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Infectious diseases 

Infectious diseases
Infectious diseases
Oxford Handbook of Clinical Medicine (10 ed.)

Ian B. Wilkinson

, Tim Raine

, Kate Wiles

, Anna Goodhart

, Catriona Hall

, and Harriet O’Neill


Fig 9.1 Leeuwenhoek’s microscope. Antoni van Leeuwenhoek (1632–1723) was an unlikely scholar: a draper with no academic education. He mixed uncomfortably in a scientific world made up of those better educated, wealthier, and with more refined manners. He felt unworthy of publication but submitted hundreds of letters to the Royal Society, always asking his readers to account for his humble origins. Despite his self-deprecation, his microscopy was sophisticated. His surviving lens magnified ×266 and resolved down to 1.35µm, comparable to that of a modern compound microscope. With it he gained one of the first insights into the ‘invisible’ living creatures of the microscopic world. His microscopes were cheap and easy to produce—he made 500 for his personal use. He plated them in gold and silver to add a prestige that the scientific world felt they lacked. But that world failed to see beyond the end of its turned up nose. Bloodletting, purging, and emetics would continue to fail patients for a further 150 years.

Fig 9.1
Leeuwenhoek’s microscope. Antoni van Leeuwenhoek (1632–1723) was an unlikely scholar: a draper with no academic education. He mixed uncomfortably in a scientific world made up of those better educated, wealthier, and with more refined manners. He felt unworthy of publication but submitted hundreds of letters to the Royal Society, always asking his readers to account for his humble origins. Despite his self-deprecation, his microscopy was sophisticated. His surviving lens magnified ×266 and resolved down to 1.35µm, comparable to that of a modern compound microscope. With it he gained one of the first insights into the ‘invisible’ living creatures of the microscopic world. His microscopes were cheap and easy to produce—he made 500 for his personal use. He plated them in gold and silver to add a prestige that the scientific world felt they lacked. But that world failed to see beyond the end of its turned up nose. Bloodletting, purging, and emetics would continue to fail patients for a further 150 years.

Infectious disease: an overview

It is not possible for any id chapter to be constructed so that it has the right balance throughout the world. Many of our readers come from communities where malaria is the primary differential, and aids-related deaths are common. In contrast, it is chest, gu, and ent infections which predominate in the uk; and aids is considered only where there is failure of either the diagnosis or treatment of hiv, which are universally available and free at the point of care. Many of the diseases in this chapter cause multisystem pathology. For these infections, it may be helpful to classify by pathogen (table 9.1). However, infectious agents do not walk in the door and introduce themselves. Detective work may be necessary based on geography; or exposure: to vectors, animals, and contaminated water/food. And so other pages in this chapter have that as their (helpful) premise. When infection is organ specific, you may need to look elsewhere (table 9.2).

Table 9.1 Infectious disease by pathogen (illustrative, not exhaustive)



Gram positive

rna viruses


  • Staph. aureus (coagulase +ve)

  • Staph. epidermidis (coagulase −ve)

Picornavirus (‘tiny rna’):

  • Rhinovirus

  • Poliovirus

  • Streptococci:

    • α‎-haemolytic, eg Strep. pneumoniae

    • β‎-haemolytic, eg Strep. pyogenes

Calicivirus (‘cup’), eg norwalk

  • Flavivirus (‘yellow’):

    • Dengue

    • Zika

    • Yellow fever


  • Clostridium species:

    • C. botulinum (botulism)

    • C. perfringens(gas gangrene)

    • C. tetani (tetanus)

    • C. difficile (diarrhoea)

Coronavirus (‘crown’): urti

Rhabdovirus (‘rod’), eg rabies

Filovirus (‘thread’), eg Ebola/Marburg

Paramyxovirus (‘near mucus’), eg mumps

Gram negative

dna viruses

  • Neisseria:

    • N. meningitidis (meningitis)

    • N. gonorrheae (gonorrhea)

Hepadnavirus (‘liver dna’): hepatitis

Parvovirus (‘small’): gastroenteritis

  • Herpesvirus (‘creeping’):

    • hsv

    • vzv

    • cmv

    • ebv

Helicobacter pylori

Escherichia coli

Shigella species

Salmonella species

Campylobacter jejuni


Klebsiella pneumoniae


Pseudomonas aeruginosa

Pneumocystis jirovecii

Haemophilus influenzae


Bordetella pertussis (whooping cough)


Vibrio cholerae (cholera)


Yersinia pestis (plague)

Entamoeba histolytica


Giardia lamblia

M. tuberculosis

Cryptosporidium species

M. leprae

Toxoplasma gondii

Intracellular bacteria

Plasmodium species (malaria)


Leishmania species (leishmaniasis)

Rickettsia (rickettsial disease)

Trypanosoma species (trypanosomiasis)

Coxiella burnetii



Soil-transmitted helminths

Borrelia burgdorferi (Lyme disease)

Filarial disease

Treponema (syphilis, yaws)


Leptospira (Weil’s disease)

Schistosoma (schistosomiasis), flukes


Hydatid disease, tapeworm

Table 9.2 Infectious disease by organ system







Empyema—infected pleural effusion


Fungal infections of the lung



Peptic ulcer disease




Colitis, proctitis, diverticulitis, appendicitis

Viral hepatitis


Tropical liver disease


Cholecystitis, cholangitis, gallbladder empyema




gu and gynaecology

Lower urinary tract infection, cystitis, pyelonephritis


Cervicitis, vulvovaginitis


Genital ulceration


Genital warts


Pelvic inflammatory disease, endometritis

ohcs p[link]


Infective endocarditis






Nervous system

Meningitis, encephalitis, subdural empyema


Infective neuropathy


Skin and soft tissue

Skin ulcers, gangrene


Tropical skin disease


Surgical wound infection

p[link], p[link]

Bone and joint


ohcs p[link]

Septic arthritis



Pharyngitis, laryngitis, otitis media

ohcs p[link]


Tropical eye disease


The management of infectious disease includes prevention whenever possible. Tracing the source of disease and contacts are essential in the management of outbreaks. Notification to your local health protection team (see is a statutory duty for the following conditions (only clinical suspicion is required, accuracy of diagnosis is secondary):

  • Acute encephalitis

  • Acute infectious hepatitis

  • Acute meningitis

  • Acute poliomyelitis

  • Anthrax

  • Botulism

  • Brucellosis

  • Cholera

  • Diphtheria

  • Enteric fever

  • Food poisoning

  • HUS

  • Infectious dysentery

  • Invasive group A strep

  • Legionnaire–s disease

  • Leprosy

  • Malaria

  • Measles

  • Meningococcal sepsis

  • Mumps

  • Plague

  • Rabies

  • Rubella

  • SARS

  • Scarlet fever

  • Small pox

  • Tetanus

  • Tuberculosis

  • Typhus

  • Viral haemorrhagic fever

  • Whooping cough

  • Yellow fever.

Infectious disease resources

The Hillis plot (fig 9.2, p[link]) tells us that id chapters will always fail to be exhaustive. We therefore direct you to the following excellent resources:

Bacterial infection: an overview

Humans and bacteria are symbiotes, with each of us host to ten times as many bacterial cells as our own human cells. Our gut, skin, and mucosal linings are covered with bacteria. We rely on this for nutrition, functioning vitamin k, anti-inflammatory effects, and immune system regulation.

Bacterial disease results from a breach of the measures that limit bacteria to their ‘normal’ roles: skin commensals moved into the bloodstream by a cannula, antibiotics altering the commensal microflora, immune system evasion or dysfunction allowing organisms to stray beyond their usual boundaries, toxin production. When treating infections we should therefore remember to look beyond the offending organism and consider what factors may have aided pathogenesis: malnutrition, ‘barrier’ breach by cancer/plastic, immunosuppression.

Infectious diseasesSee ‘Sepsis’, p[link].


A guide to antibiotic prescribing

Infectious diseasesGive antibiotics immediately in patients with a systemic inflammatory response to infection. See ‘Sepsis, p[link].

Start smart:

  1. 1 Do not prescribe2 antibiotics in the absence of clinical evidence of bacterial infection, or for a self-limiting condition. Take time to discuss:

    • why an antibiotic is not the best option

    • alternative options, eg symptomatic treatment, delayed prescribing

    • the views and expectations of the patient

    • safety-netting advice: what the patient should do if their condition deteriorates.

  2. 2 Take microbiological samples before prescribing,1 especially for:

    • hospital in-patients: review your prescription as soon as mc&s result is available

    • recurrent or persistent infection

    • non-severe infection: consider if your prescription can wait for mc&s results.

  3. 3 Follow local guidelines first: best practice is informed by local epidemiology and sensitivities.

  4. 4 Consider benefit and harm for each individual patient:

    • Allergies: clarify the patient’s reaction—the true incidence of penicillin allergy in patients who report that they are allergic is <10%. In those with a confirmed penicillin allergy, cross-reactivity with 3rd-generation cephalosporins and carbapenems is possible but rare (<1%).

    • Dose adjust for renal function and weight: use ideal body weight in extremes of bmi (or ideal weight plus a % of excess weight—see local guidelines).

    • Check for medication interactions.

    • In pregnancy and lactation, see p[link].

  5. 5 Prescribe the shortest effective course. Most antibiotics have good oral availability. Use iv antibiotics only if in line with local or national (sepsis) guidelines.

Then focus:

Review the clinical diagnosis and continuing need for antibiotics at 48h for all in-patients and all patients prescribed iv antibiotics:

  • Stop antibiotics if there is no evidence of infection.

  • Switch from iv to oral whenever possible.

  • Change to a narrower spectrum antibiotic whenever possible.

  • Continue regular clinical review whilst antibiotics are prescribed.

Inhibitors of cell wall synthesis

See fig 9.4. The bacterial cell wall is unique in nature and therefore acts as a selective target for antibiotics. Antibiotics which act on the cell wall include:

  • β‎-lactam antibiotics

  • others: glycopeptides, polymyxins.

β‎-lactams: penicillins, cephalosporins, carbapenems, monobactam

Contain a β‎-lactam ring which inhibits the formation of peptidoglycan cross-links in the bacterial cell wall. Resistance occurs when the bacteria (eg staphylococci) produce a β‎-lactamase enzyme.


See table 9.3. Include natural penicillins (penicillin g and v) and synthetic penicillins which are chemically modified to extend their spectrum of activity, eg amoxicillin, piperacillin.

In an attempt to overcome β‎-lactamase resistance, penicillins have been combined with β‎-lactamase inhibitors to create β‎-lactam-β‎-lactamase inhibitor combinations eg co-amoxiclav (amoxicillin+clavulanic acid), Tazocin® (piperacillin+tazobactam).

Staphylococcal resistance is conventionally defined by stability to meticillin, an acid-labile and iv-only equivalent of flucloxacillin (see mrsa p[link]).


See table 9.4. Contain a β‎-lactam ring attached to a six-membered nuclear structure (five in penicillin), which allows synthetic modification at two sites (one in penicillin). This means that cephalosporins are the largest groups of available antibiotics. Classification into ‘generations’ is not standardized: as a rough rule, the higher the generation, the wider the spectrum.


See table 9.5. Broadest spectrum of all β‎-lactam antibiotics. Seek expert microbiology advice before use.


Aztreonam is only active against Gram-negative species including Neisseria meningitidis, Haemophilus influenzae, Pseudomonas. Given iv/im. Inhaled preparation for chronic pulmonary Pseudomonas (cystic fibrosis). Dose adjust for renal function. ses: n&v, gi bleed, rash, ↑lfts, ↓plts, paraesthesia, seizures, bronchospasm.

Non-β‎-lactam cell wall inhibitors

See fig 9.4 and table 9.6. Includes glycopeptides, eg vancomycin, teicoplanin, and polymyxins, eg colistin.

Inhibitors of protein synthesis

See fig 9.4 and table 9.7. Includes:

  • aminoglycosides

  • macrolides

  • tetracyclines and derivatives of tetracycline

  • others: clindamycin, linezolid, chloramphenicol, fusidic acid.

Inhibitors of nucleic acid synthesis

See fig 9.4 and table 9.8. Includes:

  • folate synthesis inhibitors: trimethoprim, co-trimoxazole

  • fluoroquinolones

  • others: metronidazole, rifampicin.

Infectious diseasesNitrofurantoin is unique. Metabolites interfere with cell growth via ribosomes, dna, rna, and cell wall. Multiple sites of attack means ↓resistance. Concentrates in the urine (but not if ↓gfr), used in uncomplicated uti. ses: haemolysis, pulmonary fibrosis, hepatotoxicity.

Infectious diseasesAntibiotics for tb, see pp[link][link].

Antibiotics: summary tables

Table 9.3 Penicillins




Penicillin g (benzylpenicillin, ‘penicillin’)

Gram +ve: streptococci (chest, throat, endocarditis, cellulitis), meningococcus, diphtheria, anthrax, leptospirosis, Lyme disease.

Give iv, poor oral absorption. Dose adjust for gfr. se: allergy, rash, n&v, C. difficile, cholestasis.

Penicillin v (phenoxymethylpenicillin)

Prophylaxis: splenectomy/hyposplenism, rheumatic heart disease.

Oral bioavailability may vary.


Amino acid side chain extends penicillin spectrum to include enterobacteria (but ↓ activity against Gram +ve): urti, sinusitis, chest, otitis media, uti, H. pylori.

Ampicillin iv, amoxicillin po. Dose adjust for gfr. se: as per penicillin g, rash with ebv.

Amoxicillin+clavulanic acid (co-amoxiclav)

Used if resistance to narrower-spectrum antibiotics: chest, pyelonephritis, cellulitis, bone.

Dose adjust for gfr. se: as per amoxicillin.


Broad spectrum including Gram +ve, Gram −ve, Pseudomonas: neutropenic sepsis, hospital-acquired/complicated infection.

Tazobactam has ↓penetration of blood–brain barrier. Dose adjust for gfr. se: as per penicillin g. Myelosuppression with prolonged use (rare).


β‎-lactamase resistant, Staphylococcus: skin, bone, post-viral pneumonia.

Dose adjust for gfr. se: allergy, rash, n&v, cholestasis.

Table 9.4 Cephalosporins




Cefalexin (1st generation)

Gram +ve infection: uti, pneumonia.

  • ↓First-line use in uk due to risk of C. difficile.

  • Caution: false +ve urinary glucose and Coomb’s test.

  • se: allergy, rash, n&v, cholestasis. Ceftriaxone can precipitate in urinary tract and biliary tree = pseudolithiasis.

Cefuroxime (2nd generation)

Gram +ve and Gram −ve (Enterobacteriaceae, H. influenzae): uti, sinusitis, skin, wound.

Cefotaxime (3rd generation)

Broad spectrum (not Pseudomonas, Enterococcus spp, Bacteroides).

Ceftriaxone (3rd generation)

Meningococcus. Broad spectrum (not Pseudomonas, Enterococcus spp, Bacteroides).

Ceftazidime (3rd generation)

Broad spectrum including Pseudomonas but ↓ activity against Gram +ve: empirical treatment of neutropenic sepsis.

Table 9.5 Carbapenems





Broad spectrum (Gram +ve, Gram −ve, aerobes, anaerobes): hospital-acquired/ventilator-associated/complicated infection, neutropenic sepsis.

  • Dose adjust for gfr. Imipenem given with cilastatin to ↓renal metabolism.

  • se: n&v, C. difficile, rash, eosinophilia, ↓plts, ↑lfts, seizures.



Table 9.6 Lipopeptides and polymyxins






Complicated Gram +ve including mrsa. Oral for C. difficile (not absorbed).

Dose iv to trough serum concentration. ses: nephrotoxic (monitor creatinine, care with other nephrotoxics) ototoxic, ↓plts.



Colistin, polymyxin b

Multi-resistant Gram −ve.

Nephrotoxicity in ~50%. Inhaled colistin for ventilator-associated pneumonia.

Table 9.7 Inhibitors of protein synthesis






Gram −ve infection (↓activity against most Gram +ve and anaerobes). Tobramycin has ↑activity against Pseudomonas. Amikacin has least resistance.

ses: nephrotoxic (monitor drug levels and serum creatinine), vestibular toxicity, ototoxicity.





Gram +ve cocci (not enterococci and staphylococci), syphilis, chlamydia.

  • ses (↑ with erythromycin): gi, cholestasis, ↑qt.

  • Cytochrome p450 inhibition (↓ with azithromycin): ↑warfarin, rhabdomyolysis with statins, ↑calcineurin inhibitor levels.



Tetracyclines and derivatives


Exacerbation copd, chlamydia, Lyme disease, mycoplasma, rickettsiae, brucella, anthrax, syphilis, mrsa, malaria prophylaxis.

  • ci: pregnancy, <8y (teeth/bones).

  • ses: n&v, C. difficile, fatty liver, idiopathic intracranial hypertension.



Gram +ve and Gram −ve including β‎-lactam-resistant strains.

Dose adjust in liver dysfunction. ses: n&v, photosensitivity, ↑lfts.



Gram +ve cocci (not enterococci), mrsa, anaerobes.

↑ risk C. difficile.


Gram +ve cocci, mrsa, vre, anaerobes, mycobacteria.

maoi: check interactions, myelosuppression, optic neuropathy.


Gram +ve, Gram −ve, anaerobes, mycoplasma, chlamydia, conjunctivitis (topical).

Systemic use limited by myelosuppression.

Fusidic acid


ses: gi, ↑lfts.

Table 9.8 Inhibitors of nucleic acid synthesis




Folate synthesis inhibitors


Gram −ve: uti, prostatitis.

Inhibits creatinine secretion: ↑serum creatinine without ↓gfr.

Co-trimoxazole (sulfamethoxazole + trimethoprim)

Pneumocystis jirovecii, gi infection (eg Shigella, E. coli), protozoans (eg Cyclospora), listeria, nocardia, mrsa.

Synergistic combination. Good oral absorption and tissue/csf penetration. ses: folate deficiency, ↑K+, rash, myelosuppression, haemolysis with g6pd deficiency.



Broad including Pseudomonas: uti, prostatitis, atypical and hospital-acquired chest infection, infectious diarrhoea.

ses: gi irritation, cns effects (↓ seizure threshold, headache, drowsiness, mood change), peripheral neuropathy, tendinopathy (Achilles), ↑qt, C. difficile.





Anaerobic infection: intra-abdominal, pelvic, oral, soft-tissue. Bacterial vaginosis. C. difficile.

Good oral absorption. Dose adjust for liver function. ses: Disulfiram reaction with alcohol, inhibits warfarin metabolism.

Rifamycins: rifampicin, rifabutin, rifapentine

Mycobacteria (tb, atypical mycobacteria, leprosy), some staphylococci, Legionella, meningococcal prophylaxis.

ses: hepatitis (monitor lfts), gi, cns effects, myelosuppression, red secretions (urine, saliva, sweat, sputum, tears).

Gram-positive bacteria

Gram-positive cocci


Staphylococci are skin/nasal commensals in ~80% of adults. They can also cause infectious disease. This produces a diagnostic challenge: are the detected organisms causing infection or a contaminating commensal? The answer may lie in the presence or absence of coagulase, an enzyme which coagulates plasma.

Coagulase-negative staphylococci: eg Staphylococcus epidermidis are less virulent. Pathogenicity is likely only if there is underlying immune system dysfunction or foreign material (prosthetic valve/joint, iv line, pd catheter, pacemaker).

Staphylococcus aureus is coagulase positive. Presentation:

  1. 1 Toxin release causes disease distant from infection. Includes:

    • scalded skin syndrome—bullae and desquamation due to epidermolytic toxins (no mucosal disease, ↓skin loss compared to toxic epidermal necrolysis)

    • preformed toxin in food—sudden d&v (p[link])

    • toxic shock—fever, confusion, rash, diarrhoea, ↓bp, aki, multiorgan dysfunction.Tampon associated or occurs with (minor) local infection.

  2. 2 Local tissue destruction: impetigo, cellulitis, mastitis, septic arthritis, osteomyelitis, abscess, pneumonia, uti.

  3. 3 Haematogenous spread: bacteraemia, endocarditis, ‘metastatic’ seeding.

Diagnosis: positive culture from relevant site of infection. Treatment: Infectious diseasesSepsis, see p[link]. Drain infected foci, antibiotic (topical/oral/iv) based on illness severity and risk factors. Consider local epidemiology of resistance. If systemic treatment indicated, use β‎-lactam whenever possible (may need to cover resistant strains until sensitivity available). Preformed toxin in food: supportive, antibiotics not usually indicated.


Classification based on Lancefield group persists in terminology (fig 9.5). Includes:

  • Streptococcus pyogenes (β‎-haemolytic group a): colonizes throat, skin, anogenital tract. Range of infection: tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas, cellulitis, pneumonia, peripartum sepsis, necrotizing fasciitis. All can→streptococcal toxic shock = sudden-onset ↓bp, multiorgan failure. Post-infectious complications rare: rheumatic fever (p[link]), glomerulonephritis (p[link]). Treatment: penicillin.

  • Streptococcus agalactiae (β‎-haemolytic group b): neonatal and peurperal infection, skin, soft tissue. Invasive disease (bacteraemia, endocarditis, osteomyelitis, septic arthritis, meningitis) usually has risk factors: dm, malignancy, chronic disease. Treatment: penicillin, macrolide, cephalosporin, chloramphenicol.

