Stongyloidiasis

Background

This is a parasitic infection, often found in developing countries. However, immunosuppressed patients are also at increased risk. Patients usually present with diarrhea, fever, abdominal pain, cough, dyspnea, and constipation. In severe cases, systemic infection or hyperinfection may occur.

The diagnosis can be made by analysis of the stool for the characteristic larvae. Biopsy of the intestinal tract may also reveal the organisms. Treatment with anti-parasitic drug therapy, usually mebendazole or albendazole, is usually effective although relapses may occur.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

GEOGRAPHY

MEDITERRANEAN

Endemic strongyloidiasis on the Spanish Mediterranean coast.

Sanchez PR, Guzman AP, Guillen SM, Adell RI, Estruch AM, Gonzalo IN, Olmos CR.

Department of Internal Medicine, Requena General Hospital, Valencia, Spain.

QJM 2001 Jul;94(7):357-63 Abstract quote
Diagnosis and treatment of Strongyloides stercoralis infection can be difficult, and a high degree of clinical suspicion in patients who have visited an endemic area is required.

We describe the epidemiology and clinical features of 152 prospectively identified cases of strongyloidiasis in an European region, and identify risk factors for the development of severe forms of the disease. This was a prospective study of all patients admitted to a single institution over an 8-year period. Patients (n=152) were mainly elderly male farmers (79%) who had acquired the disease by working barefoot in contact with soil and ingesting non-drinking water. Eosinophilia was a sensitive marker for the infection (82%). Twenty patients (13%) developed severe forms of the illness and six patients (4%) died. A significant association was found between severe forms of strongyloidiasis and steroid usage (OR 9.0, 95%CI 2.1-37.6), immunodebilitating illness (OR 10.1, 95%CI 3.2-32.3) and other immunosuppressive therapy (OR 13.7, 95%CI 2.9-58.7), but by logistic regression analysis, only immunodebilitating disease was as a risk factor (OR 2.1, 95%CI 1.78-2.43). S. stercolaris infection is endemic in the Spanish Mediterranean coast.

The frequent development of severe forms of the disease, with a high mortality, makes early recognition and treatment essential.

EPIDEMIOLOGIC ASSOCIATIONS

NOSOCOMIAL

The risk of Strongyloides stercoralis transmission from patients with disseminated strongyloidiasis to the medical staff.

Maraha B, Buiting AG, Hol C, Pelgrom R, Blotkamp C, Polderman AM.

Department of Medical Microbiology, St Elisabeth Hospital, Tilburg, The Netherlands.
J Hosp Infect 2001 Nov;49(3):222-4 Abstract quote
To assess the risk of Strongyloides stercoralis transmission from two patients with disseminated strongyloidiasis to medical staff who had been in close contact with the patients, blood and stool specimens were obtained from medical staff two to three months after close contact with the patients.

Antibodies to S. stercoralis were determined in blood. Stool specimens were tested for parasites with three different procedures.Forty-one medical staff were included. Culture and stool examination were negative in all subjects. Serology was negative in all subjects but one who had a borderline titer without signs or symptoms of strongyloidiasis.

No evidence of transmission of S. stercoralis from patients with disseminated strongyloidiasis to medical staff was found.

DISEASE ASSOCIATIONS CHARACTERIZATION

HTLV-1

Treatment failure in intestinal strongyloidiasis: an indicator of HTLV-I infection.

Terashima A, Alvarez H, Tello R, Infante R, Freedman DO, Gotuzzo E.

Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Int J Infect Dis 2002 Mar;6(1):28-30 Abstract quote
BACKGROUND: The association of severe strongyloides with HTLV-I is well known; however, the seroprevalence of HTLV-I in other groups with strongyloidiasis is still unknown. We conducted a prospective study in patients with intestinal strongyloidiasis without known immunodepression who failed to respond to standard therapy with ivermectin or thiabendazole (failure was defined as one positive stool examination at the post-therapy follow up). All these patients were tested for HTLV-I by ELISA and Western Blot.

RESULTS: Forty seven patients were evaluated: 74.5% (35 out of 47) were HTLV-I positive, without significant difference between males (76%) and females (72.7%).

CONCLUSIONS: We recommend that all patients with uncomplicated intestinal strongyloidiasis, who fail standard therapy, be studied for HTLV-I infection.

Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia.

Plumelle Y, Gonin C, Edouard A, Bucher BJ, Thomas L, Brebion A, Panelatti G.

Department of Hematobiology, University Hospital, Martinique, French West Indies.

Am J Clin Pathol 1997 Jan;107(1):81-7 Abstract quote
Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis.

To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028).

Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.

NEPHROTIC SYNDROME

Strongyloidiasis associated with nephrotic syndrome.

Mori S, Konishi T, Matsuoka K, Deguchi M, Ohta M, Mizuno O, Ueno T, Okinaka T, Nishimura Y, Ito N, Nakano T.

Department of Internal Medicine, Mie Prefectural General Medical Center, Yokkaichi.
Intern Med 1998 Jul;37(7):606-10 Abstract quote
We report a nephrotic syndrome patient with eosinophilia who developed ileus, epigastralgia and malabsorption due to strongyloidiasis which became symptomatic by steroid therapy. The patient was then treated with thiabendazole and recovered.

A percutaneous renal biopsy revealed minimal change nephrotic syndrome. This renal injury may be brought on by severe infection of Strongyloides stercoralis.

It is important to rule out strongyloidiasis prior to corticosteroid therapy to patients from eosinophilia endemic areas.

PATHOGENESIS CHARACTERIZATION

GENERAL

Human strongyloidiasis in AIDS era: its zoonotic importance.

Singh S.

Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi.

J Assoc Physicians India 2002 Mar;50:415-22 Abstract quote
Human strongyloidiasis is caused by a nematode Strongyloides stercoralis. Many species cause strongyloidiasis in animals. The parasite has predilection to one host only but the host specificity is not strict. When animal species infects humans there is intense allergic reaction in the form of cutaneous larva currens and larva migrans. Therefore, strongyloidiasis in strict terms is a zoonotic disease.

The strongyloides species have three stages. The parasitic form inside the host, the free form stage in the soil or water that moults to infective third stage. The later infects the host through skin and migrate to the heart and lung and finally swallowed back to cause intestinal infection. However, in some cases intense pulmonary manifestations may take place. The Strongyloides stercoralis has unique feature of moulting from parasitic form to infective stage within the body, rather than coming out and forming free living stage and causing autoinfection. This may lead to latent infection for indefinite period in an immunocompetant person but fatal hyper or disseminated infection in immunocompromised person like patients of AIDS, organ transplant recipients, cancer and other patients put on immunosuppressive therapy, in whom it can involve any organ of the body.

Because this group of patients in last few years have increased tremendously in Africa and South-East Asia, more and more cases of strongyloidiasis are being reported in english literature. The diagnosis of intestinal strongyloidiasis is made by repeated stool smear examinations and in extraintestinal strongyloidiasis the appropriate specimen is examined for the rhabditiform larvae. Recently serological tests have also been developed that can be used for epidemiological purposes.

The drug of choice for the treatment of strongyloidiasis remains thiabendazole but due to its unacceptable side effects other medicines like albendazole and ivermectine are being used more frequently. The prevention of the infection is possible by adopting good personal hygiene and safe drinking water supply.

LABORATORY/
RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

GI TRACT

Mesenteric arteriographic findings in a patient with strongyloides stercoralis hyperinfection.

Reiman S, Fisher R, Dodds C, Trinh C, Laucirica R, Whigham CJ.

Department of Radiology, Ben Taub General Hospital, 1504 Taub Loop, Houston, Texas 77030-1608, USA
J Vasc Interv Radiol 2002 Jun;13(6):635-8 Abstract quote
The authors present a case of a Latin American patient with systemic lupus erythematosus who was referred for a mesenteric arteriogram because of acute lower gastrointestinal bleeding. Multiple segments of dilation alternating with stenosis or spasm were noted in the superior mesenteric artery/inferior mesenteric artery distributions.

At the time, these irregularities were thought to be representative of lupus vasculitis. Despite appropriate treatment for vasculitis, the patient continued to have bleeding episodes and ultimately died of multiple organ failure.

Autopsy demonstrated no evidence of vasculitis, but did demonstrate the unexpected finding of Strongyloides stercoralis hyperinfection with vessel invasion.

Comparative features of double-contrast barium studies in patients with isosporiasis and strongyloidiasis.

Hizawa K, Iida M, Eguchi K, Aoyagi K, Tada S, Kuwano Y, Mochizuki Y, Fujishima M.

Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan

Clin Radiol 1998 Oct;53(10):764-7 Abstract quote
OBJECTIVE: To compare the gastrointestinal features of isosporiasis and strongyloidiasis.

METHODS: Two patients with isosporiasis and three patients with strongyloidiasis were assessed by double-contrast radiography of the duodenum and small intestine, with reference to histology of the duodenal biopsy specimens.

RESULTS: Both conditions affected the duodenum and the proximal jejunum, and showed similar radiographic changes as the diseases progressed. Thus, three patients with diarrhoea lasting 1 year or less showed only minimal or irregularly thickened mucosal folds, which seemed to result from mucosal inflammation. Two patients with long-standing disease periods (17 years and 30 years) presented a markedly granular mucosal appearance with effacement of the folds on radiography. These chronological differences in the radiographic features seemed to reflect the degree of villous atrophy.

CONCLUSION: Isosporiasis has similar radiographic features of strongyloidiasis.

LUNG

Clinical and imaging features of pulmonary strongyloidiasis.

Woodring JH, Halfhill H 2nd, Berger R, Reed JC, Moser N.

Department of Diagnostic Radiology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
South Med J 1996 Jan;89(1):10-9 Abstract quote
We evaluated 20 patients with pulmonary strongyloidiasis for risk factors, clinical and imaging manifestations, complications, treatment, and outcome.

Eighteen (90%) had risk factors for strongyloidiasis including steroid use, age greater than 65, chronic lung disease, use of histamine blockers, or chronic debilitating illness. Pulmonary signs and symptoms, including cough, shortness of breath, wheezing, and hemoptysis, were present in 19 (95%); adult respiratory distress syndrome (ARDS) developed in 9 (45%). Pulmonary infiltrates occurred in 18 (90%). Gastrointestinal signs and symptoms were also common. Peripheral blood eosinophilia occurred in 15 (75%). Twelve (60%) had secondary infection, and 3 (15%) had bacterial lung abscesses.

All were treated with thiabendazole, 25 mg/kg twice daily; on average, patients without ARDS were treated for 3 days, versus 7 days for those with ARDS. Seventy percent responded to therapy; 30% died. Preexisting chronic lung disease and ARDS were statistically significant predictors of a poor prognosis.

LABORATORY MARKERS

SEROLOGY

Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area.

Loutfy MR, Wilson M, Keystone JS, Kain KC.

Department of Medicine, University of Toronto, Ontario, Canada

Am J Trop Med Hyg 2002 Jun;66(6):749-52 Abstract quote
Strongyloidiasis is a chronic infection that may result in significant morbidity; however, diagnosis and management remain problematic.

The objective of this study was to 1) evaluate the demographic, clinical, and laboratory features of 76 consecutive individuals who had Strongyloides stercoralis larvae identified in their fecal specimens; 2) determine the sensitivity of the Centers for Disease Control and Prevention (CDC) enzyme immunoassay (EIA) for detecting antibodies to Strongyloides in those with confirmed infection; and 3) assess the serologic responses and changes in eosinophil counts following treatment. Most (96%) cases occurred in immigrants, but some patients had immigrated as long as 40 years earlier.

The CDC Strongyloides EIA had a sensitivity of 94.6% (95% confidence interval = 92.0-97.2%) in this patient population with proven infection. Serologic and eosinophil counts decreased after therapy, suggesting that they may be useful markers of treatment success.

SERUM IgE

A three years follow-up of total serum IgE levels in three patients treated for strongyloidiasis.

Poirriez J.

CIMOT, 4-10, rue Albert Thomas, 59210 Coudekerque-Branche, France.
Parasite 2001 Dec;8(4):359-62 Abstract quote
A three years follow-up of the level of serum total IgE was made for the first time in three patients with strongyloidiasis after efficient treatment.

The decrease of IgE was slow and progressive, showing a logarithmic curve. This regular decrease of total serum IgE could be used as an additional criterion for the evaluation of the efficiency of drug therapy in patients with strongyloidiasis.

The persistence of high levels of total IgE two or three years after the elimination of the intestinal parasites, after the return of blood eosinophils to a normal level (within six months), and after the disappearance of specific antibodies, shows that the regulation of the IgE elimination seems to be a complex mechanism.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

APPENDIX

Strongyloides stercoralis infection as a cause of acute granulomatous appendicitis in an HIV-positive patient in Athens, Greece.

Felekouras E, Kontos M, Kyriakou V, Hatzianagnostou D, Dimaroggona K, Papalampros E, Kordossis T, Bastounis E.

Department of Surgery, Laikon General Hospital and Athens School of Medicine, Athens, Greece
Scand J Infect Dis 2002;34(11):856-7 Abstract quote
A case of acute granulomatous appendicitis due to Strongyloides stercoralis infection in an HIV-positive patient is described.

To our knowledge this is the first case presented in the literature.

COLON

Strongyloidiasis colitis: a case report and review of the literature.

Al Samman M, Haque S, Long JD.

Department of Medicine, Texas Tech University Health Sciences Center El Paso, 79905, USA.

J Clin Gastroenterol 1999 Jan;28(1):77-80 Abstract quote
A case is described of a nonimmunocompromised man who presented with diarrhea, weight loss, and microcytic anemia. Colonoscopy revealed a pancolitis characterized by aphthoid ulceration on endoscopy and intense tissue eosinophilic infiltrates on biopsy.

Both colonic biopsies and stool aspirates revealed the larvae of Strongyloides stercoralis, thus confirming this parasite as the causative agent for the colitis.

HYPERINFECTION

Hyperinfection syndrome in strongyloidiasis: Report of two cases.

Lemos LB, Qu Z, Laucirica R, Fred HL.

Departments of Pathology and Internal Medicine, University of Texas in Houston, Harris County Health Department Hospitals, Houston TX.

Ann Diagn Pathol 2003 Apr;7(2):87-94 Abstract quote
Hyperinfection in strongyloidiasis has been associated with corticosteroid treatment. Other immunodepressive conditions also seem to facilitate the state of hyperinfection. The etiologic diagnosis of this parasitosis can be difficult to reach and a positive urine microscopy is unusual.

We report two patients under corticosteroid therapy with disseminated strongyloidiasis; both had eosinophilia. The first patient, followed for 8 years for autoimmune hemolytic anemia, recently developed abdominal symptoms. A colonoscopy was performed 1 month before admission and the biopsy was thought to show nonspecific changes. At admission, few larvae of Strongyloides stercoralis were disclosed by urine microscopy, and a review of the colonic biopsy uncovered a few larvae of Strongyloides. The patient received anti-helmintic therapy with a dramatic improvement. The second patient, under treatment for lupus erythematosus for 3 years, was admitted with pulmonary symptoms and during admission developed massive gastrointestinal bleeding. Disseminated strongyloidiasis was discovered only at autopsy.

The low suspicion index for strongyloidiasis resulted in delaying the etiologic diagnosis in one patient and in failing to diagnose the disease in the other. The morphologic features of the parasite in the two cases are presented with emphasis on the difficulties of recognizing the larvae in the intestinal biopsy.

Hyperinfective strongyloidiasis in the medical ward: review of 27 cases in 5 years.

Adedayo O, Grell G, Bellot P.

Department of Medicine, Princess Margaret Hospital, Roseau, Dominica, West Indies.
South Med J 2002 Jul;95(7):711-6 Abstract quote
BACKGROUND: Hyperinfective strongyloidiasis is rare, but the mortality rate is very high. It occurs most commonly in immunocompromised patients. We reviewed the clinical presentation and mortality rate of cases managed in our facility.

METHOD: Twenty-seven patients with hyperinfective strongyloidiasis admitted to our medical ward over a 5-year period were prospectively studied.

RESULTS: In our study, there were 18 males and 9 females (mean age, 58 years). Weight loss, gastrointestinal symptoms, hypoproteinemia, and anemia were the main clinical presentations. Mortality rate was 26%; human T-lymphotropic virus (HTLV-1) infection, chronic alcoholism, eosinopenia, sepsis, and prerenal azotemia on admission were poor prognostic factors. HTLV-1 infection was the main underlying disease in 71% of patients, and 44% of patients had a history of chronic alcoholism.

CONCLUSION: Early diagnosis and treatment with thiabendazole may reduce mortality in hyperinfective strongyloidiasis. Hyperinfective strongyloidiasis may also be a clinical marker of HTLV-1 infection in areas where both entities are endemic or in immigrants from such areas.

LUNG

Extensive intra-alveolar haemorrhage caused by disseminated strongyloidiasis.

Kinjo T, Tsuhako K, Nakazato I, Ito E, Sato Y, Koyanagi Y, Iwamasa T.

Department of Pathology, Ryukyu University School of Medicine, Okinawa, Japan.

Int J Parasitol 1998 Feb;28(2):323-30 Abstract quote
We describe here four cases of disseminated strongyloidiasis. In Okinawa, it has been reported that about 10% of the residents are infected with Strongyloides stercoralis, but disseminated cases are rare.

Detailed histopathological examination revealed that the present four cases could clearly be separated into two groups, two acute cases and two subacute cases. The acute cases died rapidly due to extensive diffuse intra-alveolar haemorrhage in both lungs. However, there were no inflammatory infiltrates, abscesses or granulomas in the lungs. Worms were demonstrated in the alveolar spaces. No extensive bleeding was observed in any organs except the lungs. The acute cases could be diagnosed as severe diffuse intra-alveolar haemorrhage syndrome, but deposition of immune complex (parasite antigen and immunoglobulins) and complement C3c was not demonstrated in the alveolar wall and small vessels of the lung. The subacute cases exhibited no such extensive haemorrhage, but scattered microabscesses were found with sepsis.

During the migration of the worms from the colon, enteric bacteria entered the circulation in the two subacute cases. The acute cases received steroid therapy before the dissemination of the worms, but the two subacute cases did not. Steroids might have influenced the Strongyloides stercoralis dissemination and/or the course of the disease.

Pulmonary manifestations of strongyloidiasis.

Wehner JH, Kirsch CM.

Department of Medicine, Stanford University School of Medicine, San Jose, CA 95128, USA.

Semin Respir Infect 1997 Jun;12(2):122-9 Abstract quote
Strongyloides stercoralis (SS) is endemic in tropical and subtropical areas worldwide and in the southeastern United States. The lifecycle of SS is both unique and complex. Human infection begins with the penetration of skin by filariform larvae that migrate hematogenously to the lungs. Larvae then ascend the airway, are swallowed, and mature in the gut. Unlike other nematodes, SS can autoinfect the same host and persist for decades.

Categorization of infection includes acute, chronic-uncomplicated, and disseminated forms. Clinical manifestations depend on the particular organs involved. Fifteen to thirty percent of chronically infected people may be asymptomatic. On the other hand, SS may cause the adult respiratory distress syndrome, septic shock, and death. The diagnosis of SS infection is suspected in patients from endemic areas who have blood eosinophilia, and gastrointestinal or pulmonary symptoms. A definitive diagnosis is established by demonstration of SS larvae in stool, body fluids, or tissues. A presumptive diagnosis of SS infection can be achieved by serology.

Thiabendazole is the mainstay of treatment, but repeat doses may be necessary if the parasite is not initially eradicated. The low incidence of disseminated SS in areas endemic for both SS and AIDS is surprising and unexplained.

MESENTERIC LYMPHADENOPATHY

Strongyloides stercoralis mesenteric lymphadenopathy: Clue to the etiopathogenesis of intestinal pseudo-obstruction in HIV-infected patients. Ramdial PK, Hlatshwayo NH, Singh B.
Department of Pathology, Nelson R Mandela School of Medicine, Faculty of Health Sciences, University of KwaZulu Natal & Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu Natal 4058, South Africa.

Ann Diagn Pathol. 2006 Aug;10(4):209-14. Abstract quote
Mesenteric lymph node involvement in Strongyloides stercoralis hyperinfective states, described as an autopsy finding, remains a relatively poorly recognized and possibly underreported, antemortem phenomenon. Furthermore, the occurrence of S stercoralis mesenteric lymphadenopathy as a tocsin of bowel strongyloidiasis and the clue to the cause of intestinal pseudo-obstruction are undescribed.

We report S stercoralis mesenteric lymphadenopathy and intestinal pseudo-obstruction in 5 HIV seropositive male patients, 21 to 42 years, who presented with abdominal pain and variable vomiting, diarrhea, and constipation. All were pale, pyrexial, and emaciated with abdominal distension. The preoperative diagnosis was intestinal obstruction. Poor clinical response on conservative therapy necessitated laparotomy. Dilated small bowel loops, ascites, and mesenteric lymphadenopathy were consistently noted; a diagnosis of pseudo-obstruction due to underlying tuberculosis or lymphoma was made. The mesenteric lymph nodes were biopsied. The pertinent nodal features were a dense infiltrate of eosinophils, eosinophil microabscesses and degranulation, a focal Splendore-Hoeppli phenomenon, and randomly disposed, but elusive, S stercoralis filariform larvae. Clinical deterioration confirmed intestinal complications at repeat laparotomy. Intestinal resections were performed in 4 patients; histopathologic appraisal confirmed intestinal strongyloidiasis. All patients died within 3 to 7 days after surgery.

Heightened awareness of S stercoralis mesenteric lymphadenopathy as a sentinel of intestinal strongyloidiasis and etiopathogenetic clue of intestinal pseudo-obstruction may allow timely diagnosis and medical treatment and avoidance of further surgery, potentially reducing the long-term morbidity associated with S stercoralis hyperinfection.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

Histopathology of gastric and duodenal Strongyloides stercoralis locations in fifteen immunocompromised subjects.

Rivasi F,

Pampiglione S,

Boldorini R,

Cardinale L.

Department of Pathologic Anatomy and Forensic Medicine, Section of Pathological Anatomy, University of Modena and Reggio Emilia, Modena, Italy

Arch Pathol Lab Med. 2006 Dec;130(12):1792-8. Abstract quote

CONTEXT: Strongyloidiasis is a worldwide parasitic infection affecting approximately 75 million people. In Italy, it was more prevalent in the past among rural populations of irrigated areas.

OBJECTIVE: To determine the histopathologic alterations of the gastric and duodenal mucosa associated with the presence of Strongyloides stercoralis parasites.

DESIGN: Fifteen cases of strongyloidiasis were observed in immunocompromised patients during a recent 6-year period in Italy. S. stercoralis was found histologically in gastric biopsies (10 cases), in a gastrectomy (1 case), and in duodenal biopsies (9 cases). In 5 cases the parasite was present both in gastric and duodenal biopsies. Four patients were affected by lymphoma, 2 by multiple myeloma, 2 by gastric carcinoma, 1 by chronic myeloid leukemia, 1 by sideroblastic anemia, 1 by colorectal adenocarcinoma, 1 by chronic idiopathic myelofibrosis, 1 by chronic gastritis, 1 by gastric ulcers, and 1 by rheumatoid arthritis in corticosteroid therapy. No patient was affected by human immunodeficiency virus infection. Strongyloidiasis was not clinically diagnosed.

RESULTS: Histologic examination revealed several sections of S. stercoralis larvae, many eggs, and some adult forms. All the parasites were located in the gastric and/or the duodenal crypts. Eosinophils infiltrating into the lamina propria were found in all cases; their intensity was correlated with the intensity of the infection.

CONCLUSIONS: Histologic diagnosis of strongyloidiasis must be taken into consideration when examining both gastric and duodenal biopsies in immunocompromised patients, to avoid the development of an overwhelming infection of the parasite, which is dangerous for the life of the patient.

COLITIS

Strongyloides stercoralis eosinophilic granulomatous enterocolitis.

Gutierrez Y, Bhatia P, Garbadawala ST, Dobson JR, Wallace TM, Carey TE.

Department of Pathology, University Hospitals of Cleveland, OH 44106, USA.

Am J Surg Pathol 1996 May;20(5):603-12 Abstract quote
Six patients suffering from an unusual form of colitis produced by Strongyloides stercoralis hyperinfection are described. In contrast to the usual Strongyloides hyperinfection syndrome, in which small intestinal and pulmonary manifestations are seen in patients with some forms of immunodeficiency, the patients described here presented with only a characteristic transmural eosinophilic granulomatous inflammation affecting mostly the colonic wall and clinically mimicking ulcerative colitis or Crohn's disease.

This Strongyloides eosinophilic granulomatous enterocolitis apparently results from a florid inflammatory response by eosinophils, histiocytes, and giant cells with formation of granulomas that destroy the larvae entering the colon. This morphologic picture differs from that of the well-described hyperinfection syndrome, in which the bulk of the larvae pass through the colonic wall to complete the life cycle, with only a few larvae destroyed in the colon.

The probable pathophysiologic mechanism of this unusual manifestation of hyperinfection is discussed based on the anatomic and clinical observations of patients who presented at different stages in the evolution of their condition and whose length of follow-up varied.

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

ELECTRON MICROSCOPY

Strongyloides stercoralis: ultrastructural study of newly hatched larvae within human duodenal mucosa.

Dionisio D, Manneschi LI, di Lollo S, Orsi A, Tani A, Papucci A, Esperti F, Leoncini F.

Infectious Diseases Unit, Pistoia Hospital, Italy.
J Clin Pathol 2000 Feb;53(2):110-6 Abstract quote
AIM: To investigate the ultrastructural features of the newly hatched larvae of Strongyloides stercoralis in human duodenal mucosa.

METHODS: Duodenal biopsies from an AIDS patient were studied by transmission electron microscopy to investigate morphology, location, and host-worm relations of newly hatched larvae.

RESULTS: Newly hatched larvae were found in the Lieberkuhn crypts within the tunnels formed by migration of parthenogenic females. Delimiting enterocytes were compressed. Release of larvae into the gut lumen was also documented. It was shown that both a thin and a thick membrane surrounded the eggs and larvae, as a tegument derived respectively from parasite and host. Segmentary spike-like waves, caused by contractures of worm body musculature, were observed on the surface of newly hatched larvae, and their intestinal lumen was closed and empty, with no budding microvilli. Immaturity of the cuticle and some degree immaturity of amphidial neurones were found, but there was no evidence of either immaturity or signs of damage to other structures.

CONCLUSIONS: Newly hatched larvae of S stercoralis appear to be a non-feeding immature stage capable of active movement through the epithelium, causing mechanical damage. The tegument resulting from the thin and the thick membrane may protect the parasite and reduce any disadvantage caused by immaturity.

TREATMENT CHARACTERIZATION

GENERAL Thiabendazole
Mebendazole

ALBENDAZOLE

Albendazole is effective treatment for chronic strongyloidiasis.
Archibald LK, Beeching NJ, Gill GV, Bailey JW, Bell DR.

Liverpool School of Tropical Medicine.
Q J Med 1993 Mar;86(3):191-5 Abstract quote
A total of 301 British ex-Far East prisoners of war, many of whom worked on the Thai-Burma Railway during World War II, consecutively attended The Liverpool School of Tropical Medicine for clinical review between January 1987 and August 1990. Fifty-two (17%) were found to have chronic strongyloidiasis.

Diagnostic criteria included any of the following: characteristic larva currens rash, positive Strongyloides serology, and positive stool examination. Forty-seven were evaluable 6 months, after therapy with albendazole 400 mg twice daily for 3 days, which resulted in a 75% cure rate. Cure was defined as disappearance of the rash, if present, negative serology and negative stool examination. Patients who had more than one positive diagnostic feature were only considered cured if both or all had disappeared or become negative.

All 12 of the patients in whom initial treatment failed were given a second course of albendazole: three further cures were obtained in eight evaluable patients. The overall cure rate was 81%. The only side-effects recorded were mild nausea and diarrhoea in one patient. We suggest that albendazole should be the treatment of choice for chronic strongyloidiasis.

IVERMECTIN

A randomized trial of single- and two-dose ivermectin versus thiabendazole for treatment of strongyloidiasis.

Gann PH, Neva FA, Gam AA.

Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
J Infect Dis 1994 May;169(5):1076-9 Abstract quote
A randomized trial is described comparing ivermectin and thiabendazole for treatment of chronic infection with Strongyloides stercoralis.

Subjects received ivermectin (200 micrograms/kg) in a single dose, ivermectin (200 micrograms/kg) on 2 consecutive days, or thiabendazole (50 mg/kg/day) twice daily for 3 consecutive days. Most subjects (94%) had intermittent symptoms, including urticaria, epigastric pain, and diarrhea. Stools were examined 7 days and 1, 3, 6, 10, and 22 months after treatment. Fifty-three subjects completed at least 3 months of follow-up. Only 1 of 34 and 2 of 19 ivermectin and thiabendazole subjects, respectively, had a stool positive for larvae after treatment. Symptoms were relieved in all 3 groups and eosinophil levels returned to normal in 90% of all subjects by 12 months.

Nearly 95% of thiabendazole subjects had short-term adverse effects during therapy versus only 18% of those treated with ivermectin. One dose of ivermectin provides safety and efficacy equivalent to thiabendazole with a much lower prevalence of side effects and, consequently, better compliance.

Treatment of Strongyloides stercoralis infection with ivermectin compared with albendazole: results of an open study of 60 cases.

Datry A, Hilmarsdottir I, Mayorga-Sagastume R, Lyagoubi M, Gaxotte P, Biligui S, Chodakewitz J, Neu D, Danis M, Gentilini M.

Departement de Maladies Infectieuses, Tropicales et Parasitaires et de Sante Publique, Groupe Hospitalier Pitie-Salpetriere, Paris, France.

