DANIL
HAMMOUDI.MD
USMLE
REVIEW
SINOE
MEDICAL ASSOCIATION
This
information on hepatitis B is excerpted from the Centers for Disease Control
and Prevention (CDC), Epidemiology and Prevention of Vaccine-Preventable
Diseases. [1]
Clinical Features
The clinical course of acute hepatitis B is
indistinguishable from that of other types of acute viral hepatitis. The incubation
period ranges from 45 to 160 days (average, 120 days). Clinical signs and
symptoms occur more often in adults than in infants or children, who usually
have an asymptomatic acute course. However, approximately 50% of adults who
have acute infections are asymptomatic. When symptoms occur in acute HBV
infection, they may occur in the following patterns.
The preicteric, or prodromal,
phase from initial symptoms to onset of jaundice,
usually lasts from 3 to l0 days. It is characterized by insidious onset with
malaise, anorexia, nausea, vomiting, right upper quadrant abdominal pain,
fever, headache, myalgias, skin rashes, arthralgias and arthritis, and dark urine, beginning 1 to 2
days before the onset of jaundice. The icteric
phase is variable, but usually lasts from l to 3 weeks, characterized by
jaundice, light or gray stools, hepatic tenderness and hepatomegaly
(splenomegaly is less common). During convalescence,
malaise and fatigue may persist for weeks or months, while jaundice, anorexia,
and other symptoms disappear.
Most acute HBV infections in adults result in complete recovery with
elimination of HBsAg from the blood and the
production of anti-HBs creating immunity from future
infection.
|
Hepatitis B Clinical
Features Incubation period 6
weeks to 6 months May have prodrome of fever, malaise, headache, myalgia
Jaundice may persist
for days or weeks Symptoms not
specific for hepatitis B At least 50% of
infections asymptomatic |
Complications
While most acute HBV infections in adults result
in complete recovery, fulminant hepatitis occurs
in about 1% to 2% of persons, with mortality rates of 63% to 93%. About 200 to
300 Americans die of fulminant disease each year.
Although the consequences of acute HBV infection can be severe, most of the
serious complications associated with HBV infection are due to chronic
infection.
|
Hepatitis B
Complications Fulminant
hepatitis Hospitalization Cirrhosis Hepatocellular
carcinoma Death |
Chronic HBV infection
Approximately 10% of all acute HBV infections progress to chronic infection,
with the risk of chronic HBV infection decreasing with age. As
many as 90% of infants who acquire HBV infection from their mothers at birth
become carriers. Of children who become infected with HBV between 1 year
and 5 years of age, 30% to 50% become carriers. By adulthood, the risk of
becoming a carrier is 6% to 10%.
Persons with chronic infection are often asymptomatic and may not be aware that
they are infected, yet are capable of infecting others. Chronic infection is
responsible for most HBV-related morbidity and mortality, including chronic
hepatitis, cirrhosis, liver failure, and hepatocellular
carcinoma. Chronic active hepatitis develops in over 25% of carriers, and
often results in cirrhosis. An estimated 3,000 to 4,000 persons die of
hepatitis B-related cirrhosis each year in the
|
Chronic Hepatitis B
Virus Infection Chronic viremia Responsible for most
mortality Overall risk 10% Higher risk with
early infection |
Medical Management
There
is no specific therapy for acute HBV infection. Interferon is the most
effective treatment for chronic HBV infection and is successful 25% to 50% of
the time.
Persons with acute HBV infections and carriers should prevent their blood and
other potentially infective body fluids from contacting other persons. They
should not donate blood, or share eating utensils, toothbrushes, or razors with
household members.
In the hospital setting, patients with HBV infection should be managed with
Blood/Body Fluid Precautions (See CDC Guideline for Isolation Precautions in
Hospitals). Health care workers should employ universal precautions for all
patients, regardless of their blood borne infection status.
Hepatitis B Virus
HBV is a small, double-shelled virus in the
class Hepadnaviridae.
The virus contains numerous antigenic
components, including
|
Hepatitis B Virus
Infection Over 200 million
carriers worldwide Established cause of
chronic hepatitis and cirrhosis Cause of up to 80% of
hepatocellular carcinomas Second only to
tobacco among known human carcinogens |
Several well-defined antigen-antibody systems are associated with HBV
infection. HBsAg, formerly called
HBcAg is the nucleocapsid
protein core of HBV. HBcAg is not detectable in serum
by conventional techniques, but can be detected in liver tissue in persons with
acute or chronic HBV infection. HBeAg, a
soluble protein, is also contained in the core of HBV. HBeAg
is detected in the serum of persons with high virus titers and indicates high
infectivity. Antibody to HBsAg (Anti-HBs) develops during convalescence after acute HBV
infection or following hepatitis B vaccination. The presence of HbsAb antibody indicates immunity to HBV. Antibody to HbcAg (Anti-HBc) indicates
infection with HBV at an undefined time in the past. IgM
class antibody to HBcAg (IgM
anti-HBc) indicates recent infection with HBV. Antibody
to HBeAg (Anti-HBe) becomes
detectable when HBeAg is lost and is associated with
low infectivity of serum.
Haemophilus influenzae
Haemophilus influenzae is a gram-negative coccobacillus. It is generally aerobic, but can grow as a
facultative anaerobe. In vitro growth requires accessory growth factors. These
include "X" factor (hemin) and
"V" factor (nicotinamide adenine dinucleotide [NAD]).
Chocolate agar media are used for isolation. H. influenzae
will generally not grow on blood agar, which lacks NAD.
The outermost structure of H. influenzae is
composed of polyribosyl-ribitol phosphate (PRP), a
polysaccharide, which is responsible for virulence and immunity. Six antigenically and biochemically
distinct capsular polysaccharide serotypes have been described, which are
designated types a through f. Type b organisms account for 95% of all strains
that cause invasive disease.
|
Haemophilus influenzae
Aerobic gram-negative
bacteria Polysaccharide
capsule Six different
serotypes (a-f) of polysaccharide capsule 95% of invasive
disease caused by type b |
Clinical Features
Invasive disease caused by H. influenzae type
b can affect many organ systems. The most common types of invasive disease are
meningitis, epiglottitis, pneumonia, arthritis, and cellulitis.
Meningitis is infection of the membranes covering the brain and is the
most common clinical manifestation of invasive Hib
disease, accounting for 50% to 65% of cases. Hallmarks of Hib
meningitis are fever, decreased mental status, and stiff neck. The mortality
rate is 2% to 5%, despite appropriate antimicrobial therapy. Neurologic sequelae occur in 15%
to 30% of survivors.
Epiglottitis is an infection and swelling of
the epiglottis, the tissue in the throat that covers and protects the larynx
during swallowing. Epiglottitis may cause
life-threatening airway obstruction.
Septic arthritis (joint infection), cellulitis
(rapidly progressing skin infection which usually involves face, head, or
neck), and pneumonia (which can be mild focal or severe empyema) are common manifestations of invasive disease.
Osteomyelitis (bone infection), and pericarditis (infection of the sac covering the
heart) are less common forms of invasive disease.
Otitis media and acute bronchitis due to H. influenzae are generally caused by nontypable
strains. Hib strains account for only 5%-10% of H.
influenzae causing otitis
media.
The case-fatality rate for invasive H. influenzae
disease is 2% to 5%.
|
Haemophilus influenzae type b Clinical Manifestations
Meningitis: 50% Epiglottitis: 17%
Pneumonia: 15%
Arthritis: 8%
Cellulitis: 6%
Osteomyelitis: 2%
Bacteremia: 2%
|
Medical Management
Hospitalization is generally required. Antimicrobial therapy with chloramphenicol or an effective third-generation
cephalosporin (cefotaxime or ceftriaxone)
should be begun immediately. Treatment course is usually 10 to 14 days.
Ampicillin-resistant strains of Hib
are now common throughout the
|
Haemophilus influenzae type b Medical
Management Immediate treatment
with chloramphenicol or an effective 3rd generation
cephalosporin Ampicillin-resistant
strains now common throughout the Hospitalization
required |
EPIDEMIOLOGY
Occurrence
Hib disease occurs worldwide. However, the incidence
outside the
Reservoir
Humans are the only known reservoir. Hib does not
survive in the environment on inanimate surfaces.
Transmission
Primary mode is presumably by respiratory droplet spread, although firm
evidence for this mechanism is lacking.
