Understanding Dengue

2. পৃথিবীর সবচাইতে সুন্দর গাছ. জাপাতে (১৪৪ব) ওতেতেথরো:বযাপক আকাতরর । সারা পৃথিবী
থিতক অসংখ্য মােুষ এই গাছ থেখ্তে আতস। ১৯৯০ বগগ ফু ট জােগা জুতে িাকা

5. DENGUE FEVER:
UPDATES
Dr mohammad nurul huq

6. Overview
• The commonest mosquito-borne viral d
• Aka break bone F, dandy fever, DF is a systemic d. with
wide cl. spectrum: FLI to severe fatal form
• Despite its complex features, Rx is relatively simple, cheap
and v effective if timely (No specific Rx.). The key is early Dx
and knowing different phases of the d.
• Rx at the 1y and 2y levels are critical. A well-managed
front-line response reduces admissions
• Fatality rates <1%
6
Probably from Spanish, probably of African origin; compare Swahili kidinga

8. Global burden of DF
• Cases are underreported and misclassified
• 390million DF/y (96million clinical) with alarming impact on
health/economy. Half world popn. Is now at risk
• Multiple serotypes cause hyper-endemicity
• Before 1970, only 9 countries had it; now endemic in >100
countries in Africa, Americas, E. Mediterranean, SEA and W.
Pacific. The Americas, SEA and W. Pacific are worst affected
• Along with more cases, DF spreads to new areas with
explosive outbreaks
• In Europe and first cases were reported in France and Croatia
in 2010 and imported cases in 3 other countries
8

9. • In 2012 outbreak occurred on Madeira islands (Portugal)
and imported cases were detected in mainland Portugal
and 10 other countries in Europe
• 2013 saw outbreak in Florida and Yunnan; Costa Rica,
Honduras and Mexico, Laos. Singapore has more cases
after a lapse of several years
• In 2014, more cases in China, Cook Islands, Fiji, Malaysia
and Vanuatu, Tonga and French Polynesia. DF was also
reported in Japan after >70y
• In 2015 more cases occurred in Brazil and neighboring
countries 9

10. 10
Regions affected
DF 2001

13. Global dengue burden, 2014

14. Distribution Western Hemisphere

15. Distribution of DF , Eastern Hemisphere

16. History Of DF
• 1780: epidemics in in Asia, Africa, N America
• First reported in Bangladesh in 1964 (Dacca F)
• 1968: a small outbreak occurred in border with Myanmar
• 1997: sero-prevalence was 135 cases
• Recently ICDDRB found 176 cases in a hospital in Dhaka:
primarily adults: DF 60.2%, DHF 39.2%, DSS 0.6%
• In India DF was first recorded in 1812. A double peak
hemorrhagic F epidemic occurred in Calcutta in 1963-1964
• In N Delhi, outbreaks reported in 1967, 1970, 1982, 1996

17. Key facts
• Found in tropical and sub-tropical climates worldwide,
mostly in urban and semi-urban areas
• Vector: mainly female Aedes aegypti, less: A. albopictus
• 4 distinct closely related, serotypes: DENV-1, -2, -3, -4
• Causes flu-like illness (FLI), with occasional severe form
• Incidence rose dramatically in recent decades
• Half of world's popn. is now at risk; influenced by rainfall,
temp. and unplanned rapid urbanization
• Px and control solely depends on effective vector control
17

18. • DHF was first detected in 1950s in the Philippines and
Thailand. Now, it affects most Asian and LatAm countries
and is a leading c/of admn. and death among children
• 500,000 with DHF require admn/y, a large portion are
children
• All serotypes can cause severe and fatal d.
• Some genetic variants within each serotype appear to be
more virulent or with more epidemic potential
18
Key facts

19. What is the DF Virus?
• Arbovirus, flavivirus: 4 serotypes (DENV-1,2,3,4)
• Induces cytokine production in cells
• Cytotoxic factor effects endothelial cells in:
• Heart, Liver, Kidneys, Lungs
• Gut, Spleen, LN, Brain, Skin

21. LC of flavivirus

22. Transmission
• Within mosquito, the virus replicates (extrinsic IP: 8-10d).
It can transmit the virus for the rest of its life (2-3w). It is
not spread by contact
• Infected humans are the reservoir; transmit for 4–5d (max.
12d) after onset. SS appear 4-7d (3-14d) (intrinsic IP)
• Viremia starts slightly before SS; may last 3-10d (5d). The
illness persists several days after the viremia has ended
22

23. The commonest is female A aegypti (tiger mosquito). Unlike
others it is primarily a daytime feeder; peak biting early in
morning and before dusk. It lives near human urban habitats
and breeds mostly in man-made containers
A albopictus, a secondary vector in Asia, has spread to N
America and Europe. It is highly adaptive and, can survive
cold. It tolerates temp below freezing, hibernates. Most active
2h 5-6pm and 8-9am
A aegypti A albopictus

24. 24
Transmission
Infected
person
Healthy person
Infected
mosquito
IP: 3-14d
Most commonly 4-7d

