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A-65 Year-Old Heart Transplant Recipient with Abdominal Pain and Altered Mental Status 

A-65 Year-Old Heart Transplant Recipient with Abdominal Pain and Altered Mental Status
Chapter:
A-65 Year-Old Heart Transplant Recipient with Abdominal Pain and Altered Mental Status
Author(s):

Daniel Caplivski

and W. Michael Scheld

DOI:
10.1093/med/9780199735006.003.0045
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Case Presentation

A 65-year-old man from the Dominican Republic was admitted with a 2-day history of fever, rigors, abdominal pain, and confusion. The patient had a history of diabetes mellitus, hypertension, and ischemic cardiomyopathy. Four months prior to admission, he underwent an uncomplicated orthotopic heart transplant. He had no prior history of rejection, and he was maintained on tacrolimus, mycophenolate mofetil, and prednisone. He worked as a building superintendant and had not traveled back to the Dominican Republic in over 30 years.

The patient was agitated and febrile to 102.7° F with an otherwise unremarkable physical examination. His laboratory results were significant for hyponatremia (sodium 125 meq/l), mild renal insufficiency, (1.5 mg/dl), and hyperglycemia (156 mg/dl). His peripheral white blood cell count was normal (5.8 x103/μ‎l) without a leukocytosis or eosinophilia. Broad-spectrum antimicrobials were initiated for a possible systemic infection, after blood, sputum, and urine cultures were collected. Initially he defervesced, but 48 hours later he had recurrence of fevers accompanied by watery diarrhea, dyspnea, and a nonproductive cough. He became increasingly tachypneic and hypotensive, and subsequently required ventilator and vasopressor support. A petechial and purpuric rash abruptly developed over the chest and abdomen (Figure 9e.1). Radiographs of the lungs, which had been unremarkable on admission, now revealed diffuse interstitial infiltrates and bilateral consolidations (Figures 9e.2 and 9e.3).

Figure 9e.1 Diffuse petechial and purpuric rash on chest and abdomen.

Figure 9e.1
Diffuse petechial and purpuric rash on chest and abdomen.

Figure 9e.2 Chest radiograph, anterior posterior view with diffuse bilateral alveo-lar infiltrates and right sided pleural effusion.

Figure 9e.2
Chest radiograph, anterior posterior view with diffuse bilateral alveo-lar infiltrates and right sided pleural effusion.

Figure 9e.3 CT scan chest, axial view with diffuse bilateral infiltrates and right sided pleural effusion.

Figure 9e.3
CT scan chest, axial view with diffuse bilateral infiltrates and right sided pleural effusion.

After prolonged incubation, blood and sputum cultures grew a KPC carbapenemase-producing Klebsiella pneumoniae. One week into his hospitalization, the patient was not arousable off sedation, and blood cultures continued to grow the same K. pneumoniae despite systemic polymyxin B. Non-contrast head CT was unremarkable, and lumbar puncture revealed an elevated protein (953 mg/dl), hypoglycorrhachia (glucose 〈10mg/dl), and a neutrophilic pleocytosis (650 WBC/ml, 85% polymorphonuclear cells). Cerebrospinal fluid cultures also grew K. pneumoniae. The patient was treated with both systemic antimicrobials, and intrathecal polymyxin B and gentamicin. A supervisor in the microbiology laboratory noted serpentine tracks of K. pneumoniae on an agar plate of the patient’s bronchoalveolar lavage (Figure 9e.4). She performed wet mounts of the lavage sample, and discovered many motile Strongyloides stercoralis filariform larvae (Figure 9e.5).

Figure 9e.4 Sputum culture on MacConkey agar and chocolate agar. The colonies of Klebsiella pneumoniae where being dragged across the plate in serpiginous tracks.

Figure 9e.4
Sputum culture on MacConkey agar and chocolate agar. The colonies of Klebsiella pneumoniae where being dragged across the plate in serpiginous tracks.

Figure 9e.5 Wet mount of sputum revealed many motile larvae of Strongyloides stercoralis.

Figure 9e.5
Wet mount of sputum revealed many motile larvae of Strongyloides stercoralis.

Despite administration of ivermectin and thiabendazole via nasogastric tube, and daily ivermectin retention enemas, the patient demonstrated little neurologic recovery. Magnetic resonance imaging revealed a discrete abscess in caudate nucleus, as well as diffuse enhancement of the ventricles (Figure 9e.6). Due to the overall grave prognosis, palliation was pursued and the patient expired.

Figure 9e.6 MRI brain, axial view revealed a discrete abscess in the right caudate nucleus as well as diffuse enhancement of the ventricles.

Figure 9e.6
MRI brain, axial view revealed a discrete abscess in the right caudate nucleus as well as diffuse enhancement of the ventricles.

Case 9e Discussion: Strongyloides stercoralis

Clinical Features and Diagnosis

Strongyloides stercoralis is prevalent in tropical and subtropical climates. Areas of endemicity include Central and South America, Asia, Africa, the Caribbean, the southeastern United States, and Mexico. S. stercoralis has the ability to autoinfect a single human host and establish a latent infection that can persist asymptomatically for years. Hyperinfection occurs when the autoinfection process accelerates in the setting of immunosuppression, either from underlying medical conditions or medications like corticosteroids or antithymocyte immunoglobulin. Strongyloides hyperinfection syndrome (SHS) has been associated with mortality rates of as high as 87% in the immunocompromised host.

Primary strongyloidiasis begins with filariform larvae transcutaneously infecting the human host. These larvae travel through the venous circulation to the lungs, where they penetrate the alveoli. They then travel to the pharynx and are subsequently ingested. Larvae mature into adult worms within the gastrointestinal tract, and eggs are deposited within the intestinal mucosa. The hatched rhabditiform larvae are either excreted into stool or develop into filariform larvae within the intestinal tract. Autoinfection occurs when these filariform larvae migrate through the bowel wall, or through the perianal skin, into the venous circulation (Figure 9e.7). A creeping purpuric rash in the perianal or pelvic area, “larva currens,” is often suggestive of autoinfection. In the setting of endogenous or exogenous immunosuppression, the autoinfection cycle is accelerated. Massive larval migration through the lungs causes respiratory symptoms that may be as mild as cough and wheezing, to as life-threatening as acute respiratory distress syndrome and respiratory failure. Gastrointestinal symptoms range from diarrhea and abdominal pain to paralytic ileus and intestinal obstruction. The high volume parasitic migration can also lead to the development of diffuse larva currens. Biopsy of these lesions can reveal migrating larvae. Bacteremias with enteric flora are often suggestive of SHS in the appropriate host. SHS should always be considered in the differential when treating patients with Gram-negative meningitis. Visualization of larvae on biopsy or on ova, and parasite examination of stool or sputum, is diagnostic. Tracking of bacterial colonies on solid culture media is also suggestive.

Figure 9e.7 Lifecycle of Strongyloides stercoralis. Source: Centers for Disease Control and Prevention http://www.dpd.cdc.gov/dpdx.

Figure 9e.7
Lifecycle of Strongyloides stercoralis. Source: Centers for Disease Control and Prevention http://www.dpd.cdc.gov/dpdx.

In solid organ transplantation, most reported cases of SHS are the result of reactivation of latent infection in the setting of intensified immunosuppression.1 Most reports describe patients presenting within the first 3 months after transplantation. In retrospect, many case patients had evidence of occult infection prior to transplantation, including unexplained intermittent eosinophilia, chronic gastrointestinal symptoms, or a history of another intestinal parasitic infection.2 Primary Strongyloides infection in areas of endemicity and donor-derived primary infection are rare, but have been described.3

Often the diagnosis of SHS in the solid organ transplant recipient is serendipitous, as in the described case. The critical nature of Gramnegative bacteremia, respiratory failure, or altered mental status can delay the diagnosis. Hallmarks of parasitic infections like diarrhea or eosinophilia are usually absent in the setting of SHS. A thorough history, including a detailed travel history and review of any augmentation or changes in immunosuppressive medications, can be helpful.

Management

The ideal treatment of SHS is not well established. Single dose ivermectin is the treatment of choice in immunocompetent patients with intestinal strongyloidiasis. Treatment duration for SHS using thiabendazole monotherapy ranges from 5 to 14 days. More aggressive regimens for SHS employ thiabendazole or albendazole and ivermectin for variable durations. Many patients require multiple courses of therapy because of persistent parasitosis. It has been suggested that survivors of SHS should be treated monthly for at least 6 months. Reactivation can occur in transplant recipients even after initial treatment. These patients may benefit from indefinite therapy, but studies to support this practice are lacking.

A challenge in the treatment of SHS is that patients often suffer from paralytic ileus or intestinal obstruction, preventing both administration and absorption of oral agents. No accepted parenteral therapy exists, but employment of alternative treatment modalities such as subcutaneous and rectal formulations of ivermectin have been described.4,5

Pretransplant Evaluation

This case highlights the importance of developing strategies to prevent Strongyloides infections in transplant recipients. Donors and recipients who have resided in endemic areas should be screened for latent strongyloidiasis prior to transplantation. Those with a history of other helminthic infections, unexplained eosinophilia, or unexplained gastrointestinal complaints should also be screened. Serology may be less sensitive in relatively immunocompromised patients, and diagnostic yield may be greater with concomitant examination of stool for ova and parasites. Transplant candidates with evidence of Strongyloides infection should be treated with either thiabendazole 25 mg/kg twice daily for three days, or ivermectin 200 mcg/kg once daily for two days with documented negative stool ova and parasite exams prior to transplantation. At the time of transplantation, with the initiation of high-dose immunosuppression, treatment should be reinitiated. Family members and pets should also be screened and treated as potential sources of reinfection post-transplant.

Pretransplant screening of the deceased donor prior to organ procurement is not practical. Targeted serologic screening for Strongyloides in donors from endemic areas may provide useful information for the physicians caring for the recipients of organs from an untreated cadaveric donor with latent Strongyloides. Although formal studies are lacking, preemptive treatment in these recipients may prevent disease.

References

1. Roxby AC, Gottlieb GS, Limaye AP. Immunocompromised hosts: Strongyloidiasis in transplant patients. Clin Infect Dis 2009;49:1411–1423.Find this resource:

2. Schaeffer MW, Buell JF, Gupta M, Conway GD, Akhter SA, Wagoner LE. Strongyloides hyperinfection syndrome after heart transplantation: case report and review of the literature. J Heart Lung Transplant. 2004;23:905–911.Find this resource:

3. Patel G, Arvelakis A, Sauter BV, Gondolesi GE, Caplivski D, Huprikar S. Strongyloides hyperinfection syndrome after intestinal transplantation. Transpl Infect Dis. 2008;10: 137–141.Find this resource:

4. Tarr PE, Miele PS, Peregoy KS, Smith MA, Neva FA, Lucey DR. Case Report: Rectal administration of ivermectin to a patient with Strongyloides hyper-infection syndrome. Am J Trop Med Hyg. 2003;68:453–455.Find this resource:

5. Marty FM, Lowry CM, Rodriguez M, et al. Treatment of human disseminated Strongyloidiasis with a Parenteral veterinary formulation of ivermectin. Clin Infect Dis. 2005;41:5–8.Find this resource: