What do we know about the new coronavirus outbreak?

This blog post is correct as of 26/01/2020.

At the end of December 2019, Chinese authorities alerted the World Health Organisation of a new pneumonia with an unknown cause in Wuhan, a large city in Central China. An investigation was then conducted to find out what was causing the pneumonia cases and by the 7^th January, a new coronavirus, named novel Coronavirus (2019-nCoV) had been isolated from the patients in Wuhan.

Since then, cases have been reported in 14 other countries, including Korea, Thailand, Japan, the USA, Canada and France, and in multiple other provinces in mainland China. Currently, there are just over 2000 cases and 56 people have died.

Q: What is 2019-nCoV?

2019-nCoV, as it is called until a name can be decided upon, is a member of the coronavirus family of viruses. It is a large family of viruses that causes a variety of illnesses in mammals and birds. In humans, coronaviruses are often the cause of the common cold. However, also in the Coronavirus family are the viruses which caused SARS (Severe Acute Respiratory Syndrome) and MERS (Middle Eastern Respiratory Syndrome).

SARS caused a pandemic in 2002-3 of about 8000 cases and 800 deaths. It spread across the world from Guangdong in Southern China via Hong Kong, and no cases have been seen since. MERS has caused sporadic cases mostly in those with close contact with camels in Saudi Arabia, and it caused a small outbreak associated with hospitals in South Korea.

Q: So is it SARS? What about “Snake flu”?

No, it’s not SARS. nCoV is closely related to the virus that causes SARS, and is in a group with other “SARS-like” coronaviruses.

But it’s important to realise that they are different viruses, and represent separate spillovers from animals into humans. This also means they may have different clinical courses, including different transmissibility and fatality rates. However, the SARS virus gives us some good starting places for these rates until we have more information.

Some members of the UK press have also called it “Snake flu”. This is because a paper was published last week which suggested that animal that the virus usually lives in (the “animal reservoir” is a snake. This was based on science which has later been debunked, and most scientists think that the likely animal reservoir is a bat, like many other viruses. Furthermore, as discussed above, nCoV is not an influenza virus. So “Snake flu” manages to be wrong on both counts.

Q: What does it look like in patients? How does it spread?

nCoV gives symptoms of fever, dry cough and fatigue. This makes it hard to diagnose, as these symptoms are common to lots of illnesses.

Before these symptoms start, there appears to be quite a long “incubation period”. This is the period between infection and symptoms. The Chinese National Health Commission has said that patients are infectious in this incubation period, which makes this virus much harder to control, because individuals will be moving around normally and unintentionally exposing those around them.

This means infected people can get on a flight and move the virus across the world, or across the country, before they know that they’re unwell. This makes it harder to control than in an illness with a shorter incubation period, because people are more likely to travel in two weeks, rather than in two days.

It spreads between people through droplets, like flu and colds. This makes it quite hard to stop spreading, because usually diseases that spread like this don’t need much contact between people to catch the virus – ie you might be able to catch it from someone coughing on a bus, rather than having to be close for a long time. However, we don’t know this for sure about nCoV because there aren’t many clusters of human to human transmission investigated yet. There is confirmed human to human transmission though (unlike MERS).

Q. How deadly is it?

So far, the fatality rate is about 2%. It’s very difficult at this stage to confirm what the epidemic’s fatality rate will be. This is due to a number of reasons. First, we don’t know how much under-reporting there is. Because the symptoms are not specific to one illness, it’s difficult to pick up on in a doctor’s appointment, and it’s easy to misdiagnose, especially during ‘flu season. Secondly, early on in an outbreak, we tend to see the more severe cases because they’re easier to find and because they die faster – ie within three weeks. Thirdly, in lots of diseases, people that die tend to die faster than the recovery time in those that recover. So for people infected at the same time, we might have recorded deaths of those that have died, but not recoveries of those that have survived because we’ve only been looking for three weeks or so. All of these things may inflate the fatality rate beyond what it really is.

In terms of what we’re expecting to see? The fatality rate for SARS was about 11% overall, seasonal flu is less than 1%.

 

Q: Is it a pandemic?

There have been 26 cases reported in countries other than China, in nearby countries and in countries further afield, like the USA.

Until very recently, there was no evidence of human to human transmission outside of China. However, a case has been reported in Vietnam who does not have travel history to China, but is connected to a family member who does. The most likely explanation here is that there has been transmission in Vietnam, which is concerning.

Other than this, the cases are all from travellers coming from China. The definition of a pandemic is that there is human to human transmission across a wide region such as across multiple continents. So far, the epidemic is not a pandemic, even with this possible transmission in Vietnam.

 

Q: What is being done?

The Chinese public health and science authorities have moved very fast. Not only did they manage to detect a new respiratory virus during flu season (a very impressive feat), they have been very quick to analyse and share data with the global community.

It has taken a few weeks from detection to virus characterisation to genome sequences being released. Furthermore, it appears that the spillover from animals to humans occurred in early to mid-December, so the start of epidemic to detection window is very short. In comparison, it took three months for SARS to be reported internationally, and then another two months for the identification of the virus causing the epidemic.

In China, multiple cities, including Wuhan, have been put on travel lockdown. This means that flights and trains in and out of the cities have been suspended, as well as internal public transport. They have also fast-tracked the building of a new 1000 bed hospital to be completed next week to deal with the massive increase in demand for healthcare. Healthcare workers from all across China have been redeployed to Wuhan, including those who have experience with SARS from 2003.

There has been screening of patient’s temperatures on flights out of Wuhan, and many countries are screening flights that arrive from Wuhan on arrival. However, a detail of the case reported in Canada is worrying – they were symptomatic when they travelled. This means that the screening procedure is not completely effective, and so containment of the epidemic is less likely.

