Classification of bacteria

1. Cocci
A. Gram-positive (According making Catalase Enz)
Staphylococci (Catalse +Ve)
✓ Coagulase positive Staph aureus is the most important of the, highly pathogenic.

✓ Coagulase-negative Staph species

❖ Staph epidermidis (novobiocin sensitive) → Antibioticprevent skin infection
Skin commensal organisms of relatively low pathogenicity
❖ Staph saprophyticus (novobiocine Resistant)
clusters grown from the urine (UTI)
Some may still cause deeper infection or sepsis.

Streptococci (Catalse –Ve)

✓ Partial haemolysis
❖ (green colour on blood agar): α-haemolytic
❖ Optochin sensitive: S. pneumoniae
❖ Optochin resistant: S. Viridans

✓ Complete haemolysis
❖ (clear)β-haemolytic
❖ Bacitracin sensitive: Group A: S. Pyogenes
❖ bacitracin resistant: Group B: S. agalactiae

✓ No haemolysis
❖ γ-haemolytic ( enterococci)

B. Gram-negative
Neisseria meningitides → cluster together in pairs to form diplococci
 Neisseria gonorrhoeae,
1. Intracellular diplococcus, isolated from Rectum, Gental and urinay
Moraxella catarrhalis
✓ common of respiratory infections w underlying lung disease. It also sinusitis and middle ear infections.
Haemophilus influenza

2. Bacilli (Rods)
Therefore, only a small list of Gram-positive rods (bacilli) need to be memorised to categorise all bacteria - mnemonic = ABCD L
✓ Actinomyces
✓ Bacillus anthracis (anthrax)
✓ Clostridium
✓ Diphtheria: Corynebacterium diphtheriae
✓ Listeria monocytogenes

Remaining organisms are Gram-negative rods, e.g.:

✓ Escherichia coli
✓ Pseudomonas aeruginosa
✓ Salmonella sp.
✓ Shigella sp.
✓ Campylobacter jejuni
Streptococci
Alpha haemolytic streptococci (partial haemolysis)
• The most important alpha haemolytic → Streptococcus pneumoniae(pneumococcus). common cause of pneumonia, meningitis and otitis media.
• Another clinical example is Streptococcus viridans

Beta haemolytic streptococci (complete haemolysis)

These can be subdivided into groups A-H. Only groups A, B & D are important in humans.
 Group A
1. Most important organism is Streptococcus pyogenes
2. responsible for erysipelas, impetigo, cellulitis, type 2 necrotizing fasciitis and pharyngitis/tonsillitis
3. Immunological reactions → rheumatic fever or post-streptococcal glomerulonephritis
4. Erythrogenic toxins → scarlet fever

Group B → Streptococcus agalactiae → neonatal meningitis and septicaemia

Group D (No hemolysis)→ Enterococcus

Virulence factors
Bacteria employ a large number of virulence factors which enable them to colonize the host and evade/suppress the immune response.
Virulence factor Example organisms
IgA Protease 1. Strept. Pneumoniae
2. Haemophilus influenzae
3. Neisseria gonorrhoeae
M Protein Strept. Pyogenes
Polyribosyl ribitol PHosphate capsule HaemoPHilus influenzae
Bacteriophage Corynebacterium diphtheriae
Spore formation 1. Bacillus anthracis
2. Clostridium perfringens
3. Clostridium tetani
Lecithinase alpha toxin Clostridium perfringens
D-glutamate Polypeptide capsule Bacillus anthracis
Actin rockets Listeria monocytogenes
New Delhi metallo-beta-lactamase 1
1. The mutation that leads to Carbapenem resistance.
2. Found in Klebsiella pneumoniae, E. Coli, Enterobacter cloacae and others.
3. First line of management is colistin and second line may be tigecycline.

D-alanyl-D-lactate variation
1. leading to loss of affinity to antibiotics
2. Mechanism of VRE (Vancomycin resistant enterococci). Vancomycin binds to D-ala-D-ala.

The presence of MexAB-OprM efflux pumps

Pseudomonas aeruginosa is resistant to -lactams, Chloramphenicol, Fluoroquinolones, Macrolides, Novobiocin, Sulfonamides, Tetracycline, Trimethoprim
 Alteration to the Penicillin binding protein 2
The mechanism of MRSA (Mutations in the MEC gene which codes the penicillin binding proteins)

Antibiotic guidelines
Respiratory system
Condition Recommended treatment
Exacerbations of chronic bronchitis Amoxicillin or Tetracycline or Clarithromycin
Uncomplicated • Amoxicillin (Doxycycline or clarithromycin in penicillin allergic
community-acquired pneumonia • add flucloxacillin if staphylococci suspected (Influenza)
Pneumonia possibly by atypical pathogens Clarithromycin
Hospital-acquired pneumonia • Within 5 days of admission → Co-amoxiclav or Cefuroxime (only Gram –Ve)
• > 5 days of admission → Piperacillin + Tazobactam OR
Broad-spectrum Cephalosporin (Ceftazidime) OR Quinolone (Ciprofloxacin)
Urinary tract
Condition Recommended treatment
Lower urinary tract infection Trimethoprim or nitrofurantoin. Alternative: amoxicillin or cephalosporin
Acute pyelonephritis Broad-spectrum cephalosporin or quinolone
Acute prostatitis Quinolone or trimethoprim
Skin
Condition Recommended treatment
Impetigo Topical hydrogen peroxide, oral Flucloxacillin or Erythromycin if widespread
Cellulites Flucloxacillin (Clarithromycin, erythromycin or Doxycycline if penicillin-allergic)
Cellulites (near the eyes or nose) Co-amoxiclav (Clarithromycin, + Metronidazole if penicillin-allergic)
Erysipelas Flucloxacillin* (clarithromycin, erythromycin or Doxycycline if penicillin-allergic)
Animal or human bite Co-amoxiclav (doxycycline + metronidazole if penicillin-allergic)
Mastitis during breast-feeding Flucloxacillin
Ear, nose & throat
Condition Recommended treatment
Throat infections Phenoxymethylpenicillin (erythromycin alone if penicillin-allergic)
Sinusitis Amoxicillin or doxycycline or erythromycin
Otitis media Amoxicillin (erythromycin if penicillin-allergic)
Otitis Externa • Flucloxacillin (erythromycin if penicillin-allergic)
• Topical antibiotic and corticosteroid is generally used for mild/moderate cases of otitis externa
Periapical or Periodontal abscess Amoxicillin
Gingivitis / Acute Necrotizing ulcerative Metronidazole
Genital system
Condition Recommended treatment
Gonorrhea IM Ceftriaxone
Chlamydia Doxycycline OR Azithromycin
PID Oral Ofloxacin + Oral Metronidazole OR IM Ceftriaxone + Oral doxycycline + Oral metronidazole
Syphilis Benzathine benzylpenicillin OR Doxycycline OR Erythromycin
Bacterial Vaginosis Oral OR Topical metronidazole or topical Clindamycin
Gastrointestinal
Condition Recommended treatment
Clostridium difficile • 1 Episode: Metronidazole
st

• 2nd or Subsequent episode of infection → Vancomycin

Campylobacter enteritis Clarithromycin
Salmonella (non-typhoid) Ciprofloxacin
Shigellosis Ciprofloxacin
Bactericidal antibiotics
1. Aminoglycosides
2. Penicillins
 3. Cephalosporins
4. nitrofurantoin
5. Metronidazole
6. Quinolones
7. Rifampicin
8. Isoniazid
Bacteriostatic antibiotics
1. chloramphenicol
2. macrolides
3. tetracyclines
4. sulphonamides
5. trimethoprim

Cephalosporins
Type of β-lactam antibiotic (less susceptible to penicillinases than penicillins) → Bactericidal..
β-lactam antibiotics work by disrupting the synthesis of bacterial cell walls → (- -) peptidoglycan cross-linking.

Mechanism of resistance
• Changes to penicillin-binding-proteins (PBPs), which are types of transpeptidases (Bacterial Enz. cross-links peptidoglycan chains to form rigid cell walls)

penicillins and carbapenems → Also b- lactam

Linezolid
a type of oxazolidonone antibiotic → It inhibits bacterial protein synthesis by stopping formation of the 70s initiation complex (Bacteriostatic)
Spectrum, highly active against Gram positive organisms including:
1. MRSA (Methicillin-resistant Staphylococcus aureus)
2. VRE (Vancomycin-resistant enterococcus)
 3. GISA (Glycopeptide Intermediate Staphylococcus aureus)

Adverse effects
1. Thrombocytopenia (reversible on stopping)
2. Monoamine oxidase inhibitor→ avoid tyramine containing foods

Tetracyclines
• doxycycline
• tetracycline

Mechanism of action
• protein synthesis inhibitors → binds to 30S subunit blocking binding of aminoacyl-Trna

• Mechanism of resistance → → ↑↑ efflux of the bacteria by plasmid-encoded transport pumps, ribosomal protection

Indications
1. Acne vulgaris
2. Lyme disease
3. Chlamydia
4. Mycoplasma pneumoniae
Notable adverse effects
1. discolouration of teeth
✓ grey discolouration of the teeth in neonates if they are given to pregnant women in the 2nd or 3rd trimester but not if given to children or adults
✓ not be used in children < 12 years of age
2. Skin reactions to tetracyclines
✓ exfoliative dermatitis
✓ Stevens-Johnson syndrome
✓ photosensitivity
3. angioedema
 4. black hairy tongue

Tetracyclines should not be given to women who are pregnant or breastfeeding due to the risk of discolouration of the infant's teeth.

Trimethoprim
Mainly used in the management of urinary tract infections → Mechanism of action
✓ interferes with DNA synthesis by (- -) dihydrofolate reductase
✓ Therefore, interact with methotrexate, which also inhibits dihydrofolate reductase
✓ co-trimoxazole → (trimethoprim + sulfamethoxazole) → the same interaction.

Adverse effects
1. Myelosuppression
2. transient ↑↑creatinine → trimethoprim competitively (- -) tubular secretion of creatinine → temporary ↑↑ which reverses upon stopping the drug
3. trimethoprim blocks the ENaC channel in the distal nephron, → hyperkalaemic distal RTA (type 4).,
4. ↑↑creatinine by around 40 points (but not necessarily causing AKI)

Use in pregnancy
• 'Teratogenic risk in 1st trimester (folate antagonist). Manufacturers advise avoid during pregnancy.'

Vancomycin
• glycopeptide antibiotic used in the treatment of Gram-positive infections, particularly MRSA.
• Mechanism of action → (- -) cell wall formation by binding to D-Ala-D-Ala moieties, ↓↓↓ polymerization of peptidoglycans
• Mechanism of resistance → alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits (normally D-alanyl-D-alanine) to
which the antibiotic binds
• Adverse effects
1. nephrotoxicity
2. ototoxicity
 3. thrombophlebitis
4. red man syndrome
✓ W rapid infusion of Vancomycin
✓ The proposed mechanism is non IgE mediated mast cell degranulation
✓ flushing or a maculopapular rash.
✓ Treatment includes antihistamines

Antifungal agents
Drug Mechanism of action Adverse effects Notes
Azoles (- -) 14α-demethylase (produces ergosterol) (- -) P450 → Liver toxicity
Amphotericin B Binds with ergosterol → transmembrane channel→ Nephrotoxicity, flu-like S Systemic fungal infections
monovalent ion (K+, Na+, H+ and Cl) leakage ↓↓K , ↓↓ Mg
Terbinafine (- -) squalene epoxidase (Fungal Enz.) →Cellular death Oral form to treat fungal nail
Griseofulvin Interacts with microtubules to disrupt mitotic spindle (++) P450, Teratogenic
Flucytosine Converted by cytosine deaminase to 5-fluorouracil→ Vomiting
(- -) thymidylate synthase and disrupts fungal protein synthesis
Caspofungin (- -) synthesis of beta-glucan (fungal cell wall component) Flushing
Nystatin Binds with ergosterol forming a transmembrane channel → very toxic → Only topically
monovalent ion (K+, Na+, H+ and Cl) leakage (oral thrush)
Ergosterol, a component of fungal cell membranes, forming pores that cause lysis of the cell wall and subsequent fungal cell death

Antiviral agents
Drug Mechanism of action Indications Adverse effects/toxicity
Aciclovir "Guanosine analog" being phosphorylated after enter viral cell by HSV, VZV (10-30 times more specific for Crystalline nephropathy
thymidine kinase → (- -) viral DNA polymerase viral DNA polymerase Vs. human Ez.
 Drug Mechanism of action Indications Adverse effects/toxicity
Ganciclovir "Guanosine analog" (phosphorylated by thymidine kinase) CMV Myelosuppression/agranulocytosis
→ (- -) viral DNA polymerase
Ribavirin "Guanosine analog" (- -) inosine monophosphate Chronic
(IMP) hepatitis C, RSV Haemolytic anaemia
dehydrogenase →(- -) capping of viral mRNA
Amantadine (- -) uncoating (M2 protein) of virus in cell. Influenza, Parkinson's disease Confusion, ataxia, slurred speech
Also releases dopamine from nerve endings
Oseltamivir Inhibits neuraminidase Influenza GIT Upet
(Tamiflu) Zamamivir → Bronchospasm
Zmamivir
Foscarnet Pyrophosphate analog which inhibits viiral DNA polymerase CMV, HSV if not responding to aciclovir Nephrotoxicity, hypocalcaemia, h
ypomagnasaemia, seizures
Interferon-α Human glycoproteins which inhibit synthesis of mRNA Chronic hepatitis B & C, hairy cell Flu-like symptoms, anorexia,
leukaemia myelosuppression
Cidofovir Acyclic nucleoside phosphonate, and is therefore independent of CMV retinitis in HIV Nephrotoxicity
phosphorylation by viral enzymes (compare and contrast with
aciclovir/ganciclovir)

Hydroxycarbamide is an example of a ribonucleotide reductase inhibitor which decreases the production of deoxyribonucleotides reducing DNA synthesis.

