Monday 1st of March 2021

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More than 100,000 people in the UK have died from a virus, that, this time last year, felt like a far-off foreign threat. How did we come to be one of the countries with the worst death tolls?

There is no quick answer to that question, and there is sure to be a long and detailed public inquiry once the pandemic is over. But there are plenty of clues that, when pieced together, help build a picture of why the UK has reached this devastating number.

Some will point a finger at the government - its decision to lock-down later than much of western Europe, the stuttering start to its test-and-trace network, the lack of protection afforded to care home residents.

Others will spotlight deeper rooted problems with British society - its poor state of public health, with high levels of obesity, for example.

Others, still, will note that some of the UK's great strengths - its position as a vibrant hub for international air travel, for example; its ethnically diverse and densely packed urban populations - exposed its vulnerability to a virus that spreads effortlessly in the close air between people.

In some people's eyes, the UK's island status might have helped it. Other island nations such as New Zealand, Australia and Taiwan managed to stop the virus getting a foothold and deaths have been kept to a minimum - Australia has seen fewer deaths throughout the pandemic than the UK is recording every day on average.

All introduced strict border restrictions immediately and lockdowns to contain the virus before it had spread. The UK did not. It was not until June that quarantine rules were introduced for all arrivals and even then travel corridors were soon set up, relaxing the rules for travellers from certain countries. Only this month were these scrapped.

 

 

 

Read more:

https://www.bbc.com/news/health-55757790

unclear testing...

WHO Information Notice for IVD Users 2020/05Nucleic acid testing (NAT) technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-220 January 2021 Medical product alert Geneva 

Reading time: 1 min (370 words)

 


 

Product type: Nucleic acid testing (NAT) technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-2 

Date: 13 January 2021                                                                       

WHO-identifier: 2020/5, version 2 

Target audience: laboratory professionals and users of IVDs.

Purpose of this notice: clarify information previously provided by WHO. This notice supersedes WHO Information Notice for In Vitro Diagnostic Medical Device (IVD) Users 2020/05 version 1, issued 14 December 2020. 

Description of the problem: WHO requests users to follow the instructions for use (IFU) when interpreting results for specimens tested using PCR methodology.  

Users of IVDs must read and follow the IFU carefully to determine if manual adjustment of the PCR positivity threshold is recommended by the manufacturer.

WHO guidance Diagnostic testing for SARS-CoV-2 states that careful interpretation of weak positive results is needed (1). The cycle threshold (Ct) needed to detect virus is inversely proportional to the patient’s viral load. Where test results do not correspond with the clinical presentation, a new specimen should be taken and retested using the same or different NAT technology.

WHO reminds IVD users that disease prevalence alters the predictive value of test results; as disease prevalence decreases, the risk of false positive increases (2). This means that the probability that a person who has a positive result (SARS-CoV-2 detected) is truly infected with SARS-CoV-2 decreases as prevalence decreases, irrespective of the claimed specificity. 

Most PCR assays are indicated as an aid for diagnosis, therefore, health care providers must consider any result in combination with timing of sampling, specimen type, assay specifics, clinical observations, patient history, confirmed status of any contacts, and epidemiological information.

Actions to be taken by IVD users:

  1. Please read carefully the IFU in its entirety. 
  2. Contact your local representative if there is any aspect of the IFU that is unclear to you. 
  3. Check the IFU for each incoming consignment to detect any changes to the IFU.
  4. Provide the Ct value in the report to the requesting health care provider.

Contact person for further information:

Anita SANDS, Regulation and Prequalification, World Health Organization, e-mail: rapidalert@who.int

References:

1. Diagnostic testing for SARS-CoV-2. Geneva: World Health Organization; 2020, WHO reference number WHO/2019-nCoV/laboratory/2020.6.

2. Altman DG, Bland JM. Diagnostic tests 2: Predictive values. BMJ. 1994 Jul 9;309(6947):102. doi: 10.1136/bmj.309.6947.102

 

 

Read more:

https://www.who.int/news/item/20-01-2021-who-information-notice-for-ivd-users-2020-05

some of the worst flu in recent history...

[1951 flu] Abstract

Influenza poses a continuing public health threat in epidemic and pandemic seasons. The 1951 influenza epidemic (A/H1N1) [see also: all that I remember but forgot...] caused an unusually high death toll in England [and other countries in Europe]; in particular, weekly deaths in Liverpool even surpassed those of the 1918 pandemic. We further quantified the death rate of the 1951 epidemic in 3 countries. In England and Canada, we found that excess death rates from pneumonia and influenza and all causes were substantially higher for the 1951 epidemic than for the 1957 and 1968 pandemics (by >50%). The age-specific pattern of deaths in 1951 was consistent with that of other interpandemic seasons; no age shift to younger age groups, reminiscent of pandemics, occurred in the death rate. In contrast to England and Canada, the 1951 epidemic was not particularly severe in the United States. Why this epidemic was so severe in some areas but not others remains unknown and highlights major gaps in our understanding of interpandemic influenza.