The World Health Organisation convened an Emergency Committee last week to discuss whether this outbreak constitutes a Public Health Emergency of International Concern (PHEIC). This is an announcement that the WHO can make to mobilise funding and the international community. However, they decided at this point that this epidemic is not a PHEIC.  This was due to the lack of transmission in countries outside of China (at the time!), meaning that it was not yet an international emergency. This is not to say that it is not an emergency in China, and the WHO is still providing support to China and neighbouring countries to help in containing the virus. We don’t know yet whether the possible transmission in Vietnam will trigger another Emergency Committee meeting.

Q: How worried should we be?

It’s honestly difficult to tell. On the plus side, the response has been very fast and very strong. It appears from the outside that everything that should be being done, is being done. There is a decent amount of international cooperation and communication, and the scientific machinery is turning, with papers already being published about clinical aspects and modelling being done on the extent of the epidemic, and measure of transmission, such as R0.

On the downside, its long incubation period, non-specific symptoms and airborne transmission route make it hard to control. This is (probably) a virus which you can give to someone near you on a bus, one that you can carry across the world without realising. The likely start of the epidemic being in early to mid-December is positive because it was detected quickly, but negative because it means that there are over 2000 confirmed cases in just over a month.

 

So in conclusion, this is a scary new outbreak, but the response has been good so far. It is a very quickly evolving situation, with hundreds of new cases a day. The international community is watching carefully.

 

References:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30185-9/fulltext

https://www.nature.com/articles/d41586-020-00191-5

https://www.scmp.com/news/china/society/article/3047701/coronavirus-contagious-even-incubation-stage-chinas-health

Click to access 20200124-sitrep-4-2019-ncov.pdf

 

Image: The Yomiuri Shimbun via Reuters

 

 

 

 

90 days into the DRC’s 10th Ebola outbreak

A few months ago, I wrote that only one week after being declared free of Ebola, a new outbreak had begun in the Democratic Republic of Congo (DRC) (viralverity.wordpress.com/2018/08/02/new-ebola-outbreak-in-drc/). This outbreak has turned out to be much larger than the one that began in May, and has become the 5^th largest outbreak ever with 285 cases and 180 deaths, including 25 health care workers.

When I wrote before, the worry that most observers had was that the region of the DRC that this outbreak is in is an active conflict zone, with multiple armed factions causing unrest. It is also close to the border with Uganda, and only 300 miles away from Uganda’s capital Kampala, a city of near 2 million and an international transport hub.

These concerns have turned out to be extremely valid. Whilst no civilian personnel have been killed, two Congolese medical military personnel have died, and two members of an International Federation of the Red Cross (IFRC) safe burial team have been seriously injured. Furthermore, recent violence where 21 civilians were killed led to five days of mourning, interrupting contact tracing (the process by which you find everyone that a person may have exposed to Ebola during the course of their infection eg family members)  and other control efforts, and doubling the number of new cases being reported each day.

Even aside from these particular incidents, the presence of so-called “red zones” where it is unsafe for medical and epidemiological personnel to go due to the conflict, mean that contact tracing is regularly not good enough. Currently about 80% of patients being diagnosed with Ebola have no known epidemiological link to a current case. This means response teams don’t know about all of the transmission chains going on, so contacts of cases are not being found and isolated.

This lack of contact tracing is not only directly due to the conflict. Many members of the community in North Kivu are extremely resistant to the efforts being made to control the outbreak. For example, last week the husband of a case who had died refused to be monitored and wouldn’t go to a treatment centre specifically set up for Ebola. He ended up dying at a health centre that didn’t have appropriate resources for treating an Ebola patient, so he almost certainly exposed many others. For some, there is not only no trust in the government, whose army killed 100 civilians in the region in 2017, but also in UN bodies, who are viewed to be complicit in the violence.

There are also elections soon, scheduled for 23^rd December. At the moment it doesn’t look like there’s any real way out of this that won’t lead to increased tensions. One option is to go ahead with the elections as scheduled. This could divert the national leadership’s attention from the outbreak to re-election; as well as leading to mass population movement and gatherings, which could exacerbate spread of the virus. In general as well, elections can lead to higher tensions, especially in a region already experiencing conflict.  If the elections were delayed, like in Liberia in 2014, this could also lead to significant unrest as the current President is very unpopular, especially in the eastern part of DRC where this outbreak is. It could confirm people’s suspicions that this is a manufactured crisis and a political conspiracy. For now, the Congolese government is working to put the elections on as normal, with sanitary checkpoints and temperature screening at the entrance of polling stations in outbreak areas.

The WHO has decided not to class this as a “Public Health Emergency of International Concern” (PHEIC) despite having said that there is a high risk of regional spread to neighbouring countries.  To be declared a PHEIC, a committee of experts in the WHO have to decide whether or not the outbreak is “extraordinary”, which would mean that a coordinated international response is necessary to prevent a global catastrophe.

It’s not entirely clear why the WHO has declared this outbreak not extraordinary. One of the issues is that the PHEIC legislation is relatively new, and each time a PHEIC is declared it sets a new precedent. It’s possible that the WHO doesn’t want to overuse this, as it is a powerful call to action for the global community – there have been four PHEIC so far for the Swine flu pandemic, a resurgence of polio transmission, Ebola in West Africa and for Zika in South America. There are also political considerations: when a PHEIC is declared, it kickstarts a lot of things, and can include inviting foreign state actors (eg the UK army into Sierra Leone for Ebola in 2014) into the country to help. Whilst this might seem like a good thing, it removes agency from a government who likes to have the reputation that they can handle Ebola outbreaks (and to be fair, they have done well in the past), and at the moment, they have the power to invite international actors to help. Furthermore, it can lead to trade and travel restrictions and further bad press for the DRC.

It seems like the WHO does not want to jump the gun on this, but they were heavily criticised for taking too long to declare a PHEIC for the West African Ebola outbreak in 2014. By the time it was declared on the 8th August 2014, more than 1000 people had died across Guinea, Liberia and Sierra Leone, and the situation on the ground was dire with few resources and international staff being ordered to return home. It is vital that if an international response is needed, it is not left too late to kickstart it – the earlier you can stop an outbreak, the easier it is to stop.

