Microbiology Case Study: A Man with History of ALL Presents with Fever and Diarrhea

Clinical History

A man in his 40’s with a past medical history of acute lymphoblastic leukemia/lymphoma (in remission), multiple infections including bacteremia and pulmonary aspergillosis, presented to the hospital with fever and diarrhea. Over the course of his stay, he had worsening renal function and developed profound hypotension and shock, which prompted initiation of two vasopressors and high-dose steroids. Eventually he developed acute hypoxic respiratory failure, requiring intubation. Complete blood count demonstrated an absolute eosinophilia of 8.58 x109/L (reference range 0.04-0.62 x109/L). Imaging revealed bilateral pulmonary infiltrates and a pleural effusion. Respiratory culture with gram stain was ordered for his tracheal aspirate, which revealed few polymorphonuclear cells, many gram-negative rods, yeast, and larvae of Strongyloides stercoralis (Image 1A). Wet mounts of the tracheal aspirate revealed numerous larvae and a few eggs of S. stercoralis (Image 1B-C); many of the larvae were motile (Movie 1). Stool examination of ova and parasites (O & P) were positive for larvae. Given the burden of organisms and prior administration of steroids, he was diagnosed with severe strongyloidiasis, consistent with hyperinfection. Concurrent blood cultures grew Enterococcus faecalis and Stenotrophomonas maltophilia; the respiratory culture also grew S. maltophilia, and tracks from the migrating larvae were observed on respiratory culture bacterial media (Image 1D).

Image 1. Tracheal aspirate Gram stain with S. stercoralis larvae, 100x objective magnification (A). Wet mount of tracheal aspirate revealing larvae (B) and eggs (C), 40x objective magnification. Blood agar plate growing S. maltophilia in an abnormal pattern, indicating motile larvae tracking through the agar (D).

Discussion

Strongyloidiasis is a spectrum of clinical disease caused by the nematode Strongyloides stercoralis.1,2 Descriptions of acute infection have been described in other Lablogatory entries here,3,4 and the full lifecycle is described in detail on the CDC DPDx website.5

Severe strongyloidiasis includes the syndromes of hyperinfection and disseminated disease. Hyperinfection is when there is an elevated burden of the typical autoinfection cycle involving the lungs and GI-tract. Usually there is an antecedent immunosuppressive event, such as administration of corticosteroids. Within the GI-tract lumen, increased numbers of rhabditiform larvae transform into the infective filariform larvae, which traverse the GI mucosa, migrate to the lungs via bloodstream/lymphatics where they enter alveolar air spaces, then ascend the respiratory tract, and are coughed up by the host and swallowed to re-enter the GI tract. In the GI tract adult females lay eggs through parthenogenesis, which give rise to further rhabditiform larvae. In extreme cases of hyperinfection, adults can be found in the lungs, where they may also lay eggs. Finding eggs in respiratory specimens is unusual, and may be related to the burden of disease.6

Disseminated disease is when larvae can be found in any additional organs/organ systems, such as the central nervous system, kidneys, liver, adrenals, etc. Invasive sampling is not typically performed, and larvae can be observed at autopsy.

Laboratory diagnosis of S. stercoralis involves identification of rhabditiform larvae in stool O &P exam; the presence of adults or eggs in stool is rare. Rhabditiform larvae have short buccal cavities and an ovoid genital primordium structure midway through the body (Movie 2). O&P exams can be performed on other body fluids, such as sputum and CSF. Serology can be useful to identify past exposure, especially prior to initiating immunosuppressive therapeutics such as corticosteroids. A nonspecific finding can be observed, as in this case, in the complete blood cell count and differential. Relative and absolute eosinophilia can be found in patients with parasitic infections; therefore, it is reasonable to rule out parasitic infection in this subset of patients. In the case presented here, the absolute eosinophilia was likely due to a persistent S. stercoralis infection, since these nematodes can live in the human host for decades.

The treatment of choice for severe strongyloidiasis is oral ivermectin, though albendazole is an alternative therapy. In some instances, subcutaneous ivermectin administration may be used.7

Follow-up

Oral ivermectin was administered to treat the strongyloidiasis and antibiotics were administered to treat the bacterial infections. Over the coming days, serial tracheal aspirates continued to reveal many larvae and eggs, so therapy was escalated to subcutaneous ivermectin. Over the course of therapy, the patient developed a fungemia with Candida guilliermondii. Despite aggressive antimicrobial therapy and intensive care, the patient remained hypoxemic and hypotensive. The family decided to transition to comfort measures and the patient passed away.

References

  1. Maguire JH. Intestinal Nematodes (Roundworms), in Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, B. Mandell, Dolin, Editor. 2010, Elsevier: Philadelphia, PA. p. 3577-3586.
  2. Parasitology, in Koneman’s Color Atlas and Textbook of Diagnostic Microbiology, Procop et al., Editors. 2017, Lippincott Williams & Wilkins: China. p. 1452-1454.
  3. Kaur J, Stempak L. An 81 Year Old Female with Persistent Fevers. Lablogatory 2019 [cited 2019 11/5/2019]; Available from: https://labmedicineblog.com/2019/04/23/microbiology-case-study-an-81-year-old-female-with-persistent-fevers/.
  4. Mohammed M, Wojewoda C. A 47 Year Old Male with Abdominal Pain and Diarrhea. Lablogatory 2016 [cited 2019 11/5/2019]; Available from: https://labmedicineblog.com/2016/05/16/microbiology-case-study-a-47-year-old-male-with-abdominal-pain-and-diarrhea/.
  5. Centers for Disease Control. Strongyloidiasis. DPDx 2019 [cited 2019 11/5/2019]; Available from: https://www.cdc.gov/dpdx/strongyloidiasis/index.html.
  6. Keiser PB and Nutman TB. Strongyloides stercoralis in the Immunocompromised Population. Clin Microbiol Rev, 2004. 17(1): p. 208-17.
  7. Hurlimann E and Keiser J, A single dose of ivermectin is sufficient for strongyloidiasis. Lancet Infect Dis, 2019. 19(11): p. 1150-1151.

-IJ Frame, MD, PhD, Microbiology Fellow, University of Texas Southwestern Dallas, Texas

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. he has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

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