Dengue 12 January 2023

by Clerks:
Abano | Clariza | Mercado | Moises
Adepu | Chittem | Sodha
 Content of Presentation

01 Case 02 Etiology and Epidemiology

Presentation and
03 Pathogenesis 04 Diagnosis
Ddx and Lab
05 Findings 06 Treatment and
Complications
07 Prognosis and Prevention
CASE
● ID: M.R., 14 yrs old, female
● CC: fever
● History of Present Illness:
● 4 days PTA, patient experienced undocumented fever and fleeting headache. She
took Paracetamol tab 7.9 mkd which afforded relief of headache but no lysis of fever.
No consult was done. (-) cough and colds
● 3 days PTA, symptoms persisted now accompanied by crampy abdominal pain and
non projectile vomiting, more than 3 episodes, about 1/2 cup per bout of previously
ingested food. Patient took Paracetamol tab 7.9 mkd which afforded temporary lysis
of fever. Still no consult was done.
● FHPTA, persistence of symptoms were noted hence consult and subsequent
admission.
 01
Introduction
DENGUE
● most rapidly spreading mosquito borne viral disease in the world

● dengue virus is a member of the genus Flavivirus in the family Flaviviridae

○ genus also includes yellow fever, Japanese encephalitis, Zika and West Nile
encephalitis
○ leading cause of illness and death in the tropics and subtropics

● a febrile illness that affects people of all ages

Belong to Flavivirus family

• Four small single stranded RNA, closely related (DEN-1, DEN-2, DEN-3 and DEN-4)

• Each serotype provides specific lifetime immunity, and short-term cross-immunity (A person
can be infected as many as four times, once with each serotype)

• All serotypes can cause severe and fatal disease.

 02
Etiology and
Epidemiology
 ETIOLOGY

Dengue 1, 2, 3 ,4
At least 4 distinct antigenic types of dengue
virus which are members of the family
Flaviviridae

Arboviruses
May cause similar or identical febrile
diseases with rash
ETIOLOGY
EPIDEMIOLOGY

Aedes aegypti
● principal vector
● highly urbanized, breeds in water stored for
drinking or bathing and in rainwater
collected in any container

Aedes albopictus
● 2001 and 2015 Hawaiian epidemics
 EPIDEMIOLOGY
Before 1970
● Only 9 countries had experienced severe dengue epidemics

At present
● Endemic in more than 100 countries in the WHO regions of Africa,
America, Eastern Mediterranean, Southeast Asia, Western Pacific
Regions
● Asia represents ~70% of the global burden of disease
 EPIDEMIOLOGY
2010 2012 2019 2020 2021

Local Outbreak in Madeira Largest number of Affected several Continues to affect

transmission Islands of Portugal cases ever reported countries with Brazil, India,
was reported for resulting in over 2000 globally: affected all reports of case Vietnam, the
the first time in cases and imported regions; increase in Philippines, Cook
France and cases were detected transmission in Bangladesh, Brazil, Cook Islands, Colombia,
Croatia in mainland Portugal Afghanistan Islands, Ecuador, India,
Fiji, Kenya,
Indonesia, Maldives,
& 10 other countries recorded for the first Mauritania, Mayotte (Fr), Paraguay, Peru and,
in Europe time Nepal, Singapore, Sri Reunion islands
Lanka, Sudan, Thailand,
Timor-Leste and Yemen
 03
Pathogenesis
PATHOGENESIS
● incompletely understood but epidemiologic studies usually associate this syndrome
with second heterotypic infections with dengue types 1-4 or in infants born to
mothers who have had two or more lifetime dengue infections
● In humans studied early during the course of secondary dengue infections, viremia
levels directly predicted disease severity
● dengue virus immune complexes attach to monocyte/macrophage Fc receptors →
signal is sent → innate immunity suppression → enhanced viral production
● dengue hemorrhagic fever and dengue shock syndrome have been associated with
dengue types 1-4 strains of recent Southeast Asian origin
PATHOGENESIS
● Early in the acute stage of secondary dengue infections
○ rapid activation of the complement system.
● Shortly before or during shock
○ Elevated blood levels of soluble tumor necrosis factor receptor, interferon-γ,
and interleukin-2
○ Depressed C1q, C3, C4, C5-C8, and C3 proactivators
○ Elevated C3 catabolic rates
● Circulating viral nonstructural protein 1 (NS1)
○ a viral toxin that activates myeloid cells to release cytokines by attaching to toll
receptor 4
○ contributes to increased vascular permeability by activating complement,
interacting with and damaging endothelial cells, and interacting with blood
clotting factors and platelets
● Mechanism of bleeding in dengue hemorrhagic fever is not known, but a mild degree
of disseminated intravascular coagulopathy, liver damage, and thrombocytopenia
may operate synergistically
PATHOGENESIS
● Capillary damage allows fluid, electrolytes, small proteins, and, in some instances, red blood
cells to leak into extravascular spaces
● Internal redistribution of fluid + fasting, thirsting, and vomiting → hemoconcentration,
hypovolemia, increased cardiac work, tissue hypoxia, metabolic acidosis, and hyponatremia
● Usually no pathologic lesions are found to account for death
● In rare instances, death may be a result of gastrointestinal or intracranial hemorrhages
● Minimal to moderate hemorrhages are seen in the upper gastrointestinal tract, and petechial
hemorrhages are common in the interventricular septum of the heart, on the pericardium,
and on the subserosal surfaces of major viscera.
● Focal hemorrhages - occasionally seen in the lungs, liver, adrenals, and subarachnoid space
● Liver: usually enlarged, often with fatty changes
● Yellow, watery, and at times blood-tinged effusions: present in serous cavities in
approximately 75% of patients at autopsy
● Dengue virus is frequently absent in tissues at the time of death; viral antigens or RNA have
been localized to hepatocytes and macrophages in the liver, spleen, lung, and lymphatic
tissues
 o4
Clinical
Manifestations
and Diagnosis
Clinical Manifestation
- incubation period: 3 - 14 days
- three phases: ACUTE, CRITICAL, RECOVERY

ACUTE FEBRILE PHASE CRITICAL PHASE RECOVERY PHASE

- last 2 - 7 days - 3 - 7 days - gradual improvement

- generalized body ache, muscle and - pt can either improve - stabilization of the
joint pain or deteriorate hemodynamic status
- headache (Dengue with warning
- retro-orbital pain signs)
- facial flushing - increased capillary
- sore throat permeability
- hyperemic pharynx - increased hematocrit
- macular or maculopapular rash levels
- petechiae
- mild mucosal membrane bleeding

(+) Tourniquet Test

Progressive decreased total white cell
count
 Clinical Manifestation and Diagnosis
Clinical signs and symptoms of patients Risk factors associated with mortality in Clinical sign and/or laboratory findings
with confirmed or presumptive diagnosis patients with dengue: indicate significant bleeding in
of dengue in the outpatient that warrant admitted patients:
admission:

● Shortness of breath ● Hypotension on admission ● Hypotension

● Irritability or drowsiness ● Narrow pulse pressure on ● Narrow pulse pressure
● Pleural effusion admission ● Hepatomegaly
● Abdominal pain* ● DHF stage 3 and 4 (severe ● Platelet count < 50,000 / mm3
● Melena dengue) ● WBC count < 5000 / mm3
● Elevated hematocrit ● History of previous dengue ● Elevated ALT ( >3x the normal
● Decreased or decreasing platelet ● Prolonged shock values)
● Respiratory failure
Vomiting? * ● Liver failure ● Vomiting
● Renal failure ● Abdominal pain
● Significant bleeding inclusing GI ● Restlessness
● Severe plasma leakage in ● Pleural effusion or ascites
multiple sites (Pleural effusion, ● Rash
pericardial effusion, ascites)
 Initial Impression:

Dengue with
warning signs
 05
Differentials &
Lab Findings
 Differential Diagnoses
Impression Rule In Rule Out

Typhoid Fever (+) Headache (-) Remittent fever

(+) Vomiting (-)Diarrhea
(+) Abdominal pain

Urinary Tract Infection (+) Fever (-) Dysuria

(+) Headache (-) Urinary Frequency
(+) Vomiting
(+) Abdominal pain

Acute Gastroenteritis (+) Intermittent fever (-) Diarrhea

(+) Vomiting
(+) Abdominal pain

Dengue (+) Intermittent fever

(+) Headache
(+) Vomiting
(+) Abdominal pain
 Diagnostics
Diagnostic Remarks

Dengue NS1 Antigen Useful from day 1 until day 3 of the illness

Serology (Dengue IgM/IgG) ● Method of choice at the end of the acute phase of
infection
● Dengue IgM: samples should not be collected not earlier
than 5 days nor later than 6 weeks after onset
● Primary infection: dengue IgG is detectable in low titers
at the end of 1st week of illness then increases slowly
after (IgG detectable after several months)
● Secondary infection: IgG detected even in the acute
phase and persists from 10 months to life

CBC Leukopenia, then thrombocytopenia

PT/PTT ● Prolonged bleeding time

● Moderately decreased prothrombin level
 06
Treatment &
Complications
● Bed rest - febrile period
● Antipyretics - to keep body temperature <40°C
(104°F)
● Analgesics or mild sedation - to control pain
(Aspirin is contraindicated)
● Fluid and electrolyte replacement is required for
deficits caused by sweating, fasting, thirsting,
vomiting, and diarrhea
● Hypotonic fluids - Increased ADH ➡ water retention ➡
hyponatremia (<136mol/L)
● Hyponatremia - headache, nausea, general malaise (seizures,
coma)
● Fever and vomiting - rehydration solution, fruit juice; avoid fluids
with high glucose content ➡ exacerbation of hyperglycemia of
physiological stress from dengue
● Warning signs WITHOUT shock- 0.9% saline or Ringer's Lactate
● WITH SHOCK - IV fluid resuscitation with isotonic crystalloid
solution then re-assess VS, CRT, Hct, and U. O.).
● Colloids - bleeding and allergic reactions
Complications
● Fluid and electrolyte losses, hyperpyrexia, and febrile
convulsions are the most frequent complications in infants
and young children
● Epistaxis, petechiae, and purpuric lesions are uncommon but
may occur at any stage
● In endemic areas, dengue hemorrhagic fever should be
suspected in children with a febrile illness suggestive of
dengue fever who experience hemoconcentration and
thrombocytopenia
 07
Prognosis &
Prevention
Prognosis
● Usually good
● Worst symptoms of the illness typically last 1 to 2 weeks, and most patients will
fully recover within several additional weeks
● Typical dengue infection is fatal in less than 1% of cases; however, the more
severe dengue hemorrhagic fever is fatal in 2.5% of cases. If dengue
hemorrhagic fever is not treated, mortality (death) rates can be as high as
20%-50%.
Prevention
Mosquitoes that spread dengue virus bite during the day and night.

The best way to prevent these diseases is to protect yourself from mosquito bites.

Stay in places with air conditioning and with window/door screens.

Use a bed net if air conditioned or screened rooms are not available or if sleeping outdoors.

See a Healthcare Provider if you Develop The Fever or Symptoms of Dengue.

Rest and Drink Plenty of Fluids.

Use insect repellent, wear long-sleeved shirts and long pants, and control mosquitoes inside and outside your home.

Treat clothes with repellents like permethrin.

Make sure windows and doors screens are closed to avoid allowing mosquitoes into enclosed spaces.

Avoid areas with standing water. Especially at times of high mosquito activity like dawn and dusk.
References
Liegman, R. (2016). Nelson textbook of pediatrics. Philadelphia, PA: ELSEVIER. 20th ed.

Jameson JL, et. al. (1998). Harrison's Principles of Internal Medicine. 20th ed.

Centers for Disease Control and Prevention. (2022). Dengue. Retrieved at

https://www.cdc.gov/dengue/index.html on January 9, 2023.

World Health Organization. (2023). Dengue and Severe Dengue. Retrieved at

https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue on January 9,
2023.