Another Bleeding Patientthe Whys and Wherefores

Viral Haemorrhagic Fevers (VHFs)

Morphology
Monopartite, (+)ve sense ssRNA Genome length is 10 000kb 40-65nm in diameter with lipid

envelope (Capside is 25-30nm) Spheriodal (pleomorphism?) 5 methylated cap or genomelinked protein, no 3 poly(A) tail

What are VHFs? A multisystem syndrome caused by four distinct families of viruses where the bodys vasculature and regulation are impaired and haemorrhage is a common result of infection. Symptoms range from subclinical to life-threatening conditions and subsequent death.

Haemorrhagic Fever Viruses RNA viruses enclosed in lipid envelope Found naturally in zoonotic cycles Restricted geographically to regions where hosts live
Relevance to Dentistry It is possible to have a patient afflicted with the condition although highly unlikely in the UK. Some HFVs are highly Morphology

infective are could be released from these patients due to Dentistrys Exposure Prone Procedures. Manifestations of VHFs could be detected by dentists and therefore be suspected if they Have some knowledge of these diseases, patients recent travel history and contact with infectious agents. Signs and Symptoms
S Lassa Fever Facial Oedema Fluid in lungs Internal and external bleeding Low blood pressure Deafness HF caused by Tacaribe virus Myalgia and muscle weakness Exhaustion Internal and external bleeding Coma and seizures Petechiae and upper body flushing

Epidemiology
Lassa Fever occurs mainly in the region of West Africa, including Guinea, Sierra Leone, Nigeria, and Liberia.Higher occurance in the dry season. The Junin virus that causes Argentine HF, was first discovered in Beunos Aires in the Junin Partido. The virus is endemic also to Cordoba and Santa Fe.

Transmission to humns
Arenaviruses are often associated with rodents. The Muridae Signodontinae is a type of rat that could transmit the Tacaribe viruses. Transmission to humans could be due to handing mice excrement or bodily fluids or through direct contact on broken skin. Nosocomial transmission can occur through handling infected human tissues or through aerosol.

Cause of Death
Multiple organ failure and cardiovascular shock in YF. Death follows Dengue Shock Syndrome in DHF which includes circulatory collapse.

Transmission to humans
The female Aedes aegypti is the main vector in YF and CHF. Paradoxically, YF is not common in the Southeast Asia. Human-human transmission through exchange of bodily fluids can occur in YF but not DHF. The natural host of YF are primates.

Dimorphic, L-strand is (-)ve and

Image from http://jiang.bio.purdue.edu/research.php

Causes of Haemorrhage
Dengue Haemorrhagic Fever (DHF) May be due to disseminated intravascular coagulation, liver abnormalities and thrombocytopenia. Yellow Fever (YF) Multifactorial bleeding disorder due to reduced synthesis of clotting factors and DIC.

strand is (+/-)ve sense, ssRNA Diameter: 110-130nm Beaded nucleocapsid Pleomorphic

Mortality rate
20-30% in DHF, higher in children 20-50% in YF

How haemorrhage occurs

Viruses enters the host and infect macrophages. This results in the release of mediators of cell and vascular damage. T-cell immunopathology leads to destruction of tissues.

Epidemiology
Yellow Fever Possibly originated in Africa and introduced to South America through the slave trade in the 16th Century. YFV is endemic to South America and Africa tropical area. Dengue Hemorrhagic Fever Prevalent in the tropics and subtropics. Outbreaks were recorded in Cuba and Central America. DHF is common in Southeast Asia including Thailand, Vietnam and Malaysia but is endemic in 112 countries.

Treatment and vaccination

Yellow Fever Ribavirin, an antiviral drug Supportive therapy and pain relief (paracetamol, aspirin contraindicated) Attenuated virus vaccine providing 10years of immunity Dengue Haemorrhagic Fever Supportive therapy like in filoviridae and blood transfusion.

Treatment and Vaccination

Antivirals such as ribavirin is

Mortality rate
15 % -20% for Lassa Fever 20% - 30% for Argentine HF (Caused by Junin virus, a species of Tacaribe virus).

Signs and Symptoms

Myalgia and Headaches Prostration Jaundice (YF only) Internal and external bleeding Blood in vomit Lumbosacral and epigastric pain Petechiae, ecchymosis, gingival

effective against most arenavirus infections There is no treatment for deafness Antibiotics are used for opportunistic bacterial infections No vaccine is presently available No currently prophylactic treatment available

Arenaviridae virion illustration Courtesy of ViralZone 2010, Swiss Institute of Bioinformatics

bleeding

Aedes Aegypti mosquito Photo by Paul I. Howell, MPH; Prof. Frank Hadley Collins/ Centers for Disease Control and Prevention

Flaviviridae Filoviridae
Ebolavirus

Arenaviridae Bunyaviridae

Subconjunctival haemorrhage can be observed in Haemorrhagic fevers. Photo courtesy of Nature.com

Morphology
Single (-)ve sense ssRNA strand Pleomorphic: long branched to

Epidemiology

short 6 or U shaped filaments 80nm diameter, 790nm long for Marburg virus and 970nm long for Ebolavirus Genome length is about 19kb

