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.     

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.     

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.     

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.     

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.     

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.     

The cost of tsetse control using ‘Tiny Targets’ in the sleeping sickness endemic forest area of Bonon in Côte d’Ivoire: Implications for comparing costs across different settings

BackgroundWork to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d’Ivoire from 2016 to 2017.Methodology/Principal findingsSome 2000 targets were placed throughout the main gHAT transmission area of 130 km² at a density of 14.9 per km². The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km² protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations.Conclusions/SignificanceThe cost of tsetse control per km² of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km² treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected.     

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.     

Effect of Antioxidant Supplementation on Exercise-Induced Cardiac Troponin Release in Cyclists: A Randomized Trial

Background

Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists.

Methods

Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O₂ uptake 60±5 mL·kg⁻¹·min⁻¹, W_max 5.4±0.5 W·kg⁻¹; mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min).

Results

The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0–4.2) to 4.7 ng/L (IQR 3.7–6.7), immediately post-exercise (p<0.001). Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg⁻¹. However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p = 0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation.

Conclusion

Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01241877","term_id":"NCT01241877"}}NCT01241877     

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.     

Enhanced In Vivo Activity of Cefditoren in Pre-Immunized Mice against Penicillin-Resistant S. pneumoniae (Serotypes 6B, 19F and 23F) in a Sepsis Model

Background

Specific antibodies are likely to be present before S. pneumoniae infection. We explored cefditoren (CDN) total and free values of serum concentrations exceeding the MIC (t>MIC) related to efficacy in a mice sepsis model, and the effect of specific gammaglobulins on in-vitro phagocytosis and in-vivo efficacy.

Methodology/Principal Findings

We used three pneumococcal isolates (serotype, MIC of CDN): Strain 1 (6B, 1 µg/ml), Strain 2 (19F, 2 µg/ml) and Strain 3 (23F, 4 µg/ml). Hyperimmune serum (HS) was obtained from mice immunized with heat-inactivated strains. In-vitro, phagocytosis by HS diluted 1/10 in presence/absence of sub-inhibitory concentrations was measured by flow cytometry including fluorescent bacteria and a neutrophil cell line. In-vivo dose-ranging experiments with HS (dilutions 1/2–1/16) and CDN (6.25 mg/kg–100 mg/kg tid for 48 h) were performed to determine the minimal protective dilution/dose (highest survival) and the non-protective highest dilution/dose (highest mortality: HS-np dilution and CDN-np dose) over 7 days. Efficacy of CDN-np in animals pre-immunized with HS-np (combined strategy) was explored and blood bacterial clearance determined. The CDN measured protein binding was 86.9%. In-vitro, CDN significantly increased phagocytosis (vs. HS 1/10). In non pre-immunized animals, t>MIC values for CDN of ≈35% (total) and ≈19% (free) were associated with 100% survival. Significant differences in survival were found between HS-np alone (≤20%) or CDN-np alone (≤20%) vs. the combined strategy (90%, 60% and 60% for Stains 1, 2 and 3), with t>MIC (total/free) of 22.8%/14.3%, 26.8%/16.0%, and 22.4%/12.7% for Strains 1, 2 and 3, respectively. Prior to the second dose (8 h), median bacterial counts were significantly lower in animals surviving vs. dead at day 7.

Conclusions/Significance

In mice (CDN protein binding similar to humans) total t>MIC values of ≈35% (≈19% free) were efficacious, with a decrease in the required values in pre-immunized animals. This reinforces that immunoprotection to overcome resistance may provide lifesaving strategies.     

Prevalence of Buruli Ulcer in Akonolinga Health District,Cameroon: Results of a Cross Sectional Survey

Background

Buruli ulcer (BU) is a chronic, indolent necrotizing disease of the skin and underlying tissues caused by Mycobacterium ulcerans, which may result in functional incapacity. In 2002, Médecins Sans Frontières (MSF) opened a BU programme in Akonolinga Hospital, Cameroon, offering antibiotic treatment, surgery and general medical care. Six hundred patients have been treated in the project to date. However, due to the nature of the disease and its stigmatization, determining the exact prevalence and burden of disease is difficult and current estimates may not reflect the magnitude of the problem. The objectives of this survey were to estimate the prevalence of BU in the health district of Akonolinga, describe the geographic extension of the highly endemic area within the health district, and determine the programme coverage and its geographical distribution.

