Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations.

BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. METHODS: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. RESULTS: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. CONCLUSIONS: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.

Can freshwater plants and algae act as an effective feed supplement to reduce methane emissions from ruminant livestock?

Methane production by livestock is a substantial component of greenhouse gas emissions worldwide. The marine red algae, Asparagopsis taxiformis, has been identified as a possible supplement in livestock feeds due to its potent inhibition of methane production but currently is unable to be produced at scale. Finding additional taxa that inhibit methane production is therefore desirable. Here we provide foundational evidence of methanogenesis-inhibiting properties in Australian freshwater plants and algae, reviewing candidate species and testing species' chemical composition and efficacy in vitro. Candidate plant species and naturally-occurring algal mixes were collected and assessed for ability to reduce methane in batch testing and characterised for biochemical composition, lipids and fatty acids, minerals and DNA. We identified three algal mixes and one plant (Montia australasica) with potential to reduce methane yield in in vitro batch assay trials. All three algal mixes contained Spirogyra, although additional testing would be needed to confirm this alga was responsible for the observed activity. For the two samples that underwent multiple dose testing, Algal mix 1 (predominantly Spirogyra maxima) and M. australasica, there seems to be an optimum dose but sources, harvesting and storage conditions potentially determine their methanogenesis-inhibiting activity. Based on their compositions, fatty acids are likely to be acting to reduce methane in Algal mix 1 while M. australasica likely contains substantial amounts of the flavonoids apigenin and kaempferol, which are associated with methane reduction. Based on their mineral composition, the samples tested would be safe for livestock consumption at an inclusion rate of 20%. Thus, we identified multiple Australian species that have potential to be used as a feed supplement to reduce methane yield in livestock which may be suitable for individual farmers to grow and feed, reducing complexities of supply associated with marine alternatives and suggesting avenues for investigation for similar species elsewhere.

How wide, how much? A framework for quantifying the economic and ecological outcomes of altering riparian width on agricultural land.

Creating and managing riparian buffer zones (RBZs) is regarded as a global best-practice management strategy for maintaining and improving waterway health. Agricultural land often utilises RBZs as highly productive pasture, exposing waterways to increased inputs of nutrients, pollutants, and sediment, in addition to reducing carbon sequestration and habitat for native flora and fauna. This project developed a novel approach to the application of multisystem ecological and economic quantification models to the property-scale, at low cost and high speed. We developed a state-of-the-art dynamic geospatial interface to communicate these outputs when switching from pasture to revegetated riparian zone via planned restoration efforts. The tool was developed using the regional conditions of a south-east Australian catchment as a case study but is designed to be adaptable around globally using equivalent model inputs. Ecological and economic outcomes were determined using existing methods, including an agricultural land suitability analysis to quantify primary production, an estimation of carbon sequestration using historic vegetation datasets and GIS software analysis to determine spatial costings of revegetation and fencing. Economic outcomes are presented in raw values of pasture produced and carbon sequestered, and fencing and revegetation costs can be easily altered for enhanced usability and interoperability. This tool can provide property-specific data for almost 16,000 properties in a catchment area of over 130,000 km2 and 19,600 km of river length. Our results indicated that current financial incentives for revegetation rarely cover the cost of giving up pasture, but these costs may be compensated by social and ecological outcomes achieved over time. This method provides a novel way of informing alternative management approaches, such as incremental revegetation plans and the selective harvesting of timber from RBZ. The model provides an innovative framework for improved RBZ management and can be used to inform property-specific responses and guide discussion among stakeholders.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.

BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.

Individual and population level costs and health-related quality of life outcomes of third-generation cephalosporin resistant bloodstream infection in Blantyre, Malawi.

