Infection Flashcards
What is the structure of adenovirus?
- Non-enveloped
- Icosahedral
- Double stranded linear DNA
What respiratory diseases does adenovirus commonly cause?
- Acute febrile pharyngitis: Most common in infants and young children; characterised by a cough, sore throat, nasal congestion and fever.
- Pharyngoconjuctival fever: Conjunctivitis in addition to pharyngitis; occurs most commonly in school children and often within family groups or in groups using the same swimming facility.
- Acute respiratory disease: Occurs primarily in epidemics among new military recruits – thought to reflect the lowered resistance brought on by exposure to new strains, fatigue and crowded living conditions, promoting the efficient spread of the infection.
- Viral pneumonia: Progressions of the above conditions and has the mortality rate of 10% in infants.
What gastrointestinal conditions does adenovirus cause?
Infantile gastroenteritis: Adenoviruses can multiply in the GI tract and can be found in stools. Two serotypes have been associated specifically with this disease. Adenovirus infections have been estimated to account for 5 to 15% of all viral diarrheal disease in children.
What ocular conditions does adenovirus cause?
- Follicular conjunctivitis: Self-limiting and has no permanent sequelae.
- Keratoconjunctivitis: A more serious infection involving the corneal epithelium, which may be followed by corneal opacity lasting several years. Partly results from transmission via shared towels or ophthalmic solutions, person-to-person contact and improperly sterilised ophthalmological instruments.
What are less common conditions caused by adenovirus?
- Haemorrhagic cystitis: Occurs primarily in boys and characterised by haematuria.
- Left ventricular dysfunction: Infection of the heart muscle in both children and adults.
- Pneumonia: Common in immunocompromised patients who contract a respiratory infection (e.g. patient with AIDS)
What is the pathogenesis of adenovirus?
They are most commonly transmitted via the respiratory route. However, most adenoviruses also replicate efficiently and asymptomatically in the intestine and can be isolated from the stool well after the respiratory disease symptoms have ended, as well as from the stools of a healthy person. Similarly, ocular infections are transmitted by direct inoculation of the eye by virus-contaminated hands, ophthalmologic instruments or bodies of water in which groups of children swim together.
What are laboratory tests for adenovirus?
Direct test of stool specimens by ELISA
What are treatments and preventions against adenoviruses?
No antiviral agents are currently available. Prevention of the epidemic respiratory disease by immunisation has only been used for the protection of the military population. A vaccine containing live, unattenuated adenovirus types 4 and 7, formulated for oral administration has been licensed for use among the US military.
Describe the structure of Clostridium difficile
Stain: Gram positive Shape: Bacillus Obligate Anaerobe Extra: Form spores, therefore making it very resistant to antibiotics Non-encapsulated but the spores are
Name some antibiotics associated with clostridium difficile
- Ampicillin
- Cephalosporins
- Clindamycin
- Ciprofloxacin
- Amoxicillin
- Penicillins
- Sulphonamides
- Erythromycin
- Trimethoprim
- Quinolones
Where can you normally find C.difficile in the body?
Clostridium difficile (C.diff) is a minor component of the normal flora of the large intestine.
Why do use of some antibiotics increases the susceptibility to Clostridium difficile infections?
The antibiotics suppresses the more predominant C.diff in the large intestine so the number of invading C.diff increases as they have fewer organisms to compete with for attachment and resources.
What is the pathogenesis of c.difficile?
C.diff produces 2 toxins; toxins A and B.
Toxin A is an enterotoxin that causes excessive fluid secretion but also stimulates an inflammatory response. Toxin B is a cytotoxin, which disrupts protein synthesis and causes disorganisation of the cytoskeleton. They are both glucosyltransferases.
How is C.difficile found in the laboratory?
o ELISA to identify toxins A and B.
o PCR
o Cultured on blood agar
What diseases can C.difficile cause?
o Pseudomembranous colitis
What treatment do you use for C.difficile conditions?
o Oral metronidazole or vancomycin
What is the structure of Clostridium perfringes?