Vaccinations
live-attenuated type as these may pose a risk to immunocompromised patients (Corticosteriod, cytotoxics "Azathioprine", HIV W CD4 < 200).
The main types of
Live attenuated (Replicating)
1. BCG
2. measles, mumps, rubella (MMR)
3. influenza (intranasal)
 4. oral rotavirus
5. oral polio
6. yellow fever
7. oral typhoid

Live vaccines → given on the same day OR 4 week interval between further live vaccinations to (prevent the risk of immunological interference).
Inactivated preparations
1. rabies
2. hepatitis A
3. influenza (intramuscular)

Toxoid (inactivated toxin)

1. tetanus
2. diphtheria
3. pertussis

Subunit and conjugate vaccines

Subunit means that only part of the pathogen is used to generate an immunogenic response.
A conjugate vaccine → links the poorly immunogenic bacterial polysaccharide outer coats to proteins to make them more immunogenic
1. pneumococcus (conjugate)
2. haemophilus (conjugate)
3. meningococcus (conjugate)
4. hepatitis B
5. human papillomavirus
,
• influenza: different types are available, including
1. whole inactivated virus.
2. split virion (virus particles disrupted by detergent treatment)
3. sub-unit (mainly haemagglutinin and neuraminidase)
• Cholera →inactivated Inaba and Ogawa strains of Vibrio cholerae + recombinant B-subunit of the cholera toxin
 • hepatitis B → HBsAg adsorbed onto aluminium hydroxide adjuvant → prepared from yeast cells using recombinant DNA technology

Vaccine and egg allergy

• Egg protein is potentially significant quantities (CI if patient has anaphylactic allergy to egg)
1. The yellow fever vaccine.
2. killed injected and live attenuated influenza vaccines. It is not present in recombinant influenza vaccine
• Less amount (picograms to nanograms per dose)
1. MMR
2. some rabies vaccines.
• Anaphylaxis to egg protein is also a contraindication to the use of propofol (Diprivan)
Sepsis
• sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection
• septic shock → circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone.
→ clinically identified by a vasopressor requirement to maintain a MAP ≥ 65mmHg and serum lactate >2mmol/L in the absence of hypovolaemia
The term 'systemic inflammatory response syndrome (SIRS)' has also fallen out of favour.
Adult patients outside of ICU → heightened risk of mortality if they have quickSOFA (qSOFA) score meeting >= 2
1. Altered mentation
2. Systolic blood pressure < 100 mm Hg
3. Respiratory rate > 22/min

Management
For risk stratification NICE recommend using the following criteria:
Red flag criteria
1. Responds only to voice or pain/ unresponsive
2. Acute confusional state
3. Systolic B.P ≤ 90 mmHg (or drop >40 from normal)
4. Heart rate > 130 per minute
5. RR ≥25 per minute
6. Needs oxygen to keep SpO2 ≥ 92%
Amber flag criteria
1. Relatives concerned about mental status
2. Acute deterioration in functional ability
3. Immunosuppressed
4. Trauma/ surgery/ procedure in last 6 weeks
5. RR 21-24
6. Systolic B.P → 91-100 mmHg
 Red flag criteria Amber flag criteria
7. Non-blanching rash, mottled/ ashen/ cyanotic 7. Heart rate → 91-130 OR new dysrhythmia
8. Not passed urine in last 18 h/ UO < 0.5 ml/kg/hr 8. Not passed urine in last 12-18 hours
9. Lactate >=2 mmol/l 9. Temperature < 36º
10. Recent chemotherapy 10. Clinical signs of wound, device or skin infection

Cause of the sepsis and treatment and patient support regardless of the cause or severity. If any of the red flags →'sepsis six' should be started straight away:
1. Administer oxygen: Aim to keep saturations > 94% (88-92% if at risk of CO2 retention COPD)
2. Take blood cultures
3. Give broad spectrum antibiotics
4. Give intravenous fluid challenges: → bolus of 500ml crystalloid over < 15 minutes
5. Measure serum lactate
6. Measure accurate hourly urine output

Organ Failure Assessment Score (SOFA). The score grades abnormality by organ system and accounts for clinical interventions. laboratory
variables, namely, PaO2, platelet count, creatinine level, and bilirubin level, are needed for full computation.
System Score 0 Score 1 Score 2 Score 3 Score 4
PaO2 /FI O2 >400 <400 <300 <200 <100
3
Platelets x10 microlitres >150 <150 <100 <50 <20
Bilirubin µmol/L 20 20-32 33-101 102-204 >204
Cardiovascular MAP >70mmHg MAP 70mmHg Dopamine <5 or Dopamine 5.1-15 Dopamine >15 or
dobutamine (any dose) or epinephrine 0.1 epinephrine >0.1
or norepinephrine 0.1 or norepinephrine >0.1
GCS 15 13-14 10-12 6-9 <6
Creatinine µmol/L <110 110-170 171-299 300-440 >440
Urine output ml/day >500 >500 >500 <500 <200
 A SOFA score of 2 or more reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection.
Even patients presenting with modest dysfunction can deteriorate further, emphasizing the seriousness of this condition and the need for prompt
and appropriate intervention, if not already being instituted.
Staphylococcal toxic shock syndrome
severe systemic reaction to staphylococcal exotoxins. series of cases related to infected tampons →diagnostic criteria
1. fever: temperature > 38.9ºC
2. hypotension: systolic blood pressure < 90 mmHg
3. diffuse erythematous rash
4. desquamation of rash, especially of the palms and soles
5. involvement ≥ 3 organ systems→ . gastrointestinal (diarrhoea and vomiting), mucous membrane erythema, renal failure, hepatitis,
thrombocytopenia, CNS involvement (confusion)

Splenectomy
Following a splenectomy patients → risk from pneumococcus, Haemophilus, meningococcus and Capnocytophaga canimorsus* infections
Vaccination
1. if elective → 2 weeks prior to operation
2. Himophilus influenza type b
3. meningitis A & C
4. Annual influenza vaccination
5. pneumococcal vaccine every 5 years

Antibiotic prophylaxis
• penicillin V:
1. against Streptococcus pneumoniae but not Haemophilus influenzae due to the production of beta-lactamases by the organism.
2. guidelines do not exist of how long antibiotic prophylaxis should be continued.
3. penicillin should be continued for at least 2 years and at least until the patient is 16 years of age,
4. Majority of patients are usually put on antibiotic prophylaxis for life
Surgical aspects
Indications
1. Trauma → 1/4 are iatrogenic
2. Spontaneous rupture → EBV
3. Hypersplenism → hereditary spherocytosis or elliptocytosis etc
4. Malignancy → lymphoma or leukaemia
5. Splenic cysts/ hydatid cysts/ splenic abscesses
6. Elective splenectomy

✓ Elective splenectomy is a very different operation from that performed in the emergency setting. The spleen is often large (sometimes massive)
✓ Most cases can be performed laparoscopically. The spleen will often be macerated inside a specimen bag to facilitate extraction.

Complications
1. Haemorrhage (may be early and either from short gastrics or splenic hilar vessels
2. Pancreatic fistula (from iatrogenic damage to pancreatic tail)
3. Thrombocytosis → prophylactic aspirin
4. Encapsulated Bacteria infection → Strep. Pneumoniae, Haemophilus Influenzae and Neisseria Meningitidis

Post-Spleenectomy changes
1. Platelets will rise first (therefore in ITP should be given after splenic artery clamped)
2. Blood film will change over following weeks, Howell-Jolly bodies will appear
3. Other blood film changes include target cells and Pappenheimer bodies
4. ↑↑ Post-splenectomy sepsis → prophylactic antibiotics and pneumococcal vaccine should be given.

Post-Spleenectomy sepsis
1. Typically occurs with encapsulated organisms
2. Opsonisation occurs but then not recognised
Hepatitis B
Double-stranded DNA hepadnavirus → infected blood or body fluids, including vertical transmission W incubation period is 6-20 weeks.

The features of hepatitis B include fever, jaundice and elevated liver transaminases.
Complications of hepatitis B infection
1. chronic hepatitis (5-10%). 'Ground-glass' hepatocytes may be seen on light microscopy
2. fulminant liver failure (1%)
3. hepatocellular carcinoma
4. glomerulonephritis
5. polyarteritis nodosa
6. cryoglobulinaemia

Immunisation against hepatitis B

• Children born → the routine immunisation schedule. (2, 3 and 4 months)
• Risk groups who should be vaccinated include:
1. Healthcare workers
2. IV drug users, sex workers
3. Close family contacts of an individual with hepatitis B
4. individuals receiving blood transfusions regularly
5. Chronic kidney disease patients who may soon require renal replacement therapy
6. prisoners
7. chronic liver disease patients
• Vaccine contains (HBsAg adsorbed onto aluminium hydroxide) and is prepared from yeast cells using recombinant DNA.

• 10-15% of adults fail to respond or respond poorly to 3 doses of the vaccine.

✓ Risk factors → > 40 years/ obesity / smoking/ alcohol excess/ immunosuppression

• Testing for anti-HBs → only for those at risk of occupational exposure and patients with chronic kidney disease.
✓ In these patients anti-HBs levels should be checked 1-4 months after primary immunisation
 Anti-HBs level Response
> 100 adequate response, → receive booster at 5 years
10 - 100 Suboptimal response → one additional vaccine dose should be given. If immunocompetent no further testing is required
< 10 Non-responder. Test for current or past infection. Give further vaccine course (3 doses again) with testing following.
If still fails to respond then HBIG would be required for protection if exposed to the virus

Management of hepatitis B
• Pegylated interferon-alpha → only treatment (↓↓viral replication → 30% of chronic carriers). A better response is predicted
1. Female, < 50 years old.
2. Low HBV DNA levels.
3. High degree of inflammation on liver biopsy
4. Non-Asian.
5. HIV negative.
• Other antiviral medications are increasingly used with an aim to suppress viral replication (not in a dissimilar way to treating HIV patients)
✓ Ex: tenofovir, entecavir and telbivudine (Synthetic thymidine nucleoside analogue)
✓ Reverse-transcriptase (RT) is an enzyme essential for viral replication.
✓ Nucleoside analogues, nucleotide analogues and non-nucleoside RT inhibitors → three classes of drugs which disrupt the activity of this enzyme.
✓ Telbivudine is an antiviral drug typically used in chronic hepatitis B infections. It is a thymidine nucleoside analogue that inhibits the replication of
hepatitis B. Zidovudine and stavudine are two examples of drugs with the same mechanism.

Hepatitis C
• around 200,000 people are chronically infected. At risk groups → intravenous drug users and patients received a blood transfusion prior to 1991 (haemophiliacs)
• Hepatitis C is a RNA flavivirus. Incubation period: 6-9 weeks
• Transmission
1. Vertical transmission → 6%. The risk is higher W coexistent HIV
2. Sexual intercourse is probably < 5%
3. Needle stick injury is about 2%
4. Breastfeeding is not contraindicated in mothers with hepatitis C
5. there is no vaccine for hepatitis C
• After exposure to the hepatitis C virus only around 30% of patients will develop features such as:
1. a transient rise in serum aminotransferases / jaundice
2. fatigue & arthralgia

Investigations
• Anti- HCV 1st → If +Ve → HCV RNA
• HCV RNA is the investigation of choice to diagnose acute infection
• anti-HCV antibodies it should be remembered that patients who spontaneously clear the virus will continue to have anti-HCV antibodies
Outcome
• around 15-45% of patients will clear the virus after an acute infection (age and underlying health) and
• majority (55-85%) will develop chronic hepatitis C
✓ defined as the persistence of HCV RNA in the blood for 6 months.
✓ Potential complications of chronic hepatitis C
1. Rheumatological problems: arthralgia, arthritis
2. Eye problems: Sjogren's syndrome
3. cirrhosis (5-20% of those with chronic disease)
4. hepatocellular cancer
5. cryoglobulinaemia: typically type II (mixed monoclonal and polyclonal)
6. porphyria cutanea tarda (PCT): especially if there are other factors such as alcohol abuse
7. membranoproliferative glomerulonephritis

Management of chronic infection

• treatment depends on the viral genotype - this should be tested prior to treatment Interferon based treatments are no longer recommended
• Management → clearance rates of around 95%.
• the aim of treatment is sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy
• Combination of (protease inhibitors (daclatasvir + sofosbuvir or sofosbuvir + simeprevir) +/- ribavirin .
• Assessment for the tt response → Viral load.
 Complications of treatment
1. ribavirin → haemolytic anaemia, cough. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
2. interferon alpha - side-effects: flu-like symptoms, depression, fatigue, leukopenia, thrombocytopenia
Hepatitis E
• RNA hepevirus → spread by the faecal-oral route (commonly affecting shellfish, Sefood and pork products)
• incubation period: 3-8 weeks
• common in Central and South-East Asia, North and West Africa, and in Mexico
• Pregnant Female W Fulminant hepatitis (↑↑↑ ALT, Clinical)→ Hepatitis E
• causes a similar disease to hepatitis A, but carries a significant mortality (about 20%) during pregnancy
• does not cause chronic disease or an increased risk of hepatocellular cancer
• a vaccine is currently in development*, but is not yet in widespread use

HIV: seroconversion
• HIV seroconversion is symptomatic in 60-80% of patients and typically presents as a glandular fever type illness.
• ↑↑↑ symptomatic severity → poorer long term prognosis. It typically occurs 3-12 weeks after infection
Features
• sore throat
• lymphadenopathy
• malaise, myalgia, arthralgia
• diarrhoea
• maculopapular rash
• mouth ulcers
• rarely meningoencephalitis

Diagnosis
• antibodies to HIV may not be present
✓ most common and accurate test
✓ usually consists of both a screening ELISA (Enzyme Linked Immuno-Sorbent Assay) test and a confirmatory Western Blot Assay
 ✓ most people develop antibodies to HIV at 4-6 weeks but 99% do by 3 months

• HIV PCR and

• p24 antigen tests can confirm diagnosis
✓ usually positive from about 1 week to 3 - 4 weeks after infection with HIV
✓ sometimes used as an additional screening test in blood banks

• If HIV +Ve → check CD4

HIV and pregnancy

• In London the incidence may be as high as 0.4% of pregnant women.
• The aim of treating HIV positive women during pregnancy → ↓↓ harm to both the mother and fetus, and ↓↓ vertical transmission.
Factors which reduce vertical transmission (from 25-30% to 2%)
1. Maternal antiretroviral therapy
2. Neonatal antiretroviral therapy
3. Mode of delivery (caesarean section)
4. Infant feeding (bottle feeding)

Screening → to all pregnant women

Antiretroviral therapy
• all pregnant women → antiretroviral therapy once diagnosed regardless of whether they were taking it previously

Mode of delivery
• vaginal delivery → if viral load < 50 copies/ml at 36 weeks, otherwise caesarian section is recommended
• Zidovudine infusion (Nucleoside analogue ) → started 4 hours before beginning the caesarean section

Neonatal antiretroviral therapy

• zidovudine → orally to the neonate if maternal viral load is <50 copies/ml. 6w age
 • Otherwise triple ART should be used. for 4-6 weeks.

Infant feedin → not to breast feed

HIV: Kaposi's sarcoma
• Caused by HHV-8 (human herpes virus 8), Suggesting underlying HIV infection, Might history of recent Viral infection Herpes Zoster (Immunity
• presents as purple papules or plaques on the skin or mucosa (GIT and respiratory tract)
• skin lesions may later ulcerate
• Respiratory involvement may cause massive haemoptysis and pleural effusion
• radiotherapy + resection
HIV: neurocomplications
Focal neurological lesions
1. Toxoplasmosis
✓ 50% of cerebral lesions in patients with HIV
✓ constitutional symptoms, headache, confusion, drowsiness
✓ CT → usually single or multiple ring enhancing (Hypodense) lesions, mass effect may be seen.
✓ Management: sulfadiazine and pyrimethamine
✓ limited availablity of SPECT compared to CT many patients treated empirically on the basis of scoring systems, 90% if all criteria are met:
A. toxoplasmosis IgG in the serum
B. CD4 < 100 and not receiving prophylaxis for toxoplasmosis
C. multiple ring enhancing lesions on CT or MRI

2. Primary CNS lymphoma

✓ 30% of cerebral lesions → associated with EBV
✓ CT → Single or multiple homogenous enhancing lesions
✓ Treatment → Steroids (may significantly reduce tumour size), chemotherapy (methotrexate) +/- whole brain irradiation.
→ Surgical may be considered for lower grade tumours
 Toxoplasmosis Lymphoma
Multiple lesions Single lesion
Ring or nodular enhancement Solid (homogenous) enhancement
Thallium SPECT negative Thallium SPECT positive
1. Tuberculosis
✓ much less common than toxoplasmosis or primary CNS lymphoma
✓ Might be W Cough ,No fever , or –Ve tuberculin (↓↓ Immunity)
✓ CT: single enhancing lesion, might be meningeal enhancement
Generalised neurological disease
1. Encephalitis
✓ may be due to CMV or HIV itself
✓ HSV encephalitis but is relatively rare in the context of HIV
✓ CT → oedematous brain

2. Cryptococcus
✓ most common fungal infection of CNS
✓ headache, fever, malaise, nausea/vomiting, seizures, focal neurological deficit
✓ CSF → high opening pressure, India ink test positive
✓ CT → meningeal enhancement, cerebral oedema
✓ meningitis is typical presentation but may occasionally cause a space occupying lesion.

3. Progressive multifocal leukoencephalopathy (PML)

✓ widespread demyelination
✓ due to infection of oligodendrocytes by JC virus (a polyoma DNA virus)
✓ symptoms, subacute onset : behavioural changes, speech, motor, visual impairment
✓ CT → single or multiple lesions, no mass effect, don't usually enhance (↓↓↓ Attenuation diffusely)
✓ MRI is better → high-signal demyelinating white matter lesions are seen

4. AIDS dementia complex

 ✓ caused by HIV virus itself
✓ symptoms: behavioural changes, motor impairment
✓ CT: cortical and subcortical atrophy

opportunistic infections and other disorders

CD4 count 200 - 500 cells/mm³
Disorder Notes
Oral thrush Secondary to Candida albicans
Shingles Secondary to herpes zoster
Hairy leukoplakia Secondary to EBV
Kaposi sarcoma Secondary to HHV-8
CD4 count 100 - 200 cells/mm³
Disorder Notes
Cryptosporidiosis Whilst patients with a CD4 count of 200-500 may develop cryptosporidiosis the
disease is usually self-limiting and similar to that in immunocompetent hosts
Cerebral toxoplasmosis
Progressive multifocal leukoencephalopathy Secondary to the JC virus
Pneumocystis jiroveciipneumonia
HIV dementia
CD4 count 50 - 100 cells/mm³
Disorder Notes
Aspergillosis Secondary to Aspergillus fumigatus
Oesophageal candidiasis Secondary to Candida albicans
Cryptococcal meningitis
Primary CNS lymphoma Secondary to EBV
CD4 count < 50 cells/mm³
 Disorder Notes
Cytomegalovirus retinitis Affects around 30-40% of patients with CD4 < 50
Mycobacterium avium-intracellulare infection

People with poorly controlled HIV are more likely to develop the viral-related cancers
• Ebstein Barr Virus is associated with Hodgkin's lymphoma
• Human Papilloma Virus is associated with cervical cancer in women and throat and anal cancer in men
• Hepatitis B is associated with Hepatocellular carcinoma
• Human T-Lymphotrophic Virus is associated with adult T-cell lymphoma
Factors associated W increased transmission rate Factors do not increased transmission rate
1. Mucosal ceration limits barrier protection to HIV infection. 1. A low CD4 count
2. Increased HIV viral load. 2. Genital warts
3. Genito-urinary infection. 3. Diabetes
4. Circumcision is protective to HIV transmission.
HIV: Pneumocystis jiroveci pneumonia
Pneumocystis carinii → Pneumocystis jiroveci, → unicellular eukaryote, generally classified as a fungus but might consider protozoa
• PCP is the most common opportunistic infection in AIDS
• all patients with a CD4 count < 200/mm³ should receive PCP prophylaxis, Features
1. dyspnoea
2. dry cough
3. fever
4. very few chest signs → Normal chest auscultation (Characteristic)
5. Pneumothorax is a common complication of PCP.
6. Extrapulmonary manifestations are rare (1-2% of cases), may cause
✓ hepatosplenomegaly
✓ lymphadenopathy
✓ choroid lesions

Investigation
 • CXR: typically shows bilateral interstitial pulmonary infiltrates but might findings (lobar consolidation./ May be normal
• Exercise-induced desaturation
• sputum often fails to show PCP
• Bronchoalveolar lavage (BAL) often needed to demonstrate PCP (silver stain →characteristic cysts)

Management
• co-trimoxazole mix of trimethoprim and sulfamethoxazole
• IV pentamidine → severe cases
• Aerosolized pentamidine is an alternative treatment for Pneumocystis jirovecipneumonia but is less effective with a risk of pneumothorax
• Steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by 1/3)

HIV: management
• Antiretroviral therapy (ART) Start ART as soon as they have been diagnosed with HIV.
• Involves a combination of at least three drugs, (↓↓↓ viral replication & ↓↓↓risk of viral resistance)
1. 2 nucleoside reverse transcriptase inhibitors (NRTI) and
2. Either a protease inhibitor (PI) OR Non-nucleoside reverse transcriptase inhibitor (NNRTI).

Entry inhibitors
• Maraviroc (binds to CCR5, preventing an interaction with gp41), Enfuvirtide (binds to gp41, also known as a 'fusion inhibitor')
• prevent HIV-1 from entering and infecting immune cells

Integrase inhibitors
• Examples: raltegravir, elvitegravir, dolutegravir
Nucleoside analogue reverse transcriptase Protease inhibitors (PI) end in 'vir' Non-nucleoside reverse
inhibitors (NRTI) end in 'ine transcriptase inhibitors (NNRTI)
Mechanism (- -) activity of Reverse Transcriptase Enz ✓ (- -) protease needed to make the virus (- -) activity of Reverse
Action → vital for Viral replication able to survive outside the cell(Might for Transcriptase Enz → vital for Viral
Chronic hepatitis replication
 General Peripheral neuropathy •
Diabetes, hyperlipidaemia, buffalo hump, ✓ induces P450
S/E central obesity ✓ Rashes
✓ (- -) P450
Examples 1. Zidovudine (AZT) → anaemia, myopathy, 1. Indinavir,→ nephrolithiasis renal stones, 1. Nevirapine induces P450
black nails asymptomatic hyperbilirubinaemia 2. efavirenz
2. Tenofovir → renal impairment and 2. Ritonavir → potent inhibitor of the P450
ostesoporosis saquinavir
3. Didanosine → pancreatitis nelfinavir,

abacavir, emtricitabine, lamivudine,

stavudine,

Immune Reconstitution Inflammatory Syndrome

• Condition with HIV/immunosuppression → when starting anti-retrovirals → immune system begins to recover
• It might be due to respond to a previously acquired opportunistic infection that paradoxically makes the symptoms of infection worse.
• It may also represent newly acquired infection → life-threatening and require hospital admission
• Often microbiological tests -Ve.
• Tuberculosis is the most common cause of IRIS.
• IRIS can be distinguished from ARV failure by monitoring response to treatment → Patients with IRIS ( low viral loads and higher CD4 counts
• Whereas in treatment failure high viral load and low CD4 count would be typical.

HIV: immunisation
Vaccines in all HIV-infected adults Vaccines if CD4 > 200 Contraindicated in HIV
1. Hepatitis A 1. Measles, Mumps, Rubella (MMR) 1. Cholera CVD103-HgR
2. Hepatitis B 2. Varicella 2. Influenza-intranasal
3. Haemophilus influenzae B (Hib) 3. Yellow Fever 3. Poliomyelitis-oral (OPV)
 Vaccines in all HIV-infected adults Vaccines if CD4 > 200 Contraindicated in HIV
4. Influenza-parenteral 4. Tuberculosis (BCG)
5. Japanese encephalitis
6. Meningococcus-MenC
7. Meningococcus-ACWY I
8. Pneumococcus-PPV23
9. Poliomyelitis-parenteral (IPV)
10. Rabies
11. Tetanus-Diphtheria (Td)
Post-exposure prophylaxis
Hepatitis A
• Human Normal Immunoglobulin (HNIG) or hepatitis A vaccine may be used depending on the clinical situation
Hepatitis B
1. HBsAg positive source
✓ if known responder to HBV vaccine → booster dose should be given.
✓ If they are in the process of being vaccinated OR non-responder → hepatitis B immune globulin (HBIG) + vaccine
2. Unknown source
✓ known responders → booster dose of HBV vaccine.
✓ known non-responders → HBIG + vaccine should be given
✓ Those in the process of being vaccinated → accelerated course of HBV vaccine

Hepatitis C
• monthly PCR → if seroconversion then interferon +/- ribavirin

HIV
• The risk of HIV transmission depends heavily
1. incident (needle stick, type of sexual intercourse, human bite) ↑↑↑ transmission
✓ Contamination of a deep wound
✓ Visible blood on the sharp
 ✓ Hollow-bore blood-filled needle,
✓ Sharp was used to access an artery or vein.
2. the current viral load of the patient

• ↓↓ risk incidents such as human bites → don't require post-exposure prophylaxis

• Post-exposure prophylaxis → is no longer recommended following occupational exposure to a patient with an undetectable viral load.
• Combination of oral antiretrovirals (Tenofovir, emtricitabine, lopinavir and ritonavir) ASAP ( Within 1-2 hours, but may be up to 72 hours) for 4 weeks
• Nevirapine → can be used in post exposure prophylaxis in new born babies born to HIV positive mothers.
• serological testing → 12 weeks following completion of post-exposure prophylaxis
• ↓↓ risk of transmission by 80%

Varicella zoster
• VZIG for IgG negative pregnant women/immunosuppressed

Estimates of transmission risk for single needlestick injury

Hepatitis B 20-30%
Hepatitis C 0.5-2%
HIV 0.3%
Epstein-Barr virus (Glandular Fever)
One of the herpes viruses → Infectious mononucleosis (EBV, Human Herpes virus 4, HHV-4) 90% of cases.
Less frequent causes include cytomegalovirus and HHV-6. It is most common in adolescents and young adults.
The classic triad 98% of patients: resolve after 2-4 weeks.
1. Sore throat
2. Lymphadenopathy → anterior and posterior triangles of the neck (DD. tonsillitis which typically only upper anterior cervical chain)
3. Pyrexia
4. Other features include:
✓ malaise, anorexia, headache
✓ Palatal petechiae
 ✓ Splenomegaly - occurs in around 50% of patients and may rarely predispose to splenic rupture
✓ hepatitis, transient rise in ALT
✓ Lymphocytosis: presence of 50% lymphocytes with at least 10% atypical lymphocytes
✓ haemolytic anaemia secondary to cold agglutins (IgM)
✓ Maculopapular, pruritic rash develops in around 99% of patients who take ampicillin/amoxicillin.
Diagnosis
• Heterophil antibody test (Paul-Bunnel / Monospot test) → FBC and Monospot (2nd week of the illness to confirm a diagnosis of glandular
fever).

Management is supportive and includes:

• rest during the early stages, drink plenty of fluid, avoid alcohol
• simple analgesia for any aches or pains
• Avoid playing contact sports for 8 weeks after having glandular fever to reduce the risk of splenic rupture.

There is an interesting correlation between EBV and socioeconomic groups. ↓↓ socioeconomy → ↑↑ rates of EBV seropositivity (frequent EBV in early childhood)
when the primary infection is often subclinical.
↑↑ socioeconomic groups show a ↑↑ incidence as acquiring EBV in adolescence or early adulthood results in symptomatic disease.

EBV associated conditions

A. Malignancies associated with EBV infection
1. Burkitt's lymphoma* both African and sporadic Burkitt's
2. Hodgkin's lymphoma
3. Nasopharyngeal carcinoma
4. HIV-associated CNS lymphomas

B. The non-malignant condition

hairy leukoplakia
 Adult T-cell leukaemia is associated with HTLV-1 infection
Cytomegalovirus
is one of the herpes viruse → around 50% of people have been exposed to the CMV virus although it only usually causes disease in the immunocompromised,
Over 50% of renal transplant patients have a significant infection within the first 12 → highest risk → CMV-seronegative recipients who receive
a kidney from a CMV-seropositive donor. These patients are usually given antiviral prophylaxis.
Pathophysiology
• infected cells have a 'Owl's eye' appearance due to intranuclear inclusion bodies

Congenital CMV infection

✓ growth retardation,
✓ pinpoint petechial 'blueberry muffin' skin lesions,
✓ microcephaly,
✓ sensorineural deafness,
✓ encephalitiis (seizures)
✓ hepatosplenomegaly

CMV mononucleosis
• infectious mononucelosis-like illness
• may develop in immunocompetent individuals

CMV retinitis
• common in HIV patients with a low CD4 count (< 50)
• presents with visual impairment → 'blurred vision'. Fundoscopy shows retinal haemorrhages and necrosis, often called 'pizza' retina
• IV ganciclovir is the treatment of choice

CMV Encephalopathy
• seen in patients with HIV who have low CD4 counts
 CMV Pneumonitis →Atypical pneumonia
CMV colitis
Human papilloma virus vaccination
(HPV) infects the keratinocytes of the skin and mucous membranes is carcinogenic. strains of HPV
1. 6 & 11: causes genital warts
2. 16 & 18: linked to a variety of cancers, most notably cervical cancer

• HPV infection is linked to:

1. > 99.7% of cervical cancers
2. 85% of anal cancers
3. 50% of vulval and vaginal cancers
4. 20-30% of mouth and throat cancers

other risk factors important in developing cervical cancer → smoking, COCP use and high parity.
Testing for HPV has now been integrated into the cervical cancer screening programme.
If a smear is reported as borderline or mild dyskaryosis the original sample is tested for HPV
✓ if HPV negative the patient goes back to routine recall
✓ if HPV positive the patient is referred for colposcopy
Immunisation
Cervarix vaccine protected against HPV 16 & 18 but not 6 & 11.
Gardasil Vaccine protects against HPV 6, 11, 16 & 18.
all 12- and 13-year-olds (girls AND boys) in school Year 8 will be offered the human papillomavirus (HPV) vaccine.
information given to parents and available on the NHS website (daughter may receive the vaccine against parental wishes)
2 doses - girls have the 2nd dose between 6-24 months after the first, depending on local policy
HPV vaccination → men who have sex with men under the age of 45 to protect against anal, throat and penile and genital wart cancers.
Transgender men (assigned female at birth) who have sex with men are also eligible (do not require it if previously vaccinated).
Injection site reactions are particularly common with HPV vaccines.
Toxoplasmosis
• Toxoplasma gondii is a protozoa which infects the body → GI tract, lung or broken skin → It's oocysts release trophozoites → migrate widely around the body
• (Eye, brain and muscle)
• The usual animal reservoir is the cat, although other animals such as rats carry the disease.
• Most infections are asymptomatic. Symptomatic patients usually have a self-limiting infection,
• Clinical features resembling infectious mononucleosis (fever, malaise, lymphadenopathy).
✓ infectious mononucleosis → ↑↑↑pronounced pharyngitis (often described as the worst of their life) →-Ve EBV seriology
✓ acute toxoplasmosis → often presents as an isolated wide-spread lymphadenopathy, ↑↑ esenophil.
• Other less common manifestations include meningioencephalitis and myocarditis.

Investigation
1. antibody test
2. Sabin-Feldman dye test

Treatment is usually reserved for those with severe infections or patients who are Immunosuppressed
✓ Effective combination (pyrimethamine + sulfadiazine + folinic acid) for 4 to 6 weeks.
✓ The folic acid is to prevent bone marrow suppression.
✓ Other agents with pyrimethamine → azithromycin, clarithromycin and clindamycin. (would not be given as monotherapy).

• Congenital toxoplasmosis → transplacental → ( microcephaly, hydrocephalus, cerebral calcification and choroidoretinitis)

→ ↑↑ in each trimester peaking 65% in the third trimester.
Japanese encephalitis
• most common cause of viral encephalitis in South East Asia, China the Western Pacific and India, with approx. 50,000 cases annually.
• It is a flavivirus transmitted by culex mosquitos which breeds in rice paddy fields.
• The reservoir hosts are aquatic birds, but pigs are an amplification host and therefore close domestic contact with pigs is a risk factor.
• The majority of infection is asymptomatic.Clinical features
1. Parkinsonian features →indicate basal ganglia involvement. It can also present with acute flaccid paralysis.
2. headache, fever, seizures and confusion
 • Diagnosis → serology or PCR.
• Management → supportive.
• Prevention → vaccine and there are a variety of different types.

DD. Creutzfeldt-Jakob disease → typically presents with rapid onset dementia.

Viral haemorrhagic fevers

Viral haemorrhagic fevers (VHFs) are a group of viral infections that result in presentations ranging from a flu-like illness to multisystem failure.
Examples of viral haemorrhagic fever (VHF) include:
1. Flaviviridae → dengue, yellow fever Mosquitoes
2. Arenaviridae → Lassa fever
3. Filoviridae → Ebola virus, Marburg virus (Bats
4. Bunyaviridae → Hantaviruses, Crimean-Congo haemorrhagic fever, Rift Valley fever (Tick bites)

Features
1. flu-like symptoms
2. abdominal pain
3. haemorrhage
✓ petechiae, bruising
✓ bloody diarrhoea, haematemesis, haemoptysis
✓ disseminated intravascular coagulation
4. multiorgan failure

Prevention
• a yellow fever vaccine is available
• a dengue and Ebola vaccine have been developed but are now widely used at the current time
• no vaccines are available for the other VHFs
 Management
• treatment is generally supportive
• ribavirin is used to treat Lassa fever

The more common VHFs such as dengue, Ebola and yellow fever are covered in more detail elsewhere in the notes.

Lassa fever
✓ Lassa fever is contracted by contact with the excreta of infected African rats (Mastomys rodent) or by person-to-person spread.
✓ fatality rate is around 15% in those unwell enough to require inpatient treatment

Marburg virus
Causes a VHF very similar to Ebola.
Risk factors for transmissions include caves/bats and primates.

Yellow fever
• viral haemorrhagic fever (also dengue fever, Lassa fever, Ebola).
• Zoonotic infection → spread by Aedes mosquitos
• Incubation period = 2 - 14 days
• Mild flu-like illness < one week →Sudden onset of high fever, rigors, nausea & vomiting.
• Bradycardia → brief remission is followed by (Hemorrhage) jaundice, haematemesis, oliguria
• If severe jaundice → haematemesis may occur
• Councilman bodies (inclusion bodies) may be seen in the Hepatocytes

Zika virus
• Zika is a flavivirus mosquito-borne infection →It was first isolated from a monkey in the Zika forest in Uganda.
• Transmission →bite of an infected Aedes mosquito, small number of cases of sexual transmission, increasing transmission via the placenta
 • The majority Asymptoms OR mild, short (2 to 7 days) febrile disease.
1. Fever, Headache, Myalgia
2. Arthralgia/arthritis
3. Rash, Pruritis.
4. Conjunctivitis
5. Retro-orbital pain

• Serious complications in adults are not common, might be associated with Guillain-Barre syndrome, linked with microcephaly and congenital abnormalities
• Conception after 6 months → for infected female OR after returning from a category 1 or 2 area

DD. Chikungunya and Dengue can produce similar symptoms.

