Ex-ante Benefit-Cost Analysis of the Elimination of a Glossina palpalis gambiensis Population in the Niayes of Senegal

Background

In 2005, the Government of Senegal embarked on a campaign to eliminate a Glossina palpalis gambiensis population from the Niayes area (∼1000 km²) under the umbrella of the Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC). The project was considered an ecologically sound approach to intensify cattle production. The elimination strategy includes a suppression phase using insecticide impregnated targets and cattle, and an elimination phase using the sterile insect technique, necessary to eliminate tsetse in this area.

Methodology/Principal Findings

Three main cattle farming systems were identified: a traditional system using trypanotolerant cattle and two “improved” systems using more productive cattle breeds focusing on milk and meat production. In improved farming systems herd size was 45% lower and annual cattle sales were €250 (s.d. 513) per head as compared to €74 (s.d. 38) per head in traditional farming systems (p<10⁻³). Tsetse distribution significantly impacted the occurrence of these farming systems (p = 0.001), with 34% (s.d. 4%) and 6% (s.d. 4%) of improved systems in the tsetse-free and tsetse-infested areas, respectively. We calculated the potential increases of cattle sales as a result of tsetse elimination considering two scenarios, i.e. a conservative scenario with a 2% annual replacement rate from traditional to improved systems after elimination, and a more realistic scenario with an increased replacement rate of 10% five years after elimination. The final annual increase of cattle sales was estimated at ∼€2800/km² for a total cost of the elimination campaign reaching ∼€6400/km².

Conclusion/Significance

Despite its high cost, the benefit-cost analysis indicated that the project was highly cost-effective, with Internal Rates of Return (IRR) of 9.8% and 19.1% and payback periods of 18 and 13 years for the two scenarios, respectively. In addition to an increase in farmers'' income, the benefits of tsetse elimination include a reduction of grazing pressure on the ecosystems.     

Treating Cattle to Protect People? Impact of Footbath Insecticide Treatment on Tsetse Density in Chad

Background

In Chad, several species of tsetse flies (Genus: Glossina ) transmit African animal trypanosomoses (AAT), which represents a major obstacle to cattle rearing, and sleeping sickness, which impacts public health. After the failure of past interventions to eradicate tsetse, the government of Chad is now looking for other approaches that integrate cost-effective intervention techniques, which can be applied by the stake holders to control tsetse-transmitted trypanosomoses in a sustainable manner. The present study thus attempted to assess the efficacy of restricted application of insecticides to cattle leg extremities using footbaths for controlling Glossina m. submorsitans, G . tachinoides and G . f . fuscipes in southern Chad.

Methodology/Principal Findings

Two sites were included, one close to the historical human African trypanosomiasis (HAT) focus of Moundou and the other to the active foci of Bodo and Moissala. At both sites, a treated and an untreated herd were compared. In the treatment sites, cattle were treated on a regular basis using a formulation of deltamethrin 0.005% (67 to 98 cattle were treated in one of the sites and 88 to 102 in the other one). For each herd, tsetse densities were monthly monitored using 7 biconical traps set along the river and beside the cattle pen from February to December 2009. The impact of footbath treatment on tsetse populations was strong (p < 10^-3) with a reduction of 80% in total tsetse catches by the end of the 6-month footbath treatment.

Conclusions/Significance

The impact of footbath treatment as a vector control tool within an integrated strategy to manage AAT and HAT is discussed in the framework of the “One Health” concept. Like other techniques based on the treatment of cattle, this technology should be used under controlled conditions, in order to avoid the development of insecticide and acaricide resistance in tsetse and tick populations, respectively.     

Contrasting population structures of two vectors of African trypanosomoses in Burkina Faso: consequences for control

Background

African animal trypanosomosis is a major obstacle to the development of more efficient and sustainable livestock production systems in West Africa. Riverine tsetse species such as Glossina palpalis gambiensis Vanderplank and Glossina tachinoides Westwood are the major vectors. A wide variety of control tactics is available to manage these vectors, but their removal will in most cases only be sustainable if the control effort is targeting an entire tsetse population within a circumscribed area.

