More on the Ebola West African epidemic from the WHO Ebola Response Team

The WHO Ebola Response Team has reported in the September 23 issue of the New England Journal of Medicine its analysis of 3343 confirmed and 667 probable Ebola cases collected up to September 14 in 4 of the 5 West African countries to have experienced

Ebola virion CDC Public Health Image Library

cases of Ebola Virus Disease: Guinea, Liberia, Nigeria, and Sierra Leone. The team reports a typical age range of 15-44 years with no difference in gender of those affected. Its estimate of case fatality rate is higher than that noted by the Centers for Disease Control at 71% for people for whom the outcome their infection is known. Based on the number of cases to date, from this they estimate a 95% confidence interval [CI] of 69 to 73% for mortality risk.  The team notes that features of the disease, including a typical incubation period of 11 days to be similar to that for  previous outbreaks. Based on the initial periods of exponential growth of the outbreaks, they have modelled the doubling times are EVD to be 16 days for Guinea, 24 days for Liberia, and 30 days for Sierra Leone, with by November 2 the cumulative reported numbers of confirmed and probable cases predicted to be "5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone", i.e. over 20,000 total cases for this EVD epidemic.

The CDC update to 25 September notes a case count for EVD of 6263, with 2917 reported deaths and 3487 laboratory confirmed cases.


More on the Ebola Virus Disease epidemic in West Africa

Information on Ebola virus from the Centers for Disease Control and Prevention

Ebola VIrus Disease

The WHO Ebola Response Team have reported in the September 23 issue of the New England Journal of Medicine their analysis of 3343 confirmed and 667 probable Ebola cases collected up to September 14 in 4 of the 5 West African countries to have experienced cases of Ebola Virus Disease: Guinea, Liberia, Nigeria, and Sierra Leone. They report a typical age range of 15-44 years with no difference in gender of those affected. Their estimate of case fatality rate is higher than that noted by the Centers for Disease Control at 71% for people for whom the outcome their infection is known. Based on the number of cases to date, from this they estimate a 95% confidence interval [CI] of 69 to 73% for mortality risk.  They note that features of the disease, including a typical incubation period of 11 days to be similar to that for  previous outbreaks. Based on the initial periods of exponential growth of the outbreaks, they have modelled the doubling times are EVD to be 16 days for Guinea, 24 days for Liberia, and 30 days for Sierra Leone, with by November 2 the cumulative reported numbers of confirmed and probable cases predicted to be "5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone", i.e. over 20,000 total cases for this EVD epidemic.
The current Ebola outbreak is the largest to date, now affecting 4 West African countries: in Guinea, Liberia, Sierra Leone and Nigeria. A further outbreak in the Democratic Republic of Congo is considered due to a separate, independent outbreak in the DRC (reported 24 suspected cases and 13 reported DRC suspected Ebola deaths to July 28 - August 28, 2014 (and to 9th September 65 suspected cases, 32 attributed deaths and 14 laboratory confirmed cases).
Risk factors include high fever with or without associated Ebola features (see below) in people from epidemic regions, and in those who have been in contact with Ebola cases, including funeral and burial related, and in those who have prepared or eaten affected bush meat. Key public health measures in unaffected countries include health questionnaires and non-invasive temperature recording at national or remote air, land, water ports of entry.
Ebola virus disease is caused by any of 4 subtypes of the thread-like Ebola RNA virus. EVD causes a

Ebola virion CDC Public Health Image Library

systemic illness in humans associated with bleeding and multi-organ failure (Ebola haemorrhagic fever). The disease was first identified around 40 years in Sub-Saharan Africa and is named after the river Ebola north of Yambuku, in what was then called Zaire, now the Democratic Republic of Congo. Mortality may be as high as 90%, highest with the Zaire strain of the virus, mortality reduced when effective supportive treatment is provided. 

Up to late July 2014, there had been around 3800 cases, with overall reported mortality of

Based on CDC reports

around 61%, in reported outbreaks over the past 4 decades, including the current West African outbreak. In the current outbreak, 1400 cases had been reported up to July 2014 and 1848 cases (1013 deaths) up to 9 August 2014 (4253 cases reported from 1976 to 9th August). A CDC update on West African cases to 22 August from the Centers for Disease Control and Prevention in Atlanta USA reports 2615 suspected cases, 1427 suspected case deaths and 1528 laboratory confirmed cases. A further CDC update to 28th August reported a suspected and confirmed case count: 3069; suspected case deaths: 1552; and laboratory confirmed cases: 1752 in 4 West African countries: Liberia, Guinea, Sierra Leone and Nigeria. One case in a patient from Guinea has been reported from Senegal, with no further cases reported there since August 29, and no further cases reported from Nigeria since September 5.
A further update from the CDC to September 18 notes an increase to a total case count of 5347, total deaths 2630 (laboratory confirmed cases 3095).
The reported mortality rate in the current outbreak was 55% both to August 9 and to August 22, and 51% to 28 August and 49% to September 18, lower than the 66% cumulative mortality rate prior to the current epidemic. Reported mortality appears to vary widely in currently affected countries. This may reflect local differences in presentation for treatment and in disease management, but may also be in part spurious due to uncertainty in case-finding ascertainment.

