Human T-lymphotropic virus type I (HTLV-I): risk of transmission with transfusion

PATHOGENIC ROLE: The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus discovered, is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and of HTLV-I associated myelopathy or tropical spastic paraparesis (HAM/TSP) and has a widespread but uneven worldwide distribution. HTLV-I has a high seroprevalence in Southern Japan, the Caribbean basin and Sub-Sahara Africa. Blood transfusion, intravenous drug use, breast feeding and sexual contacts are major routes of contamination. IMPLICATIONS FOR BLOOD TRANSFUSION: The screening of blood donors for antibody to HTLV-I became systematic in 1989 in French West Indies and in 1991 in Continental France. This review deals with the transfusional implications of the HTLV-I, which belongs to the group of the blood-borne viruses: the prevalence of transfusion-linked HTLV-I infection before the implementation of the specific preventive measures, the parameters influencing the risk of transfusional contamination (the type of blood products, the age of the blood product with regards to its collection date, the proviral load of the blood donor), the prognosis of HTLV-I infection in patients contaminated by transfusion, the prophylactic strategies of transfusion contamination and the residual risk of infection through HTLV-I-infected risk blood products.     

The influence of human T lymphotropic virus type I infection on the outcome of cardiovascular surgery

OBJECTIVE: Human T lymphotropic virus type I infects CD4(+) T cells and affects cell-mediated immunity. Cardiopulmonary bypass transiently alters lymphocyte subsets, resulting in a reduction in CD4(+) T cells and an increase in CD8(+) T cells. We proposed that cardiovascular operations and human T lymphotropic virus type I infection may act synergistically, resulting in serious damage to cell-mediated immunity. METHODS: A total of 517 consecutive patients who were preoperatively screened for anti-human T lymphotropic virus type I antibody and underwent cardiovascular operations with cardiopulmonary bypass were enrolled in this study. Of the 517 patients, 82 (16%) had positive test results for anti-human T lymphotropic virus type I antibody. The surgical outcome of patients with positive and negative results for anti-human T lymphotropic virus type I antibody was analyzed retrospectively. RESULTS: There was no difference between the 2 groups with respect to early mortality. Distribution of survival curve was also not significantly different (P =.5; mean follow-up duration, 2.4 +/- 1.8 years [range, 0-9.4 years] and 3.2 +/- 2.8 years [range, 0-9.8 years]) in the groups with positive and negative antibody results, respectively). In particular, long-term follow-up did not reveal adult T-cell leukemia or human T lymphotropic virus type I-associated myelopathy, and occurrence of neoplasm did not differ between groups. Early infectious complication was, however, significantly higher in the group with positive antibody results than in the group with negative results (P =.02). Logistic regression analysis revealed human T lymphotropic virus type I infection as a significant risk for this complication (P =.04; odds ratio, 2.5; 95% confidence interval, 1. 0-5.8). CONCLUSION: A combination of human T lymphotropic virus type I infection and cardiovascular operation is believed to increase the potential risk of infectious complications shortly after the operation. However, this synergistic effect seems to be transient and has little influence on long-term prognosis.     

Clinical investigation of pulmonary Mycobacterium avium complex infection in human T lymphotrophic virus type I carriers