Temporal pattern
Several studies have described a bimodal seasonal
pattern in the
Communicability
The contagious potential of invasive Hib disease is
considered to be limited. However, certain circumstances, particularly close
contact with a case (e.g., household, day-care, or institutional setting) can
lead to outbreaks or direct secondary transmission of the disease.
|
Haemophilus influenzae type b Epidemiology
Reservoir: Human; Asymptomatic carriers Transmission: Respiratory droplets Temporal pattern: Bimodal - peaks Sept-Dec and March-May Communicability: Generally limited but higher in some
circumstances |
Influenza Virus
Influenza is a single-stranded, helically
shaped, RNA virus of the orthomyxovirus family. Basic
antigen types A, B, and C are determined by the
nuclear material. Type A influenza has subtypes that
are determined by the surface antigens hemagglutinin
(H) and neuraminidase (N). Three types of hemagglutinin
in humans (H1, H2, and H3) have a role in virus attachment to cells. Two types
of neuraminidase (N1 and N2) have a role in virus penetration into cells.
|
Influenza Virus Single-stranded RNA
virus Family Orthomyxoviridae 3 types: A, B, C Subtypes of type A
determined by hemagglutinin and neuraminidase |
Influenza A causes moderate to severe illness, and affects all age
groups. The virus infects humans and other animals, such as pigs and birds.
Influenza B generally causes milder disease than type A, and primarily
affects children. Influenza B is more stable than influenza A, with less
antigenic drift and consequent immunologic stability. It affects only humans.
It may be associated with Reye syndrome.
Influenza C is rarely reported as a cause of human illness, probably
because most cases are subclinical. It has not been
associated with epidemic disease.
|
Influenza Virus
Strains
|
The nomenclature to
describe the type of influenza virus is expressed in this order: (1) virus
type, (2) geographic site where it was first isolated, (3) strain number, (4)
year of isolation, and (5) virus subtype.
Antigenic changes
Hemagglutinin and neuraminidase periodically change,
apparently due to sequential evolution within immune or partially immune
populations. Antigenic mutants emerge and are selected as the predominant virus
to the extent that they differ from the antecedent virus, which is suppressed
by specific antibody arising in the population. This cycle repeats
continuously. In interpandemic periods, mutants arise
by serial point mutations in the RNA coding for hemagglutinin.
At irregular intervals of 10 to 40 years, viruses showing major antigenic
differences from prevalent subtypes appear and, because the population does not
have protective antibody against these new antigens, cause pandemic disease in
all age groups.
Antigenic shift is a major change in one or both surface antigens (H and/or
N) that occurs at varying intervals. Antigenic shifts are probably due to
genetic recombination between influenza A viruses,
usually those that affect humans and birds. An antigenic shift may result in a
worldwide pandemic if the virus is efficiently transmitted from person to
person. The last major antigenic shift occurred in 1968 when H3N2 (
Antigenic drift is a minor change in surface antigens that occurs
between major shifts. Antigenic drift may result in epidemics, since incomplete
protection remains from past exposures to similar viruses. Drift occurs in all
three types of influenza virus (A,B,C). For instance,
during most of the 1997-1998 influenza season,
A/Wuhan/359/95 (H3N2) was the predominant influenza strain isolated in the
In the past 100 years, there have been 4 antigenic shifts that led to major
pandemics (1889-1891, 1918-1920, 1957-1958, and 1968-1969). A pandemic starts
from a single focus and spreads along routes of travel. Typically, there are
high attack rates involving all age groups and mortality is usually markedly
increased. Severity is generally not greater in the individual (except for the
1918-1919 strain), but because large numbers of people are infected, the
number, if not the proportion, of severe and fatal cases will be large. Onset
may occur in any season of the year. Secondary and tertiary waves may occur
over a period of 1 to 2 years, usually in the winter.
Typically in epidemics, influenza attack rates are lower than in
pandemics. There is usually a rise in excess mortality. The major impact is
observed in morbidity, with high attack rates and excess rates of
hospitalization, especially for adults with respiratory disease. Absenteeism
from work and school is high, with an increase in visits to health care
providers. In the Northern Hemisphere, epidemics usually occur in late fall and
continue through early spring. In the Southern Hemisphere, epidemics usually
occur 6 months before or after those in the Northern Hemisphere.
Sporadic outbreaks can occasionally localize to families, schools, and
isolated communities.
EPIDEMIOLOGY
Occurrence
Influenza occurs throughout the world.
Reservoir
Humans are the only known reservoir of influenza types B and C. Influenza A may
infect both humans and animals.
Transmission
Influenza is transmitted via aerosolized or droplet transmission from the
respiratory tract of infected persons. A less important mode of transmission of
droplets is by direct contact.
Temporal pattern
Influenza peaks from December to March in temperate climates, but may occur
earlier or later. It occurs throughout the year in tropical areas.
Communicability
Maximum communicability occurs 1to 2 days before onset
to
|
Influenza
Epidemiology Reservoir: Human, animals (type A only) Transmission: Respiratory; probably airborne Temporal pattern: Peak December to March in temperate areas; may
occur earlier or later Communicability: Maximum 1-2 days before to 4-5 days after
onset |
Measles Virus
The measles virus is a paramyxovirus,
genus Morbillivirus. It is 100 to 200 nm in diameter,
with a core of single-stranded RNA, and is closely related to the rinderpest and canine distemper viruses. Measles virus has
six structural proteins, of which three are complexed
to the RNA and three are associated with the viral membrane envelope. Two of
the membrane envelope proteins are most important in pathogenesis. They are the
F (fusion) protein, which is responsible for fusion of virus and host cell
membranes, viral penetration, and hemolysis, and the
H (hemagglutinin) protein which is responsible for
adsorption of virus to cells.
There is only one antigenic type of measles virus. Although recent studies have
documented changes in the H glycoprotein, these changes do not appear to be
epidemiologically important (i.e, no change in
vaccine efficacy has been observed).
Measles virus is rapidly inactivated by heat, light, acidic pH, ether, and trypsin. It has a short survival time (<2 hours) in the
air, or on objects and surfaces.
|
Measles Virus Paramyxovirus
One antigenic type Recent variation in hemagglutinin glycoprotein identified Rapidly inactivated
by heat and light |
Clinical Features
The incubation period of measles, from
exposure to prodrome, averages 10 to 12 days. From
exposure to rash onset averages 14 days (range, 7 to 18 days).
The prodrome lasts 2 to 4 days (range 1
to 7 days). It is characterized by fever, which increases in stepwise fashion,
often peaking as high as 103° to 105°F. This is followed by the onset of cough,
coryza (runny nose), and/or conjunctivitis.
Koplik's spots, an exanthem present on mucous membranes, is considered
to be pathognomonic for measles. It occurs 1 to 2
days before the rash to
The measles rash is a maculopapular eruption
that usually lasts 5 to 6 days. It begins at the hairline, then
involves the face and upper neck. Over the next 3 days, the rash gradually
proceeds downward and outward, reaching the hands and feet.
The maculopapular lesions are generally discrete, but
may become confluent, particularly on the upper body. Initially, lesions blanch
with fingertip pressure. By 3 to 4 days, most do not blanch with pressure. Fine
desquamation occurs over more severely involved areas. The rash fades in the
same order that it appears, from head to extremities.
Other symptoms of measles include anorexia, diarrhea, especially in infants,
and generalized lymphadenopathy.
|
Measles Clinical
Features Prodrome Rash |
Complications
Approximately 30% of reported measles cases have
one or more complications. Complications of measles are more common among
children <5 and adults >20 years of age. From 1985 through 1992, diarrhea
was reported in 8% of reported cases, making this the most commonly
reported complication of measles. Otitis
media was reported in 7% of reported cases and occurs almost exclusively in
children. Pneumonia (6% of reported cases) may be viral or superimposed
bacterial, and is the most common cause of death.
Acute encephalitis is reported in approximately 0.1% of reported cases.
Onset generally occurs 6 days after rash onset (range 1 to 15 days), and is
characterized by fever, headache, vomiting, stiff neck, meningeal
irritation, drowsiness, convulsions, and coma. Cerebrospinal fluid shows pleocytosis and elevated protein. Case fatality rate can approximately 15%. Some form of residual neurologic damage occurs in as many as 25%. Seizures (with
or without fever) are reported in 0.6% to 0.7% of reported cases.
