The Prevalence of Human T-Lymphotropic Virus Infection among Blood Donors in Southeast China, 2004-2013

Background

The human T-lymphotropic virus type 1 (HTLV-1) which is associated with the diseases of adult T-cell leukemia/lymphoma, HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP) and HTLV-associated uveitis, can cause transfusion-transmitted infections. Although HTLV screening of blood donors was already routinely performed in developed countries, little is know about the HTLV prevalence among blood donors in developing countries which do not perform HTLV screening, such as China.

Objectives &Aims

To systematically characterize the prevalence of HTLV infection among bloods in southeast China.

Methods

A 10-year survey for HTLV prevalence in blood donors was performed in Xiamen, southeast China, during 2004-2013. The HTLV-1/2 of blood donations were screened by enzyme-linked immunosorbent assay, following with confirmation by western blot assay and 9nucleic acid testing. The HTLV-1 prevalences in donors from different cities were calculated. Viral sequences derived from identified HTLV-positive cases were sequenced and analyzed.

Results

Among 253,855 blood donors, 43 were confirmed to be seropositive for HTLV-1 (16.9 per 100,000 95% CI: 12.3-22.8) and none HTLV-2 infection was found. The HTLV-1 prevalence varied significantly in donors from different cities. Donors from cities in Fujian province (24.3 per 100,000, 95%CI: 17.4-33.1) had a significantly higher (p=0.001) HTLV-1 seroprevalence than those who were born in non-Fujian cities (3.4 per 100,000, 95%CI: 0.7-9.8). Among nine cities in Fujian province, the highest prevalence was found in blood donors from Ningde (171.3 per 100,000, 95%CI: 91.3-292.8) which is a coastal city in the northeast of Fujian. Molecular characterization of viral sequences from 27 HTLV-1 carriers revealed 25 were Transcontinental subtype of genotype A and 2 were Japanese subtype of genotype A. Interestingly, 12 of 25 Transcontinental subtype sequences harbored a characteristic L55P mutation in viral gp46 protein, which was only presented in the Transcontinental subtype sequences from Japan and Taiwan but not in that from other countries.

Conclusions

Although China is considered to be a non-endemic region for HTLV, the HTLV-1 prevalence in blood donors is significantly higher in Fujian province, southeast China. A higher prevalence of HTLV-1 in the Fujian may be attributed to endemic foci in the city of Ningde.     

Molecular characterization of human T-cell lymphotropic virus coinfecting human immunodeficiency virus 1 infected patients in the Amazon region of Brazil

The present work evaluated the epidemiology of human immunodeficiency virus 1/human T-cell lymphotropic virus (HIV-1/HTLV) coinfection in patients living in Belém (state of Pará) and Macapá (state of Amapá), two cities located in the Amazon region of Brazil. A total of 169 blood samples were collected. The sera were tested by enzyme-linked immunosorbent assay to determine the presence of antibodies anti-HTLV-1/2. Confirmation of infection and discrimination of HTLV types and subtypes was performed using a nested polymerase chain reaction targeting the pX and 5' LTR regions, followed by restriction fragment length polymorphism and sequencing analysis. The presence of anti-HTLV1/2 was detected in six patients from Belém. The amplification of the pX region followed by RFLP analysis, demonstrated the presence of HTLV-1 and HTLV-2 infections among two and four patients, respectively. Sequencing HTLV-1 5' LTR indicated that the virus is a member of the Cosmopolitan Group, Transcontinental subgroup. HTLV-2 strains isolated revealed a molecular profile of subtype HTLV-2c. These results are a reflex of the epidemiological features of HIV-1/HTLV-1/2 coinfection in the North region of Brazil, which is distinct from other Brazilian regions, as reported by previous studies.     

Development and evaluation of human T‐cell leukemia virus‐1 and ‐2 multiplex quantitative PCR

The diagnosis of human T ‐cell leukemia virus type 1 (HTLV‐1) infection in Japan is usually performed by serological testing, but the high rate of indeterminate results from western blotting makes it difficult to assess the infection accurately. Nucleic acid tests for HTLV‐1 and/or HTLV‐2 are used to confirm infection with HTLV‐1 and/or HTLV‐2 and are also used for the follow‐up of HTLV‐1 related diseases. To prepare a highly sensitive method that can discern infection with HTLV‐1 and HTLV‐2, a multiplex quantitative polymerase chain reaction (qPCR) by large‐scale primer screening was developed. Sensitivity and specificity were evaluated by serial dilution of cell lines and by testing with known clinical samples. The resulting multiplex qPCR can detect about four copies of HTLV‐1 provirus per 10⁵ cells. Moreover, HTLV‐1 provirus could be detected in 97.2% (205 of 211) of HTLV‐1 seropositive clinical samples. These sensitivities were sufficiently high compared with the methods reported previously. Also, all the HTLV‐2 seropositive clinical samples tested were found to be positive by this method (three of three). In conclusion, this method can successfully and simultaneously detect both types of HTLV‐1 and HTLV‐2 provirus with extremely high sensitivity.     

Prevalence and evolutionary analyses of human T-cell lymphotropic virus in Guangdong province,China: Transcontinental and Japanese subtype lineages dominate the prevalence

To systematically characterize the prevalence and evolution of human T-cell lymphotropic virus (HTLV) infection among voluntary blood donors (BDs) in Guangdong province, China. A three-year survey for HTLV epidemiology among BDs was performed in Guangdong during 2016–2018. Anti-HTLV-1/2 was screened by ELISA and ECLIA, and subsequently confirmed by western blot (WB) and nucleic acid testing (NAT). The prevalence of HTLV in donors from different cities was calculated. The identified HTLV-positive cases were phylogenetically genotyped and analyzed in a Bayesian phylogenetic framework. Among 3,262,271 BDs, 59 were confirmed positive for HTLV-1 (1.81 per 100,000) and no HTLV-2 infection was found. The prevalence of HTLV-1 varied significantly among 21 cities in Guangdong province, China. The highest prevalence was found in donors from Shanwei (13.94 per 100,000), which is a coastal city in eastern Guangdong. Viral genomic sequences genotyped from 55 HTLV-1 carriers showed that 39 were transcontinental subtype and 16 were Japanese subtype. Specially, 13 out of 39 transcontinental subtype sequences were characterized with L55P mutation and 21 out of 55 sequences were characterized with L19F mutation in viral gp46 protein. The L55P mutation seemed be specific to eastern Asia since it only presented in the sequences from Japan, mainland China, and Taiwan. Phylogenetic analysis of gp46 gene shows that HTLV-1a may have been introduced to Guangdong through four different introduction events and formed major transmission clusters: clades I(13,602 years ago), II(16, 010 years ago), III(15,639 years ago) and IV(16,517 years ago). In general, Guangdong is considered to be a low-prevalence region for HTLV-1 infection, but the prevalence is significantly higher in Shanwei city. Transcontinental and Japanese subtype lineages dominate the prevalence in Guangdong. In terms of blood safety, HTLV antibody screening for first-time blood donors can effectively reduce the risk of HTLV transmission.     

Neutralizing human monoclonal antibodies to conformational epitopes of human T-cell lymphotropic virus type 1 and 2 gp46.

Ten human monoclonal antibodies derived from peripheral B cells of a patient with human T-cell lymphotropic virus (HTLV)-associated myelopathy are described. One monoclonal antibody recognized a linear epitope within the carboxy-terminal 43 amino acids of HTLV gp21, and two monoclonal antibodies recognized linear epitopes within HTLV type 1 (HTLV-1) gp46. The remaining seven monoclonal antibodies recognized denaturation-sensitive epitopes within HTLV-1 gp46 that were expressed on the surfaces of infected cells. Two of these antibodies also bound to viable HTLV-2 infected cells and immunoprecipitated HTLV-2 gp46. Virus neutralization was determined by syncytium inhibition assays. Eight monoclonal antibodies, including all seven that recognized denaturation-sensitive epitopes within HTLV-1 gp46, possessed significant virus neutralization activity. By competitive inhibition analysis it was determined that these antibodies recognized at least four distinct conformational epitopes within HTLV-1 gp46. These findings indicate the importance of conformational epitopes within HTLV-1 gp46 in mediating a neutralizing antibody response to HTLV infection.     

