Arboviruses: Dengue, Chikungunya and zika Flashcards

1
Q

What are arboviruses?

A
  • Arthropod-borne virus
  • Viruses maintained in nature through biological transmission between susceptible vertibrae hosts by blood feeding arthropods (mostly mosquitoes)
  • Over 130 arboviruses known to cause disease in humans
  • Three virus families:
    • Togaviridae
    • Flaviviridae
    • Bunyaviridae
  • There is animal to mosquito to man transmission
  • There is man to man transmission
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2
Q

Describe some of the transmission cycles that pertain to arboviruses

A
  • Arthropod borne viruses- virus of vertebrates
  • Transmitted by insects vectors
  • Cause infections in animals and birds
  • Transmitted to man by bite of an infected mosquito, tick and sand fly
  • World-wide but more in tropical areas than temperate areas

Transmission cycle

  • Man->Arthropod->Man (within human populations)
  • Animal-> arthropod-> man (zoonosis)
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3
Q

What is zoonosis

A
  • A zoonosis is an infectious disease that has jumped from a non-human animal to humans. Zoonotic pathogens may be bacterial, viral or parasitic, or may involve unconventional agents and can spread to humans through direct contact or through food, water or the environment.
  • represent a major public health problem around the world due to our close relationship with animals in agriculture, as companions and in the natural environment.
  • Zoonoses can also cause disruptions in the production and trade of animal products for food and other uses.
  • There are over 200 known types of zoonoses
  • Zoonoses comprise a large percentage of new and existing diseases in humans
  • Some zoonoses, such as rabies, are 100% preventable through vaccination and other methods
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4
Q

Name some diseases that undergo a zoonosis

A

Zoonoses comprise a large percentage of all newly identified infectious diseases as well as many existing ones. Some diseases, such as HIV, begin as a zoonosis but later mutate into human-only strains. Other zoonoses can cause recurring disease outbreaks, such as Ebola virus disease and salmonellosis. Still others, such as the novel coronavirus that causes COVID-19, have the potential to cause global pandemics.

Arthropod borne viruses

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5
Q

Who is at risk ofaquiring a zoonotic infection?

A

Zoonotic pathogens can spread to humans through any contact point with domestic, agricultural or wild animals.

Markets selling the meat or by-products of wild animals are particularly high risk due to the large number of new or undocumented pathogens known to exist in some wild animal populations.

Agricultural workers in areas with a high use of antibiotics for farm animals may be at increased risk of pathogens resistant to current antimicrobial drugs.

People living adjacent to wilderness areas or in semi-urban areas with higher numbers of wild animals are at risk of disease from animals such as rats, foxes or raccoons.

Urbanization and the destruction of natural habitats increase the risk of zoonotic diseases by increasing contact between humans and wild animals.

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6
Q

What are the WHO guidelines against a zoonotic infection

A

WHO works with national governments, academia, non-governmental and philanthropic organizations, and regional and international partners to prevent and manage zoonotic threats and their public health, social and economic impacts.

These efforts include: fostering cross-sectoral collaboration at the human-animal-environment interface among the different relevant sectors at regional national and international levels.

WHO also works to develop capacity and promote practical, evidence-based and cost-effective tools and mechanisms for zoonoses prevention, surveillance and detection through reporting, epidemiological and laboratory investigation, risk assessment and control, assisting countries in their implementation.

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7
Q

What does the WHO One Health approach relate to zoonotic infections?

A

As part of the One Health approach, the World Health Organization collaborates with the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) on the Global Early Warning System for Major Animal Diseases (GLEWS).

This joint system builds on the added value of combining and coordinating alert mechanisms of the three agencies to assist in early warning, prevention and control of animal disease threats, including zoonoses, through data sharing and risk assessment.

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8
Q

Describe the man->arthropod-> man cycle

A

Reservoir may be in either man or arthropod vector (e.g. dengue, urban yellow fever.

This is a cycle within the human population

In the latter (reservoir in the arthropod vector), transovarial transmission may occur (transmission from the mother to eggs)

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9
Q

Describe the animal->arthropod->man cycle

A

The reservoir is in an animal (mammalian host)

The virus us maintained in nature ina transmisison cycle involving the arthropod vector and animal. Man becomes infected incidentally

E.G. Japanese encephalitis, EEE, WEE, yellow fever

For yellow fever, infection occurs in forest areas (like when someone goies hunting), then it spreads to urban populations through an arthropod man cycle.

