DENGUE, CHINKUNGUNYA, JAP ENCEPHALITIS AN D RMSF

ARTHROPOD-BORNE I NFECTI ONS 1

EPL 2017 | TPMD 201 7

DENGU E
o Dengue Fever

Benign syndrome characterized by biphasic fever, myalgia or

arthralgia, rash, leukopenia, and lymphadenopathy
o Dengue Hemorrhagic Fever

Severe, often fatal, febrile disease and is characterized by

capillary permeability, abnormalities of hemostasis and in
severe cases, a protein-losing shock syndrome (dengue shock
syndrome)
o Four serotypes: (member of Flaviviridae)

DENV- 1, DENV-2, DENV-3, DENV-4

o Each serotype produces type-specific immunity but not immunity
against other type
o Transmitted through bites of certain species of Aedes (Stegomyia)
mosquitoes (A. aegypti and A. albopictus)
o Endemic and cause epidemic in tropical regions of Asia and the
Americas

Clinical Manifestations
o Incubation period is 1-7 days
o Variable and influenced by the age of the patient
o In infants and young children

May be undifferentiated or characterized by fever for 1-5

days, pharyngeal inflammation, rhinitis, and mild cough
o In older children and adults

Experience sudden onset of fever 39.4- 41.1 C

Frontal or retro-orbital pain

Occasional severe back pain precedes the fever

Transient, macular, generalized rash that blanches under

st
pressure may be seen during the 1 24-48 hr of fever

Pulse rate may be slow relative to the degree of fever;

Myalgia and arthralgia occur soon after the onset and

increase in severity

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& COURSE OF DENGUE ILLNESS
Course,of,Dengue,Illness,
1. Febrile Phase
1. Febrile,Phase,
High-grade fever that lasts 2-7 days
Patients&typically&develop&high>grade&fever&
- Accompanied
by facial flushing, skin erythema, generalized
- body
Lasts&2&&7&days&and&is&often&accompanied&
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by&facial&flushing,&skin&erythema,&

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nausea and vomiting are common
generalized&body&ache,&myalgia,&arthralgia&

A positive tourniquet test in this phase increases the

and&headache&
probability of dengue
Anorexia,&nausea&and&vomiting&are&common&

Difficult to distinguish dengue clinically from non-dengue

Some&patients&may&have&sore&throat,&
febrile diseases in the early febrile phase
injected&pharynx&&and&conjunctival&injection&
- Clinical
features are indistinguishable between severe and
A&positive&tourniquet&test&in&this&phase&
non-severe
dengue
increases&the&probability&of&dengue&
-

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non3dengue(febrile(diseases(in(the(early(
febrile(phase(

Monitoring for warning signs and other clinical parameters

is crucial to recognizing progression to the critical phase

Critical Phase

Time of defervescence, when the temperature drops to

37.5-38 C and remains below this level, usually on days 3
7 of illness

Increase in capillary permeability in parallel with

increasing hematocrit levels may occur marks the
beginning of the critical phase

Degree of increase above the baseline hematocrit often

reflects the severity of plasma leakage (>20% increase in
baseline HCT)

Period of clinically significant plasma leakage usually lasts

24 48 hours

Progressive leukopenia followed by a rapid decrease in

platelet count usually precedes plasma leakage

Patients without an increase in capillary permeability will

improve, while those with increased capillary permeability
may become worse as a result of lost plasma volume

Pleural effusion and ascites- clinically detectable depending

on the degree of plasma leakage and the volume of fluid
therapy

Shock occurs with a critical volume of plasma leakage, often

preceded by warning signs (narrow pulse pressure: 20
mmHg)

With prolonged shock, the consequent organ

hypoperfusion results in progressive organ impairment,
metabolic acidosis and disseminated intravascular
coagulation severe hemorrhage causing the hematocrit
to decrease in severe shock

Instead of the leukopenia usually seen during this phase of

dengue, the total white cell count may increase in patients
with severe bleeding

Severe organ impairment such as severe hepatitis,

encephalitis or myocarditis and/or severe bleeding may also
develop without obvious plasma leakage or shock

