Inderpreet S. Daram, MD 1. Sumanth R. Solid organ transplantation has become the therapy of choice for various types of organ failure.

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The mortality in Strongyloides hyperinfection syndrome SHS is alarmingly high. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy.

Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus CMV and strongyloidiasis had rarely been associated. Strongyloidiasis is one of the most neglected tropical diseases. An estimated million people worldwide are infected with S. Unlike other nematodes, these worms may persist in the human body for decades following initial infection. This longevity of Strongyloides is related to its unique and complex life cycle with its alternation between free-living and parasitic cycles and the propensity for autoinfection and multiplication within the infected host [ 2 ].

A review on prisoners of World War II from the United Kingdom indicated that there are still probably — veterans who remain alive in Britain and have Strongyloides infections [ 3 ]. Although infection is mild in immunocompetent patients, a severe and fatal disseminated disease tends to occur in immunocompromised patients. Hyperinfection syndrome develops when immunosuppression reduces the immune surveillance and results in augmentation of the normal life cycle of the parasite leading to a dramatic increase in the density of the larvae.

Larvae proliferate intensely in the duodenum, migrate through the bowel wall, and then move to the lungs and back to the small bowel [ 4 ]. Immunosuppression secondary to corticosteroids is the main risk factor; however, association with human T-lymphotropic virus type I HTLV-1 confection, organ transplant patients, or patients receiving chemotherapy are all at increased risk [ 5 , 6 ].

Since the presentation of the disease is nonspecific, many patients are discovered late with an anticipated poor outcome. He received basiliximab as induction therapy, followed by daily tacrolimus, prednisolone, and mycophenolate. Mycophenolate was stopped without success. Esophagogastroduodenoscopy EGD revealed mild reflux esophagitis, while sigmoidoscopy showed no significant changes. Rectal biopsy disclosed chronic inflammation with eosinophilic infiltrates; however, no parasites were identified.

Likewise, stool analysis was negative for ova and parasites. Investigation for mycobacteria was negative including sputum smear for acid-fast bacilli AFB , polymerase chain reaction PCR , and culture. Chest computerized tomography CT , abdomen, and pelvis were normal. The complete blood count was essentially normal apart from lymphopenia.

The eosinophil count was also normal. Bone marrow aspiration and culture were normal. Specific stain for Leishmania was negative. His course in hospital was complicated by an episode of confusion. Brain CT scan disclosed old ischemic changes. Cerebrospinal fluid CSF examination was not performed. He was labeled as reactive psychosis and started on citalopram. He was treated by ertapenem for 2 weeks.

A follow-up blood culture was negative. Concurrently, the renal function started to deteriorate. A renal biopsy was consistent with an early acute vascular rejection that did not respond to 3 pulses of methylprednisolone and 4 doses of antithymocyte globulin ATG. He was reestablished on dialysis but took his own discharge on D He attended our Centre on D59 with similar symptoms. Moreover, he complained of cough, wheezes, and shortness of breath SOB.

Portable chest X-ray CXR showed bilateral perihilar infiltrates Figure 2 , while CT scan revealed bilateral widespread centrilobular nodules of ground glass opacity consistent with hypersensitivity pneumonitis or bronchiolitis Figures 3 a and 3 b.

Additionally, there was no clinical or radiological improvement despite repeated ultrafiltration sessions. Complete blood count showed hemoglobin of 8. Both blood and urine cultures were positive for multidrug-resistant MDR E. Stool examination on D66 showed numerous S. Nevertheless, repeated sputum analysis and BAL specimen were negative for parasites.

A diagnosis of recurrent E. Immunosuppressant drugs were discontinued, and steroids were tapered. The stools turned negative by the third day of treatment. He was discharged home on D83 on valganciclovir, cotrimoxazole, and prednisolone. He is now been considered for a second transplant.

In addition to reactivation in chronically infected recipients, SOT recipients may acquire this infection through infected graft or acquisition of a new infection. In general, strongyloidiasis is uncommon in Saudi Arabia; however, a number of organ donors were from the Indian subcontinent and Southeast Asia, where the infection is more prevalent.

Consequently, graft-related infection is being increasingly reported from the Middle East [ 7 , 8 ]. The donor is of Indian origin but his eosinophil count was normal and the twin recipient of the other kidney was not affected. It is worth noting that the other recipient was not on cyclosporine. Three Kuwaiti kidney transplant recipients, from two deceased donors, died within 2 months from hyperinfection with Strongyloides [ 9 ]. The fourth recipient of the twin kidney was on cyclosporine and did not manifest a disease.

There is increasing evidence that cyclosporine has direct antiparasitic activity, and it may provide protection against hyperinfection syndrome [ 8 , 10 , 11 ]. HTLV-1 infection is a well-known risk factor for hyperinfection syndrome.

Moreover, there is a decrease in the efficacy of treatment of S. Conversely, combined CMV and strongyloidiasis had been reported in only a few cases and customarily detected at postmortem [ 13 ]. CMV targets different subsets of antigen-presenting cells leading to short-lived immunosuppression in immunocompetent as well as immunosuppressed patients [ 14 ]. This patient had extensive pulmonary infiltrates with ground glass appearance and wide centrilobular nodules.

The differential diagnosis at the time included pulmonary edema and ARDS; however, aggressive fluid removal did not lead to either clinical or radiological improvement. In a Korean study of CMV pneumonia in non-AIDS immunocompromised patients, the most common finding in HRCT scans included bilateral mixed areas of ground glass opacity, poorly defined centrilobular small nodules, and consolidation [ 15 ]. Both hypersensitivity and superimposed bacterial infection could have contributed to the radiological changes that regressed prior to discharge.

Generally, hyperinfection syndrome is associated with significant morbidity and mortality that can be avoided by early diagnosis and treatment. This is partly related to a delay in the diagnosis and initiation of treatment, as well as the accompanying Gram-negative sepsis.

It is proposed that larvae carry colonic bacteria during their migration to the venous system leading to translocation into the blood and other tissues including the meninges. Commonly reported organisms include Gram-negative rods such as E. Recurrent E. Thus, S. The diagnosis of hyperinfection syndrome can be difficult. Although eosinophilia is a common finding in patients with chronic Strongyloides infection, it is a very unreliable predictor of hyperinfection syndrome. The laboratory confirmation of strongyloidiasis is based mainly on the detection of Strongyloides larvae by microscopic examination of the stools, sputum, or CSF in disseminated infection.

The initial direct fecal smear stool examination in the referring hospital was negative, while multiple specimens were positive in our hospital. This could be due to the early presentation in the first admission before the florid syndrome at the time he presented to our hospital, as well as the poor technique for parasite isolation.

Stool agar plate culture APC or Baermann culture techniques had higher yield when compared to microscopy using the Kato-Katz technique [ 21 ]. Different molecular methods were found to be more sensitive and reliable in detecting S. An early diagnosis in this patient could have been secured in the presence of serology.

Serological methods are the most sensitive available diagnostic tools. A variety of antigens have been used to develop serological tests. These tests can be used to make the diagnosis and screening and more importantly as a possible test of cure [ 22 ].

This underscores the importance of maintaining serological tests in all transplant centers in order to avoid this serious infection. Treatment options include albendazole, thiabendazole, and ivermectin. In a recent Cochrane review, ivermectin has been proven to be more effective than albendazole RR: 1.

It is usually given orally; subcutaneous injection veterinary formulation and retention enema were used, too. The duration of treatment of hyperinfection syndrome is variable. If possible, immunosuppressive therapy should be stopped or reduced. To the best of our knowledge, this is the first case report of Strongyloides hyperinfection with concurrent CMV infection and Gram-negative sepsis in a Saudi patient.

Despite a very aggressive disease, this patient had a favorable outcome and is now evaluated for a second transplant. The authors declare that there are no competing interests regarding the publication of this paper. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Academic Editor: Carl Classen. Received 11 Jun Revised 14 Aug Accepted 28 Aug Published 15 Sep Introduction Strongyloidiasis is one of the most neglected tropical diseases.


A Fatal Strongyloides Stercoralis Hyperinfection Syndrome in a Patient With Chronic kidney Disease

The mortality in Strongyloides hyperinfection syndrome SHS is alarmingly high. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus CMV and strongyloidiasis had rarely been associated.


Intestinal strongyloidiasis and hyperinfection syndrome

Metrics details. In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis , has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection.

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