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mosquito-borne viral dse of humans as

well as horses, swine, and other domestic animals


Asia, northern Japan, Korea, China, Taiwan, the Philippines, and the Indonesian archipelago and from Indochina through the Indian subcontinent


Vector: Culez tritaeniorhynchus summarosus

A night-biting mosquito that feeds preferentially on large domestic animals and birds

Infrequently on humans


Summer outbreaks


Pigs serve as an amplifying host


Pigs maintain a high sustained viremia and may be hosts to thousands of mosquitoes in


single night, thereby producing an

abundant source of infected vectors that can transmit the infection further


The annual incidencein endemic areas ranges from 1-10 per 10,000 population


Children younger than 15 y/o are principally affected, w/ nearly universal exposure by adulthood


- Lethargy, nausea or abdominal pain, headache, and feverishness

- In 2-3 days, lethargy increases and the child may exhibit behavior and motor abnormalities

- Sudden convulsion is frequently the initial symptom

- Unusual manifestations: acute psychosis and Guillain-Barré syndrome

- Signs of meningeal irritation in 2/3 of cases

- Cranial nerve palsies, central facial paralysis

- Muscle weakness, either flaccid or spastic

- W/ hyperreflexia and ankle clonus

- Focal or generalized convulsions develop on 50-75% of patients

- Patients w/ fulminant infections often die during the first 5 days of illness

infections often die during the first 5 days of illness PATHOPHYSIOLOGY - After virus is introduced


- After virus is introduced by a mosquito bite, replication locally and within regional lymphatic tissue --> viremia and infection of various organs and the brain. Neuroinvasion through cerebral capillaries --> infection crosses from the vascular side of the endothelial cells to the perivascular space

- Infiltrating T cells elicit a broad inflammatory response, with B and T cells and macrophages found in perivascular cuffs and macrophages and T cells in the parenchyma

- The rapidity of the neutralizing antibody response is the principal determinant of outcome

- Fatal causes occurring within 5 days after the onset of illness have no detectable CSF antibody response while virus is recoverable from the CSF


- Lumbar puncture

Opening pressures - normal or slightly elevated

CSF fluid - lymphocytic pleocytosis fewer than 10 cells to several thousand, with a median of several hundred per cubic millimeter

CSF glucose and protein levels are generally normal

- Electroencephalograms - diffuse theta to delta showing wave slowing

- CT - diffuse white matter edema and non- enhancing low-density areas, mainly in the thalamus, basal ganglia, and pons

Thalamic lesions frequently are associated with hemorrhage

- MRI - similar distribution of abnormalities

- Confirmed serologically by JE virus-specific IgM antibody in serum or CSF by ELISA

- 4-fold titer between acute and convalescent- phase serum

- Cross-reactions with dengue virus and other flaviviruses are common

- Real-time PCR and 17 promoter-based assays -- sensitive

- JE virus occasionally can be isolated from the blood no later than 6-7 days after onset


- No specific antiviral treatment

- A few patients have been treated with interferon alpha -- efficacy has not been evaluated in wider trials

- Supportive care and control of intracranial pressure are critical

- Mannitol is used routinely

- Other supportive measures:

Control of fever and convulsions

Fluid balance

Respiratory support

Prevention and tx of secondary infections


- Avoidance of vector mosquitoes

- Vaccine




- Mosquito-borne flavivirus (Aedes mosquitoes)

- First identified in Uganda in 1947 in monkeys

- Identified in humans in 1952 in Uganda and the United Republic of Tanzania

- Outbreaks of Zika virus dse have been recorded in Africa, the America, Asia and the Pacific

- 2015: Brazil reported an association of Guillan-Barré syndrome and microcephaly

- Can be transmitted through sexual intercourse

- Concern due to an association between Zika virus and adverse pregnancy and fetal outcomes


- Incubation period is unclear

- Symptoms are similar to dengue


Skin rashes


Muscle and joint pain

Malaise and headache

Mild and last for 2-7 days


- Clinical: travel hx and exposure

- Nucleic Acid Testing (NAT) - whole blood, serum and/or urine collected from patients presenting with onset of symptoms </=7 days

- Serology: IgM detection


- No specific tx


- Protection against mosquito bites is Key measure to prevent

- Physical barriers such as window screens or closing


- Transmitted by Aedes species and Anopheles sp.