Death from measles has been reported in approximately 1 to 2 per 1,000
reported cases in the
|
Measles
Complications
|
Subacute sclerosing
panencephalitis (SSPE) is a rare degenerative
central nervous system disease believed to be due to persistent measles virus
infection of the brain. Average onset occurs 7 years after measles (range 1
month to 27 years), and occurs in five to ten cases per million reported
measles cases. The onset is insidious, with progressive deterioration of
behavior and intellect, followed by ataxia (awkwardness), myoclonic
seizures, and eventually death. SSPE has been extremely rare since the early
1980s.
Measles illness during pregnancy results in a higher risk of premature
labor, spontaneous abortion, and low-birth-weight infants. Birth defects (with
no definable pattern of malformation) have been reported rarely, without
confirmation that measles was the cause.
Atypical measles occurs only in persons who received inactivated
("killed") measles vaccine (KMV) and are subsequently exposed to
wild-type measles virus. Between 600,000 and 900,000 persons received KMV in
the
The rash is usually maculopapular or petechial, but may have urticarial,
purpuric, or vesicular components. It appears first
on the wrists or ankles. Atypical measles may be prevented by revaccinating
with live measles vaccine. Moderate to severe local reactions with or without
fever may follow vaccination; these reactions are less severe than with
infection with wild measles virus.
Modified measles occurs primarily in patients who receivedimmune
globulin (IG) as post-exposure prophylaxis and in young infants who have some
residual maternal antibody. It is usually characterized by a prolonged
incubation period, mild prodrome, and sparse,
discrete rash of short duration. Similar mild illness has been reported among
previously vaccinated persons.
Rarely reported in the United States, hemorrhagic measles is
characterized by high fever (105° to 106°F), seizures, delirium, respiratory
distress, and hemorrhage into the skin and mucous membranes.
Measles in an immunocompromised person may be
severe, with a prolonged course. It is reported almost exclusively in persons
with T-cell deficiencies (certain leukemias,
lymphomas, and Acquired Immunodeficiency Syndrome [AIDS]). It may occur without
the typical rash, and a patient may shed virus for several weeks after the
acute illness.
Measles in developing countries has resulted in high attack rates among
children <12 months of age. Measles is more severe in malnourished children,
particularly those with vitamin A deficiency. Complications include diarrhea,
dehydration, stomatitis, inability to feed, and
bacterial infections (skin and elsewhere). The case fatality rate may be as
high as 25%. Measles is also a leading cause of blindness in African children.
EPIDEMIOLOGY
Occurrence
Measles occurs throughout the world.
Reservoir
Measles is a human disease. There is no known animal reservoir, and an
asymptomatic carrier state has not been documented.
Transmission
Measles transmission is primarily person to person via large respiratory droplets.
Airborne transmission via aerosolized droplet nuclei has been documented in
closed areas (e.g., office examination room) for up to 2 hours after a person
with measles occupied the area.
Temporal pattern
In temperate areas, measles disease occurs primarily
in the late winter and spring.
Communicability
Measles is highly communicable, with >90% secondary attack rates among
susceptible persons. Measles may be transmitted from 4 days prior to 4 days
after rash onset. Maximum communicability occurs from onset of prodrome through the first 3 to 4 days of rash.
|
Measles Epidemiology
Reservoir: Human Transmission: Respiratory - person to person; airborne Temporal pattern: Peak late winter and spring Communicability: Maximum 4 days before to 4 days after rash
onset |
Mumps Virus
Mumps virus is a paramyxovirus
in the same group as parainfluenza and
The virus can be isolated or propagated in cultures of various human and monkey
tissues and in embryonated eggs. It has been
recovered from the saliva, cerebrospinal fluid, urine, blood, milk, and
infected tissues of patients with mumps. The virus causes generalized disease.
Mumps virus is rapidly inactivated by heat, formalin, ether, chloroform, and
ultraviolet light.
|
Mumps Virus Paramyxovirus
RNA virus One antigenic type Rapidly inactivated
by chenical agents, heat and ultraviolet light |
Clinical Features
The incubation period of mumps is 14-18 days
(range, 14-25 days).
The prodromal symptoms are nonspecific,
and include myalgia, anorexia, malaise, headache, and
low-grade fever.
Parotitis is the most common manifestation,
and occurs in 30%-40% of infected persons. Parotitis
may be unilateral or bilateral and any combination of single or multiple
salivary glands may be affected. Parotitis tends to
occur within the first 2 days and may first be noted as earache and tenderness
on palpation of the angle of the jaw.Symptoms tend to
decrease after 1 week and are usually gone by 10 days
Up to 20% of mumps infections are asymptomatic. An additional 40%-50% may have
only nonspecific or primarily respiratory symptoms.
|
Mumps Clinical
Features Incubation
period 14-18 days Nonspecific prodrome of low-grade fever, headache, malaise, myalgiast Parotitis in 30%-40% Up to 20% of
infections asymptomatic May present as
lower respiratory illness, particularly in preschool-aged children |
Complications
Central nervous system (CNS) involvement in the form of aseptic
meningitis is common, occurring asymptomatically (inflammatory cells in
cerebrospinal fluid) in 50% to 60% of patients. Symptomatic meningitis
(headache, stiff neck) occurs in up to 15% of patients and resolves without sequelae in 3-10 days. Adults are at higher risk for this
complication than children, and boys are more commonly affected than girls (3:1
ratio). Parotitis may be absent in up to 50% of such
patients. Encephalitis is rare (less than 2 per 100,000).
Orchitis (testicular inflammation) is
the most common complication in postpubertal males.
It occurs in up to 20%-50% of postpubertal males,
usually after parotitis, but may precede it, begin
simultaneously, or occur alone. It is bilateral in up to 30% of affected males.
There is usually abrupt onset of testicular swelling, tenderness, nausea,
vomiting, and fever. Pain and swelling may subside in 1 week, but tenderness
may last for weeks. Approximately 50% of patients with orchitis
have some degree of testicular atrophy, but sterility is rare.
Oophoritis (ovarian inflammation)
occurs in 5% of postpubertal females. It may mimic
appendicitis. There is no relationship to impaired fertility.
Pancreatitis is infrequent, but
occasionally occurs without parotitis; the hyperglycemia
is transient and is reversible. While some single instances of diabetes
mellitus have been reported, a causal relationship has yet to be
conclusively demonstrated; many cases of temporal association have been
described both in siblings and individuals, and outbreaks of diabetes have been
reported a few months or years after outbreaks of mumps.
Deafness caused by mumps is one of the leading causes of acquired sensorineural deafness in childhood. The estimated
incidence is approximately 1 per 20,000 reported cases of mumps. Hearing loss
is unilateral in approximately 80% of cases and may be associated with
vestibular reactions. Onset is usually sudden and results in permanent hearing
impairment.
Electrocardiogram (EKG) changes compatible with myocarditis
are seen in 3%-15% of patients with mumps, but symptomatic involvement is rare.
Complete recovery is the rule, but deaths have been reported.
Other less common complications of mumps include arthralgia,
arthritis, and nephritis. Death from mumps has been reported in 1-3 cases per
10,000 in recent years.
|
Mumps Complications CNS
involvement:
15% of clinical cases Orchitis: 20%-50%
in postpubertal males Pancreatitis:
2%-5% Deafness:
1/20,000 Death:
1-3/10,000 |
EPIDEMIOLOGY
Occurrence
Mumps has been reported worldwide.
Reservoir
Mumps is a human disease. While persons with asymptomatic or nonclassical infection can transmit the virus, no carrier
state is known to exist.
Transmission
Transmission of mumps occurs through airborne transmission or direct contact
with infected droplet nuclei or saliva.
Temporal pattern
Mumps incidence peaks predominantly in winter-spring, but the disease is
endemic year-round.
Communicability
Contagiousness is similar to that of influenza and rubella, but less than that
for measles or chickenpox. The infectious period is considered to be from 3
days before to the 4th day of active disease; virus has been isolated from
saliva 7 days before to 9 days after onset of parotitis.
|
Mumps Epidemiology Reservoir: Human Transmission: Respiratory drop nuclei, saliva; subclinical infections may transmit Temporal pattern: Peak in late winter and spring Communicability: 3 days before to 4 days after onset of active
disease |
Case Definition
The
clinical case definition of mumps is an acute onset of unilateral or bilateral
tender swelling of the parotid or salivary gland lasting >2 days without
other apparent cause.
Bordetella pertussis
B. pertussis is small aerobic
gram-negative rod. It is fastidious, and requires special media for isolation. B.
pertussis produces multiple antigenic and
biologically active products, including pertussis
toxin, filamentous hemagglutinin, agglutinogens,
adenylate cyclase, pertactin, and tracheal cytotoxin.
These products are responsible for the clinical features of pertussis
disease, and an immune response to one or more produces immunity to subsequent
clinical illness. Recent evidence suggests that immunity from B. pertussis infection may not be permanent.
|
Bordetella pertussis Fastidious
gram-negative bacillus Multiple antigenic
and biologically active components: |
Clinical Features
The incubation period of pertussis is commonly 5 to 10 days, with an upper limit of
21 days. The clinical course of the illness is divided into three stages.
The first stage, the catarrhal stage, is characterized by the insidious
onset of coryza (runny nose), sneezing, low-grade
fever, and a mild, occasional cough, similar to the common cold. The cough
gradually becomes more severe, and after 1 to 2 weeks, the second, or
paroxysmal stage, begins
It is during the paroxysmal stage that the
diagnosis of pertussis is usually suspected.
Characteristically, the patient has bursts, or paroxysms of numerous, rapid
coughs, apparently due to difficulty expelling thick mucus from the tracheobronchial tree. At the end of the paroxysm, a long inspiratory effort is usually accompanied by a
characteristic high-pitched whoop. During such an attack, the patient may
become cyanotic (turn blue). Children and young infants, especially, appear
very ill and distressed. Vomiting and exhaustion commonly follow the episode.
The patient usually appears normal between attacks.
Paroxysmal attacks occur more frequently at night, with an average of 15
attacks per 24 hours. During the first 1 or 2 weeks of this stage the attacks
increase in frequency, remain at the same level for 2 to 3 weeks, and then
gradually decrease. The paroxysmal stage usually lasts 1 to 6 weeks, but may
persist for up to 10 weeks. Infants under 6 months of age may not have the
strength to have a whoop, but they do have paroxysms of coughing.
In the last stage, the convalescent stage, recovery is gradual. The
cough becomes less paroxysmal and disappears over 2 to 3 weeks. However,
paroxysms often recur with subsequent respiratory infections for many months
after the onset of pertussis. Fever is generally
minimal throughout the course of pertussis.
|
Pertussis Clinical Features Incubation
period 5-10 days (up to 21 days) Insidious
onset, similar to minor upper respiratory infection with nonspecific cough Fever usually
minimal throughout course
|
Older persons (i.e., adolescents and adults), and those partially
protected by the vaccine may become infected with B. pertussis,
but usually have milder disease. Pertussis in these
persons may present as a persistent (>7 days) cough, and may be
indistinguishable from other upper respiratory infections. Inspiratory
whoop is uncommon. In some studies, B. pertussis has
been isolated from 25% or more of adults with cough illness lasting >7 days.
Even though the disease may be milder in older persons, these infected persons
may transmit the disease to other susceptible persons, including unimmunized or underimmunized
infants. Adults are often found to be the first case in a household with
multiple pertussis cases.
|
Pertussis in Adults May account for
~25% of cough illness lasting greater than or equal to 7 days Disease often
milder than in infants and children Adult often
source of infection for children |
Complications
Young infants are at highest risk for acquiring clinical pertussis,
and for pertussis-associated complications. The most
common complication, and the cause of most pertussis-related
deaths, is secondary bacterial pneumonia. Data from 1990-1996 indicate that
pneumonia occurred among 9.5% of all reported pertussis
cases, and among 17% of infants <6 months of age.
Neurologic complications such as seizures and
encephalopathy (a diffuse disorder of the brain) may occur as a result of
hypoxia (reduction of oxygen supply) from coughing, or possibly from toxin. Neurologic complications of pertussis
are more common among infants. In 1990 to 1996, seizures and encephalopathy
were reported among 1.4% and 0.2%, respectively, of all cases, and among 2.1%
and 0.4%, respectively, of infants <6 months of age.
Other less serious complications of pertussis include
otitis media, anorexia, and dehydration.
Complications resulting from pressure effects of severe paroxysms include pneumothorax, epistaxis, subdural hematomas, hernias, and
rectal prolapse.
In 1990 to 1996, 32% of all reported pertussis cases
required hospitalization, including 72% of all infants <6 months of age. In
this 7-year period, 57 deaths were due to pertussis
(case-fatality rate 0.2%). Forty-eight (84%) of these deaths
occurred in children <6 months of age.
|
Pertussis Complications*
*Reported cases
1990-1996 (n=35,508) |
Medical Management
The medical management of pertussis cases is
primarily supportive, although antibiotics are of some value. Erythromycin is
the drug of choice. This therapy eradicates the organism from secretions,
thereby decreasing communicability and, if initiated early, may modify the
course of the illness.
Erythromycin or trimethoprim-sulfamethoxazole
prophylaxis should be administered for 14 days to all household and other close
contacts of persons with pertussis, regardless of
age and vaccination status. Although data from controlled clinical trials
are lacking, prophylaxis of all household members and other close contacts may
prevent or minimize transmission. All close contacts <7 years of age who
have not completed the four-dose primary series should complete the series with
the minimal intervals. Close contacts <7 years of age who have completed a
primary series but have not received a dose of DTP or DTaP
within 3 years of exposure, should be given a booster dose
EPIDEMIOLOGY
Occurrence
Pertussis occurs worldwide.
Reservoir
Pertussis is a human disease. No animal or insect
source or vector is known to exist. Adolescents and adults are an important
reservoir for B. pertussis and are often the
source of infection for infants.
Transmission
Transmission most commonly occurs by the respiratory route through contact with
respiratory droplets, or by contact with airborne droplets of respiratory
secretions. Transmission occurs less frequently by contact with freshly
contaminated articles of an infected person.
A silent carrier state is thought to exist, but is infrequent, transient in
duration, and probably of little importance in maintaining pertussis
organisms in the community.
Temporal pattern
Pertussis has no distinct seasonal pattern, but may
increase in the summer and fall.
Communicability
Pertussis is highly communicable, as evidenced by
secondary attack rates
of 70%-100% among unimmunized household contacts.
The contagious period is from 7 days following exposure to 3 weeks after onset
of paroxysms, with maximum contagiousness during the catarrhal stage, usually
before the diagnosis of pertusis is suspected.
|
Pertussis Epidemiology Reservoir: Human; adolescents and adults Transmission: Respiratory droplets; airborne rare Communicability: Maximum in catarrhal stage; secondary attack
rate up to 90% |
Streptococcus pneumoniae
Streptococcus pneumoniae
are
lancet-shaped, gram-positive, facultative anaerobic organisms. They are
typically observed in pairs (diplococci) but may also
occur singularly or in short chains. Some pneumococci
are encapsulated, their surfaces composed of complex polysaccharides.
Encapsulated organisms are pathogenic for humans and experimental animals,
whereas organisms without capsular polysaccharides are not. Capsular
polysaccharides are the primary basis for the pathogenicity
of the organism. They are antigenic and form the basis for classifying pneumococci by serotypes. Ninety serotypes have been
identified, based on their reaction with type-specific antisera.
Type-specific antibody to capsular polysaccharide is protective. These
antibodies and complement interact to opsonize pneumococci, which facilitates phagocytosis
and clearance of the organism. Antibodies to some pneumococcal
capsular polysaccharides may cross-react with related types as well as with
other bacteria, providing protection to additional serotypes.
Most S. pneumoniae serotypes have been shown
to cause serious disease, but only a few serotypes produce the majority of pneumococcal infections. The 10 most common serotypes are
estimated to account for about 62% of invasive disease worldwide. The ranking
and serotype prevalence differs by age group and country. In the
Pneumococci are common inhabitants of the respiratory
tract, and may be isolated from the nasopharynx of 5%
to 70% of normal adults. Rates of asymptomatic carriage vary with age,
environment, and the presence of upper respiratory infections. Only 5% to 10%
of adults without children are carriers. In schools and orphanages, 27% to 58%
of students and residents may be carriers. On military installations, as many
as 50% to 60% of service personnel may be carriers. The duration of carriage
varies and is generally longer in children than adults. In addition, the
relationship of carriage to the development of natural immunity is poorly
understood.
|
Streptococcus pneumoniae Gram-positive
bacteria 90 known serotypes Polysaccharide
capsule important virulence factor Type-specific
antibody is protective |
Pneumococcal Disease
S. pneumoniae first isolated by Pasteur in
1881
Confused with other causes of pneumonia until discovery of Gram stain in 1884
More than 80 serotypes described by 1940
>40,000 deaths per year in
|
Clinical Features The major clinical syndromes of invasive pneumococcal disease include pneumonia, bacteremia, and meningitis. The immunologic
mechanism that allows disease to occur in a carrier is not clearly
understood. However, disease most often occurs when a predisposing condition
exists, particularly pulmonary disease.
