ALS EBOLA

Ice Bucket Challenge
From Wikipedia, the free encyclopedia



Doing the ALS Ice Bucket Challenge
The Ice Bucket Challenge, sometimes called the ALS Ice Bucket Challenge, is an activity involving dumping a bucket of ice water on someone's head to promote awareness of the disease amyotrophic lateral sclerosis (ALS) and encourage donations to research. It went viral on social media during July-August 2014.[1][2] In the US, people participate for the ALS Association, and in the UK, people participate for the Motor Neurone Disease Association.[3]
The challenge dares nominated participants to be filmed having a bucket of ice water poured on their heads and challenging others to do the same. A common stipulation is that nominated people have 24 hours to comply or forfeit by way of a charitable financial donation.[4]
Contents
[hide] 
1 Origin
2 Shifting focus to ALS
3 Rules
4 Effects
5 Criticism
6 Notable participants
7 References
8 External links
Origin
The origins of the idea of dumping cold water on one's head to raise money for charity are unclear and have been attributed to multiple sources. From mid-2013 to early 2014, a challenge of unknown origin often called the "Cold Water Challenge" became popular on social media in areas of the northern United States. The task usually involved the option of either donating money to cancer research or having to jump into cold water.[5]
One version of the challenge, which took place in Salem, Indiana as early as May 15, 2014, involved dousing participants with cold water and then donating to a charity;[6] for example, the Auckland Division of the Cancer Society of New Zealand.[7] As with similar challenges, it was usually filmed so footage can be shared online.
The National Fallen Firefighters Foundation popularized the "Cold Water Challenge" in early 2014 to raise funds as an unsanctioned spin-off of the polar plunge most widely used by Special Olympics as a fundraiser.[8]
On May 20, 2014, the Washington Township, New Jersey fire department posted a video on YouTube participating in the "Cold Water Challenge" with fire hoses. Participating members of the department were subsequently punished for using fire department equipment without permission.[9]


Atlanta Falcons players, coaches, and staff take the Ice Bucket Challenge
Shifting focus to ALS
The challenge first received increased media attention in the United States on June 30, 2014, when personalities of the program Morning Drive, which airs weekdays on Golf Channel, televised the social-media phenomenon, and performed a live, on-air Ice Bucket Challenge.[10]
Soon after, the challenge was brought to mainstream audiences when television anchor Matt Lauer did the Ice Bucket Challenge on July 15, 2014 on NBC's The Today Show at Greg Norman's challenge.[11][12]
On the same day, golfer Chris Kennedy did the challenge and then challenged his cousin Jeanette Senerchia of Pelham, New York, whose husband, Anthony, has had ALS for 11 years. Kennedy "was the first ... to focus the freezing fundraiser on ALS research."[13]


Green Bay local radio and TV personality John Maino performs the ALS Ice Bucket Challenge
Former Boston College baseball player Pete Frates, who has ALS, began posting about the challenge on Twitter.[14] Frates is a patient advocate who was awarded the Stephen Heywood Patients Today Award in 2012 for his fundraising and advocacy work.[15] Frates' Boston College and sporting connections became an initial focus of the challenge and strengthened its focus on ALS.[16]
The President of the United States, Barack Obama, was challenged by Ethel Kennedy but declined, opting to contribute to the campaign with a donation of $100.[17] Justin Bieber,[18] LeBron James,[19] and "Weird" Al Yankovic[20] also challenged President Obama after completing the Ice Bucket Challenge. Former president George W. Bush completed the challenge and nominated Bill Clinton.[21] The Prime Minister of the United Kingdom, David Cameron, was challenged by both Alex Salmond[22] and Russell Brand,[23] but also declined in favour of a donation.
Rules
Within 24 hours of being challenged, participants have to record a video of themselves in continuous footage. First, they are to announce their acceptance of the challenge followed by pouring ice into a bucket of water. Then, the bucket is to be lifted and poured over the participant's head. Then the participant can call out a challenge to other people.
Whether people choose to donate, perform the challenge, or do both varies. In one version of the challenge, the participant is expected to donate $10 if they have poured the ice water over their head or donate $100 if they have not.[24] In another version, dumping the ice water over the participant's head is done in lieu of any donation, which has led to some criticisms of the challenge being a form of "slacktivism".[25] Individual videos have included the participant saying that they will be making a donation along with performing the challenge.


Governor of South Carolina Nikki Haley does the ALS Ice Bucket Challenge


Matt Damon's Ice Bucket Challenge video
Effects
In mid-2014, the Ice Bucket Challenge went viral on social media and became a pop culture phenomenon, particularly in the United States, with numerous celebrities, politicians, athletes, and everyday Americans posting videos of themselves online and on TV participating in the event.[4][17]
According to The New York Times people shared more than 1.2 million videos on Facebook between June 1 and August 13 and mentioned the phenomenon more than 2.2 million times on Twitter between July 29 and August 17.[26] Mashable called the phenomenon "the Harlem Shake of the summer".[11]
Prior to the challenge, public awareness of the disease amyotrophic lateral sclerosis (ALS) was relatively limited; the ALS Association state that prior to the challenge going viral only half of Americans had heard of the disease,[26] often referred to as "Lou Gehrig's disease", after the famous baseball player Lou Gehrig, who publicly revealed his diagnosis in 1939.[27]
After the Ice Bucket Challenge went viral on social media, public awareness and charitable donations to ALS charities soared. The New York Times reported that the ALS Association had received $41.8 million in donations from July 29 until August 21. More than 739,000 new donors have given money to the association, which is more than double the $19.4 million in total contributions the association received during the year that ended January 31, 2013.[28] Similarly, the ALS Therapy Development Institute reported a ten-fold increase in donations relative to the same period in 2014,[29] with over 2,000 donations made in a single day on August 20, 2014, while Project ALSreported a 50-fold increase.[30]
The ALS Association, which had raised $64 million in all of 2013, raised more than $10 million on Thursday, August 21, 2014 alone.[31]
In the United Kingdom, people have also been facing the challenge for the Motor Neurone Disease Association,[3] MND Scotland[32] and Macmillan Cancer Support.[33]
On August 22, 2014, the Detroit Free Press reported that scammers were taking advantage of the challenge.[34] The scam usually involves sending an email containing promises of watching videos of the challenge and then installing either spyware or malware on the user's computer or taking them to a fake website where they are asked to enter personal information.[34]
Criticism
A number of criticisms have arisen relating to the campaign, accusing it of being self-congratulatory,[35] focusing primarily on fun rather than donating money to charity, and as an example of substituting a trivial activity for more genuine involvement in charitable activities. Writing in The Daily Telegraph, Willard Foxton described the challenge as "a middle-class wet-T-shirt contest for armchair clicktivists", referring to clicktivism.[36]
William MacAskill, Vice-President of Giving What We Can, suggested that the challenge encouraged moral licensing, meaning that some people might use taking part in the challenge as a substitute for other charitable acts. He also proposed that by attracting donations for ALS, the challenge was "cannibalizing" potential donations that otherwise would have gone to other charities instead.[37]
American stunt performer and TV personality Steve-O questioned the campaign, suggesting that celebrities' videos generally forgot to share donation information for ALS charities, and that the initial $15 million dollars in funds was insignificant, given the star power of the celebrities participating. He noted that, of the videos he viewed, only Charlie Sheen and Bill Gates noted that the point is to donate money.[38]
Pamela Anderson refused to take part in the challenge because of the use of animal experimentation in ALS research.[39] Members of the pro-life movement, such as Lila Rose ofLive Action, criticised donations to the ALS Association, because it uses embryonic stem cells in its ALS research.[40] Related organisations such as the Family Research Councilsuggested that people participating in the Ice Bucket Challenge instead donate money to Midwest Stem Cell Therapy Center, Mayo Clinic, and John Paul II Medical Research Institute, all three of which run clinical trials with adult stem cells, rather than embryonic ones.[41][42] The Archdiocese of Cincinnati, with its 113 schools also recommended individuals participating in the Ice Bucket Challenge to donate to such groups, but not to the ALS Association "saying the group's funding of embryonic stem cell research is 'in direct conflict with Catholic teaching'."[43]
On August 22, 2014, Dr. Brian O'Neill, a physician at the Detroit Medical Center, warned that the challenge may have adverse health effects on participants, including potentially inducing a vagal response which might, for example, lead to unconsciousness in people taking blood pressure medications.[44] A number of participants have sustained injuries,[45] and at least one death has been linked to the challenge,[46] with another thought to be from a variation on the challenge, jumping feet first into water.[47]
Criticism has also targeted the waste of water, especially in California, due to that region's ongoing drought.[48]
Amyotrophic lateral sclerosis
From Wikipedia, the free encyclopedia
"ALS" redirects here. For other uses, see ALS (disambiguation).
"Motor neurone disease" redirects here. For a broader group of diseases that affect motor neurons, see Motor neuron disease.
Amyotrophic Lateral Sclerosis (ALS)
Classification and external resources

