Modelling RT-qPCR cycle-threshold using digital PCR data for implementing SARS-CoV-2 viral load studies

Objectives To exploit the features of digital PCR for implementing SARS-CoV-2 observational studies by reliably including the viral load factor expressed as copies/μL. Methods A small cohort of 51 Covid-19 positive samples was assessed by both RT-qPCR and digital PCR assays. A linear regression model was built using a training subset, and its accuracy was assessed in the remaining evaluation subset. The model was then used to convert the stored cycle threshold values of a large dataset of 6208 diagnostic samples into copies/μL of SARS-CoV-2. The calculated viral load was used for a single cohort retrospective study. Finally, the cohort was randomly divided into a training set (n = 3095) and an evaluation set (n = 3113) to establish a logistic regression model for predicting case-fatality and to assess its accuracy. Results The model for converting the Ct values into copies/μL was suitably accurate. The calculated viral load over time in the cohort of Covid-19 positive samples showed very low viral loads during the summer inter-epidemic waves in Italy. The calculated viral load along with gender and age allowed building a predictive model of case-fatality probability which showed high specificity (99.0%) and low sensitivity (21.7%) at the optimal threshold which varied by modifying the threshold (i.e. 75% sensitivity and 83.7% specificity). Alternative models including categorised cVL or raw cycle thresholds obtained by the same diagnostic method also gave the same performance. Conclusion The modelling of the cycle threshold values using digital PCR had the potential of fostering studies addressing issues regarding Sars-CoV-2; furthermore, it may allow setting up predictive tools capable of early identifying those patients at high risk of case-fatality already at diagnosis, irrespective of the diagnostic RT-qPCR platform in use. Depending upon the epidemiological situation, public health authority policies/aims, the resources available and the thresholds used, adequate sensitivity could be achieved with acceptable low specificity.

Rift valley fever in Africa with the emerging interest in Libya

Rift valley fever (RVF) is an acute vector-borne viral zoonotic disease of domestic and wild ruminants. The RVF virus (RVFV) belonging to the Phlebovirus genus of the Bunyaviridae family causes this disease. Studies have shown that mosquitoes are the vectors that transmit RVFV. Specifically, Aedes and Culex mosquito species are among the many vectors of this virus, which affects not only sheep, goats, buffalo, cattle, and camels but also human beings. Since the 30s of the last century, RVF struck Africa, and to a lesser extent, Asian continents, with subsequent episodes of epizootic, epidemic, and sporadic outbreaks. These outbreaks, therefore, resulted in the cumulative loss of thousands of human lives, thereby disrupting the livestock market or only those with seropositive cases. After that outbreak episode, RVF was not reported in Libya until January 13, 2020, where it was reported for the 1st time in a flock of sheep and goats in the southern region of the country. Although insufficient evidence to support RVF clinical cases among the confirmed seropositive animals exists, neither human cases nor death were reported in Libya. Yet, the overtime expansion of RVF kinetics in the Libyan neighborhoods, in addition to the instability and security vacuum experienced in the country, lack of outbreak preparedness, and the availability of suitable climatic and disease vector factors, makes this country a possible future scene candidate for RVF expansion. Urgently, strengthening veterinary services (VS) and laboratory diagnostic capacities, including improvement of monitoring and surveillance activity programs, should be implemented in areas at risk (where imported animals crossing borders from Libyan neighborhoods and competent vectors are found) at national, sub-national, and regional levels. The Libyan government should also implement a tripartite framework (one health approach) among the veterinary public health, public health authority, and environmental sanitation sectors to implement RVF surveillance protocols, along with an active partnership with competent international bodies (OIE, FAO, and WHO). Therefore, this review comprises the most updated data regarding the epidemiological situation of RVF infections and its socioeconomic impacts on African and Asian continents, and also emphasize the emerging interest of RVF in Libya.

How should we present the epidemic curve for COVID-19?

Epidemic curves are used by decision makers and the public to infer the trajectory of the COVID-19 pandemic and to understand the appropriateness of response measures. Symptom onset date is commonly used to date incident cases on the epidemic curve in public health reports and dashboards; however, third-party trackers date cases by the date they were publicly reported by the public health authority. These two curves create very different impressions of epidemic progression. On April 1, 2020, the epidemic curve based on public reporting date for Ontario, Canada showed an accelerating epidemic, whereas the curve based on a proxy variable for symptom onset date showed a rapidly declining epidemic. This illusory downward trend is a feature of epidemic curves anchored using date variables earlier in time than the date a case was publicly reported, such as the symptom onset date. Delays between the onset of symptoms and the detection of a case by the public health authority mean that recent days will always have incomplete case data, creating a downward bias. Public reporting date is not subject to this bias and can be used to visualize real-time epidemic curves meant to inform the public and decision makers.

Measures Introduced in the Slovak Republic in Response to the Public Health Crisis Caused by the COVID-19 Pandemic

The SARS-Cov-2 pandemic outbreak in the Slovak Republic in March 2020 required rapid legal response to protect lives and health of inhabitants and new complex challenges emerged. The objective of this paper is an analysis and critical assessment of measures adopted in the field of health law. As most significant problem fields in Slovakia arose: 1/ Legality and hierarchy of measures limiting everyday life and exercise of citizen rights and freedoms; 2/ the scope, proportionality, extent and duration of measures; 3/ adherence to the measures by the public and law enforcement issues. The pandemic unraveled need to innovate the legal framework of contagious diseases control, for example, constitutional emergency regimen, or powers of the Public Health Authority. Established rule of law framework served to safeguarding against some disproportionate or unwanted effects of anti-pandemic measures, however, future development of more sophisticated legal tools to control the pandemic is needed.

