BACKGROUND. We performed a Phase I clinical trial that infused CCR5 gene edited CD4 T cells to determine how these T cells can better enable HIV cure strategies. METHODS. The trial addressed the method of zinc finger nuclease (ZFN) ex vivo delivery, whether CCR5 Δ32 heterozygotes preferentially benefit, the effect of CCR5 gene edited CD4 T cells on the HIV-specific T cell response, and the ability of infused CCR5 gene edited T cells to delay viral rebound during analytical treatment interruption. We enrolled 14 people living with HIV whose viral load was well controlled by antiretroviral therapy (ART). We measured time to viral rebound after ART withdrawal, persistence of CCR5-edited CD4 T cells, and whether infusion of 10 billion CCR5-edited CD4 T cells augmented the HIV-specific immune response. RESULTS. Infusion of the CD4 T cells was well tolerated with no serious adverse events. Modest delay to the time of viral rebound was observed relative to historical controls; however, three of 14 individuals of which two were CCR5 Δ32 heterozygotes appeared to regain control of viremia before ultimately rebounding. Interestingly, only these individuals had substantial restoration of HIV-specific CD8 T cell responses. Immune escape to one of these re-invigorated responses was observed at viral recrudescence, illustrating a direct link between viral control and enhanced CD8 T cell responses. CONCLUSION. These findings demonstrate how CCR5 gene edited CD4 T cell infusion could aid HIV cure strategies by augmenting pre-existing HIV-specific immune responses.

Infectious diseases are emerging and re-emerging due to climate change. Understanding how climate variability affects the transmission of infectious diseases is important for both researchers and the general public. Yet, the widespread knowledge of the general public on this matter is unknown, and quantitative research is still lacking. A survey was designed to assess the knowledge and perception of 1) infectious diseases, 2) climate change and 3) the effect of climate change on infectious diseases. Participants were recruited via convenience sampling, and an anonymous cross-sectional survey with informed consent was distributed to each participant. Descriptive and inferential analyses were performed primarily focusing on the occupational background as well as nationality of participants. A total of 458 individuals participated in this study, and most participants were originally from Myanmar, the Netherlands, Spain, United Kingdom and the United States. Almost half (44%) had a background in natural sciences and had a higher level of knowledge on infectious diseases compared to participants with non-science background (mean score of 12.5 and 11.2 out of 20, respectively). The knowledge of the effect of climate change on infectious diseases was also significantly different between participants with and without a background in natural sciences (13.1 and 11.8 out of 20, respectively). The level of knowledge on various topics was highly correlated with nationality but not associated with age. The general population demonstrated a high awareness and strong knowledge of climate change regardless of their background in natural sciences. This study exposes a knowledge gap in the general public regarding the effect of climate change on infectious diseases, and highlights that different levels of knowledge are observed in groups with differing occupations and nationalities. These results may help to develop awareness interventions for the general public.

Acinetobacter baumannii is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended periods imposes a pressing public health threat. Two MDR A. baumannii outbreaks occurred in 2012 and 2014 in a companion animal intensive care unit (caICU) in the Netherlands. Whole-genome sequencing (WGS) was performed on dog clinical isolates (n = 6), environmental isolates (n = 5), and human reference strains (n = 3) to investigate if the isolates of the two outbreaks were related. All clinical isolates shared identical resistance phenotypes displaying multidrug resistance. Multi-locus Sequence Typing (MLST) revealed that all clinical isolates belonged to sequence type ST2. The core genome MLST (cgMLST) results confirmed that the isolates of the two outbreaks were not related. Comparative genome analysis showed that the outbreak isolates contained different gene contents, including mobile genetic elements associated with antimicrobial resistance genes (ARGs). The time-measured phylogenetic reconstruction revealed that the outbreak isolates diverged approximately 30 years before 2014. Our study shows the importance of WGS analyses combined with molecular clock investigations to reduce transmission of MDR A. baumannii infections in companion animal clinics.