25. • Linked to the host immune response to inf. with DENV
• Primary inf. is usually benign; but, 2y inf. with a different
serotype/multiple serotypes may cause DHF/DSS
ADE (antibody-dependent enhancement): by non-
neutralizing, cross-reactive Ab from a primary inf., cause a
heavy viral load. Monocytes are main sites, but liver, brain,
pancreas, heart are also infected
• Memory T cells and cytokines like interferon-gamma, TNF-
alpha, IL-10, cause vascular leakage. Nitric oxide and some
complements are reduced. NS1 lowers complements
• Specific cross-reactive Ab, as well as CD4+ and CD8+ T
cells, remain for years
Pathophysiology

27. • Transient dysfunction of the endothelium causes vascular
leakage: the hallmark of DHF (raised hct., low albumin, pl.
effusions, ascites, Hge with severe thrombocytopenia and
coagulation d.
• Loss of IVF causes hypoperfusion (lactic acidosis),
hypoglycaemia, hypocalcaemia, finally, multiple organ
failure
• Infants can have DHF during a primary infection due to
transplacental antibodies
Pathophysiology …

28. • Inf. with 1 serotype confers life-long immunity only against
that with a v. brief period of partial heterotypic immunity
• Everyone can be infx. by all 4. Several serotypes can be in
circulation during an epidemic
• Subsequent inf. by other serotypes increase the risk DHF
• Differential targeting of specific vascular beds triggers the
localized vascular hyperpermeability underlying DSS
Pathophysiology …

29. 3 Cl. Syndromes of DF:
1. Undifferentiated fever;
2. Classic DF
3. DHF. DSS is the severe form of DHF
Case Definition for DF
Classical DF or Break bone F is an ac. viral F frequently
presenting with HA, bone/joint pain, muscular pains, rash,
and leucopenia

30. DF VIRUS INFECTION
Asymptomatic Symptomatic
Undiffrentiated fever
(viral syndrome)
DF
(syndrome)
DF Haemorrhagic
fever
No Shock
DF Shock
Syndrome (DSS)
(Plasma
leakage)DF
DF Haemorrhagic
fever

31. 31
SS Classical DF
a severe, FLI that affects infants, young children and adults,
but seldom causes death
• Suspect it if a HGF (40°C) is accompanied by 2 of: severe
HA, pain behind eyes, backache, muscle and joint pains,
NV, swollen glands or rash on 3rd/4th d
• Duration: 2–7dF: 3-5d
• Slight gum and nasal bleeding
• Pts. may also have itching, altered taste, particularly a
metallic taste, extreme fatigue and severe depression after
the ac. Phase

33. Skin rash
Symptoms

34. 4 Dx Criteria for DHF
F, or recent F
Bleeds: skin, gum, nose, GIT, urine, Increased menstrual flow
Low platelet (100,000/mm3 or less)
Leaky capillaries: raised hct. 20% or more over baseline
• low albumin
• pleural or other effusions
4 Grades of DHF
Grade 1: F and nonsp. SS and +ve tourniquet test is only as
bleeding feature
Grade 2: above + spontaneous bleeding
Grade 3: circulatory failure
Grade 4: Profound shock

35. Warning signs DHF (Severe DF)
occur 3–7d after the first SS with a fall in temp (100F): severe
AP, HA, HGF (2-7d), rash, persistent V, tachypnea, bleeding
gums or nose, fatigue, restlessness and hematemesis,
melena
• The next 48h is critical. Organ failure may occur
• It is due to double inf. The first inf. sensitizes the pt and
the 2nd produces immunological catastrophe
35

36. DHF causes death through dysfunction of
endothelium and coagulopathy

37. Definition for DSS:
DHF +
• Evidence of shock: rapid thready pulse, narrow pulse
pressure (< 20 mm Hg) OR hypotension, late cap.refill, cold,
clammy skin and altered mental status
SS of Encephalitis/Encephalopathy in DF
• Decreased level of consciousness: lethargy, confusion, coma
• Seizures
• Nuchal rigidity
• Paresis

38. Danger Signs in DHF
•Intense and sustained AP
• Persistent V
• Abrupt hypothermia, sweating, prostration
• Restlessness or somnolence
All these show impending shock and should alert clinicians
that the patient needs close observation and fluids

39. Dx of DF

40. Dx of DF…
• Direct: DENV isolation, genome detection, Ag detection are
specific
• Indirect: IgM and IgG (mostly available)
– IgM to DENV or a ≥x4 rise in IgG in paired sample (ac.
and convalescence serum)
• PCR and Ab (65.9%). NS1 and Ab (62.0%)
• PCR during first 5d of symptoms and/or early conval. (>5d)
Sample: serum or autopsy tissues
• Genome is detected by reverse transcription PCR from
serum, CSF, or autopsy tissues
• NS1 is detected by IMMUNOHISTOCHEMISTRY, IF, ELISA

41. Flavivirus replication complex

42. • Pts. who have IgM but a negative RT–PCR have a recent
probable DF. IgM may remain elevated for 2-3 mo
• Also, there is cross reactivity with flaviviruses (W Nile V, St.
Louis encephalitis V, Japanese Encephalitis V, Yellow FV). Dr
should review past illness, recent travel, vax. record
(especially YF) to Dx DF
• Often paired specimens are needed for Dx. as Ag and IgM
may be undetectable initially

