BACKGROUND: The performance of two piperonyl butoxide (PBO-synergist) insecticide-treated net (ITN) brands, PermaNet(®) 3.0 and Olyset(®) Plus, were evaluated under field conditions in two neighboring districts in Sierra Leone over 36 months to estimate median ITN survival, understand insecticidal efficacy, and identify factors influencing ITN durability. This assessment can help guide future PBO-synergist ITN procurement and replacement strategies. METHODS: This prospective study tracked 370 households and 652 campaign-distributed ITNs from 2020, followed annually for 36 months. Districts were purposefully selected based on shared characteristics. Household surveys were conducted, and 30 ITNs per round were tested for bioefficacy and chemical residue. Key indicators included ITN survival, 24-h mosquito mortality, and chemical content reduction compared to manufacturer targets doses. Cox proportional hazard models identified factors influencing ITN survival. RESULTS: Median useful life was 3.0 (95% CI 2.7-3.5) years for PermaNet(®) 3.0 ITNs in Bo and 2.2 (95% CI 2.0-2.4) years for Olyset(®) Plus ITNs in Moyamba. PermaNet(®) 3.0 ITNs displayed 13% 24-h mortality against pyrethroid-resistant mosquitoes on roof panels, with a 46% reduction in PBO content 34 months post-distribution. Olyset(®) Plus ITNs had 3% f24-hour mortality against pyrethroid-resistant mosquitoes, with a 77% reduction in PBO content. Several factors were associated with improved ITN survival, including cohort ITNs from Bo (adjusted hazard ratio [aHR] = 0.33, p < 0.001), households without children under five (CU5) (aHR = 0.64, p = 0.003), highest socio-economic status tertile (aHR = 0.63, p = 0.016), exposure to social and behaviour change (SBC) messages combined with positive net attitudes (aHR = 0.63, p = 0.008), lack of food storage in sleeping spaces (aHR = 0.56, p = 0.006), exclusive adult use of ITNs (aHR = 0.72, p = 0.048), net folding when not in use (aHR = 0.67, p = 0.015), and drying nets outside (aHR = 0.44, p = 0.008). CONCLUSION: ITNs in Bo outperformed those in Moyamba in both physical and insecticidal performance. However, ITN survival is highly context specific, and further investigation into field performance of new ITN types is necessary across diverse epidemiological settings.

BACKGROUND: Information on the status of insecticide resistance in malaria vectors is critical for implementing effective malaria vector control. The Sierra Leone National Malaria Control Programme, in collaboration with the PMI VectorLink project, assessed the resistance status to insecticides commonly used in public health, and associated resistance mechanisms in Anopheles gambiae, the main vector of malaria in Sierra Leone. METHODS: The susceptibility of An. gambiae against pyrethroids with and without piperonyl butoxide (PBO), chlorfenapyr, clothianidin, bendiocarb and pirimiphos-methyl was evaluated in four districts of Sierra Leone in 2018 and 2019 using WHO and CDC bottle bioassay protocols. A subset of samples that were exposed to the insecticides were screened for molecular markers of insecticide resistance, knock-down resistance (kdr) L1014F, 1014S and N1575Y, and (ace-1-G119S). RESULTS: Anopheles gambiae from all sites were resistant to the diagnostic doses of three pyrethroids: deltamethrin, permethrin and alpha-cypermethrin. Intensity of resistance to all three pyrethroids was high, with less than 95% mortality at 10X concentration. However, pre-exposure of An. gambiae to PBO increased overall mortality by 41.6%, 50.0% and 44.0% for deltamethrin, permethrin and alpha-cypermethrin, respectively. The vector was susceptible to chlorfenapyr, clothianidin and pirimiphos-methyl, while bendiocarb showed possible resistance. The frequency of kdr alleles was 98.2% for L1014F, 2.1% for 1014S and 8.9% for N1575Y, while the frequency of the Ace-1 G119S allele was 13.6%. Significant deviation from the Hardy-Weinberg equilibrium and deficiency of heterozygotes was detected only at the G119S locus of An. gambiae (p < 0.0001). Of the 191 An. gambiae sensu lato that were molecularly identified to the species level, 81.7% were An. gambiae sensu stricto (95% CI 75.3-86.7), followed by Anopheles coluzzii (17.8%, 95% CI (12.8-24.1) with one hybrid of An. gambiae/An. coluzzii 0.5%, 95% CI (0.03-3.3). CONCLUSION: Malaria vectors were highly resistant to pyrethroids but exposure to PBO partially restored susceptibility in An. gambiae s.l. in Sierra Leone. Malaria vectors were susceptible to chlorfenapyr, clothianidin and pirimiphos-methyl with possible resistance to bendiocarb. These data informed the selection and distribution of ITN PBO in Sierra Leone's mass campaigns in 2020 and selection of clothianidin for indoor residual spraying in 2021.

Background: Annual estimates of seasonal influenza vaccine effectiveness can guide global risk communication and vaccination strategies to mitigate influenza-associated illness. We aimed to evaluate vaccine effectiveness in countries using the 2023 southern hemisphere influenza vaccine formulation.

BACKGROUND: Circumcision is a protective measure against sexually transmitted infections (STIs), reducing the risk of HIV infection. This study reported coverage of male circumcision and assessed the factors associated with male uncircumcision in a peri-urban area in Maputo City, Mozambique. METHODS: This cross-sectional study of the Health Demographic Surveillance System in the Polana Caniço neighborhood investigated the sociodemographic and behavioral factors associated with uncircumcised males aged 15-49 y from October 2019 to June 2021. Data were collected from an HIV risk factors questionnaire and descriptive analyses conducted comparing self-reported male circumcision status by sociodemographic factors and sexual behaviors. The association was assessed via χ2 tests, and a multivariable logistic regression model was constructed. Adjusted ORs and 95% CIs were reported for factors associated with uncircumcised status. RESULTS: Of the 3481 males aged 15-49 y who responded to the questionnaire, 79.5% (2766) self-reported being circumcised. The percentage of uncircumcised men steadily increased with age, ranging from 12.4% (95) among males aged 15-19 y to 34.5% (148) of men aged 40-49 y. Men without education or with primary education, as well as those not practicing Islam, were 3-4 times more likely to be uncircumcised. Uncircumcised men were more likely to self-report an STI and a lack of condom use. CONCLUSIONS: Being uncircumcised was associated with not using condoms and having STIs, highlighting the need to further emphasize combination HIV-prevention programs and regular HIV/STI screening. Targeting males with lower education and across religions can help reach those with lower coverage of this effective prevention intervention.

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.Competing Interest StatementClare Whitehead declares a a relationship with the following entities, Ferring Pharmaceuticals COVID19 Investigational, Grant, NHMRC Fellowship (salary support). Alice Panchaud declares the following research grants to institution: H2020-Grant (Consortium member of Innovative medicine initiative call 13 topic 9) (ConcePTION), Efficacy and safety studies on Medicines EMA/2017/09/PE/11, Lot 4, WP 2 lead (CONSIGN: Study on impact of COVID-19 infection and medicines in pregnancy), Safety monitoring of COVID-19 vaccines in the EU Reopening of competition no. 20 under a framework contract following procurement procedure EMA/2017/09/PE (Lot 3) 4. Federal Office of Public Health (207000 CHF). (The COVI-Preg registry). Edward Mullins declares a relationship with the following entities National Institute for Health Research (Project grant for PAN COVID study) Deborah Money declares a relationship with the following entities, Canadian Institutes of Health Research (payments to my institution only), Public Health Agency of Canada (payments to my institution only), BC Womens Foundation (payments to my institution only) and is a Member of the COVID-19 Immunity Task Force sponsored by the Canadian government. Torri D. Metz declares a relationship with the following entities, Pfizer (site Principal Investigator for SARS-CoV-2 vaccination in pregnancy study, money paid to institution and member of Medical Advisory Board for SARS-CoV-2 vaccination in pregnancy study, money paid to me), NICHD (subcommittee Chair for the NICHD Maternal-Fetal Medicine Units Network Gestational Research Assessments of COVID-19 (GRAVID) study), and Society for Maternal-Fetal Medicine (board member). Erica Lokken declares a relationship with the following entity, US NIH (paid institution). Karen L. Kotloff declares a relationship with the following entity, Bill and Melinda Gates Foundation. Siran He declares a relationship with the following entity, Bill and Melinda Gates Foundtion (payments made to my institution). Valerie Flaherman declares a relationship with the following entities, Bill and Melinda Gates Foundation (payments to my institution), Yellow Chair Foundati n (payments to my institution), Robert Woods Johnson Foundation (payments to my institution), CDC Foundation, California Health Care Foundation (payments to my institution), Tara Health Foundation (payments to my institution), UCSF Womens Health Center of Excellence (payments to my institution) and California Department of Health Care Services (payments made to my institution). Jose Sanin-Blair declares a relationship with the following entity, Ferring Pharmaceuticals which give a grant ($10,000) for the expenses of RECOGEST trial and is a part of the Columbian Federation of Perinatology Yalda Afshar declares a relationship with the following entities, Bill and Melinda Gates Foundation (payments made to my institution), CDC Foundation (payments made to my institution), Robert Woods Johnson Foundation (payments made to my institution), and UCLA Deans Office COVID-19 research (payments made to my institution). Rebecca Cliffton declares a relationship with the following entity, NIH HD36801 (MFMU Network DCC).Clinical TrialPROSPERO ID: 188955Funding StatementFunded by the Bill &amp; Melinda Gates Foundation grant to Emily Smith (INV-022057) at George Washington University and a grant to Emily Smith via a grant from the Bill &amp; Melinda Gates Foundation to Stephanie Gaw (INV-017035) at University of California San Francisco.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This is a protocol paper and thus exempt from ethical approval. Ultimately, the meta-analysis study is exempt from human research ethics approval as the study authors will be synthesizing de-identified or aggregate data.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThis is a protocol paper and there is no related data to share.

To reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) and its associated impacts on health and society, COVID-19 vaccines are essential. The U.S. government is working to produce and deliver safe and effective COVID-19 vaccines for the entire U.S. population. The Advisory Committee on Immunization Practices (ACIP)1 has broadly outlined its approach for developing recommendations for the use of each COVID-19 vaccine authorized or approved by the Food and Drug Administration (FDA) for Emergency Use Authorization or licensure.1 ACIP’s recommendation process includes an explicit and transparent evidence-based method for assessing a vaccine’s safety and efficacy as well as consideration of other factors, including implementation.2 Because the initial supply of vaccine will likely be limited, ACIP will also recommend which groups should receive the earliest allocations of vaccine. The ACIP COVID-19 Vaccines Work Group and consultants with expertise in ethics and health equity considered external expert committee reports and published literature and deliberated the ethical issues associated with COVID-19 vaccine allocation decisions. The purpose of this report is to describe the four ethical principles that will assist ACIP in formulating recommendations for the allocation of COVID-19 vaccine while supply is limited, in addition to scientific data and implementation feasibility: (1) maximize benefits and minimize harms; (2) promote justice; (3) mitigate health inequities; and (4) promote transparency. These principles can also aid state, tribal, local, and territorial public health authorities as they develop vaccine implementation strategies within their own communities based on ACIP recommendations.

This study aimed to assess temporary and permanent auditory effects associated with occupational coexposure to low levels of noise and solvents. Cross-sectional study with 25 printing industry workers simultaneously exposed to low noise (&lt;80 dBA TWA) and low levels of solvents. The control group consisted of 29 industry workers without the selected exposures. Participants answered a questionnaire and underwent auditory tests. Auditory fatigue was measured by comparing the acoustic reflex threshold before and after the workday. Workers coexposed to solvents and noise showed significantly worse results in auditory tests in comparison with the participants in the control group. Auditory brainstem response results showed differences in III-V interpeak intervals (p = 0.046 in right ear; p = 0.039 in left ear). Mean dichotic digits scores (exposed = 89.5 ± 13.33; controls = 96.40 ± 4.46) were only different in the left ear (p = 0.054). The comparison of pre and postacoustic reflex testing indicated mean differences (p = 0.032) between the exposed (4.58 ± 6.8) and controls (0 ± 4.62) groups. This study provides evidence of a possible temporary effect (hearing fatigue) at the level of the acoustic reflex of the stapedius muscle. The permanent effects were identified mainly at the level of the high brainstem and in the auditory ability of binaural integration.