Data which accurately enumerate the economic costs of antimicrobial resistance (AMR) in low- and middle- income countries are essential. This study aimed to quantify the impact of third-generation cephalosporin resistant (3GC-R) bloodstream infection (BSI) on economic and health related quality of life outcomes for adult patients in Blantyre, Malawi. Participants were recruited from a prospective, longitudinal cohort study of hospitalised patients with bloodstream infection caused by Enterobacterales at Queen Elizabeth Central Hospital (QECH). Primary costing studies were used to estimate the direct medical costs associated with the inpatient stay. Recruited participants were asked about direct non-medical and indirect costs associated with their admission and their health-related quality of life was measured using the EuroQol EQ-5D questionnaire. Multiple imputation was undertaken to account for missing data. Costs were adjusted to 2019 US Dollars. Cost and microbiology surveillance data from QECH, Blantyre was used to model the annual cost of, and quality-adjusted life years lost to, 3GC-R and 3GC-Susceptible BSI from 1998 to 2030 in Malawi. The mean health provider cost per participant with 3GC-R BSI was US$110.27 (95%CR; 22.60-197.95), higher than for those with 3GC-S infection. Patients with resistant BSI incurred an additional indirect cost of US$155.48 (95%CR; -67.80, 378.78) and an additional direct non-medical cost of US$20.98 (95%CR; -36.47, 78.42). Health related quality of life outcomes were poor for all participants, but participants with resistant infections had an EQ-5D utility score that was 0.167 (95% CR: -0.035, 0.300) lower than those with sensitive infections. Population level burden estimates suggest that in 2016, 3GC-R accounted for 84% of annual societal costs from admission with bloodstream infection and 82% of QALYs lost. 3GC-R bloodstream infection was associated with higher health provider and patient level costs than 3GC-S infection, as well as poorer HRQoL outcomes. We demonstrate a substantial current and future economic burden to society as a result of 3GC-R E. coli and Klebsiella spp. BSI, data urgently needed by policy makers to provide impetus for implementing strategies to reduce AMR.

Bacterial shedding and serologic responses following an outbreak of Salmonella Typhi in an endemic cohort.

BACKGROUND: Salmonella enterica serovar Typhi (Salmonella Typhi) is the cause of typhoid fever. Salmonella Typhi may be transmitted through shedding in the stool, which can continue after recovery from acute illness. Shedding is detected by culturing stool, which is challenging to co-ordinate at scale. We hypothesised that sero-surveillance would direct us to those shedding Salmonella Typhi in stool following a typhoid outbreak. METHODS: In 2016 a typhoid outbreak affected one in four residents of a Nursing School in Malosa, Malawi. The Department of Health asked for assistance to identify nursing students that might spread the outbreak to other health facilities. We measured IgG antibody titres against Vi capsular polysaccharide (anti-Vi IgG) and IgM / IgG antibodies against H:d flagellin (anti-H:d) three and six months after the outbreak. We selected participants in the highest and lowest deciles for anti-Vi IgG titre (measured at visit one) and obtained stool for Salmonella culture and PCR. All participants reported whether they had experienced fever persisting for three days or more during the outbreak (in keeping with the WHO definitions of 'suspected typhoid'). We tested for salmonellae in the Nursing School environment. RESULTS: We obtained 320 paired serum samples from 407 residents. We cultured stool from 25 residents with high anti-Vi IgG titres and 24 residents with low titres. We did not recover Salmonella Typhi from stool; four stool samples yielded non-typhoidal salmonellae; one sample produced a positive PCR amplification for a Salmonella Typhi target. Median anti-Vi and anti-H:d IgG titres fell among participants who reported persistent fever. There was a smaller fall in anti-H:d IgG titres among participants who did not report persistent fever. Non-typhoidal salmonellae were identified in water sampled at source and from a kitchen tap. CONCLUSION: High titres of anti-Vi IgG did not identify culture-confirmed shedding of Salmonella Typhi. There was a clear serologic signal of recent typhoid exposure in the cohort, represented by waning IgG antibody titres over time. The presence of non-typhoidal salmonellae in drinking water indicates sub-optimal sanitation. Developing methods to detect and treat shedding remains an important priority to complement typhoid conjugate vaccination in efforts to achieve typhoid elimination.

Investigating One Health risks for human colonisation with extended spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study.

BACKGROUND: Low-income countries have high morbidity and mortality from drug-resistant infections, especially from enteric bacteria such as Escherichia coli. In these settings, sanitation infrastructure is of variable and often inadequate quality, creating risks of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales transmission. We aimed to describe the prevalence, distribution, and risks of ESBL-producing Enterobacterales colonisation in sub-Saharan Africa using a One Health approach. METHODS: Between April 29, 2019, and Dec 3, 2020, we recruited 300 households in Malawi for this longitudinal cohort study: 100 each in urban, peri-urban, and rural settings. All households underwent a baseline visit and 195 were selected for longitudinal follow-up, comprising up to three additional visits over a 6 month period. Data on human health, antibiotic usage, health-seeking behaviours, structural and behavioural environmental health practices, and animal husbandry were captured alongside human, animal, and environmental samples. Microbiological processing determined the presence of ESBL-producing E coli and Klebsiella pneumoniae, and hierarchical logistic regression was performed to evaluate the risks of human ESBL-producing Enterobacterales colonisation. FINDINGS: A paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites. A total of 11 975 samples were cultured, and ESBL-producing Enterobacterales were isolated from 1190 (41·8%) of 2845 samples of human stool, 290 (29·8%) of 973 samples of animal stool, 339 (66·2%) of 512 samples of river water, and 138 (46·0%) of 300 samples of drain water. Multivariable models illustrated that human ESBL-producing E coli colonisation was associated with the wet season (adjusted odds ratio 1·66, 95% credible interval 1·38-2·00), living in urban areas (2·01, 1·26-3·24), advanced age (1·14, 1·05-1·25), and living in households where animals were observed interacting with food (1·62, 1·17-2·28) or kept inside (1·58, 1·00-2·43). Human ESBL-producing K pneumoniae colonisation was associated with the wet season (2·12, 1·63-2·76). INTERPRETATION: There are extremely high levels of ESBL-producing Enterobacterales colonisation in humans and animals and extensive contamination of the wider environment in southern Malawi. Urbanisation and seasonality are key risks for ESBL-producing Enterobacterales colonisation, probably reflecting environmental drivers. Without adequate efforts to improve environmental health, ESBL-producing Enterobacterales transmission is likely to persist in this setting. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Risk Factors, Temporal Dependence, and Seasonality of Human Extended-Spectrum ß-Lactamases-Producing Escherichia coli and Klebsiella pneumoniae Colonization in Malawi: A Longitudinal Model-Based Approach.

BACKGROUND: Sub-Saharan Africa has the highest estimated death rate attributable to antimicrobial resistance, especially from extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E). However, the dynamics of human colonization in the community with ESBL-E are not well described. Inadequate water, sanitation, and hygiene infrastructure and associated behaviors are believed to play an important role in transmission of ESBL-E, and an improved understanding of the temporal dynamics of within-household transmission could help inform the design of future policies. METHODS: In this 18-month study, using microbiological data and household surveys, we built a multivariable hierarchical harmonic logistic regression model to identify risk factors for colonization with ESBL-producing Escherichia coli and Klebsiella pneumoniae, reflecting household structure and temporal correlation of colonization status. RESULTS: Being male was associated with a lower risk of colonization with ESBL-producing E. coli (odds ratio [OR], 0.786; credible interval [CrI], .678-.910), whereas the use of a tube well or a borehole was associated with an increased risk (OR, 1.550; CrI, 1.003-2.394). For ESBL-producing K. pneumoniae, recent antibiotic exposure increased risk of colonization (OR, 1.281; CrI, 1.049-1.565), whereas sharing plates decreased that risk (OR, 0.672; CrI, .460-.980). Finally, the temporal correlation range of 8 to 11 weeks provided evidence that within-household transmission occurs within this time frame. CONCLUSIONS: We describe different risks for colonization with different enteric bacterial species. Our findings suggest interventions to reduce transmission targeted at the household level need to focus on improving water, sanitation, and hygiene infrastructure and associated behaviors, whereas at the community level, they should focus on both environmental hygiene and antibiotic stewardship.

Acute effects of flavored Black and mild cigars among young adult cigarette smokers.

The U.S. Food and Drug Administration proposed new product standards that would ban characterizing flavors (other than tobacco) in cigars. To inform this regulatory action, we compared physiological effects, use behavior, and subjective effects of four popular cigar flavors in cigar-naïve young adult cigarette smokers. Across five laboratory visits, participants (n = 25) used and evaluated own brand (OB) cigarettes or Black & Mild cigars (original, wine, apple, and cream flavors). Linear mixed models tested differences in saliva nicotine, exhaled carbon monoxide (CO), heart rate (HR), blood pressure (BP), puff topography, and subjective effects (p < .05). Compared to all cigars, OB resulted in higher nicotine boost (953 vs. < 300 ng/ml) and lower CO boost (4 vs. 8-9 ppm). Nicotine boost for original cigars (283 ng/ml) was significantly higher than wine (190 ng/ml). All products significantly increased HR/BP relative to baseline, but across time wine and apple cigars were associated with significantly lower HR than OB and BP effects varied. Relative to OB, participants took approximately 0.5 s longer puffs for all cigars and took significantly larger puffs (+ 21%-24%) of original, wine, and apple cigars. OB was rated more positively than all cigars, which had similar subjective effects. Wine cigars were disliked most and were less effective in reducing tobacco abstinence symptoms than OB; cream cigars were harsher and had stronger flavor intensity than original. The consistency in toxicant exposure, use behavior, and subjective effects across cigar flavors, including original, highlights the need for product standards to interpret characterizing flavors subject to prohibition broadly. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Clinical predictors of bacteraemia in neonates with suspected early-onset sepsis in Malawi: a prospective cohort study.

OBJECTIVES: We studied neonates with suspected early-onset sepsis (EOS, sepsis developing in the first 72 hours after delivery) in Malawi to (1) describe clinical characteristics and microbiological findings, (2) identify which patient characteristics may be associated with pathogen positivity on blood culture, and (3) describe mortality and its potential determinants. DESIGN: Prospective observational study (May 2018-June 2019). SETTING: Neonatal ward in Queen Elizabeth Central Hospital, the largest government hospital in Malawi. PATIENTS: All neonates with suspected EOS in whom a blood culture was obtained. RESULTS: Out of 4308 neonatal admissions, 1244 (28.9%) had suspected EOS. We included 1149 neonates, of which 109 blood cultures had significant growth (9.5%). The most commonly isolated pathogens were Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli and Acinetobacter baumanii. Many of the Gram negatives were extended-spectrum beta lactamase-producing Enterobacteriaceae, and these were 40-100% resistant to first-line and second-line antimicrobials. Gestational age (GA) of <32 weeks was associated with pathogen-positive blood cultures (<28 weeks: adjusted OR (AOR) 2.72, 95% CI 1.04 to 7.13; 28-32 weeks: AOR 2.26, 95% CI 1.21 to 4.21; p=0.005). Mortality was 17.6% (202/1149) and associated with low birth weight (<1000 g: AOR 47.57, 95% CI 12.59 to 179.81; 1000-1500 g: AOR 11.31, 95% CI 6.97 to 18.36; 1500-2500 g: AOR 2.20, 95% CI 1.42 to 3.39; p<0.001), low Apgar scores at 5 min (0-3: AOR 18.60, 95% CI 8.81 to 39.27; 4-6: AOR 4.41, 95% CI 2.81 to 6.93; p<0.001), positive maternal venereal disease research laboratory status (AOR 2.53, 95% CI 1.25 to 5.12; p=0.001) and congenital anomalies (AOR 7.37, 95% CI 3.61 to 15.05; p<0.001). Prolonged rupture of membranes was inversely associated with mortality (AOR 0.43, 95% CI 0.19 to 0.98; p 0.007). CONCLUSION: In Malawi, EOS was suspected in nearly a third of neonatal admissions and had a high mortality. Ten per cent were culture-confirmed and predicted by low GA. To reduce the impact of suspected neonatal sepsis in least developed countries, improved maternal and antenatal care and development of rapid point of care methods to more accurately guide antimicrobial use could simultaneously improve outcome and reduce antimicrobial resistance.

