Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis

Tsetse flies (Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host’s metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma, was recently discovered to reside within multiple tissues of field captured and laboratory colonized tsetse flies grouped in the Palpalis subgenera. In various arthropods, Spiroplasma induces reproductive abnormalities and pathogen protective phenotypes. In tsetse, Spiroplasma infections also induce a protective phenotype by enhancing the fly’s resistance to infection with trypanosomes. However, the potential impact of Spiroplasma on tsetse’s viviparous reproductive physiology remains unknown. Herein we employed high-throughput RNA sequencing and laboratory-based functional assays to better characterize the association between Spiroplasma and the metabolic and reproductive physiologies of G. fuscipes fuscipes (Gff), a prominent vector of human disease. Using field-captured Gff, we discovered that Spiroplasma infection induces changes of sex-biased gene expression in reproductive tissues that may be critical for tsetse’s reproductive fitness. Using a Gff lab line composed of individuals heterogeneously infected with Spiroplasma, we observed that the bacterium and tsetse host compete for finite nutrients, which negatively impact female fecundity by increasing the length of intrauterine larval development. Additionally, we found that when males are infected with Spiroplasma, the motility of their sperm is compromised following transfer to the female spermatheca. As such, Spiroplasma infections appear to adversely impact male reproductive fitness by decreasing the competitiveness of their sperm. Finally, we determined that the bacterium is maternally transmitted to intrauterine larva at a high frequency, while paternal transmission was also noted in a small number of matings. Taken together, our findings indicate that Spiroplasma exerts a negative impact on tsetse fecundity, an outcome that could be exploited for reducing tsetse population size and thus disease transmission.

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis

Tsetse flies ( Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host’s metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma , was recently discovered to reside within multiple tissues of field captured and laboratory colonized tsetse flies grouped in the Palpalis subgenera. In various arthropods, Spiroplasma induces reproductive abnormalities and pathogen protective phenotypes. In tsetse, Spiroplasma infections also induce a protective phenotype by enhancing the fly’s resistance to infection with trypanosomes. However, the potential impact of Spiroplasma on tsetse’s viviparous reproductive physiology remains unknown. Herein we employed high-throughput RNA sequencing and laboratory-based functional assays to better characterize the association between Spiroplasma and the metabolic and reproductive physiologies of G. fuscipes fuscipes ( Gff ), a prominent vector of human disease. Using field-captured Gff , we discovered that Spiroplasma infection induces changes of sex-biased gene expression in reproductive tissues that may be critical for tsetse’s reproductive fitness. Using a Gff line composed of individuals heterogeneously infected with Spiroplasma , we observed that the bacterium and tsetse host compete for finite nutrients, which negatively impact female fecundity by increasing the length of intrauterine larval development. Additionally, we found that when males are infected with Spiroplasma , the motility of their sperm is compromised following transfer to the female spermatheca. As such, Spiroplasma infections appear to adversely impact male reproductive fitness by decreasing the competitiveness of their sperm. Finally, we determined that the bacterium is maternally transmitted to intrauterine larva at a high frequency, while paternal transmission was also noted in a small number of matings. Taken together, our findings indicate that Spiroplasma exerts a negative impact on tsetse fecundity, an outcome that could be exploited for reducing tsetse population size and thus disease transmission.

Modelling the impact of climate change on the distribution and abundance of tsetse in Northern Zimbabwe

