Microbiology: Fungi, parasites and travel-related infection

🦠 Fungi, parasites and travel-related infection. Fungal infections range from trivial skin infections to life-threatening invasive disease in neutropenic, transplant and intensive care patients. Parasites - protozoa and helminths - matter in the UK mainly in returning travellers and migrants, though some (Giardia, Cryptosporidium, Toxoplasma, threadworms, scabies, lice) are acquired here. Malaria is the most important diagnosis never to miss in a febrile returning traveller. This chapter covers the clinically important fungi and parasites and an approach to fever in the returning traveller.
Your four questions: Where has the patient been, when, and what did they do (exposure history)? How long since return (incubation period)? Is the patient immunocompromised? Is there eosinophilia?

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Fungal Biology and Antifungals

• Fungi are eukaryotes with a cell wall (chitin, β-glucan) and ergosterol (instead of cholesterol) in their membranes. Yeasts (single cells - Candida, Cryptococcus), moulds (hyphae - Aspergillus, Mucorales, dermatophytes), and dimorphic fungi (yeast in tissue, mould in the environment - Histoplasma).

Class	Mechanism	Examples	Key issues
Polyenes	Bind ergosterol → membrane pores	Amphotericin B (liposomal), nystatin (topical)	Nephrotoxicity, hypokalaemia, hypomagnesaemia, infusion reactions
Azoles	Inhibit ergosterol synthesis (14α-demethylase - CYP450)	Fluconazole (Candida, Cryptococcus; no mould activity), itraconazole, voriconazole (Aspergillus first line - visual disturbance, photosensitivity, skin cancer, hepatitis), posaconazole, isavuconazole; clotrimazole, miconazole (topical)	CYP3A4 inhibitors - major interactions (statins, warfarin, ciclosporin, tacrolimus); QT prolongation; hepatotoxicity; teratogenic
Echinocandins	Inhibit β-glucan synthesis (cell wall)	Caspofungin, micafungin, anidulafungin	First line for candidaemia; IV only; well tolerated
Allylamines	Inhibit squalene epoxidase	Terbinafine	Dermatophyte nail and skin infection; hepatotoxicity (check LFTs)
Others	Flucytosine (with amphotericin for cryptococcal meningitis); griseofulvin (tinea capitis in children)	-	Marrow toxicity (flucytosine)

Superficial and Mucocutaneous Fungal Infections

• Dermatophytes (Trichophyton, Microsporum, Epidermophyton) - tinea corporis (ringworm - annular scaly plaque with central clearing), cruris (groin), pedis (athlete's foot - interdigital), unguium (onychomycosis - confirm with nail clippings before oral terbinafine), capitis (children - kerion; oral treatment needed). Tinea incognito - modified by topical steroids. Do skin scrapings for microscopy and culture.
• Candida albicans - oral thrush (inhaled steroids, antibiotics, dentures, diabetes, HIV), vulvovaginal candidiasis (clotrimazole pessary or oral fluconazole - avoid oral azoles in pregnancy), intertrigo, nappy rash, angular cheilitis, oesophageal candidiasis (HIV - AIDS-defining), chronic paronychia.
• Malassezia - pityriasis versicolor (hypo- or hyperpigmented scaly patches on the trunk; ketoconazole shampoo), seborrhoeic dermatitis, folliculitis.

Invasive Fungal Infections

• Risk factors - prolonged neutropenia (leukaemia, stem cell transplant), solid organ transplant, high-dose steroids, ICU stay, central lines, broad-spectrum antibiotics, TPN, abdominal surgery, advanced HIV, uncontrolled diabetes (mucormycosis), biologics.
• Candidaemia - from central lines or gut translocation; remove the line, echinocandin then step down to fluconazole per sensitivity, ophthalmology review (endophthalmitis) and echo, treat for 14 days after the first negative culture. Candida auris - multidrug-resistant, spreads in hospitals; strict infection control.
• Aspergillus fumigatus:
  • Allergic bronchopulmonary aspergillosis (ABPA) - asthma or CF with eosinophilia, raised total IgE and Aspergillus IgE/IgG, central bronchiectasis; steroids ± itraconazole.
  • Aspergilloma - fungal ball in a pre-existing cavity (old TB, sarcoid) - haemoptysis; "air crescent" sign.
  • Chronic pulmonary aspergillosis - progressive cavitation in COPD/old TB; long-term azoles.
  • Invasive aspergillosis - neutropenic patients: fever despite antibiotics, nodules with halo sign on CT; serum/BAL galactomannan; voriconazole or isavuconazole.
• Mucormycosis (Rhizopus, Mucor) - diabetic ketoacidosis, neutropenia, iron overload (desferrioxamine): rhino-orbital-cerebral infection with black necrotic eschar on palate or nasal turbinate; surgical debridement plus liposomal amphotericin B - emergency.
• Cryptococcus neoformans - pigeon droppings; meningitis in advanced HIV (CD4 <100): headache, raised intracranial pressure; India ink stain, cryptococcal antigen (serum and CSF); amphotericin + flucytosine, then fluconazole; repeated lumbar punctures for raised pressure.
• Pneumocystis jirovecii pneumonia (PCP) - a fungus; HIV with CD4 <200, transplant, high-dose steroids plus other immunosuppression; progressive breathlessness, dry cough, exertional desaturation, bilateral perihilar ground-glass, raised LDH and β-D-glucan; high-dose co-trimoxazole plus steroids if PaO₂ <9.3 kPa; prophylaxis with co-trimoxazole.
• Endemic dimorphic fungi (in returning travellers) - Histoplasma (caves, bats - Americas, Africa), Coccidioides (south-west USA), Blastomyces, Talaromyces (South-East Asia - HIV).

