Chapter 8 – Infectious Diseases: General Principles of Microbial Pathogenesis Flashcards

1
Q

CATEGORIES OF INFECTIOUS AGENTS

A
  • * Prions :30–50 kD Intracellular
  • * Viruses: 20–300 nm
    • Obligate intracellular
  • Bacteria : 0.2–15 μm
    • * Obligate intracellular
    • * Extracellular
    • Facultative intracellular
  • Fungi : 2–200 μm
    • * Extracellular
    • * Facultative intracellular
  • Protozoa 1–50 μm
    • * Extracellular
    • * Facultative intracellular
    • * Obligate intracellular
  • Helminths : 3 mm–10m
    • * Extracellular
    • * Intracellular
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2
Q

What are prions?

A

Prions are composed of abnormal forms of a host protein, termed prion protein (PrP). [3]

These agents cause transmissible spongiform encephalopathies, including kuru (associated withhuman cannibalism), Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy(BSE; better known as mad cow disease), and variant Creutzfeldt-Jakob disease (vCJD; probably transmitted to humans from BSE-infected cattle).

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3
Q

What is a PrP and its pathophysiology?

A

PrP is normally found in neurons.

Diseases occur when the PrP undergoes a conformational change that confers resistance toproteases.

The protease-resistant PrP promotes conversion of the normal protease-sensitive PrP to the abnormal form, explaining the infectious nature of these diseases.

Accumulation ofabnormal PrP leads to neuronal damage and distinctive spongiform pathologic changes in thebrain.

Spontaneous or inherited mutations in PrP, which make PrP resistant to proteases, havebeen observed in the sporadic and familial forms of CJD, respectively. CJD can be transmittedfrom person to person iatrogenically, by surgery, organ transplant, or blood transfusion.

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4
Q

What are viruses?

A

Viruses are obligate intracellular parasites that depend on the host cell’s metabolic machinery for their replication.

They consist of a nucleic acid genome surrounded by a protein coat (called a capsid) that is sometimes encased in a lipid membrane.

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5
Q

How are viruses classified?

A

Viruses are classified by their:

  • nucleic acid genome (DNA or RNA but not both),
  • the shape of the capsid (icosahedral or helical),
  • the presence or absence of a lipid envelope,
  • their mode of replication,
  • the preferred cell type for replication (called tropism),
  • or the type of pathology.
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6
Q

Because of the very small size of the virus, they are best seen under the electron microscope.

At what instances do these viruses are seen under the light microscope.

A

Because viruses are only 20 to 300 nm insize, they are best visualized with the electron microscope.

However, some viral particles aggregate within the cells they infect and form characteristic inclusion bodies, whichmay be seen with the light microscope and are useful for diagnosis.

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7
Q

What examples of Viruses show inclusion bodies?

A
  • cytomegalovirus (CMV)-infected cells are enlarged and show a large eosinophilic nuclear inclusion and smaller basophilic cytoplasmic inclusions
  • herpesviruses form a large nuclear inclusion surrounded by a clear halo
  • both smallpox and rabies viruses form characteristic cytoplasmic inclusions
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8
Q

What are bacteria?

A

Bacteria are prokaryotes, meaning that they have a cell membrane but lack membrane-boundnuclei and other membrane-enclosed organelles.

Most bacteria are bound by a cell wallconsisting of peptidoglycan, a polymer of long sugar chains linked by peptide bridges.

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9
Q

How are bacteria classifed?

A

Bacteria are classified by

  • * Gram staining (positive or negative),
  • * shape (spherical ones are cocci; rod-shaped ones are bacilli) ( Fig. 8-3 ),
  • * and need for oxygen (aerobic or anaerobic).
  • Many bacteria have flagella,long helical filaments extending from the cell surface that enable bacteria to move.
  • Some bacteria possess pili, another kind of surface projection that can attach bacteria to host cells or extracellular matrix.
  • Most bacteria synthesize their own DNA, RNA, and proteins, but they depend on the host for favorable growth conditions.
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10
Q

Thereare two forms of bacterial cell wall structures:

A
  • thick wall surrounding the cell membrane that retainscrystal-violet stain (gram-positive bacteria) or
  • a thin cell wall sandwiched between twophospholipid bilayer membranes (gram-negative bacteria) ( Fig. 8-2 ).
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11
Q

Normal healthy people can be colonized by as many as _____________ on the skin

A

10^ 12 bacteria on the skin

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12
Q

Normal healthy people can be colonized by as many as _____________ on the mouth.

A

10^ 10
bacteria in the mouth,

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13
Q

Normal healthy people can be colonized by as many as _____________ on the GIT

A

10 ^14 bacteria in the gastrointestinal tract

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14
Q

Bacteria colonizing the
skin include __________ and _______

A

Staphylococcus epidermidis and Propionibacterium acnes, the cause of acne.

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15
Q

the cause of acne.

A

Propionibacterium acnes,

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16
Q

Aerobic and anaerobic bacteria in the mouth, particularly ________ contribute to
dental plaque, a major cause of tooth decay

A

Streptococcus mutans,

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17
Q

What is facultative intracellular bacteria?

A

can survive and replicate either
outside or inside of host cells

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18
Q

What is an obligate intracellular bacteria?

