Intestinal threadworm Strongyloides stercoralis is a parasite of dog, cat and primates that occurs worldwide being most prevalent in tropical and subtropical countries. The adult parasitic worm is about 2 mm long and slender. It possesses both parasitic and free-living lifecycles. The parasitic worms are females. Strongyloides stercoralis infects the host via percutaneous, peroral or transmammary transmission in addition to autoinfection. Clinical disease varies from inapparent to severe enteritis and pneumonia. The diagnosis is based on demonstration of larvae in fresh faeces, which is best made by Baermann technique.
Strongyloides stercoralis infection was diagnosed in autopsy in a 10-week-old puppy born and raised in a Finnish kennel. Prior to its sudden death, the puppy had suffered from gastrointestinal disturbance for three weeks. Subsequent sampling of the dogs in the kennel revealed that three adult dogs in the kennel were also infected.
The present case shows that S. stercoralis can complete its life cycle and cause disease in dogs also in Northern Europe. Infection can be maintained also in a temperate climate and may become a chronic problem in a kennel environment. Infection may be underdiagnosed as Baermann technique is not routinely performed in small animal practice.
Summary: This review starts with discussions of several infectious causes of eosinophilic pneumonia, which are almost exclusively parasitic in nature. Pulmonary infections due specifically to Ascaris, hookworms, Strongyloides, Paragonimus, filariasis, and Toxocara are considered in detail. The discussion then moves to noninfectious causes of eosinophilic pulmonary infiltration, including allergic sensitization to Aspergillus, acute and chronic eosinophilic pneumonias, Churg-Strauss syndrome, hypereosinophilic syndromes, and pulmonary eosinophilia due to exposure to specific medications or toxins.
To communicate the presence of adult females, rabditoid larvae and eggs of Strongyloides stercoralis (S. stercoralis) in the respiratory secretions obtained by tracheal aspirate from a HIV-negative patient who was suffering from polymyositis, and treated with corticoids and amethopterin and assisted by pneumonia.
The respiratory secretions submitted to the Parasitology Laboratory of the Muñiz Hospital were made more concentrated by centrifugation (1 500 r/min for 15 seconds). Wet mount microscopy was performed with the pellet.
It revealed adult females, rabditoid larvae and eggs of S. stercoralis. Further parasitological studies performed after the start of the treatment with ivermectin on fresh fecal samples, gastric lavages and tracheal aspirates showed scanty mobile filariform and rabditoid larvae of the same parasite.
The presence of adult female S. stercoralis which has never been observed before in the clinical samples submitted to our Laboratory for investigation can be considered as an indirect marker of the severe immunosupression of the patient.
Strongyloidiasis; Strongyloides stercoralis; Hyperinfection; Parasitological diagnosis; Adult female
Two cases of unsuspected Strongyloides stercoralis infection were elucidated by the displacement of bacterial colonies on primary plating media. Observation of primary plates inoculated for the diagnosis of bacterial pneumonia or gastroenteritis revealed that normal flora colonies had been moved and were aligned in a pathway, or track. This unusual colony alignment prompted us to request a stool for the examination of parasites, and S. stercoralis was found. It was concluded that the parasite is capable of motility on agar surfaces, resulting in the displacement of bacterial colonies that make up the normal flora.
Infection with the helminthic parasite, Strongyloides stercoralis, is usually acquired by skin invasion (or occasionally via ingestion of larvae). After transformation to the adult form, the parasite preferentially localises in the small intestine, especially in the duodenal and jejunal part. A remarkable feature of Strongyloides is its property of endogenous reinfection. In the case of an immunocompromised host a massive infection, called hyperinfections Strongyloides, may occur. Numerous gastrointestinal complications of strongyloides infections, sometimes with a lethal outcome, have been reported. The intestinal manifestations are usually limited to the small bowel, and rarely involve the stomach. We report a patient with complicated strongyloides infection of the stomach.
Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia–lymphoma (ATLL) in about 5% of infected individuals. Coinfection by Strongyloides stercoralis has been suggested to be a cofactor for development of ATLL. We describe a patient who presented with HTLV-1-associated chronic ATLL and Strongyloides infection. Studies of this patient’s viral RNA levels demonstrated stimulation of HTLV-1 replication by Strongyloides, which resolved with anti-helminthic therapy. This case provides support for the hypothesis that Strongyloides is a cofactor for ATLL via T-cell stimulation.
