China MOA: ASF Returns To Tianjin

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A little over 6 weeks ago China's MOA announced the first African Swine Fever outbreak in Tianjin (one of the 9 National Central Cities of China), located about 100km from Beijing.

While most of China's ASF action during the month of November has been relegated to the Southern provinces, today their MOA announces a second outbreak in Tianjin.

Today's report comes just one week after the announcement that ASF had finally reached Beijing, and brings China's total to at least 80 outbreaks since August 1st (cite).

The Ninghe District of Tianjin Province has detected the epidemic situation of African swine fever

Date: 2018-11-30 10:17 Author: Source: Ministry of Agriculture and Rural Press Office 

The Information Office of the Ministry of Agriculture and Rural Affairs was released on November 29, and the Ninghe District of Tianjin Province detected the African swine fever epidemic.

At 21:00 on November 29, the Ministry of Agriculture and Rural Affairs received a report from the China Animal Disease Prevention and Control Center and was diagnosed by the China Center for Animal Health and Epidemiology (National Center for Animal Disease Research). 

A farm in Ninghe District of Tianjin was found in Africa. Pig plague. Up to now, the farm has 361 pigs and 67 deaths.

Immediately after the outbreak, the Ministry of Agriculture and Rural Affairs sent a steering group to the local area. The local government has started the emergency response mechanism as required, and adopted measures such as blockade, culling, harmless treatment, disinfection, etc., to treat all the sick and culled pigs harmlessly. At the same time, all pigs and their products are prohibited from being transferred out of the blockade, and pigs are prohibited from being transported into the blockade. At present, the above measures have been implemented.

ASF has never been reported in North America, but the potential exists for its importation. The USDA has released a new African Swine Fever Factsheet that discusses their preparations for a possible introduction of the virus into this country.

(Excerpt)

Keeping ASF Out

Because of the concern over ASF, USDA recently reviewed and further strengthened its longstanding stringent protections against the spread of the disease.These include:

• Collaborating with states, industry and producers to ensure everyone follows on-farm biosecurity and best practices (including for garbage feeding in states where that is allowed);
• Restricting imports of pork and pork products from affected countries; and
• Working with CBP staff at ports of entry to increase passenger and baggage screening for prohibited products from affected countries.

While ASF doesn't pose a direct health risk to humans, it is a serious threat to the pig industry - and with no vaccine available - the only way to control it is to cull all of the pigs that may have been exposed.

Meanwhile, ASF continues to make inroads in Europe, and further spread there and in Asia seems inevitable (see FAO: African swine fever (ASF) threatens to spread from China to other Asian countries).

MMWR: Multistate Infestation with the Exotic Disease–Vector Tick Haemaphysalis longicornis

Where Haemaphysalis longicornis has been reported (N = 45

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Just over two weeks ago, in CDC: Record Number Of Tickborne Infections Reported In 2017, we looked at the latest statistics on what has become an increasing and worrisome public health threat in the United States.  

While Lyme disease currently makes up about 80% of the reported infections, over the past decade we've seen the rise of several new threats, including the recently discovered Heartland and Bourbon Viruses.

Many of these diseases are vector specific, meaning that only certain ticks can carry them.  All of which makes the recent discovery of an Asian tick species - Haemaphysalis longicornis - in the United States a particular concern.

Also called the Asian longhorned tick, this species is native to Eastern China and East Asia, and is known to carry and spread a number of animal and human pathogens, including Severe Fever and Thrombocytopenia Syndrome Virus (SFTSV).

SFTSV - a tickborne Phlebovirus - was first discovered in China in 2009, and has since been reported in Japan & Korea as well. It is genetically similar to the recently identified Heartland Virus (see MMWR: Heartland Virus Disease — United States, 2012–2013) and to a Novel Bunyavirus In Livestock – Minnesota first reported in 2013.

Yesterday the CDC's MMWR published a review of this exotic invasive tick, and the potential public health risks from its recent arrival into the United States.  As this is a fairly long report, I've only posted some excerpts.

Follow the link to read it in its entirety.

Multistate Infestation with the Exotic Disease–Vector Tick Haemaphysalis longicornis — United States, August 2017–September 2018

Weekly / November 30, 2018 / 67(47);1310–1313

C. Ben Beard, PhD¹; James Occi, MA, MS²; Denise L. Bonilla, MS³; Andrea M. Egizi, PhD⁴; Dina M. Fonseca, PhD²; James W. Mertins, PhD³; Bryon P. Backenson, MS⁵; Waheed I. Bajwa, PhD⁶; Alexis M. Barbarin, PhD⁷; Matthew A. Bertone, PhD⁸; Justin Brown, DVM, PhD⁹; Neeta P. Connally, PhD¹⁰; Nancy D. Connell, PhD¹¹; Rebecca J. Eisen, PhD¹; Richard C. Falco, PhD⁵; Angela M. James, PhD³; Rayda K. Krell, PhD¹⁰; Kevin Lahmers, DVM, PhD¹²; Nicole Lewis, DVM¹³; Susan E. Little, DVM, PhD¹⁴; Michael Neault, DVM¹⁵; Adalberto A. Pérez de León, DVM, PhD¹⁶; Adam R. Randall, PhD¹⁷; Mark G. Ruder, DVM, PhD¹⁸; Meriam N. Saleh, PhD¹⁴; Brittany L. Schappach¹⁰; Betsy A. Schroeder, DVM¹⁹; Leslie L. Seraphin, DVM³; Morgan Wehtje, PhD³; Gary P. Wormser, MD²⁰; Michael J. Yabsley, PhD²¹; William Halperin, MD, DrPH²²

Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six species of domestic animals, six species of wildlife, and humans.

