Investigation of mechanisms of bendiocarb resistance in Anopheles gambiae populations from the city of Yaoundé, Cameroon

BACKGROUND Resistance to the carbamate insecticide bendiocarb is emerging in Anopheles gambiae populations from the city of Yaoundé in Cameroon. However, the molecular basis of this resistance remains uncharacterized. The present study objective is to investigate mechanisms promoting resistance to bendiocarb in An. gambiae populations from Yaoundé. METHODS The level of susceptibility of An. gambiae s.l. to bendiocarb 0.1 % was assessed from 2010 to 2013 using bioassays. Mosquitoes resistant to bendiocarb, unexposed and susceptible mosquitoes were screened for the presence of the Ace-1(R) mutation using TaqMan assays. Microarray analyses were performed to assess the pattern of genes differentially expressed between resistant, unexposed and susceptible. RESULTS Bendiocarb resistance was more prevalent in mosquitoes originating from cultivated sites compared to those from polluted and unpolluted sites. Both An. gambiae and Anopheles coluzzii were found to display resistance to bendiocarb. No G119S mutation was detected suggesting that resistance was mainly metabolic. Microarray analysis revealed the over-expression of several cytochrome P450 s genes including cyp6z3, cyp6z1, cyp12f2, cyp6m3 and cyp6p4. Gene ontology (GO) enrichment analysis supported the detoxification role of cytochrome P450 s with several GO terms associated with P450 activity significantly enriched in resistant samples. Other detoxification genes included UDP-glucosyl transferases, glutathione-S transferases and ABC transporters. CONCLUSION The study highlights the probable implication of metabolic mechanisms in bendiocarb resistance in An. gambiae populations from Yaoundé and stresses the need for further studies leading to functional validation of detoxification genes involved in this resistance

Rapid evolution of pyrethroid resistance prevalence in Anopheles gambiae populations from the cities of Douala and Yaoundé (Cameroon)

Background The adaptation of malaria vectors to urban areas is becoming a serious challenge for malaria control. The study presents the evolution of pyrethroid resistance in mosquito populations from the cities of Douala and Yaoundé between 2010 and 2013. Methods Susceptibility tests to permethrin and deltamethrin were carried out with two- to four-day old unfed Anopheles gambiae sensu lato adults raised from larvae collected from the field. Mosquitoes resistant to permethrin and deltamethrin and control were screened to detect the presence of the kdr alleles using the TaqMan assays. Mosquitoes belonging to the An. gambiae complex were subjected to PCR assays designed for species and molecular forms identifications. The genomic region containing the upstream of intron-1 of the voltage-gated sodium channel was sequenced and compared between mosquitoes originating from different breeding habitats. Results Anopheles gambiae s.l. specimens collected from the city of Douala were all Anopheles coluzzii. In Yaoundé, both An. gambiae and An. coluzzii were recorded. A rapid decrease of mosquito mortality to permethrin and deltamethrin was recorded between 2010 and 2013 in the two cities. The mortality rate varied from 80.3 to 22.3% and 94.4 to 59.7% for permethrin and deltamethrin, respectively. Both kdr alleles L1014F and L1014S were recorded. The frequency of kdr alleles increased rapidly over the study period, varying from 44 to 88.9% in Yaoundé and from 68 to 81% in Douala. The sequencing of a 1,228 bp region of intro-1 of the voltage-gated sodium channel revealed the presence of five different haplotypes. A high number of these haplotypes were recorded in An. coluzzii samples. No evidence for a recent selective sweep on intron-1 sequence within samples originating from different breeding habitat was detected using Fu’s and Tajima Fs statistics. Conclusion The present study supports rapid evolution of pyrethroid resistance in vector populations from the cities of Douala and Yaoundé and calls for immediate action to fight against the increasing prevalence of pyrethroid-resistant mosquitoes

The Maunakea Spectroscopic Explorer Book 2018

(Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is intended as a concise reference guide to all aspects of the scientific and technical design of MSE, for the international astronomy and engineering communities, and related agencies. The current version is a status report of MSE's science goals and their practical implementation, following the System Conceptual Design Review, held in January 2018. MSE is a planned 10-m class, wide-field, optical and near-infrared facility, designed to enable transformative science, while filling a critical missing gap in the emerging international network of large-scale astronomical facilities. MSE is completely dedicated to multi-object spectroscopy of samples of between thousands and millions of astrophysical objects. It will lead the world in this arena, due to its unique design capabilities: it will boast a large (11.25 m) aperture and wide (1.52 sq. degree) field of view; it will have the capabilities to observe at a wide range of spectral resolutions, from R2500 to R40,000, with massive multiplexing (4332 spectra per exposure, with all spectral resolutions available at all times), and an on-target observing efficiency of more than 80%. MSE will unveil the composition and dynamics of the faint Universe and is designed to excel at precision studies of faint astrophysical phenomena. It will also provide critical follow-up for multi-wavelength imaging surveys, such as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation Very Large Array.Comment: 5 chapters, 160 pages, 107 figure

Bionomics of Anopheline species and malaria transmission dynamics along an altitudinal transect in Western Cameroon

<p>Abstract</p> <p>Background</p> <p>Highland areas of Africa are mostly malaria hypoendemic, due to climate which is not appropriate for anophelines development and their reproductive fitness. In view of designing a malaria control strategy in Western Cameroon highlands, baseline data on anopheline species bionomics were collected.</p> <p>Methods</p> <p>Longitudinal entomological surveys were conducted in three localities at different altitudinal levels. Mosquitoes were captured when landing on human volunteers and by pyrethrum spray catches. Sampled <it>Anopheles </it>were tested for the presence of <it>Plasmodium </it>circumsporozoite proteins and their blood meal origin with ELISA. Entomological parameters of malaria epidemiology were assessed using Mac Donald's formula.</p> <p>Results</p> <p>Anopheline species diversity and density decreased globally from lowland to highland. The most aggressive species along the altitudinal transect was <it>Anopheles gambiae </it>s.s. of S molecular form, followed in the lowland and on the plateau by <it>An. funestus</it>, but uphill by <it>An. hancocki</it>. <it>An. gambiae </it>and <it>An. ziemanni </it>exhibited similar seasonal biting patterns at the different levels, whereas different features were observed for <it>An. funestus</it>. Only indoor resting species could be captured uphill; it is therefore likely that endophilic behaviour is necessary for anophelines to climb above a certain threshold. Of the ten species collected along the transect, only <it>An. gambiae </it>and <it>An. funestus </it>were responsible for malaria transmission, with entomological inoculation rates (EIR) of 90.5, 62.8 and zero infective bites/human/year in the lowland, on the plateau and uphill respectively. The duration of gonotrophic cycle was consistently one day shorter for <it>An. gambiae </it>as compared to <it>An. funestus </it>at equal altitude. Altitudinal climate variations had no effect on the survivorship and the subsequent life expectancy of the adult stage of these malaria vectors, but most probably on aquatic stages. On the contrary increasing altitude significantly extended the duration of gonotrophic cycle and reduced: the EIR, their preference to human blood and consequently the malaria stability index.</p> <p>Conclusion</p> <p>Malaria epidemiological rooting in the outskirts of Western Cameroon highlands evolves with increasing altitude, gradually from stable to unstable settings. This suggests a potential risk of malaria epidemic in highlands, and the need for a continuous epidemiological surveillance.</p

Multiscale characterization of the 3D network structure of metal carbides in a Ni superalloy by synchrotron X-ray microtomography and ptychography

Synchrotron X-ray microtomography and ptychography were used to characterize the 3D network structure, morphology and distribution of metal carbides in an as-cast IN713LC Ni superalloy. MC typed carbides were found to distribute mainly on the grain boundary between the matrix γ and γ' phase. The differences in solidification cooling rate had a minor influence on the volume fraction of the MC type carbides, but significantly affected the carbide size, distribution and network morphology. Depending on the local composition of the remaining liquid phase and geometric constraints, the carbides can form either spherical or strip or network morphologies. The research demonstrated clearly the advantage and technical potential of using the two complementary tomography techniques synergistically to characterize non-destructively complex multiple-phase structures in three dimensional space with a spatial resolution of ~30 nm

Early-onset catatonia associated with SHANK3 mutations: looking at the autism spectrum through the prism of psychomotor phenomena

BackgroundIndividuals with Phelan-McDermid syndrome (PMS) present with a wide range of diagnoses: autism spectrum disorder, intellectual disability, or schizophrenia. Differences in the genetic background could explain these different neurodevelopmental trajectories. However, a more parsimonious hypothesis is to consider that they may be the same phenotypic entity. Catatonic disturbances occasionally reported from adolescence onwards in PMS prompts exploration of the hypothesis that this clinical entity may be an early-onset form of catatonia. The largest cohort of children with childhood catatonia was studied by the Wernicke-Kleist-Leonhard school (WKL school), which regards catatonia as a collection of qualitative abnormalities of psychomotricity that predominantly affecting involuntary motricity (reactive and expressive). The aim of this study was to investigate the presence of psychomotor signs in three young adults carrying a mutation or intragenic deletion of the SHANK3 gene through the prism of the WKL school conception of catatonia.MethodsThis study was designed as an exploratory case study. Current and childhood psychomotor phenomena were investigated through semi-structured interviews with the parents, direct interaction with the participants, and the study of documents reporting observations of the participants at school or by other healthcare professionals.ResultsThe findings show catatonic manifestations from childhood that evolved into a chronic form, with possible phases of sub-acute exacerbations starting from adolescence.ConclusionThe presence of catatonic symptoms from childhood associated with autistic traits leads us to consider that this singular entity fundamentally related to SHANK3 mutations could be a form of early-onset catatonia. Further case studies are needed to confirm our observations

Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial – CADOT

IntroductionAmong treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines.MethodOut of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity – QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning – GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st – 3rd quartile) of 4 (1–9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11–33) months after remission.ResultsAt the end of DATA step 1, 25 patients were in remission (QIDS &lt;6; 52% [38–66%]). After DATA step 2, 37 patients were in remission (77% [65–89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78–97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62–95%]).ConclusionThese results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s)

Anopheles gambiae distribution and insecticide resistance in the cities of Douala and Yaoundé (Cameroon): influence of urban agriculture and pollution

Background: Urban malaria is becoming a major health priority across Africa. A study was undertaken to assess the importance of urban pollution and agriculture practice on the distribution and susceptibility to insecticide of malaria vectors in the two main cities in Cameroon. Methods: Anopheline larval breeding sites were surveyed and water samples analysed monthly from October 2009 to December 2010. Parameters analysed included turbidity, pH, temperature, conductivity, sulfates, phosphates,nitrates, nitrites, ammonia, aluminium, alkalinity, iron, potassium, manganese, magnesium, magnesium hardness and total hardness. Characteristics of water bodies in urban areas were compared to rural areas and between urban sites. The level of susceptibility of Anopheles gambiae to 4% DDT, 0.75% permethrin, 0.05% deltamethrin, 0.1% bendiocarb and 5% malathion were compared between mosquitoes collected from polluted, non polluted and cultivated areas. Results: A total of 1,546 breeding sites, 690 in Yaoundé and 856 in Douala, were sampled in the course of the study. Almost all measured parameters had a concentration of 2- to 100-fold higher in urban compare to rural breeding sites. No resistance to malathion was detected, but bendiocarb resistance was present in Yaounde. Very low mortality rates were observed following DDT or permethrin exposure, associated with high kdr frequencies. Mosquitoes collected in cultivated areas, exhibited the highest resistant levels. There was little difference in insecticide resistance or kdr allele frequency in mosquitoes collected from polluted versus non-polluted sites. Conclusion: The data confirm high selection pressure on mosquitoes originating from urban areas and suggest urban agriculture rather than pollution as the major factor driving resistance to insecticide

Buffalo, cattle and their interactions at the edge of transfrontier conservation areas: synthesis of research carried out 2008-2015 in Hwange NP, Gonarezhou NP and their peripheries (Zimbabwe)

The coexistence of protected areas and neighbouring communal areas in Southern Africa is jeopardised by negative interactions between wildlife and villagers and their livestock. The African buffalo (Syncerus caffer) has often been blamed for a significant proportion of the “human-wildlife conflicts”, mainly through the transmission of pathogens to cattle, competition with livestock for grazing and water resources, and also occasionally involved in crop destruction and threat to people's physical integrity. We present the results of several multidisciplinary studies carried out since 2008 on buffalo-cattle interactions at the periphery of Gonarezhou National Park, Hwange National Park and adjacent communal lands in Zimbabwe. Movements of sympatric buffalo and cattle have been described at various scales using GPS collars, revealing daily/seasonal patterns and occasional events of long-distance dispersal of young buffalo females. Habitat preferences, especially for open grassland habitats, were similar between the two species, and surface availability was the key determinant of their distributions. Overall, buffalo appeared to avoid cattle, although their ranges overlapped more extensively with cattle in Gonarezhou area than in Hwange. We defined contacts between buffalo and cattle using spatial-temporal windows compatible with the transmission of parasites and pathogens through direct contact or indirect contact with contaminated environment. Results of serological tests for various pathogens and analysis of their relationship with buffalo/cattle contacts rates confirmed the likely role of reservoir played by buffalo for several diseases (FMD, theileriosis…), whereas the results were inconclusive for several others (brucellosis, tick-borne diseases, BTB…). Socio-economic surveys carried out in the study areas highlighted the importance of livestock keeping for small-scale farmers' livelihoods. Livestock management strategies have been elicited using participatory approaches and role-playing games, demonstrating that crop production had a major impact on cattle distribution, and thus largely determined contact patterns with buffalo. Surveys of farmers' perceptions of wildlife indicated that they were usually aware of diseases risks associated with buffalo, especially for FMD transmission to cattle. Although our results provide evidence for competitive and negative interactions, we believe that coexistence between these two species is possible, as it already occurs in many interface areas. We discuss several livestock management strategies likely to reduce the negative impacts, while enhancing habitat quality for wildlife by maximizing grassland structural heterogeneity and providing incentives to communities to protect key seasonal ranges through grazing concessions. (Texte intégral