Compare Surface Infections to Systemic Infections.
Surface Infections: microbes multiply in the epithelial
cells at the site of entry.
Systemic Infections: microbes spread systematically
through the body via blood and lymph.
What are the two types of pathogens?
Primary pathogens, which cause disease in otherwise healthy people (i.e. chlamydia) v. Opportunistic pathogens, which cause disease when the immune system is compromised or when the environment is altered (i.e. E. coli in urinary tract).
What is a non-pathogen?
A microorganism that does not cause disease; may be part of the normal flora.
What is a pathogen?
A microorganism capable of causing disease.
Compare Pathogenicity v. Toxigenicity.
Pathogenicity: The ability of an infectious agent to cause disease.
Toxigenicity: The ability of a microorganism to produce a toxin that contributes to the development of disease.
What is an infection?
The multiplication of an infectious pathogenic agent within the body (even if the person is asymptomatic)
However, multiplication of normal flora of the gastrointestinal tract, skin, etc is NOT considered an infection.
What is invasion?
The process whereby bacteria, parasites, fungi, and
viruses enter host cells or tissues and spread in the body.
What is adherence?
The process by which bacteria stick to the surfaces of host cells.
The quantitative ability of an agent to cause disease.
Virulent agents cause disease when introduced into the host in small numbers; involves adherence, invasion, and toxigenicity
Describe 3 categories of host-pathogen relationships, and give examples.
Mutualism: reciprocal benefits for both (i.e. lactobacilli in the vagina)
Commensalism: one benefits, other no harm (i.e. Staph epidermidis, which lives on the skin)
Parasitism: only one benefits (i.e. Toxoplasmosis gondii)
Name and describe the first step in microbial infection.
Colonization: Establishment of a pathogen at an appropriate site of entry.
Pathogens usually colonize host tissues that are in
contact with external environment
• Urogenital tract
• Digestive tract
• Respiratory tract
Name and give examples of the routes of infection with the portal of entry in the baby.
Prenatal: placenta, maternal blood vessels, cervix, umbilical cord blood vessel, amnion, etc.
Perinatal: maternal blood passage through placenta, uterus, rectum, or cervix
Postnatal: Through milk, blood, saliva contact with the baby's eyes, umbilical stump, etc.
Name three ways pathogens avoid the host's immune system.
1. Overcome mechanical barriers
-Specific receptors and adhesins for binding
2. Resist phagocytosis
-Specialized structures to "escape" phagocyte (capsule, slime, coagulase)
- Inhibit chemotaxis
-Produce toxins to kill phagocyte (catalase, toxins)
3. Evade detection
-Live inside host cell
-Colonize in areas difficult for immune cells to reach
What are the typical stages of an infectious disease?
There are often four discrete stages
•Time between the moment the person is exposed to the microbe (or toxin) and the appearance of symptoms
• Time during which nonspecific symptoms occur
3.Specific-illness period (peak illness)
• Time during which the characteristic features of the disease occur
• Time during which symptoms resolve and health is restored
What are the basic differences between prokaryotes and eukaryotes?
- Lack a distinct nucleus;
- Contain DNA in the form of a single circular chromosome (as well as additional DNA carried in plasmids);
- Transcription and translation can be carried out simultaneously;
- DNA is carried on several chromosomes with a membrane-bound nucleus;
- Transcription requires formation of mRNA, which must move into the cytoplasm where translation takes place on ribosomes;
- The cytoplasm is rich in membrane-bound organelles such as mitochondria, ER, Golgi apparatus, lysosomes;
What are the four phases of bacterial growth?
• Lag: vigorous metabolic activity occurs but cells do not divide (lasts a few minutes up to many hours)
• The log (logarithmic) phase is when rapid cell division occurs
• The stationary phase: nutrient depletion or toxic
products cause growth to slow
• The death phase: which is marked by a decline in
the number of viable bacteria
What are the three shape classifications and arrangements of bacteria?
- Pairs (diplococci)
- Chains (streptococci)
- Grape-like clusters (staphylococci)
What is a cell wall?
A cell wall is a multilayered structure located external to the plasma membrane, and part of what makes prokaryotes different from most eukaryotes.
It is composed of an inner layer of peptidoglycan and an outer membrane that varies in thickness and
chemical composition depending upon the
bacterial type. The peptidoglycan provides structural support and maintains the characteristic shape of the
What is the difference between Gram-positive and Gram-negative bacteria?
In Gram-positive bacteria, the cell wall forms the external surface of the cell. Compared to Gram-negative bacteria, the cell wall is much thicker.
In Gram-negative bacteria, there is an additional outer layer rich in lipopolysaccharides, which protect the cell against the immune system and chemotherapeutic agents. (It is harder to kill Gram-negative bacteria.)
Why do gram stain?
It is a useful way to identify bacteria and influence the choice of antibiotic:
- In general, gram-positive bacteria are more susceptible to penicillin G than are gram-negative bacteria.
Gram-positive bacteria stain purple; Gram-negative bacteria stain pink.
What is the bacterial capsule?