Methodology/Principal Findings

In the present study, genetic variation at microsatellite DNA loci was used to examine the population structure of G. p. gambiensis and G. tachinoides inhabiting four adjacent river basins in Burkina Faso, i.e. the Mouhoun, the Comoé, the Niger and the Sissili River Basins. Isolation by distance was significant for both species across river basins, and dispersal of G. tachinoides was ∼3 times higher than that of G. p. gambiensis. Thus, the data presented indicate that no strong barriers to gene flow exists between riverine tsetse populations in adjacent river basins, especially so for G. tachinoides.

Conclusions/Significance

Therefore, potential re-invasion of flies from adjacent river basins will have to be prevented by establishing buffer zones between the Mouhoun and the other river basin(s), in the framework of the PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign) eradication project that is presently targeting the northern part of the Mouhoun River Basin. We argue that these genetic analyses should always be part of the baseline data collection before any tsetse control project is initiated.     

Prospects for Developing Odour Baits To Control Glossina fuscipes spp., the Major Vector of Human African Trypanosomiasis

We are attempting to develop cost-effective control methods for the important vector of sleeping sickness, Glossina fuscipes spp. Responses of the tsetse flies Glossina fuscipes fuscipes (in Kenya) and G. f. quanzensis (in Democratic Republic of Congo) to natural host odours are reported. Arrangements of electric nets were used to assess the effect of cattle-, human- and pig-odour on (1) the numbers of tsetse attracted to the odour source and (2) the proportion of flies that landed on a black target (1×1 m). In addition responses to monitor lizard (Varanus niloticus) were assessed in Kenya. The effects of all four odours on the proportion of tsetse that entered a biconical trap were also determined. Sources of natural host odour were produced by placing live hosts in a tent or metal hut (volumes≈16 m³) from which the air was exhausted at ∼2000 L/min. Odours from cattle, pigs and humans had no significant effect on attraction of G. f. fuscipes but lizard odour doubled the catch (P<0.05). Similarly, mammalian odours had no significant effect on landing or trap entry whereas lizard odour increased these responses significantly: landing responses increased significantly by 22% for males and 10% for females; the increase in trap efficiency was relatively slight (5–10%) and not always significant. For G. f. quanzensis, only pig odour had a consistent effect, doubling the catch of females attracted to the source and increasing the landing response for females by ∼15%. Dispensing CO₂ at doses equivalent to natural hosts suggested that the response of G. f. fuscipes to lizard odour was not due to CO₂. For G. f. quanzensis, pig odour and CO₂ attracted similar numbers of tsetse, but CO₂ had no material effect on the landing response. The results suggest that identifying kairomones present in lizard odour for G. f. fuscipes and pig odour for G. f. quanzensis may improve the performance of targets for controlling these species.     

Use of vector control to protect people from sleeping sickness in the focus of Bonon (Côte d’Ivoire)

BackgroundGambian human African trypanosomiasis (gHAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies (Glossina). In Côte d’Ivoire, Bonon is the most important focus of gHAT, with 325 cases diagnosed from 2000 to 2015 and efforts against gHAT have relied largely on mass screening and treatment of human cases. We assessed whether the addition of tsetse control by deploying Tiny Targets offers benefit to sole reliance on the screen-and-treat strategy.Methodology and principal findingsIn 2015, we performed a census of the human population of the Bonon focus, followed by an exhaustive entomological survey at 278 sites. After a public sensitization campaign, ~2000 Tiny Targets were deployed across an area of 130 km² in February of 2016, deployment was repeated annually in the same month of 2017 and 2018. The intervention’s impact on tsetse was evaluated using a network of 30 traps which were operated for 48 hours at three-month intervals from March 2016 to December 2018. A second comprehensive entomological survey was performed in December 2018 with traps deployed at 274 of the sites used in 2015. Sub-samples of tsetse were dissected and examined microscopically for presence of trypanosomes. The census recorded 26,697 inhabitants residing in 331 settlements. Prior to the deployment of targets, the mean catch of tsetse from the 30 monitoring traps was 12.75 tsetse/trap (5.047–32.203, 95%CI), i.e. 6.4 tsetse/trap/day. Following the deployment of Tiny Targets, mean catches ranged between 0.06 (0.016–0.260, 95%CI) and 0.55 (0.166–1.794, 95%CI) tsetse/trap, i.e. 0.03–0.28 tsetse/trap/day. During the final extensive survey performed in December 2018, 52 tsetse were caught compared to 1,909 in 2015, with 11.6% (5/43) and 23.1% (101/437) infected with Trypanosoma respectively.ConclusionsThe annual deployment of Tiny Targets in the gHAT focus of Bonon reduced the density of Glossina palpalis palpalis by >95%. Tiny Targets offer a powerful addition to current strategies towards eliminating gHAT from Côte d’Ivoire.     

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy

Background

Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT.

Methods and Findings

The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km² field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km²). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings.

Interpretation

The Ugandan census suggests population density in the HAT foci is approximately 500 per km². The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised.     

Identification of a Tsetse Fly Salivary Protein with Dual Inhibitory Action on Human Platelet Aggregation

Background

Tsetse flies (Glossina sp.), the African trypanosome vectors, rely on anti-hemostatic compounds for efficient blood feeding. Despite their medical importance, very few salivary proteins have been characterized and functionally annotated.

Methodology/Principal Findings

Here we report on the functional characterisation of a 5′nucleotidase-related (5′Nuc) saliva protein of the tsetse fly Glossina morsitans morsitans. This protein is encoded by a 1668 bp cDNA corresponding at the genomic level with a single-copy 4 kb gene that is exclusively transcribed in the tsetse salivary gland tissue. The encoded 5′Nuc protein is a soluble 65 kDa glycosylated compound of tsetse saliva with a dual anti-hemostatic action that relies on its combined apyrase activity and fibrinogen receptor (GPIIb/IIIa) antagonistic properties. Experimental evidence is based on the biochemical and functional characterization of recombinant protein and on the successful silencing of the 5′nuc translation in the salivary gland by RNA interference (RNAi). Refolding of a 5′Nuc/SUMO-fusion protein yielded an active apyrase enzyme with K_m and V_max values of 43±4 µM and 684±49 nmol Pi/min×mg for ATPase and 49±11 µM and 177±37 nmol Pi/min×mg for the ADPase activity. In addition, recombinant 5′Nuc was found to bind to GPIIb/IIIa with an apparent K_D of 92±25 nM. Consistent with these features, 5′Nuc potently inhibited ADP-induced thrombocyte aggregation and even caused disaggregation of ADP-triggered human platelets. The importance of 5′Nuc for the tsetse fly hematophagy was further illustrated by specific RNAi that reduced the anti-thrombotic activities in saliva by approximately 50% resulting in a disturbed blood feeding process.

Conclusions/Significance

These data show that this 5′nucleotidase-related apyrase exhibits GPIIb/IIIa antagonistic properties and represents a key thromboregulatory compound of tsetse fly saliva.     

Abdominal Regional Fat Distribution on MRI Correlates with Cholecystolithiasis

Aims

To determine whether abdominal regional fat distribution pattern on MRI is correlated with cholecystolithiasis.

Methods

Magnetic resonance imaging (MRI) of 163 patients with cholecystolithiasis and 163 non-cholecystolithiasis control subjects admitted to our institution between March 2011 and September 2013 were included in this cross-sectional evaluation. There were 98 women and 65 men in cholecystolithiasis group with an average age of 57±16 years (range 25–86 years). There were 87 women and 76 men in the control group with an average age of 41±16 years (range 14–77 years). Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and total abdominal adipose tissue (TAT) of all the subjects at navel level were measured on abdominal MRI. According to the visceral adipose area (cut-off point VAT = 100 cm²), study subjects were divided into 1) increased accumulation of intra-abdominal fat and 2) normal distribution of intra-abdominal fat. Logistic regression was used to assess the association of fat with the presence of cholecystolithiasis, adjusted for age and sex.

Results

The incidence of increased intra-abdominal fat accumulation in the cholecystolithiasis group was significantly higher than that of the control group (P = 0.000). After adjusting for age and sex, cholecystolithiasis was associated with a one standard deviation increment in the waist circumference (WC) (OR = 1.44; 95%CI: 1.01,1.93; p = 0.00), VAT (OR = 4.26; 95%CI: 1.85,5.29; p = 0.00), VAT/SAT (OR = 8.66; 95%CI: 1.60,12.63; p = 0.00), and VAT/TAT (OR = 6.73; 95%CI: 4.24,12.18; p = 0.00), but not with fat content in the abdominal subcutaneous fat (p = 0.19).

