Wednesday, 22 April 2015

Ebolaradication around the corner..?

The downward trend for new, confirmed, Ebola virus disease (EVD) cases continues as we can see in the graph below.

This graph plots the number (each blue data point or dot) of newly confirmed cases in each World Health Organization situation report of summary. The joining lines don't mean anything (the WHO doesn't provide any numbers to place between dots)- they just make it cleared how think go up and down. You can see a little about Monday'itis and its role in the bumpy road to zero cases here.

Below is part of one of the charts from my Ebola virus disease numbers page -  you can get to it from any page on this blog by clicking on that tab up there^.

The line indicating the linear trend of fewer cases over time has a p-value of  0.023 and was
calculated within Tableau Public Edition v9.0
Click on image to enlarge.

I've zoomed in the graph to highlight distinct data points (thanks to Ramon i.e. @HlthAnalysis for helping me learn to make the separately coloured dots I missed so much from my Excel graphs). Without the zooming we can see from the full dataset that it's getting a bit hard to see each data point as time goes by, and case numbers shrink (yay!).



Tuesday, 21 April 2015

WHO reconsiders openly wanting to be a new organization

Yesterday I stumbled across this statement by the World Health Organization (WHO). It's reprinted in full below, but the original version is no longer on the WHO site (more on that in a minute).

It was a powerful human, feeling, mea culpa on the Ebola response along with a very strong and detailed plan to move forward and a fiery desire to be the group that keeps the world safe. I tweeted a few bits of it and stated my respect.


Then I noticed some tweets, including this from @cymeaton indicating that the WHO had released a new and different version.. (also story with more details of the changes, here).
This new revision (copied below the original version) has some nice general changes, removal of contractions, removal of the numbering etc., but is weakened by the deletion of some other phrases leaving it feeling colder and covered by the fingerprints of bureaucracy - something that the first version felt like it was climbing above.

I'm disappointed. 

While I won't delete my tweets from yesterday, I would not have tweeted my respect for this version. Whomever you are that wrote that version - well done. I feel the retention of some of your key parts would have been better received by the world and they show you are indeed ready to move forward, acknowledging that everyone made and makes mistakes, or errors in judgement - that is to human - but that you own those and will seek to do better.
Original Statement 
At time of writing it was found here; some remove but humanising words are underlined

Joint statement on the Ebola response and WHO reforms

Statement by WHO Director-General, Deputy Director-General and Regional Directors, on the Ebola outbreak and response, and reforms to the work of WHO in outbreaks and humanitarian emergencies. 
  1. The Ebola outbreak which started in Dec 2013 became a public health, humanitarian and socioeconomic crisis, with devastating impact on families, communities and affected countries. It also served as a reminder that the world, including WHO, is ill prepared for a large sustained disease outbreak.
  2. We welcome the recommendations of the Special Session of the WHO Executive Board, in particular the proposed assessment of all aspects of the WHO response. Based on the lessons learnt, we commit ourselves to reforms that will enable WHO to play its rightful place in disease outbreaks, humanitarian emergencies and in global health security.

