This webinar is organized by MyICID and Institute for Clinical Research (ICR), NIH, Ministry of Health in conjunction with Neglected Tropical Disease Day 2022. The purpose of this webinar is to refresh and update our knowledge on Dengue fever, which has been overshadowed by COVID-19 since the beginning of the pandemic. Presenter: Dr Ong Hang Cheng, Infectious Disease Physician at University Malaya Medical Center #dengue #WorldNTDDay #BeatNTDs #BestScienceforAll

1. COVID-19 vs DENGUE
Differentiating the Two Severe Diseases
Dr Ong Hang Cheng
12th February 2022

2. Disclaimer
• This slide was prepared for the Webinar Series on COVID-19 session on
3rd March 2021, by Dr Ong Hang Cheng, Infectious Disease
Physician at University Malaya Medical Center, Malaysia.
• This is intended to share within healthcare professionals, not for public.
• This webinar is organised by Malaysian Society of Infection Control and
Infectious Diseases (MyICID) & Institute for Clinical Research, NIH in
conjunction of World NTD Day 2022.

3. Outline
• Introduction – Dengue Fever and Covid-19
• Epidemiology of dengue and Covid-19
• Similarities of both diseases
• Differences of both diseases
• Management of both diseases
• Prevention of both diseases
• Conundrums

4. Dengue Fever
• Mosquito-borned Viral infection
• Tropical and sub- tropical climates
• Urban and semi-urban areas.
• The virus responsible for causing dengue, is called dengue virus (DENV).
• 4 DENV serotypes and CAN be infected 4 times.
• DENV infection can develop potentially lethal complications.

5. Dengue virus
• Flaviviridae family
• 4 closely related but distinct serotypes (DEN-1, DEN-2, DEN-3, DEN-4)
• Recover from one serotype provide lifelong immunity against that
serotype
• Cross immunity to other serotypes is partial and temporary
• Secondary infection with other serotypes increase risk of developing
severe dengue

6. Dengue virus under the electron microscope
Nature, 2005

7. Dengue Fever:
Global incidence and deaths
• Estimated that 390 million dengue virus infections per year
• 96 million manifest clinically (with any severity of disease) with 70% of actual burden is in Asia.
• Increasing incidence 8-fold over the last 20 years.
• 505,430 in 2000 > 2.4 million in 2010> 5.2 million in 2019.
• Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific.
• The Americas, South-East Asia and Western Pacific regions are the most seriously affected, with Asia
representing ~70% of the global burden of disease.
Bhatt, S., et al., The global distribution and burden of dengue. Nature, 2013. 496(7446): p. 504–507.

8. Dengue Fever: Malaysia statistics

9. Vector

10. Life cycle
Source: CDC

11. Dengue Fever: Clinical Disease
WIDE SPECTRUM
• Subclinical disease (may not even be aware they are being infected)
• Severe flu-like symptoms
• Severe dengue with complications
• Severe bleeding
• Organ impairment
• Plasma leakage

13. 3 Phases of dengue fever

14. Diagnosis
1. Viral components or
2. Serology

15. NS-1 (Non-structural protein-1)
• NS1 protein is a hallmark of flavivirus infecting mammalian cells
• Can be found in dengue , yellow fever and West Nile virus infection.
• False positive results have been reported in chronic diseases and haematological
malignancies
• The detection rate of primary infection (75%-97%) and secondary infection (60%-70%)
• The sensitivity of NS1 antigen detection drops from day 4-5 of illness onwards and
undetectable in the convalescence phase (may predict severe dengue if present beyond 5
days)

16. Dengue Viral RNA Detection
(Real time RT-PCR)
• Viral genotype
• Molecular method - target specific genome of the virus for amplification
and detection.
• Viraemic stage ONLY – 5 days from symptom
• Expensive
• Special storage temperatures and short transportation time between
collection and extraction
• Limited centres and trained personnel

17. Virus Isolation
• Institute for Medical Research (IMR),
• National Public Health Laboratory
• University Malaya Medical Centre for research

18. Serological tests
• IgM - detected 4 days of illness by LFA or IgM antibody capture enzyme-
linked immunosorbent assay
• IgM seroconversion : paired acute and convalescent phase (10 to 14 days
after the acute phase); 4-fold or greater rise in antibody titre.

