Insect bites (dengue, Chikungunya, Zika, Tick-Borne)
Prof (Dr) Yee-Sin LEO
Clinical Director Communicable Disease Centre
Director Institute of Infectious Disease and Epidemiology
Tan Tock Seng Hospital
July 2017 – Medicine Review Course
Chikununya virusAlphavirusFirst described in 1953 –Tanzania Africa“to bent over”“Buka-buka” – “broken-broken”
Zika virusFlavivirusFirst isolated in 1947 in Monkey in Uganda, AfricaHuman cases in 1952 in Uganda and Tanzania
Dengue virusFlavivirus4 genetically diverse sero-types
Chikungunya virus
Zika virus
Dengue
• Disease burden
• Classification
• Clinical features and usefulness of warning signs
• vaccine
30 most highly endemic countries
Dengue in Singapore
Despite vector
control, low
breeding index,
Singapore faces
successive waves
of dengue epidemic
Predominantly
adult dengue
Increasing
recognition of
atypical dengue
WHO 1997
WHO 1997
Dengue Fever
Dengue Hemorrhagic fever
Dengue Shock Syndrome
Dengue hemorrhagic fever (DHF)
A case must meet all 4 criteria
1. Fever lasting 2-7 days
2. Haemorrhagic tendency shown by positive tourniquet test or spontaneous bleeding
3. Thrombocytopenia (<100K/L)
4. Evidence of plasma leakage shown by either hemoconcentration or development of pleural effusions/ascites, or both
DHF is further classified into 4 severity grades based on presence/absence of shock
WHO 1997
SEARO 2011
WHO 2009
Warning signs (7)
Persistent vomiting
Abd pain / tenderness
Mucosal bleeding
Clinical fluid
accumulation
Lethargy-restlessness
Enlarged liver >2cm
Rapid HCT - Plt
WHO 2009RT-PCR, NS1 IgM IgG serology
Primary Care
• Early recognition / suspicion of dengue
POCT / rapid combined Ag/Abs
Daily monitoring
•Early recognition of warning signs
Febrile phase
Secondary Care Hospitalization
Critical phase
• Adequate trained staff
• Lab support
• Adequate consumables
Tertiary Care ICU
Final Outcome
Recovery
Dengue management
WHO 2009
Specialized dengue care unit
hospitalisation
Pleural effusion
Typically on the Right
34Y Indian man with gum bleeding
Platelet nadir 12
Haematocrit lowest 41, highest 52.6
AST 232 ALT 123
Dengue IgM and IgG positive
US abdomen: ascites
DHF3=DSS1
Presence of warning sign/s are common – particularly mucosal bleeding
Absence of warning sign/s rarely will progress to severe disease
Watch closely patients with 2 or more warning signs
Interval from onset of warning sign/s to severe disease can be short
Local evidence on utility of warning signs
Majority had WS 1 day prior to onset of severe illness
DHF – age in 2o Infection, 1981 Cuba Outbreak
Guzman IJID 2002;6:118
Age distribution of adult dengue deaths Singapore 2004-2008
0
2
4
6
8
10
12
15-24 25-34 35-44 45-54 55-64 >65
Age group (years)
Fa
taliti
es
Older adults with dengue have more atypical presentations, more organ involvement, more
pre-existing comorbidities, higher mortality, require higher index of suspicion to diagnose,
closer monitoring and careful management
2012
Dengvaxia licensed in 5 countries
Imperfect – but good enough for Singapore?
2016
Take home message - Dengvaxia
SAGE Apr 2016
Age 45> with seroprevalence more
than 70%
4th Oct 2016 Dengvaxia approved in
Singapore for use in sero-positive
individuals from 12 to 45 years
6th March 2017 Dengvaxia available
in Singapore
Sudden onset of fever
Severe headache, chills
Nausea, vomiting
Severe, sometime persistent
joint pain
Incubation period:
3-7 days (3-12
days)
Overlapping presentations
with dengue
Laboratory diagnosis of Chikungunya
Aug 08 Outbreak
R knee swelling
J Clin Virol 2010
J Clin Virol 2010
N=48
202187
176 180 183 190 185208
270
300325
0
50
100
150
200
250
300
350
1 2 3 4 5 6 7 8 9 10 11
Day of illness
Plt
co
un
t
N = 48
13.6 14 14.3 14.7 15 15 14.9 14.8 14.8 14.7 14.8
39.9 40.5 41.5 42.9 43.7 43.7 43.4 43.2 43 42.6 42.8
0
5
10
15
20
25
30
35
40
45
50
1 2 3 4 5 6 7 8 9 10 11
Day of illness
Hb Haematocrit
N = 48
5.9
5.2
4.3 4.1 44.5
5 5.2
66.3
6.8
0
1
2
3
4
5
6
7
8
1 2 3 4 5 6 7 8 9 10 11
Day of illness
TW
C
N = 48
76.670.6
61.5
52.7 50.855.7 56.4 54.9 56.1 55.2 55.9
13.217.4
25.2
32 32.526.7 26.6 26.5 27.5 28.5 29.1
0
10
20
30
40
50
60
70
80
90
1 2 3 4 5 6 7 8 9 10 11
Day of illness
Neutrophils(%) Lymphocytes(%)
Total White cells
Platelet
neutrophils
lymphocytes
HB
Hematocrit
Unusual CHIKV manifestations
• Lalitha Am J Ophthalmol 2007; 144: 552
Uveitis, optic neuritis
– N=37 (IgM=26), unilateral=30, onset from acute mean 33D, resolved 8W-3M
– Initial VA 20/20-20/120 65%, <20/200 19%, hand 6%, treated topical and systemic steroid
