ARTHROPOD BORNE DISEASES
DENGUE
Four serotypes of virus
o DENV-1, DENV-2, DENV-3, DENV-4
o Each serotype produces type specific
immunity against other type
Member of class Flaviviridae
Transmitted through bites of certain species of
Aedes (stegomyia) mosquitoes (A. aegypti and
A. albopictus)
Endemic and cause epidemics in tropical
regions of Asia and the Americas
Dengue fever
o A benign syndrome
o Biphasic fever, myalgia or arthralgia, rash,
leucopenia and lymphadenopathy
o Incubation period: 1-7 days
o Clinical manifestations are variable and
influenced by age.
o Clinical Manifestations
Infants and young children
Undifferentiated or characterized
by fever for 1-5 days, pharyngeal
inflammation, rhinitis and mild
cough.
Older children
Sudden inset of high grade fever
(biphasic pattern)
Frontal or retro-orbital pain
Occasional severe back pain
precedes the fever
Transient, macular, generalized
rash: blanches under pressure
(during 1st 24th-48th hour of fever)
Pulse rate: slow relative to the
degree of fever
Myalgia and arthralgia occur soon
after the onset and increase in
severity
Platelet rarely falls below 100,
000
Dengue Hemorrhagic fever
o A severe often fatal, febrile disease
o Capillary permeability, abnormalities of
hemostasis and in severe cases, a protein-
losing shock syndrome (Dengue shock
syndrome)
o Mild first phase: fever, malaise, vomiting,
headache, anorexia, cough
o Followed by 2-5 days of rapid clinical
deterioration and collapse
Course of dengue illness
o Febrile phase
High grade fever
Lasts 2-7 days, accompanied by facial
flushing, skin erythema, non-specific
signs and symptoms
A positive tourniquet test in this phase
increases the probability of dengue
Systolic + diastolic
2
(+) TT: >10-20 petechiae per
square inch
Difficult to distinguish dengue clinically
from non-dengue febrile diseases in
the early febrile phase
o Critical phase
Time of defervescence: temperature
drops to 37.5-38 C on days 3-7 of
illness
An increase in capillary permeability
parallel increasing hematocrit levels-
marks the beginning of critical phase
The degree of increase of hematocrit
often reflects the severity of plasma
leakage
The period of clinically significant
plasma leakage usually lasts 24-48
hours
Usually preceded by progressive
leucopenia
Patients without an increase in
capillary permeability will improve
Those with increased capillary
permeability may become worse as a
result of loss of plasma volume
Pleural effusion and ascites clinically
detectable depending on the degree of
plasma leakage and the volume of fluid
therapy
MDR-C7-2017 Page 1
 SHOCK occurs with a critical volume of fluid have been administered
plasma leakage. It is often preceded by
warning signs.
Complications
Severe organ impairment such as
sever 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
o Recovery phase
If the patient survives the 24-48 hours
of critical phase, a gradual Diagnosis of dengue
reabsorption of extravascular o Derived from high index of suspicion and
compartment fluid takes place in 48-72 knowledge of the geographic distribution
hours and environmental cycles of causal
General well-being improves, viruses
symptoms abate, hemodynamic o The classification into levels of severity
statues stabilizes and dieresis ensues has a high potential for being of practical
May have a rash of “isles of white in use in the clinicians’ regarding treatment
the sea of red”-HERMAN’S RASH o Overall assessment
Bradycardia and ECG changes: The history should include
common Date of onset of fever/illness
HCT stabilizes or may be lower due to Quantity of oral intake
the dilutional effect of reabsorbed Assessment for warning signs
fluid Diarrhea
WBC count usually starts to rise soon Change in mental
after defervescence but the recovery state/seizure/dizziness
of platelet count is typically later than Other important relevant
that of WBC count histories such as
Respiratory distress from massive o Family or neighborhood
pleural effusion and ascites will occur dengue
at any time if excessive intravenous o Travel to dengue endemic

MDR-C7-2017 Page 2
 areas
o Co-existing conditions (eg.