Accurate diagnosis of infection with the parasite Strongyloides stercoralis is hampered by the low concentration of larvae in stool, rendering parasitological diagnosis insensitive. Even if the more sensitive agar plate culture method is used repeated stool sampling is necessary to achieve satisfactory sensitivity. In this manuscript we describe the development of a coproantigen ELISA for diagnosis of infection. Polyclonal rabbit antiserum was raised against Strongyloides ratti excretory/secretory (E/S) antigen and utilized to develop an antigen capture ELISA. The assay enabled detection of subpatent rodent S. ratti and human S. stercoralis infection. No cross-reactivity was observed with purified E/S from Schistosoma japonicum, the hookworms Ancylostoma caninum, A. ceylanicum, nor with fecal samples collected from rodents harboring Trichuris muris or S. mansoni infection. Strongyloides coproantigens that appear stable when frozen as formalin-extracted fecal supernatants stored at −20°C remained positive up to 270 days of storage, whereas supernatants stored at 4°C tested negative. These results indicate that diagnosis of human strongyloidiasis by detection of coproantigen is an approach worthy of further development.
Strongyloides stercoralis is almost unique among human nematode infections in its ability to replicate within a patient's body, potentially leading to life-long infections if left untreated. Given the potential for severe life threatening Strongyloides infections and the unsatisfactory results of current parasitologic and antibody tests, there is a need for more efficient diagnostic tools. In this study we generated an assay to specifically detect proteins expelled by Strongyloides. Initially this assay for Strongyloides detection was not specific for the parasite; however, after developing a methodology using formaldehyde preservation of feces we specifically detected Strongyloides antigens in rodent and human stool. This methodology was then tested for cross-reactivity with purified proteins from closely related parasites and furthermore for cross-reactivity against faeces collected from animals harbouring single parasitic infections. Using this approach we found no non-specific reactivity with host or to various parasite antigens, suggesting that this assay is truly specific for Strongyloides detection.
Strongyloides stercoralis is an intestinal nematode that causes strongyloidiasis, which affects 30 to 100 million people worldwide. Risk factors for hyperinfection and disseminated disease include immunosuppressive drug therapy, human T-lymphotropic virus-1 (HTLV-1) infection, solid organ and bone marrow transplantation, hematologic malignant diseases, hypogammaglobulinemia, and severe malnutrition and associated conditions. The diagnosis can be difficult because a single stool examination fails to detect larvae in up to 70% of the cases, and the symptoms are nonspecific. Although eosinophilia is a common finding in patients with chronic Strongyloides infection, it is an unreliable predictor of hyperinfection. Furthermore, the lack of eosinophilia while receiving immunosuppressive therapy cannot reliably exclude the underlying chronic Strongyloides infection. We report here a fatal Strongyloides hyperinfection in a patient receiving allogeneic stem cell transplantation; risk factors and outcome in this clinical setting are discussed.
Axenic Pelodera strongyloides matured in a completely defined culture medium were homogenized and the homogenate separated into "nuclear," "mitochondrial," and supernatant fractions. Medium, homogenate and fractionates were analyzed using standard biochemical techniques. Ammonia was the only purine catabolite detected in the medium, but the electrolytes and enzymes of the major metabolic pathways in warm-blooded animals were found in the homogenate and fractionates. Nine months of artificial selection of an X-ray-induced mutant P. strongyloides yielded a strain with a 16-fold greater incidence of endotokia matricida (death of the mother due to internal birth of the young). Crossing with recently isolated wild-type individuals (low endotokia) reduced the frequency of endotokia in the succeeding generations to the level observed in the wild populations. The authors conclude P. strongyloides will be a suitable nematode for metabolic and genetic investigations when improved fully-defined media are developed.
Pelodera strongyloides; Metabolic pathways; Endotokia matricida; Genetic marker; Fully-defined artificial medium
Disseminated strongyloides is a rarely reported phenomenon and occurs in immuno-suppressed patients with chronic Strongyloides stercoralis infection. Typically, patients present with pulmonary symptoms but subsequently acquire Gram-negative sepsis. Several cases have been noted in Minnesota, and their presentation, diagnostic evaluation, and clinical outcomes were reviewed.
A retrospective chart review was conducted of complicated strongyloides infections from 1993 to 2002 in Minneapolis and St. Paul, MN. Cases were identified by reviewing hospital microbiology databases.
Metropolitan hospitals with large immigrant populations.