To forestall adverse consequences in humans, pets, livestock, and wildlife, several critical actions are indicated, including expanded surveillance to determine the evolving distribution of H. longicornis, detection of pathogens that H. longicornis currently harbors, determination of the capacity of H. longicornis to serve as a vector for a range of potential pathogens, and evaluation of effective agents and methods for the control of H. longicornis.

(SNIP)

Discussion

Cooperative efforts among federal, state, and local experts from agricultural, public health, and academic institutions during the last year have documented that a tick indigenous to Asia is currently resident in several U.S. states. The public health and agricultural impacts of the multistate introduction and subsequent domestic establishment of H. longicornis are not known. At present, there is no evidence that H. longicornis has transmitted pathogens to humans, domestic animals, or wildlife in the United States. 

This species, however, is a potential vector of a number of important agents of human and animal diseases in the United States, including Rickettsia, Borrelia, Ehrlichia, Anaplasma, Theileria, and several important viral agents such as Heartland and Powassan viruses. Consequently, increased tick surveillance is warranted, using standardized animal and environmental sampling methods.

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Summary

What is already known about this topic?

Haemaphysalis longicornis is a tick indigenous to Asia, where it is an important vector of human and animal disease agents, which can result in human hemorrhagic fever and substantive reduction in dairy production.

What is added by this report?
During 2017–2018, H. longicornis has been detected in Arkansas, Connecticut, Maryland, New Jersey, New York, North Carolina, Pennsylvania, Virginia, and West Virginia on various species of domestic animals and wildlife, and from two humans.

What are the implications for public health practice?

The presence of H. longicornis in the United States represents a new and emerging disease threat. Characterization of the tick’s biology and ecology are needed, and surveillance efforts should include testing for potential indigenous and exotic pathogens.

The CDC lists a growing number of diseases carried by ticks in the United States, including: Anaplasmosis, Babesiosis , Ehrlichiosis, Rickettsia parkeri Rickettsiosis, Rocky Mountain Spotted Fever (RMSF), STARI (Southern Tick-Associated Rash Illness), Tickborne relapsing fever (TBRF), Tularemia, and 364D Rickettsiosis.

The following CDC website offers advice on: Preventing Tick Bites

HK CHP: Update On Flu Vaccine Recall

Credit Taiwan FDA

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In a follow up to Tuesday's report Taiwan FDA & HK HA Reject 2 Batches Of Sanofi Flu Vaccine For `Impurities', Hong Kong's CHP has issued the following update indicating that no similar `contaminants' have been found among 1000 randomly selected samples checked in Hong Kong.

Use of the suspected lot remains suspended, and more quality checks are underway.  New batches of vaccine have been ordered from Sanofi and another supplier, and no adverse reactions due to contaminants have been reported.

While reports of flu activity have started to increase in South Korea and Canada, so far Hong Kong reports only low levels of Flu (see Flu Express Week 47).

DH provides updates on quadrivalent seasonal influenza vaccines

 

The Department of Health (DH) announced today (November 29) the latest follow-up actions taken on quadrivalent seasonal influenza vaccines (SIVs), following its announcement concerning the suspension of supply of a batch of quadrivalent SIVs and the dispatch arrangements of another batch of vaccines by a licensed drug wholesaler, Sanofi-Aventis Hong Kong Limited (Sanofi), this Tuesday (November 27).

The DH collected over 1 000 samples of quadrivalent SIVs by Sanofi from Sanofi's storehouse and dispensaries of the DH clinics for inspection on a random basis yesterday (November 28). Among them, about 700 samples were from the affected batch while about 300 samples were from other batches. The inspection result revealed that no particles were detected in the samples.

Meanwhile, the DH has also collected vaccine samples for quality testing by the Government Laboratory and accredited laboratories. The results will be announced as soon as possible.

Preliminary information by Sanofi also revealed that it has not received any report regarding the presence of white particles in the same batch of SIVs currently supplied to Hong Kong, and that there is so far no evidence showing that the quality, safety or efficacy of the SIVs supplied to Hong Kong have been affected, or that safety risk is imposed to those receiving the vaccines. The DH has requested Sanofi to submit a full investigation report regarding the presence of white particles in the affected batch of SIVs.

"We have been working on the incident in the past days and have traced and compiled further information on the distribution locations of the affected batch of vaccines. The information, including a list of the DH's clinics, the Hospital Authority (HA)'s clinics, and other healthcare facilities, has been uploaded to the website of the Centre for Health Protection (www.chp.gov.hk/en/features/101125.html)," a spokesman for the DH said.

The HA has set up a hotline (2300 6028) and the DH has also set up a hotline (2125 1133). Members of the public may call the hotline during office hours, Monday to Friday, for enquiries.

Regarding the healthcare facilities supplied with the affected batch of SIVs, the DH has already instructed them to suspend the use of the affected vaccines, and to seal and not to use the remaining unused vaccines until the DH's further instruction.

To maintain a stable supply of SIVs, the DH has been keeping close contact with Sanofi and closely monitoring the progress of the dispatch arrangements of vaccines. The DH has also asked Sanofi and another supplier providing quadrivalent SIVs to Hong Kong to import additional quantities of vaccines to meet the local demand.