Conclusions

The visceral adipose tissue and distribution proportion of abdominal adipose tissue are correlates of cholecystolithiasis.     

Impact of Health Education on Soil-Transmitted Helminth Infections in Schoolchildren of the Peruvian Amazon: A Cluster-Randomized Controlled Trial

Background

To control soil-transmitted helminth (STH) infections, the World Health Organization recommends school-based deworming programs with a health hygiene education component. The effect of such health hygiene interventions, however, has not been adequately studied. The objective of the present study was to determine the effectiveness of a health hygiene education intervention on the occurrence of STH re-infection four months post-de-worming.

Methodology/Principal Findings

An open-label pair-matched cluster-randomized trial was conducted in Grade 5 schoolchildren of 18 primary schools (9 intervention and 9 control) in the Peruvian Amazon. Baseline assessment included interview with a pre-tested questionnaire and collection of single stool specimens that were examined using the single Kato-Katz thick smear. All schoolchildren were then treated with single-dose albendazole (400 mg). Schoolchildren in intervention schools then received 1) an initial one hour in-class activity on health hygiene and sanitation and 30-minute refresher activities every two weeks over four months; and 2) a half-day workshop for teachers and principals, while children in control schools did not. Four months later, STH infection was re-assessed in all schools by laboratory technologists blinded to intervention status. From April 21–October 20, 2010, a total of 1,089 schoolchildren (518 and 571 from intervention and control schools, respectively) participated in this study. Intervention children scored significantly higher on all aspects of a test of STH-related knowledge compared with control children (aOR = 18·4; 95% CI: 12·7 to 26·6). The intensity of Ascaris lumbricoides infection at follow-up was statistically significantly lower (by 58%) in children in intervention schools compared with children in control schools (aIRR = 0·42; 95% CI = 0·21 to 0·85). No significant changes in hookworm or Trichuris trichiura intensity were observed.

Conclusions/Significance

A school-based health hygiene education intervention was effective in increasing STH knowledge and in reducing Ascaris lumbricoides infection. The benefits of school-based periodic deworming programs are likely to be enhanced when a sustained health hygiene education intervention is integrated into school curricula.     

The Smart Aerial Release Machine,a Universal System for Applying the Sterile Insect Technique

Background

Beyond insecticides, alternative methods to control insect pests for agriculture and vectors of diseases are needed. Management strategies involving the mass-release of living control agents have been developed, including genetic control with sterile insects and biological control with parasitoids, for which aerial release of insects is often required. Aerial release in genetic control programmes often involves the use of chilled sterile insects, which can improve dispersal, survival and competitiveness of sterile males. Currently available means of aerially releasing chilled fruit flies are however insufficiently precise to ensure homogeneous distribution at low release rates and no device is available for tsetse.

Methodology/Principal Findings

Here we present the smart aerial release machine, a new design by the Mubarqui Company, based on the use of vibrating conveyors. The machine is controlled through Bluetooth by a tablet with Android Operating System including a completely automatic guidance and navigation system (MaxNav software). The tablet is also connected to an online relational database facilitating the preparation of flight schedules and automatic storage of flight reports. The new machine was compared with a conveyor release machine in Mexico using two fruit flies species (Anastrepha ludens and Ceratitis capitata) and we obtained better dispersal homogeneity (% of positive traps, p<0.001) for both species and better recapture rates for Anastrepha ludens (p<0.001), especially at low release densities (<1500 per ha). We also demonstrated that the machine can replace paper boxes for aerial release of tsetse in Senegal.

Conclusions/Significance

This technology limits damages to insects and allows a large range of release rates from 10 flies/km² for tsetse flies up to 600 000 flies/km² for fruit flies. The potential of this machine to release other species like mosquitoes is discussed. Plans and operating of the machine are provided to allow its use worldwide.     

Community Acceptance of Tsetse Control Baits: A Qualitative Study in Arua District,North West Uganda

Background

There is renewed vigour in efforts to eliminate neglected tropical diseases including sleeping sickness (human African trypanosomiasis or HAT), including attempts to develop more cost-effective methods of tsetse control. In the West Nile region of Uganda, newly designed insecticide-treated targets are being deployed over an area of ∼500 km². The operational area covers villages where tsetse control has not been conducted previously. The effectiveness of the targets will depend, in part, on their acceptance by the local community.

Methodology/Principal Findings

We assessed knowledge, perceptions and acceptance of tsetse baits (traps, targets) in villages where they had or had not been used previously. We conducted sixteen focus group discussions with male and female participants in eight villages across Arua District. Discussions were audio recorded, translated and transcribed. We used thematic analysis to compare the views of both groups and identify salient themes.

Conclusions/Significance

Despite the villages being less than 10 km apart, community members perceived deployed baits very differently. Villagers who had never seen traps before expressed fear, anxiety and panic when they first encountered them. This was related to associations with witchcraft and “ghosts from the river” which are traditionally linked with physical or mental illness, death and misfortune. By contrast, villagers living in areas where traps had been used previously had positive attitudes towards them and were fully aware of their purpose and benefits. The latter group reported that they had similar negative perceptions when tsetse control interventions first started a decade ago. Our results suggest that despite their proximity, acceptance of traps varies markedly between villages and this is related to the duration of experience with tsetse control programs. The success of community-based interventions against tsetse will therefore depend on early engagements with communities and carefully designed sensitization campaigns that reach all communities, especially those living in areas new to such interventions.     

Climate,Cattle Rearing Systems and African Animal Trypanosomosis Risk in Burkina Faso

Background

In sub-Saharan countries infested by tsetse flies, African Animal Trypanosomosis (AAT) is considered as the main pathological constraint to cattle breeding. Africa has known a strong climatic change and its population was multiplied by four during the last half-century. The aim of this study was to characterize the impact of production practices and climate on tsetse occurrence and abundance, and the associated prevalence of AAT in Burkina Faso.

Methodology/Principal Findings

Four sites were selected along a South-north transect of increasing aridity. The study combines parasitological and entomological surveys. For the parasitological aspect, blood samples were collected from 1,041 cattle selected through a stratified sampling procedure including location and livestock management system (long transhumance, short transhumance, sedentary). Parasitological and serological prevalence specific to livestock management systems show a gradual increase from the Sahelian to the Sudano-Guinean area (P<0.05). Livestock management system had also a significant impact on parasitological prevalence (P<0.05). Tsetse diversity, apparent densities and their infection rates overall decreased with aridity, from four species, an apparent density of 53.1 flies/trap/day and an infection rate of 13.7% to an absence at the northern edge of the transect, where the density and diversity of other biting flies were on the contrary highest (p<0.001).

Conclusions/Significance

The climatic pressure clearly had a negative impact on tsetse abundance and AAT risk. However, the persistency of tsetse habitats along the Mouhoun river loop maintains a high risk of cyclical transmission of T. vivax. Moreover, an “epidemic mechanical livestock trypanosomosis” cycle is likely to occur in the northern site, where trypanosomes are brought in by cattle transhuming from the tsetse infested area and are locally transmitted by mechanical vectors. In Burkina Faso, the impact of tsetse thus extends to a buffer area around their distribution belt, corresponding to the herd transhumance radius.     

Prospects for the Development of Odour Baits to Control the Tsetse Flies Glossina tachinoides and G. palpalis s.l.

Field studies were done of the responses of Glossina palpalis palpalis in Côte d''Ivoire, and G. p. gambiensis and G. tachinoides in Burkina Faso, to odours from humans, cattle and pigs. Responses were measured either by baiting (1.) biconical traps or (2.) electrocuting black targets with natural host odours. The catch of G. tachinoides from traps was significantly enhanced (∼5×) by odour from cattle but not humans. In contrast, catches from electric targets showed inconsistent results. For G. p. gambiensis both human and cattle odour increased (>2×) the trap catch significantly but not the catch from electric targets. For G. p. palpalis, odours from pigs and humans increased (∼5×) the numbers of tsetse attracted to the vicinity of the odour source but had little effect on landing or trap-entry. For G. tachinoides a blend of POCA (P = 3-n-propylphenol; O = 1-octen-3-ol; C = 4-methylphenol; A = acetone) alone or synthetic cattle odour (acetone, 1-octen-3-ol, 4-methylphenol and 3-n-propylphenol with carbon dioxide) consistently caught more tsetse than natural cattle odour. For G. p. gambiensis, POCA consistently increased catches from both traps and targets. For G. p. palpalis, doses of carbon dioxide similar to those produced by a host resulted in similar increases in attraction. Baiting traps with super-normal (∼500 mg/h) doses of acetone also consistently produced significant but slight (∼1.6×) increases in catches of male flies. The results suggest that odour-baited traps and insecticide-treated targets could assist the AU-Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) in its current efforts to monitor and control Palpalis group tsetse in West Africa. For all three species, only ∼50% of the flies attracted to the vicinity of the trap were actually caught by it, suggesting that better traps might be developed by an analysis of the visual responses and identification of any semiochemicals involved in short-range interaction.     

Towards Monitoring Biodiversity in Amazonian Forests: How Regular Samples Capture Meso-Scale Altitudinal Variation in 25 km2 Plots

Background

Ecological monitoring and sampling optima are context and location specific. Novel applications (e.g. biodiversity monitoring for environmental service payments) call for renewed efforts to establish reliable and robust monitoring in biodiversity rich areas. As there is little information on the distribution of biodiversity across the Amazon basin, we used altitude as a proxy for biological variables to test whether meso-scale variation can be adequately represented by different sample sizes in a standardized, regular-coverage sampling arrangement.

Methodology/Principal Findings

We used Shuttle-Radar-Topography-Mission digital elevation values to evaluate if the regular sampling arrangement in standard RAPELD (rapid assessments (“RAP”) over the long-term (LTER [“PELD” in Portuguese])) grids captured patters in meso-scale spatial variation. The adequacy of different sample sizes (n = 4 to 120) were examined within 32,325 km²/3,232,500 ha (1293×25 km² sample areas) distributed across the legal Brazilian Amazon. Kolmogorov-Smirnov-tests, correlation and root-mean-square-error were used to measure sample representativeness, similarity and accuracy respectively. Trends and thresholds of these responses in relation to sample size and standard-deviation were modeled using Generalized-Additive-Models and conditional-inference-trees respectively. We found that a regular arrangement of 30 samples captured the distribution of altitude values within these areas. Sample size was more important than sample standard deviation for representativeness and similarity. In contrast, accuracy was more strongly influenced by sample standard deviation. Additionally, analysis of spatially interpolated data showed that spatial patterns in altitude were also recovered within areas using a regular arrangement of 30 samples.

Conclusions/Significance

Our findings show that the logistically feasible sample used in the RAPELD system successfully recovers meso-scale altitudinal patterns. This suggests that the sample size and regular arrangement may also be generally appropriate for quantifying spatial patterns in biodiversity at similar scales across at least 90% (≈5 million km²) of the Brazilian Amazon.     

Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease

Rationale

There is growing evidence that obstructive sleep apnea is associated with coronary artery disease. However, there are no data on the course of coronary stenosis after percutaneous coronary intervention in patients with obstructive sleep apnea.

Objectives

To determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention.

Methods

78 patients with coronary artery disease who underwent elective percutaneous coronary intervention were divided in 2 groups: 43 patients with an apnea hypopnea – Index < 10/h (group I) and 35 pt. with obstructive sleep apnea and an AHI > 10/h (group II). Late lumen loss, a marker of restenosis, was determined using quantitative coronary angiography after 6.9 ± 3.1 months.

Main results

Angiographic restenosis (>50% luminal diameter), was present in 6 (14%) of group I and in 9 (25%) of group II (p = 0.11). Late lumen loss was significant higher in pt. with an AHI > 10/h (0.7 ± 0.69 mm vs. 0.38 ± 0.37 mm, p = 0.01). Among these 35 patients, 21(60%) used their CPAP devices regularly. There was a marginally lower late lumen loss in treated patients, nevertheless, this difference did not reach statistical significance (0.57 ± 0.47 mm vs. 0.99 ± 0.86 mm, p = 0.08). There was no difference in late lumen loss between treated patients and the group I (p = 0.206).

Conclusion

In summary, patients with OSA and coronary artery disease have a higher degree of late lumen loss, which is a marker of restenosis and vessel remodeling after elective percutaneous intervention.     

