Prescott’s Microbiology, 9th Edition
38
Human Diseases Caused by Viruses and Prions
CHAPTER OVERVIEW
This chapter discusses viruses and prions that are pathogenic to humans, with emphasis on those diseases
occurring in the United States.
LEARNING OUTCOMES
After reading this chapter you should be able to:
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report the common viral diseases spread by airborne transmission
identify typical signs and symptoms of viral diseases spread by airborne transmission
correlate airborne viral infection and disease severity with viral virulence factors
report the two common arthropod-borne viral diseases
identify typical signs and symptoms of arthropod-borne viral diseases
correlate arthropod-borne virus infection with geography and time of year
report the common viral diseases spread by direct contact
identify typical signs and symptoms of viral diseases spread by direct contact
correlate direct contact virus infection and disease severity with viral virulence factors
report the common food-borne and waterborne viral diseases
identify typical signs and symptoms of food-borne and waterborne viral diseases
correlate food-borne and waterborne virus infection and disease severity with viral virulence factors
report the common viral diseases spread by contact with infected animals
identify typical signs and symptoms of zoonotic viral diseases
correlate zoonotic virus infection and disease severity with viral attachment factors
describe diseases caused by prions
differentiate prion diseases by route of infection
CHAPTER OUTLINE
I.
Airborne Diseases
A. Chickenpox (varicella) and shingles (herpes zoster)
1. Chickenpox
a. Caused by the enveloped DNA varicella-zoster virus (VZV), a member of Herpesviridae;
is acquired by inhaling virus-laden droplets into the respiratory system
b. Incubation period is 10 to 23 days after which small vesicles appear on face and upper
trunk; vesicles fill with pus, rupture, and crust with scabs; intensely itchy
c. Can be prevented or infection shortened with attenuated vaccine or the drug acyclovir (or
a derivative such as Valtrex)
d. Infection confers permanent immunity from chickenpox, but does not rid individual of
virus; instead, virus enters a latent stage in the nuclei of neurons in the dorsal root
ganglion
2. Shingles
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a.
B.
C.
D.
E.
F.
G.
If an adult who harbors the virus becomes immunocompromised due to stress, age, or
illness, etc., the virus can emerge and cause sensory nerve damage and painful vesicle
formation (postherpetic neuralgia), a condition known as shingles (herpes zoster)
b. Treated with acyclovir, famciclovir, or other antiviral agents in immunocompromised
patients (e.g., AIDS patients)
Influenza (flu)
1. Caused by orthomyxoviruses; four groups are known, influenza A, B, or C, and Thogoto
viruses
2. Have a negative-strand RNA genome with 7 to 8 linear segments that can undergo frequent
antigenic variation, particularly in surface hemagglutinin (HA) and neuraminidase (NA).
a. Antigenic drift—small variations due to the accumulation of point mutations of HA and
NA; lead to local increases in cases every 2–3 years
b. Antigenic shift—large variations due to reassortment of RNA genome segments between
two strains (typically an animal and a human strain) into progeny virions; the greater
change leads to epidemics or pandemics
3. Animal reservoirs are important (e.g., chickens and pigs) and contribute to antigenic shifts;
designate strains by the 16 HA and 9 NA antigenic forms known (e.g., H5N1)
4. Virus is acquired by inhalation or ingestion of virus-contaminated respiratory secretions; it
enters host cells by receptor-mediated endocytosis
5. Influenza is characterized by chills, fever, headache, malaise, and general muscular aches and
pains; diagnosis can be confirmed by rapid serological tests
6. Treatment is focused on alleviating symptoms, but some antiviral drugs (Relenza, Tamiflu)
have been shown to decrease duration and symptoms of type A influenza
7. Neurominidase inhibitors such as Zanamivir slow progression of type A and B influenza
Measles (rubeola)
1. A skin disease with respiratory spread caused by a negative-strand enveloped RNA
Morbillivirus, a member of family Paramyxoviridae
2. After 10–21-day incubation, cold-like symptoms develop, followed by a rash of small, raised
spots; useful diagnostically are Koplick's spots, which form in the mouth; on rare occasions
can develop into subacute sclerosing panencephalitis
3. No specific treatment; MMR (measles, mumps, and rubella) vaccine is used for prevention
