Tag Archives: pandemic

Could Measles virus and Ebola virus be working together in the DRC?

Oops! Anti-Vaxers endanger us more than we thought!?!

Measles, resulting from measles virus (MeV) infection can cause immune suppression and “immune amnesia”. MeV infection most often affects non-immune children but can occur in any age group. Immune amnesia is a result of MeV infection. Key cells that remember past infections and produce responses to prevent disease if you get infected again are drastically reduced in number. There’s a lot of measles in the Democratic Republic of the Congo (DRC) right now. Know what else there is there? Ebola virus. In kids. Could Measles virus and Ebola virus be working together in the DRC?

While the ongoing Ebola virus disease (EVD) outbreak in the DRC attracts most of the infectious disease media attention, there is also a huge surge in easily transmitted MeV infections happing at the same time, in the same region of the DRC.[1] To confuse matters, some of the signs and symptoms of EVD – fever, redness around the eyes, diarrhoea – are virtually indistinguishable from those experienced when suffering measles, malaria or cholera.[2,5]

Even more alarming is that there have been more deaths attributed to MeV (2,758 from Jan to late Aug 2019) in the DRC, than to EVD (2,052 reported since Jul 20918) in 2019.[3]

The young have been hit harder by EVD

A particularly unwanted feature of the unwanted 2018-19 DRC EVD outbreak has been the high number of children diagnosed compared to previous EVD outbreaks.[4,7,9,10,13]

Women and children have been disproportionately affected by EVD in the DRC.
Source: United Nations photo.

Of 1,994 deaths to 26th of August this year, 801 (40%) have been children.[6] Children also bear the brunt of disease and death due to MeV infection.[8]

The impact of EVD in children during the ongoing outbreak is unprecedented so what might be different about this outbreak compared to the previous ones? Some things to consider include:

  • are infections occurring when children are inadvertently exposed to the Ebola virus during visits to clinics for other infections such as measles or malaria?[13,15]
  • is infection control among traditional healers, hospitals and health centres worse now than in past outbreaks?
  • are there more infections via breastfeeding – an area that is in desperate need of more research [11]?
  • could there be less shielding of children from their infected family members than in previous outbreaks?
  • is nutrition – and its impact on a healthy immune response – an issue here when it hasn’t been previously?
  • are children somehow being even more affected by dehydration due to vomiting, diarrhoea and blood loss than is usual for EVD? [12]
  • are children being better identified in this outbreak?
  • are more deaths among children due to carers waiting longer because of what initially looks like a “normal” childhood infection before presenting for the specialized medical care needed for paediatric EVD cases?[14]
  • are children being made to work in outbreak-related roles more than has been usual in the past?

Measles virus infection does more than produce measles

It’s been known for over 100 years that MeV infection is immunosuppressive [16,17]; it silences the effective immune response to other infections. Measles also reduces immune memory for 2 to 3 years and can result in increased deaths over this period compared to MeV-immune people.[20]

The mechanism for suppression and amnesia revolves around which cells MeV infects and destroys.[20] You guessed it. It kills off the immune memory blood cells that hold the ability to rapidly respond – with antibodies and killer and control immune cells – to the return of a multitude of viral and bacterial nemeses from days gone past.

These memory B cells and memory T cells are a precious asset to our ongoing health.

After recovery from MeV infection, cell numbers return to normal levels, but we now lack the strength and spectrum of our immune memory. Ironically for MeV, measles doesn’t stop us mounting a good immune response to it though. It resets the clock and restocking our immune pantry with anti-MeV responses. And not much else. We’ve forgotten our infectious enemies.

Restarting the clock on all those accrued immune memories that help you to fend off disease from infections you’ve previously had…thanks a lot, measles virus!

Despite this being known for decades, we don’t hear a lot about it. Which is really strange. Especially in these times of worldwide measles-palooza.

Do you know something that effectively protects us from measles without ablating our immune memory and giving us immune amnesia? The answer to that would be measles-containing vaccines. Not only does a measles vaccine dramatically reduce the risk of serious outcomes like encephalitis and death, but this safe vaccine also lets us keep all our happy immune memories intact.