A

some grow only inside host
cells

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19
Q

Obligate intracellular bacteria include____________ which replicate inside
membrane-bound vacuoles in epithelial and endothelial cells, respectively

These bacteria get
most or all of their energy source, ATP, from the host cell

A

Chlamydia and Rickettsia,

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20
Q

__________ is the most
frequent infectious
cause offemale sterility(byscarring and narrowing of the fallopian tubes)
and blindness (by chronic inflammation of the conjunctiva that eventually causes scarring and
opacification of the cornea).

A

Chlamydia trachomatis

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21
Q

What does Rickettsiae injure and causes what?

A

Rickettsiae injure the endothelial cells in which they grow, and so
cause a hemorrhagic vasculitis, often visible as a rash, but they may also injure the central
nervous system (CNS) and cause death (Rocky Mountain spotted fever [RMSF] and epidemic
typhus).

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22
Q

Rickettsiae are transmitted by ___________

A

arthropod vectors, including lice (epidemic typhus), ticks
(RMSF and ehrlichiosis), and mites (scrub typhus

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23
Q

Why do Mycoplasma organisms and those belonging to the related genus Ureaplasma are unique
among extracellular bacterial pathogens,

A

because they do not have a cell wall. These are the
tiniest free-living organisms known (125–300 nm).

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24
Q

What are Fungi?

A

Fungi are eukaryotes that possess thick chitin-containing cell walls and ergosterol-containing
cell membranes.

