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Description of a “Trans-Saharan” Strain of Human T-Lymphotropic Virus Type 1 in West Africa
Abstract
The aim of this study was to assess the prevalence and the molecular epidemiology of human T-lymphotropic virus type 1 (HTLV-1) in a group of pregnant women living in Guinea Bissau. We studied 427 consecutive pregnant women attending 10 centers for HIV-1 infection monitoring in Bissau. HTLV-1 infection was found in 2.6% of the patients. Phylogenetic analysis of the long terminal repeat region showed that 10 isolates were of the cosmopolitan subtype (HTLV-1a) and that only 1 was of the widespread Central African subtype (HTLV-1b). All the cosmopolitan isolates belonged to the HTLV-1aD subgroup, which was first described in North Africa and clustered with other Senegal and Guinea isolates to form a significant West African clade. Our data show a high prevalence of HTLV-1 in Guinea Bissau and suggest the existence of a trans-Saharan strain distributed in North and West Africa, which probably crossed the desert in the past as a result of contacts between nomadic and sedentary populations or along trading routes.
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... More recently, the E/a-Per subgroup, comprising 2 strains from Black Peruvian, was defined [22]; based on partial segment of LTR, a F subgroup has also been identified, especially in an Ethiopian patient [23]. Lastly, we have added in 2006, a Senegalese subgroup (a-Sen), which has also been named "Trans-Saharan" or clade W within the HTLV-1aD subgroup [24][25][26]. ...
... • The Senegalese subgroup represents, by definition, the major subgroup present in Senegal (Fig. 2) [25,26]. It is also present in neighboring countries such as Gambia, Guinea-Bissau, and Mali [24,44]. In addition, the a-Sen strains are found, but more rarely, in Côte d'Ivoire and Ghana. ...
Human T cell leukemia virus (HTLV-1) is an oncoretrovirus that infects at least 10 million people worldwide. HTLV-1 exhibits a remarkable genetic stability, however, viral strains have been classified in several genotypes and subgroups, which often mirror the geographic origin of the viral strain. The Cosmopolitan genotype HTLV-1a, can be subdivided into geographically related subgroups, e.g. Transcontinental (a-TC), Japanese (a-Jpn), West-African (a-WA), North-African (a-NA), and Senegalese (a-Sen). Within each subgroup, the genetic diversity is low. Genotype HTLV-1b is found in Central Africa; it is the major genotype in Gabon, Cameroon and Democratic Republic of Congo. While strains from the HTLV-1d genotype represent only a few percent of the strains present in Central African countries, genotypes -e, -f, and -g have been only reported sporadically in particular in Cameroon Gabon, and Central African Republic. HTLV-1c genotype, which is found exclusively in Australo-Melanesia, is the most divergent genotype. This reflects an ancient speciation, with a long period of isolation of the infected populations in the different islands of this region (Australia, Papua New Guinea, Solomon Islands and Vanuatu archipelago). Until now, no viral genotype or subgroup is associated with a specific HTLV-1-associated disease. HTLV-1 originates from a simian reservoir (STLV-1); it derives from interspecies zoonotic transmission from non-human primates to humans (ancient or recent). In this review, we describe the genetic diversity of HTLV-1, and analyze the molecular mechanisms that are at play in HTLV-1 evolution. Similar to other retroviruses, HTLV-1 evolves either through accumulation of point mutations or recombination. Molecular studies point to a fairly low evolution rate of HTLV-1 (between 5.6E-7 and 1.5E-6 substitutions/site/year), supposedly because the virus persists within the host via clonal expansion (instead of new infectious cycles that use reverse transcriptase).
... After removing duplicates and screening titles, abstracts, and full texts, we included 18 publications that met our criteria and proceeded with systematic review and meta-analysis. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Study characteristics. The study design and characteristics are shown in Table 2. ...
... 26 In the second study conducted in Guinea-Bissau (Western Africa), analysis showed that the cosmopolitan subtype (HTLV-1a) was prevalent and only one isolate belonged to the b subtype (HTLV-1b). 36 ...
Human T-cell lymphotropic virus type 1 (HTLV-1) imposes a substantial disease burden in sub-Saharan Africa (SSA), which is arguably the world's largest endemic area for HTLV-1. Evidence that mother-to-child transmission persists as a major mode of transmission in SSA prompted us to estimate the pooled prevalence of HTLV-1 among pregnant women throughout the region. We systematically reviewed databases including EMBASE, MEDLINE, Web of Science, and the Cochrane Database of Systemic Reviews from their inception to November 2018. We selected studies with data on HTLV-1 prevalence among pregnant women in SSA. A random effect meta-analysis was conducted on all eligible data and heterogeneity was assessed through subgroup analyses. A total of 18 studies, covering 14,079 pregnant women, were selected. The evidence base was high to moderate in quality. The pooled prevalence, per 100 women, of the 18 studies that screened HTLV-1 was 1.67 (95% CI: 1.00-2.50), a figure that masks regional variations. In Western, Central, Southern, and Eastern Africa, the numbers were 2.34 (1.68-3.09), 2.00 (0.75-3.79), 0.30 (0.10-0.57), and 0.00 (0.00-0.21), respectively. The prevalence of HTLV-1 infection among pregnant women in SSA, especially in Western and Central Africa, strengthens the case for action to implement routine screening of pregnant women for HTLV-1. Rigorous studies using confirmatory testing and molecular analysis would characterize more accurately the prevalence of this infection, consolidate the evidence base, and further guide beneficial interventions.
... HTLV-1a-North Africa (HTLV-1 a-NA), HTLV-1a-Senegalese (HTLV-1 a-Sen), HTLV-1a-West Africa (HTLV-1 a-WA), HTLV-1b and HTLV-1a-Transcontinental (HTLV-1a-TC) are most prevalent throughout the continent in the North, West, Central and Austral regions respectively. HTLV-1 d, -e, -fand-g have been identified in Central Africa (Cameroon, Central African Re-Open Access Library Journal public and Gabon)[93]. In Côte d'Ivoire and Ghana, the majority of HTLV-1 strains belong to the West African subgroup[110] [112]. ...
The human leukemia virus HTLV-1 is caused by an oncogenic retrovirus responsible for adult T cell leucemia associated with tropical myelopathy/paraparesis. The mode of transmission of the HTLV-1 virus from one individual to another occurs by following three routes namely: vertical i.e. from mother to child by breastfeeding, sexually and intravenously on contact with blood-contaminated
objects. In Africa, the disease remains little known and is endemic in the tropical region of Africa. This review presents the origin of the virus, the molecular aspects as well as the molecules involved in the penetration of the virus into the host cell, the genomic structure. Whatever epidemiological and prevalence data from certain studies carried out in Africa on the human leukemia virus are included in this work.
... However, it seems our estimates are lower than those in pregnant women in other locations. In general, studies from Africa [66][67][68][69][70][71][72][73] reported prevalence higher than our estimate, ranging around 2.0%, with the highest prevalence of HTLV-1, at 5.5%, in pregnant women who attended an antenatal clinic in Nigeria 72 . Our estimates of HTLV-1 were also lower than those in pregnant women who emigrated from endemic areas, such as the Caribbean (1.42%) 74 . ...
Human T-lymphotropic virus type 1 (HTLV-1) infection may cause serious disease, while pathogenicity of HTLV-2 is less certain. There are no screening or surveillance programs for HTLV-1/-2 infection in Brazil. By performing this systematic review, we aimed to estimate the prevalence of HTLV-1/-2 infections in pregnant women in Brazil. This review included cohort and cross-sectional studies that assessed the presence of either HTLV-1/-2 infection in pregnant women in Brazil. We searched BVS/LILACS, Cochrane Library/CENTRAL, EMBASE, PubMed/MEDLINE, Scopus, Web of Science and gray literature from inception to August 2020. We identified 246 records in total. Twenty-six of those were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. The prevalence of HTLV-1 in Brazilian pregnant women, as diagnosed by a positive screening test and a subsequent positive confirmatory test, was 0.32% (95% CI 0.19–1.54), while of HTLV-2 was 0.04% (95% CI 0.02–0.08). Subgroup analysis by region showed the highest prevalence in the Northeast region (0.60%; 95% CI 0.37–0.97) for HTLV-1 and in the South region (0.16%; 95% CI 0.02–1.10) for HTLV-2. The prevalence of HTLV-1 is much higher than HTLV-2 infection in pregnant Brazilian women with important differences between regions. The prevalence of both HTLV-1/-2 are higher in the Northeast compared to Center-West region.
... Studies have shown 3.60%, 26.19%, and 2.60% HTLV-1 prevalence among urban adult population, STD patients, and pregnant women of Guinea-Bissau, respectively. 26,44,45 van Tienen et al. 46 reported HTLV-1 prevalence to be 5.2% in 1990, 5.9% in 1997 and 4.6% in 2007, while noting a continued association with HIV (Table 1). In a survey carried out on the rural population, it was discovered that the Cosmopolitan HTLV-1 1aD subtype was predominant 47 in the rural Bissau community. ...
Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing the possible re-emergence of HTLV in West Africa since discovery, a systematic review was carried out, focusing on the distribution of the virus types and significance of frequent indeterminate reports, while highlighting the need for mandatory routine blood screening. Capturing relevant data from discovery till date, sources searched were Google Scholar, CrossRef, NCBI (PubMed), MEDLINE, Research Gate, Mendeley, abstracts of Conferences and Proceedings, organization websites and reference lists of selected papers. A total of 2626 references were initially retrieved using search terms: Worldwide prevalence of HTLV, HTLV in Africa, HTLV in West Africa, HTLV subtypes, HTLV 3 and 4 in Africa, HTLV of African origin, HTLV seroindeterminate results, Spread of HTLV. These references were rigorously trimmed down to 76. Although evidence shows that HTLV is still endemic in the region, West Africa lacks recent epidemiological prevalence data. Thorough investigations are needed to ascertain the true cause of indeterminate Western Blot results. It is imperative that routine screening for HTLVs be mandated in West African health care facilities.
... However, the transcontinental subgroup of the cosmopolitan subtype (HTLV-1aA) is spread worldwide (Gessain and Cassar, 2012), mainly in Latin America and southern Africa (Alcantara et al., 2006). The HTLV-1aC genotype is described in West Africa while recent reports of HTLV-1aD have been documented in West African countries like Guinea-Bissau, Gambia, Ghana, Ivory Coast and Senegal (Zehender et al., 2008;van Tienen et al., 2012;Desrames et al., 2014). Furthermore, a recent report described viral recombination between HTLV-1 strains currently present in North Africa and West Africa (Desrames et al., 2014). ...
Introduction:
Human T-lymphotropic virus (HTLV) is an endemic virus in some parts of the world, with Africa being home to most of the viral genetic diversity. In Brazil, HTLV-1 is endemic amongst Japanese and African immigrant populations. Multiple introductions of the virus in Brazil from other epidemic foci were hypothesized. The long terminal repeat (LTR) region of HTLV-1 was used to infer the origin of the virus in Brazil, using phylogenetic analysis.
Methods:
LTR sequences were obtained from the HTLV-1 database (http://htlv1db.bahia.fiocruz.br). Sequences were aligned and maximum-likelihood and Bayesian tree topologies were inferred. Brazilian specific clusters were identified and molecular-clock and coalescent models were used to estimate each cluster's time to the most recent common ancestor (tMRCA).
Results:
Three Brazilian clusters were identified with a posterior probability ranged from 0.61 to 0.99. Molecular clock analysis of these three clusters dated back their respective tMRCAs between the year 1499 and the year 1668. Additional analysis also identified a close association between Brazilian sequences and new sequences from South Africa.
Conclusion:
Our results support the hypothesis of a multiple introductions of HTLV-1 into Brazil, with the majority of introductions occurring in the post-Colombian period. Our results further suggest that HTLV-1 introduction into Brazil was facilitated by the trans-Atlantic slave trade from endemic areas of Africa. The close association between southern African and Brazilian sequences also suggested that greater numbers of the southern African Bantu population might also have been part of the slave trade than previously thought.
... Within the latter subtype, one large transcontinental clade (a-TC) and three geographically restricted clades were identified: we named these the Senegalese (a-Sen), North African (a-NA), and West African (a-WA) clades. Of note, the a-Sen group has previously been described and named "trans-Saharan" or "clade N" (within the subgroup HTLV-1a D) (23,24). ...
... The phylogenetic analysis based on the LTR region confirmed that CV21 and CV79 belong to the HTLV-1aD subgroup, which is spread in North African countries such as Senegal and Guinea-Bissau (Zehender et al. 2008). ...
We characterised and reported the first full-length genomes of Human T-cell Lymphotropic Virus Type 1 subgroup HTLV-1aD (CV21 and CV79). This subgroup is one of the major determinants of HTLV-1 infections in North and West Africa, and recombinant strains involving this subgroup have been recently demonstrated. The CV21 and CV79 strains from Cape Verde/Africa were characterised as pure HTLV-1aD genomes, comparative analyses including HTLV-1 subtypes and subgroups revealed HTLV-1aD signatures in the envelope, pol, and pX regions. These genomes provide original information that will contribute to further studies on HTLV-1a epidemiology and evolution. © 2016 Memorias do Instituto Oswaldo Cruz. All rights reserved.
... Within the latter subtype, one large transcontinental clade (a-TC) and three geographically restricted clades were identified: we named these the Senegalese (a-Sen), North African (a-NA), and West African (a-WA) clades. Of note, the a-Sen group has previously been described and named "trans-Saharan" or "clade N" (within the subgroup HTLV-1a D) (23,24). ...
Unlabelled:
Although recombination is a major source of genetic variability in retroviruses, no recombinant strain had been observed for human T-lymphotropic virus type 1 (HTLV-1), the first isolated human-pathogenic retrovirus. Different genotypes exist for HTLV-1: Genotypes b and d to g are restricted to central Africa, while genotype c is only endemic in Australo-Melanesia. In contrast, the cosmopolitan genotype a is widely distributed. We applied a combination of phylogenetics and recombination analysis approaches to a set of new HTLV-1 sequences, which we collected from 19 countries throughout Africa, the continent where the virus has the largest endemic presence. This led us to demonstrate the presence of recombinants in HTLV-1. Indeed, the HTLV-1 strains currently present in North Africa have originated from a recombinant event between strains from Senegal and West Africa. This recombination is estimated to have occurred around 4,000 years ago. This recombination seems to have been generated during reverse transcription. In conclusion, we demonstrate that, albeit rare, recombination can occur in HTLV-1 and may play a role in the evolution of this retrovirus.
Importance:
A number of HTLV-1 subtypes have been described in different populations, but none of the genetic differences between these subtypes have been ascribed to recombination events. Here we report an HTLV-1 recombinant virus among infected individuals in North Africa. This demonstrates that, contrary to what was thought, recombination can occur and could play a role in the evolution of HTLV-1.
... Within the latter subtype, one large transcontinental clade (a-TC) and three geographically restricted clades were identified: we named these the Senegalese (a-Sen), North African (a-NA), and West African (a-WA) clades. Of note, the a-Sen group has previously been described and named "trans-Saharan" or "clade N" (within the subgroup HTLV-1a D) (23,24). ...
Although recombination is a major source of genetic variability in retroviruses, no recombinant strain had been observed for human T-lymphotropic virus type 1 (HTLV-1), the first isolated human-pathogenic retrovirus. Different genotypes exist for HTLV-1: Genotypes b and d to g are restricted to central Africa, while genotype c is only endemic in Australo-Melanesia. In contrast, the cosmopolitan genotype a is widely distributed. We applied a combination of phylogenetics and recombination analysis approaches to a set of new HTLV-1 sequences, which we collected from 19 countries throughout Africa, the continent where the virus has the largest endemic presence. This led us to demonstrate the presence of recombinants in HTLV-1. Indeed, the HTLV-1 strains currently present in North Africa have originated from a recombinant event between strains from Senegal and West Africa. This recombination is estimated to have occurred around 4,000 years ago. This recombination seems to have been generated during reverse transcription. In conclusion, we demonstrate that, albeit rare, recombination can occur in HTLV-1 and may play a role in the evolution of this retrovirus.
IMPORTANCE A number of HTLV-1 subtypes have been described in different populations, but none of the genetic differences between these subtypes have been ascribed to recombination events. Here we report an HTLV-1 recombinant virus among infected individuals in North Africa. This demonstrates that, contrary to what was thought, recombination can occur and could play a role in the evolution of HTLV-1.
... HTLV-1 infection in a large cohort study from Caio was found to be associated with increased mortality, especially among younger people and an increased proviral load was associated with increased mortality[32]. HTLV-1aD was the predominant variant in our study population, consistent with other studies from Bissau and Senegal[33,34]. Recently, this variant was also described in Europe in patients from West Africa who had emigrated to Portugal[35]. HTLV-1 phylogeny has been examined in a historical context to trace the origin of the virus and movement of people. ...
Human T-Lymphotropic Virus Type 1 (HTLV-1) infection causes lethal adult T-cell leukemia (ATL) and severely debilitating HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in up to 5% of infected adults. HTLV-1 is endemic in parts of Africa and the highest prevalence in West Africa (5%) has been reported in Caio, a rural area in the North-West of Guinea-Bissau. It is not known which HTLV-1 variants are present in this community. Sequence data can provide insights in the molecular epidemiology and help to understand the origin and spread of HTLV-1.
To gain insight into the molecular diversity of HTLV-1 in West Africa.
HTLV-1 infected individuals were identified in community surveys between 1990-2007. The complete Long Terminal Repeat (LTR) and p24 coding region of HTLV-1 was sequenced from infected subjects. Socio-demographic data were obtained from community census and from interviews performed by fieldworkers. Phylogenetic analyses were performed to characterize the relationship between the Caio HTLV-1 and HTLV-1 from other parts of the world.
LTR and p24 sequences were obtained from 72 individuals (36 LTR, 24 p24 only and 12 both). Consistent with the low evolutionary change of HTLV-1, many of the sequences from unrelated individuals showed 100% nucleotide identity. Most (45 of 46) of the LTR sequences clustered with the Cosmopolitan HTLV-1 subtype 1a, subgroup D (1aD). LTR and p24 sequences from two subjects were divergent and formed a significant cluster with HTLV-1 subtype 1g, and with the most divergent African Simian T-cell Lymphotropic Virus, Tan90.
The Cosmopolitan HTLV-1 1aD predominates in this rural West African community. However, HTLV-1 subtype 1g is also present. This subtype has not been described before in West Africa and may be more widespread than previously thought. These data are in line with the hypothesis that multiple monkey-to-man zoonotic events are contributing to HTLV-1 diversity.
... However, HTLV-1 and STLV-1 strains from western African segregate clearly in phylogenetic analyses; most humans are infected with HTLV-1A, the only humanrestricted molecular subtype (6)(7)(8)(9). Therefore, in western compared with central Africa, human infections with viruses closely related to local STLV-1 strains are much more likely to refl ect direct zoonotic transmission. ...
Simian T-lymphotropic virus type 1 (STLV-1) strains occasionally infect humans. However, the frequency of such infections is unknown. We show that direct transmission of STLV-1 from nonhuman primates to humans may be responsible for a substantial proportion of human T-lymphotropic virus type 1 infections in rural Côte d'Ivoire, where primate hunting is common.
... In this study, HIV and HTLV-1 infections showed a crosssectional association, as has been shown before in this study area in 1990 [25] and in the general adult popula- tion [16,41], elderly people [10], an occupational cohort [42] and pregnant women [43] in Bissau. Why this association is stronger for women than for men remains unclear. ...
HTLV-1 is endemic in Guinea-Bissau, and the highest prevalence in the adult population (5.2%) was observed in a rural area, Caió, in 1990. HIV-1 and HIV-2 are both prevalent in this area as well. Cross-sectional associations have been reported for HTLV-1 with HIV infection, but the trends in prevalence of HTLV-1 and HIV associations are largely unknown, especially in Sub Saharan Africa. In the current study, data from three cross-sectional community surveys performed in 1990, 1997 and 2007, were used to assess changes in HTLV-1 prevalence, incidence and its associations with HIV-1 and HIV-2 and potential risk factors.
HTLV-1 prevalence was 5.2% in 1990, 5.9% in 1997 and 4.6% in 2007. Prevalence was higher among women than men in all 3 surveys and increased with age. The Odds Ratio (OR) of being infected with HTLV-1 was significantly higher for HIV positive subjects in all surveys after adjustment for potential confounding factors. The risk of HTLV-1 infection was higher in subjects with an HTLV-1 positive mother versus an uninfected mother (OR 4.6, CI 2.6-8.0). The HTLV-1 incidence was stable between 1990-1997 (Incidence Rate (IR) 1.8/1,000 pyo) and 1997-2007 (IR 1.6/1,000 pyo) (Incidence Rate Ratio (IRR) 0.9, CI 0.4-1.7). The incidence of HTLV-1 among HIV-positive individuals was higher compared to HIV negative individuals (IRR 2.5, CI 1.0-6.2), while the HIV incidence did not differ by HTLV-1 status (IRR 1.2, CI 0.5-2.7).
To our knowledge, this is the largest community based study that has reported on HTLV-1 prevalence and associations with HIV. HTLV-1 is endemic in this rural community in West Africa with a stable incidence and a high prevalence. The prevalence increases with age and is higher in women than men. HTLV-1 infection is associated with HIV infection, and longitudinal data indicate HIV infection may be a risk factor for acquiring HTLV-1, but not vice versa. Mother to child transmission is likely to contribute to the epidemic.
HTLV-1 prevalence in Portugal is low and mainly affects immigrants from endemic areas where HIV infection represents a public health problem. Despite the majority of HTLV-1 infected individuals remains asymptomatic, severe pathologies may develop after prolonged viral persistence, namely, an aggressive form of leukemia. An increase mortality rate and faster progression to death is often related to HTLV-1/HIV coinfection. Nevertheless, studies showed that some antiretrovirals used in HIV treatment lead to a positive immune response against HTLV-1. This study aimed to analyse epidemiological and clinical data, and to assess the diversity of HTLV-1 strains circulating in infected-residents diagnosed in the Portuguese national reference laboratory between 2010 and 2021. LTR and env proviral sequences derived from 20 individuals were used to generate phylogenetic trees along with multiples reference sequences from different geographic origin retrieved from the database. Three samples belong to Portuguese natives and 17 belong to immigrants: 15 from several countries of Africa, one from South America and one from Europe; six patients (30%, mean age 40.3 years) showed HTLV-1 related diseases and six (30%, mean age 45.2 years) were coinfected with HIV/AIDS. The results show that the Cosmopolitan subtype is circulating in Portugal, with ten sequences being classified as subgroup A, that include Portuguese and natives from S. Tomé and Príncipe with a mean age of 39.4 years, and ten sequences that segregated into the Senegal cluster derived from natives born in Guinea-Bissau with a mean age of 43.5 years. A high proportion of HTLV-1 related diseases and HIV/AIDS coinfection was observed. Risk behaviour practices and the absence of specific control measures, including diagnostic and treatment, may contribute to a silent dissemination of a broad diversity of HTLV-1 strains and, therefore, the increased rate of progression to debilitating diseases. In this manner, an early diagnostic and a molecular surveillance of HTLV-1 transmission remains necessary in Portugal.
Background: HTLV-1 infection in Spain is rare and mainly affects immigrants from endemic regions and native Spaniards with prior history of sexual intercourse with persons from endemic countries. Herein, we report the main clinical and virological features of cases reported in Spain. Methods: All individuals with HTLV-1 infection recorded at the national registry since 1989 were examined. Phylogenetic analysis was performed based on the LTR region. Results: A total of 229 HTLV-1 cases had been reported up to December 2012. Mean age was 41 years-old and 61% were female. Their country of origin was Latin America in 59%, Africa in 15% and Spaniards in 20%. Transmission had occurred following sexual contact in 41%, parenteral exposure in 12% and vertically in 9%. HAM/TSP was diagnosed in 27 cases and ATLL in 17 subjects. HTLV-1 subtype could be obtained for 45 patients; all but one belonged to the Cosmopolitan subtype a. One Nigerian pregnant woman harboured HTLV-1 subtype b. Within the Cosmopolitan subtype a, two individuals (from Bolivia and Peru, respectively) belonged to the Japanese subgroup B, another two (from Senegal and Mauritania) to the North African subgroup D, and 39 to the Transcontinental subgroup A. Of note, one divergent HTLV-1 strain from an Ethiopian branched off from all five known Cosmopolitan subtype 1a subgroups. Conclusions: Divergent HTLV-1 strains have been introduced and currently circulate in Spain. The relatively large proportion of symptomatic cases (19%) suggests that HTLV-1 infection is underdiagnosed in Spain.
The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea-Bissau, where HTLV-1 is endemic (prevalence of 5% in the adult population). A cross-sectional survey was performed among mothers and their children (aged <15 years) in a rural community in Guinea-Bissau. A questionnaire to identify risk factors for infection and a blood sample were obtained. HTLV-1 proviral load in peripheral blood was determined and PCR was performed to compare long terminal repeat (LTR) sequences in mother-child pairs. Fourteen out of 55 children (25%) of 31 HTLV-1-infected mothers were infected versus none of 70 children of 30 uninfected mothers. The only factor significantly associated with HTLV-1 infection in the child was the proviral load of the mother; the risk of infection increased significantly with the log(10) proviral load in the mother's peripheral blood (OR 5.5, 95% CI 2.1-14.6, per quartile), adjusted for weaning age and maternal income. HTLV-1 sequences of the LTR region obtained from mother-child pairs were identical within pairs but differed between the pairs. Vertical transmission plays an important role in HTLV-1 transmission in this community in Guinea-Bissau. The risk of transmission increases with the mother's proviral load in the peripheral blood. Identical sequences in mother-child pairs give additional support to the maternal source of the children's infection.
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.
To assess the HTLV-1 molecular epidemiology in Mozambique and to investigate their relationship with HTLV-1 lineages circulating worldwide.
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.
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.
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.
Over the past decade, Portugal and Spain received large numbers of immigrants from HTLV-1 endemic areas. Our aim was to investigate the diversity of subtypes circulating in these two countries and the introduction of new variants. We performed a molecular analysis of HTLV-1 strains in patients diagnosed since 1998. LTR and env proviral sequences from 26 individuals were analyzed to generate phylogenetic trees along with reference HTLV-1 subtypes from several geographic origins. Epidemiological and clinical data were recorded. Most subjects were immigrants (57.7%) from South America and Africa. All isolates belonged to the cosmopolitan A subtype. Most carried the transcontinental subgroup A, but five subjects carried subgroup D and one carried subgroup C, previously unreported in Europe. HTLV strains showed separate clusters linked to the patients' geographic origin. Although subjects with HTLV-1 infection tend not to be engaged in high-risk practices, silent dissemination of a broad diversity of HTLV-1 viruses may still occur.
Human T-cell lymphotropic virus type 1 prevalence estimates are usually based on serological screening of blood donors, pregnant women, and other selected population groups. Previously, data on the global epidemiology of human T-cell lymphotropic virus type 1 infection have been summarized unsystematically and without a focus on general populations. To assess the implications of the virus for healthcare systems it is essential to know its past and present prevalence. The widely cited estimate that 10-20 million people are infected with human T-cell lymphotropic virus type 1 worldwide was calculated from data that are now 25 years old. This estimate may therefore no longer reflect the global epidemiology. The objective of this study was to collate published data that are truly representative of the general population through a systematic review of the literature. Fifty-nine relevant studies were identified and the 17 that met the inclusion criteria were all cross-sectional designs; none reported incidence. The prevalence of human T-cell lymphotropic virus type 1 was highest in the two studies of Japanese islands (36.4%; 95% CI: 29.9-42.8) and lowest in studies from Mongolia, Malaysia and India. In Haiti the prevalence was 3.8% (95% CI: 1.78-5.86); in Africa between 6.6% (95% CI: 4.0-9.9) and 8.5% (95% CI: 6.99-10.10) in Gabon, and 1.05% (95% CI: 0.63-1.47) in Guinea. Only three studies were from West Africa and none were from the South; the only study from India was from the north of the country. We conclude that there is a paucity of general population data from countries in which human T-cell lymphotropic virus type 1 is endemic, and that new studies are required to reevaluate the global burden of infection.
With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes. The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release, MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.
The prevalence of antibodies to human T-cell lymphotropic virus type I (HTLV-I) was determined in high-risk groups and normal adults in Egypt. Among 647 individuals tested, 6 (0.9%) were confirmed positive by western blot analysis. These included 2 (0.7%) of 279 drug addicts, 1 (3.3%) of 30 patients with sexually transmitted diseases, and 3 (2.2%) of 133 healthy individuals. Antibody was not detected in 47 blood recipients or 158 prostitutes. There was no correlation between sex or geographical location and HTLV-I infection. Fifty-three of the 647 sera (8%) were initially reactive by ELISA, but only 12 sera were repeatedly reactive. Since only 4 of these repeatedly reactive sera were confirmed by the western blot, the frequency of false positives using the DuPont screening ELISA was 1.2% (8/643). Two additional sera, confirmed positive by western blot, had been reactive, but not repeatedly, by ELISA. In comparison to the prevalence of HTLV-I antibody among risk groups in many parts of the world, the prevalence in Egypt was low.