The electronic nicotine delivery system (ENDS) purchase task: Are results sensitive to price framing?

Extension of the cigarette purchase task (CPT) to electronic nicotine delivery systems (ENDS) is complicated by the heterogeneous nature of this product class, as ambiguity exists regarding the appropriate price-frame (i.e., unit of the product being purchased). We explored correlations between ENDS purchase task (E-CPTs) outcomes featuring two common price-frames: 10 puffs and 1 mL of liquid. Adult exclusive ENDS users (N = 19) and dual users of ENDS and cigarettes (N = 16) completed two own-brand E-CPTs. One E-CPT used "10 puffs" as its price-frame; the other used "1 mL of liquid." Five outcomes were generated for each E-CPT: breakpoint, intensity, Omax, Pmax, and α. Exploratory Factor Analyses (EFA) considered how these outcomes captured latent structures of demand for ENDS. Spearman correlations in E-CPT outcomes assessed within-person variation between price-frames. Analyses also considered whether correlations differed by user group. E-CPT outcomes were highly correlated across price-frames (ρs > 0.57, ps < .001), and EFA revealed little difference in how outcomes from the tasks loaded onto two latent structures of demand ("Persistence" and "Amplitude") reported in the previous literature. The magnitude of correlations for E-CPT outcomes tended to be higher for exclusive ENDS users than for dual users. Participant responses to purchase task outcomes were similar across two E-CPT price-frames. Using "10 puffs" as a price-frame may be a generalizable approach among heterogenous groups of ENDS users, but researchers should consider their target population and structure the E-CPT to reflect participants' knowledge and purchasing behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Examining the Etiology and Treatment of Mental Illness Among Vodou Priests in Northern Haiti.

This study assesses the perspectives and experiences of Vodou priests (ougan) in the treatment of mental illness in northern Haiti. Our goal is to explore the etiology and popular nosologies of mental illness in the context of Haitian Vodou, through understandings of illness and misfortune which are often viewed as a result of sent spirits-or spirits sent supernaturally by others with the intent to cause harm. Using a qualitative approach, this study conducted semi-structured in-depth interviews with 20 ougan living near the city of Cap-Haïtien. Interviews highlight a sample of healers with little formal training who maintain beliefs and practices that differ significantly from current biomedical models. Ougan treat mental illness through a variety of means including prayer and conjuring of spirits, leaves for teas and baths, as well as combinations of perfumes, rum, human remains, and other powdered concoctions that are either imbibed or rubbed on the skin. The primary purpose of these treatments is to expel the spirit causing harm, yet they can often result in additional harm to the patient. Findings suggest that while ougan are willing to collaborate with biomedical practitioners, significant barriers remain preventing cooperation between these two groups.

Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study.

BACKGROUND: The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. METHODS: In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. FINDINGS: 156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30-44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3 (IQR 349-828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2-9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. INTERPRETATION: Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital. FUNDING: None.

Effect of resistance to third-generation cephalosporins on morbidity and mortality from bloodstream infections in Blantyre, Malawi: a prospective cohort study.

BACKGROUND: The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections. METHODS: We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival. FINDINGS: Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died. INTERPRETATION: Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa. FUNDING: Wellcome Trust and Wellcome Asia and Africa Programme.