  • Streptococcus milleri: if found in blood culture look for an abscess—mouth, liver, lung, brain. Treatment: penicillin.

  • Streptococcus pneumoniae: pneumonia (pp[link][link]), otitis media, meningitis, septicaemia. Treatment: penicillin. Vaccination: childhood, hyposplenism, >65y (p[link]).

  • Viridans streptococci: commonest cause of oral/dental origin endocarditis (p[link]).

  • Streptococcus bovis: bacteraemia→endocarditis. Look for colon/liver disease.

Fig 9.5 Streptococci are grouped by haemolytic pattern (α‎, β‎, or non-haemolytic), by Lancefield antigen (a–g), or by species. Rebecca Lancefield (1895–1981) is shown with her hand lens, typing streptococci with a variety of m protein-specific antibodies. Her lab became known as the ‘Scotland Yard of Streptococcal Mysteries’ after she found that the most grievous crimes of streptococci almost always involve m as a secret accomplice. Although she arrested m on many occasions, m outlived her, and still stalks our wards and clinics.

Fig 9.5
Streptococci are grouped by haemolytic pattern (α‎, β‎, or non-haemolytic), by Lancefield antigen (ag), or by species. Rebecca Lancefield (1895–1981) is shown with her hand lens, typing streptococci with a variety of m protein-specific antibodies. Her lab became known as the ‘Scotland Yard of Streptococcal Mysteries’ after she found that the most grievous crimes of streptococci almost always involve m as a secret accomplice. Although she arrested m on many occasions, m outlived her, and still stalks our wards and clinics.

©Dr V Fischetti, Rockefeller University, NY.


Gut commensal. Resistance to cephalosporins and quinolones leads to nosocomial colonization and infection. Most common is Enterococcus faecalis: if found in blood culture, assume endocarditis until proven otherwise. Treatment: intrinsic and acquired resistance including vancomycin-resistant enterococci (vre). Seek expert help.

Gram-positive bacilli


Caused by Listeria monocytogenes which lives in soil. Able to multiply at low temperatures. Found in pâté, raw vegetables/salad, unpasteurized milk/cheese. Presentation: most asymptomatic, or mild flu-like illness. In immunosuppressed (including elderly): gastroenteritis, local infection (abscess, osteomyelitis, septic arthritis, endocarditis, pneumonia), meningoencephalitis, life-threatening septicaemia. Listeria in pregnancy may cause mild disease in mother but transplacental infection→placentitis, amnionitis, preterm delivery, neonatal sepsis, intrauterine death. Diagnosis: culture: blood, placenta, amniotic fluid, csf. pcr. Serology is non-specific. Treatment: ampicillin plus gentamicin (synergistic action) for systemic disease. Also co-trimoxazole (cns disease), macrolides, tetracycline, rifampicin, vancomycin, carbopenem. Infectious diseasesResistant to cephalosporins which are often 1st-line empirical treatment for meningitis so remember additional antimicrobial cover if listeria is a possibility.


  • Clostridium difficile, see p[link], p[link].

  • Clostridium perfringens:

    • Gastroenteritis, see p[link].

    • Gas gangrene due to exotoxin production (alpha toxin most common). Previously Clostridium welchii. Presentation: sudden, severe pain due to myonecrosis, tissue crepitus, systemic shock. Most post surgery (gi, biliary), or following soft-tissue trauma/open fracture. If spontaneous, look for malignancy. Treatment: early recognition, surgical debridement, protein synthesis inhibitors, eg clindamycin inhibit toxins >penicillins. Hyperbaric O2 unproven in trials (fig 9.4, table 9.7).

  • Clostridium botulinum, see p[link].

  • Clostridium tetani, see p[link].


Caused by Corynebacterium diphtheriae toxin. Preventable with vaccine. Presentation: tonsillar pseudomembrane with fever, painful dysphagia, cervical lymphadenopathy (see ohcs p[link]). Diagnosis: culture, toxin detection, pcr. Treatment: antitoxin within 48h. Benzyl-penicillin/erythromycin. Airway support.


Due to Actinomyces israelii, a mucous membrane commensal. Presentation: subacute granulomatous/suppurative infection adjacent to mucous membrane. Diagnosis: culture. ‘Sulphur’ granules in pus/tissue are pathognomonic. Treatment: antibiotics covering actinomycetes and concomitant microbes.


Rare cause of disease. Presentation: tropical skin abscess, lung/brain abscess, disseminated infection if immunosuppressed. Treatment: usually co-trimoxazole.


See p[link].

Gram-negative bacteria

Gram-negative cocci


Neisseria meningitidis (meningococcus) is an upper respiratory tract commensal in ~10% (~25% adolescents) adhering to non-ciliated epithelial cells in nasopharynx and tonsils. Person-to-person transmission via droplets or upper respiratory tract secretions. Most strains are harmless but induce immunity. Pathogenic, virulent strains are mostly encapsulated and have the potential to cause septicaemia and meningitis. Serogroups a, b, c, w and y account for nearly all invasive forms. ↓Group c following introduction of vaccination in uk. ↑ in serotype w in uk since 2009. Incubation 2–7d. Peak ages: <2yr, ~18yr. Risk factors: complement system defects, hyposplenism, hiv. Presentation:

  1. 1 Meningitis (~50% cases). Main proliferation of bacteria is in csf. Insidious onset with malaise, nausea, headache, vomiting. May be misdiagnosed as gastroenteritis, urti, or childhood viral illness. Later meningism: headache, vomiting, nuchal/back rigidity, photophobia, altered consciousness. Complications in up to 20%: sensorineural hearing loss, impaired vestibular function, epilepsy, diffuse brain injury.

  2. 2 Meningococcaemia. Symptoms/signs depends on amount of circulating bacteria. Mild disease presents with fever, macular rash (fig 9.6) but no signs of shock. High-grade meningococcaemia (~30% cases) causes pyrexia and septic shock within 6–12h due to rapidly escalating endotoxin levels: circulatory failure, coagulopathy with skin haemorrhage (fig 9.7), thrombosis of extremities/adrenals, aki, ards. Meningism may be absent. Complications: amputation, skin necrosis, pericarditis, arthritis, ocular infection, pneumonia (especially serotypes y and w), permanent adrenal insufficiency.

Fig 9.6 Macular lesions on legs.

Fig 9.6
Macular lesions on legs.

Reproduced from Warrell et al. Oxford Textbook of Medicine, 2010, with permission from Oxford University Press.

Fig 9.7 Massive skin haemorrhage with fulminant meningococcal septicaemia.

Fig 9.7
Massive skin haemorrhage with fulminant meningococcal septicaemia.

Reproduced from Warrell et al. Oxford Textbook of Medicine, 2010, with permission from Oxford University Press.

Diagnosis: Infectious diseasesStart treatment immediately if meningitis/meningococcal sepsis is a possible diagnosis. Do not wait for confirmation: delay can be deadly. Intra- and extracellular diplococci on microscopy of csf/blood/skin lesion. pcr of csf/blood/skin lesion. Treatment: urgent antibiotic treatment: benzylpenicillin, ceftriaxone (see pp[link][link]). Cefotaxime, chloramphenicol, meropenem also bactericidal. Prevention: routine infant vaccination against capsular group c in uk. Capsular group b vaccine in uk infants since 2015: induces bacteriocidal antibodies, no population data, duration of protection unknown. Quadrivalent acwy vaccine at age 14 and if high-risk travel. Additional b, c, acwy doses if hyposplenism and complement deficiency. Prophylaxis of contacts: ciprofloxacin/ceftriaxone (single dose), or rifampicin 600mg bd for 48h.

Neisseria gonorrhoea: see pp[link][link].

Moraxella catarrhalis:

Colonizes upper respiratory tract in children (↓ in adults). Resembles Neisseria commensal so may be overlooked. Presentation: pneumonia, exacerbation of copd, up to 20% of acute otitis media, sinusitis. Bacteraemia is rare. Diagnosis: culture of sputum, ear effusion, sinus aspirate, blood. ‘Hockey puck sign’: colonies can be pushed along agar surface without disruption. Treatment: macrolide, cephalosporin.

Gram-negative bacilli


Enterobacteriaceae family is large: >50 genera, >170 named species. In the clinical setting, 3 species make up 80–95% of isolates:

  1. 1 Escherichia coli: part of normal colonic flora. Pathogenic forms can cause:

    Intestinal disease:

    Enterotoxigenic: a major cause of traveller’s diarrhoea (pp[link][link]).

    Enterohaemorrhagic: diarrhoea, haemorrhagic colitis eg o157:h7 (p[link]).

    Enteropathogenic: infants in areas of poor sanitation.

    Enteroinvasive: dysentery-like syndrome.

    Enteroadherent: traveller’s diarrhoea, chronic diarrhoea in children/hiv.

    Extra-intestinal disease: usually patient’s own flora that is not pathogenic in the intestine but causes disease elsewhere: uti (pp[link][link]); neonatal meningitis; nosocomial infection: pneumonia, meningitis, sepsis. Treat according to sensitivity: trimethoprim, ampicillin, cephalosporin, ciprofloxacin, aminoglycoside.

  2. 2 Klebsiella pneumoniae: colonizes skin, nasopharynx, gi tract, hospitalized patients. Associated with antibiotic exposure, in-dwelling catheters, immunosuppression. Causes pneumonia (necrotizing disease and sepsis if immunosuppressed). Also uti, nasopharyngeal inflammation. Treat according to sensitivity: aminoglycoside, cephalosporin, carbapenem, quinolone.

  3. 3 Proteus mirabilis: gut commensal. Causes uti (pp[link][link]). Stone formation due to urease production: breaks down urea to produce ammonia, struvite stones (‘infection stones’) then form in the presence of magnesium, calcium, and phosphate (pp[link][link]).

Other Enterobacteriaceae include Salmonella, Shigella, Yersinia: see enteric fever (p[link]), gastroenteritis (pp[link][link]), plague (p[link]).

Resistance: widespread antibiotic use has led to the development of highly virulent, multiple resistant E. coli and Klebsiella species including:

  • extended-spectrum β‎-lactamase (esbl) producing Enterobacteriaceae. Resistant to penicillins, cephalosporins, fluoroquinolones, trimethoprim, tetracycline, with possible extension to other antibiotic groups

  • carbapenem-resistant Enterobacteriaceae (cre).

Resistance requires antimicrobial stewardship (p[link]), surveillance, robust infection control, research into resistance risk and transmission (p[link]).

Pseudomonas aeruginosa:

Found in environment. Spread by contact/ingestion. Presentation: important cause of nosocomial infection. Infection if compromised tissue, eg wound, pneumonia with lung disease or ventilation, uti with catheterization. Septicaemia if immunosuppressed. Treatment: options include ceftazidime/carbapenem, aminoglycoside, colistin. Combination may be needed. Impermeability of membrane and biofilm colonization lead to ↑antibiotic resistance. ↑Multidrug-resistance. Infectious diseasesSeek expert help.

Haemophilus influenzae:

Divided into encapsulated, typeable forms (a-f); and unencapsulated, non-typeable forms. Upper respiratory tract carriage, transmitted by droplets. H. influenzae b (Hib) causes meningitis, epiglottitis, otitis media, pneumonia, cellulitis, septic arthritis, and bacteraemia. Fatal in ~5%. Routine immunization in childhood and splenectomy/hyposplenism (p[link]). Non-typeable forms cause pneumonia and sinusitis. Treatment: amoxicillin, macrolide, cephalosporin, chloramphenicol, rifampicin.

Whooping cough:

Bordetella pertussis. Presentation: catarrhal phase 1–2wk, then paroxysmal coughing. ‘Whoop’ is a breath through partially closed vocal cords, seen mainly in children. Cough is prolonged (‘100 day cough’). Infants have ↑complications/mortality. Diagnosis: pcr nasal/throat swab. Culture sensitivity 10–60%. Treatment: macrolides ↓infectivity, but may not alter disease course. Routine childhood vaccination. Vaccination in pregnancy ↑placental antibody transfer to protect neonate (p[link]).


Brucellosis (p[link]), cholera (p[link]), melioidosis (p[link]).

Tuberculosis (tb): presentation


  • 9.6 million new cases/yr of which 37% are unreported/undiagnosed (fig 9.8).

  • 3.3% of new cases, and 20% of previously treated cases are drug resistant (p[link]).

  • Co-infection with hiv in 12% of new cases.

  • Leading cause of death worldwide, 1.5 million deaths/yr.

  • Effective diagnosis and treatment saved 43 million lives between 2000 and 2014.

  • uk: ~8000/yr, ~12 per 100 000. 73% born outside uk, 70% in deprived areas, 30% with pulmonary disease wait >4 months from symptoms to treatment.

Fig 9.8 Estimated tb incidence rate worldwide.

Fig 9.8
Estimated tb incidence rate worldwide.

Reproduced with permission from World Health Organization, Global tuberculosis report 2016. © World Health Organization 2016.


Caused by infection with Mycobacterium tuberculosis.

Active infection

occurs when containment by the immune system (t-cells/macrophages) is inadequate. It can arise from primary infection, or re-activation of previously latent disease. Transmission of tb is via inhalation of aerosol droplets containing bacterium. This means only pulmonary disease is communicable.

Latent tb

is infection without disease due to persistent immune system containment (ie granuloma formation prevents bacteria growth and spread). Positive skin/blood testing (p[link]) shows evidence of infection but the patient is asymptomatic and non-infectious (normal sputum/cxr). ~2 billion persons worldwide (~⅓ of world’s population) are estimated to have latent tb. Lifetime risk of reactivation is 5–10%. Risk factors for reactivation: new infection (<2y), hiv, organ transplantation, immunosuppression (including corticosteroids), silicosis, illicit drug use, malnutrition, high-risk settings (homeless shelter, prison), low socio-economic status, haemodialysis.


Infectious diseasestb, or not tb—that is the question. Maintain a high index of suspicion. tb can affect any organ in the body (table 9.9).

Table 9.9 uk tb case reports by site of disease

Site of disease

Number of cases in uk (%)


4096 (52)

Extra-thoracic lymph nodes

1874 (24)

Intra-thoracic lymph nodes

916 (12)


673 (9)


432 (6)


353 (5)

Other bone

220 (3)


211 (3)


172 (3)


145 (2)

From: Tuberculosis in the UK 2014 Report, Public Health England.

Tuberculosis (tb): diagnosis and treatment


Antibiotics used in the treatment3 of tb are detailed in table 9.10.

Table 9.10 Antibiotics used in the treatment of tb


Standard course for active disease



  • 2 months intensive

  • 4 months continuation

Enzyme inducer: care with warfarin, calcineurin inhibitors, oestrogens, phenytoin; body secretions coloured orange-red (includes contact lens staining); altered liver function.


  • 2 months intensive

  • 4 months continuation

Inhibits formation of active pyridoxine (Vit B6) which causes a peripheral neuropathy (↑risk with dm, ckd, hiv, malnutrition) ∴ give with prophylactic pyridoxine; hepatitis.


2 months intensive

Idiosyncratic hepatotoxicity, ↓dose if egfr<30.


2 months intensive

Colour blindness, ↓visual acuity, optic neuritis. Check visual acuity at start of treatment, monitor for symptoms. Monthly visual check if treatment > 2 months. Monitor levels if egfr<30.

Latent tb

Balance the risk of development of active disease with the possible side-effects of treatment. Consider treatment in all at ↑risk of active disease: hiv, transplantation, chemotherapy, biological agents eg anti-tnfα‎ (see p[link]), diabetes, ckd including dialysis, silicosis, bariatric surgery, and recent close contact with pulmonary/laryngeal tb. Offer hiv, hepatitis b and c testing prior to treatment.

Treat with 3 months of isoniazid (with pyridoxine) and rifampicin or 6 months of isoniazid (with pyridoxine).

If concerns about hepatotoxicity then 3 months of isoniazid and rifampicin may be preferred. In severe liver disease, seek specialist advice. If interactions with rifamycins are a concern (eg hiv, transplant) then 6 months of isoniazid may be preferred.

Active tb

All forms of active tb are statutorily notifiable in uk. This includes both clinical and culture diagnoses. Notification is via your local public health protection team ( Treatment is given under the care of a specialist tb clinician/service according to table 9.10. Exceptions include:

  • active cns disease (including spinal cord involvement): continuation phase of treatment is extended from 4 to 10 months

  • cns and pericardial disease: use adjunctive high-dose steroids (with weaning and withdrawal during the intensive treatment period)

  • drug-resistant tb.

Adherence is important for treatment to be effective and to prevent drug resistance. Directly observed therapy (dot) should be considered if: previous treatment for tb, homelessness, drug/alcohol misuse, prison, psychiatric or cognitive disorder, multi-drug resistant disease, patient request.

Universal access to diagnosis and treatment of tb is part of social justice. who has developed an ‘End tb’ strategy aiming to reduce tb deaths by 90% by 2030, and tb incidence by 90% by 2035 (

Drug-resistant tb

naat (p[link]) for drug resistance should be requested for all patients with risk factors for drug-resistance: previous tb treatment, contact with drug-resistant disease, birth or residence in a country where ≥5% new cases are drug resistant (fig 9.10). Drug resistance may be:

  • to any single agent in table 9.10.

  • multidrug-resistant tb (mdr-tb): resistant to rifampicin and isoniazid.

  • extensively drug-resistant tb (xdr-tb): resistant to rifampicin, isoniazid, one injectable agent (capreomycin, kanamycin or amikacin) and one fluoroquinolone.

Fig 9.10 Percentage of new tb cases with multi-drug resistant tb.

Fig 9.10
Percentage of new tb cases with multi-drug resistant tb.

Reproduced with permission from World Health Organization, Global tuberculosis report 2016. © World Health Organization 2016.

If rifampicin resistance is detected, treat with at least six agents to which the mycobacterium is likely to be sensitive. Test for resistance to 2nd-line drugs. Remember infection control measures. Seek expert advice for all drug-resistant cases.


Influenza is common throughout the world, affecting ~5–10% of adults, and 20–30% of children each year. In most, it is a self-limiting illness. Complications can be life-threatening in the elderly, pregnant women, and those with chronic disease. There are ~4 million cases of severe influenza and ~500 000 deaths worldwide/yr.

Seasonal influenza

Acute viral infection of lungs and airways. Rapid person-to-person spread by aerosolized droplets and contact. Infectivity from 1d prior, to ~7d after symptoms. Includes three subtypes of virus: a, b, and c. Type a influenza is subdivided according to combinations of virus surface proteins eg a(h1n1), a(h3n2). Seasonal epidemics peak during the winter in temperate countries. Acquired immunity is specific to the virus subtype.


Incubation: 1–4d. Fever, dry cough, sore throat, coryzal symptoms, headache, malaise, myalgia, conjunctivitis, eye pain ± photophobia. Complications include pneumonia, exacerbation of chronic lung disease, croup, otitis media, d&v, myositis, encephalitis, Reye syndrome (encephalopathy + fatty degenerative liver failure).


Clinical: acute onset + cough + fever has positive predictive value >79%. Testing limited to outbreaks, and public health surveillance. Includes: viral pcr, rapid antigen testing, viral culture of clinical samples (throat swab, nasal swab, nasopharyngeal washings, sputum).


  • Uncomplicated influenza symptomatic treatment eg paracetamol. Antivirals only if high risk:

    • Chronic disease: lung, heart, kidney, liver, CNS, DM

    • Immunosuppression: immunodeficiency, current or planned or within 6 months of immunosuppressive therapy, ↓CD4 (<200 in adults, <500 if child <5yr)

    • Pregnancy

    • >65yr

    • BMI>40

    • <6 months old.

  • Complicated influenza includes lower respiratory tract infection, exacerbation of any underlying medical condition, all needing hospital admission. Give antiviral4 inhibitors of influenza neuraminidase:

    1. 1 Oseltamivir: po or ng. Adult dose: 75mg bd. 5d course. 1st line in uk.

    2. 2 Zanamivir: inhaled (10mg bd, 5d course, confirm technique), nebulized, or iv (respiratory disease affecting nebulizer delivery, itu). Used if: oseltamivir resistance (eg a(h1n1)), poor clinical response to oseltamivir, concerns re gi absorption of oseltamivir.

Retrospective observational data, and animal studies of oseltamivir and zanamivir show no evidence of harm in pregnancy. Supportive treatment for all. Extracorporeal membrane oxygenation (ecmo) has been used to support gas exchange in severe acute lung injury due to influenza.


  • Post-exposure prophylaxis: if high risk (see ‘Treatment’) and not protected by vaccination: oseltamivir po od (inhaled zanamivir od if oseltamivir resistance) for 10d.

  • Annual vaccination in uk: all high risk (see ‘Treatment’), children>2yrs, healthcare workers. See p[link].

Pandemic influenza

Seasonal influenza is subject to antigenic drift: small genetic changes during replication which can be accounted for in the annual vaccine. Antigenic shift is a major change in influenza a resulting in new haemgglutinin (h) and neuraminidase proteins (n) for which there is no pre-existing immunity in the population. Any non-human influenza viruses which transfer to humans are novel. If they also have, or develop, capacity for rapid human-to-human transmission a pandemic results. Based on previous pandemics, up to 50% of the uk population may become infected leading to 20 000–750 000 excess deaths.