The spokesman stressed that the use of the affected batch of SIVs has been suspended and reminded the public that vaccination is one of the most effective ways to prevent influenza to protect themselves against influenza and its complications.

 

Ends/Thursday, November 29, 2018

Issued at HKT 19:53

Nigeria CDC: Monkeypox Update Week 46

Credit Nigerian CDC

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It's been just over a month since the Nigerian CDC updated their Monkeypox Surveillance (see Nigeria CDC: Monkeypox Update Epi Week 41), and nearly three months since the first of 3 exported cases (2 to the UK, 1 to Israel) showed up outside of Nigeria. 

Nigeria reported their first outbreak of Monkeypox in nearly 40 years in the fall of 2017, one which appeared to be about over in February.  Until their September (Epi Week 37), update, Nigeria issued their last outbreak update in epi week 9 of 2018.

The Nigerian CDC has now issued an update for Epi Week 46 - current through Nov. 13th - which indicates that low levels of transmission continue in the country, and suggest a recent uptick in suspected cases (29 vs 10 in the last report).  

Whether this increase is the result of more disease activity, or of better surveillance and reporting is impossible to say. 

Due to a changing way that Key Indicators are being presented (see graphic below), direct comparisons to the previous updates are cumbersome.

In some reports, numbers reflect totals of confirmed cases only, while others combine confirmed and suspected. In other cases, totals are since Sept 2017, while others reflect only 2018 cases.

NIGERIA MONKEYPOX OUTBREAK REPORT

027
November 13, 2018

SUMMARY OF OUTBREAK INDICATORS FOR 2018 KEY INDICATORS

• Nigeria continues to report sporadic cases of monkeypox since the beginning of the outbreak- September 2017
• A total of nine new confirmed cases were recorded in 4 states (Bayelsa 4; Rivers – 2; Delta – 2; Oyo – 1) out of twenty-nine (29) new cases reported to the NCDC in the last one month
• A total of 104 cases have been reported in 2018 from 19 States (Rivers, Akwa-Ibom, Bayelsa, Cross River, Delta, Ebonyi, Edo, Enugu, Imo, Kebbi, Lagos, Nasarawa, Oyo, Abia, Anambra, Bauchi, Plateau, Adamawa and the FCT)
• Of the 104 cases reported, there are 38 confirmed cases, one probable case and one death
• Rivers state and Bayelsa state in South-south Nigeria remain the most affected states
• Males are more affected with a female to male ratio of 1: 3
• The most affected age group in confirmed cases is 21-40 years (Median Age = 31).
• Since the beginning of the outbreak in September 2017, 126 confirmed cases, four probable cases and seven deaths have been recorded
• Genetic sequencing suggests multiple sources of introduction of monkeypox virus into the human population with some evidence of human to human transmission
• Ongoing analysis of findings from monkeypox animal surveillance activities

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A little over a month ago (Oct 18th) the CDC issued a travelers' advisory for Monkeypox in Nigeria (see below):

Monkeypox in Nigeria

Alert - Level 2, Practice Enhanced Precautions

Key Points

• An outbreak of monkeypox has been ongoing since September 2017 in Nigeria.
• Monkeypox is spread through contact with an infected person or animal (alive or dead), or with material contaminated with the virus. It can also be spread through droplets when infected people cough, sneeze, or talk.
• Travelers to Nigeria should protect themselves from monkeypox by washing hands often with soap and water, and avoiding contact with animals or people that may be sick.

What is the current situation?

As of September 2018, health officials in Nigeria have reported more than 100 confirmed cases of monkeypox, including multiple deaths. As of October 2018, three cases of monkeypox have been reported in travelers to the United Kingdom (2) and Israel (1), including one to GeoSentinel (a global travel surveillance network).

What is monkeypox?

Monkeypox is a rare disease that occurs throughout remote parts of Central and West Africa, often near tropical rainforests. It is spread through contact with the monkeypox virus from an animal or human (alive or dead) or with materials contaminated with the virus. Symptoms begins with fever, headache, muscle aches, swollen lymph nodes and exhaustion, and is followed by a rash. Patients are usually ill for 2-4 weeks. Monkeypox is fatal in as many as 10% of people who get it.

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Nigeria continues to struggle with a number of other infectious disease outbreaks, including Lassa Fever, Yellow Fever, and Cholera. That, combined with the Boko Haram conflict in the northeast, and ongoing political and societal challenges, likely hinders the CDC's ability to conduct surveillance in some parts of the country.

Fortunately, the West African Monkeypox virus is considered to be less virulent, and less easily transmitted, than its Central African counterpart (cite).

For a more detailed look at the Monkeypox virus in Africa, and a limited 2003 outbreak in the United States - you may wish to revisit this blog from last May.

MMWR: Emergence of Monkeypox — West and Central Africa, 1970–2017

WHO: Clarification On Reports Of Ebola Case In Uganda (tests come back negative)

WHO Ebola Dashboard

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A couple of days ago there were multiple media reports of a suspected Ebola case dying at a Fort Portal regional referral hospital in western Uganda last Monday (see here and here).

Were this story to be true, it would represent a long-feared expansion of the DRC's Ebola outbreak into a neighboring country (see WHO: Uganda Begins Targeted Vaccination Of Front-Line HCWs Against Ebola), and a major setback for the current containment efforts.

