This slideset by Professor Ivan Hung analyzes two different cases of fever in returned travelers: history, differentials, diagnosis and management, indicating also signs, symptoms and how to prevent it.

1. Two Cases of Fever in
Returned Travelers
Ivan Hung
MD FRCP (Lon, Edin)

2. Case 1

3. History
• 55 M; Dutch
• Admitted to A&E QMH 9 Jan 13
• Acute onset seizure
• Past Hx of asthma

4. History
" Occupation: businessman
" Travel: Arrived from Thailand the day before
" Contact: no contact with febrile patient or
animal
" Cluster: none

5. History
" Initially visited HK 16-18 Dec 12 with cousin
" Travelled to Thailand (Bangkok and Sanmui)
18 Dec 12 – 8 Jan 13
" Stayed in **** Hotel
" Sunbathed and swam in Sanmui: Insect/
mosquito bites +/ jellyfish sting 3 Jan 13
" Developed fever and generalized rash 4 Jan 13
" Denied sexual contact
" Denied needle or blood exposure

6. History
" Arrived in HK 1 day before admission
" Persistent fever, malaise, loose stools
and nausea
" LOC for 15 seconds (without witnessed
convulsion)in restaurant
" Spontaneous recovery
" Mild drowsiness
" Denied palpitation, chest pain,
photophobia or headache

7. History
" Admitted to QMH A&E; 1 Jan 13
" 3 episodes of GTC convulsion in
A&E
" 5 sec each with spontaneous
abortion; Hstix 7.6mmol/L
" Cardiac monitor: asystole with
spontaneous reversion to sinus
bradycardia of 30-40bpm
" Physical examination:
erythematous rash over limbs,
back and trunks; no LNs or
eschar; otherwise unremarkable
" T/F CCU care

8. ECG: 1st Degree HB

9. Cardiac Telemetry
• Asystole
• CPR artifacts

10. Differentials?

11. Differentials:
" Dengue fever
" Typhoid fever
" Rickettsioses
" Leptospirosis
" Malaria
" Borrelia burgdorferi
" Influenza/ parainfluenza
" Enterovirus

12. Investigation
" CBC
" LRFT
" Blood/urine/stool culture
" Blood smear for malaria
" Serology: dengue/ Leptospirosis/ Rickettsiae
" Throat swab/ culture/ NPA
" CXR
" CT brain
" EEG

13. Results
" WCC 3.2 x 10*9/L (L
0.92 x 10*9/L)
" Platelet 61 x 10*9/L
" Hb 10.5 g/dL
" ALT 108 U/L; AST
113 U/L
" Normal bilirubin,
RFT and clotting
" Troponin I/ CK
normal
" TSH normal
" Serum/ urine
toxicology –ve
" Ustix: -ve
" Blood culture –ve
" CT brain normal
" TTE: EF 60%; trivial
MR
" CXR: clear

14. Management
" CCU care
" Levetiracetam 1g q12h IV
" Transcutaneous pacing (independent of
pacing)
" MRI brain: L frontal lobe microvascular
ischemia; R maxillary sinusitis
" EEG mild encephalopathy/ CSF examination
normal
" Empirical acyclovir 500mg q8h, ceftriaxone 2g
12h, doxycycline 100mg bid PO

15. Diagnosis & Management
" First anti-dengue IgM –ve (10/1); convalescent
anti-dengue IgM +ve (16/1)
" Dengue virus type III RNA RT-PCR +ve (14/1)
" Weil-Felix and Widal test –ve
" Blood smear for malaria –ve
" Fever and rash subsided
" HR returned to 80bpm and heart block
resolved
" Returned to the Netherlands

16. Dengue
" 50 millions; 12,000 deaths
" tropical and subtropical
" Outbreaks: Singapore, Rio de Janeiro, Pueto Rico,
Hawaii
" Aedes aegypti
" Flavivirus
" 4 different serotypes
" Life-long immunity after primary infection of the same
serotypes (not the others)

17. Dengue Fever: primary infection
" Incubation period: 4-7 days
" Asymptomatic for children under 15 years
" Classic dengue fever: Influenza like illness: fever (5-7 days),
headache, retro-orbital pain and myalgia
" 50% lymphdenopathy, diffuse erythema, non-specific
maculopapular rash (more common in primary dengue)
" Nausea and vomiting
" Cough/ sore-throat
" Hemorrhage: skin > nose > GIB
" O/E: pharyngeal erythema, lymphadenopathy, hepatomegaly,
conjunctival injection
" Leucopenia, thrombocytopenia, raised AST

18. Dengue Hemorrhagic Fever: secondary infection
" 4 cardinal features
" Increased vascular permeability:
hemoconcentration (20% rise in hematocrit),
pleural effusion or ascites
" Marked thrombocytopenia
" Fever 2-7 days
" Hemorrhagic tendency: positive tourniquet test
or spontaneous bleeding
" + shock – becomes DSS