Infancy, pregnancy, obesity,
DM, HPN)
o Jungle trekking and
swimming in waterfall
(consider leptospirosis,
typhus, malaria)
o Recurrent unprotected sex
or drug abuse (consider
acute HIV seroconversion
illness)
PE should include
Assessment of mental state
Assessment if hydration statues
Assessment of hemodynamic
status
Checking for
tachypnea/acidotic
breathing/pleural effusion
Examination for rash and
bleeding manifestations
Tourniquet test (repeat if
previously negative or if there is
no bleeding manifestation)
Management of dengue: depends on clinical
manifestations and other circumstances
o Group A patients
Suspected dengue cases without
warning signs particularly when
fever subsides
Able to tolerate adequate volumes
of oral fluids and pass urine at least
once every 6 hours
Can be sent home if hematocrit is
stable but advise to return to the
hospital immediately if they
develop any warning signs
o Group B patients
Those with co-existing conditions
that may make dengue or its
management more complicated
(such as pregnancy, old age,
obesity, DM, renal failure, chronic
hemolytic disease)
Those with certain social
circumstances (such as living alone,
or living far from a health facility
without reliable means of
transport)
Patient should be referred for in-
hospital management for close
observation, particularly as they
approach the critical phase
Obtain a reference hematocrit
before fluid therapy
Give only isotonic solutions
such as 0.9% saline/ringer’s
lactate solution
Reassess the clinical status and
repeat hematocrit
Give the minimum IV fluid
required to maintain good
perfusion and urine output of
about 0.5 ml/kg/hr.
o Group C patients
Patients with severe dengue who
are in critical phase of the disease
i.e. when they have:
Severe plasma leakage leading
to dengue shock and/or fluid
accumulations with respiratory
distress
Severe hemorrhage
Severe organ impairment
(hepatic damage, renal
impairment, cardiomyopathy,
encephalopathy, or
encephalitis)
Should be admitted to a hospital
with access to intensive care
facilities and blood transfusion.
DHF complications
o Fluid and electrolyte loses
o Bleeding (intracranial or gastrointestinal)
o Mental depression, bradycardia and
ventricular extrasystoles
Dengue 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 death should occur in <1%
o Survival is directly related to early and
intense supportive treatment
Dengue prevention
o Dengue vaccine-under development
o Avoid mosquito bites (insecticides,
repellents, body covering, screening of
houses, and destruction of A. aegypti
breeding sites)
o If water storage is mandatory, a tight
fitting lid or thin layer of oil may prevent
egg laying or hatching
o A larvicide (abate) may be added safely
to drinking water
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 o Ultra low volume spray equipment
effectively dispenses the adulticide
Malathion from truck or airplane for
rapid intervention
CHIKUNGUNYA VIRUS
Alphavirus genus of the family togaviridae
Phylogenetic analysis of the E1 envelope
glycoprotein divides chikungunya virus into 3
genotypes corresponding to their geographic
distribution:
o West Africa genotype (Senegal and
Nigeria)
o Central and east African genotype
o Asian genotype
Aedes species: (A. aegypti and A albopictus)
principal vectors for transmission
Has the ability to replicate in a broad spectrum
of vertebrate species
Produce disease in urban setting just like
dengue virus
Clinical manifestations
o 3-7 days after mosquito bite: high
fever, severe joint symptoms (hands,
feet ankles, wrists)
o Headaches, myalgia, conjunctivitis,
weakness, lymphopenia, macular rash
Diagnosis
o In the initial stage of the disease,
difficult to use the clinical
manifestations for the diagnosis-
observe the evolution of the disease
o Laboratory criteria
Virus isolation
Presence of viral mRNA
Specific IgM antibodies
Fourfold increase in IgG titers
Treatment
o No specific therapy. Purely supportive
Prognosis
o In children in general, the prognosis is
good for some infant who may
experience residual neurologic deficits
after febrile convulsions
o Arthralgia may persist for weeks and
may resemble rheumatoid arthritis
Prevention
o Vaccine: not available
o Avoid mosquito bites
MALARIA
Overwhelming and important problem in
worldwide (esp. in developing countries)
An estimated 300-500 million cases and more
than 1 million deaths
Most malarial deaths occur among infants and
young children
The principal areas of transmission are Africa,
Asia, and south Americas.
