Higher HTLV-1c proviral loads are associated with blood stream infections in an Indigenous Australian population

BackgroundAn association between blood stream infections (BSI) and HTLV-1 seropositivity in Indigenous Australians might result from HTLV-1 mediated inflammation and parasite coinfections that provide portals of entry for bacteria.ObjectivesTo determine whether BSI risk increases with HTLV-1c proviral load (PVL) and to identify the pathogens responsible in the context of HTLV-1 related conditions.Study designIndigenous adults admitted to Alice Springs Hospital, central Australia, were recruited as cases or controls according to whether they had a BSI. Clinical data were extracted from case notes and the hospital pathology database. HTLV-1 serology and PVL assays were then performed and risk factors for BSI were determined for HTLV-1 infected subjects.ResultsRisk factors were compared between 44 cases and 30 controls who were HTLV-1 Western blot positive. In a multivariable model, high HTLV-1c PVL was predictive of BSI during the study period (OR, 9.10; 95% CI, 2.40–34.4). Median (IQR) HTLV-1c PVL (copies per 100 PBL) was 39-fold higher for patients recording any BSI (0.116 (0.009, 0.277)) relative to those who had no BSI (0.003 (0.000, 0.067))(p = 0.0007). Mean (SD) PVL for subjects with no BSI (n = 27), 1 BSI (n = 37) and ≥2 BSI (n = 10) during the study period were 0.120 (0.301), 0.271 (0.622) and 0.500 (0.654) copies per 100 PBL, respectively (p = 0.0007). Five BSI were associated with possible complications of HTLV-1; strongyloidiasis (3), infective dermatitis (1), HTLV-1 associated bronchiectasis (1).ConclusionsHigher HTLV-1c PVL predicts BSI risk; however; most BSI were not associated with recognised complications of HTLV-1 infection.     

Low DNA HTLV-2 proviral load among women in São Paulo City

BACKGROUND: HTLV-2 infections are almost always asymptomatic, and diseases associated with the infection are rarely reported. Little information is available on the relationship between HTLV-2 proviral load and gender or expression of disease, especially among patients with HIV-1 co-infection. METHODS: We studied 77 HTLV-2-infected subjects followed in our clinic for the last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in 10(4) PBMCs. RESULTS: Six of 53HTLV-2/HIV-1 cases had a myelopathy (all of them had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless of their HIV status women had significantly lower PVL than men (10 vs. 43 copies/10(4) PBMCs, p<0.05). CONCLUSIONS: We noticed the occurrence of myelopathy in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There was a sex difference in viral load for HTLV-2, what may be the result in mode of transmission or acquisition of the virus.     

The Association between Asthma and Invasive Pneumococcal Disease: A Nationwide Study in Korea

The purpose of this study was to investigate the association between asthma and invasive pneumococcal disease (IPD) in Korea. A retrospective population-based cohort study was conducted using the Korean Health Insurance Review and Assessment database 2010-2011. The subjects included 935,106 (2010) and 952,295 (2011), of whom 398 (2010) and 428 (2011) patients with IPD were identified. There was significant difference in the prevalence of IPD in patients with and without asthma (0.07% vs. 0.02% in 2010 and 0.08% vs. 0.01% in 2011; P<0.001). After adjusting for age and gender, patients with asthma showed over a three-fold increased risk of IPD compared with patients without asthma (adjusted odds ratio [aOR] 3.90, 95% confidence interval [CI] 3.02-5.03 in 2010 / aOR, 5.44; 95% CI, 4.10-7.22 in 2011; P<0.001). These findings were also significant in children (aOR, 2.08; 95% CI, 1.25-3.45 in 2010; P=0.005 / aOR, 3.26; 95% CI, 1.74-6.11 in 2011; P<0.001). Although diabetes mellitus was also significantly associated with IPD, relatively low ORs compared with those of asthma were noted (aOR, 1.85; 95% CI, 1.35-2.54 in 2010 / aOR, 2.40; 95% CI, 1.78-3.24 in 2011; P<0.001). Both children and adults with asthma are at increased risk of developing IPD.