External to the cell wall may be an additional capsule that gives the cell a slimy surface. This provides protection against phagocytosis by host cells and is important in determining virulence. It appears as a "halo-like" clear area around the cell. (Mostly a feature of Gram-negative bacteria.)
Define flagella and pili.
Flagella are long helical filaments extending from the cell surface, which enable bacteria to move in their environment.
Pili (fimbriae) are more rigid and function in attachment, either to other bacteria ('sex' pili) or to host cells ('common' pili).
Describe metabolism in pathogenic bacteria.
Metabolism may be aerobic, where oxygen is required for production of ATP, or anaerobic, where oxygen is not required. Anaerobic metabolism is less efficient in producing ATP. The requirement for oxygen in respiration may be 'obligate' (required) or it may be 'facultative', some organisms being able to switch between aerobic and anaerobic pathways.
What is an example of an obligate anaerobe?
What is an example of a facultative anaerobe?
What is hemolysis? What is the difference between alpha-hemolysis, beta-hemolysis, and gamma-hemolysis?
Hemolysis is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly useful in classifying streptococcal species.
- streptococci form a green zone around their colonies as a result of incomplete lysis of red blood cells in the agar
- e.g. Strep. pneumoniae
- streptococci form a clear zone around their colonies because complete lysis of the red cells occurs
- Beta-hemolysis is due to the production of enzymes
(hemolysins) called streptolysin O and streptolysin S
- e.g. Group B Strep
- No change: organism does not induce hemolysis
- e.g. Group D Strep (Enterococcus faecalis)
What are the general stages of bacterial infection?
1. Transmission from an external source to the portal of entry;
2. Evasion of primary host defenses such as skin or stomach acid;
3. Adherence to host cell (specific to each type of bacteria);
4. Colonization (at site of adherence or inside cell);
5. Further invasion, colonization and/or release of
toxins leading to development of disease symptoms;
6. Progression or resolution of the disease (dependent on immune responses of the host and virulence of the pathogen);
What is the concern for pregnant women with chlamydia or gonorrhea?
It has been associated with Pelvic Inflammatory Disease (PID), infertility, ectopic pregnancy,
PROM, Preterm births, and neonatal infections. There is a risk of transmission from infected mother
to the neonate during delivery, with risk of conjunctivitis (ophthalmia neonatorum) and pneumonia.
In the newborn:
- 20-50% acquire infections
- 15-20% will present eye symptoms
- 10-20%: pneumonia
What is the difference between a lower and upper UTI?
Lower = up to the bladder; presents with acute frequency and dysuria;
Upper = up to the kidneys; has a more severe presentation with fever and loin pain;
Why are pregnant women predisposed to UTIs?
- Dilation of ureters and renal pelvis;
- Mechanical compression of the expanding uterus causes swelling of the urethers and kidneys and displaces bladder;
- Smooth muscle relaxation due to progesterone causes decreased peristalsis of ureters and increased bladder capacity -> urinary stasis and incomplete emptying;
- Urine pH and composition change;
What pathogen that is primary cause of UTIs?
E. coli, a gram-negative, rod shaped bacteria.
Describe the morphology of Staphylococcus bacteria.
Assignment of a strain to the genus Staphylococcus requires that it is a Gram-positive coccus that forms grape-like clusters, produces catalase, has an appropriate cell wall structure (including peptidoglycan type and teichoic acid presence).
What is catalase?
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen.
Where is Staph aureus commonly found?
It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of staphylococci to cause Staph infections.
What is the coagulase test?
The coagulase test is used to differentiate Staphylococcus aureus from coagulase-negative staphylococci. Coagulase is a protein produced by several microorganisms that enables the conversion of fibrinogen to fibrin. S.aureus produces two forms of coagulase (i.e., bound coagulase and free coagulase). Bound coagulase otherwise known as "Clumping factor" can be detected by carrying out a slide coagulase test and free coagulase can be detected by doing a tube coagulase test. Coagulase negativity excludes S. aureus. That is to say, S. aureus is coagulase-positive.
Give some examples of Staph aureus infections.
Toxic Shock Syndrome (TSS):
Due to the release of TSS toxin (an exotoxin)
High fever, vomiting, diarrhea, myalgias, rash, and hypotension with cardiac and renal failure in the most severe cases
Systemic, 5-10% of cases are fatal
Scalded Skin Syndrome (SSS):
Due to the release of exfoliative toxin (an exotoxin)
Causes the cells in the stratum granulosum of skin to separate and fall off
Entry of bacteria into milk duct, usually from baby's mouth
Milk stasis due to blocked duct
Local inflammation of the breast tissue (heat, redness, swelling)
Abscess can result if left untreated
Where is Staph epidermidis commonly found?
Staph epidermidis is part of the normal human flora on the skin and mucous membranes.
How does S. epidermidis cause infections?
Although S. epidermidis is not usually pathogenic, people with a compromised immune system are often at risk for developing an infection. These infections can be both nosocomial or community acquired, but they pose a greater threat to hospital patients. This phenomenon may be the result of continuous use of antibiotics and disinfectants within hospitals, leading to evolutionary pressure toward more virulent strains of the organism. S. epidermidis is also a major concern for people with catheters or other surgical implants because it is known to cause biofilms that grow on these devices. S. epidermidis strains are often resistant to antibiotics including penicillin, amoxicillin, and methicillin. Resistant organisms are most commonly found in the intestine, but organisms living freely on the skin can also become resistant due to routine exposure to antibiotics secreted in sweat.