- Similar to dengue

- Outbreaks occur

- Incubation period: 2-4 days


- In infants --abrupt onset of fever, followed by flushing of the ski

Febrile convulsion in 1/3 of patients

After 3-5 days of fever, a generalized maculopapular rash and lymphadenopathy

Conjunctival injection, swelling of the eyelids, pharyngitis, and symptoms and signs of URT diseases are common

No enanthem occurs; some infants have a biphasic fever curve, and arthralgia may be severe

- In older children

Fever, headache, myalgia, and arthralgia involving various joints

Macular blush and a maculopapular rash and marked lymphadenopathy precede defervescence

(+) tourniquet test -- rare

- Maculopapular rash, arthralgia or arthritis, and conjunctival injection were more common symptoms in chikungunya than in dengue

- Shock and bleeding are rare




- IgM capture ELISA after 5 days of onset of illness


- Viral culture


- Supportive

- Symptoms are refractory to aspirin or other NSAIDs

- Chloroquine phosphate (250mg/day) provides prompt relief from chronic arthralgia in a high proportion of sufferers

- Analgesics or mild sedation to control pain

- Febrile convulsions: phenobarbital or diazepam

- Fluids


- Vaccines - not yet available

- Avoidance of mosquito bites

- Control of mosquitoes

- Epidemic measures

- Health education

MEASLES (Rubeola or Morbilli) ETIOLOGY

- Family Paramyxovirus

- Genus morbillivirus

- Has an outer envelope composed pf M- protein, H-protein, F-protein, and internal core is RNA

- Acute highly contagious

- Fever, URT catarrhial inflammation, koplik's spots and maculopapular rash


- Routes or administration


Direct contact with infectious droplet

Transplacentally acquired immunity is protective for 4-6 mos; disappear at variable rates

- Susceptibility of population

90% of susceptible contact acquire the disease

Permanent immunity acquired after disease

- Period of communicability

1-2 days before the onset of symptoms (3 days before to 4-6 days after the onset of rash)

Incubation period: 8-12 days

after the onset of rash) • Incubation period: 8-12 days Prodrome : • 3-5 days •
after the onset of rash) • Incubation period: 8-12 days Prodrome : • 3-5 days •


3-5 days Fever Colds, cough, conjunctivitis Kopliks spot -- pathognomonic enanthem

Rashconjunctivitis • Kopliks spot -- pathognomonic enanthem - 1st 24 hrs --> faint macules behind ears,

- 1st 24 hrs --> faint macules behind ears, along the hairline; become confluent maculopapular as it spreads to face, neck, upper arms and chest

- 2nd 24 hrs --> spreads over back, abdomen, entire arms/thighs

- 3rd-4th days --> rash reaches legs and feet --> fading from head to feet --> fine branny desquamation and brownish discoloration

- Severity of disease is directly related to extent and confluence of rash

Feveris directly related to extent and confluence of rash - Temperature rises as rash appears -

- Temperature rises as rash appears

- Fever and symptoms subside w/in 2 days once rashes are on legs and feet

- If persistent after day 3-4 of exanthem, may indicate complication

Convalescent stage:

- Brown staining

- Fine branny desquamation

- Course: 10-14 days

Other manifestations:



Diarrhea and vomiting

Abdominal pain

Slight splenomegaly


- Clinical/epidemiological basis

- Definitive diagnosis:

Measles IgM

Increase in measles IgG in paired sera

Viral isolation (urine, blood, NP secretions)


- Otitis media - most common

- Laryngitis, tracheitis, bronchitis

- Interstitial pneumonia

- Bronchopneumonia

Mc cause of death

due to secondary bacterial infection (pneumococcus, streptococcus, staphylococcus, Hin)

- Exacerbation of an existing Tuberculous process

Temporary loss of hypersensitivity reaction to tuberculin for 4-6 wks

- Neurologic

More common than in any other exanthems

Encephalitis: 1-2/1000 cases

Sub-acute sclerosing panencephalitis

- Rare, degenerative CNS diseases

- Persistent measles virus infection

- Infections before 18 months increases risk

- Boys > girls

Subtle changes in behavior, deterioration of school work --> bizarre behavior --> frank dementia