Mumps
1. Caused by mumps virus, a helical, enveloped negative-strand enveloped RNA Rubulavirus in
the family Paramyxoviridae
2. Spread in saliva and respiratory droplets; portal of entry is the respiratory tract
3. Causes swelling of salivary (parotid) glands; meningitis and inflammation of testes (orchitis)
are complications, especially in postpubescent male
4. Therapy is supportive and the MMR vaccine is used for prevention
Respiratory syndromes and viral pneumonia
1. Acute respiratory syndromes
a. Caused by a variety of viruses collectively referred to as acute respiratory viruses
b. Associated with rhinitis, tonsillitis, laryngitis, and bronchitis; immunity resulting from
infection is incomplete and reinfection is common
2. Viral pneumonia is clinically nonspecific, and symptoms may be mild or severe (death is
possible)
3. Respiratory syncytial virus (RSV) is the most dangerous cause of respiratory infection in
young children; it is a negative-strand enveloped RNA virus in the family Paramyxoviridae
Rubella (German measles)
1. Caused by rubella virus, an enveloped positive-strand RNA virus of family Togoviridae
2. Virus is spread by respiratory droplets, and the resulting infection is mild in children (a rash),
but disastrous for pregnant women in first trimester; in pregnant women it causes congenital
rubella syndrome, which leads to fetal death, premature delivery, or congenital defects
3. No treatment is indicated; a vaccine (MMR) is available
Severe acute respiratory syndrome (SARS)
1. Highly contagious, helical enveloped, positive-strand RNA coronavirus
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2.
Causes sudden severe illness with high fever, flu-like discomfort, and a dry cough that will
most likely develop into pneumonia; transmitted by respiratory droplets
3. Relatively recent health threat; no treatment available; diligent monitoring and rapid detection
seen as preventive measures
H. Smallpox (variola)
1. Highly contagious disease caused by variola (major or minor) virus, a dsDNA orthopoxvirus
of the Poxviridae; a brick-shaped virus that is slightly larger than the smallest bacterium;
replicates in host cell’s cytoplasm
2. Virus is transmitted by aerosol or contact; it rapidly moves from respiratory tract membranes
to regional lymph nodes, where is replicates in the monocyte-macrophage system during the
incubation period; after 12–14 days the prodromal period begins, followed in 2–3 days by
clinical manifestations of severe fever, prostration, vesicular rash, toxemia, and septic shock;
historically 20 to 50% fatal
3. Long history of vaccination using live, related vaccinia virus; an important prevention method,
but discontinued when virus declared eradicated
4. Virus was eradicated as the result of a vigorous worldwide vaccination program; eradication
was made possible for several reasons
a. Disease has easily identifiable clinical features
b. There are virtually no asymptomatic carriers
c. It infects only humans (there are no animal or environmental reservoirs)
d. It has a short period of infectivity
5. There is concern that the virus could be used as a bioweapon by terrorists
II. Arthropod-Borne Diseases
A. General features of arthropod-borne diseases
1. Viruses multiply in tissues of insect vectors without producing disease, and vector acquires a
lifelong infection
2. Three clinical syndromes are common
a. Undifferentiated fevers, with or without a rash
b. Encephalitis—often with a high case fatality rate
c. Hemorrhagic fevers—frequently severe and fatal
3. Infection provides permanent immunity; for many of the diseases, no vaccines are available;
treatment is usually supportive
B. Equine encephalitis
1. Caused by a positive-strand enveloped RNA Alphavirus in the family Togaviridae
2. Transmitted by mosquitoes from animal reservoirs; presents as fever, headache, meningitis,
and encephalitis, progressing to seizures, paralysis, coma, and death
3. Treatment is supportive; no vaccine available; prevention relies on mosquito avoidance
C. West Nile fever (encephalitis)
1. Caused by a positive-strand RNA flavivirus indigenous to the Middle East, Africa, and
southwest Asia; first appeared in USA in 1999
2. Transmitted to humans by Culex mosquitoes that have fed on infected birds; can also be
transmitted by blood transfusions and organ transplants
3. Produces mild febrile disease in 20% of infected individuals; can produce meningitis or
encephalitis in 0.7% of infected individuals
4. Diagnosis is by a serological test that detects a rise in neutralizing antibodies in the patient’s
serum; PCR methods also are available
