Why onchocerciasis transmission persists after 15 annual ivermectin mass drug administrations in South-West Cameroon

Introduction Onchocerciasis is targeted for elimination mainly with annual community-directed treatment with ivermectin (CDTI). High infection levels have been reported in South-West Cameroon, despite ≥15 years of CDTI. The aim of this study was to assess factors associated with continued onchocerciasis transmission and skin disease. Methods A large-scale cross-sectional study was conducted in 2017 in 20 communities in a loiasis-risk area in South-West Cameroon. A mixed-methods approach was used. Associations between infection levels, skin disease and adherence to CDTI were assessed using mixed regression modelling. Different community members’ perception and acceptability of the CDTI strategy was explored using semi-structured interviews. Results Onchocerciasis prevalence was 44.4% among 9456 participants. 17.5% of adults were systematic non-adherers and 5.9% participated in ≥75% of CDTI rounds. Skin disease affected 1/10 participants, including children. Increasing self-reported adherence to CDTI was associated with lower infection levels in participants aged ≥15 years but not in children. Adherence to CDTI was positively influenced by perceived health benefits, and negatively influenced by fear of adverse events linked with economic loss. Concern of lethal adverse events was a common reason for systematic non-adherence. Conclusion CDTI alone is unlikely to achieve elimination in those high transmission areas where low participation is commonly associated with the fear of adverse events, despite the current quasi absence of high-risk levels of loiasis. Such persisting historical memories and fear of ivermectin might impact adherence to CDTI also in areas with historical presence but current absence of loiasis. Because such issues are unlikely to be tackled by CDTI adaptive measures, alternative strategies are needed for onchocerciasis elimination where negative perception of ivermectin is an entrenched barrier to community participation in programmes

Implementation of test-and-treat with doxycycline and temephos ground larviciding as alternative strategies for accelerating onchocerciasis elimination in an area of loiasis co-endemicity: the COUNTDOWN consortium multi-disciplinary study protocol

Background Onchocerciasis is a priority neglected tropical disease targeted for elimination by 2025. The standard strategy to combat onchocerciasis is annual Community-Directed Treatment with ivermectin (CDTi). Yet, high prevalence rates and transmission persist following > 12 rounds in South-West Cameroon. Challenges include programme coverage, adherence to, and acceptability of ivermectin in an area of Loa loa co-endemicity. Loiasis patients harbouring heavy infections are at risk of potentially fatal serious adverse events following CDTi. Alternative strategies are therefore needed to achieve onchocerciasis elimination where CDTi effectiveness is suboptimal. Methods/design We designed an implementation study to evaluate integrating World Health Organisation-endorsed alternative strategies for the elimination of onchocerciasis, namely test-and-treat with the macrofilaricide, doxycycline (TTd), and ground larviciding for suppression of blackfly vectors with the organophosphate temephos. A community-based controlled before-after intervention study will be conducted among > 2000 participants in 20 intervention (Meme River Basin) and 10 control (Indian River Basin) communities. The primary outcome measure is O. volvulus prevalence at follow-up 18-months post-treatment. The study involves four inter-disciplinary components: parasitology, entomology, applied social sciences and health economics. Onchocerciasis skin infection will be diagnosed by skin biopsy and Loa loa infection will be diagnosed by parasitological examination of finger-prick blood samples. A simultaneous clinical skin disease assessment will be made. Eligible skin-snip-positive individuals will be offered directly-observed treatment for 5 weeks with 100 mg/day doxycycline. Transmission assessments of onchocerciasis in the communities will be collected post-human landing catch of the local biting blackfly vector prior to ground larviciding with temephos every week (0.3 l/m3) until biting rate falls below 5/person/day. Qualitative research, including in-depth interviews and focus-group discussions will be used to assess acceptability and feasibility of the implemented alternative strategies among intervention recipients and providers. Health economics will assess the cost-effectiveness of the implemented interventions. Conclusions Using a multidisciplinary approach, we aim to assess the effectiveness of TTd, alone or in combination with ground larviciding, following a single intervention round and scrutinise the acceptability and feasibility of implementing at scale in similar hotspots of onchocerciasis infection, to accelerate onchocerciasis elimination