Describe the morphology of Streptococcus bacteria.
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs. Most streptococci are oxidase- and catalase-negative, and many are facultative anaerobes.
Describe the classification of Steptococcus.
As a rule, individual species of Streptococcus are classified based on their hemolytic properties. In the medical setting, the most important groups are the alpha-hemolytic streptococci, S. pneumoniae and Streptococcus Viridans-group, and the beta-hemolytic streptococci of Lancefield groups A and B (also known as "Group A strep" and "Group B strep"). Beta-hemolytic streptococci are further characterised via the Lancefield serotyping - based on specific carbohydrates in the bacterial cell wall.
What is Group A Strep?
The group A streptococcus bacterium (Streptococcus pyogenes, or GAS) is a form of β-hemolytic Streptococcus bacteria responsible for most cases of streptococcal illness. S. pyogenes is the cause of many important human diseases, ranging from mild superficial skin infections to life-threatening systemic diseases. Infections typically begin in the throat or skin. Examples of mild S. pyogenes infections include pharyngitis ("strep throat") and localized skin infection ("impetigo").
What is Group B Strep?
Streptococcus agalactiae (also known as Group B streptococcus or GBS) is a beta-hemolytic Gram-positive streptococcus. S. agalactiae is a member of the gastrointestinal normal flora in some humans and can spread to secondary sites - including the vagina in 10-30% of women. S. agalactiae can be transferred to a neonate passing through the birth canal and can cause serious group B streptococcal infection.
What is Newborn GBS Disease?
In the western world, S. agalactiae is the major cause of bacterial septicemia of the newborn, which can lead to death or long-term sequelae. S. agalactiae invades via alveolar and pulmonary epithelial cells; newborns are especially susceptible to infection because they lack alveolar macrophages to prevent invasion. Newborn GBS disease is separated into early-onset disease occurring on living days 0-7 and late-onset disease which starts on days 7-90. Early-onset septicemia is more prone to be accompanied by pneumonia, while late-onset septicimia is more often accompanied by meningitis.
What is Group D Strep?
Many former Group D streptococci have been reclassified and placed in the genus Enterococcus (including S. faecalis, S. faecium, S. durans, and S. avium). For example, Streptococcus faecalis is now Enterococcus faecalis. Enterococci are members of the normal flora of the colon and are noted for their ability to cause urinary, biliary, and cardiovascular infections
How are women screened for GBS in pregnancy?
- Culture with vagino-anorectal swab;
- Women are screened between 35-37 wks or when risk factors are present (ROM >18 hrs, fever, preterm labour)
What is Bacterial Vaginosis?
Bacterial vaginosis (BV) is characterized by major change in vaginal flora from predominantly Lactobacilli to large mix of other anaerobic bacteria. BV is associated with the presence of Gardnerella vaginalis plus anaerobic infection and a fishy-smelling vaginal discharge. BV infections are associated with preterm birth, PROM, miscarriage, postpartum infection/endometritis.
Discuss the role of Lactobacilli in a healthy vagina.
A healthy vaginal environment is characterized by mutualism between vagina epithelial cells and Lactobacilli:
- Vaginal epithelial cells contain glycogen due to the action of circulating estrogens, promote colonisation by Lactobacilli;
- Lactobacilli metabolize the glycogen and produce lactic acid; results in low vaginal pH ~5.0 -> Inhibits colonisation by other microbes;
How is BV diagnosed?
Screening should be done in early pregnancy. To make a diagnosis of bacterial vaginosis, a swab from inside the vagina should be obtained. These swabs should be tested for:
- A characteristic "fishy" odor on wet mount: This test, called the whiff test, is performed by adding a small amount of potassium hydroxide to a microscopic slide containing the vaginal discharge. A characteristic fishy odor is considered a positive whiff test and is suggestive of bacterial vaginosis.
- Loss of acidity: A pH greater than 4.5 is considered alkaline and is suggestive of bacterial vaginosis.
- The presence of clue cells on wet mount: Similar to the whiff test, the test for clue cells is performed by placing a drop of sodium chloride solution on a slide containing vaginal discharge. If present, clue cells can be visualized under a microscope. They are so-named because they give a clue to the reason behind the discharge. Clue cells are epithelial cells of the vagina that get their distinctive stippled appearance by being covered with bacteria.
Two positive results in addition to the discharge itself are enough to diagnose BV. If there is no discharge, then all three criteria are needed.
BV is also associated with discharge that is homogeneous, low viscosity, and uniformly coats the vaginal walls.
What is a virus?
Viruses are neither prokaryotes nor eukaryotes. They are small infectious agents that can replicate only inside the living cells of organisms; they cannot live independently.
Viruses are metabolically inert:
Can replicate only after infection of a host;
Need to attach to living cells: NOT epidermis;
They parasitize the host's ability to transcribe/translate genetic information;
Describe the structure of viruses?
