Factors Affecting the Propensity of Tsetse Flies to Enter Houses and Attack Humans Inside: Increased Risk of Sleeping Sickness in Warmer Climates

Background Sleeping sickness, or human African trypanosomiasis, is caused by two species of Trypanosoma brucei that are transmitted to humans by tsetse flies (Glossina spp.) when these insects take a bloodmeal. It is commonly assumed that humans must enter the normal woodland habitat of the flies to become infected, but recent studies found that tsetse frequently attack humans inside buildings. Factors affecting human/tsetse contact in buildings need identification. Methodology/Principal Findings In Zimbabwe, tsetse were allowed access to a house via an open door. Those in the house at sunset, and those alighting on humans in the house during the day, were caught using hand-nets. Total catches were unaffected by: (i) the presence of humans in the house and at the door, (ii) wood smoke from a fire inside the house or just outside, (iii) open windows, and (iv) chemicals simulating the odor of cattle or of humans. Catches increased about 10-fold with rising ambient temperatures, and during the hottest months the proportion of the total catch that was taken from the humans increased from 5% to 13%. Of the tsetse caught from humans, 62% consisted of female G. morsitans morstans and both sexes of G. pallidipes, i.e., the group of tsetse that normally alight little on humans. Some of the tsetse caught were old enough to be effective vectors. Conclusion/Significance Present results confirm previous suggestions that buildings provide a distinctive and important venue for transmission of sleeping sickness, especially since the normal repellence of humans and smoke seems poorly effective in such places. The importance of the venue would be increased in warmer climates

Identification of the area sampled by traps: A modelling study with tsetse

Background Sampling with traps provides the most common means of investigating the abundance, composition and condition of tsetse populations. It is thus important to know the size of the area from which the samples originate, but that topic is poorly understood. Methods and principal findings The topic was clarified with the aid of a simple deterministic model of the mobility, births and deaths of tsetse. The model assessed how the sampled area changed according to variations in the numbers, arrangement and catching efficiency of traps deployed for different periods in a large block of homogeneous habitat subject to different levels of fly mortality. The greatest impacts on the size of the sampled area are produced by the flies’ mean daily step length and the duration of trapping. There is little effect of trap type. The daily death rate of adult flies is unimportant unless tsetse control measures increase the mortality several times above the low natural rates. Conclusions Formulae for predicting the probability that any given captured fly originated from various areas around the trap are produced. Using a mean daily step length (d) of 395m, typical of a savannah species of tsetse, any fly caught by a single trap in a 5-day trapping period could be regarded, with roughly 95% confidence, as originating from within a distance of 1.3km of the trap that is from an area of 5.3km2

Modeling the Control of Trypanosomiasis Using Trypanocides or Insecticide-Treated Livestock

In Uganda, cattle are an important reservoir for Trypanosoma brucei rhodesiense, the causative agent of Rhodesian sleeping sickness (human African trypanosomiasis), transmitted by tsetse flies Glossina fuscipes fuscipes, which feed on cattle, humans, and wild vertebrates, particularly monitor lizards. Trypanosomiasis can be controlled by treating livestock with trypanocides or insecticide – killing parasites or vectors, respectively. Mathematical modeling of trypanosomiasis was used to compare the impact of drug- and insecticide-based interventions on R0 with varying densities of cattle, humans and wild hosts. Intervention impact changes with the number of cattle treated and the proportion of bloodmeals tsetse take from cattle. R0 was always reduced more by treating cattle with insecticide rather than trypanocides. In the absence of wild hosts, the model suggests that control of sleeping sickness (R0<1) could be achieved by treating ∼65% of cattle with trypanocides or ∼20% with insecticide. Required coverage increases as wild mammals provide increasing proportion of tsetse bloodmeals: if 60% of non-human bloodmeals are from wild hosts then all cattle have to be treated with insecticide. Conversely, it is reduced if lizards, which do not harbor trypanosomes, are important hosts and/or if insecticides are used at a scale where tsetse numbers decline

Negative density-dependent dispersal in tsetse (Glossina spp): An artefact of inappropriate analysis