Examining the pattern of nucleotide substitution for the control region of mitochondrial DNA (mtDNA) in humans and chimpanzees, we developed a new mathematical method for estimating the number of transitional and transversional substitutions per site, as well as the total number of nucleotide substitutions. In this method, excess transitions, unequal nucleotide frequencies, and variation of substitution rate among different sites are all taken into account. Application of this method to human and chimpanzee data suggested that the transition/transversion ratio for the entire control region was approximately 15 and nearly the same for the two species. The 95% confidence interval of the age of the common ancestral mtDNA was estimated to be 80,000-480,000 years in humans and 0.57-2.72 Myr in common chimpanzees.
To gain new insights on the origin, evolution, and modes of dissemination of human T-cell leukemia virus type 1 (HTLV-1), we performed a molecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of remote areas of Cameroon and the Central African Republic (CAR), considered to be the oldest inhabitants of these regions. Eight long-term activated T-cell lines producing HTLV-1 gag and env antigens were established from peripheral blood mononuclear cell cultures of HTLV-1 seropositive individuals, including three from Pygmies. A fragment of the env gene encompassing most of the gp21 transmembrane region was sequenced for the 58 new strains, while the complete long terminal repeat (LTR) region was sequenced for 9 strains, including 4 from Pygmies. Comparative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). Within or alongside the previously described Zairian cluster (HTLV-1 subtype B), we discovered a number of new HTLV-1 variants forming different subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered together within this Central African subtype, suggesting a common origin. Furthermore, three new strains (two originating from Pygmies from Cameroon and the CAR, respectively, and one from a Gabonese individual) were particularly divergent and formed a distinct new phylogenetic cluster, characterized by specific mutations and occupying in most analyses a unique phylogenetic position between the large Central African genotype and the Melanesian subtype... (D'après résumé d'auteur)
Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which are frequently suspected to be of viral origin. As very few data were available concerning cutaneous T cell lymphomas in tropical Africa, we undertook a clinical, histopathological, immunological and viro-molecular study of patients with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to this study, no case of CTCL had been reported in this country, 14 patients (five women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were seen over a period of 30 months (1992-1994) in the only dermatological department in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed. All these cutaneous tumors were T cell lymphoproliferations, only one expressing the CD8+ antigen. A comprehensive analysis of all the available data permitted characterization of three cases of adult T cell leukemia/lymphoma (ATL) associated with HTLV-I (one definitive case, of leukemic type, with demonstration of clonal integration of HTLV-I proviral genome and two probable ATL cases), three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I serological and/or molecular markers were restricted to the three ATL cases. From the unique definitive ATL case, a T cell line was established from culture of peripheral blood mononuclear cells and sequence analysis of the env gene and the U3-LTR region demonstrated that the virus present in this patient belonged to the cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I infection and associated ATL in Mali. This is the second ATL case described for the whole Sahelian region (one ATL of the lymphoma type was reported previously in a Mauritanian patient). Furthermore, we demonstrate that the main types of CTCL described in Europe and North America are also present in this African area and that the prevalence of these diseases is greatly underestimated in such regions. Furthermore, no association was observed between HTLV-I/II infection and SS, MF or pleomorphic cutaneous lymphoma in Mali in contrast to other studies.
To investigate the origin and dissemination of human T-cell lymphotropic virus type I in Latin America, we performed phylogenetic analysis on the LTR and env sequences of 13 HTLV-I isolates from Peruvians of four different ethnic groups: blacks and some mulattos of African origin; Quechuas of Inca origin; Nikkei of Japanese descendance; and Mestizos, a mixed population of white and Indian origin. All Peruvian samples could be situated within the cosmopolitan subtype HTLV-Ia, yet one sample showed an indeterminate Western blot pattern, lacking reactivity towards the HTLV-I type specific MTA1 peptide. Within the LTR, we could confirm the previously reported subdivision into four subgroups--one big transcontinental clade A, a Japanese clade B, a West African/Caribbean clade C and a North African clade D--and we identified a new separate subgroup E of black Peruvian strains. The clustering of the Peruvian samples seemed to depend on the ethnic origin of the host. The largest heterogeneity was observed in the black Peruvian samples. The mitochondrial DNA type of one of these black Peruvian strains of subgroup E was identical to that of West African source populations of the slave trade. Both findings support the idea of multiple post-Columbian introductions of African HTLV-Ia strains into the black Latin American population. Additionally, a tight cluster of Nikkei and Japanese samples implied a separate and rather recent transmission of a Japanese lineage of HTLV-I into Peru. A well-supported cluster of Latin American strains (including Peruvian Quechuas and Colombian Amerindians) could be situated within the transcontinental group. Molecular clock analysis of the Latin American and Japanese clade resulted in an equal evolutionary rate for those strains. Along with the anthropologically documented peopling of the Americas, the analysis was more in favour of a recent (400 to 100 years ago) introduction of HTLV-Ia into the American continent rather than a Palaeolithic introduction.
The program MODELTEST uses log likelihood scores to establish the model of DNA evolution that best fits the data.
AVAILABILITY: The MODELTEST package, including the source code and some documentation is available at http://bioag.byu. edu/zoology/crandall_lab/modeltest.html.
The Clustal series of programs are widely used in molecular biology for the multiple alignment of both nucleic acid and protein
sequences and for preparing phylogenetic trees. The popularity of the programs depends on a number of factors, including not
only the accuracy of the results, but also the robustness, portability and user-friendliness of the programs. New features
include NEXUS and FASTA format output, printing range numbers and faster tree calculation. Although, Clustal was originally
developed to run on a local computer, numerous Web servers have been set up, notably at the EBI (European Bioinformatics Institute)
(http://www.ebi.ac.uk/clustalw/).
The matrilineal genetic composition of 372 samples from the Republic of Guiné-Bissau (West African coast) was studied using RFLPs and partial sequencing of the mtDNA control and coding region. The majority of the mtDNA lineages of Guineans (94%) belong to West African specific sub-clusters of L0-L3 haplogroups. A new L3 sub-cluster (L3h) that is found in both eastern and western Africa is present at moderately low frequencies in Guinean populations. A non-random distribution of haplogroups U5 in the Fula group, the U6 among the "Brame" linguistic family and M1 in the Balanta-Djola group, suggests a correlation between the genetic and linguistic affiliation of Guinean populations. The presence of M1 in Balanta populations supports the earlier suggestion of their Sudanese origin. Haplogroups U5 and U6, on the other hand, were found to be restricted to populations that are thought to represent the descendants of a southern expansion of Berbers. Particular haplotypes, found almost exclusively in East-African populations, were found in some ethnic groups with an oral tradition claiming Sudanese origin.
With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein
sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating
rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes.
The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques
and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has
been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and
analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release,
MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic
trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical
methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.
In 2002, human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 seroprevalence was 0.16% (8/4,900) in blood donors from Dakar,
Senegal. Most of the positive donors originated from the country’s southern region. Seven donors were infected by HTLV-1 (of
cosmopolitan subtype), and one was infected by HTLV-2. These data highlight the problem of transfusion safety in this area
where HTLV-1-associated lymphoproliferative and neurological diseases are endemic.
Infection with human T-cell lymphotropic virus type I (HTLV-I) occurs mainly in Japan, Central and West Africa and the Caribbean Basin. Although antibody to HTLV-I has been reported among pregnant women in several endemic countries, there is no information regarding the seroprevalence in pregnant Ghanaian women. The reported seroprevalence of HTLV-I among healthy Ghanaian blood donors is between 0.5 and 4.2 %. Therefore, this study was conducted to determine the seroprevalence of HTLV-I among pregnant women attending the antenatal clinic at the 37 Military Hospital, Accra, Ghana, between the months of January and December 2003. The presence of antibodies specific for HTLV-I/II was tested using a particle agglutination test (PAT) kit and confirmed by Western blotting (WB). Of the 960 sera tested, HTLV-I/II antibodies were detected in 24 samples using the PAT kit. WB results indicated that, of the 24 positive PAT specimens, 20 specimens (83.3 %) were HTLV-I positive, one (4.2 %) was HTLV-II positive, two (8.3 %) were HTLV positive and one (4.2 %) was indeterminate. Therefore, the overall seroprevalence of HTLV-I was 2.1 %. Seroprevalence increased with age, suggesting sexual contact as the primary mode of transmission among women of childbearing age, rather than breastfeeding during infancy. The seroprevalence of 2.1 % reported here for HTLV-I in pregnant women in Accra is comparable to that of human immunodeficiency virus among the same population. In conclusion, the results indicate that HTLV-I is prevalent among asymptomatic Ghanaian pregnant women and thus there is a need to consider introducing antenatal screening for HTLV-I in Ghana.
Archaeological investigations in southern Mauretania have revealed a wealth of rather spectacular stone masonry villages which were occupied by prehistoric cultivators as early as 1000 B.C. It is argued that the inhabitants of these villages were Negro and very probably Soninke, and that the basic elements of their culture had developed without major influences from outside the area. The apparent sophistication and complexity of this cultural manifestation, combined with the close fit of developments in this area with Carneiro's theory of state formation, suggests that this prehistoric complex represented at least a powerful chiefdom which embodied many of the characteristics of subsequent West African states. The first demonstrable outside influences in the area began about 600 B.C. with the arrival of Libyco-Berbers from North Africa. Rather than causing still further cultural advances, the initial effect of this contact was the collapse of this sociopolitical organization. But with subsequent adjustment, plus the potential from trans-Saharan trade carried out by the North Africans, the basic, pre-existing pattern re-emerged, resulting eventually in a second and much more powerful African political organization in this area – the Ghana Empire.
A seroprevalence study was carried out of six different human pathogenic viruses, namely human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus (HTLV), human herpesvirus type 8 (HHV-8), and dengue virus among pregnant women and blood donors from rural (Nouna) and urban (Ouagadougou) Burkina Faso, West Africa. A total of 683 samples from blood donors (n = 191) and pregnant women (n = 492) were collected from both sites and screened for the different virus infection markers resulting in the following prevalence values for Nouna or Ouagadougou, respectively: HIV 3.6/4.6, anti-HBV core (anti-HBc) 69.6/76.4, HBV surface antigen (HBsAg)14.3/17.3, HCV 2.2/1.5, HTLV 1.4/0.5, HHV-8 11.5/13.5, dengue virus 26.3/36.5. Individuals aged ≥25 years were more likely to be infected with HIV than those below 24 years (P < 0.05). Infection with HIV increased the likelihood of co-infection with other viruses, such as HHV-8, HBV and HTLV. Co-infection studies involving five viruses (HBV-HBsAg, HHV-8, HIV, HCV, and HTLV) showed that 4.8% (33/683) of the studied population were dually infected, with HBsAg+ HHV-8 (13/33), HBsAg+HIV (8/33) and HIV+HHV-8 (8/33) being the most common co-infections. Of the population studied 0.6% (4/683) was triply infected, the most common infection being with HBV+HIV+HHV-8 (3/4). There was no difference in the prevalence of HIV, anti-HBc, HBsAg, HCV, HTLV, and HHV-8 either among blood donors or pregnant women in urban or rural setting, while dengue virus prevalence was relatively lower in rural (26.3%) than in urban (36.5%) Burkina Faso. J. Med. Virol. 78:683–692, 2006. © 2006 Wiley-Liss, Inc.
In 1989, a population-based cohort of persons aged ≥50 years was established in an urban area of Guinea-Bissau, West Africa. Overall, 346 persons were interviewed in detail about risk behaviors and had capillary blood drawn. Among women, 12.4% were HTLV-1 seropositive, compared with 4.6% in men. No HTLV-2 was found. Seropositivity varied considerably according to place of birth and ethnic group. In women, but not in men, HTLV-1 seropositivity was strongly associated with early sexual debut (10–14 yrs, 33.3%; 15–17 yrs, 26.0%; 18–20 yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend = 0.006), and the male partner's number of co-wives (ptrend = 0.006). There was also a 3.1-fold increased risk of being HTLV-1 seropositive if the woman was also HIV-2 seropositive. In a multivariate-risk-factor analysis, the strongest association with HTLV-1 was a history of having been bitten by a monkey (n = 11; combined ORadjusted = 10.1; 95% CI 2.3–44.4). Ornamental scarification was associated with a 3.3-fold increased risk. Ethnic affiliation also significantly influenced the risk of being HTLV-1 seropositive. Follow-up performed in January 1996 revealed no difference in survival between HTLV-1-seropositive and -seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7–2.8). In conclusion, this population, which has very high HIV-2 seroprevalence, is also highly endemic for HTLV-1. Whereas sexual behaviors are clearly important for HTLV-1 spread in women, non-sexual risk factors were the only ones of potential importance in men. HTLV-1 had no impact on survival in this older population. Int. J. Cancer 76:293–298, 1998.© 1998 Wiley-Liss, Inc.
Six new HTLV-I strains from seroindeterminate individuals were analyzed: four from Gabon, one from a Mbuti Efe pygmy in Congo (formerly Zaire), and one from a Congolese patient residing in Belgium. The LTR andenvregions were sequenced and phylogenetic analyses were performed to characterize the new strains. Nucleotide divergence and phylogeny results showed that four of the new strains belong to the HTLV-Ib Central African subtype. The other two strains, one from the Efe pygmy and one from Gabon, lie on distinct branches of the LTR andenvtrees with respect to the four major HTLV-I subtypes. Despite the low bootstrap values, likelihood mapping analyses proved that these strains can be considered two new HTLV-I molecular subtypes, putatively named HTLV-Ie and HTLV-If. A relation exists in the phylogenetic trees and in the likelihood maps between the new subtypes and African STLV-I strains fromPapiospp. andCercopithecusspp., suggesting one or more interspecies transmission events in the past. This study demonstrates that the phylogenetic subtyping of HTLV-I in the African continent is far from being completed and that samples presenting an indeterminate serology can potentially belong to new subtypes in humans. In addition, present day serological tests do not reliably type strains within the HTLV-Ib Central African subtype.
Two T-cell lines were established from peripheral blood mononuclear cells of two Moroccan patients with tropical spastic paraparesis and then named PR52 and PR144. The two cell lines showed a T lineage of activated CD4+ with high density of Tac+ (IL2 receptor). No expression of CD8 was observed. The virus particles were detected by reverse transcriptase activity and the viral antigens were also detected by immunofluorescence (IF) and Western blot. After six months of culture greater than 90% of the cells exhibited HTLVI antigen by IF. Lysate virus particles on Western blot analysis revealed p19,p24, and p53 gag protein similar to those detected in C91/PL virus particles from an adult T-cell leukemia (ATL) patient. gp46 and gp61 were also weakly detected. These two T-cell lines established will serve as substrate for further comparative studies on TSP and ATL isolates.