In early 2018, we investigated a large national multiple-serotype Salmonella outbreak linked to contaminated kratom, a raw minimally processed botanical substance. Kratom is a plant consumed for its stimulant effects and as an opioid substitute. A case was defined as a laboratory-confirmed Salmonella infection with one of the outbreak strains (serotypes I 4,[5],12:b:-, Heidelberg, Javiana, Okatie, Weltevreden, or Thompson) with illnesses onset during January 11, 2017-May 8, 2018. State and local officials collected detailed information on product consumption and sources. Suspected products were tested for Salmonella and traceback was conducted to determine product distribution chains and suppliers. We identified 199 cases from 41 states; 54 patients were hospitalized. Early interviews indicated kratom was an exposure of interest. Seventy-six (74%) of 103 people interviewed reported consuming kratom in pills, powders, or teas. Multiple serotypes of Salmonella were detected in samples of kratom collected from the homes of the patients and from retail locations. Several companies issued recalls of kratom products due to Salmonella contamination. To the authors' knowledge, this investigation is the first to establish kratom as a vehicle for Salmonella infection. Our findings underscore the serious safety concerns regarding minimally processed botanical substances intended for oral consumption and the challenges in investigating outbreaks linked to novel outbreak vehicles.

Schumacher Amy C, Elbadawi Lina I, DeSalvo Traci, Straily Anne, Ajzenberg Daniel, Letzer David, Moldenhauer Ellen, Handly Tammy L, Hill Dolores, Dardé Marie-Laure, Pomares Christelle, Passebosc-Faure Karine, Bisgard Kristine, Gomez Carlos A, Press Cindy, Smiley Stephanie, Montoya José G, Kazmierczak James J. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2022

OBJECTIVE: Rotavirus A (RVA) remains the main causative agent of gastroenteritis in young children and the young of many mammalian and avian species. In this study we describe a RVA strain detected from a 6-month-old child from Central African Republic (CAR). RESULTS: We report the 11 open reading frame sequences of a G29-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 rotavirus strain, RVA/Human-wt/CAR/CAR91/2014/G29P[6]. Nine genes (VP1-VP3, VP6, NSP1-NSP5) shared 90-100% sequence similarities with genogroup 2 rotaviruses. Phylogenetically, backbone genes, except for VP3 and NSP4 genes, were linked with cognate gene sequences of human DS-1-like genogroup 2, hence their genetic origin. The VP3 and NSP4 genes, clustered genetically with both human and animal strains, an indication genetic reassortment human and animal RVA strains has taken place. The VP7 gene shared nucleotide (93-94%) and amino acid (95.5-96.7%) identities with Kenyan and Belgian human G29 strains, as well as to buffalo G29 strain from South Africa, while the VP4 gene most closely resembled P[6]-lineage I strains from Africa and Bangladesh (97%).

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for use of the Pfizer-BioNTech COVID-19 vaccine (Pfizer, Inc; Philadelphia, Pennsylvania) in persons aged ≥16 years (1); on December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the vaccine in the same age group (2). As of May 12, 2021, approximately 141.6 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥16 years.* On May 10, 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years (1). On May 12, 2021, ACIP issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(§) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥12 years under an EUA is interim and will be updated as additional information becomes available.

On May 13, 2020, Chicago established a free community-based testing (CBT) initiative for SARS-CoV-2, the virus that causes COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR). The initiative focused on demographic groups and geographic areas that were underrepresented in testing by clinical providers and had experienced high COVID-19 incidence, including Hispanic persons and those who have been economically marginalized. To assess the CBT initiative, the Chicago Department of Public Health (CDPH) compared demographic characteristics, economic marginalization, and test positivity between persons tested at CBT sites and persons tested in all other testing settings in Chicago. During May 13-November 14, a total of 253,904 SARS-CoV-2 RT-PCR tests were conducted at CBT sites. Compared with those tested in all other testing settings in Chicago, persons tested at CBT sites were more likely to live in areas that are economically marginalized (38.6% versus 32.0%; p<0.001) and to be Hispanic (50.9% versus 20.7%; p<0.001). The cumulative percentage of positive test results at the CBT sites was higher than that at all other testing settings (11.1% versus 7.1%; p<0.001). These results demonstrate the ability of public health departments to establish community-based testing initiatives that reach communities with less access to testing in other settings and that experience disproportionately higher incidences of COVID-19.