There is a fear in latin america due to the forests

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10
Q

Name examples of important arboviruses in the Americas

A

Generally there is one serotyp, however dengue has 4 serotypoes

Chikungunya is an alphavirus

(The rest are flaviviruses (RNA virises))

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11
Q

What arthropod are dengue, chikungunya and zika transmitted by?

A
  • Aedes mosquito
  • Both A.aegypti & a.albopictus
  • A.aegypti has a lyre shaped marking, whereas A.albopictus has a single white line on the thorax
  • Typically, aegypti has a lighter colour than albopictus
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12
Q

Describe the geographic distribution of Aedes

A
  • Restricted by tropics
  • Different isotherms
  • When looking at A.aegypti, it has a 10 degree celcius isootherm. Below the 10 degree isotherm, it cannot survive or proliferate
    • Present in the northern hemisphere isotherm
  • When looking at A.albopictus, is can survive and proliferate above the 10 degree isotherm, therefore there is more of a widespread albopictus proliferation
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13
Q

Describe the distribution of dengue infection

A

Largely restricted by isotherms, bwteen the Jan 10 degree to the July 10 degree isotherms. You get good DENV replication in this isotherm.

Outbreak in southern India in the 1940s. Outbreak of different dengue serotypes but they may not occur at the same time.

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14
Q

Describe temporal trends in Dengue serotypes (Thailand)

A
  • Each line represents a dengue serotype
  • In this interendemic period, you get outbreaks of other serotypes
  • Sometimes there are all 4 serotypes occuring at the same time
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15
Q

What are the features of a classic dengue infection?

A
  • Incubation 2-7 days
  • Classic
    • Shirt-lived
    • High-fever 40oC (saddleback fever, which means that the high fever goes away and comes back)
    • Severe muscle pains (break bone fever)
    • Erythematous rash followed by morbiliform rash starting on extremities (measles type rash)
    • Generalised lymphadenopathy
    • Moderately enlarged liver
    • Profound leucopenia (dropped white cell count)]May have protracted convalesence
      • Means takes people a long time to recover
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16
Q

Describe the initial viraemia process in dengue

A
  • During the initial fever, you have an onset of viraemia
  • Immune response kicks in
  • During viraemia, you get the greatest risk of severe dengue, which is associated with shock (when plasma goes into the periphery)
  • You get a lower circulatory volume as the plasma leaves the circulatory tissue
  • Then the concentration of blood cells in blood increases (increased haematocrit concentration)
  • Then thrombocytopaenia occurs
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17
Q

Describe how haematocrit relates to dengue

A
  • Haematocrit concentration goes down with anaemia
  • However, in dengue when the plasma leaves the circulation and goes into the periphery, you get an increase in the concentration of red blood cells
  • Therefore, haematocrit concentration increases with dengue
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18
Q

What type of rashes do you get in dengue fever?

A

Erythematous (blanching) rash

Milliborm rash (measles type rash)

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19
Q

What is dengue haemorrhagic fever/dengue shock syndrome

A
  • Presents on the 3rd-6th day of classic dengue
  • Associated with second ot later infections
    • You get more severe dengue with a severe infection
  • Increased capillary permeability–>shock
    • When the plasma leaves the circulation into peripheral tissues, you get hypovolaemic shock
  • Diagnosis:
    • Positive tourniquet test
    • Spontaeneous haemorrhages (in the eyes & skin)
    • Thrombocytopaenia (loss of platelets)
    • Increase in haematocrit
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20
Q

What are petechial haemorrhages and other haemorrhages that may occur in DHF?

A

Mild hemorrhagic manifestations such as petechiae, purpura, epistaxis, and gingival bleeding are relatively common even in nonsevere dengue cases; they occur in as many as one third of these cases. While the etiology of hemorrhage in patients with dengue is poorly understood, mild hemorrhagic manifestations might be due to increased capillary fragility as a result of thrombocytopenia or platelet dysfunction

Bleeding spots in the skin

Small haemorrhages in the skin

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21
Q

What is a tourniquet test?

A
  • The tourniquet test is part of the new World Health Organization case definition for dengue.
  • The test is a marker of capillary fragility and it can be used as a triage tool to differentiate patients with acute gastroenteritis, for example, from those with dengue.
  • Even if a tourniquet test was previously done, it should be repeated if:
    • It was previously negative
    • There is no bleeding manifestation
22
Q

How would you perform the tourniquet test?

A
  • Perfomed by taking a blood pressure cuff to a point midway between the systolic and diastolic pressures for 5 minutes
  • A test is considered positive when 10 or more petechoae per 2.5cm2 (1 inch) are observed
  • In DHF, the test usually gives a definite positive result (i.e. >20 petechiae)
  • The test may be negative/ mildly positive during the phase of the profound shock
23
Q

Describe the classification of dengue fever

A
24
Q

Describe the dengue pathogenesis & disease

A
  1. You get bitten by an infected Aedes vector
  2. Vector transmits the DENV virus
  3. DENV is taken up by dendritic cells with the DC-Sign receptor
  4. DR by macrophages with the mannose receptor
  5. Immune response occurs
  6. depending on the type of immune response triggered, depends on the risk of getting severe dengye

Also, remember this occurs early in viraemia. Proinflammatory cytokines increase capillary permeability. Increased plasma leakage occurs then shock.

25
Q

Who are the most at risk of getting DHF/DSS?

A
  • Infants with declining levels of maternal antibodies
  • Children (under 10) with a previous infection
  • This is explained by antibody dependent enhancement
26
Q

What is antibody dependent enhancement?

A
  1. Antibody (Ab)-dependent enhancement of infection occurs when preexisting antibodies present in the body from a primary (first) dengue virus (DENV) infection bind to an infecting DENV particle during a subsequent infection with a different dengue serotype.
  2. The antibodies from the primary infection cannot neutralize the virus (they cannot bind efficiently to viruses).
  3. Instead, the Ab–virus complex attaches to receptors called Fcγ receptors (FcγR) on circulating monocytes/macrophages.
  4. It doesn’t switch on the macrophage
  5. The antibodies help the virus infect monocytes more efficiently. It gives the DENV the oppotunity to replicate inside the macrophage
  6. The outcome is an increase in the overall replication of the virus and a higher risk of severe dengue.
27
Q

When would you diagnose DHF?

A

You diagnose before fever onset

early viraemia

IgG response occurs later

28
Q

What is the treatment of dengue (DHF)?

A

Supportive treatment

Paracetamol (No aspirin because it enhances the bleeding)

Tepid sponging for fever

Fluid replacement when necessary

If someone has hypovolaemic shock, replace water cautiously to prevent water overload

This fluid replacement increases circulating volume

29
Q

What is the prevention and control of Dengue?

A
  • Vaccine
    • Tetravalent vaccine (SANOFI)
      • Recognoses all 4 dengue serotyoes
    • However there are questions of usefulness
  • Vector control
    • Insecticide spraying
    • Mosquito nets/screens
    • Wolbachia (coinfect mosquito cells) and GM mosquito (could genetically modify mosquito cells)
30
Q

How can we protect against all DENV serotypes?

A
  • Live attenuated tetravalent vaccine (Dengvaxia)
  • Three dose schedule (cost>US$200)
  • Vaccine efiicacy
    • 76% against seropositives prior to vaccination
    • 39% against seronegatives
    • Excess severe dengue among seronegatives in children
      • Low efficacy
  • If they are vaccinated with seronegativesm it increases the risk of having more severe illness
31
Q

What is the Dengvaxia vaccine?

A
  • WHO recommends countries should consider vaccination with the tetravalent dengue vaccine only if the risk of severe dengue in seronegative individuals can be minimised either through :
    • Pre-vaccination screening
    • Recent documentation of high seroprevalence rates in the area (at least 80% by the age of 9 years to any of the 4 serotypes)
32
Q

Describe the graph showing dengue seroprevalence in population sample in coastal ecuador

A

Risk of dengue increases with age

33
Q

Describe the geographic distribution of chikungunya

A

Chikungunya fever (CHIKF) is a re-emerging mosquito-borne disease caused by a virus endemic to Africa and Asia. Due to the ease with which its vectors propagate, the virus has spread to India and Europe, and more recently it arrived to the Caribbean, eventually extending into North, Central, and South America.

