Download Problem 06- Fever

Fever
Contents
1. Thermoregulation and physiology of fever
2. History taking- undiagnosed fever
3. Sepsis
4. Childhood rashes
5. Childhood vaccination schedule
6. Common viral infections
7. Common bacterial infections (community)
8. Hospital acquired infections
9. Tropical infections
a. Gastroenteritis
b. Hepatitis
c. Malaria
d. Neglected tropical diseases
e. Tuberculosis
f. HIV
10. Pyrexia of unknown origin, including:
a. Infectious causes
b. Non-infectious causes
i. Inflammatory and tissue damaging conditions
ii. Kawasaki disease
iii. Malignant conditions
iv. Other, including factitious and drug-induced
11. Malignant hyperpyrexia
12. Investigations used in fever
13. Management of fever
a. Antifungals
b. Antivirals
c. Antibiotics
d. Febrile convulsions
e. Heat exhaustion
14. Notifiable diseases
1. Thermoregulation and physiology
Heat loss
 From skin by radiation, conduction and convection
 From skin and respiratory mucosa due to evaporation
Heat production
 Metabolic activity
 Skeletal muscle activity
Fever – the ‘thermostat’ of the hypothalamus is reset up
 ‘Thermostat’ resetting is triggered by endogenous pyrogens (interleukins and
possibly other molecules) released by macrophages in liver and other tissues in
presence of stimuli e.g. infection
 This triggers prostaglandin release in the hypothalamus (this is where aspirin acts as
antipyretic), and the ‘thermostat’ is altered
 The person then feels cold despite being a normal temperature
 This triggers events to increase temperature: vasoconstriction, shivering, curling up,
and behaviour such as more blankets
 Body temperature rises to target and stabilises
 When the ‘thermostat’ normalises, the person feels hot, there is sweating and
vasodilation, and they throw the covers off
2. Taking a history for undiagnosed fever
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Any focal symptoms?
Time course
Travel history
Food and water history
Occupational history
Animal contact
Sexual activity
Family history
Intravenous drug use
Leisure activities (exposure to water born infections/zoonoses)
3. Sepsis
Definitions:
Sepsis
Signs and sumptoms of a systemic inflammatory response to
localised infection. Positive blood culture with clinical features: fever,
tachycardia, tachypnoea)
Severe sepsis
Complicated by organ dysfunction, hypotension OR hypoperfusion.
Look for low BP, oliguria, hypoxia, confusion, lactic acidosis.
Septic shock
Complicated by organ dysfunction AND hypotension unresponsive to
adequate fluid replacement.
Other general symptoms: Sweats, chills or rigors, breathlessness, headache, confusion
especially in the elderly. May have nausea, vomiting or diarrhoea.
Management- from Surviving Sepsis Campaign Guidelines
Resuscitate:
Airway: Check airway is clear.
Breathing: Give high flow oxygen, if refractory hypoxia intubate and ventilate.
Circulation: Crystalloid or colloid, fluid challenge e.g. 300-500mls colloid or 1000mls
crystalloid over 30 mins to restore circulating volume.
Disability: Manage blood glucose,
Exposure: Search for origin of infection- examination, x-ray, echo, other imaging.
Resus aims: Maintain MAP of at least 65 mmHg, Central venous pressure 8-12mmHg,
Oxygen saturation ≥70%, Urine output ≥ 0.5/ml/Kg/Hr
Investigations: Blood culture (x2, plus 1 from each vascular access device in situ for 48 hours
or more), urine culture, pus, swabs, bronchial lavage/biopsy if indicated. Consider prompt
imaging to confirm site of infection, as appropriate and safe.
Start empiric antibiotics (within 1 hour of recognition), broad spectrum, consider
combination in neutropenic. Reassess daily, duration dependent on results but usually 7-10
days.
Empiric Antibiotic Regimens
Suspected source of sepsis
Pneumonia (community)
Pneumonia (hospital)
Intra-abdominal
UTI
Skin and soft tissue
Throat
Multiple organisms/ Unknown
Meningococcal
Neutropenic sepsis
Antibiotics
Co-amoxiclav/Cefotaxime + Clarithromycin
Ceftazidine OR
Piperacillin + Gentamicin OR
If S. aureus suspected: Flucloxacillin (MSSA) or
Vancomycin (MRSA)
Cefuroxime + Metronidazole/Piptazobactam
Cefuroxime + Gentamicin
Co-amoxiclav OR
Amoxicillin + Flucloxacillin
Benzylpenicillin
Cefuroxime + Gentamicin + Metronidazole
Ceftriaxone
OR for pen/cef allergic Vancomycin / Rifampicin
Tazocin + Netilmicin
ITU/HDU:
 Circulatory support with vasopressor (noradrenaline or dopamine), consider
inotrope (dobutamine) if cardiac output remains low.
 Renal replacement as needed (continuous veno-venous haemofiltration).
 Maintain nutrition. Glucose management, give insulin to maintain below 8.3.
 Maintain haemoglobin above 7 with blood transfusion, and give platelet transfusion
if risk of bleeding and level falls below 30 x 109/L.
 Manage any ARDS with mechanical ventilation- minimise plateau pressures and tidal
volumes, use positive end expiratory pressure, try regular spontaneous breathing
trials and follow a weaning protocol
 Sedation as necessary- bolus or infusion
Recombinant activated protein C: anti-inflammatory, anti-coagulant and profibrinolytic. May
be considered in high risk of mortality.
Source control: Abscess drainage (except in pancreatic necrosis), debridement, removal of
suspect lines etc.
Supportive treatments:
 Consider corticosteroids (hydrocortisone) if hypotension poorly responsive to Tx
 DVT prophylaxis (LMW heparin unless contraindicated)
 Gastric protection from stress ulcers (PPI/H2 blocker).