Those who improve after defervescence are said to have

non-severe dengue

Some patients progress to the critical phase of plasma

leakage without defervescence and, in these patients,
changes in the full blood count should be used to guide the
onset of the critical phase and plasma leakage

Recovery phase

If the patient survives the 24 48 hours critical phase, a

gradual reabsorption of extravascular compartment fluid
takes place in the following 48 72 hours

General well-being improves, appetite returns,

gastrointestinal symptoms abate, hemodynamic status
stabilizes and diuresis ensues

Some patients may have a rash of isles of white in the sea

of red Hermans rash

Some may experience generalized pruritus

Bradycardia and electrocardiographic changes are common

Hematocrit stabilizes or may be lower due to the

dilutional effect of reabsorbed fluid

White blood cell count usually starts to rise soon after

defervescence but the recovery of platelet count is
typically later than that of white blood cell count

Respiratory distress from massive pleural effusion and

ascites will occur at any time if excessive intravenous fluids
have been administered

PEDIATRICS 2| Arthropod-Borne Infections 1 of 2| Page 1

classification&
Low&sensitivity&of&criteria&in&detecting&DHF&
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life&threatening&dengue&which&do&not&fulfil&&all&
criteria&for&DHF&

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DIAGNOSIS OF DENGUE

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&place&in&the&following&48&&
DHF)&
A diagnosis of dengue fever derives from a high index of suspicion and

Poor&management&resulting&to&fatal&outcomes&
oves,&appetite&returns,&knowledge of the geographic distribution and environmental cycles of
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ids&have&been&

Step I: Overall Assessment
o
History should include:

Date of onset of fever/illness

Quantity of oral intake

Assessment for warning signs

Diarrhea

Change in mental state/seizure/dizziness

Other important relevant histories such as:

Family or neighborhood dengue

Travel to dengue endemic areas

Co-existing conditions (e.g., Infancy, pregnancy,

obesity, diabetes mellitus, hypertension)

Jungle trekking and swimming in waterfall (consider

leptospirosis, typhus, malaria)

Recent unprotected sex or drug-abuse (consider

acute HIV seroconversion illness)
o Physical examination should include:

Assessment of mental state

Assessment of hydration status

Assessment of hemodynamic status

Checking for tachypnea/acidotic breathing/pleural effusion

Examination for rash and bleeding manifestation

Tourniquet test (Repeat if previously negative or if there is

no bleeding manifestation)

(+) test = > 20 per square inch after 5 mins

o
Investigation

CBC should be done at the first visit

HCT in the early febrile phase establishes the patients own

baseline

Decreasing WBC count makes dengue very likely

A rapid decrease in platelet count in parallel with a rising

hematocrit compared to the baseline is suggestive of
progress to the plasma leakage/critical phase of the disease

Laboratory test should be performed to confirm the

diagnosis. However, it is not necessary for the acute
management of patients, except in cases with unusual
manifestations.

Additional tests should be considered as indicated. (and if

available). These should include tests of liver function,
glucose, serum electrolytes, urea and creatinine,
bicarbonate or lactate, cardiac enzymes, ECG and urine
specific gravity

Step II: Diagnosis, Assessment of Disease Phase and Severity
o
Clinicians should be able to determine whether the disease is
dengue ( NS1)
o
Which phase it is in (Febrile, Critical or Recovery)
o
Whether there are warning signs
o
Hydration and hemodynamic status of the patient
o
If the patient requires admission

MANAGEMENT OF DENGUE
o
Suggested criteria for early notification of suspected cases

Patient has lives in or has travelled to a dengue- endemic

area Has fever for three days or more Has low or decreasing
white cell counts and/or has thrombocytopenia positive
tourniquet test
o
Management decisions: depending on the clinical manifestations
and other circumstances

Group A

Group B

Group C

GROUP A PATIENTS
o
Suspected dengue cases without warning signs particularly
when fever subsides
o
Able to tolerate adequate volumes of oral fluids and pass urine
at least once every 6 hrs
o
Can be sent home if hematocrit is stable but advise to return to
the hospital immediately if they develop any of the warning
signs.
o
Plan of Action for Group A Patients

Encourage oral intake of oral rehydration solution (ORS),

fruit juice and other fluids containing electrolytes and sugar
to replace losses from fever and vomiting

If oral fluid not tolerated, start intravenous fluid

therapy of 0.9% Saline or Ringers lactate with or
without dextrose at maintenance rate.

