Behavioral and phylogenetic correlates of limb length proportions in extant apes and monkeys: Implications for interpreting hominin fossils.

The body proportions of extant animals help inform inferences about the behaviors of their extinct relatives, but relationships between body proportions, behavior, and phylogeny in extant primates remain unclear. Advances in behavioral data, molecular phylogenies, and multivariate analytical tools make it an opportune time to perform comprehensive comparative analyses of primate traditional limb length proportions (e.g., intermembral, humerofemoral, brachial, and crural indices), body size-adjusted long bone proportions, and principal components. In this study we used a mix of newly-collected and published data to investigate whether and how the limb length proportions of a diverse sample of primates, including monkeys, apes, and modern humans, are influenced by behavior and phylogeny. We reconfirm that the intermembral index, followed by the first principal component of traditional limb length proportions, is the single most effective variable distinguishing hominoids and other anthropoids. Combined limb length proportions and positional behaviors are strongly correlated in extant anthropoid groups, but phylogeny is a better predictor of limb length proportion variation than of behavior. We confirm convergences between members of the Atelidae and extant apes (especially Pan), members of the Hylobatidae and Pongo, and a potential divergence of Presbytis limb proportions from some other cercopithecoids, which correlate with adaptations for forelimb-dominated behaviors in some colobines. Collectively, these results substantiate hypotheses indicating that extinct hominins and other hominoid taxa can be distinguished by analyzing combinations of their limb length proportions at different taxonomic levels. From these results, we hypothesize that fossil skeletons characterized by notably disparate limb length proportions are unlikely to have exhibited similar behavioral patterns.

One health transmission of fluoroquinolone-resistant Escherichia coli and risk factors for their excretion by dogs living in urban and nearby rural settings.

Rates of fluoroquinolone resistance in Escherichia coli, a key opportunistic human pathogen, are problematic. Taking a One Health approach, we investigated the excretion of fluoroquinolone-resistant (FQ-R) E. coli by 600 dogs (303 from rural and 297 from urban environments) recruited from a 50 × 50 km region where we have also surveyed FQ-R E. coli from cattle and from human urine. FQ-R E. coli were detected in faeces from 7.3% (rural) and 11.8% (urban) of dogs. FQ-R E. coli from rural dogs tended to be of sequence types (STs) commonly excreted by cattle, whilst those from urban dogs tended to carry plasmid-mediated quinolone resistance genes, common in human E. coli in our study region. Phylogenetic evidence was obtained for sharing FQ-R E. coli - particularly for STs 10, 162 and 744 - between cattle, dogs and humans. Epidemiological analysis showed a strong association between feeding dogs uncooked meat and the excretion of FQ-R E. coli, particularly for STs 10, 162 and 744. This practice, therefore, could serve as a transmission link for FQ-R E. coli from farmed animals entering the home so we suggest that dogs fed uncooked meat should be handled and housed using enhanced hygiene practices.

The reconstructed cranium of Pierolapithecus and the evolution of the great ape face.

Pierolapithecus catalaunicus (~12 million years ago, northeastern Spain) is key to understanding the mosaic nature of hominid (great ape and human) evolution. Notably, its skeleton indicates that an orthograde (upright) body plan preceded suspensory adaptations in hominid evolution. However, there is ongoing debate about this species, partly because the sole known cranium, preserving a nearly complete face, suffers from taphonomic damage. We 1) carried out a micro computerized tomography (CT) based virtual reconstruction of the Pierolapithecus cranium, 2) assessed its morphological affinities using a series of two-dimensional (2D) and three-dimensional (3D) morphometric analyses, and 3) modeled the evolution of key aspects of ape face form. The reconstruction clarifies many aspects of the facial morphology of Pierolapithecus. Our results indicate that it is most similar to great apes (fossil and extant) in overall face shape and size and is morphologically distinct from other Middle Miocene apes. Crown great apes can be distinguished from other taxa in several facial metrics (e.g., low midfacial prognathism, relatively tall faces) and only some of these features are found in Pierolapithecus, which is most consistent with a stem (basal) hominid position. The inferred morphology at all ancestral nodes within the hominoid (ape and human) tree is closer to great apes than to hylobatids (gibbons and siamangs), which are convergent with other smaller anthropoids. Our analyses support a hominid ancestor that was distinct from all extant and fossil hominids in overall facial shape and shared many features with Pierolapithecus. This reconstructed ancestral morphotype represents a testable hypothesis that can be reevaluated as new fossils are discovered.