Etiology
o Cause: intracellular Plasmodium
protozoa transmitted to human by
female anopheles mosquitoes
o Prior to 2004, only 4 species of
plasmodium were known to cause
malaria in human: P. falciparum, P.
malariae, P. ovale and P. vivax
o In 2004, P. knowlesi ( a primate malaria
species) was also shown to cause human
malaria (Malaysia, Indonesia, Singapore
and the Philippines)
o Most of the Fatal cases were caused by
P. Falciparum
Epidemiology
o Plasmodium species: exist in a variety of
forms with complex life cycle that
enables them to survive in different
cellular environment in the human host
(asexual phase) and the mosquito
(sexual phase)
o P. Ovale and P. vivax: two species
known to cause malaria RELAPSE.
schizont of these two remain dormant in
the liver for quite some time (days,
months or even years)
Pathogenesis
o Four important pathologic processes
have been identified in patient with
malaria
Fever: occurs when
erythrocytes rupture and
release merozoites into the
circulation
Anemia: caused by hemolysis,
sequestration of erythrocytes in
the spleen and other organs,
and bone marrow suppression
Immunopathologic events:
excessive production of
proinflammatory cytokines
(TNF) that may be responsible
for most of the pathology of the
disease including
Tissue anoxia
Polyclonal activation
resulting in
hyperglobulinemia and
the formation of
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 immune complexes
Immunosuppression
Tissue anoxia:
Cytoadherence of infected
erythrocytes to vascular
endothelium: leading to
obstruction of blood flow and
capillary damage, with resultant
vascular leakage of blood,
protein and fluid and tissue
anoxia. (In addition,
hypoglycemia and lactic
academia caused by anaerobic
metabolism of glucose)
The cumulative effects of these pathologic processes
may lead to cerebral, cardiac, pulmonary, intestinal
and hepatic failure
Clinical manifestations
o Children and adults are asymptomatic
during the initial phase of infection,
the incubation period of malarial
infection
o The usual incubation period
P. falciparum: 9-14 days
P. vivax: 12-17 days
P. ovale: 16-18 days
P. Malaria: 18-20 days
o Prodromal symptoms of malaria lasting
2-3 days: in some patients before
parasites are detected in the blood
include:
Headache
Fatigue
Anorexia
Myalgia
Slight fever
Chest, abdomen and joint pain
o Classic presentation of malaria:
paroxysms of fever alternating with
periods of fatigue but otherwise
relative wellness
o Febrile paroxysms: characterized by
high fever, sweats and headache, as
well as myalgia, back pain, abdominal
pain, nausea, vomiting, diarrhea, pallor
and jaundice
o The paroxysms coincide with the
rupture of schizonts that occurs:
Every 48 hrs: P vivax and P ovale
Every 72 hrs: P. malariae
Periodicity is less apparent-P.
falciparum and mixed infections
o Children with malaria: often lack typical
paroxysms and have nonspecific
symptoms including fever (may be low
grade) headache, drowsiness, anorexia,
nausea, vomiting and diarrhea
o Distinctive physical signs may include
splenomegaly (common),
hepatomegaly, and pallor due to
anemia
o Typical laboratory findings include
anemia, thrombocytopenia, and normal
or low leucocyte count. The erythrocyte
sedimentation rate (ESR) is often
elevated.
o P. falciparum infection is the most
severe form of malaria and is
associated with higher parasitemia
(60%) and a number of complications
such as
Anemia (most common severe
complication)
Cerebral malaria (coma)
Acute renal failure
Respiratory distress (due to
metabolic acidosis) poor
prognostic indicator
o Severe malaria (WHO criteria, 2000)
Impaired consciousness
Prostration
Respiratory distress
Multiple seizures
Jaundice
Hemoglobulinuria
Abnormal bleeding
Severe anemia
Circulatory collapse
Pulmonary edema
Congenital malaria
o Usually occurs in the offspring of a
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 non-immune mother with P. vivax or P.
malariae infection (although it can be
observed with any of the human
malaria species)
o 1st sign or symptom most commonly
occurs between 10-30 days of age
(range 14 hr to several months of age)
o Signs and symptoms include fever,
restlessness, drowsiness, pallor,
jaundice, poor feeding, diarrhea,
cyanosis, and hepatosplenomegaly
Malaria: diagnosis
o Any child who presents with fever or
unexplained systemic illness and has
travelled or resided in a malaria-
endemic area within the previous year
should be assumed to have life-
threatening malaria until proven
otherwise
o Identification of organisms on Giemsa-
stained smears of peripheral blood
(thick or thin) or by rapid
immunochromatographic assay
o The timing of smears is less important
than their being obtained several times
a day over a period of 3 successive days.
A single negative smear does not
excluded malaria.
Treatment
o Physicians caring for patients with
malaria or travelling to endemic areas
need to be aware of current
information regarding malaria because
the problem of resistance to anti-
malarial drugs is changing and has
greatly complicated therapy and
prophylaxis
o P. falciparum
Chloroquine: individuals travelling
from areas with chloroquine-
susceptible P. falciparum (if they
do not have severe malaria_
If choloroquine-resistant or
unknown resistance
Atovaquone-proguanil
Artemether-
lumefantrine
Quinine sulfate plus
doxycycline, tetracycline
or clindamycin
Mefloquine
o P. vivax, P. ovale, P. malariae, P.
knowlesi
Choloroquine: for uncomplicated
cases
Indications for using alternative
therapy are worsening or new
symptoms, persistent P. vivax
parasitemia after 72 hours,
possibly acquisition of infection in
Oceania and India
Patients with P, vivax or P. ovale
should also be given Primaquine
once daily for 14 days to prevent
relapse from the hypnozoite
forms that remain dormant in the
liver
o Severe Malaria
Intravenous quinidine or quinine
PLUS a second line drug
(clindamycin, doxycycline, or
tetracycline) should be used.
o Supportive therapy
Red blood cell transfusion to
maintain hematocrit at more than
20%
Exchange transfusion in P.
Falciparum with parasitemia
greater than 10% and evidence of
severe complications (e.g. severe
malarial anemia, cerebral malaria)
Supplemental oxygen and
ventilator support for pulmonary
edema or cerebral malaria
Careful intravenous rehydration
for severe malaria
Intravenous glucose for
hypoglycemia
Anticonvulsants for cerebral
malaria with seizures
Dialysis for renal failure
Prevention
o Vaccine-not available yet
o Reducing exposure to infected
mosquitoes
Travelers in endemic areas should
remain in well screened areas
from dusk to dawn
Should sleep under permethrin-
treated mosquito netting
Spray insecticides indoor at
sundown
During the day, should wear
clothing that covers the arms and
legs, with trousers tucked into
shoes or boots
Mosquito repellent should be
applied to thin clothing and
MDR-C7-2017 Page 6
 exposed areas of the skin, with
application repeated every 1-2
hrs (DEET)
o Prophylaxis
Choloroquine susceptible
Chloroquine
phosphate*
Choloroquine resistant
Mefloquine*
Doxycycline*
Atovaquone-proguanil
*once weekly dosing
JAPANESE ENCEPHALITIS
JE virus originated from an ancestral virus in the
area of the Malay archipelago
First clinical case of JE was in Japan in 1871
Half a century later-large outbreak >6000 cases
of encephalitis
JE virus: single stranded RNA virus of the family
Flaviviridae
Mosquito-borne viral disease of humans
(horses, swine, and other domestic animals)
Seen in a vast area of Asia (northern Japan,
Korea, china, Taiwan, Philippines, and the
Indonesian archipelago and from Indochina
through Indian subcontinent)
Culex tritaeniorhychus summarosus: principal
vector of zoonotic and human JE in northern
Asia
Pigs serve as the amplifying host
Annual incidence in endemic areas ranges from
1-10/10,000 population
Common: children <15 years of age
Incubation period: 4-14 days
Cases typically progress through the following
four stages:
o Prodromal illness (2-3 days)
o Acute stage: (3-4 days)
o Subacute stage: (7-10 days)
o Convalescence: ( 4-7 weeks)
Abrupt onset of fever, headache, respiratory
symptoms, anorexia, nausea, abdominal pain,
vomiting and sensory changes, including
psychotic episodes
Grand mal seizures are seen in 10-24% of
children
Particularly characteristic: rapidly changing
central nervous system signs
Course and lab data
o The sensory status of the patient may
vary from confusion through
disorientation and delirium to
somnolence, progressing to coma.
o Fatal cases usually progress to coma,
and the patient dies.
o There is usually mild pleocytosis (10-
1,000 leucocytes/mm3) in the CSF,
initially polymorphonuclear but in a few
days predominantly lymphocytic.