Vector-borne disease control relies on efficient vector surveillance, mostly carried out using traps whose number and locations are often determined by expert opinion rather than a rigorous quantitative sampling design. In this work we propose a framework for ecological sampling design which in its preliminary stages can take into account environmental conditions obtained from open data (i.e. remote sensing and meteorological stations) not necessarily designed for ecological analysis. These environmental data are used to delimit the area into ecologically homogeneous strata. By employing Bayesian statistics within a model-based sampling design, the traps are deployed among the strata using a mixture of random and grid locations which allows balancing predictions and model-fitting accuracies. Sample sizes and the effect of ecological strata on sample sizes are estimated from previous mosquito sampling campaigns open data. Notably, we found that a configuration of 30 locations with four households each (120 samples) will have a similar accuracy in the predictions of mosquito abundance as 200 random samples. In addition, we show that random sampling independently from ecological strata, produces biased estimates of the mosquito abundance. Finally, we propose standardizing reporting of sampling designs to allow transparency and repetition/re-use in subsequent sampling campaigns

Modelled impact of Tiny Targets on the distribution and abundance of riverine tsetse

Background The insecticide-treated baits known as Tiny Targets are one of the cheapest means of controlling riverine species of tsetse flies, the vectors of the trypanosomes that cause sleeping sickness in humans. Models of the efficacy of these targets deployed near rivers are potentially useful in planning control campaigns and highlighting the principals involved. Methods and principal findings To evaluate the potential of models, we produced a simple non-seasonal model of the births, deaths, mobility and aging of tsetse, and we programmed it to simulate the impact of seven years of target use against the tsetse, Glossina fuscipes fuscipes, in the riverine habitats of NW Uganda. Particular attention was given to demonstrating that the model could explain three matters of interest: (i) good control can be achieved despite the degradation of targets, (ii) local elimination of tsetse is impossible if invasion sources are not tackled, and (iii)with invasion and target degradation it is difficult to detect any effect of control on the age structure of the tsetse population. Conclusions Despite its simplifications, the model can assist planning and teaching, but allowance should be made for any complications due to seasonality and management challenges associated with greater scale

Tumor Repression of VCaP Xenografts by a Pyrrole-Imidazole Polyamide

Pyrrole-imidazole (Py-Im) polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE)-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model. In addition to the effects on AR regulated transcription, RNA-seq analysis revealed inhibition of topoisomerase-DNA binding as a potential mechanism that contributes to the antitumor effects of polyamides in cell culture and in xenografts. These studies support the therapeutic potential of Py-Im polyamides to target multiple aspects of transcriptional regulation in prostate cancers without genotoxic stress

HIV decline in Zimbabwe due to reductions in risky sex? Evidence from a comprehensive epidemiological review

Background Recent data from antenatal clinic (ANC) surveillance and general population surveys suggest substantial declines in human immunodeficiency virus (HIV) prevalence in Zimbabwe. We assessed the contributions of rising mortality, falling HIV incidence and sexual behaviour change to the decline in HIV prevalence. Methods Comprehensive review and secondary analysis of national and local sources on trends in HIV prevalence, HIV incidence, mortality and sexual behaviour covering the period 1985-2007. Results HIV prevalence fell in Zimbabwe over the past decade (national estimates: from 29.3% in 1997 to 15.6% in 2007). National census and survey estimates, vital registration data from Harare and Bulawayo, and prospective local population survey data from eastern Zimbabwe showed substantial rises in mortality during the 1990s levelling off after 2000. Direct estimates of HIV incidence in male factory workers and women attending pre- and post-natal clinics, trends in HIV prevalence in 15-24-year-olds, and back-calculation estimates based on the vital registration data from Harare indicated that HIV incidence may have peaked in the early 1990s and fallen during the 1990s. Household survey data showed reductions in numbers reporting casual partners from the late 1990s and high condom use in non-regular partnerships between 1998 and 2007. Conclusions These findings provide the first convincing evidence of an HIV decline accelerated by changes in sexual behaviour in a southern African country. However, in 2007, one in every seven adults in Zimbabwe was still infected with a life-threatening virus and mortality rates remained at crisis leve

Minimally Invasive Mitral Valve Surgery III: Training and Robotic-Assisted Approaches.

Minimally invasive mitral valve operations are increasingly common in the United States, but robotic-assisted approaches have not been widely adopted for a variety of reasons. This expert opinion reviews the state of the art and defines best practices, training, and techniques for developing a successful robotics program

Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection

Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery