Latest Posts by t-b-a-blr-blog - Page 5

Immuno

ANTIBIOTICS CHEAT SHEET :)

Also, REMEMBER!!!!

* Sulfonamides compete for albumin with:

Bilirrubin: given in 2°,3°T, high risk or indirect hyperBb and kernicterus in premies

Warfarin: increases toxicity: bleeding

* Beta-lactamase (penicinillase) Suceptible:

Natural Penicillins (G, V, F, K)

Aminopenicillins (Amoxicillin, Ampicillin)

Antipseudomonal Penicillins (Ticarcillin, Piperacillin)

* Beta-lactamase (penicinillase) Resistant:

Oxacillin, Nafcillin, Dicloxacillin

3°G, 4°G Cephalosporins

Carbapenems 

Monobactams

Beta-lactamase inhibitors

* Penicillins enhanced with:

Clavulanic acid & Sulbactam (both are suicide inhibitors, they inhibit beta-lactamase)

Aminoglycosides (against enterococcus and psedomonas)

* Aminoglycosides enhanced with Aztreonam

* Penicillins: renal clearance EXCEPT Oxacillin & Nafcillin (bile)

* Cephalosporines: renal clearance EXCEPT Cefoperazone & Cefrtriaxone (bile)

* Both inhibited by Probenecid during tubular secretion.

* 2°G Cephalosporines: none cross BBB except Cefuroxime

* 3°G Cephalosporines: all cross BBB except Cefoperazone bc is highly highly lipid soluble, so is protein bound in plasma, therefore it doesn’t cross BBB.

* Cephalosporines are "LAME“ bc they  do not cover this organisms 

L  isteria monocytogenes

A  typicals (Mycoplasma, Chlamydia)

M RSA (except Ceftaroline, 5°G)

E  nterococci

* Disulfiram-like effect: Cefotetan & Cefoperazone (mnemonic)

* Cefoperanzone: all the exceptions!!!

All 3°G cephalosporins cross the BBB except Cefoperazone.

All cephalosporins are renal cleared, except Cefoperazone.

Disulfiram-like effect

* Against Pseudomonas:

3°G Cef taz idime (taz taz taz taz)

4°G Cefepime, Cefpirome (not available in the USA)

Antipseudomonal penicillins

Aminoglycosides (synergy with beta-lactams)

Aztreonam (pseudomonal sepsis)

* Covers MRSA: Ceftaroline (rhymes w/ Caroline, Caroline the 5°G Ceph), Vancomycin, Daptomycin, Linezolid, Tigecycline.

* Covers VRSA: Linezolid, Dalfopristin/Quinupristin

* Aminoglycosides: decrease release of ACh in synapse and act as a Neuromuscular blocker, this is why it enhances effects of muscle relaxants.

* DEMECLOCYCLINE: tetracycline that’s not used as an AB, it is used as tx of SIADH to cause Nephrogenic Diabetes Insipidus (inhibits the V2 receptor in collecting ducts)

* Phototoxicity: Q ue S T  ion?

Q uinolones

Sulfonamides

T etracyclines

* p450 inhibitors: Cloramphenicol, Macrolides (except Azithromycin), Sulfonamides

* Macrolides SE: Motilin stimulation, QT prolongation, reversible deafness, eosinophilia, cholestatic hepatitis

* Bactericidal: beta-lactams (penicillins, cephalosporins, monobactams, carbapenems), aminoglycosides, fluorquinolones, metronidazole.

* Baceriostatic: tetracyclins, streptogramins, chloramphenicol, lincosamides, oxazolidonones, macrolides, sulfonamides, DHFR inhibitors.

* Pseudomembranous colitis: Ampicillin, Amoxicillin, Clindamycin, Lincomycin.

* QT prolongation: macrolides, sometimes fluoroquinolones

Bacteria and fungi in petri dishes

Klari Reis uses plastics, paints and other mediums to create the idea of bacteria and biological matter within petri dishes

05-11-18 bio notes! i tried out a new background and i think it looks really pretty!! i hope you guys like it :). i had my first test for my dissection lab and my group ended up getting 100%! the next few tests are harder, but i think we’ll all do gr8. i hope you all had a great week!