Virus particles (known as virions) consist of two or three parts: the genetic material made from either DNA or RNA; a protein coat that protects these genes (a capsid--the complete unit of nucleic acid and capsid is called nucleocapsid); and in some cases an envelope of lipids that surrounds the protein coat when they are outside a cell (that is derived from the host's cell membrane). The shapes of viruses range from simple helical and icosahedral forms to more complex structures.
Discuss the differences between DNA and RNA viruses.
A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is usually double-stranded DNA (dsDNA) but may also be single-stranded DNA (ssDNA). They take over the DNA reading apparatus of the cell they infect. The genome replication of most DNA viruses takes place in the cell's nucleus. e.g. herpes virus, CMV
An RNA virus is a virus that has RNA (ribonucleic acid) as its genetic material. This nucleic acid is usually single-stranded RNA (ssRNA) but may be double-stranded RNA (dsRNA). Replication usually takes place in the cytoplasm. RNA viruses are further classified according to the sense or polarity of their RNA into negative-sense and positive-sense, or ambisense RNA viruses. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation.
RNA viruses generally have very high mutation rates compared to DNA viruses, because viral RNA polymerases lack the proof-reading ability of DNA polymerases. This is one reason why it is difficult to make effective vaccines to prevent diseases caused by RNA viruses. e.g. rubella
Provide an example of a positive-sense RNA virus.
- Rubella, Hep A, polio, Hep C
Provide an example of a negative-sense RNA virus.
- influenza, measles, mumps
What is the purpose of the 'envelope' that some viruses acquire?
Some species of virus envelop themselves in a modified form of one of the cell membranes, either the outer membrane surrounding an infected host cell or internal membranes such as nuclear membrane or endoplasmic reticulum, thus gaining an outer lipid bilayer known as a viral envelope. This membrane is studded with proteins coded for by the viral genome and host genome; the lipid membrane itself and any carbohydrates present originate entirely from the host. The influenza virus and HIV use this strategy. Most enveloped viruses are dependent on the envelope for their infectivity.
Give an example of en enveloped virus and a naked virus.
Enveloped --> herpes simplex, CMV, HIV, influenza, varicella zoster, Hep B, rubella, Hep C, measles, mumps,
Naked --> HPV, parvovirus,
What is a retrovirus?
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA. Retroviruses are enveloped viruses. Reverse transcribing viruses with RNA genomes (retroviruses), use a DNA intermediate to replicate, e.g. HIV.
How do viruses enter the hosts?
Oral transmission: contaminated food or drink, saliva (e.g. Hepatitis A)
Droplet transmission: inhalation (e.g. rhinovirus, influenza)
Direct Inoculation: injections, trauma, insect bites (e.g. yellow fever, West Nile)
Sexual transmission: e.g. HIV
Transplacental: e.g. CMV
What are the stages of viral infection and replication?
Attachment: a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. This mechanism has evolved to favour those viruses that infect only cells in which they are capable of replication. Attachment to the receptor can induce the viral envelope protein to undergo changes that results in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface proteins that allow the virus to enter. e.g. influenze w/ sialic acid receptors or HIV with CD4 receptor
Penetration follows attachment: Virions enter the host cell through receptor-mediated endocytosis or fusion with the cell's plasma membrane. This is often called viral entry.
Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral enzymes or host enzymes or by simple dissociation; the end-result is the releasing of the viral genomic nucleic acid ('eclipse phase').
Replication of viruses primarily involves multiplication of the genome. DNA viruses undergo replication using processes similar to cellular replication; RNA viruses can be read directly as an mRNA or reverse transcribed by reverse transcriptase into DNA.
Assembly involves association of replicated nucleic acids with proteins made for the new capsid. In viruses such as HIV, this protein modification (sometimes called maturation) occurs after the virus has been released from the host cell.
Release: Viruses can be released from the host cell by lysis, a process that kills the cell by bursting its membrane and cell wall if present (produces a naked virus). Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal membrane.
Describe how a viral infection can present in the body.
Viral infection may be:
- Lytic: replication of virus, released via cell lysis
- Persistent: replication of virus, cell lives and continues to slowly release virus particles
- Latent: virus remains quiescent, genetic material may
exist in host cytoplasm or be incorporated into host
genome, replication takes place when a signal triggers
release from latency
• Viruses can transform the host cell into a tumor or cancer cell
- Interfering with normal cell regulation
- E.g. human papillomavirus transforms cervical cells into carcinoma cells
Describe some basic characteristics of the influenza virus.
- single stranded negative-sense RNA virus
- transmitted through air
- 3 types: A, B, and C
- type A viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease
- influenza A virus can be subdivided into different serotypes based on the antigens present on the virus' cell membrane (ie. H or N):
->Hemagglutinin (H): binds to the cell surface sialic
acid to initiate infection
• Antibody neutralizes infectivity of the virus
-> Neuraminidase (N): Cleaves sialic acid to release
progeny virus from the infected cell
• Enhances the ability of the virus to infect the
• Antibody against the neuraminidase does not
neutralize infectivity but does reduce disease
Discuss the two types of antigenic changes that are common to the influenza virus.
