In Brazil, preventive chemotherapy targeting soil-transmitted helminthiasis is being scaled-up. Hence, spatially explicit estimates of infection risks providing information about the current situation are needed to guide interventions. Available high-resolution national model-based estimates either rely on analyses of data restricted to a given period of time, or on historical data collected over a longer period. While efforts have been made to take into account the spatial structure of the data in the modelling approach, little emphasis has been placed on the temporal dimension. We extracted georeferenced survey data on the prevalence of infection with soil-transmitted helminths (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura) in Brazil from the Global Neglected Tropical Diseases (GNTD) database. Selection of the most important predictors of infection risk was carried out using a Bayesian geostatistical approach and temporal models that address non-linearity and correlation of the explanatory variables. The spatial process was estimated through a predictive process approximation. Spatio-temporal models were built on the selected predictors with integrated nested Laplace approximation using stochastic partial differential equations. Our models revealed that, over the past 20 years, the risk of soil-transmitted helminth infection has decreased in Brazil, mainly because of the reduction of A. lumbricoides and hookworm infections. From 2010 onwards, we estimate that the infection prevalences with A. lumbricoides, hookworm and T. trichiura are 3.6%, 1.7% and 1.4%, respectively. We also provide a map highlighting municipalities in need of preventive chemotherapy, based on a predicted soil-transmitted helminth infection risk in excess of 20%. The need for treatments in the school-aged population at the municipality level was estimated at 1.8 million doses of anthelminthic tablets per year. The analysis of the spatio-temporal aspect of the risk of infection with soil-transmitted helminths contributes to a better understanding of the evolution of risk over time. Risk estimates provide the soil-transmitted helminthiasis control programme in Brazil with useful benchmark information for prioritising and improving spatial and temporal targeting of interventions.

Background: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of theL. (V.) braziliensisisolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance ofL. (V.) braziliensisto NO and nonresponsiveness to antimony therapy and cytokine production.Methods: We evaluated thein vitrotoxicity of NO against the promastigotes stages ofL. (V.) braziliensisisolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants fromLeishmaniainfected macrophage were used to measure TNF-α and IL-10 levels.Results: Using NaNO₂(pH 5.0) as the NO source,L. (V.) braziliensisisolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) thanL. (V.) braziliensisisolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistantL. (V.) braziliensisisolated from responsive and refractory patients. NO-resistantL. (V.) braziliensisisolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptibleL. (V.) braziliensisisolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistantL. (V.) braziliensisas compared to macrophages infected with NO-susceptibleL. (V.) braziliensis(p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels.Conclusion: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.

Background: L. braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. Wound healing neutrophil (PMN) and macrophage responses made following the bite of the vector sand fly contribute to disease progression in mice. To look at the interplay between PMN and macrophages in disease progression in humans we asked whether polymorphisms at genes that regulate their infiltration or function are associated with different clinical phenotypes. Specifically, CXCR1 (IL8RA) and CXCR2 (IL8RB) are receptors for chemokines that attract PMN to inflammatory sites. They lie 30-260 kb upstream of SLC11A1, a gene known primarily for its role in regulating macrophage activation, resistance to leishmaniasis, and wound healing responses in mice, but also known to be expressed in PMN, macrophages and dendritic cells. Methods: Polymorphic variants at CXCR1, CXCR2 and SLC11A1 were analysed using Taqman or ABI fragment separation technologies in cases (60 CL; 60 ML), unrelated controls (n = 120), and multicase families (104 nuclear families; 88 ML, 250 CL cases) from Brazil. Logistic regression analysis, family-based association testing (FBAT) and haplotype analysis (TRANSMIT) were performed. Results: Case-control analysis showed association between the common C allele (OR 2.38; 95% CI 1.23-4.57; P = 0.009) of CXCR1_rs2854386 and CL, supported by family-based (FBAT; Z score 2.002; P = 0.045) analysis (104 nuclear families; 88 ML, 250 CL cases). ML associated with the rarer G allele (Z score 1.999; P = 0.046). CL associated with a 3' insertion/deletion polymorphism at SLC11A1 (Z score 2.549; P = 0.011). Conclusions: The study supports roles for CXCR1 and SLC11A1 in the outcome of L. braziliensis infection in humans. Slc11a1 does not influence cutaneous lesion development following needle injection of Leishmania in mice, suggesting that its role here might relate to the action of PMN, macrophage and/or dendritic cells in the wound healing response to the sand fly bite. Together with the CXCR1 association, the data are consistent with hypotheses relating to the possible role of PMN in initiation of a lesion following the delivery of parasites via the sand fly bite. Association of ML with the rare derived G allele suggests that PMN also have an important positive role to play in preventing this form of the disease.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis occurs predominantly in adult males. Herein, we compare the clinical presentation and the response to antimony therapy of CL in children versus adults. Participants included 571 patients with CL; of these, 129 were children (age ≤ 12 years). Cure was defined as the complete healing of ulcer in the absence of raised borders at day 90 after initiation of therapy. Failure was defined by the presence of an active ulcer or a scar with elevated borders at day 90. In comparison with adults, children had shorter duration of illness, more lesions in the head, and smaller ulcers. Risk factors for therapeutic failure were younger age, shorter duration of disease, higher number of lesions, and larger size of the biggest ulcer. When age was categorized in ≤ 12-year-olds (children versus adults), it predicted therapeutic failure with statistical significance at day 60 but not at day 90. In conclusion, our data indicate that there are significant differences in the clinical presentation of CL between children and adults. Physicians caring for children with CL should be aware that lesions may take longer to heal and remain alert for the possibility of higher odds of therapeutic failure in this group.