Detecção pré-natal de infecção pelo vírus T-linfotrópico humano (HTLV) 1/2 em gestantes / Prenatal detection of human T-lymphotropic virus (HTLV) 1/2 infection in pregnant women

INTRODUÇÃO: O vírus T-linfotrópico humano HTLV-1 e HTLV-2 são retrovírus com potencial oncogênico, sendo particularmente associados à gênese da leucemia de células T do adulto (ATL). Além disso, estes se relacionam a diversas doenças não-neoplásicas de natureza inflamatória, sendo a mielopatia associada ao HTLV/paraparesia espástica tropical (HAM/TSP) e uveíte pelo HTLV-1 (HU) as mais conhecidas. A infecção pelo HTLV-1/2 tem distribuição mundial, com uma estimativa de até 15 a 20 milhões de pessoas afetadas e, uma vez estabelecida, permanece por toda a vida do indivíduo e na maioria dos casos permanece assintomática, tornando estes indivíduos reservatórios virais. Cerca de 4% dos portadores de HTLV-1 desenvolverão ATL, uma malignidade de células T CD4+ altamente agressiva. Por sua vez, a incapacitante HAM, afeta 2 a 3% das pessoas infectadas. As principais formas de transmissão do HTLV-1e 2 são a relação sexual desprotegida, a transmissão vertical, a amamentação e a exposição direta a sangue ou tecidos infectados. Independentemente da região do mundo, a soroprevalência aumenta com a idade, particularmente nas mulheres, tendo em vista a facilidade da transmissão sexual

Pooling of sera for human T-cell lymphotropic virus (HTLV) screening in a time of increasing health care expenditure and limited resources.

Identifying the true prevalence of human T-cell lymphotropic virus, mostly type 1 (HTLV-1), and the number of patients with HTLV-1-associated diseases, in addition to introducing HTLV-1/2 serology during the prenatal of pregnant women and in individuals infected with other viruses that share transmission routes with HTLV-1, are actions that could help to recognize the importance of this virus by WHO and national health organizations, and to control its transmission/dissemination. As Brazil is endemic to HTLV and there is an increase in health care expenditure, but resources are limited, any strategy that could reduce the cost of HTLV screening is needed and welcomed. This study aimed to determine whether the strategy of pooling sera for HTLV antibody determination is feasible and reduces the costs. Two enzyme immunoassays (EIA Murex HTLV-I+II, Diasorin, UK, and Gold ELISA HTLV-1+2, REM Ind. Com. Ltda., SP, Brazil), and serum samples that resulted in different levels of HTLV-1/2 antibodies by EIA and of which a volume allowed assay validation were employed for analysis. The diagnostic sensitivity and specificity and Cohen's Kappa value, as well as the accuracy and precision were analyzed. After validating the five-sample pool using the EIA Murex (Cohen's Kappa = 1.0), the technique was employed for individual cost comparison in 2,625 serum samples from populations at risk of HTLV infections (HBV, HCV, and HIV-infected individuals). The results from individual and pooled samples confirmed the diagnostic sensitivity (100%) and specificity (100%) of the pooling and a cost minimization varying from 60.7% to 73.6%. In conclusion, the results of this study suggest the use of pooling sera in sero-epidemiological surveillance studies and possibly in prenatal care screening programs in Brazil.

Health economic implications of testing blood donors in South Africa for HTLV 1 & 2 infection.

BACKGROUND AND OBJECTIVES: Currently, HTLV screening is not performed in South Africa (SA). This report describes an economic assessment (budget impact and cost-effectiveness) of implementing different HTLV screening strategies. METHODS: A modified version of the Alliance of Blood Operators risk-based decision-making framework was used to assess the risk and consequences of HTLV in the blood supply in SA. We developed a deterministic model of the cost and consequences of four screening strategies: none, universal, all donors once and first time donors only assuming a transfusion-transmission (TT) efficiency of 10% and a manifestation of clinical disease of 6%. RESULTS: Unscreened blood results in 3·55 symptomatic TT-HTLV cases and a total healthcare cost of Rand (R)3 446 950 (US Dollars (USD)229 800) annually. Universal screening would cost R24 000 000 (USD1 600 000) per annum and prevent 3·54 (99·8%) symptomatic TT-HTLV cases in the first year and 0·55 (98·4%) symptomatic TT-HTLV cases in the second year at a cost per TT-HTLV prevented of R6 780 000 (USD450 000) in year one and R43 254 000 (USD2 890 000) in year two. Screening all donors once would cost R16,200,000 (USD1 080 000) or R4 600 000 (USD306 000) per symptomatic TT-HTLV infection prevented in year one. Total costs decrease to R5 100 000 (USD340 000) in year 2 but the cost per TT-HTLV prevented increases to R10 700 000 (USD713 333). CONCLUSION: This analysis contributed to the decision not to implement HTLV screening as the healthcare budget and particularly the budget for blood transfusion in SA is insufficient to provide appropriate treatment. Arguably, available resources can be more efficiently utilized in other healthcare programs.

Testing for HTLV 1 and HTLV 2 among blood donors in Western Saudi Arabia: prevalence and cost considerations.

BACKGROUND: Screening all blood donors for human T-cell lymphotropic viruses 1 and 2 (HTLV 1 and HTLV 2) is mandatory in Saudi Arabia. The aim of this study is to evaluate the results and costs associated with the current testing policy for HTLV 1 and HTLV 2 in blood donors at King Abdulaziz University Hospital (KAUH), Jeddah. STUDY DESIGNS AND METHODS: Donor-testing results from Blood Transfusion Services at KAUH were reviewed over a 10-year period, from January 2006 through December 2015. All donors were screened using chemiluminescent microparticle immunoassay. Reactive samples were then tested by Western blot for confirmation. Costs associated with testing were calculated. RESULTS: Data of 107 419 donations in the study period were reviewed. Saudi nationals constituted 51 168 donors (47·6%). Of 107 419 blood donors tested for HTLV 1 and HTLV 2 antibody, and 95 (0·088%) donors were reactive to screening tests. None of the samples found to be reactive to screening tests was positive by Western blot. The average cost of testing was US$ 171 870 per year. CONCLUSION: No donors were confirmed to have HTLV 1 and HTLV 2 in this cohort exceeding 100 000 donors. We propose changes to the policy mandating universal testing by replacing it with universal leukodepletion coupled with targeted screening to donors coming from endemic area or donors at risk. Such changes are expected to lead to a reduction of testing cost without affecting safety.

Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): Implications for blood transfusion safety.

Many countries currently perform antibody screening for HTLV-1 infection in blood donors, and this intervention is likely cost-effective in preventing HTLV-1 related diseases in high prevalence countries. However, a number of high-income countries with low prevalence of HTLV-1 infection also perform universal HTLV-1 screening and debate has arisen regarding the cost-effectiveness of these strategies. Filter-based leukoreduction is likely to substantially reduce HTLV-1 transmission by removing infected lymphocytes, but actual laboratory data on its efficacy is currently lacking. Similarly, cost-effectiveness research on HTLV-1 prevention strategies is limited by poor data on prevalence, transmission efficacy and the cost of treating HTLV1 diseases.

Human T-lymphotropic virus and transfusion safety: does one size fit all?

Human T-cell leukemia viruses (HTLV-1 and HTLV-2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV-infected donors are HTLV-1 positive, whereas in the United States a higher prevalence of HTLV-2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost-effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries.

High prevalence of human T-lymphotropic virus infection in indigenous women from the peruvian Amazon.

BACKGROUND: In an earlier study, we detected an association between human T-cell lymphotropic virus (HTLV) infection and cervical human papillomavirus (HPV) in indigenous Amazonian Peruvian women of the Shipibo-Konibo ethnic group. As both HTLV and HPV can be transmitted sexually, we now report a population-based study examining the prevalence and risk factors for HTLV-1 and HTLV-2 infection in this population. METHODS: Between July and December 2010, we conducted a comprehensive screening for HTLV among Shipibo-Konibo women 15 to 39 years of age living in two communities located in Lima and in 17 communities located within four hours by car or boat from the Amazonian city of Pucallpa in Peru. RESULTS: We screened 1,253 Shipibo-Konibo women for HTLV infection 74 (5.9%) tested positive for HTLV-1, 47 (3.8%) for HTLV-2 infection, and 4 (0.3%) had indeterminate results. In the multivariate analysis, factors associated with HTLV-1 infection included: older age (Prevalence Ratio (PR): 1.04, 95% CI 1.00-1.08), primary education or less (PR: 2.01, 95% CI: 1.25-3.24), younger or same age most recent sex partner (PR: 1.66, 95% CI: 1.00-2.74), and having a most recent sex partner who worked at a logging camp (PR: 1.73, 95% CI: 1.09-2.75). The only factor associated with HTLV-2 infection was older age (PR: 1.08, 95% CI: 1.03-1.12). CONCLUSION: HTLV infection is endemic among Shipibo-Konibo women. Two characteristics of the sexual partner (younger age and labor history) were associated with infection in women. These results suggest the need for implementation of both HTLV screening during the antenatal healthcare visits of Shipibo-Konibo women, and counseling about the risk of HTLV transmission through prolonged breastfeeding in infected women. We also recommend the implementation of prevention programs to reduce sexual transmission of these viruses.

[HTLV and "donating" milk]. / HTLV-1 et don de lait maternel.

In France, the screening for human T-cell leukemia/ lymphoma virus type 1 and 2 (HTLV-1 and HTLV-2) during the donation of human milk has been carried out from 1992 with the application of the circular DGS 24 November 1992. The screening for antibodies against these viruses is regulated and done systematically during every donation of milk. Breast feeding being the main mode of transmission of the HTLV-1, the last ministerial decree of 25 August 2010 has made the screening test compulsory for the anonymous donation and for the personalized donation (of a mother for her own child) from all women including those affected by the infection. The milk delivered by milk banks is pasteurized (62.5 °C for 30 minutes) before freezing at -18 °C, which inactivates the pathogens. This double means of prevention of the transmission of the HTLV-1 paradoxically seems disproportionate in the absence of any precautionary measure in the case of direct breast-feeding and the use of mother's raw milk. Indeed, in most neonatal intensive care units in maternity hospitals, unpasteurized milk is administered to the neonates without any systematic preliminary testing of the serological HTLV-1 status of the mother. An increased sensitization of the community of the obstetricians, midwives and neonatologists by the Association of the Milk Banks of France (ADLF) and the Société de pathologie exotique could address the issue of screening for HTLV-1 in "donated" milk and breast-feeding.

Increased all-cause and cancer mortality in HTLV-II infection.

BACKGROUND: Human T-lymphotropic virus (HTLV)-I and HTLV-II cause chronic human retroviral infections, but few studies have examined the impact of either virus on survival among otherwise healthy individuals. The authors analyzed all-cause and cancer mortality in a prospective cohort of 155 HTLV-I, 387 HTLV-II, and 799 seronegative subjects. METHODS: Vital status was ascertained using death certificates, the US Social Security Death Index or family report, and causes of death were grouped into 9 categories. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: After a median follow-up of 15.9 years, there were 105 deaths: 22 HTLV-I, 41 HTLV-II, and 42 HTLV-seronegative. Cancer was the predominant cause of death, resulting in 8 HTLV-I, 17 HTLV-II, and 15 HTLV-seronegative deaths. After adjustment for confounding, HTLV-I status was not significantly associated with increased all-cause mortality, though there was a positive trend (HR: 1.6, 95% CI: 0.8 to 3.1). HTLV-II status was strongly associated with increased all-cause (HR: 2.4, 95% CI: 1.4 to 4.4) and cancer mortality (HR: 3.8, 95% CI: 1.6 to 9.2). CONCLUSIONS: The observed associations of HTLV-II with all-cause and cancer mortality could reflect biological effects of HTLV-II infection, residual confounding by socioeconomic status or other factors, or differential access to health care and cancer screening.

Strategies for diagnosis of HTLV-I and -II.

BACKGROUND: No gold standard exists for diagnosis of HTLV infection. The aim of thus study was to compare the accuracy of a combination of two sensitive ELISAs with Western blot (WB), a line immunoassay, and PCR for diagnosis of HTLV infection. STUDY DESIGN AND METHODS: Nine hundred eighty-five specimens were tested for the presence of HTLV antibodies by HTLV-I and/or HTLV-II EIAs (Murex and Ortho), WB (Diagnostic Biotechnology), line immunoassay (INNO-LIA, Innogenetics), and/or presence of HTLV DNA by PCR. The results were compared with the probable HTLV infection status of each subject, as determined by detailed review of all available laboratory, clinical, and epidemiologic data. RESULTS: The sensitivity for diagnosis of HTLV-I infection was high for all assays evaluated, but both PCR and WB had a lower sensitivity rate (approx., 80%) for confirmation of HTLV-II. INNO-LIA detected 94 percent of the HTLV-II-positive samples. However, Murex EIA in combination with Ortho EIA was 100-percent sensitive for the detection of both HTLV-I and HTLV-II antibodies. Furthermore, the number of samples giving indeterminate results in the ELISA combination was much lower as compared with WB (2.5% vs. 50%). CONCLUSION: Based on these findings, a new, more sensitive and specific test strategy for HTLV diagnosis than the current algorithm, which includes WB, is proposed. Thereby, both the direct and indirect costs can be substantially reduced.

HLTV I/II: triagem e diagnóstico em unidades hemoterápicas e laboratórios de saúde pública

Ao final deste curso o técnico será capaz de identificar os procedimentos e as técnicas recomendadas pela CN - DST/AIDS/MS e COSAH/MS para a triagem sorológica de doadores de sangue e para o diagnóstico sorológico da infecção pelo HTLV – I/II, obedecendo a critérios técnicos e de controle de qualidade. As pessoas identificadas como soropositivas para HTLV-I/II, de acordo com os critérios de USPHS, e positivas para HTLV-II por teste adicional, indicando que estão infectadas pelo HTLV-II, deveriam ser avisadas e esclarecidas de que o HTLV-II não é o vírus da aids, que não causa aids, e que aids é causada por um vírus diferente chamado HIV. Os retrovírus pertencem à família Retroviridae e infectam principalmente animais vertebrados, podendo causar várias doenças como tumores malignos, imunodeficiência e doenças neurológicas. Pode ainda ocorrer infecção assintomática, isto é, o vírus pode estar presente sem causar nenhum problema de saúde no hospedeiro. São exemplos de retrovírus: os vírus da imunodeficiência humana (HIV-1 e HIV-2), o vírus da leucemia de bovinos (BLV), o vírus da imunodeficiência de felinos (FIV), o vírus linfotrópico humano tipo I e II (HTLV I / II – Human T Lymphotropic Virus Type I / II). Os HTLV-I/II podem ser transmitidos por meio de linfócitos infectados presentes no leite materno, durante relações sexuais, por meio de transfusões de sangue ou de hemocomponentes ou ainda por meio de agulhas de seringas compartilhadas por usuários de drogas injetáveis. Devido ao risco de transmissão parenteral pelo sangue e seus derivados, os testes para HTLV –I/II no sangue doado foram introduzidos no Japão em 1986, nos EUA em 1988 e em 1993 no Brasil. (Au)

HLTV I/II: triagem e diagnóstico em unidades hemoterápicas e laboratórios de saúde pública

Ao final deste curso o técnico será capaz de identificar os procedimentos e as técnicas recomendadas pela CN - DST/AIDS/MS e COSAH/MS para a triagem sorológica de doadores de sangue e para o diagnóstico sorológico da infecção pelo HTLV – I/II, obedecendo a critérios técnicos e de controle de qualidade. As pessoas identificadas como soropositivas para HTLV-I/II, de acordo com os critérios de USPHS, e positivas para HTLV-II por teste adicional, indicando que estão infectadas pelo HTLV-II, deveriam ser avisadas e esclarecidas de que o HTLV-II não é o vírus da aids, que não causa aids, e que aids é causada por um vírus diferente chamado HIV. Os retrovírus pertencem à família Retroviridae e infectam principalmente animais vertebrados, podendo causar várias doenças como tumores malignos, imunodeficiência e doenças neurológicas. Pode ainda ocorrer infecção assintomática, isto é, o vírus pode estar presente sem causar nenhum problema de saúde no hospedeiro. São exemplos de retrovírus: os vírus da imunodeficiência humana (HIV-1 e HIV-2), o vírus da leucemia de bovinos (BLV), o vírus da imunodeficiência de felinos (FIV), o vírus linfotrópico humano tipo I e II (HTLV I / II – Human T Lymphotropic Virus Type I / II). Os HTLV-I/II podem ser transmitidos por meio de linfócitos infectados presentes no leite materno, durante relações sexuais, por meio de transfusões de sangue ou de hemocomponentes ou ainda por meio de agulhas de seringas compartilhadas por usuários de drogas injetáveis. Devido ao risco de transmissão parenteral pelo sangue e seus derivados, os testes para HTLV –I/II no sangue doado foram introduzidos no Japão em 1986, nos EUA em 1988 e em 1993 no Brasil