5. No vaccine is available; prevention relies on mosquito abatement
III. Direct Contact Diseases
A. Acquired immune deficiency syndrome (AIDS)
1. Caused by human immunodeficiency virus (HIV), a positive-strand enveloped lentivirus within
the family Retroviridae; believed to have evolved in Africa from viruses that infect other
primates such as SIV
2. Disease occurs worldwide, but certain groups are more at risk; these include
homosexual/bisexual men, intravenous drug users, transfusion patients and hemophiliacs,
prostitutes, and newborn children of infected mothers
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Prescott’s Microbiology, 9th Edition
Virus is acquired by direct exposure of the person’s bloodstream to body fluids containing the
virus; also can be transmitted via breast milk
4. Virus targets CD4+ cells such as T-helper cells, macrophages, dendritic cells, and monocytes
5. After penetration and uncoating, the RNA is copied into DNA by reverse transcriptase; the
DNA provirus then is integrated into the host cell chromosome
6. CDC classification scheme for the stages of HIV-related conditions
a. Acute infection stage is a brief illness 2 to 8 weeks after infection with some fever,
malaise, and a macular rash; large burst of new virions in blood; viral titers eventually
reduced through immune response
b. Asymptomatic stage may last 6 months to 10 years; lower levels of virus in blood; attack
of lymphoid tissue continues and there is some immune system dysfunction
c. Chronic symptomatic stage can last for months to years; virus proliferation decreases
CD4+ populations; significant immune dysfunction ensues with development of
opportunistic infections such as candidiasis and Kaposi's sarcoma
d. AIDS follows with severe immune dysfunction and increased susceptibility to
opportunistic infections such as Pneumocystis pneumonia, toxoplasmosis, cryptococcal
meningitis, and histoplasmosis; nervous system effects can include dementia and ataxia;
cancer rates increase with Kaposi’s sarcoma (caused by human herpesvirus 8; HHV-8),
carcinoma of the mouth and rectum, and B-cell lymphomas
7. Diagnosis is by viral antigen detection or more commonly by viral antibody detection
(ELISA); PCR and Western blots can be used
8. Four types of antiviral agents are used to treat HIV disease, often in combination
a. Nucleoside analogues that inhibit HIV reverse transcriptase (e.g., AZT, ddC, and 3TC)
b. Nonnucleoside inhibitors of HIV reverse transcriptase (e.g., delaviridine)
c. Inhibitors of HIV protease (e.g., ritonavir and indinavir)
d. Fusion inhibitors prevent HIV entry into cells (e.g., enfuvirtide)
e. a cocktail of these: HAART therapy is effective in reducing viral load
9. Vaccines are currently under investigation
10. Prevention and control involve screening of blood and blood products, education, and
protected sexual practices (use of condoms)
Cold sores—fever blisters
1. Typically caused by herpes simplex type 1 (HSV-1), an enveloped dsDNA virus; passed by
direct contact of epithelial tissues
2. Blister at site of infection is due to viral- and host-mediated tissue destruction
3. Lifetime latency is established when virus migrates to trigeminal nerve ganglion; is
periodically reactivated in times of physical or emotional stress
4. Herpetic keratitis—recurring infections of the cornea; can result in blindness
5. Drugs are available that are effective against cold sores (e.g., acyclovir and vidarabine);
diagnosed by ELISA or PCR
Common cold
1. Caused by many different rhinoviruses as well as other viruses; many do not confer durable
immunity
2. Understanding rhinovirus structure has suggested approaches to developing vaccines and drugs
3. Invades upper respiratory tract causing nasal discharge, sore throat, and malaise
4. At one time, common cold was thought to be spread by explosive sneezing, but now it is
believed to be primarily spread by hand-to-hand contact; treatment is supportive
Cytomegalovirus inclusion disease
1. Caused by an enveloped dsDNA virus in the family Herpesviridae
2. Most infections are asymptomatic but infection can be serious in immunologically
compromised individuals; virus persists in the body and is shed for several years in saliva,
urine, semen, and cervical secretions
3. Infected cells have intranuclear inclusion bodies as well as cytoplasmic inclusions
4. Diagnosis is by viral isolation and serological tests
5. Some antiviral agents are available for treatment; these are only used in high-risk patients;
prevention is by avoiding close personal contact with infected individual and by using blood or
organs from seronegative donors
3.
