2.5 Fever in the Returning Traveler: Eosinophilia and Parasites

Question 1

Can exist as free-living or as a parasite (e.g. Strongyloides)

Answer 1

Facultative parasite

Question 2

Lives permanently in a host and cannot live without host (e.g. Trichomonas)

Answer 2

Obligate parasite

Question 3

Foreign and pass through the alimentary canal without any effect/invasion

Answer 3

Coprozoic (spurious) parasite

Question 4

Harbours the adult/final/sexual stages in the development of the parasite

Answer 4

Definitive host

Question 5

Harbours the larva/intermediate stages in the parasite life cycle

Answer 5

Intermediate host

Question 6

Well adapted to the parasite (can tolerate infection) → source of infection to other organisms and hosts

Answer 6

Reservoir (Carrier)

Question 7

EOSINOPHILIA
Eosinophil count follows a _______________ (peaks in the morning and drops over the day):
• Highest at birth and decreases during childhood, and are found more abundantly in tissues than in peripheral blood
• Absence of eosinophilia does not exclude parasitic infections (only certain parasites in certain life stages elicit eosinophilia)

Answer 7

diurnal variation

Question 8

There are many causes of eosinophilia (absolute eosinophil count > 450), including:

Allergic diseases: Atopy (and related diseases), medication-related eosinophilia

Infectious diseases

• Parasitic infections (mostly _____________, ectoparasites like scabies)
• Specific fungal infections (____________)
• Other infections (infrequent)

Haematologic/ neoplastic disorders:
- Hypereosinophilic syndrome, leukaemia, lymphomas, tumour-associated, mastocytosis (excessive mast cells)

Diseases with specific organ involvement:
- Skin and subcutaneous diseases, pulmonary diseases, GI diseases, rheumatological diseases (Churg-Strauss syndrome), renal diseases

Immunologic:
- Specific immunodeficiencies (hyper IgE syndrome), transplant rejection

Endocrine:
- Hypoadrenalism

Answer 8

tissue-invasive helminths;

coccidioidomycosis

Question 9

Eosinophilia due to parasitic causes is usually higher in the _______________
• Occurs in helminthic infections with migrating larvae or extended life cycle in tissues (e.g. Ascaris pneumonia, Strongyloidiasis, Filariasis, acute Schistosomiasis)
o May also occur when larvae are lost as they pass through the accidental human host (e.g. Toxocara, Trichinosis, Gnathostomiasis)
o _______________do not cause eosinophilia except when infected tissue is exposed to organs (e.g. Echinococcus, Cysticercosis)
• Protozoans do not cause eosinophilia except ___________________ fragilis (rare and mild)
• Most common cause: intestinal nematodes (e.g. Filariasis, Schistosomiasis, Strongyloidiasis, Gnathostomiasis)
• Asymptomatic eosinophilia is important as many parasites have long lifespans or auto-infection cycles which lead to lifelong persistence

Answer 9

acute tissue invasive phase:

Intraluminal helminths ;

Isospora beli and Dientamoeba

Question 10

Schistosomiasis is an important global infection caused by the _______________ belonging to the genus Schistosoma:
• About 200 million people are infected globally (1 in 30), and 200 000 die
• One of the most common causes of______________ in the world

LIFE CYCLE
The life cycle of Schistosoma occurs in ________ (intermediate) and humans (definitive):
• When water is contaminated by eggs (released from human faeces/urine), there is a part of the life cycle occurring within snails (_________ → _________)
• Free-swimming infectious cercariae are released by the snail into the freshwater, and penetrate human skin (losing tails → schistosomulae)
• Parasites enter the circulation and travels to ____________ (e.g. portal blood, bladder venous plexus) and mature into adults and lay eggs
• Risk factor: swimming/wading/bathing/washing in freshwater with infectious cercariae

Answer 10

flat, leaf-shaped trematodes (blood fluke);

non-cirrhotic portal hypertension;

snails;

miracidia → sporocysts;

various venous plexuses

Question 11

[Schistosomasis: Infection course]

Acute infections tend to present with Swimmer’s itch and Katayama fever:
- Swimmer’s itch: _______________ at the site of larval entry (lasts for 1 – 2 days to 1 week)
- Katayama fever: _______________ against migrating parasites (occurs 2 – 8 weeks following exposure):
• Similar to serum sickness (e.g. fever, malaise)
• Presents with possible lymphadenopathy and hepatosplenomegaly (resolves within weeks)
• ____________ in peripheral blood and _____________ on X-ray

Chronic infections are relatively rare in travellers with one-off exposure, and typically occurs in untreated infections or repeated exposures:
• Due to body’s reaction to ______________ → hepatic schistosomiasis

• Inflammatory: Hepatomegaly and severe splenomegaly Chronic (GI)
  • Typically in young/middle-aged adults with long intense infections:
  • _____________ leads to non-cirrhotic portal hypertension (hepatocellular function is normal)
  • Granuloma formation (walls off eggs in the centre)
  • Bowel wall _________________ and further periportal fibrosis with heavy infections

Chronic (urogenital)
- Caused by Schistosoma haematobium in the urinary tract:
• Dysuria and haematuria
• Later calcification in the bladder (with increased risk of bladder cancer/ ________________)

CNS
- Rare; due to migration of adult worms or eggs and deposition in the spinal cord or brain → granuloma formation

Answer 11

Localised pruritic dermatitis;

Systemic hypersensitivity reaction;

Eosinophilia; patchy infiltrates

eggs (not adult worm);

Periportal fibrosis;

ulceration, hyperplasia and polyposis;

squamous cell carcinoma

Question 12

[Schistosomasis]

Diagnosis

• Stool microscopy for parasite eggs (S. mansoni or S. japonicum) or urine (_______________)
• Tissue biopsies
• Serology

Treatment

• _____________ (kills adult worms by exposing antigens to host immune defences)
• 85% cure rate; 90% reduction in infection intensity with regression of periportal fibrosis and portal vein thickening

Answer 12

S. haematobium;

Praziquantel

Question 13

[Amoebiasis]
Amoebiasis is caused by ______________ (protozoan) in contaminated food/water.

