6. Overview of Dengue Fever
The commonest mosquito-borne viral d.
• Aka ‘break bone F’, dandy fever
• Found in tropical & sub- climates, mostly in urban &
semi-urban areas
• A multisystem inf. with wide clinical spectrum: ILI – fatal
• Risks: rainfall, temp., unplanned rapid urbanization
• Severe DF is a leading c/of serious illness & death among
children in some Asian & LatAm countries
6
Probably from Spanish, probably of African origin; compare Swahili kidinga
7. • Despite its complex features, Rx is relatively simple, cheap
& v. effective if timely done. Maintenance of body fluid
is critical in severe DF
• The key is early Dx & knowing its different phases
• Rx at the primary & secondary levels are critical. A well-
managed front-line response reduces admissions
• No specific Rx.
• Fatality <1%
• Prevention & control depends on effective vector
control measures
• A vaccine has been licensed for use in 9-45yoa
8. • Vectors: mainly female A aegypti, less: A. albopictus
• 4 closely related serotypes: DENV-1, -2, -3, -4
• Every serotype can cause severe & fatal d.
• Recovery from 1 gives lifelong immunity against that.
Cross-immunity to the other serotypes is partial &
temporary. Subsequent inf. by another increases the
risk of severe DF
• Some genetic variants within each serotype are more
virulent or with more epidemic potential
• 500k DHF are admitted/y, a large portion are children
8
9. The commonest is F A aegypti (tiger mosquito). Unlike others
it is primarily a daytime feeder; peak biting: early in
morning & before dusk. It lives near urban habitats &
breeds mostly in man-made containers
A albopictus, less common in Asia; has spread to N America &
Europe. It is highly adaptive & can survive cold. It
hibernates. Most active 5-6pm & 8-9am (2hours)
A aegypti (5mm) A albopictus
10. Global burden of DF
Underreported & misclassified
• 390million DF/y (25% clinical). Incidence has grown x30
in recent decades. 50% global popn. is now at risk
• <1970, only 9 countries had DF. Now >100. The Americas, SEA
& W. Pacific are worst affected
• DF spreads to new areas with explosive outbreaks
• For a given country DF knows only the entry but not the exit
• In Europe first cases were reported in France & Croatia in
2010 & imported cases in 3 other countries
10
11. • 2012: outbreak occurred on Madeira islands (Portugal)
& imported cases were detected in mainland Portugal
& 10 other countries in Europe
• 2013 saw outbreak in Florida & Yunnan; Costa Rica,
Honduras & Mexico, Laos. Singapore has more cases
after a lapse of several years
• 2014: more cases in China, Cook Islands, Fiji, Malaysia &
Vanuatu, Tonga & French Polynesia. DF was also
reported in Japan after >70y
• 2015: more cases occurred in Brazil & neighbors
11
16. History of DF
• 1780: epidemics in in Asia, Africa, N America
• First in Bangladesh in 1964 (Dacca Fever)
• 1968: a small outbreak occurred in border with Myanmar
• In India DF was first recorded in 1812. A double peak
hemorrhagic F epidemic occurred in Calcutta 1963-64
• In N Delhi, outbreaks reported in 1967, 1970, 1982, 1996
20. Transmission
• Within mosquito: virus replicates (extrinsic IP: 8-10d). It
can transmit for the rest of its life (2-3w)
• Within infected humans: the reservoir; transmit for 4–5d
(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
20
22. • Depends on the host immune response
• Primary inf. is usually benign; but, 2y inf. with different
serotype(s) may cause DHF/DSS
Antibody-dependent enhancement: by non-neutralizing,
cross-reactive Ab from a primary inf., cause a heavy
viral load mainly in monocytes. Multisystem spread
• Memory T cells & cytokines (IF-gamma, TNF-alpha, IL- 10)
cause vascular leakage. No inflam! NO & complements
are reduced. NS1 lowers complements
• Specific cross-reactive Ab, as well as CD4+ & CD8+ T cells,
remain for years
NO: nitric oxide
Pathogenesis
23.
24. • Transient dysfunction of endoth. causes leakage: hallmark
of DHF (raised hct., low albumin, pl. effusions, ascites,
Hge. with severe thrombocytopenia & coagulation d.)
• Loss of Intravascular fluid causes hypoperfusion (lactic
acidosis), hypoglyc., hypoCa, finally, multi-organ failure
• Infants can have DHF during a primary inf. due to
transplacental antibodies
Pathogenesis …
25. • Inf. with 1 serotype gives life-long immunity only for that
with a very brief period of partial cross immunity (3mo)
• Everyone can be inf. 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 local
vascular hyperpermeability. No generalized edema
Pathogenesis …
26. 3 Cl. Syndromes of DF:
1. Undifferentiated fever;
2. Classic DF
3. Severe DF: DHF, DSS
Case Definition for DF
an ac. viral biphasic F, frequently presenting with HA,
bone/joint & muscular pains, rash, & leucopenia
28. 28
SS Classical DF
a severe, ILI that affects infants, young children & adults, but
seldom causes death
• Suspect DF if a HGF (40°C) is accompanied by 2 of: severe
HA, pain behind eyes, backache, muscle & joint pains,
NV, swollen glands or rash on 3rd/4th d
• Age: commonly 2-7y
• Duration: 2–7d. F: 3-5d
• Slight gum & nasal bleeding
• Pts. may also have itching, altered taste, particularly a
metallic taste, extreme fatigue & severe depression
31. 4 Dx Criteria for DHF
• F/recent F
• Bleeds: skin, gum, nose, GIT, urine, mens.
• Low platelet (100,000/mm3 or less)
• Leaky capillaries: raised hct. (≥20% over baseline)
• low albumin
• pleural or other effusions
4 Grades of DHF
Grade 1: +ve tourniquet test is only as bleeding feature
Grade 2: above + spontaneous bleeding
Grade 3: above + circulatory failure
Grade 4: above + profound shock
32. Warning Signs of DHF
3–7d after onset with a fall in temp.: severe AP, HA, F., rash,
persistent vomiting, tachypnea, bleeding gums/nose,
fatigue, restlessness & internal hge
All these show impending shock & should alert clinicians:
close observation & fluids
• The next 48h is critical for organ failure
32
33. Definition for DSS:
DHF +
• Evidence of shock: rapid thready pulse, narrow pulse
pressure (<20mmHg), hge., hypotension, late cap.refill,
cold, clammy skin & altered mental status
SS of Encephalitis/Encephalopathy in DF
• Decreased consciousness: lethargy, confusion, coma
• Seizures
• Nuchal rigidity
• Paresis
34. DHF causes death through dysfunction of
endothelium & coagulopathy
35. Dx of DF
• Direct: DENV isolation, genome detection (PCR), Ag.
detection
• Indirect: IgM & IgG
– IgM to DENV or a ≥x4 rise in IgG in paired sample (ac. &
convalescence serum)
• Reverse transcription PCR (RT-PCR) & Ab (65.9%). PCR
during first 5d of SS and/or early conval. (>5d)
• NS1 & Ab (62.0%)
Sample: serum or autopsy tissues
38. • Pts. who have IgM but a negative RT–PCR have probably
a recent DF. IgM may remain elevated for 2-3mo
• Also, there is cross reactivity with 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 & IgM
may be undetectable initially
39.
40. 40
Treatment
• No specific Rx.
• For severe DF, medical care can decrease MR to <1%
• Maintenance of fluid is critical
• Classical DF recovers in 11d
• DHF: intensive supportive Rx
• No NSAIDs as they worsen the hemorrhage
41. DHF: emergency!
• shock and/or fluid accumulation with SoB; bleeds
• severe organ impairment
• BT
• IVF is the essential & is the sole intervention. Fluid is
isotonic (no glucose) for effective circulation. 10−20
ml/kg/h boluses are given for a limited period under
close supervision; can avoid of pulmonary edema
• Follow urine output
• In shock, colloid solution is preferred
• Hct. before & after IVF. Base Hct: 35−40% in adult females,
40−45% in males
42. Goals of fluid resuscitation:
• improving circulation (less H. Rate, improving BP & pulse
pressure, warm & pink limbs, a cap-refill <2sec;
• improving end-organ perfusion: stable mentation, urine
≥0.5ml/kg/h or decreasing metabolic acidosis
• IV volume in DSS varies. Input is typically much more than
output, & the input/output ratio is of no help
• Later, IVF is given 10ml/kg/h for 1−2h; then 7ml/kg/h
x2−4h & finally 3-5ml/kg/h for 24−48h
• BT: whole blood or fresh PCV for severe bleeding
43. Prognosis
• DF is typically self-limiting. CFR: <1%
• When treated: DHF has a CFR of 2-5%; untreated: 50%
• Usually recover without sequelae with serotype immunity
• CFR varies by country, from 12-44%
• Predictors of death: atypical cases, comorbidities,
abnormal albumin & coagulopathy, 2y inf.
• Factors for severity: age, preg., nutritional status,
ethnicity, inf. with different serotypes, virus genotype,
quality & extent of available medical care
44. 44
Prevention & control
Only by combating vector:
Prevention of Mosquito Bites:
• avoid going out when vector feeds
• wear light-colored, long-sleeved
clothing & trousers
• mosquito-repellents over exposed
parts of body & clothes
every 4-6h
45. 45
Prevention of Mosquito Bites
Your accommodation should
be air-conditioned or have
mosquito nets
Use insecticides or coil
incenses
46. 46
Elimination of Mosquitoes
The most effective way is to
keep environment clean &
to remove stagnant water
Cover water containers
tightly so that mosquitoes
can’t get in to lay eggs.
47. 47
Elimination of Mosquitoes
• Dispose of domestic wastes
properly to prevent stagnant water
• Dispose of empty bottles, cans &
lunchboxes properly
48. 48
Elimination of Mosquitoes
• Change water for vases &
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
51. 51
Elimination of Mosquitoes
Remove stagnant water
immediately if mosquitoes are
found to be breeding. Use
environmentally friendly
insecticides such as lavicidal oil if
necessary
Biological controls such as keeping
fishes to eat mosquito larvae
would be a good option
61. WHO
• provides technical support & guidance for effective
management of DF outbreaks
• supports to improve reporting systems & capture the true
burden of the disease
• provides training on Rx, Dx & vector control
• formulates evidence-based strategies & policies
• develops new tools, including insecticide products &
application technologies
• gathers official records of DF & severe DF from over 100
Member States
• publishes guidelines & handbooks for case Mx, prevention
& control for Member States
63. C H I K U N G U N Y A
Facts
• C. is a mosquito-borne viral d. 1st reported in Tanzania 1952
• An RNA virus. “Chikungunya” means “to be contorted”,
stooped appearance with arthralgia
• F & severe arthralgia; myalgia, HA,, nausea, fatigue & rash
• Arthralgia is often debilitating & varies in duration
• C. shares some SS with DF & zika (misdiagnosed)
• No cure! Rx is supportive & simple
• Mosquito breeding sites are a significant risk factor
• C. mostly occurs in Africa, Asia & Indian sub-. But a major
outbreak; 2015 affected several countries in Americas
64.
65. Signs & Symptoms
• Typical: abrupt F, frequent arthralgia, myalgia, HA, nausea,
fatigue & rash. Arthralgia is often v. debilitating, but
usually lasts for a few days. May be prolonged to weeks
Hence it can be acute, subacute or chronic
• Most recover fully. Some may have joint pain for several
mo., or even years
• Rarely eye, neurological & heart complications are reported
as well as GI complaints. Serious complications are not
common, but in elderly, C. can cause death
• Often SS are mild & unrecognized, or be misdiagnosed in
areas where DF occurs
66.