Is there any good news? The best news for this outbreak is that so far 25,000 people have been vaccinated. As this vaccine so far looks to be 100% effective, this has the potential to stop the formation of many transmission chains. Furthermore, Uganda and Rwanda have been conducting what looks to be very effective screening of those crossing the border, and have already isolated some individuals which had concerning symptoms (they turned out to be negative for Ebola). There are also four experimental treatments being offered to patients, although it is as of yet unclear whether they are helping.

In terms of conflict and cooperation, a senior WHO official has said that people living in transmission hotspots are starting to understand more about Ebola. After a recent bout of violence, community leaders in Beni (the urban centre of the epidemic) decided not to have the five day mourning period that affected control efforts before. This suggests that the outbreak is starting to be viewed as a real threat, and that the control efforts are important. There is also an increase in demand for the vaccine, again suggesting increased trust in those attempting to control the outbreak. This will help with contact tracing too: in order to be vaccinated as a member of the public (as opposed to a frontline medical worker), people must be listed as a contact, as only contacts are vaccinated. This will therefore increase cooperation with contact tracing efforts, as those being traced will get something out of it, as opposed to just the annoyance of having daily checks from the response team.

 

This outbreak then is still a huge concern, and it looks like it will last for several more months at least. A break in the violence, and a subsequent step up in the success of contact tracing is likely to be key in preventing this from spreading further.

 

Sources:

@HelenBranswell twitter account is highly recommended for regular updates

https://www.sciencemag.org/news/2018/10/ebola-outbreak-congo-not-yet-international-emergency

At a dangerous point in the Ebola outbreak, residents increase cooperation with containment efforts

https://www.csis.org/analysis/north-kivus-ebola-outbreak-day-90-what-be-done

 

 

 

New Ebola outbreak in DRC

Less than one week after declaring the country free of the Ebola outbreak that began in the spring (https://viralverity.wordpress.com/2018/05/24/ebola-virus-outbreak-in-the-democratic-republic-of-congo-whats-going-on/), a new outbreak has begun in the Democratic Republic of Congo.

Concerns were first raised when 25 cases of “fever” were reported in North Kivu province on the border with Rwanda and Uganda (about 1500 miles from the 9th outbreak which has just finished) on the 30th July.  Six samples were sent to the National Institute of Biomedical Research (INRB) in Kinshasa, where four of them tested positive for Ebolavirus a couple of days later. The ministry of health announced yesterday (the 1st August) that the DRC’s 10th Ebola epidemic has begun.

A map of DRC from Google Maps, showing North Kivu region in red

But what’s the worry? The last outbreak looked like it could be scary with its proximity to the major urban centres of Brazzaville and Kinshasa, but it was quickly controlled using traditional Ebola control techniques and the new vaccine. International teams which were in Equateur province are shuttling across the country to begin the control effort today, and new therapeutics and vaccine doses are already in the DRC.

There was a concern that this outbreak may be due to a different species in the Ebolavirus genus, as the vaccine and new therapeutic ZMapp only work on Zaire ebolavirus. However, it has been confirmed today that the outbreak is being caused by Zaire ebolavirus, which is great news for controlling it.

Traditional Ebola control techniques will of course work on whichever species is causing the outbreak. However, unlike Equateur province, this region of the DRC is an active conflict zone. A report by the UN in March found that there were 4.5 million displaced people in the DRC as a whole, and North Kivu had the largest number of internally displaced people (1,158,000 in total), with 27 families per hour being forced to flee their homes every day in 2017.

I’ve written before about how conflict complicates disease control (https://viralverity.wordpress.com/2016/10/01/war-isnt-just-about-the-military-how-boko-haram-has-ruined-everything/), and with Ebola the difficulty is with interventions like the 21 days of surveillance for every contact of a case, as well as finding the contacts in the first place. High population movement also increases transmission risk to new areas, including into Uganda, where 44,000 refugees crossed Lake Albert in the first two months of 2018. The danger to the teams being dispatched to the region is also a significant concern.

This setting then is extremely challenging for an Ebola response, and the affected population has to be safely accessed before control measures can be implemented. But the DRC has handled Ebola outbreaks well in the past, as has Uganda which will be important if it crosses the border.

A final, speculative thought: a missionary recently returned to Colorado after treating patients in “Eastern Congo”. He had reported severe symptoms on returning home, and was subsequently isolated and tested negative for Ebola. The initial response was that he was probably nowhere near the Equateur outbreak if he was in the east of DRC (although it is possible he was in the east of the Republic of Congo, which is closer to Equateur but never reported a case), and so was extremely unlikely to be treating Ebola. The moderator of the ProMED-mail post concluded “This fuss is more likely due to ignorance of central African geography than to a genuine case of Ebola”. However, it is not impossible that he was actually in Eastern DRC, and treating patients that were part of this outbreak. If this is true, it highlights the ease of international travel of unreported outbreaks, and the importance of global vigilance.

 

For more information:

New Ebola outbreak declared in DRC a week after earlier one declared over

This twitter thread; https://twitter.com/JeremyKonyndyk/status/1024737745737056262

http://www.promedmail.org/post/5941427

 

On the situation in North Kivu:

https://news.un.org/en/story/2018/03/1004542

Click to access drc_factsheet_trim4_2017_en_07022018.pdf

https://www.aljazeera.com/indepth/inpictures/fleeing-drc-uganda-africa-refugee-crisis-180301084715204.html

 

 

 

Ebola virus outbreak in the Democratic Republic of Congo: what’s going on?