Medical Management Penicillin
is the drug of choice for treatment of pneumococcal
disease. However, patients who are allergic to penicillin may be given cephalosporins (depending on the severity of the
penicillin allergy) or erythromycin for pneumonia, and chloramphenicol
for meningitis. The route, dosage, schedule, and duration of therapy depend
on the severity of the illness. Resistance to penicillin and other
antibiotics is rising and studies indicate that 5% to 15% of pneumococci are resistant. |
Occurrence
Pneumococcal disease occurs throughout the world.
Reservoir
Streptococcus pneumoniae is a human pathogen.
The reservoir for pneumococci is presumably the nasopharynx of asymptomatic human carriers. There is no
animal or insect vector.
Transmission
Transmission of Streptococcus pneumoniae occurs
as the result of direct person-to-person contact via droplets, and by
"autoinoculation" in persons carrying the bacteria in their upper
respiratory tract. The pneumococcal serotypes most
often responsible for causing infection are those most frequently found in
carriers. The spread of the organism within a family or household is influenced
by such factors as crowding, season, and the presence of upper respiratory
infections or pneumococcal disease such as pneumonia
or otitis media. The spread of pneumococcal
disease is usually associated with increased carriage rates. However, high
carriage rates do not appear to increase the risk of disease transmission in
households.
Temporal pattern
Pneumococcal infections are more common during the
winter and in early spring when respiratory diseases are more prevalent.
Communicability
The period of communicability for pneumococcal
disease is unknown, but presumably transmission can occur as long as the
organism appears in respiratory secretions.
|
Pneumococcal Disease
Epidemiology Reservoir: Human carriers Transmission: Respiratory "Autoinoculation" Communicability: Unknown; probably as long as organism in
respiratory secretions |
Poliovirus
Poliovirus is a member of the enterovirus subgroup, family Picornaviridae.
Enteroviruses are transient inhabitants of the
gastrointestinal tract, and are stable at acid pH. Picornaviruses
are small, ether-insensitive viruses with an RNA genome.
There are three poliovirus serotypes (P1, P2, and P3). There is minimal
heterotypic immunity between the three serotypes.
The poliovirus is rapidly inactivated by heat, formaldehyde, chlorine, and
ultraviolet light.
|
Poliovirus Enterovirus (RNA) Three serotypes: 1,2,3 Minimal heterotypic immunity between serotypes Rapidly inactivated by heat, formaldehyde, chlorine, ultraviolet
light |
Clinical Features
The
incubation period for poliomyelitis is commonly 6 to 20 days with a
range from
The response to poliovirus infection is highly variable and has been
categorized based on the severity of clinical presentation.
Up to 95% of all polio infections are inapparent
or subclinical without symptoms. Estimates of the
ratio of inapparent to paralytic illness vary from
50:1 to 1,000:1 (usually 200:1). Infected persons without symptoms shed virus
in the stool, and are able to transmit the virus to others.
Approximately 4% to 8% of polio infections consist of a minor, nonspecific
illness without clinical or laboratory evidence of central nervous system
invasion. This syndrome is known as abortive poliomyelitis, and is
characterized by complete recovery in less than a week. Three syndromes
observed with this form of poliovirus infection are upper respiratory tract
infection (sore throat and fever), gastrointestinal disturbances (nausea,
vomiting, abdominal pain, constipation or, rarely, diarrhea), and
influenza-like illness. These syndromes are indistinguishable from other viral
illnesses.
Nonparalytic aseptic meningitis (symptoms
of stiffness of the neck, back, and/or legs), usually following several days
after a prodrome similar to that of minor illness,
occurs in 1% to 2% of polio infections. Increased or abnormal sensations can
also occur. Typically these symptoms will last from
Less than 2% of all polio infections result in flaccid paralysis.
Paralytic symptoms generally begin 1 to 10 days after prodromal
symptoms and progress for 2 to 3 days.
Generally, no further paralysis occurs after the temperature returns to normal.
The prodrome may be biphasic, especially in children,
with initial minor symptoms separated by a 1- to 7-day period from more major
symptoms. Additional prodromal signs and symptoms can
include a loss of superficial reflexes, initially increased deep tendon
reflexes and severe muscle aches and spasms in the limbs or back. The illness
progresses to flaccid paralysis with diminished deep tendon reflexes, reaches a
plateau without change for days to weeks, and is usually asymmetrical. Strength
then begins to return. Patients do not experience sensory losses or changes in
cognition.
Many persons with paralytic poliomyelitis recover completely and, in most,
muscle function returns to some degree. Patients with weakness or paralysis 12
months after onset will usually be left with permanent residua.
Paralytic polio is classified into three types, depending on the level of
involvement. Spinal polio is most common, and accounted for 79% of
paralytic cases from 1969-1979. It is characterized by asymmetric paralysis
that most often involves the legs. Bulbar polio accounted for 2% of
cases and led to weakness of muscles innervated by cranial nerves. Bulbospinal polio accounted for 19% of cases
and was a combination of bulbar and spinal paralysis.
The death-to-case ratio for paralytic polio is generally 2% to 5% in children
and up to 15% to 30% in adults (depending on age). It increases to 25% to 75%
with bulbar involvement.
EPIDEMIOLOGY
Occurrence
At one time poliovirus infection occurred throughout the world. Transmission of wild poliovirus ceased in the
Reservoir
Humans are the only known reservoir of poliovirus, which is transmitted most
frequently by persons with inapparent infections.
There is no asymptomatic carrier state except in immune deficient persons.
Transmission
Person-to-person spread of poliovirus via the fecal-oral route is the most
important route of transmission, although the oral-oral route may account for
some cases.
Temporal Pattern
Poliovirus infection typically peaks in the summer months in temperate
climates. There is no seasonal pattern in tropical climates.
Communicability
Poliovirus is highly infectious, with seroconversion
rates in susceptible household contacts of children nearly 100% and over 90% in
susceptible household contacts of adults. Cases are most infectious from
|
Poliovirus
Epidemiology Reservoir: Human Transmission: Fecal-oral; oral-oral possible Communicability: 7-10 days before onset; virus present in stool
3-6 weeks |
Rubella Virus
Rubella virus was first isolated in 1962 by
Parkman and Weller. Rubella virus is classified as a togavirus,
genus Rubivirus. It is most closely related to
group A arboviruses, such as
Eastern and Western Equine Encephalitis viruses. It is an enveloped RNA virus,
with a single antigenic type that does not cross-react with other members of
the togavirus group.
Rubella virus is relatively unstable and is inactivated by lipid solvents, trypsin, formalin, ultraviolet
light, extremes of pH and heat, and amantadine.
|
Rubella Virus Togavirus RNA virus One antigenic type Rapidly inactivated by chemical agents, low pH, heat and
ultraviolet light |
Clinical Features
Acquired rubella
The incubation period varies from
Symptoms are often mild, and 30%-50% of cases may be subclinical
or inapparent. In children, rash is usually
the first manifestation and a prodrome is rare. In
older children and adults, there is often a 1 to 5 day prodrome
with low-grade fever, malaise, swollen glands, and upper respiratory infection
(URI) preceding the rash. The rash of rubella usually occurs initially on the
face and then progresses from head to foot. It lasts about 3 days and is
occasionally pruritic. The rash is fainter than
measles rash and does not coalesce.
Lymphadenopathy may begin 1 week before the rash and
last several weeks. Postauricular, posterior cervical, and suboccipital nodes
are commonly involved.
Arthralgia and arthritis occur so frequently in
adults that they are considered by many to be an integral part of the illness
as opposed to a complication. Other symptoms of rubella include conjunctivitis,
testalgia, or orchitis. Forschheimer spots may be noted on the soft palate, but are
not diagnostic for rubella.
|
Rubella Clinical
Features Incubation
period 12-23 days Lymphadenopathy in second week Maculopapular rash 14-17 days after exposure Rash on face
and neck - may be more prominent after hot shower |
Complications
Complications are uncommon, but tend to occur
more often in adults than in children.
Arthritis or arthralgia may occur in up to 70%
of adult women who contract rubella, but are rare in children or adult males.
Fingers, wrists, and knees tend to be affected. Joint symptoms tend to occur
about the same time or shortly after appearance of the rash and may last for up
to 1 month; chronic arthritis is rare.
Encephalitis occurs in one in 5,000 cases, more frequently in adults
(especially in females) than in children. Mortality estimates vary from 0 to
50%.
