Common arbovirus infections Flashcards
What are arboviruses and the three virus families?
Arthropod-borne virus – virus of vertebrates
- Viruses maintained in nature through biological transmission between susceptible vertebrate hosts by blood feeding arthopods (mostly mosquitoes)
- Over 130 arboviruses known to cause disease in humans
Three virus families
- Togaviridae
- Flaviviridae
- Bunyavirida
What are the two transmission cycles?
Man – arthropod – man
Animal – arthropod – man
reservoir may either be in either man or arthopod vector e.g dengue, urban yellow fever
Viruses of medical interest in the Americas
Important arboviruses
Dengue has 4 different serotypes.
Dengue, zika and yellow fever flavivirus
chikungunya is alphavirus.
What are all of the arboviruses transmitted by?
Aedes mosquitos - albopictus and aegypti
Ageypti has white lyre shaped markings on its thorax
Albopictus has median longitudinal white stripe
aegyptic most commonly in tropical regions, can’t survive when too cold
albopictus can survive in north and south us and europe, mostly in summer months
Dengue infection classic
Short lived
High fever 40C (saddleback)
Severe muscle pains (break bone fever)
Erythematous rash followed by morbilliform rash starting on extremities
Generalised lymphadenopathy
Moderately enlarged liver
Profound leucopenia
May have protracted convalescence
Dengue haemorrhagic fever/ shock syndrome
2nd to 5th day of classic dengue
Associated with second or later infections
Increased capillary permeability – shock
Increased bleeding, petechial haemorrhages etc
Increase in haematocrit because plasma leaves circulation and goes to tissues, blood concentration increases, drop in platelets – increased risk in bleeding
Diagnosing dengue
Positive touniquet test
Spontaneous haemorrhages
Thrombocytopenia
Increase in haematocrit
Why does the haemtocrit increase in severe dengue?
When you centrifuge the elements of blood separate
Dense red cells at bottom, layer of white blood cells and platelets and then plasma on top
In severe dengue there is increase in capillary permeability, plasma leaves vessels and goes into tissues, such that you lose plasma and get increase in haemoconcentration – increase in RBC column
What is erythematous (blanching) and morbilliform rash?
Erythematous (blanching) rash - Put hand on someone with dengue and press, you get blanching
Morbilliform rash
Appears after erythematous rash
Start from extremities and move inwards
What is petechial haemorrhages?
Small bleeding patches get bleeding directly from capillaries in skin, causing small haemorrhages in the skin
Larger haemorrhages called purpura
Can get bleeding to gums too
Dengue vaccines and efficacy
Live attenuated tetravalent (Dengvaxia)
Three dose schedule (cost >US$200)
Vaccine efficacy
- 76% against seropositives prior to vaccination
- 39% against seronegatives
- Excess severe dengue among seronegatives
How is a tourniquet test done?
Inflating a blood pressure cuff to a point mid-way between systolic and diastolic pressures for five minutes
A test is considered positive when 10 or more petechiae per 2.5cm2 (1 inch) are observed.
In DHF the test usually gives a definite positive result ie. >20 petechiae.
The test may be negative or mildly positive during the phase of profound shock
How is dengue transmitted?
Bitten by dengue infected mosquito, dengue virus injected
Virus attaches to immune cells e.g DC sign on dendritic cells or attach through mannose type receptor on a macrophage
Infects various immune cells
Outcome of infection varies on number of factors
Can get dengue fever, DHF, or undifferentiated fever
What two groups are most at risk of severe dengue?
Infants with declining levels of maternal antibodies, low levels of circulating antibodies, more susceptible to severe outcomes
Children (often <10yrs) with previous infection
Due to antibody-dependent enhancement – antibodies can bind dengue virus in circulation but binding is not very strong because they’re from a different serotype – doesn’t give right signals, virus is taken up in cell, survives and replicates within cells, releasing more virus – more severe disease
Diagnosing dengue
Early diagnosis with onset of fever if there is virus circulating by doing molecular test e.g PCR, antigen test
Antibodies appear at time viremia start to fall, IgM antibodies around day 3-4 from onset of symptoms
Week later from symptoms you get IgG produced
Treatment of dengue
Supportive
Paracetamol – no aspirin because these affect ability of platelets to enhance clotting, can increase bleeding tendency
Tepid sponging for fever
Fluid replacement where necessary etc – carefully to prevent fluid overload
Prevention and control of dengue
Vaccine
- Tetravalent vaccine (Sanofi)
Vector control
- Insecticide spraying
- Mosquito nets/screens
- Wolbachia and GM mosquitos
What does WHO recommend regarding dengue vaccination?
WHO recommends that countries should consider vaccination (Sanofi-pasteur) with the tetravalent dengue vaccine only if the risk of severe dengus in seronegative individuals can be minimized either through:
Pre-vaccination screening – blood test to see if they have antibodies, if they don’t have antibodies against dengue you don’t give vaccine
Recent documentation of high seroprevalence rates in the area (at least 80% by 9 years old)
What are the limitations of WHO’s recommendation of vaccinating?