Methodology/Principal Findings

We conducted a cross-sectional population survey using centric systematic area sampling (CSAS). A 15×15 km grid (quadrats of 225 km²) was overlaid on a map of Akonolinga district with its position chosen to maximize the area covered by the survey. Quadrats were selected if more than 50% of the quadrat was inside of the health district. The chiefdom located closest to the centre of each quadrat was selected and Buruli cases were identified using an active case finding strategy (the sensitivity of the strategy was estimated by capture-recapture). WHO-case definitions were used for nodules, plaque, ulcer, oedema and sequelae. Out of a total population of 103,000 inhabitants, 26,679 were surveyed within the twenty quadrats. Sensitivity of the case finding strategy was estimated to be 84% (95%CI 54–97%). The overall prevalence was 0.47% (n = 105) for all cases including sequelae and 0.25% (n = 56) for active stages of the disease. Five quadrats had a high prevalence of >0.6% to 0.9%, 5 a prevalence >0.3% to 0.6% and 10 quadrats <0.3%. The quadrats with the high prevalence were situated along the rivers Nyong and Mfoumou. Overall coverage of the project was 18% (12–27%) for all cases and 16% (9–18%) for active cases, but was limited to the quadrats neighbouring Akonolinga Hospital.

Conclusions/Significance

Prevalence was highest in the area neighbouring the Nyong River. Coverage was limited to the area close to the hospital and efforts have to be made to increase access to care in the high prevalence areas. Use of the CSAS method was particularly useful for project planning and to identify priority areas of intervention. An added benefit of the method is that the survey procedure incorporated an awareness campaign, providing information about the disease and treatment to the population.     

Radiotherapy dose enhancement using BNCT in conventional LINACs high-energy treatment: Simulation and experiment

Aim

To employ the thermal neutron background that affects the patient during a traditional high-energy radiotherapy treatment for BNCT (Boron Neutron Capture Therapy) in order to enhance radiotherapy effectiveness.

Background

Conventional high-energy (15–25 MV) linear accelerators (LINACs) for radiotherapy produce fast secondary neutrons in the gantry with a mean energy of about 1 MeV due to (γ, n) reaction. This neutron flux, isotropically distributed, is considered as an unavoidable undesired dose during the treatment. Considering the moderating effect of human body, a thermal neutron fluence is localized in the tumour area: this neutron background could be employed for BNCT by previously administering ¹⁰B-Phenyl-Alanine (¹⁰BPA) to the patient.

Materials and methods

Monte Carlo simulations (MCNP4B-GN code) were performed to estimate the total amount of neutrons outside and inside human body during a traditional X-ray radiotherapy treatment.Moreover, a simplified tissue equivalent anthropomorphic phantom was used together with bubble detectors for thermal and fast neutron to evaluate the moderation effect of human body.

Results

Simulation and experimental results confirm the thermal neutron background during radiotherapy of 1.55E07 cm⁻² Gy⁻¹.The BNCT equivalent dose delivered at 4 cm depth in phantom is 1.5 mGy-eq/Gy, that is about 3 Gy-eq (4% of X-rays dose) for a 70 Gy IMRT treatment.

Conclusions

The thermal neutron component during a traditional high-energy radiotherapy treatment could produce a localized BNCT effect, with a localized therapeutic dose enhancement, corresponding to 4% or more of photon dose, following tumour characteristics. This BNCT additional dose could thus improve radiotherapy, acting as a localized radio-sensitizer.     

Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people

Background

Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population.

Methods and Findings

As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm² and 126.9±55.2 cm² in men (P = 0.045) and 120.0±46.7 cm² and 211.8±65.9 cm² in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area.

Conclusions

Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution.     

The Potential of a High Protein-Low Carbohydrate Diet to Preserve Intrahepatic Triglyceride Content in Healthy Humans

Background

Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG) content induced by acute hypercaloric high-fat and high-fructose diets in humans.

Objective

To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC) diet compared with an iso-energetic high carbohydrate-low protein (HCLP) diet on IHTG content in healthy non-obese subjects, at a constant body weight.

Design

Seven men and nine women [mean ± SD age: 24±5 y; BMI: 22.9±2.1 kg/m²] were randomly allocated to a HPLC [30/35/35% of energy (En%) from protein/carbohydrate/fat] or a HCLP (5/60/35 En%) diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by ¹H-magnetic resonance spectroscopy before and after the dietary intervention.

Results

IHTG content changed in different directions with the HPLC (CH₂H₂O: 0.23±0.17 to 0.20±0.10; IHTG%: 0.25±0.20% to 0.22±0.11%) compared with the HCLP diet (CH₂H₂O: 0.34±0.20 vs. 0.38±0.21; IHTG%: 0.38±0.22% vs. 0.43±0.24%), which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055).

Conclusions

A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01551238","term_id":"NCT01551238"}}NCT01551238     

Early Impact of a National Multi-Faceted Road Safety Intervention Program in Mexico: Results of a Time-Series Analysis

Background

In January 2008, a national multifaceted road safety intervention program (IMESEVI) funded by the Bloomberg Philanthropies was launched in Mexico. Two years later in 2010, IMESEVI was refocused as part of a 10-country international consortium demonstration project (IMESEVI/RS10). We evaluate the initial effects of each phase of the road safety intervention project on numbers of RT crashes, injuries and deaths in Mexico and in the two main target cities of Guadalajara-Zapopan and León.

Methods

An interrupted time series analysis using autoregressive integrated moving average (ARIMA) modeling was performed using monthly data of rates of RT crashes and injuries (police data), as well as deaths (mortality system data) from 1999–2011 with dummy variables representing each intervention phase.

Results

In the period following the first intervention phase at the country level and in the city of León, the rate of RT crashes decreased significantly (p<0.05). Notably, following the second intervention phase although there was no reduction at the country level, there has been a decrease in the RT crash rate in both Guadalajara-Zapopan (p = 0.029) and in León (p = 0.029). There were no significant differences in the RT injury or death rates following either intervention phase in either city.

Conclusion

These initial results suggest that a multi-faceted road safety intervention program appears to be effective in reducing road crashes in a middle-income country setting. Further analysis is needed to differentiate the effects of various interventions, and to determine what other economic and political factors might have affected this change.     

A pilot crossover study: effects of an intervention using an activity monitor with computerized game functions on physical activity and body composition

Background

Wearing an activity monitor as a motivational tool and incorporating a behavior-based reward system or a computerized game element might have a synergistic effect on an increase in daily physical activity, thereby inducing body fat reduction. This pilot crossover study aimed to examine the effects of a short-term lifestyle intervention using an activity monitor with computerized game functions on physical activity and body composition.

Methods

Twenty healthy volunteers (31 ± 3 years) participated in a 12-week crossover study. The participants were randomly assigned to either Group A (a 6-week game intervention followed by a 6-week normal intervention) or Group B (a 6-week normal intervention followed by a 6-week game intervention). The participants wore both a normal activity monitor (Lifecorder EX) and an activity monitor with computerized game functions (Yuuhokei) during the game intervention, whereas they only wore a normal activity monitor during the normal intervention. Before, during, and after the intervention, body composition was assessed.

Results

Significantly more daily steps were recorded for the game intervention than for the normal intervention (10,520 ± 562 versus 8,711 ± 523 steps/day, P < 0.01). The participants performed significantly more physical activity at an intensity of ≥ 3 metabolic equivalents (METs) in the game intervention than in the normal intervention (3.1 ± 0.2 versus 2.4 ± 0.2 METs · hour/day, P < 0.01). Although body mass and fat were significantly reduced in both periods (P < 0.01), the difference in body fat reduction was significantly greater in the game intervention than in the normal intervention (P < 0.05).

Conclusions

A short-term intervention using an activity monitor with computerized game functions increases physical activity and reduces body fat more effectively than an intervention using a standard activity monitor.     

Comparison of the Effects of Flexion and Extension of the Thumb and Fingers on the Position and Cross-Sectional Area of the Median Nerve

Objective

To assess the separate effects of thumb and finger extension/flexion on median nerve position and cross-sectional area.

Methods

Ultrasonography was used to assess median nerve transverse position and cross-sectional area within the carpal tunnel at rest and its movement during volitional flexion of the individual digits of the hand. Both wrists of 165 normal subjects (11 men, 4 women, mean age, 28.6, range, 22 to 38) were studied.

Results

Thumb flexion resulted in transverse movement of the median nerve in radial direction (1.2±0.6 mm), whereas flexion of the fingers produced transverse movement in ulnar direction, which was most pronounced during flexion of the index and middle fingers (3.2±0.9 and 3.1±1.0 mm, respectively). Lesser but still statistically significant movements were noted with flexion of the ring finger (2.0±0.8 mm) and little finger (1.2±0.5 mm). Flexion of the thumb or individual fingers did not change median nerve cross-sectional area (8.5±1.1 mm²).

Conclusions

Volitional flexion of the thumb and individual fingers, particularly the index and middle fingers, produced significant transverse movement of the median nerve within the carpal tunnel but did not alter the cross-sectional area of the nerve. The importance of these findings on the understanding of the pathogenesis of the carpal tunnel syndrome and its treatment remains to be investigated.