Give paracetamol for high fever, tepid sponge bath if

patient still has high fever (Do not give aspirin, ibuprofen or
other non-steroidal anti-inflammatory agents )

Instruct the care-giver that the patient should be brought to

hospital immediately if any of the following occur:

No clinical improvement

Deterioration around the time of defervescence

Severe abdominal pain

Persistent vomiting

Cold and clammy extremities

Lethargy / restlessness

Bleeding (Black stools or coffee-ground vomiting)

Not passing urine for more than 4 6 hours

Patients who are sent home should be monitored daily by

health care providers

GROUP B PATIENTS
o
Patients with warning signs
o
Those with co-existing conditions that may make dengue or its
management more complicated (such as pregnancy, infancy, old
age, obesity, diabetes mellitus, renal failure, chronic hemolytic
disease)
o
Those with certain social circumstances (such as living alone, or
living far from a health facility without reliable means of
transport
o
Patients should be referred for in-hospital management for close
observation, particularly as they approach the critical phase
o
Plan of Action for Group B Patients

Obtain a reference hematocrit before fluid therapy

Give only isotonic solutions such as 0.9% Saline, Ringers

Lactate, or Hartmanns solution

Start with 5 -7 ml/kg/hour for 1 2 hours

Then reduce to 3 5 ml/kg/hour for 2 4 hours

And then reduce to 2 3 ml/kg/hour or less according

to the clinical response

Reassess the clinical status and repeat hematocrit

If the hematocrit remains the same or rises minimally,

continue with the same rate 3 5 ml/kg/hr for 2 4
hours

If the vital signs are worsening and hematocrit is rising

rapidly, increase the rate to 5 10
ml/kg/hr for 1 2 hours. Reassess
the clinical status, repeat the
hematocrit and review fluid infusion

PEDIATRICS 2| Arthropod-Borne Infections 1 of 2| Page 2

rate accordingly.
Give the minimum intravenous fluid required to maintain
good perfusion and urine output of about 0.5 ml/kg/hr.
Intravenous fluids are usually needed for only 24 48
hours
Reduce intravenous fluids gradually when the rate of
plasma leakage decreases towards the end of the critical
phase. This is indicated by urine output and/or oral fluid
intake that is/are adequate or hematocrit decreasing below
the baseline value in a stable patient
Patients with warning signs should be monitored by health
care providers until the period of risk is over.

A detailed fluid balance should be maintained

Parameters that should be monitored include:

Vital signs and peripheral perfusion (1 4 hours)

until the patient is out of the critical phase

Urine output (4 6 hourly)

Hematocrit (Before and after fluid replacement,

then 6 12 hours)

Blood glucose and other organ functions as

indicated.

GROUP C PATIENTS
o
Patients with severe dengue who are in the critical phase of the
disease, i.e. when they have:

Severe plasma leakage leading to dengue shock and/or fluid

accumulation with respiratory distress

Severe hemorrhages

Severe organ impairment (hepatic damage, renal

impairment,
cardiomyopathy,
encephalopathy
or
encephalitis)
o
Should be admitted to a hospital with access to intensive care
facilities and blood transfusion.
o
Plan of Action for Group C Patients

Judicious intravenous fluid resuscitation is the essential and

usually sole intervention required

Crystalloid solution should be isotonic and the volume just

sufficient to maintain an effective circulation during the
period of plasma leakage

Plasma losses should be replaced immediately and rapidly

with isotonic crystalloid solution or in the case of
hypotensive shock, colloid solutions

