[Review of current issues of diagnosis and prevention of blood-borne nosocomial viral infections.]

Provision of infection security in transplantology and transfusiology is a challenging and significant problem that depends on the quality of medical donor selection and laboratory diagnosis of the blood collected. At present, a large number of blood-borne viruses are known; nevertheless, in Russia, the list of viral agents to be tested during the examination by the blood service boils down to three ones: HIV, hepatitis C and hepatitis B viruses. The review article demonstrates the need for implementation of additional laboratory tests for the agents of the priority healthcare-associated blood-borne infections (HAI) using a risk-based approach, i.e., on specified sites and in high risk groups. It presents a methodology for determination of a quantitative blood-induced infection residual risk (BIRR) index to be used while evaluating the efficiency of viral security provision in the blood service.

Dia Mundial do HTLV - 10 de Novembro / World HTLV Day - November 10th

O dia 10 de novembro foi instituído como Dia Mundial do HTLV pela Associação Internacional de Retrovirologia (IRVA – International Retrovirology Association). O objetivo deste ato foi de informar e mobilizar a sociedade e o poder público para o significado da infecção ocasionada pelo primeiro retrovírus humano descrito, o vírus linfotrópico de células T humanas do tipo 1 (HTLV1), as doenças a ele associadas, seu impacto na saúde pública e os meios de contê-lo. Como o Brasil é o país da América Latina com o maior número absoluto de casos desta infecção viral, foi elaborado o presente texto que traz as informações relevantes sobre o HTLV-1 para a comunidade científica.

The November 10th was instituted as the World HTLV Day by the International Retrovirology Association (IRVA), aiming informing and mobilizing the society and the public authorities on the significance of this infection caused by the first known human retrovirus, the human T-cell lymphotropic virus type 1 (HTLV-1). The associated diseases, the impact in the public health, and the means to block its transmission were reviewed. Considering that Brazil, the country in the Latin America, has been presenting the highest number of HTLV-1-infected individuals, this text was written for giving the relevant information concerning the HTLV-1 infection to the scientific community.

Bushmeat Hunting and Zoonotic Transmission of Simian T-Lymphotropic Virus 1 in Tropical West and Central Africa.

Simian T-lymphotropic virus 1 (STLV-1) enters human populations through contact with nonhuman primate (NHP) bushmeat. We tested whether differences in the extent of contact with STLV-1-infected NHP bushmeat foster regional differences in prevalence of human T-lymphotropic virus 1 (HTLV-1). Using serological and PCR assays, we screened humans and NHPs at two Sub-Saharan African sites where subsistence hunting was expected to be less (Taï region, Côte d'Ivoire [CIV]) or more (Bandundu region, Democratic Republic of the Congo [DRC]) developed. Only 0.7% of human participants were infected with HTLV-1 in CIV (n = 574), and 1.3% of humans were infected in DRC (n = 302). Two of the Ivorian human virus sequences were closely related to simian counterparts, indicating ongoing zoonotic transmission. Multivariate analysis of human demographic parameters and behavior confirmed that participants from CIV were less often exposed to NHPs than participants from DRC through direct contact, e.g., butchering. At the same time, numbers of STLV-1-infected NHPs were higher in CIV (39%; n = 111) than in DRC (23%; n = 39). We conclude that similar ultimate risks of zoonotic STLV-1 transmission-defined as the product of prevalence in local NHP and human rates of contact to fresh NHP carcasses-contribute to the observed comparable rates of HTLV-1 infection in humans in CIV and DRC. We found that young adult men and mature women are most likely exposed to NHPs at both sites. In view of the continued difficulties in controlling zoonotic disease outbreaks, the identification of such groups at high risk of NHP exposure may guide future prevention efforts.IMPORTANCE Multiple studies report a high risk for zoonotic transmission of blood-borne pathogens like retroviruses through contact with NHPs, and this risk seems to be particularly high in tropical Africa. Here, we reveal high levels of exposure to NHP bushmeat in two regions of Western and Central tropical Africa. We provide evidence for continued zoonotic origin of HTLV-1 in humans at CIV, and we found that young men and mature women represent risk groups for zoonotic transmission of pathogens from NHPs. Identifying such risk groups can contribute to mitigation of not only zoonotic STLV-1 transmission but also transmission of any blood-borne pathogen onto humans in Sub-Saharan Africa.