How does measles make us forget previous infections?

MeV uses CD150, molecules on the surface of our immune cells, as a receptor. It can infect these and hitch a ride to travel all over our body. It also kills these cells.

In one well-observed introduction of MeV to the isolated, immunologically naive island of Rotuma, more than half of the children in the 1910 and 1911 birth-year cohorts died during their first two years of life.[19] Overall, 13% of the population died due to causes attributed to measles. Measles-related deaths occurred at a higher rate among Rotuman women in 1911. As well as children, women have also been over-represented among fatal EVD cases during this latest outbreak. Gastrointestinal complications were the main feature among fatal cases on Rotuma. Tuberculosis-related death rates were also higher among those studied in 1911 than among eth same group in any of the following 50 years. These were impacts attributed to measles.

Could measles be an important cofactor for EVD?

Could measles be paving the way for more EVD cases, and more severe outcomes, among children and women in the DRC? I don’t have an answer and I haven’t seen any data that rule it out or in.

This seems like a question that should be asked and investigated if it hasn’t already been.

Laboratory investigations could shed light on the role of MeV infection preceding Ebola virus disease.
Image by Michal Jarmoluk from Pixabay

This entire MeV story is yet another reason why vaccination programs are such an essential part of a healthy population. The measles outbreaks we are seeing in countries all over the world – apart from being worrying and expensive to contain – indicate that immunity has lapsed in pockets and is absent in entire countries.

Getting measles from MeV infection is only the first step on a path to poor health in the ensuing years. #Vaccineswork in more than just the most obvious ways.

References

  1. Measles vaccination begins in Ebola-hit Congo amid fears of ‘massive loss of life’
    https://www.theguardian.com/global-development/2019/jul/12/measles-vaccination-begins-in-ebola-hit-congo-amid-fears-of-massive-loss-of-life
  2. Mass measles vaccination campaign begins in Ebola-hit DR Congo province
    https://news.un.org/en/story/2019/07/1042221
  3. Measles has killed more people in DR Congo this year than Ebola epidemic, MSF says
    https://www.france24.com/en/20190817-drcongo-measles-killed-more-ebola-epidemic-msf-vaccine
  4. https://www.bignewsnetwork.com/news/262262737/one-in-five-ebola-fatalities-in-past-year-have-been-children
  5. https://www.unicef.org/emergencies/ebola
  6. https://www.unicef.org/drcongo/en/what-we-do/emergency-response/ebola-outbreak
  7. https://www.unicef.org.uk/press-releases/protecting-children-and-engaging-communities-key-to-ending-ebola-outbreak-in-the-democratic-republic-of-the-congo-as-deaths-pass-2000/
  8. https://www.who.int/news-room/fact-sheets/detail/measles
  9. https://www.pbs.org/newshour/health/an-ebola-outbreak-presents-a-new-mystery-involving-children
  10. https://www.savethechildren.org/us/about-us/media-and-news/2019-press-releases/ebola-spike-in-democratic-republic-of-congo
  11. Ebola virus disease and breastfeeding: time for attention
    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32005-7/fulltext
  12. https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/Children-and-Disasters/Pages/ebola_faqs.aspx
  13. An Ebola outbreak presents a new mystery involving children
    https://www.statnews.com/2018/10/19/ebola-outbreak-new-mystery-children/
  14. https://www.voanews.com/africa/children-hardest-hit-ebola-epidemic-dr-congo
  15. Ebola detectives race to identify hidden sources of infection as outbreak spreads
    https://www.nature.com/articles/d41586-018-07618-0
  16. Natural measles causes prolonged suppression of interleukin-12 production
    https://www.ncbi.nlm.nih.gov/pubmed/11398102
  17. Measles Virus-Mononuclear Cell Interactions.
    https://www.ncbi.nlm.nih.gov/pubmed/7789164
  18. https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-83-6-1431#tab2
  19. Extreme Mortality After First Introduction of Measles Virus to the Polynesian Island of Rotuma, 1911
    https://academic.oup.com/aje/article/173/10/1211/184695
  20. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality
    https://science.sciencemag.org/content/348/6235/694