    What have we learned?
  3. We have learned lessons of humility. We have seen that old diseases in new contexts consistently spring new surprises. We have taken serious note of the criticisms of the Organization that, inter alia, the initial WHO response was slow and insufficient, we were not aggressive in alerting the world, our surge capacity was limited, we did not work effectively in coordination with other partners, there were shortcomings in risk communications, and there were was confusion of roles and responsibilities at the three levels of the Organization.
  4. We have learned lessons of fragility. We have seen that health gains –fewer child deaths, malaria coming under control, more women surviving child birth – are all too easily reversed, when built on fragile health systems, which are quickly overwhelmed and collapse in the face of an outbreak of this nature.
  5. We have learned the importance of capacity. We can mount a highly effective response to small and medium-sized outbreaks, but when faced with an emergency of this scale, our current systems – national and international – simply have not coped.
  6. We have learned lessons of community and culture. A significant obstacle to an effective response has been the inadequate engagement with affected communities and families. This is not simply about getting the right messages across; we must learn to listen if we want to be heard. We have learned the importance of respect for culture in promoting safe and respectful funeral and burial practices. Empowering communities must be an action, not a cliché.
  7. We have learned lessons of solidarity. In a disease outbreak, all are at risk. We have learned that that the global surveillance and response system is only as strong as its weakest links, and in an increasingly globalised world, a disease threat in one country is a threat to us all. Shared vulnerability means shared responsibility and therefore requires sharing of resources, and sharing of information.
  8. We have learned the challenges of coordination. We have learnt to recognise the strengths of others, and the need to work in partnership when we don’t have the capacity ourselves.
  9. We have been reminded that market-based systems do not deliver on commodities for neglected diseases – endemic nor epidemic. But we have been encouraged by the desire of the scientific community, manufacturers and regulators to work together in this crisis to develop effective diagnostics, drugs and vaccines for Ebola.
  10. Finally, we have learned the importance of communication – of communicating risks early, of communicating more clearly what is needed, and of involving communities and their leaders in the messaging.

    What must we do?
  11. We will intensify our advocacy with national authorities to keep outbreak prevention and management at the top of national and global agendas.
  12. We will develop the capacity to respond rapidly and effectively to disease outbreaks and humanitarian emergencies. This will require a directing and coordinating mechanism to bring together the world’s resources to mount a rapid and effective response. We commit to expanding our core staff working on diseases with outbreak potential and health emergencies so we will have at least [1,000] skilled staff always available at the three levels of WHO. We will also create surge capacity of teams of trained and certified staff so that we have at least [1000] additional staff available as a reserve force in the event of an emergency.
  13. We will create a Global Health Emergency Workforce – combining the expertise of public health scientists, the clinical skills of doctors, nurses and other health workers, the management skills of logisticians and project managers, and the skills of social scientists, communication experts and community workers. This Global Health Emergency Workforce will be made up of teams of trained and certified responders who can available immediately. A key principle must be to build capacity in countries, with training and simulation exercises.
  14. We will establish a Contingency Fund to enable WHO to respond more rapidly to disease outbreaks. We must ensure adequate resources – domestic and international – are available BEFORE the next outbreak. We welcome the proposal to create a pandemic financing facility.
  15. We will change our way of working. Disease outbreaks demand a command and control approach – very different from the consensus building culture of most of our work in global public health. We commit to clarifying our roles and responsibilities within health emergencies, and organize ourselves to deliver on these roles. We will develop new systems for human resources, planning, logistics, information management and other areas that are so critically important in health emergencies.
  16. We will establish partnerships with other organizations such as OCHA, UNICEF and WFP and other partners, to create a scalable operational response capacity for large scale disease outbreaks
  17. We will strengthen the International Health Regulations – the international framework for preparedness, surveillance and response for disease outbreaks and other health threats. We commit to strengthening our capacity to assess, plan and implement preparedness and surveillance. We will scale up our support to countries to develop the minimum core capacities to implement the IHR. We will establish mechanisms for independent verification of national capacity to detect and respond to disease threats.
  18. We will develop expertise in community engagement in outbreak preparedness and response. We will emphasise the importance of community systems strengthening and work with partners to develop multidisciplinary approaches to community engagement , informed by anthropology and other social sciences.
  19. We will communicate better. We commit to provide information on disease outbreaks and other health emergencies as they occur, rapidly and transparently. We will strengthen our capacity for risk communications and for community engagement.