19. Expanded Dengue Syndrome:
• Liver failure (secondary to hypoperfusion)
• Neurological manifestation: encephalopathy or
seizures (CSF viral isolation or PCR)
• Guillain-Barre Sx
• Myocarditis, cholecystitis and retinal vasculitis

20. WHO Classification
• Dengue vs. Severe Dengue
• Severe dengue: severe plasma leakage, severe
hx or severe organ impairment
• AST/ ALT > 1000, impaired consciousness,
severe involvement of heart or other organs
• Warning signs: abdominal pain, persistent
vomiting, mucosal bleeding, restlessness,
hepatomegaly > 2cm, raised HCT with rapid
drop in platelet counts

21. Diagnosis
• 4x rise in HI assay between acute and
convalescent samples (baseline then 10
days) early and higher titre for
secondary infection
• Dengue virus specific IgM Ab by MAC-
ELISA (by 6th day of illness)
• Virus isolation (1-2 wks) vs RT-PCR (1-2
days)

22. Our case
• Likely SA node involvement leading to
asystole
• Cerebral hypoperfusion and seizure
• Normal trop I/ CK
• Other reported cases: myocarditis, SA
or AV nodal block
• Mostly pediatric cases

23. Prevention
" Mosquito control, long sleeve clothing
" Insect repellent
" Vaccination: Phase II, CYD-TDV, a
recombinant live attenuated tetravalent
dengue vaccine
" Reduced risk by 30% in Thailand (4000
participants); failed to protect DENV-2
" Phase III underway

24. Case 2

25. History
• 77M; retired businessman
• AF on warfarin; L ICA aneurysm
• Traveled to Bali, Indonesia with family for 1 week (6-13 Feb
13)
• Multiple mosquito bites

26. Signs & Symptoms
• Fever 39C on the last day of the trip
• Severe finger joint and muscle pains; malaise
• Mild headache and skin rash
• Loose stool
• Admitted to QMH 2nd day upon returning to HK
• Generalized erythematous rash over trunk and limbs
• No hepatosplenomegaly, no lymphdenopathy or eschar
• CXR clear; NPA respiratory virus -ve

27. Differentials?

28. Differentials:
" Dengue fever
" Chikungunya
" Typhoid fever
" Rickettsioses
" Leptospirosis
" Malaria

29. Progress
• WCC 4.35 x 10*9/L (N3.24; L0.52), platelet 116
• CRP 10.4mg/L and ESR 132 mm/h; INR 2.5
• Normal LRFT
• Malaria –ve; Weil-Felix and Widal test –ve
• Blood culture –ve; anti-HIV Ab -ve
• Empirically started on augmentin + clarithromycin
• Switched to levofloxacin + doxycycline
• Fever and rash settled after 1 week admission and
discharged; SOPD FU
• Persistent joints pain

30. Diagnosis
• Day 3 IgM for rickettsiae, dengue and
chikungunya all –ve
• Day 11 IgM for chikungunya +ve (1:160)
• RT-PCR for chikungunya virus +ve for
both samples
• ….. Routine eye check-up

32. Complications
• Diagnosis: retinitis secondary to chikungunya
• CT brain/ TTE/ carotid doppler –ve
• Rheumatological markers –ve
• Retinitis resolving slowly; visual acuity not
affected

33. Epidemiology
• Arthropod-borne; single-stranded RNA virus
of the genus Alphavirus
• First isolated in outbreak in Tanzania 1952-3
• Endemic in West Africa; seropositive 50%
population
• Outbreaks in India and SEA
• Vector: Aedes mosquitoes (aegypti and
albopictus); tropical weather
• Vertical transmission; corneal grafts
• A226V mutation of viral gene encoding env
protein: enhanced replication in Aedes

34. Clinical Manifestations
• Incubation period 2-4 days
• High fever and malaise
• Polyarthralgia involving multiple joints 2 days after fever
(symmetrical distal joints: TNF-A, IFN-G and MCP-1
• MP rash limbs and trunks with islands of normal skin; pruritis;
Hx uncommon
• Cervical LNs and conjunctivitis
• Persistent joint stiffness/ tenosynovitis (>80%)
• New onset Raynaud
• Majority self-limiting; rarely meningoencephalitis, myocarditis;
acute hepatitis, renal/ resp failure, flaccid paralysis, GBS or
death (outbreaks in Mauritius, Reunion, India)

35. Ocular Involvement
Mahendradas et al. J of Ophthalm Inflammation & Infection 2013,3:35

36. Diagnosis
• ELISA: IgM 5 days; IgG 2 weeks
• RT-PCR (first 5 days)

37. Treatment & Prevention
• No active antiviral (in-vitro activity:
ribavirin/ IFN-A)
• Systemic steroid (in severe patients)
insufficient data
• Role of immunodysregulation
• No vaccine available
• Insect repellent/ long-sleeves