Different anatomy notes form this semester Supplies used (not all at once, I mix and match): Faber-Castell Coloured Pencils (48 Pack) - https://amzn.to/2Kd1mUy Staedtler Triplus Fineliners - http://amzn.to/2pghonI Stabilo Point 88 Fineliner - https://amzn.to/2qU8fC9 Sharpie Pens - https://amzn.to/2HTRmP2 Uni Pin 0.1 Fineliner - https://amzn.to/2HmXp1z Crayola Supertips - https://amzn.to/2HVW1jr Bic Ballpoint Pen - https://amzn.to/2HmCjk0 Stabilo Swing Cool Highlighters - https://amzn.to/2HKxPTu

This bedroom is soooo pretty, this colour palette is everything.

Tumblr room🕯

Tumblr room🌹

Pizza heaven! Quick and easy! Recipe up on blog: www.studydiaryofamedstudent.wordpress.com

Flashcards  with quizlet!

For more: instagram: https://www.instagram.com/studydiaryofamedstudent/

New background! Download higher quality photo here!

https://drive.google.com/file/d/1F5SlJmB8YiNNtGuKrc-QtMnrrjZ1tOHL/view?usp=sharing

April Background

I created this new background for April! A reminder to all the great girls out there who are awesome human beings!

For a high quality foto, check out the link in my previous post!

https://www.instagram.com/studydiaryofamedstudent/

20.1.18 // studygram: alimastudies

i don’t normally upload pictures of my homework because i don’t tend to spend a lot of effort or time on them as i know i won’t be using it again, but for this biology homework i thought i would do it nicely and use it for my future notes! i need to work on my handlettering oh dear god ahhh i used a crayola supertip for it

be patient, good things are coming your way :)

Me this week

Motivation can be experienced differently for each of us. While some people just get this kind of impulsive motivation, others develop their motivation through actions.

@masterposts @studymasterposts

I would like to show you why it is wrong to wait for your motivation and why you should just do something instead - it doesn’t matter how big your action is.

How to gain motivation

OK, so just like I told you above there exists a concept of just doing some random shit. That means that you start small even though you know that you should do more.

You need to write an essay in two days but you’re spending all the time watching a cat jumping from a window? (if you followed the link - yeah, it’s funny but please continue reading my bullshit lol)

The solution to your stressful task is to start doing something even if it doesn’t seem big or challenging. (In our example with the essay this would mean, starting the writing program/ writing “Outline for my essay” on a paper/ starting a draft as small as possible etc.)

You need to clean your room? Search the smallest task and do this one: put your old pizza that’s laying on the floor in the trash can and your underwear where it belongs - you don’t want your dog to eat it, right?

You want to get fit and start working out? Maybe you had an impulse of motivation one week ago, but now you’re laying on the couch like the cutest panda ever, eating sweets and asking yourself where your motivation went.

You already have an idea what you need to do now, right? Just do one push-up/ lunge/ crunch whatever.

It doesn’t matter how small your action is, but if you experience the feeling of this small success you’ll keep going.

How to stay motivated (Part 1)

Now that you’re finally motivated (doesn’t matter how), you really need to stick on that workflow or whatever you’re trying to achieve. One of the simplest things to maintain your motivation is to think of why you started. Here are some examples:

I know that I’m able to get this shit done.

I want to prove that I can do more than I thought.

I want to show everybody that I’m taking my responsibilities seriously.

I need to pass that exam.

Failing is worse than studying.

etc. (the reason needs to come from your heart - if it isn’t true, it won’t work)

Another way (which is pretty simple and works pretty good for most of the people) is the chain system: 

Draw 31 boxes (for one month) and tick one each day after completing your task. This method is pretty common because it is pretty simple and works for no matter how much time you want to do your habit. (The lovely @emmastudies has created a lot of wonderful printables, maybe you find more details there for study tracking.) After keeping up with the growing chain, you’ll be thinking twice before interrupting the chain and stopping your chain.

Part 2 will be posted on Friday, 06.01.

