Sunday, 10 August 2014

The Outbreak.


Between 1 September and 24 October 1976, 318 cases of acute viral hemorrhagic fever occurred in northern Zaire. The outbreak was centred in the Bumba Zone of the equator region and most of the cases were recorded within a radius of 70 km of Yambuku, although a few patients sought medical attention in Bumba, Abumombazi, and the capital city of Kinshasa, where individual secondary and tertiary cases occurred. There were 280 deaths, and only 38 serologically confirmed survivors. 

The index case in this outbreak had onset of symptoms on 1 September 1976, five days after receiving an injection of chloroquine for presumptive malaria at the outpatient clinic at Yambuku Mission Hospital (YMH). He had a clinical remission of his malaria symptoms. Within one week several other persons who had received injections at YMH also suffered from the same haemorrhagic fever. On further research by  United States Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland, it was found to be a virus known as Ebola virus, whose name originates from river named Ebola which runs through Democratic Republic of Congo(then Zaire). 

    Ebola virus(Also known as EBOV) is a zoonotic virus included in genus Ebolavirus of family Filoviridae. It is a single stranded RNA virus which encodes seven structural proteins namely nucleoprotein(NP), polymerase cofactor(VP35) and (VP40), glycoprotein transcription factor (VP 30) and (VP24) and enzyme RNA polymerase. The genome of the virus is 19kb in length. It has a characteristic thread like structure and is cylindrical in shape. It contains a viral envelope, matrix and nucleocaspid components. Viral proteins VP 40 and VP24 are located in the matrix space. The nucleocaspid contains negative sense RNA without 3'-polyadenylation and 5'-capping. The RNA is hellically wounded and complexed with the NP, VP 35, VP 30 and L proteins. 

Each virion contains 18959 to 18961 nucleotides. It is found that 472 nucleotides from 3' end and 731 nucleotides from 5' end are sufficient for replication. The gene order is 3- leader- NP- VP35- VP40- sGP- VP30- VP24- L- trailer- 5'. It is found that the host encoded Neiman-Pick C1, a cholesterol transporter protein is essential for entry of virions in to the host cell and for its further replication. So, NPC1 can be a potential drug target for an Ebola anti-viral drug.
       
On infection, the virus causes an extremely hemorrhagic fever in humans and other primates. the infection mainly spreads through-
 1. Direct contact with blood or the secretions of infected person. OR
 2. The exposure to the objects like needle that have been contaminated with                                       the infected secretions.
The fatality rate of the disease was found to be 64%. The vector which was found to spread the virus is a type of fruit bat which drops partially eaten fruits and pulp on which land mammals feed. Symptoms may appear anywhere from 2 to 21 days after exposure to Ebolavirus though 8-10 days is most common.
Symptoms of Ebola HF typically include:
• Fever
• Headache
• Joint and muscle aches
• Weakness
• Diarrhea
• Vomiting
• Stomach pain
• Lack of appetite
• Rash
• Red Eyes

The main targets of the virus are endothellial cells, mono nuclear phagocytes and hepatocytes. After infection the virus synthesizes a secret glycoprotein called bola glycoprotein which takes over the protein synthesis of infected cells and host's immune defenses. The GP forms a trimeric complex which binds the virus to the endothellial cells lining. Further it forms a dimeric protein that interferes with the signalling of neutrophila which allows the virus to evade the immune system. These leukocytes also serve as carriers to transport the virions through out the body especially lymph nodes and spleen. This triggers release of cytokines like TNF-α, IL-6,IL-8 etc. which elevate body temperature and inflammation and lead to loss of vascular integrity. 
          
The diagnosis of the disease is usually done by Polymerase Chain Reaction(PCR) or ELISA. The treatment is primarily supportive in nature which includes balancing fluids and electrolytes to counter dehydration, administration of anticoagulants to prevent or control disseminated intravascular coagulation, administration of procoagulant to control bleeding, maintain oxygen levels, pain management and use of medications to treat secondary bacterial and fungal infections. Currently, many NCEs are under investigation. One July 31, 2014, an experimental drug ZMapp was first tested on two infected Americans and gave positive results. Other promising reatments rely on anti sense technology. TKPF-Ebola is a small interfering RNA compound currently tested in Phase 1 clinical trails in people. The only preventive measure which can be taken is by keeping as many infected patients as possible in the quarantine.