Bacteria ang PROKARYOTES

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25
What is the content of the cell wall of fungi?
Fungi are eukaryotes that possess **thick chitin-containing cell walls**
26
What is the content of the cell membranes of Fungi?
**ergosterol**-containing cell membranes.
27
Fungi can grow either as:
* *rounded yeast cells** or as **slender filamentous** * *hyphae.**
28
Hyphae may be :
* **septate** (with cell walls separating individual cells) * or **aseptate**, which is an important distinguishing characteristic in clinical material
29
Some of the most important pathogenic fungi exhibit thermal dimorphism which means?
that is, **they grow as hyphal forms at room** temperature but as **yeast forms at body temperature** **San nakikita ang YEAST kiban? Dba sa Katawan? Anong temp ng katawan? ok?**
30
What is conidia?
Fungi may produce sexual spores or, more commonly, **asexual spores** referred to as **conidia.** The l**atter are produced on specialized** **structures or fruiting bodies** arising **along the hyphal filament.** Fungi may cause superficial or deep infections.
31
What is a dermatophyte?
Superficial infections involve the skin, hair, and nails. Fungal species that are **confined to superficial layers** of the human skin are **known as dermatophytes**. These infections are commonly referred to by the term **“tinea”** followed by the **area of the body affected** (e.g., tinea pedis, “athlete's foot”; tinea capitis, “ringworm of the scalp”).
32
Certain fungal species invade the **subcutaneous tissue,** causing abscesses or granulomas \_\_\_\_\_\_\_\_\_\_\_\_
(e.g., sporotrichosis and tropical mycoses).
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Deep fungal infections can spread **systemically and invade tissues,** destroying vital organs in immunocompromised hosts, but usually heal or remain latent in otherwise normal hosts.
34
Some deep fungal species are **limited to a particular geographic region,** give an example.
(e. g., **Coccidioides** in the * *southwestern United States and Histoplasma in the Ohio River Valley**).
35
Opportunistic fungi ____________ by contrast, are **ubiquitous organisms** that e**ither colonize individuals** or are **encountered from environmental sources**
(e.g., **Candida**, **Aspergillus**, **Mucor ,** and **Cryptococcus**),
36
In **immunodeficient individuals,**opportunistic fungi give rise to**life-threatening infections characterized by tissue necrosis, hemorrhage, and vascular occlusion, with little or no inflammatory response.** AIDS patients are often infected by the opportunistic fungus \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
``` Pneumocystis jiroveci (previously called Pneumocystis carinii). ```
37
What is protozoa?
Parasitic protozoa are **single-celled eukaryotes** that are **major causes of disease and death in** **developing countries.**
38
Protozoa can replicate intracellularly within a variety of cells ___________ .
(e.g., **Plasmodium in red blood cells**, **Leishmania in macrophages)**
39
Protozoa can replicate:
**intracellularly or extracellularly** in the urogenital system, intestine, or blood
40
\_\_\_\_\_\_\_\_\_- are flagellated protozoal parasites that are **sexually transmitted** and **can colonize the vagina and male urethra**
Trichomonas vaginalis
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The **most prevalent intestinal protozoans:**
Entamoeba histolytica and Giardia lamblia,
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The most prevalent intestinal protozoans, Entamoeba histolytica and Giardia lamblia, have two forms:
(1) **motile** **trophozoites** that attach to the intestinal epithelial wall and may invade, and (2) **immobile cysts** that are resistant to stomach acids and are infectious when ingested.
43
Blood-borne protozoa \_\_\_\_\_\_\_\_\_\_- are transmitted by insect vectors, in which they replicate before being passed to new human hosts.
(e.g., Plasmodium, Trypanosoma, and Leishmania)
44
**Intestinal protozoa** are acquired by ingestion of\_\_\_\_\_ from contaminated food or water.
cysts
45
Toxoplasma gondii is acquired either by contact with \_\_\_\_\_\_\_\_\_\_\_
oocyst-shedding kittens or by eating cyst-ridden, undercooked meat.
46
What are Helminths?
Parasitic worms are **highly differentiated multicellular organisms.** Their **life cycles are complex;** **most alternate between sexual reproduction** in the **definitive host and asexual multiplicatio**n in an **intermediary host or vector**. ``` Thus, depending on parasite species, humans could harbor adult worms (e.g., Ascaris lumbricoides) or immature stages (e.g., Toxocara canis) or asexual larval forms (e.g., Echinococcus species). Once adult worms take up residence in humans, they do not multiply but they produce eggs or larvae that are usually passed out in stool. ``` Often, the severity of disease is in proportion to the number of organisms that have infected the individual (e.g., **10 hookworms cause little disease**, whereas **1000 hookworms cause severe anemia** by consuming **100 mL of blood per da**y). In some helminthic infections, disease is caused by **inflammatory responses to the eggs or larvae rather than to the adults** (e.g., schistosomiasis).
47
What are Ectoparasites?
Ectoparasites are **insects (lice, bedbugs, fleas**) or **arachnids (mites, ticks, spiders)** that attach to and live on or in the skin. Arthropods may produce disease directly by damaging the human host or indirectly by serving as the vectors for transmission of an infectious agent into a human host.
48
Some arthropods cause **itching and excoriations** (e.g., \_\_\_\_\_\_\_\_- **caused by lice** attached to hair shafts, or scabies caused by mites burrowing into the stratum corneum).
pediculosis
49
At the site of the bite, **mouth parts may be found associated** with a **mixed infiltrate of lymphocytes,** **macrophages, and eosinophils.** In addition, **attached arthropods** can be **vectors for other** pathogens. For example, **deer ticks transmit the Lyme disease spirochete Borrelia burgdorferi.**
50
SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIOUS AGENTS
* Gram stain * Acid-fast stain * Silver stains * Periodic acid–Schiff * Mucicarmine * Giemsa * Antibody probes * Culture * DNA probes
51
Gram stain
Most bacteria
52
Acid-fast stain
Mycobacteria, nocardiae (modified)
53
Silver stains
* Fungi, l * egionellae, * pneumocystis
54
Periodic acid–Schiff
Fungi, amebae
55
Mucicarmine
Cryptococci
56
Giemsa
Campylobacteria, leishmaniae, malaria parasites
57
Antibody probes
All classes
58
Culture
59
DNA probes
All classes
60
Acute infections can be diagnosed serologically by detecting **pathogen-specific antibodies** in the serum. The presence of specific ______ **shortly after the onset of symptoms is often** diagnostic.
IgM antibody
61
Alternatively, specific antibody titers can be measured early (“acute”) and **4–6 weeks** (“convalescent”) after infection; a **four-fold rise** in titer is **usually considered diagnostic** **T or F**
T
62
What are molecular diagnostics?
Nucleic acid–based tests, collectively called molecular diagnostics, have become routine methods for detecting and quantifying several pathogens. For instance, in people infected with the human immunodeficiency virus (HIV), quantification of HIV RNA is an important guide to antiretroviral therapy. [7] The management of HBV and HCV infections is similarly guided by nucleic acid–based viral quantification or typing to predict resistance to antiviral drugs.
63
Nucleic acid amplification tests, such as polymerase chain reaction (PCR) and transcriptionmediated amplification, have become routine for diagnosis of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
gonorrhea, chlamydial infection, tuberculosis, and herpes encephalitis
64
In some cases, molecular assays are much more sensitive than conventional testing. [8,] [9] **PCR testing of cerebrospinal fluid (CSF)** for\_\_\_\_\_\_\_\_\_\_\_\_ has a sensitivity of about **80%,** while viral culture of CSF has a sensitivity of less than 10%.
``` herpes simplex virus (HSV) encephalitis ```
65
Similarly, **nucleic acid tests** for genital chlamydia detect 10% to 30% more infections than does conventional chlamydia culture. In other cases, such as gonorrhea, the sensitivity of nucleic acid testing is similar to that of culture.
66
Some infectious agents or their products **can be directly observed in hematoxylin and eosi**n –stained sections: give examples
(e.g., the inclusion bodies formed by CMV and herpes simplex virus (HSV
67
What stains blue H and E?
* bacterial clumps, which usually stain blue * Candida and Mucor among the fungi * most protozoans; and all helminths)
68
Many infectious agents, however, are best visualized by **special stains**that**identify organisms**on the basis of particular**characteristics of their cell wall or coat** —**Gram, acid-fast, silver, mucicarmine, and Giemsa stains**—or after labeling with specific antibody probes
69
NEW AND EMERGING INFECTIOUS DISEASES The infectious causes of some diseases with significant morbidity and mortality were previously unrecognized, because some of the infectious agents are difficult to culture; examples include \_\_\_\_\_\_\_\_\_\_\_\_\_
Helicobacter pylori gastritis, HBV and HCV, and Legionnaires pneumonia
70
NEW AND EMERGING INFECTIOUS DISEASES Some infectious agents are genuinely **new to humans**,
e.g., HIV, which causes AIDS, and B. burgdorferi, which causes Lyme disease.
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NEW AND EMERGING INFECTIOUS DISEASES Other infections have become **much more common** because of immunosuppression caused by AIDS or therapy for transplant rejection and some cancers. Give examples.
(e.g., CMV, Kaposi sarcoma herpesvirus, Mycobacterium avium-intracellulare, P. jiroveci, and Cryptosporidium parvum
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NEW AND EMERGING INFECTIOUS DISEASES Finally, infectious diseases that are c**ommon in one area** may be introduced into a new area. For example,\_\_\_\_\_\_\_\_\_\_ has been common in Europe, Asia, and Africa for years b**ut was first described in the United States in 1999**
West Nile virus
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TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1977 :Ebola virus Manifestation:
Epidemic Ebola hemorrhagic fever
74
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1977 :Hantaan virus Manifestation:
Hemorrhagic fever with renal syndrome
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TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1977 :Legionella pneumophila Manifestation:
Legionnaires disease
76
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1977 :Campylobacter jejuni Manifestation:
Enteritis
77
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1980 HTLV-I Manifestation:
T-cell lymphoma or leukemia, HTLV-associated myelopathy
78
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1981 Staphylococcus aureus Manifestation:
Toxic shock syndrome
79
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1982 Escherichia coli O157:H7 Manifestation:
Hemorrhagic colitis, hemolytic-uremic syndrome
80
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1982 : Borrelia burgdorferi Manifestation:
Lyme disease
81
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1983 HIV Manifestation:
AIDS
82
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1983 :Helicobacter pylori Manifestations
Gastric ulcers
83
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1988 Hepatitis E Manifestations
Enterically transmitted hepatitis
84
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1989 Hepatitis C Manifestations
Hepatitis C
85
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1992 Vibrio cholerae O139 Manifestations
New epidemic cholera strain
86
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1992 Bartonella henselaedisease Manifestations
Cat-scratch
87
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1995 KSHV (HHV-8) Manifestations
Kaposi sarcoma in AIDS
88
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 1999 West Nile virus Manifestations
West Nile fever, neuroinvasive disease
89
TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations 2003 SARS coronavirus Manifestations
Severe acute respiratory syndrome
90
Human demographics and behavior are among the many variables that contribute to the emergence of infectious diseases. AIDS was first recognized in the United States as predominantly a disease of homosexuals and drug abusers, but heterosexual transmission is now common. In sub-Saharan Africa, the area of the world with the highest number of AIDS cases, it is predominantly a heterosexual disease
91
Changes in the environment occasionally drive rates of infectious diseases. Reforestation of the eastern United States has led to massive increases in the populations of deer and mice, which carry the ticks that transmit Lyme disease, babesiosis, and ehrlichiosis
92
Failure of DDT to control the mosquitoes that transmit malaria and the development of drug-resistant parasites have dramatically increased the morbidity and mortality of Plasmodium falciparum in Asia, Africa, and Latin America. Microbial adaptation to widespread antibiotic use contributed to the emergence of drug resistance in many species of bacteria, including Mycobacterium tuberculosis, Neisseria gonorrhoeae, Staphylococcus aureus, and Enterococcus faecium. Infections with antibioticresistant bacteria are becoming a serious problem, such as methicillin-resistant staphylococcus (discussed later).
93
AGENTS OF BIOTERRORISM has three categories: What is Category A?
**Category A** agents **pose the highest risk** and can be **readily disseminated** or transmitted from person to person, can cause **high mortality with potential for major public health impact,** might **cause public panic and social disruption,** and might **require special action** for public health preparedness
94
Explain why small pox belongs to category A