Features indicating poor prognosis:
 Age >60
 Multi-organ failure (>3)/ Renal failure/ Hepatic failure/ Resp failure (ARDS))
 Hypothermia or leucopenia (i.e. not mounting response)
 Hospital acquired infection
 DIC
 Underlying disease
Toxic Shock Syndrome
 Infection localised, systemic features caused by toxins
 Toxin-producing gram positive bacteria, usually staph or strep
 Associated with tampons, post-partum, and nasal packing. Can occur in any infection
with causative organism.
Features:
 Fever > 38.9
 Diffuse maculopapular rash, commonly with mucus membrane involvement.
Desquamation 1-2 weeks later.
 Non-purulent conjunctivitis
 Systolic BP < 90, or postural hypotension
 Diarrhoea and vomiting
 DIC and petechial rash
 Multi-organ failure
 Ix- Normochromic normocytic anaemia, Leucocytosis, Renal/hepatic failure. Elevated
CPK. Pyuria. CSF sterile pleiocytosis. Blood culture usually negative.
 Tx- Source control and supportive care as in septic shock. High dose Flucloxacillin IV.
4. Childhood Rashes
Rash
Macular (flat)/ Papular
(raised)- blanching
Rubella (Macular), measles,
HHV6/7, enterovirus, scarlet
fever, Kawasaki
Purpuric/ Petecial- nonblanching
Meningococcal, HenochSchonlein purpura, enterovirus,
thrombocytopenia
Vesicular- small raised lesion,
containing clear fluid
Chickenpox, shingles, herpes
simplex, hand foot and mouth
disease
Pustular/ Bullous- large raised
lesion (>0.5cm diametet)
containing clear or purulent
fluid
Impetigo, Scalded skin
syndrome
Desquamation- dry, flaky,
peripheries
Post-scarlet fever, Kawasaki
5. Childhood vaccination schedule
Schedule
Age
Newborn
8 weeks
3 months
4 months
12 months
13 months
4-5 years
13-16
Immunisation(s)
BCG and Hep B if indicated (at risk)
Diptheria, Tetanus, Pertussis, Polio, Hib
(DTaP/IPV/Hib)
Pneumococcal (PCV)
DTaP/IPV/Hib, MenC
DTaP/IPV/Hib, MenC, PCV
Hib
MenC
MMR
PCV
MMR
DTaP/IPV
Td (tetanus and diphtheria)/IPV
6. Common viral infections
Measles
 Incubation 6-19 days, infectious 1-2 days before rash and 6 days after, exclude from
school for 5 days from onset of rash
 Cough, conjunctivitis and coryza
 Koptik spots: white spots on bright red buccal mucosa
 Rash: spreads down from behind ears to all over body
 Complications:
o Encephalitis- 1 in 5000, occurs around day 8. Headache, lethargy, irritability
→ convulsions, coma, 15% mortality. 40% of survivors have long term
sequelae e.g. deafness, seizures, learning difficulty
o Subacute sclerosing panencephalitis- rare, manifests about 7 years after
infection, progressive loss of neurological function, dementia and death
o Respiratory: Pneumonia, Secondary bacterial infection, Tracheitis
o Others: diarrhoea, hepatitis, appendicitis, corneal ulceration, myocarditis
 Symptomatic treatment
 Isolation if hospitalised
 Ribavirin in immunocompromised
Mumps
 Incubation 15-24 days, exclude from school for 7 days from onset of parotitis, 30% of
infection subclinical
 Fever, malaise, parotitis (usually bilateral, may begin on one side)
 Fever last 3-4 days
 Complications:
o Pancreatitis- raised amylase, abdominal pain
o Meningitis and encephalitis
o Orchitis- usually unilateral, infertility extremely unusual
Rubella
 Incubation 15-20 days
 Mild illness- low grade fever, macuopapular rash spreading from face, prominent
lymphadenopathy
 Complications rare: arthritis, encephalitis, thrombocytopenia, myocarditis
 Congenital infection serious: sensorineural deafness, cataract and microphthalmia,
congenital heart disease (patent ductus arteriosus)
Human herpesviruses
 Herpes simplex 1 and 2, Varicella zoster, Cytomegalovirus, Epstein-Barr, HHV 6,7,8
 HSV-1:
o Predominates in childhood
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o Transmitted in bodily fluids e.g. saliva
o Many asymptomatic
o Gingivostomatitis: most common, 10 months- 3 years, vesicular lesions on
lips, gums, anterior tongue and hard palate, progressing to ulceration which
is painful and bleeds, high fever. Aciclovir and IV fluids if severe.
o Cold sore: usually mucocutaneous junctions and damaged skin
o Eczema herpeticum: serious, widespread vesicular lesions on eczematous
skin, vulnerable to secondary bacterial infection
o Herpes whitlows: painful, erythematous, oedematous white pustules on
broken skin site. Autoinoculation from infected site
o Eye disease: Blepharitis or conjunctivitis, may involve cornea producing
ulceration, scarring and vision loss.
o Asceptic meningitis: rare in children, may occur in sexually active adolescents
(complication of HSV2), within 10 days of primary infection, self limiting
o Encephalitis: serious, untreated mortality over 70%. May follow primary or
recurrent infection.
o Neonatal: May have a focus or be disseminated. High morbidity and
mortality.
o Severe in immunocompromised, progressing to pneumonia and multiple
organ infection.
Varicella zoster (Chicken pox):
o Respiratory spread, infectious -2 to +5 days, exclude from school until lesions
crust, almost always symptomatic
o Fever, Rash: Papules → Vesicles → Pustules → Crusts
o Complications:
 Secondary bacterial infection (staph/ strep), may lead to necrotising
fasciitis, toxic shock. Consider if new onset fever or persistent after
the first few days.
 Encephalitis- occurs early (within 1 week of rash), generalised, good
prognosis, Cerebellitis characteristic- ataxic with cerebellar signs.
 Purpura fulminans- rare, caused by vasculitis in skin and
subcutaneous tissues. Antiviral antibodies cross react and inactivate
coag factor protein S.
 Increased risk of stroke (v. Rare)
 In immunocompromised- severe, progressive, disseminated, mortality
up to 20%, vesicles persist and become haemorrhagic. Give human VZ
immunoglobulin after exposure of these patients e.g. bone marrow
transplant, congenital T cell problem, high dose steroids. Once
developed, give 8cyclovir
Herpes zoster (Shingles)
o Reactivation of latent VZV
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Can affect any dermatome, but most commonly thoracic.
Children rarely get neuralgic pain
More common if the primary infection was in the first year
Recurrent shingles may indicate immunosuppression, in whom it may
become severe and disseminated.
Epstein-Barr
o Transmitted orally, most infections subclinical
o Causes glandular fever, involved in Burkitt’s lymphoma, lymphoproliferative
disease in the immunocompromised, and nasopharyngeal carcinoma.
o Glandular fever:
 Fever, malaise, tonsillopharyngitis (often severe), lymphadenopathy,
soft palate petechiae, splenomegaly (50%), hepatomegaly (10%),
maculopapular rash (5%)
 Atypical lymphocytes on blood film
 Monospot blood test
 IgM and IgG to Epstein-Barr antigens
 Supportive treatment, antibiotics if tonsils grow strep- give penicillin
NOT AMP/AMOXICILLIN as can cause rash
Cytomegalovirus
o Transmitted by saliva, genital secretions or breast milk
o Mild or subclinical in normal hosts
o Can also cause mononucleosis syndrome- pharyngitis and lymphadenopathy
less prominent and negative monospot
o Congenital infection
o Immunocompromised: retinitis, pneumonitis, bone marrow failure,
encephalitis, hepatitis, colitis, oesophagitis. Can be treated with ganciclovir or
foscarnet (serious side effects).
Human herpes virus 6 and 7
o Transmitted by saliva, most children have had by age 2
o Exanthem subitum- high fever and malaise for a few days followed by
generalised macular rash
o Highly associated with febrile convulsions
Human herpes virus 8 → Kaposi’s sarcoma in immunocompromised
Parvovirus B19 (/ Fifth disease/ Slapped cheek)
 Commonly outbreaks during spring
 Transmitted by respiratory secretions/ vertically/ blood products
 Infects erythroblast red cell precursors in bone marrow
 Asymptomatic/
 Erythema infectiosum- fever, malaise, headache and myalgia → facial rash one week
later (slapped cheek) → maculopapular rash on trunk and limbs
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Immunodeficiency/ chronic haemolytic anaemia e.g. sickle cell → Aplastic crisis
Fetal infection can cause hydrops and death
Enteroviruses
 Numerous inc. Coxsackie, echo, polio
 Mostly in summer and autumn, faecal-oral spread
 90% asymptomatic or non-specific febrile illness
 Can cause several clinical syndromes:
o Herpangina- vesicular, ulcerated lesions on soft palate and uvula. Pain on
swallowing, anorexia, fever.
o Hand, foot and mouth disease- painful vesicular lesions on hands, feet,
mouth and tongue. Mild systemic symptoms. Resolves in a few days.
o Asceptic meningitis/ Encephalitis- may have rash (can be petechial). Recover
fully.
o Pleurodynia (Bornholm’s disease)- Fever, pleuritic chest pain (may hear
pleural rub), muscle tenderness. Resolves in a few days.
o Myocarditis/ Pericarditis- heart failure with febrile illness, ECG evidence.
o Poliomyelitis More than 90% asymptomatic
 5 % mild- fever, headache, malaise, sore throat, vomiting, within 4
days of exposure, recover well.
 2% progress to central nervous system involvement = asceptic
meningitis, stiff back, neck and hamstrings
 <1% paralytic polio, 4 days after mild illness subsided, varying degree
of paralysis, may recover or be permanent. Due to anterior horn cell
and cerebral cortex involvement.
o Enteroviruses can cause severe disease in the immunocompromised. Echo →
persistent and sometimes fatal CNS infection in IgA deficiency.
7. Common bacterial infections
Staphylococcus and Group A Streptococcus
 Act either by direct effect, toxin mediated, or post infectious disease
 Impetigo- localised, highly contagious, skin infection common in infeants and young
children, and more with underlying skin disease. Face/ neck/ hands, erythematous
macules → vesicular → exudates → crust
 Tx- mild give topical antibiotic, otherwise flucloxacillin or erythromycin
 Can use nasal cream to eradicate source if recurrent impetigo/boils
 Boils- usually staph aureus
 Periorbital cellulitis- Fever + erythema and oedema of eye lid. Unilateral. HiB in
young unimmunised, may be after local trauma, or spread from sinus infection in
older children. Treat promptly with IV antibiotics to prevent spread to orbital
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cellulitis (proptosis, painful/limited eye movement, reduced visual acuity, can lead to
meningitis, abscess, cavernous sinus thrombosis).
Scalded skin syndrome- Exfoliative staphylococcal toxin. Epidermis separates from
underlying granular layers, can be done with gentle pressure (Nikolsky’s sign). Fever,
malaise, starts as focal skin infection then widespread erythema and tenderness. IV
antibiotics.
Necrotising fasciitis/cellulitis- Severe subcutaneous infection, often down to fascia
and muscle. Rapid swelling leaves poor perfusion. Severe pain and systemic illness,
may need intensive care. Staph/ Group A Strep +/- anaerobe. Urgent surgical
intervention required.
Streptococcus pneumoniae
 Asymptomatic carriage common.
 Spread by respiratory droplets.
 Can cause pharyngitis, otitis media, conjunctivitis, sinusitis, pneumonia, bacterial
sepsis, and meningitis.
 Children with hyposlenism more susceptible
Meningitis
 Most commonly viral, self resolving
 Bacterial: 5-10% mortality, 10% neurological disability. Usually follows bacteraemia.
Inflammatory response → Cerebral oedema → Raised ICP → Decreased cerebral
blood flow
 Causative organisms:
Neonatal - 3 months
Group B Strep
E. coli and other coliforms
Listeria monocytogenes
1 month - 6 years
Neisseria meningitidis
Strep pneumoniae
Haemophilus influenza
> 6 years
Neisseria meningitidis
Strep pneumoniae
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Presenting featureso Infant- fever, poor feeding, vomiting, irritability, lethargy, hypotonia,
drowsiness, seizures, reduced consciousness.
o Older children- headache, neck stiffness, photophobia
Late signs- bulging fontanelle, neck stiffness, infant lying with arched back.
Signs of shock- tachycardia, prolonged capillary refill, oliguria, hypotension.
Always take purpura seriously in a febrile child even if fairly well
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Investigations:
o FBC and differential
o Blood glucose and blood gas
o Coagulation screen, CRP
o U+E, LFTs
o Culture: blood, throat swabs, urine, stool for bacteria + viruses
o Rapid antigen tests for organisms (blood/CSF/urine)
o Lumbar puncture unless contraindicated
o + serum for titre comparison
o PCR of blood and CSF
o TB suspected: mantoux test, chest x-ray, gastric washing or sputum, early
morning urine
o Consider CT/MRI and EEG
8. Post-operative and hospital acquired infections
= development > 48hrs after admission
Pneumonia
Gram negative enterobacteria
Escherichia coli
Klebsiella pneumonia
Staphylococcus aureus
Pseudomonas aeruginosa
Aspiration → Oral anaerobes
Clostridium
 Post-antibiotics
difficile
 Mild: watery diarrhoea, crampy abdominal pain, nausea, fever
 Pseudomembranous colitis: bloody diarrhoea, abdominal pain
and distension, perforation
 Stool toxin test
 Tx- Vancomycin/ Metronidazole, Stop other ABx, Fluids
Infection control measures
MRSA
Asymptomatic colonisation: commonly anterior nares
Decolonisation- chlorhexidine wash for showering
Usually only progresses to secondary infection in immune compromised
Sites of infection:
 Respiratory tract
 Urinary tract
 Open wounds
 IV access devices
 Sepsis, toxic shock
Tx: Vancomycin/ Teicoplanin, Linezolid 2nd line with expert advice
Infection control measures
9. Travel associated infections
GASTROENTERITIS
The bug
Salmonella enterica
Campylobacter jejuni/coli
Shigella sonnei
Shigella dysenterei
Staphylococcus aureus
Clostridium perfringens
Clostridium difficile
Bacillus cereus
Escherichia coli 0157
Salmonella typhi (typhoid)
Vibrio cholerae
Cryptospiridium
Giardia lamblia
Entamoeba histolytica
Rotavirus
The symptoms
Bloody diarrhoea +/- fever + vomiting
Fever, profuse bloody diarrhoea, severe abdo pain
Diarrhoea +/- blood
Severe bloody diarrhoea of small volume + pus, cramps,
fever
Vomiting, fever
Explosive diarrhoea, colicky pain, short lasting
Profuse vomiting + diarrhoea
Profuse bloody diarrhoea (haemorrhagic colitis), abdo
pain
The story
Cooked eggs/poultry contaminated with raw
Undercooked chicken (/other meat)
Nursery school outbreaks
Found throughout the world, outbreaks common in
war or natural disasters (poor sanitation)
Finger food (buffet) 1-6 hours earlier
Red meat
Hospitals, 4-9 days after ABx
Rice wasn’t reheated properly (after 0.5-6 hrs)
Undercooked beef
Haemolytic uraemic syndrome =
 Acute renal failure
 Haemolytic anaemia
 Thrombocytopenia
‘Pea soup’ diarrhoea
Foreign travel: Africa/ South Asia
Dry cough, high fever, abdo
 Canned meat
pain, hepatosplenomegaly
 Shellfish
Headache/ meningitis/ coma
 Waterborne
Profuse ‘rice water’ diarrhoea Contaminated water: natural disasters particularly floods
Flu-like illness
Immunocompromised
Diarrhoea, flatulence,
Contaminated water (1-3 weeks before) e.g. camper drinking from stream
bloating, abdo pain
Found throughout the world, particularly developing countries + Eastern Europe
Bloody diarrhoea, abdo pain,
Prevalent in central and south America, Africa, and Asia
hepatomegaly (liver abscess)
Projectile vomiting, diarrhoea Infants/ Institutional
Hepatitis- presentation etc should be covered in other core problems
Transmission
Investigations
Anti-HAV:
IgM- Acute
IgG- Previous
exposure
** see below
A
RNA
Faecal-oral e.g. contaminated
shellfish/food/water
Incubation 2-6 weeks
B
DNA
Blood-borne (needles,
transfusions), Sexual
C
RNA
D
RNA
E
RNA
Blood-borne, Sexual
Incubation 2-26 weeks
Only occurs when already
infected with hepatitis B,
blood-borne
Faecal-oral
Found in Asia, sometimes
epidemics
** Hepatitis B serology interpretation:
ELISA +ve from 10 wks
PCR +ve in chronic
Can test anti-HDV but
PCR gold standard
HEV-specific IgM
IgG rises later
Chronic
form?
No
Vaccine?
Yes
Yes
Yes
90% kids
5% adults
Yes,
No
50-85%
Yes,
No
5%
No
No
Malaria
Pathophysiology
Presentation
Paroxysms, lasting 6-10hrs, classically with 32hr gaps between in vivax and ovale (tertian
fever) or 66hr gaps in malariae (quartan fever).