If possible, obtain hematocrit levels before and after fluid

resuscitation

Blood typing and cross-matching should be done for all

shock patients

Blood transfusion should be given only in cases with

suspected/severe bleeding

COMPLICATION
o
Fluid and electrolyte losses
o
Bleeding (intracranial or gastrointestinal)
o
Mental depression, bradycardia and ventricular extrasystoles

PROGNOSIS
o
May be adversely affected by passively acquired antibody or
prior infection with a closely related virus that predisposes to
development of DHF
o
Death has occurred in 40-50% of patients with shock, but with
adequate intensive care deaths should occur in <1%
o
Survival is directly related to early and intense supportive
treatment

PREVENTION
o
Dengue vaccine not yet available
o
Avoid mosquito bites
o
If water storage is mandatory, a tight-fitting lid or a thin layer of
oil may prevent egg laying or hatching.
o
A larvicide (Abate) may be added safely to drinking water.
o
Ultra-low-volume spray equipment effectively dispenses the
adulticide malathion during epidemic

CH IK UN GUN YA
CHIKUNGUNYA VIRUS
o
Enveloped, positive-sense RNA Alphavirus of Togaviridae
o
Emerging pathogen in the United States carried by day biting
mosquitos (Aedes aegypti, Aedes albopictus)

CLINICAL MANIFESTATION
o
Incubation period of 3-7 days
o
High fever with severe symmetric bilateral polyarthralgia or
arthritis (hands, feet, ankles, wrist) lasting for 7-10 days
o
Some may have prolonged joint symptoms (tenosynovitis,
arthritis) lasting over a year
o
Convulsions may occur during high fever
o
Mortality is rare

DIAGNOSIS
o
Testing for Acute-phase serum 5 days after onset for IgM
antibodies
o
Convalescent sera tested for a 4-fold or greater increase in ELISA,
hemagglutination inhibition or neutralizing igG antibody titer
Diagnostic Criteria for Chikungunya Virus Fever

PROGNOSIS
o
Generally good, resolve without residua
o
No vaccine available, killed vaccine is efficacious but under
development

JA PA N ES E ENCEPHA LITIS
ETIOLOGY
o
JE virus - positive-sense, single-stranded RNA virus of the family
Flaviviridae

EPIDEMIOLOGY
o
Mosquito-borne viral disease of humans
o
Asia, northern Japan, Korea, China, Taiwan, the Philippines, and
the Indonesian archipelago and from Indochina through the
Indian subcontinent.
o
Culex tritaeniorhynchus summarosus

Principal vector of zoonotic and human JE in northern Asia

Night-biting mosquito

Feeds preferentially on large domestic animals and birds

but only infrequently on humans
o
Pigs serve as an amplifying host
o
Annual incidence in endemic areas: 1-10 per 10,000 population
o
Children younger than 15 yr of age are principally affected
o
A travel history in the diagnosis of encephalitis is critical

CLINICAL MANIFESTATIONS
o
Incubation period: 4-14 days
o
Four stages:

Prodromal illness (2-3 days)

Acute stage (3-4 days)

Subacute stage (7-10 days)

Convalescence (4-7 wk)

PEDIATRICS 2| Arthropod-Borne Infections 1 of 2| Page 3

o
o
o

Abrupt onset of fever, headache, respiratory symptoms,

anorexia, nausea, abdominal pain, vomiting, and sensory
changes, including psychotic episodes
Grand mal seizures (10-24% of patients)
Rapidly changing central nervous system (e.g., hyper- reflexia
followed by hyporeflexia or plantar responses that change)
Laboratory Findings:

Mild pleocytosis in CSF (PMN lymphocytic)

Albuminuria

Fatal cases usually progress rapidly to coma, and the

patient dies within 10 days

DIAGNOSIS
o
Should be suspected in patients reporting exposure to night-
biting mosquitoes in endemic areas during the transmission
season
o
Diagnosis:

Presence of virus-specific IgM antibodies

Fourfold or greater increase in IgG antibody titers by testing

paired acute and convalescent sera

PCR

TREATMENT
o
No specific treatment
o
Intensive supportive care, including control of seizures

PROGNOSIS
o
Fatality rates for JE:

24-42%

Highest in children 5-9 yr of age and in adults older than 65

yr of age.
o
Sequelae:

