Population-based prevalence of human T-lymphotropic virus type 1 in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1), the causative agent of adult T-cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is endemic in sub-Saharan Africa (SSA) and poses a high morbidity and mortality risk. Its prevalence in the general population is poorly understood. The potential for prevention motivated us to do a systematic review and meta-analysis of population-based studies to estimate the prevalence of HTLV-1 in SSA. METHODS: A comprehensive, no-limit search was conducted in EMBASE, PubMed, Web of Science and the Cochrane Library from their inception dates to March 2019. Population-based studies presenting data on HTLV-1 in sub-Saharan Africa were included. Pooled prevalence was estimated using a random-effects meta-analysis. RESULTS: A total of 21 studies were included, representing 42 297 participants. The pooled HTLV-1 seroprevalence was 3.19% (95% CI 2.36-4.12%) with variations across year of study. Prevalence of HTLV-1 positively correlated with year of study (ß = 0.0036, P = 0.007). Participants from Central, Western and Southern Africa had a seroprevalence of 4.16% (95% CI 2.43-6.31%), 2.66% (95% CI 1.80-3.68%) and 1.56% (95% CI 0.48-3.15%), respectively. CONCLUSIONS: Our findings suggest that HTLV-1 infection is a public health concern in SSA and highlight the need to implement effective preventive programmes and interventions aimed at reducing the burden of this common yet neglected infection.

PRÉVALENCE DANS LA POPULATION DU VIRUS T-LYMPHOTROPIQUE HUMAIN DE TYPE 1 (HTLV-1) EN AFRIQUE SUBSAHARIENNE: OBJECTIF: Le virus lymphotropique T humain 1 (HTLV-1), l'agent causal de la leucémie T de l'adulte/lymphome (ATL) et la myélopathie associée à HTLV-1/paraparésie spastique tropicale (HAM/TSP), est endémique en Afrique subsaharienne (ASS) et présente un risque élevé de morbidité et de mortalité. Sa prévalence dans la population générale est mal comprise. Le potentiel de prévention nous a incité à procéder à une revue systématique et à une méta-analyse des études basées sur la population afin d'estimer la prévalence du HTLV- 1 en ASS. MÉTHODES: Une recherche approfondie et sans limite a été effectuée dans EMBASE, PUBMED, Web of Science et dans la Cochrane Library, depuis leur création jusqu'à mars 2019. Des études basées sur la population présentant des données sur HTLV-1 en ASS ont été incluses. La prévalence poolée a été estimée à l'aide d'une méta-analyse à effet aléatoire. RÉSULTATS: Un total de 21 études ont été incluses, représentant 42.297 participants. La séroprévalence poolée du HTLV-1 était de 3,19% (IC95%: 2,36% à 4,12%), avec des variations au cours de l'année de l'étude. La prévalence du HTLV-1 était corrélée positivement avec l'année d'étude (bêta = 0,0037, p = 0,007). Les participants d'Afrique centrale, de l'Ouest et Australe présentaient une séroprévalence de 4,16% (IC95%: 2,43% à 6,31%), de 2,66% (IC95%: 1,80% à 3,68%) et 1,56% (IC95%: 0,48% à 3,15%), respectivement. CONCLUSIONS: Nos résultats suggèrent que l'infection au HTLV-1 est une préoccupation de santé publique en ASS et soulignent la nécessité de mettre en œuvre des programmes et des interventions préventives efficaces visant à réduire la charge de cette infection commune mais négligée.

Prevalence and Molecular Epidemiology of Human T-Lymphotropic Virus Type 1 among Women Attending Antenatal Clinics in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

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.

Seroprevalence of human T-lymphotropic virus (HTLV) in blood donors in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Human T-cell lymphotropic viruses (HTLV) 1 and 2 are endemic in sub-Saharan Africa (SSA), transfusion-transmissible and causally linked to various severe diseases. However, even in SSA countries with moderate to high endemicity, routine blood donor screening for HTLV is rarely, if ever, performed. Information on seroprevalence is limited. The aim of this review is to establish the prevalence of HTLV-1 and HTLV-1/2 among blood donors in sub-Saharan Africa. MATERIALS AND METHODS: We systematically reviewed databases including EMBASE, MEDLINE and the Cochrane database library from their inception to June 2018. Studies presenting data on HTLV prevalence among blood donors in sub-Saharan Africa were included. A random-effect meta-analysis was conducted on all eligible studies. RESULTS: A total of 25 studies were included, representing 74 119 blood donors, of whom over 80% (61 002) were only tested for HTLV-1. The evidence base was high and moderate in quality. The pooled prevalence of the 17 studies that screened only for HTLV-1 and the nine studies that screened for HTLV-1/2 was 0·68 (95% CI: 0·29-1·60) and 1·11 (95% CI: 0·47-2·59) per 100 blood donors, respectively. CONCLUSION: The prevalence of HTLV-1 infection among blood donors is relatively low. The current review is intended to inform debates and decisions about best practices to prevent transfusion-transmitted HTLV in sub-Saharan Africa. Further work is required to determine the risk of infections by transfusion and the cost-effectiveness of any new measures such as routine screening.

Early events in hepatitis B virus infection: From the cell surface to the nucleus.

While most adults are able to clear acute hepatitis B virus (HBV) infection, chronic HBV infection is recalcitrant to current therapy because of the persistence of covalently closed circular DNA in the nucleus. Complete clearance of the virus in these patients is rare, and long-term therapy with interferon and/or nucleoside analogues may be required in an attempt to suppress viral replication and prevent progressive liver damage. The difficulty of establishing HBV infection in cell culture and experimental organisms has hindered efforts to elucidate details of the HBV life cycle, but it has also revealed the importance of the cellular microenvironment required for HBV binding and entry. Recent studies have demonstrated an essential role of sodium-taurocholate cotransporting polypeptide as a functional receptor in HBV infection, which has facilitated the development of novel infection systems and opened the way for more detailed understanding of the early steps of HBV infection as well as a potential new therapeutic target. However, many gaps remain in understanding of how HBV recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate cotransporting polypeptide, as well as events that are triggered after binding, including entry into the cell, intracellular transport, and passage through the nuclear pore complex. This review summarizes current knowledge of the initial stages of HBV infection leading to the establishment of covalently closed circular DNA in the nucleus.

Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection.

Public health concern about dengue diseases, caused by mosquito-borne infections with four serotypes of dengue virus (DENV-1-DENV-4), is escalating in tropical and subtropical countries. Most of the severe dengue cases occur in patients experiencing a secondary infection with a serotype that is different from the first infection. This is believed to be due to antibody-dependent enhancement (ADE), by which one DENV serotype uses pre-existing anti-DENV antibodies elicited in the primary infection to facilitate entry of a different DENV serotype into the Fc receptor-positive macrophages. Recently, we prepared a number of hybridomas producing human monoclonal antibodies (HuMAbs) by using peripheral blood lymphocytes from Thai patients at acute phase of secondary infection with DENV-2. Here, we characterized 17 HuMAbs prepared from two patients with dengue fever (DF) and one patient with dengue hemorrhagic fever (DHF) that were selected as antibodies recognizing viral envelope protein and showing higher neutralization activity to all serotypes. In vivo evaluation using suckling mice revealed near perfect activity to prevent mouse lethality following intracerebral DENV-2 inoculation. In a THP-1 cell assay, these HuMAbs showed ADE activities against DENV-2 at similar levels between HuMAbs derived from DF and DHF patients. However, the F(ab')2 fragment of the HuMAb showed a similar virus neutralization activity as original, with no ADE activity. Thus, these HuMAbs could be one of the therapeutic candidates against DENV infection.