✓ Zika is prevalent in South America W mild fever ↑↑ conjunctivitis
✓ Dengue and Chikungunya → Abrupt onset of high fever. ↑↑↑ joint pain and conjunctivitis is less common.
Chikungunya
• Alphavirus disease caused by infected mosquitoes. Areas affected are Africa, Asia and Indian subcontinent
• Symptoms
1. Severe joint pain → debilitating the range of movement, might be swollen.
2. Skin Rash (Maculopapular) +/-
3. Abrupt onset of high fever (flu-like illness of muscle ache, headache, and fatigue.

Treatment: Relief of symptoms.

No specific treatment.
DD. Dengue Fever → low platelets and Skin rash

Dengue fever
• Dengue fever is a viral infection which can progress to viral haemorrhagic fever (yellow fever, Lassa fever, Ebola)
• transmitted by the Aedes aegypti mosquito
• incubation period of 7 days
 • Form of (DIC) known as dengue haemorrhagic fever (DHF) may develop. Around 20-30% of these patients go on to develop dengue shock syndrome (DSS)

Features
• causes headache (often retro-orbital)
• fever
• myalgia
• pleuritic pain
• facial flushing (dengue)
• maculopapular rash + ↓↓ platlet + ↑↑ALT

Treatment
• entirely symptomatic e.g. fluid resuscitation, blood transfusion etc
• no antivirals are currently available

Listeria
a Gram-positive bacillus → unusual ability to multiply at low temperatures. It is typically spread via contaminated food( unpasteurised dairy products.
Infection is particularly dangerous to the unborn child where it can lead to miscarriage.Features - can present in a variety of ways
1. Diarrhoea, flu-like illness
2. pneumonia → meningoencephalitis
3. Ataxia and Seizures
Investigated
blood cultures.
CSF → reveals a pleocytosis, with 'tumbling motility' on wet mounts

Management
• Amoxicillin/ampicillin (cephalosporins usually inadequate)
• Listeria meningitis should be treated with IV amoxicillin/ampicillin + gentamicin
 In pregnant women
• almost 20 times more likely to develop listeriosis compared with the rest of the population due to changes in the immune system
• fetal/neonatal infection can occur both transplacentally and vertically during child birth
• complications → miscarriage, premature labour, stillbirth and chorioamnionitis
• Diagnosis can only be made from blood cultures
• treatment is with amoxicillin

Meningitis
Immunosuppressed
• Listeria monocytogenes
0 - 3 months • > 60 years • 3 months - 6 years 6 years - 60 years
• B Streptococcus (most common • Streptococcus pneumoniae • Neisseria meningitidis • Neisseria meningitidis
• Listeria monocytogenes • Listeria monocytogenes • Streptococcus pneumoniae • Streptococcus pneumoniae
• E. coli • Neisseria meningitidis • Haemophilus influenzae

Meningiococci (Nisseria) →Rash and petechiae

Pneumococci (Strept. Pneumonia) → Common following ear infection.

CNS analysis

Bacterial Viral Tuberculous Fungal

Appearance Cloudy Clear/cloudy Slight cloudy, fibrin web Cloudy
Glucose Low (< 1/2 plasma) 60-80% of plasma glucose* Low (< 1/2 plasma) Low
↓↓ (Mumps & Herpes encephalitis)
Protein High (> 1 g/l) Normal/raised High (> 1 g/l) High
White cells 10 - 5,000 polymorphs/mm³ 15 - 1,000 lymphocytes/mm³ 30 - 300 lymphocytes/mm³ 20 - 200 lymphocytes/mm³
Investigations
1. full blood count
 2. CRP
3. coagulation screen
4. blood culture
5. whole-blood PCR
6. blood glucose
7. blood gas
8. Lumbar puncture if no signs of raised intracranial pressure
9. The Ziehl-Neelsen stain is only 20% sensitive in TB meningitis → PCR is sometimes used (sensitivity = 75%)

Meningococcal septicaemia →It is associated with a high morbidity and mortality unless treated early -cause of death in early childhood. Presentation of meningococcal
1. 15% → meningitis
2. 25% → septicaemia
3. 60% → a combination of meningitis and septicaemia

Investigations
1. Blood cultures
2. Blood PCR → sensitivity of over 90%. If antibiotic was given as the culture would be –Ve
3. lumbar puncture is usually contraindicated
4. full blood count and clotting to assess for disseminated intravascular coagulation

Management
All patients should be transferred to hospital urgently.
In a pre-hospital setting and meningococcal disease is suspected then intramuscular benzylpenicillin may be given.
Scenario BNF recommendation
Initial empirical therapy aged < 3 months Intravenous cefotaxime + amoxicillin (Cover Listeria)
> 3 months is intravenous ceftriaxone
Initial empirical therapy aged 3 months - 50 years Intravenous cefotaxime
Initial empirical therapy aged > 50 years Intravenous cefotaxime + amoxicillin (Cover Listeria)
Meningococcal(Nisseria) meningitis Intravenous benzylpenicillin or cefotaxime
 Scenario BNF recommendation
Pneuomococcal (Pstrept. Pneumonia) meningitis Intravenous cefotaxime
Meningitis caused by Haemophilus influenzae Intravenous cefotaxime
Meningitis caused by Listeria Intravenous amoxicillin + gentamicin
▪ IV dexamethasone
✓ Should also be given ↓↓ risk of neurological sequelae. ↓↓↓ Hearing loss
✓ Given W or after antibiotic → if pneumocci is confirmed →continued for 4 days.
✓ It should be stopped if another causative organism is strongly suspected or confirmed.

▪ If the patient has a history of immediate hypersensitivity reaction to penicillin or to cephalosporins → chloramphenicol.

Management of contacts
1. Offered for
✓ Close contacts/ people exposed to respiratory secretion of patients affected with meningococcal meningitis.
✓ people exposed to a patient with confirmed bacterial meningitis if they have close contact within 7 days before onset
2. (Chemoprophylaxis) →Oral ciprofloxacin or rifampicin (1*2→ 2 days) or may be used.
3. Ciprofloxacin is the drug of choice as it is widely available and only requires one dose
4. The risk is highest in the first 7 days but persists for at least 4 weeks
5. Meningococcal vaccination → if serotype results are available, including booster doses to those who had the vaccine in infancy
6. Pneumococcal meningitis
✓ No prophylaxis is generally needed.
✓ Exceptions → If a cluster of cases of (protocol for offering close contacts antibiotic prophylaxis.

Rabies
• The rabies virus is classed as a RNA rhabdovirus (specifically a lyssavirus) and has a bullet-shaped capsid.
• The vast majority of cases are caused by dog bites but it may also be transmitted by bat, raccoon and skunk bites.
• Following a bite the virus travels up the nerve axons towards CNS in a retrograde fashion.--> causes an acute encephalitis.
Rabies is estimated to still kill around 25,000-50,000 people across the world each year.
 • The vast majority of the disease burden falls on people in poor rural areas of Africa and Asia. Children are particularly at risk. Features
1. prodrome: headache, fever, agitation
2. hydrophobia: water-provoking muscle spasms
3. hypersalivation
4. Negri bodies → cytoplasmic inclusion bodies found in infected neurons
Following an animal bite in at-risk countries:
• the wound should be washed
• if an individual is already immunised → 2 further doses of vaccine should be given
• if not previously immunised → immunoglobulin should be given along with a full course of vaccination. (the dose administered locally around the wound
• If untreated the disease is nearly always fatal.

MRSA
Methicillin-resistant Staphylococcus aureus (MRSA) was one of the first organisms → hospital-acquired infections.

Who should be screened for MRSA?

1. all patients awaiting elective admissions
✓ Exceptions → (Day patients terminations of pregnancy and ophthalmic surgery)/ Patients admitted to mental health
2. all emergency admissions will be screened

How should a patient be screened for MRSA?

1. nasal swab and skin lesions or wounds
2. the swab should be wiped around the inside rim of a patient's nose for 5 seconds
3. the microbiology form must be labelled 'MRSA screen'
Suppression of MRSA from a carrier once identified
• Nose → mupirocin 2% in white soft paraffin, → 1*3/ 5 days
• Skin → chlorhexidine gluconate, 1*1/ 5 days → Apply all over but particularly to the axilla, groin and perineum
• hand hygiene is the single most important step

The following antibiotics are commonly used in the treatment of MRSA infections:
 1. vancomycin
2. teicoplanin
3. linezolid

Some strains may be sensitive to the antibiotics listed below but they should not generally be used alone because resistance may develop:
1. rifampicin
2. macrolides
3. tetracyclines
4. aminoglycosides
5. clindamycin

Relatively new antibiotics such as linezolid, quinupristin/dalfopristin combinations and tigecycline have activity against MRSA but should
be reserved for resistant cases

Although ciprofloxacin is not a beta-lactam antibiotic → its use is strongly linked to the acquisition of MRSA as with all quinolone antibiotics.

Animal and human bites

Animal bites
These are generally polymicrobial → the most common Pasteurella multocida "Gram -Ve coccobacillus"

Management
1. cleanse wound. Puncture wounds should not be sutured closed unless cosmesis is at risk
2. co-amoxiclav
3. if penicillin-allergic then doxycycline + metronidazole is recommended

Tularaemia Disease
• A zoonotic infection → Francisella Tularensis commonly
• Transmitted through lagomorphs (Rabbits, Hares , aquatic rodents and Ticks).
• Symptoms → Erythematous Papulo-ulcerative lesion at the site of the bite + Reactive and ulcerating Lymphadenopathy.
 • Treatment → Doxycycline.

Human bites
commonly cause multimicrobial infection, including both aerobic and anaerobic bacteria.
1. Streptococci spp.
2. Staphylococcus aureus
3. Eikenella → 10-30% of human bite wounds.
4. Fusobacterium
5. Prevotella
6. The risk of viral infections such as HIV and Hepatitis C
Treatment → Co-Amoxiclav

Antibiotic prophylaxis
1. For: Hand/Foot/Facial injuries,
2. Deep puncture wounds
3. wounds requiring surgical debridement,
4. wounds involving joints/tendons/ligaments, suspected fractures,
5. Immunosuppressed, diabetic, cirrhotic, asplenic, or elderly.

Anthrax
• Also known as Woolsorters' disease Caused by Bacillus Anthracis, Spore-gram +Ve rod → Tripartite protein toxin W is
1. Protective antigen
2. Oedema factor: a bacterial adenylate cyclase which ↑↑ cAMP
3. Lethal factor: toxic to macrophages
• The cutaneous form → the most common, It is spread by infected Carcasses "Cadevers", handling infected animals → Butcher and Farmers at risk

Features
• Painless Escher → ulceration W black centre (eschar) W surrounding oedema (cutaneous 'malignant pustule', but no pus)
• May cause marked oedema
 • Can cause GIT bleeding

Management
• Initial management of cutaneous anthrax is ciprofloxacin
• Further treatment is based on microbiological investigations and expert advice

DD. Scrub typhus would give an eschar but would be accompanied by muscle pain, cough, and GI upse
.
Leprosy
Leprosy is a granulomatous disease primarily affecting the peripheral nerves and skin. It is caused by Mycobacterium leprae. Features
1. patches of hypopigmented skin typically affecting the buttocks, face, and extensor surfaces of limbs
2. sensory loss
3. The degree of cell mediated immunity determines the type of leprosy a patient will develop.
• Low degree of cell mediated immunity → lepromatous leprosy ('multibacillary')
✓ extensive skin involvement
✓ symmetrical nerve involvement
1. High degree of cell mediated immunity → tuberculoid leprosy ('paucibacillary')
✓ limited skin disease
✓ asymmetric nerve involvement → hypesthesia
✓ hair loss
Management
• Multibacillary → Triple therapy: rifampicin, dapsone and clofazimine for 12 months
• Paucibacillary → rifampicin and dapsone for 6 months.

Pityriasis versicolor → hypopigmentation without sensory loss.

Vitiligo → causes hypopigmentation without sensory loss.

H1N1 influenza pandemic

 (swine flu), H1N1 virus is a subtype of the influenza A virus and the most common cause of flu in humans. The 2009 pandemic was caused by a
new strain of the H1N1 virus.Groups are particularly at risk:
1. patients with chronic illnesses and those on immunosuppressants
2. pregnant women
3. young children under 5 years old
Features
1. fever > 38ºC
2. myalgia
3. lethargy
4. headache
5. rhinitis
6. sore throat
7. cough
8. diarrhoea and vomiting
9. A minority of patients may go ARDS which may require ventilatory support.

Treatment
There are two main treatments currently available:
Oseltamivir (Tamiflu)
1. oral medication
2. a neuraminidase inhibitor → prevents new viral particles from being released by infected cells
3. S/E nausea, vomiting, diarrhoea and headaches

Zanamivir (Relenza)
1. inhaled medication → intravenous preparations are available for patients who are acutely unwell
2. also a neuraminidase inhibitor
3. may induce bronchospasm in asthmatics

Lemierre's syndrome
 • Infectious thrombophlebitis of the internal jugular vein (IJV)
• It most often occurs secondary to a bacterial sore throat caused by Fusobacterium necrophorum leading to a peritonsillar abscess.
• A combination of spread of the infection laterally from the abscess and compression lead to thrombosis of the IJV.
• Presentation → history of bacterial sore throat followed by neck pain, stiffness and tenderness (may be mistaken for meningitis) and systemic involvement
(fevers↑↑↑, rigors, etc).
• Serioud Complication → Showering Septic pulmonary emboli may also occur.
• TTT→ IV Antibiotics
Diphtheria
Gram positive bacterium Corynebacterium diphtheriae

Pathophysiology
• releases an exotoxin encoded by a β-prophage
• exotoxin (- -) protein synthesis by catalyzing ADP-ribosylation of elongation factor EF-2
• 'diphtheric membrane' on tonsils caused by necrotic mucosal cells.
• Systemic distribution may produce necrosis of myocardial, neural and renal tissue

Possible presentations
• recent visitors to Eastern Europe/Russia/Asia
• sore throat with a 'diphtheric membrane' - see above
1. bulky cervical lymphadenopathy
2. neuritis e.g. cranial nerves
3. heart block
Aspergilloma
An aspergilloma is a mycetoma (mass-like fungus ball) which often colonises an existing lung cavity (e.g. secondary to tuberculosis, lung cancer or cystic
fibrosis) → (–Ve with ZN stain)

Pathophysiology
Macrophages are the first line immune response, → recruit neutrophils (crucial components in fighting aspergillosis).
 Patients with deficiencies in macrophages and neutrophils are prone to aspergillosis.
In healthy individuals when aspergillosis spores are inhaled, mucociliary clearance is initiated and spores are phagocytosed, clearing the infection.

Usually asymptomatic but features may include

• cough
• haemoptysis (may be severe)

Investigations
• chest x-ray containing a rounded opacity. A Fungal ball W crescent sign may be present → soft tissue attenuating masses in a surrounding cavity
• Serology →high titres Aspergillus precipitins
Invasive Aspergillosis

Seen in the immunocompromised host to include patients with a chronic granulomatous disease, patients undergoing chemotherapy and patients receiving a
bone marrow transplant.

Presentation - Pulmonary symptoms are most common, presenting with a cough, fever, haemoptysis (which can be severe), dyspnoea and pleuritic chest pain
but may be atypical. There is haematogenous spread to other organs, most commonly bone resulting in osteomyelitis.

Investigations - can be hard to diagnose. Chest X-ray may show consolidation, nodules, infiltrates, or cavitating lesions. Chest CT may show the 'halo' sign
(however aspergillosis in patients with chronic granulomatous disease typically does not produce this sign). Cultures can be obtained from sputum, broncho-
alveolar lavage, lung tissue via trans-thoracic percutaneous biopsy. In addition, there is an assay to detect Galactomannan which a component aspergillosis cell
wall.