Stain: Gram positive
Shape: Rod
Anaerobic
Encapsulated and produces endospore
Where is clostridium perfringes seen as normal flora in the body?
GI tract and vagina
What is the pathogenesis of C.perfringes?
o α Toxin – a lecithinase that degrades lecithin in mammalian cell membranes causing lysis of endothelial cells as well are erythrocytes, leukocytes and platelets.
o Enterotoxins act in the lower portion of the small intestine. LThe molecule binds to receptors on the epithelial cell surface and alters the cell membrane disrupting ion transport leading to loss of fluid and intracellular proteins.
o Produces a variety of hydrolytic enzymes.
What are the laboratory findings for C.perfringes?
o Produces double zone of β haemolysis on blood agar
What diseases do C.perfringes usually cause?
o Gas gangrene (myonecrosis) o Anaerobic cellulitis o Food poisoning o Necrotic enteritis o Clostridial endometritis
What is the treatment for C.perfringes conditions?
o Penicillin G
o Clindamycin
o Metronidazole
What is the structure of Escherichia Coli?
Stain: Gram negative Shape: Short rods Facultative Anaerobe Catalase positive Encapsulated
What diseases does E.coli cause?
o UTI
o Neonatal meningitis
o Hospital acquired infections
What is the physiology of E.coli?
E. Coli can generate energy by aerobic or anaerobic respiration by using nitrate, nitrite or fumarate as terminal electron acceptors. There are many different serotypes.
What are laboratory findings of E.coli?
o Stool cultures
o Cultured on MacConkey agar
o Serology
o Isolation of E. Coli from normally sterile body sites is diagnostically significant
What is the treatment used for E.coli conditions?
UTI
o Ciprofloxacin/Trimethoprim
o Nitrofurantoin
Local or systemic disease o Ampicillin o Cefotaxime o Ciprofloxacin o Trimethoprim
Neonatal meningitis
o Cefotaxime
What is the structure of Haemophilus influenza?
Stain: Gram negative
Shape: Pleomorphic in shape ranging from small coccobacilli to long slender filaments – USUALLY RODS.
Anaerobic
Encapsulated
What are the diseases caused by H.infleunza?
◦Bacterial meningitis
◦Otitis media
◦Sinusitis
◦Pneumonia
◦Epiglottitis
◦Septic arthritis
Where is H.influenza usually found?
A normal component of the upper respiratory tract flora.
Illnesses are usually sporadic in occurrence.
What is the pathogenesis of H.influenza?
H. influenzae is transmitted by respiratory droplets. Bacteria produce an IgA protease that cleaves IgA1 and thus evade the immunoglobulins of this class. It can also enter the bloodstream and disseminate to distant sites. Therefore diseases caused by this bacterium can be separated into two categories – contiguous spread e.g. otitis media and invasion of the bloodstream e.g. Septic arthritis.
How do you test for H.influenza in a laboratory?
Culture on chocolate agar with NAD+ and haemin.
What is the treatment for H.infleunza diseases?
◦Ampicillin
◦Cefotaxime
◦Ceftriaxone
◦Trimethoprim
What is the structure of helicobacter pylori?
Stain: Gram negative
Shape: Rod
Microaerophilic
Multiple polar flagella, which give organism rapid corkscrew motility
What is the pathogenesis of H.pylori?
◦Colonises gastric epithelial cells in stomach and metaplastic gastric epithelium in the duodenum or oesophagus.
◦Survives in mucus layer that coats epithelium and causes chronic inflammation of the mucosa.
◦The organism is non invasive but recruits and activates inflammatory cells.
◦H. pylori penetrate mucus layer lining of the stomach’s epithelium, attracted to chemotactic substances haemin and urea.
◦Recruits and activates inflammatory cells; they release urease that cleaves urea, producing NH3 that neutralises stomach acid and also to protect itself.
◦H. pylori cytotoxin and the ammonia produced by its urease cause destruction of the mucus-producing cells, exposing underlying connective tissues to stomach acid.
What tests are carried out to find H.pylori?
◦Blood antibody
◦Stomach biopsy
◦Stool antigen
◦Endoscopy
◦Urease breath test - Radioactively labelled urea is administered orally and if H. pylori is present in the patient’s stomach, the urease produced by the organism will split the urea to CO2, which will be radioactively labelled and then exhaled. The amount exhaled is measured.
What diseases are caused by H.pylori?
◦Acute gastritis
◦Stomach and duodenal ulcers
What is the treatment for H.pylori conditions?
A combination therapy of two or more antibiotics:
◦Amoxicillin
◦Clarithromycin
◦PPIs – Omeprazole
What is the structure of Hepatitis B?
Hepadnaviridae; It is divided into genotypes A-D.
- Circular DNA
- Partly double stranded and partly single stranded
- Non covalently closed genome with four overlapping genes
- Enveloped
- Icosahedral
- Multifunctional reverse transcriptase/DNA polymerase in virion
How is hepatitis B transmitted?
Infectious HBV is present in all body fluids of an infected individual – therefore blood, semen, saliva and breastmilk, for example, serve as sources of infection. In areas of high endemicity, the majority of the population becomes infected at or shortly after birth from a chronically infected mother or from an infected sibling. Individuals infected at a young age have a significant chance of becoming chronic carriers and they also have an increased risk of developing hepatocellular carcinoma later in life.
HBV is primarily a disease of infants in the developing world and in Western countries, it is mostly confined to adults who usually contract the infection through sexual intercourse or blood exposure from shared needles during IV drug use.
What is the pathogenesis of hepatitis B?
Fully differentiated hepatocytes are the primary cell type infected by HBV. The primary cause of hepatic cell destruction appears to be cell-mediated immune response, which results in inflammation and necrosis.
How does hepatitis B cause acute infections?
Following infection, HBV has a long but variable incubation period of between 45 and 120 days. Following this period, there is a prejaundice phase, characterised by mild fever, malaise, anorexia, myalgia and nausea. The acute icteric phase then follows and lasts for 1 to 2 months. During this phase, dark urine, due to bilirubinuria and jaundice are evident. The liver is usually enlarged and tender.
During the incubation period, HbsAg and HBeAg are the first indicators of a HBV infection and their presence indicates and active infection – however it does not distinguish between an acute and chronic infection.
Fulminant hepatitis: Where extensive necrosis of the liver occurs in 1-2% of the population with a HBV infection.
How does hepatitis B cause chronic infections?
The asymptomatic carriers of HBsAg are the most common type of persistently infected individuals. They usually have anti-HBeAg antibodies and little or no infectious virus in their blood.
Severe chronic hepatitis results in more frequent exacerbations of acute symptoms including progressive liver damage and potentially leading to cirrhosis and/or hepatocellular carcinoma.
Hepatocellular carcinoma typically appears many years after the primary HBV infection and the tumour itself is rather slow growing and only occasionally metastasises. Clinically, a patient exhibits weight loss, right upper-quadrant pain, fever and intestinal bleeding.
How is hepatitis B found in investigations?
- Elevation of ALTs, ASTs, bilirubin and prothrombin
- ELISA for detection of antigens and antibodies can distinguish between genotypes A-D
- Identification of specific antiviral antibodies and viral antigens permits differentiating between acute and chronic HBV infections
What is the treatment for hepatitis B infections?
In acute hepatitis, the immune system controls the infection and eliminates the virus in about 6 months. Drug therapy may be required with acute severe liver impairment that accompanies fulminant hepatitis.
The goal for treatment in patients with chronic hepatitis is to reduce the risk of progressive chronic liver disease and other long-term complications from chronic HBV such as cirrhosis and hepatocellular carcinoma. The most commonly used drugs include interferon-α or one of a large number of nucleoside/nucleotide antiviral agents e.g.:
- Adefovir
- Entecavir
- Tenofovir
What is the prevention for hepatitis B infections?
- Generalised and targeted vaccination
- Safe sexual intercourse
- Mother to child interventions (when the child is born, it will get vaccinated and immunoglobulins)
- Screening blood and products in healthcare
- Post exposure prophylaxis e.g. needlestick injury
What is the structure of Hepatitis C?
- Flaviviridae
- A positive strand, single-stranded, nonsegmented RNA genome.
- Enveloped
- Icosahedral
- Genomic RNAs serve as messenger RNAs and are infectious
- Virions do not contain any enzymes
How is hepatitis C transmitted?
- IV drug use
- Blood transfusion
- Patients on haemodialysis
- Tattoos
- Mother to infant
- Sexual intercourse
What is the pathogenesis of hepatitis C?
In the infected individual, viral replication occurs in the hepatocyte and in the lymphocytes and macrophages as well. Certain strains of HCV have been associated with hepatocellular carcinoma development, even in the absence of cirrhosis.
How do hepatitis C infection individuals present?
About 25% of infected individuals present with acute hepatitis and jaundice. Infections can progress to chronic hepatitis and cirrhosis and some of these individuals go on to develop hepatocellular carcinoma.
How is hepatitis C tested for?
- Reverse transcriptase of the viral RNA followed by PCR
* Antibodies that react with a combination of recombinant viral proteins
What is the treatment for hepatitis C infections?
- IFN-γ plus ribavirin – cure rate is 40-80% as side effects are sometimes rate limiting
- No vaccine is available
How is hepatitis C prevented?
- Use of clean needles
- Generalised and targeted vaccination
- Safe sexual intercourse
- Mother to child interventions (when the child is born, it will get vaccinated and immunoglobulins)
- Screening blood and products in healthcare
- Post exposure prophylaxis e.g. needlestick injury
What is the structure of HIV?
- A lentivirus (which is a slow replicating retrovirus).
- A single stranded, positive-sense, linear RNA virus
- Has two copies per virion
- Enveloped
- Icosahedral
What are the two types of HIV?
There are two types of HIV, HIV-1 and HIV-2.
HIV-1 is more virulent, more infective and more widespread geographically, whereas HIV-2 is not as virulent and is localised exclusively to Western Africa.
How does HIV replicate?
- Attachment to a specific cell surface receptor - bind to CD4 receptor. The virus infects helper T cells, lymphocytes, monocytes and dendritic cells.
- Entry of the virus into the cell - chemokine receptor needed
- Reverse transcription of viral RNA - after entering host cell, HIV RNA transcribed into DNA by reverse transcriptase. Reverse transcriptase cannot proofread, so errors often occur during conversion into DNA provirus.
- Integration of the provirus into the host cell DNA - in nucleus, viral integrase cleaves chromosomal DNA and inserts provirus, becoming stable part of genome. The insertion is random. Therefore HIV has two genomic forms: single-stranded RNA present in the extracellular virus and proviral double-stranded DNA within the cell.
- Transcription and translation of integrated viral DNA sequences - With host cell activation, DNA is transcribed to mRNA and viral genomic RNA. Viral mRNAs are translated to give viral enzymes and structural proteins.
- Regulation - Rev and Tat proteins are made from spliced mRNAs, which prevent premature dissociation from the DNA template and transport out of the nucleus, bypassing the splicing machinery. This enables viral mRNAs to be correctly translated into polypeptides, which will be packaged into new virions.
- Assembly and maturation of infectious progeny - As the virion buds from the surface, viral protease is activated and cleaves the polyproteins into their component proteins, which then assemble into the mature virion. Cleavage is a necessary step into the maturation of the infectious virus.