Trans R Soc Trop Med Hyg 1994 May-Jun;88(3):344-5 Abstract quote
Ivermectin is highly effective against animal intestinal nematodes and is used in the treatment of onchocerciasis in humans. A study was undertaken to compare the efficacy of the drug with that of albendazole in the treatment of uncomplicated strongyloidiasis. Sixty patients with confirmed Strongyloides stercoralis infection were enrolled in an open randomized study and given either albendazole, 400 mg/d for 3 d or ivermectin, 150-200 micrograms/kg in a single dose. Efficacy and tolerance were evaluated on days 7, 30 and 90.

Each visit included a parasitological examination of 3 stool specimens, using saline and Kato smears and formalin-ether and Baermann concentrations. Fifty-three patients were eligible for evaluation. Parasitological cure was obtained in 24 of the 29 patients treated with ivermectin (83%) and in 9 of the 24 patients who were given albendazole (38%); ivermectin was significantly more effective than albendazole (P < 0.01).

Clinical and biological adverse reactions were negligible in both treatment groups. The 20 patients who failed therapy were given a second treatment course with 150-200 micrograms/kg of ivermectin in a single dose or on 2 consecutive days. Sixteen patients were cured and the other 4 had only incomplete follow-up. Ivermectin therefore constitutes an acceptable therapeutic alternative for uncomplicated strongyloidiasis.

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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DISEASE ASSOCIATIONS	CHARACTERIZATION
HTLV-1
Treatment failure in intestinal strongyloidiasis: an indicator of HTLV-I infection. Terashima A, Alvarez H, Tello R, Infante R, Freedman DO, Gotuzzo E. Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.	Int J Infect Dis 2002 Mar;6(1):28-30 Abstract quote BACKGROUND: The association of severe strongyloides with HTLV-I is well known; however, the seroprevalence of HTLV-I in other groups with strongyloidiasis is still unknown. We conducted a prospective study in patients with intestinal strongyloidiasis without known immunodepression who failed to respond to standard therapy with ivermectin or thiabendazole (failure was defined as one positive stool examination at the post-therapy follow up). All these patients were tested for HTLV-I by ELISA and Western Blot. RESULTS: Forty seven patients were evaluated: 74.5% (35 out of 47) were HTLV-I positive, without significant difference between males (76%) and females (72.7%). CONCLUSIONS: We recommend that all patients with uncomplicated intestinal strongyloidiasis, who fail standard therapy, be studied for HTLV-I infection.
Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia. Plumelle Y, Gonin C, Edouard A, Bucher BJ, Thomas L, Brebion A, Panelatti G. Department of Hematobiology, University Hospital, Martinique, French West Indies.	Am J Clin Pathol 1997 Jan;107(1):81-7 Abstract quote Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis. To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.
NEPHROTIC SYNDROME
Strongyloidiasis associated with nephrotic syndrome. Mori S, Konishi T, Matsuoka K, Deguchi M, Ohta M, Mizuno O, Ueno T, Okinaka T, Nishimura Y, Ito N, Nakano T. Department of Internal Medicine, Mie Prefectural General Medical Center, Yokkaichi.	Intern Med 1998 Jul;37(7):606-10 Abstract quote We report a nephrotic syndrome patient with eosinophilia who developed ileus, epigastralgia and malabsorption due to strongyloidiasis which became symptomatic by steroid therapy. The patient was then treated with thiabendazole and recovered. A percutaneous renal biopsy revealed minimal change nephrotic syndrome. This renal injury may be brought on by severe infection of Strongyloides stercoralis. It is important to rule out strongyloidiasis prior to corticosteroid therapy to patients from eosinophilia endemic areas.

