Pharmacokinetics, safety, and efficacy of a single co-administered dose of diethylcarbamazine, albendazole and ivermectin in adults with and without Wuchereria bancrofti infection in Cote d\u27Ivoire

BackgroundA single co-administered dose of ivermectin (IVM) plus diethylcarbamazine (DEC) plus albendazole (ALB), or triple-drug therapy, was recently found to be more effective for clearing microfilariae (Mf) than standard DEC plus ALB currently used for mass drug administration programs for lymphatic filariasis (LF) outside of sub-Saharan Africa. Triple-drug therapy has not been previously tested in LF-uninfected individuals from Africa. This study evaluated the pharmacokinetics (PK), safety, and efficacy of triple-drug therapy in people with and without Wuchereria bancrofti infection in West Africa.MethodsIn this open-label cohort study, treatment-naïve microfilaremic (>50 mf/mL, n = 32) and uninfected (circulating filarial antigen negative, n = 24) adults residing in Agboville district, Côte d’Ivoire, were treated with a single dose of IVM plus DEC plus ALB, and evaluated for adverse events (AEs) until 7 days post treatment. Drug levels were assessed by liquid chromatography and mass spectrometry. Persons responsible for assessing AEs were blinded to participants’ infection status.FindingsThere was no difference in AUC0-inf or Cmax between LF-infected and uninfected participants (P>0.05 for all comparisons). All subjects experienced mild AEs; 28% and 25% of infected and uninfected participants experienced grade 2 AEs, respectively. There were no severe or serious adverse events. Only fever (16 of 32 versus 4 of 24, PConclusionsModerate to heavy W. bancrofti infection did not affect PK parameters for IVM, DEC or ALB following a single co-administered dose of these drugs compared to uninfected individuals. The drugs were well tolerated. This study confirmed the efficacy of the triple-drug therapy for clearing W. bancrofti Mf and has added important information to support the use of this regimen in LF elimination programs in areas of Africa without co-endemic onchocerciasis or loiasis.Trial registrationClinicalTrials.gov NCT02845713.</div

Assessing the presence of Wuchereria bancrofti in vector and human populations from urban communities in Conakry, Guinea

The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 with the goal of interrupting transmission of lymphatic filariasis (LF) through multiple rounds of mass drug administration (MDA). In Guinea, there is evidence of ongoing LF transmission, but little is known about the most densely populated parts of the country, including the capital Conakry. In order to guide the LF control and elimination efforts, serological and entomological surveys were carried out to determine whether or not LF transmission occurs in Conakry.; The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in people recruited from all five districts of Conakry. Mosquitoes were collected over a 1-year period, in 195 households in 15 communities. A proportion of mosquitoes were analysed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR).; CFA test revealed no infection in the 611 individuals examined. A total of 14,334 mosquitoes were collected; 14,135 Culex (98.6 %), 161 Anopheles (1.1 %) and a few other species. Out of 1,312 Culex spp. (9.3 %) and 51 An. gambiae (31.7 %) dissected, none was infected with any stage of the W. bancrofti parasite. However, the LAMP assay revealed that 1.8 % of An. gambiae and 0.31 % of Culex spp. were positive, while PCR determined respective prevalences of 0 % and 0.19 %.; This study revealed the presence of W. bancrofti DNA in mosquitoes, despite the apparent absence of infection in the human population. Although MDA interventions are not recommended where the prevalence of ICT is below 1 %, the entomological results are suggestive of the circulation of the parasite in the population of Conakry. Therefore, rigorous surveillance is still warranted so that LF transmission in Conakry would be identified rapidly and adequate responses being implemented

Efficacy of ICON® Maxx in the laboratory and against insecticide-resistant Anopheles gambiae in central Côte d'Ivoire