This MRI (parasagittal FLAIR) demonstrates increased T1 signal within the posterior part of the internal capsule and can be tracked to thesubcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS. However, typically MRI is unremarkable in a patient with ALS.
ICD-10
G12.2
ICD-9
335.20
OMIM
105400
DiseasesDB
29148
MedlinePlus
000688
eMedicine
neuro/14 emerg/24 pmr/10
MeSH
D000690
Amyotrophic lateral sclerosis (ALS)—also referred to as motor neurone disease (MND), Lou Gehrig's disease in the United States, and rarely Charcot disease—is a neurodegenerative disease with various causes. ALS is characterised by musclespasticity, rapidly progressive weakness due to muscle atrophy, and difficulty in speaking (dysarthria), swallowing (dysphagia), and breathing (dyspnea). ALS is the most common of the five motor neuron diseases.
In the U.S., more than 5,600 are diagnosed every year, and up to 30,000 Americans are currently affected. ALS is responsible for 2 deaths per 100,000 people.[1]
Median survival time from onset to death is 39 months, and only 4% survive longer than 10 years, although rare cases survive 50 years or more. Most die from respiratory failure, usually within three to five years from onset of symptoms.[2]
Contents
[hide] 
1 Signs and symptoms
1.1 Initial symptoms
1.2 Progression
1.3 Late stages
2 Extraocular and skeletal motor units
2.1 Eye movement impairment
2.2 Roles of lactate and cinnamate
3 Causes
3.1 Genetics
3.1.1 SOD1
3.2 Other factors
4 Pathophysiology
5 Diagnosis
6 Management
6.1 Medications
6.2 Therapy
6.3 Nutrition
6.4 Breathing support
6.5 Palliative care
7 Epidemiology
8 History
8.1 Etymology
9 Clinical research
10 Charity fundraising
11 See also
12 References
13 External links
Signs and symptoms[edit]
The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel function and the muscles responsible for eye movement are usually spared until the final stages of the disorder.[3]
Cognitive function is generally spared for most patients, although some (about 5%) also develop frontotemporal dementia.[4] A higher proportion of patients (30–50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. Infrequently ALS coexists in individuals who also experience dementia, degenerative muscle disorder, and degenerative bone disorder as part of a syndrome called multisystem proteinopathy.[5] Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS will maintain hearing, sight, touch, smell, and taste.[6]
Initial symptoms[edit]
The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include trouble swallowing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people contracting the disorder experience "limb onset" ALS, i.e., first symptoms in the arms or legs. Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a "dropped foot" which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.
About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. Other symptoms include difficulty swallowing and loss of tongue mobility. A smaller proportion of patients experience "respiratory onset" ALS, where the intercostal muscles that support breathing are affected first. A small proportion of patients may also present with what appears to be frontotemporal dementia, but later progresses to include more typical ALS symptoms.
Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). Around 15–45% of patients experience pseudobulbar affect, a neurological disorder also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor expressions of emotion.[citation needed]To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.
Progression[edit]
Although the order and rate of symptoms varies from person to person, eventually most patients are not able to walk or use their hands and arms. They also lose the ability to speak and swallow food, while most end up on a portable ventilator, called a BiPAP. The rate of progression can be measured using an outcome measure called the "ALS Functional Rating Scale Revised (ALSFRS-R)", a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). Though there is a high degree of variability and a small percentage of patients have much slower disorder, on average, patients lose about 0.9 FRS point per month. A survey-based study amongst clinicians showed that they rated a 20% change in the slope of the ALSFRS-R would be clinically meaningful.[7]Regardless of the part of the body first affected by the disorder, muscle weakness and atrophy spread to other parts of the body as the disorder progresses. In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in bulbar-onset ALS symptoms typically spread to the arms before the legs.
Disorder progression tends to be slower in patients who are younger than 40 at onset,[8][9] are mildly obese,[10] have disorder restricted primarily to one limb, and those with primarily upper motor neuron symptoms.[11] Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disorder, respiratory-onset disorder, and fronto-temporal dementia.[11]
CX3CR1 allelic variants have also been shown to modify the survival time and the progression of patients.[12]
Late stages[edit]
Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years.[2]Guitarist Jason Becker has lived since 1989 with the disorder, while physicist Stephen Hawking has survived for more than 50 years, but they're considered unusual cases.[13]
Difficulty in chewing and swallowing makes eating very difficult and increases the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. In respiratory onset ALS, this may occur before significant limb weakness is apparent. External ventilation machines that use the ventilation mode of bilevel positive airway pressure (BiPAP) are frequently used to support breathing, initially at night, and later during the daytime as well. The use of BPAP (more often referred to as non-invasive ventilation, NIV) is only a temporary remedy, however, and it is recommended that long before BPAP stops being effective, patients should decide whether to have a tracheotomy and long term mechanical ventilation. At this point, some patients choose palliative hospice care. Most people with ALS die of respiratory failure or pneumonia.
In late stages the oculomotor nerve that controls the movements of the eye, can be affected as can the extraocular muscles. The eye movements remain unaffected largely until the later stages due to differences in the extraocular muscles compared to the skeletal muscles that are initially and readily affected.
Finally, patient condition may be mimicking locked-in syndrome.[14]
Extraocular and skeletal motor units[edit]