Cost >US200
Three dose schedule with doses spaced 6 months apart
Need for pre-vaccination screening with seroprevalence data for regions where it is to be used >70% seroprevalence
Age restriction, 9-45 years
Poor efficacy in preventing symptomatic infections with DENV-1 and DENV-2
What is the takeda TAK 003 vaccine?
Tetravalent live attenuated
Currently being evaluated in trials in 8 countries
- Efficacy against seronegatives
- Robust antibody responses to all 4 serotypes lasting >4 years
- 4-60 years
- Prevents 62% classical dengue and 83% hospitalisations
Chikungunya disease
Incubation 2-7 days
High fever >39c
Rash – itchy maculopapular rash, follows fever
(poly)-Arthralgia – arthritis
- 30-90% cases
- Joints of wrist, ankle, fingers and the back
- Characteristic ‘bent-over’ posture
- Exacerbation of existing arthritis
- Swelling of joints, interphalangeal joints
How to diagnose chikungunya
A week after infection you get viraemia, coincides with fever, arthralgia
Skin rash after fever
During early stage you can pick up viraemia via PCR
After first week you get IgM antibodies appearing in circulation
Treatment of chikungunya
Bed rest, fluid, paracetamol
No aspirin but ibuprofen and other NSAIDs can be used because there’s overlap in symptoms with dengue
Chloroquine for persistent joint pain
Acute illness generally lasts no more than a week
Arthralgia generally resolves within a year
What is zika virus?
Single stranded RNA virus from family Flaviviridae
3 genotypes – W, E Africa and asia with relatively little nucleotide divergence
Closely related to other flaviviruses (dengue, YF, etc(
Virus with neural tropism
How is zika transmitted?
Via a vector
Mainly aedes aegypti but also other Aedes species – albopictus etc
Might also be spread by Anopheles and Culex spp
Direct human to human
- In utero, perinatal including breastfeeding, transfusion, sexual
Clinical presentation
Incubation period <7 days and illness lasts 7 days
Onset symptoms associated with viraemia
80% asymptomatic
Mild self limiting illness
- Mild fever <38C 65%
- Maculopapular and pruritic rash 90%
- Non-purulent conjunctivitis 55%
- Arthralgia 65%
Clinical neurological complications of zika, guillain-barre syndrome
First noted in Polynesia (incidence <1 in 1000)
3 or so weeks after infection
Anti-ganglioside Ab negative
EPS-acute motor axonal neuropathy – can result in respiratory paralysis in severe cases
Clinical neurological complication of zika microcephaly
Small head for gestational size, <2nd centile
Increase first noted in brazil and retrospectively in Polynesia
Highest risk probably during first trimester
Risk of microcephaly now estimated at 3-4% - cf rubella in 1st trimester causes 90% congenital abnormalities
Severe neurological development problems relating to how virus damages cerebral cortex
As brain develops, it pushes out developing skull, if you don’t get development of cortex you get a smaller skull because brain isn’t developing and pushing out skull
Diagnosis of zika
Specific RT-PCR for RNA
- RNA detectable in blood for up to week after onset
- 10 days in urine
- weeks in semen
Specific IgM and IgG ELISAs
- IgM persists for several months, IgG for years
- Problem with cross-reactivity with other flaviviruses
(eg dengue)
Neutralization tests (PRNT) for 4-fold increase in
titers
- More specific than ELISA
- Costly and labour-intensive, specialised
How to prevent zika
No treatment or vaccine
Repellents/screens/residual spraying/breeding sites
Postpone travel to endemic areas to not get infected
Postpone pregnancy
Safe sex
Clinical presentation of yellow fever
Red eyes
Fever
Vomiting
Back pain
Headache
Bleeding
Jaundice
Muscle aches
Hepatomegaly
Yellow fever clinical disease
Incubation 3-6 days
3-4 days of fever, headache, chills, back pain, muscle pain, nausea, vomiting
15% go on to develop more severe illness
- Recurring fever
- Jaundice and abdominal pain
- Bleeding and haematemesis
- Death 5% but 20-50% of those with jaundice
Yellow fever vaccine
17D developed in 1937
Liver attenuated vaccine
Single dose, lifelong protection
Cases of reversion to virulence
How can arbovirus infections be controlled?
Aedes aegypti domesticated vector that breeds around households
- Water containers, bottles, used tyres
Eggs resistant, can survive more than 6 months in desicated state
- Eggs need very little water to develop e.g teaspoon
Rapid urbanisation in overcrowded slums without drainage and rubbish disposal provide perfect environment for vectors
Personal and household protection
- Clothes, repellents, nets, window and door screens, covering water sources
Spraying
- Residual insecticides
community education
GM mosquitoes
Wolbachia
Insecticides
Community campaigns and insecticides can be effective in mosquito control
- Synthetic insecticides can have adverse health and ecological effects
Insecticide resistance growing problem
- Pyrethroids have been replaced by malathion
- Malathion persists in clothes etc
- Abate (temephos) in water
Larval surveys important in surveillance - Needs to be done at regular intervals
- Resource intensive
