Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Bacterial meningitis and COVID-19: a complex patient journey.

A woman in her 70s presented to the emergency department with fever, fluctuating cognition and headache. A detailed examination revealed neurological weakness to the lower limbs with atonia and areflexia, leading to a diagnosis of bacterial meningitis, alongside a concurrent COVID-19 infection. The patient required critical care escalation for respiratory support. After stepdown to a rehabilitation ward, she had difficulties communicating due to new aphonia, hearing loss and left third nerve palsy. The team used written communication with the patient, and with this the patient was able to signal neurological deterioration. Another neurological examination noted a different pattern of weakness to the lower limbs, along with new urinary retention, and spinal arachnoiditis was identified. After more than 10 weeks in the hospital, the patient was discharged. Throughout this case, there were multiple handovers between teams and specialties, all of which were underpinned by good communication and examination to achieve the best care.

Diverse novel resident Wolbachia strains in Culicine mosquitoes from Madagascar.

Wolbachia endosymbiotic bacteria are widespread throughout insect species and Wolbachia transinfected in Aedes mosquito species has formed the basis for biocontrol programs as Wolbachia strains inhibit arboviral replication and can spread through populations. Resident strains in wild Culicine mosquito populations (the vectors of most arboviruses) requires further investigation given resident strains can also affect arboviral transmission. As Madagascar has a large diversity of both Culicine species and has had recent arboviral outbreaks, an entomology survey was undertaken, in five ecologically diverse sites, to determine the Wolbachia prevalence. We detected diverse novel resident Wolbachia strains within the Aedeomyia, Culex, Ficalbia, Mansonia and Uranotaenia genera. Wolbachia prevalence rates and strain characterisation through Sanger sequencing with multilocus sequence typing (MLST) and phylogenetic analysis revealed significant diversity and we detected co-infections with the environmentally acquired bacteria Asaia. Mosquitoes were screened for major arboviruses to investigate if any evidence could be provided for their potential role in transmission and we report the presence of Rift Valley fever virus in three Culex species: Culex tritaeniorhynchus, Culex antennatus and Culex decens. The implications of the presence of resident Wolbachia strains are discussed and how the discovery of novel strains can be utilized for applications in the development of biocontrol strategies.

Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa.

Background:  Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the  Anopheles (An.) genera, but has recently been found in  An. gambiae s.l. populations in West Africa.  As there are numerous  Anopheles species that have the capacity to transmit malaria, we analysed a range of species across five malaria endemic countries to determine  Wolbachia prevalence rates, characterise novel  Wolbachia strains and determine any correlation between the presence of  Plasmodium,  Wolbachia and the competing bacterium  Asaia. Methods:  Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017.  Molecular analysis was undertaken using quantitative PCR, Sanger sequencing,  Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial  16S rRNA gene.  Results: Novel  Wolbachia strains were discovered in five species:  An. coluzzii,  An. gambiae s.s.,  An. arabiensis,  An. moucheti and  An. species A, increasing the number of  Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with  Wolbachia supergroup B strains.  We also provide evidence for resident strain variants within  An. species A.  Wolbachia is the dominant member of the microbiome in  An. moucheti and  An. species A but present at lower densities in  An. coluzzii.  Interestingly, no evidence of  Wolbachia/Asaia co-infections was seen and  Asaia infection densities were shown to be variable and location dependent.  Conclusions: The important discovery of novel  Wolbachia strains in  Anopheles provides greater insight into the prevalence of resident  Wolbachia strains in diverse malaria vectors.  Novel  Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other  Anopheles mosquito species, which could be used for population replacement or suppression control strategies.