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WHO: Influenza Vaccine Response During The Start Of A Pandemic

https://apps.who.int/iris/handle/10665/325973

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We have often talked about the importance of NPIs (Nonpharmaceutical Interventions) like flu hygiene, school closures, and social distancing in the opening months of any pandemic because the creation, mass production, and distribution of an emergency  vaccine is a difficult, uncertain, and time consuming endeavor.

We were lucky in 2009, in that the pandemic virus required a relatively simple `strain change’, and it did not require – as first feared – two shots spaced a month apart to produce immunity. 

Even so, the first batches of the emergency vaccine arrived after the peak of the pandemic, and in much smaller quantities than predicted.  Fortunately, the novel H1N1 virus proved to be relatively mild compared to past pandemics.

image

Last May, in Manufacturing Pandemic Flu Vaccines: Easier Said Than Done, we looked at a Japanese pharmaceutical manufacturer (Daiichi Sankyo Company, Limited) – which in 2011 received a Japanese government contract to supply H5N1 vaccines for 40 million people in the time frame allotted (6 months) – having to formally apologize for being unable to fulfill the terms of the contract.

Illustrating that gearing up to produce a pandemic flu vaccine in quantity, and in a timely manner – even when we are not hampered by an active pandemic – is a tall order.

While novel influenza is – at least based on recent history – the most likely cause of the next pandemic, it isn’t the only possibility. And non-influenza vaccines are often harder to create.

Despite 16 years of research, there is still no commercially available SARS vaccine. Seven years after MERS emerged in the Middle East, a vaccine remains elusive (see Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism), and twenty years after its discovery, a Nipah vaccine is still in the works.

None of this is meant to diminish the importance of developing, and distributing, a safe and effective pandemic vaccine in the shortest time frame possible. Even if it isn’t made available for the first wave, once it arrives, it could still save millions of lives.

But for that to happen, governments and vaccine manufacturers will have to work together, share information and virus strains, and agree to how (and where) the first vaccines available are allocated.  

The World Health Organization has been working for years to develop a global framework for emergency pandemic vaccine production, and has recently published the results of their Third WHO Informal Consultation, which was held in Geneva, Switzerland, in June of 2017.

This 37-page PDF file outlines the anticipated obstacles and bottlenecks to emergency vaccine production, which includes not only scientific and logistical problems, but political ones as well.

From the Executive Summary:

This meeting report provides an overview of discussions and outcomes from the third WHO informal consultation on influenza vaccine response during the start of a pandemic, held in June 2017. The aim of the meeting was to address challenges and bottlenecks in vaccine response at the start of an influenza pandemic, including issues associated with the decision to start the pandemic vaccine production which might entail the switch from seasonal to pandemic vaccine production.

The first WHO informal consultation on this topic, which took place in 2015, analysed the complexities of vaccine response at the start of an influenza pandemic and provided clarity and understanding among key players on roles and responsibilities of the response. The 2 nd WHO informal consultation in 2016 furthered the discussion to developing principles and processes of decision making of the start of pandemic vaccine production and addressing bottlenecks surrounding the switch. Based on the outcome from the two consultations, the 2013 interim WHO pandemic guidance WHO Pandemic Risk Management Framework (PIRM) was finalized in 2017.

The third informal consultation developed operationalization of the outcomes from the previous two consultations jointly with influenza experts, public health officials, and other stakeholders to address vaccine response at the start of an influenza pandemic, in particular, issues surrounding the potential switch from seasonal to pandemic vaccine production. In addition, the specific challenges for low- and middle-income countries were discussed.

During the consultation, participants drafted an operational framework for pandemic vaccine response, developed a common understanding of an effective pandemic vaccine response, and identified key challenges and potential bottlenecks that would interfere with switching from seasonal to pandemic vaccine production. 