Because of the absence of RNA proofreading enzymes, the RNA-dependent RNA polymerase that copies the viral genome makes an error roughly every 10,000 nucleotides, which is the approximate length of the influenza vRNA. Hence, the majority of newly manufactured influenza viruses are mutants; this causes antigenic drift, which is a slow change in the antigens on the viral surface over time.
The separation of the genome into eight separate segments of vRNA allows mixing or reassortment of vRNAs if more than one type of influenza virus infects a single cell. The resulting rapid change in viral genetics produces antigenic shifts, which are sudden changes from one antigen to another. These sudden large changes allow the virus to infect new host species and quickly overcome protective immunity.
Discuss transmission of HSV-1 and its potential to be transmitted to the newborn.
Herpes simplex virus 1, aka oral herpes, is transmitted from when someone who has HSV is shedding (i.e. has open blisters) via indirect contact (i.e. sharing utensils) or direct contact (i.e. kissing). There is potential to be transmitted to neonate by caretakers with active sores.
Discuss transmission of HSV-2 and its potential to be transmitted to the newborn.
Herpes simplex virus 2, aka genital herpes, is transmitted through sexual contact.
Concern during pregnancy:
- Active lesions or asymptomatic shedding can
pass virus to neonate during delivery
- Herpes neonatorum
Skin, CNS, pneumonitis
- Presents usually at 9-14 days, often defined as >48 hrs from delivery
- Treat with acyclovir at time of recognition
Primary infection lesion - 30-50% risk
Recurrent lesion - 2.5 - 4% risk
Risk of shedding = 1%
Overall risk in non-primary HSV infected woman = 0.025 - 0.04% on any given delivery day (calculated)
Discuss transmission of Varicella-Zoster virus and its effect on the fetus.
Varicella-Zoster virus, which causes chickenpox and shingles, is transmission by respiratory secretions/saliva or direct contact with vesicles
A primary infection during pregnancy may lead to
congenital fetal infection
- Skin lesions, musculoskeletal and CNS abnormalities (<20 wks)
- Can also be a chronic carrier
If exposed during pregnancy:
- Varicella-zoster immune globulin (VZIG) can be given w/in 96 hrs
- Also to neonates in moms with
acute infection before delivery
Discuss transmission of Cytomegalovirus and its effect on the fetus.
CMV can be transmitted by saliva, urine, semen, cervical secretions, breastmilk.
90% of primary infections are asymptomatic and can cause mild disease in adults and children but has significant risks to fetus and neonate:
- IUGR/low birth weight,
- Cerebral calcifications, microcephaly, seizures, deafness
Perinatal infection is usually acquired by exposure to
maternal blood, cervical secretions, or breast milk
Discuss transmission of Parvovirus and its effect on the fetus.
Parvovirus B19 cause the disease erythema infectiosum or "fifth disease". It is transmitted primarily by the respiratory route, however, transplacental transmission also occurs. Primary infection of pregnant woman is a serious problem. Viral infection of fetus can lead to:
- Damage to RBC precursors -> fetal anemia
- Hydrops fetalis (fetal edema) can occur (only in 10% of women confirmed to be infected with Parvovirus B19) -->Abnormal accumulation of fluid in body cavities (pleural, pericardial, peritoneal)
- Does not cause developmental abnormalities
Describe transmission of Hep A and its effect on the fetus.
Hep A is a ssRNA naked virus that is transmitted by fecal-oral route and contaminated food.
Describe transmission of Hep B and its effect on the fetus.
Hep B is a DNA virus that is transmitted mainly by blood and bodily fluids but intrauterine and perinatal infections are possible. It establishes chronic infections (especially in infants)
- Major factor in the eventual development of liver
disease and hepatocellular carcinoma in chronic
- It can lead to persistent infection and chronic carrier status in the neonate.
- 90% become chronic carriers
- 25% of these die of liver disease as an adult
All pregnant women are tested for hepatitis B
- If mom is a carrier, a vaccine can protect the baby from infection
- 3 injections of vaccine over 6 month period give 90% of protection (1st one given within 24 hrs of birth)
- Hep. B immunoglobulin provides passive protection (within 12 hrs of birth)
If you perform a serological test for HBV, what results can you expect to find for an acute infection? For a chronic infection?
• Acute HBV infection: Detection of HBsAg, IgM
• Chronic HBV infection: HBsAg positive, anti-HBe
Describe transmission of Hep C and its effect on the fetus.
Hep C is a ssRNA virus that has a similar transmission pattern to HBV. 75-85% of HCV infected individuals develop chronic HCV, which is very similar to chronic HBV.
-->Modify delivery management
Prolonged ROM (>6hrs)- RR 10.2
Internal fetal monitoring - RR 8.3
Avoid fetal blood sampling
No recommendation for C/S
No confirmation of risk from breast feeding
Describe transmission of Hep E and its effect in pregnancy.
Hep E is transmitted through oral-fecal transmission and is very similar to HAV in course, pathology, and severity.
Evidence suggests that it might be a more severe
disease in pregnant women compared to HAV
- HEV has a 20% mortality rate in pregnant women vs. 1-2% for the rest of the population
- Mortality due to disseminated intravascular coagulation
• Excessive clotting, thrombosis
Describe transmission of Rubella and its effect in pregnancy.
