Strongyloides hyperinfection: a preventable complication of immunosuppression

Clinical record

A 70‐year‐old man of non‐English speaking background migrated from Vietnam to Melbourne, Victoria, in 2007. In October 2019, he was diagnosed with plasmablastic lymphoma and commenced chemotherapy with rituximab, etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin. Before chemotherapy, he was screened for tuberculosis using QuantiFERON‐TB Gold (QIAGEN) and for blood‐borne viruses using serology. Twelve days after his third cycle of chemotherapy, he developed pain in the left iliac fossa, anorexia, rigors and a dry cough.

On presentation, he was febrile (39°C) and in septic shock. He required intensive care for inotropic support and was prescribed piperacillin–tazobactam following blood culture collection. Investigations revealed pancytopenia, with neutropenia 0.2×10⁹/L (reference interval [RI], 2.0–8.0×10⁹/L) and an eosinophil count of 0.1×10⁹ (RI, 0.0–0.5×10⁹/L). Inflammatory markers were elevated, with C‐reactive protein 237mg/L (RI, <5mg/L). Blood cultures did not reveal bacteraemia. Computed tomography of the abdomen and pelvis demonstrated multifocal colonic inflammation.

He then developed non‐bloody diarrhoea, and general faecal microscopy and culture revealed multiple parasites consistent with filariform Strongyloides stercoralis (Box). Harada‐Mori culture was examined after 24 hours using light microscopy demonstrating characteristic thrashing motility (, video). S. stercoralis serology was negative. He commenced daily oral ivermectin for 14days, with stool examination at day 13 of treatment confirming clearance. Clinically, he responded rapidly to ivermectin, and continued chemotherapy with outpatient observation. One year after treatment he remains in remission.

Discussion

S. stercoralis is an intestinal parasitic roundworm with global prevalence which can lead to lifelong infection by way of its ability to autoinfect humans. At‐risk groups within Australia include migrants and returned travellers from tropical and subtropical regions, as well as Indigenous people from rural and remote areas of northern Australia.1 Immunocompetent people with chronic strongyloidiasis are often asymptomatic or exhibit mild respiratory or gastrointestinal symptoms with no serious sequelae.2

Patients undergoing immunosuppressive treatment are at risk of developing Strongyloides hyperinfection and dissemination due to the rapid proliferation of larvae, resulting in sepsis and multiorgan dysfunction. Exposure to high dose glucocorticoids is the strongest risk factor, with hyperinfection seen in patients receiving as little as 6days of high dose prednisolone.2 Therefore, patients receiving glucocorticoid‐containing regimes for haematological malignancies are at particularly high risk.

In immunocompromised hosts, the case fatality rate of hyperinfection is at least 60%.3 Lung infiltration results in cough, with chest infiltrates on imaging, which may progress to diffuse alveolar haemorrhage; gastrointestinal symptoms vary from diffuse bloody diarrhoea to paralytic ileus.2 Translocation of enteric bacteria accompanying larvae that penetrate through the intestinal wall can cause sepsis. Despite septic shock, we did not isolate an enteric organism in blood cultures.

Sensitivity of S. stercoralis serology for chronic infection is only 83–89%.2 Therefore, all patients currently living in endemic regions should receive ivermectin before immunosuppression, with ivermectin dosing schedules depending on serostatus.4 Patients who continue to live in or visit endemic regions should receive ongoing prophylactic ivermectin during immunosuppression, without further investigation if asymptomatic.4 Moreover, in patients who are already immunosuppressed, sensitivity of serology is further reduced, highlighting the importance of screening all patients who were born in, resided in or visited endemic regions before treatment.4

If hyperinfection is suspected, empiric treatment should include ivermectin together with broad spectrum coverage for enteric bacteria.2 Microscopy is particularly helpful in patients with hyperinfection, who are more likely to have visible larvae on direct inspection of faeces or sputum.3 Culture‐based techniques, such as the Harada‐Mori or agar plate culture, are more sensitive (72–89%) compared with microscopy alone but should not delay empirical treatment if hyperinfection is suspected.5 Due to the intermittent release of larvae, submission of multiple samples is recommended. Eighty per cent of patients with hyperinfection will not have eosinophilia at presentation, with concomitant corticosteroid therapy blunting eosinophilic responses, making eosinophilia an unreliable marker of disease.3

Although case reports show large variation in treatment regimens for hyperinfection, the accepted treatment of choice is ivermectin. Despite ivermectin being generally well tolerated, case reports of encephalopathy due to P‐glycoprotein polymorphisms have been reported.6 Albendazole monotherapy is likely inferior to ivermectin or mebendazole.3

A recent audit of screening for latent strongyloidiasis at the Royal Melbourne Hospital in patients undergoing immunosuppression demonstrated a screening rate of 38%.7 Moreover, patients from non‐English speaking backgrounds and older patients were 2.5 times less likely to be screened, despite clinician‐reported awareness of latency of infection. This case further highlights the importance of screening and pre‐emptive treatment, with vulnerable patients at particular risk of this neglected tropical disease.

Box – Faecal microscopy and culture showing parasites consistent with filariform Strongyloides stercoralis

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