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BackgroundWith a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. ObjectiveThe study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. MethodsThe study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. ResultsThe MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. ConclusionsThis is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. Trial RegistrationClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 International Registered Report Identifier (IRRID)DERR1-10.2196/20904

This piece investigates the complex and multiple meanings associated with one piece of Australian Aboriginal material culture, a broom made by Yanyuwa woman Emalina Evans a-Wanajabi in the 1980s. Yanyuwa people constitute one nation of the myriad Aboriginal peoples of Australia, with Yanyuwa country being in the southwest Gulf of Carpentaria, in the far north of Australia. In this piece, we explore both the uses of and the meanings associated with brooms within Aboriginal and colonial contexts. Emalina a-Wanajabi’s broom stands as a testament to her response to the colonial imposition on Yanyuwa women during the assimilationist years of 1950s Australia. The broom highlights the false and essentialist rhetoric invented concerning Aboriginal identity in the eyes of the coloniser. Emalina’s experiences of welfare intervention in her early life may have contributed to her decision to manufacture this broom in her later years. Surveillance into Aboriginal home life and routine inspections conducted by welfare administrators played a role in Emalina’s formative years, as was the case for Aboriginal people in many regions of Australia. For Emalina welfare intervention resulted in the removal of two of her children during the period we call the “Stolen Generations”. Interventions into Aboriginal family life by colonial authorities, based in racialised discourses of cleanliness and domesticity, have played key roles in the colonisation of Australia and have had particular impact on Aboriginal women. Emalina’s broom therefore becomes a particularly powerful response to colonial discourses of cleanliness. Material evidence of Aboriginal women’s resistance appears less often in studies of material culture and anthropology more generally. Exploring the meanings associated with the broom as a physical manifestation of resistance allows us to recognise a significant assertion of women’s cultural identity and essential position as holder of knowledge within the Yanyuwa community, as well as their role in resisting colonisation.

THIS REPORT UPDATES PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS ON PREFERRED PREVENTION AND TREATMENT REGIMENS REGARDING NATURALLY OCCURRING ANTHRAX. ALSO PROVIDED ARE A WIDE RANGE OF ALTERNATIVE REGIMENS TO FIRST-LINE ANTIMICROBIAL DRUGS FOR USE IF PATIENTS HAVE CONTRAINDICATIONS OR INTOLERANCES OR AFTER A WIDE-AREA AEROSOL RELEASE OF: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. CHANGES FROM PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS INCLUDE AN EXPANDED LIST OF ALTERNATIVE ANTIMICROBIAL DRUGS TO USE WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE CONTRAINDICATED OR NOT TOLERATED OR AFTER A BIOTERRORISM EVENT WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE DEPLETED OR INEFFECTIVE AGAINST A GENETICALLY ENGINEERED RESISTANT: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

Antimicrobial resistance increases infection morbidity in both adults and children, necessitating the development of new therapeutic options. Telavancin, an antibiotic approved in the United States for certain bacterial infections in adults, has not been examined in pediatric patients. The objectives of this study were to evaluate the short-term safety and pharmacokinetics (PK) of a single intravenous infusion of telavancin in pediatric patients. Single-dose safety and PK of 10 mg/kg telavancin was investigated in pediatric subjects >12 months to ≤17 years of age with known or suspected bacterial infection. Plasma was collected up to 24-h post-infusion and analyzed for concentrations of telavancin and its metabolite for noncompartmental PK analysis. Safety was monitored by physical exams, vital signs, laboratory values, and adverse events following telavancin administration. Twenty-two subjects were enrolled: 14 subjects in Cohort 1 (12-17 years), 7 subjects in Cohort 2 (6-11 years), and 1 subject in Cohort 3 (2-5 years). A single dose of telavancin was well-tolerated in all pediatric age cohorts without clinically significant effects. All age groups exhibited increased clearance of telavancin and reduced exposure to telavancin compared to adults, with mean peak plasma concentrations of 58.3 µg/mL (Cohort 1), 60.1 µg/mL (Cohort 2), and 53.1 µg/mL (Cohort 3). A 10 mg/kg dose of telavancin was well tolerated in pediatric subjects. Telavancin exposure was lower in pediatric subjects compared to adult subjects. Further studies are needed to determine the dose required in phase 3 clinical trials in pediatrics.