In 1988-1989, a national survey was conducted in Benin to determine the distribution of HTLV-I infection in a representative sample of adult individuals. This study comprised 2625 healthy subjects recruited in the six provinces of Benin and 1300 blood donors from Cotonou and from the other five provinces. Sera were screened for HTLV-I antibody by both immunofluorescence (IF) and enzyme immunoassay (EIA). Sera positive or doubtful by at least one technique were further analyzed by Western blot and radioimmunoprecipitation assay (RIPA) when indeterminate. Samples were considered as positive if they reacted with two gene products. No blood donor was positive. Over the 2625 subjects, 39 (1.5%) were positive. We observed a statistical difference between male and female (1%, 2%, p less than 0.05). A difference was also observed according to the areas studied: the HTLV-I antibody rate increased from coastal (0.3%) to northern (5.4%) provinces. HTLV-I seroprevalence increased significantly with age. This survey shows that HTLV-I infection exists in Benin but varies according to regions.
The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment
of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order
to downweight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are
varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific
gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather
than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced
gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new
program, CLUSTAL W which is freely available.
The geographic distribution of human T-cell lymphotropic/leukemia virus type I (HTLV-I) was initially believed to be limited to southwestern Japan, the Caribbean basin, and Africa. However, extensive searches in recent years have discovered its existence in other areas of the world as well as in isolated, ethnic populations such as South Amerindians, Australo-Melanesian aborigines, religiously segregated Jews, and Pygmies. Previous genetic analyses indicated that HTLV-I can be phylogenetically classified into three major lineages: Melanesian, Central African, and Cosmopolitan groups. Recently, more detailed characterization using long terminal repeat sequences (the most variable genomic region) has revealed that the Cosmopolitan group consists of four subtypes: (A) Transcontinental, (B) Japanese, (C) West African, and (D) North African. Most HTLV-I isolates of the same ethnic group from distant locations and those from different groups inhabiting the same area showed phylogenetic similarities. These observations indicate the present distribution of this virus should be interpreted from the anthropological backgrounds of the virus-possessing populations as well as spatial contact among them. Thus, the molecular epidemiology of HTLV-I and its simian counterpart, STLV-I, provides us with important clues for understanding not only the origin and dissemination of this retrovirus but past human movements over the globe.
In 1989, a population-based cohort of persons aged > or = 50 years was established in an urban area of Guinea-Bissau, West Africa. Overall, 346 persons were interviewed in detail about risk behaviors and had capillary blood drawn. Among women, 12.4% were HTLV-1 seropositive, compared with 4.6% in men. No HTLV-2 was found. Seropositivity varied considerably according to place of birth and ethnic group. In women, but not in men, HTLV-1 seropositivity was strongly associated with early sexual debut (10-14 yrs, 33.3%; 15-17 yrs, 26.0%; 18-20 yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend = 0.006), and the male partner's number of co-wives (ptrend = 0.006). There was also a 3.1-fold increased risk of being HTLV-1 seropositive if the woman was also HIV-2 seropositive. In a multivariate-risk-factor analysis, the strongest association with HTLV-1 was a history of having been bitten by a monkey (n = 11; combined OR adjusted = 10.1; 95% CI 2.3-44.4). Ornamental scarification was associated with a 3.3-fold increased risk. Ethnic affiliation also significantly influenced the risk of being HTLV-1 seropositive. Follow-up performed in January 1996 revealed no difference in survival between HTLV-1-seropositive and -seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7-2.8). In conclusion, this population, which has very high HIV-2 seroprevalence, is also highly endemic for HTLV-1. Whereas sexual behaviors are clearly important for HTLV-1 spread in women, non-sexual risk factors were the only ones of potential importance in men. HTLV-1 had no impact on survival in this older population.
A community-based survey to determine the prevalence of human T-cell lymphotropic type I (HTLV-I) and type II (HTLV-II) virus infections in mothers and children in south-western Nigeria was carried out using blood samples collected in 1993. A multistage cluster, random sampling procedure was used to select 460 mother-child pairs (476 children because there were 16 sets of twins) from 14 enumeration areas. A commercially available, whole HTLV-I lysate antigen-based ELISA method was used to screen for HTLV-I and HTLV-II antibodies in the samples. A synthetic peptide antigen-based ELISA was then used to differentiate between antibody reactivity to either HTLV-I or HTLV-II. Reactivity to HTLV-I or HTLV-II antibodies was found in 4.3 per cent (20/460) of mothers and in 1.1 per cent (5/476) of children in both rural and urban communities and all the positive children were males. None of the 16 sets of twins in this study was positive for either HTLV-I or HTLV-II. Also none of the mother-child paired sera tested showed concordance for either HTLV-I or HTLV-II antibody positivity. The lack of concordance between mother and child sera suggests that vertical transmission may not be the major route of transmission of HTLV infection to children in south-western Nigeria. Other modes of transmission, such as the re-use of unsterilized needles for injections and surgical knives in local scarification, which are common practices in the region, need to be investigated as they may prove to be more important than vertical transmission. These findings have important implications for any control programme for diseases that can be spread by the same routes as HTLV infection (the human immunodeficiency viruses, hepatitis B, and hepatitis C infections).
This article presents the results of a study conducted in 1988 at the National Blood Transfusion Centre of Tunis which determined the prevalence of HTLV-I/II antibodies in blood donors and different at-risk groups. Study participants were composed of 500 blood donors 387 multitransfused patients 232 hemodialysis patients and 25 HIV-positive patients and donors. All patients were receiving blood transfusion therapy with an average of 8 units of red blood concentrate. Antibodies for HTLV-I/II were tested by enzyme-linked immunosorbent assay (ELISA). Samples repeatedly reactive to ELISA were analyzed by Western blot. None of the multitransfused patients and only 1 blood donor produced antibodies to HTLV-I/II in ELISA. 1 of 2 hemodialysis patients who tested positive for anti-HTLV-I/II by ELISA was confirmed negative for anti-HTLV-I/II while the other was positive for HTLV-I. The results showed that Tunisia is a country with very low prevalence of HTLV-I/II antibodies and confirmed that hemodialysis is not a significant risk factor for HTLV.
To assess the prevalence and modes of transmission of HTLV-1 infection in an adult population in Bissau, and to evaluate possible interactions between the pattern of spread of HTLV-1 and HIV-1/HIV-2.
Univariate and multivariate analyses were used to evaluate gender-and age-specific HTLV-1 prevalences as well as associated risk determinants in an adult population based on a serosurvey comprising 2127 individuals from 304 randomly selected houses in Bissau.
Using stringent Western blot criteria, the overall seroprevalence of HTLV-1 was 3.6%, 2.2% among men and 4.7% among women, respectively. One individual was seropositive to HTLV-2. The prevalence of HTLV-1, which increased with age in both genders, however more markedly among women, was >4 times higher (9.4%) among older individuals (>44 years of age) than among younger individuals (2.4%). Blood transfusion and HIV-2 seropositivity were independently associated with HTLV-1 seropositivity in men. Among women, both HIV-2 seropositivity and HIV-1 seropositivity were significant risk determinants. Having had sexual partners was associated with a fivefold increased risk among women but did not reach significance.
The adult population of Guinea-Bissau has a higher prevalence of HTLV-1 than reported from most other countries in West Africa. The gender-and age-specific pattern of spread of HTLV-1 closely resembles that observed for HIV-2, another retrovirus prevalent to the region. The close correlation between HTLV-1 and HIV-2 most likely reflects the shared risk factors related to sexual behavior. The implication of the high percentage of double infections in this population needs to be determined.
Infective dermatitis (ID) is a rare dermatological condition of childhood that has been linked to human T-cell leukaemia/lymphoma virus type 1 (HTLV-1). Most cases have been reported in the Caribbean. Although several million people are estimated to be infected by HTLV-1 in sub-Saharan Africa, no case of ID has been reported in this area.
To identify and to describe cases of HTLV-1-associated ID in Senegal, West Africa.
Over a 3-year period, a serological test for HTLV-1 was performed at a dermatological centre in Dakar, Senegal, in children who presented with a picture suggestive of ID. Complementary haematological, immunological and virological investigations were performed in infected children and in their mothers.
Five patients with typical HTLV-1-associated ID were identified, of ages 17, 5, 4, 3 and 3 years; two patients belonged to the same family. They all presented with repeated flares of superinfected dermatitis involving typical sites of ID (mainly the scalp, external ears, nares and eyelids), associated with nasal discharge, and less commonly with a nonspecific papular rash on the face or trunk. Although oral antibiotic therapy always gave effective control of the symptoms, recurrences were constant. A persisting dry dermatitis of the retroauricular folds was common between flares. Infection in the oldest patient was associated with a chronic adult T-cell leukaemia/lymphoma. The mothers of three patients, and the grandmother of another, were all infected by HTLV-1 strains belonging to the Cosmopolitan molecular subtype, with a perfect nucleotide identity of long-terminal repeat and env gp21 genomic regions within each family.
We present the clinical and virological features of the first reported African cases of HTLV-1-associated ID. When compared with data from the Caribbean, infectious features seemed particularly prominent. ID appears to be overlooked in sub-Saharan Africa, where it might be easily confused with common pyoderma. Breast feeding appears to be the origin of HTLV-1 contamination of the children.
Human T-lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2) infections in Europe are limited to intravenous drug users and migrants coming from areas in which they are endemic. A survey was undertaken of HTLV-1 and HTLV-2 infections in 393 recent immigrants: 167 HIV-1 positive subjects (including 52 male-to-female transsexual sex workers) and 226 pregnant HIV-1 negative women. The prevalence of HTLV-1 was 3.6% in the HIV-1 positive group and 0.9% in the HIV-1 negative group. The highest HTLV-1 prevalence in both groups was found in persons from Latin America, particularly those born in Peru (up to 26% in the HIV-1 positive group). All of the HIV-1/HTLV-1 co-infected individuals were male-to-female transsexual sex workers in whom the overall prevalence of HTLV-1 infection was 11.5%. HTLV-2 was only found in the HIV-1 positive group (prevalence 1.2%); all of the infected subjects were transsexual sex workers from Brazil (overall prevalence 6.4%). Phylogenetic analysis showed that all of the HTLV-1 isolates were of the cosmopolitan type, clustering with other strains circulating in the patients' birthplaces; the HTLV-2 isolates were of subtype 2a, and clustered significantly with other Brazilian strains. These results suggest the independent origin of each infection in the patient's birthplace. The data raise concerns about the further spread of HTLV infections mainly through the sexual route.
HTLV is a genetically-stable retrovirus that is considered to have evolved partly in concert with human migrations. Its rate of evolution is low and therefore, difficult to estimate reliably. In the first part of this study, we provide an improved estimate of HTLV evolutionary rate using anthropological calibration of phylogenetic nodes. We investigate two different anthropological calibrations using a Bayesian method that implements a relaxed molecular clock model and can combine data from multiple genes. The analysis shows that the two calibrations are compatible. In the second part, we develop a Bayesian statistical model to combine and compare the anthropology-based estimates of evolutionary rate with a rate recently calculated using pedigree data from vertically HTLV-infected families. We compare the statistical power of the two estimates and show that the current pedigree estimate, although resulting in considerably higher evolutionary rates, is too statistically weak to warrant a re-examination of the commonly used anthropology-based estimates. Statistical uncertainty burdens HTLV rate estimates based on both anthropological calibrations and on pedigree data; the former method rests on an untested assumption, whilst that latter is affected by small sample sizes.
The factors that led to the simultaneous emergence, decades ago, of HIV-1 in central Africa and HIV-2 in West Africa remain unclear. The low HIV-2-associated mortality enables epidemiological assessment of risk factors potentially relevant in the early stages of the epidemic. In Guinea-Bissau, its epicentre, HIV-2 became highly prevalent (approximately 15%) in cohorts of individuals born before 1962, but is now disappearing whereas HIV-1 prevalence is increasing. We sought to verify the hypothesis that parenteral transmission was the key factor in the building-up of the HIV-2 epidemic.
Cross-sectional community survey of 1608 individuals aged > or = 50 years in Bissau.
Capillary blood was obtained for HIV serology. Associations between HIV-2 (alone or in dual HIV-1/HIV-2 infections) and exposures were measured with crude and adjusted odds ratios (AOR) and 95% confidence intervals (CI).
Prevalence of HIV-2 was higher in women (160/1063; 15.1%) than men (45/545; 8.3%, P < 0.001). Among women, excision (AOR, 1.54; 95% CI, 1.08-2.18) was independently associated with HIV-2, as were age and being widowed (AOR, 1.88; 95% CI, 1.29-2.74). Among men, HIV-2 was not associated with sexually transmitted infections or transactional sex. In an analysis comprising men and women that was adjusted for age, sex, ethnic group and marital status, HIV-2 was associated with having received injections for the treatment of tuberculosis (AOR, 2.12; 95% CI, 1.11-4.05) or trypanosomiasis (AOR, 1.75; 95% CI, 1.03-2.97).
Parenteral transmission through ritual excision and multiple injections during treatment of tuberculosis and trypanosomiasis contributed to the emergence of HIV-2 in Guinea-Bissau.
Human T-lymphotropic virus 1 (HTLV-1) has infected human beings for thousands of years, but knowledge about the infection and its pathogenesis is only recently emerging. The virus can be transmitted from mother to child, through sexual contact, and through contaminated blood products. There are areas in Japan, sub-Saharan Africa, the Caribbean, and South America where more than 1% of the general population is infected. Although the majority of HTLV-1 carriers remain asymptomatic, the virus is associated with severe diseases that can be subdivided into three categories: neoplastic diseases (adult T-cell leukaemia/lymphoma), inflammatory syndromes (HTLV-1-associated myelopathy/tropical spastic paraparesis and uveitis among others), and opportunistic infections (including Strongyloides stercoralis hyperinfection and others). The understanding of the interaction between virus and host response has improved markedly, but there are still no clear surrogate markers for prognosis and there are few treatment options.
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Review: across the desert and the sea: trans-Saharan and Atlantic slavery, 1500-1900.
- Richardson
Richardson D. Review: across the desert and the sea: trans-Saharan and
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Prevalences of HTLV-1 infection and associated risk determinants in an urban population in Guinea-Bissau, West Africa.
- Larsen