Nine patients, all of Southeast Asian heritage, were identified. Eight patients immigrated to the United States ≥ 3 years prior to acute presentation. All patients were receiving antecedent corticosteroids; in five patients, therapy was for presumed asthma. Absolute eosinophil counts > 500/μL occurred in only two patients prior to steroid initiation. Eight patients presented with respiratory distress, and Gram-negative sepsis developed in four patients. Four patients had evidence of right-heart strain on ECG or echocardiography at the time of presentation. Three patients died; all had eosinophil counts of < 400/μL.
Serious complications, including death, may occur in patients with chronic strongyloides infection treated with corticosteroids. Strongyloides hyperinfection usually presents as acute respiratory failure and may initially mimic an asthma exacerbation or pulmonary embolism. Southeast Asian patients presenting with new-onset “asthma,” acute respiratory distress, and/or Gram-negative sepsis should undergo evaluation to exclude strongyloides infection.
acute respiratory failure; disseminated strongyloides; Gram-negative sepsis; Strongyloides stercoralis
Significantly higher prevalence of Strongyloides stercoralis has been reported in chronic alcoholic patients. The aim of this investigation was to report the prevalence of Strongyloides larvae in stools of chronic alcoholic patients with known daily ethanol intake.
From January 2001 through December 2003 the results of fecal examinations and the daily ethanol intake were retrieved from the records of 263 chronic alcoholic and from 590 non-alcoholic male patients that sought health care at the outpatients unit of the University Hospital C A Moraes. Alcoholic patients were separated into four groups, with 150g intervals between the groups according to the daily ethanol intake.
(a) The frequency of Strongyloides was significantly higher in alcoholic patients than in control group (overall prevalence in alcoholic 20.5% versus 4.4% in control group; p = 0.001). Even in the group with a daily intake of ethanol equal to or less than 150g the prevalence was higher than in control group, although non significant (9.5%, versus 4.4% in control group; p = 0,071); (b) the prevalence of Strongyloides in alcoholic patients rises with the increase of ethanol intake (Pearson's Correlation Coefficient = 0.956; p = 0.022), even in patients without liver cirrhosis (Pearson's Correlation Coefficient = 0.927; p = 0.037).
These results confirm and reinforce the hypothesis that chronic alcoholism is associated with Strongyloides infection, which is in direct relationship with the severity of alcoholism, independently of the presence of liver cirrhosis.
It has been reported that Strongyloides stercoralis infection is more prevalent in chronic alcoholic patients than in non alcoholics living in the same country. In a retrospective study on the prevalence of S. stercoralis infection in a large sample of alcoholic patients, we demonstrate that this prevalence is significantly higher than in non-alcoholic patients admitted at the same hospital. Moreover, the frequency of the parasite was in close relationship with the daily amount of ingested ethanol, even in the absence of liver cirrhosis, reinforcing the idea that chronic alcoholism is associated with increased susceptibility to Strongyloides infection. Beside the bad hygiene profile of alcoholic patients, which explains high risk for acquisition of the parasite, the high prevalence of S. stercoralis in alcoholics may be in relationship with other effects of ethanol on the intestinal motility, steroid metabolism and immune system, which could enhance the chance of autoinfection and the survival and fecundity of females in duodenum. In this way, the number of larvae in the stools is higher in alcoholic patients, increasing the chance of a positive result in a stool examination by sedimentation method.
Strongyloides stercoralis is an intestinal nematode that can persist in the human host for decades after the initial infection and can progress to fulminant hyperinfection syndrome in immunocompromised hosts. We describe a patient who died of Strongyloides hyperinfection syndrome 2 months after orthotopic heart transplantation and discuss approaches to prevention, diagnosis, and treatment. Current practice guidelines recommend screening for and treatment of Strongyloides infection before transplantation, but physicians in the United States often miss opportunities to identify patients with chronic strongyloidiasis. Screening tests have limitations, and clinical suspicion remains an important component of the evaluation before transplantation. After immunocompromised patients develop hyperinfection syndrome, diagnosis is often delayed and mortality is high, so emphasis must be placed on screening and treatment before transplantation. We review current strategies for prevention, diagnosis, and treatment of chronic intestinal strongyloidiasis in patients who will undergo transplantation and discuss the clinical features and management of Strongyloides hyperinfection syndrome in transplant recipients.
As the prevalence and severity of anthelmintic resistance continue to rise, nematode infections in sheep correspondingly reduce the profitability of the sheep industry. In Costa Rica, sheep production systems are increasing in both number and importance. A field trial study was carried out to detect the level of anthelmintic resistance to albendazole and ivermectin in gastrointestinal nematodes (GIN) of sheep from seven farms in Costa Rica. Resistance was determined using the fecal egg count reduction test (FECRT). Three treatment groups were assessed on each farm: control, albendazole, and ivermectin. Haemonchus spp. (71%), Strongyloides sp. (57%), and Trichostrongylus spp. (43%) presented resistance levels to albendazole, whereas Strongyloides sp. (43%), Haemonchus spp. (29%), and Trichostrongylus spp. (29%) were resistant to ivermectin. Haemonchus spp., Strongyloides sp., and Trichostrongylus spp. were the most resistant GIN to both products. This study suggests that frequency of treatment, exclusive chemical control, and visual estimation of animal weight to calculate dosage may contribute to the high levels of anthelmintic resistance that were observed on the farms analyzed herein.
A wide range of biomolecules, including proteins, are excreted and secreted from helminths and contribute to the parasite's successful establishment, survival, and reproduction in an adverse habitat. Excretory and secretory proteins (ESP) are active at the interface between parasite and host and comprise potential targets for intervention. The intestinal nematode Strongyloides spp. exhibits an exceptional developmental plasticity in its life cycle characterized by parasitic and free-living generations. We investigated ESP from infective larvae, parasitic females, and free-living stages of the rat parasite Strongyloides ratti, which is genetically very similar to the human pathogen, Strongyloides stercoralis. Proteomic analysis of ESP revealed 586 proteins, with the largest number of stage-specific ESP found in infective larvae (196), followed by parasitic females (79) and free-living stages (35). One hundred and forty proteins were identified in all studied stages, including anti-oxidative enzymes, heat shock proteins, and carbohydrate-binding proteins. The stage-selective ESP of (1) infective larvae included an astacin metalloproteinase, the L3 Nie antigen, and a fatty acid retinoid-binding protein; (2) parasitic females included a prolyl oligopeptidase (prolyl serine carboxypeptidase), small heat shock proteins, and a secreted acidic protein; (3) free-living stages included a lysozyme family member, a carbohydrate-hydrolyzing enzyme, and saponin-like protein. We verified the differential expression of selected genes encoding ESP by qRT-PCR. ELISA analysis revealed the recognition of ESP by antibodies of S. ratti-infected rats. A prolyl oligopeptidase was identified as abundant parasitic female-specific ESP, and the effect of pyrrolidine-based prolyl oligopeptidase inhibitors showed concentration- and time-dependent inhibitory effects on female motility. The characterization of stage-related ESP from Strongyloides will help to further understand the interaction of this unique intestinal nematode with its host.
We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV) infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.
Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported.
We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock.
Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality.
We report strongyloides hyperinfection in two patients with generalized hypogammaglobulinemia from multiple myeloma and nephrotic syndrome, despite a significant strongyloides-specific immunoglobulin G (IgG) response. In contrast to reports on animals, where human IgG was shown to be a protective antibody, our observation suggests that in humans, immunity to the infective-stage larvae is not protective against the autoinfective larvae, which are the causative agents of strongyloides hyperinfection.
STRONGYLOIDIASIS, WHICH IS CAUSED by the nematode Strongyloides stercoralis, is a common and persistent infection, particularly in developing countries. In the setting of compromised cellular immunity, it can result in fulminant dissemination with case-fatality rates of over 70%. The majority of new Canadian immigrants come from countries where Strongyloides is highly endemic; therefore, the burden of Strongyloides may be underappreciated in Canada. Because early diagnosis and therapy can have a marked impact on disease outcome, screening for this infection should be considered mandatory for patients who have a history of travel or residence in a disease-endemic area and risk factors for disseminated disease (e.g., corticosteroid use and human T-lymphotropic virus type I infection).
