Arboviruses, Haemorrhagic Fever Viruses and Rabies
Arboviruses ★★★
Viruses from various families which are transmitted via ARTHROPODS from one vertebrate to another. The name is a contraction of ARthropod-BOrne virus.
Diseases caused by arboviruses: ENCEPHALITIS · FEBRILE DISEASES · HAEMORRHAGIC FEVERS.
| Family | Virus | Disease | Distribution | Vector |
|---|---|---|---|---|
| Flaviviridae | Encephalitis B virus (Japanese encephalitis virus) | Epidemic encephalitis B | Asia — subtropical or tropical regions | Mosquito |
| Dengue virus | Fever, haemorrhagic fever | Worldwide — tropical regions | Mosquito | |
| Forest encephalitis virus | Forest encephalitis | Worldwide | Tick | |
| Bunyaviridae | Xinjiang haemorrhagic fever virus | Xinjiang haemorrhagic fever | Xinjiang, China | Tick |
Encephalitis B virus
| Detail | |
|---|---|
| Properties | 45–50 nm · +ssRNA · spherical · ENVELOPED · ONLY ONE SEROTYPE · E (envelope) protein |
| Source | Mosquitoes and livestock |
| Vector | Mainly Culex tritaeniorhynchus |
| Region | Subtropical and tropical Asia |
| Incubation | 4–8 days |
| Process | The virus infects a human → multiplies in local endothelial cells of blood vessels and lymph nodes → blood → multiplies in liver, spleen etc. → blood → in most, fever and malaise, then recovery; in a few, the virus breaks through the blood–brain barrier and reaches the CNS, giving high fever, coma and convulsion |
| Prevention | Vector control · avoid mosquito bites · eliminate all Culex breeding places · vaccination of humans and the animal reservoir. Treatment: none |
Dengue virus
| Detail | |
|---|---|
| Family and structure | Flaviviridae · 40–60 nm · spherical · +ssRNA · icosahedral capsid · enveloped, with glycoprotein |
| Hosts | Human and monkey; epidemic in South-East Asia |
| Pathogenesis | Infects a human by mosquito sting → multiplies in capillary endothelial cells and mononuclear cells → blood → disseminated through the body |
| Dengue fever | Fever, malaise, enlargement of lymph nodes, muscle and joint pain, maculopapular rash |
| Dengue haemorrhagic fever | IN RE-INFECTION. Dengue fever PLUS haemorrhage and circulatory failure → SHOCK |
| Prevention | Kill mosquitoes; vaccine |
Zika virus
Flaviviridae; vector mosquitoes. Its name comes from the Zika Forest of Uganda, where the virus was first isolated in 1947. Zika fever often causes no or only mild symptoms; there is no specific treatment and no vaccine. Zika can also spread from a pregnant woman to her fetus, resulting in MICROCEPHALY, severe brain malformations and other birth defects.
That one phrase — in re-infection — is the most examinable line about dengue, and it is counter-intuitive enough to be worth understanding.
There are four dengue serotypes. Infection with one gives lifelong immunity to that serotype but only brief cross-protection against the others. When a different serotype arrives later, the existing antibody binds it but cannot neutralise it — and the antibody-coated virus is then taken up more efficiently into mononuclear cells through their Fc receptors.
More infected cells, more cytokines, and the result is the plasma leak, haemorrhage and circulatory failure of dengue haemorrhagic fever and dengue shock syndrome. The deck's pathogenesis line already points at it: the virus multiplies in capillary endothelial cells and mononuclear cells.
The antibody makes it worse. Which is also why a dengue vaccine is so difficult — it must protect against all four serotypes at once, or it risks priming for severe disease.
Note the contrast with Zika, the mildest of these flaviviruses in the patient and the most feared in pregnancy — microcephaly — exactly the pattern rubella showed in Unit 22 §6.
- Define an arbovirus. → Viruses from various families transmitted via arthropods from one vertebrate to another
- Which three disease groups do they cause? → Encephalitis, febrile diseases, haemorrhagic fevers
- Describe encephalitis B virus. → 45–50 nm, spherical, enveloped, +ssRNA, one serotype, E protein; vector Culex tritaeniorhynchus in subtropical and tropical Asia; incubation 4–8 days
- Give its pathogenesis. → Multiplies in local vascular endothelium and lymph nodes → blood → liver and spleen → blood; most recover with fever and malaise, a few breach the blood–brain barrier giving high fever, coma and convulsion
- When does dengue haemorrhagic fever occur, and what is added? → On re-infection; dengue fever plus haemorrhage and circulatory failure leading to shock
- What does Zika cause in pregnancy? → Microcephaly, severe brain malformations and other birth defects
Haemorrhagic fever viruses ★★★
A group of viruses that can cause viral haemorrhagic fever (VHF): HYPERPYREXIA, HAEMORRHAGE and HYPOTENSION.
The main haemorrhagic fever viruses: Hantavirus · Crimean-Congo haemorrhagic fever virus · dengue virus · Marburg virus and Ebola virus.
Hantavirus
| Detail | |
|---|---|
| Associated with HFRS (haemorrhagic fever with renal syndrome) | Hantaan virus · Dobrava-Belgrade virus · Puumala virus · Saaremaa virus · Seoul virus |
| Associated with HPS (hantavirus pulmonary syndrome) | Sin Nombre virus · Black Creek Canal virus · New York virus · Bayou virus |
| Properties | 80–120 nm average · spherical or ovoid · genome of 3 SEGMENTED ssRNA · ENVELOPED. Sensitive to lipid solvents, acid and heat — killed at 60 °C in 1 hour |
| Source | RODENTS — field, urban and sylvatic. The infection in rodents is LIFELONG and without deleterious effects. Viral contamination comes from rodent URINE, STOOL and SALIVARY SECRETION |
| Transmission | Respiratory tract · alimentary tract · contact |
| Pathogenesis | The main lesion is GENERALISED DAMAGE OF SMALL BLOOD VESSELS AND CAPILLARIES, by direct damage and immunopathological damage |
| Diagnosis | Hantavirus-specific IgM, or a FOURFOLD or greater increase in IgG titre · RT-PCR · immunohistochemical staining |
| Control | Supportive therapy. Rodent control and protection from exposure to rodent droppings · hantavirus INACTIVATED vaccines against HFRS |
Crimean-Congo haemorrhagic fever (CCHF)
| Detail | |
|---|---|
| Classification | Nairoviridae, genus Orthonairovirus |
| Distribution | Africa, Asia, the Middle East and Eastern Europe. Outbreaks have a case fatality rate of up to 40% |
| Reservoir | Wild animals (rodents, hare, fox) and domestic animals (cattle, sheep, goat, cow, horse). Vector: TICK — which is also a reservoir |
| Transmission | Stung or bitten by an infected tick · contact with blood or products of infected animals or patients |
| Clinical | 1–3 days incubation after a tick bite; 5–6 days after direct contact. Abrupt onset of fever, chills, malaise, myalgia and headache; haemorrhages may be profuse — haematomas and ecchymoses |
| Therapy | Supportive therapy and the antiviral drug RIBAVIRIN. No safe and effective vaccine; prevention is avoiding tick bites and contact with products of infected animals or patients |
Different families, different vectors, one lesion. The hantavirus slide names it exactly: generalised damage of small blood vessels and capillaries.
Damage the endothelium everywhere and three things follow, and they are the three words in the definition:
• Vessels leak → haemorrhage
• Plasma volume falls → hypotension and shock
• Massive cytokine release → hyperpyrexia
Which is the same mechanism as Rickettsia in Unit 15 — an organism that exclusively infects the endothelial cells of small blood vessels — and the same final common path as endotoxic shock in Unit 6.
And note the deck's phrase for both damage routes: direct damage AND immunopathological damage. Unit 20 §5 again — half the injury is the host's.
- Define viral haemorrhagic fever. → Hyperpyrexia, haemorrhage and hypotension caused by a group of viruses
- Name the main haemorrhagic fever viruses. → Hantavirus, Crimean-Congo haemorrhagic fever virus, dengue virus, Marburg and Ebola viruses
- Describe hantavirus. → 80–120 nm, spherical or ovoid, enveloped, with three segmented ssRNA; sensitive to lipid solvents, acid and heat (60 °C for 1 h)
- What is the hantavirus reservoir and route? → Rodents, lifelong and harmlessly infected, shedding in urine, stool and saliva; spread by respiratory tract, alimentary tract and contact
- What is the main hantavirus lesion? → Generalised damage of small blood vessels and capillaries, by direct and immunopathological damage
- Describe CCHF. → A Nairovirus spread by ticks (also a reservoir) and by contact with blood or products of infected animals or patients; abrupt fever, chills, malaise, myalgia and headache with profuse haemorrhage; up to 40% fatality; treated with ribavirin; no vaccine
⭐ Rabies ★★★
| Detail | |
|---|---|
| Cause | Rabies is caused by a RHABDOVIRUS. Unit 18 §2 gave its shape: BULLET-shaped |
| Target | The virus gets into the body and attacks the CENTRAL NERVOUS SYSTEM |
| Host range | WIDE — all warm-blooded animals. The virus is widely distributed in infected animals, especially in the nervous system, saliva, urine, lymph, milk and blood |
| Resistance | Survives storage at 4 °C for weeks and at −70 °C for years. Killed rapidly by UV, heat, lipid solvents, trypsin, detergents and extremes of pH |
| Incubation | Typically 1–3 MONTHS. Mainly depends on the DISTANCE the virus has to travel from its point of entry to the CNS, and the amount of infecting virus |
| Clinical type | Features |
|---|---|
| Encephalitic (FURIOUS) rabies | Characterised by HYPERACTIVITY and HALLUCINATIONS |
| Paralytic rabies | Characterised by PARALYSIS and COMA |
| Laboratory diagnosis | Detail |
|---|---|
| Viral antigen | On a SKIN BIOPSY, by immunofluorescence staining |
| Viral RNA | In SALIVA, by RT-PCR |
| Serology | Blood or CSF |
⭐ Post-exposure prophylaxis — three steps, in order
- Care of the wound — wash immediately for 15 MINUTES with soap, water and disinfectant; tetanus prophylaxis should be considered
- Passive immunisation — administer high-titre human rabies immunoglobulin (HRIG)
- Active immunisation — administer rabies vaccine
Pre-exposure prophylaxis is for persons at high risk of contact with rabies virus — veterinarians, laboratory workers and spelunkers. There is NO successful treatment for clinical rabies: interferons, ribavirin and other drugs have shown no beneficial effect. Symptomatic treatment may prolong life, but the outcome is almost always FATAL. WHO has set regional, progressive targets to end human deaths from dog-mediated rabies by 2030.
Rabies is essentially 100% fatal once symptoms appear — and yet it is entirely preventable after exposure. Both facts come from the same sentence: the incubation depends mainly on the distance the virus has to travel from its point of entry to the CNS.
The virus travels up a peripheral nerve, slowly — Unit 20 §3's intra-axonal spread. That takes 1–3 months, and during that time the virus is not in the blood and is invisible to the immune system.
That interval is the entire therapeutic window, and it dictates the order of the three steps:
Wash the wound for 15 minutes — the virus is still at the site, and it is killed rapidly by detergents and lipid solvents, per the resistance row. Soap physically removes and inactivates it. This alone prevents a large proportion of cases.
Immunoglobulin — ready-made antibody, acting now, neutralising virus before it enters a nerve.
Vaccine — the patient's own antibody, which takes weeks to develop, but there are weeks available. Rabies is one of the very few infections where vaccination AFTER exposure works, and it works only because the incubation is longer than the immune response.
A bite on the face is more urgent than a bite on the foot for exactly the reason the slide gives: less distance to travel.
- What causes rabies, and what shape is the virus? → A rhabdovirus — bullet-shaped
- What is its host range and distribution in the animal? → All warm-blooded animals; the virus is in the nervous system, saliva, urine, lymph, milk and blood
- Give the incubation period and what determines it. → Typically 1–3 months, depending mainly on the distance from the entry point to the CNS and the amount of virus
- Name the two clinical types. → Encephalitic (furious) rabies with hyperactivity and hallucinations; and paralytic rabies with paralysis and coma
- How is it diagnosed? → Viral antigen on skin biopsy by immunofluorescence, viral RNA in saliva by RT-PCR, and serology of blood or CSF
- Give the three steps of post-exposure prophylaxis. → Wash the wound for 15 minutes with soap, water and disinfectant (and consider tetanus prophylaxis) · passive immunisation with high-titre rabies immunoglobulin · active immunisation with rabies vaccine
- What is the prognosis of clinical rabies? → There is no successful treatment; the outcome is almost always fatal
⭐ The Negri body ★★★
Round or oval, EOSINOPHILIC, INTRACYTOPLASMIC inclusion bodies, observed under the light microscope within the cytoplasm of some NERVE CELLS infected with RABIES VIRUS.
The three supporting marks:
What it is generally — an INCLUSION BODY, defined in Unit 20 §5 as a round or oval, acidophilic or basophilic structure in the cytoplasm or nucleus, observable under the light microscope, and one of the components of cytopathic effect (CPE).