34
Q

Describe the characteristics and symptoms

A
  • Incubatation 2-7 days
  • High fever ( over 39 degrees celsius)
  • Rash
    • Itchy maculopapular rash
    • Follows fever
  • (Poly)-Arthralgia
    • 30-90% cases
    • Joints of wrist, ankles and fingers
    • Characteristic ‘bent-over’ posture
    • Exacerbation of existing arthritis

According to the World Health Organization (WHO), the most common clinical manifestations are abrupt fever, polyarthralgia, headache, maculopapular rash, myalgia, and nausea/vomiting. Severe joint pain and stiffness have been known to incapacitate some patients from a few days to several months after infection.

35
Q

What are the possible diagnosis for chikungunya?

A
  • Serological tests, such as enzyme-linked immunosorbent assays (ELISA), may confirm the presence of IgM and IgG anti-chikungunya antibodies. IgM antibody levels are highest 3 to 5 weeks after the onset of illness and persist for about 2 months.
    • The virus may be directly detected in the blood during the first few days of infection as well.
  • As such, samples collected during the first week of illness should be tested by both serological and virological methods (particularly reverse transcriptase–polymerase chain reaction (RT–PCR)).
  • Various RT–PCR methods are available but with variable sensitivity.
  • Some are suited to clinical diagnostics. RT–PCR products from clinical samples may also be used for genotyping of the virus, allowing comparisons with virus samples from various geographical sources.
36
Q

What are the treatment protocols for chikungunya?

A

There is no specific antiviral drug treatment for chikungunya. The clinical management targets primarily to relieving the symptoms, including the joint pain using anti-pyretics, optimal analgesics, drinking plenty of fluids and general rest.

Medicines such as paracetamol or acetaminophen are recommended to pain relief and reducing fever. Given the similarity of symptoms between chikungunya and dengue, in areas where both viruses circulate, suspected chikungunya patients should avoid using aspirin or Non-steroidal anti-inflammatory drugs (NSAIDs) until which time a dengue diagnosis is ruled out (because in dengue, these medicines can increase the risk of bleeding).

  • Bed rest
  • Fluids
  • Chloroquine can be used for persistant joint pain
  • Acute illness lasts for a week
  • Athralgia generally resolves within a year
37
Q

Name the brief history of Zika.

A
  • 1947 - Zika virus isolated rhesus monkey of Zika forest in Uganda. Arbovirus of the family Flaviviridae
  • First reported in humans in Nigeria in 1954
  • through 1960s - sporadic human cases in Asia and Africa
  • Only 13 naturally acquired cases reported to 2007
  • 2007 - First outbreak – Yap in Micronesia.
    • Rash, conjunctivitis, and arthralgia
    • Estimated ~70% attack rate (5000/6700)
  • • 2013-2014 - Outbreaks in French Polynesia
    • – 32,000 suspected cases
    • Description of Guillain Barré Syndrome
    • 20x greater incidence than expected
    • 2014 – Cases in Easter Island – Chile • Only sporadic cases reported in Asia
38
Q

When did Zika arrives in Latin America?

A
  • Entered Brazil in late 2013 and extended throughout Latin America into 2016 causing millions of cases
  • Feb 1 2016 – WHO declared “public health emergency of international concern”.
  • Associated with increased incidence of microcephaly
39
Q

Describe Zika in the americas

A
40
Q

How can zika be transmitted?

A
  • Through a vector
  • Diseases caused by Zika virus are predominately arboviral and transmitted by the bite of female Aedes aegypti and Aedes albopictus mosquitoes (PREDOMINANTLY AEGYPTI)
  • Person-to-person (human) contact (e.g., sexual contact), blood transfusion, organ transplantation, and perinatally (maternal-fetal vertical transmission) may also transmit infection. Zika virus is related to multiple other arboviral causes of human diseases, including Japanese encephalitis virus, tick-borne encephalitis virus, West Nile virus, dengue virus, and the yellow fever virus
    • In utero, perinatal including ?breastfeeding, transfusion, sexual…
41
Q

What is zika?

A

Single-stranded RNA virus from family Flaviviridae

3 genotypes (E. Africa, W. Africa, and Asia) with relatively little nucleotide divergence

Closely related to other flaviviruses (dengue, YF, etc)

Virus with neural tropism

42
Q

What is the clinical presentation of zika?