Influence of diet and lifestyle on epigenetic regulation of telomeres and ageing markers

„Gesundes Altern“ ist ein aktuelles Ziel, das mit großem Interesse der Gesellschaft verfolgt wird und mittlerweile wissenschaftlicher Fokus vieler Forschungsgruppen weltweit ist. Die Cytosin-Methylierungen an bestimmten genomischen Stellen, ebenso wie die Telomerlänge, sind mit dem Alter assoziiert und können daher als Alterungsmarker herangezogen werden. Diese Parameter können durch den Lebensstil, einschließlich Diät, körperliche Aktivität und Raucherstatus beeinflusst werden. Es wurden Analysen von Biomarkern (ASPA, ITGA2B, c-Myc Methylierungen sowie die Telomerlängen) in einer Gruppe von 82 Teilnehmern durchgeführt, die an einer sechsmonatigen Intervention mit einem pflanzlichen Nahrungsergänzungsmittel teilnahmen. Es wurde ein Präparat, basierend auf verschiedener bioaktiver, sekundärer Pflanzenstoffe (z. B. EGCG), verabreicht und das Blut von 82 Teilnehmer analysiert. Die DNA-Methylierung wurde mittels PCR, gefolgt von einer hochauflösenden Schmelzkurvenanalyse, analysiert. Zur Bestimmung der absoluten Telomerlänge wurde eine quantitative Echtzeit-PCR unter Verwendung spezifischer Oligomer-Standards (Telomere und 36B4) als Verdünnungsreihen bekannter Konzentration durchgeführt. Die Methylierung von ASPA und die Telomerlänge zeigten signifikante Korrelationen mit dem Alter. Nach der Intervention konnte eine leichte Abnahme der DNA-Methylierungen von ASPA und ITGA2B beobachtet werden (nicht signifikant), die c-Myc-Methylierung blieb nahezu unverändert. Die Telomerlänge zeigte einen Anstieg, der jedoch nicht signifikant war. Alle untersuchten Parameter konnten durch Diät, Lebensstil oder beides beeinflusst werden. ASPA-Methylierung und Telomerlänge haben das Potential, den Zustand des Alterns im Blut zu bestimmen. Dies könnte wiederum eine wichtige Rolle bei der Früherkennung oder sogar bei der Vermeidung von ernährungsbedingten Krankheiten spielen und sollte deswegen durch weitere wissenschaftliche Studien bestärkt werden. Auch der Lebensstil ist ein wichtiges Instrument, um modulierend in unerwünschte Prozesse einzugreifen.“Healthy ageing” is a current desirable goal of the society and focus of numerous research groups. The cytosin-methylation levels at specific genomic sites as well as length of telomeres, are associated with age and therefore serve as age-related biomarkers. These parameters can be influenced by lifestyle, including diet, physical activity and smoking status. The analyses of biomarkers (ASPA, ITGA2B, c-Myc as well as the telomere length) were performed in a group of 82 participants who attended a six-month intervention with a dietary supplement. A preparation based on various bioactive phytochemicals (e.g., EGCG) was administered and the capillary blood of the 82 participants was analysed. DNA methylation was identified by PCR followed by high resolution melting curve analysis. For determining absolute telomere length a quantitative real-time PCR, using specific oligomer standard (telomere and 36B4) dilutions with known concentrations, was done. ASPA methylation and telomere length showed significant correlations with age. After the intervention, DNA methylations of the genes of interest showed a slight decrease in ASPA and ITGA2B (not significant), c-Myc methylation nearly remained unchanged. However, telomere length showed an increase, but not significant. All examined parameters could be influenced by diet, lifestyle or both. ASPA methylation and telomere length have the potential to determine the state of ageing in blood. This in turn could play an important role in the early detection or even prevention of nutrition-associated diseases, which should be proved by further scientific studies. Lifestyle is also an important tool for modulating unwanted processes

Functional neuroanatomy of the hypnotic state.

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness". The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50%. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared to normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications