Clinical and biochemical characterization of asymptomatic carriers and symptomatic patients with hereditary transthyretin amyloidosis caused by TTR V30L mutation.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by amyloid fibril deposition. The TTR c.148G > T mutation (V30L) in ATTR is rarely reported, and its biochemical properties are unknown. METHODS: Seven patients and two asymptomatic carriers from two unrelated families diagnosed with V30L variant of ATTR were included. Data on clinical manifestations, laboratory examination, electrophysiology, ophthalmological corneal confocal microscopy (CCM), pathology and molecular biological experiments was collected and analyzed. RESULTS: Most patients initially experienced paresthesia, with varying degrees of peripheral neuropathy, autonomic dysfunction, and cardiac involvement. Nerve conduction studies showed extensive motor and sensory nerve involvement in upper and lower limbs. CCM revealed reduced corneal nerve density and fiber length. Sural nerve biopsies indicated loss of myelinated nerve fibers, with neurogenic patterns in gastrocnemius muscle biopsies. Asymptomatic carriers had nearly normal electrophysiology but mild reductions in corneal nerve fiber density and length. Sural nerve biopsies in carriers showed mild reductions in small myelinated nerve fibers. V30L mutation impaired thermodynamic and kinetic stability of the mutant protein. Plasma TTR tetramer concentration was lower in ATTR V30L patients compared to healthy donors. Small molecule stabilizers failed to exhibit satisfactory inhibition on fibril formation of V30L mutation in vitro. CONCLUSION: This study highlights the multisystem involvement in ATTR V30L patients, including neuropathy and cardiac issues. Both patients and carriers showed abnormalities in nerve conduction, corneal microscopy, and pathology. The V30L mutation impaired protein stability and reduced plasma TTR tetramer levels. Small molecule stabilizers were ineffective, indicating a need for alternative treatments.

Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers.

BACKGROUND: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the ß-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. CONCLUSION: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.

Stationary distribution and probability density for a stochastic SEIR-type model of coronavirus (COVID-19) with asymptomatic carriers.

In this paper, we propose a stochastic SEIR-type model with asymptomatic carriers to describe the propagation mechanism of coronavirus (COVID-19) in the population. Firstly, we show that there exists a unique global positive solution of the stochastic system with any positive initial value. Then we adopt a stochastic Lyapunov function method to establish sufficient conditions for the existence and uniqueness of an ergodic stationary distribution of positive solutions to the stochastic model. Especially, under the same conditions as the existence of a stationary distribution, we obtain the specific form of the probability density around the quasi-endemic equilibrium of the stochastic system. Finally, numerical simulations are introduced to validate the theoretical findings.

Genetic Diversity of Plasmodium falciparum and Distribution of Antimalarial Drug Resistance Mutations in Symptomatic and Asymptomatic Infections.

Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple parasite genotypes that could affect case management and malaria epidemiology. Here, we performed AmpSeq genotyping to capture polymorphisms associated with antimalarial resistance and the genetic diversity within natural Plasmodium falciparum infections. Known genetic polymorphisms associated with altered drug susceptibility were screened for the five most common marker genes, pfdhfr, pfdhps, pfmdr1, pfcrt, and pfK13, and genetic diversity was established from two known AmpSeq markers, cpmp and csp. Relative abundance of the different genotypes within mixed infections was calculated from the number of reads per genotype. Genotyping was performed on 117 samples, 63 from asymptomatic and 54 from symptomatic individuals. We identified up to 15 genotypes within an infection, and the median multiplicity of infection was higher in asymptomatic infections (median MOI = 5 in asymptomatics versus median MOI = 2 in symptomatics, P < 0.001). No genetic differentiation on parasites from asymptomatic and symptomatic individuals was found. No mutation associated with ART resistance was identified. Prevalence of the P. falciparum chloroquine resistance wild-type genotype (CVMNK) reached 80%, confirming a return to chloroquine (CQ) sensitive parasites in Cameroon. In addition, the CQ-associated resistant genotype (CVIET) was present at very low density in polyclonal infections. Persistence of low-density chloroquine resistant parasites indicates competition-survival trade-offs may contribute to maintaining genetic diversity in natura. Thus, monitoring the expansion of these low-density genotypes in different immune backgrounds will be critical to evaluate drug policy changes.