67.
68.
69.
70. Transmission
• C. has been identified in >60 countries
• Most commonly by A aegypti & A albopictus (also DF)
• Vectors bite all daytime, though there may be peaks of
activity in the early morning & late afternoon; bite
outdoors, but A. aegypti will also readily feed indoors
• IP: usually 4-8d (2-12d)
71. More about Disease Vectors
• Both A aegypti & A albopictus cause large outbreaks
• A aegypti is confined in tropics & sub-. But A albo. also
lives in temperate & even cold temperate. A aegypti is
more closely a/with human habitation & uses indoor
breeding sites: flower vase, water vessels & concrete
water tanks in bathrooms, as well as same artificial
outdoor habitats as A albo.
• A albopictus thrives in a wider range of water-filled
breeding sites than A aegypti: coconut husks, cocoa
pods, bamboo stumps, tree holes, rock pools, tyres &
saucers beneath plant pots. This explains abundance
of A albo. in rural as well as peri-urban areas
72.
73.
74. Diagnosis
• Confirmed by IgM & IgG anti-C. Ab. & RT-PCR during the
first week
• IgM is highest 3-5w after onset (~2 mo.)
• RT-PCR during the first week. RT–PCR samples may also
be used for genotyping, allowing comparisons with
virus samples from various areas
• C. virus may be isolated from blood in first few d. of inf.
• Treatment. No specific Rx. Supportive only (antipyretics,
analgesics & fluids)
75. Rare complications in C.
• uveitis, retinitis
• myocarditis, hepatitis, nephritis
• bullous skin lesions, hge
• Meningoencephalitis, myelitis, GBS, & cr. nerve palsies
• At risk: neonates exposed intrapartum, age >65y, & HTN,
DM, CV d. or other illnesses
• Some may have relapse of polyarthralgia, polyarthritis,
tenosynovitis in the months following acute illness
• Mortality is rare and occurs mostly in older adults
76. Prevention & Control
relies heavily on reducing natural & artificial water-filled
containers that support breeding of vectors
• Outbreaks: insecticides may be sprayed to surfaces in &
around containers. Treat water in these to kill larvae
• Protection during outbreaks: full dress, repellents on skin
or clothing according to product label instructions
• Insecticide-treated mosquito nets afford good protection.
Mosquito coils or vaporizers may also reduce biting
• Basic precautions should be taken by people travelling to
risk areas (repellents, long sleeves & pants & rooms
with screens)
• No vaccine
77. Disease Outbreaks
• 1999–00: DR Congo & in 2007 Gabon had a large outbreak
• 2005: a major outbreak occurred in islands of I. Ocean,
causing a large number of imported cases in Europe
• 2006-7: India had a large outbreak. Several SEA countries
were also affected
• Since 2005: India, Indonesia, Maldives, Myanmar &
Thailand have reported >1.9 million
• 2007: 1st local C. was reported in Italy (197 cases). It
confirmed that outbreaks by A albopictus are plausible
in Europe
79. • 2013: France reported 2 confirmed autochthonous cases in
the French Caribbean island St Martin. Since then, local
transmission has been confirmed in over 43 countries
& territories in Americas
• 2014: France confirmed 4 local cases. Outbreaks were
reported in the Pacific islands, Senegal, India
• 2015: >1,379,788 cases of C. were recorded in Caribbean
islands, LatAm countries, & the USA with 191 deaths
Canada, Mexico & USA have also imported cases
Disease Outbreaks …
80. • 2015: In Americas, >693k C. were reported, Colombia bore
the biggest burden. It was >1 million in 2014
• 2016: >349k C. cases reported; most in Brazil, Bolivia &
Colombia. First time autochthonous transmission was
reported in Argentina (>1,000 cases). In Africa: Kenya
reported an outbreak (>1,700 )
• 2017: Pakistan had a continued outbreak starting in 2016.