BACKGROUND: Little is known about pulmonary Mycobacterium avium complex (MAC) infection in human T lymphotrophic virus type I (HTLV-I) carriers. A study was undertaken to investigate and clarify the characteristics of pulmonary MAC infection in these subjects. METHODS: Twenty nine patients with pulmonary MAC infection without any underlying pulmonary disorder were investigated. The clinical features and radiographic appearance of HTLV-I carriers and non-carriers were compared and the bronchoalveolar lavage (BAL) fluid of these 29 patients and eight normal female control subjects was analysed. RESULTS: The prevalence of the HTLV-I carrier state in patients with pulmonary MAC infection was 34.5% (10/29) compared with 16.7% (529/3169) among all patients admitted to our department between 1994 and 1998 (odds ratio (OR) 2.63, 95% confidence interval (CI) 1.21 to 5.68). The HTLV-I carriers were all women and all had clinical symptoms, but they did not show systemic dissemination. Peripheral multifocal bronchiectasis with nodular shadowing was seen frequently on the chest computed tomographic (CT) scans of HTLV-I carriers. The area of the pulmonary lesions was more extensive than in non-carriers (p<0.05). White blood cell (WBC) counts and C reactive protein (CRP) levels on admission were significantly lower in HTLV-I carriers than in non-carriers (WBC: difference (D) = 1565/microl, 95% CI -68.9 to 3198.4/microl; CRP: D = 1.8 mg/dl, 95% CI -0.35 to 3.89 mg/dl). The concentrations of neutrophil elastase (NE) and interleukin (IL)-8 in BAL fluid were significantly higher in HTLV-I carriers than in non-carriers (NE: D = 1342 microg/l, 95% CI 704 to 1980.3 microg/l; IL-8: D = 304.5 pg/ml, 95% CI 89.7 to 519. 4 pg/ml). CONCLUSIONS: Pulmonary MAC infection causes more diffuse and widespread lesions in HTLV-I carriers than in non-carriers.     

Renal transplantation in patients with human T-cell lymphotropic virus type 1

Background

Renal transplantation (RTx) in carriers of human T-cell lymphotropic virus type 1 (HTLV-1) has a risk of developing overt leukemia upon immunosuppression. Although there have been a few reports of such cases, it is unclear HTLV-1 carrier if patients on the modern immunosuppressants would develop HTLV-1-associated myelopathy or adult T-cell leukemia lymphoma.

Methods

We retrospectively reviewed the clinical outcomes of RTx in nine HTLV-1 carriers to assess a risk of developing leukemia from 2002 to 2011 using immunosuppression with a calcineurin inhibitor, mycophenolate mofetil (MMF), and steroid. The anti-CD25 monoclonal antibody basiliximab was used for induction. In two cases of ABO-incompatible RTx, the rituximab was also administered before RTx.

Results

The ratio of male to female subjects was 2 to 7 with an overall mean recipient age of 54.3 ± 8.1 years. We prescribed cyclosporine (n = 5) or tacrolimus (n = 4). There was only one graft loss due to the death caused by aspiration pneumonia with a functioning graft. No one developed overt leukemia with combined treatment with MMF, basiliximab and rituximab.

Conclusion

We concluded that RTx in HTLV-1 carriers could be performed using a modern immunosuppressive regimen, without the risk of developing leukemia.     

Enhanced inhibition of lymphocyte activation by Mycobacterium avium complex in human T lymphotrophic virus type I carriers

BACKGROUND: We have previously reported that disseminated pulmonary Mycobacterium avium complex (MAC) infection is more common in human T lymphotrophic virus type I (HTLV-I) carriers than in non-carriers. However, the reason for this remains unclear. It has been shown that glycopeptidelipid (GPL), one of the lipid components of the cell envelope of MAC, is able to reduce the lymphocyte blastogenic response to mitogens. The purpose of this study was to clarify whether or not the inhibitory effect of GPL differs between HTLV-I carriers and non-carriers. METHODS: Peripheral blood lymphocytes were obtained from 29 patients who had recovered from pulmonary MAC infection (10 of whom also had HTLV-I infection) and the lymphocyte counts and T cell subpopulations of the peripheral blood lymphocytes in HTLV-I carriers and non-carriers were compared. The inhibitory effect of GPL on the lymphocyte blastogenic response to phytohaemagglutinin (PHA) was tested in these 29 cases and in 15 healthy controls who had never suffered from MAC (seven of whom also had HTLV-I infection). All HTLV-I positive cases were carriers. RESULTS: There was no significant difference in the numbers or subset proportions of T cells between HTLV-I carriers and non-carriers. Lymphocyte activation by PHA was significantly inhibited by GPL in MAC positive and negative HTLV-I carriers compared with MAC negative non-carriers and MAC negative healthy controls (p<0.001). CONCLUSIONS: We suggest that MAC infection leads to strong inhibition of lymphocyte activation in HTLV-I carriers. This may account, in part, for the severity of pulmonary MAC infection in HTLV-I carriers.     

Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes after lung transplantation correlates with HCMV pneumonitis

BACKGROUND: Human cytomegalovirus (HCMV) reactivation and disease remain relatively common in lung transplant recipients (LTR) despite the use of ganciclovir prophylaxis protocols for all HCMV at-risk patients. The specific aims of this study were to (1) describe the HCMV DNA viral load in the peripheral blood leukocytes (PBL) of a cohort of LTR during the first 6 months after lung transplantation; (2) prospectively determine whether HCMV DNA viral load predicts episodes of HCMV pneumonitis in LTR; and (3) study the effect of ganciclovir on HCMV viral load. METHODS: Competitive polymerase chain reaction using an internal standard and fluorometric detection were used to quantitate HCMV DNA in the PBL of a cohort of 26 LTR monthly for the first 6 months after transplantation (145 samples). All patients were treated with standard triple immunosuppression, and ganciclovir prophylaxis was given to all at-risk LTR (donor or recipient HCMV seropositive) for at least 8 weeks after transplantation. RESULTS: Thirteen episodes of histopathologically proven HCMV pneumonitis in nine subjects occurred during follow-up with a wide intra- and intersubject variation in the HCMV DNA PBL levels. HCMV detection had a sensitivity of 92% and specificity of 76% for HCMV pneumonitis (negative likelihood ratio, 9.5), whereas greater than 10-fold increases in HCMV DNA load had a specificity of 93% and sensitivity of 67% (positive likelihood ratio, 11). HCMV DNA detection had an adjusted odds ratio for HCMV pneumonitis of 107 (95% confidence interval, 14-821; P<0.005). In those with detectable HCMV DNA in PBL (n=44), HCMV DNA levels were 4.4 (95% confidence interval, 1.2-16.8) times higher in those with HCMV pneumonitis than in those without HCMV pneumonitis. Although ganciclovir treatment was very effective in treating HCMV pneumonitis and suppressing HCMV DNA levels, thrice weekly ganciclovir prophylaxis only partially controlled HCMV DNA levels and did not eliminate HCMV pneumonitis risk as three patients developed HCMV pneumonitis while on this regimen. CONCLUSIONS: HCMV DNA detection, absolute levels, and relative change from baseline in the PBL of LTR correlate with HCMV pneumonitis episodes and may be a useful intermediate outcome measure of the efficacy of ganciclovir prophylaxis and treatment strategies.     

Depression of evoked electromyographic (EEMG) responses by propofol in a patient with human T-cell lymphotropic virus type I-associated myelopathy (HAM)

IMPLICATIONS: We report a patient with human T-cell lymphotropic virus type I-associated myelopathy. Although muscle strength in both of the upper extremities was normal in this patient, evoked electromyogram of the adductor pollicis was depressed by propofol at the induction of anesthesia.     

Cardiac surgery in human immunodeficiency virus (HIV) carriers

Intravenous drug addicts have always been at risk for acquiring infective endocarditis. In the United States in recent years, as many as 50% of addicts have become infected also with the human immunodeficiency virus (HIV). Since testing became available in late 1984, we have knowingly performed open cardiac surgery for endocarditis 11 times in HIV-positive patients. In 7, signs of infection were still presented at the time of surgery. Four died within 2 months of continued or recurrent sepsis. The others are alive, although 1 has returned to IV drug abuse. Open heart surgery was performed 4 times in patients whose endocarditis had been cured by antibiotics but who were left with destroyed valves and severe congestive cardiac failure. All these patients left hospital alive and well. One has since died of AIDS. Ten addicts with endocarditis coming to surgery in the pre-AIDS era had similar valvular pathology but only 2 with uncontrolled infection. All were cured by the combination of antibiotics and surgery. Conclusions: in HIV-positive patients with endocarditis, continued sepsis despite appropriate antibiotic therapy signals a potentially very serious prognosis which may be due to an already seriously impaired immune state. By contrast, in the absence of uncontrolled infection, HIV-positive patients appear to have a normal response to open cardiac surgery. Data on the risk to the patient of progressing to AIDS and the risk to the surgical team of acquiring HIV infection are unknown. Testing is vital for answering these questions.     