Increasing anti-S antibody testing: a quality improvement initiative with evolving COVID-19 guidelines.

BACKGROUND: COVID-19 management guidelines are constantly evolving, making them difficult to implement practically. Ronapreve was a neutralising monoclonal antibody introduced into UK COVID-19 guidelines in 2021. It reduces mortality in seronegative patients infected with non-omicron variants. Antibody testing on admission is therefore vital in ensuring patients could be considered for Ronapreve as inpatients. LOCAL PROBLEM: We found that on our COVID-19 ward, 31.4% of patients were not having anti-S tests despite fulfilling the other criteria to be eligible for Ronapreve. This was identified as an important target to improve; by not requesting anti-S tests, we were forgoing the opportunity to use an intervention that could improve outcomes. METHODS: We analysed patient records for patients with COVID-19 admitted to our ward over 4 months to observe if awareness of the need to request anti-S increased through conducting plan-do-study-act (PDSA) cycles. INTERVENTIONS: Our first intervention was an multidisciplinary team (MDT) discussion at our departmental audit meeting highlighting our baseline findings and the importance of anti-S requesting. Our second intervention was to hang printed posters in both the doctors' room and the ward as a visual reminder to staff. Our final intervention was trust-wide communications of updated local COVID-19 guidance that included instructions for anti-S requesting on admission. RESULTS: Our baseline data showed that only 68.6% of patients with symptomatic COVID-19 were having anti-S antibody tests requested. This increased to 95.0% following our three interventions. There was also a reduction in the amount of anti-S requests being 'added on', from 57.1% to 15.8%. CONCLUSIONS: COVID-19 guidelines are constantly evolving and require interventions that can be quickly and easily implemented to improve adherence. Sustained reminders through different approaches allowed a continued increase in requesting. This agrees with research that suggests a mixture of educational sessions and visual reminders of guidelines increase their application in clinical practice.

Behavioral economic assessment of abuse liability for Black & Mild cigar flavors among young adults.

Cigars are available in a variety of flavors that may impact uptake and use, but little is known about how different flavors affect abuse liability. This study used 3 behavioral economic tasks to examine abuse liability of Black & Mild cigars differing in flavor among young adult cigarette smokers. Participants were 25 cigar-naïve young adults (aged 18-25 years) who smoked ≥ 5 cigarettes/day. In 5 Latin square-ordered laboratory visits, participants completed 3 abuse liability tasks (drug purchase task, cross-price purchase task, and multiple-choice procedure) for each of 4 cigar flavors (original, cream, wine, or apple) and own-brand cigarettes. In the drug purchase task, relative to own-brand cigarettes, all cigar flavors were associated with lower abuse liability using most measures (intensity, breakpoint, maximum total tobacco expenditure for 1 day [ps < .05]), although only wine-flavored cigars scored significantly lower using 1 measure (price at maximum total tobacco expenditure for 1 day). When cigars and cigarettes were available concurrently in the cross-price purchase task, all cigar flavors functioned as substitutes for cigarettes. Using the multiple-choice procedure, crossover points for wine- (mean = $0.61) and apple-flavored cigars (mean = $0.71) were significantly lower than own-brand cigarettes (mean = $0.86) and original-flavored cigars (mean = $1.00); no significant differences existed between own-brand cigarettes and original-flavored cigars. Thus, whereas abuse liability may be highest for participants' own-brand cigarette, young adult smokers may be willing to use flavored cigars. Furthermore, abuse liability varies by cigar flavor, with original- and cream-flavored cigars appearing to have the highest abuse liability. Characterizing flavors and flavor additives in cigars represent an important tobacco regulatory target. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mental health in academia: Hacks for cultivating and sustaining wellbeing.

Mental health concerns among university populations are on the rise. Faculty and students report increasing levels of depression, stress, anxiety, and suicidal ideation. These mental health crises reduce overall wellness and inhibit the educational process. We identify uncertainty, financial stress, disruptions to social networks, burnout, and the contemporary social/political climate as key triggers for mental health crises for faculty and students. Faculty are in a position to provide support to one another and their students and as such, we provide strategies that attend to these triggers and complement other forms of intervention. We do not intend these "hacks" to supplant structural change or reputable medical advice; rather, they are intended to help focus attention on the importance and magnitude of mental health concerns in academia and to offer some strategies that faculty can implement.

Antibiotic guideline adherence by Clinicians in medical wards at Queen Elizabeth Central Hospital (QECH), Blantyre Malawi.

Antimicrobial resistance (AMR) is a major concern in health care worldwide. In Malawi rates of AMR, in particular third-generation cephalosporin-resistant (3GC-R) Enterobacterales have rapidly increased since 2003. Antibiotic guidelines are a key component of antimicrobial stewardship (AMS). As part of stewardship, Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi developed an antibiotic guideline in the form of a smart phone application in June 2016. Aim: We conducted a study to assess clinicians adherence to the local antibiotic guideline on the adult medical wards, two years after it was introduced. Specifically assessing choice of antibiotic, time of blood culture collection and 48-hour review. Methods: A cross-sectional study was carried out using purposive sampling method. 230 case files of adult patients were audited against the antibiotic guideline. Adherence to the guideline in terms of indication for antibiotic, choice of antibiotic and antibiotic review time was reviewed. Statistical analysis was done using IBM SPSS and presented with descriptive statistics. Results: 194 (84% [95% CI 79.0-88.8]) antibiotic prescriptions were adherent to the guideline, 28 (12% [95% CI 8.2-17.1]) non-adherent and 8 (3.5% [95% CI 1.5-6.7]) antibiotic indication was not clear. The most common indication for antibiotic prescriptions was pneumonia, as documented in 89 (39% [95 % CI 32.4-45.3]) case files. 191(76% [95% CI 70.3-81.2]) of prescriptions were for ceftriaxone. There was evidence of utilising blood culture to adjust therapy as 88/230 (38% [95% CI 32.0-44.9]) had culture taken. 175(76% [95 % CI 70.0-81.4]) of files had antibiotics reviewed within 48 hours. Conclusion: There is still need to work on rational prescribing of antibiotics as ceftriaxone usage was high during this study period. Scheduled audits and point prevalence surveys should be implemented quickly to reduce the impact of antibiotic resistance and improve individual patient care.

Drivers of Resistance in Uganda and Malawi (DRUM): a protocol for the evaluation of One-Health drivers of Extended Spectrum Beta Lactamase (ESBL) resistance in Low-Middle Income Countries (LMICs).

In sub-Saharan Africa (sSA), there is high morbidity and mortality from severe bacterial infection and this is compounded by antimicrobial resistance, in particular, resistance to 3rd-generation cephalosporins. This resistance is typically mediated by extended-spectrum beta lactamases (ESBLs). To interrupt ESBL transmission it will be important to investigate how human behaviour, water, sanitation, and hygiene (WASH) practices, environmental contamination, and antibiotic usage in both urban and rural settings interact to contribute to transmission of ESBL E. coli and ESBL K. pneumoniae between humans, animals, and the environment. Here we present the protocol for the Drivers of Resistance in Uganda and Malawi (DRUM) Consortium, in which we will collect demographic, geospatial, clinical, animal husbandry and WASH data from a total of 400 households in Uganda and Malawi. Longitudinal human, animal and environmental sampling at each household will be used to isolate ESBL E. coli and ESBL K. pneumoniae. This will be complimented by a Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) survey and structured observations to understand the contextual and psychosocial drivers of regional WASH practices. Bacterial isolates and plate sweeps will be further characterised using a mixture of short-,long-read and metagenomic whole-genome sequencing. These datasets will be integrated into agent-based models to describe the transmission of EBSL resistance in Uganda and Malawi and allow us to inform the design of interventions for interrupting transmission of ESBL-bacteria.