44. 44
Treatment
• No specific Rx. For severe DF, medical care can decrease
MR to <1%
• Maintenance of fluid volume is critical
• Classical DF recovers in 1-2w
• DHF: intensive supportive Rx
• No NSAIDs as they worsen the hemorrhage

45. DHF: emergency Rx because of:
• shock and/or fluid accumulation with SoB; bleeds
• severe organ impairment, or need BT
• Judicious IVF is the essential and is the sole intervention.
Fluid is isotonic (no glucose) and just sufficient for effective
circulation for 24−48h (should not exceed 48 h). 10−20
ml/kg boluses are given for a limited period under close
supervision avoid of p. edema
• In shock, colloid solution is preferred
• Hct. before and after IVF. Base Hct: <35−40% in adult
females, < 40−45% in males
• Fluid resuscitation is separate from simple fluid admn.

46. The goals of fluid resuscitation :
• improving circulation (less HR, improving BP and pulse
volume, warm and pink limbs, a cap-refill < 2 sec;
• improving end-organ perfusion: stable mentation, urine
≥0.5 ml/kg/h or decreasing m. acidosis
• IV volume deficit in DSS varies. Input is typically much
more than output, and the input/output ratio is of no help
• Later, IVF is given 10ml/kg/h for 1−2h; then 7ml for 2−4h
and finally 3-5ml for 24−48h
• BT: whole blood or fresh PCV for severe bleeding

47. 47
Prevention and control
Only by combating vector:
Prevention of Mosquito Bites
Avoid going out when vector feeds
Wear light-colored, long-sleeved
clothing and trousers

48. 48
Prevention of Mosquito Bites
• Apply DEET-containing
mosquito-repellents over
exposed parts of body and
clothes every 4-6h
• For DEET products used by
children, its concn. should
be <10%

49. 49
Prevention of Mosquito Bites
Your accommodation should
be air-conditioned or have
mosquito nets
Use insecticides or coil
incenses

50. 50
Prevention of Mosquito Bites
Install mosquito nets to
doors and windows

51. 51
Elimination of Mosquitoes
The most effective way is to
keep environment clean
and to remove stagnant
water

52. 52
Possible Breeding Grounds of A
Albopictus
Artificial containers:
Vases, saucers of flower tubs, trays underneath air-conditioners,
buckets, jars and jugs of earthenware, cement troughs,
dumped tyres and solid wastes such as cans, disposable cups
and bowls, plastic bags
Natural containers:
The hollow space inside a bamboo, hollows of a tree and the
rachis of a leaf.

53. 53
Elimination of Mosquitoes
Cover water containers
tightly so that mosquitoes
can’t get in to lay eggs.

54. 54
Elimination of Mosquitoes
• Dispose of domestic wastes
properly to prevent stagnant water
• Dispose of empty bottles, cans
and lunchboxes properly

55. 55
Elimination of Mosquitoes
• Change water for vases and
aquatic plants/w, leaving no
water under the pots or in the
bottom saucers
• Scrub the container surfaces
thoroughly to prevent mosquito
eggs sticking on them

56. 56
Elimination of Mosquitoes
Remove or puncture any
dumped tyres to prevent
the accumulation of
stagnant water

57. 57
Elimination of Mosquitoes
Ditches should be free from blockage.

58. 58
Elimination of Mosquitoes
Fill up uneven ground to prevent stagnant water

59. 59
Elimination of Mosquitoes
Remove stagnant water
immediately if mosquitoes
are found to be breeding.
Use environmentally
friendly insecticides such as
lavicidal oil if necessary

60. 60
Elimination of Mosquitoes
Biological controls such as
keeping fishes to eat
mosquito larvae would be
a good option

61. WHO provides technical support and guidance to countries
for the effective management of DF outbreaks;
• supports countries to improve their reporting systems and
capture the true burden of the disease;
• provides training on Rx, Dx and vector control at the
regional level;
• formulates evidence-based strategies and policies;
• develops new tools, including insecticide products and
application technologies;
• gathers official records of DF and severe DF from over 100
Member States; and
• publishes guidelines and handbooks for case management,
DF prevention and control for Member States

62. 62
Immunization
• No vaccine
• Major progress: 3 live vax. are in phase II and III cl. trials,
and 3 other vax. candidates (based on subunit, DNA and
purified inactivated virus platforms) are at earlier stages of
cl. Development
• Best Px is to avoid mosquitoes

63. Potential Breeding Sites

70. • Cover rarely used gully traps. Replace the gully
trap with non-perforated ones and install anti-
mosquito valves.

72. Prevention includes use of bug spray
and other mosquito preventatives

73. থপাটগ ল্যাতের জাপাথে মযাতপল্, অতেক পুতরাতো একটি গাছ। েতব অেযােয মাতসর েু ল্োে বসন্ত
এবং গ্রীষ্মকাতল্ এ গাতছর থসৌন্দর্গ থবশী ফু তট উতে। এই গাতছর বাহাথর রঙ মােুষতক আকৃ ষ্ট কতর।