[Relevance of safety measures to avoid HTLV transmission by transfusion in 2014]. / Pertinence des mesures sécuritaires transfusionnelles vis-à-vis du HTLV en 2014.

In high-income countries, the safety of blood transfusion related to viruses has reached a very high level, especially thanks to the implementation of multiple measures aimed at reducing the transfusion risk. The cost-effectiveness of these preventive measures is frequently discussed due to global financial resources, which are more and more limited. Hence, the revision of safety strategies is a key issue, especially when these strategies are redundant, as those implemented to avoid Human T-cell Lymphotropic Virus (HTLV) transmission, which are based on both antibodies screening and leucoreduction of blood products. The residual risk of the transmission of HTLV by transfusion has been recently estimated at 1 in 20 million donations (2010-2012) in France (excluding overseas territories). This estimation did not take into account the leucoreduction, which appears to be a very efficient preventive measure as the virus is strictly intra-cellular. To help decision-making, we have evaluated some parameters related to HTLV blood transmission. Firstly, the probability that an incident occurring during the leucoreduction process affects a HTLV-positive blood donation has been estimated at 1 in 178 million. Estimation of clinical consequences of HTLV-positive transfusions would affect 1 to 2 transfused-patients without leucoreduction, and one recipient every 192 years in case of 10% failures of the filtration method. Obviously, despite a risk, which appears to be controlled, HTLV screening will be disputed as soon as the efficiency of leucoreduction to totally prevent virus blood transmission will be proven and when pathogen inactivation methods are generalized to all blood cellular products.

Vaccination against δ-retroviruses: the bovine leukemia virus paradigm.

Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy.

HTLV em gestantes de dois municípios da região sul da Bahia e avaliação da transmissão materno-infantil / HTLV in pregnant women in two cities of southern Bahia and evaluation of maternal-infant transmission

A prevalência de HTLV- 1 no Brasil é diversa, dependendo tanto da região geográfica quanto do grupo analisado. Um estudo populacional realizado em Salvador detectou prevalência de 1,76%, além de maior prevalência em mulheres e associação com menores níveis de escolaridade e renda. Como a via mais frequente de transmissão vertical do HTLV-1 é a amamentação e considerando a maior prevalência nas mulheres, é muito importante a realização de exames de triagem para HTLV-1 como parte do prénatal. Até o momento, não existem estudos publicados sobre a soroprevalência do HTLV-1 em gestantes na região sul da Bahia. No presente estudo, as gestantes foram selecionadas em dois centros de referência regionais de saúde do sul da Bahia. Um total de 2.766 gestantes atendidas na sala de pré-parto entre novembro de 2008 e maio de 2010 foram analisados. Um questionário foi aplicado, e todas as amostras de plasma reagentes foram testadas em duplicata e confirmadas por Western blot e PCR. Além disso, mulheres positivas foram contactadas e visitadas. Os membros da família que estavam presentes durante a visita foram convidados a serem testados para o HTLV...

The prevalence of HTLV-1 in Brazil is diverse, depending on both the geographic region and the group analyzed. A study conducted on general population revealed that the prevalence in Salvador was 1.76%. Besides, it was also found that the prevalence was higher amongst women and that the virus was associated with lower education and lower income. As the most frequent pathway of vertical transmission of HTLV-1 is breast-feeding, and considering the higher prevalence in women, it is very important to perform screening examinations for anti-HTLV-1...

Human T-lymphotropic virus lookback in NHS Blood and Transplant (England) reveals the efficacy of leukoreduction.

BACKGROUND: Leukoreduction of blood components was introduced in the United Kingdom during 1998. Human T-lymphotropic virus (HTLV) screening of blood donations was introduced in 2002. NHS Blood and Transplant conducted an HTLV lookback on blood components issued before 2002. A proportion of included components were nonleukoreduced, although the majority were subject to white blood cell reduction measures. STUDY DESIGN AND METHODS: A standard lookback was conducted on untested cellular blood components from donors later confirmed to be HTLV positive, for the 4 to 5 years before 2002, and on the last tested negative donation from donors who had seroconverted. RESULTS: A total of 437 red blood cell and platelet components were included and an outcome was reported for 84% of these. Just over half of identified recipients were dead at the time of lookback; blood samples for testing were obtained from 77% of identified living recipients. HTLV infection was confirmed in seven recipients, but one was discounted as not transfusion transmitted. CONCLUSION: Although numbers are small, our results provide evidence of the efficacy of leukoreduction in reducing the likelihood of HTLV transmission through transfusion of cellular blood components. The HTLV-positive rate in recipients of leukoreduced components was 3.7%, a reduction of 93% compared with nonleukoreduced components. Importantly, the one infected recipient of a leukoreduced component had existing risk factors for HTLV infection. HTLV lookback was much less efficient in identifying infected recipients than was hepatitis virus C lookback.