While the threat of regional spread remains very high (see recent WHO risk assessment), according to the following joint Ugandan MOH/WHO announcement, in this instance the suspected case has tested negative for Ebola and other hemorrhagic diseases.

 
JOINT RELEASE: Clarification on alleged Ebola death in Kabarole District.

Kampala, 28 November 2018 - Following media stories on the alleged suspected Ebola death in Kabarole District, the Ministry of Health together with the World Health Organization (WHO) wish to update the public as follows:

1. On 26th November 2018, an alert case was received at Fort Portal Regional Referral Hospital from Bundibugyo district.
2. The 38year old male alert case is one of the many alert cases received in different health facilities as a result of the heightened surveillance along all border districts.
3. Blood samples were taken off the suspect and sent to Uganda Virus Research Institute (UVRI) for further analysis.
4. Results from the UVRI indicate that the patient was negative by PCR for Ebola and other Viral Hemorrhagic Fevers. The districts are aware of these results.
5. Any persons that present with any known symptoms of Ebola is taken on as an alert case until thorough lab investigations are done. 

Currently, a number of Ebola Virus Disease (EVD) preparatory activities are going on across all high-risk districts and these include; coordination of activities; health facility and community-based EVD surveillance, collection and testing of blood samples from alert cases, capacity building for Infection, Prevention and Control, clinical management, psycho-social care and for safe and dignified burials. Risk communication, community engagement and cross-border surveillance are also going on in many districts.

In the same vein, a total of 1,316 front line and healthcare workers in three (3) districts have been vaccinated against EVD to protect this cadre of people against the deadly disease.

The Ministry of Health together with the WHO country office wish to reiterate that there is no confirmed case of Ebola Virus Disease in Uganda, and are working tirelessly to keep the country safe from the deadly disease.

DEFRA: Higher Risk Areas For Avian Flu In England, Scotland & Wales

Credit DEFRA

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While bird flu activity in Europe (aside from Bulgaria) has been subdued for months, with winter's approach DEFRA yesterday issued another reminder of the risk of avian flu carried to the UK via migratory and overwintering birds. 

New in this report is a link to an updated interactive map of Higher Risk Areas (HRAs) - areas near lakes, marshes or estuaries - where birds tend to gather (see below).

Higher Risk Areas (HRAs)

All areas in Great Britain remain at risk of bird flu in wild birds.

However, in Great Britain we’ve defined a number of areas as ‘Higher Risk Areas’ (HRAs). These are generally areas near where wild birds (and in particular gulls and wild waterfowl) gather, such as lakes, marshes or estuaries.
Check if your premises is within an HRA on our interactive map. 

If all or part of your premises is in a Higher Risk Area you should follow biosecurity advice to protect your birds. We consider that you’re in an HRA even if only part of your premises falls within the HRA.

We have defined HRA’s following our experience over the last 2 winters, coupled with the latest scientific and veterinary opinion. This indicates that migratory wild waterfowl (ducks, geese and swans) and gulls pose a continual threat for the introduction of bird flu into premises where poultry, game birds, pet and other captive birds are kept. EU regulations require that member states identify areas of the country where the risk of bird flu is deemed to be highest. We have published more detail of the rationale and approach behind Higher Risk Areas.

If you are planning a new poultry unit you should take into account the risk of HPAI where the unit is planned.

As mentioned above, DEFRA has published a 22-page rational for determining HRAs around the UK (see below).   Due to its length, I've only excerpted a small portion.  Follow the link to download and read the full report.

Disease risk considerations supporting the definition of Avian Influenza Higher Risk Areas in England, Scotland and Wales

November 2018

Summary

Great Britain (GB) has a variable risk of incursion (in wild birds and/or poultry) of notifiable avian disease throughout the year and the risk for avian influenza is generally heightened in the winter season when migratory wild waterfowl are arriving at their over-wintering sites across GB. A range of species, including, ducks, geese, swans and gulls are considered to act as reservoirs of avian influenza viruses (AIV).

The heightened probability of GB poultry contact with wild birds in autumn/winter means we consider there may be a corresponding heightened risk of AIV exposure to poultry, but this would depend on the level of infection in the wild birds and the nature of the virus itself, which may not “jump” readily into poultry.

Therefore and in accordance with the EU legislation (Commission Decision (EU) 2018/1136) we have conducted an analysis of higher risk areas across GB where the probability of finding wild birds infected with avian influenza viruses is greater at certain times of the year.

Expert analyses have taken place of 1) the disease introductions into the UK and across Europe, 2) the evidence from the widespread surveillance to date across Europe, 3) the wild bird species where infection has been identified and 4) the risk factors associated with spread from wild birds to domestic poultry identified. This has led to  an understanding that “higher risk areas” may be identified within the country. Typically these are close to inland or coastal bodies of water, where large numbers of wild birds collect, with wild waterbirds, specifically duck species, being highlighted.

The presence of virus in the environment surrounding a poultry farm means it can be carried into the farm by various means, bridging species (birds visiting both poultry farms and waterbird areas), such as gulls and corvids, humans, equipment, rodents etc.

Therefore the closer a poultry premises is to locations where high numbers of potentially infected wild birds are present, the greater is the risk that disease will be carried into it by one of these pathways. The level of risk reduces as the distance from wild bird resting places increases, as the likelihood of somehow bringing contamination into the farm is considered to decline. Hence whilst best practice biosecurity must be practised in all areas of the country, in these higher risk areas, biosecurity protective measures may need to be enhanced at certain times of the year.