If you’ve been able to dig through the news beyond the royal wedding, you may have come across the story about a new Ebola outbreak in the Democratic Republic of Congo (DRC). With the memory of the devastating West African outbreak in 2014 still fresh in everyone’s minds, it is vitally important that this outbreak is stopped before the chains of transmission spiral out of control. But the DRC has been historically good at dealing with Ebola-they had an outbreak last year that barely made the news before it was contained after infecting only 8 people, so why is this one different? And should we be worried about another West African scenario?

What’s going on?

The first cases in this outbreak were reported on the 8^th May 2018, and were in Bikoro, a small town in northwestern DRC.

[Map showing location of Bikoro, where the outbreak was first reported, Mbandaka, an urban centre now reporting cases, and Kinshasa, the capital of the DRC. Image from Irin News: https://www.irinnews.org/news-feature/2018/05/21/ebola-outbreak-congo-what-you-need-know]

With its rural location and small population, Bikoro fits the same profile as most previous Ebola outbreaks in the DRC. This is both an advantage and a disadvantage, as it is harder for the virus to spread, but also harder for healthworkers and public health professionals to arrive quickly with supplies.

The outbreak was announced when two people tested positive for Ebolavirus using the gold standard diagnostic. The first note of concern arose when a probably case was found in a town about 40 miles away on poor roads, showing that the virus has travelled by road, and so the outbreak was probably going undetected for at least a few weeks. There was also evidence of human to human transmission, with caregivers, healthcare workers and funeral attendees among the suspected cases.

The real concern however came when a case was reported in Mbandaka on 16^th May, a city with one million occupants. This is bad enough in of itself, as any disease will travel more efficiently in a densely packed urban population, but Mbandaka also lies on the Congo river. With very few paved roads in the DRC, the Congo river is a major trade route, connecting Mbandaka to the capital Kinshasa (population: 11million) and the capital of the Republic of Congo, Brazzaville (population: 1.9 million). It’s been established that transmission in urban centres in West Africa was key to the size and persistence of the outbreak, so spread to urban populations is a major concern.

As of the 21^st of May there are 58 cases and 27 deaths attributed to this Ebola outbreak.

What’s the response?

What interventions work for Ebola? We’re still trying to figure out the nitty gritty of it, but broadly: isolate patients and treat with fluids, bury those that die safely and with dignity, engage with communities, and follow up all possible contacts of the cases that could be infected.

The first step is to get organised: within 24 hours of the outbreak being reported, the World Health Organisation (WHO) and the Ministry of Health in the DRC set up an Incident Management Centre to be a hub for all news, case reports and intervention activities. Within a few days the WHO and Medecins sans Frontiers (MSF) had sent a team of 50 experts to the region to assess the situation and provide technical and logistical support to the Congolese public health teams. The Wellcome Trust in the UK, and the US government have both made millions of dollars available to fund the response.

Currently over 600 contacts are being followed up to check for symptoms. Those that do develop symptoms will therefore receive prompt treatment, which increases their chance of recovery, and will be isolated before they can pass the virus onto anyone else.

The Red Cross, who conducted over half of the burials in West Africa, and UNICEF have mobilised Congolese volunteers to conduct safe burials and to make speeches in churches, markets and schools in the surrounding area. The aim is to decrease fear and increase community engagement with the response.

There is an exciting aspect to this epidemic: for the first time in history, a vaccine will be used as part of an Ebola response! The vaccine, which uses an Ebola protein expressed on a harmless virus (to be clear, there is no risk of getting Ebola from this vaccine, there is no live Ebolavirus used), was tested initially in the last few months of the West African epidemic, and was shown to have very high efficacy. Whilst it hasn’t been licensed, it is proven safe and effective, and so has been made available on “compassionate grounds”. Ring vaccination, a strategy where contacts of cases are vaccinated, began in Mbandaka and Bikoro on 21^st May. Healthcare workers, both local and foreign, will also be vaccinated. Merck, the pharmaceutical company which makes the vaccine, has provided just over 7000 doses, and will be providing 8000 more in the next few days. Not only will the vaccine help to control the outbreak, but with it being deployed so quickly, this outbreak will provide valuable information about the vaccine, and hopefully lead to licensing.

Usage of the experimental drug ZMapp (which was used on American healthcare workers in West Africa) is currently being discussed by the Ministry of Health, WHO and MSF. This is a bit more controversial, as there is much less definitive evidence of its efficacy. Furthermore, it is administered intravenously over several hours (which has to be observed!), requires refridgeration, and the number of doses available is high limited.

What’s the outcome of all this? Is this a big concern?

At this stage it’s difficult to tell. There are valid concerns for further spread, and if it reaches Kinshasa, it may well develop into a much more complicated epidemic with potential for international spread.

However, the global community appears to have learnt lessons from the West African outbreak. The WHO was accused then of dragging its heels, thinking that the outbreak would fizzle out as Ebola always had done before. They’re certainly getting their act together quickly now. Other countries aren’t taking any chances wither, with screening checkpoints being set up across Central and Eastern Africa at borders and airports. One passenger on the way to Nairobi was intercepted in Entebbe, Uganda, and isolated whilst they tested him rapidly for Ebola at the nearby research unit.

In terms of vaccines and experimental drugs, the study designs have been considered and approved. Ethical debates, about how to obtain necessary data during a devastating outbreak without compromising public health efforts and patient care, have been had. This time, these interventions can be implemented calmly at the start of the outbreak, rather than thrown at it in a panic after thousands of people have already died.

Key to this response however is the public health teams in the DRC. The DRC has a really good handle on Ebola, having had at least 7 outbreaks in the past. They have decent laboratory capacity in Kinshasa, with available helicopters to transport samples quickly from remote regions for testing. Public understanding of Ebola is also higher than in pretty much every other country, so a) there are fewer conspiracy theories about it and communities have a higher acceptance of control measures and b) healthcare workers are good at recognising and reporting cases, even when there is no ongoing epidemic.