For example, smallpox is a category A agent because of its **high transmissibility** in **any climate or season**, case **mortality rate of 30% or** greater, and **lack of effective antiviral** **therapy.** This agent can be **easily disseminated** because of the **stability of the virus in aerosol** **form and the very small dose** **needed for infection.** Smallpox **naturally spreads from person to person mainly by direct contact with virus in skin lesions or contaminated clothing or bedding.** Symptoms appear after **7 to 17 day**s. Initially there is **high fever, headache, and backache,** f**ollowed by the appearance of the rash**, which **first appears on the mucosa of the mouth** and **pharynx, face, and forearms** and **later spreads** to the **trunk and legs and becomes vesicular** and later pustular. Because people can be contagious during the incubation period, this virus has the potential to continue to spread throughout an unprotected population. Since vaccination ended in the United States in 1972 and vaccination immunity has waned, the population is highly susceptible to smallpox. Recent concern that smallpox could be used for bioterrorism has led to a return of vaccination for selected groups in the United States and Israel.
95
AGENTS OF BIOTERRORISM What is category B?
Category B agents are **moderately easy to disseminate, produce moderate morbidity** but **low** **mortality**, and **require specific diagnostic** and **disease surveillance.** Many of these agents are food-borne or water-borne
96
What is Bioterrorism category C?
**Category C** agents include emerging pathogens that could be engineered for mass dissemination because of availability, ease of production and dissemination, potential for high morbidity and mortality, and great impact on health.
97
TRANSMISSION AND DISSEMINATION OF MICROBES Microbes can enter the host by :
* *inhalation, ingestion**, **sexual transmission**, **insect or animal bites,** * *or injection**.
98
What is the first defense against infection?
The first defenses against infection are : **intact skin and mucosal surfaces,** which provide **physical barriers and produce antimicrobial substances**. In general, respiratory, gastrointestinal, or genitourinary tract infections that occur in healthy persons are caused by relatively virulent microorganisms that are capable of damaging or penetrating intact epithelial barriers. **In contrast, most skin infections in healthy persons are caused by less virulent organisms entering the skin through damaged sites (cuts and burns).**
99
TRANSMISSION AND DISSEMINATION OF MICROBES Routes of Entry of Microbes
* Skin. * Gastrointestinal Tract. * Respiratory Tract. * Urogenital Tract.
100
How does skin protect us from microbeS?
The **dense, keratinized outer layer of skin** is a natural barrier to infection, and the **low pH of the skin (∼5.5)**and the**presence of fatty acids inhibit growth** of microorganisms other than residents of the normal flora.
101
Human skin is normally inhabited by a variety of bacterial and fungal species, including some **potential opportunists**, such as \_\_\_\_\_\_\_\_
S. epidermidis and Candida albicans
102
Although skin is usually an effective barrier, certain types of fungi \_\_\_\_\_\_\_\_\_\_\_- can infect the **stratum corneum, hair, and nails,** and a few microorganisms are able to traverse the unbroken skin
(dermatophytes)
103
How does Shistosoma penetrate the skin?
Schistosoma larvae -released from freshwater snails **penetrate** ## Footnote **swimmers' skin by releasing collagenase, elastase, and other enzymes that dissolve the extracellular matrix**
104
Most microorganisms, however, penetrate through breaks in the skin, including superficial pricks \_\_\_\_\_\_\_\_\_\_,
(fungal infections)
105
Most microorganisms, however, penetrate through breaks in the skin, including wounds\_\_\_\_\_\_\_\_,
(staphylococci)
106
Most microorganisms, however, penetrate through breaks in the skin, including burns \_\_\_\_\_\_\_\_\_\_\_\_and diabetic and pressure-related foot sores (multibacterial infections).
(Pseudomonas aeruginosa),
107
Intravenous catheters in hospitalized patients can produce \_\_\_\_\_\_\_\_\_\_\_\_
local or systemic infection (bacteremia).
108
Needle sticks can expose the recipient to potentially infected blood and may transmit \_\_\_\_\_\_\_\_\_\_\_\_\_
transmit HBV, hepatitis C virus (HCV), or HIV
109
Some pathogens penetrate the skin via an insect or animal bite. For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and transmit arboviruses causing\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
(causes of yellow fever and encephalitis
110
Some pathogens penetrate the skin via an insect or animal bite. For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and transmit causing:, \_\_\_\_\_\_\_\_- (Rocky Mountain spotted fever [RMSF])
rickettsiae
111
Some pathogens penetrate the skin via an insect or animal bite. For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and transmit bacteria \_\_\_\_\_\_\_\_\_\_\_\_,
(plague, Lyme disease)
112
Some pathogens penetrate the skin via an insect or animal bite. For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and transmit protozoa\_\_\_\_\_\_\_\_\_\_\_,
(malaria, leishmaniasis)
113
Some pathogens penetrate the skin via an insect or animal bite. For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and transmit and helminths\_\_\_\_\_\_
(filariasis).
114
Animal bites can lead to infections with bacteria or certain viruses such as \_\_\_\_\_\_\_\_-
rabies.
115
Most gastrointestinal pathogens are transmitted by \_\_\_\_\_\_\_\_\_\_\_\_\_l.
food or drink contaminated with fecal materia Where hygiene fails, diarrheal disease becomes rampant.
116
\_\_\_\_\_\_\_ are important defenses within the gastrointestinal tract and are lethal for many gastrointestinal pathogens.
Acidic gastric secretions
117
Healthy volunteers do not become infected by Vibrio cholerae unless they are fed\_\_\_\_\_\_\_\_-
10 ^11 organisms,
118
whereas volunteers given V. cholerae and sodium bicarbonate have a 10,000-fold increase in susceptibility to cholera
119
In contrast, some ingested agents, such as \_\_\_\_\_\_\_\_, are **relatively resistant to gastric acid;** hence, **as few as 100 organisms** of each are **sufficient to cause illness.**
Shigella and Giardia cysts
120
Other normal defenses within the gastrointestinal tract include :
* (1) the layer of **viscous mucus** covering the intestinal epithelium * (2) **lytic pancreatic enzymes** and **bile detergents,** * (3) **mucosal antimicrobial peptides** called **defensins**, * (4) **normal flora,** and * (5**) secreted IgA antibodies**. IgA antibodies are made by plasma cells located in mucosa-associated lymphoid tissues **(MALT).**
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What is an M cell?
These **lymphoid aggregate**s are covered by a **single layer of specialized epithelial cells** called M cells. M cells are **important for transport** of **antigens to mucosa-associated lymphoid tissue**s and for **binding and uptake of numerous gut pathogens,** including **poliovirus, enteropathic** **Escherichia coli, V. cholerae, Salmonella typhi, and Shigella flexneri.**