19. Management
• Outpatient
• Inpatient

20. Outpatient or inpatient?

21. Management of dengue fever
1. Oral fluids (Don’t forget the electrolytes)
2. Intravenous crystalloids
3. Intravenous colloids
4. Blood products if bleeding

22. How about Dengue Vaccine?
• Dengvaxia
• Pre-Vaccination Screening- Laboratory confirmation of previous dengue
virus infection required

23. Dengue Vaccine anyone?
Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD).
Last reviewed: December 20, 2021:

24. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD).
Last reviewed: December 20, 2021:

25. Hemophagocytic Syndrome in Dengue
• Haemophagocytic syndrome (HPS) is a potentially fatal syndrome
• Extreme immune activation leading to cytokine storm.
• Increased IL-2, TNF-α, IL-6, IL-8, interferon γ generated by uncontrolled
activation of histiocytes and T-cells.
• Clinical course is generally severe and may mimic sepsis
• Milder forms of HPS recover spontaneously.
• Severe HPS, may need IV methylprednisolone or dexamethasone (KIV
IVIg)

26. Dengue: Prevention and Control
• Prevention of mosquito breeding
• Personal protection from mosquito bites
• Community engagement
• Active mosquito and virus surveillance

27. COVID-19
Coronavirus disease (COVID-19) is an infectious disease caused by the
SARS-CoV-2 virus

28. Why is it important?
Isn’t it “just another flu”?
Many people lost their lives or lost their loved ones

29. Why is it important?
• Planet earth turned topsy turvy
• Businesses closed
• Borders closed
• Vehicles stopped – air, water and land
• Everybody must take vaccines
• Everybody must mask up
• Then vaccine again
• Then vaccine again

30. COVID-19 Global Cases and Deaths
Confirmed cases: 398 241 445
Confirmed deaths: 5 769 246
WHO: Last update: 8th February 2022, 00:06 am GMT+8

31. COVID-19 Malaysia
Total Cases: 2,906,232
Total Deaths: 32,043
WHO: Last update: 8th February 2022, 00:06 am GMT+8

32. What is a coronavirus?
• Coronaviruses are widespread among birds and mammals, with bats
being host to the largest variety of genotypes (Anthony, 2017)
• COVID-19: A novel coronavirus discovered at the end of 2019, previously
designated 2019-nCoV

33. Coronaviruses phylogenetic tree

34. Model of coronavirus structure: A
schematic diagram of virion structure

35. Coronaviruses under electron
microscopy
CDC;JHU
Magnification 144,000x

36. Variants? Why so many?
tenor.com
Variants being monitored
Variants of interest
Variants of concern
Variants of high consequence
Ability to spread
Severity of symptoms
How variants respond
to treatment
How well vaccines protect
against the variant
What
are the
variants
How are they
classified?

38. Covid-19 Symptoms
• Fever or chills
• Cough
• Shortness of breath or difficulty breathing
• Fatigue
• Muscle or body aches
• Headache
• New loss of taste or smell
• Sore throat
• Congestion or runny nose
• Nausea or vomiting
• Diarrhea
• Difficulty breathing
• Persistent pain or pressure in the chest
• Confusion
• Delirious
• Cyanosis

39. Covid staging
ovid-19.moh.gov.my/garis-panduan/garis-panduan-
kkm/ANNEX_2e_CLINICAL_MANAGEMENT_OF_CONFIRMED_COVID-
19_CASE_IN_ADULT_AND_PAEDIATRIC_13082021.pdf

40. Diagnosis
• Respiratory specimens for nucleic acid amplification testing (NAAT)
i.e: reverse transcription polymerase chain reaction (RT-PCR).
• Repetitive testing of upper respiratory tract (URT) and/or lower
respiratory tract (LRT) might be needed
• If deceased, consider the collection of post-mortem specimens.
• SARS-CoV-2 antibody tests are not recommended for diagnosis of
current infection with COVID-19.
(please don’t ask again)
WHO, 23rdNov 2021

41. Risk factors associated with
severe disease
• Age > 60 years (increasing with age).
• (NCDs): DM, HTN, cardiac disease, chronic lung disease, cerebrovascular disease, dementia,
mental disorders, CKD, immunosuppression, HIV, obesity and cancer have been associated
with higher mortality.
• smoking
• Higher (SOFA) score and D-dimer >1 µg/L on admission were associated with higher
mortality
• In pregnancy, increasing maternal age, high BMI, non-white ethnicity, chronic conditions and
pregnancy specific conditions such as gestational diabetes and pre-eclampsia

43. Management of Covid-19
Isolation measures
Mild COVID-19:
• Symptomatic treatment: antipyretics for fever and pain,
• Adequate nutrition
• Appropriate rehydration.
Moderate COVID-19: pneumonia treatment
For patients at high risk for deterioration, isolation and management in hospital is preferred.
WHO, 2021

44. Antivirals?
• Favipiravir
• Nirmatrelvir/Ritonavir (Paxlovid) and
• Molnupiravir

45. When should corticosteroids be used in
Covid-19?
• Corticosteroid is NOT recommended in non-hypoxic cases (unless for
other indications)
• Category 4 : IV Dexamethasone phosphate 8mg od (12mg if BMI >30)
• Duration 10-14 days or until discharge
• (Note: 8mg of IV dexamethasone phosphate = 6 mg of IV dexamethasone
base = 6mg of oral dexamethasone)
• Step-down to oral dexamethasone 6mg PO once there is improvement

46. Antivirals and immune modulators
• Dexamethasone AND IV Remdesivir 200 mg loading and 100 mg daily
(D2-D5)
• Corticosteroid AND Tocilizumab OR
• Corticosteroid AND Baricitinib (If Tocilizumab is not available)

47. Prevention of COVID-19
• Get vaccinated
• Stay at least 1 metre apart
• Wear properly fitted mask when physical distancing is not possible or when in
poorly ventilated settings.
• Choose open, well-ventilated spaces over closed ones.
• Open a window if indoors.
• Wash hands regularly with soap and water or clean them with alcohol-based
hand rub.
• Cover mouth and nose when coughing or sneezing.
• If unwell, stay home and self-isolate until recover
WHO 2022

48. Vaccination worldwide
• 9 620 105 525 Vaccine doses administered
WHO: Last update: 25 January 2022, 00:06 am GMT+8

49. Vaccination Malaysia

50. Similarities and differences at a glance

51. What are the similarities?
Both are caused by
viruses
Both cause fever and
myalgia
Symptoms range
from mild to severe
for both

53. • Shortness of breath and diarrhoea were more common in COVID-19
patients than in influenza patients, while fever, cough, running nose and
sore throat were less common.
• Cough, shortness of breath, running nose and sore throat were more
common in COVID-19 patients than in dengue patients.
• A lower proportion of COVID-19 patients had fever, diarrhoea, muscle
aches, fatigue/malaise, abdominal pain, bleeding, conjunctivitis, headache,
joint pain, skin rash and vomiting/nausea compared with dengue
patients.

54. Who are at risk?
• Travelling to or living in
an area with uncontrolled
community spread of the
virus
• Seniors and those with
underlying medical
condition
Covid-19
• Travelers or locals in
tropical and subtropical
regions
• Previous dengue
infection
Dengue

55. Differences
Can you tell them apart?
Dengue Fever Covid 19
Transmission
Mosquito bite Infected droplets

56. How to protect against COVID-19
• Wear mask
• Wash hands
• Avoid crowded areas especially indoors
• Physical distancing
How to protect against dengue
• Remove mosquito breeding areas
• Wear long sleeve clothing
• Use mosquito repellents

57. Dengue and COVID-19 conundrums

58. False positive dengue serology
Serological tests for dengue have been shown to cross-react with:
• Other flavivirus – Japanese Encephalitis
• Non-flavivirus – malaria, leptospirosis, toxoplasmosis, syphilis
• Connective tissue diseases – rheumatoid arthritis
Malaysia Dengue CPG, 2015

61. How about COVID-19 and dengue co-
infection?

63. What about dengue incidence during
the Covid-19 pandemic?

64. Stay safe
Ecdc 2022

65. References
• World Health Organization. https://www.who.int/news-room/fact-
sheets/detail/dengue-and-severe-dengue
• Bhatt, S., et al., The global distribution and burden of dengue. Nature,
2013. 496(7446): p. 504–507.
• Anthony SJ, Johnson CK, Greig DJ, et al. Global patterns in coronavirus
diversity. Virus Evol 2017; 3:vex012.
• CDC
• Covid-19.moh.gov.my/garis-panduan/garis-panduan-
kkm/ANNEX_2e_CLINICAL_MANAGEMENT_OF_CONFIRMED_COVID-
19_CASE_IN_ADULT_AND_PAEDIATRIC_13082021.pdf

66. Thank you