Main article: Extraocular muscles
Despite sharing fixed sequences of recruitment, extraocular muscles (EOMs) and skeletal muscles exhibit different characteristics. The following are characteristics of EOMs that differ from skeletal motor units.[15]
One neural fiber connects with only 1 or 2 muscle fibers
No ocular stretch reflexes, despite being rich in muscle spindles
No recurrent inhibition
No special fast-twitch or slow-twitch muscles
All eye motor neurons participate equally in all types of eye movements—not specialized for saccades or smooth pursuit
There are also noted differences between healthy and affected EOMs. EOMs from postmortem donors preserved their cytoarchitecture, as compared to limb muscles. Healthy EOMs consist of a central global layer (GL) facing the globe and a thin orbital layer (OL) facing the walls of the orbit.[16] EOMs affected by ALS preserve the GL and OL organization.[16] EOMs possess the neurotrophic factors brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), and these neuroprotective factors are also preserved in EOMs affected by ALS.[16] Laminin is a structural protein typically found in the neuromuscular junction (NMJ). Lnα4 is a laminin isoform that is a hallmark of skeletal muscle NMJs.[17] Patients with ALS showed preserved Lnα4 expression in EOM NMJs, but this expression was non-existent in limb muscle NMJs from the same patients.[17] Preservation of laminin expression may play a role in preserving EOM integrity in ALS patients. Patients with sporadic ALS (sALS) have increased levels of intracelluar calcium, causing increased neurotransmitter release.[18] Passive transfer of sera from sALS patients increases spontaneous transmitter release in spinal but not EOM terminals;[18] therefore, it is assumed that EOMs are resistant to changes in physiologic conditions typically found in ALS.
However, some effects of the disorder were noted. EOMs affected by ALS had a larger variation in fiber size compared to those in age-matched healthy controls.[16] EOMs exhibited both clustered and scattered atrophic and hypertrophic fibers that are characteristic of disorder; however, these muscles showed significantly less damage compared to limb muscles from the same donors.[16] These EOMs also showed an increase in connective tissue and areas of fatty replacement in compensation of fiber loss and atrophy.[16]Ophthalmoplegia, a loss of neurons in and around the ocular motor nuclei, has been noted in ALS patients.[19] Additionally, there was altered myosin heavy chain content of the EOM fibers, with a loss of normal expression of MyHCslow tonic in the GL and the OL did not contain MyHCemb, which is normally expressed in this layer.[16] This change may represent a change in innervation pattern that may include reinnervation by a different type of motor neuron or loss of multiple innervations. Changes in MyHCslow and MyHCemb are the only fiber changes seen in EOMs, leaving the EOM fiber composition relatively normal.[16] Because EOMs are normally highly innervated, any denervation, is compensated for by neighbouring axons which preserve function.[16]
Eye movement impairment[edit]
Patients with ALS may have difficulty in generating voluntary saccades, fast movements of the eye.[19] Saccade velocity is significantly slower in patients with ALS.[19] Problems in generating smooth pursuit and convergence movements have also been noted in patients with ALS.[19] Testing the vestibulo-ocular reflex (VOR) should help in identifying these deficits in ALS patients.[20] Electrooculography (EOG) is a technique that measures the resting potential of the retina. EOG findings in patients with ALS show progressive changes that correlate with disorder progression, and provide a measurement for clinically evaluating the effects of disorder progression on oculomotor activity.[20] Additionally, EOG may allow earlier, subclinical, detection of oculomotor abnormalities in patients with ALS.
The embryonic lineage of EOMs differs from that of somite-derived muscles. EOMs are unique because they continuously remodel through life and maintain a population of activesatellite cells during aging.[21] EOMs have significantly more myogenic precursor cells than limb skeletal muscles.[21]
Roles of lactate and cinnamate[edit]
Lactic acid is an end product of glycolysis and is known to cause muscle fatigue. Lactate dehydrogenase (LDH) is an enzyme that exerts its effects bidirectionally and is able to oxidize lactate into pyruvate so it can be used in the Krebs Cycle. In EOM, lactate sustains muscle contraction during increased activity levels. EOM that have high LDH activity are thought to be resistant to ALS.[22]
Cinnamate is a blocker of lactate transport and exogenous lactate on fatigue resistance. Cinnamate is able to cause fatigue in EOM, while decreasing EOM endurance and residual force; however, cinnamate has no effect on extensor digitorum longus muscle, a muscle in the leg.[22] In contrast, replacing glucose with exogenous lactate increases fatiguability of EDL muscles but not EOM.[22] Fatiguability in EOM was only found when a combination of exogenous lactacte plus cinnamate replaced glucose.[22]
Causes[edit]
Genetics[edit]
There is a known hereditary factor in familial ALS, where the condition is known to run in families. A defect on chromosome 21, which codes for superoxide dismutase, is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall.[23][24][25] This mutation is believed to be transmitted in an autosomal dominantmanner, and has over a hundred different forms of mutation. The most common ALS-causing mutation is a mutant SOD1 gene, seen in North American patients; this is characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A-SOD1, is more slowly progressive than typical ALS and patients with this form of the disorder survive for an average of 11 years.[26]
In 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD,[27] and accounts for some 6% of cases of ALS among white Europeans.[28] The gene is also found in people of Filipino descent.[28]
The world's largest genetic study, called project MinE, initiated by two ALS patients is currently ongoing. It is a crowdfunded research project with many countries involved to discover more genes.[29]
To date, a number of genetic mutations have been associated with various types of ALS. The currently known associations are as follows:
Type
OMIM
Gene
Locus
Remarks
ALS1
105400
SOD1
21q22.1
The most common form of familial ALS
ALS2
205100
ALS2
2q33.1

