-28/11/17-

Strep throat.

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

PSEUDOmonas aeroginosa.

Pneumonia 

Sepsis (black lesion on skin).

External otitis (swimmers ear)

UTI,Drug use .

Diabetic osteomylitis

Aminoglycoside„,extended spectrum penicillin(pipracilin,ticarcillin)

Think pseudomonas in burn victims

One possible cover design for The Book

Coming soon.

be patient, good things are coming your way :)

Diphtheria is known for creating a slimy/sticky/smelly exudate in the throat and mouth, but there are quite a few variations on its etiology and presentation.

A. Common type of diphtheria. Child three years old, seen on fourth day of illness. Exudate covering pharynx, tonsils, and uvula. Received 16,000 units of antitoxin. Throat clear on sixth day. Discharged cured.

B. Follicular type of diphtheria. Child seven years old, seen on second day of illness. The membrane involved the lacunae of the tonsils. Resembles follicular tonsillitis. Received 6,000 units of antitoxin total.

C. Hemorrhagic type of diphtheria. Child seven-and-a-half years old, seen on sixth day of illness. Tonsillar and post-pharyngeal exudate. Severe nasal and post-pharyngeal hemorrhages during exfoliation of membrane. Received in all 15,000 units of antitoxin. Throat clear on ninth day of illness. Myocarditis developed. Case discharged cured four weeks after admission. 

D. Septic type of diphtheria. Child eight years old, seen on fifth day of illness. The pseudo-membrane in this case covered the hard palate and extended in one large mass down the pharynx, completely hiding the tonsils.

Diseases of Infancy and Childhood. Louis Fischer, M.D., 1917.

desmosome a circular, dense body that forms the site of attachment between certain epithelial cells, especially those of stratified epithelium of the epidermis, which consist of local differentiations of the apposing cell membranes.

-Exfoliatin

A staphylococcus toxin - Cleaves the desmosomes in the stratum granulosum - Separates layers of skin. - Example: Scalded skin syndrome (occurs more often in infants)

New background! Download higher quality photo here!

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

Amazing web site!

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