Each year in Latin America and the Caribbean, seasonal influenza is associated with an estimated 36,500 respiratory deaths and 400,000 hospitalizations. Since the 2009 influenza A(H1N1) pandemic, the Region has made significant advances in the prevention and control of seasonal influenza, including improved surveillance systems, burden estimates, and vaccination of at-risk groups. The Global Influenza Strategy 2019-2030 provides a framework to strengthen these advances. Against the backdrop of this new framework, the University of Colorado convened in October 2020 its Immunization Advisory Group of Experts to review and discuss current surveillance, prevention, and control strategies for seasonal influenza in Latin America and the Caribbean, also in the context of the COVID-19 pandemic. This review identified five areas for action and made recommendations specific to each area. The Region should continue its efforts to strengthen surveillance and impact evaluations. Existing data on disease burden, seasonality patterns, and vaccination effectiveness should be used to inform decision-making at the country level as well as advocacy efforts for programmatic resources. Regional and country strategic plans should be prepared and include specific targets for 2030. Existing investments in influenza prevention and control, including for immunization programs, should be optimized. Finally, regional partnerships, such as the regional networks for syndromic surveillance and vaccine effectiveness evaluation (SARInet and REVELAC-i), should continue to play a critical role in continuous learning and standardization by sharing experiences and best practices among countries.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged <50 years, as well as the availability of alternative COVID-19 vaccines, is required to guide vaccine decision-making and ensure early recognition and clinical management of TTS.

Candida auris is an emerging fungal pathogen of rising concern due to global spread, the ability to cause healthcare-associated outbreaks, and antifungal resistance. Genomic analyses revealed that early contemporaneously detected cases of C. auris were geographically stratified into four major clades. While Clades I, III, and IV are responsible for ongoing outbreaks of invasive and multidrug-resistant infections, Clade II, also termed the East Asian clade, consists primarily of cases of ear infection, is often susceptible to all antifungal drugs, and has not been associated with outbreaks. Here, we generate chromosome-level assemblies of twelve isolates representing the phylogenetic breadth of these four clades and the only isolate described to date from Clade V. This Clade V genome is highly syntenic with those of Clades I, III, and IV, although the sequence is highly divergent from the other clades. Clade II genomes appear highly rearranged, with translocations occurring near GC-poor regions, and large subtelomeric deletions in most chromosomes, resulting in a substantially different karyotype. Rearrangements and deletion lengths vary across Clade II isolates, including two from a single patient, supporting ongoing genome instability. Deleted subtelomeric regions are enriched in Hyr/Iff-like cell-surface proteins, novel candidate cell wall proteins, and an ALS-like adhesin. Cell wall proteins from these families and other drug-related genes show clade-specific signatures of selection in Clades I, III, and IV. Subtelomeric dynamics and the conservation of cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggest an explanation for the different phenotypes observed between clades.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc, a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey). The Janssen COVID-19 vaccine is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector vaccine, encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19 (1). Vaccination with the Janssen COVID-19 vaccine consists of a single dose (5 × 1010 virus particles per 0.5-mL dose) administered intramuscularly. On February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Janssen COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. This vaccine is the third COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendations (EtR) framework,† following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.§ The ACIP recommendation for the use of the Janssen COVID-19 vaccine under an EUA is interim and will be updated as additional information becomes available.

BACKGROUND: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. METHODS: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). RESULTS: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. CONCLUSIONS: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

We report an analysis of the genomic diversity of isolates of Burkholderia pseudomallei, the cause of melioidosis, recovered in Colombia from routine surveillance during 2016-2017. B. pseudomallei appears genetically diverse, suggesting it is well established and has spread across the region.