ALS3
606640
 ?
18q21

ALS4
602433
SETX
9q34.13

ALS5
602099
 ?
15q15.1–q21.1
Juvenile onset
ALS6
608030
FUS
16p11.2

ALS7
608031
 ?
20p13

ALS8
608627
VAPB
20q13.3

ALS9
611895
ANG
14q11.2

ALS10
612069
TARDBP
1p36.2

ALS11
612577
FIG4
6q21

ALS12
613435
OPTN
10p13

ALS13
183090
ATXN2
12q24.12

ALS14
613954
VCP
9p13.3
Recent new study shows strong link in ALS mechanism[5][30]
ALS15
300857
UBQLN2
Xp11.23–p11.1
Described in one family[31]
ALS16
614373
SIGMAR1
9p13.3
Juvenile onset, very rare, described only in one family[32]
ALS17
614696
CHMP2B
3p11
Very rare, reported only in a handful of patients
ALS18
614808
PFN1
17p13.3
Very rare, described only in a handful of Chinese families[33]
ALS19
615515
ERBB4
2q34
Very rare, as of late 2013 described only in four patients[34]
ALS20
615426
HNRNPA1
12q13
Very rare, as of late 2013 described only in two patients[35]
ALS-FTD
105550
C9orf72
9p21.2
Accounts for around 6% of ALS cases among white Europeans
SOD1[edit]
In 1993, scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase (SOD1) enzyme were associated with approximately 20% of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive molecules produced by cells during normal metabolism. Free radicals can accumulate and cause damage to DNA and proteins within cells.
To date, over 110 different mutations in SOD1 have been linked with the disorder, some of which (such as H46R) have a very long clinical course, while others, such as A4V, are exceptionally aggressive.
When the defenses against oxidative stress fail, programmed cell death (apoptosis) is upregulated.
A defect in SOD1 could be a loss or gain of of function. A loss of SOD1 function could lead to an accumulation of free radicals. A gain of SOD1 function could be toxic in other ways. [36][37]
Studies involving transgenic mice have yielded several theories about the role of SOD1 in mutant SOD1 familial amyotrophic lateral sclerosis. Mice lacking the SOD1 gene entirely do not customarily develop ALS, although they do exhibit an acceleration of age-related muscle atrophy (sarcopenia) and a shortened lifespan (see article on superoxide dismutase). This indicates that the toxic properties of the mutant SOD1 are a result of a gain in function rather than a loss of normal function. In addition, aggregation of proteins has been found to be a common pathological feature of both familial and sporadic ALS (see article on proteopathy). Interestingly, in mutant SOD1 mice (most commonly, the G93Amutant), aggregates (misfolded protein accumulations) of mutant SOD1 were found only in diseased tissues, and greater amounts were detected during motor neuron degeneration.[38] It is speculated that aggregate accumulation of mutant SOD1 plays a role in disrupting cellular functions by damaging mitochondria, proteasomes, protein foldingchaperones, or other proteins.[39] Any such disruption, if proven, would lend significant credibility to the theory that aggregates are involved in mutant SOD1 toxicity. Critics have noted that in humans, SOD1 mutations cause only 2% or so of overall cases and the etiological mechanisms may be distinct from those responsible for the sporadic form of the disease. To date, the ALS-SOD1 mice remain the best model of the disease for preclinical studies but it is hoped that more useful models will be developed.
There is an online database available which was designed to provide both the scientific community and the wider public with up-to-date information on ALS genetics. This is known as ALSOD - website originally designed for the SOD1 gene in 1999, but since upgraded to include over 40 ALS-related genes.
Other factors[edit]
Where no family history of the disease is present – i.e., in around 90% of cases – there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, frequent drug use, and participation in contact sports. More recently, some research has suggested that there may be a link between ALS and food contaminated by blue-green algae.[40][unreliable medical source?]
Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared with healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid.[24] Riluzole is currently the only FDA approved drug for ALS and targets glutamate transporters. It only has a modest effect on survival, however, suggesting that excess glutamate is not the sole cause of the disease.
Certain studies suggested a link between sporadic ALS, specifically in athletes, and a diet enriched with branched-chain amino acids. BCAAs, a common dietary supplement among athletes, cause cell hyper-excitability resembling that usually observed in ALS patients. The proposed underlying mechanism is that cell hyper-excitability results in increased calcium absorption by the cell and thus brings about cell death of neuronal cells, which have particularly low calcium buffering capabilities.[41][42]
There is evidence that superoxide dismutase 1 (SOD1) protein misfolding propagates between molecules in a similar fashion to prions.[43]
Another very common cause of ALS is a lesion to the motor system in areas such as the frontotemporal lobes.[44] Lesions in these areas often show signs of early deficit, which can be used to predict the loss of motor function, and result in the spread of ALS.[44] The mechanisms of ALS are present long before any signs or symptoms become apparent.[45] It is estimated that before any muscular atrophy becomes apparent during ALS, roughly one-third of the motor neurons must be destroyed.[45]
Many other potential causes, including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock, have been investigated but without consistent findings.[46]
Pathophysiology[edit]
The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop protein-rich inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.[47] These inclusions often contain ubiquitin, and generally incorporate one of the ALS-associated proteins: SOD1, TAR DNA binding protein (TDP-43, or TARDBP), or FUS.
Diagnosis[edit]
No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases.[48] Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.