Epidemiology of childhood tuberculosis after ceasing universal Bacillus Calmette–Guérin vaccination

Universal Bacillus Calmette–Guérin (BCG) vaccination is recommended in countries with high tuberculosis (TB) burden. Nevertheless, several countries have ceased universal BCG vaccination over the past 40 years, with scarce comparative epidemiological analyses regarding childhood TB after the policy change. We analysed data on childhood TB in countries that ceased universal BCG vaccination. Data sources included national/international databases, published papers, annual TB reports, and public health authority websites. Childhood TB notification rate increased in one of seven countries with available data. Pulmonary TB and TB lymphadenitis were the main causes of increasing childhood cases, while changes in severe forms of TB cases were minor. Maintaining high vaccine coverage for the target group was a common challenge after shifting selective vaccination. In some countries showing no increase in childhood TB after a BCG policy change, the majority of childhood TB cases were patients from abroad or those with overseas parents; these countries had changed immigration policies during the same period. Heterogeneity in childhood TB epidemiology was observed after ceasing universal BCG vaccination; several factors might obscure the influence of vaccination policy change. Lessons learned from these countries may aid in the development of better BCG vaccination strategies.

We need to work differently in a crisis: peer-professional leadership to redesign physicians’ work

BackgroundUnderstanding physician leadership is critical during pandemics and other health crises when formal organisational leaders may be unable to respond expeditiously. This study examined how physician leaders managed to quickly design a new model for acute-care physicians’ work, adopted across four large hospitals in a public health authority in Canada during the COVID-19 pandemic.MethodsThe research employed a qualitative case study methodology, with inductive analysis of interview transcripts and documents. Shortly after a physician work model redesign, we interviewed key informants: the physician leaders and others who participated in or supported the model’s development. Participants were chosen based on their leadership role and through snowballing. All those who were approached agreed to participate.ResultsA process model describes leadership actions during four phases of work model development (priming, early planning, readying for operations and transition). These actions were: (1) recognising the threat, (2) committing to action, (3) forming and organising, (4) building and relying on relationships, (5) developing supporting processes and (6) designing functions and structure. We offer three additional contributions to knowledge about leadership in a time of crisis: (1) leveraging peer-professional leadership to initiate, formalise and organise change processes, (2) designing a new work model on existing and emerging evidence and (3) building and relying on relationships to unify various actors.ConclusionsThe model of peer-professional leadership can deepen understanding of how to lead professionals. Our findings could assist peer-professional and organisational leaders to encourage quick redesign of professionals’ work in response to new phases of the COVID-19 pandemic or other crises.

Public Health Crisis during COVID-19 pandemic

During the COVID pandemic, biomedicine and the rapid development of anti-COVID vaccines has been widely praised, while the global public health response has been questioned. Fifteen United States based combined experts in primary healthcare and public health responded to an open question focusing on this issue. Eleven of these experts responded. Four major themes emerged from their answers, including: fragmentation between public health and biomedicine; underfunding of public health; lack of centralized public health authority; business interests over the public good and well-being.

Hygiene measures in supermarkets, retail food stores, and grocery shops during the COVID-19 pandemic in Slovakia

The article presents the hygiene measures that are applied in the Slovak Republic in supermarkets, food stores, grocery stores as a result of the COVID-19 pandemic situation in Slovakia. These measures have been published by the Public Health Authority of the Slovak Republic in the relevant legal regulations and are based on the decisions of the Government of the Slovak Republic, which took into account the opinions of the experts of the Pandemic Commission of the Government of the Slovak Republic. In general, these measures are based on the mask-distance-hand principle. In public areas outside and inside, it was ordered to wear masks and later wear a respirator of FFP2 class in exterior and interior, gloves on hands or disinfection of customers' hands before entering the store, observance of 2 m distance of people standing in a row at the cash registers, maximum capacity of persons in stores was determined one person per 25 m2 of sales area and later, this measure was tightened to 15 m2 of sales area. Also, to perform regular ventilation of the premises and to have as many cash registers as possible so as not to create long lines of customers. All shops were closed at 8:00 PM. In the case of shopping centers, entry is prohibited for people with a body temperature higher than 37 °C, and disinfection of hands is mandatory, wearing a mask and later wear respirators of FFP2 class is necessary. In a stricter regime, during the peak of the pandemic, there was a restriction for persons to shop food only in the nearest retail/grocery or similar place from the place of residence to the extent necessary to procure the essential needs of life.

Correcting COVID-19 PCR Prevalence for False Positives in the Presence of Vaccination Immunity

Many public health authority reports on COVID-19 cases confound positive test results with population prevalence. As the population prevalence approaches the PCR test false positive rate (FPR), for example during a vaccination campaign, it is necessary to adjust the the raw test results for the false positive rate. This paper provides a technique for estimating the test false positive rate and making the correction to test population prevalence in the absence of accurate and definitive specificity. Using current data providing by the Public Health England as of the most recent complete data, a false positive rate of 1.16% (95% CI 1.09 - 1.23% ) was found for the PHE PCR test for the period 1 January through 29 March 2021. During this period, the test population prevalence is decreasing, starting at a decay rate estimated as 3.0% per day (CI 2.79 - 3.14%). This rate of decay increased to an estimated 14.7% by the end of the period (CI 13.30 - 16.16%) Finally, mean test population prevalence was estimated at 14.3% (CI 13.75 - 14.87%) on 1 January and is estimated to have declined significantly to 0.06% (CI 0.00 - 0.13%). If PCR test positivity are used without the application of the false positive rate, the percent positive PCR tests will eventually "flatline" at the false positive rate, and produce a false positive bias even if test population prevalence should fall to zero.