Rubella (aka German measles) is transmitted via respiratory droplets or from mother to fetus transplacentally.
Infection during pregnancy is of great concern as
rubella is a teratogen.
• When a non-immune pregnant woman is
infected during the first trimester -> congenital
malformations can occur
• The malformations are widespread and involve:
-> Heart (e.g., patent ductus arteriosus)
-> Eyes (e.g., cataracts)
-> Brain (e.g., deafness and mental retardation)
In a pregnant woman exposed to rubella, the presence
of IgM antibody indicates recent infection
- IgG antibody indicates immunity and consequent protection of the fetus
Are fungi eukaryotes or prokaryotes?
Describe the general morphology of fungi?
Fungi exist as branched filaments (hyphae) or as
single-celled yeasts. Characteristically, they are multinucleate or multicellular with thick carbohydrate cell walls containing glucans and chitin (resistant chitinous coat is an antiphagocytic factor).
Describe the three types of fungal infections.
• Superficial mycoses
- Fungus grows on body surfaces like skin, hair, nails, mouth, vagina
- E.x.: Athlete's foot, vaginal candidiasis
• Subcutaneous mycoses
- Deeper layers of tissue are involved
- E.x.: Madura foot
• Systemic/deep mycoses
- Affects internal tissues
- E.x.: Histoplasmosis, systemic candidiasis
Are protozoa eukaryotes or prokaryotes?
Discuss the risks associated with trichomoniasis in pregnancy?
• Small risk of preterm delivery
• Low birth weight
• May be acquired during birth (5% of the cases)
Discuss the risks associated with toxoplasmosis gondii in pregnancy?
Acute infection in pregnancy can be transmitted to the fetus:
- Congenital infection causes various
malformations in the fetus including visual
defects, mental retardation, convulsions, etc
Name the five mechanisms of action of antibacterial drugs (i.e. where/what they target).
1. Cell Wall (peptidoglycan) Synthesis
2. Nucleic Acid Synthesis
3. Cell Membrane Integrity
4. Metabolic Pathways (folate biosynthesis)
5. Protein Synthesis
What are beta-lactams? Give a couple examples.
β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics.
What is the mechanism of action of beta-lactams?
β-Lactam antibiotics are bacteriocidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms, being the outermost and primary component of the wall. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs). B-lactams bind to "penicillin binding proteins" (PBP). Irreversible inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis, and weakening/distorting the cell wall leading to cell lysis and death.
What bacteria do beta-lactams work well for?
What is the mechanism of action of macrolides/Clindamycin/Tetracycline?
Antibiotic macrolides are used to treat infections caused by Gram-positive bacteria, Streptococcus pneumoniae, and Haemophilus influenzae infections such as respiratory tract and soft-tissue infections. Macrolides are protein synthesis inhibitors. The mechanism of action of macrolides is inhibition of bacterial protein biosynthesis, and they are thought to do this by preventing peptidyltransferase from adding the peptidyl attached to tRNA to the next amino acid.
This action is mainly bacteriostatic, but can also be bactericidal in high concentrations. Macrolides tend to accumulate within leukocytes, and are, therefore, transported into the site of infection.
What antibiotic is used to treat chlamydia in nonpregnant people and in pregnancy?
Macrolides or Tetracyclines
In nonpregnant people --> azithromycin or doxycycline
In pregnancy --> erythromycin
What is the mechanism of action of fluoroquinolones?
Fluoroquinolones are chemotherapeutic bactericidal drugs, eradicating bacteria by interfering with DNA replication (nucleic acid synthesis). They inhibit the bacterial DNA gyrase or the topoisomerase II enzyme, thereby inhibiting DNA replication and transcription. Fluoroquinolones can enter cells easily via porins and, therefore, are often used to treat Gram-negative bacteria, such as E.coli.
What is the mechanism of action of metabolism inhibitors such as sulfa drugs?
Also called folate inhibitors, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis. As such, the microorganism will be "starved" of folate and die. It is considered bacteriostatic.
What type of treatment is used for the 3 vaginitis'?
Antifungal agents --> azoles
What are nucleoside analogues?
Nucleoside analogues are a range of antiviral products used to prevent viral replication in infected cells. They inhibit viral DNA polymerase thus halting viral
DNA synthesis. The most commonly used is Acyclovir. These agents can be used against Varicella-Zoster, hepatitis B virus, hepatitis C virus, herpes simplex, and HIV.
What type of antimicrobial is used to treat influenza?
Viral Uncoating Blockers: Amantadine and rimantadine, have been introduced to combat influenza. These agents act on penetration/uncoating phase of replication.
Neuraminidase Inhibitors: Zanamivir (Relenza) and oseltamivir (Tamiflu) that have been recently introduced to treat influenza prevent the release of viral particles by blocking a molecule named neuraminidase that is found on the surface of flu viruses.
Early treatment with neuraminidase inhibitors may:
• Reduce influenza complications
- Duration of fever
- Need for antibiotics
- Asthma exacerbations
Describe the basic morphology of Chlamydia trachomatis.