A
  • 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 & pruritic rash (90%)
    • Non-purulent conjunctivitis (55%)
    • Arthralgia (65%)
    • Myalgia, headache, retro-orbital pain, oedema, vomiting, haematospermia, hearing problems, swelling of hands and feet, subcutaneous bleeding
43
Q

What are some of the symptoms of zika?

A
  • In symptomatic infections, the most common symptoms\signs include: rash (90% or more), conjunctivitis (55% to 82%), fever (65% to 80%), and headache (45% to 80%).
  • The rash is typically maculopapular, and the fever is often low grade, and short-lived. Other common symptoms and signs include arthralgia (65% to 70%, myalgia (48% to 65%), and retro-orbital pain (39% to 48%).
  • Less commonly:
    • edema
    • vomiting
    • abdominal pain.
    • In areas with dengue fever and chikungunya, which have many symptoms and signs in common, it may be difficult to diagnose the etiology of the illness correctly.
  • Conjunctivitis and rash more commonly are seen in Zika virus infections than dengue fever and chikungunya.
44
Q

What are the clinical symptoms of dengue, chikungunya and zika?

A
45
Q

What are some clinical neurological complications of zika?

A
  • An increase in cases of the acute Guillain-Barre syndrome (a type of acute paralytic neuropathy) was observed during the French Polynesia outbreak.
    • – ~3 or so weeks after infection
    • Anti-ganglioside Ab negative
    • EPS – acute motor axonal neuropathy
  • Although not proven to be the cause, it is suspected that Zika virus infection is likely a trigger of Guillain-Barre syndrome.
  • Cases of acute myelitis and meningoencephalitis (very rare) have also been reported following Zika virus infection.
  • A complete neurologic examination is recommended when Zika virus is suspected.
46
Q

Describe Clinical-microcephaly that may occur in a zika virus infection

A
  • Small head for gestational size (<2nd centile)
  • Increase first noted in Brazil and retrospectively in Polynesia
  • Highest risk during first trimester
  • 20% have neurological abnormality
  • Risk of microcephaly ~3%
47
Q

Describe the diagnosis for Zika

A
  • 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
48
Q

Prevention of zika

A
  • No treatment or vaccine
  • Repellants/ screens / residual spraying /breeding sites
  • Postpone travel to endemic areas
  • Postpone pregnancy
  • Safe sex
49
Q

Describe the treatment of Zika

A
  • Most cases of Zika virus disease is asymptomatic or mild.
  • Treatment is supportive, encouraging rest, maintaining adequate hydration and the use of analgesics and antipyretics.
  • If dengue fever is a possible etiology of the patient’s symptoms, aspirin and other nonsteroidal anti-inflammatory drugs should be avoided due to the hypothetical risk of hemorrhage and Reye syndrome.
  • Individuals with Zika infection should be protected from mosquito exposure to reduce the risk of local transmission.
50
Q

Describe the vector control options of zika

A

Targeted residual spraying

  • primary vector control intervention for immediate response.
  • performed using appropriate insecticides applied on Ae. aegypti resting sites:
    • exposed lower sections of walls (<1.5m)
    • under furniture
    • inside closets
    • in dark and moist surface where mosquitoes may rest
    • , around houses.
  • Targeted residual spraying is applied selectively to areas known to be resting sites for the Aedes mosquito
  • does not require the spraying of all exposed surfaces in houses. Suitable insecticides can be applied with hand-operated compression sprayers.
  • Power sprayers can be used to treat large accumulations of discarded containers (e.g. tyre dumps) rapidly, if no other option is possible.
  • Care must be taken not to treat containers used to store water intended for drinking or cooking.

Space spraying

  • In the event of a vector-borne disease outbreak, authorities should implement space spraying with the objective of killing adult vectors in order to reduce virus transmission.
  • insecticide should be selected3 on the basis on information on the susceptibility of the local Aedes population.
  • Indoor space spraying is more effective than outdoor treatment if deployed properly inside buildings where Aedes mosquitoes rest and bite.
  • Recommended application techniques include ultra-low volume space spraying (cold fog or thermal fog) and using portable backpack sprayers or thermal foggers, which vaporize liquid insecticide into droplets to form an aerosol or fog with a rapid “knockdown effect” on mosquitoes.