Cost-effectiveness of additional blood screening tests in the Netherlands.

BACKGROUND: During the past decade, blood screening tests such as triplex nucleic acid amplification testing (NAT) and human T-cell lymphotropic virus type I or I (HTLV-I/II) antibody testing were added to existing serologic testing for hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV). In some low-prevalence regions these additional tests yielded disputable benefits that can be valuated by cost-effectiveness analyses (CEAs). CEAs are used to support decision making on implementation of medical technology. We present CEAs of selected additional screening tests that are not uniformly implemented in the EU. STUDY DESIGN AND METHODS: Cost-effectiveness was analyzed of: 1) HBV, HCV, and HIV triplex NAT in addition to serologic testing; 2) HTLV-I/II antibody test for all donors, for first-time donors only, and for pediatric recipients only; and 3) hepatitis A virus (HAV) for all donations. Disease progression of the studied viral infections was described in five Markov models. RESULTS: In the Netherlands, the incremental cost-effectiveness ratio (ICER) of triplex NAT is €5.20 million per quality-adjusted life-year (QALY) for testing minipools of six donation samples and €4.65 million/QALY for individual donation testing. The ICER for anti-HTLV-I/II is €45.2 million/QALY if testing all donations, €2.23 million/QALY if testing new donors only, and €27.0 million/QALY if testing blood products for pediatric patients only. The ICER of HAV NAT is €18.6 million/QALY. CONCLUSION: The resulting ICERs are very high, especially when compared to other health care interventions. Nevertheless, these screening tests are implemented in the Netherlands and elsewhere. Policy makers should reflect more explicit on the acceptability of costs and effects whenever additional blood screening tests are implemented.

Incidence of lymphoma in a captive-bred colony of hamadryas baboons (Papio hamadryas).

OBJECTIVE: To assess the incidence of lymphoma and wasting-related deaths in the National Baboon Colony of Australia and relate it to the presence of simian T-cell lymphotrophic virus 1 (STLV-1) infection. DESIGN AND PROCEDURE: The records of all animals that had died since establishment of the National Baboon Colony in Australia were reviewed retrospectively. The clinical signs and histopathological findings were recorded and assessed to determine the involvement of lymphoma in the deaths. The presence of STLV-1 was recorded if known and correlated with the STLV-1 status of the colony. RESULTS: Of the deaths from disease or illness, 53% were diagnosed as or suspected to be lymphoma, occurring in mature animals with no sex predisposition. The most common presentation was rapidly occurring generalised lymphadenomegaly. CONCLUSIONS: This study has described a relatively high prevalence of lymphoma in a colony of captive-bred baboons, and it is evident that STLV-1 may play a role in the disease. Management practices in baboon colonies need to take into account the possible presence of STLV-1 and aim to reduce the transmission of the virus by preventing sexual contact between positive and negative animals. Lymphoma needs to be considered as one of the more common causes of wasting and death.

Intestinal Shiga toxin-producing Escherichia coli bacteria mitigate bovine leukemia virus infection in experimentally infected sheep.

Ruminants often carry gastrointestinal Shiga toxin (Stx)-producing Escherichia coli (STEC). Stxs belong to a large family of ribosome-inactivating proteins (RIPs), found in many plants and some bacteria. Plant RIPs, secreted into extracellular spaces, limit the spread of viruses through plant tissues by penetrating and killing virally infected cells. Previously, we showed Stx activity against bovine leukemia virus (BLV)-infected cells in vitro and hypothesized that STEC bacteria have antiviral activity in ruminant hosts. Here, we investigated the impact of STEC on the initial phases of BLV infection in sheep. Sheep were treated with biweekly oral doses of E. coli O157:H7 (an STEC) or an isogenic stx mutant strain. A different group of sheep were similarly treated with five naturally occurring ovine STEC isolates or stx-negative E. coli. Intestinal STEC bacteria were enumerated and identified by standard fecal culture and DNA hybridization. Oral STEC treatment did not always result in carriage of STEC, although many animals consistently presented with >10(4) CFU/g feces. BLV viremia was assessed by spontaneous lymphocyte proliferation (SLP) in cultures of blood mononuclear cells and by syncytium formation in cocultures of the same with F-81 indicator cells. SLP was lower (P < 0.05) and syncytia were fewer (P < 0.05) in STEC-treated sheep than in untreated sheep. Both lower SLP and fewer syncytia positively correlated with fecal STEC numbers. Average weight gain post-BLV challenge was higher in STEC-treated sheep than in untreated sheep (P < 0.05). These results support the hypothesis that in ruminants, intestinal STEC bacteria have antiviral activity and mitigate BLV-induced disease.

HTLV in the Americas: challenges and perspectives.

The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.

HTLV in the Americas: challenges and perspectives

La primera descripción del virus de la leucemia humana de células T tipo 1 (VLHT-1) se hizo en 1980, y al poco tiempo, en 1982, se descubrió el VLHT-2. Desde entonces las características principales de estos virus, a los que a menudo se les llama VLHT-1/2, se han estudiado exhaustivamente. Centroamérica, América del Sur y el Caribe son áreas con una alta prevalencia de VLHT-1 y VLHT-2 donde hay conglomerados de personas infectadas. Las principales vías de transmisión han sido el contacto sexual, la sangre y sus derivados, y la de madre a hijo por la leche materna. El VLHT-1 se asocia con la leucemia o el linfoma de células T maduras (LTM), la mielopatía o paraparesia tropical espástica ligada al VLHT (M/PTE), y la uveítis ligada al VLHT, así como con la dermatitis infecciosa de la infancia. Se necesita más información acerca del posible papel que desempeña el VLHT en la aparición de enfermedades reumáticas, psiquiátricas e infecciosas. En vista de que no se dispone de ninguna cura para la LTM ni la M/PTE, como tampoco de ninguna vacuna para prevenir la transmisión del VLHT-1 y VLHT-2, estas enfermedades acarrean enormes costos sociales y económicos para las personas infectadas, sus parientes y los sistemas de salud. Por este motivo, las intervenciones sanitarias orientadas a asesorar e instruir a personas y poblaciones en alto riesgo revisten una importancia crítica. En el continente americano esto cobra aun más importancia en zonas de alta prevalencia.

The spectrum of safety: a review of the safety of current hemophilia products.

The safety of whole blood and blood products has been ensured by several different mechanisms introduced over the years, each of which reduces the risk of blood-borne infectious diseases. An exhaustive donor selection and screening process aims to exclude individuals at risk for infectious disease, and numerous screening tests are used to detect infectious pathogens in collected blood. During processing, blood is further subjected to various removal or inactivation procedures directed against specific pathogens, as well as additional screening with nucleic acid testing or polymerase chain reaction (PCR)-based assays. Despite these measures, sporadic cases of infection continue to occur, caused by both known pathogens and newly emergent ones. Other challenges remain to be met, including the detection of infectious blood donated during the seronegative window period of infection and the rapid identification of and screening for emerging infectious diseases.

Protective effects of vaccination with bovine leukemia virus (BLV) Tax DNA against BLV infection in sheep.

A DNA vaccination trial was performed on sheep to determine whether vaccination with bovine leukemia virus (BLV) transactivator Tax DNA is effective against BLV infection. Immunization was carried out with cationic liposomes containing the Tax-expressing plasmid DNA and subsequently all sheep were challenged with BLV. BLV titers in peripheral blood mononuclear cell (PBMC) determined by syncytium formation assay and BLV provirus load detected by genomic PCR analysis showed higher levels of virus titers in control sheep than those in Tax-vaccinated sheep. Higher levels of IFN-gamma mRNA expression have been demonstrated in vaccinated sheep after the challenge. These results suggested that Th1 type immune response induced by Tax DNA vaccine inhibited BLV propagation in vaccinated sheep at the early phase of infection.

Towards the prevention of transfusion-transmitted infectious diseases.

Transfusion-transmission of viral infections, such as HIV and hepatitis C virus, were once the scourge of blood transfusion. However, due to remarkable progress over the last 30 years, tests for viral proteins, antibody responses and more recently, viral nucleic acids, have virtually eliminated these risks. This review summarizes these advances in an historical context, describes new methodologies on the horizon, and discusses residual infectious risks associated with blood transfusion.