Biology subjects

Lehane, M. J.

Publications and source records attributed to Lehane, M. J..

6 recordsLinked to original sources

bioRxiv2024

Impact of a national tsetse control programme to eliminate Gambian sleeping sickness in Uganda: a spatio-temporal modelling study.

IntroductionTsetse flies (Glossina) transmit Trypanosoma brucei gambiense which causes gambiense human African trypanosomiasis (gHAT). As part of national efforts to eliminate gHAT as a public health problem, Uganda implemented a large-scale programme of deploying Tiny Targets, which comprise panels of insecticide-treated material which attract and kill tsetse. At its peak, the programme was the largest tsetse control operation in Africa. Here, we quantify the impact of Tiny Targets and environmental changes on the spatial and temporal patterns of tsetse abundance across north-western Uganda. MethodsWe leverage a 100-month longitudinal dataset detailing Glossina fuscipes fuscipes catches from monitoring traps between October 2010 and December 2019 within seven districts in north-western Uganda. We fitted a boosted regression tree model assessing environmental suitability which was used alongside Tiny Target data to fit a spatio-temporal geostatistical model predicting tsetse abundance across our study area ([~]16,000 km2). We used the spatio-temporal model to quantify the impact of Tiny Targets and environmental changes on the distribution of tsetse, alongside metrics of uncertainty. ResultsEnvironmental suitability across the study area remained relatively constant over time, with suitability being driven largely by elevation and distance to rivers. By performing a counterfactual analysis using the fitted spatio-temporal geostatistical model we show that deployment of Tiny Targets across an area of 4000 km2 reduced the overall abundance of tsetse to low levels (median daily catch = 1.1 tsetse/trap, IQR = 0.85-1.28) with no spatial-temporal locations having high (>10 tsetse/trap/day) numbers of tsetse compared to 18% of locations for the counterfactual. ConclusionsIn Uganda, Tiny Targets reduced the abundance of G. f. fuscipes and maintained tsetse populations at low levels. Our model represents the first spatio-temporal model investigating the effects of a national tsetse control programme. The outputs provide important data for informing next steps for vector-control and surveillance. Key questionsO_ST_ABSWhat is already known on this topic?C_ST_ABSSmall panels of insecticide-treated fabric, called Tiny Targets, are used to attract, and kill riverine tsetse, the vectors of T. b. gambiense which causes gambiense human African trypanosomiasis (gHAT). In large-scale (250-2000 km2) trials conducted in five countries, deployment of Tiny Targets reduced the densities of tsetse by between 60 and >90%. What this study addsWe report an analysis of, and data from, a large-scale ([~]4,000km2) national tsetse control programme, implemented in Uganda to eliminate gHAT as a public health problem. We found that Tiny Targets reduced tsetse abundance across the study period (2011-2019) and maintained densities at low (<1 tsetse/trap/day) levels. We produce maps which detail spatial variances in tsetse abundance in response to vector control. How this study might affect research, practice, or policyIn 2022, Uganda received validation from the World Health Organisation (WHO) that it had eliminated gHAT as a public health problem. The large-scale deployment of Tiny Targets contributed to this achievement. Our findings provide evidence that Tiny Targets are an important intervention for other countries aiming to eliminate gHAT.

ecology↗

bioRxiv2020

Tsetse salivary glycoproteins are modified with paucimannosidic N-glycans, are recognised by C-type lectins and bind to trypanosomes

African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional downregulation of tsetse genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission and the possible role of glycans in insect bloodfeeding, we characterized the N-glycome of tsetse saliva glycoproteins. Tsetse salivary N-glycans were enzymatically released, tagged with either 2-aminobenzamide (2-AB) or procainamide, and analyzed by HILIC-UHPLC-FLR coupled online with positive-ion ESI-LC-MS/MS. We found that the N-glycan profiles of T. brucei-infected and naive tsetse salivary glycoproteins are almost identical, consisting mainly (>50%) of highly processed Man3GlcNAc2 in addition to several other paucimannose, high mannose, and few hybrid-type glycans. In overlay assays, these sugars were differentially recognized by the C-type lectins mannose receptor and DC-SIGN. We also show that salivary glycoproteins bind strongly to the surface of transmissible metacyclic trypanosomes. We suggest that although the repertoire of tsetse salivary N-glycans does not change during a trypanosome infection, the interactions with mannosylated glycoproteins may influence parasite transmission into the vertebrate host.

biochemistry↗

bioRxiv2020

Impact of Tiny Targets on Glossina fuscipes quanzensis, the primary vector of Human African Trypanosomiasis in the Democratic Republic of Congo.