    We call on world leaders to take the following steps
  20. First, take disease threats seriously. We don’t know when the next major outbreak will come or what will cause it. But history tells us it will come.
  21. Second, remain vigilant. This Ebola outbreak is far from over, and we must sustain our support to the affected countries until the outbreak is over, in the face of increasing complacency and growing fatigue. We must continue to maintain a high level of surveillance. Ebola has demonstrated its capacity to spread – it may do so again.
  22. Third, engage to re-establish the services, systems and infrastructure which have been devastated in Guinea, Liberia and Sierra Leone. This recovery must be country-led, community-based, and inclusive – engaging the many partners who have something to contribute – bilateral and multilateral partners, national and international NGOs, the faith community, and the private sector.
  23. Fourth, focus on prevention. This means investing domestically and internationally in essential public health systems for preparedness, surveillance and response, which are fully integrated and aligned with efforts to strengthen health systems, and included in the scope of development assistance for health. It means working across sectors – health and agriculture in particular. These resources will be substantial, but as the well-known aphorism goes, prevention is better (and less costly) than cure.
  24. Fifth, be transparent in reporting. Accurate and timely information is the basis for effective action. Speedy detection facilitates speedy response and prevents escalation.
  25. Sixth, invest in research and development for the neglected diseases with outbreak potential – diagnostics, drugs, and vaccines. This will require innovative financing mechanisms, and public-private partnerships.
  26. Finally, hold us to account. We commit ourselves to ensuring that WHO is reformed and well positioned to play its rightful role in disease outbreaks and in global health security generally. Some have said the world needs a new organization to be created. We agree, and we want WHO to be that organization.
New version
At the time of writing it was found here

WHO leadership statement on the Ebola response and WHO reforms

The Ebola outbreak that started in December 2013 became a public health, humanitarian and socioeconomic crisis with a devastating impact on families, communities and affected countries. It also served as a reminder that the world, including WHO, is ill-prepared for a large and sustained disease outbreak.

We, the Director-General, Deputy Director-General, and Regional Directors of WHO, are making this commitment of collective leadership to Member States and their peoples in line with recommendations made by the Special Session of the Executive Board on Ebola held in January 2015. We have taken note of the constructive criticisms of WHO’s performance and the lessons learned to ensure that WHO plays its rightful place in disease outbreaks, humanitarian emergencies and in global health security.

What have we learned?

We have learned that new diseases and old diseases in new contexts must be treated with humility and an ability to respond quickly to surprises. Greater surge capacity contributes to a flexible response.

We have learned lessons of fragility. We have seen that health gains – fewer child deaths, malaria coming under control, more women surviving child birth – are all too easily reversed, when built on fragile health systems, which are quickly overwhelmed and collapse in the face of an outbreak of this nature.

We have learned the importance of capacity. We can mount a highly effective response to small and medium-sized outbreaks, but when faced with an emergency of this scale, our current capacities and systems – national and international – simply have not coped.

We have learned lessons of community and culture. A significant obstacle to an effective response has been the inadequate engagement with affected communities and families. This is not simply about getting the right messages across; we must learn to listen if we want to be heard. We have learned the importance of respect for culture in promoting safe and respectful funeral and burial practices. Empowering communities must be an action, not a cliché.

We have learned lessons of solidarity. In a disease outbreak, all are at risk. We have learned that the global surveillance and response system is only as strong as its weakest links, and in an increasingly globalized world, a disease threat in one country is a threat to us all. Shared vulnerability means shared responsibility and therefore requires sharing of resources, and sharing of information.

We have learned the challenges of coordination. We have learnt to recognise the strengths of others, and the need to work in partnership when we do not have the capacity ourselves.

We have been reminded that market-based systems do not deliver on commodities for neglected diseases – endemic nor epidemic. Incentives are needed to encourage the development of new medical products for diseases that disproportionately affect the poor. The scientific community, the pharmaceutical industry, and regulators have come together in a collaborative effort to vastly compress the time needed to develop and approve Ebola vaccines, medicines, and rapid diagnostic tests. In future, this ad hoc emergency effort needs to be replaced by more routine procedures that are part of preparedness.

Finally, we have learned the importance of communication – of communicating risks early, of communicating more clearly what is needed, and of involving communities and their leaders in the messaging.

What must we do?

We will engage with national authorities and request them to keep outbreak prevention, preparedness and response management at the top of national and global agendas.

We will develop the capacity to respond rapidly and effectively to disease outbreaks and humanitarian emergencies. This will require a directing and coordinating mechanism to bring together the world’s resources to mount a rapid and effective response. We commit to expanding our core staff working on diseases with outbreak potential and health emergencies so we will have skilled staff always available at the three levels of WHO. We will also create surge capacity of teams of trained and certified staff so that we have a reserve force in the event of an emergency.

We will create a Global Health Emergency Workforce – combining the expertise of public health scientists, the clinical skills of doctors, nurses and other health workers, the management skills of logisticians and project managers, and the skills of social scientists, communication experts and community workers. This Global Health Emergency Workforce will be made up of teams of trained and certified responders who can be available immediately. A key principle must be to build capacity in countries, with training and simulation exercises.

We will establish a Contingency Fund to enable WHO to respond more rapidly to disease outbreaks. We must ensure adequate resources – domestic and international - are available before the next outbreak.

We recognize that emergency situations demand a command and control approach and we commit to seamless collaboration between headquarters, regional offices, and country offices. Better WHO systems for rapid staff deployments, data collection and reporting, expansion of laboratory services, logistics, and coordination were developed as the outbreak evolved. These systems will be institutionalized.

The massive international response revealed the unique strengths of multiple partners, including UN agencies. We will build on these partnerships, concentrating on capacities that are most critically needed under the demanding conditions of emergencies.

We will strengthen the International Health Regulations – the international framework for preparedness, surveillance and response for disease outbreaks and other health threats. We commit to strengthening our capacity to assess, plan and implement preparedness and surveillance measures. We will scale up our support to countries to develop the minimum core capacities to implement the IHR. We will establish mechanisms for independent verification of national capacity to detect and respond to disease threats.

We will develop expertise in community engagement in outbreak preparedness and response. We will emphasise the importance of community systems strengthening and work with partners to develop multidisciplinary approaches to community engagement , informed by anthropology and other social sciences.

We will communicate better. We commit to provide timely information on disease outbreaks and other health emergencies as they occur. We will strengthen our capacity for outbreak and risk communications.

We call on world leaders to take the following steps

First, take disease threats seriously. We do not know when the next major outbreak will come or what will cause it. But history tells us it will come. This means investing domestically and internationally in prevention and in essential public health systems for preparedness, surveillance and response, which are fully integrated and aligned with efforts to strengthen health systems, and included in the scope of development assistance for health.

Second, remain vigilant. This Ebola outbreak is far from over, and we must sustain our support to the affected countries until the outbreak is over, in the face of increasing complacency and growing fatigue. We must continue to maintain a high level of surveillance. Ebola has demonstrated its capacity to spread – it may do so again.

Third, engage to re-establish the services, systems and infrastructure which have been devastated in Guinea, Liberia and Sierra Leone. This recovery must be country-led, community-based, and inclusive – engaging the many partners who have something to contribute; including bilateral and multilateral partners, national and international NGOs, the faith community, and the private sector.

Fourth, be transparent in reporting. Accurate and timely information is the basis for effective action. Speedy detection facilitates speedy response and prevents escalation.

Fifth, invest in research and development for the neglected diseases with outbreak potential – diagnostics, drugs, and vaccines. This will require innovative financing mechanisms, and public-private partnerships.

This is our commitment; together we will ensure that WHO is reformed and well positioned to play its rightful role in disease outbreaks, humanitarian emergencies and in global health security.

Monday, 20 April 2015

Viruses never forget...but we do..


References...
  1. As Attention Fades, Presidential Commission Says Ebola Is Still A Grave Concern
    http://www.talkradionews.com/health/2015/02/09/attention-fades-presidential-commission-says-ebola-still-grave-concern.html#.VTRa0CHzp1O
  2. Amnesia and Other Side Effects of Epidemicshttp://blog.bioethics.gov/2015/02/05/amnesia-other-side-effects-epidemics/

Wednesday, 15 April 2015

An Ebola virion enters a cell, replicates and leaves....

The code to embed this animation has kindly been provided to me by the team at Scientific Animations IncI'd made a few suggestions about an earlier version (no payment was received), which they added in. 

I think this gives a clear idea, both to the layperson - and to different types of professional microbiologist and virologist - of the processes of this virus as it commandeers a cell to make more of itself.

You can also see the movie one a page at their website site http://ebola-virus-disease.scientificanimations.com/ebola-mechanism-of-action/


Saturday, 11 April 2015

Perhaps Bili|1956 was an Ebola virus disease outbreak...

I didn't blog this one earlier in April when it was mentioned in the literature, but have been reminded of it by Secret Squirrel D in relation to my last post.[1]

The main gist of the Letter to Lancet Infectious Diseases by Colebunders and Van den Ende [2] is that there was a clinically compatible outbreak of disease in Bili, Democratic Republic of Congo in 1956 - 20 years earlier than the first documented and laboratory-confirmed EVD outbreak there - when the DRC was called Zaire.

The 5-week disease outbreak manifested as a fever and rash followed after 10 or so days by bleeding from the mouth and nose and some times bloody diarrhoea. Vomiting blood was a precursor to death. Those without any bleeding survived and recovered after 3-weeks.

About 80 of at least 215 people died (37%), with cases clustering among family groups. A very good survival rate for some filovirus infections. Quarantine efforts and safe burials  seemed to halt the outbreak although some bodies were "recovered" by family for re-burial under more traditional circumstances. Its not clear if this process caused any new infections as it did in west Africa in 2014.

The authors of this letter conclude that the disease course, consumption of monkey meat (but not bats, despite the proximity of colonies) suggests the outbreak could have been due to a filovirus of some sort.[1]

Unfortunately we don't know which filovirus, if a filovirus at all, was responsible since there was no laboratory testing to confirm the specific agent. 

So this one remains a "could be" for now. If only there were stored samples.

References...

  1. Yes, there were signs that Ebola was in west Africa, perhaps as far back as 1973...
    http://virologydownunder.blogspot.com.au/2015/04/yes-there-were-signs-that-ebola-was-in.html
  2. Filovirus epidemic in 1956 in Bili, DRC
    http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70092-7/fulltext

Thursday, 9 April 2015

Yes, there were signs that Ebola was in west Africa, perhaps as far back as 1973...

If a bat carries Ebola virus in the forest, people find signs of infection in humans, publish it and read about it, but no-one remembers, does it make a sound?

Apparently, it now does. The New York times [3] has found that there were studies reporting signs of Ebola virus antibodies in humans in Liberia in samples collected back in 1982.

I'll see your 1982 and raise you 1973! [1] That's when some other samples were collected that were found to contain antibodies to Ebola virus. This doesn't come up in the abstract for this article, but is buried in the Methods and Materials section.
"..antibodies specific for Marburg virus and Ebola virus antigens tested by immunoblotting (21% and 14%,respectively)"
We noted this paper in 2014 - in a piece for the Conversation [2] - and listed some other articles which found similar signs of prior human exposure to Ebola virus or something related. The NYT piece has also captured some of these papers by the looks of it.

In many (most?) cases, these scientific papers can only be reached after paying a fee, or being affiliated with an Institutions that has a good library. Many researchers, clinicians and public health professionals can be described as such.

For me, it seems clear that there were many people aware of the possibility the Ebola virus was pretty much "always" (in the context of our history with Ebola virus disease[EVD]) in the forests within the regions underneath the flyways of some likely filovirus-host bat species.

But seemingly no action was taken on these reports. Was that because...