Diagnosis of severe malaria:
 ‘cold stage’: Abrupt onset rigors
 Impaired consciousness
 ‘hot stage’: Fever often > 400, restless, vomiting,
 Respiratory distress
convulsions
 Multiple convulsions
 ‘sweating stage’: Temperature returns to normal and
 Circulatory collapse
patient may sleep
 Pulmonary oedema
Falciparum less predictable, fever may be continuous, and
 Abnormal bleeding
 Jaundice
accompanied by:
 Haemoglobinuria
 Headache
 Severe anaemia
 Cough
 Hypoglycaemia
 Myalgia
 Acidosis, hyperlactataemia
 Diarrhoea
 Hyperparasitaemia
 Mild jaundice
Investigations
Blood films: thick and thin, need at least 3 negative at different times to exclude
Rapid diagnostic test: antigen capture tests, only detect falciparum and only reliable in first
infection
Management
Supportive treatment, including antipyretics and analgesics
Antimalarial treatment:
Benign types: chloroquine (+ primaquine for ovale and vivax to eliminate liver schizonts)
Falciparum: Artemisinin-based combination therapy e.g. artemether + lumefantrine
Severe → Quinine
Neglected tropical diseases (WHO list)
Buruli Ulcer
Chagas disease
(American
trypanosomiasis)
Cysticercosis/
Taeniasis
Dengue
Mycobacterium ulcerans
Nodule (mobile, painless) → Tissue destruction → Extensive ulceration
Early treatment important to minimise lasting disability
Treatment: Rifampicin + Streptomycin for 8 weeks, plus debridement
Parasite: Trypanosoma cruzi
Transmitted by triatomine bug faeces
Acute phase with parasitaemia commonly asymptomatic, may have
fever, localised lymphadenopathy, chancre. Many other possible Sx,
including meningoencephalitis in AIDS
Chronic phase with parasites in heart and GI smooth muscle, may
remain asymptomatic, or have complications:
Cardiac: arrhythmia, cardiomyopathy, heart failure
GI lesions: achalasia → megaoesophagus (dysphagia),
megacolon (constipation)
Tx: benznidazole
Tapeworms
Cysticercosis = larva, can get into many tissues, inc. CNS (a
common cause of epilepsy in developing countries)
Taeniasis = adult tapeworms in GI tract. Mild abdominal pain,
nausea, diarrhoea/constipation
Tx: praziquantel
Arbovirus
Mosquito-borne (aedes aegypti)
1st infection:
 Flu-like symptoms
 Arthralgia
 Rash
 Retro-orbital pain
Dracunculiasis
Echinococcosis
Fascioliasis
 Infants: simple fever
Subsequent infections, risk of:
 Dengue haemorrhagic fever +/- Dengue shock syndrome
o Fever
o Haemorhagic tendencies: purpura/petechiae, mucosal
bleeding, haematemesis/melena
o Thrombocytopenia
o Plasma leakage: ↑ haematochrit, effusions
Tx: Supportive
Guinea worm
Lifecycle
 Burning sensation causes patients to put foot into water,
causing worm to expel eggs
 Larval development in water fleas
 These are ingested by human and broken down by stomach
acid releasing larva
 Larva migrate through intestinal wall
 Male and female meet, mate, then male dies
 Female migrates down muscle planes
Presentation
 Emerges on foot- intense pain, oedema, ulceration, fever,
nausea and vomiting
Tx: No treatment, just careful removal of worm. Can be eradicated by
safe drinking water and water filtering to remove fleas.
Parasite: echinococcosus granulosus/ multilocularis
Infection with larval stage of dog tapeworm
Sheep meat → Dogs → Infected dog faeces → Contact with humans
e.g. direct/ contamination of food/water
Symptoms depend on site of cyst, most commonly liver or lung
Tx: surgery and/or long term albendazole +/- praziquantel
Trematodes (worms): fasciola hepatica and fasciola gigantica
Zoonosis with many reservoir species: cattle, donkeys, sheep, pigs,
buffalo, horses, goats, rodents and others
Faecal-oral transmission, with aquatic lifecycle stage in snail
Large worms (several cms) migrate through liver causing haemorrhage
and inflammation
 Fever
 Abdominal pain
 Respiratory distress
 Rash
Human African
trypanosomiasis
Leishmaniasis
Worms reach bile ducts and a chronic phase with mild, non-specific
symptoms → Chronic inflammation → Fibrosis and obstruction →
Biliary colic → Eventual cirrhosis may occur from multiple infections
Tx: triclabendazole
= Sleeping sickness
Parasitic infection, transmitted by tsetse fly
Remote rural areas in Africa
Initially multiplies in lymph and blood:
 Fever
 Headache
 Joint pain and stiffness
 Weakness
Crosses blood-brain barrier:
 Psychiatric disorders
 Seizures
 Coma
 Death
Timecourse: T.b. rhodesiense is acute, over weeks to months,
T.b. gambiense is more chronic, over several years
Difficult to confirm diagnosis- must find parasite by microscopy of
blood/other bodily fluids but difficult as low parasite count. Can also
do serology but only for gambiense and not specific.