Human immunodeficiency virus (hiv): diagnosis

hiv is a retrovirus which infects and replicates in human lymphocytes (cd4 + t-cells) and macrophages. This leads to progressive immune system dysfunction, opportunistic infection, and malignancy = Acquired Immunodeficiency Syndrome (aids). The virus is transmitted via blood, sexual fluids, and breast milk. Virus subtypes include hiv1 (global epidemic) and hiv2 (↓ pathogenic, predominantly West Africa).


~37 million adults and children are estimated to be living with hiv worldwide (fig 9.11), with 1.2 million deaths/yr. Africa has most of the disease (~26 million), most of the mortality (790 000/yr), and ~1% of the world’s wealth.

Fig 9.11 Adult hiv prevalence (15–49 years).

Fig 9.11
Adult hiv prevalence (15–49 years).

Reproduced with permission from World Health Organization, ‘Adult HIV prevalence (15–49 years), 2015 by who region’. ©World Health Organization 2016.

uk: estimated ~100 000 living with hiv (=1.9/1000) including 5% of men who have sex with men (msm). ~17% of those with hiv in uk are unaware of their infection.


hiv binds, via its gp120 envelope glycoprotein, to cd4 receptors on helper t cells, monocytes, and macrophages. These ‘cd4 cells’ migrate to lymphoid tissue where the virus replicates, producing billions of new virions. These are released, and in turn infect new cd4 cells. As infection progresses, depletion or impaired function of cd4 cells leads to ↓immune function. hiv is a retrovirus: it encodes reverse transcriptase, allowing dna copies to be produced from viral rna. This is error prone, meaning a significant mutation rate, which contributes to treatment resistance.


Sexual transmission:

Consistent and correct use of (male and female) condoms ↓ transmission by ~90%. Serosorting is the restriction of (unprotected) sex depending on hiv status. It is unsafe due to inaccuracies in hiv status (which is only as reliable as a person’s last test) and failure to disclose. It does not consider transfer of treatment resistance, other stis, or hepatitis.

Post-exposure prophylaxis (pep):

The short-term use of antiretroviral therapy (art) after potential hiv exposure (sexual or occupational) should be considered an emergency method of hiv prevention. Can be given up to 72h (ideally <24h) after exposure. Not recommended if exposure is to a person on art with a confirmed and sustained (>6 months) undetectable (<200 copies/mL) viral load. 1st-line pep6 in uk is Truvada® (tenofovir/emtricitabine) and raltegravir for 28 days (2015) (refer to local guidelines). Test for hiv 8–12 weeks after exposure.

Pre-exposure prophylaxis (prep):

The use of art in those at high risk of acquiring hiv including serodifferent relationships without suppression of viral load, condomless anal sex in msm. Trials (proud, ipergay) show an 86% reduction in hiv incidence. A large scale trial of prep provision (2017–2020) will inform future nhs funding decisions.

Vertical transmission:

All pregnant women with hiv should have commenced art by 24 weeks gestation. Caesarean delivery indicated if viral load >50 copies/mL. Neonatal pep is given from birth to 4wks old with formula-feeding.


With symptoms of early HIV infection:

  • Primary HIV infection is symptomatic in ~80%, typically 2–4 weeks after infection (= seroconversion illness, acute retroviral syndrome). Maintain a high index of suspicion. Offer hiv testing to anyone (regardless of risk) presenting with flu-like symptoms and an eythematous/maculopapular rash. Consider primary hiv as a differential in any combination of fever, rash, myalgia, pharyngitis, mucosal ulceration, lymphadenopathy, and headache/aseptic meningitis. Diagnosis of primary hiv is a unique opportunity to prevent transmission (↑viral load and genital shedding). hiv antibody testing may be negative but hiv rna levels are high—seek expert help regarding viral load testing (see hiv testing later in topic).

  • Persistant generalized lymphadenopathy = swollen/enlarged lymph nodes >1cm in two or more non-contiguous sites (not inguinal) persisting for >3 months. Due to follicular hyperplasia caused by hiv infection. Exclude tb, infection, and malignancy.

In the asymptomatic, latent phase of chronic hiv infection:

In the uk there is universal testing in sexual health clinics, antenatal services, drug dependency programmes, and in patients with tb/hepatitis b/hepatitis c/lymphoma. Where hiv prevalence is >2/1000 universal testing by gps and medical admissions units should be considered. Any request for a hiv test should be met.

With complications of immune system dysfunction:

See pp[link][link].

HIV testing

The prognosis for patients with hiv in the uk is much better than for many other serious illness for which doctors routinely test. hiv testing6 should not be viewed differently. Any doctor can consent for a hiv test: explain the benefits of testing and detail how results will be given. Written consent is unnecessary. Arrange follow-up with a local hiv/gum service within 2 weeks (preferably <48h) for patients testing positive for the first time.

  • elisa for hiv antibody and antigen (p[link]): 4th-generation assays test for hiv antibody and p[link] antigen. This reduces the ‘window period’ (time of false-negative testing between infection and the production of measurable antigen/antibody) to average ~10 days. Diagnosis in uk is confirmed by a confirmatory assay.

  • Rapid point-of-care testing: Immunoassay kit which gives a rapid result from a finger-prick or mouth swab. Only ce-marked kits should be used. Needs serological confirmation.

  • Viral load: Quantification of hiv rna. Used to monitor response to art. Not diagnostic due to possibility of a false-positive result ∴ care if used to test for symptomatic primary hiv in the ‘window period’—confirmation of seroconversion is still required.

  • Nucleic acid testing/viral pcr: Qualitative test for the presence of viral rna. Used to test for vertical transmission in neonates as placental transfer of maternal antibodies can affect elisa antibody testing up to 18 months of age.

  • cd4 count: Cannot diagnose hiv. Used to monitor immune system function and disease progression in patients with hiv. <200 cells/microlitre is one of the defining criteria for aids.

Infectious diseasesSee for available hiv testing and country-specific resources.

Complications of hiv infection

Complications of hiv can be divided into:

  • complications of immune dysfunction (opportunistic infection/malignancy)

  • complicating comorbidity

  • complications of treatment, ie adverse drug effects (see pp[link][link]).

The differential diagnosis for symptoms presenting in a person with hiv is given in table 9.11. This is not exhaustive. Infectious diseasesDo not forget your usual differentials, the presentation may not relate to the patient’s hiv status.

Table 9.11 Differential diagnoses in hiv


Differential diagnosis


Intraoral abscess, sinusitis, pneumonia, tb, endocarditis, meningitis, encephalitis, pyomyositis, lymphoma, immune-reconstitution after commencement of art, any non-hiv cause.


Persistent generalized lymphadenopathy (p[link]), tb, syphilis, histoplasmosis, cryptococcus, lymphoma, Kaposi’s sarcoma, local infection.


Drug reaction, herpes zoster, scabies, cutaneous cryptococcus or histoplasmosis, Kaposi’s sarcoma, seborrhoeic dermatitis.


Community-acquired pneumonia, Pneumocystis jirovecii, tb, bronchial compression (tb, lymphoma, Kaposi’s sarcoma), pulmonary Kaposi’s sarcoma (uncommon), cardiac failure (hiv cardiomyopathy, infective pericardial effusion, hiv vasculopathy).


Salmonella, Shigella, Clostridium difficile, amoebiasis, Giardia, Cryptosporidia, cmv, hiv enteropathy is a diagnosis of exclusion.

Abdominal pain

tb, cmv colitis, pancreatitis (cmv, tb or secondary to art). Infectious diseasesDo not forget a pregnancy test.


Candidiasis, hsv.

↑Liver enzymes

Viral hepatitis (a, b, c, cmv, hsv, ebv), drug-induced liver injury (anti-tb or art), hiv cholangiopathy, lymphoma, congestion due to cardiac disease (pericardial effusion?).


Pre-renal due to sepsis/dehydration, interstitial nephritis secondary to medication, hiv-associated nephropathy (proteinuria, ckd).

Headache/seizures/focal neurology

Meningitis (bacterial, tb, cryptococcal, syphilis), empyema, space-occupying lesion (toxoplasmosis, lymphoma, tuberculoma), adverse drug reaction, hiv encephalopathy, progressive multifocal leukoencephalopathy (pml), stroke (hiv vasculopathy). See p[link].

Eye disease

Herpes zoster, cmv retinitis. See pp[link][link].

Peripheral neuropathy

art, cmv, hiv neuropathy, nutritional deficiency.

Opportunistic disease

Infectious diseasesart is part of the treatment regimen of all opportunistic infections (see pp[link][link]).

  • Pneumocystis jirovecii: (‘yee-row-vet-zee’) Presentation: progressive sob on exertion, malaise, dry cough. Haemoptysis and pleuritic pain rare. Examination: ↑respiratory rate, often normal breath sounds. Investigation: SpO2 (compare rest and exertion). cxr: classically perihilar infiltrates (fig 9.12), but may be normal. Induced sputum or bal with staining or nucleic acid amplification. Treatment: iv co-trimoxazole (convert to oral if favourable response). 21-day course. Steroids in moderate–severe disease (PaO2 <9.3KPa/SpO2 <92%). 2nd-line: clindamycin, pentamidine, atovaquone. Prophylaxis: co-trimoxazole if cd4 <200 cells/microlitre.

  • Candidiasis: Oral or oesophageal. Pain in the tongue, dysphagia, odynophagia. Diagnosed clinically or endoscopically. Treated with systemic ‘-azole’, eg fluconazole.

  • Cryptococcus neoformans: Commonest systemic fungal infection in hiv (5–10% pre-art). Presentation: meningitis: headache, fever, meningism variable. May be associated skin (molluscum-like papules) and lung disease. Investigation: lp with manometry. csf stain (India ink), csf/blood cryptococcal antigen. Treatment: induction with liposomal amphotericin b (se: renal tubular damage and aki). Addition of flucytosine has shown benefit in patients not on art (se: haematological toxicity). Maintenance treatment with fluconazole. Normalize icp with repeat lps/shunt.

  • Toxoplasma gondii: Toxoplasma abscesses are commonest cause of intracranial mass lesions when cd4 <200 cells/microlitre. Presentation: focal neurological signs ± seizures. Headache and vomiting if raised icp. Investigation: ring-enhancing lesions on mri (ΔΔ‎ lymphoma) with associated oedema. csf pcr for T. gondii is specific but only moderately sensitive. Blood serology is not diagnostic as most cases are a reactivation of previous infection. Treatment: consider in any brain mass lesion with cd4 <200 cell/microlitre. Pyrimethamine, sulfadiazine, folinic acid.

  • Cytomegalovirus (cmv): Severe primary or reactivated disease (see p[link]). Presentation: retinitis (blurred then loss of vision), encephalitis, gi disease (oesophagitis, colitis), hepatitis, bone marrow suppression, pneumonia. Diagnosis: serial cmv viral load, retinal lesions (p[link]), gi ulceration, ‘owl’s eye’ inclusions on biopsy. Treatment: ganciclovir/valganciclovir. Side-effects: rash, diarrhoea, bone myelosuppression.

  • Cryptosporidium: Common cause of chronic diarrhoea in hiv pre-art. Presentation: acute or sub-acute non-bloody, watery diarrhoea. Also cholangitis, pancreatitis. Investigation: stool microscopy (multiple samples as oocyst excretion intermittent), pcr, enzyme immunoassay, direct fluorescent antibody. Treatment: supportive, art.

  • Kaposi’s sarcoma: Most common tumour in hiv and aids defining. Caused by Kaposi sarcoma herpes virus (human herpesvirus 8, p[link]). Presentation: cutaneous or mucosal lesions: patch, plaque, or nodular. Visceral disease less common. Investigation: histological confirmation. Treatment: art. Intralesional retinoids or vinblastine. Radiotherapy for cosmesis/pain. Chemotherapy (+art) in advanced disease.

  • Lymphoma: Increased risk of non-Hodgkin’s lymphoma in hiv. Includes: diffuse large b-cell lymphoma, Burkitt’s lymphoma, primary cns lymphoma. Presentation: dependent upon area of involvement. Includes lymphadenopathy, cytopenia, cns symptoms. Treatment: combined art and chemotherapy. Rituximab for non-cns disease. Whole-brain radiotherapy for cns disease if excess toxicity with chemotherapy.

Fig 9.12 Bilateral interstitial infiltrates in P. jirovecii.

Fig 9.12
Bilateral interstitial infiltrates in P. jirovecii.

Reproduced from Lim, Acute Respiratory Infections, 2012, with permission from Oxford University Press.

hiv: antiretroviral therapy (art)

Infectious diseases Antiretroviral therapy (art)7 is recommended for everyone with hiv, regardless of cd4 count.

Aims of art

To reduce the hiv viral load to a level undetectable by standard laboratory techniques leading to immunological recovery, reduced clinical progression, and reduced mortality. These aims should be met with the least possible side-effects.

Mechanism of action

(See fig 9.13.)

  • ccr5 antagonists inhibit the entry of the virus into the cell by blocking the ccr5 co-receptor.

  • Nucleos(t)ide and non-nucleoside reverse transcriptase inhibitors (nrtis, nnrtis) inhibit reverse transcriptase and the conversion of viral rna into dna.

  • Integrase strand transfer inhibitors (instis) inhibit integrase and prevent hiv dna integrating into the nucleus.

  • Protease inhibitors (pis) inhibit protease, an enzyme involved in the maturation of virus particles.

  • Pharmacokinetic enhancers/boosters increase the effectiveness of antiretroviral drugs allowing lower doses eg cobicistat, ritonavir.

Fig 9.13 Mechanism of action of art.

Fig 9.13
Mechanism of action of art.

Starting treatment

Infectious diseasesSeek expert help.

  1. 1 Counselling: hiv transmission and sexual health, benefits of therapy (not cure), adherence (life long), resistance, side-effects of treatment, necessary monitoring, disclosure to partner/family/friends, partner testing.

  2. 2 Screen for infections and malignancy (pp[link][link]). Includes tb, hepatitis b&c. Treat or offer prophylaxis with co-trimoxazole if cd4 <200 cells/microlitre. For latent tb see p[link]. Aim to start art within 2 weeks of initiation of antimicrobial treatment for opportunistic or serious infection (seek expert advice if drug interactions or intracerebral disease).

  3. 3 Baseline tests: cd4, viral load, fbc, lft, electrolytes, creatinine, pregnancy test, viral genotype for drug resistance.

  4. 4 Review usual medications for possible drug interactions. Advise the patient to check for drug interactions with any new medication.

    Infectious diseasesSee

Herpes viruses

Herpes simplex virus (hsv) (human herpesvirus 1 and 2)

Includes hsv1 and hsv2. hsv1 infection in ⅔ of world’s population (~3.7 billion <50yrs), and hsv2 in ~11% (~400 million). Viruses multiply in epithelial cells of mucosal surface producing vesicles or ulcers. Lifelong latent infection when virus enters sensory neurons at infection site. Can then reactivate, replicate, and infect surrounding tissue. Disseminated infection if impaired t-cell immunity: pneumonitis, hepatitis, colitis.


Primary infection: subclinical or sensory nerve (tingling) prodrome, then vesicles, shallow ulcers. Systemic symptoms possible: fever, malaise, lymphadenopathy. Heals 8–12d. Reactivation: usually ↓severe unless immunosuppressed. Anatomy of infection:

  • Herpes labialis: cold sore lesion at lip border, predominantly hsv1.

  • Genital herpes: predominantly hsv2 (see p[link]).

  • Gingivostomatitis: fever, sore throat followed by tender oropharyngeal vesicles.

  • Keratoconjunctivitis: corneal dendritic ulcers. Infectious diseasesAvoid steroids. See ohcs p[link].

  • Herpetic whitlow: painful vesicles on distal phalanx due to inoculation through a break in the skin.

  • Herpes encephalitis: most common treatable viral encephalitis. Transfer of virus from peripheral site to brain via neuronal transmission. Prodrome: fever, malaise, headache, nausea. Then encephalopathy: general/focal signs of cerebral dysfunction including psychiatric symptoms, seizure, focal neurology (temporal involvement in ~60%), memory loss. Predominantly hsv1 in immunocompetent patients.

  • Secondary infection: eg hsv infection of eczematous skin—eczema herpeticum.


Clinical diagnosis. Confirmation required in encephalitis, keratoconjunctivits, or immunosuppression: viral pcr of csf, swab, or vesicle scraping. Also culture, immunofluorescence, serology.


Aciclovir: ↓symptoms and viral shedding, will not prevent latent infection. Infectious diseasesGive empirical iv aciclovir as soon as hsv encephalitis is suspected, mortality ~70% in untreated disease (see p[link]).

Varicella zoster virus (vzv) (human herpesvirus 3)

Primary infection transmitted by respiratory droplets. Incubation 14–21d. Invades respiratory mucosa, replicates in lymph nodes. Disseminates via mononuclear cells to infect skin epithelial cells. Leads to virus containing vesicles = chicken pox. Virus then remains dormant in sensory nerve roots. Reactivation is dermatomal = shingles.


  • Chicken pox: prodrome 1–2d: fever, malaise, headache, abdominal pain. Then rash (fig 9.14): pruritic, erythematous macules→vesicles, crust in ~48h. Infectious 1–2d pre-, to 5d post-rash development (lesions scabbed). Complications ↑ in immunosuppression: encephalitis (cerebellar ataxia), vzv pneumonia, transverse myelitis, pericarditis, purpura fulminans/dic.

  • Shingles: painful, hyperaesthetic area, then macular→vesicular rash in dermatomal distribution. Disseminated infection if immunosuppressed. Infectious until scabs appear. Chicken pox risk in non-immune contacts. Complications: post-herpetic neuralgia, Ramsay Hunt syndrome (p[link]).

Fig 9.14 Chicken pox (vzv).

Fig 9.14
Chicken pox (vzv).

© D A Warrell.


Clinical diagnosis unless immunosuppressed: viral pcr, culture, immunofluorescence.


Oral aciclovir/valaciclovir for uncomplicated chicken pox/shingles in adults, aim to give within 48h of rash. iv aciclovir if pregnant, immunosuppressed, severe/disseminated disease (including ocular).


Vaccination: not routine in children in uk, given at aged 70 to prevent shingles reactivation. vzv immunoglobulin if non-immune exposure in immunosuppression, pregnancy, neonates.

Epstein-Barr virus (ebv) (human herpesvirus 4)

Virus targets circulating b lymphocytes (lifelong latent infection) and squamous epithelial cells of oropharynx.


Usually asymptomatic infection in childhood. Infectious mononucleosis in ~50% of primary infection in adults: sore throat, fever, anorexia, lymphadenopathy (esp. posterior triangle of neck), palatal petechiae, splenomegaly, hepatomegaly, jaundice. Malaise is prominent. Resolution of symptoms usually within 2 weeks. Chronic active infection and recurrence are rare. Oncogenicity: see box ‘Oncogenic viruses’.


  • Blood film: lymphocytosis. Atypical lymphocytes (large, irregular nuclei) also occur in other viral infection (cmv, hiv, parvovirus, dengue), toxoplasmosis, typhus, leukaemia, lymphoma, drug reactions, lead poisoning.

  • Heterophile antibody tests (eg Monospot®, Paul-Bunnell) detect non-ebv heterophile antibodies which are present in ~85% of infectious mononucleosis sera. False positive: pregnancy, autoimmune disease, lymphoma/leukaemia.

  • Serology: igm to ebv viral capsid antigen in acute infection. igg if past infection.

  • Reverse transcriptase viral pcr.


Supportive. Infectious diseasesSeek expert help if severe disease/immunosuppression: observational data on the use of antivirals and steroids.

Cytomegalovirus (cmv) (human herpesvirus 5)

50–100% of adults are seropositive depending on socioeconomic and sexual risk. Latent infection: periodic, asymptomatic (but infectious) viral shedding in bodily fluids including blood transfusion, transplantation (cmv+ve donor to cmv−ve recipient).


Asymptomatic in most. Symptoms mimic infectious mononucleosis (see earlier in topic) or hepatitis. Severe disease in immunosuppressed (post-transplantation, hiv): oesophagitis, gastritis, colitis, retinitis (p[link]), pneumonitis, hepatitis. Infection in pregnancy is associated with congenital abnormality.


Primary infection in immunocompetent: igm. Immunosuppressed: quantitative nucleic acid amplification testing (qnat) in blood greater than a defined threshold, or rising titre. Invasive disease: tissue qnat, histopathology.


Given in severe infection/immunosuppression. Ganciclovir, valganciclovir (↑oral bioavailability). Foscarnet and cidofovir: nephrotoxicity limit use. Pre-emptive treatment in transplant patients based on qnat results. Risk/benefit for antivirals/immunoglobulin in pregnancy remains unclear. Use cmv−ve, irradiated blood for transfusion if immunosuppressed and at risk: transplant, hiv, leukaemia.

Other herpes viruses

Human herpesvirus 6 (hhv6):

Roseola infantum, febrile illness without rash.

Human herpesvirus 8 (hhv8):

Oncogenic (see box ‘Oncogenic viruses’), Castleman’s disease.

Other viruses

Respiratory tract viruses

Include rhinovirus, coronovirus, adenovirus, respiratory syncytial virus (rsv). Transmission by direct contact, infected fomites, airborne droplets.


Coryza, pharyngitis, croup, bronchiolitis, pneumonia.


Clinical. Viral culture, antigen detection, pcr.


None in uncomplicated disease/immunocompetent. Limited evidence for specific treatments in high-risk complicated disease, immunosuppression: cidofovir for adenovirus; aerosolized ribavarin, immunoglobulin, monoclonal antibody in rsv. For influenza see pp[link][link].

Human papilloma virus (hpv)

>120 hpvs. Pathology:

  • Skin warts, verrucas (hpv 1, 2). Treatment: none, topical salicylic acid, freezing.

  • Anogenital warts (hpv 6, 11). Treatment: topical podophyllin, imiquimod; ablation.

  • Cervical cancer (hpv 16, 18), other cancers (see p[link]).

Vaccination in uk: ♀ only, age 12–13, hpv 6, 11, 16, and 18 since 2012.


~100% exposure. Disease only with immunosuppression: bk virus causes renal transplant nephropathy; jc virus causes progressive multifocal leucoencephalopathy.


Transmitted by respiratory droplets. Incubation 10–18d. Highly contagious: >95% population coverage needed for ‘herd’ immunity.


Prodrome (2–4d): fever, conjunctivitis, coryza, diarrhoea, Koplik spots (white spots on red buccal mucosa, fig 9.15). Then generalized, maculopapular rash, classically face/neck→trunk→limbs (fig 9.16). Complications:

  • Secondary infection: bacterial pneumonia, otitis media, ocular herpes simplex, oral/gi candidiasis.

  • Acute demyelinating encephalitis: 1 in 1000, usually within 2wk of rash. Seizures, fever, irritability, headache, ↓conscious level.

  • Subacute sclerosing panencephalitis: 5–10yr after infection, disturbances in intellect, personality, seizures, motor dysfunction, decerebration. No treatment available.

Fig 9.15 Koplik spots.

Fig 9.15
Koplik spots.

Courtesy of CDC.

Fig 9.16 Measles rash.

Fig 9.16
Measles rash.

Reproduced from Gardiner et al., Training in Paediatrics, 2008, with permission from Oxford University Press.


Clinical. igm. Antigen in saliva/urine.


Prevent with vaccination. Human immunoglobulin within 3d of exposure in non-immune. Supportive. No benefit shown for dexamethasone in encephalitis.


Respiratory droplet spread. Incubation 14–21d. Common cause of encephalitis pre-vaccination.


Can be subclinical. Prodrome: fever, myalgia, headache. Infection and tender swelling of salivary glands: parotid > submandibular. Complications: meningoencephalitis, epididymo-orchitis if pubertal/post-pubertal infection (warm, swollen, tender testes 4d-6wk after parotitis→subfertility in ~10%, infertility rare), oophoritis, pancreatitis, deafness.


Clinical. If confirmation needed eg meningitis/encephalitis: mumps specific igm/iga, pcr.



Rubella (German measles)

Respiratory droplet spread.


Usually mild/subclinical. Prodrome: fever, conjunctivitis, rhinorrhoea. Rash: generalized, pink, maculopapular. Lymphadenopathy: occipital, cervical, post-auricular.

Congenital infection:

Up to 90% risk of fetal malformation in 1st trimester, sensorineural hearing loss/retinopathy in 2nd trimester. Offer igm/igg testing. Immunoglobulin may ↓viraemia but will not prevent infection. Infectious diseasesVaccinate pre-pregnancy, live vaccines are contraindicated in pregnancy.


Passive immunity

uses pre-formed antibody to protect against infection. It offers immediate but short-lived protection. Natural passive immunity occurs in the placental transfer of maternal antibodies to the fetus; acquired passive immunity includes treatment with immunoglobulin eg hepatitis b, rabies, tetanus, varicella-zoster.

Active immunity

follows exposure to an antigen, which generates an adaptive immune response. Natural active immunity occurs following infection. Acquired active immunity is provided by vaccination. Routine vaccinations in the uk are shown in table 9.13. Additional vaccines are offered to specific vulnerable groups (table 9.14). Immunosuppression is a contraindication to live vaccines due to the risk of disseminated disease. Includes immunodeficiency, immunosuppressive treatment, hiv. Inactivated vaccines can be given but the antibody response may be less: aim to give >2wks prior to immunosuppressive therapy when possible (or vaccinate whilst on treatment and considered repeat re-immunization when/if treatment complete).

Table 9.13 uk vaccination summary (*=live vaccine)


Age (m=months, y=years)







12y ♀



























Haemophilus influenzae b (hib)












Meningitis b




Meningitis c


Measles, mumps, rubella*






hpv 6, 11, 16, 18


Meningitis acwy


Varicella zoster*


Table 9.14 Additional vaccination of specific groups in uk (*=live vaccine)


Offered to


Infants/children where tb incidence >40/100 000 or parent/grandparent born in country where incidence >40/100 000, tb contacts.


Hyposplenism, complement disorders.

Meningitis b, acwy

Hyposplenism, complement disorders.


Hyposplenism, dm, chronic heart disease, chronic respiratory disease, ckd, chronic liver disease, chronic neurological disease, immunosuppression, pregnancy.


Hyposplenism, cochlear implants, complement disorders, dm, chronic heart disease, chronic respiratory disease, ckd, chronic liver disease, chronic neurological disease, immunosuppression.

Hepatitis a, b

Chronic liver disease, haemophilia, ckd (hepatitis b only).


Pregnancy 16–32 weeks (neonatal protection).


Travel advice (food/drink, insect repellent, malaria prophylaxis, condoms) is more important than vaccination. Check routine vaccinations are up to date. Vaccination depends upon area of travel and planned activities: bcg (live), rabies, yellow fever (live), hepatitis a/b, cholera, Japanese encephalitis, tick-borne encephalitis, typhoid. For up-to-date recommendations see


Worldwide ↑ in fungal infection with new pathogenicity, ↑virulence, and new infective mechanisms. Incidence data limited by failures in recognition and diagnosis. Divided into superficial/cutaneous and systemic/invasive.

Superficial/cutaneous mycoses

  • Dermatophytosis: Dermatophyte fungi digest keratin. Cause infection of skin and keratinized structures, eg hair, nails. Presentation: Scale and pruritus. Skin lesion may be annular with central healing, eg ring worm, tinea corporis. Tinea pedis affects up to 15% of healthy population: skin erosions and blisters in toe web spaces, dry scale on soles. Fungal nail disease = onychomycosis/tinea unguium: discolouration, nail thickening. Tinea capitis: scalp scaling, alopecia.

  • Superficial candidiasis: Usually Candida albicans (fig 9.17), a commensal in mouth, vagina, and gi tract. Risk factors: immunosuppression, antibiotic treatment. Presentation: Oropharyngeal: white patches on erythematous background (plaque type); sore, inflamed areas (erythematous type). gu: soreness, white patches/discharge (fig 9.18). Skin: usually in folds/interdigital (fig 9.19).

  • Malassezia: Commensals of greasy skin. Presentation: Pityriasis versicolor: scaly hypo/hyperpigmented rash with scaling (fig 9.20). Seborrhoeic dermatitis: scaling of face, scalp (dandruff), anterior chest. Malassezia folliculitis: itchy, follicular rash on back and shoulders (ΔΔ‎ acne).

Fig 9.17 Candida albicans.

Fig 9.17
Candida albicans.

Courtesy of P-Y Guillaume.

Diagnosis: Clinical, microscopy of skin scrapings. Treatment: All superficial mycoses: topical ‘-azole’ antifungal or terbinafine 1–4wk. Also topical nystatin and amphotericin in superficial candidiasis. Tinea capitis: griseofulvin, terbinafine, itraconazole. Nail infection requires systemic treatment (terbinafine, itraconazole)∴ confirm diagnosis, and caution re side-effects including hepatotoxicity.

Systemic/invasive mycoses

  • Invasive candidiasis: Typically occurs in immunocompromised, comorbidity, or itu settings. Genetic susceptibility likely contributes. Estimated 250 000/yr with 50 000 deaths. Candidaemia in ~7/1000 icu patients. Presentation: Risk factors for invasive fungal disease (see p[link]), febrile with no microbiological evidence of infection, new murmur, muscle tenderness, skin nodules. Diagnosis: (Repeated) blood/tissue culture. pcr. Candida in respiratory secretions alone is insufficient. Treatment: Remove all possible catheters. Echinocandins (caspofungin, anidulafungin, micafungin), fluconazole, amphotericin (liposomal for ↓renal toxicity). Consider fluconazole prophylaxis if risk factors for invasive disease (p[link]). Consider empirical treatment if persistent fever, unresponsive to other therapy (discuss with microbiologist, choice depends on local epidemiology, comorbidity).

  • Cryptococcus: See hiv p[link]. Causes meningitis, pneumonia. Presentation: Usually immunosuppression, eg hiv, sarcoid, Hodgkin’s, haematological malignancy, post-transplant. History may be long, non-specific. Headache, confusion, ataxia, focal neurological signs, fever, cough, pleuritic pain, sob. Diagnosis: Indian ink csf stain, culture blood/csf/bal, antigen testing in blood/csf. Treatment: Amphotericin + flucytosine, fluconazole.

  • Histoplasmosis: Worldwide distribution of Histoplasma, ↑ in soil contaminated with bird/bat faeces. Illness depends on host immunity, estimated ~1%. Presentation: Flu-like symptoms, fever, malaise, cough, headache, myalgia, pneumonia, lung nodules/cavitation, pericarditis, mediastinal fibrosis/granuloma (ΔΔ‎ sarcoid, tb). Diagnosis: Serology, antigen testing. Treatment: Moderate-severe lung disease or any cns involvement: amphotericin, itraconazole.

  • Blastomycosis: Blastomyces in decomposing matter, mainly usa/Canada. Presentation: Fever, cough, night sweats, ards. ↑risk of extra-pulmonary disease with immunosuppression: skin, bone, gu, cns. Diagnosis: Culture, antigen detection (cross-reacts with histoplasmosis). Treatment: Amphotericin, itraconazole.

Infectious diseasesSee also: Fungi and the lung p[link], Pneumocystis jirovecii p[link].

Healthcare-associated (nosocomial) infection

Healthcare-associated, or nosocomial, infections include diseases which occur:

  • As a direct result of treatment or contact in a hospital or healthcare setting.

  • As a result of healthcare delivered in the community.

  • Outside a healthcare setting but are brought in by patients, staff, or visitors and transmitted to others.

7–25% of hospital admissions are complicated by a nosocomial infection resulting in morbidity, mortality, and cost. The causal microbe may be benign in normal circumstances, but is able to cause disease when the patient:

  1. 1 has been given broad-spectrum antibiotics (eg antibiotic-resistant organisms, Clostridium difficile colitis)

  2. 2 is unwell/immunosuppressed (opportunistic infection)

  3. 3 has compromised barriers (indwelling catheter/line, ventilation, surgery).

Management of healthcare-associated infection


Screening (eg hospital admissions for mrsa) allows isolation and decolonization before harm. Be alert to new infections.


Isolate multi-antibiotic-resistant microbes (eg mrsa), highly transmissible infections (eg norovirus), and high-risk groups including reverse barrier nursing (avoids transmission to, rather than from, patients, eg neutropenia). Patients with high-risk infections may need negative-pressure rooms (to prevent potentially infected air leaving the room), or in severe immunosuppression, positive-pressure rooms (to prevent potentially infected air entering the room). When many patients have the same nosocomial infection (eg norovirus) they may be barrier nursed together in dedicated bays.


Refer to local guidelines, seek expert help. Initial antibiotic choice may differ for healthcare-associated infection.


Modify risk factors, eg nutrition, post-operative incentive spirometry to reduce pneumonia risk. Use/convert to narrow-spectrum antibiotics whenever possible. Remove catheters, intravascular access devices, and wean off ventilators as soon as clinically appropriate. Take measures to ↓ person-to-person transmission:

  1. 1 Hand hygiene. Wash hands before and after each patient contact (fig 9.22). Alcohol-based gels are helpful but soap is needed to kill C. difficile spores.

  2. 2 Personal attire. In the uk there is a bare-below-the-elbows policy. Long hair should be tied back. In areas where infection risk is particularly high (theatre, icu), staff change into scrubs on arrival.

  3. 3 Personal protective equipment (PPE).Used for isolated patients and during procedures. Includes gloves, aprons, caps, respiratory protection/mask according to risk, eg fffp[link] respirators in aerosolized infection.

  4. 4 Procedures. Strict aseptic techniques for any procedure which breaches the body’s defences including insertion/maintenance of invasive devices, iv infusions, wound care.

  5. 5 Environment. Should be clean and safe, with effective decontamination.

Fig 9.22 Areas commonly missed when washing hands.

Fig 9.22
Areas commonly missed when washing hands.

Contains public sector information licensed under Open Government Licence v3.0,

System interventions:

Up-to-date infection guidelines, audit, education, training.8

Sexually transmitted infection (sti)

stis6 are common with increasing rates of diagnosis: ~×2 for Chlamydia trachomatis, N. gonorrhoeae, genital herpes, and syphilis since 2006. Prevalence highest in young adults (<25yr) and msm. For hiv see pp[link][link]. For hepatitis b and c see p[link].

Taking a sexual history

  • Symptoms: ♂: urethral discharge, dysuria, genital skin problems, testicular pain/swelling, peri-anal or anal symptoms in msm. ♀: unusual vaginal discharge, vulval skin problems, abdominal pain, dyspareunia, unusual vaginal bleeding (post-coital, intermenstrual, consider referral for urgent colposcopy).

  • Exposure: Sexual contacts within last 3 months including sex of partner(s), type of contact (oral, vaginal, anal), contraceptive method (properly used?), type and duration of relationship, symptoms in partner(s), risk factors for hiv/hepatitis in partner(s), whether partner(s) can be contacted. sti history in all. Ask men whether they have ever had sex with another man.

  • Other: Last menstrual period, menstrual pattern, date of last cervical cytology (smear). Current contraceptive, difficulties with use/supply. Current/recent antimicrobial therapy. hpv vaccine history. There may be disclosure of non-consensual sex, or intimate partner violence. Do not be afraid to ask for help: ‘Everything you tell me today is confidential unless you tell me something that worries me about your safety, at which point I may need to discuss this with another professional in order to keep you safe.’


♂: retract foreskin, inspect urethral meatus for discharge, scrotal contents/tenderness/swelling (stand patient up). ♀: vulval examination (lithotomy), speculum of vagina/cervix, bimanual examination for adnexal tenderness, abdomen/pelvis for masses. In all: genitoanal area, protoscopy if anal symptoms, inguinal lymph nodes, oral mucosa if orogenital sex. Use a chaperone and document their name.

Urethritis/vaginal discharge

See table 9.16.

Table 9.16 Overview of urethritis and vaginal discharge






Chlamydia trachomatis

  • Often asymptomatic: detected on screening.

  • ♀: dyspareunia, dysuria, post-coital/inter-menstrual bleeding, ↑vaginal discharge.

  • ♂: dysuria, urethral discharge.

  • Nucleic acid amplification test (naat) on:

  • ♀: vulvovaginal swab—can be done by patient. Endocervical swabs and urine samples less sensitive.

  • ♂: first-pass urine.

  • Oral/anal swabs if oral/anal sex.

  • Azithromycin 1g po (single dose) or

  • 100mg doxycycline bd for 7d.

  • Partner tracing, screening, treatment.

  • Avoid sexual intercourse until treatment complete.

  • Pharyngeal and rectal infection may be asymptomatic. Complications:

  • ♀: pelvic inflammatory disease, salpingitis, infertility, ectopic pregnancy, reactive arthritis, perihepatitis (Fitz-Hugh–Curtis syndrome).

  • ♂: epididymo-orchitis, reactive arthritis.

  • Eye disease see p[link].

Neisseria gonorrhoeae

  • Urethral/vaginal discharge, dysuria.

  • Asymptomatic: 50% ♀, 10% ♂, most pharyngeal/rectal infection.

  • Nucleic acid amplification test (naat) on:

  • ♀: vaginal swab or endocervical swab. Urine samples less sensitive.

  • ♂: first-pass urine.

  • Culture (endocervical/urethral swab prior to antibiotics) for sensitivity.

  • Ceftriaxone 500mg im + azithromycin 1g po. Complicated disease: add doxycycline ± metronidazole.

  • Partner tracing, screening, treatment.

  • Avoid sexual intercourse until treatment complete.

  • ↑Antibiotic resistance. Complications:

  • ♀: pelvic inflammatory disease: salpingitis, infertility, ectopic pregnancy.

  • ♂: epididymitis, prostatitis, increased hiv transmission, reactive arthritis; infective endocarditis, disseminated gonococcal infection.

Non-gonococcal urethritis (ngu)

Urethral discharge, dysuria, urethral discomfort. Only assess symptomatic patients/visible discharge for urethritis.

↑Polymorphonuclear leucocytes on microscopy of urethral swab. Needs testing for chlamydia and gonorrhoea. Exclude uti.

  • As for Chlamydia trachomatis.

  • 5d course of azithromycin if patient/partner known to be positive for Mycoplasma genitalium.

ngu refers to a pattern of infection rather than a cause. The main causes are Chlamydia trachomatis (11–50%) and Mycoplasma genitalium (6–50%).

Trichomonas vaginalis

  • ♀: vaginal discharge (~70%), itch.

  • ♂: asymptomatic (~70%), discharge.

naat, culture, microscopy (mobile trichomonads).

Metronidazole (2g single dose or 5–7d course). Partner tracing, screening, treatment. Avoid sexual intercourse until treatment complete.

  • Pregnancy: ↑risk of preterm delivery, low birth weight.

  • May enhance hiv transmission.

Bacterial vaginosis

  • Thin, white, fishy-smelling vaginal discharge. No itch or soreness.

  • Asymptomatic in ~50%.

Gram stain to examine vaginal flora (predominance/absence of lactobacilli), clue cells, vaginal pH >4.5.

  • Oral or pv metronidazole

  • or

  • pv clindamycin.

Elevated vaginal pH alters vaginal flora: ↑anaerobic bacteria. Not sexually transmitted but associated with sti.

Genital candidiasis

Genital itch, burning, cottage cheese-like discharge, dyspareunia.

Microscopy and culture for Candida (see p[link]).

-azoles: pessary, eg clotrimazole, cream if vulval symptoms, oral fluconazole if severe.

Very common. No evidence for treatment of sexual partners. ↑Risk: pregnant, antibiotic therapy, dm, immunosuppressed.

Genital warts

Caused by human papilloma virus (hpv). See p[link].

Genital ulcer(s)

  • Genital herpes: hsv. Presentation: flu-like prodrome, then vesicles/papules around genitals, anus, throat. These burst, forming painful shallow ulcers. Also urethral discharge, dysuria, urinary retention, proctitis. Diagnosis: pcr. Treatment: analgesia, topical lidocaine. Antivirals within 5d: aciclovir, valaciclovir, famciclovir.

  • Syphilis: Treponema pallidum. Presentation:

    1. 1 Primary: <90d after innoculation (median 3wk). Macule→papule→typically painless ulcer (chancre). Central slough, defined rolled edge. Highly infectious.

    2. 2 Secondary: dissemination ~4–10wks after chancre. Rash (maculopapular in 50–75%, on palms/soles in 11–70%), mucous patches, condyloma lata (raised, pale plaques, often flexural), fever, headache, myalgia, lymphadenopathy, hepatitis.

    3. 3 Tertiary: 20–40yr after infection. Neurosyphilis: aseptic meningitis, focal neurological deficits, seizures, psychiatric symptoms, Argyll Robertson pupil (p[link]), tabes dorsalis (areflexia, extensor plantar reflex, dorsal column deficits, Charcot joints). Gummatous syphilis: destructive granulomata in skin, mucus membranes, bones, viscera. Cardiovascular: aortitis, aortic regurgitation/aneurysm.

    Diagnosis: pcr. Serology: non-specific (rpr, vdrl) sensitive in early infection then decline; specific (T. pallidum as antigen, eg tpha, tppa) reacts in early infection and persists. Treatment: parenteral benzylpenicillin (eg benzathine penicillin im), duration depends on stage. Procaine benzylpenicillin boosted with probenicid in csf disease.

  • Lymphogranuloma venerum: Chlamydia trachomatis. Presentation: mostly msm in uk. Painless papule/ulcer→lymphadenopathy, fever, arthritis, pneumonitis. Direct transmission to rectal mucosa causes haemorrhagic proctitis: pain, rectal bleeding/discharge, tenesmus. Diagnosis: pcr. Treatment: doxycycline.

  • Tropical infections: Chancroid (Haemophilus ducreyi), Donovanosis (Klebsiella granulomatis). Presentation: both cause genital ulceration, and lymphadenitis with spread of infection into overlying tissue (pseudobubo). Diagnosis: H. ducreyi pcr, Donovan bodies in tissue. Treatment: azithromycin, ceftriaxone.

Fever in the returning traveller

Infectious diseasesExclude malaria in all travellers from the tropics (p[link][link]).

Infectious diseasesExclude hiv in all (p[link]).

Infectious diseasesMost travellers have self-limiting illnesses that could have been acquired in uk. Look for tropical infection9 but don’t forget your usual differentials.


Detailed geography of travel (table 9.17)9 including setting (rural/urban), time of onset of symptoms, duration of symptoms (table 9.18).9 Ask about activities and events: bites, diet, fresh-water exposure (schistosomiasis, leptospirosis), dust exposure, sexual activity, game parks (tick typhus, anthrax, trypanosomiasis), farms, caves (histoplasmosis, rabies, Ebola), unwell contacts.

Table 9.17 Differential diagnosis by geography

Area of travel



Rare but do not miss

Sub-Saharan Africa

South-East Asia

  • Leptospirosis (p[link])

  • Melioidosis2

South and Central Asia

Middle East Mediterranean North Africa

Visceral leishmaniasis (p[link])

South America Caribbean

Eastern Europe Scandinavia

Lyme disease (p[link])

  • Hanta virus (p[link])

  • Tick-borne encephalitis



North America


Table 9.18 Differential diagnosis according to incubation time

Incubation period


Short <10d

Dengue, chikungunya, gastroenteritis, relapsing fever, rickettsiae

Medium 10–21d

Malaria, hiv, brucellosis, enteric fever, leptospirosis, melioidosis, q-fever, coccidioidomycosis, vhf, Chagas’ disease, trypanosomiasis

Long >21d

Malaria, hiv, tb, viral hepatitis, brucellosis, schistosomiasis, amoebic liver abscess, trypanosomiasis, visceral leishmaniasis

Chronic fever <14d

tb, hiv plus opportunistic infection, pyogenic deep seated abscess, infective endocarditis, brucellosis, enteric fever, fungal infection, schistosomiasis, visceral leishmaniasis, pe

Associated symptoms:

  • Respiratory: S. pneumoniae, H. influenzae, legionella, influenza, viral respiratory disease (sars, mers), tb, hiv-associated disease, melioidosis.2

  • Neurological: malaria, meningococcal meningitis, hiv, syphilis, Lyme disease, leptospirosis, brucellosis, tick-borne encephalitis, relapsing fever, trypanosomiasis.



  • Maculopapular: dengue, chikungunya, ebv, hiv seroconversion, vhf.

  • Purpuric: dengue, meningococcal infection, plague, dic, vhf.

  • Ulcer: trypanosomiasis, Yesinia pestis, tick typhus, anthrax, tropical ulcer.


Viral hepatitis, severe falciparum malaria, enteric fever, leptospirosis, relapsing fever, typhus, vhf, bartonellosis


Viral hepatitis, hiv, enteric fever, brucellosis, leptospirosis, rickettsial infection, relapsing fever, schistosomiasis, amoebic liver abscess, trypanosomiasis, visceral leishmaniasis.


Directed by travel history and examination. In undifferentiated fever:

  • Malaria film/rapid diagnostic testing (p[link]).

  • hiv test (p[link]).

  • fbc: lymphopenia in viral infection including hiv; eosinophilia in parasitic/fungal eg soil-transmitted helminths, filiariasis, schistosomiasis, hydatid disease; ↓platelets in malaria, dengue, hiv, typhoid, severe sepsis.

  • Blood culture ×2: prior to antibiotics.

  • lft.

  • Consider: save serum, specific serology, or edta sample for pcr.


  • Local infectious diseases team (including on-call).

  • Disease notification:

  • Public Health England imported fever service 0844 778 8990.

  • National Travel Health Network and Centre (nathnac)/TravelHealthPro (0845 602 6712).

  • Hospital for Tropical Diseases 0203 456 7890.

  • Travel fever diagnostic website:

Malaria: diagnosis


  • 3.2 billion people at risk in 95 countries = half the world’s population (fig 9.23).

  • 214 million/cases per year with 438 000 deaths.

  • Sub-Saharan Africa: 88% of malaria cases, 90% of deaths (most age <5yr).

  • Most common tropical disease imported into uk, ~2000 cases/yr.

  • ~20% fever in travellers from Africa presenting to uk hospitals is due to malaria.

  • Plasmodium falciparum is the most prevalent parasite in Africa and responsible for most malaria deaths worldwide (=~75% of malaria presenting in uk).

  • Plasmodium vivax is the dominant parasite outside of sub-Saharan Africa.

  • Preventable and treatable: incidence ↓ by 37% and deaths ↓ by 60% since 2000.

Fig 9.23 Countries with malaria transmission.

Fig 9.23
Countries with malaria transmission.

Reproduced with permission from World Health Organization, World malaria report 2015. © World Health Organization 2015.

Malaria parasites

Malaria parasites belong to the genus Plasmodium. >100 species exist of which 5 cause human disease (see table 9.19). Transmission occurs through the bite of an infected Anopheles mosquito. Only female mosquitoes transmit Plasmodium as only females require a blood meal for egg development. Transmission in the absence of a mosquito is rare: vertical (congenital transfer from mother to child), transfusion, organ transplantation, needle-sharing.

Table 9.19 Malaria species in humans


Average incubation (range)

Persistent liver stage


P. falciparum (fig 9.24)

12 days (6 days–6 months)


Africa, India, South East Asia, Indonesia, Oceania, Central America, Middle East

P. vivax (fig 9.25)

14 days (days–years)


South Asia, South and Central America, Africa, Middle East

P. malariae (fig 9.26)

30 days (28 days–years)


Africa, South and Central America, South East Asia

P. ovale

11–16 days (years)



P. knowlesi

9–12 days


South East Asia

Reproduced from Detels et al., Oxford Textbook of Global Public Health, 2015, with permission from Oxford University Press.

Fig 9.24 P. falciparum sausage-like gametocytes in rbc.©-S Upton, Kansas Univ.

Fig 9.24
P. falciparum sausage-like gametocytes in rbc-S Upton, Kansas Univ.

Fig 9.25 P. vivax ring partly hidden by Schuffner’s dots.

Fig 9.25
P. vivax ring partly hidden by Schuffner’s dots.

Stained and examined in the field by jml.

Fig 9.26 P. malariae ring and band forms from 2 specimens.

Fig 9.26
P. malariae ring and band forms from 2 specimens.

©S Upton, Kansas Univ.

The life cycle of malaria is dependent on both humans and mosquitoes (fig 9.27). Sporozoites are transferred to a human host when an infected mosquito bites. These travel via the blood-stream to the liver where maturation occurs to form schizonts containing ~30 000 merozoite offspring. If a dormant stage exists (vivax, ovale, see table 9.19), and is inadequately treated, merozoites can be released from the liver weeks, months, or years later causing recurrent disease. The rupture of schizonts releases merozoites which enter rbcs (‘what a fantastic niche!’). In the rbc, merozoites form larger trophozoites and erthrocytic schizonts (poor prognostic indicator if seen on blood film). The rupture of erthrocytic schizonts produces the clinical manifestations of malaria.

Fig 9.27 Malaria lifecycle.

Fig 9.27
Malaria lifecycle.

Clinical features

Infectious diseasesConsider in anyone with a fever who has previously visited a malarial area (fig 9.23), regardless of prophylaxis.


P. falciparum has a minimum incubation of 6 days and most commonly occurs within 3 months of return from an endemic area. Take a careful travel history: country, area of travel, date of return. Do not forget to ask about stopovers. Symptoms are non-specific: fever, headache, malaise, myalgia, diarrhoea, cough. Fever patterns are described but only occur if rupture of infected rbcs is synchronized: alternate day for P. falciparum, P. vivax, P. ovale (‘tertian’); every 3rd day for P. malariae (‘quartan’). Infectious diseasesMost patients have no specific fever pattern.


Fever, otherwise unremarkable. If diagnosis is delayed or severe disease then may present with jaundice, confusion, seizures.


Immediate blood testing is mandatory in uk:

  • Microscopy of thick and thin blood smear. Sensitive and specific in experienced hands.

  • Rapid diagnostic test (rdt) detection of parasite antigen. Used for initial screen if expert microscopy is unavailable, eg out-of-hours. Used in addition to (not instead of) blood film.

Results should be available within 4h. Infectious diseasesIf malaria is suspected but blood film is negative: repeat at 12–24h and after further 24h. Malaria is unlikely if three expert serial blood films are negative. ΔΔ‎ dengue, typhoid, hepatitis, meningitis/encephalitis, hiv, viral haemorrhagic fever. Care in pregnancy: thick films can be negative despite parasites in the placenta. Seek expert help.

If P. falciparum (or P. knowlesi) estimated % parasitized red cells should be given:

  • >2% = ↑ chance of severe disease (indication for parenteral treatment see pp[link][link]).

  • >10% = severe disease.

Other: fbc (anaemia, thrombocytopenia), creatinine and urine output (aki), clotting (dic), glucose (hypoglycaemia), abg/lactate (acidosis), urinalysis (haemoglobinuria).

Malaria is notifiable to public health:

Reproduced from Beeching et al., Returned travellers. In: Principles and Practice of Travel Medicine, 2013, John Wiley and Sons. Copyright © 2013 by Blackwell Publishing Ltd.

Malaria: treatment

Falciparum malaria

Risk of deterioration ∴ admit to hospital. Treatment10 depends upon whether the disease is uncomplicated, or severe. Features of severe disease are:

  • Impaired consciousness/seizures (consider lp)

  • aki (oliguria <0.4mL/kg/h, creatinine>265μ‎mol/L)

  • Shock (bp <90/60) = ‘Algid malaria’

  • Hypoglycaemia (<2.2mmol/L)

  • Pulmonary oedema/ards

  • Hb <80g/L

  • Spontaneous bleeding/dic

  • Acidosis (pH <7.3)

  • Haemoglobinuria

  • Parasitaemia >10%.

Remember other poor prognostic indicators: peripheral blood schizonts (see p[link]), elevated serum lactate, ↑age.

Uncomplicated falciparum malaria:

Artemisinin combination therapies (act) achieve rapid clearance of parasites by combined action at different stages of the parasite cycle (p[link]):

  1. 1 Artemether-lumefantrine: 4 tablets at 0, 4, 8, 24, 36, 48, and 60h.

    1st line in uk (including pregnant >13wks), take with high-fat food to ↑ absorption.

  2. 2 Dihydroartemisinin (dha)-piperaquine: 4 tablets od for 3d (if weight >60kg).

    Take >3h before and after food to prevent excessive peak levels. Possible ↑qtC ∴ avoid in arrhythmia.

Options if act not available:

  • Atovaquone-proguanil: 4 tablets od for 3 days. Parasite clearance ~66% after 3d, gi side-effects in ~25%.

  • Oral quinine sulphate 600mg tds for 5–7d plus doxycycline 200mg od (or clindamycin 450mg tds if pregnant) for 7d. Parasite monitoring required. Can cause ‘cinchonism’: nausea, deafness, ringing in ears.

Infectious diseasesResistance to act is emerging in Asia.

Infectious diseases↑Failure rates with antifolate drugs mean Fansidar® is no longer used.

Infectious diseasesChloroquine is not used in the treatment of falciparum malaria.

Non-falciparum malaria

P. vivax, P. ovale, P. malariae, P. knowlesi:

  • If mixed infection with falciparum, treat as falciparum.

  • If severe/complicated non-falciparum disease, treat as severe falciparum.

  • If uncomplicated disease, treat with act as uncomplicated falciparum.

Chloroquine can be used for non-falciparum disease. Dosing in adult: 620mg base at 0h, 310mg base at 6–8h, 310mg base on day 2 and 3. But:

  • do not use if P. falciparum cannot be excluded

  • be aware that act may work more quickly on both fever and parasite count

  • chloroquine resistance exists in P. vivax (Papua New Guinea, Indonesia).

Infectious diseasesIn addition to other treatment, P. vivax and P. ovale require eradication of liver hypnozoites with primaquine:

  • P. vivax: adult 30mg (0.5mg/kg) daily for 14d.

  • P. ovale: adult 15mg (0.25mg/kg) daily for 14d.

Infectious diseasesRisk of haemolysis with primaquine in g6pd deficiency so screen prior to use. Seek expert advice for dosing/monitoring patients with g6pd deficiency, and in pregnancy.

Mosquito-borne disease

Mosquito-borne diseases12 are transmitted by the bite of a mosquito infected with a virus, bacteria, or parasite. The mosquito acts as the disease vector. Mosquitoes are arthropods (see table 9.21). Mosquito-borne diseases can therefore also be described as vector-borne or arthropod-borne disease. When a virus is transmitted by an arthropod it is termed an arbovirus (arthropod-borne virus).

Table 9.21 Vector-borne disease









Dengue, Chikungunya, yellow fever, Zika



Lymphatic filariasis, Japanese encephalitis, West Nile



Lyme disease, rickettsial disease, relapsing fever, tickborne encephalitis, Crimean-Congo haemorrhagic fever

422–3, 426–7


Leishmaniasis, trypanosomiasis, onchocerciasis, loiasis

423, 439




Infectious diseases Malaria

See pp[link][link].


Most important arbovirus in humans. Dengue viruses (Flaviviruses denv 1–4) are transmitted by day-biting Aedes mosquito. 120 countries (fig 9.28). Symptoms in 100 million/yr. uk: ~500 imported cases/yr.

Fig 9.28 Countries at risk of dengue (dotted line = 10°C isotherm).

Fig 9.28
Countries at risk of dengue (dotted line = 10°C isotherm).

Reproduced from Johnson et al., Oxford Handbook of Expedition and Wilderness Medicine, 2016, with permission from Oxford University Press.


Incubation 3–14d. Fever (up to 40°C), n&v, headache, retro-orbital pain, myalgia, arthralgia, +ve tourniquet test (inflate bp cuff to midway between systolic and diastolic for 5 min→≥10 petechiae/inch2). Infectious diseasesWarning signs/critical phase may occur 3–7d into illness and needs hospital admission: abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, hepatomegaly, ↑haematocrit + ↓plt. Infectious diseasesSevere disease: shock (includes postural bp drop >20mmHg), respiratory distress, severe bleeding, organ involvement (transaminases >1000, ↓gcs, other organ failure).


pcr for virus/elisa antigen3 during viraemia (~1st 5d of fever). Serology (igm, igg) after 5d. Also ↓plt, ↓wcc, transaminitis. (ΔΔ‎: Chikungunya, Zika.)


Supportive: prompt but careful fluid balance due to potential for plasma leak. iv crystalloid, to maintain effective circulation, only in severe disease. 20mL/kg over 15–30min if hypotensive shock. Monitor clinically and via haematocrit. Reduce iv fluid as soon as stable. Beware: plasma leak maintains haemocrit unless bleeding. Consider transfusion if ↓haematocrit without clinical improvement. Avoid nsaids.


Arbovirus (Alphavirus) transmitted by Aedes mosquito. Widespread: Asia, Africa, Europe, and Americas. Name derives from Kimakonde language meaning ‘to become contorted’ due to arthralgia. Blood-borne and vertical transmission possible, but rare.


Incubation 1–12d. Fever. Polyarthralgia: bilateral, symmetrical, can be severe, persistent. Headache, myalgia, n&v, maculopapular rash.


Viral culture/pcr (~1st 8d), serology.


Supportive. Analgesia.

Yellow fever

Arbovirus (Flavivirus) spread by Aedes mosquitoes in Africa, South America.


Incubation ~3–6d. Viraemia ~3d with fever, headache, myalgia, anorexia, n&v, relative bradycardia (ΔΔ‎: enteric fever p[link]). ~15% have remission followed by severe symptoms ~48h later: epigastric pain, jaundice, aki, cardiac instability, bleeding. Mortality 5%-30%.


Clinical and travel history. Virus/pcr in 1st 3d.3 Serology: cross reacts with other flaviviruses, igm can persist after vaccination.


Supportive. Live vaccine, effective for life (certificate for 10yr).

West Nile and Japanese encephalitis,

see Neurological disease pp[link][link].

Lymphatic filariasis (elephantiasis)

>40 million affected and disfigured. >1 billion at risk (80% in sub-Saharan Africa). Filarial parasites (nematodes) transmitted via mosquitoes which bite infected hosts and ingest microfilaria. These mature in the mosquito with infective larvae transferring to new hosts during feeding. Adult worms form nests in lymphatic vessels causing damage and lymphoedema. Transmission prevented by an annual dose of two drugs—5.63 billion treatments delivered by who since 2000.12 Types of filarial worm:

  • Wuchereria bancrofti (fig 9.29) ~90% of disease.

  • Brugia malaya ~10%.

  • Brugia timori possible cause of disease.

Fig 9.29 Blood smear of W. bancrofti (290×8.5µm).

Fig 9.29
Blood smear of W. bancrofti (290×8.5µm).

Courtesy of Prof. S. Upton, Kansas University.


Asymptomatic infection ± subclinical lymphatic damage. Acute episodes of local inflammation: pain, fever. Chronic damage: lymphoedema (fig 9.30), hydrocele, chylocele, scrotal/penile swelling. ckd: proteinuria, haematuria. Immune hyper-reactivity →tropical pulmonary eosinophilia (cough, wheeze, fibrosis, ↑eosinophil counts, ↑IgE).

Fig 9.30 Lymphoedema.

Fig 9.30

Reproduced with permission from World Health Organization. © World Health Organization.


Microfilariae in blood smear (fig 9.29), antifilarial igg, visualization of worms on uss/tissue sample.


Lymphoedema care. Prevention in high-risk populations: albendazole plus either diethylcarbamazine (dec) or ivermectin. dec is contraindicated in onchocerciasis (p[link]), care with ↑circulating Loa Loa (p[link]) due to risk of encephalopathy and renal failure. Household salt can be fortified with dec.

Vector-borne disease

Vector borne diseases are infections transmitted by the bite of infected arthropod species including mosquitoes, ticks, flies, and bugs (table 9.21).

Lyme disease (Lyme borreliosis)

Tick-borne multisystem disease caused by the spirochaete Borrelia burgdorferi (or related Borrelia spp). ~All cases limited to northern hemisphere (mainly Europe and us). ~2000–3000 cases/yr in uk. Risk of infection from tick bite is 3–12% in Europe.


Infectious diseases≤75% remember the tick bite. Peak infection with 48–72h of attachment. Disease stages:

  • Early localized (3–30d after bite): erythema migrans (fig 9.31), pain/pruritus, lymphadenopathy, ± constitutional symptoms: fever, malaise, headache. ⅓ do not see a rash.

  • Early disseminated (wks–months): borrelial lymphocytoma = bluish-red plaque/nodule: check earlobes, nipples, genitals. Neuroborreliosis: lymphocytic meningitis, ataxia, amnesia, facial/cranial nerve palsies, neuropathy (severe pain, worse at night), encephalomyelitis. Carditis: acute onset 2nd/3rd-degree heart-block, myocarditis.

  • Late disseminated (months–yr): acrodermatitis chronic atrophicans = focal inflammation then atrophic skin; Lyme arthritis.

Fig 9.31 Erythema migrans: distinct advancing edge.

Fig 9.31
Erythema migrans: distinct advancing edge.

Reproduced from Lewis-Jones, Paediatric Dermatology 2010, with permission from Oxford University Press.


Clinical: erythema migrans with known exposure or evidence of infection. Borrelia culture (↓sensitivity: 40–70% for erythema migrans, <20% for csf), pcr.4 Two-tier serology due to false-positive reaction with other spirochaete infection: enzyme immunoassay/immunofluorescence + immunoblot. Sensitivity ↓ due to slow seroconversion: igm 1–2wks (and may persist), igg 4–6wks and background positivity 3–15%.


Erythema migrans: doxycycline 100mg bd po for 10–21d (ci <8y, pregnant). Alternatives: amoxicillin, phenoxymethylpenicillin, azithromycin. Neuroborreliosis: ceftriaxone or iv benzylpenicillin or doxycycline for 10–30d. Arthritis/carditis: doxycyline or amoxicillin or ceftriaxone for 14–30d.15


Keep limbs covered; use insect repellent (deet); inspect skin and remove ticks (use tweezers, hold close to head/mouth).

Rickettsial disease

Rickettsiae are obligate, intracellular coccobacillary forms lying between bacteria and viruses. Mammals and arthropods are natural hosts. ↑Risk with rural activities eg camping, hiking, hunting. Divided into:

  • Spotted fevers: eg Rocky Mountain spotted fever (Americas); rickettsialpox (ΔΔ‎ chicken-pox).

  • Typhus: scrub typhus in Asia-Pacific regions; endemic (flea-borne) typhus in tropical areas; epidemic (louse-borne) typhus in homeless populations, eg refugees.

  • Other emerging illnesses: eg ehrlichia, anaplasma.


Incubation ~1–2wks. Fever, headache, malaise, rash (maculopapular, vesicular or petechial), n&v, myalgia. Check for local lymphadenopathy and an eschar at the site of the bite (scrub typhus). Wide variation in severity depending on aetiology. Fulminant, life-threatening infection possible with Rocky Mountain spotted fever, louse-borne typhus, scrub typhus.


Clinical: fever + rash + travel to an endemic area. Serology, culture/pcr of blood/skin biopsy.


Antibiotics in severe cases: doxycycline, azithromycin, chloramphenicol.


Caused by protozoan parasites of Leishmania12 species, transmitted by infected female phlebotomine sandflies. 556 million at risk. Risk factors: poverty, malnutrition, displacement, deforestation, dam building/irrigation.


  • Cutaneous, most common form, ulceration (fig 9.56, p[link]).

  • Mucocutaneous (fig 9.32): leads to tissue destruction of nose, mouth, throat. 90% occurs in Bolivia, Brazil, Peru.

  • Visceral leishmaniasis (vl, kala-azar, ‘black sickness’) (fig 9.33): fever, weight loss, hepatosplenomegaly, anaemia. >95% mortality without treatment. Endemic in Indian subcontinent, East Africa. 90% of new cases occur in Bangladesh, Brazil, Ethiopia, India, South Sudan, Sudan. 300 000 cases/yr, 20 000 deaths/yr. Post kala-azar is a complication of Leishmania donovani = a hypopigmented macular/nodular rash (ΔΔ‎ leprosy), 6 months–1yr after apparent cure, can heal but is a reservoir for parasites and maintains transmission.

Fig 9.56 Cutaneous leishmaniasis with central crusting.

Fig 9.56
Cutaneous leishmaniasis with central crusting.

Reproduced from Lewis-Jones, Paediatric Dermatology, 2010, with permission from Oxford University Press.

Fig 9.32 Mucocutaneous leishmaniasis.

Fig 9.32
Mucocutaneous leishmaniasis.

Reproduced with permission from World Health Organization. © World Health Organization.

Fig 9.33 Visceral leishmaniasis.

Fig 9.33
Visceral leishmaniasis.

Reproduced with permission from World Health Organization. © World Health Organization.


Clinical. Microscopy of tissue samples (skin, bone marrow) for parasite. Antibody detection in vl (indirect fluorescence, elisa, western blot, direct agglutination test, or immunochromatographic test) is limited due to:

  1. 1 Ab levels detectable for years after cure, cannot distinguish vl relapse/active infection.

  2. 2 Tests are +ve in many with no history of vl.

  3. 3 Serology may be −ve if hiv;+ve.


Liposomal amphoterin (single dose), oral miltefosine, pentavalent antimonials (resistance in India). The who Kala-azar Elimination Programme (including donated liposomal amphotericin) has achieved a 75% reduction in new cases of vl.

Human African trypanosomiasis (hat, sleeping sickness)

Infection with Trypanosoma protozoan parasites16, transmitted by the tsetse fly in sub-Saharan Africa. Divided into:

  • Rhodesiense hat, incubation <21d, high fever, gi disturbance, lymphadenopathy, headache. Chancre at bite site in ~84%, maculopapular rash. Progresses to myopericarditis, arrhythmias, and neurological symptoms.

  • Gambiense hat, chronic disease in African population, presents years after infection (can present with acute febrile illness in travellers). Low-grade fever. Sleep disorder: reversal of sleep–wake cycle, uncontrollable sleep episodes. Weakness, abnormal gait, psychiatric symptoms.


↓Hb, ↓plt, aki, ↑lfts, polyclonal ↑IgM. Microscopy of parasite (blood, lymph node, chancre, csf). Serology and pcr if available.


According to disease type and stage. Available from who. Includes suramin, melarsoprol, pentamidine, nifurtimox-eflornithine. Seek specialist advice—side-effects from all.

Chagas’ disease (American trypanosomiasis)

Life-threatening illness due to protozoan Trypanosoma cruzi transmitted by triatomine bugs. Endemic in Latin America: ~6–7 million infected.


Acute phase (~2 months): skin lesion (chagoma), fever, headache, myalgia, lymphadenopathy, unilateral conjunctivitis, periorbital oedema (Romaña’s sign), myocarditis, meningoencephalitis. Chronic phase (yrs): cardiac: dilated cardiomyopathy; gi: megaoesophagus (dysphagia, aspiration), megacolon (abdominal distension, constipation); cns symptoms.


Acute: trypomastigotes in blood, csf, node aspirate. Chronic: serology (Chagas’ igg elisa).


Benznidazole, nifurtimox. ↓effective in chronic disease.

Relapsing fever

Caused by spirochaete Borrelia recurrentis (louse-borne, sub-Saharan Africa, refugee camps) or other Borrelia (tick-borne, world-wide).


Intermittent fever ‘crisis’ due to antigenic variation (~3d fever, then afebrile ~7d), headache, myalgia, ↓bp.


Spirochaetes on blood smear, false +ve serology for Lyme disease.


Doxycyline/macrolides (single dose if louse-borne). Neuroborreliosis treatment if cns disease (p[link]). Jarisch–Herxheimer reaction due to endotoxins (?tnfα‎) can mimic fever ‘crisis’: observe 1st ~4h treatment, use cooling/antipyretics.


Anthrax (Bacillus anthracis)

Gram-positive, aerobic bacillus found in soil worldwide. Humans exposed via infected livestock or animal products, eg hide, wool, tusks. Infection via inhalation, ingestion, contamination of broken skin (includes iv drug use). Bacteria secrete exotoxins: oedema toxin and lethal toxin.


  • Cutaneous (~95%): itchy papule→vesicle→necrotic eschar. Oedema may be striking. Regional lymphadenopathy, malaise.

  • Inhalation: fever, cough, myalgia, sob, pleural effusion (haemorrhagic mediastinitis), stridor, death.

  • gi (rare): fever, abdominal pain, ascites, mucosal ulcers, gi perforation.


Vesicular fluid culture (care, do not disseminate), blood culture, antibody elisa, pcr. (nb: not pneumonic so sputum cultures are −ve).


Quinolone/doxycycline. Two agents if systemic disease, eg ciprofloxacin+clindamycin or linezolid (then narrow according to sensitivity). Consider anti-anthrax monoclonal antibody/immunoglobulin as adjunct in inhalational disease.


  • B. henselae (cat-scratch disease): from infected cat fleas. Low-grade fever, regional lymphadenopathy. Encephalitis rare. Skin lesions mimic Kaposi’s sarcoma.

  • B. quintana (trench fever): from human body louse. Fever, headache, bone pain.

  • B. bacilliformis (bartonellosis): from infected sandflies in Andes mountains. Oroya fever = fever, headache, myalgia, haemolysis. Later nodular→vascular skin lesions.


Clinical, blood culture (fastiduous ∴ needs prolonged culture), serology.


Cat-scratch disease often self-limiting. Azithromycin, aminoglycoside.


Most common zoonosis worldwide: 500 000 cases/yr. Gram −ve infection of cattle, swine, goats, sheep, dogs. Human infection via ingestion of infected meat/unpasteurized milk/cheese; or through inhalational/mucosal contact with animal body fluids (eg farmers, slaughterhouse workers, meat packers, hunters). ↑Risk in countries without animal health programmes.


Acute (<1 month), sub-acute (1–6 months), or chronic (>6 months). Non-specific: fever, anorexia, sweats, weight loss, malaise (ΔΔ‎ tb). Localized infection: septic arthritis, spondylitis, meningitis, endocarditis, orchitis, abscess.


Culture with prolonged incubation due to slow doubling time.17 Serology (four assays performed by Public Health England Brucella Reference Unit 0151 529 4900).


Doxycycline, rifampicin, aminoglycoside, ceftriaxone, co-trimoxazole. Needs prolonged course as intracellular with slow doubling time. Relapse usually due to inadequate dose/duration/adherence.

Coxiella burnetii (q fever)

q fever is derived from the label ‘query’ fever attributed to an unexplained disease in Australian abattoir workers. C. burnetii is now recognized as the pathogenic agent. Sheep, goats, cattle are main sources of infection (also cats, dogs, rabbits, ducks, ticks). Occurs worldwide. Spores can survive in soil, animal products, and water for months–yr. Transmitted by contact, inhalation of dust, or consumption of raw milk products.


Incubation 3–30d. ~50% asymptomatic. Non-specific symptoms: fever (1–3wks), nausea, fatigue, headache. Pneumonia in 1–2%: typical or atypical, may have rapid progression. Also splenomegaly, granulomatous hepatitis, aseptic meningitis, encephalitis, osteomyelitis. Endocarditis is the most common form of chronic disease.


Coxiella cannot be cultured using routine lab methods.17 pcr is rapid. Serology can take 2–6wks to become positive and detects variation in lipopolysaccharide (lps) coat. Phase ii lps appears before phase i lps ∴ acute infection = igm/igg to phase ii lps, chronic infection = igg to phase i lps. Serology on paired sera 2–4wks apart provides best diagnostic evidence.


Doxycycline. Also rifampicin, chloramphenicol, fluoroquinolone, macrolide. Hydroxychloroquine alkalinizes the phagosomes in which the bacteria resides and may ↑ bactericidal effect.

Leptospirosis (Weil’s disease)

Pathogenic leptospire spirochaetes belonging to the subgroup Leptospira interrogans. >250 pathogenic serovars. Chronic renal infection of carrier animals: rodent, cattle, pigs. Spread by water/soil/food contaminated by infected animal urine.


Incubation ~7d (2–30d). 1st (acute/septicaemic) phase: fever, non-specific flu-like symptoms. Mild/subclinical in ~90%. Followed by recovery or 2nd (immune/leptospiruric) phase: conjunctival suffusion, myalgia (↑ck), jaundice, meningitis, uveitis, aki, pulmonary haemorrhage, ards, myo/pericarditis. (Weil’s disease described in 1886: fever, jaundice splenomegaly, renal failure, cns symptoms. Term now applied to all severe disease.)


In uk18 via National Leptospirosis Service ( Culture (blood/csf) +ve during 1st phase. Serology. pcr.


Doxycycline, penicillin. Conflicting evidence of benefit for steroids in severe disease.

Yersinia pestis (plague)

Gram −ve, obligate intracellular pathogen transmitted by small animals and their fleas by bite, direct contact, inhalation or ingestion (rare). ~300 cases/yr worldwide.


Incubation: 3–7d. Flu-like symptoms, then one of three disease forms:

  1. 1 Bubonic: most common form. Yersinia pestis enters at bite and travels via lymphatics. Inflamed, painful lymph node is termed ‘bubo’ and can suppurate.

  2. 2 Septicaemic: direct spread without ‘bubo’, or advanced stage after ‘bubo’.

  3. 3 Pneumonic: lung disease. Most virulent, least common. Usually from advanced bubonic form but can then transmit via droplets to other humans without fleas/animals.


Culture bubo fluid, blood, sputum. Rapid antigen testing available.


Reduces mortality from 60% to <15%: streptomycin, tetracycline.12


Caused by protozoan Toxoplasma gondii. Found worldwide. Life cycle (fig 9.34). Infection is lifelong (~⅓ of population). hiv may cause reactivation (p[link]).

Fig 9.34 Oocysts in cat faeces can stay in the soil for months, where rats eat them. The rats get infected, and, under the direction of Toxoplasma in the amygdala, the rats lose their fear of cats, and so get eaten in turn. So the parasite ensure success by facilitating a jump from intermediate to definitive host. How does the parasite overwhelm the innate fear of cats? By causing a sexual attraction to normally aversive cat odour through limbic activity.

Fig 9.34
Oocysts in cat faeces can stay in the soil for months, where rats eat them. The rats get infected, and, under the direction of Toxoplasma in the amygdala, the rats lose their fear of cats, and so get eaten in turn. So the parasite ensure success by facilitating a jump from intermediate to definitive host. How does the parasite overwhelm the innate fear of cats? By causing a sexual attraction to normally aversive cat odour through limbic activity.

From Fernando Monroy:


Asymptomatic in ~90%. Self-limiting cervical lymphadenopathy, low-grade fever if normal immune system. Disseminated disease if immunosuppressed: cerebral abscess, encephalitis, choroidoretinitis, myocarditis, myositis, pneumonitis, hepatitis. Congenital infection: pregnancy loss, neurocognitive deficit, retinal damage.


In uk via Toxoplasma Reference Laboratory (0179 228 5058). Serology: igg=previous exposure (high avidity igg suggests infection >3–5 months ago, used in pregnancy); igm=acute infection, false +ve or chronic infection with persistent igm; iga in cord serum=congenital infection. pcr: blood/csf/urine/amniotic fluid/aqueous/vitreous humour.


If eye disease, immunosuppressed or neonate: pyrimethamine + sulfadiazine + folinic acid. Corticosteroids for eye inflammation. Spiramycin reduces vertical transmission. Prophylaxis: co-trimoxazole (see hiv, p[link]).

Echinococcosis (hydatid disease)




Hanta virus


Viral haemorrhagic fever (vhf)

Viral haemorrhagic fever (vhf) is a term used for severe, multi-organ disease in which the endothelium is damaged, and homeostasis is impaired. Haemorrhage complicates the disease course and can be life-threatening. vhf classification by viral subtype is shown in table 9.22.

Table 9.22 vhf classification (hf=haemorrhagic fever)

Virus family

Disease (virus subtype)




See Ebola, this page


See Marburg, p[link]


Lassa fever (Lassa)

See Lassa, p[link]

Argentinian HF (Junin)

South American vhf are rare causes of infection in travellers. Incubation 2–16d. Resemble Lassa fever. Severe disease with bleeding in ~ ⅓. Supportive treatment. Live vaccine available for Junin virus.

Bolivian HF (Chapare, Machupo)

Brazilian HF (Sabia)

Venezualan HF (Guanarito)


Crimean-Congo HF

See cchf, p[link]


Rodent host. Incubation 2d-8wk. Causes: 1 hf with renal syndrome: fever, headache, gi symptoms, and aki. 2 Hanta virus pulmonary syndrome: bilateral interstitial pulmonary infiltrates, mortality 30–40%. Supportive treatment.

Rift valley fever

Endemic in Africa. 80% asymptomatic or self-limiting febrile illness. <2% cns involvement/haemorrhagic.



see p[link]

Yellow fever

see p[link]

The Advisory Committee on Dangerous Pathogens (acdp) classifies a pathogen as Group 4 (highest) when it causes severe human disease, with high risk of spread, and no effective prophylaxis or treatment. Ebola,19 Marburg, Lassa, and Crimean-Congo haemorrhagic fever (cchf) are all Hazard Group 4 haemorrhagic fever viruses. They are largely confined to Africa (fig 9.35), with the exception of cchf which occurs in Africa, the Middle East, Eastern Europe, and Asia.

Fig 9.35 vhf risk in Africa.

Fig 9.35
vhf risk in Africa.

Reproduced with permission from Viral haemorrhagic fevers: origins, reservoirs, transmission and guidelines, Crown copyright 2016. Contains public sector information licensed under the Open Government Licence v3.0.


Incubation 2–21d (usually 3–12d). Evidence for fruit bats as reservoir. Outbreaks with ↑mortality. Largest epidemic (2014–16) due to Ebola virus (ebov, formally Zaire ebolavirus): 28 646 cases and 11 323 deaths in Guinea, Liberia, and Sierra Leone. Cytokine activation→endothelial damage, oedema, coagulopathy, tissue necrosis, multi-organ failure. Transmission from index case via mucous membranes, or contact with body fluids (including burial contact), viral shedding in semen.


  • Undifferentiated (0–3d). Fever (>38°C axillary), myalgia, weakness, anorexia, headache, sore throat. May not look unwell.

  • gi (4–10d). Epigastric/abdominal pain, liver tenderness, n&v, hiccups, diarrhoea, hypovolaemia.

  • Late organ stage (>10d). Haemorrhagic: petechiae, ecchymoses, mucosal haemorrhage, gi bleeding, haemoptysis. Neurological: extreme weakness, confusion, agitation, bradypsychia, coma. Other: hypoglycaemia, electrolyte abnormalities, secondary infection, shock, dic, multi-organ failure, death.

  • Post-infection: arthralgia, hepatitis, orchitis, transverse myelitis, meningitis, uveitis, vision/hearing impairment, social isolation, psychological effects.


Infectious diseasesppe (see box ‘Equipment’) if high possibility (see ‘Risk assessment). ↓wcc, ↓plt, ↑ast>alt. igm (~day 3), igg (~day 7), reverse transcriptase pcr on blood/urine/saliva/throat swab. Infectious diseasesExclude malaria.


Supportive: fluid resuscitation, correct electrolytes/coagulation/glucose, treat secondary infection, nutrition. Ribavirin not effective. Trace contacts, support family. Experimental: anti-rna agents, immunotherapy with blood/plasma from survivors, monoclonal antibodies (ZMapp™), Ebola vaccine (rvsv-zebov, Ebola ça suffit! trial).


Randomization versus compassionate use: is it ethical to withhold even potentially beneficial therapy to a control group with a life-threatening condition? Is observational data gained through the compassionate use of experimental therapy sufficient to guide clinical decisions? Where should resources be directed to improve outcome: drug development or basic healthcare provision, eg would the capacity to check K+ improve mortality?

Marburg, Lassa, and cchf

Differentiating features are given in table 9.23.

Table 9.23 Differentiation between vhf


Clinical features


Incubation typically 5–9d. Clinically identical disease course to Ebola. Ebola/Marburg suggested by liver tenderness.


~80% mild/asymptomatic. Haemorrhage in ~20%. Variable mortality in different epidemics 25–80%. Exudative pharyngitis. Convalescent hearing loss. Observational data shows response to ribavarin if given in first 6d.


Tick-borne. Sudden onset prodrome. Haemorrhagic stage common, develops rapidly, but usually short-lived 2–3d. Ribavarin used in treatment (↓evidence).

Risk assessment for vhf in uk

Assess for possible transmission and fever.

  • Transmission:

    1. 1 Travel to endemic area (rural for Lassa fever; caves/primates/antelopes/bats for Ebola/Marburg; tick/animal slaughter for cchf).

    2. 2 Travel to known outbreak (

    3. 3 Contact with infected specimen.

  • Fever: >37.5°C in the past 24h.

If possible transmission and fever consider ‘high possibility’ (≠high probability), isolate, ppe (see box ‘Equipment’). Inform local infectious disease team and contact the Imported Fever Service (0844 778 8990) for vhf investigation. Infectious diseasesBruising, bleeding, and uncontrolled d&v also warrant isolation and discussion if relevant contact history.

Gastroenteritis: an overview

Gastroenteritis = diarrhoea (± vomiting) due to enteric infection with viruses, bacteria, or parasites.

Diarrhoea can be defined as:

  • acute diarrhoea: ≥3 episodes partially formed or watery stool/day for <14d

  • dysentery: infectious gastroenteritis with bloody diarrhoea

  • persistent diarrhoea: acutely starting diarrhoea lasting >14d

  • traveller’s diarrhoea: starting during, or shortly after, foreign travel

  • food poisoning: disease (infection or toxin) caused by consumption of food/water. Infectious diseasesFood poisoning is notifiable in the uk (

Gastroenteritis can be classified according to infectious aetiology (table 9.24) or predominant clinical presentation (table 9.25, also see p[link]).

Table 9.24 Gastroenteritis by infectious aetiology






Virus ~50–60%



Important cause of epidemic gastroenteritis. 600 000–1million cases/yr in uk.




Affects nearly all children by age 5y. Routine, childhood (live) vaccine in uk.




Often less severe than norovirus.



Enteric adenovirus. Mainly children.



Children. Not common in food-borne disease.



Usually asymptomatic. If immunosuppression: colitis, hepatitis, retinitis, pneumonia.

[link], [link]

Bacteria ~30–40%

Salmonella (non-typhoidal)


Under-cooked eggs, poultry, meat.




Under-cooked meat, cross-contamination, unpasteurized milk, water.


E. coli

1–10d (usually 3–4d)

Bloody diarrhoea if Shiga-toxin producing E. coli (stec) eg 0157. Can cause hus. Under-cooked beef, unpasteurized milk most common.

[link], [link], [link]



S. sonnei most common. Deadly epidemics with S. dysenteriae in low-income countries.


Staphylococcus aureus


Unpasteurized milk/cheese, uncooked food. Multiplication leads to toxin production.


Clostridium perfringens


Raw meat. Inadequately reheated food.


Clostridium difficile

Antibiotic-associated diarrhoea. Spore-forming therefore persists: wash your hands.




Cold meat, soft cheese, refrigerated pâté. Diarrhoea, fever, myalgia. ↑Severity in immunosuppression and pregnancy (bacteraemia, fetal loss).


Vibrio cholerae


Human and aquatic reservoirs. Epidemics due to inadequate environmental management.


Yersinia enterocolitica


Main source is undercooked pork. Most infection in young children.


Bacillus cereus


Leftover food, rice. Emetic or diarrhoeal toxins.

Parasites <2%



Intestinal parasite. Cyst transfer via infected faeces, eg contaminated water. Malabsorption.




Transfer via infected faeces. Symptoms and ↑severity with immunosuppression, eg hiv.

[link], [link]

Entamoeba histolytica

2–4wks (can be years)

Asymptomatic carrier, intestinal disease and/or extra-intestinal disease (liver, skin, lung, brain).


Cyclospora cayetanensis


Transfer via infected faeces. May have relapsing course.




Enteral at 1–2d. Parenteral at 2–8wks: larval migration, facial swelling, myocarditis, encephalitis.