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Short-term virological efficacy, immune reconstitution, tolerance, and adherence of once-daily dosing of didanosine, lamivudine, and efavirenz in HIV-1-infected African children: ANRS 12103 Burkiname

Access to antiretroviral therapy (ART) and routine laboratory monitoring are limited for HIV-1-infected children from sub-Saharan Africa. This trial conducted in Bobo-Dioulasso, Burkina Faso, aimed to describe the biological efficacy, tolerance, and adherence of the combination of didanosine, lamivudine, efavirenz in once-daily administration among eligible HIV-1-infected children. From February 2006 to November 2007, 51 HIV-1-infected children aged from 30 months to 15 years and eligible for ART were enrolled in a phase II open clinical trial with follow-up visits every 3 months. HIV-1 genotype testing was performed in children with plasma viral load (PVL) >1000 copies per milliliter after ART initiation. Children were followed for a median of 13.4 months [interquartile range (IQR) 12.8-14.2]. At enrollment, median CD4 count was 8% (IQR = 4.5-12). PVL was 341,032 (IQR = 127,838-761,539) copies per milliliter. At 12 months, median CD4 increased significantly by +15% (P < 10(-3)), and median PVL decreases significantly by -290,500 copies per milliliter (P < 10(-4)). Hemoglobin and platelets counts increased significantly by +1.05 g/dL (P < 10(-5)) and 108,500 cells per milliliter (P < 10(-3)), respectively. Based on pill count, mean yearly adherence was 97.3%, and 48% of the children had an adherence rate ≥ 95% at the four quarterly visits. Adherence was better for girls than for boys independently of other sociodemographic variables or markers of HIV disease progression. Drug-resistant mutations were found in 11 children (21.6%). This once-daily drug combination is associated with excellent virological efficacy, immune reconstitution, and good adherence. However, the high prevalence of drug resistance mutations is a matter of concern.     

Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial

BACKGROUND: Whether structured treatment interruptions (STIs) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy (HAART) in patients with primary HIV infection is controversial. METHODS: In this multicenter, prospective trial, patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks. Afterward, patients with plasma viral load (PVL) <50 copies/mL entered the STI phase, which consisted of 3 consecutive periods of 2, 4, and 8 weeks off HAART, each separated by 12 weeks on HAART. HAART was permanently stopped at week 84 and patients were followed up for 24 weeks. The primary endpoint for definition of virologic success was a PVL <50 copies/mL during the 6 months following HAART discontinuation. RESULTS: Of the 29 patients enrolled, 26 completed the trial. Six months after HAART discontinuation, only 1 patient (3.8%, 95% CI: 0.1% to 19.6%) had PVL <50 copies/mL, whereas 6 of 26 (23.1%, 95% CI: 9.0% to 43.7%) had PVL <1000 copies/mL. Female gender was the only parameter significantly associated with a PVL <1000 copies/mL. No other parameter, either at baseline or before HAART discontinuation, predicted virologic success at week 108. A major protease inhibitor resistance mutation (L90M) developed in 3 patients. CONCLUSIONS: This trial failed to confirm that a significant proportion of patients with primary HIV infection can maintain suppression of viremia after a sequence of HAART/STIs followed by HAART discontinuation.     

Immunological responses and long-term treatment interruption after human immunodeficiency virus type 1 (HIV-1) lipopeptide immunization of HIV-1-infected patients: the LIPTHERA study

We studied the time course of immunological and virological markers after highly active antiretroviral therapy (HAART) interruption in chronically human immunodeficiency virus type 1 (HIV-1)-infected patients immunized with an HIV lipopeptide preparation. In a prospective open pilot study, 24 HIV-1-infected HAART-treated patients with undetectable plasma viral loads (pVLs) and CD4⁺ T-cell counts above 350/mm³ were immunized at weeks 0, 3, and 6 with a candidate vaccine consisting of six HIV lipopeptides. At week 24, patients with pVLs of <1.7 log₁₀ copies/ml were invited to stop taking HAART. Antiretroviral therapy was resumed if the pVL rose above 4.47 log₁₀ copies/ml and/or if the CD4⁺ cell count fell below 250/mm³. Immunological and virologic parameters were studied before and after HAART interruption. The median baseline and nadir CD4⁺ cell counts were 482 (interquartile range [IQR], 195 to 826) and 313 (IQR, 1 to 481)/mm³, respectively. New specific CD8⁺ cell responses to HIV-1 epitopes were detected after immunization in 13 (57%) of 23 assessable patients. Twenty-one patients were evaluated 96 weeks after HAART interruption. The median time to pVL rebound was 4 weeks (IQR, 2 to 6), and the median peak pVL was 4.26 (IQR, 3 to 5) log₁₀ copies/ml. Thirteen of these 21 patients resumed HAART a median of 60 weeks after immunization (IQR, 9.2 to 68.4 weeks), when the median pVL was 4.8 (IQR, 2.9 to 5.7) log₁₀ copies/ml and the median CD4⁺ cell count was 551 (IQR, 156 to 778)/mm³. Eight patients were still off therapy at 96 weeks, with a median pVL of 4 (IQR, 1.7 to 4.6) log₁₀ copies/ml and a median CD4⁺ cell count of 412 (IQR, 299 to 832)/mm³. No clinical disease progression had occurred. Despite the lack of a control arm, these findings warrant a randomized study of therapeutic vaccination with HIV lipopeptides followed by long-term HAART interruption in AIDS-free chronically infected patients.     