LIFE CYCLE
Hosts are infected upon ingestion of contaminated food or water containing mature cysts:
• Mature cysts then excyst to form the _______________ which migrate to the large intestines and multiply via binary fission
• Trophozoites are invasive forms which cause invasive infection through the bloodstream to other sites (e.g. liver, brain, lungs)
• Encystation occurs to form immature cysts which are released into the environment, where the cycle of infection is repeated

CLINICAL MANIFESTATIONS
Amoebiasis may be asymptomatic (80 – 90%) or symptomatic (4 – 10%):
• Infection is cleared within _______________ in most individuals; only 4 – 10% develop disease within 1 year of exposure
• Asymptomatic individuals still have cysts shed in their stool → continue infection

Intestinal Dysentery (bloody diarrhoea), colitis: 
- Shed trophozoites (non-infectious) in diarrhoeal stool 

Extraintestinal: _________________ (most common; 10%) → acute/insidious onset
- Rarely shed cysts or trophozoites in stool

Answer 13

Entamoeba histolytica;

trophozoites;

12 – 18 months;

Amoebic liver abscess

Question 14

Other supportive diagnostic features of amoebic liver abscess (large abscess on CT liver) include deranged LFTs (raised ALP), neutrophilia, raised CRP, hepatomegaly and raised right hemidiaphragm:
• Treatment: ________________ (luminal agent) + aspiration (in some cases depending on size of abscess → anchovy paste aspirate)
• Metronidazole and paromomycin are used even if the _________________

Answer 14

metronidazole + paromomycin;

stool OCP exam is negative

Question 15

[Strongyloides sterocralis]
Strongyloides stercoralis is a _________________ which causes disease with a variable symptomatic spectrum:
• Ranges from subclinical (acute and chronic infections) to severe and fatal (hyperinfection syndrome and disseminated strongyloidiasis → 90% fatality rates)
• Symptoms occur due to migration of larva through various organs
• Prevalence: high in certain parts of South America, Africa and Southern Asia (community-based studies) → different from health services studies
o Consider travel history before including as a potential differential

LIFE CYCLE
Before infection of the human host, the larva (____________) develops into an infective form (______________) which can penetrate _________ (e.g. human host walking barefoot):
• Initiates infection cycle by migrating through various pathways to the small intestines, then mature to adult worms
• Adult worms can complete the entire sexual cycle and autoinfection within the human host, so burden of adult worms can increase substantially (chronic infection)

Answer 15

nematode (roundworm);

rhabditiform;

filariform;

intact skin

Question 16

[Strongyloides: Clinical Manifestations]
Acute strongyloidiasis may present with the following signs and symptoms:
-________________ s rash: Initial sign which occurs at the site of skin penetration (may not be apparent in all individuals)
- Tracheal irritation, _________: Larvae migrate from lungs up through the trachea
- GI symptoms: Larvae swallowed into the GI tract (e.g. diarrhoea, constipation, abdominal pain, anorexia)

Chronic strongyloidiasis is generally asymptomatic but may cause specific syndromes:

• Gastrointestinal: Epigastric pain, postprandial fullness, heartburn, intermittent diarrhoea and constipation
• Less common: faecal occult blood (FOB) or massive colonic and gastric haemorrhage
• Skin: Chronic urticaria, _________________ (recurrent serpiginous maculopapular or urticarial rash along the buttocks, perineum, thighs → may advance as rapidly as 10cm/hour)
• Rare: Arthritis, cardiac arrhythmias, chronic malabsorption, duodenal obstruction, nephrotic syndrome, recurrent asthma
• Up to 75% have mild peripheral eosinophilia or elevated IgE levels.

Answer 16

Localised pruritic erythematous;

Dry cough;

pathognomonic larva currens

Question 17

For patients receiving high-dose corticosteroids (e.g. for asthma, COPD), impaired host immunity may cause the subclinical infection to progress to an __________________
• Overwhelming number of migrating larvae to numerous organs
• Patients with HIV/AIDS can have disseminated strongyloidiasis or hyperinfection syndrome, but there is no increased risk
• Multi-system manifestations: recurrent Gram-negative bacteraemia/sepsis from larvae carrying bacteria which penetrate intestinal mucosal walls
• If left untreated, the mortality rates may approach 90%

Answer 17

accelerated autoinfection:

Question 18

The gold standard of diagnosis is a __________________ (sensitivity is limited for Strongyloides → requires 7 stool exams for ~100% sensitivity):
• Other specialised stool exams exist (lab-dependent)
• Disseminated strongyloidiasis: larvae seen on_______________ from BAL fluid, sputum, or pleural fluid
• Serology is sensitive and used regularly (but cross-reacts with other filarial parasites, schistosomes, and Ascaris lumbricoides → decreases specificity)

Answer 18

serial stool examination;

simple wet mount

Question 19

[Strongyloides: Treatment]
Uncomplicated infection
- __________________ either consecutive days or 2 weeks apart
- _________________

Disseminated disease/ hyperinfection syndrome

• If possible, immunosuppressive therapy should be stopped or reduced
• Ivermectin,200 µg/kg per day orally, duration depends on clinical response, and until stool and/or sputum exams are negative for 2 weeks (one autoinfection cycle)

Answer 19

Ivermectin 200 µg/kg 2 single doses;

Albendazole 400mg BD 3-7 days