Innate Immunity - intro

First line of defence + first to act

A primitive response (exists in animals and some plants)

Non-specialised and without ‘memory’

Consists of:

Physical barriers (eg skin and mucosa//tight junctions, airflow)

Chemical barriers (eg enzymes, lung surfactant, antimicrobals)

Soluble mediators of inflammation (eg cytokines)

Microbal defence (eg commensal competition, secreted antimicrobals)

Cells (eg phagocytes)

Receptors to recognise presence of pathogen/injury - results in inflammation

Soluble Mediators

Complement Proteins

liver-derived 

circulate in serum in inactive form

activated by pathogens during innate response

functions include lysis, chemotaxis and opsonisation

Auxiliary Cells

Mediate inflammation as part of the immune response. The main auxiliary cells involved in the immune response are Basophils, Mast cells and Platelets.

Basophils 

Leukocyte containing granules 

on degranulation release histamine + platelet activating factor

causing increased vascular permeability and smooth muscle contraction

also synthesise and secrete other mediators that control the development of immune system reactions

Mast Cells

Also contain granules 

However they are not circulating cells - found close to blood vessels in all types of tissue especially mucosal and epithelial tissues.

rapidly release inflammatory histamine but this is IgE dependant so not innate

Platelets 

normally function in blood clotting

also release inflammatory mediators

Cytokines and chemokines

Produced by many cells but especially mØ (macrophages), initiate inflammatory response and act on blood vessels 

interferons - antiviral protection

chemokines - recruit cells

interleukines - fever inducing, IL-6 induces acute phase proteins 

IL-1 - encourages leukocytes to migrate to infected/damaged tissue

as does tumour necrosis factor (TNFa)

Acute phase proteins

Liver derived proteins 

plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation

called the acute-phase reaction 

triggered by inflammatory cytokines ( IL-1, IL-6, TNFα)

help mediate inflammation ( fever, leukocytosis, increased cortisol, decreased thyroxine, decreased serum iron, etc)

activate complement opsonisation 

Inflammation 

Cells

Cytotoxic Cells

Eosinophils/natural killer cells, cytotoxic T cells

kill target via release of toxic granules 

dendritic cell derived IL-12 helps activate NK cells

Phagocytes

mono-nuclear = long-lived; polynuclear = short-lived

engulf, internalize and destroy 

phagosome forms around microbe

enzyme filled with lysosomes fuses to form phagolysosome

organism is digested

fragments are either ‘presented’ or exocytosed

phagocytosis requires recognition of microbe via receptors for

PAMPs (pathogen associated molecular patterns - eg flagella or capsule) - recognised by toll-like receptors 

activated complement

antibody

The innate immune response primes for the adaptive 

B-cells are primed by activated complement

Th1 cell differentiation needs pro-inflammatory cytokines

Passive Immunotherapy

Active immunotherapies:

Cytokines (TNFa IL-2, IFNs)

Cancer vaccines

tumour CTL and APC

DC priming

Passive immunotherapy:

Administration of monocolnal (clone derived asexually from a single individual or cell) antibodies which target either tumour-specific or over expressed antigens

Generally comprised of antibodies made outside of the body (in a lab)

administered to patients to provide immunity against a disease, or to help fight existing disease

do not stimulate a patient’s body to ‘actively’ respond to a disease the way a vaccine does

immunogen is given several times to induce a strong secondary response

blood serum contains many different antibodies to the immunogen

most immunogens have multiple antigenic epitopes 

each stimulates a different B cell clone/receptor –> polyclonal antibody (PAb) response 

Monoclonal antibody (mAb) therapy is the most widely used form of cancer immunotherapy. Monoclonal antibodies cannot be purified from a polyclonal sample and are derived from a single clone/specific for a single epitope.