Polymorphisms of human platelet alloantigens HPA-1 and HPA-2 associated with severe coronary artery disease

ObjectivesInsofar as platelet membrane glycoprotein (GP) polymorphisms were identified as potential risk factors for coronary artery disease (CAD), we investigated the contribution of human platelet antigen (HPA)-1 (GPIIb/IIIa) and HPA-2 (GPIb/IX) alleles and haplotypes to CAD pathogenesis.MethodsStudy subjects comprised 247 middle-age CAD patients and 316 age-, gender-, and race-matched controls; HPA genotyping was performed by polymerase chain reaction with sequence specific primers.ResultsThe frequencies of HPA-1b (P<.001) and HPA-2b (P<.001) alleles and HPA-1a/1b (P<.001), HPA-1b/1b (P<.001), and HPA-2a/2b (P<.001) genotypes were higher in patients than control subjects. Select HPA haplotypes comprising the HPA-1b/2a (Pc=2.2×10^?4) and HPA-1b/2b (Pc=.001) haplotypes which were positively associated, and the HPA-1a/2a (Pc=3.2×10^?5) which was negatively associated with CAD, confer a disease susceptibility and protective nature to these haplotypes. Multivariate analysis confirmed the positive association of HPA-1b/2a [adjusted odds ratio (aOR)=3.63; 95% CI=2.42–5.43] and HPA-1b/2b (aOR=2.92; 95% CI=1.43–5.94) haplotypes with CAD, after adjustment for a number of covariates.ConclusionsOur results suggest that HPA-1/HPA-2 haplotypes may be considered to be a major risk factor for CAD in middle-aged Tunisians.     

Delay in commencement of palliative care service episodes provided to Indigenous and non-Indigenous patients: cross-sectional analysis of an Australian multi-jurisdictional dataset

Background

Rapid effective responsiveness to patient needs is pivotal to high quality palliative care. Aboriginal and Torres Strait Islander (Indigenous) people are susceptible to life-limiting illnesses at younger ages than other Australians and experience inequity of health service provision. The Palliative Care Outcomes Collaboration collects Australia-wide health service data on patient care, and has established performance benchmarks for specialist palliative care services. We investigated whether the benchmark for timely commencement of palliative care episodes (occurrence of delay >1?day after being designated ‘ready for care’ in <10% instances) is being met for Indigenous Australians in participating services. Additionally, we investigated the association between identification as Indigenous and delay.

Methods

Using multi-jurisdictional Palliative Care Outcomes Collaboration data, this cross-sectional analytical study investigated all episodes of care (n =?84,238) provided to patients ≥18?years (n =?61,073: Indigenous n =?645) in hospital and community settings commenced and completed during the period 01/07/2013–30/06/2015. Proportions of episodes resulting in delay were determined. Crude and adjusted odds of delay among Indigenous compared with non-Indigenous patients were investigated using multiple logistic regression, with missing data handled by multiple imputation.

Results

The benchmark was met for both Indigenous and non-Indigenous patients (delay in 8.3 and 8.4% episodes respectively). However, the likelihood of delay was modestly higher in episodes provided to Indigenous than non-Indigenous patients (adjusted odds ratio [aOR], 1.41; 95% confidence interval [CI] 1.07–1.86). Excess delay among Indigenous patients was accentuated in first episodes (aOR, 1.53; 95% CI 1.14–2.06), in patients aged <?65?years (aOR, 1.66; 95% CI 1.14–2.41), and among those residing in Inner Regional areas (aOR, 1.97; 95% CI 1.19–3.28), and also approached significance among those in outer regional, remote and very remote areas collectively (aOR, 1.72; CI 0.97–3.05).