Hemorrhagic manifestations occur with an approximate incidence of 1 per
3,000 cases, occurring more often in children than in adults. These
manifestations may be secondary to low platelets and vascular damage, with
thrombocytopenic purpura being the most common
manifestation. Gastrointestinal, cerebral, or intrarenal
hemorrhage may occur. Effects may last from days to months, and most patients
recover.
Additional complications include orchitis, neuritis,
and a rare late syndrome of progressive panencephalitis.
|
Rubella
Complications
|
|||||||||||||||||||||||||||
Congenital Rubella Syndrome (CRS)
Prevention of CRS is the main objective of rubella vaccination programs in the
The 1964 rubella epidemic resulted in 12.5 million cases of rubella infection
and about 20,000 newborns with CRS. The estimated cost of the epidemic was $840
million. This does not include the emotional toll on the families involved. The
estimated lifetime cost of one case of CRS today is estimated to be in excess
of $200,000.
Rubella can be a disastrous disease in early gestation, leading to fetal death,
premature delivery, and an array of congenital defects. Spontaneous abortion
and stillbirths are common. The severity of the effects of rubella virus on the
fetus depends largely on the time of gestation at which infection occurs. Up to
85% of infants infected in the first trimester of pregnancy will be found to be
affected if followed after birth. While fetal infection may occur throughout
pregnancy, defects are rare when infection occurs after the 20th week of
gestation. The overall risk of defects during the third trimester is probably
no greater than that associated with uncomplicated pregnancies.
Congenital infection with rubella virus can affect virtually all organ systems.
Deafness is the most common and often the sole manifestation of
congenital rubella infection, especially after the 4th month of gestation. Eye
defects, including cataracts, glaucoma, retinopathy, and microphthalmia may occur. Cardiac defects such as
patent ductus arteriosus,
ventricular septal defect, pulmonic
stenosis, and coarctation
of the aorta are possible. Neurologic abnormalities,
including microcephaly and mental retardation, and
other abnormalities, including bone lesions, splenomegaly,
hepatitis, and thrombocytopenia with purpura may
occur. Manifestations of CRS may be delayed from
CRS infants may have low hemagglutination inhibition
(HI) titers, but may have high titers of neutralizing antibody that may persist
for years. Reinfection may occur. Impaired
cell-mediated immunity has been demonstrated in some children with CRS.
EPIDEMIOLOGY
Occurrence
Rubella occurs worldwide.
Transmission
Rubella is spread from person-to-person via airborne transmission or droplets
shed from the respiratory secretions of infected persons. There is no evidence
of insect transmission.
Rubella may be transmitted by subclinical cases
(approximately 30% to 50% of all rubella infections).
Reservoir
Rubella is a human disease. There is no known animal reservoir. Although
infants with CRS may shed rubella virus for an extended period, a true carrier
state has not been described.
Temporal Pattern
In temperate areas, incidence is usually highest in late winter and early
spring.
Communicability
Rubella is only moderately contagious. The disease is most contagious when the
rash is erupting, but virus may be shed from 7 days before to
Infants with CRS shed large quantities of virus from body secretions for up to
one year and can therefore transmit rubella to persons caring for them who are
susceptible to the disease.
|
Rubella Epidemiology
Reservoir: Human Transmission: Respiratory - person-to-person; subclinical cases may transmit Temporal pattern: Peak in late winter and spring Communicability: 7 days before to 5-7 days after rash onset;
infants with CRS may shed virus for a year or more |
Clostridium tetani
C. tetani is a slender,
gram-positive, anaerobic rod that may develop a terminal spore, giving it a
drumstick appearance. The organism is sensitive to heat and cannot survive in
the presence of oxygen. The spores, in contrast, are very
resistant to heat and the usual antiseptics. They can survive
autoclaving at 121Ί C for 10 to 15 minutes. The spores are also relatively
resistant to phenol and other chemical agents.
The bacilli are widely distributed in soil and in the intestine and feces of
horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens.
Manure-treated soil may contain large numbers of spores. In agricultural areas,
a significant number of human adults may harbor the organism. The spores can
also be found on skin surfaces and in contaminated heroin.
|
Clostridium tetani Anaerobic
gram-positive, spore-forming bacteria Spores found in soil,
dust, animal feces; may persist for months to years Multiple toxins
produced with growth of bacteria Tetanospasmin
estimated human lethal dose = 150 ng |
Clinical Features
The incubation period varies from
On the basis of clinical findings, three different forms of tetanus have been
described.
Local tetanus is an uncommon form of the disease, in which patients have
persistent contraction of muscles in the same anatomic area as the injury
preceding the tetanus. These contractions may persist for many weeks before
gradually subsiding. Local tetanus may precede the onset of generalized
tetanus, but is generally milder. Only about 1% of cases are fatal.
Cephalic tetanus is a rare form of the disease,
occasionally occurring with otitis media (ear
infections) in which C. tetani is present in
the flora of the middle ear, or following injuries to the head. There is
involvement of the cranial nerves, especially in the facial area.
The most common type (about 80%) of reported tetanus is generalized tetanus.
The disease usually presents with a descending pattern. The first sign is trismus or lockjaw, followed by stiffness of the neck,
difficulty in swallowing, and rigidity of abdominal muscles. Other symptoms
include a temperature rise of 2° to 4°C above normal, sweating, elevated blood
pressure, and episodic rapid heart rate. Spasms may occur frequently and last
for several minutes. Spasms continue for 3 to 4 weeks. Complete recovery may
take months.
|
Tetanus Clinical
Features Incubation period 8
days (range, 3 to 21 days) Three clinical forms:
Local (uncommon), cephalic (rare), generalized (most common) Generalized tetanus:
descending symptoms of trismus (lockjaw),
difficulty swallowing, muscle rigidity, spasms Spasms continue for 3
to 4 weeks; complete recovery may take months |
Neonatal tetanus is a form of generalized tetanus that occurs in newborn
infants. Neonatal tetanus occurs in infants born without protective passive
immunity, because the mother is not immune. It usually occurs through infection
of the unhealed umbilical stump, particularly when the stump is cut with an unsterile instrument. Neonatal tetanus is common in some
developing countries (estimated >270,000 deaths worldwide per year), but
very rare in the
|
Neonatal Tetanus Generalized tetanus
in newborn infant Infant born without
protective passive immunity High fatality rate
without therapy Estimated 270,000
deaths worldwide in 1998 |
Complications
Laryngospasm (spasm of the vocal
cords) and/or spasm of the muscles of respiration leads
to interference with breathing. Fractures of the spine or long bones may
result from sustained contractions and convulsions. Hyperactivity of the
autonomic nervous system may lead to hypertension and/or an abnormal heart
rhythm.
Nosocomial infections are common
because of prolonged hospitalization. Secondary infections,
which may include sepsis from indwelling catheters, hospital-acquired
pneumonias, and decubitus ulcers. Pulmonary
embolism is particularly a problem in drug users and elderly patients. Aspiration
pneumonia is a common late complication of tetanus, found in 50% to 70% of
autopsied cases.
Death. Approximately 30% of reported
cases are fatal. In the
Due to the extreme potency of the toxin, tetanus disease does not confer
immunity. Patients who survive the disease should be given a complete series of
vaccine.
|
Tetanus
Complications Laryngospasm
Spasms of vocal cords and respiratory muscles
Fractures
Spine and long bones due to muscle spasms and seizures Other Hypertension,
coma, nosocomial infections,
Death 30%,
higher at extremes of age |
Medical Management
All
wounds should be cleaned; necrotic tissue and foreign material should be
removed. If tetanic spasms are occurring, supportive
therapy, primarily maintenance of an adequate airway, is critical.
Tetanus immune globulin (TIG) is recommended for persons with tetanus. TIG can
only help remove unbound tetanus toxin. It cannot affect toxin bound to nerve
endings. A single intramuscular dose of 3000 to 5000 units is generally
recommended for children and adults, with part of the dose infiltrated around
the wound if it can be identified. Intravenous immune globulin (IVIG) contains
tetanus antitoxin and may be used if TIG is not available.
Tetanus disease does not result in tetanus immunity. Active immunization with
tetanus toxoid should begin or continue as soon as theperson's condition has stabilized.
EPIDEMIOLOGY
Occurrence
Occurrence is worldwide, but is most frequently encountered in densely
populated regions in hot, damp climates with soil rich in organic matter.
Reservoir
Organisms are found primarily in the soil and intestinal tracts of animals and
humans.