Antibodies in cancer therapy:

Trigger immune system to attack cancer cells 

Block molecules that stop the immune system working (checkpoint inhibitors)

 Block signals telling cancer cells to divide 

Carry drugs or radiation to cancer cells

Checkpoint inhibitors

Immune system uses particular molecules to stop it being over activated and damaging healthy cells  - these are known as checkpoints

some cancers make high levels of checkpoint molecules to switch of immune system T cells which would normally attack cancer cells

examples of targets include CTLA-4, PD-1 and PD-L1 (programmed death ligand 1)

Blocking cell division signals 

Cancer cells often express large amounts of growth factor receptors on their surface –> rapid cell division when growth factors stimulate them

some monoclonal antibodies stop growth factor receptors working

either by blocking the signal or the receptor itself 

cancer no longer gets signal to divide

Carrying drugs/radiation

drugs or radioisotopes can be attached to monoclonal antibodies

the mAB binds to the cancer cell, delivering directly

known as conjugated MABs

Antibodies (Human)

The ‘foot’ (bottom) of the antibody is known as the Fc fragment - binds to cells, binds to complement = effector function (kills or removes antigen)

The top (antigen binding) is the Fab fragment

Chains are held together with disulphide binds

Associated molecules allow intracellular signalling 

Normally 3X constant heavy chain domains per chain and a hinge region (except μ and ε which have 4 and no hinge region)

Classes of Immunoglobulins

The five primary classes of immunoglobulins are IgG, IgM, IgA, IgD and IgE,  distinguished by the type of heavy chain found in the molecule. 

IgG - gamma-chains

IgMs - mu-chains

IgAs - alpha-chains

IgEs - epsilon-chains

IgDs - delta-chains.

Differences in heavy chain polypeptides allow different types of immune responses. The differences are found primarily in the Fc fragment. There are only two main types of light chains: kappa (κ) and lambda (λ), and any antibody can have any combination of these 2 (variation).

IgG 

monomer

Gamma chains

70-85% of Ig in human serum. 

secondary immune response 

only class that can cross the placenta - protection of the newborn during first 6 months of life

principle antibody used in immunological research and clinical diagnostics

21 day half life

Hinge region (allows it to make Y and T shapes - increasing chance of being able to bind to more than one site)

Fc strongly binds to Fcγ receptor on phagocyte - opsono-phagocytosis

Activates complement pathway

IgM

Serum = pentamer 

Primary immune responses - first Ig to be synthesised

complement fixing 

10% of serum Ig 

also expressed on the plasma membrane of B lymphocytes as a monomer - B cell antigen receptor

H chains each contain an additional hydrophobic domain for anchoring in the membrane

Monomers are bound together by disulfide bonds and a joining (J) chain.

Each of the five monomers = two light chains (either kappa or lambda) and two mu heavy chains.

heavy chain = one variable and four constant regions (no hinge region)

can cause cell agglutination as a result of recognition of epitopes on invading microorganisms. This antibody-antigen immune complex is then destroyed by complement fixation or receptor mediated endocytosis by macrophages.

In humans there are four subclasses of IgG: IgG1, IgG2, IgG3 and IgG4. IgG1 and IgG3 activate complement.

IgD 

B cell receptor

<1% of blood serum Ig

has tail pieces that anchor it across B cell membrane

forms an antigen specific receptor on mature B cells - consequently has no known effector function (don’t kill antigens, purely a receptor) (IgM as a monomer can also do this)

IgE 

Extra rigid central domain

has the most carbohydrates

IgE primarily defends against parasitic invasion and is responsible for allergic reactions.

basophils and tissue mast cells express very high affinity Fc receptors for IgE - mast cells then release histamine

so high that almost all IgE is bound

sensitizes (activates) mucosal cells and tissues 

protects against helminth parasites

IgE’s main purpose is to protect against parasites but due to improved sanitation these are no longer a prevalent issue across most of the world. Consequently it is thought that they become over activated and over sensitive while looking for parasites and start reacting to eg pollen and causing allergies.

IgA

Exists in serum in both monomeric (IgA1) and dimeric (IgA2) forms (dimeric when 2 Fcs bind via secretory complex)

15% of the total serum Ig.