Conclusions

Although the timeliness benchmark is being met for Indigenous Australians in palliative care, they may experience delayed initiation of care episodes, particularly if younger, and especially at first encounter with a service. Qualitative research is required to explore determinants of delay in initiating palliative care episodes. The timeliness of initial referral for specialist palliative care in this population remains to be determined.

     

Predictors of Default from Treatment for Tuberculosis: a Single Center Case–Control Study in Korea

Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case–control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (< 2,000 US dollars/month, 88.1% vs. 68.4%, P = 0.015), absence of TB stigma (4.3% vs. 61.3%, P < 0.001), treatment by a non-pulmonologist (74.1% vs. 25.9%, P < 0.001), history of previous treatment (37.0% vs. 19.0%, P = 0.019), former defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078–265.365, P < 0.001), treatment by a non-pulmonologist (aOR: 14.567, 95% CI: 3.260–65.089, P < 0.001), former defaulters (aOR: 33.226, 95% CI: 2.658–415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249–22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default.     

Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and HIV-2-infected women in a community-based cohort in The Gambia

OBJECTIVES: To estimate and compare the all-cause mortality rates among HIV-1-infected, HIV-2-infected, and uninfected women and to assess the predictive value of baseline plasma viral load (PVL) and CD4 cell percentage (CD4%) for mortality. DESIGN: Cohort study. METHODS: At presentation to antenatal clinics in The Gambia in 1993-1995, pregnant women were screened for antibodies to HIV-1 and HIV-2. Seropositive subjects and a similar number of seronegative controls were enrolled, and baseline PVL and CD4% were measured. Participants were visited regularly by field-workers until 18 months after delivery and again 4-7 years later. RESULTS: Thirty-two of 101 women infected with HIV-1, 23 of 243 infected with HIV-2, and 9 of 468 seronegative women died during a median follow-up of 6.9 years. The mortality rate was 56 deaths per 1000 person years of observation (pyo) for HIV-1-infected, 16 deaths per 1000 pyo for HIV-2-infected, and 3.1 deaths per 1000 pyo for HIV-uninfected women. After 8 years of follow-up, >50% of HIV-1-infected women were still alive. In multivariate analysis, a 1-log increase of HIV-1 PVL was associated with a 1.8-fold higher rate of mortality (95% confidence interval [CI], 0.9-3.4). In HIV-2 infection, women with a high PVL (>10,000 copies/mL) had an 8.7-fold (95% CI, 2.8-28) higher rate of mortality than did those with a low PVL (<1000 copies/mL). A 10% decrease in CD4% was associated with higher mortality rates among HIV-1-infected (1.6-fold; 95% CI, 1.1-2.3) and HIV-2-infected (1.5-fold; 95% CI, 1.0-2.3) subjects. DISCUSSION: Survival of HIV-1-infected women in The Gambia is similar to that in industrialized countries before the introduction of antiretroviral treatment. Survival of HIV-2-infected women is much better. However, women with high PVLs die as quickly as their HIV-1-infected counterparts.     

Genetic polymorphisms in the cytochromes P-450 (1A1, 2E1), microsomal epoxide hydrolase and glutathione S-transferase M1, T1, and P1 genes, and their relationship with chronic bronchitis and relapsing pneumonia in children