Bangladesh also had a large outbreak
Disease Outbreaks …
81. WHO Response for Chikungunya
• formulates evidence-based outbreak management plans
• provides technical support & guidance
• supports improve reporting systems
• provides training on Dx & Rx & vector control & publishes
guidelines & handbooks on these
• Encourages to develop social communication strategies to
reduce mosquito vectors
82. Mosquito-borne d.
• 1 of the deadliest animals; cause millions of deaths/y
• 2015: malaria alone caused 438k deaths
• Incidence of DF has risen x30 in the past 30y, & more
countries are affected
• A aegypti: Zika, DF, chikungunya, & YF, filariasis, Rift Valley F
• Culex: West Nile virus, Japanese encephalitis, filariasis
• Anopheles: malaria, filariasis
• > half of world’s popn. live in areas where it is present
• Sustained mosquito control is essential
83. Vector-borne diseases
Facts
• VBD cause >17% of all IDs, with >700k deaths/y
• >3.9 billion people in >128 countries are at risk of DF, with
96 million cases/y
• Malaria causes 438k deaths/y, most are U-5 children
• Chagas d., leishmaniasis & schistosomiasis affect hundreds
of millions
• Many of these are preventable
84. Main vectors & d. they transmit
• Vectors are living organisms that can transmit infectious
diseases between humans or from animals to humans.
Many of these vectors are bloodsucking insects, which
ingest disease-producing microorganisms during a blood
meal from an infected host (human or animal) & later inject
it into a new host during their subsequent blood meal.
• Mosquitoes are the best known disease vector. Others
include ticks, flies, sandflies, fleas, triatomine bugs & some
freshwater aquatic snails.
85. • Mosquitoes
– Aedes:
– Anopheles:
– Culex:
• Sandflies: Leishmaniasis, Sandfly F (phelebotomus F)
• Ticks:
– Crimean-Congo haemorrhagic F
– Lyme d
– Relapsing F (borreliosis)
– Rickettsial d. (spotted F &Q F)
– Tick-borne encephalitis
– Tularaemia
86. • Triatomine bugs
– Chagas d (American trypanosomiasis)
• Tsetse flies
– Sleeping sickness (African trypanosomiasis)
• Fleas
– Plague (fleas from rats to humans)
– Rickettsiosis
• Black flies
– Onchocerciasis (river blindness)
• Aquatic snails
– Schistosomiasis (bilharziasis)
• Lice
– Typhus & louse-borne relapsing F
87. Vector-borne Diseases
• VBD are c/by parasites, viruses & bacteria
• >700k deaths/y by VBD
• Major VBD, together, account for 17% of IDs
• Burden is highest in tropics & sub- . VBD affect the
poorest. Since 2014, major outbreaks of DF, malaria,
C., YF & Zika have claimed lives & overwhelmed health
systems
• Distribution of VBD is determined by complex
demographic, environmental & social factors. Global
travel & trade, unplanned urbanization & climate
change can impact on transmission, making period
longer or more intense or causing d. to emerge in de
novo countries
88. • Changes in agricultural practices due to variation in temp.
& rainfall can affect the transmission of VBD
• The growth of urban slums, lacking reliable piped water or
adequate solid waste management, can render large
populations in towns & cities at risk of viral d. spread by
mosquitoes
• Together, such factors influence the reach of vector
populations & the transmission patterns of disease-
causing pathogens
Vector-borne Diseases …
89. WHO response
• The Global vector control response (GVCR) 2017–
2030 approved by the World Health Assembly (2017)
provides strategic guidance to countries & development
partners for urgent strengthening of vector control as a
fundamental approach to preventing disease & responding
to outbreaks. To achieve this a re-alignment of vector
control programmes is required, supported by increased
technical capacity, improved infrastructure, strengthened
monitoring & surveillance systems, & greater community
mobilization. Ultimately, this will support implementation
of a comprehensive approach to vector control that will
enable the achievement of disease-specific national &
global goals & contribute to achievement of the Sustainable
90. 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।