Treatment - is with antifungals. The first line is voriconazole

Allergic bronchopulmonary aspergillosis (ABPA) is a result of an exaggerated immune response to Aspergillus fumigatus, which frequently occurs within
patients who have asthma or cystic fibrosis. High-attenuation mucus is a radiological finding that is associated with ABPA.
Pneumonia:
Community acquired pneumonia (CAP) may be caused by the following infectious agents:
 • Streptococcus pneumoniae (Pneumococi)(accounts for around 80% of cases)
1. rapid onset
2. high fever
3. pleuritic chest pain
4. herpes labialis
5. If a patient presented W HIV → presented W pneumonia (clinical finding and Pneumonic Patch in X-rey) → Pneumococcal even
if CD4< 200 as Pneumocystis Jurovitchi has minimal clinical and x- ray finding.

• Haemophilus influenzae
• Staphylococcus aureus: commonly after the 'flu
• atypical pneumonias (Due to Mycoplasma pneumoniae)
• viruses

Staphylococcus aureus Pneumonia often is preceded by a viral illness such as influenza

✓ Might be associated W development of cavitating lung lesions in the context of pneumonia(Cavity W surrounding consolidation)
✓ producing a cytotoxin (Panton-Valentine Leukocidin) → necrotic, hemorrhagic pneumonia.

Mycoplasma pneumoniae 'Walking pneumonia' → mild cases of pneumonia, ↓↓ Systemic symptoms, and it usually presents with a non-productive cough.
Klebsiella pneumoniae often causes cavitating lung lesions and is most commonly associated with pneumonia in patients with a history of alcohol excess.
cardiomyopathies with upper lobar involvement

Legionella
• Legionnaire's disease is caused by intracellular bacterium Legionella pneumophilia. →Colonizes water tanks ( air-conditioning systems) → foreign holidays.
• Person-to-person transmission is not seen, ↑↑ males.
• The mortality rate → 15%.
• 3 risk factors ↑↑ mortality (Immunocompromized/ Delay in antibiotic/ Extreme Age → "elderly or very young <1".
• Features
1. flu-like symptoms including fever (present in > 95% of patients)
 2. Dry cough
3. relative bradycardia
4. confusion
5. lymphopaenia
6. hyponatraemia
7. deranged liver function tests
8. pleural effusion: seen in around 30% of patients

Diagnosis → urinary antigen

Management → Treat with erythromycin/clarithromycin (Might Macrolides + Quinolones)

Mycoplasma pneumoniae
• A cause of atypical pneumonia (younger patients).
• Characteristic complications → erythema multiforme and cold autoimmune haemolytic anaemia.
• Epidemics of Mycoplasma pneumoniae → every 4 years.
2. It is important to recognise atypical pneumonia → may not respond to penicillins or cephalosporins due to it lacking a peptidoglycan cell wall.

Features
1. typically has a prolonged and gradual onset
2. flu-like symptoms classically precede a dry cough
3. bilateral consolidation on x-ray
4. complications may occur as below
✓ Cold agglutins (IgM) → Haemolytic anaemia, Thrombocytopenia
✓ Erythema multiforme, Erythema nodosum
✓ Bullous myringitis: painful vesicles on the tympanic membrane
✓ Meningoencephalitis, Guillain-Barre syndrome and other immune-mediated neurological diseases
✓ pericarditis/ Myocarditis
✓ Gastrointestinal: Hepatitis, pancreatitis
✓ Renal: acute glomerulonephritis
 Investigations
• diagnosis is generally by Mycoplasma serology
• positive cold agglutination test

Management
• Doxycycline or a Macrolide (e.g. erythromycin/clarithromycin)

Tuberculosis
9th cause of death worldwide by Mycobacterium tuberculosis. Rarely (Mycobacterium bovis or Mycobacterium africanum).
In many cases, TB may remain dormant before it progresses to its active form. It most commonly lungs.
TB is a notifiable disease. Epidemiology
1. Tuberculosis mostly affects adults in their most productive years.
2. > 95% of cases and deaths are in developing countries

Risk factors - Stronng Risk factors - Weak

1. Living for years in Asia, Latin America, Eastern Europe, or Africa 1.Malignancy
 2. Exposure to infectious TB case 2. End-stage renal disease
3. People infected with HIV 3. IV drug use
20 to 30 times more likely to develop active TB 4. Malnutrition
4. Immunocompromised (diabetics, immunosuppressive therapy, 5. Alcoholism
malnourished, Hematological Malignancies) 6. Diabetes
5. Silicosis 7. Congested residence (Nursing homes, homeless shelters)
6. Apical fibrosis 8. Smoking

Diagnostic features
Common Uncommon
1. Presence of risk factors. 1. Pleuritic chest pain
2. Cough →initially dry later productive (50% 2. Haemoptysis → <10% patients (advanced disease) - may be as a result of
"cough over 2 weeks) complication such as bronchiectasis and not representative of active disease.
3. Low-grade fever →20% may have no fever. 3. Dyspnoea → late finding in the setting of extensive lung destruction or effusion
4. Night sweats, if present usually drenching 4. Weight loss
5. Anorexia 5. Psychological symptoms ; depression or hypomania
6. Malaise → may only be noticed in hindsight, 6. Asymptomatic (coincidental findings or screening)
after treatment 7. Hypoadrenalism (1ry TB symptoms + ↑↑k + hypotension)

Signs:
• Chest examination (normal in mild/moderate) → Crackles, bronchial breath sounds, or Amphoric breath sounds (distant hollow breath sounds over cavities).
• Clubbing - if longstanding disease
• Erythema nodosum

Investigations:
1. If there is clinical suspicion of TB, the patient should be isolated
2. Chest x-ray → Fibronodular opacities in upper lobes +/- cavitation
3. Sputum acid-fast bacilli smear (3 sputum samples) → +Ve for acid-fast bacilli
 4. Sputum culture → most sensitive and specific test: positive in TB
5. FBC: ↑↑ WBC, ↓↓Hb
6. Nucleic acid amplification tests (NAAT) → (on at least one of the sputum samples) +Ve Mycobacterium tuberculosis
7. All patients with TB have an HIV test within 2 months of diagnosis of TB
8. if the diagnosis is clinical then this should be stated

Screening for TB (only for ↑↑ risk)

1. Who born in high-incidence countries.
2. HIV patients
3. intravenous drug users
4. health care workers who serve high-risk populations.
5. Contacts of individuals with pulmonary TB.

Tuberculin skin test or interferon gamma release assays are the standard methods for identifying persons infected with the mycobacterium.
Tuberculin skin tests type IV (delayed) hypersensitivity reactions → are mediated by interferon-γ secreted by Th1 cells → stimulates macrophage activity.

Screening for latent tuberculosis

1. The Mantoux test is the main technique used to screen for latent tuberculosis.
2. Interferon-gamma blood test → It is used in a number of specific situations such as:
✓ the Mantoux test is +Ve or equivocal
✓ people where a tuberculin test may be falsely negative
1. miliary TB
2. sarcoidosis
3. HIV
4. lymphoma
5. very young age (e.g. < 6 months)
6. Renal failure (might be not CKD 3)

Mantoux test
• 0.1 ml of 1:1,000 purified protein derivative (PPD) injected intradermally
• result read 2-3 days later
Diameter of induration Positivity Interpretation
< 6mm -Ve No significant hypersensitivity to tuberculin protein Unvaccinated individuals → may be given the BCG
6 - 15mm +Ve hypersensitive to tuberculin protein Should not be given BCG → Previous TB infection or BCG
> 15mm Strongly +Ve - strongly hypersensitive to tuberculin protein Tuberculosis infection.
Heaf test
Has been discontinued → injection of PPD (100,000 units per ml) over the flexor surface of the left forearm. It was then read 3-10 days later.

Diagnosis of active tuberculosis

Chest x-ray Sputum smear Sputum culture Nucleic acid amplification tests (NAAT)
1. upper lobe cavitation 1. 3 specimens are needed 1. Gold standard ↑↑ sensitive allows rapid diagnosis (24-48 hours)
classical finding of 2. rapid and inexpensive test than a sputum smear and NAAT • ↑↑sensitive than smear but less sensitive
reactivated TB 3. Stained for the presence of acid-fast bacilli (ZN) 2. Can assess drug sensitivities than cultur
2. Bilateral hilar 4. + Ve in all mycobacteria (nontuberculous 3. Can take 1-3 weeks (if using
lymphadenopathy mycobacteria) liquid media, longer if solid
5. Sensitivity 50-80% → ↓↓ in individuals with media)
HIV to around 20-30%

A. Drug Therapy for active tuberculosis:

1. Initial phase - first 2 months (RIPE)
✓ Rifampicin →GIT upset, rashes and in severe cases hepatitis.
✓ Isoniazid → gastrointestinal upset and hepatitis.
✓ Pyrazinamide

2. Ethambutol Continuation phase - next 4 months

✓ Rifampicin
✓ Isoniazid

B. Drug Therapy for Latent tuberculosis:

 if a Mantoux test is positive (>5mm) → patient should be screened for active TB.
If there is no evidence of active TB → interferon-gamma release assay is positive → consider treatment for latent TB
The treatment for latent tuberculosis
• 3 months of isoniazid (with pyridoxine) and rifampicin OR
• 6 months of isoniazid (with pyridoxine)

C. Meningeal tuberculosis
Treated for a prolonged period (at least 12 months) + Steroids

D. Directly observed therap with a 3 times/ week dosing regimen may be indicated in certain groups, including:
1. homeless people with active tuberculosis
2. patients who are likely to have poor concordance
3. all prisoners with active or latent tuberculosis
BCG vaccine
• live attenuated vaccine
• Offers limited protection against tuberculosis (TB). ↑↑↑ preventing extrapulmonary manifestations of tuberculosis
• offers limited protection against leprosy.
• In the UK it is given to high-risk infants. The vaccine is administered to the following groups
1. all infants (0 - 12 months) living in areas of the UK (Annual incidence ≥ 40/100,000)
2. all infants (0 - 12 months) with a parent or grandparent born in a country where the annual incidence ≥40/100,000
3. older children ≥ 6 years → require a tuberculin skin test first
4. previously unvaccinated tuberculin-negative contacts of cases of respiratory TB
5. previously unvaccinated, tuberculin-negative new entrants <16 years of age who were born in or who have lived for a prolonged period
(at least three months) in a country with an annual TB incidence of 40/100,000 or greater
6. healthcare workers
7. prison staff
8. staff of care home for the elderly
9. those who work with homeless people, Camps
 Administration
• must first be given a tuberculin skin test. The only exceptions are children < 6 years old who have had no contact with tuberculosis
• given intradermally, normally to the lateral aspect of the left upper arm
• at the same time as other live vaccines OR 4 week interval

Contraindications
1. previous BCG vaccination
2. a past history of tuberculosis
3. HIV
4. pregnancy
5. positive tuberculin test (Heaf or Mantoux)
6. The BCG vaccine is not given > 35 → no evidence that it works for people of this age group.

Gastroenteritis: causes
Home or whilst Travelling abroad (travellers' diarrhoea)
1. Travellers' diarrhea
✓ at least 3 loose to watery stools in 24 hours +/- ≥ (abdominal cramps, fever, nausea, vomiting or blood in the stool.
✓ The most common cause is Escherichia coli.

2. 'acute food poisoning

✓ sudden onset of nausea, vomiting and diarrhoea after the ingestion of a toxin.
✓ Acute food poisoning is typically caused by Staphylococcus aureus, Bacillus cereus or Clostridium perfringens.
Infection Typical presentation
Escherichia • Common amongst travelers
coli • Watery stools
• Abdominal cramps and nausea
Giardiasis • Prolonged incubation period, non-bloody diarrhea
 Infection Typical presentation
• foul-smelling and fatty
Cholera • painless Profuse, watery diarrhea
• Severe dehydration resulting in weight loss
• Not common amongst travellers
Shigella • Bloody diarrhea
• Vomiting and abdominal pain
Staphylococcus • enterotoxins A-E Severe vomiting
aureus • Short incubation period
Campylobacter • A flu-like → followed by crampy abdominal pains, fever and diarrhea (may be bloody)
• May mimic appendicitis
• Complications include Guillain-Barre syndrome
Bacillus cereus • Two types of illness are seen
1. vomiting within 6 hours, stereotypically due to Reheated rice
2. diarrhoeal illness occurring after 6 hours
Amoebiasis Gradual onset bloody diarrhoea, abdominal pain and tenderness which may last for several weeks
Incubation period
• 1-6 hrs: Staphylococcus aureus, Bacillus cereus*
• 12-48 hrs (1-2 days): Salmonella, Escherichia coli
• 48-72 (2-3 days): Shigella, Campylobacter
• > 7 days: Giardiasis, Amoebiasis

Bloody Diarrhea Amoebic dysentery, Enterohemorrhagic E. colia and possibly Campylobacter.

Clostridia
• Clostridia are gram-positive, obligate anaerobic bacilli.
C. perfringens
 • produces α-toxin,(lecithinase) → causes gas gangrene (myonecrosis) and haemolysis
• features →tender, oedematous skin with haemorrhagic blebs and bullae. Crepitus may present on palpation

C. botulinum
• typically seen in canned foods and honey
• prevents acetylcholine (ACh) release leading to flaccid paralysis

C. difficile
• causes pseudomembranous colitis, typically seen after the use of broad-spectrum antibiotics
• produces both an exotoxin and a cytotoxin

C. tetani
• produces an exotoxin (tetanospasmin) that prevents the release of glycine from Renshaw cells in the spinal cord causing a spastic paralysis
Botulism
Clostridium botulinum
• gram positive anaerobic bacillus
• 7 serotypes A-G
• produces botulinum toxin, a neurotoxin which irreversibly blocks the release of acetylcholine
• may result from eating contaminated food (e.g. tinned) or intravenous drug use (IV track lines)
• neurotoxin often affects bulbar muscles and autonomic nervous system

Features
• Syndrome produced by botulinum toxin → an afebrile, descending, flaccid paralysis.
1. difficulty speaking or slurred speech, blurred or double vision, and/or dysphagia. ptosis and facial muscle weakness
2. patient usually fully conscious with no sensory disturbance
3. flaccid paralysis
4. diplopiaa, Ataxia
5. Bulbar palsy
6. Respiratory Ms paralysis, Disease is fatal in 5-10% of cases.
 Treatment
• Botulism antitoxin and supportive care
✓ Antitoxin is only effective if given early → once toxin has bound its actions cannot be reversed
✓ Most cases of botulism make a full recovery if treated appropriately → recovery period can be many months, especially if diagnosis is delayed.
• Supportive care, including serial measurements of forced vital capacity,
• Benzylpenicillin → is also administered in patients with abscess formation at the injection site

Tetanus
is caused by the tetanospasmin exotoxin from Clostridium tetani. →Tetanus spores are in soil and introduced into the body from a wound,unnoticed.
Tetanospasmin prevents release of GABA. Features
1. Prodrome fever, lethargy, headache
2. Trismus (lockjaw)
3. Risus sardonicus
4. opisthotonus (arched back, hyperextended neck)
5. Spasms (e.g. dysphagia)

Management
• supportive therapy including ventilatory support and muscle relaxants (diazepam)
• IM human tetanus immunoglobulin for high-risk wounds
1. compound fractures
2. delayed surgical intervention
3. Wounds burns needing surgery delayed > than 6 hours
4. Wounds containing foreign bodies
5. Wounds/burns in people with systemic sepsis
6. significant degree of devitalised tissue)
7. Wounds contaminated with soil
8. Compound fractures

• IV Metronidazole is now preferred to benzylpenicillin as the antibiotic of choice.

 • Tetanus antitoxin in developing countries as it is cheaper but it has a higher rate of anaphylaxis and a shorter half life so is not recommended in the UK
• Vaccination history → incomplete or unknown →a dose of tetanus vaccine should be given
• Vaccination →A cell-free purified toxin given as part of a combined vaccine routine immunisation schedule 5 doses is now considered to provide adequate
long-term protection against tetanus.
✓ 2 months
✓ 3 months
✓ 4 months
✓ 3-5 years
✓ 13-18 years

• For low risk Wounds and the Vaccine History is unknown → Requires tetanus vaccine + complete vaccine course at a later date

Amoebiasis
• Caused by Entamoeba histolytica (an amoeboid protozoan) → faecal-oral route → 10% of the world's population is chronically infected.
• Infection can be asymptomatic, cause mild diarrhoea or severe amoebic dysentery. Amoebiasis also causes liver and colonic abscesses.
• Amoebic dysentery
1. Profuse, Bloody diarrhoea
2. May be a long incubation period.
• Amoebic liver abscess
1. Usually a single mass in the right lobe (may be multiple). The contents →'Anchovy sauce'
2. fever, RUQ pain
3. serology is positive in > 90%
• Amoebic colitis
1. a severe and occasionally life threatening condition .
2. Trophozoite stage → cause significant damage to the bowel mucosa and can metastasise (Most commonly amoebic liver abscess).
Investigation
1. Stool microscopy → Trophozoites
✓ Within 15 minutes or kept warm 'hot stool' → diagnosis of intestinal amoebiasis
✓ Once cooled Entamoeba histolytic returns to its cystic state and becomes indistinguishable from the non-pathogen Entamoeba dispar
 2. Blood serology → first line extraintestinal amoebiasis where the sensitivity is higher.
3. Intestinal amoebiasis → Seroconversion does not typically occur until day 7th
4. Stool PCR → The gold standard is now largely accepted to be
5. Stool leukocytes → ↓↓ due to suppression by parasite

Treatment
1. Metronidazole and Tinidazole (Effective to Trophozoite stage)
2. Treatment for invasive amoebiasis → Metronidazole and Tinidazole (7 Days) followed by a luminal amoebicide (10 Days)
✓ To eradicate the cystic stage → resistant.
✓ 10 days of diloxanide furoate → Paromomycin "second line" North America
✓ Low/middle income countries treatment of the cystic stage is not recommended as re-infection is common.
✓ But in returning travellers with low chance of re-infection it is invariably given if available.
• DD. Enterohaemorrhagic E.coli → dysentery and pyogenic liver abscess.
→ Incubation Period 2-9 day
→ Hemolytic Uremic Syndrome
• Shigella → Short Incubation Period 1-2 days

Cholera
• caused by Vibro cholerae - Gram negative bacteria
• Features
1. profuse 'rice water' diarrhoea
2. dehydration
3. hypoglycaemia
• Management
1. oral rehydration therapy
2. antibiotics: Doxycycline, Ciprofloxacin

Brucellosis
 Brucellosis is a zoonosis more common in the Middle East and in farmers. Four major species cause infection in humans: B melitensis (sheep),
B abortus (cattle), B canis and B suis (pigs). Brucellosis has an incubation period 2 - 6 weeks
Brucella melitensis is the bacteria found in contaminated animal fluids (unpasteurised milk)

Features
• non-specific: fever, malaise
• hepatosplenomegaly
• sacroilitis: spinal tenderness may be seen
• complications: osteomyelitis, infective endocarditis, meningoencephalitis, orchitis
• leukopenia often seen

Diagnosis
• the Rose Bengal plate test can be used for screening but other tests are required to confirm the diagnosis
• Brucella serology is the best test for diagnosis
• blood and bone marrow cultures may be suitable in certain patients, but these tests are often negative

Management
• Doxycycline and streptomycin

Enteric fever (typhoid/paratyphoid)

• The Salmonella group many members, most cause diarrhoeal diseases. They are aerobic, Gram-negative rods , not normally present as commensals in the gut.
• Typhoid and paratyphoid are caused by Salmonella typhi and Salmonella paratyphi (types A, B & C) respectively.
• Producing systemic symptoms such as headache, fever, arthralgia.
• typhoid is transmitted via the faecal-oral route (also in contaminated food and water
• Features
1. initially systemic upset as above
2. Relative bradycardia → (Faget sign) is typical of typhoid fever.
3. Abdominal pain, distension
4. constipation: although Salmonella is a recognised cause blooy diarrhoea, constipation is more common in typhoid
 5. Rose spots: → present on the trunk in 40% of patients, and are more common in paratyphoid
→Also in Chlamydia psittaci

Possible complications include

1. Osteomyelitis (especially in sickle cell disease where Salmonella is one of the most common pathogens)
2. delirium/encephalitis and abdominal perforation (which the patient in the vignette has experienced) typically occur in the third week of
illness
3. GIT bleed/perforation → +/- Hepatospleenomegaly.
4. Meningitis
5. Leukopenia is sometimes seen
6. Cholecystitis
7. Chronic carriage (1%, more likely if adult females)

Investigation
1. The test of choice is a large volume blood culture (the large volumes are need to increase the yield as few bacteria are circulating).
2. The Widal test → not recommended low sensitivity and specificity.
3. Bone marrow cultures → increased sensitivity compare to blood cultures are considered in exceptional circumstances.
4. CSF has the potential to yield a definitive diagnosis but with lower sensitivity than a large volume blood culture and is more technically difficult to obtain.

Shigella
• causes diarrhoea (may be bloody), abdominal pain
• severity depends on type → S sonnei (UK) may be mild → S. flexneri or S. dysenteriae from abroad may cause severe disease
• Shigella infection is usually self-limiting and does not require antibiotic treatment
• Antibiotics (ciprofloxacin) are indicated
1. People with severe disease
2. immunocompromised
3. with bloody diarrhoea
Giardiasis
Giardiasis is caused by the flagellate protozoan Giardia lamblia. It is spread by the faeco-oral route
Features (Long incubation period, Traveller, Non bloody diahrea)
1. often asymptomatic
2. lethargy, bloating, abdominal pain
3. flatulence
4. non-bloody diarrhoea
5. chronic diarrhoea, malabsorption and lactose intolerance can occur
6. stool microscopy → for trophozoite and cysts are classically negative.
7. therefore duodenal fluid aspirates or 'string tests' (fluid absorbed onto swallowed string) are sometimes needed

Treatment is with metronidazole.

Cryptosporidiosis
• the commonest protozoal cause of diarrhoea in the UK. intracellular protozoa and has an incubation period of 7 days
• Two species, Cryptosporidium hominis and Cryptosporidium parvum account for the majority cases.
• more common in immunocompromised patients (e.g. HIV) and young children.
• Features
1. watery diarrhoea
2. abdominal cramps
3. fever
4. in immunocompromised patients → entire GIT may be → complications such as sclerosing cholangitis and pancreatitis

Diagnosis
• stool: modified Ziehl-Neelsen stain (acid-fast stain) of the stool may reveal the characteristic red cysts of Cryptosporidium

Management
• largely supportive
• Nitazoxanide → for immunocompetent patients
HIV: diarrhoea
Diarrhoea is common in patients with HIV. Causes
1. The effects of the virus itself (HIV enteritis)
2. Opportunistic infections
✓ Cryptosporidium + other protozoa (most common)
✓ Cytomegalovirus
✓ Mycobacterium avium intracellulare
✓ Giardia

Cryptosporidium
• Presentation is very variable, ranging from mild to severe diarrhoea. A modified Ziehl-Neelsen stain (acid-fast stain) of the stool→ red cysts Cryptosporidium.
• Treatment → being supportive therapy (nitazoxanide is licensed in the US for immunocompetent patients)

Mycobacterium avium intracellulare

• is an atypical mycobacteria → CD4 count < 50.
• Typical features include fever, sweats, abdominal pain and diarrhoea. There may be hepatomegaly and deranged LFTs.
• Diagnosis is made by blood cultures and bone marrow examination.
• Management is with rifabutin, ethambutol and clarithromycin

HIV: Mycobacterium avium complex

• (MAC) is an atypical mycobacterial infection seen in HIV patients → caused by both Mycobacterium avium and Mycobacterium intracellulare,
• and is often referred to as Mycobacterium avium-intracellulare (MAI).
• Over 95% of MAC infections in patients with HIV are caused by Mycobacterium avium. ( CD4 count<50 cells/mm³)
Features
1. fever, sweats
2. abdominal: pain, diarrhoea
3. lung: dyspnoea, cough
4. anaemia
5. lymphadenopathy
 6. hepatomegaly/deranged LFTs

Diagnosis
• blood cultures
• bone marrow aspirate

Prophylaxis
• clarithromycin or azithromycin when CD4 < 100 cells/mm³

Management
• rifampicin + ethambutol + clarithromycin
✓ A minimum of two drugs → clarithromycin + ethambutol.
✓ In severe disease, rifabutin can be added. This is recommended due to fewer side-effects than rifampicin however rifampicin is still the third drug
in severe disease due to its cheaper cost.
✓ Azithromycin can be also substituted for clarithromycin in severe disease.

Mycobacterium tuberculosis can present similarly→ mycobacterium avium complex(marked hepatomegaly),Mycobacterium tuberculosis (focal lesions in the liver

Leptospirosis
spirochaete Leptospira interrogans (serogroup L. icterohaemorrhagiae), classically being spread by contact with infected rat urine.
• leptospirosis is commonly seen in questions referring to sewage workers, farmers, vets or people who work in an abattoir, considered in the returning traveler
• Weil's disease should always be considered in high-risk patients with hepatorenal failure Features
1. Early phase is due to bacteraemia and lasts around a week
✓ may be mild or subclinical
✓ fever
✓ flu-like symptoms
✓ subconjunctival suffusion (redness)/haemorrhage
2. second immune phase may lead to more severe "Fulminant" (Weil's disease)10% only
✓ Acute kidney injury (seen in 50% of patients)
 ✓ hepatitis: jaundice, hepatomegaly
✓ aseptic meningitis
✓ Pulmonary Complications → Rare as it is only Severe disease may result in acute respiratory distress syndrome or pulmonary haemorrhag

Investigation
• serology: antibodies to Leptospira develop after about 7 days
• PCR
• culture
• growth may take several weeks so limits usefulness in diagnosis
• blood and CSF samples are generally positive for the first 10 days
• In case of minigism lumbar puncture should ideally be done first to confirm meningeal involvement.
• urine cultures become positive during the second week of illness

Management
• high-dose benzylpenicillin or doxycycline
Lyme disease
Caused by the spirochaete Borrelia burgdorferi and is spread by ticks. Features
1. History of being bitten by a tick, Hiking
2. Early: →Erythema chronicum migrans (70 - 80%)
small papule often at site of the tick bite which develops into a larger annular lesion with central clearing, ('bulls-eye') rash is
➔ fever, arthralgia
3. Late
1. CVS → heart block, myocarditis
2. CNS →Unilateral facial nerve palsy(3-10%),, other nerve palsies meningitis
3. Polyarthiritis
Investigation
• Lyme disease can be diagnosed clinically if erythema migrans is present → erythema migrans is therefore an indication to start antibiotics
• Enzyme-linked immunosorbent assay (ELISA) antibodies → first-line test
✓ -Ve + Lyme disease is still suspected in people tested within 4 weeks from symptom onset→ repeat the ELISA 4-6 weeks after the first test.
 ✓ If still suspected in people W symptoms ≥ 12 weeks → immunoblot test should be done
✓ +Ve or equivocal → immunoblot test for Lyme disease should be done

Management of asymptomatic tick bites

1. tick bites can cause significant anxiety → NO routine antibiotic for tick bite
2. Suspected/confirmed Lyme disease → Doxycycline (14-21) if early disease. Amoxicillin is an alternative if contraindicated (pregnancy)
3. People with erythema migrans →commenced on antibiotic without the need for further tests
4. Ceftriaxone if disseminated disease
5. Jarisch-Herxheimer reaction → after initiating therapy: fever, rash, tachycardia after first dose of antibiotic (>commonly seen in syphilis, another
spirochaetal disease)
Typhus
• Rickettsial diseases → Transmitted between hosts by arthropods
• cause widespread vasculitis, Features
1. fever, headache
2. Black eschar at site of original inoculation
3. Rash (maculopapular or vasculitis)
4. Complications → deranged clotting, renal failure, DIC
Rocky Mountain spotted fever Tick typhus
• Caused by R rickettsii • caused by R conorii
• initially macular rash or hands and feet then spread • rash initially in axilla then spreads
Treatment
Doxycycline is effective against all of the tropical rickettsial infections → initially may need to be given down an nasogastric tube.
The likely diagnosis here is one of scrub typhus, which is caused by the obligate intracellular bacteria Orientia tsutsugamushi and is one of a group of related
conditions collectively known as the 'tropical rickettsial infections'.

Scrub typhus is the most common tropical rickettsial infection in South-east Asia, where it is a common cause of febrile illness. It is transmitted by the bite of
a 'chigger' which live in dry grassy areas. It presents as a vasculitis-like illness with regional or generalised lymphadenopathy and there is typically a black
crusted lesion at the site of the bite called an 'eschar'. Complications include hepatic and renal failure, myocarditis and (as seen in this case)
meningoencephalitis.
The diagnosis of scrub typhus is almost invariably a clinical one and rests on plausible epidemiology and compatible symptoms. Given that the clinical
spectrum of disease is wide this can often be difficult and a very careful search for the eschar (often at the joins of clothing where the chigger mite is unable
to climb further) is warranted as its discovery all but seals the diagnosis.
Leishmaniasis
intracellular protozoa Leishmania→ spread by sand flies. Cutaneous, mucocutaneous leishmaniasis and visceral forms are seen

Cutaneous Mucocutaneous Visceral (kala-azar)

Organism Leishmania tropica or Leishmania mexicana
Symptoms •Crusted lesion at site of bite
•may be underlying (Patch or papule that ulcerate
→ central depression and a raised indurated
border
Epidemiology • South or Central America (Myxicana)→ treatment
due to risk of mucocutaneous (Brazilines)
• Africa or India → managed more conservatively
The duration of the lesion depends on
The species of leishmania, host immune response but is typically 6-12 months.
Leishmania braziliensis Leishmania donovani
• skin lesions may spread 1. Fever, sweats, rigors
to involve mucosae of 2. massive splenomegaly. hepatomegaly
nose, pharynx etc 3. poor appetite, weight loss OR
↑↑ appetite with paradoxical weight loss
4. Grey skin - 'kala-azar' → black sickness
5. Pancytopaenia →2ry to hypersplenism
6. Gold standard for diagnosis
bone marrow or splenic aspirate
7. Mediterranean, Asia(Afghanistan)
8. South America, Africa

Treatment
Most lesions will self resolve systemic therapy (Miltefosine )is considered if
1. Cutaneous leishmaniasis acquired in South America
2. Multiple (>4) lesions
3. large lesions (>5cm)
 4. lesions involve the face, hands or genital
5. host is immunocompromised
Local treatment has failed
Trypanosomiasis
2 main form of this protozoal disease
sleeping sickness
African
Trypanosoma Gambiense →West
Trypanosoma Rhodesiense →East (More Acute)
Spread by Tsetse fly → Painful
Features 1. Trypanosoma chancre - painless subcutaneous
nodule at site of infection
2. intermittent fever
3. Enlargement of posterior cervical LN
4. Later → CNS involvement (somnolence,
headaches, mood changes, meningoencephalitis 1. Heart (Leading cause of death) → Myocarditis → Dilated
• Early disease: IV Pentamidine or Suramin
Management
• later disease or CNS involvement → IV
Melarsoprol
Q fever
Chagas' disease
American
Trypanosoma Cruzi.
Triatomine bug, a type of reduviid bug → via a painless fly
Acute Phase
1. 95% are asymptomatic
2. Chagoma (erythematous nodule at site of infection)
3. Periorbital oedema are sometimes seen.
Chronic Chagas' disease
cardiomyopathy (apical atophy) & arrhythmias
2. GIT → Megaoesophagus malnutrition, oesophagitis, oesophageal cancer.
and Megacolon → fecaloma, sigmoid volvulus and constipation
• Treatment is most effective in the acute phase → Azole or Nitroderivatives
(Benznidazole or Nifurtimox) → target the p450 system to (- -)the growth
• Chronic disease management → treating the complications ( heart failure
 Caused by Coxiella burnetii, a rickettsia. The source of infection is typically an abattoir, cattle/sheep or it may be inhaled from infected dust

Features
1. Typically prodrome → fever, malaise
2. causes pyrexia of unknown origin
3. Transaminitis
4. Atypical pneumonia
5. Endocarditis → (signs of endocarditis + TEE → endocarditis but –Ve culture )

Management
Doxycycline

Cat scratch disease

Cat scratch disease is generally caused by the Gram negative rod Bartonella henselae. Features
1. fever
2. history of a cat scratch
3. regional lymphadenopathy
4. headache, malaise

Other Zoonosis →Coxiella burnetii is a gram-negative rod and the causative agent of Q fever, exposure to farm animals, flu-like symptoms, pneumonia,
hepatitis and a potentially fatal endocarditis.