Tx
Early
Late
Gambiense
Pentamidine
Eflornithine + Nifurtimox
Rhodesiense
Suramin
Melarsoprol
Protozoa transmitted by sandfly
Ix: anti-leishmania antibodies, rapid test available
Visceral (= kala azar): 90% in Bangladesh, Brazil, India, Nepal, Sudan
2 weeks to 2 months of:
 Fever, night sweats
 Fatigue
 Weakness
 Appetite loss, weight loss
 Abdominal discomfort, organomegaly
 Anaemia
 Thinning hair, scaly grey ashen skin
 Children- Fever, cough, diarrhoea, vomiting
Confirmed by spleen aspirate
Untreated mortality 100% in 2 years
Tx: 1st line: meglumine antimoniate/ sodium stibogluconate
Leprosy
Lymphatic
filariasis
Onchocerciasis
(risk of fatal arrhythmias due to antimony)
2nd line: amphotericin B
Cutaneous: 90% in Afghanistan, Iran, Brazil, Peru, Saudi Arabia, Syria
 Nodule → ulcer. Relatively painless. On exposed areas. Heal
after several months but leave scars
 Diffuse type: disseminated chronic skin lesions, difficult to treat
Confirmed by Giemsa-stained parasites in ulcer edge smears
Tx:
Local: intralesional injections of meglumine antimoniate/ sodium
stibogluconate, heat pads
Systemic (if severe): fluconazole/ miltefosine
Mucocutaneous: 90% in Bolivia, Brazil and Peru
 Nose, mouth and throat affected
o Ulceration
o Blocked nose/runny nose, nosebleeds
o Dysphagia
o Difficulty breathing
Tx as for cutaneous
Mycobacterium leprae, mode of transmission unclear
Skin- depigmented or red-copper lesion(s), flat/raised/popular, loss of
pin-prick and soft touch sensation in lesion
Peripheral nerves- thickened, causing sensory/motor neuropathy
Upper respiratory mucosa
Eye disease- including corneal opacity and cataract
Tx: rifampicin + dapsone (+ clofazimine if high bacterial load)
= elephantiasis
Species of nematode worms called filariae
Mosquito borne
Grow to 3-10 cms and form ‘nests’ in lymphatic system
Most cases asymptomatic but lymphatic damage present, and renal
disease is present in up to 40% (proteinuria and haematuria)
Acute painful attacks with fever
 Lymphoedema of the limbs
 Genital: hydrocele, swelling of scrotum and penis
Tx: Albendazole + Ivermectin for 3 weeks
Control: mass population treatment with yearly single dose A+I
= River blindness
Another filarial worm- Onchocerca volvulus
Transmitted by blackflies
Larvae form subcutaneous nodules → Mature and mate → Release
microfilariae → These travel around the body, die and cause disease
Rabies
Schistosomiasis
Skin: rashes, lesions, depigmentation, intense itching
Eyes: sclerosing keratitis, iridocyclitis, optic atophy, blindness
Tx: Ivermectin single dose to clear microfilariae, need to give when
symptoms recur (every 6-12 months) for 15-20 years (lifespan of adult
worms)
Control: mass population treatment with ivermectin
RNA virus
Transmitted by saliva of biting infected animal, mostly dogs
Incubation 3-78 days
Peripheral nerves → Grey matter → Salivary glands
 Prodromal illness
o Fever
o Headache
o Malaise
 Pain at bite site
 Hallucinations
 Convulsions
 Vomiting
 Hydrophobia
 Coma
Fatal once symptomatic
Give rabies specific immunoglobulin after exposure
Vaccine available with post-exposure boosters needed
Trematode
Cercariae released by snails into fresh water → Penetrate skin → Liver
→ Mature and migrate to veins draining bladder and intestines → Eggs
penetrate intestinal/bladder wall and are excreted → Hatch into
miracidia → Infect freshwater snails
Swimmer’s itch: hours after infection. Pruritic popular rash with
oedema, erythema, and eosinophilia, resolves in 10 days
Katayama fever: rare, can be severe, immune-complex mediated, 1-3
months after initial infection. Fever, rash, chillds, sweating, anorexia,
headache, diarrhoea, cough, hepatosplenomegaly, lymphadenopathy.
Eosinophilia, raised immunoglobulins, rising anti-schistosomal ABs.
Only occurs after a first exposure. Treat with prednisolone then
praziquantel, with repeat prazi at 1 month. Resolves after a few weeks.
Chronic disease: eggs cause granulomatous inflammation + fibrosis,
eggs can embolize to any site.
Hepatosplenic: portal hypertension, periportal fibrosis, pancytopenia
Intestinal: intermittent bloody diarrhoea, tenesmus,
hypoalbuminaemia, anaemia, intussusception
Soil transmitted
helminthiasis
Trachoma
Yaws
Genitourinary: bladder fibrosis, calcification and reduced volume,
ureteric obstruction, hydroureter, terminal haematuria,
haemospermia, ↑ risk squamous cell carcinoma of the bladder
CNS: rare, meningoencephalitis, focal epilepsy, cauda equina,
paraplegia
Pulmonary: pulmonary hypertension (fatigue, syncope, chest pain)
Ix: eggs on microscopy of urine/faeces, serology
Tx: Praziquantel
Caused by hookworms, whipworms (trichuris trichura), ascaris
lumbricoides
Faecal-oral transmission
Eggs in contaminated soil ingested → Larva cross intestinal mucosa
and enter bloodstream → Lungs → Coughed up and swallowed →
Mature in GI tract
 Diarrhoea
 Abdominal pain
 General malaise and weakness
 Anaemia (from chronic intestinal blood loss with hookworms)
Tx: albendazole
Control: mass population treatment, targeted at children, pregnant
women, and high risk occupation (e.g. farming)
Chlamydia trachomatis transmitted by contact with infected eye
discharge e.g. on towels
Conjunctivitis, only leads to permanent damage after multiple
episodes of reinfection…
Trichiasis: eyelids turn inwards → Lashes cause corneal scarring and
opacity → Blindness
Tx: azithromycin, surgery for trichiasis
Bacterium: treponema pertenue
Transmitted by skin contact
Peak incidence in children aged 6-10
Single skin lesion appears after 2-4 weeks, followed by multiple skin,
bone or cartilage lesions if untreated
Can lead to chronic disfigurement and disability