Taxonomic attribution of the KNM-ER 1500 partial skeleton from the Burgi Member of the Koobi Fora Formation, Kenya.

Paranthropus boisei is well represented in the eastern African fossil record by craniodental remains, but very few postcranial fossils can be securely attributed to this taxon. For this reason, KNM-ER 1500 from East Turkana, Kenya, is especially important. KNM-ER 1500 is a badly weathered and fragmented postcranial skeleton associated with a small piece of mandibular corpus. It derives from the Burgi Member, which has yielded diagnostic craniodental fossils attributable to P. boisei, Homo habilis, Homo rudolfensis and Homo erectus. Although it has been proposed that KNM-ER 1500 may be attributable to P. boisei based on the small mandibular fragment, this hypothesis remained challenging to test. Here we re-examine the preserved portions of KNM-ER 1500 and reassess support for its taxonomic attribution. There are compelling features of the mandible, proximal femur, and especially the proximal radius that support attribution of KNM-ER 1500 to P. boisei. These features include the absolute width of the mandible and its lack of a lateral intertoral sulcus, an anteroposteriorly compressed femoral neck with a distinctive posteroinferior marginal ridge, the rim of the radial head that is proximodistally uniform in thickness around its circumference, and a long radial neck that is elliptical in cross section. No feature serves to align KNM-ER 1500 with Homo to the exclusion of Paranthropus. KNM-ER 1500 was a small-bodied individual and attributing this specimen to P. boisei confirms that significant postcranial-size dimorphism was present in this species.

Oral and gut microbial biomarkers of susceptibility to respiratory tract infection in adults: A feasibility study.

We conducted a feasibility cohort study which aimed to recruit and retain adults from the community to collect saliva (oral) and stool (gut) samples at three time points, at the start of the study (baseline), during a respiratory tract infection (RTI) and post-RTI. Community RTIs place a huge burden on health care services, and a non-invasive microbial diagnostic tool to predict the most vulnerable to respiratory infection would be ideal. To this aim, we analysed oral-gut baseline samples comparing those who reported RTI symptoms to those who remained healthy throughout the study for microbial biomarkers of respiratory susceptibility. Amplicon sequence variants (ASV) were identified by 16S sequence profiling to reveal oral-gut microbes. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to target common respiratory microbes. Two general practices were recruited, and the participant recruitment rate was 1.3%. A total of 40 adult participants were retained, of which 19 acquired an RTI whereas 21 remained healthy. In healthy baseline oral and gut samples, ASVs from participants with RTI symptoms compared to those who remained healthy were similar with a high relative abundance of Streptococcus sp., and Blautia sp., respectively. Linear discriminant analysis effect size (LEfSe) revealed baseline oral microbes differed, indicating participants who suffered RTI symptoms had enhanced Streptococcus sobrinus and Megamonas sp., and depletion of Lactobacillus salivarius, Synergistetes, Verrucomicrobia and Dethiosulfovibrio. Furthermore, a random forest model ranked Streptococcus (4.13) as the highest mean decrease in accuracy (MDA) and RT-PCR showed a higher level of carriage of coagulase-negative Staphylococcus. Baseline core gut microbes were similar in both participant groups whereas LEfSe analysis revealed enhanced Veillonella, Rikenellaceae, Enhydobacteria, Eggerthella and Xanthomonsdales and depleted Desulfobulbus and Coprobacillus. Sutterella (4.73) had a high MDA value. Overall, we demonstrated the feasibility of recruiting and retaining adult participants from the community to provide multiple biological samples for microbial profiling. Our analyses identified potential oral-gut microbial biomarkers of respiratory infection susceptibility in otherwise healthy participants.

Pliocene hominins from East Turkana were associated with mesic environments in a semiarid basin.

