Evaluation of the humoral response to the third dose of SARS-COV-2 vaccines in liver transplant recipients.

Solid organ transplant recipients (SOTR) commonly develop an unsatisfactory humoral response to vaccines compared to immunocompetent individuals (IC). We have previously evaluated the humoral response in liver transplant recipients (LTR) who received two-dose vaccines against SARS-CoV-2 and reported that 38 % of LTR did not produce anti-Spike antibodies. Thus, we set out to evaluate the humoral response after the third dose of SARS-CoV-2 vaccines. For this purpose, samples from a cohort of 81 LTR and 27 IC were extracted between 21 and 90 days after the third dose. Serology for anti-Spike IgG antibodies and neutralizing antibodies against Wuhan, Delta and Omicron variants were evaluated. We found that 73.5 % of LTR were responders for anti-Spike IgG, while all the IC mounted a measurable response. LTR who responded to the third dose showed significantly lower anti-Spike IgG levels and neutralizing antibodies than IC. We found that there is less neutralization in LTR compared to IC across all variants. Specifically, the neutralization titers in both groups decrease when encountering the Delta variant, and this decline is even more pronounced with the Omicron variant, compared to the Wuhan variant. Furthermore, we identified that the use of high doses of mycophenolate and advanced age were factors that negatively affected the development of anti-Spike IgG antibodies. Regarding vaccine regimes, the regime viral vector/mRNA/mRNA elicited significantly higher responses in LTR compared to other vaccine schemes. In addition to the recommended and necessary booster doses in this population, strategies that achieve adequate immunization should be evaluated.

Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study.

BACKGROUND: Despite that pediatric COVID-19 is usually asymptomatic or mild, SARS-CoV-2 infection typically results in the development of an antibody response. Contradictory observations have been reported when the antibody response of children and adults were compared in terms of strength, specificity and perdurability. METHODS: This observational study includes three cohorts infected with SARS-CoV-2 between March 2020-July 2021: unvaccinated infected children (n=115), unvaccinated infected adults (n=62), and vaccinated infected children (n=76). Plasma anti-spike IgG antibodies and neutralising activity against Wuhan, Delta and Omicron variants after 7-17 months post-infection were analysed. FINDINGS: More than 95% of unvaccinated infected children and adults remained seropositive when evaluated at 382-491 and 386-420 days after infection, respectively. Anti-spike IgG titers and plasma neutralising activity against Wuhan, Delta and Omicron variants were higher in children compared to adults. No differences were found when unvaccinated infected children were stratified by age, gender or presence/absence of symptoms in the acute phase of SARS-CoV-2 infection, but a slight decrease in the antibody response was observed in those with comorbidities. Vaccination of previously infected children with two doses of the inactivated BBIBP-CorV or the mRNA vaccines, BNT162b2 and/or mRNA-1273, further increased anti-spike IgG titers and neutralising activity against Wuhan, Delta and Omicron variants. INTERPRETATION: Unvaccinated infected children mount a more potent and sustained antibody response compared with adults, which is significantly increased after vaccination. Further studies including not only the analysis of the immune response but also the effectiveness to prevent reinfections by the different Omicron lineages are required to optimise vaccination strategy in children. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (PICTO-COVID-SECUELAS-00007 and PMO-BID-PICT2018-2548).

Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection.

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of γδ T cells in HTLV-1 infection remains unclear. Here, demonstrate that there is a decrease in the amount of Vγ9Vδ2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies. This suggests that γδ T cells could be involved in controlling the virus. Indeed, we found that Vγ9Vδ2 T cells, expanded from non-infected individuals, can kill cells expressing the viral proteins HBZ and Tax and this phenotype is reversed in the presence of mevastatin. Cytotoxicity by Vγ9Vδ2 T cells was not associated with an increase of INF-γ production. In sharp contrast, killing by NK cells was reduced by Tax expression. Thus, our study provides initial evidence for a potential protective role of Vγ9Vδ2 T cells against HTLV-1 infection. Therapeutic exploitation of these insights is feasible with current technologies of T-cell therapies and could provide novel tools to prevent and treat HTLV-1-associated malignancies and neurologic complications.

Heterologous adenovirus-vector/messenger RNA regimen is associated with improved severe acute respiratory syndrome coronavirus 2 humoral response in liver transplant recipients.

Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti-spike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21-90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03-0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2-0.7; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA-1273 (OR, 13.1; 95% CI, 2.3-72.9; p = 0.003). In LTRs anti-spike IgG concentrations showed a very good correlation with NA titers (R2 = 0.949; 95% CI, 0.919-0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA-1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response.

An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p = 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR = 100%, n = 8; complete response 62.5%) compared to chemotherapy (OR = 33.3%, n = 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement.

Case Report: Relevance of an Accurate Diagnosis and Monitoring of Infective Dermatitis Associated With Human T-Lymphotropic Virus Type 1 in Childhood.

Human T-lymphotropic virus type 1 (HTLV-1) is a neglected retrovirus distributed worldwide and the ethiological agent of several pathologies, such as adult T-cell leukemia/lymphoma (ATLL), a chronic myelopathy known as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). HTLV-1 presents tropism for CD4+ T cells and induces deregulation of the cytokine profile. IDH is a severe, chronic superinfected eczema generally associated with Staphylococcus aureus and/or Streptococcus beta haemolyticus infection that responds partially to antibiotic therapy but prompt recurrence develops upon treatment withdrawal. IDH could be a risk factor for progression toward both HAM/TSP and ATLL and, similarly to other diseases associated with HTLV-1, it is sub-diagnosed particularly in non-endemic areas. Here, we present a case of IDH in a young boy living in Buenos Aires with symptoms since 2010, at the age of 5. HTLV-1 infection was suspected and confirmed in 2016. The patient exhibited chronic dermatosis with exudative eruption involving mainly the scalp, retroauricular regions, neck and abdomen. Clinical evaluations, routine laboratory tests, full blood count, and HTLV-1 diagnosis for this case are included.

Real-World Data on Adult T-Cell Leukemia/Lymphoma in Latin America: A Study From the Grupo de Estudio Latinoamericano de Linfoproliferativos.

PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.

Autophagy in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Induced Leukemia.

Viruses play an important role in the development of certain human cancers. They are estimated to contribute 16% to all human cancers. Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy with poor prognosis. HTLV-1 viral proteins interact with mechanisms and proteins present in host cells for their own benefit, evading the immune system and promoting the establishment of disease. Several viruses manipulate the autophagy pathway to achieve their infective goals, and HTLV-1 is not the exception. HTLV-1 Tax viral protein engages NF-κB and autophagy pathways prone favoring viral replication and T cell transformation. In this review we focus on describing the relationship of HTLV-1 with the autophagy machinery and its implication in the development of ATLL.

Leucemia asociada al virus linfotrópico T humano tipo 1 (HTLV-1) y transmisión intrafamiliar de la infección en Santiago del Estero / Leukemia associated to human T cell lymphotropic virus type 1 (HTLV-1) infection and intrafamily transmission in Santiago del Estero

Resumen La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.

Abstract Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.

[Leukemia associated to human T cell lymphotropic virus type 1 (HTLV-1) infection and intrafamily transmission in Santiago del Estero]. / Leucemia asociada al virus linfotrópico T humano tipo 1 (HTLV-1) y transmisión intrafamiliar de la infección en Santiago del Estero.

Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.

La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.

First molecular epidemiological study of hepatitis B and D in individuals infected with human T-lymphotropic virus 1/2 from Argentina.

Human T-lymphotropic virus 1/2 (HTLV-1/2), hepatitis B virus (HBV), and hepatitis D virus (HDV) share transmission routes. Argentina shows low prevalence of HTLV-1/2, HBV, and HDV infections; however, this situation may vary according to the geographic region and group studied. The aim of this study was to estimate the prevalence of HBV and HDV infections and detect both viral genotypes in HTLV-1/2 individuals from Argentina. A total of 202 HTLV-1/2 confirmed samples (blood donors [BD] and individuals with risk factors for HTLV-1/2 [RF]) were tested for HBsAg and total anti-HBc by enzyme-linked immunosorbent assay. All reactive samples for some HBV markers were analyzed for HBV DNA characterization and HDV serological and molecular analysis. Total prevalence was 1.5% for HBsAg and 6.4% for anti-HBc. Prevalence was 23.1% for anti-HDV in all HBV-reactive samples. No significant difference was observed for HBV and HDV prevalence within HTLV subtypes. The population study showed that prevalence of anti-HBc was higher in the RF than in the BD population, with no significant differences between them. The HBsAg marker and anti-HDV were only found in RF, showing significant differences when compared to BD. Regarding molecular detection, one sample amplified for HBV DNA and none for HDV RNA. HBV sequence was classified as subgenotype F1b. New and updated background on serological markers of HBV and HDV infection in patients with HTLV-1/2 was provided.

