Ziegler – Multisystem Viral Infections
Introduction
 Systemic infections in which symptoms don’t predominate in a specific part of the body; several organs or
systems involved
 Congenital infections can occur
 Disease ranges from asymptomatic to life-threatening
 Vaccines are available for some early childhood diseases like measles
 Several arboviral diseases included here
Clinical Disease
 Symptoms don't predominate in one part of the body.
 The skin is frequently involved, but the viruses are not dermatotrophic like human papilloma virus.
 Some aspects of these viral infections have been covered previously.
Viruses
 Measles Virus
o Enveloped, ss negative-sense RNA virus (Paramyxovirus family)
o HN glycoprotein referred to as H since only hemagglutinin activity (no neuraminidase activity)
o Induces cell-cell fusion which cause syncytial formation (giant cells)
o Transmitted in respiratory droplets and rapidly inactivated by desiccation
o Only one serotype
o Pathogenesis:
 Infects epithelial cells of respiratory tract, spreads to lymphatic system and then by cellassociated viremia
 Maculopapular rash due to T cell response to viral infection of endothelial cells in small
vessels
 Cell-mediated immunity needed to stop infection due to cell-cell virus spread
 During clinical disease and for several weeks after, causes temporary
immunosuppression due to lymphocyte infection
o Clinical Disease:
 A childhood infection whose prodromal period is characterized by a high fever and the
three “C’s” – cough, coryza and conjunctivitis with some photophobia
 Koplik's spots appear on buccal mucosa about 12-24 hours before a maculopapular rash
first seen below the ears
 Complications include a post-infectious encephalitis, giant-cell pneumonia, atypical
measles, and after many years, SSPE
o Epidemiology:
 95% of infected individuals who are not immune will get the disease
 Peak seasons in winter and spring
 Poor compliance with vaccine programs has result in a number of cases in 1989-1991
 Immunocompromised individuals suffer a more serious outcome
 Most important cause of death in children 1-5 years old is countries with poor medical
care and malnutrition
o
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Diagnosis:
 Clinical
o Treatment and Prevention:
 No antivirals
 Live attenuated vaccine containing Enders virus
 Vaccine strain usually combined with mumps and rubella vaccine strains
Mumps Virus
o Enveloped, ss negative-sense RNA virus (Paramyxovirus family)
o Transmitted in respiratory droplets, salivary secretions and possible urine; inactivated by
desiccation
o Only one serotype
o Pathogenesis:
 Infects epithelial cells of respiratory tract and spreads systemically in lymphocytes and
monocytes and by viremia
 Infects parotid glands via Stensen's duct or viremia (parotitis in 30-40% of infections)
 Cell-mediated immunity needed to stop progression of infection
o Clinical Disease:
 Sudden onset parotitis and fever perhaps accompanied by orchitis, pancreatitis and
meningoencephalitis
 CNS involved in 50% of those infected, but symptoms in only 10%
o Epidemiology:
 Often asymptomatic infections
 Late winter and early spring disease; occurs in crowded conditions, e.g., schools, ships
 More serious in immunocompromised individuals.
 Not a significant cause of male sterility
o Diagnosis:
 Clinical diagnosis if symptoms present
 Virus isolation from saliva, CSF or urine
 ELISA of mumps-specific IgM
o Treatment and Prevention:
 No antivirals
 Live attenuated vaccine (Jeryl Lynn strain)
 Vaccine strain is combined with measles and rubella vaccine strains
Rubella Virus
o Enveloped, ss-positive sense RNA virus (Togavirus family)
o Transmitted by respiratory droplets.
o Only one serotype
o Pathogenesis:
 Infects epithelial cells of the respiratory tract, spread to local lymph nodes and systemic
viremia
 Congenital infection leading to severe teratogenic effects can occur in non-immune
pregnant mothers
 Antibody can stop viremic spread of virus, but cell-mediated immunity eliminates virus
o
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Clinical Disease:
 Disease is usually benign in children who after a 14-21 day incubation period have a 3-day
maculopapular rash with fever, malaise and swollen glands
 Adult infection is more severe and can lead to arthralgia, arthritis and post-infectious
encephalitis
 Congenital infections characterized by cataracts, mental retardation, deafness and
frequently death within one year if infection occurs during first twenty weeks of
pregnancy
o Epidemiology:
 ~20% of childbearing women escape childhood infection and are susceptible unless
vaccinated
 Daycare center epidemics possible in unvaccinated children
o Diagnosis:
 Sometimes a clinical diagnosis, but ELISA for IgM done for active infection
 ELISA for IgG early in pregnancy to determine immune status of pregnant women
o Treatment and Prevention:
 No antivirals
 Live attenuated, cold-adapted RA 27/3 vaccine strain usually combined with measles and
mumps vaccine strains
Varicella Zoster Virus
o Causes chickenpox, previously discussed in “Viral Infections of the Skin,” could also be considered
with this grouping of viruses
Dengue Virus
o Enveloped, ss positive-sense RNA virus (Flavivirus family)
o An arbovirus with a mosquito vector; monkeys are the reservoir
o Four serotypes
o Pathogenesis:
 Virus replicates in monocytes and vascular endothelium
 Antibody from previous infection can increase efficiency of infection by different
serotype
 Enhancing antibody effect due to Fc portion of antibody (Figure 1)
o Clinical Disease:
 Adults — fever/rash syndrome with headache and severe joint and muscle pain
 Children — in endemic areas dengue hemorrhagic shock syndrome with up to 10%
mortality
o Epidemiology:
 Endemic areas include SE Asia, Pacific area, India and the Caribbean
o Diagnosis:
 Clinical
o Treatment and Prevention:
 Very effective treatment includes replacement of fluids, correction of electrolyte balance
and blood transfusion if hemorrhaging is severe
 No vaccine since it may enhance possibility of serious disease
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Arboviruses
o Various Togaviruses, Flaviviruses and Bunyaviruses cause systemic infections with fever in
endemic areas
o Infections are usually subclinical or mild, but may be serious in some people
o Diseases include 1) encephalitis (discussed in nervous system course), 2) hemorrhagic fevers, and
3) febrile illnesses with or without rashes
o Colorado Tick Fever, a usually mild disease with fever, headache, myalgia, and rash, needs to be
distinguished from Rocky Mountain Spotted Fever, a rickettsial disease
EPIDEMIOLOGY OF IMPORTANT ARBOVIRUS
DISEASES IN THE UNITED STATES
Disease
Vector
Animal Reservoir
Geographic Distribution
Approximate Incidence per Year
EEE
Mosquito
Wild birds
Atlantic and Gulf States
0-4
WEE
Mosquito
Wild birds
West of Mississippi
5-20
SLE
Mosquito
Wild birds
Widespread in southern,
central, and western states
10-30
CE
Mosquito
Small mammals
North-central states
40-80
CTF
Tick
Small mammals
Rocky Mountains
100-300