Massive, repetitive, symmetrical myoclonic jerks

True seizures --> progresses to stupor and coma

High measles antibody titers (HI&CF) in sera and CSF

Occur 10.8 years after original infection

- Others: Guillain-Barré syndrome, hemiplegia, cerebral thrombophlebitis, retrobulbar neuritis

- Other complications


Diarrhea w/ dehydration

Idiopathic thrombocytopenia




- Supportive (antipyretics, fluids and electrolytes)

- Appropriate antibiotics for bronchopneumonia and otitis media

- Oral Vitamin A

6 mos - 1y/o: 100,00 IU

1y/o and older: 200,00 IU

Dose repeated the next day and at 4 wks if w/ ophthalmic evidence of vitamin A deficiency


- Acute immunization

Post-exposure immunization

- Measles vaccine if given w/in 72 hrs after exposure may provide protection in some cases

Pre-exposure immunization

- 1st dose: at age 6 mos

- 2nd dose: 6-9 mos after 1st dose, as monovalent vaccine or MMR

- 3rd dose: monovalent vaccine or MMR at 4-6y/o or 11-12y/o

- Passive immunization

Immune globulin can be given to prevent or modify measles in a susceptible person w/in 6 days of exposure

Dose: 0.25mL/K IM


- Susceptible household contacts especially <1 y/o

- Pregnant women

- Immunocompromised children

RUBELLA (German measles)


- Rubella virus

- Togaviridae family

- German measles - first described by German physicians, Friedrich Hoffman, in the mid-eighteenth century

- Derived from the Latin, meaning little red

- "3-day measles"

That starts initially on the face and neck

Spreads centrifugally to the trunk and extremities within 24 hours

Begins to fade on the face on the second day

- Congenital rubella syndrome (CRS) described by Gregg in 1941


- Person to person via respiratory route

Droplet from nose & throat

Droplet nuclei (aerosols)

Maintain in human population by chain transmission

- Acquired during pregnancy -- vertical transmission

Virus can enter via the placenta & infect the fetus in utero (CRS)

- Period of communicability

Few days before up to 5-7 days after the rash

- Incubation period

14-21 days


the rash - Incubation period • 14-21 days PATHOGENESIS CLINICAL MANIFESTATIONS - Lymph nodes - suboccipital,


• 14-21 days PATHOGENESIS CLINICAL MANIFESTATIONS - Lymph nodes - suboccipital, postauricular, and anterior

- Lymph nodes - suboccipital, postauricular, and anterior cervical lymph nodes are most prominent

- Rash - first manifestation

Begins on the face and neck as small, irregular pink macules that coalesce, and it spreads centrifugally to involve the torso and extremities, where it tends to occur as discrete macules

- Forchheimer spots - time of onset of the rash, examination of the oropharynx -- tiny rose-colored lesions (Pathognomonic sign)

Fleeting enanthema

Pinpont or larger petechiae that usually occur on the soft palate in 20% of patients

Similar spots can be seen in measles and scarlet fever



The primary symptom of the rubella virus infection is the appearance of a rash (exanthema) on the face which spreads to the trunk and limbs and usually fades after three days w/ no straining or peeling of the skin.

"Blueberry muffin lesions"


tender lymphadenopathy (particularly post auricular and suboccipital LN) persist up to a week


fever rarely rises above 38 C (100.4 F)


Eye pain on lateral and upward eye movement (troublesome complaint)


Sore throat


General body aches

Low-grade fever






- May produce transient arthritis, particularly in women

- Serious complications

Thrombocytopenic purpura



- Antibodies appear in serum as rash fades and antibody titer raise

- Rapid raise in 1-3wks

- Rash in association with detection of IgM indicates recent infection

- IgG antibodies persist for life


- Occurs during the 1st trimester of pregnancy

- Affects the development of the fetus

- May lead to several birth defects

- Infection may affect all organs

- May lead to fetal death or premature delivery

- Severity of damage to fetus depends on gestational age

- Infants: virus is isolated from urine and feces


- Before 11 wk of gestation - at 90%

- 11-12 wks - at 33%

- 13-14 wks - at 11%

- 15-16 wks - at 24%

- After 16 wks of gestation - uncommon


- Sensorineural hearing loss - 58%

- Cataract, infantile glaucoma, micro- ophthalmia, pigmentary retinopathy occur in approximately 43%

- Congenital heart disease PDA and pulmonary artery stenosis - 50%

- Bone lesions

- Psychiatric dso

- T1DM

- Hypogammaglobulinemia

- Generalized lymphadenopathy

- Intrauterine growth restriction

- Liver and spleen damage

Hepatosplenomegaly, hepatitis, jaundice

Thrombocytopenic purpura, with petechiae and "blueberry muffin" lesions


Retardation, microcephaly

Motor delay, behavioral dso, autism

Intellectual disability - 13%

A rare complication of panencephalitits can occur in second decade with congenital rubella syndrome may progress to death



Cardiac abnormalities



- Clinical diagnosis is unreliable

- Many viral infections mimic Rubella

- Specific diagnosis of infection with

1. Isolation of virus

2. Evidence of seroconversion


- Nasopharyngeal or throat swabs taken 6 days prior or after appearance of rash is a good source or Rubella virus

- Using cell cultured in shell vial antigens can be detected by immunofluorescent methods


- Post natal

Mild illness

Antipyretics and analgesics

IVIg or corticosteroids can considered for severe, non-remitting thrombocytopenia


Pediatric, cardiac, audiologic, ophthalmologic, and neurologic evaluation

Follow-up because many manifestations may not be readily apparent initially or may worsen with time

Hearing screening


- MMR: live and attenuated; confers lifelong immunity

Given to children 12-15 months and again between 4-6 y/o

- Immunization of the young children and teenage girls remain the best option to prevent CRS

ROSEOLA INFANTUM (Exanthem subitu, or Sixth disease)

- Mild febrile, exanthematous illness occurring almost exclusively during infancy

- More than 95% of roseola cases occur in children younger than 3 yrs w/ a peak of 6-15 mos of age

- Transplacental antibodies likely protect most infants until 6 mos of age

- Infants w/ classic roseola exhibit a unique constellation of findings displayed over a short period of time


- HHV-6: more common

- HHV-7

- Belong to the B-herpes virus subfamily of herpes viruses

- CD4-T cells: principal target in vivo

- HHV 6 can also infect other cells

CD8-T cells (suppressor), NK T-cells, delta gamma cells, glial cells, epithelial cells, monocytes, megakaryocytes, and endothelial cells


- Incubation period: averages 10 days (range of 5-15 days)

- Prodromal period: usually asymptomatic

- Mild upper respiratory tract signs e.g. Minimal rhinorrhea, slight pharyngeal inflammation

- Mild conjunctival redness

- Fever - sudden onset, high grade accompanied by fussiness w/o apparent cause

Usually resolves acutely after 72 hrs

- Rash coincident w/ the appearance of a faint pink or rose-colored, non-pruritic, 2-3mm morbilliform rash on the trunk usually lasts 1-3 days but is often described as evanescent and may be visible only for hours, spreading from the trunk to the face and extremities

- Associated signs & symptoms

Bulging fontanels - 26-30%

Seizures - 5-35%

Occipital or cervical lymphadenopathy -


Respiratory signs & symptoms - 55-70%

Edematous eyelids - 0-30%

Mild diarrhea - 55-70%

- in asian countries, ulcers at the uvulopalatoglossal junction (Nagayama spots) are common in infants w/ roseola

- Exanthems associated with roseola

The roseola rash begins as discrete, small (2-5mm), slightly raised pink lesions on the trunk and usually spreads to the neck, face, and proximal extremities


- Clinically recognized based on fever, defervescence and exanthem pattern

- CBC show leukopenia w/ lymphocytosis

- Definitive diagnosis (research labs)

Viral isolation (peripheral lymphocytes)

4-fold rise in Ab titer (new infection or reactivation)

Detection of HHV-6 Ag by PCR


- Rubella

- Measles

- Roseola-like illness i.e. Enteroviruses

- Scarlet fever

- Drug hypersensitivity


- Supportive care - antipyretic hydration

- Unusual or severe manifestations of primary or presumed reactivated HHv-6B infections such as encephalitis/PALE, especially in immunocompromised patients, may benefit from treatment,