Housing or covering areas with netting where domestic poultry are kept or range should therefore continue to protect farms in these higher risk areas. Published studies indicate that a distance of 5km from such bodies of water would exceed the likely maximum daily foraging distance of most duck species and therefore be the proposed edge for Higher Risk Area, however 2km foraging distance would cover the majority of the spatial risk. The risk of contact with bridging species, such as gulls and corvids, exists for all areas of GB and therefore general biosecurity awareness for poultry keepers are necessary in all areas of GB.

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Last April, in ESA Epidemiological Update: Global Circulation Of Avian Flu, we looked at the general pattern of avian flu outbreaks around the world, and the tendency for years with high levels of activity to be followed by one or more years of lesser activity.

From ESA Report

Based the above chart, 2006, 2008, 2014-15, and 2016-17 were all high activity periods, with a highly noticeable 6 year quiescent period between 2009 and late 2014. In contrast, two shorter gaps are shown (2007 & 2015-17), illustrating the unpredictability of avian flu.

At this point - as with seasonal flu - we can't really predict what this winter will bring. The best we can hope for is to be prepared to deal with whatever comes.

EID Journal: Complexity of the Basic Reproduction Number (R0)

  R₀ (pronounced R-nought) or
  Basic Reproduction Number


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One of the most important - yet difficult to determine - pieces of information epidemiologists and statisticians seek on infectious disease outbreaks is just how contagious is it? 

Some viruses – like measles or diphtheria – spread through a susceptible population rapidly, while others - like MERS-CoV - have demonstrated only limited transmissibility (see The Elusive R₀ of MERS).

The yardstick by which disease transmissibility is measured is by its R₀ (pronounced R-nought) or Basic Reproductive Number. Essentially, the number of new cases in a susceptible population likely to arise from a single infection. 

In the simplest of terms, with an R₀ below 1.0, a virus (as an outbreak) begins to sputter and dies out. Above 1.0, and an outbreak can have `legs’. 

Calculating the R₀ is notoriously difficult, however - even years after an epidemic has passed. Much hinges upon the existence and subtle differences between viral strains, the accuracy of surveillance and reporting, `seasonality’, and individual host responses to the virus (i.e. number of `super spreaders’).

Like the CFR (Case Fatality Ratio), the R₀ can vary considerably over time or geography, often ends up being described as a `range’, and usually isn’t well established (or at least, generally agreed upon) until long after an outbreak has ended.

Credit Wikipedia

Over the years we've looked at some attempts to quantify the R₀ of recent outbreaks and epidemics, including:

Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia

Eurosurveillance: Estimating The Odds Of Secondary/Tertiary Cases From An Imported MERS Case

Eurosurveillance: Stopping Ebola & R0 Calculations

PLoS Currents: Calculating An R0 For Ebola

The Lancet: Transmissibility Of MERS-CoV

In theory, the R₀ is a simple enough concept, but outbreaks have a lot of moving parts, and not everyone is on the same page when it comes to defining terms. Helping us sort through all of this, we have an excellent Perspective published in the EID Journal on the science behind calculating an outbreak's R_{0 .}

I've only reproduced the author's opening salvo, so follow the link to read it in its entirety. 

Volume 25, Number 1—January 2019
Perspective

Complexity of the Basic Reproduction Number (R₀)

Metric Details
Paul L. Delamater , Erica J. Street, Timothy F. Leslie, Y. Tony Yang, and Kathryn H. Jacobsen
Abstract

The basic reproduction number (R₀), also called the basic reproduction ratio or rate or the basic reproductive rate, is an epidemiologic metric used to describe the contagiousness or transmissibility of infectious agents. R₀ is affected by numerous biological, sociobehavioral, and environmental factors that govern pathogen transmission and, therefore, is usually estimated with various types of complex mathematical models, which make R₀ easily misrepresented, misinterpreted, and misapplied.

R₀ is not a biological constant for a pathogen, a rate over time, or a measure of disease severity, and R₀ cannot be modified through vaccination campaigns. R₀ is rarely measured directly, and modeled R₀ values are dependent on model structures and assumptions. Some R₀ values reported in the scientific literature are likely obsolete. R₀ must be estimated, reported, and applied with great caution because this basic metric is far from simple.

The basic reproduction number (R₀), pronounced “R naught,” is intended to be an indicator of the contagiousness or transmissibility of infectious and parasitic agents. R₀ is often encountered in the epidemiology and public health literature and can also be found in the popular press (1–6). R₀ has been described as being one of the fundamental and most often used metrics for the study of infectious disease dynamics (7–12). An R₀ for an infectious disease event is generally reported as a single numeric value or low–high range, and the interpretation is typically presented as straightforward; an outbreak is expected to continue if R₀ has a value > 1 and to end if R₀ is < 1 (13). The potential size of an outbreak or epidemic often is based on the magnitude of the R₀ value for that event (10), and R₀ can be used to estimate the proportion of the population that must be vaccinated to eliminate an infection from that population (14,15). R₀ values have been published for measles, polio, influenza, Ebola virus disease, HIV disease, a diversity of vectorborne infectious diseases, and many other communicable diseases (14,16–18).