 


Influenza is responsible for large increases in deaths in pandemic seasons when emerging viral subtypes with novel surface antigens become predominant, and also in some interpandemic seasons, when established subtypes exhibit antigenic drift (1). The circulating viral subtype is associated with varying severity of influenza epidemics (2): in the last 2 decades in the United States, estimated excess death rates were on average 2.8-fold higher in A/H3N2-dominated seasons than in A/H1N1 and B seasons (3). Within a given subtype, however, the strain-specific determinants of epidemic severity are still poorly understood. For instance in the United States in the same period, excess death rates varied nearly 4-fold among A/H3N2 seasons, even after adjustments for population aging (3). Better characterizations of past severe influenza epidemics can help understand and perhaps help predict the occurrence of severe epidemics.


Thumbnail of Comparison of 1951 epidemic (A/H1N1) with the 1918 and 1957 pandemics (A/H1N1 and A/H2N2, respectively) in Liverpool, England. Time series of weekly death rates from A) respiratory causes (pneumonia, influenza and bronchitis) and B) all causes. Epidemics were aligned at the week of peak mortality (peak week = week ended Feb 22, 1919; Jan 13, 1951; Oct 12, 1957). The 1918 pandemic occurred in 3 waves in Liverpool (summer 1918, autumn 1918, winter 1919); the "third wave" was associate

Figure 1. Comparison of 1951 epidemic (A/H1N1) with the 1918 and 1957 pandemics (A/H1N1 and A/H2N2, respectively) in Liverpool, England. Time series of weekly death rates from A) respiratory causes (pneumonia, influenza and...

Anecdotal accounts exist in the literature of historical influenza epidemics associated with unusual numbers of deaths, such as occurred in the 1951 epidemic in England in the midst of the first era of A/H1N1 viruses (1918–1957) (4). In Liverpool, where the epidemic was said to originate, it was "the cause of the highest weekly death toll, apart from aerial bombardment, in the city's vital statistics records, since the great cholera epidemic of 1849" (5). This weekly death toll even surpassed that of the 1918 influenza pandemic (Figure 1).


The international pattern of influenza-related deaths in 1951 has not been adequately quantified in the past because of lack of methodologic tools and historical death records. However, this historical epidemic is a good example to illustrate major gaps in our current understanding of influenza virus epidemiology. We revisited the 1951 epidemic by quantifying its death rate in 3 countries (England and Wales, Canada, the United States) and comparing its age-specific mortality pattern with that of surrounding epidemic and pandemic seasons (1).


Methods

Data


We obtained monthly pneumonia and influenza (P&I) and all-cause numbers of deaths for 1950 to 1999 from Health Canada (6), by 5-year age groups (details on the International Classification of Diseases codes used are given in Table 1). Canada was the only country with detailed age-specific mortality data for the 1950s readily available in electronic format.


Thumbnail of Time series of monthly mortality from pneumonia and influenza (P&I, represented as death rate/100,000) from 1950 to 1972 in A) Canada and B) England and Wales. Black line: observed deaths, Red line: baseline deaths predicted by a seasonal regression model. Note the 2 arrows for the 1968 pandemic in England, representing the 2 waves of the smoldering A/H3N2 pandemic (1968–69 and 1969–70, respectively) (18).

Figure 2. Time series of monthly mortality from pneumonia and influenza (P&I, represented as death rate/100,000) from 1950 to 1972 in A) Canada and B) England and Wales. Black line: observed deaths, Red...

For England and Wales (referred to as "England" for simplicity), we compiled P&I and all-cause deaths by month for 1950 to 1999 from the Registrar General (1950–1958 [7], ), and National Statistics (1959–1999 [8], ). In both countries, monthly deaths were normalized by population size to obtain comparable death rates over time and these were standardized to 30.5-day months (Figure 2). Population data were obtained from the same agencies (6,8).


As US monthly vital statistics were not available electronically since 1950, we compiled excess death estimates from various historical publications (9–12). These estimates were based on National Vital Statistics and death records from P&I and all causes in major American cities compiled by the Centers for Disease Control and Prevention and derived from excess mortality models similar to ours (see below).


We also conducted a literature search to compile reports describing the local patterns and geographic spread of the 1951 influenza epidemic in the 3 countries (5,9,13,14). Moreover, we obtained mortality data specifically for Liverpool, where the 1951 epidemic had the highest impact and death records have been previously described (5,13,15,16) (Figure 1).


