Molecular epidemiology, clinical manifestations and public health implications of HTLV-1 infection in Spain
A. Treviño1, C. de Mendoza1, R. Benito2, E. Caballero3, A. Aguilera4, R. Ortiz de Lejarazu5, J.M. Ramos6, P. Parra1, J. del Romero7, V. Soriano1, HTLV Spanish Study Group
1Hospital Carlos III, Madrid, Spain, 2Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, 3Hospital Vall d´Hebron, Barcelona, Spain, 4Hospital de Conxo, Santiago de Compostela, Spain, 5Hospital Clinico Universitario, Valladolid, Spain, 6Hospital General Elche, Elche, Spain, 7Centro Sanitario Sandoval, Madrid, Spain
Background: A national registry of HTLV infection was created in year 1988. Herein, we describe the main characteristics of subjects with HTLV-1 infection reported in Spain up to December 2009.
Methods: All HTLV-1+ individuals registered were firstly diagnosed using an enzyme immunoassay and confirmed by Western blot and/or PCR. Subtype analysis was performed on LTR sequences. Quantitation of HTLV-I proviral load was made using real-time PCR (pol region) on PBMC.
Results: A total of 144 cases of HTLV-1 infection have been recorded. Mean age 41 years (range 4 to 78), 57% female. Country of origin: native Spaniards 36 (26%), Latin America 72(54%), and Sub-Saharan Africa 234(18%). Route of transmission: 53 heterosexual, 22 parenteral (12 IDUs, 6 transfusion and 4 recipients of solid organs), 10 vertical. Overall 23 were coinfected with HIV-1. Phylogenetic analysis demonstrated that 16 out of 18 samples analyzed belonged to the transcontinental subgroup of the HTLV-1 cosmopolitan subtype (1a). The remaining 2 subjects: a 4-year old boy from Ethiopia and a 41-year old woman from West Sahara. Sequences from these two patients grouped into a new subgroup in the Cosmopolitan subtype. TSP/HAM was diagnosed in 21 cases and ATL in 13. Median HTLV-1 proviral load was higher in TSP and ATL patients than in asymptomatic HTLV-1 carriers: 2917 vs 1993 vs < 500 HTLV-DNA copies per 104 PBMC. Based on the unique mechanism of action of raltegravir preventing retroviral integration, two TSP/HMA patients were treated with raltegravir for 6 months: no significant reductions in proviral HTLV-DNA was seen, neither clinical improvement.
Conclusions: The large immigration wave from Latin-America and Subs-Saharan Africa to Spain over the last decade is the main source of HTLV-1 infection in Spain. HTLV-associated diseases, namely TSP/HAM and ATL, are seen in a substantial proportion (~20%) of subjects diagnosed with HTLV-1 infection, suggesting that HTLV-1 misdiagnosis is common.
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