B.
C.
D.
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Prescott’s Microbiology, 9th Edition
E.
F.
G.
H.
I.
Genital herpes
1. Caused by herpes simplex type 2 (HSV-2), an enveloped dsDNA virus that is a member of
Herpesviridae; virus is most frequently transmitted by sexual contact
2. Disease has active and latent phases
a. Active phase—the virus rapidly reproduces; can be symptom free or painful blisters in
the infected area may occur
b. Latent phase—after resolution of active phase, virus retreats to nerve cells; the viral
genome resides in the nuclei of host cells and can be periodically reactivated
3. Congenital (neonatal) herpes is spread to an infant during vaginal delivery; therefore, children
of infected females should be delivered by caesarean section; life threatening, causing
neurological damage and blindness
4. Diagnosis is by ELISA, antibody staining, or PCR; there is no cure, but acyclovir decreases
healing time, duration of viral shedding, and duration of pain
Human herpesvirus 6 infection (HHV-6)
1. Etiologic agent of roseola infantum (sixth disease) in infants, a short-lived disease
characterized by a high fever of 3 to 4 days’ duration, followed by a macular rash (exanthem
subitum)
2. CD4+ cells are the main sites of viral replication and the tropism of the virus is wide and
includes CD8+ T cells, natural killer cells, and probably epithelial cells; transmission is
probably by way of saliva; provirus often found integrated into chromosome and transmitted in
germline
3. Virus produces latent and chronic infections and can be reactivated in immunocompromised
individuals, leading to pneumonitis; virus has been implicated in a variety of other diseases,
including chronic fatigue syndrome and lymphadenitis; diagnosis is by immunofluorescence or
enzyme immunoassay; there is neither treatment nor prevention currently available
Human parvovirus B19 infection
1. Icosahedral, naked, ssDNA virus in the Parvoviridae family; extremely small genome with
overlapping genes
2. Mild symptoms (fever, headaches, chills, malaise) in most normal adults; erythema
infectiosum (fifth disease) in children; joint disease in some adults; serious aplastic crisis in
immunocompromised individuals or those with sickle-cell disease or autoimmune hemolytic
anemia; anemia and fetal hydrops (the accumulation of fluid in the tissues) in infected fetuses
3. Spread by a respiratory route
4. Antiviral antibodies are the principal means of defense, and treatment is by means of
commercial anti-B19 immunoglobulins; infection is usually followed by lifelong immunity
Mononucleosis (infectious)
1. Caused by the Epstein-Barr virus (EBV), a herpesvirus (enveloped dsDNA virus), that is
spread by mouth-to-mouth contact (“kissing disease”) or by shared bottles and glasses; virus
replicates briefly in epithelial cells of throat and eventually infects memory B cells
2. Causes enlargement of lymph nodes and spleen, sore throat, headache, nausea, general
weakness and tiredness, and a mild fever
3. Disease is self-limited; treatment is largely supportive and requires plenty of rest; diagnosis is
made by serological tests
4. EBV is also associated with Burkitt’s lymphoma and nasopharyngeal carcinoma in certain
parts of the world
Viral hepatitides
1. Hepatitis is any inflammation of the liver; currently 11 viruses are recognized as causing
hepatitis; some have not been well characterized
2. Hepatitis B (serum hepatitis)
a. Caused by Hepatitis B virus (HBV), an enveloped, circular dsDNA virus in the family
Hepadnaviridae
b. Virus is transmitted by blood transfusions, contaminated equipment, unsterile needles, or
any body secretion; transplacental transmission to fetus also occurs
c. Most cases are asymptomatic; sometimes fever, appetite loss, abdominal discomfort,
nausea, and fatigue develop; death can result from liver cirrhosis or HBV-related liver
cancer
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Prescott’s Microbiology, 9th Edition
d.