MRI (axial FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule, consistent with the clinical diagnosis of ALS.
Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis.
Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urinesamples to eliminate the possibility of other diseases as well as routine laboratory tests. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.
Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease,[49] syphilis[50] andtick-borne encephalitis[51] viruses can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, spinal muscular atrophy and spinal and bulbar muscular atrophy (SBMA) can also mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis.
ALS must be differentiated from the "ALS mimic syndromes" which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants.[52]Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients should always obtain a specialist neurological opinion, so that alternative diagnoses are clinically ruled out.
However, most cases of ALS are readily diagnosed and the error rate of diagnosis in large ALS clinics is less than 10%.[53][54] In one study, 190 patients who met the MND / ALS diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. Thirty of these patients (16%) had their diagnosis completely changed, during the clinical observation development period.[55] In the same study, three patients had a false negative diagnoses, myasthenia gravis (MG), an auto-immune disease. MG can mimic ALS and other neurological disorders leading to a delay in diagnosis and treatment. MG is eminently treatable; ALS is not.[56] Myasthenic syndrome, also known as Lambert-Eaton syndrome (LES), can mimic ALS and its initial presentation can be similar to that of MG.[57][58]
Current research focuses on abnormalities of neuronal cell metabolism involving glutamate and the role of potential neurotoxins and neurotrophic factors.[59]
Management[edit]
Riluzole (Rilutek) is the only treatment that has been found to improve survival but only to a modest extent.[60] It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage (occurring in ~10% of people taking the drug).[61] It is approved by Food and Drug Administration (FDA) and recommended by the National Institute for Clinical Excellence (NICE).
Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible.
Medications[edit]
Medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, dysphagia, and constipation. Baclofen and diazepam are often prescribed to control the spasticity caused by ALS, and trihexyphenidyl oramitriptyline may be prescribed when ALS patients begin having trouble swallowing their saliva.[3]
Therapy[edit]
Physical therapists and occupational therapists play a large role in rehabilitation for individuals with ALS. Specifically, physical and occupational therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, preventing complications, and promoting functional independence.[62]
Occupational therapy and special equipment such as assistive technology can also enhance patients' independence and safety throughout the course of ALS. Gentle, low-impactaerobic exercise such as performing activities of daily living (ADL's), walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.) and wheelchairs that help patients remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable people to retain as much safety and independence in activities of daily living as possible.
ALS patients who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) and/or low tech communication techniques such as alphabet boardsor yes/no signals.
Nutrition[edit]
Patients and caregivers can learn from speech-language pathologists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. Occupational therapists can assist with recommendations for adaptive equipment to ease the physical task of self-feeding. Speech language pathologists make food choice recommendations that are more conducive to their unique deficits and abilities. When patients can no longer get enough nourishment from eating, doctors may advise inserting afeeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.
Researchers have stated that "ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake"[63] and that patients suffer from a severe loss of appetite.[64] Both animal[65] and human research[63][unreliable medical source?] [66][unreliable medical source?] suggest that ALS patients should be encouraged to consume as many calories as possible and not to restrict their calorie intake. As of 2012 there remained "a lack of robust evidence for interventions" for the management of weight loss.[67]
Research has found that people who ate fruits and vegetables containing carotenoids, an oxidative compound which strengthens the immune system response, had reduced chance of developing ALS.[68] There are three primary carotenoids that act as oxidative compounds called beta-carotene, lycopene, and lutein found in fruits and vegetables each found in different foods like carrots, watermelon, and tomatoes.[69]
Breathing support[edit]
When the muscles that assist in breathing weaken, use of ventilatory assistance (intermittent positive pressure ventilation (IPPV), bilevel positive airway pressure (BiPAP), orbiphasic cuirass ventilation (BCV) may be used to aid breathing. Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time. BCV has the added advantage of being able to assist in clearing secretions by using high-frequency oscillations followed by several positive expiratory breaths.[70] Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheotomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck.
Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support and have deep discussions on quality of life. Some patients under long-term tracheotomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheotomy tubes (leak ventilation) are able to speak, provided their bulbar muscles are strong enough, though in all cases speech will be lost as the disease progresses. This technique preserves speech in some patients with long-term mechanical ventilation. Other patients may be able to utilize a speaking valve such as a Passey-Muir Speaking Valve with the assistance and guidance of a speech-language pathologist.
Palliative care[edit]
Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Home nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving feedings, and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.
Epidemiology[edit]
ALS is classified as a rare disease but is the most common motor neuron disease. People of all races and ethnic backgrounds are affected. One or two out of 100,000 people develop ALS each year.[71] Amyotrophic lateral sclerosis affects approximately 30,000 Americans.[59] ALS cases are estimated at 1.2–4.0 per 100,000 individuals in Caucasian populations with a lower rate in other ethnic populations.[72] Filipinos are second to Caucasians in terms of ALS prevalence with 1.1-2.8 per 100,000 individuals.[59]
Although the incidence of ALS is thought to be regionally uniform, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS. This seems to be declining in recent decades. The largest is the area of Guam inhabited by the Chamorro people, who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of symptoms similar to ALS, parkinsonism, and dementia. Lytico-Bodig disease has been linked to the consumption and topical use of cycad seeds and in particular, the chemical found in cycad seeds, β-methylamino-L-alanine (BMAA).[73] Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan, both with topical cycad seed use.[74][75]
There have been reports of several "clusters" including three American football players from the San Francisco 49ers, more than fifty association football players in Italy,[76] three association football-playing friends in the south of England,[77] and reports of conjugal (husband and wife) cases in the south of France,.[78][79][80][81][82] Although many authors consider ALS to be caused by a combination of genetic and environmental risk factors, so far the latter have not been firmly identified, other than a higher risk with increasing age.
History[edit]
Year
Event
1850
English scientist Augustus Waller describes the appearance of shriveled nerve fibers
1869
French doctor Jean-Martin Charcot first describes ALS symptoms in autopsy patients[83]
1874
Charcot publishes a paper describing the disease whose title is the first formal use of the term ALS (De la sclérose latérale amyotrophique)[83]
1881
"Amyotrophic Lateral Sclerosis" is translated into English and published in a three-volume edition of Lectures on the Diseases of the Nervous System
1939
ALS becomes a cause célèbre in the United States when baseball legend Lou Gehrig's career—and, two years later, his life—is ended by the disease. He gives his farewell speech on 4 July 1939.[84]
1950s
ALS epidemic occurs among the Chamorro people on Guam
1991
Researchers link chromosome 21 to FALS (Familial ALS)
1993
SOD1 gene on chromosome 21 found to play a role in some cases of FALS
1996
Rilutek becomes the first FDA-approved drug for ALS
1998
The El Escorial criteria is developed as the standard for classifying ALS patient in clinical research
1999
The revised ALS Functional Rating Scale (ALSFRS-R) is published and soon becomes a gold standard measure for rating decline in ALS patient in clinical research
2011
Noncoding repeat expansions in C9ORF72 are found to be a major cause of ALS and frontotemporal dementia
2014
Various videos across the web spread awareness of ALS and raise funds for research with the "ALS Ice Bucket Challenge"
Etymology[edit]
Amyotrophic comes from the Greek word amyotrophia: a- means "no", myo refers to "muscle", and trophia means "nourishment"; amyotrophia therefore means "no muscle nourishment," which describes the characteristic atrophy of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region.
Clinical research[edit]
A number of clinical trials are underway globally for ALS; a comprehensive listing of trials in the US can be found at ClinicalTrials.gov.
A phase II trial on tirasemtiv has been completed with a follow-on Phase IIb study in progress under the name "BENEFIT-ALS". Results of the first study are available here.[85][unreliable medical source?][86][verification needed] The current trial is an international, placebo-controlled, multi-center study on 680 participants. This makes it one of the largest studies to date. A phase II trial on Ozanezumab is in progress. It is a large multi-site international research project sponsored by GlaxoSmithKline (GSK).
A phase II clinical trial is being conducted by BrainStorm Cell Therapeutics at the Hadassah Medical Center in Israel and interim results "demonstrated a tendency toward stabilization in some parameters in the ALS Functional Rating Scale."[87][88] Patients in the trial have bone marrow stem cells removed and differentiated in a clean room into cells that express neurotropic factors. The cells are injected back into the same patient via an intrathecal injection and intramuscular injections. A second phase II trial is expected to open in the United States at several institutions including the Mayo Clinic.[89]
Charity fundraising[edit]
Main article: Ice Bucket Challenge
In August 2014, a challenge went viral online which was commonly known as the "ALS Ice Bucket Challenge".[90] A contestant will fill a bucket full of ice and water; they will then state who nominated them to do the challenge and will nominate three other individuals of their choice to take part in it. The contestant then dumps the bucket of ice and water onto themselves. The contestant should then donate US $10 (or a similar amount in their local currency) to ALS research at the ALS Association, or Motor Neurone Disease Association in the UK. Any contestant who refuses to have the ice and water dumped on them is expected to donate US $100 to ALS research. As of August 25, the Ice Bucket Challenge raised $79.7 million for the ALS Association, compared to $2.5 million raised over the same period in 2013.
Many celebrities have taken part in the challenge, including Cristiano Ronaldo, Chris Pratt,[91] Roger Federer, David Beckham, Cheryl Cole, George W. Bush,[90] Lady Gaga,[92]Mark Zuckerberg, Oprah Winfrey, Charlie Sheen and Bill Gates, among many other well-known personalities and members of the general public.[93]
Ebola virus
From Wikipedia, the free encyclopedia
For the genus, see Ebolavirus. For the current outbreak, see 2014 West Africa Ebola virus outbreak.
Ebola virus

