The epidemiological, clinical and laboratory features of 13 cases of neuroparacoccidioidomycosis (NPCM) were analysed. All patients were men, with a mean age of 41.6 years. The lungs were involved in 11 cases (84.6%) and only two cases had mycosis limited to the central nervous system. Co-morbidity was observed in four patients (malignant neoplasm in three and diabetes mellitus in one). The most frequent neurological manifestations were paresis (eight cases), headache (five cases) and gait disturbance (four cases). Neuroimaging diagnosis showed a predominance of multiple round lesions with ring enhancement following contrast medium injection. Lesions were seen in the brain hemispheres (nine cases), thalamus (nine cases), cerebellum (four cases), brainstem (four cases) and spinal cord (four cases). Most cases responded well to therapy. Lesions with enhancement following contrast medium injection persisted in four patients for a period of 6 months to 8 years. These findings emphasize the importance of considering NPCM in the differential diagnosis of brain and spinal cord lesions in endemic areas of paracoccidioidomycosis.

Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of this study was to investigate the intrafamilial transmission of HTLV-1 among Japanese immigrants and their descendants living in a non-endemic area of central Brazil. Six families were investigated. Thirty-seven relatives of the six index cases were tested by ELISA for the presence of anti-HTLV antibodies, and the positive cases were confirmed by Western blot. HTLV-1 isolates were genotyped by partial nucleotide sequencing (5' LTR) of the proviral DNA. All individuals, including index cases and relatives, were asymptomatic. In five families, at least one relative was infected with HTLV-1. In all, eight (22%) relatives (one mother, four wives, one brother, and two brothers-in-law) were infected. However, none of the 22 individuals under 55 years of age was infected. In each family, the HTLV-1 sequences from the relatives were identical or almost identical to that of the index case, except in one case. Pedigrees of the families, together with socio-demographic data of the HTLV-1 infected individuals, strongly suggested the occurrence of both vertical and sexual transmission, with breastfeeding as an important risk factor. Whether and why the virus transmission is less effective among younger generations deserves to be further investigated.

Aims: To evaluate the potential use of synthetic oligonucleotides as a standard curve for proviral load (PVL) of human T-cell leukaemia virus type 1 (HTLV-1) quantification in peripheral blood mononuclear cells (PBMC) of HTLV-1infected individuals by quantitative real-time polymerase chain reaction (qPCR) analysis. Methods and results: Synthetic oligonucleotides based on HTLV-1 genome were customized to use as a standard curve. Twelve anti-HTLV-1-positive samples with known HTLV-1 PVL, previously quantified by qPCR assay using TARL-2 cells as a conventional standard curve, were submitted to the new protocol. The proviral quantification levels had a high concordance with qPCR results using a conventional standard curve. The results demonstrate that the conventional standard curve can be replaced by a synthetic standard curve due to its ability to quantification based on the linearity and qPCR efficiency and similar results with a validated qPCR assay using a conventional standard curve. Conclusions: Synthetic oligonucleotides standard curves could be a very useful tool on HTLV-1 diagnosis and absolute HTLV-1 PVL quantification. Significance and Impact of the Study: HTLV-1 PVL determination using synthetic oligonucleotides standard curve by qPCR could be a helpful alternative for the laboratories that monitor infected patients as an important prognostic factor in HTLV-1-associated diseases progression. Also, it can decrease costs and overcome the biological limitations of the plasmid curve.

The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic background to better understand the low frequency of HAM/TSP in Japanese HTLV-1-infected individuals.

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