Subcutaneous ivermectin as a safe salvage therapy in Strongyloides stercoralis hyperinfection syndrome: a case report

Strongyloides stercoralis hyperinfection syndrome due to the acceleration of the autoinfective cycle of the nematode is a life-threatening form of the infection occurring in immunocompromised hosts. Intestinal ileus, which is commonly encountered in this form, may reduce the bioavailability and thus the efficacy of oral anthelminthic drugs used in the treatment of the S. stercoralis hyperinfection syndrome. We report the efficacy and safety of subcutaneous administration of ivermectin in a patient infected with human T cell lymphotropic virus type I with S. stercoralis hyperinfection syndrome who was unresponsive to an oral combination of ivermectin and albendazole.     

Strongyloides stercoralis hyperinfection in a patient with acquired immunodeficiency syndrome

Strongyloides stercoralis hyperinfection is a rare but know complication in patients with intestinal parasitism. Immunosuppressive therapy and acquires immunodeficiency syndrome (AIDS) are major risk factors for dissemination. Diagnosis requires identification of larvae in body fluids or biopsy and the mortality rates can be as high as 80%. The enteric bacteria are carried by invasive larvae and this can result in septicemia, pneumonia, meningitis, and disseminated bacterial infection in many parts of the body. We present a case of Strongyloides stercoralis hyperinfection complicated by Escherichia coli bacteraemia in a 45-year-old man African with AIDS.     

Strongyloides stercoralis infestation associated with septicemia due to intestinal transmural migration of bacteria

Strongyloides stercoralis infestation is common in the tropics and is usually asymptomatic. Patients with immunocompromised states may develop hyperinfection and fulminant disease. It has been suggested that bacteria accompany S. stercoralis during its passage across the bowel wall, resulting in systemic sepsis. Herein is a report on a 30-year-old man with S. stercoralis infestation and small bowel bacterial overgrowth presenting as malabsorption syndrome. He developed extensive duodenojejunal ulceration, septicemia and fatal hypokalemia. Blood and jejunal fluid grew Escherichia coli with the same antibiotic sensitivity patterns. This supports the hypothesis of migration of bacteria from the intestinal lumen as a cause of septicemia in patients with fulminant S. stercoralis infestation.     

Risk factors for strongyloidiasis hyperinfection and clinical outcomes

Strongyloidiasis, caused by Strongyloides stercoralis, consists of various clinical syndromes. Strongyloidiasis hyperinfection leads to morbidity and mortality particularly in immunocompromized patients. This study aimed to determine the risk factors for strongyloidiasis hyperinfection and clinical outcomes. The medical records for hospitalized patients infected with S. stercoralis at Ramathibodi Hospital during 1994-2005 were retrospectively reviewed. Risk factors for strongyloidiasis hyperinfection were determined. There were 123 episodes of strongyloidiasis in 111 patients. The mean age was 46.8 +/- 17.8 years; 61% were males. Of 123 episodes, 37 (30.1%) had strongyloidiasis hyperinfection; the others had chronic strongyloidiasis. All the patients with strongyloidiasis hyperinfection and 88.3% of those with chronic strongyloidiasis were immunocompromized (p = 0.032); 89.2% of the former and 55.8% of the latter had received corticosteroids (p < 0.001). There were no significant differences in the type of immunocompromized host and the corticosteroid dosage between the two groups (p > 0.05). The hyperinfection group had a lower mean serum protein (p = 0.026) and albumin (p = 0.027) but a higher frequency of sepsis (p = 0.029), asthma-like symptoms (p = 0.025), adult respiratory distress syndrome (p = 0.026), and a longer duration of treatment (p=0.004). By logistic regression, corticosteroids use was a risk factor for hyperinfection (OR = 6.5, 95% CI = 2.1-20.0, p = 0.001). Most of the patients were treated with albendazole or thiabendazole, with a cure rate of 76.9%, whereas other recent cases treated with ivermectin had an average cure rate of 83.3%. The overall mortality rate was 8.1%.     

Eosinophilic Ascites Due to Hyperinfection with Strongyloides stercoralis

We report the case of a patient with cryptogenic cirrhosis, new onset ascites, and hyperinfection with Strongyloides stercoralis who had significant eosinophilia of the peritoneal fluid. The eosinophilia resolved with treatment of the S. stercoralis infection, and did not recur during two subsequent episodes of ascites and spontaneous bacterial peritonitis. Eosinophilic ascites is rare in parasitic infection, but it has been described in a variety of disorders which are discussed.     

Strongyloidiasis following long-term corticosteroid therapy

A 64-year-old man who was born and raised in Fukuoka Prefecture was admitted because of dyspnea. The chest X-ray film showed multiple pulmonary cysts. Corticosteroid therapy was given because of repeated episodes of dyspnea and wheezing. He complained of epigastric pain 20 months after administration of corticosteroid therapy. Gastro-endoscopic examination showed inflammatory changes of the gastric mucosa and the biopsy specimens revealed the filariform larvae of Strongyloides stercoralis. Furthermore, the larvae were frequently detected in both sputum specimens and stools. Pyrvinium pamoate was initially administered and was switched to thiabendazole because of the presence of hyperinfection. Although two cycles of thiabendazole treatment were given, the larvae were not eradicated. This case report suggests that long term corticosteroid therapy caused the hyperinfection syndrome of Strongyloides stercoralis in a patient who was auto-infected with this nematode.     

Strongyloides stercoralis infection and small intestinal lymphoma

A West Indian man who was infected with Strongyloides stercoralis developed small intestinal obstruction. Treatment with thiabendazole did not relieve the obstruction which was found at laparotomy to be due to a poorly differentiated small intestinal lymphoma. There was no blood eosinophilia or accumulation of eosinopohils in the sites of infection. There was no reaction in the skin to delayed hypersensitivity antigens and the blood T lymphocyte count and serum C3 levels were low. From these findings and a review of the literature it was concluded that the immune response in man to Strongyloides stercoralis may depend on T lymphocyte mediated reactions including granuloma formation, and mast cell and eosinophil responses in tissues. We suggest that the association of strongyloides hyperinfection and small bowel lymphoma in this patient may not have been fortuitous. The lymphoma may have led to a reduction in cellular immunity, with the subsequent development of strongyloides hyperinfection.     

Strongyloides stercoralis hyperinfection syndrome after liver transplantation: case report and literature review

Abstract: Strongyloides stercoralis is an intestinal nematode that causes human infections and whose life cycle has special features, including autoinfection. Strongyloides infection may be asymptomatic for years, owing to a low parasite load. During immunosuppressive therapy, however, if cellular immunity is depressed, autoinfection can occur at a higher rate, resulting in hyperinfection syndrome. In this specific circumstance, it can become a fatal illness. We describe a case of hyperinfection syndrome in a liver transplant recipient and also review the literature.     

Endoscopic and histopathological study on the duodenum of Strongyloides stercoralis hyperinfection

AIM： To investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis （S. stercoralis） hyperinfection. METHODS： Over a period of 23 years （1984-2006）, we investigated 25 patients with S. stercoralis hyperinfection who had had an esophagogastroduodenoscopy before undergoing treatment for strongyloidiasis. The clinical and endoscopic findings were analyzed retrospectively. RESULTS： Twenty-four （96%） of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 （HTLV-1） infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 （92%） patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings. The histopathologic yield for identifying larvae was 71.4% by duodenal biopsy. The endoscopic findings of duodenitis were more severe in patients whose biopsies were positive for larvae than those whose biopsies were negative （Endoscopic severity score： 4.86 ± 2.47 vs 2.71 ±1.38, P 〈 0.05）. CONCLUSION： Our study clearly demonstrates that, in addition to stool analysis, endoscopic observation and biopsies are very important. We also emphasize that S. stercoralis and HTLV-1 infections should be ruled out before immunosuppressive therapy is administered in endemic regions.     

Risk factors for strongyloidiasis. A case-control study

Although infection with Strongyloides stercoralis is usually only mildly symptomatic, it can persist for many years and occasionally progress to the hyperinfection syndrome, with a resultant high mortality rate. We studied factors associated with S stercoralis infection by comparing 28 domestic cases of S stercoralis infection with 76 controls with negative stool samples for ova and parasites. The relative risk (RR) of S stercoralis infection was increased for white patients (RR = 5.6), men (RR = 3.9), and patients who had recently used corticosteroids (RR = 3.3), had a hematologic malignancy (RR = 5.28) or had prior gastric surgery (RR = 11.5). These risk factors might be for initial infection, persistence of infection, or both. Although they are not necessarily causal, knowledge of them may lead to earlier recognition of this dangerous and treatable disease.     