So are we worried? The WHO set up an emergency committee last week to discuss the situation, and they decided that the outbreak didn’t meet the criteria of a Public Health Emergency of International Concern (PHEIC). They will meet again if the situation escalates (eg if there are cases reported in Kinshasa), but for now they seem to be happy with the interventions running as they are. It’s impressive that the outbreak was reported two weeks ago, and there are already effective interventions in place to prevent further spread, as well as a vaccination programme already up and running.

It would be bad luck if it spread further, but not out of the realm of possibility. At least this time, everyone is taking it seriously from the start and knows what they are doing. Fingers crossed we can avoid a repeat of 2014.

 

Sources:

Vaccines and drugs: https://www.nature.com/articles/d41586-018-05205-x

Burial teams and community engagement: https://www.reuters.com/article/us-health-ebola-congo/dont-touch-the-bodies-congo-volunteers-race-to-stop-ebola-spreading-idUSKCN1IO2XG

General outbreak news: http://www.who.int/csr/don/23-may-2018-ebola-drc/en/

Reports from the DRC: http://www.promedmail.org/post/5791247

Featured image from https://thenerveafrica.com/18413/ebola-outbreak-in-drc/

 

 

 

 

 

 

 

Monkey malaria and more reasons why we have to stop cutting down forests

It’s not unreasonable to say that pathogens probably jump from animals to humans all the time. We even have a name for them: zoonoses. We’re not aware of most of them because usually they don’t infect many people, and many acute illnesses have fairly similar symptoms: fever, muscle pain, headache etc. So when we find a new bug that has stuck around long enough for us to actually notice it, something interesting is going on.

Human malaria is actually four, possibly five (depending on who you ask), different species of pathogen. The main two are Plasmodium falciparum which causes cerebral malaria, killing hundreds of thousands of children every year, and Plasmodium vivax which doesn’t have a very high mortality rate but causes a lot of people to be very sick across the world. There are also different species that infect many other animals, from birds to mice.

This year, we found a new one for humans: Plasmodium cynomogli. Well ok, it’s been around for longer than this year, but has only ever been recorded in one human outside of lab experiments, in 2014. It usually lives in monkeys, specifically macaques. However, on investigation, a cluster of human cases in Borneo has been found. It’s thought that this species of malaria may be frequently mistaken for another species, which looks similar under the microscope.

So what does this mean? Well first of all, the researchers presenting the cases say that it’s unlikely to cause a public health emergency. For now there’s no evidence to the contrary, but it is worth saying that this is a different malaria parasite which has recently emerged from macaques, and is now a public health problem in South East Asia. It’s called Plasmodium knowlesi and it accounts for 57% of malaria cases in Malaysia, with a 2% case fatality rate. The key here is that both of these species are still fully susceptible to anti-malarial treatment, and with care we can try to make them stay that way.

The more interesting side to this story is that provides us with information about zoonoses. Both of these malaria parasites which have recently emerged have come from macaques which live in the dense forests of Borneo.  Since the 1980s however, it’s lost approximately half of its forest cover. This means that the non-human primates that live in those forests, like macaques, are losing their habitats and food sources. This pushes them out of the forest and into contact with the humans that live on their edges. It’s no surprise then that humans are starting to catch animal pathogens more frequently: all of the patients  in the P. cynomolgi cluster were also infected with P. knowlesi, suggesting a high level of contact with the forest-dwelling macaques.

In this case, we are lucky that the pathogen in question appears to not be too dangerous. But it still complicates efforts to control and ultimately eliminate malaria from the region if new species keep appearing from the animal population, and animal populations are much harder to control disease in compared to human ones-you can’t make a macaque sleep under a bed net. There’s also nothing stopping more harmful pathogens from crossing the species barrier if the opportunity of animal to human contact is there (and the other way around! Human diseases have decimated populations of gorillas and chimpanzees in particular). Nipah virus is an example that springs to mind: it is thought that it emerged from bats as they were forced out of their forest habitat and fed instead on commercial fruit trees, bringing them into contact with the pigs that lived underneath them, which amplified the virus and passed it onto humans.

As humans encroach more into forests and interact more with animals like non-human primates and bats, we give pathogens more opportunities to cross the species barrier. Deforestation then is not only a question of conservation and climate change, but also of human health. Epidemiologists are always searching for the Next Big One, and there’s a decent chance it will emerge from a forest that should never have been disturbed.

 

 

Deforestation in Borneo: http://wwf.panda.org/about_our_earth/deforestation/deforestation_fronts/deforestation_in_borneo_and_sumatra/

Report about Plasmodium cynomolgi: https://www.nature.com/articles/d41586-018-04121-4

Australian Flu: What’s going on?

The news this week across the Northern Hemisphere is filled with worries about “Australian ‘Flu”. A cursory google of the term returns articles about whether we should be worried, reports of deaths and hospitalisation, and referring to it as a “killer strain”.

What is it and where did it come from?

Australian Flu is a specific strain of Influenza A H3N2. The main bit here is the second bit. H3N2 is a normal seasonal flu strain, and has been circulating as seasonal flu since the pandemic in 1968. The other normal circulating Influenza A strain is H1N1, which has been circulating since 1977. You’d also expect to find an Influenza B strain in a flu season.

All flu viruses pick up mutations each year which enable them to evade your immune system and make you sick again, in a process known as antigenic drift. So when we hear about a “new strain” of flu, most of the time it means a new circulating form of H3N2 or H1N1.

Virologists love to name viruses from where they came from. A few examples that jump to mind are Ebola, Zika and Marburg, but those that name influenza viruses are a little vaguer. In the last 50 years, we’ve had Honk Kong Flu, Russian Flu and Asian Flu, and of course the notorious Spanish Flu in 1918. For these, it’s not necessarily inaccurate: influenza strains often originate in South-east Asia, due to the high population density and farming methods; and Russian Flu did actually escape from a laboratory in Russia.