Whipworm. Dysentery with heavy infection.


Intestinal flukes


Eg Fasciolopsis buski.

Table 9.25 Gastroenteritis by clinical presentation

Diarrhoea without blood (enteritis)

Diarrhoea with blood (dysentery)


Shigellosis (bacillary dysentery)*


Enterohaemorrhagic E. coli


Campylobacter enterocolitis*

Enteric adenovirus

Salmonella enterocolitis*

Enterotoxigenic E. coli

Clostridium difficile

Enteropathogenic E. coli

Yersinia enterocolitis

Toxin-producing Staph. aureus

Entamoebic histolytica (amoebic dysentery)


Trichuriasis (whipworm)

Clostridium perfringens




Cyclospora cayetanensis

* Milder disease may present as diarrhoea without blood.

Gastroenteritis: specific infections

Diarrhoea without blood


Single-stranded rna virus. Highly infectious. Transmission by contact with infected people, environment, food (~10%). Most common cause of infectious gi disease, ~600 000 cases in England/yr. Presentation: 12–48h after exposure, lasting 24–72h: acute-onset vomiting, watery diarrhoea, cramps, nausea. Virus shed in stool even if asymptomatic. Numerous genotypes and unknown longevity of immunity ∴ repeat infection occurs. Diagnosis: clinical, stool sample reverse transcriptase pcr. Treatment: supportive, anti-motility agents, usually self-limiting.


Double-stranded rna virus. Wheel-like appearance on em ∴ ‘rota’. Commonest cause of gastroenteritis in children (~50%). Most infected by 5y. Presentation: incubation ~2d. Watery diarrhoea and vomiting for 3–8d, fever, abdominal pain. Diagnosis: clinical, antigen in stool. Treatment: supportive. Routine vaccination in uk (p[link]). Virus shed in stool post vaccine ∴ careful hygiene if immunosuppressed and changing nappies. Live vaccine ∴ delay vaccination if in utero biological agents with active transfer across placenta (eg infliximab, adalimumab).

Enterotoxigenic E. coli:

Gram −ve anaerobe. Disease due to heat-stable or heat-labile toxin which stimulates Na+, Cl- and water efflux into gut lumen. ~20% of all infective diarrhoea, ~80% of traveller’s diarrhoea. Presentation: incubation 1–3d. Watery diarrhoea, cramps. Lasts ~3–4d. Diagnosis: clinical, identification of toxin from stool culture. Treatment: supportive. See Traveller’s diarrhoea p[link].

Clostridium perfringens (type a):

Gram +ve, anaerobe. Produces enterotoxin. Spores survive cooking and germinate during unrefrigerated storage. 2–30 outbreaks/yr in uk. Presentation: sudden-onset diarrhoea, cramps, usually lasts <24h. Diagnosis: stool toxin, quantification of faecal bacteria. Treatment: supportive. β‎-toxin of C. perfringens type c can cause a necrotizing enteritis with fulminant disease, pain, bloody diarrhoea, septic shock. β‎-toxin is sensitive to trypsin proteolysis so ↑ risk with trypsin inhibition by sweet potatoes, ascaris infection ∴ occurs in New Guinea (‘pigbel’), central/south America, south-east Asia, China.


Vibrio cholerae is a Gram −ve, aerobic, ‘comma-shaped’ flagellated motile vibrating/swarming rod. Found in faecally contaminated water. Serovars o1 and o139 cause disease. ~190 000 cases in 2014 (fig 9.36). Last indigenous case in uk in 1893. Presentation: incubation 2h–5d. ~75% asymptomatic but shed bacteria. Profuse (1L/h) diarrhoea (‘rice-water’ stool), vomiting, dehydration, metabolic acidosis, circulatory collapse, death. Diagnosis: Clinical: death due to dehydration from watery diarrhoea age >5y, or any watery diarrhoea age >5y during known epidemic. Identification of serovars 01 or 0139 in stool. Rapid dipstick testing available but culture confirmation recommended. Treatment: Infectious diseasesoral rehydration salts (who/unicef ors sachet) will treat12 up to 80%. Needs safe water. Adults may need 1L/hr initially: offer 100mL/5 min. ng if vomiting. iv fluids if severely dehydrated: Ringer’s lactate or 0.9% saline plus ors (beware ↓ K+) up to 200mL/kg in first 24h. Antibiotics in severe dehydration to ↓ diarrhoea: doxycycline (single dose 300mg) or tetracycline (3d course) guided by local susceptibility (azithromycin in children/pregnancy). Zinc shortens illness in children (10–20mg/24h). Prevention: cholera loves filth: clean water (and clean politics) abolishes it. Oral cholera vaccines (56–94% efficacy in adults) dependent on logistics, cost, production capacity. Antibiotic prophylaxis breeds resistance.

Fig 9.36 Cholera: areas reporting outbreaks 2010–2014.

Fig 9.36
Cholera: areas reporting outbreaks 2010–2014.

Reproduced with permission from World Health Organization, Countries reporting cholera, 2010–2015. ©World Health Organization 2016.

Diarrhoea with blood (dysentery)

Shigella (sonnei, flexneri, dysenteriae, boydii):

Gram −ve anaerobe. Presentation: watery or bloody diarrhoea, pain, tenesmus, fever 1–2d after exposure. Lasts ~5–7d. ↑ in msm. Complications: bacteraemia, reactive arthritis (~2% of flexneri), hus (Shiga-toxin-producing dysenteriae, p[link]). Diagnosis: stool culture. pcr/enzyme immunoassay. Treatment: supportive. Nutrition: green bananas (↑short-chain fatty acids in colon), zinc if age <6y, vitamin a. Antibiotics if systemically unwell, immunosuppressed. Guided by local sensitivities (ciprofloxacin, azithromycin). Avoid antidiarrhoeal agents: risk of toxic dilatation.

Enterohaemorrhagic/Shiga-toxin producing E. coli (stec), eg O157:H7:

Gram −ve anaerobe. Produces veratoxins which are ‘Shiga-like’ due to similarity with Shigella dysenteriae. Presentation: incubation 3–8d. Diarrhoea, haemorrhagic colitis. hus in up to 10% (p[link]). Diagnosis: stool culture. pcr/enzyme immunoassay for Shiga-toxin.


Supportive. Do not give antibiotics: ↑ risk of hus.


Gram −ve, spiral-shaped rod. Presentation: incubation 1–10d (usually 2–5d). Bloody diarrhoea, pain, fever, headache. Complications: bacteraemia, hepatitis, pancreatitis, miscarriage, reactive arthritis, Guillain–Barré. Diagnosis: stool culture. pcr/enzyme immunoassay. Treatment: supportive. Antibiotics only in invasive cases, refer to local sensitivities (macrolide, doxycycline, quinolone).

Salmonella enterocolitis (non-typhoidal):

Gram −ve, anaerobic, motile bacilli. Presentation: diarrhoea, cramps, fever, usually within 12–36h of exposure. Invasive infection (<10%) can cause bacteraemia/sepsis, meningitis, osteomyelitis, septic arthritis. Diagnosis: stool culture. pcr. Treatment: supportive. Meta-analysis shows no evidence of benefit for antibiotics in healthy people. Consider in severe/extra-intestinal disease according to local sensitivities (quinolone, macrolide).

Yersinia enterocolitica:

Gram −ve rod. Presentation: incubation 4–7d. Diarrhoea, fever, pain (may mimic appendicitis), vomiting. May last 1–3wk. Also erythema nodosum, reactive arthritis (~1 month after diarrhoea). Diagnosis: stool culture, agglutination titres. Treatment: antibiotics in severe disease depending on local sensitivities (aminoglycosides, co-trimoxazole, quinolone).

Infectious diseasesSee also: Staph. aureus pre-formed toxin (p[link]), gi parasites (pp[link][link]), Clostridium difficile (p[link]).

Gastrointestinal parasites


Giardia lamblia (fig 9.38) is a flagellate protozoan. Faecal–oral spread from infected drinking water/food/fomites.

Fig 9.38 Giardia: the only diplomonadid to trouble us.

Fig 9.38
Giardia: the only diplomonadid to trouble us.


Asymptomatic in the majority. Incubation 1–3wks. Diarrhoea, flatulence, bloating, pain, malabsorption. Duration of symptoms typically ~2–6wks. Most common diagnosis if persistent traveller’s diarrhoea (p[link]).


Stool microscopy for cysts and trophozoites. Intermittent shedding so multiple samples (≳3) may ↑ sensitivity. Faecal immunoassay. pcr for diagnosis/subtype. Duodenal fluid aspirate analysis.


Hygiene to prevent transmission. Metronidazole (treatment failure in up to 20%), tinidazole (single dose), albendazole (↓ side-effects, simultaneous treatment of other parasites). Lactose-intolerance develops in 20–40%. No treatment for asymptomatic disease in endemic areas due to likelihood of re-infection.


Apicomplexan protozoan (fig 9.39). Ingestion of oocytes in infected water. Asymptomatic or self-limiting diarrhoea in immunocompetent hosts. Chronic/severe diarrhoea with immunosuppression: hiv (p[link]), transplantation, hypogammaglobulinaemia, immunosuppressive therapy.

Fig 9.39 Cryptosporidium immunofluorescence.

Fig 9.39
Cryptosporidium immunofluorescence.

© Prof. S Upton; Kansas Univ.


Protozoan Entamoeba histolytica (fig 9.40) ~10% world’s population, mortality ~100 000/yr. Faecal–oral spread. Boil water to destroy cysts.

Fig 9.40 The lifecycle of Entamoeba histolytica is in two stages: cysts and trophozoites. Cysts (10–15µm across) typically contain four nuclei (upper right image). During excystation in the gut lumen, nuclear division is followed by cytoplasmic division, giving rise to eight trophozoites. Trophozoites (10–50µm across) contain one nucleus with a central karyosome (lower right image). Trophozoites inhabit the caecum and colon. Re-encystation of the trophozoites occurs in the colon, and excretion of cysts in faeces perpetuates the lifecycle.

Fig 9.40
The lifecycle of Entamoeba histolytica is in two stages: cysts and trophozoites. Cysts (10–15µm across) typically contain four nuclei (upper right image). During excystation in the gut lumen, nuclear division is followed by cytoplasmic division, giving rise to eight trophozoites. Trophozoites (10–50µm across) contain one nucleus with a central karyosome (lower right image). Trophozoites inhabit the caecum and colon. Re-encystation of the trophozoites occurs in the colon, and excretion of cysts in faeces perpetuates the lifecycle.

Left hand image from Hutson C et al., ‘Molecular-based diagnosis of Entamoeba histolytica infection’, Expert Reviews in Molecular Medicine, 1(9): 1–11, 1999, reproduced with permission from Cambridge University Press. Upper and lower right images courtesy of Prof. S Upton, Kansas University.


  • Asymptomatic passage of cysts in ~90% (‘luminal amoebiasis’).

  • Intestinal amoebiasis: dysentery (often insidious onset/relapsing), pain, colitis, appendicitis, toxic megacolon. Amoeboma = inflammatory abdominal mass, usually caecal/rif ± obstruction.

  • Extra-intestinal (invasive) disease. Amoebic liver abscess in ~1%. Single mass containing ‘anchovy-sauce’ pus. High swinging fever, ruq pain/tenderness. lft normal or ↑ (cholestatic). 50% have no history of amoebic dysentery. Also peritonitis (rupture of colonic abscess), pleuropulmonary abscess, cutaneous/genital lesions.


Microscopy of stool (cysts and trophozoites, fig 9.40), aspirate or biopsy sample. Enzyme immunoassay: antigen detection as adjunct to microscopy, antibody detection in extra-intestinal disease. pcr can distinguish E. histolytica from morphologically identical but non-invasive E. dispar.


Metronidazole/tinidazole for amoebic dysentery and invasive disease. Diloxanide furoate: luminal agent, 10d course to destroy gut cysts, given in asymptomatic gut carriers and symptomatic disease, in addition to other treatment. Abscess may require (image-guided) drainage.


Coccidean protozoan Cyclospora cayetanensis. ~50 imported cases/yr in uk.


Flu-like prodrome, watery diarrhoea, weight loss, marked fatigue, low-grade fever in ~25%. Self-limiting after 7–9wks in immunocompetent.


Autofluorescent oocytes in stool (appear blue-green under uv fluorescence fig 9.41), pcr.

Fig 9.41 Cyclospora oocysts fluorescence.

Fig 9.41
Cyclospora oocysts fluorescence.

Credit: CDC DPDx.



Nematodes (soil-transmitted helminths and Trichinella)

  • Roundworm: Ascaris lumbricoides ~1 billion affected, Trichinella spiralis (contaminated meat source).

  • Whipworm: Trichuris trichiura, 600–800 million affected.

  • Hookworm: Necator americanus, Ancylostoma duodenale ~700 million affected.

  • Threadworm: eg Strongyloides stercoralis, 30–100 million affected.

One of most common infections worldwide, affects poor and deprived (fig 9.42). Parasites live in intestines, producing 1000s egg/day in faeces. Humans infected by eggs (ascariasis, trichinosis) or larvae (Ancylostoma) in contaminated food; or via direct penetration of the skin (hookworm, Strongyloides).

Fig 9.42 Larva currens: a serpinginous maculopapular rash pathognomonic of chronic strongyloidiasis. Oedema, an urticarial appearance, and speed of migration (>5cm/hr) distinguish this from cutaneous larva migrans which is caused by animal (dog/cat) hookworm.

Fig 9.42
Larva currens: a serpinginous maculopapular rash pathognomonic of chronic strongyloidiasis. Oedema, an urticarial appearance, and speed of migration (>5cm/hr) distinguish this from cutaneous larva migrans which is caused by animal (dog/cat) hookworm.

Reproduced from Johnson et al., Oxford Handbook of Expedition and Wilderness Medicine, 2016, with permission from Oxford University Press.


Diarrhoea, abdominal pain, blood/protein loss, impaired growth/cognitive development. Pruritus/urticaria if migration involves skin (Strongyloides fig 9.42). Lung invasion (ascariasis, hookworm, Strongyloides) can lead to a Loeffler-like syndrome: cough, sob, wheeze, haemoptysis, consolidation, eosinophilia. Other tissue invasion (trichinosis): myalgia, conjunctivitis, photophobia, meningitis, encephalitis, neuropathy.


Clinical, eggs in stool sample (fig 9.43). Eosinophilia. Strongyloides serology/pcr.

Fig 9.43 Ascaris eggs (45× 40µm) & ♂ worm (20cm).

Fig 9.43
Ascaris eggs (45× 40µm) & ♂ worm (20cm).

Courtesy of Prof. S Upton; Kansas University.


table 9.26.

Table 9.26 Anthelmintic drugs





Irreversible block of glucose/nutrient uptake

Roundworm, whipworm, hookworm


atp, immobilization and death of worm

Ascariasis, hookworm, (strongyloides)


↑Cl- permeability, hyperpolarization, paralysis

Strongyloides, ascariasis

Pyrantel pamoate

Depolarizing neuromuscular blockade causing spastic paralysis of worm

Single dose in threadworm, roundworm, hookworm


Flaccid paralysis of worm, expel live worm

(Ascariasis), pregnancy

Taeniasis (tapeworm)

Includes Taenia solium (pork, 2–8m, 50 000 eggs/worm), Taenia saginata (beef, 4–12m, 100 000 eggs/worm), Taenia asiatica (Asian, 4–8m, millions of eggs).


No or mild gi symptoms, tapeworm segments (proglottids) through anus/in faeces.


Eggs/proglottids in faeces.


Praziquantel, niclosamide.

Infectious diseasesSee also toxoplasmosis (p[link]), schistosomiasis (p[link]), cysticercosis (p[link]).

Schistosomiasis and liver disease

Schistosomiasis (bilharzia)

Caused by blood-flukes (trematode worms) of the genus Schistosoma (table 9.27). 258 million people in 78 countries required treatment in 2014. The life cycle is shown in fig 9.44. Disease develops after contact with contaminated freshwater (swimming, washing). Symptoms are due to an immune complex response to the migrating parasite (Katayama syndrome), or deposition of parasite eggs in body tissues.

Table 9.27 Parasite species and geographical distribution

Disease form




S. mansoni

Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname

S. japonica

China, Indonesia, Philippines


S. mekongi: Cambodia, Laos; S. guineensis/intercalatum: rainforests of central Africa


S. haematobium

Africa, Middle East, France

Fig 9.44 Schistosomiasis life cycle.

Fig 9.44
Schistosomiasis life cycle.

Reproduced from: Coltart C, CJM Whitty. Schistosomiasis in non-endemic countries. Clin Med 2015;15:67–9. Copyright © 2015 Royal College of Physicians. Reproduced with permission.


~50% asymptomatic or non-specific symptoms. Clinical syndromes:

  • Larval penetration: pruritic papular rash (‘swimmer’s itch’).

  • Migration of schistosomules: Katayama syndrome 2–8wks after exposure: fever, urticaria, diarrhoea, cough, wheeze, hepatosplenomegaly, eosinophilia.

  • Host response to egg deposition:

    • Intestinal disease: pain, diarrhoea, blood in stool, (granulomatous) hepatomegaly, splenomegaly. Heavy chronic infection can cause bowel perforation, hyperplasia, polyposis, liver fibrosis, portal hypertension→varices.

    • Urogenital disease: haematuria, dysuria, ureteric fibrosis→hydronephrosis, ckd, bladder fibrosis/cancer, genital lesions, vaginal bleeding, dyspareunia, vulval nodules, haemospermia, prostatitis.

    • Lung disease: pulmonary hypertension and cor pulmonale.

    • cns disease: rare, acute lower limb paraplegia, transverse (‘traveller’s’) myelitis.


Ova in urine (S. haematobium) or faeces (all other species) is specific, but sensitivity <50% if light infection. Serology for egg antigen becomes +ve once mature flukes lay eggs ∴ will be −ve in Katayama fever. Bowel/bladder histology. Chronic S. haematobium: bladder calcification on axr, renal obstruction, hydronephrosis ± thick bladder wall on uss.


two doses of praziquantel 20mg/kg po separated by 4h. Steroids for Katayama fever. If ↑eosinophils >3months after treatment look for other helminths (+ve serology can persist for years).

Echinococcosis (hydatid disease)

Zoonotic disease caused by tapeworms of the genus Echinococcus. Clinically important disease forms in humans are:

  • Cystic echinococcosis (hydatid disease, hydatosis): E. granulosus. Found worldwide. Usual host is dog. Also goats, swine, horses, cattle, camels, yaks.

  • Alveolar echinococcosis: E. multilocularis. Found in northern hemisphere. Usual hosts are foxes and rodents.

Human ingest parasite eggs via food/water contaminated by animal faeces, or by handing animals which are infected with the tapeworm. Disease is due to the development of cyst-like larvae in viscera, usually liver/lungs.


Slow growing cysts may be asymptomatic for many years. Symptoms and signs depends on location:

  • Liver: abdominal pain, nausea, hepatomegaly, obstructive jaundice, cholangitis, puo.

  • Lung:: dyspnoea, chest pain, cough, haemoptysis.

  • cns: space-occupying signs.

  • Bone: an interesting osteolytic cause of knee pain, cord compression.

  • Silent disease in breast, kidney, adrenals, bladder, heart, psoas.


uss/ct/mri: avascular fluid-filled cysts ± calcification (ΔΔ‎ benign cyst, tb, mycoses, abscess, neoplasm). Serology. Positive echinococcal antigen.


Get help (including surgical). Depends on cyst type, location, size, and complications. Prolonged treatment (months/years) with albendazole. pair: Puncture, Aspirate, Inject (hypertonic saline/chemicals), Reaspirate. Beware spillage of cyst contents: praziquantel can be given peri-operatively.

Fasciola hepatica (common liver fluke)

Parasitic infection. ~2 million infected worldwide. Highest rates of infection in Bolivia and Peru. Infective larvae develop in aquatic snail hosts. Humans infected via contaminated water, waterplants eg watercress, or by eating the undercooked liver of another host animal eg sheep, goat. Disease caused by migration of parasite to bile ducts.


Acute phase with migration from intestine through liver (2–4 months): abdominal pain, nausea, fever, urticarial rash, eosinophilia. Chronic phase with egg production in the bile ducts: cholecystitis, cholangitis, pancreatitis, cirrhosis.


Serology in acute and chronic phase. Ova in stool/bile aspirate only in chronic phase.


Triclabendazole as a single dose. Treat all suspected cases in endemic areas.

Other liver flukes: opisthorchiasis and clonorchiasis

Opisthorchis and clonorchis are liver flukes acquired by eating contaminated fish, mainly in south-east Asia. Adult worms lodge in the small bile ducts and gallbladder.


Abdominal pain, gi disturbance, cholecystitis, cholangitis, cholangiocarcinoma.


Ova in stool.



Neurological disease


Neuroparalytic infection caused by neurotoxin from anaerobic, spore-forming Clostridium botulinum (rarely C. butyricum, C. barattii). Food-borne due to toxin production in food (botulus is Latin for sausage), or wound botulism due to spore germination in wound (includes iv drug use). Toxin blocks release of acetyl-choline at neuromuscular junction causing flaccid paralysis.