  • the serology assays were perhaps too non-specific or otherwise unreliable (were they cross-reacting with as-yet unknown filoviruses perhaps (h/t Stephen Goldstein)
  • no-one thought much of EVD's capacity to cause a big outbreak? 
  • we didn't care about smaller outbreaks because they had always been controlled previously?
  • we just didn't care because it was "over there" (in Africa)?
  • we just forgot about it as soon as it was published?
It really doesn't matter what the reason(s) was, because global political willingness to invest the mental and physical capital in a program that could think about, monitor and foresee the risks associated with anything found, and one with a very long view of protecting the public from possible infectious threats...just does not exist. 

This is not a problem specific to EVD of course. Trying to stay ahead of infectious threats will take much more devotion than the world has shown it can muster to date. Even when we can see their potential for harm, there are only so many resources we will mobilize for an infectious threat that is not knocking on our specific door.

References...

  1. Neppert J, Göhring S, Schneider W, Wernet P.
    No evidence of LAV infection in the Republic of Liberia, West Africa, in the year 1973.
    http://www.ncbi.nlm.nih.gov/pubmed/3015288
  2. How Ebola started, spread and spiralled out of control
    https://theconversation.com/how-ebola-started-spread-and-spiralled-out-of-control-32137
  3. Yes, We Were Warned About Ebola
    http://www.nytimes.com/2015/04/08/opinion/yes-we-were-warned-about-ebola.html

Saturday, 4 April 2015

Ebola - the lesser transmission risks are still risks...

The United Nations (UN) Foundation blog has used some pretty strong language in their latest post of the 5 Things to Know on Ebola This Week.

Number 2 on their list stated (by highlighting)...
First detected case of Ebola transmitted through sexual intercourse
Earlier research suggested that three months of abstinence or condom use among male survivors would suffice to prevent the transmission of Ebola through intercourse. But an Ebola patient in Liberia who died last week had just one known risk factor: her boyfriend was an Ebola survivor, treated last September. This is the first case detected of the Ebola virus being transmitted through sexual intercourse, which has necessitated updated recommendations. Read the full story here: http://unfoundationblog.org/ebola/5-things-to-know-on-ebola-this-week-10/#sthash.2HkUbbYT.dpuf
While there is reported to be ongoing testing (and presumably virus genotyping), I've yet to hear publicly the outcome of such testing. 

Perhaps the results are known behind closed doors and perhaps that testing has firmly pointed to a sexual transmission route. The UN post above certainly seems very sure and it also seems that this event has triggered an update to recommendations. There is solid literature about the presence of infectious Ebola virus in seminal fluids so the possibility shouldn't be far beyond belief.[4]

Another possible, albeit also unproven, transmission route is urine. This fluid seems to me to be a far more likely source of trouble. One cannot abstain from urination. So why worry about urine as a risk for transmission of Ebola virus? An EVD case study last year showed very nicely that infectious Ebola virus could be cultured from urine for about 12 days longer than it could be from blood.[1] Viral RNA has also been found in urine for four weeks.[1,2] 

Perhaps urine should be a more noteworthy concern for its potential to remain infectious after blood test become negative. This concern might be greater wherever toilet and hand-washing facilities and sewers, are minimal or poorly maintained.

Urine and seminal fluids are not considered to be major transmission routes for Ebola virus. But let's not forget that it was probably an unlikely transmission event, and route - a single jump from an animal to a human - that triggered >25,000 EVD cases in this epidemic. Even a rare risk must be given serious consideration when such a large public health impact can realistically result.

References...

  1. Kreuels B, Wichmann D, Emmerich P et al. A Case of Severe Ebola Virus Infection Complicated by Gram-Negative Septicemia. N Engl J Med. 2014 Oct 22. 371:2394-2401
  2. Lyon GM, Mehta AK, Varkey JB et al. Clinical Care of Two Patients with Ebola Virus Disease in the United States.  N Engl J Med. 2014 Nov 12. 371:2401-2409
  3. Ebola Virus Disease (EVD). Key questions and answers concerning water, sanitation and hygiene. World Health Organization. http://apps.who.int/iris/bitstream/10665/137181/1/WHO_EVD_WSH_14_eng.pdf?ua=1
  4. Mackay IM, Arden KE. Ebola virus in the semen of convalescent men. Lancet Infect Dis. 2015 Feb;15(2):149-50.

Friday, 3 April 2015

Publishing on 'ebola' is a booming pastime...

One of my jobs since October last year has been to keep up on the literature for Ebola virus and Ebola virus disease. 

At this stage I have a lot of reading to catch up on.


There were 1,858 publications during the 37 years including 1977 to 2013. In 2014 and 2015 (so far), there have been 1,485 publications. 

Click on image to enlarge.
According to a basic search of PubMed using the term 'ebola' - there have been over 1,500 publications - and those are the ones captured by PubMed - to be found using that search term.


Hans Rosling, a micro-outbreak of Ebola in Liberia and trust issues in Guinea...

As is always the case, Prof Rosling can be seen in front of an audience here, providing a beautifully articulated example of how trust in the Ebola virus disease (EVD) treatment centre/unit plays such a pivotal role in (a) the containment of EVD, even witting a family and its contacts, and (b), the likelihood of survival of EVD patients.

Frame taken from a BBC News video which was being hosted in
an African Geographic Magazine story here. Red dots are survivors,
black dots are deaths
Click on image to enlarge.
In this example, which you can listen to in its entirety here, as time went on, trust grew and this fewer transmission occurred and more f those infected, survived.

This would seem to be a great example of what is lacking in Guinea - trust - a lack of trust that others are be able to stop the spread of virus and to save the lives of those infected. Thus people are not presenting for help at all and still being managed in the community - possibly infecting others - or else they are not presenting early enough, before the disease has done too much damage to the person. Trust and communication is increasingly seen as being as important to the successful reduction of cases in Liberia and Sierra Leone as the building of treatment centres - the two must co-occur.

Trust comes from understanding, and that is heavily influenced by communication. Communication of accurate information, of clear and digestible information. Communication to the right people using the moist effective channels is also essential.

It still feels like communication, or at least accurate and successful communication accessing the key important and influential people, may be the weakest part of the response in Guinea. It seems to have been better implemented in Liberia and Sierra Leone - or maybe just better received. Is it a groundwork thing? Difference in the way science is presented in different countries? I know far too little to guess further.

There continue to be more security incidents and other types of refusal to cooperate in Guinea compared to the other two countries afflicted with the Makona variant of Ebola virus. These incidents are a marker of a community that does not believe or trust those claiming to be here to help. And that's a problem for stopping the constant rivulet of EVD cases in Guinea; a rivulet that never became the river of hundreds of EVD cases per week seen in Liberia or Sierra Leone, but was still a flow that seeded infection across the region and the world. A case anywhere is a threat everywhere, to paraphrase others.


Location of laboratories in Guinea, Liberia, and Sierra Leone
 Location of laboratories in Guinea,
Liberia, and Sierra Leone.
From WHO SitRep 01APR2015.
But there may be other issues to consider and question. 

There are fewer treatment centres and laboratories in Guinea than in Liberia or Sierra Leone - strange given that Guinea is larger and that it still has a geographically widespread distribution of cases. 

While it has lately been noted that new cases in Guinea could be adding to the tally more simply because of success in reaching more remote areas, this seems only to add support to the need for better communication and to provide more of a presence in these remote areas. Hopefully, now that this happening through the efforts of the US CDC and others, we will soon see the pay off as a reduction of EVD cases. But the rainy season is near and travel will be made into a muddy mess by that. Time has never been on the side of those trying to stop this epidemic.

Wednesday, 1 April 2015

DNA structure... a primer

A DNA Down Under post
For an organism, or a virus, to grow or replicate, it must make new pieces of itself and assemble those pieces into something functional.

Simple pieces or units can form larger and larger structures. In humans this process starts with proteins then moves on to form cells, then tissues, then organs and eventually whole bodies. 

In viruses the process of assembly is much shorter and less complex than in humans, with proteins assembled into a relatively simple final product, a virion or single virus particle.