Ceftolozane/tazobactam is approved for the treatment of patients from birth to

The provenance of GEMS (glass with embedded metal and sulfides) in cometary type interplanetary dust particles is investigated using analytical scanning transmission electron microscopy and secondary ion mass spectrometry. We review the current state of knowledge and closely examine the densities, elemental compositions and distributions, iron oxidation states, and isotopic compositions of a subset of GEMS in chondritic porous interplanetary dust. We find that GEMS are underdense with estimated densities that are 35–65% of compositionally equivalent crystalline aggregates. GEMS low densities result in a lower contribution to the bulk compositions of IDPs than has been assumed based on their volume fraction. We also find that element/Si ratios, assumed to be primary (indigenous), are instead perturbed by contamination and secondary alteration, including pulse heating during atmospheric entry. Fe in pyrrhotite inclusions was oxidized and Mg, S, Ca, and Fe were depleted relative to lithophile Al and Si, resulting in reduction in element/Si ratios. Because they trap outgassing elements, Fe-rich oxide rims that formed on the surface of GEMS are serendipitous “witness plates” to the changes in composition that accompany atmospheric entry. As a result of alteration, GEMS elemental compositions cannot reliably inform about their provenance. Except for highly anomalous oxygen isotope ratios measured in some large GEMS grains that indicate a contribution from circumstellar dust, oxygen isotope compositions are generally poor indicators of provenance. Prior work indicates that most GEMS fall close to the terrestrial oxygen isotope composition, which, however, does not exclude a presolar interstellar origin. Nitrogen isotopic compositions are more diagnostic. Elevated 15N/14N ratios indicate that GEMS accreted in conjunction with formation of organic matter by ion–molecule reactions in a cold (

Measures to limit SARS-CoV-2 transmission in 2020 reduced other viral infections. Among 7 US children's hospitals, invasive pneumococcal disease cumulative incidence decreased by 46% in 2020 vs 2017-2019. Limited droplet transmission of pneumococci and preceding viral pathogens may be responsible.

Guidelines for management of Melody transcatheter pulmonary valve (TPV) infective endocarditis (IE) are lacking. We aimed to identify factors associated with surgical valve removal versus antimicrobial therapy in Melody TPV IE. Multicenter retrospective analysis of all patients receiving Melody TPV from 10/2010 to 3/2019 was performed to identify cases of IE. Surgical explants versus non-surgical cases were compared. Of the 663 Melody TPV implants, there were 66 cases of IE in 59 patients (59/663, 8.8%). 39/66 (59%) were treated with IV antimicrobials and 27/66(41%) underwent valve explantation. 26/59 patients (44%) were treated medically without explantation or recurrence with average follow-up time of 3.5 years (range:1-9). 32% of Streptococcus cases, 53% of MSSA, and all MRSA cases were explanted. 2 of the 4 deaths had MSSA. CART analysis demonstrated two important parameters associated with explantation: a peak echo gradient ≥ 47 mmHg at IE diagnosis(OR 10.6, p  24 mmHg compared to baseline (OR 6.7, p = 0.01). Rates of explantation varied by institution (27 to 64%). In our multicenter experience, 44% of patients with Melody IE were successfully medically treated without valve explantation or recurrence. The degree of valve stenosis at time of IE diagnosis was strongly associated with explantation. Rates of explantation varied significantly among the institutions.

Increasing prevalence of infections caused by antimicrobial-resistant gram-negative bacteria represents a global health crisis, and while several novel therapies that target various aspects of antimicrobial resistance have been introduced in recent years, few are currently approved for children. Ceftazidime-avibactam is a novel β-lactam β-lactamase inhibitor combination approved for adults and children 3 months and older with complicated intra-abdominal infection, and complicated urinary tract infection or hospital-acquired ventilator-associated pneumonia (adults only in the United States) caused by susceptible gram-negative bacteria. Extensive population pharmacokinetic (PK) data sets for ceftazidime and avibactam obtained during the adult clinical development program were used to iteratively select, modify, and validate the approved adult dosage regimen (2,000-500 mg by 2-hour intravenous (IV) infusion every 8 hours (q8h), with adjustments for renal function). Following the completion of one phase I (NCT01893346) and two phase II ceftazidime-avibactam studies (NCT02475733 and NCT02497781) in children, adult PK data sets were updated with pediatric PK data. This paper describes the development of updated combined adult and pediatric population PK models and their application in characterizing the population PK of ceftazidime and avibactam in children, and in dose selection for further pediatric evaluation. The updated models supported the approval of ceftazidime-avibactam pediatric dosage regimens (all by 2-hour IV infusion) of 50-12.5 mg/kg (maximum 2,000-500 mg) q8h for those ≥6 months to 18 years old, and 40-10 mg/kg q8h for those ≥3 to 6 months old with creatinine clearance > 50 mL/min/1.73 m2 .