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Download Problem 06- Fever
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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 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 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 o o o o 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 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 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 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 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