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Abstract & Commentary
Strongyloidiasis in a Patient with HTLV-1 Infection
By Maria D. Mileno, MD, Director, Travel Medicine, The Miriam Hospital, and Associate Professor of Medicine, Brown University, Providence, RI
Peter Ackerman, MD, is an Infectious Disease Fellow, The Miriam Hospital, Brown University.
Drs. Mileno and Ackerman report no financial relationship to this field of study. This article originally appeared in the August 2011 issue of Travel Medicine Advisor. At that time it was peer reviewed by Lin Chen, MD, Assistant Clinical Professor, Harvard Medical School; Director, Travel Medicine Center, Mt. Auburn Hospital, Cambridge, MA. Dr. Chen has received research grants from the Centers for Disease Control and Prevention and Xcellerex.
Synopsis: The risk of travelers acquiring acute strongyloidiasis while walking barefoot in tropical and subtropical areas is highlighted in a case published in the Journal of Travel Medicine, and presented at the annual meeting of the Infectious Disease Society of America.
Sources: Caumes E, Keystone J. Acute strongyloidiasis: A rarity. Chronic strongyloidiasis: A time bomb! J Travel Med 2011;18:71-72; Wang S, Ackerman P. Disseminated cryptococcosis in Liberian Female with new Diagnosis of HTLV-1 and Adult T-cell Leukemia. Submitted for presentation at the Annual meetings of the Infectious Disease Society of America. Boston, MA; October, 2011.
A 58-year-old Liberian-born woman was in excellent general health, living and working in a large academic medical center in Rhode Island for more than 20 years, when she developed nonspecific gastrointestinal symptoms and underwent endoscopy, which revealed Strongyloides stercoralis larvae on a duodenal biopsy in March 2010. Symptoms resolved with ivermectin therapy. No immunologic work-up was performed.
In February 2011 the patient began to experience fevers, night sweats, non-productive cough, and shortness of breath. Her symptoms were refractory to outpatient management and she was briefly admitted to the hospital on two separate occasions in early March. Chest radiographs showed a persistent left upper lobe consolidation. She had mild neurologic complaints during those admissions, including headache and dizziness. She was discharged each time with a diagnosis of community-acquired pneumonia and treated with oral antibiotics.
Two days after her second hospital discharge she returned to the emergency room with meningismus. At that time a lumbar puncture showed an opening pressure of 30 cm H2O and a WBC count of 23 with 56% neutrophils, 20% monocytes, and 14% lymphocytes. The cerebrospinal fluid (CSF) protein and glucose were within normal limits (42 mg/dL and 54 mg/dL, respectively). Routine gram stain demonstrated many yeast forms and special staining showed encapsulated fungal elements consistent with Cryptococcus infection. Serum cryptococcal antigen was positive with a titer > 1:256. Ultimately, CSF, blood, and urine cultures grew Cryptococcus neoformans. The patient clinically improved during her 2-week course of induction therapy with liposomal amphotericin B (5 mg/kg IV daily) and flucytosine (25 mg/kg every 6 hours) followed by consolidation therapy with fluconazole 800 mg, daily, prior to her discharge. Epidemiologic investigation did not reveal any obvious cryptococcal exposure risk in this compromised host.
Rapid HIV and HIV-ELISA tests were negative. Analysis of the patient's peripheral blood smear showed a very small subset of small to medium sized lymphoid cells with irregularly lobulated nuclei resembling "flower-like cells." Flow cytometry immunophenotype was most consistent with adult T-cell leukemia-lymphoma. Serologic and nucleic acid testing confirmed a new diagnosis of human T-cell lymphotropic virus-type 1 (HTLV-I).
Multiple sputum and urine samples were negative on staining for acid-fast organisms, and mycobacterial cultures showed no growth to date. Strongyloides serological testing and direct microscopy of stool for ova and parasites were negative. The patient's CD4+ cell count was 203 cells/µL (11.3%) and she received prophylactic doses of trimethoprim-sulfamethoxazole. Given the grave prognosis for adult T-cell leukemia, the patient underwent a staging CT of the abdomen and pelvis, which showed extensive retroperitoneal lymphadenopathy. The hematology oncology and infectious disease consultants have been justifiably concerned about potential Strongyloides stercoralis hyperinfection, if and when chemotherapy must be initiated for this immunocompromised patient.
Caumes and Keystone discuss the presentation of chronic strongyloidiasis as one that is usually asymptomatic or as seen in our patient with mild gastrointestinal symptoms and occasionally peptic ulcer-like symptoms. Disseminated infection resulting from decreased cell-mediated immunity is a clear possibility in our patient with HTLV- 1 infection and profound depression of CD4+ cell counts. The authors cite additional references that describe mortality rates ranging from 50% to 87% even with treatment. Our patient has presumably carried this infection for at least 20 years — since she moved to the United States from Liberia. This is made possible by the fascinating property of the nematode to persist via autoinfection of the host. Although this disease has classically been associated with immigration, recent Canadian data showed numerous cases of strongyloidiasis in tourists.1 Of 43 travelers with strongyloidiasis in Canada, the infection was associated with visiting friends and relatives in 37% of cases, tourism in 30%, and immigration in only 21%.
The patient was treated with the recommended course of ivermectin 200 µg/kg for 2 days in 2010. Although we cannot presently demonstrate larvae or serologic evidence of disease, we chose to presumptively repeat the regimen again in anticipation of potential life-threatening disseminated strongyloidiasis and hyperinfection syndrome.
Acute T-cell leukemia (ATL) is characterized by clonal proliferation of CD4+ T cells that may be identified on peripheral blood smear by their hyperlobulated nuclei (referred to as "flower cells"). There are actually four distinct clinical forms of ATL. The smoldering subtype, seen in this patient, is the least common and generally has a more favorable prognosis with median survival of more than 5 years. While there are no standard treatment recommendations for the management of HTLV-I disease, progressive adult T-cell leukemia-lymphoma is generally treated with conventional chemotherapeutic regimens such as cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP). Combination therapy with nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT), plus interferon-alpha may also be effective. The clonal CD4+ T cells proliferating during this process are numerous, yet they are clearly ineffective against opportunistic pathogens. For example, infections associated with Cryptococcus neoformans are typically seen in patients with compromised cell-mediated immunity such as those with advanced HIV infection or, much less commonly, HTLV-1 infections. The most common clinical manifestation of cryptococcal disease is meningitis, which can present with little or no meningeal signs.
HTLV-1 is a human retrovirus that infects an estimated 10-20 million people worldwide. Transfer of bodily fluids such as breast milk, blood, or genital secretions is the primary means of transmission. Endemic in parts of the South American, Asian, and African continents, it rarely causes clinical disease in infected individuals (~5% lifetime risk). Primary disease manifestations include HTLV-I-associated myelopathy (HAM) or adult T-cell leukemia-lymphoma (ATL). Its association with strongyloidiasis is well described and our case is presented both here and at the annual meetings of the Infectious Disease Society of America to illustrate the complexities involved in diagnosing and treating immunocompromised hosts, as well as the insidious nature of infection with Strongyloides stercoralis.