From a study of strongyloides infections in man and animals in this region, it has been determined, in confirmation of the view of Grassi, Calmette, and others, that they are not causative factors in the production of diarrhea. The mother worm, however, burrows into the mucosa and deposits her ova there. Certain tissue reactions take place and are evidenced by the cellular proliferation in those portions of the intestines occupied by the nematodes. In animals, there is an associated anemia, not positively attributable to the strongyloides, but, on the other hand, not attributable to any other cause. It is possible that S. stercoralis may cause some degree of anemia in man. The amount is indeterminable in this region among hospital cases on account of the associated hookworm disease or malaria. Portals of entry for various microörganisms are made by the female mother worm and her larvæ in the small intestine, and, while no case of general bacterial infection has been proved to have arisen in this way, its occurrence is possible and highly probable. In the cultures of strongyloides of man, there is among natives, who presumably are infected with purely tropical strains, a very marked predominance of development by the indirect or sexually differentiated mode, in some cases, an absolutely pure culture of the indirect mode larvæ being obtained. There are, however, natives, cultures from whose stools contain from a single filariform larva of the direct phase up to a very definite predominance of this mode. Cultures from natives of the temperate zones contain a marked predominance of the direct phase larvæ. The presence of the filariform (direct mode), larva is perhaps best accounted for by its being an attempt at more perfect parasitism (Stiles). From a correlation of culture study with the results of a histological examination of the invaded mucosa, this explanation of the derivation of the two phases is suggested. The mother worm in the intestinal tract has two kinds of progeny: (a) those expelled into the crypts or lumen, and (b) those imbedded in the intestinal wall. One lot becomes larvæ of either the direct or indirect phase; the other lot of the opposite phase. It appears to me that the intraepithelial cell-developed larvæ furnish the direct phase, while the embryos expelled directly from the mother become the indirect phase larvæ. This will require for its confirmation a study of cultures in connection with a histological examination of the infected intestinal wall. Cold merely inhibits the development of the larvγaelig; into either the filariform (direct) or into the sexually differentiated adults, and does not alter the anlage. The resistant as well as the infecting form is the filariform larva, and all chemical larvicides must be directed against this form. Thymol and an alkaline cresol resin soap were found to be effective larvicides for the filariform larvæ. Two new strongyloides of the monkey and ant bear are described. Cultures of these nematodes show a predominance of the indirect mode of development.
Super-imposed infection with intestinal organisms can mimic a flare-up of underlying disease in patients with inflammatory bowel disease (IBD). We report a case of patient with long standing ulcerative colitis (UC), who presented with abdominal pain, diarrhea and low-grade fever after receiving systemic corticosteroids for an unrelated disorder. Despite a negative stool examination, a peripheral eosinophilia reappeared upon tapering down of a corticosteroid dose. Subsequently, duodenal biopsies showed evidence for Strongyloides, presumably acquired 20 years ago when the patient was residing in Brazil. The patient fully recovered following anti-helmintic therapy. This case underscores the importance of considering Strongyloides in the work-up of flaring-up IBD patients, even if a history of residing or traveling to endemic areas is in the distant past.
Ulcerative colitis; Infection; Parasites; Eosinophilia; Strongyloides
Cryptosporidiosis and strongyloidiasis have been reported to be associated with HIV/AIDS. The present study was designed to determine the prevalence of Cryptosporidium and Strongyloides stercoralis infections among people with and without HIV infection and also assess the efficient methods for detection of Strongyloides.
A cross-sectional study was conducted in Yirgalem Hospital, southern Ethiopia from March, 2007 to October, 2007. Demographic data and stool samples were collected from 384 individuals (192 from each HIV serogroup). Samples were processed using the modified Ziehl-Neelsen technique for detection of Cryptosporidium species. Stool samples were also processed using the direct saline mount, the formol-ether and the water-emergence techniques for diagnosis of S. stercoralis. The prevalence of Cryptosporidium and S. stercoralis among HIV infected individuals was 25% and 12.0%, respectively. HIV positive individuals had significantly higher rate of infection with Cryptosporidium (OR = 15.7; 95% CI 5.5 to 44.5) and S. stercoralis (OR = 6.4; 95% CI 2.2 to 18.9). Among the three diagnostic methods, the larvae of S. stercoralis were more efficiently detected by the water-emergence technique.
In this study, the prevalence of Cryptosporidium and S. stercoralis infections was significantly higher among people with HIV/AIDS. Educating HIV infected individuals to prevent acquisition of Cryptosporidium infection and screening for S. stercoralis using the water-emergence technique is likely to be helpful.
Strongyloides stercoralis affects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations.
