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1.  Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection 
Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole.
To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection.
Search methods
We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts.
Selection criteria
Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection.
Data collection and analysis
Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions.
Main results
We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe).
In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence).
In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence).
In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials).
Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death.
Authors' conclusions
Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole.
Ivermectin versus benzimidazoles for treating Strongyloides stercoralis infection
What is strongyloides infection and how might ivermectin work
Strongyloides stercoralis is a parasite that lives in the gut of infected people. The infection is not serious for most people, but it can be fatal in people with immune deficiency. People become infected when they come in contact with soil or water contaminated with infectious worms. The chronic infection usually causes skin rash, vomiting, diarrhoea, and constipation, and respiratory problems, such as asthma-like illness. This disease may be treated with ivermectin or albendazole or thiabendazole. We wanted to know if ivermectin was better or worse than the other alternative therapies.
What the research says
We reviewed the evidence about the effect of ivermectin compared with albendazole and thiabendazole. After searching for relevant trials up to August 2015, we included seven randomized controlled trials, enrolling 1147 adults with chronic strongyloides infection, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America, and Europe). Four trials assessed the effectiveness of ivermectin compared with albendazole and three trials assessed the effectiveness of ivermectin compared with thiabendazole.
Comparison ivermectin versus albendazole
Treatment with ivermectin probably cures more people than albendazole (moderate quality evidence), and may be equally or better tolerated (low quality evidence). The included trials did not report serious adverse events or death.
Comparison ivermectin versus thiabendazole
Treatment with ivermectin and thiabendazole may cure similar numbers of people with strongyloides infection (low quality evidence), but ivermectin is probably better tolerated (moderate quality evidence). The included trials did not report serious adverse events or death.
PMCID: PMC4916931  PMID: 26778150
2.  Treatment of strongyloidiasis in HTLV-1 and Strongyloides stercoralis coinfected patients is associated with increased TNFα and decreased soluble IL2 receptor levels 
Human T cell lymphotropic virus type 1 (HTLV-1) infection has been associated with recurrent and disseminated strongyloidiasis and adult T cell leukemia/lymphoma (ATLL).
We compared immunological aspects and markers for ATLL in HTLV-1 patients with or without strongyloidiasis, and evaluated the influence of Strongyloides stercoralis treatment on the immune response and clinical outcomes of HTLV-1 infection.
Levels of TNFα and IFNγ were lower in patients coinfected with HTLV-1 and S. stercoralis than in patients with HTLV-1 only (p < 0.05), and there was an increase in TNFα levels after anthelmintic treatment. Levels of sIL-2R were higher in patients with HTLV-1 coinfected with S. stercoralis and anthelmintic treatment decreased sIL-2R levels (p < 0.05). The one patient who developed ATLL was coinfected with S. stercoralis.
These data show that helminthic infection has a modulatory role in HTLV-1 infection and that S. stercoralis may be a cofactor in the development of ATLL.
PMCID: PMC3735360  PMID: 23843560
HTLV-1; Strongyloides stercoralis; Leukemia; ATLL; Interleukin-2 receptor; sIL-2R
3.  Regulatory T Cell Expansion in HTLV-1 and Strongyloidiasis Co-infection Is Associated with Reduced IL-5 Responses to Strongyloides stercoralis Antigen 
Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite.
To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection.
Peripheral blood mononuclear cells (PBMCs) were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production.
Patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm3, p = 0.09, Mann-Whitney test). The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA). Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test). Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells.
Regulatory T cell counts are increased in patients with HTLV-1 and Strongyloides stercoralis co-infection and correlate with both low circulating eosinophil counts and reduced antigen-driven IL-5 production. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection.
Author Summary
Human strongyloidiasis varies from a mild, controlled infection to a severe frequently fatal disseminated infection depending on the hosts. Patients infected with the retrovirus HTLV-1 have more frequent and more severe forms of strongyloidiasis. It is not clear how human strongyloidiasis is controlled by the immune system and how HTLV-1 infection affects this control. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite. In our study, patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens than patients with only strongyloidiasis. Eosinophils play an essential role in control of strongyloidiasis in animal models, and eosinophil counts were decreased in the HTLV-1 and Strongyloides stercoralis co-infected subjects compared to patients with only strongyloidiasis. The proportion of T cells with a regulatory cell phenotype was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis. IL-5 is a key host molecule in stimulating eosinophil production and activation, and Strongyloides stercoralis antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients. Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of regulatory T cells. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection.
PMCID: PMC2686100  PMID: 19513105
4.  Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis 
Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined.
A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up.
Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups.
This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness.
Trial Registration NCT00765024
Author Summary
Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. We conducted a prospective, clinical study to compare the efficacy and safety of a 7-day course of oral albendazole with a single dose of oral ivermectin, or double doses, given 2 weeks apart, of ivermectin in Thai patients who developed this infection. Patients were regularly followed-up after initiation of treatment, until one year after treatment. Ninety patients were studied (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). The average duration of follow-up were 19 (range 2–76) weeks in albendazole group, 39 ( range 2–74) weeks in single dose ivermectin group, and 26 ( range 2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively. No serious adverse event associated with treatment was found in any of the groups. Therefore this study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis.
PMCID: PMC3091835  PMID: 21572981
5.  Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality in vivo 
PLoS Pathogens  2013;9(4):e1003263.
Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called “DivE” was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1+ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1+ clones.
Author Summary
HTLV-1 is a human retrovirus estimated to infect 20 million people world-wide and is causing in a small proportion of the infected individuals an inflammatory disease or a leukemia/lymphoma. HTLV-1 persists lifelong by driving clonal proliferation of infected T-cells. Strongyloidiasis, a gastrointestinal infection by an helminth (Strongyloides stercoralis) and Infective Dermatitis associated with HTLV-1 (IDH), a skin inflammation with bacterial infection, appear to increase the risk of developing HTLV-1-related diseases. It is well known that the chance of developing HTLV-1-related diseases increases with the number of cells infected by the virus (also called proviral load). It is also known that HTLV-1-infected individuals co-infected by Strongyloides or affected by IDH have a higher proviral load, but the mechanism is still unclear. Consequently, the aim of this study was to test if co-infection increases the total number and/or the abundance (or size) of HTLV-1-infected T-cell clones. We have shown that the significantly increased proviral load in HTLV-1-infected individuals with IDH or strongyloidiasis is due to an increase in the mean clone abundance (bigger clones), not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone.
PMCID: PMC3617147  PMID: 23592987
6.  Strongyloides stercoralis hyperinfection in a patient with rheumatoid arthritis and bronchial asthma: a case report 
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.
PMCID: PMC2949791  PMID: 20849666
7.  Hyperinfection strongyloidiasis in renal transplant recipients 
BMJ Case Reports  2014;2014:bcr2014205068.
Strongyloidiasis is infection caused by the nematode Strongyloides stercoralis. Chronic uncomplicated strongyloidiasis is known to occur in immunocompetent individuals while hyperinfection and dissemination occurs in selective immunosuppressed hosts particularly those on corticosteroid therapy. We report two cases of hyperinfection strongyloidiasis in renal transplant recipients and document endoscopic and pathological changes in the involved small bowel. One patient presented with features of dehydration and malnutrition while another developed ileal obstruction and strangulation, requiring bowel resection. Oesophagogastroduodenoscopy showed erythematous and thickened duodenal mucosal folds. Histopathological examination of duodenal biopsies revealed S. stercoralis worms, larvae and eggs embedded in mucosa and submucosa. Wet mount stool preparation showed filariform larvae of S. stercoralis in both cases. Patients were managed with anthelmintic therapy (ivermectin/albendazole) and concurrent reduction of immunosuppression. Both patients had uneventful recovery. Complicated strongyloidiasis should be suspected in immunocompromised hosts who present with abdominal pain, vomiting and diarrhoea, particularly in endemic areas.
PMCID: PMC4154012  PMID: 25150235
8.  Strongyloides stercoralis: there but not seen 
Purpose of review
Diagnosis of S. stercoralis is often delayed due to patients presenting with non-specific gastrointestinal complaints, a low parasite load and irregular larval output. Although several diagnostic methods exist to detect the presence of S. stercoralis there is no gold standard. In immunocompromised hosts (patients with malignancy, organ transplantation or concurrent HTLV-1 infection or those on corticosteroid therapy), autoinfection can go unchecked where large numbers of invasive Strongyloides larvae disseminate widely and cause hyperinfection with dissemination, which can be fatal. This review will highlight current published research on improved diagnostic methods for S. stercoralis and the immune mechanisms thought to be responsible for hyperinfection syndrome.
