Local infection rates at the herd level could be as high as 46% (Supporting Information S1). ...the Government of Tanzania requested assistance from the International Atomic Energy Agency (IAEA) in ...1983 to assess whether the sterile insect technique (SIT) could be integrated with other proposed control tactics for the eradication of G. austeni from Unguja Island. ...the disease prevalence in the northern half of the island decreased to very low levels (<5%), but little impact was noticed in the cattle residing around the forests in the southern part of the island as domestic animals could not penetrate these areas 4.
African animal trypanosomosis (AAT), or nagana, is widespread within the tsetse-infested belt of sub-Saharan Africa. Although a wealth of information on its occurrence and prevalence is available in ...the literature, synthesized and harmonized data at the regional and continental scales are lacking. To fill this gap the Food and Agriculture Organization of the United Nations (FAO) launched the Atlas of tsetse and AAT, jointly implemented with the International Atomic Energy Agency (IAEA) in the framework of the Programme Against African Trypanosomosis (PAAT).
The Atlas aims to build and regularly update a geospatial database of tsetse species occurrence and AAT at the continental level. The present paper focuses on the methodology to assemble a dynamic database of AAT, which hinges on herd-level prevalence data as estimated using various diagnostic techniques. A range of ancillary information items is also included (e.g. trypanosome species, survey period, species and breed of animals, husbandry system, etc.). Input data were initially identified through a literature review.
Preliminary results are presented for Ethiopia, Kenya and Uganda in East Africa: 122 papers were identified and analyzed, which contained field data collected from January 1990 to December 2013. Information on AAT was extracted and recorded for 348 distinct geographic locations. The presented distribution maps exemplify the range of outputs that can be directly generated from the AAT database.
Activities are ongoing to map the distribution of AAT in all affected countries and to develop the tsetse component of the Atlas. The presented methodology is also being transferred to partners in affected countries, with a view to developing capacity and strengthening data management, harmonization and sharing. In the future, geospatial modelling will enable predictions to be made within and beyond the range of AAT field observations. This variety of information layers will inform decisions on the most appropriate, site-specific strategies for intervention against AAT. Data on the occurrence of human-infective trypanosomes in non-human hosts will also provide valuable information for sleeping sickness control and elimination.
An area-wide integrated tsetse eradication project was initiated in Zanzibar in 1994 by the International Atomic Energy Agency and the governments of Tanzania and Zanzibar, to eradicate Glossina ...austeni Newstead from Unguja Island (Zanzibar) using the sterile insect technique. Suppression of the tsetse population on Unguja was initiated in 1988 by applying residual pyrethroids as a pour-on formulation to livestock and by the deployment of insecticide impregnated screens in some of the forested areas. This was followed by sequential releases of gamma-sterilized male flies by light aircraft. The flies, packaged in carton release containers, were dispersed twice a week along specific flight lines separated by a distance of 1–2 km. More than 8.5 million sterile male flies were released by air from August 1994 to December 1997. A sterile to indigenous male ratio of >50:1 was obtained in mid-1995 and it increased to >100:1 by the end of 1995. As a consequence the proportion of sampled young females (1–2 ovulations), with an egg in utero in embryonic arrest or an uterus empty as a result of expulsion of a dead embryo, increased from <25% in the 1st quarter to >70% in the last quarter of 1995. In addition, the age structure of the female population became significantly distorted in favor of old flies (≥4 ovulations) by the end of 1995. The apparent density of the indigenous fly population declined rapidly in the last quarter of 1995, followed by a population crash in the beginning of 1996. The last trapped indigenous male and female flies were found in weeks 32 and 36, 1996, respectively. Time for 6 fly generations elapsed between the last catch of an indigenous fly and the end of the sterile male releases in December 1997.
Local infection rates at the herd level could be as high as 46% (Supporting Information S1). ...the Government of Tanzania requested assistance from the International Atomic Energy Agency (IAEA) in ...1983 to assess whether the sterile insect technique (SIT) could be integrated with other proposed control tactics for the eradication of G. austeni from Unguja Island. ...the disease prevalence in the northern half of the island decreased to very low levels (<5%), but little impact was noticed in the cattle residing around the forests in the southern part of the island as domestic animals could not penetrate these areas 4.
Collecting blood samples is an important aspect of wildlife studies where data on physiological parameters are required. To avoid stress to the test animals and its potential influence on the test ...parameters, minimally invasive blood sampling offers numerous advantages. Here, we describe using the African tsetse fly (Glossina brevipalpis) to sample blood from meerkats (Suricata suricatta) habituated to human presence. Prior to the experiments, test animals were trained with positive reinforcement to tolerate a box that enclosed the insects being attached to their neck. This method allows drawing blood samples at defined points of time and from specific individuals during captive studies. Additionally, because it presents the first example of an African haematophagous insect suitable for sampling blood, African field studies might benefit from this minimally invasive blood-sampling technique without the risk of importing potentially invasive species.
Abstract Background Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Three prospectively randomized trials demonstrated an advantage for ...adjuvant radiotherapy (ART) compared with a wait-and-see (WS) policy. Objective To determine the efficiency of ART after a 10-yr follow-up in the ARO 96–02 study. Design, setting, and participants After RP, 388 patients with pT3 pN0 prostate cancer (PCa) were randomized to WS or three-dimensional conformal ART with 60 Gy. The present analysis focuses on intent-to-treat patients who achieved an undetectable prostate-specific antigen after RP (ITT2 population)—that is, 159 WS plus 148 ART men. Outcome measurements and statistical analysis The primary end point of the study was progression-free survival (PFS) (events: biochemical recurrence, clinical recurrence, or death). Outcomes were compared by log-rank test. Cox regression analysis served to identify variables influencing the course of disease. Results and limitations The median follow-up was 111 mo for ART and 113 mo for WS. At 10 yr, PFS was 56% for ART and 35% for WS ( p < 0.0001). In pT3b and R1 patients, the rates for WS even dropped to 28% and 27%, respectively. Of all 307 ITT2 patients, 15 died from PCa, and 28 died for other or unknown reasons. Neither metastasis-free survival nor overall survival was significantly improved by ART. However, the study was underpowered for these end points. The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity. No grade 4 events occurred. Conclusions Compared with WS, ART reduced the risk of (biochemical) progression with a hazard ratio of 0.51 in pT3 PCa. With only one grade 3 case of late toxicity, ART was safe. Patient summary Precautionary radiotherapy counteracts relapse after surgery for prostate cancer with specific risk factors.
Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared ...with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.
After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.
Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.
Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine ...environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets. The prototypic JMJD3/UTX (Jumonji domain–containing protein 3) H3K27 demethylase inhibitor GSK-J4 increased global levels of the repressive H3K27me3 mark around transcription start sites of effector cytokine genes. Moreover, GSK-J4 reduced IFN-γ, TNFα, granulocyte–macrophage colony-stimulating factor (GM-CSF), and interleukin-10 levels in cytokine-stimulated NK cells while sparing their cytotoxic killing activity against cancer cells. The anti-inflammatory effect of GSK-J4 in NK cell subsets, isolated from peripheral blood or tissue from individuals with rheumatoid arthritis (RA), coupled with an inhibitory effect on formation of bone-resorbing osteoclasts, suggested that histone demethylase inhibition has broad utility for modulating immune and inflammatory responses. Overall, our results indicate that H3K27me3 is a dynamic and important epigenetic modification during NK cell activation and that JMJD3/UTX-driven H3K27 demethylation is critical for NK cell function.
T helper (Th) cells are CD4⁺ effector T cells that play a critical role in immunity by shaping the inflammatory cytokine environment in a variety of physiological and pathological situations. Using a ...combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A and KDM6B as central regulators of human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels of the repressive H3K27me3 chromatin mark and leads to suppression of the key transcription factor RORγt during Th17 differentiation. In mature Th17 cells, GSK-J4 induces an altered transcriptional program with a profound metabolic reprogramming and concomitant suppression of IL-17 cytokine levels and reduced proliferation. Single-cell analysis reveals a specific shift from highly inflammatory cell subsets toward a resting state upon demethylase inhibition. The root cause of the observed antiinflammatory phenotype in stimulated Th17 cells is reduced expression of key metabolic transcription factors, such as PPRC1. Overall, this leads to reduced mitochondrial biogenesis, resulting in a metabolic switch with concomitant antiinflammatory effects. These data are consistent with an effect of GSK-J4 on Th17 T cell differentiation pathways directly related to proliferation and include regulation of effector cytokine profiles. This suggests that inhibiting KDM6 demethylases may be an effective, even in the short term, therapeutic target for autoimmune diseases, including ankylosing spondylitis.
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