Experiences from Two Decades of HTLV-1/2 Testing in a Low-Prevalence Area in Southern Germany, 2004 to 2024

Human T-cell lymphotropic virus type 1 (HTLV-1) is a neglected pathogen with a heterogeneous global distribution. In low-prevalence areas, diagnostic testing is challenged by limited clinical awareness and the low positive predictive value of screening tests. We retrospectively analyzed 10,891 HTLV-1/2 test results from 7719 patient samples submitted to a specialized laboratory in Germany between 2004 and 2024. Antibody screening had a positive predictive value (PPV) of 31.7% for the Diasorin Murex HTLV I + II assay (39 of 123 reactive samples confirmed) and 34.5% for the Abbott Architect rHTLV-1/2 assay (67 of 194 reactive samples confirmed). Raising the sample/cutoff (s/co) threshold to ≥5 would have increased the PPV to >80%, with only two missed diagnoses per assay. HTLV-1 infection was confirmed in 124 carriers and HTLV-2 infection in three carriers. The vast majority of carriers originated from countries with higher endemicity. A delayed antibody response was observed in HTLV-1 infections via organ transplantation. In four patients with neurological disease, elevated HTLV-1/2-specific antibody indices showed antibody production in cerebrospinal fluid (CSF). HTLV-1 proviral load was measured in 83 carriers, with a median of 20,000 HTLV-1 DNA copies per 10⁶ cells (interquartile range, 4000-119,600). Seventy-four percent (17/23) of high-dose intravenous immunoglobulin (IVIg) preparations contained HTLV-1/2 antibodies, which can lead to false-positive HTLV-1/2 antibody screening results in recipients without underlying infection. Therefore, HTLV-1/2 testing presents two major pitfalls: false-negative results in immunosuppressed patients and false-positive results following IVIg administration.