Helminth Serology

Helminth serology detects antibodies to parasitic worms when direct detection of eggs, larvae or adult worms is not possible or too insensitive. Tests are enzyme immunoassays, immunoblots, indirect haemagglutination and rapid immunochromatographic assays, usually for IgG (and for some, IgG4).

Targets include Strongyloides stercoralis, schistosomes, filariae (Wuchereria, Brugia, Onchocerca, Loa), Toxocara, Echinococcus (hydatid), Taenia solium (cysticercosis), Trichinella, Fasciola and Ascaris in selected circumstances. Serology shows exposure and is often unable to separate past from active infection, so it is interpreted with eosinophil count, imaging and parasite detection.

Soil transmitted helminths affect about 1.5 billion people. Schistosomiasis affects over 200 million people (90% in Africa), lymphatic filariasis about 50 million, onchocerciasis about 20 million, strongyloidiasis 100 to 370 million, cysticercosis over 50 million with neurocysticercosis the commonest cause of acquired epilepsy in endemic regions, and cystic echinococcosis about 1 million. Eosinophilia in a returning traveller or migrant is the usual trigger for testing.

Components.

• Strongyloides IgG. Sensitivity 85 to 95% and specificity 90 to 95%. Used for screening before immunosuppression (steroids, transplant, chemotherapy) in anyone who has lived in or visited endemic areas, because autoinfection allows persistence for decades and hyperinfection with Gram negative sepsis can be fatal. Stool microscopy and culture have sensitivity of only 30 to 70% from a single sample.
• Schistosoma IgG. Detects infection 6 to 8 weeks after exposure. Cross-reaction between species. Positive serology persists for years after treatment, and cannot date infection. Eggs in urine (Schistosoma haematobium) or stool (S. mansoni, S. japonicum) or rectal biopsy confirm active disease, and circulating anodic or cathodic antigen in urine is used for active infection.
• Filarial antibodies and antigen. Wuchereria bancrofti circulating filarial antigen (immunochromatographic card) is the preferred test for lymphatic filariasis in adults. Night blood film (10 pm to 2 am) detects microfilariae. Onchocerca IgG4 (Ov16) with skin snip. Loa loa microfilariae in daytime blood film (10 am to 2 pm) before ivermectin because of risk of encephalopathy at loads over 20 000 in each mL.
• Toxocara IgG (ELISA). Visceral and ocular larva migrans, with eosinophilia. Titres over the cut off with compatible illness, and ocular disease may have low serum titres with positive intraocular fluid antibody.
• Echinococcus IgG. Cystic echinococcosis (E. granulosus) sensitivity 80 to 95% for liver cysts and 50 to 60% for lung cysts, with false negatives for calcified or inactive cysts. Alveolar echinococcosis (E. multilocularis) with Em2 and Em18 antigens.
• Taenia solium cysticercosis antibody (enzyme linked immunoelectrotransfer blot, EITB). Sensitivity over 90% for multiple lesions and 50 to 60% for a single lesion, with specificity near 100%. Diagnosis rests on imaging (CT or MRI showing cystic lesions with scolex, calcifications).
• Trichinella IgG. Positive from week 3 to 5 of infection, with muscle pain, fever, periorbital oedema and eosinophilia.
• Fasciola IgG. Positive from 2 to 4 weeks after infection, before eggs appear in stool (3 to 4 months).

Indications. Unexplained eosinophilia (over 0.5 x 10^9/L, or over 1.5 x 10^9/L when persistent) in a migrant or traveller. Before immunosuppression or transplantation in people from endemic regions (Strongyloides). Haematuria in a patient who swam in African freshwater (schistosomiasis). Lymphoedema, hydrocoele or elephantiasis.

Subcutaneous nodules, pruritus, eye disease (onchocerciasis). Liver or lung cysts on imaging. Epilepsy in a person from an endemic region with brain lesions. Myalgia, fever and facial swelling after eating undercooked meat. Screening of refugees and migrants.

Specimen. Serum 1 to 2 mL, no fasting. Stable for days at 2 to 8 °C and longer frozen. For parasite detection: stool (three samples on different days), terminal urine (collected between 10 am and 2 pm), night or day blood, skin snips, cyst fluid, CSF and tissue.