Global epidemic of human T-cell lymphotrophic virus type-I (HTLV-I): an update

Infection with human T-cell lymphotrophic virus-I (HTLV-I) is now a global epidemic, affecting 10 to 20 million people. This virus has been linked to life-threatening, incurable diseases, adult T-cell leukemia/lymphoma (ATLL), and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), as well as several chronic illnesses, such as uveitis and dermatitis. The cumulative lifetime risk of developing these incurable diseases is approximately 5% in asymptomatic patients. For operating room personnel performing surgery among patients from high-risk groups, HTLV-I and its associated diseases are presenting an increasing challenge. This report describes its transmission, seroprevalence, treatment, and public health initiatives that must be instituted to prevent the spread of this retrovirus. Coinfection with HTLV-I and human immunodeficiency virus (HIV) has been shown to accelerate the progression of acquired immune deficiency syndrome (AIDS).     

Bronchoalveolar lavage cell analysis in patients with human immunodeficiency virus related diseases

The value of differential cell counts in bronchoalveolar lavage fluid in patients who were serologically positive for the human immunodeficiency virus (HIV) was studied in 30 patients with classified into four groups according to the severity of illness: (1) seven subjects with the AIDS related complex without clinical or radiological evidence of pulmonary infection; (2) eight patients with the AIDS related complex and pulmonary tuberculosis; (3) eight patients with AIDS and Pneumocystis carinii pneumonia; and (4) seven patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure. All four groups had a similar percentage of lymphocytes, significantly higher than that of a control group of 15 healthy volunteers. A significant increase in the percentage of neutrophils was observed in groups 2, 3, and 4. The lavage fluid differential cell count does not therefore appear to help in the differential diagnosis of pulmonary infections in HIV positive patients. The abnormal percentage of lymphocytes observed in some patients with the AIDS related complex without clinical evidence of pulmonary infection suggests that lung injury may exist before clinical or radiological abnormalities develop. This might be related to an immunological mechanism or might be caused by an undetected subclinical infection.     

Rapid development of subacute myelopathy in three organ transplant recipients after transmission of human T-cell lymphotropic virus type I from a single donor

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) causes a subacute myelopathy in less than 5% of chronic carriers. However, the risk of neurologic disease appears to increase in persons infected through blood transfusion. METHODS: We report three recipients of solid organ transplants who developed a subacute myelopathy within 2 years after becoming infected with HTLV-I from a single asymptomatic HTLV-I donor. Genetic studies were performed in and sequences in proviral DNA, and HTLV-I proviral load was measured by real-time quantitative polymerase chain reaction. RESULTS: HTLV-I sequences were obtained in two of these individuals, and they were almost identical and clustered within the Cosmopolitan A HTLV-I subtype, which indicates a common source. All typical changes in Tax amino acid sequence of the HTLV-I Cosmopolitan A were identified, plus two additional changes were noted. Although A has been associated with a greater risk of neurologic disease, both patients were positive for human leukocyte antigen-A*02, which is considered a protective factor. CONCLUSION: Rapid development of subacute myelopathy may occur in recipients of organ transplants from asymptomatic HTLV-I donors. A particular virulence of the virus strain, the large size of the virus inoculum, and the immunosuppressed condition after transplantation may have contributed to produce this unusual rapid development of HTLV-I associated myelopathy.     

Clinical investigations of lymphadenopathy, including lymph node biopsies, in 24 homosexual men with antibodies to the human T-cell lymphotropic virus type III (HTLV-III)

The findings of 27 lymph node biopsies performed on 24 homosexual patients with lymphadenopathy are presented. Six had acquired immune deficiency syndrome (AIDS) and 18 lymphadenopathy only, of whom one subsequently developed AIDS. All these patients had antibodies to the human T-cell lymphotropic virus type III (HTLV-III) suggesting that HTLV-III is currently the commonest cause of lymphadenopathy in homosexual men. The histopathological findings of six of seven nodes from AIDS patients showed either follicular depletion alone or follicular and paracortical lymphocyte depletion. Nodes from four patients showed Kaposi's sarcoma, three of which also showed follicular hyperplasia. In two of these patients there were no cutaneous manifestations of this condition. One lymph node from a patient with persistent generalized lymphadenopathy (PGL) showed Mycobacterium tuberculosis. Six nodes from six other patients have had features of toxoplasmosis although there was no serological or clinical evidence of recent toxoplasma infection. The remaining 11 lymph nodes from patients with PGL and one node from a patient with transient lymphadenopathy, showed reactive follicular hyperplasia only. We conclude that homosexuals with lymphadenopathy who are HTLV-III antibody positive do not need a routine node biopsy unless an alternative diagnosis is strongly suspected.     

Repair type I aortic dissection in a patient with human immunodeficiency virus infection

A 57-year-old man with human immunodeficiency virus (HIV) infection was evaluated in October 1997 with complaints of weakness of the right lower extremity. A chest computerized axial tomographic scan revealed a type I aortic dissection. He underwent surgical repair including resuspension of the aortic valve and placement of a 32-mm interposition graft between the aortic root and the transverse arch. Postoperatively he required abdominal aorta fenestration and stenting for ischemia of the left lower extremity. Follow-up magnetic resonance imaging 3(1)/(2) years postoperatively showed a normal-sized ascending and transverse aorta and the residual dissection in the descending thoracic and abdominal aorta. The thoracic and abdominal aorta diameters have remained stable. Select patients with type I aortic dissection and HIV infection are candidates for surgical repair.     

Epstein–Barr virus DNA load in tumour tissues correlates with poor differentiation status in non‐muscle invasive urothelial carcinomas

What’s known on the subject? and What does the study add? Epstein‐Barr virus (EBV) could be detected in bladder cancer. In our paper, we showed that DNA of EBV could be detected more in the high grade urothelial carcinoma. In superficial bladder cancer, although high grade tumour associated with higher EBV titers, the recurrence free survival was not compromised by high EBV DNA load.

OBJECTIVE

To detect the correlation between the clinical staging, grading and genomic Epstein–Barr virus (EBV) viral numbers in tumour tissues of urothelial carcinoma patients.

PATIENTS AND METHODS

From June 2004 to May 2008, 60 urothelial carcinoma patients (50 cases of bladder carcinoma and 10 of upper tract urothelial carcinoma (UTUC) were enrolled in the study. Eight patients who underwent transurethral resection of prostate for prostate hyperplasia and two patients receiving nephrectomy for non‐function kidney were used as normal controls. The EBV viral copy numbers in genomic DNA were evaluated using a real‐time PCR‐based study. The BamHI W region of the Namalwa cell line was constructed to the plasmid clone and was used as standard curve for absolute quantitative PCR (Q‐PCR).

RESULTS

Epstein–Barr virus DNA was detected in 56% (28/50) and 60% (6/10) of the bladder and UTUC patients, respectively. The EBV DNA could not be detected in the normal control group. By pooling the UTUC and bladder patients in stage Ta,T1, the high copy number in fixed genomic DNA amount (100 ng/20 µL) was correlated with the high grading in stage Ta,T1 urothelial carcinoma (P= 0.014). The overall grading was not statistically associated with EBV copy number (P= 0.25). Although the copy numbers between paired tumour and normal tissues were not statistically different (P= 0.169), there were more copies of EBV in the normal tissues adjacent to the tumours than in those free from urothelial carcinoma. There was no significant difference between recurrence of non‐muscle invasive bladder cancer and the presence of EBV (P > 0.05).

CONCLUSIONS

Epstein–Barr virus DNA could be detected in the genome of the urothelial carcinoma specimens. The poor differentiation status was correlated with the high load of the EBV genome in non‐muscle invasive urothelial carcinoma. However, recurrence‐free survival was not greater in EBV‐positive patients than in EBV‐negative patients.     

Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue.

BACKGROUND: DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period. METHODS: DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively. RESULTS: PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other. CONCLUSIONS: Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.