Virus classification
Group:
Group V ((-)ssRNA)
Order:
Mononegavirales
Family:
Filoviridae
Genus:
Ebolavirus
Species:
Zaire ebolavirus
Member virus (Abbreviation)
Ebola virus (EBOV)
Ebola virus (EBOV, formerly designated Zaire ebolavirus) is the sole member of the Zaire ebolavirus species, and the most dangerous of the five known viruses within the genus Ebolavirus.[1] Four of the five known ebolaviruses cause a severe and often fatal hemorrhagic feverin humans and other mammals, known as Ebola virus disease. The virus and its species were both originally named for Zaire (now theDemocratic Republic of Congo), the country where it was first described,[1] and was at first suspected to be a new "strain" of the closely related Marburg virus;[2][3] the virus (but not its species) was renamed to "Ebola virus" in 2010 to avoid confusion. The species is avirological taxon species included in the genus Ebolavirus, family Filoviridae (whose members are called Filovirus[4]), orderMononegavirales.[1] The Zaire ebolavirus species is also the type species (reference or example species) for ebolavirus. Its natural reservoir is believed to be bats, particularly fruit bats, and it is primarily transmitted between humans and from animals to humans, throughbody fluids.
The EBOV genome is approximately 19,000 base pairs long. It encodes seven structural proteins: nucleoprotein (NP), polymerase cofactor(VP35), (VP40), GP, transcription activator (VP30), VP24, and RNA polymerase (L).[5] Its is difficult to study due to the virulent nature of the virus.
Because of its high mortality rate, EBOV is also listed a select agent, World Health Organization Risk Group 4 Pathogen (requiring Biosafety Level 4-equivalent containment), a U.S. National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, U.S. CDC Centers for Disease Control and Prevention Category A Bioterrorism Agent, and listed as a Biological Agent for Export Control by the Australia Group.
Contents
[hide] 
1 Structure
2 Genome
3 Entry
4 Replication
5 Ecology
6 Ebola virus disease
7 History
7.1 Previous names
8 Species inclusion criteria
9 See also
10 References
11 External links
Structure[edit]


Phylogenetic tree comparing the Ebolavirus and Marburgvirus. Numbers indicate percent confidence of branches.
EBOV carries a negative-sense RNA genome in virions that are cylindrical/tubular, and contain viral envelope, matrix, and nucleocapsid components. The overall cylinders are generally approx. 80 nm in diameter, and having a virally encoded glycoprotein (GP) projecting as 7-10 nm long spikes from its lipid bilayer surface.[6][not specific enough to verify] The cylinders are of variable length, typically 800 nm, but sometimes up to 1000 nm long. The outer viral envelope of the virion is derived by budding from domains of host cell membrane into which the GP spikes have been inserted during their biosynthesis.[citation needed] Individual GP molecules appear with spacings of about 10 nm.[citation needed] Viral proteins VP40and VP24 are located between the envelope and the nucleocapsid (see following), in the matrix space.[7] At the center of the virion structure is the nucleocapsid, which is composed of a series of viral proteins attached to a 18–19 kb linear, negative-sense RNA without 3 -polyadenylation or 5 -capping (see following);[citation needed] the RNA is helically wound and complexed with the NP, VP35, VP30, and L proteins;[8][better source needed] this helix has a diameter of 80 nm and contains a central channel of 20–30 nm in diameter.
The overall shape of the virions after purification and visualization (e.g., by ultracentrifugation and electron microscopy, respectively) varies considerably; simple cylinders are far less prevalent than structures showing reversed direction, branches, and loops (i.e., U-, shepherd's crook-, 9- or eye bolt-shapes, or other or circular/coiled appearances), the origin of which may be in the laboratory techniques applied.[9] The characteristic "threadlike" structure is, however, a more general morphologic characteristic of filoviruses (alongside their GP-decorated viral envelope, RNA nucleocapsid, etc.).[9]
Genome[edit]

This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2014)
Each virion contains one molecule of linear, single-stranded, negative-sense RNA, 18,959 to 18,961 nucleotides in length. The 3 terminus is not polyadenylated and the 5 end is not capped. It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end are sufficient for replication.[9] It codes for seven structural proteins and one non-structural protein. The gene order is 3 – leader – NP – VP35 – VP40 – GP/sGP – VP30 – VP24 – L – trailer – 5 ; with the leader and trailer being non-transcribed regions, which carry important signals to control transcription, replication, and packaging of the viral genomes into new virions. The genomic material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA polymerase, are necessary to transcribe the viral genome into mRNAs because it is a negative sense RNA virus, as well as for replication of the viral genome. Sections of the NP and the L genes from filoviruses have been identified as endogenous in the genomes of several groups of small mammals.[10]
Entry[edit]

This section relies on references to primary sources. Please add references to secondary or tertiary sources. (August 2014)
There are two candidates for host cell entry proteins. The first is the host-encoded Niemann–Pick C1 (NPC1), a cholesterol transporter protein, appears to be essential for entry of Ebola virions into the host cell, and for its ultimate replication.[11][12] In one study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse-adapted Ebola virus.[ambiguous][jargon][11] In another study, small molecules were shown to inhibit Ebola virus infection by preventing viral envelope glycoprotein (GP) from binding to NPC1.[12][13] Hence, NPC1 was shown to be critical to entry of this filovirus, because it mediates infection by binding directly to viral GP.[12]
When cells from Niemann Pick Type C patients lacking this transporter were exposed to Ebola virus in the laboratory, the cells survived and appeared impervious to the virus, further indicating that Ebola relies on NPC1 to enter cells;[citation needed] mutations in the NPC1 gene in humans were conjectured as a possible mode to make some individuals resistant to this deadly viral disease.[citation needed][speculation?] The same studies[which?] described similar results regarding NPC1's role in virus entry for Marburg virus, a relatedfilovirus. A further study has also presented evidence that NPC1 is critical receptor mediating Ebola infection via its direct binding to the viral GP, and that it is the second "lysosomal" domain of NPC1 that mediates this binding.[14]
The second candidate is TIM-1 (aka HAVCR1).[15] TIM-1 was shown to bind to the receptor binding domain of the EBOV glycoprotein, to increase the receptivity of Vero cells. Silencing its effect with siRNA prevented infection of Vero cells. TIM1 is expressed in tissues known to be seriously impacted by EBOV lysis (trachea, cornea, and conjunctiva). A monoclonal antibody against the IgV domain of TIM-1, ARD5, blocked EBOV binding and infection.
Together, these studies suggest NPC1 and TIM-1 may be potential therapeutic targets for an Ebola anti-viral drug and as a basis for a rapid field diagnostic assay.[citation needed]
Replication[edit]