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
GI TRACT
Mesenteric arteriographic findings in a patient with strongyloides stercoralis hyperinfection. Reiman S, Fisher R, Dodds C, Trinh C, Laucirica R, Whigham CJ. Department of Radiology, Ben Taub General Hospital, 1504 Taub Loop, Houston, Texas 77030-1608, USA	J Vasc Interv Radiol 2002 Jun;13(6):635-8 Abstract quote The authors present a case of a Latin American patient with systemic lupus erythematosus who was referred for a mesenteric arteriogram because of acute lower gastrointestinal bleeding. Multiple segments of dilation alternating with stenosis or spasm were noted in the superior mesenteric artery/inferior mesenteric artery distributions. At the time, these irregularities were thought to be representative of lupus vasculitis. Despite appropriate treatment for vasculitis, the patient continued to have bleeding episodes and ultimately died of multiple organ failure. Autopsy demonstrated no evidence of vasculitis, but did demonstrate the unexpected finding of Strongyloides stercoralis hyperinfection with vessel invasion.
Comparative features of double-contrast barium studies in patients with isosporiasis and strongyloidiasis. Hizawa K, Iida M, Eguchi K, Aoyagi K, Tada S, Kuwano Y, Mochizuki Y, Fujishima M. Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan	Clin Radiol 1998 Oct;53(10):764-7 Abstract quote OBJECTIVE: To compare the gastrointestinal features of isosporiasis and strongyloidiasis. METHODS: Two patients with isosporiasis and three patients with strongyloidiasis were assessed by double-contrast radiography of the duodenum and small intestine, with reference to histology of the duodenal biopsy specimens. RESULTS: Both conditions affected the duodenum and the proximal jejunum, and showed similar radiographic changes as the diseases progressed. Thus, three patients with diarrhoea lasting 1 year or less showed only minimal or irregularly thickened mucosal folds, which seemed to result from mucosal inflammation. Two patients with long-standing disease periods (17 years and 30 years) presented a markedly granular mucosal appearance with effacement of the folds on radiography. These chronological differences in the radiographic features seemed to reflect the degree of villous atrophy. CONCLUSION: Isosporiasis has similar radiographic features of strongyloidiasis.
LUNG
Clinical and imaging features of pulmonary strongyloidiasis. Woodring JH, Halfhill H 2nd, Berger R, Reed JC, Moser N. Department of Diagnostic Radiology, University of Kentucky Medical Center, Lexington 40536-0084, USA.	South Med J 1996 Jan;89(1):10-9 Abstract quote We evaluated 20 patients with pulmonary strongyloidiasis for risk factors, clinical and imaging manifestations, complications, treatment, and outcome. Eighteen (90%) had risk factors for strongyloidiasis including steroid use, age greater than 65, chronic lung disease, use of histamine blockers, or chronic debilitating illness. Pulmonary signs and symptoms, including cough, shortness of breath, wheezing, and hemoptysis, were present in 19 (95%); adult respiratory distress syndrome (ARDS) developed in 9 (45%). Pulmonary infiltrates occurred in 18 (90%). Gastrointestinal signs and symptoms were also common. Peripheral blood eosinophilia occurred in 15 (75%). Twelve (60%) had secondary infection, and 3 (15%) had bacterial lung abscesses. All were treated with thiabendazole, 25 mg/kg twice daily; on average, patients without ARDS were treated for 3 days, versus 7 days for those with ARDS. Seventy percent responded to therapy; 30% died. Preexisting chronic lung disease and ARDS were statistically significant predictors of a poor prognosis.
LABORATORY MARKERS
SEROLOGY
Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area. Loutfy MR, Wilson M, Keystone JS, Kain KC. Department of Medicine, University of Toronto, Ontario, Canada	Am J Trop Med Hyg 2002 Jun;66(6):749-52 Abstract quote Strongyloidiasis is a chronic infection that may result in significant morbidity; however, diagnosis and management remain problematic. The objective of this study was to 1) evaluate the demographic, clinical, and laboratory features of 76 consecutive individuals who had Strongyloides stercoralis larvae identified in their fecal specimens; 2) determine the sensitivity of the Centers for Disease Control and Prevention (CDC) enzyme immunoassay (EIA) for detecting antibodies to Strongyloides in those with confirmed infection; and 3) assess the serologic responses and changes in eosinophil counts following treatment. Most (96%) cases occurred in immigrants, but some patients had immigrated as long as 40 years earlier. The CDC Strongyloides EIA had a sensitivity of 94.6% (95% confidence interval = 92.0-97.2%) in this patient population with proven infection. Serologic and eosinophil counts decreased after therapy, suggesting that they may be useful markers of treatment success.
SERUM IgE
A three years follow-up of total serum IgE levels in three patients treated for strongyloidiasis. Poirriez J. CIMOT, 4-10, rue Albert Thomas, 59210 Coudekerque-Branche, France.	Parasite 2001 Dec;8(4):359-62 Abstract quote A three years follow-up of the level of serum total IgE was made for the first time in three patients with strongyloidiasis after efficient treatment. The decrease of IgE was slow and progressive, showing a logarithmic curve. This regular decrease of total serum IgE could be used as an additional criterion for the evaluation of the efficiency of drug therapy in patients with strongyloidiasis. The persistence of high levels of total IgE two or three years after the elimination of the intestinal parasites, after the return of blood eosinophils to a normal level (within six months), and after the disappearance of specific antibodies, shows that the regulation of the IgE elimination seems to be a complex mechanism.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
APPENDIX
Strongyloides stercoralis infection as a cause of acute granulomatous appendicitis in an HIV-positive patient in Athens, Greece. Felekouras E, Kontos M, Kyriakou V, Hatzianagnostou D, Dimaroggona K, Papalampros E, Kordossis T, Bastounis E. Department of Surgery, Laikon General Hospital and Athens School of Medicine, Athens, Greece	Scand J Infect Dis 2002;34(11):856-7 Abstract quote A case of acute granulomatous appendicitis due to Strongyloides stercoralis infection in an HIV-positive patient is described. To our knowledge this is the first case presented in the literature.
COLON
Strongyloidiasis colitis: a case report and review of the literature. Al Samman M, Haque S, Long JD. Department of Medicine, Texas Tech University Health Sciences Center El Paso, 79905, USA.	J Clin Gastroenterol 1999 Jan;28(1):77-80 Abstract quote A case is described of a nonimmunocompromised man who presented with diarrhea, weight loss, and microcytic anemia. Colonoscopy revealed a pancolitis characterized by aphthoid ulceration on endoscopy and intense tissue eosinophilic infiltrates on biopsy. Both colonic biopsies and stool aspirates revealed the larvae of Strongyloides stercoralis, thus confirming this parasite as the causative agent for the colitis.
HYPERINFECTION
Hyperinfection syndrome in strongyloidiasis: Report of two cases. Lemos LB, Qu Z, Laucirica R, Fred HL. Departments of Pathology and Internal Medicine, University of Texas in Houston, Harris County Health Department Hospitals, Houston TX.	Ann Diagn Pathol 2003 Apr;7(2):87-94 Abstract quote Hyperinfection in strongyloidiasis has been associated with corticosteroid treatment. Other immunodepressive conditions also seem to facilitate the state of hyperinfection. The etiologic diagnosis of this parasitosis can be difficult to reach and a positive urine microscopy is unusual. We report two patients under corticosteroid therapy with disseminated strongyloidiasis; both had eosinophilia. The first patient, followed for 8 years for autoimmune hemolytic anemia, recently developed abdominal symptoms. A colonoscopy was performed 1 month before admission and the biopsy was thought to show nonspecific changes. At admission, few larvae of Strongyloides stercoralis were disclosed by urine microscopy, and a review of the colonic biopsy uncovered a few larvae of Strongyloides. The patient received anti-helmintic therapy with a dramatic improvement. The second patient, under treatment for lupus erythematosus for 3 years, was admitted with pulmonary symptoms and during admission developed massive gastrointestinal bleeding. Disseminated strongyloidiasis was discovered only at autopsy. The low suspicion index for strongyloidiasis resulted in delaying the etiologic diagnosis in one patient and in failing to diagnose the disease in the other. The morphologic features of the parasite in the two cases are presented with emphasis on the difficulties of recognizing the larvae in the intestinal biopsy.
Hyperinfective strongyloidiasis in the medical ward: review of 27 cases in 5 years. Adedayo O, Grell G, Bellot P. Department of Medicine, Princess Margaret Hospital, Roseau, Dominica, West Indies.	South Med J 2002 Jul;95(7):711-6 Abstract quote BACKGROUND: Hyperinfective strongyloidiasis is rare, but the mortality rate is very high. It occurs most commonly in immunocompromised patients. We reviewed the clinical presentation and mortality rate of cases managed in our facility. METHOD: Twenty-seven patients with hyperinfective strongyloidiasis admitted to our medical ward over a 5-year period were prospectively studied. RESULTS: In our study, there were 18 males and 9 females (mean age, 58 years). Weight loss, gastrointestinal symptoms, hypoproteinemia, and anemia were the main clinical presentations. Mortality rate was 26%; human T-lymphotropic virus (HTLV-1) infection, chronic alcoholism, eosinopenia, sepsis, and prerenal azotemia on admission were poor prognostic factors. HTLV-1 infection was the main underlying disease in 71% of patients, and 44% of patients had a history of chronic alcoholism. CONCLUSION: Early diagnosis and treatment with thiabendazole may reduce mortality in hyperinfective strongyloidiasis. Hyperinfective strongyloidiasis may also be a clinical marker of HTLV-1 infection in areas where both entities are endemic or in immigrants from such areas.
LUNG
Extensive intra-alveolar haemorrhage caused by disseminated strongyloidiasis. Kinjo T, Tsuhako K, Nakazato I, Ito E, Sato Y, Koyanagi Y, Iwamasa T. Department of Pathology, Ryukyu University School of Medicine, Okinawa, Japan.	Int J Parasitol 1998 Feb;28(2):323-30 Abstract quote We describe here four cases of disseminated strongyloidiasis. In Okinawa, it has been reported that about 10% of the residents are infected with Strongyloides stercoralis, but disseminated cases are rare. Detailed histopathological examination revealed that the present four cases could clearly be separated into two groups, two acute cases and two subacute cases. The acute cases died rapidly due to extensive diffuse intra-alveolar haemorrhage in both lungs. However, there were no inflammatory infiltrates, abscesses or granulomas in the lungs. Worms were demonstrated in the alveolar spaces. No extensive bleeding was observed in any organs except the lungs. The acute cases could be diagnosed as severe diffuse intra-alveolar haemorrhage syndrome, but deposition of immune complex (parasite antigen and immunoglobulins) and complement C3c was not demonstrated in the alveolar wall and small vessels of the lung. The subacute cases exhibited no such extensive haemorrhage, but scattered microabscesses were found with sepsis. During the migration of the worms from the colon, enteric bacteria entered the circulation in the two subacute cases. The acute cases received steroid therapy before the dissemination of the worms, but the two subacute cases did not. Steroids might have influenced the Strongyloides stercoralis dissemination and/or the course of the disease.
Pulmonary manifestations of strongyloidiasis. Wehner JH, Kirsch CM. Department of Medicine, Stanford University School of Medicine, San Jose, CA 95128, USA.	Semin Respir Infect 1997 Jun;12(2):122-9 Abstract quote Strongyloides stercoralis (SS) is endemic in tropical and subtropical areas worldwide and in the southeastern United States. The lifecycle of SS is both unique and complex. Human infection begins with the penetration of skin by filariform larvae that migrate hematogenously to the lungs. Larvae then ascend the airway, are swallowed, and mature in the gut. Unlike other nematodes, SS can autoinfect the same host and persist for decades. Categorization of infection includes acute, chronic-uncomplicated, and disseminated forms. Clinical manifestations depend on the particular organs involved. Fifteen to thirty percent of chronically infected people may be asymptomatic. On the other hand, SS may cause the adult respiratory distress syndrome, septic shock, and death. The diagnosis of SS infection is suspected in patients from endemic areas who have blood eosinophilia, and gastrointestinal or pulmonary symptoms. A definitive diagnosis is established by demonstration of SS larvae in stool, body fluids, or tissues. A presumptive diagnosis of SS infection can be achieved by serology. Thiabendazole is the mainstay of treatment, but repeat doses may be necessary if the parasite is not initially eradicated. The low incidence of disseminated SS in areas endemic for both SS and AIDS is surprising and unexplained.
MESENTERIC LYMPHADENOPATHY
Strongyloides stercoralis mesenteric lymphadenopathy: Clue to the etiopathogenesis of intestinal pseudo-obstruction in HIV-infected patients. Ramdial PK, Hlatshwayo NH, Singh B. Department of Pathology, Nelson R Mandela School of Medicine, Faculty of Health Sciences, University of KwaZulu Natal & Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu Natal 4058, South Africa.	Ann Diagn Pathol. 2006 Aug;10(4):209-14. Abstract quote Mesenteric lymph node involvement in Strongyloides stercoralis hyperinfective states, described as an autopsy finding, remains a relatively poorly recognized and possibly underreported, antemortem phenomenon. Furthermore, the occurrence of S stercoralis mesenteric lymphadenopathy as a tocsin of bowel strongyloidiasis and the clue to the cause of intestinal pseudo-obstruction are undescribed. We report S stercoralis mesenteric lymphadenopathy and intestinal pseudo-obstruction in 5 HIV seropositive male patients, 21 to 42 years, who presented with abdominal pain and variable vomiting, diarrhea, and constipation. All were pale, pyrexial, and emaciated with abdominal distension. The preoperative diagnosis was intestinal obstruction. Poor clinical response on conservative therapy necessitated laparotomy. Dilated small bowel loops, ascites, and mesenteric lymphadenopathy were consistently noted; a diagnosis of pseudo-obstruction due to underlying tuberculosis or lymphoma was made. The mesenteric lymph nodes were biopsied. The pertinent nodal features were a dense infiltrate of eosinophils, eosinophil microabscesses and degranulation, a focal Splendore-Hoeppli phenomenon, and randomly disposed, but elusive, S stercoralis filariform larvae. Clinical deterioration confirmed intestinal complications at repeat laparotomy. Intestinal resections were performed in 4 patients; histopathologic appraisal confirmed intestinal strongyloidiasis. All patients died within 3 to 7 days after surgery. Heightened awareness of S stercoralis mesenteric lymphadenopathy as a sentinel of intestinal strongyloidiasis and etiopathogenetic clue of intestinal pseudo-obstruction may allow timely diagnosis and medical treatment and avoidance of further surgery, potentially reducing the long-term morbidity associated with S stercoralis hyperinfection.