Chlamydia is a Gram-negative bacteria with a coccoid or rod shape. It is an obligate intracellular pathogen meaning it require growing cells in order to remain viable since it cannot synthesize its own ATP. Without a host organism, C. trachomatis cannot survive on its own .
It has a cytoplasmic membrane and outer membrane similar to Gram-negative bacteria (thus, it being classified as Gram-negative) but, it lacks a peptidoglycan cell wall.
Briefly outline the life cycle of Chlamydia.
The life cycle of Chlamydia trachomatis consists of two stages: elementary body and reticulate body. The elementary body is the dispersal form, which is analogous to a spore. Once inside the endosome, the elementary body germinates into the reticulate body as a result of the glycogen that is produced. The reticulate body divides through binary fission at approximately 2-3 hours per generation. The cell body has an incubation period of 7-21 days in the host. It contains no cell wall and is detected as an inclusion in the cell. After division, the reticulate body transforms back to the elementary form and is released by the cell by exocytosis.
What infections are routinely screened for in pregnancy?
UTIs, Syphilis, Hepatitis B, Rubella, HIV, GBS
What are some of the body's innate defense mechanisms against UTIs?
The regular flushing action of urine is a major urethral defence; the bladder wall has an intrinsic defense mechanism (protective mucous layer, ability to generate inflammatory response and produce secretory antibodies-IgAs).
Why are women more susceptible to UTIs?
Women have shorter urethra's that allows easier access to bacteria; contributing to contamination, the warm moist vulva and rectum are both in close proximity; sexual intercourse increases bladder inoculation
What is the most common bacterial infection in pregnancy?
What are the two types of UTIs?
Asymptomatic bacteriuria (ABU)=presence of >10^4 CFU/mL of one bacterial species on two successive urine cultures in a client with no symptoms
Acute Pyelonephritis=renal infection is the most common serious medical complication of pregnancy
What is the danger of a UTI in pregnancy?
- sepsis-->presence of bacteria and their toxins in tissues, which can lead to systemic inflammation and septicemia (blood poisoning)
- maternal renal failure
What is the pathogen involved in syphilis?
Treponema pallidum, an anaerobic spirochete
How is syphilis transmitted?
Transmission requires close personal contact because the organism doesn't survive well outside of the body.
Can be transmitted via sexual contact and transplacentally to the fetus.
What are the stages of Syphilis infection?
Primary Stage: Approximately three to 90 days after the initial exposure (average 21 days) a skin lesion, called a chancre, appears at the point of contact. The most common location in women is the cervix (44%). The lesion is due to multiplication of T. pallidum at the site of infection.
Secondary Stage: Secondary syphilis occurs approximately four to ten weeks after the primary infection. While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucus membranes, and lymph nodes. There may be a symmetrical reddish-pink non-itchy rash on the trunk and extremities, including the palms and soles. Hematogenous dissemination of T. pallidum causes systemic symptoms (fever, malaise, headaches)
Latent Stage: Latent syphilis is defined as having serologic proof of infection without symptoms of disease. Lasts 2-20 years after initial exposure.
Tertiary Stage: T. pallidum disseminates further. Manifestations are optic atrophy, tabes dorsalis, aortic aneurism, gummas of the skin and bone.
How does congenital syphilis present?
Classified into early or late congenital syphilis depending on whether it presents before or after 2 yrs of age. It is associated with serious neurological, developmental, and musculoskeletal sequelae. Early cong. syph. presents like 2nd stage in adults. Late presents as neurosyphilis.
>50% of all infants are asymptomatic at birth, and signs in symptomatic infants may be subtle and non-specific.
Characteristically, prematurity, low birthweight (IUGR), failure to thrive.
How is syphilis diagnosed?
Cannot be grown in vitro (cultured); diagnosis via microscopy and serology.
Two types of serological tests:
(1) Non-treponemal tests, which detect non-specific treponemal antibodies (based on the reactivity of IgG and IgM antibodies to T pallidum with a cardiolipin-lecithin-cholesterol antigen; VDRL and RPR tests);
(2) Treponemal tests, which detect specific treponemal antibodies (EIAs, hemagglutination assay TPHA, agglutination assay TPPA, immunofluorescence FTA-abs)
Followed by fluorescent staining and microscopy.
How is syphilis treated?
What is vertical transmission?
Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period.
How is HepB diagnosed?
The 3-part hepatitis B blood panel includes the following:
1. Hepatitis B Surface Antigen (HBsAg): The "surface antigen" is part of the hepatitis B virus that is
found in the blood of someone who is infected. If this test is positive, then the hepatitis B virus is
2. Hepatitis B Surface Antibody (HBsAb or anti-HBs): The "surface antibody" is formed in response
to the hepatitis B virus. Your body can make this antibody if you have been vaccinated, or if you have
recovered from a hepatitis B infection. If this test is positive, then your immune system has successfully
developed a protective antibody against the hepatitis B virus. This will provide long-term protection
against future hepatitis B infection.