     The following table is the timeline of the Ebola virus outbreaks.-

Year
Country
Type
Reported human cases
Reported deaths
Fatality
Description
1976
Zaire (Democratic Republic of Congo)
ZEBOV
318
280
88%
Occurred in Yambuku and surrounding area. Disease was spread by close personal contact and by use of contaminated needles and syringes in hospitals/clinics. This outbreak was the first recognition of the disease.[10]
1976
Sudan
SEBOV
284
151
53%
Occurred in Nzara, Maridi and the surrounding area. Disease was spread mainly through close personal contact within hospitals. Many medical care personnel were infected.[11]
1977
Zaire (Democratic Republic of Congo)
ZEBOV
1
1
100%
Noted retroactively in the village of Tandala.[12]
1979
Sudan
SEBOV
34
22
65%
Occurred in Nzara, Maridi. Recurrent outbreak at the same site as the 1976 Sudan epidemic.[13]
1989
USA
REBOV
0
0
0%
REBOV was introduced into quarantine facilities in Virginia and Pennsylvania by monkeys imported from the Philippines.[14]
1990
USA
REBOV
4 (asymptomatic)
0
0%
REBOV was introduced once again into quarantine facilities in Virginia and Texas by monkeys imported from the Philippines. Four humans developed antibodies but did not get sick.[15]
1989–1990
Philippines
REBOV
3 (asymptomatic)
0
0%
High mortality among cynomolgus macaques in a primate facility responsible for exporting animals in the USA.[16] Three workers in the animal facility developed antibodies but did not get sick.[17]
1992
Italy
REBOV
0
0
0%
REBOV was introduced into quarantine facilities in Siena by monkeys imported from the same export facility in the Philippines that was involved in the episodes in the United States. No humans were infected.[18]
1994
Gabon
ZEBOV
52
31
60%
Occurred in Mékouka and other gold-mining camps deep in the rain forest. Initially thought to be yellow fever; identified as Ebola hemorrhagic fever in 1995.[19]
1994
Ivory Coast[nb 1]
CIEBOV
1
0
0%
Scientist became ill after conducting an necropsy on a wild chimpanzee in the Tai Forest.
1995
Zaire (Democratic Republic of Congo)
ZEBOV
315
250
79%
Occurred in Kikwit and surrounding area. Traced to index case-patient who worked in forest adjoining the city. Epidemic spread through families and hospitals.[21]
1996 Jan–Apr
Gabon
ZEBOV
37
21
57%
Occurred in Mayibout area. A chimpanzee found dead in the forest was eaten by people hunting for food. Nineteen people who were involved in the butchery of the animal became ill; other cases occurred in family members.[19]
1996–1997 Jul–Jan
Gabon
ZEBOV
60
45
75%
Occurred in Booué area with transport of patients to Libreville. Index case-patient was a hunter who lived in a forest camp. Disease was spread by close contact with infected persons. A dead chimpanzee found in the forest at the time was determined to be infected.[19]
1996
South Africa
ZEBOV
2
1
50%
A medical professional traveled from Gabon to Johannesburg, South Africa, after having treated Ebola virus-infected patients and thus having been exposed to the virus. He was hospitalized, and a nurse who took care of him became infected and died.[22]
1996
USA
REBOV
0
0
0%
REBOV was introduced into a quarantine facility in Texas by monkeys imported from the Philippines. No human infections were identified.[23]
1996
Philippines
REBOV
0
0
0%
REBOV was identified in a monkey export facility in the Philippines. No human infections were identified.[24]
2000–2001
Uganda
SEBOV
425
224
53%
Occurred in Gulu, Masindi, and Mbarara districts of Uganda. The three most important risks associated with Ebola virus infection were attending funerals of Ebola hemorrhagic fever case-patients, having contact with case-patients in one's family, and providing medical care to Ebola case-patients without using adequate personal protective measures.[25]
2001–2002 Oct–Mar
Gabon
ZEBOV
65
53
82%
Outbreak occurred over the border of Gabon and the Republic of the Congo.[26]
2001–2002 Oct–Mar
Republic of Congo
ZEBOV
57
43
75%
Outbreak occurred over the border of Gabon and the Republic of the Congo. This was the first time that Ebola hemorrhagic fever was reported in the Republic of the Congo.[26]
2002–2003 Dec–Apr
Republic of Congo
ZEBOV
143
128
90%
Outbreak occurred in the districts of Mbomo and Kéllé in Cuvette Ouest Département.[27]
2003 Nov–Dec
Republic of Congo
ZEBOV
35
29
83%
Outbreak occurred in Mbomo and Mbandza villages located in Mbomo district, Cuvette Ouest Département.[28]
2004
Sudan
SEBOV
17
7
41%
Outbreak occurred in Yambio county in Western Equatoria of southern Sudan. This outbreak was concurrent with an outbreak of measles in the same area, and several suspected EHF cases were later reclassified as measles cases.[29]
2007
Democratic Republic of Congo
ZEBOV
264
187
71%
Outbreak occurred in Kasai-Occidental Province. The outbreak was declared over on November 20. Last confirmed case on October 4 and last death on October 10.[30]
2007–2008 Dec–Jan
Uganda
BDBV
149
37
25%
Outbreak occurred in Bundibugyo District in western Uganda. First reported occurrence of a new strain.[2][3][4]
2008 Nov
Philippines
REBOV
6 (asymptomatic)
0
0%
Outbreak in the Philippines and the first known occurrence of REBOV in pigs. Strain closely similar to earlier strains. Six workers from the pig farm and slaughterhouse developed antibodies but did not become sick.[31][32]
2008–2009 Dec–Feb
Democratic Republic of Congo
ZEBOV
32
14
45%
Outbreak occurred in the Mweka and Luebo health zones of the Province of Kasai-Occidental.[33]
2012 Jun–Aug
Uganda
SEBOV
24
17
71%
Outbreak occurred in the Kibaale District.[34]
2012 Jun–Nov
Democratic Republic of Congo
BDBV
77
36
47%
Outbreak occurred in Province Orientale.[35][36]
Guinea
Liberia[nb 2]
Sierra Leone
Nigeria
ZEBOV
1779
961
54%
Outbreak is currently ongoing in Guinea (the country of origin), and the neighboring countries of Sierra Leone and Liberia. Several cases have occurred in Nigeria, in travelers from infected areas, and subsequently in health care workers.[38] This outbreak is the most severe in recorded history in regards to both the number of human cases and fatalities.[39]
  Many other countries like Germany, India, Saudi Arabia, Spain are suspected to have the Infected cases.
World Health Organization head Margaret Chan admitted that the Ebola outbreak is spreading faster than the efforts to control it. Stay Safe.
                                                                                                                 -CURIE.
(P.S.- Some of the images & information is taken from en.wikipedia.org and www.cdc.gov/vhf/ebola/resources/pdfs/ebola-factsheet.pdf)