HLA-B*35 as a new marker for susceptibility to human T-cell lymphotropic virus type 1 (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in patients living in Argentina.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2-5% of the infected individuals. Host genetic background might play a role in disease progression. Several previous studies across many countries report HLA haplotype to be one such factor. Here, we sequenced HLA-A, -B and -C of 66 individuals by Sequence-Based Typing (SBT), and compared the frequency of different alleles among ATLL patients, HAM/TSP patients, asymptomatic carriers and non-infected individuals living in Argentina. RESULTS: The frequency of HLA-A, -B and -C alleles largely matched that of the general population in Argentina. We identified HLA-A*02, HLA-B*35 and HLA-C*07 as associated to protection from ATLL (p = 0.031), susceptibility to HAM/TSP (p < 0.001) and susceptibility to ATLL (p = 0.017), respectively. We also found a strong correlation between high proviral load (PVL) and disease (p = 0.008), but were unable to identify any particular allele associated with high or low PVL. CONCLUSIONS: We have found HLA-A*02, HLA-B*35 and HLA-C*07 to be associated to protection from ATLL (HLA-A*02) and susceptibility to HAM/TSP (HLA-B*35) or to ATLL (HLA-C*07), respectively. Whereas HLA-A*02 protection from ATLL has already been extensively described in other regions of the world, this is the first report that links HLA-B*35 and an increased susceptibility to HAM/TSP. As for HLA-C*07 it has previously been associated to susceptibility to HAM/TSP in other countries but in our population it has been linked to ATLL.

Hallazgo del virus linfotrópico T humano 1 (HTLV-1) subtipo Cosmopolita subgrupo Transcontinental (Aa) y del HTLV-2 subtipo b en donantes de sangre de Corrientes / Detection of Human T lymphotropic virus 1 (HTLV-1) Cosmopolitan subtype Transcontinental subgroup (Aa) and HTLV-2 subtype b in blood donors of Corrientes

Resumen Se realizó un estudio epidemiológico molecular en una población de 9.422 donantes de sangre de la provincia de Corrientes (noreste de Argentina), con el fin de determinar la prevalencia del virus linfotrópico T del humano tipos 1 y 2 (human T-cell lymphotropic virus: HTLV-1/2), de identificar filogenéticamente a los subtipos/subgrupos de HTLV-1 y 2 encontrados y de realizar el análisis de mutaciones. Sobre la base de los resultados obtenidos, se demostró que tanto el HTLV-1 como el HTLV-2 se encuentran circulando en una población de bajo riesgo de Corrientes, si bien con una prevalencia similar a las de áreas no endémicas. Los estudios filogenéticos identificaron al subtipo Cosmopolita subgrupo Transcontinental (Aa) del HTLV-1 y al subtipo b del HTLV-2. Los donantes infectados no manifestaron antecedentes de riesgo tales como transfusiones, uso de drogas inyectables ni parejas sexuales de riesgo o seropositivas para HTLV-1/2. Estos resultados indican que estos virus fueron transmitidos de madre a hijo, posiblemente de generación en generación, y que estas cepas fueron introducidas en la población caucásica de esta región a partir de ascendientes originarios de áreas endémicas del país o por contacto producido tiempo atrás con individuos infectados de otros países. Nuestros resultados demuestran por primera vez la presencia de HTLV-1 y HTLV-2 en la provincia de Corrientes. Y si bien se puede considerar a esta provincia como área no endémica, se destaca la necesidad de incluir a estos retrovirus en un programa nacional de salud pública, con el fin de contar con profesionales capacitados para realizar su diagnóstico y brindar la información necesaria en relación con la atención primaria y el seguimiento de los pacientes.

Abstract A molecular epidemiological study was conducted in a population of 9422 blood donors in the province of Corrientes, Northeastern Argentina, to determine the prevalence of Human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2), the phylogenetic identification of HTLV-1 and 2 subtypes/subgroups and perform a mutation analysis. Based on the results obtained, it was shown that both HTLV-1 and HTLV-2 are circulating in a low-risk population of Corrientes, although with a similar prevalence to that of non-endemic areas. Phylogenetic studies identified the HTLV-1 Cosmopolitan subtype Transcontinental subgroup (Aa), and the HTLV-2 subtype b. Infected donors reported neither a history of risk factors such as transfusions, intravenous drug use, nor risky or HTLV-1/2 seropositive sexual partners. These results suggest that these viruses were transmitted from mother to child, possibly from generation to generation, and that these strains were introduced into the Caucasian population of this region from ancestors originating from endemic areas of the country either from or through contact with individuals from other countries years ago. Our results demonstrate for the first time the presence of HTLV-1 and HTLV-2 in the province of Corrientes. Moreover, although the province can be considered a non-endemic area, the need to include these retroviruses in a national Public Health program is highlighted, in order to have qualified professionals duly trained to make their diagnosis and provide the necessary information in relation to primary care and patient follow-up.

Oral Pharmacokinetics of a Chitosan-Based Nano- Drug Delivery System of Interferon Alpha.

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the study of the oral pharmacokinetics of nanoencapsulated IFNα in BalbC mice revealed two maxima and area-under-the-curve of 56.9 pg*h/mL.

Molecular detection of human T-lymphotropic virus type 1 infection among oncology patients in Germany: A retrospective view.