Tx: azithromycin (single oral dose)
TB- should be addressed in other core problems
Consider in patients:
 Recently arrived from high-incidence country- should be screened
 Born in high-incidence country- may have latent infection
 Close family/visitors from high-incidence country
HIV
Pathophysiology: RNA retrovirus, attaches to CD4 membrane protein
Epidemiology:
Transmission:
 Sexual contact- transmission rate is increased by
coexisting STIs
 Mother-to-child transmission
 Blood products
 Unsterilized needles- drug users, needlesticks to
healthcare workers
Presentation
 Seroconversion illness (occurs in 50%): 3 weeks
after infection, cold/flu like symptoms, fever,
lymphadenopathy, diarrhoea, maculopapular
rash
Acquired Immunodeficiency
Syndrome =
CD4 < 200 cells/μL
OR AIDS defining illness:
Candidiasis- oesophagus/trachea
Kaposi’s sarcoma
Persistent herpes simplex
Pneumocystis jirovecii pneumonia
TB
Recurrent pneumonia
Neurological CMV, toxoplasma,
encephalopathy
Lymphoma
HIV wasting syndrome


Mild immunosuppression: lymphadenopathy, parotitis
Moderate: recurrent bacterial infections, candidiasis, chronic diarrhoea, lymphocytic
interstitial pneumonitis
 Severe: pneumocystis jiroveci pneumonia, severe failure to thrive, encephalopathy
Investigations
 CD4 count
 Viral load (undetectable = < 50 copies/ml)
 Antibodies- take 3 months to become positive after infection
 Paediatric:
 > 18 months: antibody testing
 < 18 months: viral RNA PCR
 LFT and amylase when on treatment
Management
PCP prophylaxis- if CD4 < 200/ 15%
→ co-trimoxazole
Do not give BCG (live, may disseminate)
Combination antiviral medications: 2 NRTIs + 1 NNRTI/ 1 PI
 Nucleotide analogue reverse transcriptase inhibitors (NRTIs) e.g. zidovudine, abacavir
 Non-nucleotide reverse transcriptase inhibitors (NNRTI) e.g. nevirapine
 Protease inhibitors (PI) e.g. ritonavir (as Kaletra with lopinivir)
Family clinics with psychosocial support, dietician, social worker etc
Preventing mother to child transmission
 Encourage maternal testing
Undetectable maternal viral load…
 NVD possible
 Start zidovudine ASAP after birth + continue for 4 weeks
 Infant bloods for PCR at 24-48 hours
 Follow-up with PCR at 6-8 weeks + 3-4 months
 Serology at 18 months
Detectable maternal viral load…
 Planned caesarean section
 Maternal IV zidovudine during delivery
 Start triple therapy: zidovudine + lamivudine, + nevirapine for first 2
weeks (tailor to mother’s resistance)
 Follow-up with PCR at 6-8 weeks, 3-4 months + 6 months
 Start co-trimoxazole at 6-8 weeks until next negative PCR
 Serology at 18 months
 Avoid breast feeding
10. Pyrexia of unknown origin
= source not clear from examination and simple investigations, for a fever lasting more than
2 weeks. Cause may be infectious, inflammatory, malignant or other.
Infectious causes:
 Pyogenic abscess
 Tuberculosis
 Infective endocarditis
 Toxoplasmosis
 EBV/CMV *see above
 HIV seroconversion
 Brucellosis
 Lyme disease
Non-infectious causes of PUO
Inflammatory and tissue damaging disorders
 Still’s disease
 Rheumatoid arthritis
 SLE
 Wegener’s granulomatosis
 Giant cell arteritis
 Polymyalgia rheumatic
 Inflammatory bowel disease
 Sarcoidosis
 Granulomatous hepatitis
Kawasaki disease
 6 months to 4 years, peak at end of first year
 Japanese > Afro-Caribbean > Caucasian
 Cause unknown, but similarity to toxic shock suggests bacterial superantigen
 Features: Fever > 5 days, and four others of- conjunctival infection, red mucous
membranes, cervical lymphadenopathy, rash, red and oedematous palms and soles,
peeling fingers and toes
 Vasculitis of small and medium vessels, including coronary arteries in 1/3 of cases
within 6 weeks. Aneurysms, check with echo. Subsequent scarring and narrowing
can lead to ischaemia and sudden death.
 Mortality 1-2%
 Tx- Immunoglobulin within 10 days (↓ risk of aneurysm), Aspirin
Malignancy
 Lymphoma
 Leukaemia
 Renal cell carcinoma
 Hepatocellular carcinoma
Other
 Factitious fever
 Drug induced fever:
 Familial Mediterranean fever: Recurrent attacks of fever, arthritis (monoarticular)
and serositis (peritonitis, pleurisy). Tx- regular Colchicine. Complications- 25%
develop renal amyloidosis, otherwise benign.
 Thyrotoxicosis
11. Malignant hyperpyrexia





Genetic defect in the sarcoplasmic reticulum muscle ryanodine receptor (RyR1)
calcium-release channel. May be autosomal dominant.
PLUS General anaesthetic or neuroleptic drug e.g. haloperidol
Features: hyperpyrexia + muscle rigidity
Can cause death during or after an anaesthetic
Dantrolene can help rigidity
12. Investigation of fever
Interpreting blood cultures:
Certain species usually only present due to contamination: coagulase-negative staph,
corynebacterium (unless suspected medical device infection), P. acnes, bacillus species
If present in more than 1 culture, likely to be true infection not contamination
Lumbar puncture:
Complications:
 Headache
 Nerve root trauma- if needle does not stay in midline. Sharp pains/ paraesthesia
down leg.
 Bleeding
 Coning- extremely rare unless there is raised ICP (a contraindication for LP)
 Infection
Interpreting results:
Normal values
 Polymorphs 0 mm3, Lymphocytes < 4 mm3
 Protein < 0.4 g/L
 Glucose < 2.2mmol/L or > 70% of plasma glucose
 Opening pressure < 20cm CSF
Bloody tap or subarachnoid haemorrhage?
Bloody tap
SAH
Progressively fever red cells in successive
bottles.
Consist number of red cells in successive
bottles.
No xanthochromia (yellowing)
Xanthochromia
True CSF WBC = CSF WBC - (Blood WBC x CSF RBC)/ Blood RBC
Simpler- subtract 1 white cell for every 1000 red cells (assuming blood count normal).
WBC are raised in SAH due to inflammatory response.
Very high protein:
 Acoustic neuroma
 Spinal tumour
 Guillain-Barre
Meningitis
Bacterial
Appearance Cells (mm3)
Turbid
5-2000
Main type
Neutrophil
Viral
TB
Clear
Clear
Lymphocyte Normal
Lymphocyte Low
5-500
5-1000
Glucose
Very low
Protein
Often >
1
0.5-0.9
Often >
1
Other
Gram stain
Bacterial Ag
PCR
Zeihl-Neelsen
Flurescence
PCR
13. Management of fever
Antifungals
Class
Polyenes
Alter cell walls, contents leak and cell dies
Azoles
Inhibit enzyme
lanosterol 14-αdemethylase
Imidazoles
Nystatin
Clotrimazole
Ketoconazole
Triazoles
Flucoazole
Thiazoles
Itaconazole
Abafungin
Butenafine
Allylamines
Inhibit enzyme squalene epoxidase
Echinocandins
Inhibit synthesis of glucan in cell wall
Antivirals
Lifecycle stage
targeted
Un-coating
Reverse transcription
DNA polymerisation
Protease- cut protein
chains up ready for
assembly
Examples
Amphotericin B
Class
Nucleoside
analogue
Non-nucleoside
reverse
transcriptase
inhibitor
Pyrophosphate
mimic
Protease
inhibitors
Terbinafine
Caspofungin
Purpose
Oral candida, Systemic inc.
cryptococcal meningitis
Candida
Candida, Tinea
Candida, Tinea inc.
versicolor
Candida, Tinea,
Onychomycosis,
Cryptococcus
Aspergillus
Candida, Tinea,
Cryptococcus, Aspergillus
Tinea, Onychomycosis
Aspergillus,
General invasive candida
Examples
Purpose
Amantadine
Acyclovir
Ganciclovir
Zidovudine
Lamivudine
Tenofovir
Efavirenz
Nevirapine
Influenza
Herpesviruses
CMV
HIV
HIV, Hepatitis B
HIV, Hepatitis B
HIV
HIV
Foscarnet
Herpesviruses, including
drug resistant CMV and
herpes simplex
HIV
HIV- these two given in
combo (Kaletra)
Atazanavir
Ritonavir
Lopinavir
Release
Stimulate immune
response
Neuraminidase
inhibitor
Interferons
Antibodies
Oseltamivir
(Tamiflu)
Pegylated
interferon α
Palivizumab
Influenza
Hepatitis B and C
RSV
Antibiotics
Mechanism
Beta
lactans
Group
Penicillins
Inhibit cell
wall
synthesis
Cephalosporin
Carbapenem
Inhibit cell
wall
synthesis
Monobactam
Glycopeptide
Macrolide
Inhibit
ribosome
activity +
protein
synthesis
Examples
Benzylpenicillin
Penicillin V
Flucloxacillin
Amoxi/ampicillin
Pipperacillin = Extended spectrum
Can add beta lactamase inhibitor:
Amox. + clavulanic acid = Co-amoxiclav
Piperacillin + Tazobactam = Tazocin
Cephalexin 1st gen
Cefuroxime 2nd gen
Cefotaxime 3rd gen
Meropenem
Ertapenem
Vancomycin
Lincosamide
Erythromycin
Clarithromycin
Gentamicin
Tobramycin
Streptomycin
Clindamycin
Tetracycline
Doxycycline
Aminoglycoside
Inhibit DNA
Fluroquinolone Ciprofloxacin
gyrase
Inhibits nucleic
Metronidazole
acid synthesis by
breaking DNA
strand
Dihydrofolate
Folate
Sulphonamides
reductase inhibitor antagonist Trimethoprim
+ sulfamethoxazole = Co-trimoxazole
Spectrum
+ narrow
+ narrow
Staph aureus
+/Broad inc.
pseudomonas
+
+/Broad
+ inc. MRSA,
severe C. diff
+/Intracellular
- inc.
pseudomonas
+ staph/strep
Anaerobes
Broad +/-/
Intracellular
-/Intracellular
Anaerobes/
Parasites
(Giardia)
PCP
Management of febrile convulsions
Simple febrile convulsion = single tonic-clonic generalised seizure lasting < 20 minutes and
occurring as the temperature rises rapidly during a febrile illness in a child aged 6 months to
5 years.
Tx Lie prone
 If fit lasts for > 5 minutes give Lorazepam IV / Diazepam PR
 Tepid sponging and paracetamol syrup
 Reassure parents- the risk of epilepsy is less than 2%
 30% have recurrent febrile convulsions- teach parents to give diazepam PR
 All fevers should be treated with an antipyretic, though this does not necessarily
prevent fits.
Management of heat exhaustion
Risk factors: Elderly, Children, Obese, Exercising in the heat (military, athletes), Acute febrile
illness, Chronic illness, Dehydration, Drugs (cocaine, ecstasy, LSD, tricyclic antidepressants,
amphetamines, phenothiazines- various antipsychotics and antihistamines)
Heat exhaustion/syncope- Fatigue, light-headed, nausea and vomiting, cramps.
Core Temp < 400. Tx- copious oral fluids, cool spray, fan
Heat stroke- Acute neurological impairment. Core temp > 400. Tachypnoea, tachycardia,
hypotension, irritability, confusion, coma. Complications: CCF, centrilobular liver necrosis,
acute renal failure, DIC, permanent neurological deficit. Tx- cool as above. Can also use cold
gastric and peritoneal lavages.
14. Notifiable diseases
Notification aims to achieve prompt recognition and response to outbreaks and epidemics,
including contact tracing. Doctors have a statutory obligation to notify the local authority or
local health protection unit upon suspicion of any of the following diseases, not awaiting
laboratory confirmation.









Acute encephalitis
Acute infectious hepatitis
Acute meningitis
Acute poliomyelitis
Anthrax
Botulism
Brucellosis
Cholera
Diphtheria
 Enteric fever (typhoid or
paratyphoid fever)
 Food poisoning
 Haemolytic uraemic syndrome
(HUS)
 Infectious bloody diarrhoea
 Invasive group A streptococcal
disease
 Legionnaires’ Disease
 Leprosy
















Malaria
Measles
Meningococcal septicaemia
Mumps
Plague
Rabies
Rubella
SARS
Scarlet fever
Smallpox
Tetanus
Tuberculosis
Typhus
Viral haemorrhagic fever (VHF)
Whooping cough
Yellow fever