During the middle Pliocene (∼3.8-3.2 Ma), both Australopithecus afarensis and Kenyanthropus platyops are known from the Turkana Basin, but between 3.60 and 3.44 Ma, most hominin fossils are found on the west side of Lake Turkana. Here, we describe a new hominin locality (ET03-166/168, Area 129) from the east side of the lake, in the Lokochot Member of the Koobi Fora Formation (3.60-3.44 Ma). To reconstruct the paleoecology of the locality and its surroundings, we combine information from sedimentology, the relative abundance of associated mammalian fauna, phytoliths, and stable isotopes from plant wax biomarkers, pedogenic carbonates, and fossil tooth enamel. The combined evidence provides a detailed view of the local paleoenvironment occupied by these Pliocene hominins, where a biodiverse community of primates, including hominins, and other mammals inhabited humid, grassy woodlands in a fluvial floodplain setting. Between <3.596 and 3.44 Ma, increases in woody vegetation were, at times, associated with increases in arid-adapted grasses. This suggests that Pliocene vegetation included woody species that were resilient to periods of prolonged aridity, resembling vegetation structure in the Turkana Basin today, where arid-adapted woody plants are a significant component of the ecosystem. Pedogenic carbonates indicate more woody vegetation than other vegetation proxies, possibly due to differences in temporospatial scale and ecological biases in preservation that should be accounted for in future studies. These new hominin fossils and associated multiproxy paleoenvironmental indicators from a single locale through time suggest that early hominin species occupied a wide range of habitats, possibly including wetlands within semiarid landscapes. Local-scale paleoecological evidence from East Turkana supports regional evidence that middle Pliocene eastern Africa may have experienced large-scale, climate-driven periods of aridity. This information extends our understanding of hominin environments beyond the limits of simple wooded, grassy, or mosaic environmental descriptions.

Non-communicating rudimentary horn pregnancy presenting as sudden unexpected maternal death: an autopsy diagnosis.

Pregnancy on a rudimentary uterine horn is a rare condition that can lead to a catastrophic outcome when it ruptures. The majority of cases are diagnosed late, after the rupture has occurred. We present the case of a 29-year-old female G2 P1 who complained of abdominal pain. She consulted a medical practitioner who prescribed her analgesics. In the next day, she was found dead in her bedroom. The pregnancy was undiagnosed as she was not aware that she was in a gravid state. At autopsy, there was massive haemoperitoneum and a 24-week gestation foetus lying outside the uterus. The uterus revealed an anomaly in keeping with a non- communicating rudimentary horn. Forensic pathologists do encounter undiagnosed ectopic pregnancies in practice. However, abdominal ectopic pregnancy with a uterine anomaly remains uncommon. These cases are often associated with a high maternal and foetal mortality.

Risk factors for community-acquired respiratory infections in a non-pandemic context: Secondary analysis of the PRIMIT study.

OBJECTIVES: Respiratory tract infection (RTI) incidence varies between people, but little is known about why. The aim of this study is therefore to identify risk factors for acquiring RTIs. METHODS: We conducted a secondary analysis of 16,908 participants in the PRIMIT study, a pre-pandemic randomised trial showing handwashing reduced incidence of RTIs in the community. Data was analysed using multivariable logistic regression analyses of self-reported RTI acquisition. RESULTS: After controlling for handwashing, RTI in the previous year (1 to 2 RTIs: adjusted OR 1.96, 95% CI 1.79 to 2.13, p<0.001; 3 to 5 RTIs: aOR 3.89, 95% CI 3.49 to 4.33, p<0.001; ≥6 RTIs: OR 5.52, 95% CI 4.37 to 6.97, p<0.001); skin conditions that prevent handwashing (aOR 1.39, 95% CI 1.24 to 1.55, p<0.001); children under 16 years in the household (aOR 1.27, 95% CI 1.12, 1.43, p<0.001); chronic lung condition (aOR 1.16, 95% CI 1.02 to 1.32, p = 0.026); female sex (aOR 1.10, 95% CI 1.03 to 1.18, p = 0.005), and post-secondary education (aOR 1.09, 95% CI 1.02 to 1.17, p = 0.01) increased the likelihood of RTI. Those over the age of 65 years were less likely to develop an infection (aOR 0.89, 95% CI 0.82 to 0.97, p = 0.009). Household crowding and influenza vaccination do not influence RTI acquisition. A post-hoc exploratory analysis found no evidence these subgroups differentially benefited from handwashing. CONCLUSIONS: Previous RTIs, chronic lung conditions, skin conditions that prevent handwashing, and the presence of household children predispose to RTI acquisition. Further research is needed to understand how host and microbial factors explain the relationship between previous and future RTIs.

The taxonomic attribution of African hominin postcrania from the Miocene through the Pleistocene: Associations and assumptions.