Hepatitis C virus infection from blood and blood products

Abstract: The addition of second-generation HCV epitopes in antibody detection assays has increased the sensitivity and specificity of blood donor testing, to prevent post-transfusion hepatitis non-A, non-B (PTH-NANB), later characterized as Hepatitis C. However, it is not clear whether all HCV infectious donors are detected by second generation anti-HCV testing. Prospective studies on PTH-NANB were left with some unresolved cases. The use of second-generation anti-HCV assays in blood banks presented a problem with a relatively large number of indeterminate reactivities in supplemental assays such as RIBA-2. These indeterminate reactivities may be solved by the use of polymerase chain reaction (PCR). PCR is more and more used as an extra confirmatory assay to resolve RIBA indeterminate results on blood donors. However, a European study on the proficiency of HCV PCR in different countries revealed that only a minority of the reference laboratories perform this test faultness. Lately, third generation RIBA was developed, which was originally designed to resolve RIBA-2 indeterminate cases. RIBA-3 was shown to be more sensitive and specific in early HCV infection and blood donors than RIBA-2. Third generation anti-HCV testing will become standard practice. Some questions, however, remain unanswered. Do we miss any rare HCV infectious donors, of other genotypes, with third-generation assays, based only on the type 1 sequence of HCV? Can we improve HCV detection in the early phase of infection? What is the role of sporadic HCV transmission? How can we standardize HCV nucleic acid detection methods?     

Genetic characterization of human T-cell lymphotropic virus type 1 in Mozambique: transcontinental lineages drive the HTLV-1 endemic

Background

Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been estimated that 10–20 million people are infected worldwide, but no successful treatment is available. Recently, the epidemiology of this virus was addressed in blood donors from Maputo, showing rates from 0.9 to 1.2%. However, the origin and impact of HTLV endemic in this population is unknown.

Objective

To assess the HTLV-1 molecular epidemiology in Mozambique and to investigate their relationship with HTLV-1 lineages circulating worldwide.

Methods

Blood donors and HIV patients were screened for HTLV antibodies by using enzyme immunoassay, followed by Western Blot. PCR and sequencing of HTLV-1 LTR region were applied and genetic HTLV-1 subtypes were assigned by the neighbor-joining method. The mean genetic distance of Mozambican HTLV-1 lineages among the genetic clusters were determined. Human mitochondrial (mt) DNA analysis was performed and individuals classified in mtDNA haplogroups.

Results

LTR HTLV-1 analysis demonstrated that all isolates belong to the Transcontinental subgroup of the Cosmopolitan subtype. Mozambican HTLV-1 sequences had a high inter-strain genetic distance, reflecting in three major clusters. One cluster is associated with the South Africa sequences, one is related with Middle East and India strains and the third is a specific Mozambican cluster. Interestingly, 83.3% of HIV/HTLV-1 co-infection was observed in the Mozambican cluster. The human mtDNA haplotypes revealed that all belong to the African macrohaplogroup L with frequencies representatives of the country.

Conclusions

The Mozambican HTLV-1 genetic diversity detected in this study reveals that although the strains belong to the most prevalent and worldwide distributed Transcontinental subgroup of the Cosmopolitan subtype, there is a high HTLV diversity that could be correlated with at least 3 different HTLV-1 introductions in the country. The significant rate of HTLV-1a/HIV-1C co-infection, particularly in the Mozambican cluster, has important implications for the controls programs of both viruses.     

Prevalence and genetic characterisation of HTLV-1 and 2 dual infections in patients with pulmonary tuberculosis in Central-West Brazil

Human T-cell lymphotropic virus (HTLV) may impact the clinical course of tuberculosis (TB). Both infections are highly endemic in Brazil. The aim of this study was to assess the prevalence of HTLV-1/2 in TB patients in Central-West Brazil and to perform a genetic characterisation of the respective isolates. Of the 402 patients, six (1.49%) were positive for anti-HTLV and five (1.24%; 95% confidence interval: 0.46-3.05) were infected with HTLV-1/2. Genetic characterisation demonstrated that the four HTLV-1 isolates belonged to the Transcontinental subgroup A of the Cosmopolitan subtype a and that the HTLV-2 isolate belonged to subtype a (HTLV-2a/c). The prevalence of HTLV infection observed in this study is higher than that observed in local blood donors and the HTLV-1 and 2 subtypes identified are consistent with those circulating in Brazil.     

mPSQed: a software for the design of multiplex pyrosequencing assays

Molecular-based diagnostic assays are the gold standard for infectious diseases today, since they allow a rapid and sensitive identification and typing of various pathogens. While PCR can be designed to be specific for a certain pathogen, a subsequent sequence analysis is frequently required for confirmation or typing. The design of appropriate PCR-based assays is a complex task, especially when conserved discriminating polymorphisms are rare or if the number of types which need to be differentiated is high. One extremely useful but underused method for this purpose is the multiplex pyrosequencing technique. Unfortunately there is no software available to aid researchers in designing multiplex pyrosequencing assays. Here, we present mPSQed (Multiplex PyroSeQuencing EDitor), a program targeted at closing this gap. We also present the design of an exemplarily theoretical assay for the differentiation of human adenovirus types A-F using two pyrosequencing primers on two distinct PCR products, designed quickly and easily using our software.     

中国HTLV-Ⅰ env基因的克隆及Ⅰ＋Ⅱ型嵌合基因的原核表达与抗原活性检测

为尽快研制出国产HTLV抗体诊断试剂,首先从福建HTLV流行区1名HTLV感染者外周血细胞中克隆出HTLV-Ⅰ的全长膜基因（env）,继而结合文献报道、PSA1软件的新疏水性分析和EPI软件的B细胞表位分析数据,选择了gp46中段开始延伸至gp21N端212个氨基酸（aa185-aa396)的基因,并在3‘端通过（GlySer)2与人工合成的HTLV-Ⅱ型的型特异性表位区基因嵌合,插入原核表达载体pRSET,在E.coli中得到了高效表达目的蛋白产量约占菌体总蛋白的30％。通过Triton-X100洗涤,低湿度尿素逐步变性处理,8mol/L尿素溶解后纯度在75％左右,经电泳洗脱纯化,最终纯度可达95%短期,纯蛋白得率约为40％。经Western blottiong检测,该蛋白对4份HTLV-Ⅰ型和2份HTLV-Ⅱ型均有较强反应,而对4份阴性,血清无反应,从而可能用于研究HTLV抗体诊断试剂盒。     

The Gammaretroviral p12 protein has multiple domains that function during the early stages of replication

Background

Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression.

Results

We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway.

Conclusions

This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection.     

TM domain swapping of murine leukemia virus and human T-cell leukemia virus envelopes confers different infectious abilities despite similar incorporation into virions.

We investigated the influence of transmembrane protein (TM) domains on incorporation of retroviral envelopes into virions and on infectivity. We introduced complete, truncated, or chimeric Friend murine leukemia virus (F-MuLV) and human T-cell leukemia virus type 1 (HTLV-1) envelopes into an MuLV particle-producing complementation cell line. As shown previously for HTLV-1 envelopes containing extracellular domains of F-MuLV TM (C. Denesvre, P. Sonigo, A. Corbin, H. Ellerbrok, and M. Sitbon, J. Virol. 69:4149-4157, 1995), reverse chimeric F-MuLV envelopes containing the extracellular domain of HTLV-1 TM were not processed. In contrast, a chimeric MuLV envelope containing the entire HTLV membrane-spanning and cytoplasmic domains (FHTMi) was efficiently processed, fusogenic as tested in a cell-to-cell assay, and efficiently incorporated into MuLV particles. However, these MuLV particles bearing FHTMi envelope proteins could not infect mouse or rat cells which are susceptible to wild-type F-MuLV. Therefore, envelopes which are readily fusogenic in cell-to-cell assays and also efficiently incorporated into virions may not necessarily confer virus-to-cell fusogenicity. HTLV envelopes, whether parental, chimeric (containing the MuLV cytoplasmic tail) or with a truncated cytoplasmic domain, were incorporated into MuLV particles with equal efficiencies, indicating that the cytoplasmic tails of these envelopes did not determine their incorporation into virions. In contrast to FHTMi envelope, HTLV-1 envelopes with F-MuLV membrane-spanning and cytoplasmic domains, as well as wild-type HTLV-1 envelopes, conferred virion infectivity. These results help to define requirements for envelope incorporation into retroviral particles and their cell-free infectivity.     

Serodiagnosis of Lyme borreliosis with bead based immunoassays using multiplex technology

The serological diagnosis of Lyme borreliosis is accomplished by the detection of IgG and IgM antibodies specific for relevant antigens of the spirochetal pathogen Borrelia burgdorferi. Instead of the usual enzyme immune assay for screening and the Western blot technique for confirmation, bead based multiplex assays with multiple simultaneously performed distinct reactions can provide quick, automatically derived and reliable results in a single run by flow cytometer technology. The broad analytical dynamic range of assay signals and the high sensitivity and specificity of the multiplex formats allow even for a reliable use in CSF based analyses for antibody specificity index in supposed neuroborreliosis. Fluorescence intensity of the bead based reactions can be transformed into quantified values as U/ml, either for each single antigen or summed up for a group of relevant key antigens. Additionally or alternatively distinct reactions of single bead populations can be transformed to Western blot band equivalents. Internal and external quality controls with the multiplex systems show characteristic data equivalent to the conventional assay formats, so that the advantages of the multiplex assays are ready for use in the routine diagnostic laboratory.     

Evaluation of Strongyloides stercoralis infection in patients with HTLV-1

Introduction: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response.Objective: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil.Materials and methods: We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot.Results: The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S. stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/ gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). Conclusions: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.     

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.     

False-Positive FNA Due to Highly Sensitive BRAF Assay

ObjectiveFalse-positive BRAF analysis on fine-needle aspiration (FNA) has rarely been reported in the literature but may become more common with the advent of assays that can detect the BRAF V600E mutation in only 2% of otherwise wild-type thyroid cells. We present the case of an indeterminate BRAF-positive FNA that showed no evidence of cancer on final surgical pathology.MethodsCase report and literature review.ResultsAn 87-year-old female with an indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in tumor cells from the nodule was identified, labeled, and microdissected for molecular testing, which demonstrated only wild-type BRAF, at the analytical limit of the assay.ConclusionIncreasingly sensitive BRAF assays using dual-priming oligonucleotide-based multiplex polymerase chain reaction analysis can detect the BRAF V600E mutation when present in only 2% of a population of wild-type cells. This increases the risk of false-positive results, particularly in cases of indeterminate FNA. Clinicians must caution patients in these circumstances that BRAF molecular testing may not have a 100% positive predictive value. (Endocr Pract. 2014;20:e8-e10)     

Association between Human Papillomavirus and Human T-Lymphotropic Virus in Indigenous Women from the Peruvian Amazon

Background

No association between the Human T-cell lymphotropic virus (HTLV), an oncogenic virus that alters host immunity, and the Human Papillomavirus (HPV) has previously been reported. Examining the association between these two viruses may permit the identification of a population at increased risk for developing cervical cancer.

Methods and Findings

Between July 2010 and February 2011, we conducted a cross-sectional study among indigenous Amazonian Peruvian women from the Shipibo-Konibo ethnic group, a group with endemic HTLV infection. We recruited women between 15 and 39 years of age who were living in the cities of Lima and Ucayali. Our objectives were to determine the association between HTLV and: (i) HPV infection of any type, and (ii) high-risk HPV type infection. Sexually active Shipibo-Konibo women were screened for HTLV-1 and HTLV-2 infections. All HTLV-1 or -2 positive women, along with two community-matched HTLV negative sexually active Shipibo-Konibo controls were later tested for the presence of HPV DNA, conventional cytology, and HIV. We screened 1,253 Shipibo-Konibo women, observing a prevalence of 5.9% (n = 74) for HTLV-1 and 3.8% (n = 47) for HTLV-2 infections. We enrolled 62 (60.8%) HTLV-1 positive women, 40 (39.2%) HTLV-2 positive women, and 205 community-matched HTLV negative controls. HTLV-1 infection was strongly associated with HPV infection of any type (43.6% vs. 29.3%; Prevalence Ratio (PR): 2.10, 95% CI: 1.53–2.87), and with high-risk HPV infection (32.3% vs. 22.4%; PR: 1.93, 95% CI: 1.04–3.59). HTLV-2 was not significantly associated with either of these HPV infections.

Conclusions

HTLV-1 infection was associated with HPV infection of any type and with high-risk HPV infection. Future longitudinal studies are needed to evaluate the incidence of high-risk HPV infection as well as the incidence of cervical neoplasia among HTLV-1 positive women.     

