Fatal Strongyloides Hyperinfection Syndrome in an Immunocompromised Patient

Background

Manifestations of Strongyloides stercoralis infection in an immunocompromised host can range from asymptomatic eosinophilia to a life-threatening hyperinfection syndrome that includes cutaneous, gastrointestinal, and pulmonary symptoms. Therefore, Strongyloides hyperinfection should be suspected in any immunosuppressed patient with unexplained GI symptoms who has been exposed to the parasite or who has unexplained eosinophilia [1]. We present here a case report of S. stercoralis hyperinfection in a 76-year-old man with membranous glomerulopathy, who was receiving immunosuppression in the form of corticosteroids and cyclophosphamide.

Case Report

A 76-year-male patient from Guyana with membranous glomerulopathy secondary to chronic NSAID use came to the Emergency Department with diarrhea, diffuse abdominal pain, and tenesmus that had started 6 weeks after the initiation of oral cyclophosphamide [100-mg oral tablet twice a day] and prednisone [30-mg oral tablet daily]. He was diagnosed with membranous glomerulopathy 2 months prior to admission, proven by renal biopsy. Baseline creatinine was 1.14. Upon admission, his laboratory workup was as indicated in Table 1.

The patient had visited Guyana 10 years previously, but had no other significant travel history. He was admitted with the impression of gastroenteritis/colitis and intravenous hydration and antibiotics (ciprofloxacin and metronidazole) were administered. The suspicion of bacterial gastroenteritis was also entertained, as he was on immunosuppressive therapy. Stool cultures were taken on admission, and were negative.

Gastroenterology was consulted because of a drop in hemoglobin, but the patient went into hypercapnic respiratory failure and required bilevel positive airway pressure [BiPAP] before endoscopy/colonoscopy could be performed. A CT chest scan was performed, which showed small bilateral pleural effusions, micronodules, ground glass opacities, and consolidations in both lungs. BiPAP improved the gas exchange but the patient’s condition continued to deteriorate during his hospital stay, with persistent diarrhea and severe renal failure that eventually required hemodialysis. ELISA testing for HIV and hepatitis B and C panel was negative. HTLV testing was not performed. Strongyloides stercoralis larvae were seen on examination of the stool for ova and parasites. An infectious disease team was consulted, the determination of Strongyloides hyperinfection syndrome was made, and the patient was started on Ivermectin. The patient’s respiratory status began to deteriorate, with desaturation even on BiPAP, and he finally required intubation. Antibiotic coverage was broadened to include Vancomycin, Imipenem, and Gentamicin. The patient did not improve and died a few days later with the diagnosis of Strongyloides hyperinfection syndrome complicated by bacterial septicemia. Later, on review of the patient’s laboratory data, it was found that he had persistent eosinophilia [WBC 13 with 20% eosinophils] even prior to the beginning of Cyclophosphamide/steroids. The eosinophilia was attributed to chronic NSAID use [ibuprofen and naproxen] and no investigation had been conducted to assess any potential parasitic infestation before initiating immunosuppression.

Discussion

Strongyloides is unique among the commonly occurring helminths, as it can complete its life cycle within the human host, thereby allowing it to persist and replicate indefinitely. In the life cycle of other helminths, such as hookworms and roundworms, 1 larva gives rise to only 1 adult worm. Strongyloides infection, in contrast, can lead to autoinfection in which rhabditiform larvae can re-penetrate the gastrointestinal mucosa or the perianal skin [2,3]. Hyperinfection syndrome exacerbates the gastrointestinal and pulmonary symptoms and increased numbers of larvae may be detected in stool and/or sputum [4]. This commonly establishes a latency that results in asymptomatic, chronic autoinfection of the gut, where it can remain undetected for years (the longest latency recorded is approximately 65 years) [5]. The autoinfection, which is reactivated during immunosuppression, can result in a life-threatening Strongyloides hyperinfection syndrome that is characterized by increased numbers of filariform larvae in the stool and sputum. Clinical manifestations of the increased parasite burden and migration are gastrointestinal bleeding and respiratory distress with high mortality rates (up to 87%) [6]. Inherently, patients with the nephrotic syndrome in membranous glomerulopathy are susceptible to infection [7] due to the impairment of normal defense mechanisms. Several hypotheses for this susceptibility have been advanced, including urinary loss of protein [8] leading to decreased immune globulin G, immunologic defect [9], decreased serum factor B [10], or lymphocytotoxins associated with certain renal diseases [11]. Inhibition of Th2 cell-mediated, humoral, or mucosal immunity with corticosteroid use is the most frequent risk factor for hyperinfection syndrome [12]. There is no definitive criterion standard for diagnosing Strongyloides stercoralis infection. Stool examination is the primary technique used for the detection of strongyloides larva, with a sensitivity of 50% if 3 consecutive daily samples are examined, and sensitivity reaching 100% if 7 consecutive daily stool specimens are examined in a specialized laboratory [13]. Serological testing for Strongyloides, like ELISA IgG antibody tests, has an approximate sensitivity of 90% for patients from non-endemic areas, but has potential false-positive results [14]. Agar plate culture method is a newer method, with infection detection rates 2–3 times higher than those estimated by the other methods [15].

Conclusions

Most of the deaths from helminthic infections in United States result from S. stercoralis hyperinfection [16]. Although pre-transplant patients are evaluated routinely for infection, thorough assessment for parasitic infections is not conducted in non-transplant patients. Even though it is endemic primarily to tropical and subtropical regions, it is still prevalent in the Unites States due to its long latency periods and the large immigrant population. Given the high mortality rates [17] of hyperinfection syndrome, as well as the preventable nature of the condition, it is vital that a detailed workup for this parasitic infection is conducted before initiating immunosuppression in any patient with eosinophilia.