4-7 day half life

Secretory IgA2 (dimer) = primary defense against some local infections

Secreted as a dimer in mucous (e.g., saliva, tears)

prevents passage of foreign substances into the circulatory system

Isotype: class of antibody (IgD, IgM etc)

Allotype: person specific alleles 

Idiotype: (hyper) variable region - antibody specificity 

Leukocyes (WBCs) & Defence

A summary

Neutrophils -  non-specific defence against bacteria and fungi

Eosinophils -Defence against parasites; dampen allergic response

Basophils  - Anaphylactic & inflammation response

Monocytes - Mature into macrophages, engulf foreign substances;  remove aged RBCs and other debris

Lymphocyes - Recognise antigens, various roles

Haematology

White Blood Cells (Leukocytes)

Neutrophils, eosinophils and basophils = granulocytes (polymorphonuclear leukocytes)

Monocytes & lymphocyes = mononuclear

Neutrophils

Most numerous (~60% of WBC)

Nucleus divided into lobes

Cytoplasm contains small granules

Stains pink with Romanowsky dyes

Lifespan of 6-10hrs

Exit into tissues - non-specific defence against bacteria and fungi

Eosinophils

1% of circulating leukocytes 

Large cytoplasmic granules - stain strongly with acidic dye eosin

Nucleus is bilobed

Circulate for 4-5hrs

Exit to tissues –> 

Defence against parasites 

Dampen allergic response

Tissue eosinophils are also capable of responding to bacterial and fungal infection in a similar way to neutrophils.

Basophils

Least numerous (<1%)

Large granules stain strongly with basic dye methylene blue

Involved in anaphylactic hypersensitivity and inflammatory reactions

Monocytes

5% of circulating leukocytes

Large cell

Kidney/clefted shaped nucleus

Scattering of delicate azurophilic granules

Circulate for 10hrs

Mature into phagocytic tissue macrophages

Responsible for the removal of aged RBCs and other debris

Process and present antigens to T-lymphocytes 

(Macrophages are formed in response to an infection or accumulating damaged or dead cells. Large, specialized cells that recognize, engulf and destroy target cells.)

Lymphocytes

Second most common leukocyte (33%)

Much less cytoplasm - nucleus almost fills cell

Variable lifespan

Receptors on surface recognise foreign substances

Several types of lymphocyte - click here

Archaea

Archaeans are single-celled and join bacteria to make up the Prokaryotes.  The Archaea classification is a very recent discovery, due to the similarities in appearance and behaviour to bacteria they weren’t separated until the late 1970′s. They mostly live in extreme environments and can be sub grouped: 

Methanogens - produce methane gas as a waste product of their “digestion,” or process of making energy.

Halophiles - live in salty environments.

Thermophiles - live at extremely hot temperatures.

Psychrophiles — those that live at unusually cold temperatures.

Like bacteria, archaea lack a true nucleus. Both bacteria and archaea usually have one DNA molecule suspended in the cell’s cytoplasm contained within a cell membrane. Most, but not all, have a tough, rigid outer cell wall.

use a variety of substances for energy, including hydrogen gas, carbon dioxide and sulfur. 

many archaea thrive in conditions mimicking those found more than 3.5 billion years ago. [eg oceans that regularly reached boiling point — an extreme condition not unlike the hydrothermal vents and sulfuric waters where archaea are found today]

Antimicrobial Agents  - Cell wall inhibitors

Based on mode of action • divided into families based on chemical structure

 Modes of action Interference with: 

cell wall synthesis 

protein synthesis 

nucleic acid synthesis 

plasma membrane integrity 

metabolic pathway 

Inhibitors of Bacterial Cell Wall (peptidoglycan) Synthesis 

The Beta-lactam Family 

The Glycopeptides 

Peptidoglycan is composed of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) repeat units, and amino acids.  Each NAM is linked to peptide chain and the peptide chains are cross-linked.

β-lactams 

Includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems.

class of broad-spectrum antibiotics containing a β-lactam ring

Bacterial transpeptidase enzymes are responsible for catalysing cross-linking of the peptide chains

β-lactam ring bind to these transpeptidases – this inhibits cross-linking between peptide chains and prevents synthesis of stable PG

Cell wall synthesis ceases and the bacterial cells eventually die due to osmotic instability or autolysis. 