Incubation up to 8d (usually 12–36h). Afebrile, descending, flaccid paralysis: diplopia, ptosis, dysarthria, dysphagia, progressive paralysis of limbs, respiratory failure. Autonomic signs: dry mouth, fixed/dilated pupils, urinary/cardiac/gi dysfunction. Infectious diseasesNo sensory signs.


Clinical: do not delay treatment. Take samples (serum, faeces, wound swab) for later confirmation by culture/pcr. In uk contact gi Bacteria Reference Unit (020 8327 7887).


Get help. Admit to itu. Botulinum antitoxin (from Public Health England, Colindale 020 8200 4400), benzylpenicillin, metronidazole.


Caused by anaerobic Clostridium tetani spores universally present in soil. Enters body via a breach in skin. Produces a neurotoxin (tetanospasmin) which disseminates via blood/lymphatics and interferes with neurotransmitter release causing unopposed muscle contraction and spasm (tetanus = ‘to stretch’). ~6 cases/yr in England and Wales (2015). Maternal and neonatal tetanus important cause of preventable mortality in low–middle income countries.


Site of entry may be trivial/unnoticed. Incubation ~3–21d. Prodrome: fever, malaise, headache. Trismus (lockjaw, Greek ‘trismos’ = grinding). Risus sardonicus = a grin-like posture of hypertonic facial muscles. Opisthotonus (fig 9.45). Muscular spasms induced by movement, injections, noise, then spontaneous. Dysphagia. Autonomic dysfunction: arrhythmias ± fluctuating bp. Respiratory arrest.

Fig 9.45 Spasm causing opisthotonus (arching of body with neck hyperextension). ΔΔ‎ tetanus, rabies, cerebral malaria, neurosyphilis, acute cerebral injury, catatonia.

Fig 9.45
Spasm causing opisthotonus (arching of body with neck hyperextension). ΔΔ‎ tetanus, rabies, cerebral malaria, neurosyphilis, acute cerebral injury, catatonia.

© Centers for Disease Control and Prevention.


Clinical. Detection of tetanus toxin/isolation of C. tetani.


Infectious diseasesGet help on itu: level of supportive care predicts outcome. Tetanus immunoglobulin (tig) im (or equine antitetanus serum if not available). Take blood for detection of tetanus-toxin and anti-tetanus antibodies first. Wound debridement, metronidazole. Management of spasm: diazepam/lorazepam/midazolam (may need high doses iv), iv magnesium sulphate, baclofen (intra-thecal administration needed for penetration of blood–brain barrier ∴ only with icu ventilatory support), dantrolene, botulinum toxin-a.23


Routine in uk (p[link]). Prophylaxis following injury: tig if heavy contamination. If vaccination history unknown/incomplete: tig plus dose of vaccine in a different site. Precautionary travel booster if >10y since last dose.


A highly infectious picornavirus, transmitted via faeco–oral route or contaminated food/water. Replicates in intestine. Invades nervous system with destruction of anterior horn cells/brain stem→irreversible paralysis. Incidence ↓by 99% since formation of Global Polio Eradication Initiative in 1988. 74 cases in 2015. Remains endemic in Afghanistan and Pakistan (2016).12


Incubation 7–10d. Flu-like prodrome in ~25%. Pre-paralytic stage: fever, ↑hr, headache, vomiting, neck stiffness, tremor, limb pain. ~1 in 200 progress to paralytic stage: lmn/bulbar signs ± respiratory failure. Infectious diseasesNo sensory signs. Post-polio syndrome in ~40% of survivors (up to 40y later): new progressive muscle weakness, myalgia, fatigue.


Viral culture of stool (most sensitive, 2 samples >24h apart), pharyngeal swabs, blood, csf. pcr can differentiate wild-type from vaccine. Paired serology.




Salk (inactivated, im) or Sabin (live, oral). In previously endemic areas 200 million volunteers have vaccinated 3 billion children, preventing 1.5 million deaths in the last 20y.


Rhabdovirus transmitted through saliva or cns tissue, usually from the bite of an infected mammal, eg bat (in uk), dog (95% of transmissions to humans), cat, fox. Disease is fatal once symptoms appear. Worldwide distribution. ~50 000 deaths/yr, most in Africa/Asia.


Incubation ~9–90d. Prodrome: headache, malaise, odd behaviour, agitation, fever, paraesthesia at bite/wound site. Progresses to one of two disease forms:

  • Furious rabies’: hyperactivity and terror (hydrophobia, aerophobia)

  • Paralytic rabies’: flaccid paralysis in the bitten limb→coma→death.


Clinical: potential exposure + signs of myelitis/encephalitis (non-progressive disease and disease >3wk are negative indicators). Viral pcr (saliva, brain, nerve tissue) or csf antibodies may offer later (post-mortem) confirmation.


If bitten, or lick to broken skin, wash (>15min) with soap and seek urgent help. Post-exposure prophylaxis: vaccination ± rabies immunoglobulin. Experimental treatments: ribavirin, interferon alfa, ketamine. Preventable and elimination feasible with pre-exposure vaccination of all at risk. Vaccination of dogs can ↓ human cases.

Japanese encephalitis virus

Flavivirus spread by mosquitoes. Endemic transmission (~3 billion at risk) and common cause of viral encephalitis in Asia and west Pacific. Severe disease is rare (1 in 250) but leads to neurological or psychiatric sequelae in up to 50%, mortality up to 30%.


Incubation 5–15d. Most asymptomatic, or mild fever and headache only. Severe disease: high fever, headache, meningism, altered mental status, coma, seizures, spastic paralysis, death.


Clinical in endemic area. Serum/csf serology, pcr.7


Supportive. Vaccination.

West Nile virus

Mosquito-borne flavivirus with transmission in Europe, Middle East, Africa, Asia, Australia, and Americas.


Incubation 2–14d. Asymptomatic in ~80%. West Nile fever in ~20%: fever, headache, n&v, lymphadenopathy. Neuroinvasive in ~1%: encephalitis, meningitis, flaccid paralysis, mortality ~10%.


Serum/csf igm, viral pcr.


Supportive. Vaccine awaited (2016).


Most common helminthic disease of the cns and most frequent cause of preventable epilepsy (~50% of epilepsy in endemic areas, fig 9.46). Caused by pork tapeworm Taenia solium. Consumption of infected pork leads to intestinal infection (taeniasis) and the shedding of T. solium eggs in stool. Invasive disease occurs when the shed eggs are ingested via faeco–oral transmission. Neurocysticercosis is due to larval cysts infecting the cns.

Fig 9.46 Endemicity (red) and suspected endemicity (orange) of Taenia solium 2015.

Fig 9.46
Endemicity (red) and suspected endemicity (orange) of Taenia solium 2015.

Reproduced with permission from who, Endemicity of Taenia solium, 2015. ©World Health Organization 2016.–1000x706.jpg?ua=1


Determined by site and number of lesions (cysticerci) within the brain/spinal cord. Epilepsy in 70%. Focal neurology in ~20%: motor/sensory loss, language disturbance, involuntary movements. Also headache, visual loss, meningitis, hydrocephalus, cognitive impairment.


ct/mri imaging plus serology.


Seizure control (↓evidence on drug choice, length of treatment or prophylaxis). Neurosurgical advice if hydrocephalus/↑icp. Albendazole for non-calcified lesions (better penetration of cns than praziquantel). Beware inflammatory response provoked by treatment—consider dexamethasone.

Eye disease


Common in tropical areas. Vision is normal. Differentiation between common infectious causes is outlined in table 9.29.

Table 9.29 Common causes of conjunctivitis







Red and swollen

Topical antibiotics for 5d



± Corneal lesion


Trachoma (chlamydial)


Follicles and papillae on lid

Azithromycin po or topical tetracycline

Reproduced from Brent et al., Oxford Handbook of Tropical Medicine, 2014, with permission from Oxford University Press.


Leading infectious cause of blindness worldwide: visual impairment/blindness in 1.9 million, 200 million at risk. Prevalence in endemic areas 60–90% (Africa, Central and South America, Asia, Middle East). Caused by Chlamydia trachomatis. Human-to-human transmission with contact, or via flies which land on noses/eyes.


Active infection causes purulent discharge and follicular inflammation of the eyelid (fig 9.47a)→scarring (fig 9.47b)→eyelids turn inwards (entropion) and irritate the cornea (trichiasis) (fig 9.47c) leading to visual loss.

Fig 9.47 (a) Follicular trachoma. (b) Scarring. (c) Trichiasis.

Fig 9.47
(a) Follicular trachoma. (b) Scarring. (c) Trichiasis.

Reproduced from Warrell et al., Oxford Textbook of Medicine, 2010, with permission from Oxford University Press.


who public health strategy SAFE: surgery to treat blinding disease (trichiasis), antibiotics (azithromycin) to clear infection (mass administration in endemic areas through International Trachoma Initiative), facial cleanliness, environmental improvement with access to water and sanitation.12

Immunosuppression and the eye

  • Herpes zoster ophthalmicus:

    Due to reactivation of latent varicella zoster virus (p[link]) in the ophthalmic branch of the trigeminal nerve. ↑ Risk of reactivation and ocular complications in immunosuppression: hiv, post-transplantation. Presentation: vesiculomacular skin rash and dysaesthesia in ophthalmic division of the trigeminal nerve (fig 9.48). Hutchinson’s sign = lesion at tip/side of nose indicates involvement of nasociliary branch of v1 and ↑chance of eye involvement. Complications: corneal opacification, uveitis, ocular nerve palsy, eyelid deformity, optic neuritis, post-herpetic neuralgia. Can be sight-threatening ∴ recognition and urgent treatment are required. Diagnosis: clinical. Antibody staining/pcr of skin scrapings. Treatment: oral famciclovir/valacyclovir or systemic aciclovir reduce complications if given within 72h of symptoms. Analgesia. If retinitis iv cidofovir ± intravitreal ganciclovir or foscarnet.

Fig 9.48 Herpes zoster ophthalmicus.

Fig 9.48
Herpes zoster ophthalmicus.

©MN Oxman, University of California.

  • cmv retinitis:

    Reactivation of cmv infection (p[link]). Presentation: floaters due to inflammatory cells in vitreous, flashing lights, scotomata, eye pain, visual loss. Peripheral lesions may be asymptomatic. Routine examination for those at risk (cd4<100 cells/microlitre). Diagnosis: clinical. Fundoscopy: granular white dots, haemorrhage (fig 9.49). Can progress to an arcuate/triangular zone of infection, or can be linear following vessels/nerve fibres. Treatment: systemic valganciclovir (oral, iv). Also ganciclovir, foscarnet, cidofovir. art if underlying hiv (see p[link]).

  • Ocular toxoplasmosis:

    Causes posterior uveitis. Presentation: blurred vision/floaters. Diagnosis: clinical. Fundoscopy (fig 9.50): focus of choroiditis, chorioretinal scar from previous infection, overlying vitreal haze due to inflammatory response. Multiple/bilateral/extensive lesions if ↑ immunosuppression. Serology. Ocular fluid pcr. Treatment: atovaquone (↓toxicity), sulfadiazine, and pyrimethamine.

Fig 9.49 cmv retinitis (mozzarella pizza fundus).

Fig 9.49
cmv retinitis (mozzarella pizza fundus).

©Prof Trobe.

Fig 9.50 Retinal toxoplasmosis.

Fig 9.50
Retinal toxoplasmosis.

©Prof Trobe.

Skin disease

Dermatoses occur in 8–23% of travellers and are the 3rd most common health problem in travellers after diarrhoea and fever. The differential of skin problems in travellers in outlined in fig 9.54.

Fig 9.54 Skin problems in travellers.

Fig 9.54
Skin problems in travellers.

Adapted from Travel Medicine and Infectious Disease, 7(3), O’Brien, BM, ‘A practical approach to common skin problems in returning travellers’, 125–46. Copyright 2009, with permission from Elsevier.


Caused by microscopic mite Sarcoptes scabiei. Found worldwide, ~300 million cases/yr. Female mites burrow into the epidermis and deposit eggs. Symptoms due to an allergic reaction to the parasite. Transmission via direct and prolonged skin-to-skin contact. Epidemics linked to poverty, overcrowding, and poor water supply.


Severe (nocturnal) pruritus, papular/scaly rash, burrows may be visible (fig 9.55). Itch can lead to secondary bacterial infection.

Fig 9.55 Scabies burrow.

Fig 9.55
Scabies burrow.

Reproduced from Burge et al., Oxford Handbook of Medical Dermatology, 2016, with permission from Oxford University Press.


Clinical. Skin scraping for mite/eggs/faeces.


Topical permethrin 5% or malathion 0.5%. Ivermectin given for filariasis (p[link]) may effectively treat concurrent scabies.

Cutaneous leishmaniasis

Most common form of leishmaniasis. Estimated 0.7–1.3 million new cases/yr: Americas, Mediterranean basin, north Africa, Middle East, central Asia.


Lesions develop at the bite site, beginning as an itchy papule; crusts fall off to leave a painless ulcer with a well-defined, raised border and a crusted base = ‘Chiclero’s ulcer’ (fig 9.56).


Skin biopsy + pcr.


Most heal in ~2–15 months with scarring (disfiguring if extensive). ‘New World‘ disease (South America) needs treating due to risk of mucocutaneous disease: pentavalent antimony, eg meglumine antimoniate, sodium stibogluconate. (See p[link].)


Infection with fly larvae/maggot. Can affect living and necrotic tissue. In south and central America the human botfly lays its eggs on mosquitoes which deposit them when they bite. In sub-Sahran Africa the tumbu fly lays its eggs on clothing which then transfer to skin.


Painful swelling. May have sensation of movement within the lesion. May open to reveal larval breathing tubes (fig 9.57).

Fig 9.57 Myiasis.

Fig 9.57

Reproduced under Creative Commons CC0 1.0 Universal Public Domain from


Clinical. Identification of larvae in lesion.


Petroleum or pork fat cause asphyxiation of the maggot causing it to protrude further out of the skin enabling removal with tweezers. Care: backward-facing spines in American disease may prevent complete removal unless done surgically. Ensure tetanus vaccination is up to date.


Infection of the skin by the sand/jigger flea Tunga penetrans. Acquired (usually walking barefoot) in sandy soil, rainforests, and banana plantations in south and central America, sub-Saharan Africa, Asia, Caribbean.


Painful, itchy papule on the feet. May be visible extrusion of eggs. Black crusting when flea dies.




None, self-limiting.

Leprosy (Hansen’s disease)

Caused by slow-growing, acid-fast Mycobacterium leprae which affects skin, nerves, and mucous membranes. Incubation 5–20y. Transmitted via droplets from nose/mouth during close and frequent contact. Classified as:

  • Multibacillary (‘lepromatous’): ↓immune response, ↑bacilli, +ve smear.

  • Paucibacillary (‘tuberculoid’): ↑immune response, granulomata with ↓bacilli, smears may be −ve.

Free treatment through who since 1995: prevalence ↓ by 99% to 176 000 in 2014 (5.2 million in 1985).12


Hypopigmented skin lesions (fig 9.58, less well demarcated than vitiligo), sensory loss, thickened nerves, nodules, plaques, nasal congestion, epistaxis, muscle weakness, paralysis, neuropathic ulcers. Eye involvement: chronic iritis, scleritis, episcleritis, ↓corneal sensation (v nerve palsy), ↓blinking and lagophthalmos (vii nerve palsy), trauma from eyelashes (trichiasis).

Fig 9.58 Leprosy: hypopigmented macules.

Fig 9.58
Leprosy: hypopigmented macules.

Courtesy of Prof. Jayakar Thoma.


Clinical, +ve skin smear, skin biopsy. Serology unreliable.


who multidrug therapy:

  • Multibacillary: Rifampicin 600mg/month, dapsone 100mg od, clofazimine 300mg/month and 50mg od. Duration: 1yr.

  • Paucibacillary: rifampicin 600mg/month, dapsone 100mg od. Duration: 6 months. If single lesion: rifampicin 600mg+ofloxacin 400mg+minocycline 100mg (single dose).


Chronic granulomatous disease caused by Treponema pertenue. Found in humid/rainforest areas in Africa, Asia, Latin American, Pacific. Associated with ↓socio-economic conditions. Transmission via direct contact.


Primary disease = papilloma. If untreated will ulcerate (fig 9.59). Secondary disease: yellow skin lesions, dactylitis. cvs and cns complications do not occur.

Fig 9.59 Ulceropapillomatous yaws.

Fig 9.59
Ulceropapillomatous yaws.

Courtesy of Dr B Hudson, Sydney, Australia.


Serology is indistinguishable from syphilis (Treponema pallidum). Dual-path platform (dpp) assay can distinguish between current and past infection. pcr.


Single-dose azithromycin po.

Pyrexia of unknown origin (puo)

This chapter gives guidance on hundreds of pyrexia-causing infections; but what should you do if your patient has a fever that you cannot explain? Pyrexia of unknown origin (puo)24 has a differential of >200 diseases. 15–30% of these patients will eventually be given an infective diagnosis (depending on your corner of the globe). ~20% will remain undiagnosed, but in most of these the fever will resolve within 4wks.

Diagnostic criteria

Pyrexia >3wks with no identified cause after evaluation in hospital for 3d or ≥ 3 out-patient visits.

Fever may also be undiagnosed in specific subgroups despite appropriate evaluation for 3d, including negative cultures at ≥ 2 days:

  • Nosocomial puo: Patient hospitalized for >48h with no infection at admission.

  • Immunodeficient puo: Pyrexia in patient with <500 neutrophils/microlitre.

  • hiv puo: Pyrexia in hiv infection lasting 3d as an in-patient or >4wks as an outpatient.


Most puo are due to common diseases with atypical presentation. Consider all details as potentially relevant. Include: travel (p[link]), diet, animal contact, changes in medication, recreational drug use, obstetric/sexual history, family history (table 9.30).

Table 9.30 puo differential according to history and examination findings



Animal contact

Brucellosis, toxoplasmosis, Bartonella, leptospirosis, q fever, psittacosis


tb, pe, q fever, enteric fever, sarcoidosis, legionnaire’s disease

Nasal symptoms

Sinusitis, gpa, relapsing fever, psittacosis


tb, Cryptococcus, sarcoid, carcinomatosis, brucellosis, enteric fever


sle, infective endocarditis, Lyme disease, brucellosis, tb, ibd

Weight loss

Malignancy, vasculitis, tb, hiv, ibd, thyrotoxicosis

Family history

Familial Mediterranean fever

Drug history

Drug-induced fever (~7–10d after new drug)




Leptospirosis, relapsing fever, spotted fever, trichinosis


tb, sarcoid, adult Still’s disease, sle, Behçet’s disease


Dental abscess, Behçet’s disease, cmv, ibd


Lymphoma, tb, ebv, cmv, hiv, toxoplasmosis, brucellosis, Bartonella


hiv, ebv, sle, vasculitis, Still’s disease, endocarditis


tb, ebv, malignancy, malaria, enteric fever, granulomatous hepatitis, q fever, visceral leishmaniasis


Leukaemia, lymphoma, tb, brucellosis, infective endocarditis, cmv, ebv, rheumatoid arthritis, sarcoid, enteric fever, relapsing fever


Chronic pyelonephritis, perinephric abscess, renal tumour


tb, lymphoma, ebv, brucellosis, leptospirosis


Confirm fever. Pattern of fever is rarely helpful (contrary to the textbooks, most malaria has no specific pattern). Do not forget: mouth, genitals, skin, thyroid, lymphatic system, eyes including retina, temporal arteries (table 9.30).


Infectious diseasesExtent of investigation depends on immune status and how well the patient is.

  • Blood tests: fbc, u&e, lft, crp, esr, electrophoresis, ldh, ck, ana, anca, rheumatoid factor, hiv test, malaria smear, interferon-gamma release assay for tb (p[link]).

  • Microscopy and culture: Blood ×3, urine, sputum (including afb), stool, csf.

  • Imaging: cxr, abdominal/pelvic uss, venous Doppler. Consider: ct(pa), mri, echo (toe). Fluorodeoxyglucose-pet (fdg-pet) highlights areas of ↑glucose uptake including tumour and inflammation. It may aid/direct diagnosis in up to 50% of puo.

  • Other: Hepatitis serology, cmv, ebv, autoimmune screen, cryoglobulins, toxoplasmosis, brucellosis, Coxiella, lymph node biopsy, endoscopy, temporal artery biopsy.


We thank Dr Chris Conlon, our Specialist Reader for this chapter.

1 Clinical diagnosis of low-severity community-acquired pneumonia is an exception, see also uti p[link].

2 Burkholderia pseudomallei in tropical water/soil. Causes pneumonia, pleural effusions, pulmonary abscess. Systemic abscess if haematogenous spread: liver, spleen, skin, muscle. Treat with co-amoxiclav, doxycycline, co-trimoxazole. In severe disease: ceftazidime, meropenem.

3 In uk testing done via Rare and Imported Pathogens Laboratory (ripl):

4 Specialist diagnostic service and advice in uk via Rare and Imported Pathogens Laboratory (ripl):

7 Specialist diagnostic service and advice in uk via Rare and Imported Pathogens Laboratory (ripl):

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