Mode of transmission
Transmission is primarily by contaminated wounds (apparent and inapparent). The wound may be major or minor. In recent
years, however, a higher proportion of cases had minor wounds, probably because
severe wounds are more likely to be properly managed. Tetanus may follow
elective surgery, burns, deep puncture wounds, crush wounds, otitis media (ear infections), dental infection, animal
bites, abortion, and pregnancy.
Communicability
Tetanus is not contagious from person to person. It is the only
vaccine-preventable disease that is infectious, but not contagious.
|
Tetanus Epidemiology
Reservoir: Soil and intestine of animals and humans Transmission: Contaminated wounds; tissue injury Temporal pattern: Peak in summer or wet season Communicability: Not contagious |
Varicella Zoster Virus (VZV)
VZV is a DNA virus, and is a member of the
herpes virus group. Like other herpes viruses, VZV has the capacity to persist
in the body after the primary (first) infection as a latent infection. VZV
persists in sensory nerve ganglia. Primary infection with VZV results in
chickenpox. Herpes zoster (shingles) is the result of recurrent infection. The
virus has a short survival time outside the infected host.
|
Varicella Zoster Virus Herpes virus (DNA) Primary infection
results in varicella (chickenpox) Recurrent infection
results in herpes zoster (shingles) Short survival in
environment |
Clinical Features
The incubation period is from 14 to 16 days from exposure, with a range
of 10 to 21 days. This may be prolonged in immunocompromised
patients and those who have received varicella zoster
immune globulin (VZIG). The incubation period may be up to 28 days after VZIG.
Primary infection (chickenpox)
A mild prodrome may precede the onset
of a rash. Adults may have 1 to 2 days of fever and malaise prior to rash
onset, but in children the rash is often the first sign of disease.
The rash is generalized, pruritic, and rapidly
progresses from macules to papules to vesicular
lesions before crusting. The rash usually appears first on the scalp, moves to
the trunk, and then the extremities, with the highest concentration of lesions
on the trunk. Lesions also can occur on mucous membranes of the oropharynx, respiratory tract, vagina, conjunctiva, and the
cornea. Lesions are usually 1 to 4 mm in diameter. The vesicles contain clear
fluid on an erythematous base that may rupture or
become purulent before they dry and crust. Successive crops appear over several
days, with lesions present in several stages of evolution. For example, macular
lesions may be observed in the same area of skin as mature vesicles. Healthy
children usually have 200-500 lesions in 2 to 4 successive crops.
The clinical course in normal children is generally mild, with malaise, pruritus (itching), and fever up to 102°F for 2 to 3 days.
Adults may have more severe disease and have a higher incidence of
complications. Respiratory and gastrointestinal symptoms are absent. Children
with lymphoma and leukemia may develop a severe progressive form of varicella characterized by high fever, extensive vesicular
eruption, and high complication rates. Children infected with human
immunodeficiency virus may also have severe, prolonged illness.
Recovery from primary varicella infection results in
lifetime immunity. In otherwise healthy persons, clinical illness after reexposure is rare, but may occur, particularly in immunocompromised persons. As with other viral diseases, reexposure to natural (wild) varicella
may lead to reinfection that boosts antibody titers
without causing clinical illness or detectable viremia.
|
Varicella Clinical Features Mild prodrome (fever, malaise) for 1-2 days Successive crops (2-4
days) of pruritic vesicles Generally appear
first on head; most concentrated on trunk Generally mild in
healthy children |
Recurrent disease (herpes zoster)
Herpes zoster, or shingles, occurs when latent VZV reactivates and causes
recurrent disease. The immunologic mechanism that controls latency of VZV is
not well understood. However, factors associated with recurrent disease include
aging, immunosuppression, intrauterine exposure to
VZV, and varicella at a young age (<18 months). In
immunocompromised persons, zoster may disseminate,
causing generalized skin lesions, and central nervous system, pulmonary, and
hepatic involvement.
The vesicular eruption of zoster generally occurs unilaterally in the
distribution of a dermatome supplied by a dorsal root or extramedullary
cranial nerve sensory ganglion. Most often, this involves the trunk or the area
of the fifth cranial nerve. Two to four days prior to the eruption there may be
pain and paresthesia in the segment involved. There
are few systemic symptoms. Post-herpetic neuralgia, or pain in the area of the
recurrence which persists after the lesions have resolved, is a distressing
complication of zoster, with no adequate therapy currently available.
Post-herpetic neuralgia may last as long as a year after the episode of zoster.
Ocular nerve and other organ involvement with zoster can occur, often with
severe sequelae.
|
Herpes Zoster Reactivation of varicella zoster virus Associated with: |
Complications
Acute varicella is
generally mild and self-limited, but may be associated with complications. The
most common complications of varicella include secondary
bacterial infections of skin lesions, dehydration, pneumonia, and central
nervous system involvement. Secondary bacterial infections of skin lesions with
staphylococcus or streptococcus are the most common cause of hospitalization
and outpatient medical visits. Secondary infection with invasive group A streptococci may cause serious illness and lead to
hospitalization or death. Pneumonia following varicella
is usually viral, but may be bacterial. Secondary bacterial pneumonia is more
common in children <1 year of age. Up to 30% of pneumonia cases among
healthy adults are fatal.
Central nervous system manifestations of varicella
range from aseptic meningitis to encephalitis. Involvement of the cerebellum,
with resulting cerebellar ataxia, is the most common
and generally has a good outcome. Encephalitis is an infrequent complication of
varicella (estimated 1.8 per 10,000 cases), and may
lead to seizures and coma. Diffuse cerebral involvement is more common in
adults than in children.
Reye syndrome is an unusual complication of varicella
and influenza and occurs almost exclusively in children who take aspirin during
the acute illness. The etiology of Reye syndrome is unknown. There has been a dramatic
decrease in the incidence of Reye syndrome during the past decade, presumably
related to decreased use of aspirin by children.
Rare complications of varicella include aseptic
meningitis, transverse myelitis, Guillain-Barre
syndrome, thrombocytopenia, hemorrhagic varicella, purpura fulminans, glomerulonephritis, myocarditis,
arthritis, orchitis, uveitis,
iritis, and clinical hepatitis.
|
Varicella Complications Bacterial infection
of lesions CNS manifestations Pneumonia (rare in
children) Hospitalization ~3
per 1000 cases Death ~1 per 60,000
cases |
In the pre-vaccine era, approximately 10,000 persons with varicella
required hospitalization each year. Hospitalization rates were approximately
2-3 per 1,000 cases among healthy children and 8 per 1,000 cases among adults.
Death occurred in approximately 1 in 60,000 cases. From 1990 through 1996, an
average of 103 deaths from varicella was reported
each year. Most deaths occur in immunologically
normal children and adults.
The risk of complications from varicella varies with
age. Complications are infrequent among healthy children. They are much higher
in persons >15 years of age and infants <1 year of age. For instance,
among children 1-14 years of age, the fatality rate of varicella
is approximately 1 per 100,000 cases. Among persons 15-19 years, the fatality
rate is 2.7 per 100,000 cases, and among adults 30-49
years of age, 25.2 per 100,000 cases. Adults account for only 5% of reported
cases of varicella, but account for approximately 35%
of mortality.
Immunocompromised persons have a high risk of serious
varicella infection and a high risk of disseminated
disease (up to 36% in one report). These persons may have multiple organ system
involvement, and the disease may become fulminant and
hemorrhagic. The most frequent complications in immunocompromised
persons are pneumonia and encephalitis. Children with HIV infection are at
increased risk for morbidity from varicella and
herpes zoster.
Perinatal infection
The onset of maternal varicella from 5 days before to
2 days after delivery may result in overwhelming infection of the neonate and a
fatality rate as high as 30%. This severe disease is believed to result from
fetal exposure to varicella virus without the benefit
of passive maternal antibody. Infants born to mothers with
onset of maternal varicella 5 days or more prior to
delivery usually have a benign course, presumably due to passive transfer of
maternal antibody across the placenta.
Congenital VZV infection
Primary varicella infection in the first 20 weeks of
gestation is occasionally associated with a variety of abnormalities in the
newborn, including low birth weight, hypoplasia of an
extremity, skin scarring, localized muscular atrophy, encephalitis, cortical
atrophy, chorioretinitis, and microcephaly.
This constellation of abnormalities, collectively known as congenital varicella syndrome, was first recognized in 1947. The risk
of congenital abnormalities from primary maternal varicella
infection during the first trimester is felt to be very low (<2%). Rare
reports of congenital birth defects following maternal zoster exist, but virologic confirmation of maternal lesions is lacking.
Intrauterine infection with VZV, particularly after 20 weeks gestation, is
associated with zoster in those infants at an earlier age; the exact risk is
unknown.
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Varicella Normal adults Immunocompromised
persons Newborns with
maternal rash onset within 5 days before to 48 hours after delivery |
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EPIDEMIOLOGY
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Corynebacterium diphtheriae
C. diphtheriae is an aerobic
gram-positive bacillus. Toxin-production (toxigenicity)
occurs only when the bacillus is itself infected (lysogenized)
by a specific virus (bacteriophage) carrying the
genetic information for the toxin (tox gene). Only toxigenic strains can cause severe disease.
Culture of the organism requires selective media containing tellurite.
If isolated, the organism must be distinguished in the laboratory from other Corynebacterium species that normally inhabit the nasopharynx and skin (e.g., diphtheroids).
There are three biotypes - gravis, intermedius, and mitis. The most severe disease is associated with the
gravis biotype, but any strain may produce toxin. All isolates of C. diphtheriae should be tested by the laboratory for toxigenicity.
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Corynebacterium diphtheriae Aerobic gram-positive
bacillus Toxin production
occurs only when C. diphtheriae infected by
virus (phage) carrying tox gene If isolated, must be
distinguished from normal diphtheroid |
Clinical Features
The incubation period of diphtheria is 2-5 days
(range, 1-10 days).
Disease can involve almost any mucous membrane. For clinical purposes, it is
convenient to classify diphtheria into a number of manifestations, depending on
the site of disease.
Anterior nasal diphtheria
The onset is indistinguishable from that of the common cold and is usually
characterized by a mucopurulent nasal discharge
(containing both mucus and pus) which may become blood-tinged. A white membrane
usually forms on the nasal septum. The disease is usually fairly mild because
of apparent poor systemic absorption of toxin in this location, and can be
terminated rapidly by antitoxin and antibiotic therapy.
Pharyngeal and tonsillar diphtheria
The most common sites of infection are the tonsils and the pharynx. Infection
at these sites is usually associated with substantial systemic absorption of
toxin. The onset of pharyngitis is insidious. Early
symptoms include malaise, sore throat, anorexia, and low-grade fever. Within
2-3 days, a bluish-white membrane forms and extends, varying in size from
covering a small patch on the tonsils to covering most of the soft palate.
Often by the time a physician is contacted, the membrane is greyish-green
in color, or black if there has been bleeding. There is a minimal amount of
mucosal erythema surrounding the membrane. The
membrane is adherent to the tissue, and forcible attempts to remove it cause
bleeding. Extensive membrane formation may result in respiratory obstruction.
The patient may recover at this point; or if enough toxin
is absorbed, develop severe prostration, striking pallor, rapid pulse, stupor,
coma, and may even die within 6 to 10 days. Fever is usually not high, even
though the patient may appear quite toxic. Patients with severe disease may
develop marked edema of the submandibular areas and
the anterior neck along with lymphadenopathy, giving
a characteristic "bullneck" appearance.
Laryngeal diphtheria
Laryngeal diphtheria can be either an extension of the pharyngeal form or the
only site involved. Symptoms include fever, hoarseness, and a barking cough.
The membrane can lead to airway obstruction, coma, and death.
Cutaneous (skin) diphtheria
In the United States, cutaneous diphtheria has been
most often associated with homeless persons. Skin infections are quite common
in the tropics and are probably responsible for the high levels of natural
immunity found in these populations. Skin infections may be manifested by a
scaling rash or by ulcers with clearly demarcated edges and membrane, but any chronic
skin lesion may harbor C. diphtheriae, along
with other organisms. Generally, the organisms isolated from recent cases in
the
Other sites of involvement include the mucous membranes of the
conjunctiva and vulvo-vaginal area, as well as the
external auditory canal.
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Diphtheria Clinical
Features Incubation period 2-5
days (range, 1-10 days) May involve any
mucous membrane Classified based on
site of infection: |
Complications
Most complications of diphtheria, including
death, are attributable to effects of the toxin. The severity of the disease
and complications are generally related to the extent of local disease. The
toxin, when absorbed, affects organs and tissues distant from the site of
invasion. The most frequent complications of diphtheria are:
Myocarditis
Abnormal cardiac rhythms can occur early in the course of the illness or weeks
later, and can lead to heart failure. If myocarditis
occurs early, it is often fatal.
Neuritis
This complication most often affects motor nerves and usually clears
completely. Paralysis of the soft palate is most frequent during the third week
of illness. Eye muscles, limbs, and diaphragm paralysis can occur after the
fifth week. Secondary pneumonia and respiratory failure may result from
diaphragmatic paralysis.
Other complications include otitis media and
respiratory insufficiency due to airway obstruction, especially in infants.
Death
The overall case-fatality rate for diphtheria is 5%-10%, with higher death
rates (up to 20%) in persons <5 and >40 years of age. The case-fatality
rate for diphtheria has changed very little during the last 50 years.
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Diphtheria
Complications Most complications
and death attributable to toxin Severity of
complications generally related to extent of local disease Most common
complications are myocarditis and neuritis Death occurs in
5%-10% for respiratory disease, higher in <5 and >40 years |
Medical Management
Diphtheria antitoxin
Diphtheria antitoxin, produced in horses, was first used in the
Antitoxin will not neutralize toxin that is already fixed to tissues, but will
neutralize circulating (unbound) toxin and will prevent progression of disease.
The patient must be tested for sensitivity before antitoxin is given.
Consultation on the use of diphtheria antitoxin is available at all times
through the Centers for Disease Control and Prevention (CDC) operator at (404)
639-2889 or 2888. During office hours, 8:00 am to 4:30 pm EST, contact staff at
the Child Vaccine Preventable Diseases Branch, National Immunization Program,
(404) 639-8255.
Persons with suspected diphtheria should be given antibiotics and antitoxin in
adequate dosage and placed in isolation after the provisional clinical
diagnosis is made and appropriate cultures are obtained. Respiratory support
and airway maintenance should also be administered as needed.
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Diphtheria Antitoxin
First used in 1891 Produced in horses Used only for
treatment of diphtheria Neutralizes only
unbound toxin |
Antibiotics
Treatment with erythromycin orally or by injection (40 mg/kg/day; maximum, 2
gm/day) for 14 days, or procaine penicillin G daily, intramuscularly (300,000
U/day for those weighing 10 kg or less and 600,000 U/day for those weighing
more than 10 kg) for 14 days. The disease is usually not contagious 48
hours after antibiotics are instituted. Elimination of the organism should be
documented by two consecutive negative cultures after therapy is completed.
Preventive measures
For close contacts, especially household
contacts, a diphtheria booster, appropriate for age, should be given.
Contacts should also receive antibioticsbenzathine
penicillin G (600,000 units for persons less than 6 years old and 1,200,000
units for those 6 years old and older) or a 7- to 10-day course of oral
erythromycin, (40 mg/kg/day for children and 1 g/day for adults). For
compliance reasons, if surveillance of contacts cannot be maintained, they
should receive benzathine penicillin G. Identified
carriers in the community should also receive antibiotics. Maintain close
surveillance and begin antitoxin at the first signs of illness
Contacts of cutaneous diphtheria should be handled as
above; however, if the strain is shown to be non-toxigenic,
investigation of contacts can be discontinued.
EPIDEMIOLOGY
Occurrence
Diphtheria occurs worldwide, but clinical cases
are more prevalent in temperate zones. In the
Reservoir
Human carriers are usually asymptomatic. In
outbreaks, high percentages of children are found to be transient carriers.
Transmission
Transmission is most often person-to-person
spread from the respiratory tract. Rarely, transmission may occur from skin
lesions or articles soiled with discharges from lesions of infected persons (fomites).
Temporal pattern
In temperate areas, diphtheria most frequently
occurs during winter and spring.
Communicability
Transmission may occur as long as virulent
bacilli are present in discharges and lesions. The time is variable, but
organisms usually persist 2 weeks or less, and seldom more than 4 weeks,
without antibiotics. Chronic carriers may shed organisms for 6 months or more.
Effective antibiotic therapy promptly terminates shedding.
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Diphtheria
Epidemiology Reservoir: Human carriers, usually asymptomatic Transmission: Respiratory; skin and fomites
rarely Temporal pattern: Winter and spring Communicability: Up to several weeks without antibiotics |