Diagnosis:
o JE should be suspected in patients
reporting exposure to night biting
mosquitoes in endemic areas during
the transmission season.
o Testing an acute-phase serum collected
early in the illness for the presence of
virus-specific IgM antibodies or
alternatively demonstrating a fourfold
or greater in IgG antibody titers by
testing paired acute and convalescent
sera.
Treatment
o There is no specific treatment for JE
o The treatment is intensive supportive
care including control of seizures.
Prognosis
o Fatality rates for JE are 24-42% and are
highest in children 5-9 years of age
adults older than 65.
o Sequelae are most common in patients
younger than 10 years old at the onset
of disease
o The more common sequelae: mental
deterioration, severe emotional
instability, personality changes, motor
abnormalities and speech
disturbances.
Prevention
o Travellers to endemic countries who
plan to be in rural areas of the endemic
region during the expected period of
seasonal transmission should receive JE
VACCINE
Two doses of inactivated IM
one month apart
Single dose for live attenuated
(china)
o Personal measures should be taken to
reduce exposure to mosquito bites esp.
for short-term residents in endemic
areas.
Avoiding evening outdoor
exposure
Using insect repellants
Covering body with clothing
Using bed nets or house
screening
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ROCKY MOUNTAIN SPOTTED FEVER
Systemic infection of endothelial cells by
Rickettsia rickettsii
Most frequently identified and most severe
rickettsial disease in the US
Highest among children >5 years
Boys > Girls
90% occur between April and September
Transmission
o TICKS: natural hosts, reservoir and vector
of Rickettsia rickettsii
o Dogs can act as reservoir and develop
contact with humans
o Humans can get infected: via exposure
to R. rickettsii-containing tick fluids or
feces when removing an attached tick
Clinical Manifestations
o Incubation period: 2-14 days
o Clinical triad: fever, headache, rash
o Other symptoms:
50% nausea, vomiting, headache,
conjunctival infection, abdominal
pain/diarrhea, altered mental
status, lymphadenopathy,
peripheral edema.
o Calf tenderness common among
children
o Rash of RMSF
Appears 1-2 days of illness
Initially discrete, pale rose-red
blanching macules or
maculopapules initially observed
on the extremities
Rapidly spreads to involve palms
and soles and may become
petechial and even hemorrhagic
Severe forms: gangrenous and
necrotic
Diagnosis
o Based on epidemiologic, clinical and
laboratory features
o Non-specific laboratory abnormalities-
normal WBC, thrombocytopenia,
hyponatremia, high AST/ALT
o History of exposure
o Gold standard: fourfold increase in IgG
antibody titer
Treatment
o Drug of choice: Doxycycline
o Alternative: Tetracycline
o For pregnant women or those with
Doxycycline or Tetracycline sensitivity:
Chloramphenicol
o Duration of treatment: 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 hours—duration is usually <10
days
ESSENTIALS
DENGUE
Most common arthropod borne viral
(arbovirus) illness in humans
Transmitted by female day biting mosquitoes
(Aedes aegypti)
Presents with non-specific febrile syndrome
Three phases of DHF: febrile, critical and
recovery
Management is purely supportive.
CHIKUNGUNYA
One of a group of arbovirus and is transmitted
by female day biting mosquitoes (Aedes sp.)
Fever with severe muscle and joint pains:
prominent symptoms
Management is purely supportive
Malaria
Acute and chronic illness characterized by
paroxysms of fever, chills, sweats, anemia and
splenomegaly
Caused by intracellular Plasmodium protozoa
transmitted by female Anopheles mosquitoes
Treatment is based on the information of
resistance to anti-malarial drugs in a particular
area.
Japanese encephalitis
Most develop mild symptoms or no symptom
at all.
Severe cases: fever, chills, fatigue, nausea,
vomiting—progress to encephalitis
No specific therapy
Rocky Mountain spotted fever
Tick-borne disease caused by bacterium
Rickettsia rickettsii
Typical triad: fever, headache and rash
Doxycycline: drug of choice.
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