Exploration of mRNAs and miRNA classifiers for various ATLL cancer subtypes using machine learning.

BACKGROUND: Adult T-cell Leukemia/Lymphoma (ATLL) is a cancer disease that is developed due to the infection by human T-cell leukemia virus type 1. It can be classified into four main subtypes including, acute, chronic, smoldering, and lymphoma. Despite the clinical manifestations, there are no reliable diagnostic biomarkers for the classification of these subtypes. METHODS: Herein, we employed a machine learning approach, namely, Support Vector Machine-Recursive Feature Elimination with Cross-Validation (SVM-RFECV) to classify the different ATLL subtypes from Asymptomatic Carriers (ACs). The expression values of multiple mRNAs and miRNAs were used as the features. Afterward, the reliable miRNA-mRNA interactions for each subtype were identified through exploring the experimentally validated-target genes of miRNAs. RESULTS: The results revealed that miR-21 and its interactions with DAAM1 and E2F2 in acute, SMAD7 in chronic, MYEF2 and PARP1 in smoldering subtypes could significantly classify the diverse subtypes. CONCLUSIONS: Considering the high accuracy of the constructed model, the identified mRNAs and miRNA are proposed as the potential therapeutic targets and the prognostic biomarkers for various ATLL subtypes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral positivity and their burden in saliva of asymptomatic carriers - a systematic review and meta-analysis.

AIMS: The coronavirus disease 2019 (COVID-19) due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can present either as an asymptomatic carrier state or an acute respiratory disease, with or without severe pneumonia. The asymptomatic carriers are a challenge for the dental profession as the infection could be transmitted via virus-laden, and saliva in dental settings through aerosol-generating procedures (AGPSs). The aim of this review was to perform a systematic review of SARS-CoV-2 in the saliva of asymptomatic individuals. MATERIALS AND METHODS: PubMed, Google scholar, and MedRxiv databases were searched between and a systematic review and meta-analysis of the available data were performed to assess the viral burden in the saliva of asymptomatic carriers of SARS-CoV-2. All investigators of the included studies used qRT-PCR to detect SARS-CoV-2 and yield quantitative data (the Ct values) appertaining to the viral load. RESULTS: A total of 322 records in the English literature were identified, and eight studies with 2642 SARS-CoV-2-positive and asymptomatic individuals were included in the final analysis. Of these, 16.7% (95% CI: 11-23%) yielded SARS-CoV-2-positive saliva samples in comparison to 13.1% (95% CI: 12-17%) of the respiratory specimens (nasopharyngeal or nose-throat swabs). CONCLUSION: As approximately 1 in 5 to 1 in 10 asymptomatic individuals harbour SARS-CoV-2 in either saliva or respiratory secretions, our results highlight the need for continued vigilance and the critical importance of maintaining strict, additional infection control regimens for the foreseeable future to mitigate the potential risks of COVID-19 transmission in dentistry.

Analysis of current SARS-CoV-2 infection in a large population of blood donors evidenced that RNAemia is rare in plasma.

BACKGROUND: Transmission of SARS-CoV-2 by asymptomatic individuals and by blood transfusion are important issues to understand to control the viral spread. In this work, we estimated the current SARS-CoV-2 infection rate in blood donors from Belo Horizonte, Brazil. STUDY DESIGN AND METHODS: Saliva and blood samples were collected from 4103 blood donors from June 15 to September 30, 2020. Saliva samples were tested by real-time RT-PCR for SARS-CoV-2 in mini-pools of four samples. Individual samples were tested for positive or inconclusive pools, and positive donors had their plasma tested. RESULTS: Twenty-seven (0.66%) blood donors were positive for SARS-CoV-2 in their saliva, but their plasma was negative, except for one, who presented a high viral load in saliva and nasopharyngeal samples and RNAemia in the plasma close to the limit of detection. Fourteen (56%) positive blood donors reported mild symptoms related to COVID-19 after donation, but the viral load levels were not statistically different between symptomatic and asymptomatic individuals. DISCUSSION: Despite the measures taken by Blood Centers to avoid blood donors with SARS-CoV-2 infection, asymptomatic or presymptomatic carriers are able to donate. The risk of the virus transmission by transfusion seems to be negligible since plasma RNAemia was seen at a very low level in only one (3.7%) of the positive donors, but other studies must be performed to confirm this finding.

Shiga toxin-producing Escherichia coli in household members of children with hemolytic uremic syndrome.

The objective is to establish the frequency of STEC infections in household contacts of HUS patients. We studied 292 household contacts of 82 HUS patients attended from 2010 to 2018. In HUS cases, diagnostic criteria were (1) isolation and characterization of STEC strains, (2) detection of free fecal Shiga toxin (FFStx), and (3) detection of anti-O serogroup-specific antibodies. Contacts were studied by screening of stx genes by polymerase chain reaction and/or STEC isolation from stool samples. Clonal relation of STEC strains was established by pulsed-field gel electrophoresis (PFGE). Frequencies of HUS patients without STEC isolation with STEC-positive contacts were determined. Serotypes and stx-genotypes in patients and contacts were analyzed. Thirty (36.6%) HUS patients had 36 STEC-positive contacts. Fourteen (38.8%) were children, 20 adults, and 2 dogs. One sibling developed HUS, 6 contacts had gastrointestinal symptoms, and the rest were asymptomatic. In 5 of 30 HUS patients, STEC infection could not be confirmed, and 2 cases were diagnosed only by FFStx detection. Of the remaining 23 HUS patients, 16 had E. coli O157 and 7 E. coli O145 infection. Serotype and/or stx-genotype concordance was established in 19 (83%) of 23 HUS patients and their contacts. Five HUS cases and their contacts studied by PFGE showed macrorestriction patterns with more than 90% similarity. Nearly one third of HUS patients had STEC-positive family contacts, and one third of them were children. Early identification is important to prevent ongoing contamination among family and institutional contacts and to facilitate prompt detection of HUS in STEC-positive contacts.

Fecal carriage and molecular epidemiologic characteristics of carbapenemase-producing Enterobacterales in primary care hospital in a Japanese city.

BACKGROUND: The worldwide spread of organisms with antimicrobial resistance is of concern, especially the trend of significantly increasing carbapenemase-producing Enterobacterales (CPE). In this study, we investigated the annual trend of intestinal CPE carriage rates in inpatients and healthy adults in a primary care hospital in Tenri, Japan. METHODS: We collected 551 samples of feces from inpatients in our institution and 936 samples from healthy people living in Tenri city from December 2012 to April 2015. All samples were cultured on MacConkey agar plates containing 4 µg/mL ceftazidime for screening test. The colonies grown on the screening medium were detected for carbapenemase genes (blaIMP-1, blaIMP-2, blaVIM, blaKPC, blaGES, blaNDM, and blaOXA-48 groups) by multiplex PCR, and CPE were identified by MALDI-TOF MS. Plasmid replicon typing and pulsed-field gel electrophoresis (PFGE) were performed on PCR-positive strains. RESULTS: The CPE carriage rate was 1.6% (9/551) in the inpatient group and 0% (0/936) in the healthy adults group. The numbers of strains positive for the carbapenemase gene were 4 for Enterobacter cloacae, 2 for Klebsiella pneumoniae, 1 for Citrobacter freundii, 1 for Raoultella ornithinolytica and 1 for Escherichia coli. In all CPE strains, the carbapenemase gene was blaIMP-6 and the plasmid replicon type was IncN. The 4 E. cloacae strains showed a similar pattern in PFGE. CONCLUSION: In the same city in Japan, CPE intestinal carriers were detected only in the inpatient group in this study but not in a healthy adults, suggesting that the spread of asymptomatic CPE carriers was confined to inpatients.

[Laboratory testing, prevention and control of asymptomatic carriers of coronavirus disease 2019].

With many hard efforts, the epidemic prevention and control work in China has borne successful, accelerating the gradual restoration of production, living order and routine medical work. However, there is increasing evidence that many patients with COVID-19 are asymptomatic, but they are potential transmitter of the virus. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. Therefore, it is urgent to develop better screening and laboratory testing for asymptomatic infections with COVID-19 with high speed, sensitivity and specificity. It is also important to improve our risk assessment, prevention and control strategies to further prevent the spread of the epidemic.

CD4+ CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia/lymphoma.

We recently took advantage of the universal expression of cell adhesion molecule 1 (CADM1) by CD4+ cells infected with HTLV-1 and the downregulation of CD7 expression that corresponds with the oncogenic stage of HTLV-1-infected cells to develop a flow cytometric system using CADM1 versus CD7 plotting of CD4+ cells. We risk-stratified HTLV-1 asymptomatic carriers (AC) and indolent adult T-cell leukemia/lymphoma (ATL) cases based on the CADM1+ percentage, in which HTLV-1-infected clones are efficiently enriched. AC and indolent ATL cases were initially classified according to their CADM1+ cell percentage. Follow-up clinical and flow cytometric data were obtained for 71 cases. In G1 (CADM1+ ≤ 10%) and G2 (10% < CADM1+ ≤ 25%) cases, no apparent clinical disease progression was observed. In G3 (25% < CADM1+ ≤ 50%) cases, five out of nine (55.5%) cases progressed from AC to smoldering-type ATL. In G4 (50% < CADM1+ ) cases, the cumulative incidence of receiving systemic chemotherapy at 3 years was 28.4%. Our results indicate that the percentage of the CD4+ CADM1+ population predicts clinical disease progression: G1 and G2 cases, including AC cases, are stable and considered to be at low risk; G3 cases, including advanced AC cases and smoldering-type ATL cases based on the Shimoyama criteria, are considered to have intermediate risk; and G4 cases, which are mainly indolent ATL cases, are unstable and at high risk of acute transformation.

Anti-phospholipid antibody syndrome occurrence in patients with persistent anti-phospholipid antibodies.

We investigated the overall frequency of anti-phospholipid syndrome (APS) occurrence in Korean patients with consecutively detected anti-phospholipid antibodies with an interval of 12 weeks (persistent aPLs). We retrospectively reviewed the results of blood tests of aPLs in 14,889 patients in whom aPL tests were performed at Yonsei University College of Medicine, Severance Hospital, from January 2012 to August 2018, and included 833 patients with persistent aPLs. We obtained clinical and laboratory data including anti-cardiolipin antibodies IgM and IgG, anti-beta2 glycoprotein1 IgM and IgG, and lupus anticoagulant (LAC). Of 833 patients with persistent aPLs, 96 patients (11.5%) had APS (84 patients had thrombotic events and 12 had pregnancy morbidity). Among aPLs, LAC was detected in patients with APS more frequently than asymptomatic carriers of aPLs (46.9% vs. 25.9%, p < 0.001). Patients with LAC (relative risk (RR) 2.558, p < 0.001) and aPLs ≥ 2 (RR 1.731, p = 0.014) exhibited the higher rate of APS occurrence than those without. Moreover, patients with aPLs ≥ 3 and aPLs ≥ 4 exhibited the higher rates of APS occurrence than those without (RR 2.753, p < 0.001 and RR 3.209, p = 0.013). Meanwhile, patients with ANA, anti-dsDNA, anti-SSA/Ro, and SLE exhibited the increased frequency of LAC positivity, compared to those without (RR 3.304, p = 0.005, RR 4.269, p = 0.032, RR 3.750, p = 0.041 and RR 8.828, p < 0.001, respectively). APS occurs in 11.5% of Korean patients with persistent aPLs. LAC positivity and aPLs ≥ 2 were significantly associated with APS occurrence. SLE and SLE-related autoantibodies were associated with LAC positivity.

The treatment of anti-phospholipid syndrome: A comprehensive clinical approach.

Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease that predisposes to thrombotic events and/or obstetric complications, in the persistent presence of anti-phospholipid antibodies (aPL). Life long moderate-intensity anticoagulation is the option of choice for aPL-positive patients with a previous thrombosis; critical issues concern the management of those with a history of arterial event due to the high rate of recurrence. Alternatives comprise anti-platelet agents and high-intensity anticoagulation. Low dose aspirin (LDASA) and low molecular weight heparin provide the mainstay of the treatment of obstetric APS, allowing a birth rate in 70% of cases. The management of refractory APS, thrombotic as well as obstetric, is highly debated, but an increasing burden of evidence points towards the beneficial effects of multiple treatments. Similarly, a management envisaging multiple drugs (anticoagulation, steroids, plasma exchange and/or intravenous immunoglobulins) is the most effective approach in catastrophic APS. Asymptomatic aPL carriers are at higher risk of thrombotic and obstetric complications compared to the general population, thus potentially benefitting of a pharmacological intervention. LDASA and hydroxychloroquine can be considered as options, in particular in case of high risk aPL profile, concomitant cardiovascular risk factors or associated autoimmune disease. APS is apparently a simple condition, but its multifaceted nature requires a complex and tailored treatment.

Comparison between patients with norovirus-related gastroenteritis and asymptomatic carriers with respect to distribution of antibody-complexed viral particles and intestinal flora.

Asymptomatic carriers have a major influence on the spreading of norovirus infections. The objective of this study was to examine the characteristics of patients and asymptomatic carriers affected by norovirus-related community gastroenteritis outbreaks. No significant difference between the two groups was observed in terms of the number of norovirus-antibody complexes with respect to total numbers. Principal coordinates analysis of the intestinal flora based on ß-diversity analysis, revealed a different bacterial composition between patients and asymptomatic carriers, particularly regarding the genera Pseudomonas, Bacteroides, and Erwinia, as well as the Ruminococcaceae family. Although the proportional changes between these intestinal microorganisms were not sufficient to explain gastroenteritis symptoms, they represent possible markers shared by asymptomatic norovirus carriers.

Identification and characterization of areas of high and low risk for asymptomatic malaria infections at sub-village level in Ratanakiri, Cambodia.

BACKGROUND: Malaria elimination needs a concentration of activities towards identification of residual transmission foci and intensification of efforts to eliminate the last few infections, located in so-called 'malaria hotspots'. Previous work on characterizing malaria transmission hotspots has mainly focused on falciparum malaria and especially on symptomatic cases, while the malaria reservoir is expected to be mainly concentrated in the asymptomatic human population when transmission is low. For Plasmodium vivax, there has been less effort in identifying transmission hotspots. The main aim of this study was to uncover micro-epidemiological mechanisms of clustering of malaria infections at a sub-village level, based on geographical or behavioural features. METHODS: A cross-sectional survey was performed in three villages within the highest malaria endemic province of Cambodia. The survey took place in the dry season, when the malaria reservoir is expected to be low and residing in the asymptomatic part of the population. Village and field locations of households were georeferenced, blood samples were taken from as many residents as possible and a short questionnaire probing for individual risk factors was taken. Asymptomatic malaria carriers were detected by PCR, and geographical clustering analysis (SaTScan) as well as risk factor analysis were performed. RESULTS: A total of 1540 out of 1792 (86%) individuals were sampled. Plasmodial DNA was detected in 129 individuals (8.4%). P. vivax was most prevalent (5.5%) followed by Plasmodium malariae (2.1%) and Plasmodium falciparum (1.6%). Mixed infection occurred in 12 individuals. In two out of three villages geographical clustering of high and low malaria infection risk was clearly present. Cluster location and risk factors associated with the infection differed between the parasite species. Age was an important risk factor for the combined Plasmodium infections, while watching television at evenings was associated with increased odds of P. vivax infections [OR (CI): 1.86 (0.95-3.64)] and bed net use was associated with reduced odds of P. falciparum infections [OR (CI): 0.25 (0.077-0.80)]. CONCLUSIONS: Clusters of malaria carriers were malaria species specific and often located remotely, outside village centres. As such, at micro-epidemiological level, malaria is not a single disease. Further unravelling the micro-epidemiology of malaria can enable programme managers to define the interventions likely to contribute to halt transmission in a particular hotspot location.

Secondary Shiga Toxin-Producing Escherichia coli Infection, Japan, 2010-2012.

To evaluate the potential public health risk caused by secondary Shiga toxin-producing Escherichia coli (STEC) infections in Japan, we investigated the prevalence and characteristics of STEC isolated from healthy adults during 2010-2012. Although prevalence among healthy adults was high, most STEC organisms displayed characteristics rarely found in isolates from symptomatic patients.

Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers.

Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRNA encoding Tax were quantified by PCR and real-time RT-PCR, respectively. Intracellular Tax in CD4(+)CD25(+) cells occurred in 100% and 86.7% of HAM/TSP patients and asymptomatic carriers, respectively. Percentage of CD4(+)CD25(+) Tax+, proviral load and mRNA encoding Tax were significantly higher in HAM/TSP patients. Western blot analyses showed higher secretion levels of ubiquitinated Tax in HAM/TSP patients than in asymptomatic carriers. In HTLV-1-infected subjects, Western blot of plasma Tax showed higher levels in HAM/TSP patients than in asymptomatic carriers, whereas no Tax was found in non-infected subjects. Immunoprecipitated plasma Tax resolved on SDS-PAGE gave two major bands of 57 and 48 kDa allowing identification of Tax and Ubiquitin peptides by mass spectrometry. Relative percentage of either CD4(+)CD25(+) Tax+ cells, or Tax protein released from PBMCs, or plasma Tax, correlates neither with tax mRNA nor with proviral load. This fact could be explained by a complex regulation of Tax expression. Tax secreted from PBMCs or present in plasma could potentially become a biomarker to distinguish between HAM/TSP patients and asymptomatic carriers.

Plasmatic proinflammatory chemokines levels are tricky markers to monitoring HTLV-1 carriers.

The human T-cell leukemia virus type 1 (HTLV-1) is present throughout the world and is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory conditions. The pathogenesis of HAM/TSP involves a chronic inflammatory response in central nervous system (CNS), with the presence of HTLV-1 infected cells and HTLV-1-specific CD8+ lymphocytes. Chemokines may have a role in the infiltration of these cells into the CNS. In this context, the present study analyzed the level of plasmatic chemokines CCL2 (MCP-1), CCL5 (RANTES), IL8 (CXCL8), CXCL9 (MIG), and CXCL10 (IP-10) and HTLV-1 proviral load from peripheral blood in 162 asymptomatic carriers and 136 HAM/TSP patients to determine the differences that be associated with the clinical status of the HTLV-1 infection. The results showed that patients with HAM/TSP have significantly higher levels of IL8 and CXCL9, and that the level of IL8, CXCL9 and CXCL10 was significantly greater in HTLV-1 infected individuals with high (>1%) than those with low proviral load (<1%). However, the levels of the chemokines tested have not showed high sensitivity to discriminate HAM/TSP patients from asymptomatic carriers. In addition, chemokine profiles in asymptomatic carriers and HAM/TSP groups were similar, with no significant increased frequency of higher producers of chemokines in HAM/TSP individuals. Results indicate that the heterogeneity of the individuals in the groups regarding time of infection, duration of disease, proviral load level and other possible confound factors may impair the use of chemokines levels to monitor HTLV-1 carriers in clinical practice. J. Med. Virol. 88:1438-1447, 2016. © 2016 Wiley Periodicals, Inc.

High prevalence of asymptomatic carriers of Tropheryma whipplei in different populations from the North of Spain.

INTRODUCTION: Tropheryma whipplei is the causative agent of Whipple disease. T. whipplei has also been detected in asymptomatic carriers with a very different prevalence. To date, in Spain, there are no data regarding the prevalence of T. whipplei in a healthy population or in HIV-positive patients, or in chronic fatigue syndrome (CFS). Therefore, the aim of this work was to assess the prevalence of T. whipplei in stools in those populations. METHODS: Stools from 21 HIV-negative subjects, 65 HIV-infected, and 12 CFS patients were analysed using real time-PCR. HIV-negative and positive subjects were divided into two groups, depending on the presence/absence of metabolic syndrome (MS). Positive samples were sequenced. RESULTS: The prevalence of T. whipplei was 25.51% in 98 stool samples analysed. Prevalence in HIV-positive patients was significantly higher than in HIV-negative (33.8% vs. 9.09%, p=0.008). Prevalence in the control group with no associated diseases was 20%, whereas no positive samples were observed in HIV-negative patients with MS, or in those diagnosed with CFS. The prevalence observed in HIV-positive patients without MS was 30.35%, and with MS it was 55.5%. The number of positive samples varies depending on the primers used, although no statistically significant differences were observed. CONCLUSIONS: There is a high prevalence of asymptomatic carriers of T. whipplei among healthy and in HIV-infected people from Spain. The role of T. whipplei in HIV patients with MS is unclear, but the prevalence is higher than in other populations.