3. Hepatitis B Core Antibody (HBcAb or anti-HBc): This antibody does not provide any protection or
immunity against the hepatitis B virus. A positive test indicates that a person may have been exposed
to the hepatitis B virus. This test is often used by blood banks to screen blood donations. However, all
three test results are needed to make a diagnosis.
What is the Hep B immunoglobulin
HBIG is indicated as a postexposure prophylaxis for people at risk to develop hepatitis B because they have been recently exposed to body fluids of individuals who have hepatitis B. This includes babies of mothers with hepatitis B, sexual partners, healthcare workers, police and fire workers, and morticians. It provides a temporarily-induced immunity by the transfer of immunoglobulins (antibodies).
What kind of virus is Rubella?
Positive-sense RNA virus.
How does congenital rubella syndrome present?
<12 weeks - spontaneous abortion or severe abnormalities
- IUGR, cardiac (PDA or pulm artery stenosis), hearing defects, visual impairment (catarracts), encephalitis, blueberry muffin syndrome (purpura)
>12 weeks - less severe
- hearing, language, autism, endocrine, visual, dental
**Risk of infection goes down with increasing gestational age.
What kind of a virus is HIV?
It is an enveloped RNA virus with a specific affinity for helper T cells with CD4 proteins.
How does an HIV infection present?
Infection with HIV-1 is associated with a progressive decrease of the CD4+ T cell count and an increase in viral load, the level of HIV in the blood. The stage of infection can be determined by measuring the patient's CD4+ T cell count and viral load.
The stages of HIV infection are acute infection (also known as primary infection), latency and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, lymphadenopathy (swollen lymph nodes), pharyngitis (sore throat), rash, myalgia (muscle pain), malaise, and mouth and esophageal sores. The latency stage involves few or no symptoms and can last anywhere from two weeks to twenty years or more, depending on the individual, with a CD4+ count of >500. AIDS, the final stage of HIV infection, is defined by low CD4+ T cell counts (fewer than 200 per microliter), various opportunistic infections, cancers and other conditions.
Treatment started at CD4 of 350 +/-
How is HIV treated?
There is currently no cure for HIV infection. Treatment consists of highly active antiretroviral therapy, or HAART. Current HAART options are combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents. Typically, these classes are two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
NO perinatal transmissions in 282 women on HAART
What are some maternal risk factors for perinatal HIV transmission?
- Increased illness severity (higher viral load, low CD4+ count, AIDS)
- Lack of receipt of antiretroviral therapy
- Maternal drug use
- Obstetrical factors
- Preterm delivery
Where is the focus being placed to try to prevent transmission to the baby?
- Prevent women from acquiring HIV
- Prevent unintended pregnancies
- Diagnose HIV infection in women
- PMTCT - antepartum most effective but intrapartum and postpartum has added benefit
- Care of infant - pre/post exposure prophylaxis and prevention of ongoing exposure (breast feeding)
Primary Strategy: antenatal antiretroviral therapy
- ALL women are to be treated with combination effective and safe antiretroviral therapy from at least the 2nd half of pregnancy through delivery
- CD4 count based specifics:
< 200 - start ASAP and include relevant opportunistic infection prevention
200-350 - start soon
> 350 - start by 20 weeks ideally
> 500 - can consider stopping post partum - all others continue post partum
What are the delivery options for a woman who is HIV+?
- Vaginal delivery is safest if mother is on antenatal ARV's and VL suppressed (< 1,000 c/ml)
- Minimize duration of ROM
- Minimize breach of infant skin - no scalp electrodes, avoid instrument delivery
- Elective or prelabour/early labour C/S if VL unknown or estimated to be > 1,000 c/ml
- NO proven benefit for an 'in labour' emergency C/S for prevention of HIV transmission
- IV AZT at onset of labour or pre-C/S
What is Neisseria gonorrhoeae?
It is a Gram-negative diplococcus bacteria.
How is gonorrhea transmitted?
Transmission is direct
- From person to person, usually via sexual contact
- From mother to baby during childbirth
- Does not survive outside body so intimate contact is required
- Usual site of entry is via the vagina or the urethra of the penis
- Other sexual practices may result in infection of throat and rectal mucous membranes
- Following adhesion, gonococci spread to cervix in women and up urethra in men
- Can also infect Bartholin's (greater vestibular) and Skene's (paraurethral) glands
How does gonorrhea present clinically?
Clinical findings in pregnant women:
- Vaginal discharge
- Pelvic pain
What are the risks associated with gonorrhea in pregnancy?
- Premature rupture of membranes
- Preterm labor
- Postpartum infection
- Gonococcal conjunctivitis (ophthalmia neonatorum) is the most common manifestation of perinatal infection
-->It is usually transmitted during delivery
-->Profuse, purulent discharge is evident a few days after birth
-->Diagnosed by microscopy and culture of an eye swab
-->Systemic antibiotics are required
What is the Nugent Score?
The Nugent Score is a Gram stain scoring system for pap tests to diagnose bacterial vaginosis. The Nugent score is calculated by assessing for the presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0 to 4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0 to 4), and curved Gram-variable rods (Mobiluncus spp. morphotypes; scored as 0 to 2) and can range from 0 to 10. A score of 7 to 10 is consistent with bacterial vaginosis.