This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2014)
Being acellular, viruses such as Ebola do not replicate through any type of cell division; rather, they use a combination of host- and virally encoded enzymes, alongside host cell structures, to produce multiple copies of themselves; these then self-assemble into viral macromolecular structures in the host cell.[8][better source needed] The virus completes a set of steps when infecting each individual cell:[citation needed]
The virus begins its attack by attaching to host receptors through the glycoprotein (GP) surface peplomer and is endocytosed into macropinosomes in the host cell.[16][non-primary source needed] To penetrate the cell, the viral membrane fuses with vesicle membrane, and the nucleocapsid is released into the cytoplasm. Encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis (3'-5') of polyadenylated, monocistronic mRNAs[jargon] and, using the host cell's ribosomes, tRNA molecules, etc., the mRNA is translated into individual viral proteins.
These viral proteins are processed, a glycoprotein precursor (GP0) is cleaved to GP1 and GP2, which are then heavily glycosylated using cellular enzymes and substrates. These two molecules assemble, first into heterodimers, and then into trimers to give the surface peplomers. Secreted glycoprotein (sGP) precursor is cleaved to sGP and delta peptide, both of which are released from the cell.[citation needed] As viral protein levels rise, a switch occurs from translation to replication. Using the negative-sense genomic RNA as a template, a complementary +ssRNA is synthesized; this is then used as a template for the synthesis of new genomic (-)ssRNA, which is rapidly encapsidated.
The newly formed nucleocapsids and envelope proteins associate at the host cell's plasma membrane; budding occurs, destroying the cell.
Ecology[edit]
Ebolavirus is a zoonotic pathogen. Intermediary hosts have been reported to be "various species of fruit bats ... throughout central and sub-Saharan Africa", but infection in bats has not been proven yet.[17] End hosts are humans and great apes, infected through bat contact or through other end hosts. Pigs on the Philippine islands have been reported to be infected with Restonvirus, so other interim or amplifying hosts may exist.[17]
Ebola virus disease[edit]
Main article: Ebola virus disease
Ebola virus is one of the four ebolaviruses known to cause disease in humans. It has the highest case-fatality rate of these ebolaviruses, averaging 83% since first described in 1976, although fatality rates up to 90% have been recorded in one epidemic (2002–03). There have also been more outbreaks of ebola virus than of any other ebolavirus. The first outbreak occurred on 26 August 1976 in Yambuku.[18] The first recorded case was Mabalo Lokela, a 44year-old schoolteacher. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact.
History[edit]
Zaire ebolavirus is pronounced /zɑːˈɪər iːˈboʊləvaɪərəs/ (zah-eer ee-boh-lə-vy-rəs). Strictly speaking, the pronunciation of "Ebola virus" (/iːˌboʊlə ˈvaɪərəs/) should be distinct from that of the genus-level taxonomic designation "ebolavirus/Ebolavirus/ebolavirus", as "Ebola" is named for the tributary of the Congo River that is pronounced "Ébola" in French,[19]whereas "ebola-virus" is an "artificial contraction" of the words "Ebola" and "virus," written without a diacritical mark for ease of use by scientific databases and English speakers. According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Zaire ebolavirus is always to be capitalized, italicized, and to be preceded by the word "species". The names of its members (Zaire ebolaviruses) are to be capitalized, are not italicized, and used without articles.[1]
Ebola virus (abbreviated EBOV) was first described in 1976.[2][3][20] Today, the International Committee on Taxonomy of Viruses lists the virus as the single member of the speciesZaire ebolavirus, which is included into the genus Ebolavirus, family Filoviridae, order Mononegavirales. The name Ebola virus is derived from the Ebola River — a river that was at first thought to be in close proximity to the area in Democratic Republic of Congo, previously called Zaire, where the first recorded Ebola virus disease outbreak occurred — and the taxonomic suffix virus.[1]
The species was introduced in 1998 as Zaire Ebola virus.[21][22] In 2002, the name was changed to Zaire ebolavirus.[23][24]
Previous names[edit]
Ebola virus was first introduced as a possible new "strain" of Marburg virus in 1977 by two different research teams.[2][3] At the same time, a third team introduced the name Ebola virus.[20] In 2000, the virus name was changed to Zaire Ebola virus,[25][26] and in 2002 to Zaire ebolavirus.[23][24] However, most scientific articles continued to refer to Ebola virus or used the terms Ebola virus and Zaire ebolavirus in parallel. Consequently, in 2010, the name Ebola virus was reinstated.[1] Previous abbreviations for the virus were EBOV-Z (for Ebola virus Zaire) and most recently ZEBOV (for Zaire Ebola virus or Zaire ebolavirus). In 2010, EBOV was reinstated as the abbreviation for the virus.[1]
Species inclusion criteria[edit]
To be considered a member of the species Zaire ebolavirus, a virus of the genus Ebolavirus is required to fulfill certain requirements:[1]
it is found in the Democratic Republic of the Congo, Gabon, or the Republic of the Congo
it has a genome with two or three gene overlaps (VP35/VP40, GP/VP30, VP24/L)
it has a genomic sequence that differs from the type virus by less than 30%
Ebola virus disease
Fact sheet N°103
Updated April 2014

Key facts
Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe, often fatal illness in humans.
EVD outbreaks have a case fatality rate of up to 90%.
EVD outbreaks occur primarily in remote villages in Central and West Africa, near tropical rainforests.
The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.
Fruit bats of the Pteropodidae family are considered to be the natural host of the Ebola virus.
Severely ill patients require intensive supportive care. No licensed specific treatment or vaccine is available for use in people or animals.

