Major depressive disorder (MDD) associated with chronic neglected tropical diseases (NTDs) has been identified as a significant and overlooked contributor to overall disease burden. Cutaneous leishmaniasis (CL) is one of the most prevalent and stigmatising NTDs, with an incidence of around 1 million new cases of active CL infection annually. However, the characteristic residual scarring (inactive CL) following almost all cases of active CL has only recently been recognised as part of the CL disease spectrum due to its lasting psychosocial impact. We performed a multi-language systematic review of the psychosocial impact of active and inactive CL. We estimated inactive CL (iCL) prevalence for the first time using reported WHO active CL (aCL) incidence data that were adjusted for life expectancy and underreporting. We then quantified the disability (YLD) burden of co-morbid MDD in CL using MDD disability weights at three severity levels. Overall, we identified 29 studies of CL psychological impact from 5 WHO regions, representing 11 of the 50 highest burden countries for CL. We conservatively calculated the disability burden of co-morbid MDD in CL to be 1.9 million YLDs, which equaled the overall (DALY) disease burden (assuming no excess mortality in depressed CL patients). Thus, upon inclusion of co-morbid MDD alone in both active and inactive CL, the DALY burden was seven times higher than the latest 2016 Global Burden of Disease study estimates, which notably omitted both psychological impact and inactive CL. Failure to include co-morbid MDD and the lasting sequelae of chronic NTDs, as exemplified by CL, leads to large underestimates of overall disease burden. Cutaneous leishmaniasis is a highly prevalent vector-borne disease affecting large parts of Latin America and the Middle East, as well as parts of Northern Africa. There are several types of Cutaneous leishmaniasis, almost all of which have an active phase characterized by a disfiguring lesion (typically on exposed parts of the body), which then becomes a permanent scar (the inactive phase). We recently published an article highlighting the impact of the inactive scarring phase of CL on affected individuals, which is associated with high levels of stigma. Nevertheless, this aspect of the disease is not considered in its own right when calculating the overall disease burden by the Global Burden of Disease (GBD) Studies. In this article we estimate the prevalence of depression (major depressive disorder) in cutaneous leishmaniasis, in both the active and inactive forms. We then show the contribution of inactive CL to the overall disease burden estimates when included, which is due to the large psychological impact it has on those affected by it. We also highlight the importance of further similar efforts for other NTDs which have a chronic course, and which are also not sufficiently included in disease burden calculations at present.

Blood feeding evolved independently in worms, arthropods and mammals. Among the adaptations to this peculiar diet, these animals developed an armament of salivary molecules that disarm their host's anti-bleeding defenses (hemostasis), inflammatory and immune reactions. Recent sialotranscriptome analyses (from the Greek sialo = saliva) of blood feeding insects and ticks have revealed that the saliva contains hundreds of polypeptides, many unique to their genus or family. Adult tsetse flies feed exclusively on vertebrate blood and are important vectors of human and animal diseases. Thus far, only limited information exists regarding the Glossina sialome, or any other fly belonging to the Hippoboscidae. As part of the effort to sequence the genome of Glossina morsitans morsitans, several organ specific, high quality normalized cDNA libraries have been constructed, from which over 20,000 ESTs from an adult salivary gland library were sequenced. These ESTs have been assembled using previously described ESTs from the fat body and midgut libraries of the same fly, thus totaling 62,251 ESTs, which have been assembled into 16,743 clusters (8,506 of which had one or more EST from the salivary gland library). Coding sequences were obtained for 2,509 novel proteins, 1,792 of which had at least one EST expressed in the salivary glands. Despite library normalization, 59 transcripts were overrepresented in the salivary library indicating high levels of expression. This work presents a detailed analysis of the salivary protein families identified. Protein expression was confirmed by 2D gel electrophoresis, enzymatic digestion and mass spectrometry. Concurrently, an initial attempt to determine the immunogenic properties of selected salivary proteins was undertaken. The sialome of G. m. morsitans contains over 250 proteins that are possibly associated with blood feeding. This set includes alleles of previously described gene products, reveals new evidence that several salivary proteins are multigenic and identifies at least seven new polypeptide families unique to Glossina. Most of these proteins have no known function and thus, provide a discovery platform for the identification of novel pharmacologically active compounds, innovative vector-based vaccine targets, and immunological markers of vector exposure.

War, infection, and disease have always made intimate bedfellows, with disease recrudescence characterizing most conflict zones (1). Recently, increasing violence from civil war and terrorist activity in the Middle East has caused the largest human displacement in decades. A neglected consequence of this tragedy has been the reemergence of a cutaneous leishmaniasis epidemic

Tsetse flies serve as biological vectors for several species of African trypanosomes. In order to survive, proliferate and establish a midgut infection, trypanosomes must cross the tsetse fly peritrophic matrix (PM), which is an acellular gut lining surrounding the blood meal. Crossing of this multi-layered structure occurs at least twice during parasite migration and development, but the mechanism of how trypanosomes do so is not understood. In order to better comprehend the molecular events surrounding trypanosome penetration of the tsetse PM, a mass spectrometry-based approach was applied to investigate the PM protein composition using Glossina morsitans morsitans as a model organism. PMs from male teneral (young, unfed) flies were dissected, solubilised in urea/SDS buffer and the proteins precipitated with cold acetone/TCA. The PM proteins were either subjected to an in-solution tryptic digestion or fractionated on 1D SDS-PAGE, and the resulting bands digested using trypsin. The tryptic fragments from both preparations were purified and analysed by LC-MS/MS. Overall, nearly 300 proteins were identified from both analyses, several of those containing signature Chitin Binding Domains (CBD), including novel peritrophins and peritrophin-like glycoproteins, which are essential in maintaining PM architecture and may act as trypanosome adhesins. Furthermore, 27 proteins from the tsetse secondary endosymbiont, Sodalis glossinidius, were also identified, suggesting this bacterium is probably in close association with the tsetse PM. To our knowledge this is the first report on the protein composition of teneral G. m. morsitans, an important vector of African trypanosomes. Further functional analyses of these proteins will lead to a better understanding of the tsetse physiology and may help identify potential molecular targets to block trypanosome development within the tsetse. African trypanosomes are transmitted by the haematophagous tsetse vector. For transmission to occur, bloodmeal ingested trypanosomes must overcome numerous barriers imposed by the fly. The first obstacle is the crossing of peritrophic matrix (PM), a cell-free structure that protects the midgut epithelial cells from coming under attack by the hosts' digestive enzymes, aids in water retention and helps prevent harmful pathogens from establishing a systemic infection. Trypanosomes cross the tsetse PM at least twice in their development but how they do so remains to be elucidated. Despite being a recognised barrier to trypanosome infections, there is limited knowledge of the molecular components of the tsetse PM. In this study we identified nearly 300 PM proteins using two mass spectrometry approaches. Several of the identified components were peritrophins, which are a key group of glycoproteins essential for PM integrity. In addition, we detected proteins from Sodalis glossinidius, a commensal bacterium linked to increased susceptibility to trypanosome infection in tsetse. Our study provides the first comprehensive identification of proteins from the tsetse PM, which provides a starting point for research into potential targets for vector control.