TREATMENT	CHARACTERIZATION
GENERAL	Thiabendazole Mebendazole
ALBENDAZOLE
Albendazole is effective treatment for chronic strongyloidiasis. Archibald LK, Beeching NJ, Gill GV, Bailey JW, Bell DR. Liverpool School of Tropical Medicine.	Q J Med 1993 Mar;86(3):191-5 Abstract quote A total of 301 British ex-Far East prisoners of war, many of whom worked on the Thai-Burma Railway during World War II, consecutively attended The Liverpool School of Tropical Medicine for clinical review between January 1987 and August 1990. Fifty-two (17%) were found to have chronic strongyloidiasis. Diagnostic criteria included any of the following: characteristic larva currens rash, positive Strongyloides serology, and positive stool examination. Forty-seven were evaluable 6 months, after therapy with albendazole 400 mg twice daily for 3 days, which resulted in a 75% cure rate. Cure was defined as disappearance of the rash, if present, negative serology and negative stool examination. Patients who had more than one positive diagnostic feature were only considered cured if both or all had disappeared or become negative. All 12 of the patients in whom initial treatment failed were given a second course of albendazole: three further cures were obtained in eight evaluable patients. The overall cure rate was 81%. The only side-effects recorded were mild nausea and diarrhoea in one patient. We suggest that albendazole should be the treatment of choice for chronic strongyloidiasis.
IVERMECTIN
A randomized trial of single- and two-dose ivermectin versus thiabendazole for treatment of strongyloidiasis. Gann PH, Neva FA, Gam AA. Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois 60611.	J Infect Dis 1994 May;169(5):1076-9 Abstract quote A randomized trial is described comparing ivermectin and thiabendazole for treatment of chronic infection with Strongyloides stercoralis. Subjects received ivermectin (200 micrograms/kg) in a single dose, ivermectin (200 micrograms/kg) on 2 consecutive days, or thiabendazole (50 mg/kg/day) twice daily for 3 consecutive days. Most subjects (94%) had intermittent symptoms, including urticaria, epigastric pain, and diarrhea. Stools were examined 7 days and 1, 3, 6, 10, and 22 months after treatment. Fifty-three subjects completed at least 3 months of follow-up. Only 1 of 34 and 2 of 19 ivermectin and thiabendazole subjects, respectively, had a stool positive for larvae after treatment. Symptoms were relieved in all 3 groups and eosinophil levels returned to normal in 90% of all subjects by 12 months. Nearly 95% of thiabendazole subjects had short-term adverse effects during therapy versus only 18% of those treated with ivermectin. One dose of ivermectin provides safety and efficacy equivalent to thiabendazole with a much lower prevalence of side effects and, consequently, better compliance.
Treatment of Strongyloides stercoralis infection with ivermectin compared with albendazole: results of an open study of 60 cases. Datry A, Hilmarsdottir I, Mayorga-Sagastume R, Lyagoubi M, Gaxotte P, Biligui S, Chodakewitz J, Neu D, Danis M, Gentilini M. Departement de Maladies Infectieuses, Tropicales et Parasitaires et de Sante Publique, Groupe Hospitalier Pitie-Salpetriere, Paris, France.	Trans R Soc Trop Med Hyg 1994 May-Jun;88(3):344-5 Abstract quote Ivermectin is highly effective against animal intestinal nematodes and is used in the treatment of onchocerciasis in humans. A study was undertaken to compare the efficacy of the drug with that of albendazole in the treatment of uncomplicated strongyloidiasis. Sixty patients with confirmed Strongyloides stercoralis infection were enrolled in an open randomized study and given either albendazole, 400 mg/d for 3 d or ivermectin, 150-200 micrograms/kg in a single dose. Efficacy and tolerance were evaluated on days 7, 30 and 90. Each visit included a parasitological examination of 3 stool specimens, using saline and Kato smears and formalin-ether and Baermann concentrations. Fifty-three patients were eligible for evaluation. Parasitological cure was obtained in 24 of the 29 patients treated with ivermectin (83%) and in 9 of the 24 patients who were given albendazole (38%); ivermectin was significantly more effective than albendazole (P < 0.01). Clinical and biological adverse reactions were negligible in both treatment groups. The 20 patients who failed therapy were given a second treatment course with 150-200 micrograms/kg of ivermectin in a single dose or on 2 consecutive days. Sixteen patients were cured and the other 4 had only incomplete follow-up. Ivermectin therefore constitutes an acceptable therapeutic alternative for uncomplicated strongyloidiasis.

