Mixed inflammatory/regulatory cytokine profile marked by simultaneous raise of interferon-g and interleukin-10 and low frequency of tumour necrosis factor-a + monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagasi infection

We investigated the cytokine profile of cells of the innate immune response and its association with active

BackgroundThe live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine.MethodsNeutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees.Results and discussionThe results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10).ConclusionsThe analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.

Peripheral blood samples of 138 co-habitants from 25 families with recently diagnosed cases of visceral leishmaniasis in the Metropolitan Region of Belo Horizonte, Minas Gerais, Brazil, were analyzed by indirect fluorescent antibody test (IFAT), rK39 and Leishmania chagasi Enzyme Linked Immunosorbent Assay (ELISA), intradermal skin-test and Polymerase Chain Reaction (PCR) over a 12-month period. The cumulative positivity was significantly higher by PCR (29.7%) than by IFAT, rK39 ELISA, L. chagasi ELISA and intradermal skin-test (5.1%, 6.5%, 14.5% and 2.9%, respectively). In addition, the cytokine profile was measured in 16 of the 138 volunteers, of whom eight were asymptomatic carriers and eight were non-infected co-habitants. The innate immunity cells from asymptomatic carriers displayed, upon in vitro antigenic stimulation, a modulated increase in cytokine synthesis that was distinct from that observed in non-infected volunteers. This study suggests that the identification of a large proportion of asymptomatic carriers is facilitated when more than one diagnostic method is applied and that a mixed pattern of immune response is correlated with clinical status of asymptomatic individuals. These observations suggest also that asymptomatic infection by L. chagasi is a frequent event and that control programs could benefit by including this indicator in their interventions.

| HAM/TSP patients experience impaired functional capacity. The use of categorical scales to accurately describe motor ability in these patients has been questioned. Aim: To evaluate the functional capacity of HAM/TSP patients by using the individual tests comprising the GDLAM protocol. Methods: Cross-sectional study carried out in the CHTLV, Salvador, Brazil. Functional capacity was evaluated using the tests of the GDLAM protocol (timed 10-minute walk, getting up from a sitting position, rising from a prone position, getting up from a chair, and moving around the house). Functional classifications were made by comparing patient performance to that of uninfected control individuals. Results: Twenty-four HAM/TSP and 25 healthy individuals were enrolled. Only 75% HAM/TSP patients completed the GDLAM protocol. Six patients failed to perform the RPP test. Timed measurements were significantly higher in the HAM/ TSP patients in comparison to uninfected controls. Conclusion: The use of alternative methods, such as the individual tests comprising the GDLAM protocol, may more accurately assess motor function in HAM/ TSP patients.