Influence of Oxygen on Wound Healing Dynamics: Assessment in a Novel Wound Mouse Model under a Variable Oxygen Environment

Introduction

Although oxygen is essential for the wound healing process, tissue hypoxia is known to stimulate angiogenesis. To explore these inconsistent findings, we estimated the influence of the oxygen environment on wound healing with our original model.

Methods

Experiment 1 (Establishment of the model): To modify the topical oxygen tension, oxygen impermeable (polyvinylidene chloride) and permeable (polymethylpentene) membranes were applied to symmetrical excisional wounds in ddy mice (n = 6). Oxygen tension under the membrane was quantified with a device using photo-quenching technique. Experiment 2 (Influence of oxygen environment on wound healing): The wound area, granulation thickness and vascular density were analyzed under different oxygen environments (n = 24).

Results

Experiment 1: The permeable group maintained equivalent oxygen level to atmosphere (114.1±29.8 mmHg on day 7), while the impermeable group showed extremely low oxygen tension (5.72±2.99 mmHg on day 7). Accordingly, each group was defined as the normoxia group and the hypoxia group. Experiment 2: Percent decrease in wound size was significantly enhanced in the normoxia group (11.1±1.66% on day 7) in comparison with the hypoxia group (27.6±3.47% on day 7). The normoxia group showed significantly thicker granulation tissue than the hypoxia group (491.8±243.2 vs. 295.3±180.9 µm). Contrarily, the vascular density of the hypoxia group significantly increased on day 7 (0.046±0.025 vs. 0.011±0.008 mm²/mm²).

Conclusions

Our original model successfully controlled local oxygen concentration around the wound, and the hypoxic wounds showed increased angiogenesis but with a smaller amount of granulation tissue and delayed wound closure. Enhanced neovascularization in the hypoxic group likely implies compensative response to an insufficient ambient oxygen supply.     

Is the Even Distribution of Insecticide-Treated Cattle Essential for Tsetse Control? Modelling the Impact of Baits in Heterogeneous Environments

Background

Eliminating Rhodesian sleeping sickness, the zoonotic form of Human African Trypanosomiasis, can be achieved only through interventions against the vectors, species of tsetse (Glossina). The use of insecticide-treated cattle is the most cost-effective method of controlling tsetse but its impact might be compromised by the patchy distribution of livestock. A deterministic simulation model was used to analyse the effects of spatial heterogeneities in habitat and baits (insecticide-treated cattle and targets) on the distribution and abundance of tsetse.

Methodology/Principal Findings

The simulated area comprised an operational block extending 32 km from an area of good habitat from which tsetse might invade. Within the operational block, habitat comprised good areas mixed with poor ones where survival probabilities and population densities were lower. In good habitat, the natural daily mortalities of adults averaged 6.14% for males and 3.07% for females; the population grew 8.4× in a year following a 90% reduction in densities of adults and pupae, but expired when the population density of males was reduced to <0.1/km²; daily movement of adults averaged 249 m for males and 367 m for females. Baits were placed throughout the operational area, or patchily to simulate uneven distributions of cattle and targets. Gaps of 2–3 km between baits were inconsequential provided the average imposed mortality per km² across the entire operational area was maintained. Leaving gaps 5–7 km wide inside an area where baits killed 10% per day delayed effective control by 4–11 years. Corrective measures that put a few baits within the gaps were more effective than deploying extra baits on the edges.

Conclusions/Significance

The uneven distribution of cattle within settled areas is unlikely to compromise the impact of insecticide-treated cattle on tsetse. However, where areas of >3 km wide are cattle-free then insecticide-treated targets should be deployed to compensate for the lack of cattle.     

Amiodarone Inhibits Apamin-Sensitive Potassium Currents

Background

Apamin sensitive potassium current (I _KAS), carried by the type 2 small conductance Ca²⁺-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.

Objective

To test the hypothesis that amiodarone inhibits I _KAS in human embryonic kidney 293 (HEK-293) cells.

Methods

We used the patch-clamp technique to study I _KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.