Mental deterioration, severe emotional instability,

personality changes, motor abnormalities, and speech
disturbances

Frequency - 5-70%

Directly related to the age of the patient and severity of

disease

More common if younger than 10 yr at the onset of disease

PREVENTION
o
JE vaccine

Administered intramuscularly as 2 doses of 0.5 mL each, 28

days apart

Final dose should be completed at least 1 wk prior to the

patients expected arrival in a JE endemic area

Some vaccines are available as single-dose regimen

o
Personal measures: avoiding evening outdoor exposure, using
insect repellents, covering the body with clothing, and using bed
nets or house screening.
o
Pesticides and insecticides

ROCKY MOU NT AIN S POTTED FEVER

ETIOLOGY
o
Rickettsia rickettsia - obligate intracellular bacterium
o
Rocky Mountain spotted fever - agent was discovered in the
Bitterroot Range of the Rocky Mountains of Montana

EPIDEMIOLOGY
o
Most frequently identified and most severe rickettsial disease in
the United States
o
Most common vector-borne disease in the United States after
Lyme disease
o
Should be considered in the differential diagnosis of fever,
headache, and rash in the summer months, especially after tick
exposure
o
2010 - CDC reporting criteria for Rocky Mountain spotted fever
changed to spotted fever group rickettsiosis
o
Highest age-specific incidence - children older than 5 yr of age,
with boys outnumbering girls

TRANSMISSION
o
Ticks are the natural hosts, reservoirs, and vectors of R. rickettsii
o
Ticks transmit the infectious agent to mammalian hosts via
infected saliva during feeding
o
Principal tick hosts:

Dermacentor variabilis (the American dog tick)

Dermacentor andersoni (the wood tick)

Rhipicephalus sanguineus (the common brown dog tick)

Amblyomma cajennense and Amblyomma aureolatum

o
Dogs can serve as reservoir hosts, can be infected, and can bring
infected ticks into contact with humans
o
Other ways of acquiring the disease:

R. rickettsiicontaining tick fluids or feces can be rubbed

into the open wound at the bite site or into the
conjunctivae by contaminated fingers

Inhalation of aerosolized rickettsiae

PATHOLOGY AND PATHOGENESIS
o
Systemic infection is most obvious on the skin (rash), but nearly
all organs and tissues are affected
o
Proliferate and damage the host cells by oxidative membrane
alterations, protease activation, or continued phospholipase
activity
o
Initial macular or maculopapular rash - perivascular infiltration
of lymphoid and histiocytic cells with edema but without
significant endothelial damage
o
Petechial rash - endothelial injury and lymphohistiocytic or
leukocytoclastic vasculitis of small venules and capillaries, leading
to extravasation of intravascular erythrocytes into the dermis
o
Tissue infarction or hemorrhagic necrosis when small and large
vessels become completely obliterated by thrombi,
o
Interstitial pneumonitis and vascular leakage in the lungs can
lead to noncardiogenic pulmonary edema
o
Meningoencephalitis can cause significant cerebral edema and
herniation

o
Major determinants of severity and outcome:

Timing and balance between rickettsia- mediated increases

in vascular permeability

Benefits of induction of innate and adaptive immunity

CLINICAL MANIFESTATIONS
o
Incubation period: 2-14 days (median: 7 days)
o
Clinical triad of fever, headache, and rash is observed in 58% of
pediatric patients overall, but is present in only 3% of all patients
at presentation

Fever can exceed 40C (104F) and may be persistently

elevated or can fluctuate dramatically

Headache is severe, unremitting, and unresponsive to

analgesics

Rash usually appears after only 1-2 days of illness

o
CNS infection:

Changes in mental status (33%)

Photophobia (18%)

Seizure (17%)

Meningismus (16%)

CSF parameters are usually normal, but 1/3 have

pleocytosis, and some protein elevations
o
Other manifestations:

Pulmonary disease - more often in adults than in children.