Seasonal Excess Death Rate Estimates, Canada and England


Our primary goal in this study was to compare the death rate of the 1951 epidemic with that of the 1957 and 1968 pandemics. For this purpose, we fit a seasonal model to P&I and all-cause deaths for 1950 to 1971, capturing all 3 influenza seasons of interest, as described below. We present monthly time series and seasonal estimates for this period (20 seasons, see Figure 2 for P&I). A secondary goal was to compare the age mortality pattern of the 1951 epidemic with that of other influenza seasons. To have more statistical power and analyze several influenza seasons with substantial death rates, we also used an extended study period, 1950–1999.


For Canada and England, we applied a modified version of Serfling's classical seasonal regression model to monthly data on death rates for each country (17), as described elsewhere (3,18). We obtained a baseline for deaths in the absence of influenza, separately for each outcome (P&I and all-cause) and available age group (see Figure 2 for P&I). Seasonal excess deaths were then estimated as the number of deaths in excess of the baseline during months of increased influenza activity.


Standardization of Seasonal Excess Death Rates


Since our goal was to compare influenza deaths across multiple seasons and countries, we had to control for baseline differences in demography, healthcare, and socioeconomic status that may affect influenza-related deaths. To this end, we calculated age-adjusted seasonal excess death estimates in a manner previously described (3,18). Further, to control for residual differences in baseline death rates related to health and socioeconomic status, we adjusted the seasonal estimates for temporal changes in mortality in the summer months, when influenza is absent (18). We used year 1960, midpoint of the main study period 1950–1971, as an index.


Age-Specific Patterns of Seasonal Excess Death Rates, Canada


We examined whether the 1951 epidemic had an epidemic or pandemic mortality age pattern, as indicated by a shift in the age distribution of deaths towards younger age groups (1). In Canada, the 1950–51 season was the first season in our mortality records with complete age details. Hence, we could not evaluate a potential age shift between earlier seasons and the 1950–51 season, as described elsewhere (1).


We therefore developed an alternative method to identify a pandemic signature, in which we compared the gradual increase of influenza-related deaths with age between epidemic and pandemic seasons. We first used all moderate-to-severe influenza seasons in the interpandemic periods to obtain a null distribution of mortality age patterns during epidemics (we chose the 17 seasons above the median). Second, we checked that we could actually detect a pandemic age pattern by comparing the null epidemic pattern with those of the 1957 and 1968 pandemics. Then, we compared the null pattern with that of the 1951 epidemic. To model the gradual increase of influenza-related deaths with age in adults, we fitted an exponential to unadjusted P&I excess death rates by 5-year age groups for persons >55 years of age. The test then relied on comparing between seasons the values of the age and intercept coefficients of the exponential models. Bootstrap resampling of influenza seasons in the interpandemic periods yielded a p value for the test.

 

 

Read more:

https://wwwnc.cdc.gov/eid/article/12/4/05-0695_article#:~:text=Influenza

 

 

5 of the Worst Flu Outbreaks In Recent History


By Simone M. Scully


January 31, 2020


he current 2019-2020 flu season is on track to be one of the worst in a decade. According to the CDC, between 19-26 million people have caught the flu since October and between 10,000-25,000 people have died. But as bad as the seasonal flu is this year, it pales in comparison to some of the biggest flu pandemics in history. 

This is largely because we have a much better scientific understanding of flu viruses, improved hygiene standards and flu vaccines, which, while never 100% effective, are powerful defenses to help protect people from getting sick.

However, even after the invention of the vaccine, pandemics still happen because flu viruses evolve very quickly. Here are five of the largest epidemics in recent history:


The "Russian Flu" Epidemic of 1889


Known as the “Russian Flu,” this influenza outbreak is believed to have begun in St. Petersburg but it soon spread across Europe and the world. It was one of the first epidemics that was covered regularly by the developing daily press. Newspapers wrote about the local spread of the disease and also discussed the situation in other distant European cities thanks to telegraph reports. It is estimated that around 1 million people died of the Russian Flu.


The 1918-19 “Spanish Flu” Pandemic


Known at the time as the “Spanish Flu,” this flu pandemic was the most severe pandemic in recorded history. It was caused by an H1N1 virus. According to the CDC, an estimated 500 million people — or 1/3rd of the world’s population — caught the virus during the pandemic and between 50 million and 100 million people were killed. 675,000 died in the United States alone. Some victims died within mere hours or days of developing symptoms. 

The pandemic was so far reaching in part because of World War I troop movement. There were also no vaccines stop the spread of the virus at the time, no antiviral medications to help treat it, and no antibiotics to treat secondary bacterial infections that can come with the flu. All that people could do to contain the spread of the disease was wash their hands, avoid public gatherings and quarantine the sick.

 

etc

 

Read more:

https://weather.com/health/cold-flu/news/2020-01-31-5-worst-flu-outbreaks-in-recent-history

 

 

 

Note: the 1951 flu is not listed in the five worse flu seasons, yet it could have been worse than the "Spanish flu" which came from the USA around 1918... Read from top.