Malaria

• Plasmodium falciparum (sub-Saharan Africa - most UK cases and nearly all deaths), P. vivax and P. ovale (dormant liver hypnozoites → relapse months later), P. malariae, P. knowlesi (South-East Asia - can be severe).
• Life cycle - Anopheles mosquito injects sporozoites → liver (schizonts; hypnozoites in vivax/ovale) → merozoites invade red cells → cyclical fever as red cells rupture; gametocytes are taken up by mosquitoes.
• Presentation - fever, rigors, headache, myalgia, diarrhoea, vomiting - often non-specific and "flu-like"; usually within 3 months of return from an endemic area (falciparum - mostly within 1 month), but vivax/ovale can present up to a year or more later. Thrombocytopenia, raised bilirubin and LDH.
• Diagnosis - three thick and thin blood films over 48–72 hours (or film plus rapid diagnostic antigen test) - same-day results; quantify parasitaemia. Any fever in a traveller returning from a malarial area is malaria until proven otherwise.
• Severe falciparum malaria - impaired consciousness or seizures (cerebral malaria), parasitaemia >2% (UK threshold for severity - >10% in some definitions), severe anaemia, AKI, acidosis, hypoglycaemia, ARDS/pulmonary oedema, shock, DIC, haemoglobinuria. IV artesunate (first line) with ICU input; then complete with oral therapy.
• Uncomplicated falciparum - artemisinin combination therapy (artemether–lumefantrine - Riamet - or dihydroartemisinin–piperaquine) or atovaquone–proguanil; usually admitted.
• Non-falciparum - ACT or chloroquine (where sensitive); then primaquine or tafenoquine to eradicate hypnozoites (vivax and ovale) - check G6PD first.
• Prevention - ABCD: Awareness of risk, Bite avoidance (DEET 50%, nets, covering up), Chemoprophylaxis (atovaquone–proguanil, doxycycline, mefloquine - matched to region and patient), prompt Diagnosis. People who grew up in endemic areas and now live in the UK ("visiting friends and relatives") lose immunity and are at high risk - the commonest group with imported malaria.

Other Protozoa

• Giardia lamblia - contaminated water (hikers, travel, also UK acquired); prolonged diarrhoea, bloating, steatorrhoea, malabsorption and weight loss, lactose intolerance; stool antigen or PCR; metronidazole or tinidazole. IgA deficiency predisposes.
• Cryptosporidium - farm visits (lambs, calves), swimming pools (resists chlorine); watery diarrhoea in children; severe chronic diarrhoea in advanced HIV.
• Entamoeba histolytica - amoebic dysentery (bloody diarrhoea, flask-shaped ulcers) and amoebic liver abscess (fever, right upper quadrant pain, single abscess - "anchovy sauce" pus; serology); metronidazole then a luminal agent (paromomycin or diloxanide).
• Toxoplasma gondii - cat faeces, undercooked meat; usually asymptomatic or glandular-fever-like in healthy adults; cerebral toxoplasmosis in AIDS (multiple ring-enhancing lesions - pyrimethamine + sulfadiazine + folinic acid); congenital toxoplasmosis (chorioretinitis, hydrocephalus, intracranial calcification); ocular toxoplasmosis.
• Trichomonas vaginalis - STI; frothy green-yellow offensive discharge, "strawberry cervix", pH >4.5; metronidazole; treat partners.
• Leishmania - sandfly; cutaneous (chronic painless ulcer after travel - Middle East, South America, soldiers) and visceral (kala-azar) - fever, weight loss, massive splenomegaly, pancytopenia, hypergammaglobulinaemia; liposomal amphotericin.
• Trypanosoma - African sleeping sickness (tsetse fly - chancre, fever, then CNS disease) and Chagas disease (T. cruzi - Latin America - cardiomyopathy, megaoesophagus, megacolon; screen Latin American migrants and pregnant women at risk).