Epidemiology
Electron micrograph of Ebola Zaire virus. (13/10/76) by Dr. F. A. Murphy. 160 000X Magnification

Morphology
Tripartite(-)ve sense ssRNA strand Diameter: 90-100nm Enveloped (Gn and Gc glycopro-

Signs and symptoms

Filoviridae virion Illustration Courtesy of ViralZone 2010, Swiss Institute of Bioinformatics

Haemorrhage through disseminated intravascular coagulation (DIC)

Marburg Virus: Incubation period of 5-10 days Ebolavirus: Incubation period of 2-21 days

(not a comprehensive list) Severe headaches and discomfort Fever and chills Impaired blood coagulation Internal and external bleeding including orifices Myalgia, chest and abdominal pain Vomiting and diarrhea Maculopapular rash

Marburg virus Initial breakout in Marburg and Frankfurt, Germany and Yugoslavia 1967 due to imported infected monkeys from Uganda. Outbreaks were reported in Congo and Angola. Ebolavirus Outbreaks first occurred in Congo (then Zaire) and Sudan in 1976. Further outbreaks occurred in Uganda and the Ivory Coast. Four species have been found and named after the places their outbreaks first occurred. The Reston Ebolavirus is non-pathogenic to humans.

teins) Genome length is about 10.5 to 22.7kb

Illustration of a Bunyaviridae Virion Courtesy of ViralZone 2010, Swiss Institute of Bioinformatics

Cause of Death
Multiple organ failure or shock due to fluid and blood loss.

Causes of haemorrhage
Endothelial damage contributes to and termination of haemostasis resulting in the activation of coagulation process and thrombocytopenia occurs (disseminated intravascular coagulation). Rift Valley Fever Virus Incubation period: 2-6 days Crimean-Congo HF Virus: Incubation period: 3-21 days

Transmission to humans
Bats may be potential carriers Contact with infected animals Contact with human bodily fluids Aerosol spatter

Fatality rate
23% - 80% for Marburg HF 50% - 90% for Ebola HF Filoviridae are classified as Biosafety Level 4 by Centers for Disease Control and Prevention *CDC+. Both diseases are rare but cause severe outbreaks with high mortality rates.

Treatment and vaccination

Only supportive therapy available: Ensure electrolyte and fluid levels are maintained Maintain O2 status and blood pressure to alleviate nausea Treat opportunistic infections due to compromised immune system Both disease display similar signs and symptoms, differentiating them can only be done through isolation and analysis of the virus from a blood sample.

Rift Valley Fever First identified in Kenya, 1931. Generally East Africa regions. Recent Signs and symptoms outbreaks have occurred in MadaRift Valley Fever gascar and South Africa this year. Biphasic disorder. In severe cases Crimean-Congo HF some of the signs and symptoms of During the Second World War, Crithe HF form are: mea recorded 200 cases of sever Severe liver impairment, jaundice haemorrhagic fever. A similar out Blood in vomit and stools break later occurred in Congo. Virus Internal and external bleeding is endemic to Africa, the Balkans including orifices and Middle East, south of 50 paral Ecchymoses lel North (geographical limit for tick Onset occurs about 4 days after entry of genus Hyalomma). to second phase. Fatality rates Crimean-Congo HF 30-50% for Crimean-Congo HF Biphasic. Haemorrhagic higher in nosocomial infections manifestations in second phase. than naturally acquired by tick bites Petichiae probably due to virus dose. Cerebral and GI haemorrhage 50% for Rift Valley Fever that Haematuria which results in haemorrhagic Neurological problems fever. Bradycardia and hypotension Treatment and vaccination leading to shock Supportive therapy is the main Transmission to humans treatment of CCHF and RVF with similar aims as in the treatment of Rift Valley Fever filoviridae. Ribavirin, and antiviral Contact with animal carcasses and drug, has been used to treated blood established infection. Inoculation or inhalation of A formalin-inactivated cell culture aerosols vaccine for RVF is available and Haematophagous flies and Aedes effective and safe however it is mosquito expensive and exclusive to Crimean-Congo HF laboratory and veterinary workers. Bite from ticks of Hyalomma genus Direct contact with blood or infected tissues of livestock

Cutaneous ecchymosis on the arm of a CCHF patient (7-10days after clinical onset. Photographed by Dr Robert Swanepoel, National Institute of Virology, South Africa Table derived from The Bunyaviridae by Gary Overturn MD from the Paediatric Infectious Disease Journal (2009)

Hyalomma marginatum (bont-legged tick) photographed by Jim Occi, BugPics, Bugwood.org

Treating an Ebola patient. Ebola is highly contagious hence the protective gear donned by a health care worker. Photo courtesy of AFP.

Information sourced from the following sites: http://www.cdc.gov/ http://virology-online.com/viruses/ http://www.vbrc.org/viruses.asp http://www.who.int/en/

By Group 5 Aleeza Cheema Bavan Kang Kavisha Thakar Paras Malde

Prabhroop Kohli Ruchika Aggarwal Steve Conteh Sumeet Oberai Tracie Ooi