For Australian Flu though, it’s a little different. We don’t yet have the data that would provide us with an answer of where exactly this flu strain acquired its mutations that enabled it to spread effectively, but it is true that it circulated in Australia. However, almost every flu strain that we have has gone through Australia at some point, because their flu season is six months ahead of ours! It’s their flu strains (and others across the Southern Hemisphere) that provide information on what should be included in the vaccine that is given in the Northern Hemisphere, and vice versa. That’s not to say that “Aussie Flu” definitely didn’t start in Australia, but seasonal flu most commonly originates in China or South-East Asia according to genetic data.

Why are there so many cases?

Even accounting for how difficult it is to accurately measure numbers of flu cases (to help with this, go join flu survey! Link at the bottom), it’s true that there may be more cases globally than usual. Australia, whose flu season is sometimes predictive of ours, had a particularly bad flu season, with twice the number of cases reported in 2017 as in 2016. However, in the UK numbers are still comparable with last year’s flu season, and match what we would expect for this time of year.

Why could there be more cases though? As previously mentioned, flu seasons are normally made up of about three circulating strains: an H3N2, an H1N1 and an Influenza B strain, and it’s our best guess of what these three strains look like this year which go into the vaccine. Here’s the rub with this year: it’s been found before that seasons that are dominated by H3N2, as this season is, tend to be more severe and lead to more hospitalisations. Also, a general trait of H3N2 is that vaccines don’t work as well against it as against H1N1 or Influenza B, so fewer people are protected by the vaccine, leading to more cases. (That’s not to say of course that it’s pointless to get the vaccine if you’re in an at risk group! Some protection is better than none, and the more people that get it, the less circulation of the virus there will be, regardless of the level of vaccine efficacy.)

But the deaths!

In terms of flu-related deaths, again a cursory google search reveals multiple concerning reports. It’s difficult to tell at this point whether there are more deaths than usual (Flu is really hard to diagnose), but it’s worth remembering that seasonal flu kills around 500,000 people globally every year, and so death numbers which seem very high may actually well be within normal limits.

If there are more deaths, it could be due to a phenomenon known as original antigenic sin, which I have discussed before (https://viralverity.wordpress.com/2016/11/13/a-small-amount-of-flu-astrology/). Essentially, the immune system is biased towards the first flu strain you encounter as a child, and reacts less effectively to subsequent strains. Therefore, those born after 1968 will have a better immune reaction to H3N2 than those born before, when H2N2 (if you were born between 1957 and 1968) or H1N1 (before 1957) were dominant. This combined with flu being more dangerous in the elderly means that the most at risk group has an increased risk of severe illness in an H3N2 dominated year as compared to an H1N1 dominated year. In summary, those who are more at risk of severe flu in general have an increased risk this year because of the strain which is dominating.

 

It’s very tempting to over-dramatise flu, due to the cultural significance of Spanish Flu in 1918, and a number of recent scary epidemics that resulted in many unexpected deaths. At worst, this should just be a nasty flu season.

Sources

FluSurvey! Help with flu-like symptom monitoring to inform better public health data https://flusurvey.org.uk/

ProMedMail Archive number 20180104.5534440 (general case numbers, information about Australia, and information about H3N2 dominated flu seasons)

Lemey et al 2014: Shows genetic evidence that most flu epidemics seem to start in South-East Asia or China  (http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003932)

http://www.bbc.co.uk/news/health-42602394 (General information about UK numbers)

 

 

 

Colonialism, racism and disease

As multiple terrifying hurricanes make their way through the Caribbean, many people are concerned about the effect it will have on these nations. Of particular concern is Haiti, as it is still recovering from Hurricane Matthew last year, as well as a major earthquake in 2010. Of course, this means that articles are being written about Haiti as a country, and one stood out in particular to me with this sentence:

“Haiti has been blighted by natural disasters, poor governance and violence in recent years, a turnaround from its days in the 18th century as one of the richest colonies in the French empire, with huge wealth from sugar cane and coffee plantations.”

That’s right folks, today we’re going to talk about how colonialism is still impacting free countries.

So why is this sentence so wrong? I imagine a lot of people would read that sentence and say well yes, these are facts. The issue that I take with it is a) suggesting that being a colony was a positive thing for Haiti (spoiler alert: being a colony is never a positive thing) and b) suggesting that it is the Haitians fault that they are poor-the “poor governance” and “violence”.

I’m not denying that Haiti has had its troubles with in-country violence and poor governance, but it’s wrong to suggest that it these are independent of their history, and that colonialism was positive. Haiti won its independence from the French through a successful slave rebellion (hilariously, they were inspired by the French revolution), after years of fighting in 1804. Anyone who accepted that Haiti was a republic ruled by black people and rejected the French could become a citizen.

You may recognise this date as being in the height of colonialism (the European colonial period was from the mid-16^th Century to the mid-20^th Century), and it made France look weak. What’s more, the other colonial powers did not want to encourage their own colonies built on slavery to fight for their independence.

So France made Haiti pay for it. Literally. After independence, Haiti was completely ostracized from all trade deals and international diplomacy by the white ruled nations which held power (also let’s not forget racism-the idea that a country could be successfully ruled by black people was directly opposed to the status quo at the time). Clearly, this made it difficult for Haiti to set up profitable relationships with other countries, especially needed after 13 years of civil war. So France kindly offered to bring them out of exile-as long as Haiti paid France 150 million gold francs as reparations, to pay them back for all the sugar and people they used to own. Haiti didn’t finish paying this debt until 1947.

France and the colonial powers therefore destroyed any hope that Haiti had of becoming a functioning and prosperous country. Despite at one point having the natural resources to make money (as the French found-that’s why they were so angry to lose it), they had to pay all the money they had (plus money they didn’t) to even get a seat at the table.

If you’re wondering why me, a disease person, is writing about colonial politics and racism, it’s because they’re not separate. The money that Haitians should have been getting from trade, or just not giving to the French, would have gone into building infrastructure: sanitation, schools, hospitals. In addition, a lot of the natural resources in Haiti were plundered for more money to give to the French, including cutting down a large proportion of their trees, causing flooding and soil erosion. As a direct result of colonial punishment, Haiti was made a lot more vulnerable to diseases such as cholera, as we saw when it was introduced to the island in 2010 and spread (and is still spreading by the way) rampantly.

But the French don’t cause hurricanes, I hear you say. Setting aside for another day the ideas that climate change disproportionately affects poor people of colour, and that ex-colonial powers have heavily benefitted from fossil fuels in a way that Haiti never has, a country’s resilience to natural disasters is strongly linked to its level of wealth. With heavy deforestation and weak infrastructure, any natural disaster is going to affect the people who live in Haiti extremely negatively-compare the effect of the 2010 earthquake in Haiti to any earthquake in Japan for example.

Of course, Haiti has had its fair share of dictators, leading to the violence and poor governance the article refers to. But it’s not unreasonable to link this to the political instability brought on by extreme poverty.

So when you read about Haiti, and the troubles it’s had, and how it once was a prosperous country: remember that it was the colonial powers, and the French in particular who made it impossible for Haiti to remain prosperous when it became independent. Remember that the legacy of racism and colonialism is still killing people today, and that it’s not just hurricanes and earthquakes and cholera.

http://library.brown.edu/haitihistory/11.html

http://www.slate.com/articles/life/history/2015/08/the_most_successful_slave_rebellion_in_history_created_an_independent_haiti.html

Haitian Revolution (1791-1804)

 

 

 

 

Mysterious outbreak alert

There’s been a number of concerning outbreak reports recently-there’s cholera in Yemen, Ebola in DRC and Hepatitis E in Niger. One that rings a particular number of alarm bells though, is the announcement of a cluster of unexplained deaths in Liberia.

You may remember Liberia as being one of the three countries severely affected by Ebola in the outbreak beginning in 2014 (well technically 2013 but it was the end of December so hey ho). This outbreak devastated the already weak healthcare system of Liberia, and so it would struggle to deal with another serious outbreak.

On the 22nd April, an 11 year old was admitted to hospital and died within the hour, complaining of nausea, vomiting and mental confusion. The real concerning thing here is that the child had attended a funeral of a religious leader the day before. The Ebola outbreak was strongly linked to traditional funeral rites, which involve kissing and touching the body. More generally, funerals are related to outbreaks all over the world, especially those involving food or water borne pathogens.

On the 27th April, a man presented to a hospital in Monrovia with fever, headache and vomiting. He had also attended the funeral, and also died. His partner, who had not attended the funeral, also became ill and died shortly afterwards. The human to human transmission is tragic, but not necessarily too worrying-even if this disease was purely foodborne, it is easy to contaminate water or food in a shared home and pass the disease on. The problem here is that these people had travelled to the capital city of Monrovia, which is densely populated. If this unknown disease is highly transmissible between people, then he could have seeded multiple transmission chains.

Ok I’ll stop scaremongering now. As of the 4th May, 28 cases and 12 deaths have been reported. 26 of these people attended the funeral, and the number of new cases has dropped after April 25th. These two pieces of information together strongly suggest a single exposure at the funeral (whether this is the body, or contaminated food/water) and minimal onwards transmission. This is known as a point source outbreak, and is common with foodborne illnesses or toxins.

The health ministry in Liberia has learnt a lot from Ebola. They picked up on this outbreak and notified the WHO quickly, and have tested patient specimens for 28 different diseases, including Ebola and Lassa (a local haemorrhagic fever). Their conclusion is that it is probably a meningitis outbreak, which is treatable and preventable.

This brings up a couple of interesting points. The first is that it shows how difficult it is to classify the pathogen causing an outbreak based on symptoms. The main idea that occurred to me (and probably to a lot of people to be honest) was Ebola, especially because of the funeral connection. Another was cholera. These two pathogens are very different to each other and meningitis, with different exposures, pathologies and control measures. And yet, from the information of symptoms and some idea of the exposure, all seem likely. The other interesting point is that meningitis outbreaks have not been seen before in Liberia. They usually occur in the “meningitis belt” of Africa, which includes countries such as Mauritania, Sudan, and Ethiopia; which have long and hot dry seasons. This suggests that climate change is having an impact on where meningitis is going to cause outbreaks. This idea of climate change affecting disease spread is normally applied to vector borne diseases, where, for example, the mosquito can live in more temperate areas as they warm up. The idea of it applying to meningitis is concerning, although there is a vaccine at least.

So this outbreak is hopefully solved. But if it’s not, at least it’s not Ebola!

http://www.promedmail.org/post/5023267

http://www.who.int/csr/don/05-may-2017-unexplained-cluster-of-deaths-liberia/en/

The story of vaccination: not quite what you think

We’ve all heard this story at some point in our education (I think I had to draw a cartoon when I was about 8): the story of Edward Jenner and smallpox vaccination.

The story goes like this. Milkmaids have been figures of purity and beauty in all english-speaking literature for hundreds of years. This is likely to be because, unlike what shows like Game of Thrones and The Tudors would have you think, most people would have been walking around with the pits and scars of smallpox on their faces and bodies. Milkmaids were the exception to this, and their exceptionally clear skin led to this enshrinement in myth as figures of beauty.

Jenner realised this, and wondered why milkmaids did not contract smallpox with the same regularity as the rest of the population. He realised it was because they seemed to contract cowpox and that this protected them from getting smallpox. With the help of Sarah Nelmes, a millkmaid, Blossom the cow, and a small boy called James Phipps, Jenner developed the practise of vaccination.

So that’s all well and good, and Jenner rightly deserves his place in the history of science (although it is worth noting that his paper was rejected from the peer reviewed Proceedings of the Royal Society B because he only had a sample size of one) but as with most science, he most certainly did not come out of a vacuum.

In 1717 (32 years before Jenner was born), Lady Mary Wortely Montagu wrote to her friend, Sarah Chiswell, describing the practise of variolation. Variolation differs from vaccination in that the former involves introducing material from an infected person into a healthy person (in this case bits of smallpox sores) as compared to vaccination which normally uses almost harmless weakened or dead pathogens to achieve the same effect of immunity.

Lady Montagu lived in Istanbul with her husband, who was the British Ambassador to the Ottoman Empire. She noticed a group of elderly women that would go to any house that had reported smallpox cases and take a vial of the “best sort of smallpox” (ie material from a mild infection) ready to place into the veins of willing and happy recipients. She had the procedure performed on her two young children, and brought the practise to Britain. Well, she tried, but given that the practise came from somewhere foreign, and Lady Mary was a woman (and to be fair, it is quite dangerous), she received a lot of resistance. It was a combination of her words reaching the Princess of Wales and an epidemic of smallpox in London in 1721 that led to the experimentation and adoption of variolation in Britain.

So is Lady Montagu the one to thank? She brought the practise to Britain, which helped disseminate it further because of the power of Britain at that time. Her advocacy was instrumental in its widespread adoption and therefore Jenner’s consideration of it when he was developing vaccination.

It is worth noting though, that she did not come up with the practise, she simply observed something which had been ongoing in Turkey for centuries. In fact, the earliest recorded clear reference to variolation is from China in 1549, with the practise becoming widespread in China later that century. It made it to the states via the slave trade, and it was recorded that many of the slaves from West Africa had been inoculated.

It is therefore an oversimplification to suggest Jenner is the originator of innoculation. His work relied on centuries of practise of non-Europeans, as well as the advocacy of Lady Montagu. Like much of science, the contributions of non-European culture and practises, and those of women (in this case Lady Montagu and the Turkish women who performed variolation), have been largely skated over in order to venerate the white englishman who came at the end.

That’s not to discredit Jenner (he really is a pioneer) but all scientists are standing on the shoulders of giants.

Making a vaccine ~before~ a disaster? How novel!

This week at Davos, the annual world economic forum, a new private-public coalition was launched. It’s the Coalition for Epidemic Preparedness Innovations (CEPI), and its aim is basically to stop another Ebola happening.

So how are they doing this? The main way is by pouring funding into the development of new vaccines, which would not be economically viable to make as part of a traditional business model. This is because they are aiming to make vaccines for diseases that (so far) have only affected a few hundred people, but which might later become hugely important. This is what happened with Ebola: before 2013, the largest outbreak only infected 425 people. It was a disease that was viewed as self limiting and easy to control, even when cases were rising steadily above 10,000 in West Africa.

In some respects we got lucky with Ebola: there was a vaccine that was ready to go into humans, for which all of the animal work had been done for. This was because fears of bioterrorism after 9/11 ended up directing a lot of funding to diseases, like most of the haemorrhagic fevers, which paralyse nations with fear and damage healthcare systems even when case numbers remain low.

CEPI is aiming to get vaccines for a few key scary diseases to as developed a stage as possible so that should an outbreak happen, larger trials can be carried out. A quick note, is might seem callous to use an outbreak for a vaccine trial, but for rare diseases which only exist in epidemic form (like Ebola) it is the only way. Also, the vaccine trials are often protective-the new Ebola vaccine was so successful in its trial in Sierra Leone that the trial was stopped and everyone received the vaccine who needed it.

The idea behind CEPI is brilliant, a way to get around the difficulties posed by pharmaceutical companies operating in the free market. It would have been a high risk business proposition to make an Ebola vaccine before 2013, because it was essentially unpredictable that this specific disease would devastate West Africa to that extent. CEPI is also working vaccine access and equity for those it funds, as well as ensuring a rapid response to any outbreak that occurs.

On the other hand though, vaccines are only one part of disease control. Whilst an Ebola vaccine would have been useful, the biggest reason that the virus was so devastating was due to weak healthcare systems ravaged by decades of unrest and civil war, and a slow and inadequate international response stifled by bureaucracy. It is important that we don’t view the making of vaccines as the only way to prevent another disaster, when actually the strengthening of healthcare systems in low income countries is the single best way to cope with any outbreak. Think of when Ebola cases were imported to high income countries such as the UK or the US: the patients were put straight into state of the art isolation wards, with highly trained medical staff looking after them with the resources needed.

A selection of CEPI’s diseases:

1. Filoviruses: the family that includes Ebolavirus also has Marburg, and a new filovirus found exclusively in Spanish bats-we wait with baited breath to see if it jumps to humans.

2. Coronaviruses: these are where your cold comes from, but also SARS and MERS. The latter has been bubbling away in the middle east for a few years, until it broke out in South Korea., signifying that it can easily spread between humans without relying on its reservoir species of the camel.

3. Plague: yup this is still a thing

4. Lassa fever: a nasty haemorrhagic fever endemic to Sierra Leone. It’s spread through rats, and complicated diagnosis of the first few Ebola cases in the country.

5. Nipah: A scary little virus that behaves much like Ebola used to-it pops up, infects a few hundred people, kills about half and then goes away. It spread from fruit bats to humans via pigs due to deforestation and intensive pig farming, and it’s what the film Contagion is based on.

…and there’s also a few more, including Zika.

Take home message: CEPI is brilliant, we’re starting to pre-empt epidemics as opposed to react to them, when it is too late. However, unless we help low income countries to strengthen their health systems (by, oh I don’t know, forgiving their debts), deal with climate change and deforestation, and look at safer farming practises (like not feeding pigs with duck poo, honestly that’s like a supervillain plan to get a new pandemic flu strain) then we will still struggle with a new disease that we couldn’t anticipate emerging from a previously undisturbed rainforest somewhere.

CEPI proposal to the WHO:   http://www.who.int/medicines/ebola-treatment/TheCoalitionEpidemicPreparednessInnovations-an-overview.pdf