Postcranial bones may provide valuable information about fossil taxa relating to their locomotor habits, manipulative abilities and body sizes. Distinctive features of the postcranial skeleton are sometimes noted in species diagnoses. Although numerous isolated postcranial fossils have become accepted by many workers as belonging to a particular species, it is worthwhile revisiting the evidence for each attribution before including them in comparative samples in relation to the descriptions of new fossils, functional analyses in relation to particular taxa, or in evolutionary contexts. Although some workers eschew the taxonomic attribution of postcranial fossils as being less important (or interesting) than interpreting their functional morphology, it is impossible to consider the evolution of functional anatomy in a taxonomic and phylogenetic vacuum. There are 21 widely recognized hominin taxa that have been described from sites in Africa dated from the Late Miocene to the Middle Pleistocene; postcranial elements have been attributed to 17 of these. The bones that have been thus assigned range from many parts of a skeleton to isolated elements. However, the extent to which postcranial material can be reliably attributed to a specific taxon varies considerably from site to site and species to species, and is often the subject of considerable debate. Here, we review the postcranial remains attributed to African hominin taxa from the Late Miocene to the Middle and Late Pleistocene and place these assignations into categories of reliability. The catalog of attributions presented here may serve as a guide for making taxonomic decisions in the future.

Portable x-ray fluorescence spectroscopy geochemical sourcing of Miocene primate fossils from Kenya.

Understanding the biogeography and evolution of Miocene catarrhines relies on accurate specimen provenience. It has long been speculated that some catarrhine specimens among the early collections from Miocene sites in Kenya have incorrect provenience data. The provenience of one of these, the holotype of Equatorius africanus (NHM M16649), was previously revised based on x-ray fluorescence spectroscopy. Here we use nondestructive portable x-ray fluorescence spectroscopy to test the provenience of additional catarrhine specimens that, based on morphology and/or incomplete provenience information, were identified as possibly having been collected at a different site from that recorded at museum accession. We test the hypotheses that two specimens purportedly from the Early Miocene site of Rusinga (KNM-RU 1681 and KNM-RU 1999) are instead from Maboko, three specimens purportedly from the Middle Miocene site of Fort Ternan (KNM-FT 8, KNM-FT 41, and KNM-FT 3318) are instead from Songhor, and one specimen accessioned as being from Songhor (KNM-SO 5352) is from that site. Elemental data reveal that two of the specimens (KNM-FT 3318 and KNM-RU 1681) are likely to have been collected at sites other than their museum-accessioned provenience, while two others (KNM-RU 1999, and KNM-FT 41) were confirmed to have correct provenience. Results for both KNM-FT 8 and KNM-SO 5352, while somewhat equivocal, are best interpreted as supporting their accessioned provenience. Our results have implications for the distribution of certain catarrhine species during the Miocene in Kenya. Confirmation of the provenience of the specimens also facilitates taxonomic attribution, and resulted in additions to the morphological characterizations of some species. The protocol presented here has potential for wider application to assessing questions of provenience for fossils from other locations and periods.

Molecular ecology and risk factors for third-generation cephalosporin-resistant Escherichia coli carriage by dogs living in urban and nearby rural settings.

OBJECTIVES: To compare faecal third-generation cephalosporin-resistant (3GC-R) Escherichia coli isolates from dogs living in a city and in a rural area ∼30 km away; to compare isolates from dogs, cattle and humans in these regions; and to determine risk factors associated with 3GC-R E. coli carriage in these two cohorts of dogs. METHODS: Six hundred dogs were included, with faecal samples processed to recover 3GC-R E. coli using 2 mg/L cefotaxime. WGS was by Illumina and risk factor analyses were by multivariable linear regression using the results of an owner-completed survey. RESULTS: 3GC-R E. coli were excreted by 20/303 rural and 31/297 urban dogs. The dominant canine 3GC-R ST was ST963 (blaCMY-2), which also accounted for 25% of CMY-2-producing E. coli in humans. Phylogenetic overlap between cattle and rural dog CTX-M-14-producing E. coli ST117 was observed as well as acquisition of pMOO-32-positive E. coli ST10 by a rural dog, a plasmid common on cattle farms in the area. Feeding raw meat was associated with carrying 3GC-R E. coli in rural dogs, but not in urban dogs, where swimming in rivers was a weak risk factor. CONCLUSIONS: Given clear zoonotic potential for resistant canine E. coli, our work suggests interventions that may reduce this threat. In rural dogs, carriage of 3GC-R E. coli, particularly CTX-M producers, was phylogenetically associated with interaction with local cattle and epidemiologically associated with feeding raw meat. In urban dogs, sources of 3GC-R E. coli appear to be more varied and include environments such as rivers.