Helminths - Worms

Worm	Acquisition	Disease	Treatment
Enterobius vermicularis (threadworm)	Faeco-oral, very common in UK children	Perianal itch at night; Sellotape test	Mebendazole for the whole household plus hygiene measures for 6 weeks
Ascaris lumbricoides (roundworm)	Eggs in soil-contaminated food	Usually asymptomatic; Löffler's syndrome (pulmonary eosinophilia), bowel or biliary obstruction	Mebendazole, albendazole
Hookworm (Ancylostoma, Necator)	Larvae penetrate bare feet	Iron deficiency anaemia; cutaneous larva migrans (dog hookworm - serpiginous itchy track, often on feet after beach holiday)	Albendazole; ivermectin
Strongyloides stercoralis	Larvae penetrate skin	Larva currens rash, eosinophilia; autoinfection persists for decades; hyperinfection syndrome with steroids or HTLV-1 → Gram-negative sepsis and meningitis	Ivermectin; screen at-risk migrants before steroids or immunosuppression
Schistosoma (S. haematobium, mansoni, japonicum)	Swimming in fresh water in Africa (Lake Malawi, Lake Victoria, Nile)	Swimmer's itch; Katayama fever (fever, urticaria, eosinophilia 2–8 weeks after exposure); haematuria and bladder squamous cell carcinoma (haematobium); hepatic periportal fibrosis and portal hypertension (mansoni)	Praziquantel (repeat after 6–8 weeks)
Taenia solium (pork tapeworm)	Undercooked pork; eggs (faeco-oral) → cysticercosis	Neurocysticercosis - commonest cause of acquired epilepsy worldwide; cysts and calcifications on CT/MRI	Albendazole + steroids (specialist); antiepileptics
Echinococcus granulosus (hydatid)	Dog faeces (sheep-farming areas - Wales, Mediterranean, Middle East)	Hydatid cysts in liver and lung; anaphylaxis if ruptured	Albendazole, surgery or PAIR
Toxocara	Dog and cat faeces (children)	Visceral larva migrans, ocular toxocariasis (retinal granuloma - may mimic retinoblastoma)	Albendazole
Filariae (Wuchereria, Onchocerca, Loa loa)	Insect bites in the tropics	Lymphatic filariasis (elephantiasis), river blindness, Calabar swellings and eye worm	Specialist (diethylcarbamazine, ivermectin, doxycycline)

Ectoparasites

• Scabies (Sarcoptes scabiei) - intensely itchy rash, worse at night, burrows in finger webs, wrists, genitals, axillae; outbreaks in care homes; crusted (Norwegian) scabies in the immunosuppressed and frail - highly contagious. Permethrin 5% cream to the whole body (neck down; include scalp and face in children and older people), repeated after 7 days, treat all household contacts at the same time; wash bedding at 60°C; oral ivermectin for crusted scabies or outbreaks. Itch may persist for weeks.
• Head lice (Pediculus capitis) - wet combing or dimeticone; no need to exclude from school.
• Pubic lice (Phthirus pubis) - STI; screen for other STIs.
• Body lice - homelessness; transmit trench fever (Bartonella quintana), epidemic typhus, relapsing fever.
• Ticks - Lyme disease, tick-borne encephalitis, rickettsial spotted fevers (remove promptly with fine tweezers or a tick removal tool).
• Myiasis (tumbu or bot fly larvae) - boil-like lesions with a central breathing hole after travel to Africa or Latin America.

Fever in the Returning Traveller

• History: countries and regions visited (rural or urban), dates of travel and return, activities (fresh-water swimming, safaris, caves, animal contact, sexual contact, healthcare exposure, tattoos), food and water, insect bites, pre-travel vaccines and malaria prophylaxis (and adherence), sick contacts.
• First - consider viral haemorrhagic fever (travel to an affected area within 21 days, contact with a case) → isolate and follow the VHF risk assessment algorithm. Second - exclude malaria (same-day films).
• Incubation periods help:

Incubation	Causes
<10 days	Dengue, chikungunya, Zika, rickettsiae, enteric bacteria, influenza, COVID-19, VHF (up to 21 days), plague, meningococcus
10–21 days	Malaria (falciparum), typhoid, leptospirosis, rickettsiae, acute HIV, African trypanosomiasis, Q fever, brucellosis
>21 days	Malaria (vivax, ovale), TB, hepatitis A/B/E, HIV, schistosomiasis (Katayama), amoebic liver abscess, visceral leishmaniasis, brucellosis

• Investigations: malaria films/RDT, FBC (thrombocytopenia - malaria, dengue; eosinophilia - helminths), U&E, LFTs, CRP, blood cultures (typhoid), urine, CXR, dengue NS1/serology, HIV test, store serum.
• Common UK diagnoses in returning febrile travellers: malaria, dengue, enteric fever, respiratory infections (influenza, COVID-19, pneumonia), traveller's diarrhoea, rickettsial infection, UTI, and non-travel-related causes.