Results

Amiodarone inhibited I_KAS in a dose-dependent manner (IC₅₀, 2.67±0.25 µM with 1 µM intrapipette Ca²⁺). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6±3.1% of I_KAS induced with 1 µM intrapipette Ca²⁺ (n = 3). I_KAS inhibition by amiodarone was not voltage-dependent, but was Ca²⁺-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I _KAS induced with 1 µM Ca²⁺ (n = 4), and 16.4±4.9% with 250 nM Ca²⁺ (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca²⁺ dependent inhibition of I _KAS.

Conclusion

Both amiodarone and desethylamiodarone inhibit I _KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca²⁺ concentration. SK2 current inhibition may in part underlie amiodarone''s effects in preventing electrical storm in failing ventricles.     

Effects of Sodium Bicarbonate on High-Intensity Endurance Performance in Cyclists: A Double-Blind,Randomized Cross-Over Trial

Background

While the ergogenic effect of sodium bicarbonate (BICA) on short-term, sprint-type performance has been repeatedly demonstrated, little is known about its effectiveness during prolonged high-intensity exercise in well-trained athletes. Therefore, this study aims to examine the influence of BICA on performance during exhaustive, high-intensity endurance cycling.

Methods

This was a single-center, double-blind, randomized, placebo-controlled cross-over study. Twenty-one well-trained cyclists (mean ± SD: age 24±8 y, BMI 21.3±1.7, VO_2peak 67.3±9.8 ml·kg⁻¹·min⁻¹) were randomly allocated to sequences of following interventions: oral ingestion of 0.3 g·kg⁻¹ BICA or 4 g of sodium chloride (placebo), respectively. One h after ingestion subjects exercised for 30 min at 95% of the individual anaerobic threshold (IAT) followed by 110% IAT until exhaustion. Prior to these constant load tests stepwise incremental exercise tests were conducted under both conditions to determine IAT and VO_2peak. Analysis of blood gas parameters, blood lactate (BLa) and gas exchange measurements were conducted before, during and after the tests. The main outcome measure was the time to exhaustion in the constant load test.

Results

Cycling time to exhaustion was improved (p<0.05) under BICA (49.5±11.5 min) compared with placebo (45.0±9.5 min). No differences in maximal or sub-maximal measures of performance were observed during stepwise incremental tests. BICA ingestion resulted in an increased pH, bicarbonate concentration and BLa before, throughout and after both exercise testing modes.

Conclusion

The results suggest that ingestion of BICA may improve prolonged, high-intensity cycling performance.

Trial Registration

German Clinical Trials Register (DRKS) DRKS00006198.     

Assessing the Effect of an Integrated Control Strategy for Schistosomiasis Japonica Emphasizing Bovines in a Marshland Area of Hubei Province,China: A Cluster Randomized Trial

Introduction

More than 80% of schistosomiasis patients in China live in the lake and marshland regions. The purpose of our study is to assess the effect of a comprehensive strategy to control transmission of Schistosoma japonicum in marshland regions.

Methodology/Principal Findings

In a cluster randomized controlled trial, we implemented an integrated control strategy in twelve villages from 2009 through 2011 in Gong''an County, Hubei Province. The routine interventions included praziquantel chemotherapy and controlling snails, and were implemented in all villages. New interventions, mainly consisting of building fences to limit the grazing area for bovines, building safe pastures for grazing, improving the residents'' health conditions and facilities, were only implemented in six intervention villages. Results showed that the rate of S. japonicum infection in humans, bovines, snails, cow dung and mice in the intervention group decreased from 3.41% in 2008 to 0.81% in 2011, 3.3% to none, 11 of 6,219 to none, 3.9% to none and 31.7% to 1.7%, respectively (P<0.001 for all comparisons). In contrast, there were no statistically significant reductions of S. japonicum infection in humans, bovines and snails from 2008 to 2011 in the control group (P>0.05 for all comparisons). Moreover, a generalized linear model showed that there was a higher infection risk in humans in the control group than in the intervention group (OR = 1.250, P = 0.001) and an overall significant downward trend in infection risk during the study period.

Conclusions/Significance

The integrated control strategy, designed to reduce the role of bovines and humans as sources of S. japonicum infection, was highly effective in controlling the transmission of S. japonicum in marshland regions in China.

Trial Registration

Chinese Clinical Trial Registry ChiCTR-PRC-12002405.