Simian T-cell leukemia virus (STLV) infection in wild primate populations in Cameroon: evidence for dual STLV type 1 and type 3 infection in agile mangabeys (Cercocebus agilis)

Three types of human T-cell leukemia virus (HTLV)-simian T-cell leukemia virus (STLV) (collectively called primate T-cell leukemia viruses [PTLVs]) have been characterized, with evidence for zoonotic origin from primates for HTLV type 1 (HTLV-1) and HTLV-2 in Africa. To assess human exposure to STLVs in western Central Africa, we screened for STLV infection in primates hunted in the rain forests of Cameroon. Blood was obtained from 524 animals representing 18 different species. All the animals were wild caught between 1999 and 2002; 328 animals were sampled as bush meat and 196 were pets. Overall, 59 (11.2%) of the primates had antibodies cross-reacting with HTLV-1 and/or HTLV-2 antigens; HTLV-1 infection was confirmed in 37 animals, HTLV-2 infection was confirmed in 9, dual HTLV-1 and HTLV-2 infection was confirmed in 10, and results for 3 animals were indeterminate. Prevalences of infection were significantly lower in pets than in bush meat, 1.5 versus 17.0%, respectively. Discriminatory PCRs identified STLV-1, STLV-3, and STLV-1 and STLV-3 in HTLV-1-, HTLV-2-, and HTLV-1- and HTLV-2-cross-reactive samples, respectively. We identified for the first time STLV-1 sequences in mustached monkeys (Cercopithecus cephus), talapoins (Miopithecus ogouensis), and gorillas (Gorilla gorilla) and confirmed STLV-1 infection in mandrills, African green monkeys, agile mangabeys, and crested mona and greater spot-nosed monkeys. STLV-1 long terminal repeat (LTR) and env sequences revealed that the strains belonged to different PTLV-1 subtypes. A high prevalence of PTLV infection was observed among agile mangabeys (Cercocebus agilis); 89% of bush meat was infected with STLV. Cocirculation of STLV-1 and STLV-3 and STLV-1-STLV-3 coinfections were identified among the agile mangabeys. Phylogenetic analyses of partial LTR sequences indicated that the agile mangabey STLV-3 strains were more related to the STLV-3 CTO604 strain isolated from a red-capped mangabey (Cercocebus torquatus) from Cameroon than to the STLV-3 PH969 strain from an Eritrean baboon or the PPA-F3 strain from a baboon in Senegal. Our study documents for the first time that (i) a substantial proportion of wild-living monkeys in Cameroon is STLV infected, (ii) STLV-1 and STLV-3 cocirculate in the same primate species, (iii) coinfection with STLV-1 and STLV-3 occurs in agile mangabeys, and (iv) humans are exposed to different STLV-1 and STLV-3 subtypes through handling primates as bush meat.     

Familial Transmission of Human T-cell Lymphotrophic Virus: Silent Dissemination of an Emerging but Neglected Infection

Background

HTLV-1 is a retrovirus that causes lymphoproliferative disorders and inflammatory and degenerative diseases of the central nervous system in humans. The prevalence of this infection is high in parts of Brazil and there is a general lack of public health care programs. As a consequence, official data on the transmission routes of this virus are scarce.

Objective

To demonstrate familial aggregation of HTLV infections in the metropolitan region of Belém, Pará, Brazil.

Method

A cross-sectional study involving 85 HTLV carriers treated at an outpatient clinic and other family members. The subjects were tested by ELISA and molecular methods between February 2007 and December 2010.

Results

The prevalence of HTLV was 43.5% (37/85) for families and 25.6% (58/227) for the family members tested (95% CI: 1.33 to 3.79, P = 0.0033). Sexual and vertical transmission was likely in 38.3% (23/60) and 20.4% (29/142) of pairs, respectively (95% CI: 1.25 to 4.69, P = 0.0130). Positivity was 51.3% (20/39) and 14.3% (3/21) in wives and husbands, respectively (95% CI: 0.04 to 0.63, P = 0.0057). By age group, seropositivity was 8.0% (7/88) in subjects <30 years of age and 36.7% (51/139) in those of over 30 years (95% CI: 0.06 to 0.34, P<0.0001). Positivity was 24.1% (7/29) in the children of patients infected with HTLV-2, as against only 5.8% (4/69) of those infected with HTLV-1 (95% CI: 0.05 to 0.72, P = 0.0143).

Conclusion

The results of this study indicate the existence of familial aggregations of HTLV characterized by a higher prevalence of infection among wives and subjects older than 30 years. Horizontal transmission between spouses was more frequent than vertical transmission. The higher rate of infection in children of HTLV-2 carriers suggests an increase in the prevalence of this virus type in the metropolitan region of Belém.