The concept of R₀ was first introduced in the field of demography (9), where this metric was used to count offspring. When R₀ was adopted for use by epidemiologists, the objects being counted were infective cases (19). Numerous definitions for R₀ have been proposed. Although the basic conceptual framework is similar for each, the operational definitions are not always identical. Dietz states that R₀ is “the number of secondary cases one case would produce in a completely susceptible population” (19). Fine supplements this definition with the description “average number of secondary cases” (17). Diekmann and colleagues use the description “expected number of secondary cases” and provide additional specificity to the terminology regarding a single case (13).

In the hands of experts, R₀ can be a valuable concept. However, the process of defining, calculating, interpreting, and applying R₀ is far from straightforward. The simplicity of an R₀ value and its corresponding interpretation in relation to infectious disease dynamics masks the complicated nature of this metric. 

Although R₀ is a biological reality, this value is usually estimated with complex mathematical models developed using various sets of assumptions. The interpretation of R₀ estimates derived from different models requires an understanding of the models’ structures, inputs, and interactions. Because many researchers using R₀ have not been trained in sophisticated mathematical techniques, R₀ is easily subject to misrepresentation, misinterpretation, and misapplication. Notable examples include incorrectly defining R₀ (1) and misinterpreting the effects of vaccination on R₀ (3). Further, many past lessons regarding this metric appear to have been lost or overlooked over time. 

Therefore, a review of the concept of R₀ is needed, given the increased attention this metric receives in the academic literature (20). In this article, we address misconceptions about R₀ that have proliferated as this metric has become more frequently used outside of the realm of mathematical biology and theoretic epidemiology, and we recommend that R₀ be applied and discussed with caution.

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Taiwan FDA & HK HA Reject 2 Batches Of Sanofi Flu Vaccine For `Impurities'

Credit Taiwan FDA

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Although flu season hasn't hit full stride in Hong Kong or Taiwan, South Korea raised their influenza epidemic alert 11 days ago, and both Taiwan and Hong Kong are well into their seasonal vaccination push. 

Yesterday Taiwan's FDA announced the discovery of `impurities' - black and white flecks of unidentified materials - in batches of Sanofi's quadrivalent flu vaccine.   

This follows a similar incident with Sanofi flu vaccines a month ago involving a discolored vial of vaccine, as reported by Taiwan's CDC on October 26th, which was subsequently blamed on a defect in the vial's rubber stopper.

This latest report, however, involves multiple vials, and has led to the suspension and withdrawal of two batches in Taiwan, and one batch in Hong Kong.

First from Taiwan's CDC:

Food and Drug Inspection Agency found two batches of flu vaccine abnormal appearance, not sealed release, please rest assured that the people [Date: 2018-11-26] Company: Food and Drug Administration study examined group (Tifsan)

Food and Drug Administration (hereinafter referred to as the Food and Drug Agency) in response to recently publicly funded influenza vaccine appearance of abnormal events, has been in accordance with risk mechanism immediately for time this year follow-flu vaccine test sealed application, improve the inspection ratio of the appearance of the vaccine, then check to Sanofi Co., company Pasteur Pasteur influenza vaccine and quadrivalent influenza vaccine each batch of abnormal appearance, determine the failure, not sealed release, inviting the public to rest assured.

Food and Drug Department in October this year were accepted Sanofi Pasteur influenza vaccine batch Ltd. 1 (lot number R3J711V, R3J71, 438,190 agents, August manufacture, import early October) and a batch of flu vaccine Pasteur tetravalent (lot R3J721V, R3J72, 80,215 agents, August manufacture, import late October) sealed test applications, perform 10 tests are qualified according to the Chinese Pharmacopoeia, but to strengthen the visual inspection, we found lot R3J711V, R3J71 Pasteur 4 have vaccine influenza vaccine contents black suspension was batch R3J721V, R3J72 P. tetravalent vaccine influenza vaccines nine contents white suspension (Annex shown), and the manufacturer does not meet the Chinese Pharmacopoeia specifications product testing , determine the failure, not sealed the release of the second installment of the vaccine according to the Pharmaceutical Affairs law Enforcement Rules of the provisions of Article 36, the deadline shall be returned or destroyed.

All the manufacture or import of influenza vaccine are required, pursuant to section 74, "Pharmaceutical Affairs Law" law and "bio-pharmaceutical inspection practices of sealed" requirements by the Food and Drug Agency sent to check the temperature of storage and transportation, those who pass the test or reserve samples required for extraction of the amount of drugs, the test individual who pass on the packaging affixed drug test certificate before sale. People to use public expense and at their own expense influenza vaccine Jieyi Chinese Pharmacopoeia, the implementation of the appearance, identification, pH, formaldehyde, protein content, sterility, bacterial endotoxin, abnormal toxicity, egg protein, and inactivated viral titer, a total of 11 quality safety tests using the vaccines are inspected for people, make people feel at ease vaccination.

Meanwhile, the Hong Kong Hospital Authority (HA) has announced the suspension of all flu vaccinations until at least December 1st, as affected vaccines are removed and replenished with new stock.

HA suspends seasonal influenza service

The following is issued on behalf of the Hospital Authority:

     Following the announcement by the Department of Health (DH) today (November 27) on the immediate suspension of the use of a batch of quadrivalent seasonal influenza vaccines (box label: R3J721V; syringe label: R3J72), the Hospital Authority (HA) spokesperson said today that the HA has informed all public hospitals and out-patient clinics to suspend using influenza vaccines of the affected batches immediately.
 