Conjunctival suffusion, periorbital edema, dorsal hand and

foot edema, and hepatosplenomegaly

Myocarditis, acute renal failure, and vascular collapse

Fulminant RMSF

Death from R. rickettsii infection within 5 days

Persons with G6PD deficiency are at increased risk

Profound coagulopathy and extensive thrombosis

leading to kidney, liver, and respiratory failure

PEDIATRICS 2| Arthropod-Borne Infections 1 of 2| Page 4


LABORATORY FINDINGS
o
Laboratory abnormalities are common but nonspecific
o
Thrombocytopenia (60%)
o
WBC count is most often normal

Leukocytosis (24%)

Leukopenia (9%)

Left-shifted leukocyte differential

o
Anemia (33%)
o
Hyponatremia (<135 mEq/mL in 52%),
o
Elevated serum aminotransferase levels (50%).

DIAGNOSIS
o
Delays in diagnosis and treatment are associated with severe
disease and death
o
Decision to treat must be based on compatible epidemiologic,
clinical, and laboratory features
o
Treatment should not be withheld pending definitive laboratory
results for a patient with clinically suspected illness
o
Biopsy of skin rash

Can be diagnosed as early as day 1 or 2 of illness

Very specific, but 70% sensitivity

Influenced by prior antimicrobial therapy, suboptimal

selection of skin lesions for biopsy, and examination of
insufficient tissue because of the focal nature of the
infection
o
Tissue or blood PCR

PCR on blood is less sensitive than PCR on tissue and of

similar sensitivity to tissue immunohistology
o
Gold standard for the diagnosis of RMSF:

Rise in titer is not seen until after the 1st wk of illness

4-fold increase in igG antibody titer by indirect fluorescent

antibody assay between acute and convalescent (at 2-4 wk)
sera

Demonstration of seroconversion

TREATMENT
o
Treatment of choice in patients of all ages

Doxycycline (4 mg/ kg/day divided every 12 hr PO or IV;

maximum: 200 mg/day)
o
Alternative

Chloramphenicol - reserved for patients with doxycycline

allergy and for pregnant women
o
Continued for a minimum of 5-7 days and until the patient has
been afebrile for at least 3 days to avoid relapse
o
Treated patients usually defervesce within 48 hr, so the duration
of therapy is usually <10 days

SUPPORTIVE CARE
o
Most infections resolve rapidly with appropriate antimicrobial
therapy and do not require hospitalization or other supportive
care
o
Particular attention to hemodynamic status is mandatory in
severely ill children risk of iatrogenic pulmonary or cerebral
edema

COMPLICATIONS
o
Noncardiogenic pulmonary edema from pulmonary
microvascular leakage
o
Cerebral edema from meningoencephalitis
o
Multiorgan damage mediated by vasculitis and/or the
accumulated effects of hypoperfusion and ischemia
o
Long-term neurologic sequelae can occur in any child with RMSF
but are more likely to occur in those hospitalized for 2 wk.

Learning disabilities and behavioral problems are the most

common neurologic sequelae

PROGNOSIS
o
Delays in diagnosis and therapy are significant factors associated
with death or severe illness
o
Death often occurs within 14 days
o
Deaths occur despite the availability of effective therapeutic
agents
o
Early therapy in uncomplicated cases usually leads to rapid
defervescence within 1-3 days and recovery within 7-10 days
o
Slower response may be seen if therapy is delayed
o
Fever subsides in 2-3 wks in those who survive despite no
treatment

PREVENTION
o
No vaccines are available
o
Prevention best accomplished by preventing or treating tick
infestation in dogs, avoiding areas where ticks reside, using insect
repellents, wearing protective clothing, and carefully inspecting
children after play in areas where they are potentially exposed to
ticks
o
Prompt and complete removal of attached ticks

Reduce the risk for transmission because rickettsiae in the

ticks need to be reactivated to become virulent, and this
requires at least several hours to days of exposure to body
heat or blood.

Site of attachment should then be disinfected

Should not be squeezed or crushed, because their fluids

may be infectious

Avoid accidental inoculation into conjunctivae, mucous

membranes, or breaks in skin
o
Prophylactic antimicrobial therapy is not recommended

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