Virus 3 (RNA): VHF (non-arboviral)

Question 1

Which infections cause VHF without being an arbovirus?

Answer 1

• The main ones to focus on in this chapter:
  
  • Ebola and Marburg
  • Lassa
• Mixed (arthropod and human to human)
  
  • Crimean Congo and Rift Valley

Question 2

VHF can be caused by arboviruses. Which viruses cause VHF without transmission from arthropod vector, i.e. person to person spread?

Answer 2

• Arthropods:
  
  • Dengue and Yellow Fever
  • Chikungunya
  • Zika
  • Japanese Encephalitis
• Arthropods and bodily fluids:
  
  • Crimean-Congo and Rift Valley
• Only direct transmission
  
  • Ebola
  • Marburg
  • Lassa

Question 3

What are the main clinical features of VHF?

Answer 3

• Early signs can be quite non-specific – oral ulcers, pharyngitis, conjunctivitis.
• Vascular permeability – oedema, effusions – or just haematocrit rise.
• Haemorrhage – from minor bruising to bleeding from gums, nasopharynx/rectum.
• Abdominal pain is often a prominent feature – can mimic peritonitis.
• Encephalopathy.
• Liver/renal failure, hepatosplenomegaly, cytopenia, rising haematocrit.

Remember: most suspected VHF turn out to be malaria

Question 4

What history can point us towards VHF?

Answer 4

• Recent travel - rural vs urban, timeline
• Activities
• Symptoms
• Look for signs of haemorrhagic manifestations
  
  • Petechiae, gum bleeding, microscopic haematuria
• Clinical Investigation
  
  • Haematocrit
  • Pleural effusion, etc.

Question 5

What diagnostic tests are likely going to be most useful?

Answer 5

Investigations

• Screen for DDx
• Elisa antigen testing, PCR testing, elisa antibody testing

Question 6

What is the general management approach in VHF?

Answer 6

Management

• Principles are to identify and treat cases – index case and contact tracing [contacts are monitored for fever for 3 weeks, which is maximum incubation time]
• Prevent the spread of infection – isolation/PPE/public health/etc.

Treatment

• As for septic shock
• Cover with antimalarials and antibiotics until proven
• Ribavarin indicated in all excluding Ebola, Dengue and Yellow Fever.
• Psychological aspects amongst survivors

Question 7

Where is Lassa Virus found and how is it transmitted?

Answer 7

• Found across West Africa – about 200,000 cases/year
• Transmitted via the urine/faeces of rodents - spread via aerosolised inhalation or contamination to humans. Then nosocomial spread possible.
• Clinically a febrile illness with URT and GI symptoms
• Severe cases can cause septic and haemorrhagic picture
• Sensorineural deafness a late complication in 30% of pts
• Rx Ribavarin

Question 8

What do the Ebola and Marburg virus look like and how have the appeared?

In this section: what applies for Ebola also applies for Marburg

Answer 8

• Enveloped and filamentous
• Single-stranded, non-segmented, negative sense RNA virus
• 5 biotypes: ebola-Zaire, Ebola-Sudan, Ebola-Cote d’Ivoire, Ebola-Bundibugyo, Ebola-Reston
• Found in West/Central Africa, esp DRC
• Bats and primates thought to be animal reservoir.
• Infection through blood/fluid contact of infected person.
• If no fever/no symptoms = no infectious risk
• First outbreak Marburg in 1967 and Ebola 1976.
• High mortality: 30% Marburg, 60 - 90% Ebola but depends on outbreak

Question 9

How has Ebola infected humans?

Answer 9

• Ebola virus
  
  • Enveloped and filamentous
  • Single-stranded, non-segmented, negative sense RNA virus

Question 10

What are the clinical features of Ebola virus?

Answer 10

• Starts with flu-like symptoms, then gastroenteritis and gastropathy, then MOF
• Symptoms start within 2 - 21 days of infection

Question 11

How can Ebola be transmitted between humans?

Answer 11

Question 12

What is the difference between case-fatality rate and fatality rate?

Answer 12

Question 13

How can Ebola be diagnosed?

Answer 13

PCR from blood

Question 14

Are there any vaccines for Ebola and once someone has survived EVD and cleared the virus, what precautions should they take?

Answer 14

Currently in trials

Semen stays infective with the Ebola virus after EVD recovery so condoms should be provided for all survivors. The WHO recommends that semen testing should be performed 3 months after the onset of the disease. Condoms should be used at all times during these first three months and all contact with semen should be avoided. For those that are positive from this test, further testing should be carried out every week until two negative tests are returned. For those who are unable to be tested, condoms should be used for a minimum of six months as a precaution.

Question 15

Pertinent facts about Rift valley Fever?

Answer 15

• Patchy distribution in sub-Saharan Africa, Egyp and middle east
• Low mortality
• Humans infected by mosquitoes
• Direct transmission between humans not explicitly discovered
• Usually mild febrile illness
• 5% have haemorrhagic manifestations

Question 16

Where do you find Crimean-Congo haemorrhagic Fever (CCHF)?

Answer 16

• CCHF is endemic in Africa, the Balkans, Middle East and Asia.

Question 17

How is CCHF transmitted?

Answer 17

Transmission

• The hosts of the CCHF virus include a wide range of wild and domestic animals
• The vector are ticks, particularly of the Hyalomma genus.
• The CCHF virus is transmitted to people either by tick bites or through contact with infected animal blood or tissues during and immediately after slaughter.
• Human-to-human transmission can occur resulting from close contact with the blood, secretions, organs or other bodily fluids of infected persons.

Question 18

What are the clinical features of CCHF?

Answer 18

Signs and symptoms

• Incubation is 1-5 days.
• Onset of symptoms is sudden, with fever, myalgia, etc. There may be gastric upset followed by sharp mood swings and confusion. Then the agitation may be replaced by sleepiness, depression and lassitude, and tender hepatomegaly.
• Other clinical signs include tachycardia, lymphadenopathy and a petechial rash on internal mucosal surfaces and on the skin. The petechiae may give way to larger ecchymosis, and other haemorrhagic phenomena. There is usually evidence of hepatitis +/- any other organ dysfunction.
• The mortality rate from CCHF is approximately 30% (normally 2nd week of infection)

Question 19

How is CCHF diagnosed?

Answer 19

Diagnosis

• Antigen
• PCR
• Virus isolation by cell culture
• Antibodies develop late – not helpful acutely
• Tests on patient samples present an extreme biohazard risk.

Question 20

How do we treat CCHF and prevent it from spreading?

Answer 20

Treatment

• Ribavarin – PO or IV
• Supportive

Reducing the risk of tick-to-human transmission:

• Wear protective clothing (long sleeves, long trousers); approved tick-insecticides on clothing, examine clothing/skin for ticks, etc.

Reducing the risk of animal-to-human transmission:

• Wear gloves and other protective clothing while handling animals/tissues; quarantine animals before they enter slaughterhouses.

Reducing the risk of human-to-human transmission

• Avoid close physical contact with CCHF-infected people; hand hygiene, PPE [as for Ebola], safe injection practices, trained staff in biosafety and appropriate biohazard level labs for taking/analysing serum/tissue samples, safe burial practices.