Epidemiology
Disease Associations
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Histopathological Features and Variants
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EPIDEMIOLOGY	CHARACTERIZATION
GEOGRAPHY
MEDITERRANEAN
Endemic strongyloidiasis on the Spanish Mediterranean coast. Sanchez PR, Guzman AP, Guillen SM, Adell RI, Estruch AM, Gonzalo IN, Olmos CR. Department of Internal Medicine, Requena General Hospital, Valencia, Spain.	QJM 2001 Jul;94(7):357-63 Abstract quote Diagnosis and treatment of Strongyloides stercoralis infection can be difficult, and a high degree of clinical suspicion in patients who have visited an endemic area is required. We describe the epidemiology and clinical features of 152 prospectively identified cases of strongyloidiasis in an European region, and identify risk factors for the development of severe forms of the disease. This was a prospective study of all patients admitted to a single institution over an 8-year period. Patients (n=152) were mainly elderly male farmers (79%) who had acquired the disease by working barefoot in contact with soil and ingesting non-drinking water. Eosinophilia was a sensitive marker for the infection (82%). Twenty patients (13%) developed severe forms of the illness and six patients (4%) died. A significant association was found between severe forms of strongyloidiasis and steroid usage (OR 9.0, 95%CI 2.1-37.6), immunodebilitating illness (OR 10.1, 95%CI 3.2-32.3) and other immunosuppressive therapy (OR 13.7, 95%CI 2.9-58.7), but by logistic regression analysis, only immunodebilitating disease was as a risk factor (OR 2.1, 95%CI 1.78-2.43). S. stercolaris infection is endemic in the Spanish Mediterranean coast. The frequent development of severe forms of the disease, with a high mortality, makes early recognition and treatment essential.
EPIDEMIOLOGIC ASSOCIATIONS
NOSOCOMIAL
The risk of Strongyloides stercoralis transmission from patients with disseminated strongyloidiasis to the medical staff. Maraha B, Buiting AG, Hol C, Pelgrom R, Blotkamp C, Polderman AM. Department of Medical Microbiology, St Elisabeth Hospital, Tilburg, The Netherlands.	J Hosp Infect 2001 Nov;49(3):222-4 Abstract quote To assess the risk of Strongyloides stercoralis transmission from two patients with disseminated strongyloidiasis to medical staff who had been in close contact with the patients, blood and stool specimens were obtained from medical staff two to three months after close contact with the patients. Antibodies to S. stercoralis were determined in blood. Stool specimens were tested for parasites with three different procedures.Forty-one medical staff were included. Culture and stool examination were negative in all subjects. Serology was negative in all subjects but one who had a borderline titer without signs or symptoms of strongyloidiasis. No evidence of transmission of S. stercoralis from patients with disseminated strongyloidiasis to medical staff was found.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
Histopathology of gastric and duodenal Strongyloides stercoralis locations in fifteen immunocompromised subjects. Rivasi F, Pampiglione S, Boldorini R, Cardinale L. Department of Pathologic Anatomy and Forensic Medicine, Section of Pathological Anatomy, University of Modena and Reggio Emilia, Modena, Italy	Arch Pathol Lab Med. 2006 Dec;130(12):1792-8. Abstract quote CONTEXT: Strongyloidiasis is a worldwide parasitic infection affecting approximately 75 million people. In Italy, it was more prevalent in the past among rural populations of irrigated areas. OBJECTIVE: To determine the histopathologic alterations of the gastric and duodenal mucosa associated with the presence of Strongyloides stercoralis parasites. DESIGN: Fifteen cases of strongyloidiasis were observed in immunocompromised patients during a recent 6-year period in Italy. S. stercoralis was found histologically in gastric biopsies (10 cases), in a gastrectomy (1 case), and in duodenal biopsies (9 cases). In 5 cases the parasite was present both in gastric and duodenal biopsies. Four patients were affected by lymphoma, 2 by multiple myeloma, 2 by gastric carcinoma, 1 by chronic myeloid leukemia, 1 by sideroblastic anemia, 1 by colorectal adenocarcinoma, 1 by chronic idiopathic myelofibrosis, 1 by chronic gastritis, 1 by gastric ulcers, and 1 by rheumatoid arthritis in corticosteroid therapy. No patient was affected by human immunodeficiency virus infection. Strongyloidiasis was not clinically diagnosed. RESULTS: Histologic examination revealed several sections of S. stercoralis larvae, many eggs, and some adult forms. All the parasites were located in the gastric and/or the duodenal crypts. Eosinophils infiltrating into the lamina propria were found in all cases; their intensity was correlated with the intensity of the infection. CONCLUSIONS: Histologic diagnosis of strongyloidiasis must be taken into consideration when examining both gastric and duodenal biopsies in immunocompromised patients, to avoid the development of an overwhelming infection of the parasite, which is dangerous for the life of the patient.
COLITIS
Strongyloides stercoralis eosinophilic granulomatous enterocolitis. Gutierrez Y, Bhatia P, Garbadawala ST, Dobson JR, Wallace TM, Carey TE. Department of Pathology, University Hospitals of Cleveland, OH 44106, USA.	Am J Surg Pathol 1996 May;20(5):603-12 Abstract quote Six patients suffering from an unusual form of colitis produced by Strongyloides stercoralis hyperinfection are described. In contrast to the usual Strongyloides hyperinfection syndrome, in which small intestinal and pulmonary manifestations are seen in patients with some forms of immunodeficiency, the patients described here presented with only a characteristic transmural eosinophilic granulomatous inflammation affecting mostly the colonic wall and clinically mimicking ulcerative colitis or Crohn's disease. This Strongyloides eosinophilic granulomatous enterocolitis apparently results from a florid inflammatory response by eosinophils, histiocytes, and giant cells with formation of granulomas that destroy the larvae entering the colon. This morphologic picture differs from that of the well-described hyperinfection syndrome, in which the bulk of the larvae pass through the colonic wall to complete the life cycle, with only a few larvae destroyed in the colon. The probable pathophysiologic mechanism of this unusual manifestation of hyperinfection is discussed based on the anatomic and clinical observations of patients who presented at different stages in the evolution of their condition and whose length of follow-up varied.

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
ELECTRON MICROSCOPY
Strongyloides stercoralis: ultrastructural study of newly hatched larvae within human duodenal mucosa. Dionisio D, Manneschi LI, di Lollo S, Orsi A, Tani A, Papucci A, Esperti F, Leoncini F. Infectious Diseases Unit, Pistoia Hospital, Italy.	J Clin Pathol 2000 Feb;53(2):110-6 Abstract quote AIM: To investigate the ultrastructural features of the newly hatched larvae of Strongyloides stercoralis in human duodenal mucosa. METHODS: Duodenal biopsies from an AIDS patient were studied by transmission electron microscopy to investigate morphology, location, and host-worm relations of newly hatched larvae. RESULTS: Newly hatched larvae were found in the Lieberkuhn crypts within the tunnels formed by migration of parthenogenic females. Delimiting enterocytes were compressed. Release of larvae into the gut lumen was also documented. It was shown that both a thin and a thick membrane surrounded the eggs and larvae, as a tegument derived respectively from parasite and host. Segmentary spike-like waves, caused by contractures of worm body musculature, were observed on the surface of newly hatched larvae, and their intestinal lumen was closed and empty, with no budding microvilli. Immaturity of the cuticle and some degree immaturity of amphidial neurones were found, but there was no evidence of either immaturity or signs of damage to other structures. CONCLUSIONS: Newly hatched larvae of S stercoralis appear to be a non-feeding immature stage capable of active movement through the epithelium, causing mechanical damage. The tegument resulting from the thin and the thick membrane may protect the parasite and reduce any disadvantage caused by immaturity.