ABSTRACT: BACKGROUND: Long-lasting treatment kits, designed to transform untreated nets into long-lasting insecticidal nets (LLINs), may facilitate high coverage with LLINs where non-treated nets are in place. In this study, the efficacy of ICON(R) Maxx (Syngenta) was evaluated under laboratory conditions and in an experimental hut trial in central Cote d'Ivoire, where Anopheles gambiae s.s. are resistant to pyrethroid insecticides. METHODS: In the laboratory, polyester and polyethylene net samples were treated with ICON(R) Maxx, washed up to 20 times and their efficacy determined in World Health Organization (WHO) cone assays against a susceptible laboratory An. gambiae s.s. colony. Over a 12-month period, the polyester nets were evaluated in a hut trial to determine mosquito deterrence, induced exophily, blood-feeding inhibition and mortality. RESULTS: In the laboratory, ICON(R) Maxx-treated polyethylene nets showed higher efficacy against pyrethroid-susceptible mosquitoes than polyester nets. After 20 washings, insecticidal efficacy in bioassays was 59.4% knockdown (KD) and 22.3% mortality for polyethylene, and 55.3% KD and 17.9% mortality for polyester nets. In experimental huts, treated nets showed strong deterrence, induced exophily and an over three-fold reduction in blood-fed mosquitoes. More than half (61.8%) of the mosquitoes entering the huts with treated nets were found dead the next morning despite high levels of KD resistance. After washing the treated nets, KD and mortality rates were close to or exceeded predefined WHO thresholds in cone bioassays. CONCLUSION: In contrast to previous laboratory investigation, ICON(R) Maxx-treated nets showed only moderate KD and mortality rates. However, under semi-field conditions, in an area where mosquitoes are resistant to pyrethroids, ICON(R) Maxx showed high deterrence, induced exophily and provided a significant reduction in blood-feeding rates; features that are likely to have a positive impact in reducing malaria transmission. The WHO cone test may not always be a good proxy for predicting product performance under field condition

Influence of the agrochemicals used for rice and vegetable cultivation on insecticide resistance in malaria vectors in southern Côte d’Ivoire

Background Vector control can contribute to the development of resistance to insecticides in malaria vectors. As the swamps and wetlands used for some agricultural activities constitute productive breeding sites for many mosquito species, agricultural pest control may increase the selection pressure for insecticide resistance in mosquitoes. Understanding the use of agrochemicals by farmers is important to plan and initiate effective integrated pest and vector management interventions. Methods A knowledge–attitude–practice study, using questionnaires, was undertaken with 102 rice farmers in Tiassalé and 106 vegetable farmers in Dabou (South Côte d’Ivoire) in order to generate information on pesticide usage. In addition, insecticide susceptibility bioassays were conducted using adult mosquitoes obtained from larvae collected within farms, and the persistence of agricultural pesticides in the farming environment, including sediment and mosquito breeding site water, was investigated by HPLC. Results Herbicides and insecticides appeared to be the most frequently used pesticides for both crops. Amino phosphonates (mostly glyphosate) represented the most used herbicides (45 % for rice up to 89 % for vegetables). Pyrethroids appeared to be the most used insecticides (accounting for 90 % of all the insecticide use reported). Approximately 75 % of respondents had not been to school and do not understand product labels. Only about 45 % of farmers respect the recommended pesticide dosage and about 10–15 % of pesticides used for rice and vegetable, respectively, are not recommended for these crops. As per WHO criteria, the mosquito local populations from the two localities were resistant to three of the four insecticides tested, as mortalities were less than 35 % for deltamethrin, DDT and bendiocarb. Higher susceptibility was observed for malathion, although the population was considered resistant in Dabou (80 % mortality) and susceptible in Tiassalé (98 % mortality). With the exception of glyphosate, residues from each of six chemicals tested for were detected in each of the sites visited in the two localities. Conclusion The study describes the use of insecticides and herbicides on crops and highlights the importance of considering agriculture practices when attempting to manage resistance in malaria vectors. Inter-sectoral collaboration between agriculture and public health is required to develop efficient integrated pest and vector management interventions

First Isolation and Identification of Agriphages in Vegetable Crops in West Africa (Côte d’Ivore): Potential Uses of Biocontrol in Plants