     The HA has immediately suspended the vaccination service in all public hospitals and out-patient clinics. Meanwhile, the HA has requested the pharmaceutical company concerned to replenish the stock with other unaffected batches of influenza vaccines. The seasonal influenza vaccination service is expected to resume gradually from Saturday (December 1).
 
     As of today, there has been no adverse reaction report related to vaccinations of the affected batches of influenza vaccines. Members of the public feeling unwell after vaccination should seek medical advice. The HA will continue to liaise closely with the Department of Health for an update on the latest situation.

Ends/Tuesday, November 27, 2018

Issued at HKT 19:20

Ninety minutes later Hong Kong's CHP issued the following statement: 

Dispatch arrangements of quadrivalent seasonal influenza vaccines

     The Department of Health (DH) today (November 27) was informed by a licensed drug wholesaler, Sanofi-Aventis Hong Kong Limited (Sanofi), that it has decided to take a precautionary measure to suspend the market supply of a batch of quadrivalent seasonal influenza vaccines (SIVs) (box label: R3J721V; syringe label: R3J72) and arrange to dispatch a new batch of quadrivalent SIVs to local private healthcare facilities as soon as possible.

     According to the information provided by Sanofi, around 175 000 doses of the affected batch of SIVs have been imported to Hong Kong and part of the batch has been distributed to the DH, the Hospital Authority and healthcare facilities. Based on the DH’s preliminary statistics, there are around 100 000 doses of unused vaccines in Hong Kong. Sanofi has committed to contact relevant organisations and arrange to dispatch a new batch of vaccines as soon as possible.

     "The DH has immediately suspended the use of the affected vaccines. The DH's services, including the Elderly Health Centres, will suspend seasonal influenza vaccination service until the supplier dispatched a new batch of SIVs. On the other hand, the School Outreach Vaccination Pilot Programme under the DH is not affected by the incident as SIVs used under the pilot programme are supplied by another company," a spokesman for the DH said.

     The DH also reminded residential care home operators and visiting doctors to pay attention on whether they have procured the affected quadrivalent SIVs. If they have, they should suspend the use of such vaccines and contact Sanofi for relevant arrangements.

     "The DH will be in touch with the Hospital Authority and relevant healthcare facilities. We will also closely monitor the relevant arrangements and keep in close contact with Sanofi. So far, the DH has not received any adverse reports in connection with the affected batch of SIVs. Members of the public are advised to consult healthcare professionals if they feel unwell after receiving seasonal influenza vaccination," the spokesman said.

     According to the record of Sanofi, more than 20 million doses of quadrivalent SIVs have been supplied around the world in the current influenza season. So far, it has not received any report about the safety of vaccines being affected.

     According to Sanofi, samples of the concerned batch of quadrivalent SIVs were found to contain white particles by Taiwan authority. The company said that it has not received any report regarding the presence of white particles in the same batch of SIVs currently supplied to Hong Kong, and that there is so far no evidence showing that the quality, safety or efficacy of the SIVs supplied to Hong Kong have been affected, or that safety risk is imposed to those receiving the vaccines.

     The DH has requested Sanofi to submit a full investigation report regarding the presence of white particles in the affected batch of SIVs. The DH has also asked Sanofi and another supplier providing quadrivalent SIVs to Hong Kong to import additional quantities of vaccines to meet the local demand.

Ends/Tuesday, November 27, 2018

Issued at HKT 20:57

Early reports suggest none of these tainted vaccines were distributed in Taiwan, and Hong Kong has not reported any adverse vaccine reactions. Hopefully we'll get an explanation from Sanofi of what went wrong in the next few weeks.

Sadly, despite the benefits and excellent safety record of flu vaccines, incidents like these provide aid and comfort to the strident, and well organized, anti-vax brigade. 

And ultimately, that may produce the biggest negative impact to the public's health to come out of this event.
 

Reminder: Upcoming COCA Call (Thursday) On Multi-State Hepatitis A Outbreak

Credit CDC

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Since March of 2017 a number of states have reported community outbreaks of Hepatitis A - primarily among those who use injectable or non-injectable drugs, the homeless, and their close direct contacts.

CDC Interactive Map

Five months ago, in CDC HAN Advisory On Outbreak of Hepatitis A Virus (HAV) Infections among Drug Users & The Homeless, the CDC reported:

From January 2017 to April 2018, CDC has received more than 2,500 reports of hepatitis A infections associated with person-to-person transmission from multiple states. Of the more than 1,900 reports for which risk factors are known, more than 1,300 (68%) of the infected persons report drug use (injection and non-injection), homelessness, or both.8-11

Since then, reports of community-wide outbreaks have continued, and on November 29th the CDC will hold a COCA Call for healthcare providers (Hepatitis A Outbreaks in Multiple States: CDC Recommendations and Guidance).

Date: Thursday, November 29, 2018
Time: 2:00pm-3:00pm (Eastern Time)

Overview

Hepatitis A is a highly contagious, vaccine-preventable, viral disease spread via a fecal-oral route or by exposure to contaminated food or water. Hepatitis A rates have declined substantially in the United States since the introduction of the hepatitis A vaccine in 1996.

However, since early 2017, the Centers for Disease Control and Prevention (CDC) has observed an increase in the number of community-wide hepatitis A outbreaks in multiple states. For these outbreaks, CDC recommends vaccination for persons who report drug use (injection and non-injection), persons at high risk for drug use (e.g., participating in drug substitution programs, receiving substance abuse counseling or treatment, recently or currently incarcerated), men who have sex with men, and persons experiencing homelessness.