Pathways to primate hip function.

Understanding how diverse locomotor repertoires evolved in anthropoid primates is key to reconstructing the clade's evolution. Locomotor behaviour is often inferred from proximal femur morphology, yet the relationship of femoral variation to locomotor diversity is poorly understood. Extant acrobatic primates have greater ranges of hip joint mobility-particularly abduction-than those using more stereotyped locomotion, but how bony morphologies of the femur and pelvis interact to produce different locomotor abilities is unknown. We conducted hypothesis-driven path analyses via regularized structural equation modelling (SEM) to determine which morphological traits are the strongest predictors of hip abduction in anthropoid primates. Seven femoral morphological traits and two hip abduction measures were obtained from 25 primate species, split into broad locomotor and taxonomic groups. Through variable selection and fit testing techniques, insignificant predictors were removed to create the most parsimonious final models. Some morphological predictors, such as femur shaft length and neck-shaft angle, were important across models. Different trait combinations best predicted hip abduction by locomotor or taxonomic group, demonstrating group-specific linkages among morphology, mobility and behaviour. Our study illustrates the strength of SEM for identifying biologically important relationships between morphology and performance, which will have future applications for palaeobiological and biomechanical studies.

Evidence that faecal carriage of resistant Escherichia coli by 16-week-old dogs in the United Kingdom is associated with raw feeding.

We report a survey (August 2017 to March 2018) and risk factor analysis of faecal carriage of antibacterial-resistant (ABR) Escherichia coli in 223 16-week-old dogs in the United Kingdom. Raw feeding was associated with the presence of fluoroquinolone-resistant (FQ-R) E. coli and those resistant to tetracycline, amoxicillin, and streptomycin, but not to cefalexin. Whole genome sequencing of 36 FQ-R E. coli isolates showed a wide range of sequence types (STs), with almost exclusively mutational FQ-R dominated by ST744 and ST162. Comparisons between E. coli isolates from puppies known to be located within a 50 × 50 km region with those isolated from human urinary tract infections (isolated in parallel in the same region) identified an ST744 FQ-R lineage that was carried by one puppy and caused one urinary tract infection. Accordingly, we conclude that raw feeding is associated with carriage of ABR E. coli in dogs even at 16 weeks of age and that bacteria carried by puppies are shared with humans. We therefore suggest that those who feed their dogs raw meat seriously consider the potential ABR-transmission threat their pet may become as a result and deploy appropriate hygiene practices in mitigation.

Respiratory tract infections and gut microbiome modifications: A systematic review.

Respiratory tract infections (RTIs) are extremely common and can cause gastrointestinal tract symptoms and changes to the gut microbiota, yet these effects are poorly understood. We conducted a systematic review to evaluate the reported evidence of gut microbiome alterations in patients with a RTI compared to healthy controls (PROSPERO: CRD42019138853). We systematically searched Medline, Embase, Web of Science, Cochrane and the Clinical Trial Database for studies published between January 2015 and June 2021. Studies were eligible for inclusion if they were human cohorts describing the gut microbiome in patients with an RTI compared to healthy controls and the infection was caused by a viral or bacterial pathogen. Dual data screening and extraction with narrative synthesis was performed. We identified 1,593 articles and assessed 11 full texts for inclusion. Included studies (some nested) reported gut microbiome changes in the context of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (n = 5), influenza (H1N1 and H7N9) (n = 2), Tuberculosis (TB) (n = 4), Community-Acquired Pneumonia CAP (n = 2) and recurrent RTIs (rRTI) (n = 1) infections. We found studies of patients with an RTI compared to controls reported a decrease in gut microbiome diversity (Shannon) of 1.45 units (95% CI, 0.15-2.50 [p, <0.0001]) and a lower abundance of taxa (p, 0.0086). Meta-analysis of the Shannon value showed considerable heterogeneity between studies (I2, 94.42). Unbiased analysis displayed as a funnel plot revealed a depletion of Lachnospiraceae, Ruminococcaceae and Ruminococcus and enrichment of Enterococcus. There was an important absence in the lack of cohort studies reporting gut microbiome changes and high heterogeneity between studies may be explained by variations in microbiome methods and confounder effects. Further human cohort studies are needed to understand RTI-induced gut microbiome changes to better understand interplay between microbes and respiratory health.

Predisposing factors to acquisition of acute respiratory tract infections in the community: a systematic review and meta-analysis.

BACKGROUND: Preventing respiratory tract infections (RTIs) could have profound effects on quality of life, primary care workload, antibiotic prescribing and stewardship. We aimed to identify factors that increase and decrease RTI acquisition within Organisation for Economic Cooperation and Development (OECD) member countries. METHODS: Systematic search of Medline, Embase, Cochrane and ISI Web of Knowledge for studies conducted up to July 2020 reporting predisposing factors for community RTI acquisition. Pooled odds ratios were calculated using a random-effects model. RESULTS: 23 studies investigated risk factors associated with community-acquired pneumonia (n = 15); any RTI (n = 4); influenza like illness (n = 2); and lower RTI (n = 2). Demographic, lifestyle and social factors were: underweight BMI (pooled odds ratio (ORp 2.14, 95% CI 1.58 to 2.70, p = 0.97); male sex (ORp 1.30, 95% CI 1.27 to 1.33, p = 0.66); contact with pets (ORp 1.35, 95% CI 1.16 to 1.54, p = 0.72); contact with children (ORp 1.35, 95% CI 1.15 to 1.56, p = 0.05); and ex-smoking status (ORp 1.57, 95% CI 1.26 to 1.88, p = 0.76). Health-related factors were: chronic liver condition (ORp 1.30, 95% CI 1.09 to 1.50, p = 0.34); chronic renal condition (ORp 1.47, 95% CI 1.09 to 1.85, p = 0.14); and any hospitalisation in previous five years (ORp 1.64, 95% CI 1.46 to 1.82, p = 0.66). CONCLUSIONS: We identified several modifiable risk factors associated with increased likelihood of acquiring RTIs in the community, including low BMI, contact with children and pets. Modification of risk factors and increased awareness of vulnerable groups could reduce morbidity, mortality and antibiotic use associated with RTIs. PROSPERO REGISTRATION: CRD42019134176.

Fossil apes and human evolution.

Humans diverged from apes (chimpanzees, specifically) toward the end of the Miocene ~9.3 million to 6.5 million years ago. Understanding the origins of the human lineage (hominins) requires reconstructing the morphology, behavior, and environment of the chimpanzee-human last common ancestor. Modern hominoids (that is, humans and apes) share multiple features (for example, an orthograde body plan facilitating upright positional behaviors). However, the fossil record indicates that living hominoids constitute narrow representatives of an ancient radiation of more widely distributed, diverse species, none of which exhibit the entire suite of locomotor adaptations present in the extant relatives. Hence, some modern ape similarities might have evolved in parallel in response to similar selection pressures. Current evidence suggests that hominins originated in Africa from Miocene ape ancestors unlike any living species.

New hominin remains and revised context from the earliest Homo erectus locality in East Turkana, Kenya.

The KNM-ER 2598 occipital is among the oldest fossils attributed to Homo erectus but questions have been raised about whether it may derive from a younger horizon. Here we report on efforts to relocate the KNM-ER 2598 locality and investigate its paleontological and geological context. Although located in a different East Turkana collection area (Area 13) than initially reported, the locality is stratigraphically positioned below the KBS Tuff and the outcrops show no evidence of deflation of a younger unit, supporting an age of >1.855 Ma. Newly recovered faunal material consists primarily of C4 grazers, further confirmed by enamel isotope data. A hominin proximal 3rd metatarsal and partial ilium were discovered <50 m from the reconstructed location where KNM-ER 2598 was originally found but these cannot be associated directly with the occipital. The postcrania are consistent with fossil Homo and may represent the earliest postcrania attributable to Homo erectus.

Should homes and workplaces purchase portable air filters to reduce the transmission of SARS-CoV-2 and other respiratory infections? A systematic review.

Respiratory infections, including SARS-CoV-2, are spread via inhalation or ingestion of airborne pathogens. Airborne transmission is difficult to control, particularly indoors. Manufacturers of high efficiency particulate air (HEPA) filters claim they remove almost all small particles including airborne bacteria and viruses. This study investigates whether modern portable, commercially available air filters reduce the incidence of respiratory infections and/or remove bacteria and viruses from indoor air. We systematically searched Medline, Embase and Cochrane for studies published between January 2000 and September 2020. Studies were eligible for inclusion if they included a portable, commercially available air filter in any indoor setting including care homes, schools or healthcare settings, investigating either associations with incidence of respiratory infections or removal and/or capture of aerosolised bacteria and viruses from the air within the filters. Dual data screening and extraction with narrative synthesis. No studies were found investigating the effects of air filters on the incidence of respiratory infections. Two studies investigated bacterial capture within filters and bacterial load in indoor air. One reported higher numbers of viable bacteria in the HEPA filter than in floor dust samples. The other reported HEPA filtration combined with ultraviolet light reduced bacterial load in the air by 41% (sampling time not reported). Neither paper investigated effects on viruses. There is an important absence of evidence regarding the effectiveness of a potentially cost-efficient intervention for indoor transmission of respiratory infections, including SARS-CoV-2. Two studies provide 'proof of principle' that air filters can capture airborne bacteria in an indoor setting. Randomised controlled trials are urgently needed to investigate effects of portable HEPA filters on incidence of respiratory infections.

Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review.

OBJECTIVE: The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly prescribed in UK primary care. METHODS: We searched MEDLINE, EMBASE and AMED, all years up to May 2020 including all study designs, collecting and analysing data on the effect of antibiotics prescribed for respiratory and urinary tract infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane standard methods. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Narrative synthesis was used to report the themes emerging from the data. MAIN OUTCOME MEASURES: Primary outcomes were antibiotic-induced changes in the composition and/or diversity of the gut microbiota. Secondary outcome was the time for the microbiota to return to baseline. RESULTS: Thirty-one articles with low or unclear risk of bias showed that antibiotics impact the gut microbiota by causing rapid and diminished levels of bacterial diversity and changes in relative abundances. After cessation of treatment, gut bacteria recover, in most individuals, to their baseline state within a few weeks. Some studies suggested longer term effects from 2 to 6 months. Considerable heterogeneity in methodology makes the studies prone to biases and other confounding factors. Doxycycline was associated with a marked short-term decrease in Bifidobacterium diversity. Clarithromycin decreased the populations of Enterobacteria, and the anaerobic bacteria Bifidobacterium sp and Lactobacillus sp in numbers and diversity for up to 5 weeks. Phenoxymethylpenicillin, nitrofurantoin and amoxicillin had very little effect on the gut microbiome. CONCLUSIONS: Despite substantial heterogeneity of the studies and small sample sizes, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota. Larger population-based studies are needed to fully understand how antibiotics modulate the microbiota, and to determine if these are associated with (longer term) health consequences. PROSPERO REGISTRATION NUMBER: CRD42017073750.

Antimicrobial resistance associations with national primary care antibiotic stewardship policy: Primary care-based, multilevel analytic study.

BACKGROUND: Recent UK antibiotic stewardship policies have resulted in significant changes in primary care dispensing, but whether this has impacted antimicrobial resistance is unknown. AIM: To evaluate associations between changes in primary care dispensing and antimicrobial resistance in community-acquired urinary Escherichia coli infections. METHODS: Multilevel logistic regression modelling investigating relationships between primary care practice level antibiotic dispensing for approximately 1.5 million patients in South West England and resistance in 152,704 community-acquired urinary E. coli between 2013 and 2016. Relationships presented for within and subsequent quarter drug-bug pairs, adjusted for patient age, deprivation, and rurality. RESULTS: In line with national trends, overall antibiotic dispensing per 1000 registered patients fell 11%. Amoxicillin fell 14%, cefalexin 20%, ciprofloxacin 24%, co-amoxiclav 49% and trimethoprim 8%. Nitrofurantoin increased 7%. Antibiotic reductions were associated with reduced within quarter same-antibiotic resistance to: amoxicillin, ciprofloxacin and trimethoprim. Subsequent quarter reduced resistance was observed for trimethoprim and amoxicillin. Antibiotic dispensing reductions were associated with increased within and subsequent quarter resistance to cefalexin and co-amoxiclav. Increased nitrofurantoin dispensing was associated with reduced within and subsequent quarter trimethoprim resistance without affecting nitrofurantoin resistance. CONCLUSIONS: This evaluation of a national primary care stewardship policy on antimicrobial resistance in the community suggests both hoped-for benefits and unexpected harms. Some increase in resistance to cefalexin and co-amoxiclav could result from residual confounding. Randomised controlled trials are urgently required to investigate causality.