Control measures involve excluding contact with contaminated materials, passive
immunotherapy within seven days of exposure; vaccine is available
3. Hepatitis C
a. Caused by Hepatitis C virus (HCV) (formerly called non-A, non-B hepatitis), an
enveloped ssRNA virus within the family Flaviviridae
b. Virus is spread by intimate contact with virus-contaminated blood, in utero from mother
to fetus, by the fecal-oral route, sexually, or through organ transplants
c. Diagnosis is by serological tests
d. Treated with interferon
4. Hepatitis D
a. Is caused by Hepatitis D virus (HDV) (formerly called the Delta agent), which only
causes disease if the individual is coinfected with Hepatitis B virus (which provides a
coat protein)
b. Diagnosis is by serological tests; treatment is difficult and often involves administration
of alpha interferon; prevention and control are by the use of the hepatitis B vaccine
5. Recently, hepatitis F and hepatitis G (HGV) have been identified and are currently being
investigated; HGV is a member of the Flaviviridae and can be transmitted parenterally or
sexually
J.
Warts
1. Caused by human papillomavirus (HPV), a group of DNA viruses; causative agent of plantar
warts, verrucae vulgaris, flat or plane warts, and anogenital condylomata (venereal warts)
2. Very widespread in sexually active individuals; transmitted through direct contact; most
infections are asymptomatic, but some develop into venereal warts
3. Treatment involves removal of warts, physical destruction, or injection of interferon
4. High-risk papillomaviruses play a major role in the pathogenesis of epithelial cancers of the
male and female genital tracts (e.g., cervical cancer); a vaccine is available and recommended
for young women
IV. Food-Borne and Waterborne Diseases
A. Gastroenteritis (viral)—acute viral gastroenteritis
1. Inflammation of the stomach or intestines caused mainly by noroviruses, adenoviruses,
rotaviruses and astroviruses
2. Main transmission route is fecal-oral route; after an incubation period of 1 to 2 days, typical
symptoms are mild (diarrhea with headache and fever) to severe (watery diarrhea with cramps)
3. Seen most frequently in infants with occasional fatal dehydration; disease is leading cause of
childhood death in developing countries
4. Viral gastroenteritis is usually self-limited; treatment is supportive and includes fluid
replacement and antiperistaltic medication; rotavirus vaccine is available
B. Hepatitis A
1. Caused by the Hepatitis A virus (HAV), an icosahedral, naked, positive-strand RNA
Hepatovirus in the family Picornaviridae
2. Spread by fecal contamination of food or drink, or by infected shellfish that live in
contaminated water
3. Mild intestinal infections sometimes progress to liver involvement; most cases resolve in four
to six weeks and produce strong immunity
4. Control is by hygienic measures and sanitary disposal of excreta; a killed vaccine (Havrix) is
available, greatly reducing incidence of the disease
C. Hepatitis E
1. Implicated in many epidemics in developing countries in Asia, Africa, and Central and South
America
2. Caused by Hepatitis E virus (HEV), a naked, positive-strand RNA virus
3. Infection is associated with fecal-contaminated drinking water; HEV enters the blood from the
gastrointestinal tract, replicates in the liver, is released from hepatocytes into the bile, and is
subsequently excreted in the feces
4. HEV, like HAV, usually runs a benign course and is self-limiting; can be fatal (15 to 25%) in
pregnant women in their last trimester
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Prescott’s Microbiology, 9th Edition
5.