[Cost-effective approach to the screening of HIV, HBV, HCV, HTLV in blood donors in France]. / Approche coût-efficacité du dépistage des virus VIH, VHB, VHC, HTLV chez les donneurs de sang en France.

In order to provide greater safety in blood transfusions, public health authorities have imposed the use of screening tests. The purpose of this paper is to estimate the cost-effectiveness ratios of the screening test used in France. Four risks were studied: HIV, HBV, HCV and HTLV. Two efficiency measures were used: cost per positive blood donation detected and cost per case of prevented infection transmission. Moreover, for HTLV alone, the efficiency was estimated by the cost per prevented pathology. Data concerning the costs were provided by the French Blood Agency; those concerning the results of the screening campaigns were provided by the official health authorities, the other data used in the calculations were drawn either from the French Blood Agency data or from a review of international literature. Results gave information about the expenditure devoted to the screening of virologic risks associated with blood transfusion in France (250 million francs per year for the four viruses studied). They stressed the differences in screening efficiency according to the test studied (the cost by prevented seroconversion varied from 31,795 francs for HBV, 72,180 francs for HCV, 676,596 francs for HIV to 6,137,346 francs for HTLV screening test in the base case) and especially the very low efficiency of the systematic screening of the HTLV virus (from 34 to 307 million francs per prevented leukemia).

AIDS: a new frontier in epidemiology.

HIV infection has become a pandemic. As such, it is the most recent inclusion to epidemiology studies. A review of past epidemics allows a different perspective on the current status of scientific knowledge regarding AIDS. HIV is a retrovirus, one of three groups identified. The other two groups are commonly referred to as HTLV I and II and do not cause AIDS. Two forms of HIV (HIV-1 and HIV-2) make up the third group, HTLV-III. As with any research, various theories are formed, tested, and often rejected. Some theories receive excessive publicity before testing, resulting in incorrect public beliefs that become myths. The cumulative number of cases of AIDS in the United States is 361,509, as of December 31, 1993. Healthcare workers experience multiple opportunities for exposure to the infection in the course of their duties. Based on data from the 1993 BMET/CE survey, several biohazard issues, as well as preventive measures, are discussed.

Seroepidemiology of HTLV-I/II in universal screening of blood donations in France.

OBJECTIVE: To evaluate the serological and epidemiological characteristics of HTLV-I/II-positive blood donors in continental France during the first 6 months of universal screening of blood donations (n = 1,816,927). METHOD: A collaborative investigation of all confirmed anti-HTLV-I/II-positive samples reported by blood transfusion centres was performed. Seventy-three out of 77 reported samples were retested at two reference laboratories. Epidemiological data on risk factors were compiled. RESULTS: Of the 73 retested samples, 66 were confirmed to be HTLV-I-positive and one to be HTLV-II-positive; six samples were designated false-positive, mainly because of non-specific reactivity to recombinant gp21 in Western blot. The overall prevalence of HTLV-I/II in continental France is 0.039 per thousand. The main risk factor identified for HTLV-I infection was directly (origin) or indirectly (heterosexual contact) linked to endemicity in the Caribbean. The cost per case of avoided contamination in the 6-month period of this study was 1.36 million French francs. CONCLUSIONS: Sixty-two per cent of HTLV-I/II-infected blood donations would not have been discarded through the previous targeted HTLV screening or through other mandatory tests, including anti-hepatitis B core. To avoid false-positive results, we propose a new algorithm of diagnosis.