Eosinophilia and Parasites

• Eosinophilia (>0.5 × 10⁹/L) in a traveller or migrant suggests helminth infection (especially tissue-invasive: Strongyloides, schistosomiasis, filariasis, toxocariasis, hookworm, Ascaris larval migration). Protozoa usually do not cause eosinophilia (except Cystoisospora, Sarcocystis).
• Other causes: allergy and atopy (asthma, eczema), drugs (DRESS), eosinophilic granulomatosis with polyangiitis, ABPA, Addison's disease, Hodgkin lymphoma, hypereosinophilic syndrome, eosinophilic leukaemia, cholesterol emboli.
• Investigations: stool microscopy (three samples - ova, cysts, parasites), Strongyloides and Schistosoma serology, terminal urine for S. haematobium eggs, filarial blood films (timing matters).
• Before starting steroids in someone from or with long stays in tropical or subtropical areas - screen for Strongyloides (or treat empirically with ivermectin) to prevent hyperinfection.

At a Glance

Clue	Think
Fever after travel to Africa	Malaria - films today
Neutropenia + fever on antibiotics + CT halo sign	Invasive aspergillosis - voriconazole
DKA + black palatal eschar	Mucormycosis - emergency surgery + amphotericin
AIDS + headache + raised opening pressure	Cryptococcal meningitis
AIDS + ring-enhancing lesions	Toxoplasmosis (or lymphoma)
Exertional desaturation + immunosuppression	PCP
Haematuria after Lake Malawi	Schistosomiasis
Seizure in a migrant + calcified brain cysts	Neurocysticercosis
Steroids + Gram-negative sepsis + migrant	Strongyloides hyperinfection
Night-time itch, finger webs, whole family	Scabies

Spot the Organism

• Fever 2 weeks after visiting family in Nigeria; no prophylaxis taken. → Falciparum malaria - films and admission.
• Fever, urticaria and eosinophilia 5 weeks after swimming in Lake Victoria. → Katayama fever (acute schistosomiasis).
• Bloating, steatorrhoea and weight loss after a camping trip. → Giardiasis.
• Right upper quadrant pain and fever months after travel to India; single liver abscess. → Amoebic liver abscess.
• A COPD patient with old TB cavities and haemoptysis; mobile ball in a cavity. → Aspergilloma.
• Itchy serpiginous tracks on the feet after a beach holiday. → Cutaneous larva migrans.

Exam-style Scenarios

• Scenario. A 35-year-old returned from Ghana 10 days ago with fever and confusion. Film shows 6% P. falciparum parasitaemia. What do you do?
  Answer: Severe falciparum malaria (impaired consciousness and parasitaemia >2%) - IV artesunate immediately, ICU/HDU referral, monitor glucose (hypoglycaemia), fluids cautiously (pulmonary oedema risk), check for AKI, acidosis and anaemia, repeat films 12–24 hourly; complete treatment with oral ACT once improving; notify.
• Scenario. A man from rural Vietnam is to start high-dose prednisolone for vasculitis. What screening is advisable?
  Answer: Strongyloides serology (or empirical ivermectin) to prevent hyperinfection; also screen for latent TB, hepatitis B and HIV before significant immunosuppression.
• Scenario. A patient on simvastatin and tacrolimus after a kidney transplant needs treatment for invasive aspergillosis with voriconazole. What concerns are there?
  Answer: Voriconazole strongly inhibits CYP3A4 - raises tacrolimus (nephrotoxicity - reduce dose and monitor levels) and simvastatin (rhabdomyolysis - stop it); monitor voriconazole levels, LFTs and QT interval.

Key Points

• Malaria: same-day films for any fever after travel to a malarial area; IV artesunate for severe disease; G6PD before primaquine.
• Fluconazole has no activity against moulds; voriconazole treats Aspergillus.
• Remove central lines in candidaemia and examine the eyes.
• Screen for Strongyloides before immunosuppression in at-risk patients.
• Eosinophilia suggests helminths, not protozoa.
• Treat scabies contacts simultaneously.

Guidelines and Further Reading

• UKHSA: Guidelines for malaria prevention in travellers from the UK; UK malaria treatment guidelines (Lalloo et al., J Infect)
• UKHSA / ACDP: Viral haemorrhagic fever risk assessment algorithm
• British Infection Association: Clinical guideline for the management of the febrile returning traveller
• NICE CKS: Scabies; Threadworm; Fungal skin infection
• ESCMID / ECMM guidelines on invasive fungal infection
• TravelHealthPro (National Travel Health Network and Centre)