Glycopeptides 

Polypeptide agents - basic structural elements amino acids 

Vancomycin: 

complexes with peptide portion of peptidoglycan’s precursor units 

vancomycin is a large hydrophilic molecule able to form hydrogen bonds with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides

preventing PG transglycosylation reaction – PG precursor subunits (NAG-NAM+peptide) cannot be inserted into peptidoglycan matrix;

Vancomycin also alters bacterial-cell-membrane permeability and RNA synthesis

Uses:  serious Gram positive infections e.g. MRSA wound infection

Adverse effects:

damage to auditory nerve 

hearing loss (ototoxicity) 

“Red man/neck” syndrome - rash on face, neck, upper torso 

Antimicrobial Agents - Inhibition of DNA and Protein Synthesis

Bacterial chromosome replication

DNA replication

Bacterial Topoisomerases 

maintain DNA in appropriate state of supercoiling 

cut and reseal DNA

DNA gyrase (topoisomerase II) introduces negative supercoils 

Topoisomerase IV decatenates circular chromosomes 

these are the targets of the quinolone antibacterial agents 

Quinolones

bind to bacterial DNA gyrase and topoisomerase IV after DNA strand breakage 

prevent resealing of DNA 

disrupt DNA replication and repair 

bactericidal (kill bacteria)

Fluoroquinolone is particularly useful against

Gram +ves: Staphylococcus aureus, streptococci 

Gram -ves: Enterobacteriacea; Pseudomonas aeruginosa 

Anaerobes: e.g. Bacteroides fragilis 

many applications e.g. UTIs, prostatitis, gastroenteritis, STIs 

Adverse effects

Relatively well tolerated

GI upset in ~ 5% of patients 

allergic reactions (rash, photosensitivity) in 1 - 2% of patients 

Inhibition of Bacterial Protein Synthesis 

Macrolides 

in 1952: Erythromycin was isolated as the first macrolide (Streptomyces erythreus) 

Newer macrolides: clarithromycin, azithromycin 

Structurally they consist of a lactone ring (14- to 16-membered) + two attached deoxy sugars 

Mode of action 

bind reversibly to bacterial 50S ribosomal subunit 

causes growing peptide chain to dissociate from ribosome → inhibiting protein synthesis 

bacteriostatic (stops reproduction)

Macrolides’ spectrum of activity

good antistaphylococcal and antistreptococcal activity 

treatment of respiratory & soft tissue infections and sensitive intracellular pathogens • e.g. Chlamydia, Legionella 

Adverse effects

Generally well tolerated

nausea 

vomiting 

diarrhoea 

rash 

Aminoglycosides

large family of antibiotics produced by various species of Streptomyces (“mycin”) and Micromonospora (“micin”) 

include: streptomycin, neomycin, kanamycin, gentamicins, tobramycin 

Structure = linked ring system composed of aminosugars and an aminosubstituted cyclic polyalcohol 

Mode of action of aminoglycosides

Bind irreversibly to 30S ribosomal subunit 

disrupt elongation of nascent peptide chain 

translational inaccuracy → defective proteins 

bactericidal 

Spectrum of activity 

broad spectrum; mainly aerobic G-ve bacilli (e.g. P. aeruginosa) 

used to treat serious nosocomial infections (hospital acquired infections)

First TB antibiotic

Used for cystic fibrosis 

Adverse effects

all aminoglycosides have low Therapeutic Index (only a small amount needed to become toxic)

renal damage, ototoxicity, loss of balance, nausea 

Cryptosporidium

Cryptosporidium is a microscopic parasite that causes the diarrhoeal disease cryptosporidiosis. Both the parasite and the disease are commonly known as “Crypto.”

The parasite is protected by an outer shell (oocyst)

Allows survival outside the body for long periods of time 

Very tolerant to chlorine disinfection.

Water is the most common form of spread

Poses serious risk to immunocompromised individuals, eg AIDS; cancer and transplant patients who are taking certain immunosuppressive drugs. 

Symptoms

Symptoms of cryptosporidiosis generally begin 2 to 10 days (average 7 days) after infection. 

Watery diarrhea

Stomach cramps or pain

Dehydration

Nausea

Vomiting

Fever

Weight loss

Some people with Crypto will have no symptoms at all.