Ebola virus is one of several viruses, rickettsial, treponemal and other bacterial infections, and non-infectious conditions which may cause serious haemorrhagic illnesses (associated with bleeding internally and into the skin), presenting with a similar spectrum of symptoms, clinical signs and laboratory abnormalities. In the body the ebolavirus targets the lining cells of blood vessels (endothelial cells), white blood cells and liver cells (hepatocytes).
The incubation period can be short, as rapid as 2-3 days after exposure to the virus, either from animal hosts or after contact with infected blood or other human bodily fluids. Typical incubation is reported to be around 8-10 days, in some cases up to 3 weeks before an initial 'flu'-like syndrome. Around half of the affected patients develop a flat and raised (maculo-papular) rash. It has been reported that survivors of the illness may continue to carry the virus for up 2 months after the infection.
Animal vectors of the virus are thought to include the fruit bat (without developing clinical signs). Other animal hosts (through eating fruit contaminated by fruit bats) may include non-human primates, duikers (small antelopes) and pigs.
Treatment should involve a wide range of health professionals, from acute care doctors and nurses, to experts working in laboratory diagnostic services, and public health officials who have an important role in contact tracing and containment of the disease. Care needs to include effective protective clothing for health professionals, disinfection, avoiding re-use of needles, isolation of affected patients, and quarantine.
Current approaches to treatment are supportive, from effective isolation, to monitoring for biomarkers of target organ damage, maintaining fluid and electrolyte balance, if needed, providing oxygen, treating secondary infections, and providing organ support in the event of failure of major organs, often kidneys and liver.
Acquiring effective anti-ebola drugs and vaccines are the subject of current R & D efforts. 
Specific anti-viral treatments, combined with rapid point of care tests, need to be developed, with the aim of achieving medicines which are effective and safe for prophylaxis as well as for treating all stages of the disease. In view of the very high mortality of the disease, new approaches to clinical trials need to be considered. Experimental treatments have been reported to be effective in animal models but not yet tested in humans (see below for compassionate use access to experimental treatments).
An effective vaccine is also a priority, with promising developments of candidate vaccines in recent years. Vaccine programmes will need to take into account the possible development of new Ebola viral strains over time - early September said to have been the start of human clinical testing of a vaccine to prevent the disease and November the estimated start date for clinical trials.

See information on Ebola virus infection from the Centers for Disease Control and Prevention

Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430 Nature April 2014

Ebola virus vaccines: an overview of current approaches

Compassionate use provision to Liberia of experimental antibody-based anti-Ebola treatment 

Romeo's 'Sick health'

@HealthMed One of Romeo's string of oxymorons [Romeo and Juliet Act 1, Scene 1: reflecting on his heart sickness for fair Rosalind], 'sick health' illustrates the challenge of preventing more conventional heart disease - with its long prodrome of apparent health masking the development of sub-clinical disease from unrecognized risk factors, which may however be reversible if identified and addressed.

Why don't more people engage? Many reasons, including fear of finding a problem if tested, difficulty accessing advice/health checks, lack of interest or knowledge of outcomes of 'treatment', lack of confidence in self-efficacy to achieve supporting or first-line life-style changes, in diet, exercise, weight, smoking cessation, alcohol intake ...

To find out more on challenges and solutions for success in behaviour change, look for sources on Theory of Planned Behaviour e.g. this referenced link from the University of Twente.

See my previous blogs on smoking and alcohol.

Stopping smoking: why and how?

Hip fracture risk and smoking

Smoking: literary warnings

Alcohol: literary warnings

Alcohol and the French paradox

Networks and personalized medicine for better drugs?

For more on this theme see 
- article with Andrew Marsh in the inaugural March 2012 issue of Health Policy and Technology
- article in the October 2011 issue of Public Service Review: Science and Technology Review.  

For many individual patients treatments may not exist, may not be very effective, or may result in unpleasant adverse effects. How can prescribers improve drug selection andreduce the harmful effects of medicines? Are there better ways to develop drugs for patients who are difficult to treat?  And what can we do to improve poor adherence to medicines? These elements underpin ‘personalized medicine’, in current use the concept that by considering differences among patients in genetics, disease burden and other factors, more effective and safer drugs can be developed. Personalizing medicine is a path to better disease prevention and control where limited treatment options exist, such as for many cancers, resistant infections and dementia syndromes, and better drug development for new medical challenges. These concepts have in recent years attracted interest from the Royal Society, the Nuffield Council on Bioethics and cognate international institutions.

It is clear that there needs to be consistent investment and support from policy makers and regulators to develop and sustain the academic and industry pharmacology expertise and activity needed for the long-term success of a personalized medicine strategy, so that we can continue to be able to improve the health of the public and individual patients.

NICE is an international leader in developing evidence-based treatment guidelines. Its reports increasingly recognize the need to refine drug choice based on patient characteristics. For example, updated national hypertension guidelines released in August 2011 advise drug selection guided by age, gender, ethnicity, and monitoring, with treatment modified depending on clinical response. NICE also recognizes the need for research on ways, tailored to patient preference, to improve long-term adherence to drug treatment.

