Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants.

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10µm and <5µm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5µm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.

TB prevalence in Zimbabwe: a national cross-sectional survey, 2014.

BACKGROUND: We conducted the first national TB prevalence survey to provide accurate estimates of bacteriologically confirmed pulmonary TB disease among adults aged ≥15 years in 2014.METHODS: A TB symptoms screen and chest X-ray (CXR) were used to identify presumptive TB cases who submitted two sputum samples for smear microscopy, liquid and solid culture. Bacteriological confirmation included acid-fast bacilli smear positivity confirmed using Xpert® MTB/RIF and/or culture. Prevalence estimates were calculated using random effects logistic regression with multiple imputations and inverse probability weighting.RESULTS: Of 43,478 eligible participants, 33,736 (78%) were screened; of these 5,820 (17%) presumptive cases were identified. There were 107 (1.9%) bacteriologically confirmed TB cases, of which 23 (21%) were smear-positive. The adjusted prevalences of smear-positive and bacteriologically confirmed TB disease were respectively 82/100,000 population (95% CI 47-118/100,000) and 344/100,000 (95% CI 268-420/100,000), with an overall all-ages, all-forms TB prevalence of 275/100,000 population (95% CI 217-334/100,000). TB prevalence was higher in males, and age groups 35-44 and ≥65 years. CXR identified 93/107 (87%) cases vs. 39/107 (36%) using the symptom screen.CONCLUSION: Zimbabwe TB disease prevalence has decreased relative to prior estimates, possibly due to increased antiretroviral therapy coverage and successful national TB control strategies. Continued investments in TB diagnostics for improved case detection are required.

Chronic lung disease in adult recurrent tuberculosis survivors in Zimbabwe: a cohort study.

OBJECTIVE: To examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting. METHODS: Prospective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health. RESULTS: Among 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0-19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4-8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7-22.1). Among retreatment TB survivors, 33% (95%CI 26.0-40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score 10); 26% (95%CI 19.8-33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1-Q3 440-730 m); 83% (95%CI 75.7-89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6-16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6-17.5%) major depression. CONCLUSIONS: Despite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.

Reprint of "The relationship between culinary skills and eating behaviors: Challenges and opportunities for parents and families".

Unhealthy dietary intake among American children and adults is of great concern to public health practitioners, nutritional scientists, and child development experts. Cooking skills are related to healthier dietary intake among Americans of all ages, but remain a substantial barrier for many parents who want to serve healthy meals for their families at home. Culinary education interventions are effective solutions for many parents who do not know how to cook, but issues with participation bias mean that these programs are not effective solutions for all individuals. The food industry should develop solutions to help those parents for whom learning cooking skills is not an option - specifically through the development of healthier pre-assembled or prepared foods that do not require cooking skills to make. In the future, the research community should also strive to collect comprehensive population-based data on the state of cooking skills in the United States.

Effectiveness of the Cobb-Stainsby excision arthroplasty.

BACKGROUND: Dislocated metatarsophalangeal joints from clawed or hammer toes can be a disabling consequence of several conditions. The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb). We present a retrospective, three surgeon case series of 215 toes in 126 patients. METHODS: Early results and complications were gathered from the medical charts of 126 patients who met the inclusion criteria. Seventy-five patients were contactable by phone with a follow up range of 12-82 months (median follow up 45 months). Primary outcome measures were improvement of pain and function, reduction in plantar callosities and cosmetic improvement of the deformity. RESULTS: Pre-operatively all patients presented with pain and shoe wear problems. Post-operatively seventy-two patients (96%) were satisfied, 72 (96%) reported pain relief, 55 (73%) were happy with toe control, 61 (81%) were pleased with cosmesis and 56 (75%) reported unlimited daily activities. Superficial wound infections were observed in 13 of the 126 patients (10%) and two in 75 patients (2%) developed recurrent clawing. CONCLUSION: Our case series demonstrates improved outcomes over alternatives such as the Weil's osteotomy.

Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV-infected children in Zimbabwe.

BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing. RESULTS: Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently hospitalized for a chest infection. CONCLUSION: We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available.

Fisheries, low oxygen and climate change: how much do we really know?

As a result of long-term climate change, regions of the ocean with low oxygen concentrations are predicted to occur more frequently and persist for longer periods of time in the future. When low levels of oxygen are present, this places additional pressure on marine organisms to meet their metabolic requirements, with implications for growth, feeding and reproduction. Extensive research has been carried out on the effects of acute hypoxia, but far less on long-term chronic effects of low oxygen zones, especially with regard to commercially important fishes and shellfishes. To provide further understanding on how commercial species could be affected, the results of relevant experiments must support population and ecosystem models. This is not easy because individual effects are wide-ranging; for example, studies to date have shown that low oxygen zones can affect predator-prey relationships as some species are able to tolerate low oxygen more than others. Some fishes may move away from areas until oxygen levels return to acceptable levels, while others take advantage of a reduced start response in prey fishes and remain in the area to feed. Sessile or less mobile species such as shellfishes are unable to move out of depleted oxygen zones. Some species can tolerate low oxygen levels for only short periods of time, while others are able to acclimatize. To advance the knowledge-base further, a number of promising technological and modelling-based developments and the role of physiological data within these, are proposed. These include advances in remote telemetry (tagging) and sensor technologies, trait-based analyses to provide insight into how whole assemblages might respond in the future, research into long-term adaptability of species, population and ecosystem modelling techniques and quantification of economic effects. In addition, more detailed oxygen monitoring and projections are required to better understand the likely temporal and local-scale changes in oxygen.

Systemic inflammatory response syndrome following catheter-directed thrombolysis of acute iliofemoral deep venous thrombosis.

Catheter-directed thrombolysis is becoming increasingly considered in the treatment of acute ileofemoral deep vein thrombosis. By targeting occlusive thrombi early, it is possible to mitigate the symptoms of post-thrombotic syndrome, which include oedema, pain, and ulceration. NICE guidelines recommend the use of catheter-directed thrombolysis in those without contraindications to treatment. The main risk of thrombolysis is bleeding; however, other side effects such as allergy have been reported. We present a 50-year-old man who presented with an acute left-sided ileofemoral deep vein thrombosis. He underwent catheter-directed thrombolysis in our centre to good effect, and ultimately he required stenting due to the presence of a May-Thurner lesion. His first day of thrombolysis, however, was complicated by a massive systemic inflammatory response syndrome response resulting in pyrexia and tachycardia, rigors, and myalgia. His deterioration in observations corresponded with a huge rise in D-dimer levels from an admission baseline of 1465 ng/ml to 182,835 ng/ml. We hypothesize that rapid breakdown of thrombus in this patient resulted in a lysis-type syndrome, presenting with a systemic inflammatory response syndrome response. Several questions are raised here including why the patient responded in this way, and whether there could be a way to predict response ahead of time? Fortunately, our patient came to no harm and continues to do well, with no evidence of further thrombosis on surveillance ultrasound. This case highlights an important complication of thrombolysis and reminds us that complications are not just limited to bleeding. Despite the short-term effects in this young fit patient, concerns must be raised about potential safety in the frailer and more elderly patient demographic in which such a large inflammatory response could be more detrimental.

Effects of maternal dietary egg intake during early lactation on human milk ovalbumin concentration: a randomized controlled trial.

BACKGROUND: There is limited understanding of how maternal diet affects breastmilk food allergen concentrations, and whether exposure to allergens through this route influences the development of infant oral tolerance or sensitization. OBJECTIVE: To investigate how maternal dietary egg ingestion during early lactation influences egg protein (ovalbumin) levels detected in human breastmilk. METHODS: In a randomized controlled trial, women were allocated to a dietary group for the first six weeks of lactation: high-egg diet (> 4 eggs per week), low-egg diet (one-three eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6 weeks of lactation for the measurement of ovalbumin. The permeability of the mammary epithelium was assessed by measuring the breastmilk sodium : potassium ratio. Egg-specific IgE and IgG4 were measured in infant plasma at 6 weeks, and prior to the introduction of egg in solids at 16 weeks. RESULTS: Average maternal egg ingestion was associated with breastmilk ovalbumin concentration. Specifically, for each additional egg ingested per week, there was an average 25% increase in ovalbumin concentration (95% CI: 5-48%, P = 0.01). Breastmilk ovalbumin concentrations were significantly higher in the 'high-egg' group (> 4 eggs per week) compared with the 'egg-free' group (P = 0.04). However, one-third of women had no breastmilk ovalbumin detected. No detectable associations were found between mammary epithelium permeability and breastmilk ovalbumin concentrations. Infant plasma egg-specific IgG4 levels were also positively associated with maternal egg ingestion, with an average 22% (95% CI: 3-45%) increase in infant egg-specific IgG4 levels per additional egg consumed per week (P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Increased maternal egg ingestion is associated with increased breastmilk ovalbumin, and markers of immune tolerance in infants. These results highlight the potential for maternal diet to benefit infant oral tolerance development during lactation.

Xpert(®) MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe.

BACKGROUND: Patients at elevated risk of drug-resistant tuberculosis (TB) are prioritized for Xpert(®) MTB/RIF testing; however, the clinical usefulness of the test in this population is understudied. DESIGN: From November 2011 to June 2014, consecutive out-patients with a history of previous TB in high-density suburbs of Harare, Zimbabwe, were tested using Xpert, solid and liquid culture, and the microscopic observation drug susceptibility assay. Diagnostic accuracy for rifampin (RMP) resistance and time to initiation of second-line regimens were ascertained. The rpoB gene was sequenced in cases with culture-confirmed RMP resistance and genotypic susceptibility. RESULTS: Among 352 retreatment patients, 71 (20%) were RMP-resistant, 98 (28%) RMP-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative. Xpert had a sensitivity of 86% (95%CI 75-93) and a specificity of 98% (95%CI 92-100) for RMP-resistant TB. The positive predictive value of Xpert-determined RMP resistance for multidrug-resistant TB (MDR-TB) was 82% (95%CI 70-91). Of 71 (83%) participants, 59 initiated treatment with second-line drugs, with a median time to treatment initiation of 18 days (IQR 10-44). CONCLUSION: The diagnostic accuracy of Xpert for RMP resistance is high, although the predictive value for MDR-TB was lower than anticipated. Xpert allows for faster initiation of second-line treatment than culture-based drug susceptibility testing under programmatic conditions.

Re-inventing adherence: toward a patient-centered model of care for drug-resistant tuberculosis and HIV.

BACKGROUND: Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE: To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION: Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION: It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

Elucidating the role of clofazimine for the treatment of tuberculosis.

Clofazimine (CFZ), a riminophenazine and a key component of the treatment regimen for lepromatous leprosy, has been rehabilitated clinically for the treatment of multidrug-resistant tuberculosis (MDR-TB). Observational studies and a randomized control trial suggest efficacy in the treatment of MDR-TB and the potential for treatment shortening. Animal and translational research have shown mixed results. In this article, we review key clinical, animal, and translational data to better understand the potential role of CFZ in the treatment of MDR-TB and in shortening anti-tuberculosis treatment.

Elevated IL-5 and IL-13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema.

BACKGROUND: Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure. OBJECTIVE: To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy. METHODS: Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive 'early egg' or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge. RESULTS: In 4-month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by 'early' introduction of egg. CONCLUSIONS & CLINICAL RELEVANCE: Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.

Recent advances in telemetry for estimating the energy metabolism of wild fishes.

Metabolic rate is a critical factor in animal biology and ecology, providing an objective measure that can be used in attributing a cost to different activities and to assessing what animals do against some optimal behaviour. Ideally, metabolic rate would be estimated directly by measuring heat output but, until recently, this has not been easily tractable with fishes so instead metabolic rate is usually estimated using indirect methods. In the laboratory, oxygen consumption rate is the indirect method most frequently used for estimating metabolic rate, but technical requirements preclude the measurement of either heat output or oxygen consumption rate in free-ranging fishes. There are other field methods for estimating metabolic rate that can be used with mammals and birds but, again, these cannot be used with fishes. Here, the use of electronic devices that record body acceleration in three dimensions (accelerometry) is considered. Accelerometry is a comparatively new telemetric method for assessing energy metabolism in animals. Correlations between dynamic body acceleration (DBA) and oxygen consumption rate demonstrate that this will be a useful proxy for estimating activity-specific energy expenditure from fishes in mesocosm or field studies over extended periods where other methods (e.g. oxygen consumption rate) are not feasible. DBA therefore has potential as a valuable tool for attributing cost to different activities. This could help in gaining a full picture of how fishes make energy-based trade-offs between different levels of activity when faced with conflicting or competing demands arising from increased and combined environmental stressors.

Improving emergency department management of paediatric clavicle fractures: a complete audit cycle.

A protocol was devised to address the issue of unnecessary attendance at fracture clinic by children who have a fracture of the clavicle that is deemed to be uncomplicated. For the purposes of this protocol, the clavicle was divided into three zones. Fractures of the middle clavicle for which displacement was minimal, heal quickly in the majority of cases, without the need for follow up. As a result these children can be discharged provided the parents are adequately advised. This article outlines a study which investigated the effectiveness of the protocol. The study found that implementation of the protocol reduced unnecessary attendance at clinic from 85% (47/55) to 17% (4/23). This resulted in cost savings to the trust and reduced the pressure on staff working in busy fracture clinics.

Impact of Xpert MTB/RIF on Antiretroviral Therapy-Associated Tuberculosis and Mortality: A Pragmatic Randomized Controlled Trial.

INTRODUCTION: GeneXpert® MTB/RIF (Xpert) is now widely distributed in high human immunodeficiency virus (HIV)/tuberculosis (TB)-burden countries. Yet, whether the test improves patient-important outcomes within HIV treatment programs in limited resource settings is unknown. METHODS: To investigate whether use of Xpert for TB screening prior to initiation of antiretroviral treatment (ART) improves patient-important outcomes, in a pragmatic randomized controlled trial we assigned 424 patients to Xpert or fluorescence sputum smear microscopy (FM) at ART initiation. The primary endpoint was a composite of 3-month mortality and ART-associated TB. RESULTS: There was no difference in overall TB diagnosis at ART initiation (20% [n = 43] Xpert vs 21% [n = 45] FM; P = .80), with most patients in both groups treated empirically. There was no difference in time to TB treatment initiation {5 days (interquartile range [IQR], 3-13) vs 8 days [IQR, 3-23; P = .26]} or loss to follow-up (32 [15%] vs 38 [18%]; P = 0.38). Although a nonsignificant reduction in mortality occurred in the Xpert group (11 [6%] vs 17 [10%]; 95% CI, -9% to 2%; P = .19), there was no difference in the composite outcome (9% [n = 17] Xpert vs 12% [n = 21] FM; difference -3%; 95% CI, -9% to 4%). CONCLUSIONS: Among HIV-infected initiating ART, centralized TB screening with Xpert did not reduce the rate of ART-associated TB and mortality, compared with fluorescence microscopy.