choléra et avons inclus toutes les publications ne correspondant pas à nos critères d'exclusion. Parmi les études incluses, nous avons regroupé les expositions en utilisant deux paramètres, selon que le domaine de transmission soit public ou domestique, ainsi que sur le véhicule de transmission. Nous avons extrait les données sur le lieu de l’étude, la méthode d'inclusion des cas et des témoins, le type d'analyse statistique effectuée et les expositions incluses. En outre, deux analyses parallèles de sous-groupes ont été effectuées. La première comprenait le sous-groupe de toutes les études utilisant des cas de choléra confirmés par culture et la seconde, le sous-groupe de toutes les études utilisant une analyse multivariée. Dans la seconde analyse, nous avons calculé le risque attribuable à la population. RÉSULTATS: Notre recherche a donné 2347 publications revues par des pairs, dont 65 ne correspondaient pas à nos critères d'exclusion et comprenant 69 études individuelles. Les expositions à base d'eau ont été investiguées dans 97% de ces études, parmi lesquelles 70% ont trouvé une association significative avec l'infection par le choléra. Les expositions d'origine alimentaire ont été investiguées dans 75% des études, dont 63% ont montré une association significative avec le risque d'infection par le choléra. Le contact personnel rapproché avec des cas de choléra a été investigué dans 30% des études, parmi lesquelles 52% ont trouvé une association significative avec le risque d'infection par le choléra. Les expositions liées à l'hygiène ont été étudiées dans 51% des études, dont 63% ont montré une association significative avec la transmission du choléra. Parmi les études portant sur au moins une exposition liée au domaine domestique, 76% ont trouvé une association significative avec l'infection par le choléra, contre 71% des études portant sur au moins une exposition du domaine public. Les analyses de sous-groupes ont produit des résultats similaires.Malgré de solides preuves sur la transmission du choléra par des voies d'origine alimentaire, hygiénique, d'origine hydrique et de contact rapproché, dans les domaines domestique et public, nous avons constaté que les facteurs non liés à l'eau étaient peu étudiés. Les futures études cas-témoins sur le choléra gagneraient à investiguer sur tous les véhicules et tous les domaines de transmission.

Aims The hospitalization of patients with MI has decreased during global lockdown due to the COVID-19 pandemic. Whether this decrease is associated with more severe MI, e.g. MI-CS, is unknown. We aimed to examine the association of Corona virus disease (COVID-19) pandemic and incidence of acute myocardial infarction with cardiogenic shock (MI-CS). Methods On March 11, 2020, the Danish government announced national lock-down. Using Danish nationwide registries, we identified patients hospitalized with MI-CS. Incidence rates (IR) and incidence rate ratios (IRR) were used to compare MI-CS before and after March 11 in 2015–2019 and in 2020. Results We identified 11,769 patients with MI of whom 696 (5.9%) had cardiogenic shock in 2015–2019. In 2020, 2132 MI patients were identified of whom 119 had cardiogenic shock (5.6%). The IR per 100,000 person years before March 11 in 2015–2019 was 9.2 (95% CI: 8.3–10.2) and after 8.9 (95% CI: 8.0–9.9). In 2020, the IR was 7.5 (95% CI: 5.8–9.7) before March 11 and 7.7 (95% CI: 6.0–9.9) after. The IRRs comparing the 2020-period with the 2015–2019 period before and after March 11 (lockdown) were 0.81 (95% CI: 0.59–1.12) and 0.87 (95% CI: 0.57–1.32), respectively. The IRR comparing the 2020-period during and before lockdown was 1.02 (95% CI: 0.74–1.41). No difference in 7-day mortality or in-hospital management was observed between study periods. Conclusion We could not identify a significant association of the national lockdown on the incidence of MI-CS, along with similar in-hospital management and mortality in patients with MI-CS.