Recent findings
Recent advances in diagnosis of Strongyloides stercoralis include a luciferase immunoprecipitation system that shows increased sensitivity and specificity to detect S. stercoralis specific antibodies and a real time quantitative PCR method to detect S. stercoralis in fecal samples. The severe clinical manifestations of S. stercoralis observed in HTLV-1 co-infected patients has been associated to an increased proportion of regulatory T cells that may be responsible for blunting otherwise effective granulocyte responses.
Strongyloidiasis is a major global health challenge that is underestimated in many countries. Novel diagnostic methods are expected to improve epidemiological studies and control efforts for prevention and treatment of strongyloidiasis. More studies are needed to unveil the mechanisms of severe clinical manifestations of human strongyloidiasis.
PMCID: PMC2948977  PMID: 20733481
Strongyloides stercoralis; strongyloidiasis; diagnosis; hyperinfection; immunology
9.  Wait!!! No Steroids for this Asthma… 
Patient: Female, 31
Final Diagnosis: Hyperinfection syndrome due to Strongyloides stercoralis
Symptoms: Abdominal pain • shortness of breath
Medication: Prednisone
Clinical Procedure: Bronchoscopy with BAL
Specialty: Pulmonology
Unusual clinical course
Strongyloides stercoralis (SS) is a parasite seen in certain parts of the USA and in people from other endemic areas. In these patients steroids might precipitate or exacerbate asthma. Apart from worsening of asthma, serious complications like hyperinfection syndrome and even death can occur in these patients if treated with steroids. Treatment is either ivermectin or albendazole based on severity of the disease. Clinicians have to be very careful when prescribing steroids in patients presenting with an exacerbation of asthma from areas endemic for Strongyloides stercoralis.
Case Report:
A young woman with history of asthma presented with complaints of nausea, vomiting, abdominal pain, wheezing, and dry cough. Physical examination revealed diffuse expiratory wheezing and mild diffuse abdominal pain without rebound or guarding. Laboratory results showed leukocytosis with eosinophilia. Stool studies showed Strongyloides stercoralis. Imaging revealed ground-glass opacities in the right upper and lower lobe along with an infiltrate in the lingular lobe on the left side. Bronchoscopy showed Strongyloides stercoralis. The patient was diagnosed with hyperinfection syndrome due to Strongyloides stercoralis most probably exacerbated by prednisone given for her asthma. Steroids were then discontinued and the patient was started on ivermectin. The patient improved with treatment. Repeat stool examination was negative for Strongyloides stercoralis.
Clinicians have to be very careful when prescribing steroids in patients presenting with an exacerbation of asthma who are from areas endemic for Strongyloides stercoralis and should test for it (preferably with serology test) before starting treatment.
PMCID: PMC4484613  PMID: 26114594
Asthma; Prednisone; Strongyloides
10.  Relationship among Strongyloides stercoralis Infection, Human T-Cell Lymphotropic Virus Type 1 Infection, and Cancer: A 24-Year Cohort Inpatient Study in Okinawa, Japan 
This study evaluated the prevalence of Strongyloides stercoralis infection and human T-cell lymphotropic virus type 1 (HTLV-1) infection in the population. In addition, this study investigated the relationship between S. stercoralis infection or HTLV-1 infection and a patient's risk of developing related cancers. This is a retrospective cohort study of 5,209 patients. The prevalence of S. stercoralis infection was 5.2% among all patients. The prevalence among men (6.3%) was significantly higher than among women (3.6%, P < 0.001). The prevalence of HTLV-1 infection among this population was 13.6% and the prevalence among women (15.5%) was significantly higher than that of men (12.3%, P < 0.001). HTLV-1 seroprevalence was higher in patients with liver cancer (P = 0.003, odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.24, 2.95) and in those with lymphoma other than adult T-cell leukemia/lymphoma (ATLL) (P = 0.005, adjusted OR: 2.76, 95% CI: 1.36, 5.62) if compared with patients without any neoplasm. The prevalence of both S. stercoralis and HTLV-1 in the Okinawan population has been steadily decreasing over the past 24 years. HTLV-1 infection significantly increases the odds of developing liver cancer and lymphomas other than ATLL.
PMCID: PMC4751948  PMID: 26621566
11.  Strongyloides stercoralis Infection in the Immunocompromised Host 
Strongyloides stercoralis is an intestinal nematode acquired in the tropics or subtropics. Most often, it causes chronic, asymptomatic infection, but a change in immune status can increase parasite numbers, leading to hyperinfection syndrome, dissemination, and death if unrecognized. Corticosteroid use is most commonly associated with hyperinfection syndrome. Diagnosis of Strongyloides infection is based on serology and serial stool examinations for larvae. The treatment of choice for chronic, asymptomatic infection is oral ivermectin. Alternative pharmacologic agents include albendazole and thiabendazole. For hyperinfection syndrome, ivermectin remains the drug of choice, though therapy duration must be individualized with the end point being complete parasite eradication. Recurrent strongyloidiasis should prompt an evaluation for human T-cell lymphotropic virus type 1 coinfection. No test of cure is currently available, although immunoglobulin G antibody levels have been shown to decline within 6 months of successful treatment.
PMCID: PMC3401551  PMID: 18462583
12.  Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides stercoralis Hyperinfection 
Iranian Journal of Pediatrics  2011;21(4):549-552.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Bone pain is an important symptom that can be severe. Eosinophilia without any other abnormal laboratory findings is rare in ALL. Strongyloides stercoralis in ALL causes disseminated fatal disease.
Case Presentation
This 9-year-old girl presented with bone pain in lumbar region. Bone pain was the only symptom. The patient didn't have organomegaly. The BM samples were studied by flow cytometry, which showed pre-B cell ALL. Larva of Strongyloides stercoralis was found in fecal examination. Plain chest x ray showed bilateral para-cardiac infiltration. Strongyloidiasis was treated before starting chemotherapy. After two days treatment with Mebendazol the patient developed cough, dyspnea, respiratory distress and fever. The treatment changed to Ivermectin for 2 days. Chemotherapy started five days after diagnosis of leukemia.
The patient complained merely of bone pain in lumbar region without any other signs and symptoms. Peripheral blood smear showed eosinophilia without any other abnormality. Stool examination showed Strongyloides stercoralis larvae. We suggest that all patients diagnosed as ALL in tropical and subtropical regions should be evaluated for parasitic infection especially with Strongyloides stercoralis.
PMCID: PMC3446142  PMID: 23056848
Acute Lymphoblastic Leukemia; Eosinophilia; Strongyloidiasis
13.  Prevalence of Strongyloides stercoralis in an urban US AIDS cohort 
Pathogens and Global Health  2012;106(4):238-244.
We examined the prevalence of Strongyloides stercoralis (Ss) infection in a cohort of AIDS patients from a US urban centre. We monitored our cohort for possible cases of dissemination or immune reconstitution inflammatory syndrome after antiretroviral therapy (ART) initiation.
One hundred and three HIV-infected participants were prospectively sampled from a cohort observational study of ART-naive HIV-1-infected patients with CD4 ⩽100 T cells/μl. Clinical symptoms, corticosteroid therapy, eosinophilia, CD4 count, and plasma HIV-RNA were reviewed. Sera were tested by an enzyme-linked immunosorbent assay (CrAg-ELISA) to crude Ss extract or to an Ss-specific recombinant protein (NIE) and by luciferase immunoprecipitation system assay (LIPS) for Ss-specific antibodies.
Twenty-five per cent of study participants were Strongyloides seropositive by CrAg-ELISA and 62% had emigrated from Strongyloides-endemic areas. The remaining 38% of the seropositives were US born and tested negative by NIE and LIPS. CrAg-ELISA-positive participants had a median CD4 count of 22 T cells/μl and a median HIV-RNA of 4.87 log10 copies/ml. They presented with diarrhea (27%), abdominal pain (23%), and skin manifestations (35%) that did not differ from seronegative patients. Peripheral blood eosinophilia was common among seropositive patients (prevalence of 62% compared to 29% in seronegatives, P = 0.004). Seropositive patients were treated with ivermectin. There were no cases of hyperinfection syndrome.
Strongyloidiasis may be prevalent in AIDS patients in the USA who emigrated from Ss-endemic countries, but serology can be inconclusive, suggesting that empiric ivermectin therapy is a reasonable approach in AIDS patients originating from Strongyloides endemic areas.
PMCID: PMC4001591  PMID: 23265425
AIDS; Strongyloidiasis; Antiretroviral therapy
14.  Fatal Strongyloides Hyperinfection Complicating a Gram-Negative Sepsis after Allogeneic Stem Cell Transplantation: A Case Report and Review of the Literature 
Case Reports in Hematology  2013;2013:860976.
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.
PMCID: PMC3722979  PMID: 23936693
15.  A Case of Hyperinfection with Strongyloides Stercoralis in an Immunosuppressed Patient 
We experienced a case of hyperinfection with strongyloides stercoralis in a 64-year-old housewife who complained of severe epigastric pain associated with nausea, vomiting and general weakness for the period of one month.
She received corticosteroid therapy for several months because of arthritis prior to admission. The diagnosis was confirmed by examination of gastroduodenal juice and gastrofiberoscopic biopsy. Stool examinations disclosed an abundance of the adult form of strongyloides stercoralis. Albendazole was given for treatment. The patient expired on the 79th hospital day.
PMCID: PMC4534981  PMID: 2486847
Strongyloides stercoralis; Immunosuppression
16.  Diagnosis, Treatment and Risk Factors of Strongyloides stercoralis in Schoolchildren in Cambodia 
Worldwide, an estimated 30 to 100 million people are infected with Strongyloides stercoralis, a soil-transmitted helminth. Information on the parasite is scarce in most settings. In semi-rural Cambodia, we determined infection rates and risk factors; compared two diagnostic methods (Koga agar plate [KAP] culture and Baermann technique) for detecting S. stercoralis infections, using a multiple stool examination approach; and assessed efficacy of ivermectin treatment.
Methods/Principal Findings
We performed a cross-sectional study in 458 children from four primary schools in semi-rural villages in Kandal province, using three diagnostic procedures (Kato-Katz, KAP culture and Baermann technique) on three stool samples. Infected children were treated with ivermectin (100 µg/kg/day for two days) and re-examined three weeks after treatment. Hookworm, S. stercoralis, Trichuris trichiura, and small trematode eggs were most prevalent, with 24.4% of children being infected with S. stercoralis. The sensitivity of KAP culture and Baermann technique was 88.4% and 75.0%, respectively and their negative predictive values were 96.4% and 92.5%, respectively. The cumulative prevalence of S. stercoralis increased from 18.6% to 24.4%, after analyzing three stool samples, which was close to the modeled ‘true’ prevalence of 24.8%. Children who reported defecating in latrines were significantly less infected with S. stercoralis than those who did not use latrines (p<0.001). Itchy skin and diarrhea were significantly associated with S. stercoralis infection. The cure rate of ivermectin was 98.3%.
S. stercoralis infection is highly prevalent among semi-rural Cambodian schoolchildren. The sensitivity of KAP culture is higher than that of the Baermann technique. In the absence of a “gold standard”, analysis of multiple stool samples by different diagnostic methods is required to achieve a satisfactory level of sensitivity. Almost three-quarters of the infections could have been avoided by proper sanitation. Ivermectin is highly efficacious against S. stercoralis but prohibitive costs render the drug inaccessible to most Cambodians.
Author Summary
The difficulty of diagnosing Strongyloides stercoralis infections is the reason why up to date, accurate information on its geographic distribution in endemic regions and the total global burden is lacking. We conducted a cross-sectional study among 458 schoolchildren, with the purpose of comparing two methods for diagnosing S. stercoralis infection (Koga agar plate ‘KAP’ culture and Baermann technique) on three stool samples from each individual and to assess the efficacy of ivermectin three weeks after treatment. About one quarter of the schoolchildren examined were infected with S. stercoralis. The sensitivity of KAP culture and Baermann technique was 88.4% and 75.0%, respectively. The prevalence of S. stercoralis infection increased considerably (from 18.6% to 24.4%) when three stool samples were examined. Almost three-quarters of the infections could have been avoided by proper sanitation. Ivermectin was highly efficacious against S. stercoralis infection, with a cure rate of 98.3%. In the absence of a “gold standard”, it is necessary to examine multiple stool samples using different diagnostic techniques in order to reach a “true” prevalence.
PMCID: PMC3566990  PMID: 23409200
17.  Ocular manifestations and pathology of adult T-cell leukemia/lymphoma associated with human T-lymphotropic virus type 1 
Rare Tumors  2010;2(4):e63.
The human T-cell lymphotropic virus type 1 (HTLV-1), endemic in defined geographical areas around the world, is recognized as the etiologic agent of adult T-cell leukemia/lymphoma (ATL), or HTLV-1. ATL is a rare adult onset T-cell malignancy that is characterized by the presence of ATL flower cells with T-cell markers, HTLV-1 antibodies in the serum, and monoclonal integration of HTLV-1 provirus in affected cells. Ocular manifestations associated with HTLV-1 virus infection have been reported and include HTLV-1 uveitis and keratoconjunctivitis sicca, but reports of ocular involvement in ATL are exceedingly rare. This article describes the ocular manifestations and pathology of ATL. We also report for the first time a case of a 34-year-old male with systemic ATL and prominent atypical lymphoid cell infiltration in the choroid. To our knowledge, this is the first report defining prominent choroidal involvement as a distinct ocular manifestation of ATL. ATL may masquerade as a variety of other conditions, and molecular techniques involving microdissection and PCR have proven to be critical diagnostic tools. International collaboration will be needed to better understand the presentation and diagnosis of this rare malignancy.
PMCID: PMC3019598  PMID: 21234255
adult T-cell leukemia/lymphoma; human T-lymphotrophic virus type 1; pathology; eye.
18.  Effect of treatment of Strongyloides infection on HTLV-1 expression in a patient with adult T-cell leukemia 
American journal of hematology  2007;82(10):929-931.
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.
PMCID: PMC2652703  PMID: 17617788
19.  Intestinal strongyloidiasis and hyperinfection syndrome 
In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th2 cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options.
PMCID: PMC1538622  PMID: 16734908
20.  Unsuspected Strongyloides stercoralis infection in hospital patients with comorbidity in need of proper management 
Investigate the role of latent strongyloidiasis infection in patients at the University Hospital, Honduras.
Prospective observational cohort study during 20 non consecutive months from March 2009 to February 2011. Epidemiological and clinical data obtained from patients excreting Strongyloides stercoralis larvae in stool who consulted at the hospital were recorded and analyzed.
Thirty five (5 %) of 712 patients had S. stercoralis larvae in one stool sample; 62.8 % came from rural areas and 91.7 % were poor; 68.5 % (24/35) were 21 years old or older. Eight patients (22.8 %) had no predisposing illness; 3 (8.6 %) received steroid treatment, 29/35 (82.8 %) presented with persistent diarrhea and 24/35 (68.5 %) presented following comorbidities: HIV/AIDS (31.4 %), alcoholism alone (11.4 %) or with other associated illness (8.6 %), malignancy (8.6 %), renal failure (5.7 %) and hyperthyroidism (2.8 %). A combination of symptoms suggestive of strongyloidiasis but indistinguishable from those potentially associated to their comorbid condition included severe epigastric pain, diarrhea of weeks duration, peripheral eosinophilia, astenia, adynamia, fever, anemia and weight loss in 85.7 % of the cases, 3 of whom described skin lesions compatible with larva currens. None of the diagnostic clinical impressions mentioned Strongyloides infection. Ten strongyloidiasis patients received partial treatment with albendazole or ivermectin. Incomplete data, underestimation of the parasitic infection and no laboratory follow-up of the patients limited our observations.
Strongyloides stercoralis is an unsuspected and neglected parasitic infection by health personnel in Honduras. Lack of awareness of its importance represents a strong barrier to proper treatment and follow-up, posing a threat of possible fatal complications in patients with comorbid conditions.
PMCID: PMC4770549  PMID: 26923091
Eosinophilia; HIV/AIDS; Honduras; Immunocompromised host; Strongyloidiasis; Strongyloides stercoralis
21.  Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for Intestinal Helminth Infection among US-Bound Refugees from Asia 
PLoS Neglected Tropical Diseases  2016;10(8):e0004910.
Many U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program.
An economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) “No Program,” 2) U.S. “Domestic Screening and Treatment,” 3) “Overseas Albendazole and Ivermectin” presumptive treatment, and 4) “Overseas Albendazole and Domestic Screening for Strongyloides”. Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs).
The “No Program” option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The “Overseas Albendazole and Ivermectin” option ($418,824) is less expensive than “Domestic Screening and Treatment” ($3,832,572) or “Overseas Albendazole and Domestic Screening for Strongyloides” ($2,182,483). According to the model outcomes, the most effective treatment option is “Overseas Albendazole and Ivermectin,” which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to “No Program”.
Overseas presumptive treatment for U.S.-bound refugees is a cost-effective intervention that is less expensive and at least as effective as domestic screening and treatment programs. The addition of ivermectin to albendazole reduces the prevalence of chronic strongyloidiasis and the probability of rare, but potentially fatal, disseminated strongyloidiasis.
Author Summary
Intestinal parasites including hookworm, Strongyloides stercoralis, Ascaris lumbricoides and Trichuris trichuria have been found to be prevalent in refugee populations. More than 50,000 refugees resettle in the United States annually. Since parasitic disease associated with these infections are rare in the United States, there may be delays in diagnosis or improper treatment of refugees, especially for strongyloidiasis. The Centers for Disease Control and Prevention began overseas presumptive treatment programs in some refugee populations in 1999. We examined the cost and economic impact of an overseas presumptive treatment program with albendazole and ivermectin for Asian refugees. We found that the program costs about $15.12 per refugee and that the burden of intestinal parasites would be reduced by about 80% considering cases, hospitalizations, life years, and QALYs. Overall, the cost per QALY gained was $2,219 (95% CI: 600–29,500). Compared to an alternative program in which refugees would be screened and treated for these infections after arrival in the United States, the overseas presumptive treatment program is less expensive and at least as effective.
PMCID: PMC4980012  PMID: 27509077
22.  Endoscopic and histopathological study on the duodenum of Strongyloides stercoralis hyperinfection 
AIM: To investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis (S. stercoralis) hyperinfection.
METHODS: Over a period of 23 years (1984-2006), we investigated 25 patients with S. stercoralis hyperinfection who had had an esophagogastroduodenoscopy before undergoing treatment for strongyloidiasis. The clinical and endoscopic findings were analyzed retrospectively.
RESULTS: Twenty-four (96%) of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 (HTLV-1) infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 (92%) patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings. The histopathologic yield for identifying larvae was 71.4% by duodenal biopsy. The endoscopic findings of duodenitis were more severe in patients whose biopsies were positive for larvae than those whose biopsies were negative (Endoscopic severity score: 4.86 ± 2.47 vs 2.71 ± 1.38, P < 0.05).
CONCLUSION: Our study clearly demonstrates that, in addition to stool analysis, endoscopic observation and biopsies are very important. We also emphasize that S. stercoralis and HTLV-1 infections should be ruled out before immunosuppressive therapy is administered in endemic regions.
PMCID: PMC2695917  PMID: 18350608
Strongyloides stercoralis; Strongyloidiasis; Hyperinfection; Endoscopy; Histopathology; Duodenum
23.  Strongyloidiasis associated with human T-cell lymphotropic virus type I infection in a nonendemic area. 
Western Journal of Medicine  1989;151(4):410-413.
Concomitant strongyloidiasis and human T-cell lymphotropic virus type I (HTLV-I) infection has been reported from areas in Japan where both organisms are endemic. We present four cases of concomitant infection with these organisms from an area that is not endemic for Strongyloides stercoralis. Three of the four patients had adult T-cell leukemia, an aggressive neoplasm resulting from HTLV-I infection, while the other was an asymptomatic carrier of HTLV-I. Three of the patients had spent their childhoods in an endemic location for both organisms, suggesting an initial infection at that time. Three patients were symptomatic from their parasitism. We conclude that strongyloidiasis may be found in nonendemic locations in patients with either adult T-cell leukemia or an asymptomatic HTLV-I carrier state. Whether infestation with this parasite contributes to the leukemogenesis of HTLV-I, as postulated by others, cannot at this time be determined.
PMCID: PMC1026828  PMID: 2588581
24.  Genetic Characterization of Human T-Cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic 
Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been estimated that 10–20 million people are infected worldwide, but no successful treatment is available. Recently, the epidemiology of this virus was addressed in blood donors from Maputo, showing rates from 0.9 to 1.2%. However, the origin and impact of HTLV endemic in this population is unknown.
To assess the HTLV-1 molecular epidemiology in Mozambique and to investigate their relationship with HTLV-1 lineages circulating worldwide.
Blood donors and HIV patients were screened for HTLV antibodies by using enzyme immunoassay, followed by Western Blot. PCR and sequencing of HTLV-1 LTR region were applied and genetic HTLV-1 subtypes were assigned by the neighbor-joining method. The mean genetic distance of Mozambican HTLV-1 lineages among the genetic clusters were determined. Human mitochondrial (mt) DNA analysis was performed and individuals classified in mtDNA haplogroups.
LTR HTLV-1 analysis demonstrated that all isolates belong to the Transcontinental subgroup of the Cosmopolitan subtype. Mozambican HTLV-1 sequences had a high inter-strain genetic distance, reflecting in three major clusters. One cluster is associated with the South Africa sequences, one is related with Middle East and India strains and the third is a specific Mozambican cluster. Interestingly, 83.3% of HIV/HTLV-1 co-infection was observed in the Mozambican cluster. The human mtDNA haplotypes revealed that all belong to the African macrohaplogroup L with frequencies representatives of the country.
The Mozambican HTLV-1 genetic diversity detected in this study reveals that although the strains belong to the most prevalent and worldwide distributed Transcontinental subgroup of the Cosmopolitan subtype, there is a high HTLV diversity that could be correlated with at least 3 different HTLV-1 introductions in the country. The significant rate of HTLV-1a/HIV-1C co-infection, particularly in the Mozambican cluster, has important implications for the controls programs of both viruses.
Author Summary
Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of Adult T-Cell Leukemia/Lymphoma (ATL), the Tropical Spastic Paraparesis/HTLV-1-associated Myelopathy (TSP/HAM) and other inflammatory diseases, including dermatitis, uveitis, and myositis. It is estimated that 2–8% of the infected persons will develop a HTLV-1-associated disease during their lifetimes, frequently TSP/HAM. Thus far, there is not a specific treatment to this progressive and chronic disease. HTLV-1 has means of three transmission: (i) from mother to child during prolonged breastfeeding, (ii) between sexual partners and (iii) through blood transfusion. HTLV-1 has been characterized in 7 subtypes and the geographical distribution and the clinical impact of this infection is not well known, mainly in African population. HTLV-1 is endemic in sub-Saharan Africa. Mozambique is a country of southeastern Africa where TSP/HAM cases were reported. Recently, our group estimated the HTLV prevalence among Mozambican blood donors as 0.9%. In this work we performed a genetic analysis of HTLV-1 in blood donors and HIV/HTLV co-infected patients from Maputo, Mozambique. Our results showed the presence of three HTLV-1 clusters within the Cosmopolitan/Transcontinental subtype/subgroup. The differential rates of HIV-1/HTLV-1 co-infection in the three HTLV-1 clusters demonstrated the dynamic of the two viruses and the need for implementation of control measures focusing on both retroviruses.
PMCID: PMC3075232  PMID: 21532745
25.  Microsatellite Alterations Are also Present in the Less Aggressive Types of Adult T-Cell Leukemia-Lymphoma 
PLoS Neglected Tropical Diseases  2015;9(1):e0003403.
Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasia etiologically linked to HTLV-1. Manifestations of ATL are diverse and different clinical types with different tissue involvement and aggressiveness have been described. The mechanisms that lead to the development of ATL clinical types have not yet been clarified. Considering that in ATL patients HTLV-1 infection generally occurs in childhood, a multistep carcinogenesis model has been proposed. Microsatellite alterations are important genetic events in cancer development and these alterations have been reported in the aggressive types of ATL. Little is known about oncogenesis of the less aggressive types.
Methodology/Principal Findings
In this study we investigated the role of the microsatellite alterations in the pathogenesis mediated by HTLV-1 in the different types of ATL. We examined the presence of microsatellite instability (MSI) and loss of heterozigosity (LOH) in matched pair samples (tumoral and normal) of 24 patients with less aggressive types (smoldering and chronic) and in aggressive types (acute and lymphoma) of ATL. Four microsatellite markers D10S190, D10S191, D1391 and DCC were analyzed. MSI was found in four patients, three smoldering and one chronic, and LOH in four patients, three smoldering and one acute. None of the smoldering patients with microsatellite alterations progressed to aggressive ATL.
To our knowledge, this is the first report describing the presence of MSI and LOH in the less aggressive types of ATL. These results indicate that microsatellite alterations may participate in the development of the less aggressive types of ATL.
Author Summary
Adult T cell leukemia/lymphoma (ATL) is a severe neoplasia caused by a retrovirus named human T cell lymphotropic virus type-1 (HTLV-1). There are 5 to 10 million carriers worldwide, but only 2% to 5% will manifest ATL. The patients present different clinical and laboratory features. Therefore, this neoplasia was classified in acute and lymphoma types which presented poor prognosis, with a median survival time around 6 months and the less aggressive chronic and smoldering types. The mechanisms involved in the development of this disease are not well known. Microsatellites are short tandem repeats of DNA spread throughout the genome. Alterations in these sequences have been related to the development of cancers. In Japan, one of the highest endemic areas of HTLV-1 infection, alterations in microsatellites have been observed in the aggressive types of ATL and were related to poor prognosis and progression of disease. In the current study, in which we included many chronic and smoldering patients, we showed that microsatellite alterations were also present in the less aggressive ATL and were not necessarily associated to ATL progression and aggressiveness.
PMCID: PMC4295852  PMID: 25590596

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