Occurrence of Bondar's Nesting Whitefly, Paraleyrodes bondari (Hemiptera: Aleyrodidae), on cassava in Uganda

Cassava is a valued calorific source to millions of Africans who eat it daily and a vital staple for their foodsecurity. One of the key constraints to this crop is whiteflies which are both a vector of viral diseasesand a direct pest. Although the African cassava whitefly is known to cause physical damage on cassavawith considerable tuberous yield loss, a recent whitefly outbreak caused unusually severe damage, whichprompted the current reported investigation. Molecular identification of whitefly adults sampled fromthe affected cassava field revealed the presence of a new whitefly species, Paraleyrodes bondari. Thiscommunication is the first report of the occurrence of P. bondari on cassava in Uganda

Distribution of Bemisia tabaci in different agro-ecological regions in Uganda and the threat of vector-borne pandemics into new cassava growing areas

Previous studies in sub-Saharan Africa have showed the spread of cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) pandemics into different cassava growing regions by high Bemisia tabaci populations. Studies did indicate that there were stark differences in some whitefly species, yet they have not looked extensively across agroecologies. Members of B. tabaci species complex termed sub-Saharan Africa 1 (SSA1) and SSA2 have been linked to the spread of CMD and CBSD viruses. During the period of a severe CMD pandemic in the 1990s, SSA2 was the most predominant until the resurgence of SSA1, particularly SSA1-subgroup1 (SSA1-SG1) from the early 2000s to date. Cassava being a drought resilient crop has become an important food security crop and has been introduced into new areas and regions. Considering the role B. tabaci in the spread of cassava virus pandemics into neighboring regions, we investigated the genetic diversity and distribution of B. tabaci in nine different agro-ecological regions of Uganda in 2017. Adult whiteflies were collected from cassava and 33 other host plants from cassava-growing areas, those with limited cassava and areas with no cassava, where it is being introduced as a food security crop. The partial sequences of the mitochondrial cytochrome oxidase 1 (mtCO1) gene (657 bp) were used to determine the phylogenetic relationships between the sampled B. tabaci. Cassava B. tabaci SSA1 (-SG1, -SG2, -Hoslundia (previously called SSA1-SG1/2), -SG3), SSA2 and SSA3; non-cassava B. tabaci SSA6, SSA10, SSA11, SSA12, SSA13, MED-ASL, MED-Q1, MEAM1, Indian Ocean; and other Bemisia species, Bemisia afer and Bemisia Uganda1 were identified in the study. SSA3, one of the key B. tabaci species that occurs on cassava in West Africa, was identified for the first time in Uganda. The SSA1-SG1 was widely distributed, predominated on cassava and was found on 17 other host-plants. The ability of SSA1-SG1 to exist in environments with limited or no cassava growing poses the risk of continued spread of virus pandemics. Therefore, measures must be put in place to prevent the introduction of diseased materials into new areas, since the vectors exist

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Comparative evolutionary analyses of eight whitefly Bemisia tabaci sensu lato genomes: cryptic species, agricultural pests and plant-virus vectors

The genomes, transcriptomes, and predicted protein-coding sequences are available from Ensembl Metazoa (http://metazoa.ensembl.org) and are included within the references. Raw RNA-Seq datasets generated and/or analyzed during the current study are available from the European Nucleotide Archive database repository (https://www.ebi.ac.uk/ena) under the parent project accessions: PRJEB28507, PRJEB36965, PRJEB35304, PRJEB39408. All data generated during the analyses of these datasets are included in this published article, supplementary information files, and figshare repository (https://doi.org/10.6084/m9.figshare.23666799; https://doi.org/10.6084/m9.figshare.23666832.v4; https://doi.org/10.6084/m9.figshare.23666844).International audienceBackground: The group of > 40 cryptic whitefly species called Bemisia tabaci sensu lato are amongst the world's worst agricultural pests and plant-virus vectors. Outbreaks of B. tabaci s.l. and the associated plant-virus diseases continue to contribute to global food insecurity and social instability, particularly in sub-Saharan Africa and Asia. Published B. tabaci s.l. genomes have limited use for studying African cassava B. tabaci SSA1 species, due to the high genetic divergences between them. Genomic annotations presented here were performed using the 'Ensembl gene annotation system' , to ensure that comparative analyses and conclusions reflect biological differences, as opposed to arising from different methodologies underpinning transcript model identification. Results: We present here six new B. tabaci s.l. genomes from Africa and Asia, and two re-annotated previously published genomes, to provide evolutionary insights into these globally distributed pests. Genome sizes ranged between 616-658 Mb and exhibited some of the highest coverage of transposable elements reported within Arthropoda. Many fewer total protein coding genes (PCG) were recovered compared to the previously published B. tabaci s.l. genomes and structural annotations generated via the uniform methodology strongly supported a repertoire of between 12.8-13.2 × 10 3 PCG. An integrative systematics approach incorporating phylogenomic analysis of nuclear and mitochondrial markers supported a monophyletic Aleyrodidae and the basal positioning of B. tabaci Uganda-1 to the sub-Saharan group of species. Reciprocal cross-mating data and the co-cladogenesis pattern of the primary obligate endosymbiont 'Candidatus Portiera aleyrodidarum' from 11 Bemisia genomes further supported the phylogenetic reconstruction to show that African cassava B. tabaci populations consist of just three biological species. We include comparative analyses of gene families related to detoxification, sugar metabolism, vector competency and evaluate the presence and function of horizontally transferred genes, essential for understanding the evolution and unique biology of constituent B. tabaci. s.l species.Conclusions: These genomic resources have provided new and critical insights into the genetics underlying B. tabaci s.l. biology. They also provide a rich foundation for post-genomic research, including the selection of candidate gene-targets for innovative whitefly and virus-control strategies