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M cells are important for transport of antigens to mucosa-associated lymphoid tissues and for binding and uptake of numerous gut pathogens, including :
* poliovirus, * enteropathic * Escherichia coli, * V. cholerae, * Salmonella typhi, * and Shigella flexneri.
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Infections via the gastrointestinal tract occur when local defenses are **weakened or the** **organisms develop strategies** to **overcome these** defenses. Host defenses are weakened by l**ow gastric acidity, by antibiotics** that alter the normal bacterial flora (e.g., in \_\_\_\_\_\_\_\_\_\_\_),
pseudomembranous colitis
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Infections via the gastrointestinal tract occur when local defenses are weakened or the organisms develop strategies to overcome these defenses. Host defenses are weakened by :
* low gastric acidity, * by antibiotics that alter the normal bacterial flora * or when there is **stalled peristalsis** * or mechanical obstruction **(e.g., in blind-loop** **syndrome**).
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Most enveloped viruses are **inactivated by bile and digestive enzymes**, but **nonenveloped viruses** may be resistant \_\_\_\_\_\_\_\_\_\_\_\_\_
(e. g., the hepatitis A virus, rotaviruses, reoviruses, and norovirus) .
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Enteropathogenic bacteria elicit gastrointestinal disease by a variety of mechanisms:
* While growing on contaminated food, certain **staphylococcal strains** release powerful enterotoxins that cause food poisoning without any bacterial multiplication in the gut. * • V. cholerae and toxigenic E. coli **multiply inside the mucous layer** overlying the gut epithelium and release exotoxins that cause the gut epithelium to secrete large volumes of fluid, resulting in watery diarrhea. * • Shigella, Salmonella, and Campylobacter invade and **damage the intestinal mucosa and lamina propria and so cause ulceration,** inflammation, and hemorrhage that is clinically manifested as dysentery. * • Salmonella typhi passes from the damaged mucosa through Peyer patches and mesenteric lymph nodes and into the bloodstream, resulting in a systemic infection.
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While growing on contaminated food, certain \_\_\_\_\_\_\_\_\_\_release powerful enterotoxins that cause food poisoning without any bacterial multiplication in the gut.
staphylococcal strains
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\_\_\_\_\_\_\_\_\_\_**multiply inside the mucous layer** overlying the **gut epithelium and release exotoxin**s that cause the **gut epithelium to secrete large volumes** **of fluid, resulting in watery diarrhea**
V. cholerae and toxigenic E. coli
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\_\_\_\_\_\_\_\_\_\_\_\_ invade and damage the **intestinal mucosa** and **lamina propria and so cause ulceration, inflammation, and hemorrhage that is clinically manifested as *_dysentery._***
Shigella, Salmonella, and Campylobacter
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\_\_\_\_\_\_\_\_\_ passes from the damaged mucosa through Peyer patches and **mesenteric lymph nodes and into the bloodstream, resulting in a systemic infection.**
Salmonella typhi
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Fungal infection of the gastrointestinal tract occurs mainly in \_\_\_\_\_\_\_\_\_\_\_\_
immunologically compromised people.
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\_\_\_\_\_\_\_\_\_\_\_\_ part of the normal gastrointestinal flora, shows a predilection for stratified squamous epithelium, ***_causing oral thrush or membranous esophagitis,_*** but may also spread to the **stomach, lower gastrointestinal tract, and systemic organs.**
Candida
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In what form of intestinal protozoa is essential for their transmission? WHY?
The **cyst forms** of intestinal protozoa are essential for their transmission, because **cysts resist stomach acid** re**CYST acid**
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In the **gut**, cysts convert to ______________ and attach to sugars on the intestinal epithelia through surface lectins.
motile trophozoites
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What happens next differs among pathogens. \_\_\_\_\_\_\_\_\_\_\_attaches to the epithelial brush border
Giardia lamblia
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whereas \_\_\_\_\_\_\_\_\_\_\_\_- are taken up by enterocytes, in which they form gametes and spores.
cryptosporidia
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\_\_\_\_\_\_\_\_\_\_\_ causes contact-mediated **cytolysis** through a channel-forming pore protein and thereby ulcerates and invades the colonic mucosa.
E. histolytica
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Intestinal helminths, as a rule, cause disease only when \_\_\_\_\_\_\_\_\_\_\_
``` they are present in large numbers or in ectopic sites, for example, by obstructing the gut or invading and damaging the bile ducts (Ascaris lumbricoides). ```
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\_\_\_\_\_\_\_\_\_ may cause iron deficiency anemia by chronic loss of blood sucked from intestinal villi
Hookworms
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the\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ can deplete its host of vitamin B12, giving rise to an illness resembling **pernicious anemia.**
fish tapeworm Diphyllobothrium latum
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Finally, the larvae of several helminths pass through the gut briefly on their way to another organ
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\_\_\_\_\_\_\_\_\_\_ larvae preferentially encyst in muscle,
Trichinella spiralis
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\_\_\_\_\_\_\_\_ species larvae in the liver or lung.
Echinococcus
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A large number of microorganisms, including viruses, bacteria, and fungi, are inhaled daily by every city inhabitant. In many cases, the microbes are inhaled in dust or aerosol particles. The **distance these particles travel into the respiratory system** is **inversely proportional to their size.** **T or F**
True
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Large particles are trapped in the \_\_\_\_\_\_\_\_\_\_\_\_\_\_
mucociliary blanket that lines the nose and the upper respiratory tract.
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Inhaled microorganisms are trapped in the mucus secreted by goblet cells and are then transported by ciliary action to the back of the throat, where they are swallowed and cleared. Particles smaller than _________ travel directly to the alveoli, where they are phagocytosed by alveolar macrophages or by neutrophils recruited to the lung by cytokines.
5 μm
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Microorganisms that invade the normal healthy respiratory tract **have developed specific** **mechanisms to overcome t**he **mucociliary defenses or to avoid destruction by alveolar macrophages** **T or F**