Guiding principles of technical, ethical and political aspects involved in making the decision to start pandemic vaccine production were also elaborated.

Key outcomes from the third informal consultation included the following:

  • A clear, transparent and integrated approach to initiating pandemic vaccine production was proposed; this proposed approach will be further developed by WHO working groups.
  • At the start of a pandemic, WHO will issue recommendations on pandemic vaccine composition and use which will be based on a variety of criteria clearly communicated to all stakeholders involved in the pandemics vaccine response. 
  • Such criteria will be based on risk assessment and to be developed by
    WHO working groups. These will inform the vaccine production decisions.
    Solutions to potential bottlenecks in the pandemic vaccine response at the start of a pandemic should be further prioritized, addressed or operationalized through WHO working groups
  • Communication to clarify the critical responses – including the declaration of a public health emergency of international concern (PHEIC), the declaration of an influenza pandemic, the recommendation to start pandemic vaccine production and subsequent availability of pandemic vaccines should be comprehensively incorporated into global and national pandemic preparedness planning.

These informal consultations clarified critical complexities at national, regional and global levels, and the need for WHO coordinated global response especially the decision to commence the start of pandemic vaccine production based on risk assessment.

The entire document is well worth reviewing, as many of the barriers to developing and distributing an emergency vaccine are not immediately obvious, nor easily solved.

As the chart below illustrates, their 6-months to the first vaccine availability timeline is based on everything going right. 
 

https://apps.who.int/iris/bitstream/handle/10665/325973/WHO-WHE-IHM-2019.5-eng.pdf?sequence=1&isAllowed=y

The following timelines represent ideal circumstances, when all staff, facilities, reagents, equipment and process stages are in place and function optimally. If some activities do not go well, they may take longer and this is indicated by the hatched areas of the chart. Due to the interrelatedness of many of the activities, a delay in one activity would delay others in the timeline.

The reality is, even under the best of circumstances, most of the world would not see a pandemic vaccine for a year, maybe longer. Lesser developed countries, particularly those without domestic vaccine production capabilities, would likely find themselves at the back of the line. 

But no one is guaranteed that they’ll see a vaccine in a pandemic. 

Last year Johns Hopkins presented a day-long pandemic table top exercise (see CLADE X: Archived Video & Recap), where a vaccine was expected `within 6 months’, but turned out to be a failure.

If you don’t have the time to watch the (highly recommended) entire 8 hour exercise, I would urge you to at least view the 5 minute wrap up video. It will give you some idea of the possible impact of a severe – but not necessarily`worst case’ – pandemic.

Clade%2BX%2Brecap.png
Recap Video

While telling people to wash their hands, cover their coughs, avoid crowds, and stay home while sick may seem like an inadequate response to a pandemic – they and other more disruptive measures like school closures, cancellation of public events, etc. will almost certainly be our most powerful weapons until a pandemic vaccine becomes widely available.

DRC: Media Reports 4th Ebola Case In Goma & Updated UK Travel Advisory

DRC%2BEbola%2BMap%2BUK.png
Credit UK FCO

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Twenty-four hours ago many major media outlets were breathlessly reporting that Rwanda had closed their western border with the DRC – going against WHO Guidelines and advice –  a claim that has since been revised to `increased health checks’ having caused a temporary slowdown in border crossings. 

Whatever the real truth of the matter (which I certainly have no way of knowing), the reality is that initial reports from chaotic scenes like those in Ebola zone of the DRC can sometimes be misleading. 

The instant news cycle, and the echo chamber of social media, can further contribute to the confusion.  For these reasons, I try to avoid `breaking news’ reports in this blog simply because the odds of getting it wrong are so high.

Besides, there are hundreds of other news outlets out there. Unless I can add value to the story, I hardly feel the need to join in.

That said, this morning there are media reports of a 4th Ebola case in Goma (see Reuters report Fourth Ebola case found in Congo city, raising fears of faster spread), reportedly the wife of the man who died earlier this week. 