BackgroundOver the past 20 years there has been a >95% reduction in the number of Gambian Human African trypanosomiasis (g-HAT) cases reported globally, largely as a result of large-scale active screening and treatment programmes. There are however still foci where the disease persists, particularly in parts of the Democratic Republic of the Congo (DRC). Additional control efforts such as tsetse control using Tiny Targets may therefore be required to achieve g-HAT elimination goals. The purpose of this study was to evaluate the impact of Tiny Targets within DRC. Methodology/Principal findingsIn 2015-2017, pre- and post-intervention tsetse abundance data were collected from 1,234 unique locations across three neighbouring Health Zones (Yasa Bonga, Mosango, Masi Manimba). Remotely sensed dry season data were combined with pre-intervention tsetse presence/absence data from 332 locations within a species distribution modelling framework to produce a habitat suitability map. The impact of Tiny Targets on the tsetse population was then evaluated by fitting a generalised linear mixed model to the relative fly abundance data collected from 889 post-intervention monitoring sites within Yasa Bonga, with habitat suitability, proximity to the intervention and intervention duration as covariates. Immediately following the introduction of the intervention, we observe a dramatic reduction in fly catches by > 85% (pre-intervention: 0.78 flies/trap/day, 95% CI 0.676-0.900; 3 month post-intervention: 0.11 flies/trap/day, 95% CI 0.070-0.153) which is sustained throughout the study period. Declines in catches were negatively associated with proximity to Tiny Targets, and while habitat suitability is positively associated with abundance its influence is reduced in the presence of the intervention. Conclusions/SignificanceThis study adds to the body of evidence demonstrating the impact of Tiny Targets on tsetse across a range of ecological settings, and further characterises the factors which modify its impact. The habitat suitability maps have the potential to guide the expansion of tsetse control activities in this area. Authors SummaryThere have been large declines in the number of cases of sleeping sickness as a result of programmes that actively screen and treat the at-risk population. Additional control is needed in areas where the disease persists such as parts of the Democratic Republic of Congo (DRC). The disease is transmitted by tsetse flies, and reducing the tsetse population using Tiny Targets has been shown to control the disease in other countries. Extensive tsetse monitoring has been undertaken in one Health Zone in DRC where Tiny Targets have been deployed. We used these data to gain a better understanding of tsetse habitat, to produce habitat suitability maps, and to subsequently measure the impact of Tiny Targets on the tsetse population. We show that tsetse flies are largely found along rivers and surrounding densely vegetated habitat, with there being a positive relationship between habitat suitability and the number of flies caught. Once Tiny Targets were introduced, the number of flies caught in monitoring traps decreased by >85%, with habitat suitability at the trap location, and the proximity of the trap to the nearest Tiny Target influencing the size of the effect of the intervention. This study adds to the body of evidence demonstrating the impact of Tiny Targets on tsetse distribution in addition to providing information that can be used to guide the expansion of tsetse control activities in this area.

ecology↗

bioRxiv2019

The Glossina Genome Cluster: Comparative Genomic Analysis of the Vectors of African Trypanosomes

BackgroundTsetse flies (Glossina sp.) are the sole vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood specific diet by both sexes and obligate bacterial symbiosis. This work describes comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans (G.m. morsitans), G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes) and Fusca (G. brevipalpis) which represent different habitats, host preferences and vectorial capacity. ResultsGenomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex linked scaffolds show increased rates of female specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse specific genes are enriched in protease, odorant binding and helicase activities. Lactation associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other characterized insects. Vision associated Rhodopsin genes show conservation of motion detection/tracking functions and significant variance in the Rhodopsin detecting colors in the blue wavelength ranges. ConclusionsExpanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies.

genomics↗

bioRxiv2019

Trypanosoma brucei colonises the tsetse gut via an immature peritrophic matrix in the proventriculus

The peritrophic matrix (PM) of haematophagus insects is a chitinous structure that surrounds the bloodmeal, forming a protective barrier against oral pathogens and abrasive particles. To establish an infection in the tsetse midgut, Trypanosoma brucei must colonise the ectoperitrophic space (ES), located between the PM and gut epithelium. Although unproven, it is generally accepted that trypanosomes reach the ES by directly penetrating the PM in the anterior midgut. Here we revisited this event by employing novel fluorescence and electron microscopy methodologies and found that instead, trypanosomes reach the ES via the newly secreted PM in the tsetse proventriculus. Within this model, parasites colonising the proventriculus can either migrate to the ES or become trapped within PM layers forming cysts that move along the entire gut as the PM gets remodelled. Early proventricular colonisation appears to be promoted by unidentified factors in trypanosome-infected blood, resulting in higher salivary gland infections and potentially increasing parasite transmission.

microbiology↗

bioRxiv2018

The crystal structure and localization of Trypanosoma brucei invariant surface glycoproteins suggest a more permissive VSG coat in the tsetse-transmitted metacyclic stage

Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside the tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, nothing is known about expression of invariant surface antigens by the metacyclic stage. Proteomic analysis of saliva from T. brucei-infected flies revealed a novel family of hypothetical GPI-anchored surface proteins herein named Metacyclic Invariant Surface Proteins (MISP). MISP are encoded by five homolog genes and share ~80% protein identity. The crystal structure of MISP N-terminus at 1.82 [A] resolution revealed a triple helical bundle that shares key features with other trypanosome surface proteins. However, molecular modelling combined with live fluorescent microscopy suggest that MISP N-termini are extended above the metacyclic VSG coat, exposing immunogenic epitopes. Collectively, we suggest that the metacyclic cell surface architecture appears more permissive than bloodstream forms in terms of expression of invariant GPI-anchored glycoproteins, which could be exploited for the development of novel vaccines against African trypanosomiases.

microbiology↗