Sri Lanka has one of the highest incidences of human leptospirosis worldwide. Outbreaks of this zoonotic infection are related to the monsoons and flooding. The study investigates risk factors associated with environmental, animal and occupational exposure while acknowledging the potential bias due to hanta viral infections in the study samples. Data were obtained from structured interviews with 483 patients (276 cases and 207 controls). Risk exposures were studied for the entire population and for two stratified occupational groups: non-paddy workers and paddy workers. A higher odds ratio (OR) of leptospirosis transmission for paddy workers was observed compared to non-paddy workers (OR 1.905, 95% CI 1.274-2.856). Rat exposure was not associated with a significant higher risk for any of the groups. Instead, cattle and household animals seemed to be important for transmission of leptospirosis to humans, especially among non-paddy workers (OR 10.655, 95% CI 1.213-93.582). Leptospirosis in paddy workers was associated with environmental factors linked to contamination and wetness in paddy fields. Interestingly, abandoned paddy fields were found to have a protective effect against transmission to paddy workers (OR 0.421, 95% CI 0.237-0.748). Keeping animals on these dryer fields may act as a boundary for contamination of paddy fields with infectious animal urine. This finding may be considered as a public health intervention targeting leptospirosis among paddy workers.

Background Planning interventions to respond to cholera epidemics requires an understanding of the major transmission routes. Interrupting short-cycle (household, foodborne) transmission may require different approaches as compared long-cycle (environmentally-mediated/waterborne) transmission. However, differentiating the relative contribution of short- and long-cycle routes has remained difficult, and most cholera outbreak control efforts focus on interrupting long-cycle transmission. Here we use high-resolution epidemiological and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to explore the relative contribution of short- and long-cycle transmission routes during a major urban epidemic. Methodology/Principal findings We fit a spatially explicit time-series meta-population model to 6,552 physician-reported cholera cases from Copenhagen in 1853. We estimated the contribution of long-cycle waterborne transmission between neighborhoods using historical municipal water infrastructure data, fitting the force of infection from hydraulic flow, then comparing model performance. We found the epidemic was characterized by considerable transmission heterogeneity. Some neighborhoods acted as localized transmission hotspots, while other neighborhoods were less affected or important in driving the epidemic. We found little evidence to support long-cycle transmission between hydrologically-connected neighborhoods. Collectively, these findings suggest short-cycle transmission was significant. Conclusions/Significance Spatially targeted cholera interventions, such as reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods, would likely have been more effective in this epidemic than control measures aimed at interrupting long-cycle transmission, such as improving municipal water quality. We recommend public health planners consider programs aimed at interrupting short-cycle transmission as essential tools in the cholera control arsenal., Author summary John Snow’s seminal work on the London cholera epidemic and Broadway pump helped establish cholera as a quintessential waterborne (long-cycle) pathogen. However, there is renewed interest in the role that short-cycle (e.g. food-borne and household) transmission plays in epidemic contexts. The distinction between transmission pathways can be important, as they may demand different interventions. However, disentangling these pathways requires high-quality epidemiological and contextual data that is rarely collected in outbreak situations. Here we use detailed cholera incidence and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to estimate the relative contributions of short- and long-cycle transmission to the epidemic. We find transmission between neighborhoods during the epidemic did not follow water pipe connections, suggesting little evidence of long-cycle transmission. Instead, we suggest that short-cycle transmission was likely critical to the propagation of the outbreak. Interventions targeting short-cycle transmission are important tools that merit further consideration by public health officials combating epidemic cholera.

We investigate cholera transmission using data from historical cholera epidemics. The results suggest short-cycle (household/institution level) transmission was important in early secondary transmission. This study of historical outbreaks can inform investigations in current cholera epidemic settings., Background Although cholera is considered the quintessential long-cycle waterborne disease, studies have emphasized the existence of short-cycle (food, household) transmission. We investigated singular Danish cholera epidemics (in 1853) to elucidate epidemiological parameters and modes of spread. Methods Using time series data from cities with different water systems, we estimated the intrinsic transmissibility (R0). Accessing cause-specific mortality data, we studied clinical severity and age-specific impact. From physicians’ narratives we established transmission chains and estimated serial intervals. Results Epidemics were seeded by travelers from cholera-affected cities; initial transmission chains involving household members and caretakers ensued. Cholera killed 3.4%–8.9% of the populations, with highest mortality among seniors (16%) and lowest in children (2.7%). Transmissibility (R0) was 1.7–2.6 and the serial interval was estimated at 3.7 days (95% confidence interval, 2.9–4.7 days). The case fatality ratio (CFR) was high (54%–68%); using R0 we computed an adjusted CFR of 4%–5%. Conclusions Short-cycle transmission was likely critical to early secondary transmission in historic Danish towns. The outbreaks resembled the contemporary Haiti outbreak with respect to transmissibility, age patterns, and CFR, suggesting a role for broader hygiene/sanitation interventions to control contemporary outbreaks.