Ebola first appeared in 1976 in 2 simultaneous outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo. The latter was in a village situated near the Ebola River, from which the disease takes its name.
Genus Ebolavirus is 1 of 3 members of the Filoviridae family (filovirus), along with genus Marburgvirus and genus Cuevavirus. Genus Ebolavirus comprises 5 distinct species:
Bundibugyo ebolavirus (BDBV)
Zaire ebolavirus (EBOV)
Reston ebolavirus (RESTV)
Sudan ebolavirus (SUDV)
Taï Forest ebolavirus (TAFV).
BDBV, EBOV, and SUDV have been associated with large EVD outbreaks in Africa, whereas RESTV and TAFV have not. The RESTV species, found in Philippines and the People's Republic of China, can infect humans, but no illness or death in humans from this species has been reported to date.
Transmission
Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals. In Africa, infection has been documented through the handling of infected chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest.
Ebola then spreads in the community through human-to-human transmission, with infection resulting from direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and indirect contact with environments contaminated with such fluids. Burial ceremonies in which mourners have direct contact with the body of the deceased person can also play a role in the transmission of Ebola. Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness.
Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD. This has occurred through close contact with patients when infection control precautions are not strictly practiced.
Among workers in contact with monkeys or pigs infected with Reston ebolavirus, several infections have been documented in people who were clinically asymptomatic. Thus, RESTV appears less capable of causing disease in humans than other Ebola species.
However, the only available evidence available comes from healthy adult males. It would be premature to extrapolate the health effects of the virus to all population groups, such as immuno-compromised persons, persons with underlying medical conditions, pregnant women and children. More studies of RESTV are needed before definitive conclusions can be drawn about the pathogenicity and virulence of this virus in humans.
Signs and symptoms
EVD is a severe acute viral illness often characterized by the sudden onset of fever, intense weakness, muscle pain, headache and sore throat. This is followed by vomiting, diarrhoea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding. Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes.
People are infectious as long as their blood and secretions contain the virus. Ebola virus was isolated from semen 61 days after onset of illness in a man who was infected in a laboratory.
The incubation period, that is, the time interval from infection with the virus to onset of symptoms, is 2 to 21 days.
Diagnosis
Other diseases that should be ruled out before a diagnosis of EVD can be made include: malaria, typhoid fever, shigellosis, cholera, leptospirosis, plague, rickettsiosis, relapsing fever, meningitis, hepatitis and other viral haemorrhagic fevers.
Ebola virus infections can be diagnosed definitively in a laboratory through several types of tests:
antibody-capture enzyme-linked immunosorbent assay (ELISA)
antigen detection tests
serum neutralization test
reverse transcriptase polymerase chain reaction (RT-PCR) assay
electron microscopy
virus isolation by cell culture.
Samples from patients are an extreme biohazard risk; testing should be conducted under maximum biological containment conditions.
Vaccine and treatment
No licensed vaccine for EVD is available. Several vaccines are being tested, but none are available for clinical use.
Severely ill patients require intensive supportive care. Patients are frequently dehydrated and require oral rehydration with solutions containing electrolytes or intravenous fluids.
No specific treatment is available. New drug therapies are being evaluated.
Natural host of Ebola virus
In Africa, fruit bats, particularly species of the genera Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata, are considered possible natural hosts for Ebola virus. As a result, the geographic distribution of Ebolaviruses may overlap with the range of the fruit bats.
Ebola virus in animals
Although non-human primates have been a source of infection for humans, they are not thought to be the reservoir but rather an accidental host like human beings. Since 1994, Ebola outbreaks from the EBOV and TAFV species have been observed in chimpanzees and gorillas.
RESTV has caused severe EVD outbreaks in macaque monkeys (Macaca fascicularis) farmed in Philippines and detected in monkeys imported into the USA in 1989, 1990 and 1996, and in monkeys imported to Italy from Philippines in 1992.
Since 2008, RESTV viruses have been detected during several outbreaks of a deadly disease in pigs in People's Republic of China and Philippines. Asymptomatic infection in pigs has been reported and experimental inoculations have shown that RESTV cannot cause disease in pigs.
Prevention and control
Controlling Reston ebolavirus in domestic animals
No animal vaccine against RESTV is available. Routine cleaning and disinfection of pig or monkey farms (with sodium hypochlorite or other detergents) should be effective in inactivating the virus.
If an outbreak is suspected, the premises should be quarantined immediately. Culling of infected animals, with close supervision of burial or incineration of carcasses, may be necessary to reduce the risk of animal-to-human transmission. Restricting or banning the movement of animals from infected farms to other areas can reduce the spread of the disease.
As RESTV outbreaks in pigs and monkeys have preceded human infections, the establishment of an active animal health surveillance system to detect new cases is essential in providing early warning for veterinary and human public health authorities.
Reducing the risk of Ebola infection in people
In the absence of effective treatment and a human vaccine, raising awareness of the risk factors for Ebola infection and the protective measures individuals can take is the only way to reduce human infection and death.
In Africa, during EVD outbreaks, educational public health messages for risk reduction should focus on several factors:
Reducing the risk of wildlife-to-human transmission from contact with infected fruit bats or monkeys/apes and the consumption of their raw meat. Animals should be handled with gloves and other appropriate protective clothing. Animal products (blood and meat) should be thoroughly cooked before consumption.
Reducing the risk of human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their bodily fluids. Close physical contact with Ebola patients should be avoided. Gloves and appropriate personal protective equipment should be worn when taking care of ill patients at home. Regular hand washing is required after visiting patients in hospital, as well as after taking care of patients at home.
Communities affected by Ebola should inform the population about the nature of the disease and about outbreak containment measures, including burial of the dead. People who have died from Ebola should be promptly and safely buried.
Pig farms in Africa can play a role in the amplification of infection because of the presence of fruit bats on these farms. Appropriate biosecurity measures should be in place to limit transmission. For RESTV, educational public health messages should focus on reducing the risk of pig-to-human transmission as a result of unsafe animal husbandry and slaughtering practices, and unsafe consumption of fresh blood, raw milk or animal tissue. Gloves and other appropriate protective clothing should be worn when handling sick animals or their tissues and when slaughtering animals. In regions where RESTV has been reported in pigs, all animal products (blood, meat and milk) should be thoroughly cooked before eating.
Controlling infection in health-care settings
Human-to-human transmission of the Ebola virus is primarily associated with direct or indirect contact with blood and body fluids. Transmission to health-care workers has been reported when appropriate infection control measures have not been observed.
It is not always possible to identify patients with EBV early because initial symptoms may be non-specific. For this reason, it is important that health-care workers apply standard precautions consistently with all patients – regardless of their diagnosis – in all work practices at all times. These include basic hand hygiene, respiratory hygiene, the use of personal protective equipment (according to the risk of splashes or other contact with infected materials), safe injection practices and safe burial practices.
Health-care workers caring for patients with suspected or confirmed Ebola virus should apply, in addition to standard precautions, other infection control measures to avoid any exposure to the patient's blood and body fluids and direct unprotected contact with the possibly contaminated environment. When in close contact (within 1 metre) of patients with EBV, health-care workers should wear face protection (a face shield or a medical mask and goggles), a clean, non-sterile long-sleeved gown, and gloves (sterile gloves for some procedures).
Laboratory workers are also at risk. Samples taken from suspected human and animal Ebola cases for diagnosis should be handled by trained staff and processed in suitably equipped laboratories.
WHO response
WHO provides expertise and documentation to support disease investigation and control.
Recommendations for infection control while providing care to patients with suspected or confirmed Ebola haemorrhagic fever are provided in: Interim infection control recommendations for care of patients with suspected or confirmed Filovirus (Ebola, Marburg) haemorrhagic fever, March 2008. This document is currently being updated.
WHO has created an aide–memoire on standard precautions in health care (currently being updated). Standard precautions are meant to reduce the risk of transmission of bloodborne and other pathogens. If universally applied, the precautions would help prevent most transmission through exposure to blood and body fluids.
Standard precautions are recommended in the care and treatment of all patients regardless of their perceived or confirmed infectious status. They include the basic level of infection control—hand hygiene, use of personal protective equipment to avoid direct contact with blood and body fluids, prevention of needle stick and injuries from other sharp instruments, and a set of environmental controls.
Table: Chronology of previous Ebola virus disease outbreaks

Year
Country
Ebolavirus species
Cases
Deaths
Case fatality
2012
Democratic Republic of Congo
Bundibugyo
57
29
51%
2012
Uganda
Sudan
7
4
57%
2012
Uganda
Sudan
24
17
71%
2011
Uganda
Sudan
1
1
100%
2008
Democratic Republic of Congo
Zaire
32
14
44%
2007
Uganda
Bundibugyo
149
37
25%
2007
Democratic Republic of Congo
Zaire
264
187
71%
2005
Congo
Zaire
12
10
83%
2004
Sudan
Sudan
17
7
41%
2003 (Nov-Dec)
Congo
Zaire
35
29
83%






2003 (Jan-Apr)
Congo
Zaire
143
128
90%






2001-2002
Congo
Zaire
59
44
75%
2001-2002
Gabon
Zaire
65
53
82%
2000
Uganda
Sudan
425
224
53%
1996
South Africa (ex-Gabon)
Zaire
1
1
100%
1996 (Jul-Dec)
Gabon
Zaire
60
45
75%






1996 (Jan-Apr)
Gabon
Zaire
31
21
68%






1995
Democratic Republic of Congo
Zaire
315
254
81%
1994
Cote d'Ivoire
Taï Forest
1
0
0%
1994
Gabon
Zaire
52
31
60%
1979
Sudan
Sudan
34
22
65%
1977
Democratic Republic of Congo
Zaire
1
1
100%
1976
Sudan
Sudan
284
151
53%
1976
Democratic Republic of Congo
Zaire
318
280
88%