Agriphages or bacterial viruses are ubiquitous in the environment. The discovery of virulent phages against phytobacteria improves crop growth and proposes biopesticide uses for plant diseases. In Africa, many phytobacteria like Ralstonia, Clavibacter, and Xanthomonas were reported in several regions. The study aims to evaluate the presence of agriphages for the biocontrol of phytobacteria in Côte d'Ivoire. Leaves and soil samples were collected from healthy and diseased plants, and in three sites located in Anyama, Abidjan, and Bingerville. The pretreatments occur with sterile and physiological water for leaves and soil samples respectively. The isolation of agriphages was done on specific media with Xanthomonas campestris as bacterial host. Lytic activity was tested on agar media for five bacteria strains. After DNA extraction using the Qiagen method kit, molecular confirmation of agriphages was done by Random Amplified Polymorphic DNA-PCR. From this study, five (5) agriphages were isolated in soil and leaves in site 2. These agriphages have all been isolated from Xanthomonas campestris and have a broad spectrum of lytic activity. Molecular characterization by RAPD-PCR showed that three of these agriphages are DNA phages. The dendrogram showed that phages ΦXanS1, ΦXanS2 have 93% similarities. While ΦXanS1 and ΦXanS2 are 62% similar to ΦXanF1. This study is the first reported agriphages in West Africa and their potential uses against phytobacteria for biocontrol infection in crops. &nbsp; &nbsp

First Isolation and Identification of Agriphages in Vegetable Crops in West Africa (Côte d’Ivore): Potential Uses of Biocontrol in Plants

Agriphages or bacterial viruses are ubiquitous in the environment. The discovery of virulent phages against phytobacteria improves crop growth and proposes biopesticide uses for plant diseases. In Africa, many phytobacteria like Ralstonia, Clavibacter, and Xanthomonas were reported in several regions. The study aims to evaluate the presence of agriphages for the biocontrol of phytobacteria in Côte d'Ivoire. Leaves and soil samples were collected from healthy and diseased plants, and in three sites located in Anyama, Abidjan, and Bingerville. The pretreatments occur with sterile and physiological water for leaves and soil samples respectively. The isolation of agriphages was done on specific media with Xanthomonas campestris as bacterial host. Lytic activity was tested on agar media for five bacteria strains. After DNA extraction using the Qiagen method kit, molecular confirmation of agriphages was done by Random Amplified Polymorphic DNA-PCR. From this study, five (5) agriphages were isolated in soil and leaves in site 2. These agriphages have all been isolated from Xanthomonas campestris and have a broad spectrum of lytic activity. Molecular characterization by RAPD-PCR showed that three of these agriphages are DNA phages. The dendrogram showed that phages ΦXanS1, ΦXanS2 have 93% similarities. While ΦXanS1 and ΦXanS2 are 62% similar to ΦXanF1. This study is the first reported agriphages in West Africa and their potential uses against phytobacteria for biocontrol infection in crops. &nbsp; &nbsp

Antibacterial, Anti-HIV-1 Protease and Cytotoxic Activities of Aqueous Ethanolic Extracts from Combretum Adenogonium Steud. Ex A. Rich (Combretaceae).

\ud \ud Records have shown that Combretum adenogonium Steud. Ex A. Rich (Combretaceae) is used in traditional medicine systems of several tribes in Tanzania. This study focused on the investigation of antibacterial activity, anti-HIV-1 protease activity, toxicity properties and classes of phytochemicals in extracts from C. adenogonium Steud. Ex A. Rich (Combretaceae) to evaluate potential of these extracts for development as herbal remedies. Dried plant material were ground to fine powder and extracted using 80% aqueous ethanol to afford root, leaf and stem bark extracts. The extracts were assayed for anti-HIV-1 protease activities, antibacterial activities using microdilution methods and cytotoxicity using brine shrimps lethality assay. Screening for major phytochemical classes was carried out using standard chemical tests. All extracts exhibited antibacterial activity to at least one of the test bacteria with MIC-values ranging from 0.31-5.0 mg/ml. Two extracts, namely, root and stem bark exhibited anti-HIV-1 PR activity with IC50 values of 24.7 and 26.5 μg/ml, respectively. Stem bark and leaf extracts showed mild toxicity with LC50 values of 65.768 μg/ml and 76.965 μg/ml, respectively, whereas roots were relatively non-toxic (LC50 = 110.042 μg/ml). Phytochemical screening of the extracts indicated presence of flavonoids, terpenoids, alkaloids, tannins, glycosides and saponins. These results provide promising baseline information for the potential development of C. adenogonium extracts in treatment of bacterial and HIV/AIDS-related opportunistic infections

Durability associated efficacy of long-lasting insecticidal nets after five years of household use

