HTLV-1 and Co-infections

Abstract

Human T lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes lifelong T-cell infection in humans, impacting the host immune response. This virus causes a range of clinical manifestations, from inflammatory conditions, including neuronal damage (HTLV-1 associated myelopathy, HAM) to life-threatening leukemia (adult T-cell leukemia, ATL). Human T lymphotropic virus type 1 is also associated with increased risk of all-cause mortality, but the mechanisms remain unclear. As a blood-borne and sexually transmitted infection (STI), HTLV-1 shares transmission routes to many other pathogens and although it has worldwide distribution, it affects mainly those in low- and middle-income tropical areas, where the prevalence of other infectious agents is high. These factors contribute to a high incidence of co-infections in people living with HTLV-1 (PLHTLV). This comprehensive review addresses the impact of HTLV-1 on several co-infections and vice-versa. There is evidence of higher rates of HTLV-1 infection in association with other blood borne (HCV, HBV) and sexually transmitted (Syphilis, Chlamydia, HPV, HSV) infections but whether this represents increased susceptibility or opportunity is unclear. Higher frequency of Mycobacterium tuberculosis (MTb) and Mycobacterium leprae (M. leprae) is observed in PLHTLV. Reports of opportunistic infections and high frequency of crusted scabies in patients with HTLV-1 points to immune impairment in those individuals. Human T lymphotropic virus type 1 may influence the persistence of pathogens, exemplified by the higher rates of Schistosoma mansoni and Strongyloides stercoralis (St. stercoralis) treatment failure observed in PLHTLV. This retrovirus is also associated with increased tuberculosis (TB) severity with some evidence pointing to a deleterious impact on leprosy outcome as well. These findings are supported by immune alterations observed in those co-infected individuals. Although the role of HTLV-1 in HCV outcome is debatable, most data indicate that HTLV may negatively impact the clinical course of hepatitis C. Co-infections may also influence the risk of developing HTLV-1 associated disease, but data are still limited. The impact of HTLV-1 on the response to more common infections, might contribute to the increased mortality rate of HTLV-1. Large scale prospective controlled studies on the prevalence and impact of HTLV-1 in co-infections and vice-versa are needed. Human T lymphotropic virus type 1 impact in public health is broad. Measures to increase awareness and to prevent new infections are needed.

Keywords: HBV; HCV; HTLV-1; Mycobacterium leprae; Mycobacterium tuberculosis; Schistosoma mansoni; co-infection; sexually transmitted infections.

Figure 1

Forest Plot and meta-analysis showing the Odds Ratio of HTLV-1 infection in patients with Mycobacterium tuberculosis. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies in each subgroup (those with History of TB and those with Active TB) and between subgroups is shown.

Figure 2

Forest Plot and meta-analysis showing the Odds Ratio of HTLV-1 infection in patients with Mycobaterium leprae. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies is shown.

Figure 3

Forest Plot and meta-analysis showing the Odds Ratio of Syphilis infection in people living with HTLV-1. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies in each subgroup (population under investigation) and between subgroups is shown. PLHTLV, people living with HTLV; GP, general population; BD, blood donors; PW, pregnant women; FSW, female sex workers; STI, sexually transmitted infection.

Figure 4

Forest Plot and meta-analysis showing the Odds Ratio Chlamydia trachomatis infection in people living with HTLV-1. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies is shown. PLHTLV, people living with HTLV; BD, blood donors; PW, pregnant women; FSW, female sex workers.

Figure 5

Forest Plot and meta-analysis showing the Odds Ratio HPV infection in people living with HTLV-1. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies is shown.

Figure 6

Forest Plot and meta-analysis showing the Odds Ratio HTLV-1 infection in individuals with anti-HCV antibodies. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies is shown.

Figure 7

Forest Plot and meta-analysis showing the Odds Ratio Schistosoma mansoni infection in people living with HTLV-1. The boxes and lines indicate the odds ratios (ORs) and their confidence intervals (CIs) for each study. The pooled odds ratio is represented by a black diamond. The size of the blue squares indicates the relative weight of each estimate. Statistical analysis and graph were performed using RevMan 5 Software. Odds Ratio was calculated using Random effects model and Mantel-Haenszel statistical method. Measures of heterogeneity between studies is shown.