Chronic relapsing colitis due to Strongyloides stercoralis

The small intestine is the usual site of chronic infection with Strongyloides stercoralis. Colonic involvement has generally been seen in the hyperinfection syndrome in immunosuppressed individuals. We describe an immunologically competent female who underwent multiple abdominal operations over a 5-year period for hematochezia and diffuse abdominal pain of obscure etiology. Eosinophilia had been present but never investigated until 1981, at which time stool examination revealed S. stercoralis larvae. Pathological specimens from operations in 1977 and 1981 demonstrated extensive colonic wall invasion with filariform larvae consistent with S. stercoralis. Involvement of other organs was never documented. We believe this case is consistent with chronic colitis due to strongyloidiasis. This entity has not been previously described, and expands the spectrum of this disease.     

Case report: adult T-cell leukemia/lymphoma associated with recurrent strongyloides hyperinfection

Adult T-cell leukemia/lymphoma (ATLL) was demonstrated postmortem in a 47-year-old woman initially manifesting severe hypercalcemia and a vertebral compression fracture. Hyperinfection with Strongyloides stercoralis preceded the appearance of ATLL by several months and ultimately dominated the terminal course. Although HTLV-I and S. stercoralis commonly infect the same host, only three other cases of concomitant ATLL and hyperinfection have been reported in English. The apparent rarity of this association suggests that immunologic sequelae of ATLL do not predispose to dissemination and multiplication of Strongyloides. Observations pertinent to this conclusion are reviewed.     

Strongyloides hyperinfection: a treatment dilemma

Strongyloides stercoralis infection is a common cause of abdominal pain and diarrhea worldwide. Usually a chronic and limited disease, it can present a therapeutic dilemma when infection is overwhelming, such as what might occur in an immunosuppressed patient. Here we present a case of strongyloides hyperinfection treated successfully with a veterinary formulation of parenteral ivermectin.     

Syndrome of inappropriate secretion of antidiuretic hormone and nonpalpable purpura in a woman with Strongyloides stercoralis hyperinfection

Strongyloidiasis stercoralis hyperinfection presenting as vasculitic-like skin lesions is rare. An autoinfection cycle allows intestinal strongyloidiasis, usually a benign infection, to persist for many decades. We report a woman with disseminated S stercoralis infection presenting as nonpalpable purpuric skin rash and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Upon admission, she was treated with corticosteroids for her vasculitic skin lesions, which then worsened her status. When the diagnosis was recognized, steroids were stopped, thiabendazole treatment was instituted, and she gradually recovered. Serious or fatal infection can occur in patients with strongyloidiasis who were treated with immunosuppressive drugs. Stool specimen screening and/or serological tests for S stercoralis infection in patients who require immunosuppressive therapy helps to prevent complications before embarking on such treatment. Unexplained hyponatremia, severe hypoalbuminemia without proteinuria, and unusual skin rashes, especially over the lower aspect of the abdomen and upper aspects of the thighs, in persons living in areas endemic to S stercoralis should raise suspicion of S stercoralis infection.     

Atypical gastric presentation of strongyloidiasis in HIV-infected patient—case report

Strongyloides stercoralis is an intestinal helminth of systemic distribution, which, once in its host, has the ability to perpetuate itself through an autoinfection cycle, leading to chronic infection. In healthy hosts, the parasite usually does not cause any symptoms, or only mild symptoms that are limited mainly to the small intestine. However, in immunocompromised hosts, uncontrolled multiplication with massive infection may occur, causing hyperinfection syndrome or disseminated strongyloidiasis, which are both associated with high morbidity and mortality. There are few reports of gastric involvement, particularly presenting as ulcer in the stomach. We report a case of gastric ulcer caused by S. stercoralis in HIV-infected patient.     

Hyperinfection by Strongyloides stercoralis probably associated with Rituximab in a patient with mantle cell lymphoma and hyper eosinophilia

The first report to our knowledge, of hyperinfection by Strongyloides stercoralis (HS) and hypereosinophilia, associated to immune suppression by Rituximab (the only drug received for the last one year and 10 months), in a patient with mantle-cell lymphoma (MCL), is presented. The patient has a 3-year history of MCL, and developed two accesses of HS during 2008, including meningitis, pneumonia and presence of larvae of S. stercoralis in the lungs. We had a unique chance to look at cytotoxicity of filariform larvae in the expectoration after Ivermectin treatment, showing immobilization and death of larvae, associated with eosinophils attached to the cuticle of the parasite.     

Why does HIV infection not lead to disseminated strongyloidiasis?

We investigated the hypothesis that host immunosuppression due to advancing human immunodeficiency virus (HIV) disease favors the direct development of infective larvae of Strongyloides stercoralis, which may facilitate hyperinfection and, hence, disseminated strongyloidiasis. To do this, we sought correlations between the immune status of the subjects and the development of S. stercoralis infections. Among 35 adults, there were significant negative rank correlations between CD4+ cell counts and the proportions of free-living male and female worms. Thus, in individuals with preserved immune function, direct development of S. stercoralis is favored, whereas, in individuals with lesser immune function, indirect development is relatively more common. These results may explain the notable absence of disseminated strongyloidiasis in advanced HIV disease. Because disseminated infection requires the direct development of infective larvae in the gut, the observed favoring of indirect development in individuals immunosuppressed by advancing HIV disease is not consistent with the promotion of disseminated infection.     

Epidemiological and clinical interaction between HTLV-1 and Strongyloides stercoralis

Strongyloides stercoralis is the most common human parasitic nematode that is able to complete a life cycle and proliferate within its host. The majority of patients with strongyloidiasis have an asymptomatic infection or mild disease. However, when autoinfection occurs, a high number of infecting larvae can gain access to the bloodstream by penetrating the colonic mucosa leading to a severe hyperinfection and the development of disseminated strongyloidiasis. The human T cell lymphotropic virus type 1 (HTLV-1) predominantly infects T cells and induces spontaneous lymphocyte proliferation and secretion of high levels of type 1 cytokines. Strongyloides stercoralis patients with HTLV-1 co-infection have a modified immunological responses against parasite antigens and co-infection has clinical implications for strongyloidiasis. The high production of IFN-gamma observed in patients co-infected with HTLV-1 and Strongyloides stercoralis decreases the production of IL-4, IL-5, IL-13 and IgE, molecules that participate in the host defence mechanism against helminths. Moreover, there is a decrease in the efficacy of treatment of Strongyloides stercoralis in patients co-infected with HTLV-1. Alterations in the immune response against Strongyloides stercoralis and the decrease in the efficacy of anti-parasitic drugs are responsible for the increased prevalence of Strongyloides stercoralis among HTLV-1 infected subjects and make HTLV-1 infection the most important risk factor for disseminated strongyloidiasis.     

Treatment of Strongyloides stercoralis hyperinfection-associated septic shock and acute respiratory distress syndrome with drotrecogin alfa (activated) in a renal transplant recipient

Abstract: We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal transplant recipient complicated by septic shock, acute respiratory distress syndrome, and Klebsiella pneumoniae superinfection. The patient was treated successfully with drotrecogin alfa (activated), parenteral ivermectin, albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin alfa (activated) may be useful therapy for transplant recipients who develop severe sepsis or septic shock secondary to potentially lethal opportunistic infections.     

Strongyloides stercoralis hyperinfection in hematopoietic stem cell transplantation

Abstract: Strongyloides stercoralis is endemic in tropical, subtropical, and even temperate regions, and infects up to 100 million people worldwide. The diagnosis of strongyloidiasis can be difficult because of intermittent larval output in stool and nonspecific symptoms with mild peripheral eosinophilia. In this case report, a patient with acute myelogenous leukemia underwent peripheral blood hematopoietic stem cell transplantation (HSCT) and was subsequently diagnosed with strongyloidiasis. Strongyloidiasis should be considered in immunocompromised patients from endemic areas who have unexplained peripheral eosinophilia. If screening tests are positive for S. stercoralis or if a patient has unexplained eosinophilia with even a remote history of travel to or residence in endemic areas, then ivermectin should be given before HSCT to prevent often fatal hyperinfection syndrome from occurring after HSCT.