So what tells the machinery of an organism to make proteins? Basically, the information is stored by a blueprint or template which is made of deoxyribonucleic acid, or DNA. DNA forms the basis of the genes of an organism or virus. But, even though DNA code has all the information needed to make proteins, it needs to be "decoded" into something that enzymes can recognise. In humans, this process is carried out by the ribonucleic acid, or RNA. RNA is a middle-man or mediator for the early steps required to produce an organism - be it a human, or quite often, a virus. RNA is also needed as a template to make more copies of the DNA. So you can see that there are two processes going on - making proteins from the DNA, and making new DNA copies from the original DNA.

Nucleobases.
What I've just described is a general, pretty simplistic plan. There are exceptions to these rules and a big one is found among viruses. Some viruses don't have genes made of DNA, they are made of RNA instead. Some viruses have thus developed special ways and workarounds to make proteins and copies of their genes. More on that later.


DNA was discovered in 1869 by Friedrich Miescher, a Swiss physician. He found an acidic substance in the nuclei of cells in pus that he named nuclein. 

It was not until 1878 that the German chemist Albrecht Kossel purified the protein away from these nucleic acids, and also later identified its nucleobases (see above) - or component parts.

A pentose sugar (middle) attached
to a monophosphate group (left) 

and the site where a purine or 
pyrimidine nucleobase attaches (right). 
Nucleoside=sugar + base;
Nucleotide=sugar + base 

phosphate group
In 1919 the Lithuanian-American chemist Phoebus Levene identified that units of DNA (a nitrogenous base, a sugar and a phosphate; right) associated into chains. In 1937 these structures were first revealed through X-Ray diffraction thanks to English physicist and molecular biologist, William Astbury. In 1952 Dr Rosalind Franklin captured images of the patterns DNA crystals made when scattering X-Rays. In 1953 American molecular biologist James Watson and English molecular biologist Francis Crick proposed the double-helix model of DNA structure, based on an X-ray diffraction image.

Nucleic acid is one of several macromolecules (big molecules) found in the body (others include proteins and carbohydrates) which are formed by lots of individual molecules (nucleotides) strung together to form a polynucleotide. Each nucleotide consists of a sugar, a nitrogen base and a phosphate group. In RNA the sugar is called ribose (how the name ribonucleic acid comes about), and in DNA it is called deoxyribose which means that it is missing ("deoxy") a carbon atom compared to a ribose sugar.

The combination of a sugar with a any one of five different nitrogen bases creates a nucleoside. The five bases are divided into two categories based on the structure of their molecules; purines have two ring structures (adenine and guanine) while pyrimidines have one (thymine, cytosine and uracil). Adenine, guanine, thymine and cytosine are found in DNA whereas RNA replaces thymine with uracil.

If a phosphate molecule is added to a nucleoside it becomes known as a nucleotide. Nucleotides with a ribose sugar are therefore ribonucleotides, and nucleotides with a deoxyribose sugar are deoxyrobonucleotides. Each nucleotide's name can be shortened to a single letter, A for adenine, C for cytosine, G for guanine, T for thymine and U for uracil.

The chemical bond that links one nucleotide to another is formed between the phosphate group of one nucleotide and the sugar group of the next nucleotide via an ester bond between a carbon atom and an oxygen atom. Two things remain the same no matter how many nucleotides are added to the growing polynucleotide chain; one end of the chain has a free phosphate group and the other end has a free hydroxyl (-OH) group. These ends are called 5' ("five prime") and 3' ("three prime") respectively (there's no Optimus prime).



This naming system comes from the way we present a sugar structure when we draw it on paper. We start at the "top, right-hand" carbon and count in a clock-wise manner. The phosphate group of the previous nucleotide is linked to carbon number 5, and the phosphate group of the next nucleotide is linked to carbon number 3. The naming system, 5' to 3' is used to describe the order of the nucleotides in the DNA strand. Think of the system as being similar to the way European people are taught to read and write - from the left side of a page to right side.