• Mittal Arch Ophthalmol 2007; 125: 1381
Optic neuritis
– N=14 (IgM), unilateral 64%, onset from acute mean 11D, all but 4 improved
– Initial VA 6/6-6/12 16%, 6/18-6/60 26%, <6/60 58%, treated systemic steroid
• Singh Epidemiol Infect 2008; 136: 1277
Flaccid paralysis
– Andaman Islands, n=4, IgM,, responded to steroid
• Wielanek Neurology 2007; 69: 2105
Gullian-Barre syndrome
N=3, IgM=3, PCR=1
Persisting mixed Cryoglobulinemia in Chikungunya
infection
PLoS Neg Tro Dis 2009;(Feb)3:e374
EID Vol 15, No. 2 Feb 2009
Inamadar A et al Int. J Derm 208;47:154-9
pigmentation
Inamadar A et al Int. J Derm 208;47:154-9
Zika
• Recent zika virus outbreak in Singapore – 2016
• Sexual transmission
• Vertical mother-fetus transmission
• Congenital abnormalities
• Neurological complications
Red eyes
Generelised rash
J Infect 2017
CDC-CSTE
Fever or rash or conjunctivitis or
arthralgia
WHO
Rash + arthralgia or arthritis or non-
purulent conjunctivitis
PAHO
Rash + 2> fever, arthralgia, myalgia, or
non-purulent conjunctivitis
ECDC
Rash + arthralgia or myalgia or non-
purulent conjunctivitis
Singapore
Fever and rash plus
One > headache, myalgia, arthralgia,
non-purulent conjunctivitis
Congenital abnormality
Rapid evolution of disease- rapid onset and short plateau phase
Approx 1 / 3 needs respiratory assistance
Generally favorable outcomes
Lancet Feb 2016
https://www.cdc.gov/ticks/symptoms.html
Geographic region
Fever, chillAches, pain: headache, joint pain, myalgiarash
Tick-borne relapsing feverHuman granulocytic anaplasmosisTick-borne encephalitis Q fever
How to remove a tick
Never crush a tick with your fingers
Avoid folklore remedies such as "painting" the tick with nail polish or petroleum jelly, or using heat to make the tick detach from the skin
Use fine-tipped tweezers to grasp the tick as close to the skin's surface as possible.
Pull upward with steady, even pressure.
Don't twist or jerk the tick; this can cause the mouth-parts to break off and remain in the skin. If this happens, remove the mouth-parts with tweezers. If you are unable to remove the mouth easily with clean tweezers, leave it alone and let the skin heal.
After removing the tick, thoroughly clean the bite area and your hands with rubbing alcohol, an iodine scrub, or soap and water.https://www.cdc.gov/ticks/removing_a_tick.html
Caused by the bacterium BorreliaburgdorferiTransmitted to humans through the bite of infected blacklegged ticks.
Lyme Disease
Later Signs and Symptoms (days to months after tick bite)Severe headaches and neck stiffnessAdditional EM rashes on other areas of the bodyArthritis with severe joint pain and swelling, particularly the knees and other large joints.Facial palsy (loss of muscle tone or droop on one or both sides of the face)Intermittent pain in tendons, muscles, joints, and bonesHeart palpitations or an irregular heart beat (Lyme carditis)Episodes of dizziness or shortness of breathInflammation of the brain and spinal cordNerve painShooting pains, numbness, or tingling in the hands or feetProblems with short-term memory
Early Signs and Symptoms (3 to 30 days after tick bite)Fever, chills, headache, fatigue, muscle and joint aches, and swollen lymph nodesErythema migrans (EM) rash (70-80%):At the site of a tick bite after a delay of 3 to 30 days (average is about 7 days)
Treatment
Early stages – oral doxycycline, amoxicillin, cefuroxime
Neurological or cardiac formsIv ceftriaxone or penicillin
https://www.cdc.gov/lyme/treatment/index.html
Disease of animals and humans Caused by the bacterium Francisella tularensis. Rabbits, hares, and rodents often die in large numbers during outbreaks.
Humans can become infected through several routes:Tick and deer fly bitesSkin contact with infected animalsIngestion of contaminated waterInhalation of contaminated aerosols or agricultural dustsLaboratory exposure
Tularemia
Signs and symptoms
Several forms (depending on the route of entry), high fever presence in all
Ulceroglandular – most common form, at the site of tick bite , swollen lymph nodesGlandularOculoglandularOropharygealPneumonic (most severe form)Typhoidal
Mild to life threatening
Diagnosis
Rare disease, hard to diagnoseculture
Treatment
streptomycin, gentamicin, doxycycline, ciprofloxacin. Usually lasts 10 to 21 days depending on the stage of illness and the medication used.
Although symptoms may last for several weeks, most patients completely recover.
https://www.cdc.gov/tularemia/diagnosistreatment/index.html
Phew……We make it to the end
Q & A