Where it is found — in neurons, classically the pyramidal cells of the hippocampus and the Purkinje cells of the cerebellum; stained with HE.
Why it matters — it is the classic histological diagnosis of rabies, made post-mortem on brain tissue. Note that modern diagnosis uses immunofluorescence on skin biopsy and RT-PCR on saliva (§3), because Negri bodies are absent in a proportion of proven cases.
Be precise about the two adjectives: eosinophilic and intracytoplasmic. Those are the discriminating words.
- Define a Negri body. → A round or oval, eosinophilic, intracytoplasmic inclusion body seen by light microscopy in nerve cells infected with rabies virus
- What is an inclusion body in general? → A round or oval acidophilic or basophilic structure in the cytoplasm or nucleus, visible by light microscopy — part of the cytopathic effect
- Which two adjectives are essential? → Eosinophilic and intracytoplasmic
- Is it still the diagnostic method? → It is the classic histological diagnosis, but modern diagnosis uses immunofluorescence on skin biopsy and RT-PCR on saliva
⚠️ A different exam format exists
“Final Exam. Including — Best choice: 20 for 1 point · Blanks: 20 for 1 point · Definitions: 6 for 4 points · Questions: 6 for 6 points.”
That totals 100 marks, and it differs from the 2019 and 2020 papers in two important ways:
1 · It has a 20-question MULTIPLE-CHOICE section worth 20% — which the 2019 and 2020 papers do not have at all. (The 2004–2011 papers did.)
2 · The weights are different: definitions 24% (6 × 4) rather than 32%, blanks 20% (20 × 1) rather than 16%, and questions 36% (6 × 6) rather than 42% + 10%.
What to do about it. The content examined is identical either way — the same definitions, the same comparisons, the same organisms. Nothing in these 27 units changes. But if the paper carries a multiple-choice section, the MCQs printed on the lecture decks themselves become far more valuable: every one this project found is reproduced with its answer and reasoning — in Unit 11 §7, Unit 12 §5, Unit 13 §9, Unit 14 §7, Unit 15 §7, Unit 16 §6 and Unit 17 §6.
Ask the lecturer which format applies to this sitting. Do not assume the 2019/2020 structure without checking.
Revision
The whole unit on one screen
| Question | Answer |
|---|---|
| Arbovirus? | Viruses of various families transmitted via arthropods between vertebrates |
| Their three disease groups? | Encephalitis · febrile disease · haemorrhagic fever |
| Encephalitis B vector? | Culex tritaeniorhynchus; subtropical and tropical Asia |
| Dengue haemorrhagic fever? | On RE-infection — dengue fever plus haemorrhage and circulatory failure → shock |
| Zika in pregnancy? | Microcephaly and severe brain malformation |
| VHF definition? | Hyperpyrexia, haemorrhage, hypotension |
| Hantavirus reservoir? | Rodents — lifelong infection, shed in urine, stool, saliva |
| Hantavirus lesion? | Generalised damage of small vessels and capillaries |
| CCHF? | Tick-borne Nairovirus; up to 40% fatality; ribavirin; no vaccine |
| Rabies virus? | A rhabdovirus, bullet-shaped, attacking the CNS |
| Rabies incubation? | 1–3 months, depending on distance to the CNS |
| Rabies types? | Furious (hyperactivity, hallucinations) and paralytic (paralysis, coma) |
| ⭐ Negri body? | Eosinophilic intracytoplasmic inclusion in rabies-infected nerve cells |
| Rabies PEP? | Wash 15 min → immunoglobulin → vaccine |
- Define Negri body for 4 marks. → A round or oval eosinophilic intracytoplasmic inclusion body seen by light microscopy in nerve cells infected with rabies virus; it is a form of inclusion body and the classic histological diagnosis of rabies
- Define an arbovirus and name its disease groups. → Viruses of various families transmitted by arthropods between vertebrates, causing encephalitis, febrile disease and haemorrhagic fever
- Why does dengue haemorrhagic fever occur on re-infection? → Non-neutralising antibody from the first serotype enhances uptake of the second into mononuclear cells, worsening the disease
- Describe the three steps of rabies post-exposure prophylaxis and why they work. → Wash the wound 15 minutes with soap and disinfectant (the virus is lipid-solvent sensitive) · high-titre immunoglobulin for immediate protection · vaccine, which has time to work because the incubation is 1–3 months
- What is the main lesion of viral haemorrhagic fever? → Generalised damage to small blood vessels and capillaries, giving haemorrhage, hypotension and hyperpyrexia