I haven’t found any official confirmation yet, but so far the report appears legitimate. 

While I can’t add any value to that report, this morning the UK’s Foreign and Commonwealth Office has issued updated travel warnings and advice for both the DRC and its neighbor, Rwanda.

Many of the safety concerns with visiting the DRC revolve around terrorism, street crime, and a general lack of security and infrastructure.  But the Ebola outbreak features prominently as well.

By comparison, neighboring Rwanda is described as `. . .  generally safe and crime levels are relatively low, but street crime does occur.

If nothing else, the following FCO update illustrates in stark terms just how difficult the task of containing Ebola in the DRC really is. 

Updated: 2 August 2019
The Foreign and Commonwealth Office (FCO) advise against all travel to:

  • the provinces of Kasaï, Kasaï Central, Kasaï Oriental, Haut-Uele, Haut Lomami, Ituri, North Kivu (except the city of Goma – see below), South Kivu (except the city of Bukavu – see below), Maniema and Tanganyika in eastern DRC
  • areas to the west and east of Kananga, including Tshikapa and Mwene-Ditu (as shown on the map)
  • within 50km of the border with the Central African Republic and South Sudan.

The FCO advise against all but essential travel to:

  • the city of Goma in North Kivu province
  • the city of Bukavu in South Kivu province
  • the districts of N’djili and Kimbanseke in Kinshasa, both of which are south of the main access road to N’djili airport (located in Nsele district).

Public gatherings and demonstrations can be called with little or no notice and can quickly turn violent in DRC. In all instances, you should remain vigilant and be aware of disruptions to journeys around Kinshasa, as well as to and from N’Djili airport. If a demonstration or disturbance takes place, leave quickly and don’t attempt to watch or photograph it.

The security situation in eastern DRC remains unstable. The continued presence of armed groups, military operations against them, intercommunal violence and an influx of refugees from neighbouring countries all contribute to a deterioration in the political, security and humanitarian situation. There are continued reports of attacks and kidnappings, including against staff from NGOs. There have been a number of reported attacks on Ebola responders working in affected areas. See Safety and security

Consular support is severely limited in parts of DRC. The lack of infrastructure throughout the country and continued insecurity in eastern DRC often prevent the British Embassy in Kinshasa from being able to extend normal levels of consular assistance to British nationals anywhere in the DRC other than Kinshasa. There are limits to the assistance the FCO can provide in a crisis, depending on the security and transport situation. You should not assume that the FCO will be able to provide assistance to leave the country in the event of serious unrest.

On 17 July 2019, the World Health Organisation declared a Public Health Emergency of International Concern (PHEIC) following an outbreak of the Ebola virus in North Kivu and Ituri provinces. Cases have been confirmed in Goma since 14 July 2019. New cases continue to be reported across the affected areas. If you are in these areas you should take precautions to minimise your risk of exposure. Further advice is available on the World Health Organisation website.

On 1 August 2019 border restrictions were temporarily put in place for those travelling between Goma and Rwanda, these have since been lifted but the potential for further disruption remains. The latest updates can be found on the World Health Organisation website. Public Health England’s Returning Workers Scheme provides guidance for British nationals who will be returning to the UK from areas affected by the outbreak. See Health

Street crime and robbery, including by individuals posing as plain clothes police, is common. Recent months have seen an increase in such criminal activity in and around the city of Lubumbashi. You should avoid using any taxis in DRC. If you must take a taxi, use a privately booked one. Don’t hail taxis in the street. Beware of gangs promising you cut price gold and diamonds. International non-governmental organisations in Kinshasa and Goma have been targeted. Take extra care at night. See Crime

Terrorists are likely to try to carry out attacks in the Democratic Republic of the Congo. Attacks could be indiscriminate. You should be vigilant, especially in places visited by foreigners. See Terrorism

If you’re abroad and you need emergency help from the UK government, contact the nearest British embassy, consulate or high commission.

Take out comprehensive travel and medical insurance before you travel.