Symptoms usually last about 1 to 2 weeks (with a range of a few days to 4 or more weeks) in persons with healthy immune systems. Occasionally, people may experience a recurrence of symptoms after a brief period of recovery before the illness ends. Symptoms can come and go for up to 30 days.

In immunocompromised persons Cryptosporidium infections could possibly affect other areas of the digestive tract or the respiratory tract.

Diagnosis & Detection

Cryptosporidium oocysts in a modified acid-fast stain. (CDC Photo; DPDx)

Examination of stool samples. 

Detection can be difficult - several stool samples over several days.

acid-fast staining, direct fluorescent antibody [DFA] , and/or enzyme immunoassays 

Molecular methods (e.g., polymerase chain reaction – PCR) are increasingly used in reference diagnostic labs,

Treatment

Most people who have healthy immune systems will recover without treatment. Young children and pregnant women may be more susceptible to dehydration resulting from diarrhoea. 

For those persons with AIDS, anti-retroviral therapy (improves the immune status) will also decrease or eliminate symptoms of cryptosporidiosis. However, even if symptoms disappear, cryptosporidiosis is often not curable and the symptoms may return if the immune status worsens.

Cryptosporidium and AIDS

Advanced immunosuppression — typically CD4 T lymphocyte cell (CD4) counts of <100 cells/µL — is associated with the greatest risk for prolonged, severe, or extraintestinal cryptosporidiosis. 

The three species that most commonly infect humans are Cryptosporidium hominis, Cryptosporidium parvum, and Cryptosporidium meleagridis. Infections are usually caused by one species, but a mixed infection is possible.

Up to 74% of diarrhoea stools in AIDS patients demonstrating the organism in less developed countries where potent antiretroviral therapy  is not widely available, 

cryptosporidiosis has decreased and occurs at an incidence of <1 case per 1000 person-years in patients with AIDS.4 Infection occurs through ingestion of Cryptosporidium oocysts. Viable oocysts in feces can be transmitted directly through contact with infected humans or animals, particularly those with diarrhea. Oocysts can contaminate recreational water sources such as swimming pools and lakes, and public water supplies and may persist despite standard chlorination (see Appendix: Food and Water-Related Exposures). Person-to-person transmission is common, especially among sexually active men who have sex with men.

Fever is present in approximately one-third of patients and malabsorption is common. 

The epithelium of the biliary tract and the pancreatic duct can be infected with Cryptosporidium, leading to sclerosing cholangitis and to pancreatitis secondary to papillary stenosis, 

Pulmonary infections also have been reported, and may be under-recognized.

Treatment 

ART with immune restoration to a CD4 count >100 cells/µL usually leads to resolution

Treatment of diarrhoea with anti-motility agents (AIII) may be necessary. 

Patients with biliary tract involvement may require endoscopic retrograde choledocoduodenoscopy for diagnosis. 

Immune reconstitution inflammatory syndrome (IRIS) has not been described in association with treatment of cryptosporidiosis.

No pharmacologic interventions are known to be effective in preventing the recurrence of cryptosporidiosis.

No therapy has been shown to be effective without ART. 

Penicillin

Penicillin is a widely used antibiotic prescribed to treat staphylococci and streptococci bacterial infections. 

beta-lactam family 

Gram-positive bacteria = thick cell walls containing high levels of peptidoglycan

gram-negative bacteria = thinner cell walls with low levels of peptidoglycan and surrounded by a lipopolysaccharide (LPS) layer that prevents antibiotic entry 

penicillin is most effective against gram-positive bacteria where DD-transpeptidase activity is highest.

Examples of penicillins include:

amoxicillin

ampicillin

bacampicillin

oxacillin

penicillin

Mechanism(s)

Penicillin inhibits the bacterial enzyme transpeptidase, responsible for catalysing the final peptidoglycan crosslinking stage of bacterial cell wall synthesis.

Cells wall is weakened and cells swell as water enters and then burst (lysis)

Becomes permanently covalently bonded to the enzymes’s active site (irreversible)

Alternative theory: penicillin mimics D-Ala D-Ala

Or may act as an umbrella inhibitor

Resistance

production of beta-lactamase - destroys the beta-lactam ring of penicillin and makes it ineffective (eg Staphylococcus aureus - most are now resistant)

In response, synthetic penicillin that is resistant to beta-lactamase is in use including egdicloxacillin, oxacillin, nafcillin, and methicillin. 

Some is resistant to methicillin - methicillin-resistant Staphylococcus aureus (MRSA).  

Demonstrating blanket resistance to all beta-lactam antibiotics -extremely serious health risk.

Influenza

Happy flu season! I’ve just been stuck inside for 5 days with a mild case, so this is a bit bitter

There are 3–5 million cases of flu per year, and ~375,000 deaths, usually in older, younger, and immunocompromised individuals.

Enveloped, Single-stranded RNA virus

First identified in 1933, but existed long before

Generally considered an infection of the bronchi

so effectively a form of bronchitis – i.e. it causes inflammation of the bronchi 

There are 3 types - A, B and C

B & C appear restricted to humans 

C is less common

A is found in wide range of species including pigs and poultry as well as man

Type A appears to be responsible for more severe disease

Basics

Transmission by aerosols

Incubation ~2 days

Contagious during first 3-5days of illness

Symptoms – fever, myalgia, headache, dry cough, sore throat, aches, fatigue

Recovery ~7-10 days for most

Complications – most frequent = secondary bacterial pneumonia, rarely = viral pneumonia, myocarditis, encephalitis

No specific treatment

Vaccination for high risk groups including the elderly, health care workers, those with underlying respiratory conditions.

Avian

The main reservoir is wildfowl that are resistant to the disease

doesn’t usually affect animals other than poultry and pigs

However some transfer events occur

Seasonal

Incidence highest in winter

Strains vary from year to year -  hard to predict and vaccinate (this year’s vaccine has been pretty rubbish)

Pandemic

Can be caused by any strain that has not been seen in the human population for many years

New strains evade the herd immunity that exists to previously encountered strains

1918 /19 –( Spanish) estimated 40-50 million deaths worldwide

1957 – Influenza A/H1N1 (Asian)

1968 – Influenza A/H3N2 (Hong Kong)

Eventually the virus runs out of susceptible hosts and the epidemic fizzles out

Experts generally agree another pandemic is inevitable, and may be imminent – maybe we have had some minor pandemics 

16000 confirmed H1N1 deaths in 2009 affecting over 200 countries

Consensus is that the prompt action of the Hong Kong authorities probably prevented a pandemic in 1997

The prediction is scary - for industrialised countries they predic 1.0 – 2.3 million hospitalisations

280,000-650,000 deaths 

in two years

A network of 112 centres monitor flu isolates to identify unusual strains that can then be examined further

The WHO has a Pandemic Preparedness Plan in place http://www.who.int/influenza/preparedness/pandemic/en/

Diagnosis

Generally based on GP diagnosis

Virus isolation / virus demonstration from nasopharyngeal secretions during acute phase

Demonstration of viral antigen in secretions

Antibody rise using paired sera ( 1st sample taken between days 1-3 of illness, 2nd taken around day 12 of illness) by haemagglutination inhibition or complement fixation test

Molecular methods evolving rapidly – in particular in response to the recent epidemic/pandemic strains emerging

A range of respiratory illnesses have the same symptoms, only laboratory testing can confirm the aetiological agent

Treatment/Vaccination 

In the UK NICE argue that immunisation against predicted strains is the best form of defence – traditionally focused on the elderly and those with underlying lung problems, but recently started rolling out a childhood vaccine (nasal spray)

Vaccines generally based on the H & N surface structures which mutate, however hopes of an M protein based vaccine which will give longer lasting protection raised recently

Antivirals

Antivirals not recommended in otherwise healthy people (amantadine should not be used at all) - should ride it out

However when incidence reaches a certain level zanamivir and oseltamivir should be used in those considered high risk for the development of complications – PROVIDED THAT TREATMENT IS STARTED WITHIN 48 HOURS OF ONSET OF SYMPTOMS

Resistance is becoming an issue