Dataset Information

Clinical associations of Human T-Lymphotropic Virus type 1 infection in an indigenous Australian population.

ABSTRACT:

Introduction

In resource-poor areas, infectious diseases may be important causes of morbidity among individuals infected with the Human T-Lymphotropic Virus type 1 (HTLV-1). We report the clinical associations of HTLV-1 infection among socially disadvantaged Indigenous adults in central Australia.

Methodology and principal findings

HTLV-1 serological results for Indigenous adults admitted 1(st) January 2000 to 31(st) December 2010 were obtained from the Alice Springs Hospital pathology database. Infections, comorbid conditions and HTLV-1 related diseases were identified using ICD-10 AM discharge morbidity codes. Relevant pathology and imaging results were reviewed. Disease associations, admission rates and risk factors for death were compared according to HTLV-1 serostatus. HTLV-1 western blots were positive for 531 (33.3%) of 1595 Indigenous adults tested. Clinical associations of HTLV-1 infection included bronchiectasis (adjusted Risk Ratio, 1.35; 95% CI, 1.14-1.60), blood stream infections (BSI) with enteric organisms (aRR, 1.36; 95% CI, 1.05-1.77) and admission with strongyloidiasis (aRR 1.38; 95% CI, 1.16-1.64). After adjusting for covariates, HTLV-1 infection remained associated with increased numbers of BSI episodes (adjusted negative binomial regression, coefficient, 0.21; 95% CI, 0.02-0.41) and increased admission numbers with strongyloidiasis (coefficient, 0.563; 95% CI, 0.17-0.95) and respiratory conditions including asthma (coefficient, 0.99; 95% CI, 0.27-1.7), lower respiratory tract infections (coefficient, 0.19; 95% CI, 0.04-0.34) and bronchiectasis (coefficient, 0.60; 95% CI, 0.02-1.18). Two patients were admitted with adult T-cell Leukemia/Lymphoma, four with probable HTLV-1 associated myelopathy and another with infective dermatitis. Independent predictors of mortality included BSI with enteric organisms (aRR 1.78; 95% CI, 1.15-2.74) and bronchiectasis (aRR 2.07; 95% CI, 1.45-2.98).

Conclusion

HTLV-1 infection contributes to morbidity among socially disadvantaged Indigenous adults in central Australia. This is largely due to an increased risk of other infections and respiratory disease. The spectrum of HTLV-1 related diseases may vary according to the social circumstances of the affected population.

SUBMITTER: Einsiedel L

PROVIDER: S-EPMC3894183 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Clinical associations of Human T-Lymphotropic Virus type 1 infection in an indigenous Australian population.

Einsiedel Lloyd L Spelman Tim T Goeman Emma E Cassar Olivier O Arundell Mick M Gessain Antoine A

PLoS neglected tropical diseases 20140116 1

<h4>Introduction</h4>In resource-poor areas, infectious diseases may be important causes of morbidity among individuals infected with the Human T-Lymphotropic Virus type 1 (HTLV-1). We report the clinical associations of HTLV-1 infection among socially disadvantaged Indigenous adults in central Australia.<h4>Methodology and principal findings</h4>HTLV-1 serological results for Indigenous adults admitted 1(st) January 2000 to 31(st) December 2010 were obtained from the Alice Springs Hospital path ...[more]

PMID: 24454973

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Project description:BackgroundHuman T-Lymphotropic Virus type 1 (HTLV-1) is endemic among people of Melanesian descent in Papua New Guinea, Solomon Islands and Vanuatu, and in Indigenous populations from Central Australia. Molecular studies revealed that these Australo-Melanesian strains constitute the highly divergent HTLV-1c subtype. New Caledonia is a French overseas territory located in the Southwest Pacific Ocean. HTLV-1 situation is poorly documented in New Caledonia and the molecular epidemiology of HTLV-1 infection remains unknown.ObjectivesStudying 500 older adults Melanesian natives from New Caledonia, we aim to evaluate the HTLV-1 seroprevalence and to molecularly characterize HTLV-1 proviral strains.Study designPlasma from 262 men and 238 females (age range: 60-96 years old, mean age: 70.5) were screened for anti-HTLV-1 antibodies by particle agglutination (PA) and indirect immunofluorescence assay (IFA). Serological confirmation was obtained using Western blot assay. DNAs were extracted from peripheral blood buffy coat of HTLV-1 seropositive individuals, and subjected to four series of PCR (LTR-gag; pro-pol; pol-env and tax-LTR). Primers were designed from highly common conserved regions of the major HTLV-1 subtypes to characterize the entire HTLV-1 proviral genome.ResultsAmong 500 samples, 3 were PA and IFA positive. The overall seroprevalence was 0.6%. The DNA sample from 1 New Caledonian woman (NCP201) was found positive by PCR and the complete HTLV-1 proviral genome (9,033-bp) was obtained. The full-length HTLV-1 genomic sequence from a native woman from Vanuatu (EM5), obtained in the frame of our previous studies, was also characterized. Both sequences belonged to the HTLV-1c Australo-Melanesian subtype. The NCP201 strain exhibited 0.3% nucleotide divergence with the EM5 strain from Vanuatu. Furthermore, divergence reached 1.1% to 2.9% with the Solomon and Australian sequences respectively. Phylogenetic analyses on a 522-bp-long fragment of the gp21-env gene showed the existence of two major clades. The first is composed of strains from Papua New Guinea; the second includes strains from all neighboring archipelagos (Solomon, Vanuatu, New Caledonia), and Australia. Interestingly, this second clade itself is divided into two sub-clades: strains from Australia on one hand, and strains from Solomon Islands, Vanuatu and New Caledonia on the other hand.ConclusionsThe HTLV-1 seroprevalence (0.6%) in the studied adult population from New Caledonia appears to be low. This seroprevalence is quite similar to the situation observed in Vanuatu and Solomon Islands. However it is very different to the one encountered in Central Australia. Taken together, these results demonstrated that Australo-Melanesia is endemic for HTLV-1 infection with a high diversity of HTLV-1c strains and a clear geographic clustering according to the island of origin of HTLV-1 infected persons.

Project description:HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

Dataset Information

Clinical associations of Human T-Lymphotropic Virus type 1 infection in an indigenous Australian population.

Introduction

Methodology and principal findings

Conclusion

Publications

Clinical associations of Human T-Lymphotropic Virus type 1 infection in an indigenous Australian population.

Similar Datasets

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