Background Climate change is predicted to impact the transmission dynamics of vector-borne diseases. Tsetse flies (Glossina) transmit species of Trypanosoma that cause human and animal African trypanosomiasis. A previous modelling study showed that temperature increases between 1990 and 2017 can explain the observed decline in abundance of tsetse at a single site in the Mana Pools National Park of Zimbabwe. Here, we apply a mechanistic model of tsetse population dynamics to predict how increases in temperature may have changed the distribution and relative abundance of Glossina pallidipes across northern Zimbabwe. Methods Local weather station temperature measurements were previously used to fit the mechanistic model to longitudinal G. pallidipes catch data. To extend the use of the model, we converted MODIS land surface temperature to air temperature, compared the converted temperatures with available weather station data to confirm they aligned, and then re-fitted the mechanistic model using G. pallidipes catch data and air temperature estimates. We projected this fitted model across northern Zimbabwe, using simulations at a 1 km × 1 km spatial resolution, between 2000 to 2016. Results We produced estimates of relative changes in G. pallidipes mortality, larviposition, emergence rates and abundance, for northern Zimbabwe. Our model predicts decreasing tsetse populations within low elevation areas in response to increasing temperature trends during 2000–2016. Conversely, we show that high elevation areas (> 1000 m above sea level), previously considered too cold to sustain tsetse, may now be climatically suitable. Conclusions To our knowledge, the results of this research represent the first regional-scale assessment of temperature related tsetse population dynamics, and the first high spatial-resolution estimates of this metric for northern Zimbabwe. Our results suggest that tsetse abundance may have declined across much of the Zambezi Valley in response to changing climatic conditions during the study period. Future research including empirical studies is planned to improve model accuracy and validate predictions for other field sites in Zimbabwe.

Modelling the impact of climate change on the distribution and abundance of tsetse in Northern Zimbabwe

BackgroundClimate change is predicted to impact the transmission dynamics of vector-borne diseases. Tsetse flies (Glossina) transmit species of Trypanosoma that cause human and animal African trypanosomiasis. A previous modelling study showed that temperature increases between 1990 and 2017 can explain the observed decline in abundance of tsetse at a single site in the Mana Pools National Park of Zimbabwe. Here, we apply a mechanistic model of tsetse population dynamics to predict how increases in temperature may have changed the distribution and relative abundance of Glossina pallidipes across northern Zimbabwe.MethodsLocal weather station temperature measurements were previously used to fit the mechanistic model to longitudinal G. pallidipes catch data. To extend the use of the model, we converted MODIS land surface temperature to air temperature, compared the converted temperatures with available weather station data to confirm they aligned, and then re-fitted the mechanistic model using G. pallidipes catch data and air temperature estimates. We projected this fitted model across northern Zimbabwe, using simulations at a 1 km × 1 km spatial resolution, between 2000 to 2016.ResultsWe produce estimates of relative changes in G. pallidipes mortality, larviposition, emergence rates and abundance, for northern Zimbabwe. Our model predicts decreasing tsetse populations within low elevation areas in response to increasing temperature trends during 2000-2016. Conversely, we show that high elevation areas (>1000 M.A.S.L), previously considered too cold to sustain tsetse, may now be climatically suitable.ConclusionsThe results of this research represent the first regional-scale assessment of temperature related tsetse population dynamics, and the first high spatial-resolution estimates of this metric for northern Zimbabwe. Our results suggest that tsetse abundance may have declined across much of the Zambezi valley in response to changing climatic conditions during the study period. Future research including empirical studies is planned to improve model accuracy and validate predictions for other field sites in Zimbabwe.

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

The weakest link: uncertainty and sensitivity analysis of extinction probability estimates for tsetse (Glossina spp) populations

BackgroundA relatively simple life history allows us to derive an expression for the extinction probability of populations of tsetse, vectors of African sleeping sickness. We present the uncertainty and sensitivity analysis of extinction probability for tsetse population, to offer key insights into parameters in the control/eradication of tsetse populations.MethodsWe represent tsetse population growth as a branching process, and derive closed form estimates of population extinction from that model. Statistical and mathematical techniques are used to analyse the uncertainties in estimating extinction probability, and the sensitivity of the extinction probability to changes in input parameters representing the natural life history and vital dynamics of tsetse populations.ResultsFor fixed values of input parameters, the sensitivity of extinction probability depends on the baseline parameter values. For example, extinction probability is more sensitive to the probability that a female is inseminated by a fertile male when daily pupal mortality is low, whereas the extinction probability is more sensitive to daily mortality rate for adult females when daily pupal mortality, and extinction probabilities, are high. Global uncertainty and sensitivity analysis showed that daily mortality rate for adult females has the highest impact on the extinction probability.ConclusionsThe strong correlation between extinction probability and daily female adult mortality gives a strong argument that control techniques to increase daily female adult mortality may be the single most effective means of ensuring eradication of tsetse population.Author summaryTsetse flies (Glossina spp) are vectors of Trypanosomiasis, a deadly disease commonly called sleeping sickness in humans and nagana in livestock. The relatively simple life history of tsetse enabled us to model its population growth as a stochastic branching process. We derived a closed-form expression for the probability that a population of tsetse goes extinct, as a function of death, birth, development and insemination rates in female tsetse. We analyzed the sensitivity of the extinction probability to the different input parameters, in a bid to identify parameters with the highest impact on extinction probability. This information can, potentially, inform policy direction for tsetse control/elimination. In all the scenarios we considered, the daily mortality rate for adult females has the greatest impact on the magnitude of extinction probability. Our findings suggest that the mortality rate in the adult females is the weakest link in tsetse life history, and this fact should be exploited in achieving tsetse population control, or even elimination.

Extinction probabilities, times to extinction, basic reproduction number and growth rates for tsetse (Glossina spp) populations as a function of temperature

Increases in temperature over recent decades have led to a significant reduction in the populations of tsetse flies (Glossina spp) in parts of the Zambezi Valley of Zimbabwe. If this is true for other parts of Africa, populations of tsetse may actually be going extinct in some parts of the continent. Extinction probabilities for tsetse populations have not so far been estimated as a function of temperature. We develop a time-homogeneous branching process model for situations where tsetse flies live at different levels of fixed temperatures. We derive a probability distribution pk(T) for the number of female offspring an adult female tsetse is expected to produce in her lifetime, as a function of the fixed temperature at which she is living. We show that pk(T) can be expressed as a geometric series: its generating function is therefore a fractional linear type. We obtain expressions for the extinction probability, expected number of female offspring per female tsetse, and time to extinction. No tsetse population can escape extinction if subjected, for extended periods, to temperatures outside the range 16 °C - 32°C. Extinction probability increases more rapidly as temperatures approach and exceed the upper and lower limits. If the number of females is large enough, the population can still survive even at high temperatures (28°C - 31°C). Small decreases or increases in constant temperature in the neighbourhoods of 16°C and 31°C, respectively, can drive tsetse populations to extinction. Further study is needed to estimate extinction probabilities for tsetse populations in field situations where temperatures vary continuously.Author summaryTsetse flies (Glossina spp) are the vectors of the African sleeping sickness. We derived an expression for the extinction probability, and mean time to extinction, of closed populations of the flies experiencing different levels of fixed temperatures. Temperatures play a key role in tsetse population dynamics: no tsetse populations can escape extinction at constant temperatures < 16°C > 32°C. The effect of temperature is more severe if tsetse populations are already depleted. Increasingly high temperatures due to climate change may alter the distribution of tsetse populations in Africa. The continent may witness local extinctions of tsetse populations in some places, and appearances in places hitherto too cold for them.

A Review of Ecological Factors Associated with the Epidemiology of Wildlife Trypanosomiasis in the Luangwa and Zambezi Valley Ecosystems of Zambia

Trypanosomiasis has been endemic in wildlife in Zambia for more than a century. The disease has been associated with neurological disorders in humans. Current conservation strategies by the Zambian government of turning all game reserves into state-protected National Parks (NPs) and game management areas (GMAs) have led to the expansion of the wildlife and tsetse population in the Luangwa and Zambezi valley ecosystem. This ecological niche lies in the common tsetse fly belt that harbors the highest tsetse population density in Southern Africa. Ecological factors such as climate, vegetation and rainfall found in this niche allow for a favorable interplay between wild reservoir hosts and vector tsetse flies. These ecological factors that influence the survival of a wide range of wildlife species provide adequate habitat for tsetse flies thereby supporting the coexistence of disease reservoir hosts and vector tsetse flies leading to prolonged persistence of trypanosomiasis in the area. On the other hand, increase in anthropogenic activities poses a significant threat of reducing the tsetse and wildlife habitat in the area. Herein, we demonstrate that while conservation of wildlife and biodiversity is an important preservation strategy of natural resources, it could serve as a long-term reservoir of wildlife trypanosomiasis.