Reference values. All helminth antibody and antigen tests are negative in healthy people without exposure. Results are reported as negative, equivocal or positive with index or titre, with the cut off set by each manufacturer. Absolute eosinophil count normal range: 0.04 to 0.4 x 10^9/L.

Interpretation.

• Positive serology with eosinophilia and compatible exposure: probable infection, treatment decided with the species identified and parasite detection where possible.
• Positive serology and negative parasite tests: possible low burden infection, cleared infection or cross-reaction. Treatment is often given in strongyloidiasis (before immunosuppression) and in selected schistosomiasis.
• Negative serology does not exclude infection in early disease (first 4 to 12 weeks), in immunosuppressed patients, in low burden or calcified disease, and for some species.
• Persistent eosinophilia with negative tests: repeat serology and parasite tests, consider empirical ivermectin in strongyloidiasis risk groups, and exclude drug reactions, atopy, lymphoma, hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis.
• Falling titres over 6 to 12 months suggest treatment response in Strongyloides and Echinococcus, but not in schistosomiasis or toxocariasis.
• Cross-reactivity between helminths (filaria, Strongyloides, Toxocara, Ascaris) gives false positives, and species specific tests or immunoblots confirm.

Critical values and findings needing immediate action.

• Strongyloides hyperinfection or disseminated disease (fever, abdominal pain, ileus, pulmonary infiltrates, Gram negative bacteraemia or meningitis) in a patient on steroids or immunosuppressed: urgent ivermectin, antibiotics, reduction of immunosuppression and intensive care.
• Positive Strongyloides serology before steroids or transplant: treat with ivermectin before or alongside immunosuppression.
• Loa loa microfilaraemia over 20 000 in each mL: avoid ivermectin (risk of fatal encephalopathy) and specialist advice.
• Neurocysticercosis with raised intracranial pressure or hydrocephalus: steroids and neurosurgical review before antiparasitic treatment.
• Hydatid cyst with signs of rupture, anaphylaxis, biliary obstruction or infection: urgent surgical and anthelmintic management.
• Acute schistosomiasis (Katayama fever) with neurological symptoms (spinal cord or cerebral): urgent steroids and praziquantel.

Interferences and pitfalls.

• Serology cannot distinguish active from past infection for most helminths, and persistent positivity after cure is common (schistosomiasis, filariasis).
• Cross-reactions between helminths are frequent, and a positive Strongyloides assay in a filariasis endemic patient may be filarial.
• Immunosuppressed and elderly patients have low antibody responses, and false negatives occur.
• A single stool examination misses over 50% of Strongyloides and schistosomal infections, so three samples, concentration techniques and agar plate culture are needed.
• Eosinophilia may be absent in disseminated strongyloidiasis, in steroid treatment and in chronic infection.
• Treatment can cause reactions: Mazzotti reaction after ivermectin or diethylcarbamazine in onchocerciasis, encephalopathy in loiasis, seizure exacerbation in neurocysticercosis, and rupture of hydatid cysts with albendazole alone.
• Ocular cysticercosis and onchocerciasis require ophthalmological assessment before treatment.
• Imaging (ultrasound, CT, MRI) is central in echinococcosis and cysticercosis, with serology as support.

Special groups.

• Children: soil transmitted helminths and toxocariasis cause growth faltering, anaemia and cognitive effects, and school based mass treatment is common.
• Pregnancy: praziquantel is used for schistosomiasis in pregnancy, and ivermectin is avoided where possible except in life threatening disease.
• Immunosuppressed, transplant and HIV patients: risk of Strongyloides hyperinfection and need for screening.
• Migrants and travellers: schistosomiasis after freshwater exposure in Africa, strongyloidiasis in those from Southeast Asia, the Caribbean, Africa and Latin America.
• Regions: co-endemicity with malaria, HIV and tuberculosis, and limited access to confirmatory tests.

Follow up tests. Full blood count with absolute eosinophils, stool examination for ova, cysts and parasites (three samples) with Strongyloides culture, urine microscopy for Schistosoma haematobium eggs, circulating antigen tests, night and day blood films, skin snips, chest radiograph, abdominal ultrasound, CT or MRI brain for cysticercosis, ophthalmology, liver function, IgE,

HIV test, HTLV-1 serology (co-risk for Strongyloides hyperinfection), and repeat eosinophil count after treatment.