The purpose of this study was to investigate the possible roles of the genes functioning in xenobiotic metabolism and antioxidant pathways in the development of severe chronic lung disease in children. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1 were investigated in cases of Tatar children with chronic bronchitis (n=129) and relapsing pneumonia (n=50) and in cases of ethnically matched healthy individuals (n=227) living in the city of Ufa, the Republic of Bashkortostan (South Ural region of Russia), by polymerase chain reaction–restriction fragment length polymorphism (PCR-RLFP) method. The frequency of the *2C allele of the CYP1A1 gene was significantly higher in patients than in the healthy control group (²=15.02, P=0.0007, P_cor=0.0021). This allele was associated with a higher risk of chronic bronchitis in children (OR 4.14, 95% CI 1.83–9.53; P_cor=0.0024). Similar results were obtained in cases of patients with relapsing pneumonia (OR 3.86, 95% CI 1.34–10.95; P_cor=0.027 for the *2C allele of the CYP1A1 gene). The frequency of the *5B allele of the CYP2E1 gene was higher in the relapsing pneumonia patients (7.0 vs 1.98% in the control group; ²=5.68, P=0.018, P_cor=0.054; OR 3.72, 95% CI 1.21–11.24). The increase in the GSTT1 gene deletion was significant only in cases of chronic bronchitis (39.53 compared to 21.15% in the control group; ²=12.96, P=0.001, P_cor=0.003; OR 2.44, 95% CI 1.48–4.04). Our results show that the presence of the GSTM1 gene deletion is unfavorable for the development of chronic lung disease in females (²=9.57; P=0.0029, P_cor=0.0116) and was associated with increased risk (OR 2.44, 95% CI 1.36–4.38). The distribution of EPHX1 and GSTP1 gene genotypes was similar in the control and patient groups. Our findings indicate that the polymorphisms of the CYP1A1, CYP2E1, and GSTT1 genes probably play a substantial part in susceptibility to severe airway and lung injury in cases of children with chronic bronchitis and relapsing pneumonia.     

Factors associated with re-admission in the year after acute postpartum psychiatric treatment

Purpose

To examine factors associated with being re-admitted in the year after discharge from acute postpartum psychiatric treatment.

Methods

Secondary data analysis of information collected from mothers who were admitted to acute psychiatric services in the year after childbirth between 2013 and 2017. We carried out univariable analyses and multivariable hierarchical logistic regression to examine risk factors for women’s re-admission to acute psychiatric care (inpatient or community crisis care) in the year following discharge.

Results

Sixty-seven (24.1%) of 278 women were re-admitted in the year after discharge from acute care; the median number of days to re-admission was 86 (IQR 35–214), and women who were re-admitted accessed a median of two further acute services (IQR 1–3). In adjusted analyses, reporting a history of childhood trauma (aOR 1.02; 95% CI 1.00- 1.03, p = 0.036), a higher level of difficulties in the mother–infant bond (aOR 1.03; 95% CI 1.01–1.06, p = 0.009) and younger age (aOR 0.95; 95% CI 0.90–1.00, p = 0.066) were associated with re-admission.

Conclusion

This study confirms that the role of childhood adverse experiences on mental health is relevant for outcomes in women experiencing acute postpartum psychiatric episodes. Ongoing parent–infant bonding difficulties are also independently associated with re-admission. Perinatal mental health services therefore need to offer evidence-based interventions to address histories of trauma and to support parent–infant bonding to optimise mental health in women following discharge from acute psychiatric services. However, further research is needed to explore what other factors, not measured in our study, are also influential to re-admission.

     

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative treatment option for patients with aggressive adult T cell leukemia-lymphoma (ATL). Donor human T cell leukemia virus (HTLV) 1 seropositivity is a critical concern when choosing relative donors, as they are not usually recommended due solely to the occurrence of donor-derived ATL. A previous report suggested that allo-HCT with an HTLV-1-seropositive donor increased ATL-related mortality. We updated the risk assessment for choosing an HTLV-1-seropositive allo-HCT donor for ATL. Our current registry data, which include larger numbers of HTLV-1-seropositive donors and longer observation periods, revealed no significant difference in overall survival (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P = .61) or cumulative incidence of either ATL-related (HR, 0.96; 95% CI, 0.64 to 1.45; P = .80) or non-ATL-related mortality (HR, 0.91; 95% CI, 0.61 to 1.37; P = .66). Similarly, when considering only patients with ATL in complete remission, there was no significant difference in overall survival (HR, 1.02; 95% CI, 0.70 to 1.49; P = .91) or cumulative incidence of either ATL-related (HR, 1.20; 95% CI, 0.66 to 2.20; P=0.54) or non-ATL-related mortality (HR, 0.86; 95% CI, 0.52-1.42; P = .66). These data indicate that selecting HTLV-1-seropositive donors might not be contraindicated for patients with ATL receiving allo-HCT if alternative donors are unavailable. Further risk assessment remains to be performed.     