Malaria
Falciparum malaria is the commonest, and most severe, type of malaria. Feature of severe malaria
1. Schizonts on a blood film
2. Parasitaemia > 2%
3. Severe anaemia
4. Hypoglycaemia
5. Acidosis
 6. Temperature > 39 °C
7. Complications as below
✓ Cerebral malaria → seizures, coma
✓ Acute renal failure → blackwater fever, secondary to intravascular haemolysis, mechanism unknown
✓ Acute respiratory distress syndrome (ARDS)
✓ Pulmonary Oedema, seizers, Shock.
✓ DIC
Non-falciparum
The most common non-falciparum malaria → Plasmodium vivax. Central America and the Indian
Plasmodium ovale/ Plasmodium malariae → Africa. Plasmodium knowlesi → predominantly in South East Asia.
Features
1. General features of malaria: fever, headache, splenomegaly
2. Plasmodium vivax/ovale → Cyclical fever every 48 hours.
→ have a hypnozoite stage and may relapse following treatment.--> Long Period of infection
3. Plasmodium Malariae → cyclical fever Every 72 hours W Nephrotic Syndrome.

Plasmodium sp →2 reproductive cycles

1. Exo-erythrocytic cycle → hepatocytes
2. Erythrocytic cycle
✓ In the RBCs
✓ The length of the cycle varies from species to species → P. knowlesi having the fastest cycle at around 24 hours.
✓ The end stage in the cycle → RBCs lysis and release of additional parasites → P. knowlesi (producing very high parasite counts in short time)
✓ Consequently, severe parasitaemia in Plasmodium knowlesi → defined as >1%, whereas in other species, >2% parasitaemia..

Treatment
• Areas known to be chloroquine-sensitive → either an artemisinin-based combination therapy (ACT) or chloroquine
• Areas known to be chloroquine-resistant → ACT should be used
• ACTs should be avoided in pregnant women
• Ovale or Vivax malaria → primaquine following acute treatment with chloroquine to destroy liver hypnozoites and prevent relapse
➔ G6PD deficiency should be tested before giving it → CI in G6PD deficiency
 Investigation
• The gold standard for diagnosis of malaria → blood film.
• Rapid diagnostic tests (plasmodial histidine-rich protein 2) trialled and shown sensitivities 77-99% and specificities 83-98% for falciparum malaria

Blood film - if doubt about diagnosis should be repeated

1. Thick → more sensitive (Detect the Burden/Quantity of parasite)

Other tests
1. Thrombocythaemia is characteristic
2. Normochromic Normocytic anaemia
3. normal TLC
4. Reticulocytosis.

Uncomplicated falciparum malaria

• strains resistant to chloroquine are prevalent in certain areas of Asia and Africa
• Artemisinin-based combination therapies (ACTs) as first-line therapy
Ex:Artemether + lumefantrine/ Artesunate + amodiaquine/ Artesunate + mefloquine/ artesunate + sulfadoxine-pyrimethamine/ dihydroartemisinin + piperaquine

Severe falciparum malaria

• Parasite count > 2 → parenteral treatment irrespective of clinical state
✓ IV artesunate is now recommended in preference to intravenous quinine
• Parasite count > 10% → exchange transfusion should be considered
• Shock may indicate coexistent bacterial septicaemia - malaria rarely causes haemodynamic collapse
• Non-falciparum malaria oral ACT or chloroquine if not resistant

Malaria: prophylaxis
The majority of infected travellers (around 75%) are caused by fatal Plasmodium falciparum protozoa. The majority did not take prophylaxis. It
TravellersCitizin from malaria endemic areas and quickly lose their innate immunity.
 Drug Side-effects + notes Time to begin before travel Time to end after travel
Atovaquone + proguanil (Malarone) GI upset 1 - 2 days 1 Week
Chloroquine Taken weekly → Headache 1 week 1 month
Contraindicated in epilepsy
Doxycycline Photosensitivity / Oesophagitis 1 - 2 days 1 month
Mefloquine (Lariam) Taken weekly → Dizziness 2 - 3 weeks 1 month
Neuropsychiatric disturbance → CI in epilepsy
Proguanil (Paludrine) 1 week 1 month
Proguanil + chloroquine See above 1 week 1 month

Pregnant women → avoid travelling to regions malaria is endemic.

Diagnosis is difficult as parasites may not be detectable in the blood film due to placental sequestration. If travel cannot be avoided:
1. chloroquine can be taken
2. proguanil → folate supplementation (5mg od) should be given
3. Malarone (atovaquone + proguanil): → avoid these drugs unless essential. If taken then folate supplementation should be given
4. Mefloquine: caution advised
5. doxycycline is contraindicated

Children→ avoid travel to malaria endemic regions.if travel is essential then children
✓ Should take malarial prophylaxis as they are more at risk of serious complications.
✓ Diethyltoluamide (DEET) 20-50%
❖ repel up to 100% of mosquitoes if used correctly.
❖ >2 months of age
❖ could also be used in breastfeeding women and pregnant women in their 2nd or 3rd trimester
✓ Doxycycline is only licensed >12 years

Melioidosis
• "Whitmore's disease" → caused by the gram-negative bacterium Burkholderia pseudomallei.
• Saprophyte in soil and fresh surface water in endemic regions tropics and subtropics climates →Southeast Asia (Thailand, Malaysia) and Northern America.
• 150,000 case/year worldwide, with most cases occurring in wet seasons.
• Transmission:
1. Percutaneous inoculation: contact with contaminated soil or water (most common)
2. Inhalation, aspiration, or ingestion of contaminated dust or water
3. Person-to-person transmission is rare

Risk factors:
1. D.M (the strongest risk factor)
2. Chronic renal, liver, or lung disease (cystic fibrosis)
3. Immunocompromised states (malignancy, long-term glucocorticoid use)
4. Occupational exposure: agricultural work

Sign and symptoms:

• Incubation period: 1-21 days ( mean around 9 days)
• Symptomatic cases can be acute, chronic (> 2 months), or reactivations of latent infection.
• Clinical features depend on the infected organ:
1. Acute pulmonary infection (most common): wide range of presentations (mild to severe)
2. Localized infection: skin ulcer, nodule, or abscess.
3. Visceral abscesses: especially in the prostate, spleen, kidney, and liver
4. Disseminated infection: occurs in ∼ 55% of cases and has a 20% mortality rate. Manifests with fever and septic shock.

Diagnosis:
• Culture: the mainstay of diagnosis. Gram stain of sputum or abscess pus
• Imaging: Chest radiography: may show signs of acute pneumonia

Treatment:
• Initial intensive therapy: IV ceftazidime, imipenem, or meropenem for 10–14 days
• Followed by eradication therapy: Oral CO- Triamoxazole (Trimethoprim/sulfamethoxazole) (plus doxycycline) for 3–6 months
 • Adjunct therapy: abscess drainage.

Prevention:
• In endemic areas, contact with soil and standing water should be avoided (agricultural workers should wear boots)
• Health care and laboratory workers should wear masks, gloves, and gowns to prevent infection.
• No vaccination available
Cellulitis
An inflammation of the skin and subcutaneous tissues, typically due to infection by Streptococcus pyogenes or Staphylcoccus aureus.

Features
• Commonly occurs on the shins → Erythema, pain, swelling
• there may be some associated systemic upset such as fever

The diagnosis of cellulitis is clinical.

• Bloods and blood cultures may be requested if the patient is admitted and septicaemia is suspected.
• Criteria for admission → Eron classification to guide how we manage patients with cellulitis:
Class Features
I No systemic toxicity and the person has no uncontrolled co-morbidities
II • Systemic unwell or systemically well but with a co-morbidity (PAD, chronic venous insufficiency, morbid obesity)
• May complicate or delay resolution of infection
III • Significant systemic upset (acute confusion, tachycardia, tachypnoea, hypotension), OR
• Unstable co-morbidities interfere with a response to treatment OR
• Limb-threatening infection due to vascular compromize
IV Sepsis syndrome OR a severe life-threatening infection such as Necrotizing Fasciitis
Admit for IV antibiotics the following patients
1. Has Eron Class III or Class IV cellulitis.
2. Severe or rapidly deteriorating cellulitis (Extensive areas of skin).
3. Very young ( < 1 year) or frail.
 4. Immunocompromized.
5. Significant lymphoedema.
6. Facial cellulitis (unless very mild) or Periorbital cellulitis.

Eron Class II cellulitis →Admission may not be necessary if the facilities and expertise are available → give IVantibiotics and monitor the person.
→Other patients can be treated with oral antibiotics.

Management
1. Mild/Moderate Cellulitis.
✓ Flucloxacillin → first-line treatment for
✓ Clarithromycin, Erythromycin (in pregnancy) or Doxycyline is recommended in patients allergic to penicillin.
2. Severe cellulitis → Co-amoxiclav, Cefuroxime, Clindamycin or Ceftriaxone

Necrotising fasciitis
a medical emergency that is difficult to recognise in the early stages. classified according to the causative organism:
1. type 1 is caused by mixed anaerobes and aerobes (often occurs post-surgery in diabetics). This is the most common type
2. type 2 is caused by Streptococcus pyogenes

Features
1. acute onset
2. painful, erythematous lesion/ Hemorragic Bullea develops
3. often presents as rapidly worsening cellulitis (Small wound) → pain out of keeping with physical features, disabled adjacent joint.
4. extremely tender over infected tissue

Management
• urgent surgical referral debridement
• intravenous antibiotics

Chickenpox exposure in pregnancy

• 1ry infection with varicella-zoster virus.
• Shingles is caused by the reactivation of dormant virus in dorsal root ganglion.
• In pregnancy, there is a risk to both the mother and also the fetus" fetal varicella syndrome

Risks to the mother

5 times greater risk of pneumonitis

Fetal varicella syndrome (FVS)

1. < 20 Week → risk of FVS following maternal varicella exposure is around 1%
2. 20-28 weeks → very small number of cases occurring gestation and none following 28 weeks
3. features of FVS include skin scarring, eye defects (microphthalmia), limb hypoplasia, microcephaly and learning disabilities

Other risks to the fetus

• shingles in infancy: 1-2% risk if maternal exposure in the 2nd or 3rd trimester
• severe neonatal varicella: if the mother develops rash between 5 days before and 2 days after birth there is a risk of neonatal varicella (may be fatal to the
newborn child in around 20% of cases

Management of chickenpox exposure in pregnancy

• if there is any doubt about the mother previously having chickenpox maternal blood should be urgently checked for varicella antibodies
• if the pregnant woman is not immune → varicella-zoster immunoglobulin (VZIG) as soon as possible. VZIG is effective up to 10 days post exposure

Management of chickenpox in pregnancy

• if a pregnant woman develops chickenpox in pregnancy then specialist advice should be sought
• ↑↑risk of serious chickenpox infection (maternal risk) and fetal varicella risk (fetal risk) balanced against theoretical concerns about the safety of aciclovir in
pregnancy
• oral aciclovirshould be given if the pregnant women is ≥ 20 weeks and she presents within 24 hours of onset of the rash
• if the woman is < 20 weeks the aciclovir should be 'considered with caution'
• The varicella-zoster vaccine can be offered to women pre-pregnancy or post-partum if they are not immune, but should not be given during pregnancy.
Nematodes
Ancylostoma braziliense (Hookwarm)
• most common cause of cutaneous larva migrans
• common in Central and Southern America
Strongyloides stercoralis
• The larvae are present in soil and gain access acquired percutaneously (walking barefoot) or autoinfection at perineal area →causes pruritus and
larva currens → similar appearance to cutaneous larva migrans but moves through the skin at a far greater rate → Features
1. Diarrhoea/ abdominal pain/bloating
2. Papulovesicular lesions → where the skin has been penetrated by infective larvae e.g. soles of feet and buttocks
3. larva currens: pruritic, linear, urticarial rash
4. if the larvae migrate to the lungs a pneumonitis similar to Loeffler's syndrome may be triggered
5. may cause Gram negative septicaemia due carrying of bacteria into bloodstream
6. Eosinophilia sometimes seen

• Treatment → ivermectin and albendazole, thiabendazole are used, particularly in chronic infections

Toxocara canis
• commonest cause of visceral larva migrans
• commonly acquired by ingesting eggs from soil contaminated by dog faeces
• Other features: eye granulomas, liver/lung involvement

Tape worms
Tape worms are made up of repeated segments called proglottids. → often present in faeces and are useful diagnostically
Cysticercosis
1. caused by Taenia solium (from pork) and Taenia saginata (from beef)
2. management: niclosamide

Hydatid disease
1. caused by the dog tapeworm Echinococcus granulosus
 2. life-cycle involves dogs ingesting hydatid cysts from sheep liver
3. often seen in farmers
4. may cause liver cysts
5. Management: albendazole
Schistosomiasis
A parasitic flatworm infection. The three main species of schistosome are S. mansoni, S. japonicum and S. haematobium.
Acute infections → only develop in people who travel to endemic areas, as they don't have any immunity to the worms. Manifestations
1. Swimmers' itch
2. Acute schistosomiasis syndrome (Katayama fever)
✓ Systemic reaction to Schistosoma (weeks to months after initial infection).
✓ fever
✓ urticaria/angioedema and bumpy rash
✓ arthralgia/myalgia
✓ cough,, Wheeze chest → X- ray may show bilateral infiltrates
✓ eosinophilia
✓ Hepatospleenomegaly.
✓ diarrhoea
Chronic infections
1. Schistosoma haematobium
✓ These worms deposit egg clusters (pseudopapillomas) in the bladder →inflammation → calcification seen on x-ray (calcification of the egg
clusters, not the bladder itself.
✓ Depending on the site of these pseudopapillomas in the bladder→ can cause an obstructive uropathy and kidney damage.
✓ 'swimmer's itch' in patients who have recently returned from Africa. Schistosoma haematobium is a risk factor for squamous cell bladder cancer.
✓ Features → frequency/ haematuria/ bladder calcification.
✓ Management → single oral dose of praziquantel

2. Schistosoma mansoni and Schistosoma japonicum

✓ These worms mature in the liver → travel through the portal system to inhabit the distal colon → can lead to progressive hepatomegaly and
splenomegaly due to portal vein congestion.
 ✓ These species can also lead to complications of liver cirrhosis, variceal disease and cor pulmonale.

3. Schistosoma intercalatum and Schistosoma mekongi

These are less prevalent than the other three forms, but are both attributed to intestinal schistosomiasis.
Bacterial vaginosis
• Overgrowth of predominately anaerobic organisms (Gardnerella vaginalis)→ ↓↓ lactic acid producing aerobic lactobacilli → ↑↑ vaginal pH.
• BV is not a sexually transmitted infection it is seen almost in sexually active women.

Features
• Vaginal discharge: 'fishy', offensive
• Asymptomatic in 50%

Amsel's criteria for diagnosis of BV - 3 of the following

1. Thin, white offensive, fishy homogenous discharge
2. Clue cells on microscopy → Stippled vaginal epithelial cells
3. vaginal pH > 4.5
4. +Ve whiff test → addition of K+ hydroxide → Fishy Odour.