Diagnosis is by ELISA or reverse transcriptase PCR; prevention is aimed at improving the
level of health and sanitation in affected areas
D. Poliomyelitis (polio, infantile paralysis)
1. Polio is caused by Poliovirus, a naked, positive-strand RNA virus in the Picornaviridae
family; it is stable in the environment and remains infectious in food and water
2. Once ingested, virus multiplies in throat and intestinal mucosa; subsequently enters
bloodstream and causes viremia (99% of viremia cases are transient and asymptomatic or with
mild clinical disease including fever and vomiting); with extended viremia, can enter central
nervous system (less than 1% of cases), leading to paralysis
3. Vaccines have been extremely effective in preventing and controlling the disease; global
eradication may be possible in the near future
V. Zoonotic Diseases
A. Ebola and Marburg hemorrhagic fevers
1. Viral hemorrhagic fevers include a group of severe, multisystem diseases; overall host vascular
system is damaged leading to hemorrhaging and dysfunction
2. Ebola hemorrhagic fever—caused by Ebola virus, a negative-strand RNA Filoviridae; after an
incubation period of 2 to 21 days abrupt and severe illness is observed with fever, joint pain,
and weakness, leading to diarrhea and vomiting, rash, red eyes, and bleeding; 80% of cases
result in death; transmission can be through direct contact with bodily fluids; only supportive
treatment is available
3. Marburg hemorrhagic fever—caused by an RNA Filoviridae; rare and severe disease with
symptoms similar to Ebola hemorrhagic fever; no treatment currently exists
B. Hantavirus pulmonary syndrome
1. Caused by an enveloped, negative-strand RNA Bunyaviridae
2. Transmitted by inhalation of virions in wild rodent urine, feces, or saliva; potentially fatal
disease in humans
3. Prevention relies on rodent control and avoidance
C. Rabies
1. Caused by a number of different strains of neurotropic, bullet-shaped, negative-strand RNA
Lyssavirus of the family Rhabdoviridae
2. Transmitted by bites of infected animals; aerosols in caves where bats roost; or by scratches,
abrasions, open wounds, or mucous membranes contaminated with saliva of infected animals
3. Virus multiplies in skeletal muscle and connective tissue, then migrates to central nervous
system, causing a rapidly progressing encephalitis
4. In the past, diagnosis depended on the observation of characteristic Negri bodies (masses of
virus particles or unassembled viral subunits); today diagnosis is based on immunological
tests, virus isolation, as well as the detection of Negri bodies
5. Symptoms progress and death results from destruction of the part of the brain that regulates
breathing
6. Vaccines conferring short-term immunity are available and must be given soon after exposure
(postexposure vaccination is effective because of the long incubation period of the virus);
prevention and control involve annual preexposure vaccination of dogs and cats, postexposure
vaccination of humans, and frequent preexposure vaccination of humans at special risk
VI. Prion Diseases (transmissible spongiform encephalopathies)
A. Caused by a proteinaceous infectious particle (a prion) that is a misfolded brain protein
B. Disease form (misfolded) is protease resistant and will corrupt normally folded particles in
individuals to the disease state form
C. Primary symptom is dementia and motor dysfunction; characteristic spongiform degeneration of the
brain and formation of amyloid plaques; symptoms progress for months or years, leading to death
D. Group of diseases that includes kuru, Creutzfeldt-Jakob disease, Gertsmann-Straussler disease, fatal
familial insomnia, and variants of bovine spongiform encephalopathies (mad cow disease)
CRITICAL THINKING
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Prescott’s Microbiology, 9th Edition
1.
Discuss the pathology of AIDS giving the stages of progression. Why do people develop antibodies
against HIV, the causative agent of AIDS, and yet are not protected against the disease by those
antibodies? Does this mean that an effective vaccine against the virus is not possible? Why or why not?
2.
There are at least two reasons why people continue to get the common cold throughout their lives.
Explain what they are and why permanent immunity against this disease is not possible.
3.
Postulate why some viral diseases such as hepatitis or HIV that are blood-borne are not transmitted by
mosquito bites like malaria is.
4.
Even though viruses are smaller than the pores in facemasks used to limit the spread of airborne-diseases
such as SARS, they prove to be somewhat effective in slowing transmission rates. Comment on why this
is true and what this may have to do with numbers of infectious particle necessary to transmit a disease
effectively
CONCEPT MAPPING CHALLENGE
Design a concept map that demonstrates the process by which an influenza pandemic occurs. Be sure to
identify linking words to make clear the connections between the terms you identify in chapter 38.
8
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