Pyrexia of unknown origin Index Case Year 2 Michaelmas Term.
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Transcript of Pyrexia of unknown origin Index Case Year 2 Michaelmas Term.
![Page 1: Pyrexia of unknown origin Index Case Year 2 Michaelmas Term.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649cec5503460f949b92f2/html5/thumbnails/1.jpg)
Pyrexia of unknown origin
Index Case Year 2
Michaelmas Term
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The case: John S, aged 28
• Home from holiday in Africa 6 weeks
• Developed ‘flu like illness and fever
• Feels ill with chills and muscle pains (rigours)
• Also developed cold sore on lip
• Admitted to hospital with “PUO”
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On examination:• Temp 390C, pulse 100/min• Chest clear; HS normal• Liver and spleen palpable• No lymphadenopathy• Urine: rbc++ no positive culture• Negative bacterial culture in blood• Faecal culture unremarkable• Hb 8g/dl; MCV 90; Platelets 130 x109/dl• Bilirubin 45μMol/l
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Differential diagnosis of PUO?
• History most important,
• Then examination
• Then investigations
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PUO may be caused by:
• Infection
• Tumour
• Allergy
• Connective tissue disorders
• Overheating
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Infection: some are difficult to diagnose:
• TB
• Sub-acute bacterial endocarditis (usually streptococcal)
• Hidden abscesses: may be post-op
• Osteomyelitis
• Brucellosis/lyme disease
• Tropical diseases
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Tumour
• Lymphomas
• Renal cell carcinomas
• Lung cancer with secondary chest infection
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Allergy
• May get eosinophilic reaction to infestation with worms
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Connective tissue disorders
• SLE
• Dermatomyositis
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How would you approach this case?
• History: travel
• Did he take antimalarial prophylaxis?
• How long did he carry on with it after returning home?
• Was he well whilst abroad? Y
• Does the fever vary in intensity? Y
• Other symptoms? Y headache, tiredness, muscle pain plus some abdominal pain
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Examination and investigation?
• Pallour; tinge of jaundice• Hepatosplenomegaly• No lymphadenopathy or CNS abnormality• Urine: red cells• CXR: normal• U/S abdomen: hepatosplenomegaly X2• CT brain: normal• Blood cultures no growth
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If malaria id a possibility what investigation would you ask for?
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A thick blood film, looking for infected cells
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Some facts about Malaria• Means “Bad Air”
• Caused by Plasmodium falciparum, vivax, ovale or malariae
• Vector: anopheles mosquito
• P falciparum most likely and most severe: 2000 case in UK annually
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Geographical distribution (n.b. used to endemic in the Fens: Ague)
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Life cycle: sexual in mosquito and asexual in human
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Life cycle in human:
• Female anopheles mosquito injects sporozoites from salivary glands during blood meal
• Sporozoites attach to and invade liver cells• Multiplication by division to Merozoites.• Liver cell ruptures and merozoites
released• Merozoites bind and enter into rbc• Multiply and rupture with proinflammatory
cytokines
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Consequences of infection:
• Cyclical recurrent fever and haemolytic jaundice
• Local vessel blockage from sequestrin production, leading to infarction in brain, liver, spleen gut
• Immune complex deposition: glomerulonephritis
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?immunity
• Maternal antibodies protective to babies
• Some incomplete immunity may develop: T cell activation by liver cell stage antigens
• Immunity confounded by diversity of antigens: no cross-strain protection
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Natural protection from:
• Sickle cell disease. Infection causes sickling and red cell potassium leakage kills the organism. Spleen clears affected cells
• Duffy blood type shares antigen with P vivax. Duffy negative common in Nigeria: offers protection
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Prevention?
• Vector control:
• Kill mosquitos
• Spray oil on stagnant water
• Spray walls of huts
• Chemically impregnated nets
• Avoid bites with nets, staying indoors, skin sprays
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Prophylaxis: seehttp://www.traveldoctor.co.uk/malari
a.htm• The Different Drug Regimens• Regimen 1 Mefloquine one 250mg tablet weekly. OR
Doxycycline one 100mg capsule daily. ORMalarone one tablet daily.
• Regimen 2 Chloroquine 300mg weekly (2x150mg tablets). PLUSProguanil 200mg daily (2x100mg tablets).
• Regimen 3Chloroquine 300mg weekly (2x150mg tablets) ORProguanil 200mg daily (2x100mg tablets).
• Regimen 4No prophylactic tablets required but anti mosquito measures such as insect repellents, mosquito nets, long sleeved clothing, etc. should be strictly observed.
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But drug resistance a problem:
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Treatment: see http://www.who.int/malaria/doThe
Different Drug Regimens cs/TreatmentGuidelines2006.pdf
• 1,000,000 mortality worldwide annually
• Chloroquine now ineffective for most P. falciparum
• Resistance to sulfadoxine-pyrimethamine
• NEW!! Artemisinin derivatives from China
• “ACT”- Artemisinin-based combination therapy
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Artemisia annua