Management
• Oral metronidazole for 5-7 days → 70-80% initial cure rate
• Relapse rate > 50% within 3 months
• Topical metronidazole or Topical clindamycin as alternatives

Bacterial vaginosis in pregnancy

• ↑↑ risk of preterm labour, low birth weight and Chorioamnionitis, late miscarriage
• Oral metronidazole is used throughout pregnancy → Avoid ↑↑ dose Metronidazole regimes

Trichomonas vaginalis
• A highly motile, flagellated protozoan parasite. Trichomoniasis is a sexually transmitted infection (STI). Features
 1. vaginal discharge: offensive, yellow/green, frothy
2. vulvovaginitis
3. strawberry cervix
4. pH > 4.5
5. in men → usually asymptomatic but may cause urethritis
• Investigation → microscopy of a wet mount shows motile Trophozoites
• Management → oral metronidazole for 5-7 days → supports the use of a one-off dose of 2g metronidazole

Chlamydia
The most prevalent sexually transmitted infection in the UK and is caused by Chlamydia trachomatis, an obligate intracellular pathogen.
Approximately 1 in 10 young women in the UK have Chlamydia. The incubation period is around 7-21 days, a large percentage of cases are asymptomatic

Features
• asymptomatic in around 70% of women and 50% of men
• women: cervicitis (discharge, bleeding), dysuria
• men: urethral discharge, dysuria

Potential complications
1. epididymitis
2. pelvic inflammatory disease
3. endometritis
4. increased incidence of ectopic pregnancies
5. infertility
6. Reactive arthritis
7. Perihepatitis (Fitz-Hugh-Curtis syndrome)

Investigation
• traditional cell culture is no longer widely used
• Nuclear acid amplification tests (NAATs) are now the investigation of choice
• Urine (first void urine sample), vulvovaginal swab or cervical swab may be tested using the NAAT technique
• for women → the vulvovaginal swab is first-line
• for men → the urine test is first-line
• Testing should be carried out two weeks after a possible exposure

Screening
• Screening Programme is open to all men and women aged 15-24 years
• relies heavily on opportunistic testing
Management
• Doxycycline (7 day course) or Azithromycin (1g single dose) → azithromycin first-line due to potentially poor compliance with a 7 day course of doxycycline
• if pregnant → azithromycin, erythromycin or amoxicillin may be used. The SIGN guidelines suggest azithromycin 1g stat is the drug of choice 'following
discussion of the balance of benefits and risks with the patient'
• patients diagnosed with Chlamydia should be offered a choice of provider for initial partner notification - either trained practice nurses with support from GUM,
or referral to GUM
 • for men with urethral symptoms: all contacts four weeks prior to, the onset of symptoms
• for women and asymptomatic men all partners from the last six months or the most recent sexual partner should be contacted
• Contacts of confirmed Chlamydia cases should be offered treatment prior to the results of their investigations being known (treat then test)

If the swab shows

✓ Gram negative diplococci → Gonorrhoea
✓ non-specific urethritis → Chlamydia is most likely.
If patient with gonorrhea is not responding for ttt → associated Chlamydia infection.

Gonorrhoea
• Neisseria gonorrhoeae → Intracellular gram-negative diplococcus
• Acute infection → on any mucous membrane surface (genitourinary but also rectum and pharynx)
• The incubation period of gonorrhoea is 2-5 days, Features
1. males: urethral discharge, dysuria
2. females: cervicitis (vaginal discharge)
3. rectal and pharyngeal → asymptomatic

• Microbiology
Immunisation is not possible→ reinfection is common → antigen variation of type IV pili (proteins adhere to surfaces) and Opa (surface proteins bind to
receptors on immune cells)

Local complications
urethral strictures, epididymitis and salpingitis
( Infertility secondary to PID is the most common complication) → Gonorrhea is the 2nd commonest for PID after Chlamydia
Disseminated infection may occur - see below

Management
1. ciprofloxacin → treatment of choice. (increased resistance to ciprofloxacin (around 36% in the UK) → cephalosporins widely used
2. New first-line treatment → 1 dose of IM ceftriaxone 1g (No longer add azithromycin).
 3. Ceftriaxone is refused (needle-phobic) → oral cefixime 400mg (single dose) + oral azithromycin 2g (single dose).
4. Only if known sensitive to ciprofloxacin → 1 dose of oral ciprofloxacin 500mg .
5. Disseminated gonococcal infection (DGI) and gonococcal arthritis
✓ The most common cause of septic arthritis in young adults.
✓ The pathophysiology of DGI is thought to be due to haematogenous spread from mucosal infection (Asymptomatic genital)
✓ Initially a classic triad (tenosynovitis +Asymmetrical migratory polyarthritis + dermatitis "maculopapular or vesicular")
✓ Also Concurrent W urethral and vaginal discharge.
✓ Later complications include septic arthritis, endocarditis and perihepatitis (Fitz-Hugh-Curtis syndrome)

DD. Reactive arthritis → triad (conjunctivitis, urethritis, and polyarthritis).

• joint pain is often symmetrical W migratory pattern
• occur 1 - 4 weeks after a bout of urethritis or enteritis, rather than concurrently with urethritis
• higher association with chlamydia rather than gonorrhoea.

Urinary tract infection in adults: management

Lower urinary tract infections
1. Non-pregnant women
• local antibiotic guidelines should be followed if available →Trimethoprim or Nitrofurantoin (3 days)
• send a urine culture if:
✓ aged > 65 years
✓ visible or non-visible haematuria
2. Pregnant women
• if the pregnant woman is symptomatic:
✓ a urine culture should be sent in all cases
✓ should be treated with an antibiotic for
1st -line: Nitrofurantoin (should be avoided near term)
2nd -line: Amoxicillin or Cefalexin
• asymptomatic bacteriuria in pregnant women:
✓ a urine culture should be performed routinely at the first antenatal visit (ifbateria is detected)
 ✓ Immediate antibiotic → nitrofurantoin (should be avoided near term), amoxicillin or cefalexin (7-day course)
✓ asymptomatic bacteriuria is the significant risk of progression to acute pyelonephriti
✓ a further urine culture should be sent following completion of treatment as a test of cure
3. Men
• an immediate antibiotic prescription should be offered

4. Catherised patients
• do not treat asymptomatic bacteria in catheterised patients
• if the patient is symptomatic they should be treated with an antibiotic → 7-day (rather than a 3-day)
Acute pyelonephritis
• hospital admission should be considered
• local antibiotic guidelines should be followed if available
• broad-spectrum cephalosporin or a quinolone (for non-pregnant women) for 10-14 days

Urine Analysis Interpretation

• Leukocytosis + Ve → UTI
• Nitrite
✓ If + Ve → Gram –Ve organisms (E.Coli) → they convert nitrates to nitrites for energy.
✓ If –Ve → Gram +Ve organisms (S. Saprophiticus) → are unable to reduce nitrate to nitrite

Asymptomatic bacteriuria → should not be treated except (pregnancy, children < 5 years or immunosuppressed (the risk of complications)

Non-gonococcal urethritis
Non-gonococcal urethritis (NGU, sometimes referred to as non-specific urethritis) is a term used to describe the presence of urethritis when a
gonococcal bacteria are not identifiable or the initial swab. A typical case would be a male who presented to a GUM clinic with a purulent
urethral discharge and dysuria. A swab would be taken in clinic, microscopy performed which showed neutrophils but no Gram negative
diplococci (i.e. no evidence of gonorrhoea). Clearly this patient requires immediate treatment prior to waiting for the Chlamydia test to come
back and hence an initial diagnosis of NGU is made.
 Causative organisms include:
• Chlamydia trachomatis - most common cause
• Mycoplasma genitalium - thought to cause more symptoms than Chlamydia

Management
• contact tracing
• the BNF and British Association for Sexual Health and HIV (BASHH) both recommend either oral azithromycin or doxycycline

Orf

Orf is generally a condition found in sheep and goats although it can be transmitted to humans. It is caused by the parapox virus.

In animals

• 'scabby' lesions around the mouth and nose

In humans
 • generally affects the hands and arms
• initially small, raised, red-blue papules
• later may increase in size to 2-3 cm and become flat-topped and haemorrhagic

Parvovirus B19
Parvovirus B19 is a DNA virus which causes a variety of clinical presentations. It was identified in the 1980's as the cause of erythema
infectiosum

Erythema infectiosum (also known as fifth disease or 'slapped-cheek syndrome')

The illness may consist of a mild feverish illness which is hardly noticeable. However, in others there is a noticeable rash which
appears after a few days. The rose-red rash makes the cheeks appear bright red, hence the name ‘slapped cheek syndrome’. The
rash may spread to the rest of the body but unlike many other rashes, it only rarely involves the palms and soles.

The child begins to feel better as the rash appears and the rash usually peaks after a week and then fades. The rash is unusual in
that for some months afterwards, a warm bath, sunlight, heat or fever will trigger a recurrence of the bright red cheeks and the rash
itself. Most children recover and need no specific treatment. School exclusion is unnecessary as the child is not infectious once the
rash emerges. In adults, the virus may cause acute arthritis.

Be aware that the virus can affect an unborn baby in the first 20 weeks of pregnancy. If a woman is exposed early in pregnancy
(before 20 weeks) she should seek prompt advice from whoever is giving her antenatal care as maternal IgM and IgG will need to
be checked. It is spread by the respiratory route and a person is infectious 3 to 5 days before the appearance of the rash. Children
are no longer infectious once the rash appears and there is no specific treatment.
Infection in a pregnant woman can lead to fetal hydrops and spontaneous miscarriage, particularly in the first trimester. This can be managed
with the use of fetal blood transfusion.
The child need not be excluded from school as they are no longer infectious by the time the rash occurs.

Female contact to Case → Pregnancy test

Other presentations
 Other presentations include:

• asymptomatic
• pancytopaenia in immunosuppressed patients
• aplastic crises e.g. in sickle-cell disease (parvovirus B19 suppresses erythropoiesis for about a week so aplastic anaemia is rare
unless there is a chronic haemolytic anaemia)

Genetal Ulcer
Organism Symptoms Treatment
Chancroid Haemophilus Ducreyi • Painful genital ulcers
• Unilateral, painful inguinal lymph node enlargement.(ch.ch 50%)
• The ulcers → sharply defined, ragged, undermined border.
Genetal Hereps HSV(1-2) • 1ry attacks → severe and associated with fever
• Subsequent attacks → less severe and localised to one site
• Multiple painful ulcers..
Chancer Treponema pallidum. • A painless ulcer (chancre) is seen in the primary stage.
• The incubation period= 9-90 days
Lymphogranuloma Chlamydia Risk factors • Doxycycline.
venereum Trachomatis L1, L2 • men who have sex with men • Macrolides
and L3. • the majority of patients in developed countries have HIV (azithromycin or
• historically was seen more in the tropics erythromycin)
3 stages • potential surgical
1. stage 1 small painless pustule → later forms an ulcer →self-limiting3-12 days drainage/aspiratio
 2. stage 2: 1- 6 months later Unilateralpainful inguinal Lymphadenopathy of the buboes or
known as buboes abscesses
3. may occasionally form fistulating buboes
4. stage 3: proctocolitis
• Groove sign →A separation inguinal nodes by the inguinal ligament and is
characteristic of the disease
• Diagnosis → ELISA , PCR
• Complications → Genital elephantiasis/ hepatitis/ infertility/ PID/ Arthritis/
Fitz hugh curtis syndrome.

Other causes of genital ulcers

• Behcet's disease → paiful
• carcinoma
• granuloma inguinale → Klebsiella granulomatis → Painless ulcer

Genital herpes
HSV-1 and HSV-2. Features
• primary infection: may present with a severe ulceration and pain
• urinary retention may occur
• painful genital ulceration

Management
• Genital herpes → Oral aciclovir. Some patients with frequent exacerbations may benefit from longer term aciclovir
• Pregnancy
1. Elective caesarean section at term is advised if a primary attack of herpes occurs during pregnancy at > 28 weeks gestation.
2. Vaginal delivery is usually anticipated in recurrent genital herpes
3. pregnant women with recurrent herpes → treated with suppressive therapy and be advised that the risk of transmission to their baby is low
4. Suppressive treatment is often considered from 36 weeks to reduce asymptomatic shedding and risk of transmission during delivery
5. Aciclovir, while not licensed for use in pregnancy, is commonly used in pregnancy and is thought to be safe;
 6. valaciclovir and famciclovir should be avoided.
Syphilis
Asexually transmitted infection caused by the spirochaete Treponema pallidum. → The incubation period is between 9-90 days
Primary features
1. chancre - painless ulcer at the site of sexual contact
2. local non-tender lymphadenopathy
3. often not seen in women (the lesion may be on the cervix)

Secondary features (6-10 weeks after primary infection

1. systemic symptoms: fevers, lymphadenopathy
2. rash on trunk, palms and soles
3. buccal 'snail track' ulcers (30%)
4. condylomata lata (painless, warty lesions on the genitalia )

Tertiary features
1. Gummas (granulomatous lesions of the skin and bones)
2. ascending aortic aneurysms
3. general paralysis of the insane
4. Tabes Dorsalis
5. Argyll-Robertson pupil

Features of congenital syphilis

1. blunted upper incisor teeth (Hutchinson's teeth), 'mulberry' molars
2. rhagades (linear scars at the angle of the mouth)
3. keratitis
4. saber shins
5. saddle nose
6. deafness
Investigation
T. pallidum is a very sensitive organism and cannot be grown on artificial media.The diagnosis (clinical features, serology and microscopic infected tissue

Serological tests can be divided into:

1. Cardiolipin tests (not treponeme specific)
2. Teponemal-specific antibody tests

Cardiolipin tests
✓ syphilis infection leads to the production of non-specific antibodies that react to Cardiolipin
✓ Ex: VDRL (Venereal Disease Research Laboratory) & RPR (rapid plasma reagin)
✓ insensitive in late syphilis
✓ Becomes -Ve after treatment

Treponemal specific antibody tests

✓ example: TPHA (Treponema pallidum HaemAgglutination test)
✓ remains +Ve after treatment

After treatment for syphilis:

1. VDRL becomes negative
2. TPHA remains positive

Causes of false positive cardiolipin tests:

1. pregnancy
2. SLE, anti-phospholipid syndrome
3. TB
4. leprosy
5. malaria
6. HIV
 Management
1. IM benzathine penicillin is the first-line management
2. alternatives: doxycycline
3. Jarisch-Herxheimer reaction is sometimes seen following treatment
✓ fever, rash, tachycardia → after the 1st dose of antibiotic
✓ in contrast to anaphylaxis, there is no wheeze or hypotension → (Wheezy chest → Anaphylaxisn (Adrenaline)
✓ Due to the release of endotoxins following bacterial death and typically occurs within a few hours of treatment
✓ No treatment is needed other than antipyretics if required → self limiting to 24-48 hours ( important to inform patients about prior to treatment

Genital warts
• Genital warts "condylomata accuminata" → varieties of HPV( 6 & 11).
• HPV (primarily types 16,18 & 33) predisposes to cervical cancer.
• Features
1. Small (2 - 5 mm) fleshy / protrude / slightly pigmented
2. may bleed or itch

• Management
1. Topical podophyllum or cryotherapy → first-line treatments depending on the location and type of lesion.
✓ Multiple, non-keratinised warts are generally best treated with topical agents
✓ Solitary, keratinised warts respond better to cryotherapy
2. Imiquimod is a topical cream → second line
3. genital warts are often resistant → recurrence is common → majority of anogenital with HPV clear without intervention within 1-2 years

Pubic lice
"Pediculosis pubis" or "Phthiriasis pubis". → It is most commonly a sexually transmitted infestation of the pubic hair by Phthirus pubis 'crab louse'.
The incidence steadily decreasing over the past decade, Epidemiology
1. The majority are due to sexual → sexually active patients of any age,
 2. ↑↑↑ men . 15-40 years of age.
3. The incidence has previously 4.0%, with average 2.0% UK incidence of only 0.07%, (increased pubic hair removal rates)

Risk factors
• The primary risk factor for pubic lice is sexual contact, however occasionally infest other sites of hair
• . Incubation 5 days, → time between sexual contact and symptoms may be many weeks.

Patients typically present with:

• Itching/pruritis → typically worse at night1 may be localised to the pubic region or may affect any regions of body hair and rarely eyelashes and the head.
• Sometimes patient's may notice a 'black/rust-coloured powder' appearance in their underwear.

Signs:
• It may be possible to visualise individual lice, however microscopy may be required to see them.
• Excoriation marks due to repeated scratching due to pruritus.
• Blue macules (maculae ceruleae) may be visible → due to anticoagulant saliva injected by the lice during their feeding.

Investigations
• The diagnosis is clinical.
• Microscopic/dermascopic → presence of lice or eggs if they are not visible to the naked eye.3
• Patients presenting with pubic lice should be offered a full sexual health screen.

Management
• Clothing and bed linen should be decontaminated either by washing at >50ºC or by placing in a sealed plastic bag for >7 days.
• Malathion 0.5%/ Permethrin 1% / phenothrin 0.2% or carbaryl 0.5% → applied to all body hair and left on the hair for the recommended 'treatment time'
before being washed off.
• Treatment should be re-applied after 3-7 days: this is due to the presence of lice and eggs being at different stages of their life cycle.
• Mechanical removal should also be employed using nit-combs or similar techniques.
• Shaving does not have a role in the management of pubic lice and should not be recommended.
• Re-examination should be performed approximately 1 week after treatment (reapplying) to ensure response to treatment.
• Contact tracing should also be performed and any sexual partners within the past 3 months should be examined and treated where appropriate.