Pharmacologists are developing two complementary approaches aimed at achieving “precision medicine” in as many patients as possible: better drug discovery combined with high definition biomarkers for drug selection and monitoring. Network pharmacology brings together sophisticated databases of genetic mechanisms for disease, pharmacological pathways, candidate drugs, and population data describing important variants among individuals in drug handling and responsiveness.  These methods also allow ways to find previously unexpected “off-target” actions of existing or new drugs, which may accelerate discovery of new treatments for serious diseases.

Diagnostic methods are increasingly being used to improve drug selection for individual patients. For example growth tyrosine kinase receptors can be blocked using the biological agent imatinib to treat particular patterns of Philadelphia chromosome-positive chronic myeloid leukaemia, and rare gastro-intestinal tumours. Understanding genes and drugs that influence enzymes that modify drugs in the body, improves accuracy in defining patients who will not respond to a given medicine, or may develop adverse effects.  For example, to minimize risk of serious harm, pharmacogenetic testing is recommended for variability in a specific liver enzyme before deciding whether or not to prescribe the anti-HIV drug abacavir. This knowledge also allows better prediction of a patient’s risk of harm from interactions between treatments, based on recognition of medicines and other remedies that interfere with how drugs are cleared by the body. 

See my previous blogs on 
- preventing adverse drug reactions
- new UK guidelines on managing high blood pressure

New UK guidelines on managing high blood pressure

High blood pressure is a major preventable and treatable risk factor for heart disease and stroke syndromes both in the developed and the developing world.

In an innovative partnership between a UK government agency - the National Institute for Health and Clinical Excellence (NICE) - and a professional organisation - the British Hypertension Society (BHS), NICE guidelines for managing hypertension in primary care were first issued in 2006. Key elements to those guidelines included a stepped care approach starting with different first line options for younger vs. older patients with a 55 year age boundary, and for patients of black African or Carribean origin compared to other ethnic groups. The 2006 guidelines also highlighted risks of new onset diabetes mellitus from beta-blocker treatment.

On 24th August, five years on, NICE, again supported by experts from the BHS, has released updated hypertension guidelines which include several key developments of interest to prescribers and patients. These include adding blood pressure measurements away from the clinical setting to confirm the diagnosis for patients with mild to moderate increases in clinic blood pressure readings. With even higher office readings, advice remains to treat based on those office readings. There is detailed advice both on blood pressure measurement using ambulatory devices as well as more systematic involvement of patients in their own management, supported by home blood pressure readings. It is of course important that any blood pressure monitoring device, whether for clinical or home use, should be validated. A helpful list of validated devices is is listed on the British Hypertension Society's website.

As an update on treatment options, the new 2011 guidelines now suggest systematic use of calcium channel blockers as first line treatment in older patients, with now specific, named diuretics as alternative options for specified indications. The 2011 guidelines for the first time also highlight the clinical and cost effectiveness of evidence-based treatment of hypertension in older patients, and in particular the over 80s.

For more information, see the summary documents and more detailed reports on the NICE website.

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Improving prevention of serious adverse drug reactions

Around 1 in 20  admissions to hospital are due to adverse drug reactions in the UK and other countries with well-developed health services. There are multiple causes for this surprisingly high rate of adverse reactions to medicines: the patient might not have followed established guidelines, such as avoiding alcohol; the wrong drug or dose might have been prescribed; an interaction between two drugs might have been overlooked; the patient's genetic makeup might cause an anomalous reaction; the patient might be taking contaminated drugs bought from unregulated sources on the internet; an unknown adverse reaction to a new drug might have been missed in the development and safety testing of that drug.
Many of the adverse drug reactions are preventable. We need to make sure medical students and prescribers are aware of how to prescribe safely, know common and high risk drugs well and, importantly, to make sure adverse reactions are recorded on patients' records so that they don't happen again. Now that people are able to obtain  prescription drugs on the internet, systems also need to be improved in order to better regulate drugs that are accessed in this way. 
Today's national and international regulations on medicine safety have evolved over than a century. In 1906 came a major focus on medicine safety in the USA, with the Food and Drugs Act signed by President Theodore Roosevelt. The UK went on in 1941 with the Pharmacy and Medicines Act to force manufacturers to list active ingredients on drug packaging, and restrict manufacturers from general advertising about medical claims of their products. The thalidomide disaster of the late 1950s and early 1960s brought about further major improvements: previously drug testing was very limited. Now great care is taken in assessing possible risks of medicines during pregnancy.
Many serious adverse drug reactions happen in people with genetic reasons for reduced ability to handle drugs in the body. Drug leaflets now specify if there is any known 'pharmacogenetic’ information on a medicine. The potential seriousness of these differences between people is shown by the example that the Japanese regulatory authorities are unwilling to license drugs for use in their country unless they have been tested on Japanese people.
New pharmacogenetic provide the opportunity to reduce exposure of patients to potentially harmful medicines based on recognizing an increased genetic risk. And new chemical genomics methods allow ways to identify safer and more effective use of current and new medicines.
For further details on these themes, see my interview with Amy McLeod from Warwick's Knowledge Centre.