<p>Abstract</p> <p>Background</p> <p>Long-lasting insecticidal nets (LLINs) have been strongly advocated for use to prevent malaria in sub-Saharan Africa and have significantly reduced human-vector contact. PermaNet^®2.0 is among the five LLINs brands which have been given full approval by the WHO Pesticide Evaluation Scheme (WHOPES). The LLINs are expected to protect the malaria endemic communities, but a number of factors within the community can affect their durability and efficacy. This study evaluated the durability, efficacy and retention of PermaNet^®2.0 after five years of use in a Tanzanian community.</p> <p>Method</p> <p>Two to three day- old non blood-fed female mosquitoes from an insectary susceptible colony (<it>An. gambiae </it>s.s, this colony was established at TPRI from Kisumu, Kenya in 1992) and wild mosquito populations (<it>An. arabiensis </it>and <it>Culex quinquefasciatus</it>) were used in cone bioassay tests to assess the efficacy of mosquito nets.</p> <p>Findings</p> <p>The knockdown effect was recorded after three minutes of exposure, and mortality was recorded after 24 hours post-exposure. Mortality of <it>An. gambiae </it>s.s from insectary colony was 100% while <it>An. arabiensis </it>and <it>Cx.quinquefasciatus </it>wild populations had reduced mortality. Insecticide content of the new (the bed net of the same brand but never used before) and used PermaNet^®2.0 was determined using High Performance Liquid Chromatography (HPLC).</p> <p>Conclusion</p> <p>The results of this study suggest that, in order to achieve maximum protection against malaria, public health education focusing on bed net use and maintenance should be incorporated into the mass distribution of nets in communities.</p

Parallel Evolution in Mosquito Vectors—A Duplicated Esterase Locus is Associated With Resistance to Pirimiphos-methyl in Anopheles gambiae

The primary control methods for the African malaria mosquito, Anopheles gambiae, are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programmes. The organophosphate, pirimiphos-methyl, is a relatively new chemical in the vector control armoury but is now widely used in indoor residual spray campaigns. Whilst generally effective, phenotypic resistance has developed in some areas in malaria vectors. Here, we used a population genomic approach to identify novel mechanisms of resistance to pirimiphos-methyl in Anopheles gambiae s.l mosquitoes. In multiple populations, we found large and repeated signals of selection at a locus containing a cluster of detoxification enzymes, some of whose orthologs are known to confer resistance to organophosphates in Culex pipiens. Close examination revealed a pair of alpha-esterases, Coeae1f and Coeae2f, and a complex and diverse pattern of haplotypes under selection in An. gambiae, An. coluzzii and An. arabiensis. As in Cx. pipiens, copy number variants have arisen at this locus. We used diplotype clustering to examine whether these signals arise from parallel evolution or adaptive introgression. Using whole-genome sequenced phenotyped samples, we found that in West Africa, a copy number variant in Anopheles gambiae is associated with resistance to pirimiphos-methyl. Overall, we demonstrate a striking example of contemporary parallel evolution which has important implications for malaria control programmes

Spatial risk profiling of Plasmodium falciparum parasitaemia in a high endemicity area in Côte d'Ivoire

Background. The objective of this study was to identify demographic, environmental and socioeconomic risk factors and spatial patterns of Plasmodium falciparum parasitaemia in a high endemicity area of Africa, and to specify how this information can facilitate improved malaria control at the district level. Methods. A questionnaire was administered to about 4,000 schoolchildren in 55 schools in western Ĉte d'Ivoire to determine children's socioeconomic status and their habit of sleeping under bed nets. Environmental data were obtained from satellite images, digitized ground maps and a second questionnaire addressed to school directors. Finger prick blood samples were collected and P. falciparum parasitaemia determined under a microscope using standardized, quality-controlled methods. Bayesian variogram models were utilized for spatial risk modelling and mapping of P. falciparum parasitaemia at non-sampled locations, assuming stationary and non-stationary underlying spatial dependence. Results. Two-thirds of the schoolchildren were infected with P. falciparum and the mean parasitaemia among infected children was 959 parasites/μl of blood. Age, socioeconomic status, not sleeping under a bed net, coverage rate with bed nets and environmental factors (e.g., normalized difference vegetation index, rainfall, land surface temperature and living in close proximity to standing water) were significantly associated with the risk of P. falciparum parasitaemia. After accounting for spatial correlation, age, bed net coverage, rainfall during the main malaria transmission season and distance to rivers remained significant covariates. Conclusion. It is argued that a massive increase in bed net coverage, particularly in villages in close proximity to rivers, in concert with other control measures, is necessary to bring malaria endemicity down to intermediate or low levels