Association between a promoter polymorphism (rs2192752, –1028A/C) of interleukin 1 receptor,type I (IL1R1) and location of papillary thyroid carcinoma in a Korean population

The interleukin 1 receptor, type I (IL1R1) is important in the pathogenesis of cancer. We investigated whether single nucleotide polymorphisms (SNPs) of IL1R1 contribute to the development of papillary thyroid carcinoma (PTC), in addition to the clinicopathological features such as the size, number, location, extrathyroidal invasion and metastasis of PTC. Three promoter SNPs (rs949963 ?615G/A, rs2192752 ?1028A/C and rs3917225 ?1099A/G) in IL1R1 were genotyped using direct sequencing in 118 patients with PTC and 347 controls. The odds ratio (OR), 95% confidence interval (CI) and P value were analysed using SNPStats and SNPAnalyzer Pro. For the exact results, Fisher’s exact test and Bonferroni correction (P^c) were performed. The three promoter SNPs of IL1R1 were not associated with PTC development. For the clinicopathological features of PTC, rs2192752 was associated with location (one lobe versus both lobes): dominant model, OR = 3.11, 95% CI = 1.39–6.96, P^c = 0.015; log‐additive model, OR = 2.79, 95% CI = 1.38–5.66, P^c = 0.0087. The C allele frequency of rs2192752 was higher in the both lobes group (28.0%) than the one lobe group (12.3%) (OR = 2.77, 95% CI = 1.40–5.48, P^c = 0.009). However, rs949963 and rs3917225 were not correlated with clinicopathological features including location of PTC. The IL1R1 promoter SNP rs2192752 may contribute to the location of PTC, and the C allele of rs2192752 may be a risk factor for the development of PTC in both lobes.     

Design and development of a quantitative real time PCR assay for monitoring of HTLV-1 provirus in whole blood

BackgroundProviral load quantification of human T-lymphotropic virus type 1 (HTLV-1) is an essential marker for disease progression. Therefore, accurate and precise quantification of the virus is important. However, many articles published about detection and quantification of HTLV-1 virus neither reported any databank for the pre-validation of their primer and probe sequences nor stressed on its importance. Consequently, this failure may cause proviral load measurement variations of different HTLV-1 strains.ObjectiveThe aim of this study was to develop a TaqMan assay for HTLV-1 proviral load quantification which is based on a conserved region of tax gene with minimal sequence variability.Study designFor the purpose of finding the most conserved region of tax gene, all the HTLV-1 Gene Bank records including tax gene sequence (524 records by December 2009) were aligned in order to design on the most conserved region of this gene. The specificity, sensitivity, inter and intra assay and the dynamic range of the assay were experimentally determined by their respective methodology.ResultThe assay has a dynamic range of 10–10⁷ HTLV-1 plasmid DNA/rxn (reaction) and the limit of detection (LOD) less than 10 copies/rxn. The assay gave coefficient of variation (CV) for the Ct values of less than 1% and 4.8% for intra and inter assay, respectively. Clinical sensitivity and specificity were determined to be 97.8% and 100%, respectively.ConclusionThis TaqMan assay is able to reliably quantify proviral load due to the fact that it has been designed on a conserved region of HTLV-1 tax gene with minimal sequence variability.     

Human T cell lymphotropic virus type 1 (HTLV-1) proviral load of HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients according to new diagnostic criteria of HAM/TSP

A high human T‐cell lymphotropic virus type 1 (HTLV‐1) proviral load is described in HTLV‐1‐associated diseases, especially HAM/TSP. However, the cut‐off value to define high levels of HTLV‐1 proviral load is not well established. 281 HTLV‐1‐infected patients from the HTLV reference center in Salvador, Brazil, were followed from 2005 to 2008. Patients were classified as asymptomatic, possible‐, probable‐, and definite‐HAM/TSP, in accordance with diagnostic criteria proposed by De Castro‐Costa et al. (2006): AIDS Res Hum Retroviruses 22:931–935. HTLV‐1 proviral load was determined using real‐time PCR. A receiver operator characteristic (ROC) curve was constructed using only asymptomatic individuals and definite‐HAM/TSP patients. The ROC curve was used to predict the proviral load level that differentiates these two groups. Out of 281 patients, 189 were asymptomatic and 92 were diagnosed with HAM/TSP (22 possible, 23 probable, 47 definite). The mean HTLV‐1 proviral load was higher in possible‐ (89,104 ± 93,006 copies/10⁶ PBMC), ‐probable (175,854 ± 128,083 copies/10⁶ PBMC), and definite‐HAM/TSP patients (150,667 ± 122,320 copies/10⁶ PBMC), when compared to asymptomatic individuals (27,178 ± 41,155 copies/10⁶ PBMC) (P < 0.0001). A comparison of all HAM/TSP groups showed the highest proviral loads in probable‐HAM/TSP patients, yet the differences in mean values were not statistically significant. The ROC curve suggested a value of 49,865 copies/10⁶ PBMC, with 87% sensitivity (95% CI = 74–95) and 81% specificity (95% CI = 75–86), as the best proviral load cut‐off point to differentiate definite HAM/TSP patients from asymptomatic individuals. HTLV‐1 proviral loads are higher in groups of infected patients with neurological symptoms and may represent a relevant biological marker of disease progression. J. Med. Virol. 83:1269–1274, 2011. © 2011 Wiley‐Liss, Inc.     

Keratoconjunctivitis sicca of human T cell lymphotropic virus type 1 (HTLV-1) infected individuals is associated with high levels of HTLV-1 proviral load

BackgroundA high HTLV-1 proviral load is found in HTLV-1-associated diseases, mainly HAM/TSP. However, the association between proviral load and keratoconjunctivitis sicca (KCS) has not been well established.AimTo verify the association between KCS and HTLV-1 proviral load.Study design104 HTLV-1 infected patients (51 asymptomatic and 52 with HAM/TSP) from the HTLV reference center in Salvador, Brazil were followed from June 2008 to May 2010. Evaluation of tear secretion was performed by BUT (break-up time), Rose Bengal and Schirmer I tests. The diagnosis of KCS was based upon the presence of symptoms and when at least two of three tests were positive. HTLV-1 proviral load was determined using real-time PCR.ResultsThe prevalence of KCS was 44.2%. KCS was more frequent among HAM/TSP patients (p = 0.022). Patients with KCS had higher proviral load (mean 134,672 ± 150,393 copies/10⁶ PBMC) than patients without the disease (mean 66,880 ± 109,525 copies/10⁶ PBMC) (p = 0.001). HTLV-1 proviral load > 100,000 copies/10⁶ PBMC increased significantly the risk of developing KCS (OR = 4.05 and 95% CI = 1.40–11.76). After age > 45 years and HAM/TSP status were excluded in stepway reward analysis, the variables PVL > 100,000 (OR = 4.77 and 95% CI = 1.83–12.44) still remained statistically significant.ConclusionHTLV-1 proviral loads are higher in patients with KCS and may represent a relevant biological marker of disease.     

Hepatitis B viral loads in southern African Blacks with hepatocellular carcinoma

Although viral loads are known to influence the development of hepatitis B virus‐induced hepatocellular carcinoma in a number of populations, little information is available in the Black African population. Black African patients with hepatocellular carcinoma differ from those in other populations in having a lower frequency of e antigen‐positivity and in other respects that might affect viral loads. Hepatitis B viral loads were measured using real‐time polymerase chain reaction assay in 124 Black Africans with hepatocellular carcinoma and compared with those in 125 Black adult asymptomatic viral carriers. The geometric mean viral load in the cancer patients was 553,618 copies/ml (95% CI 301,953–1,015,033 copies/ml), with 62.1% having loads >1 × 10⁵ copies/ml and 87.1% >1 × 10⁴ copies/ml, whereas that in the carriers was 16,084 copies/ml (95% CI 9,184–28,168 copies/ml), with only 15.2% having values >1 × 10⁵ copies/ml and 49.6% >1 × 10⁴ copies/ml (P < 0.001 in each instance). Mean viral load was significantly higher in e antigen‐positive than e antigen‐negative cancer patients (5,905,357 copies/ml [1,362,847–25,588,520] cf 238,173 copies/ml [97,200–685,730]: P < 0.001) after adjusting for age and sex. No statistically significant difference existed between patients in different age groups, in men and women, or in patients infected with genotype A or D after adjusting for the other variables. Conclusion: Black Africans with hepatocellular carcinoma have high hepatitis B viral loads in spite of the relative infrequency of e antigen‐positivity. J. Med. Virol. 81:1525–1530, 2009. © 2009 Wiley‐Liss, Inc.