Human T-cell lymphotropic virus (HTLV) belongs to a larger group of primate T-cell lymphotropic viruses (PTLVs) within the family Retroviridae. It is estimated that 10 to 20 million people worldwide may be infected with HTLV-1. Although most of them are asymptomatic, around 5% of infected individuals may develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukaemia/Lymphoma (ATLL). Public Health authorities in many countries have implemented routine blood-donor tests for HTLV-specific antibodies; but this is not the case for Germany since the reported prevalence is very low (7/100,000). With the aim to evaluate retrospectively the presence of HTLV-1 among oncology patients in this country, samples stored at the Universitätsklinikum Freiburg, were analyzed. For this purpose, two different nested-PCR (n-PCR) protocols have been modified and set up for HTLV-1 detection. One positive case was detected by n-PCR among 406 samples (0,25%) in a period of 5 years (2008-2012) corresponding to a T-Cell Lymphoma. Despite the low prevalence, this virus is circulating in Germany, probably due to the increasing numbers of immigrants in these last years. Physicians should consider HTLV-1 infection and suspect it taking in account the ethnic and relation to endemic regions regardless the patient's residence.

[Detection of Human T lymphotropic virus 1 (HTLV-1) Cosmopolitan subtype Transcontinental subgroup (Aa) and HTLV-2 subtype b in blood donors of Corrientes]. / Hallazgo del virus linfotrópico T humano 1 (HTLV-1) subtipo Cosmopolita subgrupo Transcontinental (Aa) y del HTLV-2 subtipo b en donantes de sangre de Corrientes.

A molecular epidemiological study was conducted in a population of 9422 blood donors in the province of Corrientes, Northeastern Argentina, to determine the prevalence of Human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2), the phylogenetic identification of HTLV-1 and 2 subtypes/subgroups and perform a mutation analysis. Based on the results obtained, it was shown that both HTLV-1 and HTLV-2 are circulating in a low-risk population of Corrientes, although with a similar prevalence to that of non-endemic areas. Phylogenetic studies identified the HTLV-1 Cosmopolitan subtype Transcontinental subgroup (Aa), and the HTLV-2 subtype b. Infected donors reported neither a history of risk factors such as transfusions, intravenous drug use, nor risky or HTLV-1/2 seropositive sexual partners. These results suggest that these viruses were transmitted from mother to child, possibly from generation to generation, and that these strains were introduced into the Caucasian population of this region from ancestors originating from endemic areas of the country either from or through contact with individuals from other countries years ago. Our results demonstrate for the first time the presence of HTLV-1 and HTLV-2 in the province of Corrientes. Moreover, although the province can be considered a non-endemic area, the need to include these retroviruses in a national Public Health program is highlighted, in order to have qualified professionals duly trained to make their diagnosis and provide the necessary information in relation to primary care and patient follow-up.

Importance of a Rapid and Accurate Diagnosis in Strongyloides Stercoralis and Human T-Lymphotropic Virus 1 Co-infection: A Case Report and Review of the Literature.

Strongyloides (S.) stercoralis and Human T-Lymphotropic Virus 1 (HTLV-1) share some endemic regions such as Japan, Jamaica, and South America and are mostly diagnosed elsewhere in immigrants from endemic areas. This co-infection has not been documented in Argentina although both pathogens are endemic in the Northwest. We present a case of S. stercoralis and HTLV-1 co-infection with an initial presentation due to gastrointestinal symptoms which presented neither eosinophilia nor the presence of larvae in stool samples in a non-endemic area for these infections. A young Peruvian woman living in Buenos Aires attended several emergency rooms and finally ended up admitted in a gastroenterology ward due to incoercible vomiting, diarrhea, abdominal pain, fever, and weight loss. Gastrointestinal symptoms started 3 months before she returned to Argentina from a trip to Peru. She presented malnutrition and abdominal distension parameters. HIV-1 and other immunodeficiencies were discarded. The serial coproparasitological test was negative. Computed tomography showed diffuse thickening of duodenal and jejunal walls. At the beginning, vasculitis was suspected and corticosteroid therapy was initiated. The patient worsened rapidly. Skin, new enteral biopsies, and a new set of coproparasitological samples revealed S. stercoralis. Then, HTLV-1 was suspected and infection was confirmed. Ivermectin and albendazole were administrated, until the stool sample remained negative for 2 weeks. Larvae were not observed in fresh stool, Ritchie method, and agar culture 1 week post-treatment. Although she required initial support with parenteral nutrition due to oral intolerance she slowly progressed favorably. It has been highly recommended to include a rapid and sensitive PCR strategy in the algorithm to confirm Strongyloides infection, which has demonstrated to improve early diagnosis in patients at-risk of disseminated strongyloidiasis.