- Gancyclovir, foscarnet, and cidovodir


- Varicella - zoster virus

- Herpes viridae family

- Herpes virus (DNA)

- Primsry infection results in varicella (chicken pox)

- Recurrent infection results in herpes zoster (shingles)

- Short survival in environment


- Mode of transmission

Direct inoculation w/ skin lesions (varicella or herpes zoster)

Airborne spread (varicella)

Highly contagious; 80-90% household transmission rate

- Period of communicability

1-2 days before the rash start until 5-7 days after the rash and the lesions have crusted

- Incubation period:

10-21 days

1-16 days in infant born to mother w/ active varicella

PATHOGENESIS Respiratory transmission of virus


Replication in nasopharynx and regional lymph nodes


Repeated episodes of viremia



Multiple tissues, including sensory ganglia, infected during viremia


Virus is transported in a retrograde manner through sensory axons to the dorsal root ganglia throughout the spinal cord (latency)



virus reach the ganglia by the hematogenous

Subsequent reactivation of latent virus


Herpes zoster


- Incubation period 14-16 days (range 10-21 days)

- Mild prodrome for 1-2 days

24-48hrs before rash

- Fever, malaise, anorexia, headache and mild abdominal pain


Generally appear first on the head; most concentrated on trunk

Appear as very pruritic macules on scalp, face or trunk

- Macules rapidly progress to vesicular -- > pustular --> crusting stages

- New crops of lesions daily x 3-7 days

- Various stages of evolution

- Ulcerative lesions in oropharynx, conjunctivae and genital mucus membranes

in oropharynx, conjunctivae and genital mucus membranes PROGRESSIVE SEVERE VARICELLA - Continuing eruption of


- Continuing eruption of lesions (large, umbilicated and hemorrhagic) w/ high fever unto 2nd week of illness

- Primary varicella pneumonia, hepatitis, encephalitis

- Seen in healthy adolescent and adults, newborn infants and immunocompromised patients


- Reactivation of varicella zoster virus

- Associated with

Aging immunosuppression

Intrauterine exposure

Varicella at <18 month of age

- Localized, unilateral vesicular lesions in 1-3 dermatomes

- Infrequently associated with localized pain, hyperesthesia, pruritus and low grade fever

- Complete resolution in 1-2 wks

- Postherpetic neuralgia (pain >1 month) unusual in children

- Disseminated cutaneous disease and/or visceral dissemination in immunocompromised patients

and/or visceral dissemination in immunocompromised patients Groups at increased risk of complications of varicella: -

Groups at increased risk of complications of varicella:

- Normal adults

- Immunocompromised persons

- Newborns with maternal rash onset w/in 5 days before to 48 hrs after delivery


- Pneumonia

Most common complication in adults

- Hepatitis

Relatively common; usually subclinical

- Encephalitis and Cerebellar ataxia

- Others

Thrombocytopenia, nephritis/nephrotic syndrome, hemolytic-uremic syndrome, myocarditis/pericarditis, pancreatitis, orchitis

- Bacterial superinfection


- S.pyogenes or S.aureus

- Range from superficial impetigo to cellulitis, lymphadenitis and subcutaneous abscesses

- Suspected if with erythema of the base of new vesicle or recrudescence of fever 3-4 days after initial rash

More invasive infections:

- Sepsis

- Pneumonia

- Arthritis

- Osteomyelitis


Long term salicylate therapy

- Varicella gangrenosa


Short, intermittent or

- Necrotizing fasciitis

aerosolized courses of

- Toxic shock syndrome






- Results from maternal infection during pregnancy

- Period of risk may extend through first 20 wks of pregnancy

- Atrophy of extermity with skin scarring (Cicatrix), low birth weight, eye and neurologic abnormalities

- Risk appears to be small (<2%)

Stigmata of Varicella-Zoster Virus Fetopathy

- Damage to sensory nerves:

Cicatricial skin lesions


- Damage to optic stalk and lens vesicle




Optic atrophy

- Damage to brain/Encephalitis:

Microcephaly/ hydrocephaly

Calcifications/aplasia of brain

- Damage to cervical or lumbar cord

Hypoplasia of extremity

Motor/sensory deficits

Absent DTRs

Anisocoria/Horner syndrome

Anal/vesical sphincter dysfunction


- Clinical

- Definitive diagnosis:

Tissue culture - distinguishes VZV from HSV

Direct fluorescent antigen - more rapid/ sensitive than culture

Tzanck smear - not specific for VZV

PCT - distinguish wild type strains from vaccine virus

Varicella IgG - retrospective diagnosis


- Acyclovir - DOC for varicella/herpes zoster when indicated

For Varicella:

- Not routine in healthy children

- Considered in patients at increased risk of moderate to severe varicella

A. >12 y/o

B. Chronic cutaneous or pulmonary disorders

Immunocompetent hosts

- Oral: 80mg/k/day in 4 divided doss x 5 days (max 3200mg/day)

Immunocompromised hosts

- IV

<1 y/o - 30mg/k/day in 3 divided doses x 7-10 days

>1 y/o - 1500mg/m2/day in 3 divided doses x 7-10 days

For Zoster:

- Immunocompetent host

IV: all ages - 30mg/k/day x 7-10 days

Oral: >/= 12y/o - 4000mg/day in 5 divided doses x 5-7 days

- Immunocompromised host


- <12y/o: 60mg/k/day q8 x7-10 days

- >12 y/o: 30mg/k/day q8 x 7 days

Varicella vaccine:

- Live attenuated wild Oka strain

- Dose: 0.5mL SQ

- 2 doses:

<13 y/o - at 12 mos and after 3 mos or at 4-6 y/o

13 y/o and older - 2 dose, 1 month apart

- Efficacy:

85-95% effective for prevention of varicella in Children during outbreaks

100% effective for prevention of moderate or severe disease


- Passive immunization

Varicella zoster immunoglobulin

- Candidates for VZIg after significant exposure:

1. Immunocompromised patients w/o previous infection

2. Susceptible pregnant women

3. New born whose mother had chicken pox 5 days before or within 48 hrs after delivery

4. Hospitalized premature (>28wks AOG) whose mother w/o varicella or negative serostatus

5. Hospitalized premature (<28wks AOG) regardless pf maternal hx of varicella or serostatus


- Small, DNA-containing virus


- Humans are the only known hosts

- Transmitted primarily by respiratory secretion

- Transmissible in blood/ blood products

- Most adults have been infected

Most infections are subclinical

IgG is detectable in most healthy people

- Sporadic outbreaks, usually among children, occur each year

- Transmission from patient to health care staff is not uncommon

Role in nosocomial transmission to other patients

Parvovirus infections

- Diseases

Fifth disease (cutaneous rash)

Transient aplastic crisis (Severe acute anemia)

Pure red cell aplasia (chronic anemia)

Hydrops fetalis (fatal fetal anemia)


- Target is RBC progenitors

- Pain in joints

- Results in lysis of cells, thus depleting source of mature red cells

- Anemia ensues

- Rarely fatal and w/o complications


- B 19 infection of those with other hemolytic anemias

Sickle cell disease


- Can complicate crises

- Sometimes fatal

Other clinical manifestations:

- Arthritis/ arthralgia

- Fetal infections

Occur with primary infection in mother

2nd trimester = most sensitive time

Mom-immune hydrops and/or fetal death

Lytic infection of erythrocyte precursors -- > red cell aplasia --> profound anemia --> high output failure --> Hydrops

Infected infants in utero born normally at term ecen with evidence of hydrops by UTZ


- Persistent arthritis after EI

- Thrombocytopenic purpura

- Aseptic meningitis

- Virus - associated hemophagocytic syndrome


- Laboratory tests not routinely available

- Not isolated by culture

- Based on observation of Typical Rash and exclusion of other conditions

- (+) IgM anti-B19 - best marker of recent or acute infection

- IgG anti-B19 - past infection or immunity


- No specific antiviral treatment

- IVIg for immunodeficient patients w/ chronic anemia

- Transfusion a d supportive care for patients w/ aplastic crisis

- Intra-uterine blood transfusion in some cases of B-19 infected hydrops fetalis