Strongyloides Hyperinfection Syndrome and Disseminated Disease with Negative Serology

Ashton D. Hall Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;

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Divya Salibindla Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio

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Keith M. Luckett Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;

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A 65-year-old man with a history of stage IV follicular lymphoma, who discontinued rituximab monotherapy 3 weeks ago, presented with acute hypoxia and dyspnea. Laboratories revealed leukocytosis (12.6 × 103 cells/µL) with chronic eosinophilia (49%; 6,174 cells/µL). Initial concern was for eosinophilic pneumonitis or a chronic obstructive pulmonary disease exacerbation. Blood cultures and a respiratory viral panel were negative. Computed tomography pulmonary angiography revealed ground-glass opacities in the upper lobes (Figure 1). He was discharged after 5 days with levofloxacin and dexamethasone.

Figure 1.
Figure 1.

Computed tomography pulmonary angiography at the patient’s initial presentation revealed patchy ground-glass opacities in the upper lobes (red arrows, A). Chest X-ray 2 days before death revealed bibasilar airspace opacities, especially prominent within the left lung base and obscuring the left heart border, with decreased left lower lobe aeration (B). Courtesy of M. B. Burch at the University of Cincinnati.

Citation: The American Journal of Tropical Medicine and Hygiene 111, 6; 10.4269/ajtmh.24-0460

He presented 2 weeks later with dyspnea, diarrhea, abdominal pain, and a pruritic rash on the groin and legs. He denied a history of serpiginous skin eruptions but reported fishing in a reservoir 6 weeks ago. Laboratories revealed leukocytosis (21.6 × 103 cells/µL) without eosinophilia. Toxoplasma serology and blood cultures were negative. Levofloxacin, prednisone, albuterol, and tiotropium were started without clinical improvement. The patient’s code status was changed to do-not-resuscitate and do-not-intubate, which precluded bronchoscopy. Skin biopsy and sputum culture demonstrated many filariform larvae morphologically consistent with Strongyloides stercoralis (Figures 2 and 3). Stool ova and parasite studies were not done. Steroids were tapered, and he was started on ivermectin (215 µg/kg/day). He withdrew from life-saving measures owing to respiratory and renal failure. Strongyloides IgG serology was negative on samples collected 3 weeks before his first hospitalization and 1 day before death. The patient had several epidemiologic risk factors for Strongyloides hyperinfection syndrome (SHS), including a 10-year history of non-Hodgkin lymphoma, multiple courses of steroids, and recent rituximab therapy.

Figure 2.
Figure 2.

Skin examination revealed numerous 1–2-mm round, nonblanching purpuric macules involving the groin and thighs with a few well-defined, slightly scaly, red-purple papules and plaques (A). Hematoxylin and eosin stain of skin biopsy specimens from the left hip and left abdomen at 40× magnification showed filariform larvae in coronal and transverse sections (black arrows, B and C). Courtesy of K. E. Spicknall at the University of Cincinnati.

Citation: The American Journal of Tropical Medicine and Hygiene 111, 6; 10.4269/ajtmh.24-0460

Figure 3.
Figure 3.

Sputum culture with Papanicolaou staining on hospital day 7 of his second admission revealed many L3 (filariform) larvae consistent with Strongyloides stercoralis at 20Ă— and 40Ă— magnification (A and B). Courtesy of D. Salibindla at the University of Cincinnati.

Citation: The American Journal of Tropical Medicine and Hygiene 111, 6; 10.4269/ajtmh.24-0460

Strongyloides stercoralis, or threadworm, is a soil-transmitted helminth endemic to tropical, subtropical, and warm temperate climates, including Appalachia and rural parts of the southeastern United States.1 Approximately 30–100 million people worldwide have strongyloidiasis, although an accurate estimate of disease prevalence is skewed by asymptomatic infections.1 Strongyloides hyperinfection syndrome often occurs in immunocompromised patients through autoinfection, where filariform larvae penetrate the intestinal mucosa or perianal skin, increasing host worm burden, morbidity, and mortality.2 At-risk populations for SHS include transplant recipients, patients with hematologic malignancies, and patients receiving immunosuppressive medications.2 Strongyloides serology is sensitive (88–98%) but may be unreliable early in the course of illness among vulnerable populations.3,4 Patients at increased risk of SHS may benefit from empiric treatment, even when serologic testing is negative, because of its high mortality rate (15–87%) and limited physician experience with the disease outside endemic areas.2,5 Duration of ivermectin (200 µg/kg/day) relies on negative stool or sputum studies for 14 days.6

ACKNOWLEDGMENT

We acknowledge the patient and the multidisciplinary care team who contributed to his care.

REFERENCES

  • 1.↑

    Vadlamudi RS, Chi DS, Krishnaswamy G, 2006. Intestinal strongyloidiasis and hyperinfection syndrome. Clin Mol Allergy 4: 8.

  • 2.↑

    Kassalik M, Mönkemüller K, 2011. Strongyloides stercoralis hyperinfection syndrome and disseminated disease. Gastroenterol Hepatol (N Y) 7: 766–768.

  • 3.↑

    Schär F, Trostdorf U, Giardina F, Khieu V, Muth S, Marti H, Vounatsou P, Odermatt P, 2013. Strongyloides stercoralis: Global distribution and risk factors. PLoS Negl Trop Dis 7: e2288.

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    • Search Google Scholar
    • Export Citation
  • 4.↑

    Arifin N, Hanafiah KM, Ahmad H, Noordin R, 2019. Serodiagnosis and early detection of Strongyloides stercoralis infection. J Microbiol Immunol Infect 52: 371–378.

  • 5.↑

    Marcos LA, Terashima A, DuPont HL, Gotuzzo E, 2008. Strongyloides hyperinfection syndrome: An emerging global infectious disease. Trans R Soc Trop Med Hyg 102: 314–318.

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    • Export Citation
  • 6.↑

    Ramanathan R, Nutman TB, 2008. Strongyloides stercoralis infection in the immunocompromised host. Curr Infect Dis Rep 10: 105–110.

Author Notes

Authors’ contributions: A. D. Hall: Conceptualization, Writing – original draft preparation, Figures 1–3, and revisions. D. Salibindla: Writing – reviewing and editing, Figure 3. K. M. Luckett: Supervision, Writing – reviewing and editing.

Current contact information: Ashton D. Hall and Keith M. Luckett, Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, E-mails: hall3ah@mail.uc.edu and lucketkm@ucmail.uc.edu. Divya Salibindla, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, E-mail: salibida@ucmail.uc.edu.

Address correspondence to Ashton D. Hall, Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, 3230 Eden Ave., Cincinnati, OH 45267. E-mail: hall3ah@mail.uc.edu
  • Figure 1.

    Computed tomography pulmonary angiography at the patient’s initial presentation revealed patchy ground-glass opacities in the upper lobes (red arrows, A). Chest X-ray 2 days before death revealed bibasilar airspace opacities, especially prominent within the left lung base and obscuring the left heart border, with decreased left lower lobe aeration (B). Courtesy of M. B. Burch at the University of Cincinnati.

  • Figure 2.

    Skin examination revealed numerous 1–2-mm round, nonblanching purpuric macules involving the groin and thighs with a few well-defined, slightly scaly, red-purple papules and plaques (A). Hematoxylin and eosin stain of skin biopsy specimens from the left hip and left abdomen at 40× magnification showed filariform larvae in coronal and transverse sections (black arrows, B and C). Courtesy of K. E. Spicknall at the University of Cincinnati.

  • Figure 3.

    Sputum culture with Papanicolaou staining on hospital day 7 of his second admission revealed many L3 (filariform) larvae consistent with Strongyloides stercoralis at 20Ă— and 40Ă— magnification (A and B). Courtesy of D. Salibindla at the University of Cincinnati.

  • 1.

    Vadlamudi RS, Chi DS, Krishnaswamy G, 2006. Intestinal strongyloidiasis and hyperinfection syndrome. Clin Mol Allergy 4: 8.

  • 2.

    Kassalik M, Mönkemüller K, 2011. Strongyloides stercoralis hyperinfection syndrome and disseminated disease. Gastroenterol Hepatol (N Y) 7: 766–768.

  • 3.

    Schär F, Trostdorf U, Giardina F, Khieu V, Muth S, Marti H, Vounatsou P, Odermatt P, 2013. Strongyloides stercoralis: Global distribution and risk factors. PLoS Negl Trop Dis 7: e2288.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Arifin N, Hanafiah KM, Ahmad H, Noordin R, 2019. Serodiagnosis and early detection of Strongyloides stercoralis infection. J Microbiol Immunol Infect 52: 371–378.

  • 5.

    Marcos LA, Terashima A, DuPont HL, Gotuzzo E, 2008. Strongyloides hyperinfection syndrome: An emerging global infectious disease. Trans R Soc Trop Med Hyg 102: 314–318.

    • PubMed
    • Export Citation
  • 6.

    Ramanathan R, Nutman TB, 2008. Strongyloides stercoralis infection in the immunocompromised host. Curr Infect Dis Rep 10: 105–110.

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