Strongyloides stercoralis is a soil-transmitted intestinal nematode that has been estimated to infect at least 60 million people, especially in tropical and subtropical regions. Strongyloides infection has been described in immunosupressed patients with lymphoma, rheumatoid arthritis, diabetes mellitus etc. Our case who has rheumatoid arthritis (RA) and bronchial asthma was treated with low dose steroids and methotrexate.
A 68 year old woman has bronchial asthma for 55 years and also diagnosed RA 7 years ago. She received immunusupressive agents including methotrexate and steroids. On admission at hospital, she was on deflazacort 5 mg/day and methotrexate 15 mg/week. On her physical examination, she was afebrile, had rhonchi and mild epigastric tenderness. She had joint deformities at metacarpophalengeal joints and phalanges but no active arthritis finding.
Oesophagogastroduodenoscopy was performed and it showed hemorrhagic focus at bulbus. Gastric biopsy obtained and showed evidence of S.Stercoralis infection. Stool and sputum parasitological examinations were also all positive for S.stercoralis larvae. Chest radiography result had no pathologic finding. Albendazole 400 mg/day was started for 23 days. After the ivermectin was retrieved, patient was treated with oral ivermectin 200 μg once a day for 3 days. On her outpatient control at 15th day, stool and sputum samples were all negative for parasites.
S.stercoralis may cause mortal diseases in patients. Immunosupression frequently causes disseminated infections. Many infected patients are completely asymptomatic. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. In immunosupressed patients, to detect S.stercoralis might help to have the patient survived and constitute the exact therapy.
Differences between noninfective first-stage (L1) and infective third-stage (L3i)
larvae of parasitic nematode Strongyloides stercoralis at the
molecular level are relatively uncharacterized. DNA microarrays were developed and
utilized for this purpose.
Methods and Findings
Oligonucleotide hybridization probes for the array were designed to bind 3,571
putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags
(ESTs) obtained as part of the Nematode EST project. RNA obtained from S.
stercoralis L3i and L1 was co-hybridized to each array after labeling
the individual samples with different fluorescent tags. Bioinformatic predictions
of gene function were developed using a novel cDNA Annotation System software. We
identified 935 differentially expressed genes (469 L3i-biased; 466 L1-biased)
having two-fold expression differences or greater and microarray signals with a p
value<0.01. Based on a functional analysis, L1 larvae have a larger number of
genes putatively involved in transcription (p = 0.004), and
L3i larvae have biased expression of putative heat shock proteins (such as
hsp-90). Genes with products known to be immunoreactive in
S. stercoralis-infected humans (such as SsIR
and NIE) had L3i biased expression. Abundantly expressed L3i
contigs of interest included S. stercoralis orthologs of
cytochrome oxidase ucr 2.1 and hsp-90, which may
be potential chemotherapeutic targets. The S. stercoralis
ortholog of fatty acid and retinol binding protein-1, successfully used in a
vaccine against Ancylostoma ceylanicum, was identified among the
25 most highly expressed L3i genes. The sperm-containing glycoprotein domain,
utilized in a vaccine against the nematode Cooperia punctata, was
exclusively found in L3i biased genes and may be a valuable S.
stercoralis target of interest.
A new DNA microarray tool for the examination of S. stercoralis
biology has been developed and provides new and valuable insights regarding
differences between infective and noninfective S. stercoralis
larvae. Potential therapeutic and vaccine targets were identified for further
Strongyloides stercoralis is a soil-transmitted helminth that
affects an estimated 30–100 million people worldwide. Chronically infected
persons who are exposed to corticosteroids can develop disseminated disease, which
carries a high mortality (87–100%) if untreated. Despite this, little is
known about the fundamental biology of this parasite, including the features that
enable infection. We developed the first DNA microarray for this parasite and used it
to compare infective third-stage larvae (L3i) with non-infective first stage larvae
(L1). Using this method, we identified 935 differentially expressed genes. Functional
characterization of these genes revealed L3i biased expression of heat shock proteins
and genes with products that have previously been shown to be immunoreactive in
infected humans. Genes putatively involved in transcription were found to have L1
biased expression. Potential chemotherapeutic and vaccine targets such as
far-1, ucr 2.1 and hsp-90 were
identified for further study.
Human T cell lymphotropic virus type 1 (HTLV-1) infection is a risk factor for Strongyloides stercoralis infection. HTLV-1 also predisposes to the development of T cell malignancies. We report a case of a patient with severe, treatment resistant Strongyloides infection and HTLV-1 infection who progressed to develop an advanced high grade T cell lymphoma of the intestine.