CDC also encourages vaccination in certain settings such as emergency departments and corrections facilities in outbreak-affected areas when feasible. During this COCA call, subject matter experts from CDC will discuss vaccination to stop these outbreaks and current CDC recommendations for the hepatitis A vaccine.

While Hepatitis A infection in a healthy adult usually results in a mild illness of a few week's duration - for some - particularly for those with compromised immune systems, it can be far more serious. 

The CDC describes the way the virus spreads as:

Transmission / Exposure

How is hepatitis A spread?
Hepatitis A usually spreads when a person unknowingly ingests the virus from objects, food, or drinks contaminated by small, undetected amounts of stool from an infected person. Hepatitis A can also spread from close personal contact with an infected person such as through sex or caring for someone who is ill.

Contamination of food (this can include frozen and undercooked food) by hepatitis A can happen at any point: growing, harvesting, processing, handling, and even after cooking. Contamination of food or water is more likely to occur in countries where hepatitis A is common and in areas where there are poor sanitary conditions or poor personal hygiene. In the United States, chlorination of water kills hepatitis A virus that enters the water supply. The Food and Drug Administration (FDA) routinely monitors natural bodies of water used for recreation for fecal contamination so there is no need for monitoring for hepatitis A virus specifically.

For more on Hepatitis A, the CDC has a webpage:

Hepatitis A Questions and Answers for the Public

CDC Update: 10 New Confirmed AFM Cases

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The CDC has updated their weekly surveillance number on cases of Acute Flaccid Myelitis (AFM) - a rare, polio-like illness that has been tentatively linked to several viral infections - adding 10 new confirmed cases since last week's update.

The CDC has now confirmed 116 AFM cases out of 286 patients under investigation (PUIs) in 2018. Investigating each case takes time, and so more from this group may be confirmed in the weeks to come.

Outbreaks of AFM in the United States first surged in 2014, and were originally linked to coincident outbreaks in EV-D68, a relatively rare non-polio enterovirus (NPEV).  A second, similar outbreak was reported in the fall of 2016, but no concurrent outbreak of EV-D68 was noted (see graph below).

This 2018 outbreak looks on track to equal - or even exceed - the first two outbreaks, although better awareness could be affecting the reporting of cases.

While the cause of these polio-like outbreaks remain a mystery, a number of enteroviruses (EV-71, EV-D68, etc.) are high on the suspect list. The CDC notes, however, that most cases have tested negative for any virus.

Paralysis - while exceedingly rare - can appear days or even weeks following a suspected viral infection, which may help explain the lack of positive lab tests. 

It is also possible that this paralysis is due to some sort of autoimmune response to more than one virus,  or even that some unknown virus - not currently picked up by testing - is at work. 

Some excerpts from the latest CDC update: 

What CDC has learned since 2014

• Most of the patients with AFM (more than 90%) had a mild respiratory illness or fever consistent with a viral infection before they developed AFM.
  • Viral infections such as from enteroviruses are common, especially in children, and most people recover. We don’t know why a small number of people develop AFM, while most others recover. We are continuing to investigate this.
• These AFM cases are not caused by poliovirus; all the stool specimens from AFM patients that we received tested negative for poliovirus.
• We detected coxsackievirus A16, EV-A71, and EV-D68 in the spinal fluid of four of 440 confirmed cases of AFM since 2014, which points to the cause of their AFM. For all other patients, no pathogen (germ) has been detected in their spinal fluid to confirm a cause.
• Most patients had onset of AFM between August and October, with increases in AFM cases every two years since 2014. At this same time of year, many viruses commonly circulate, including enteroviruses, and will be temporally associated with AFM.
• Most AFM cases are children (over 90%) and have occurred in 46 states and DC.

Two weeks agp the CDC posted an hour-long COCA Call AFM: What Healthcare Providers Need To Know, published an MMWR Early Release Increase in Acute Flaccid Myelitis — United States, 2018, and held a tele-briefing (audio 5mb) to update reporters.

If you suspect you or your child are suffering from unexplained muscle weakness or paralysis, it is important to seek medical care immediately. The CDC continues to investigate, but until more is known, the CDC can only offer the following advice.

Prevention

Poliovirus and West Nile virus may sometimes lead to AFM.

• You can protect yourself and your children from poliovirus by getting vaccinated.
• You can protect against bites from mosquitoes, which can carry West Nile virus, by using mosquito repellent, staying indoors at dusk and dawn (when bites are more common), and removing standing or stagnant water near your home (where mosquitoes can breed).

While we don’t know if it is effective in preventing AFM, washing your hands often with soap and water is one of the best ways to avoid getting sick and spreading germs to other people. Learn about when and how to wash your hands.

For more information on what CDC is doing, see our AFM Investigation page.

Although Enterovirus D68 and EV-A71 have both been implicated in past cases (along with a number of other viral suspects), for now the jury is out on what has caused the bulk of these cases. A few recent studies include:

mBio: Contemporary EV-D68 Strains Have Acquired The Ability To Infect Human Neuronal Cells

Notes from the Field: Enterovirus A71 Neurologic Disease in Children — Colorado, 2018

Eurosurveillance Review: Association Between Acute Flaccid Myelitis (AFM) & Enterovirus D68 (EV-D68)