FALSE
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Some successful respiratory pathogens evade these defenses by attaching to epithelial cells in the lower respiratory tract and pharynx. For example are \_\_\_\_\_\_\_\_\_\_\_
influenza viruses
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How does influenza virus evade the defenses of the epithelial cells of the respiratory tract?
influenza viruses possess **hemagglutinin proteins** that project from the surface of the virus and bind to sialic acid on the surface of epithelial cells. This **attachment induces the host cell to engulf the virus,** leading **to viral entry and replication** within the **host cell**. However, sialic acid also interferes with shedding of newly synthesized viruses from the host cell. Influenza viruses have another cell surface protein, **neuraminidase**, which cleaves sialic acid and allows virus to release from the host cell. Neuraminidase also lowers the viscosity of mucus and facilitates viral transit within the respiratory tract. Interestingly, some anti-influenza drugs are sialic acid analogues that inhibit neuraminidase and prevent viral release from host cells.
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What does hemagglutinin proteins do?
possess hemagglutinin proteins that project from the surface of the virus and bind to sialic acid on the surface of epithelial cells. This attachment induces the host cell to engulf the virus, leading to viral entry and replication within the host cell. However, sialic acid also interferes with shedding of newly synthesized viruses from the host cell.
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What does neuramidase do?
Influenza viruses have another cell surface protein, neuraminidase, which **cleaves sialic acid and allows virus to release from the** **host cell.** Neuraminidase also lowers the viscosity of mucus and facilitates viral transit within the respiratory tract. Interestingly, some anti-influenza drugs are sialic acid analogues that inhibit neuraminidase and prevent viral release from host cells.
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Certain bacterial respiratory pathogens can impair ciliary activity.
* Haemophilus influenzae and * Bordetella pertussis elaborate * P. aeruginosa * M. pneumoniae * Streptococcus pneumoniae or * Staphylococcus
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\_\_\_\_\_\_\_\_\_\_\_ elaborate toxins that **paralyze mucosal cilia**
Haemophilus influenzae and Bordetella pertussis
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\_\_\_\_\_\_\_\_\_\_\_\_ a cause of severe respiratory infection in persons with cystic fibrosis
P. aeruginosa
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\_\_\_\_\_\_\_\_\_\_\_- produce ciliostatic substances
M. pneumoniae
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Some bacteria such as **\_\_\_\_\_\_\_\_\_\_\_-** species lack specific adherence factors and often gain access after viral infection causes loss of ciliated epithelium, making individuals with a viral respiratory infection more susceptible to these secondary bacterial superinfections.
**Streptococcus pneumoniae or Staphylococcus**
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Chronic damage to mucociliary defense mechanisms occurs in\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
smokers and people with **cystic fibrosis**,
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acute injury damage to mucociliary defense mechanisms occurs in \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
intubated patients and in those who aspirate gastric acid.
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Some respiratory pathogens avoid phagocytosis or destruction after phagocytosis. Give an example.
M. tuberculosis, for example, gains its foothold in normal alveoli because it is able to escape killing within the phagolysosomes of macrophages.
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Opportunistic fungi infect the lungs when cellular immunity is depressed or when leukocytes are reduced in number. Give example.
e.g., P. jiroveci in AIDS patients and Aspergillus species following chemotherapy).
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The urinary tract is almost always invaded from the exterior via\_\_\_\_\_\_\_\_\_\_\_\_
the urethra .
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What is the natural defense of the U?rogenital tract
The r**egular flushing of the urinary tract**with urine serves as a defense against invading microorganisms.
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Urine in the bladder is normally sterile, and successful pathogens such as\_\_\_\_\_\_\_\_\_\_\_adhere to the urinary epithelium
* N. gonorrhoeae, * E. coli
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Anatomy plays an important role in infection. Women have m**ore than 10 times as many urinary tract infections** as men, because \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
the distance between the urinary bladder and skin (i.e., the length of the urethra) is **5 cm in women**, in contrast to 20 cm in men.
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\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ can compromise normal defenses and increase susceptibility to urinary tract infections.
Obstruction of urinary flow and/or reflux Urinary tract infections can spread retrogradely from the bladder to the kidney and cause acute and chronic pyelonephritis, which is the major preventable cause of renal failure.
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From puberty until menopause the vagina is protected from pathogens by a \_\_\_\_\_\_\_\_\_\_\_\_\_
low pH resulting from catabolism of glycogen in the normal epithelium by lactobacilli. Antibiotics can kill the lactobacilli and make the vagina susceptible to infection.
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**Sexually transmitted pathogens** have developed specific mechanisms for attaching to the vaginal or cervical mucosa, or they enter via local breaks in the mucosa during sexual intercourse such as:
**(HIV, HPV, Treponema pallidum).**
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Spread and Dissemination of Microbes Some microorganisms **proliferate locally,** at the site of infection, whereas **others penetrate the epithelial barrier**and**spread to distant sites via the lymphatics, the blood, or nerves** (
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Pathogens that cause superficial infections stay confined to the lumen of hollow viscera \_\_\_\_\_\_\_\_\_\_\_
(e.g., Vibrio cholera
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Pathogens that cause superficial infections adhere to or proliferate exclusively in or on epithelial cells
(e.g., papillomaviruses, dermatophytes).
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A variety of pathogenic bacteria, fungi, and helminths are invasive by virtue of their **motility or ability to secrete lytic enzymes** (e.g., \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_secrete hyaluronidase, which degrades the extracellular matrix between host cells).
streptococci and staphylococci
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Microbial spread initially follows tissue planes of least resistance and to sites drained by regional lymphatics. For example, **staphylococcal** infections may progress from a localized abscess or furuncle to regional lymph nodes. This can sometimes leads to bacteremia and colonization of distant organs (heart, liver, brain, kidney, bone). Within the blood, microorganisms may be transported free or within host cells.
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What microbes are transported free in the plasma?
``` Some viruses (**e.g., poliovirus and** **HBV),** most bacteria and fungi, some protozoa **(e.g., African trypanosomes)**, and all helminths are transported free in the plasma ```
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Leukocytes can carry which organisms?
* herpesviruses, * HIV, * mycobacteria, * and Leishmania * and Toxoplasma organisms.
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What viruses and parasites are carried by the RBC?
``` Certain viruses (e.g., Colorado tick fever virus) and parasites (Plasmodium and Babesia) are carried by red blood cells. ```
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Most viruses spread from **\_\_\_\_\_\_\_\_\_\_\_\_\_**
**cell to cell by replication** and **release of infectious virions,**
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Give example of virus that may propagate from c**ell to cell by fusion or transport within nerves**
(e.g., rabies virus).
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What are secondary foci?
Infectious foci seeded by blood are called secondary foci. They c**an be single and large** (a solitary abscess or tuberculoma) or **multiple and tin**y (**e.g., miliary tuberculosis or Candida microabscesse**s in many tissues) .
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Sporadic bloodstream invasion by low-virulence or nonvirulent microbes (e.g., during brushing of teeth) is common but is quickly controlled by normal host defenses
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By contrast, **disseminated viremia, bacteremia, fungemia, or parasitemia by virulent pathogens** is a serious insult and manifests itself by _____________ by bacteria or their endotoxins can rapidly become fatal, even for previously healthy individuals.
fever, low blood pressure, and multiple other systemic signs and symptoms of sepsis.
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FIGURE 8-4 Routes of entry and dissemination of microbes.
To enter the body microbes penetrate the epithelial or mucosal barriers. Infection may remain localized at the site of entry or spread to other sites in the body. Most common microbes (selected examples are shown) spread through the lymphatics or bloodstream (either freely or within inflammatory cells) . However, certain viruses and bacterial toxins may also travel through nerves.
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What is the major manifestation of infectious disease?
The major manifestations of infectious disease may **appear at sites distant from the point of microbe entry.**
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The major manifestations of infectious disease may appear at sites distant from the point of microbe entry. For example, \_\_\_\_\_\_\_\_\_\_\_\_viruses enter through the airways but cause rashes in the skin;
chickenpox and measles
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The major manifestations of infectious disease may appear at sites distant from the point of microbe entry. For example: __________ enters through the intestine but kills motor neurons.
poliovirus
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The major manifestations of infectious disease may appear at sites distant from the point of microbe entry. For example: \_\_\_\_\_\_\_\_\_\_\_parasites penetrate the skin but eventually localize in blood vessels of the portal system and mesentery, damaging the liver and intestine.
Schistosoma mansoni
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The major manifestations of infectious disease may appear at sites distant from the point of microbe entry. For example: \_\_\_\_\_\_\_\_\_\_\_- on the other hand, localizes to the urinary bladder and causes cystitis.
Schistosoma hematobium,
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The major manifestations of infectious disease may appear at sites distant from the point of microbe entry. For example: The __________ travels to the brain in a retrograde fashion within nerves
RABIES
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The major manifestations of infectious disease may appear at sites distant from the point of microbe entry. For example: the \_\_\_\_\_\_\_\_\_\_\_\_- hides in dorsal root ganglia, and on reactivation, travels along nerves to cause shingles.
varicella zoster virus (VZV)
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The placental-fetal route is an important mode of transmission ( Chapter 10 ). When infectious organisms reach the pregnant uterus through the cervical orifice or the bloodstream and are able to traverse the placenta, severe damage to the fetus can result. Bacterial or mycoplasmal placentitis can cause premature delivery or stillbirth. Viral infections can cause maldevelopment of the fetus, with infection early in pregnancy resulting in the most severe disease.
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\_\_\_\_\_\_\_\_\_\_\_\_\_ infection during the **first trimester** can cause congenital heart disease, mental retardation, cataracts, or deafness in the infant, while little damage is caused by this during the third trimester.
Rubella
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Transmission of treponemes leads to congenital syphilis only when T. pallidum infects the mother late in the _________ but then causes severe **fetal osteochondritis** and **periostitis that leads to multiple bony lesions.**
second trimester
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Infection also can occur during passage through the birth canal \_\_\_\_\_\_\_\_\_\_\_or through maternal milk (e.g., CMV, HBV, human T-cell leukemia virus-1 [HTLV-1]).
(e.g., gonococcal or chlamydial conjunctivitis)
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Infection also can occur during passage through maternal milk \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
(e. g., * *CMV, HBV, human T-cell leukemia virus-1 [HTLV-1]).**
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\_\_\_\_\_\_\_\_\_\_\_\_ is the major cause of AIDS in children.
Maternal transmission of HIV
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Maternal transmission of HBV can later cause \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
chronic hepatitis or liver cancer.
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