Burkholderia pseudomallei is a Gram-negative bacterium that causes the sapronotic disease melioidosis. An outbreak in 2003 in the state of Ceara, Brazil, resulted in subsequent surveillance and environmental sampling which led to the recognition of B. pseudomallei as an endemic pathogen in that area. From 2003 to 2015, 24 clinical and 12 environmental isolates were collected across Ceara along with one from the state of Alagoas. Using next-generation sequencing, multilocus sequence typing, and single nucleotide polymorphism analysis, we characterized the genomic diversity of this collection to better understand the population structure of B. pseudomallei associated with Ceara. We found that the isolates in this collection form a distinct subclade compared to other examples from the Western Hemisphere. Substantial genetic diversity among the clinical and environmental isolates was observed, with 14 sequence types (STs) identified among the 37 isolates. Of the 31,594 core single-nucleotide polymorphisms (SNPs) identified, a high proportion (59%) were due to recombination. Because recombination events do not follow a molecular clock, the observation of high occurrence underscores the importance of identifying and removing recombination SNPs prior to evolutionary reconstructions and inferences in public health responses to B. pseudomallei outbreaks. Our results suggest long-term B. pseudomallei prevalence in this recently recognized region of melioidosis endemicity.IMPORTANCE B. pseudomallei causes significant morbidity and mortality, but its geographic prevalence and genetic diversity are not well characterized, especially in the Western Hemisphere. A better understanding of the genetic relationships among clinical and environmental isolates will improve knowledge of the population structure of this bacterium as well as the ability to conduct epidemiological investigations of cases of melioidosis.

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multi-ethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth type 2 diabetes cases (mean age 15.1±2.9 y) and 6,061 diabetes-free adult controls (mean age 54.2±12.4 y). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified 7 genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P=3.2×10(-8), odds ratio [OR]=1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P=8.0×10(-20), OR 1.58), rs72982988 near MC4R (P=4.4×10(-14), OR=1.53), rs200893788 in CDC123 (P=1.1×10(-12), OR= 1.32), rs2237892 in KCNQ1 (P=4.8×10(-11), OR=1.59), rs937589119 in IGF2BP2 (P=3.1×10(-9), OR=1.34) and rs113748381 in SLC16A11 (P=4.1×10(-8), OR=1.04). Secondary analysis with 856 diabetes-free youth controls uncovered an additional locus in CPEB2 (P=3.2×10(-8), OR=2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome wide association study (GWAS) of youth-onset type 2 diabetes.

Thirty Clostridioides difficile isolates collected in 2016 through the Centers for Disease Control and Prevention Emerging Infections Program were selected for reference antimicrobial susceptibility testing and whole-genome sequencing. Here, we present the genetic characteristics of these isolates and announce their availability in the CDC & FDA Antibiotic Resistance Isolate Bank.

BACKGROUND: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. METHODS: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0-14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. RESULTS: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). CONCLUSIONS: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed.

The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) (1) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020.* However, demand for COVID-19 vaccines is expected to exceed supply during the first months of the national COVID-19 vaccination program. ACIP advises CDC on population groups and circumstances for vaccine use.(†) On December 1, ACIP recommended that 1) health care personnel(§) and 2) residents of long-term care facilities(¶) be offered COVID-19 vaccination first, in Phase 1a of the vaccination program (2). On December 20, 2020, ACIP recommended that in Phase 1b, vaccine should be offered to persons aged ≥75 years and frontline essential workers (non-health care workers), and that in Phase 1c, persons aged 65-74 years, persons aged 16-64 years with high-risk medical conditions, and essential workers not recommended for vaccination in Phase 1b should be offered vaccine.** These recommendations for phased allocation provide guidance for federal, state, and local jurisdictions while vaccine supply is limited. In its deliberations, ACIP considered scientific evidence regarding COVID-19 epidemiology, ethical principles, and vaccination program implementation considerations. ACIP's recommendations for COVID-19 vaccine allocation are interim and might be updated based on changes in conditions of FDA Emergency Use Authorization, FDA authorization for new COVID-19 vaccines, changes in vaccine supply, or changes in COVID-19 epidemiology.

On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Moderna COVID-19 (mRNA-1273) vaccine (ModernaTX, Inc; Cambridge, Massachusetts), a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). This vaccine is the second COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). Vaccination with the Moderna COVID-19 vaccine consists of 2 doses (100 μg, 0.5 mL each) administered intramuscularly, 1 month (4 weeks) apart. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Moderna COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,(†) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.(§) Use of all COVID-19 vaccines authorized under an EUA, including the Moderna COVID-19 vaccine, should be implemented in conjunction with ACIP's interim recommendations for allocating initial supplies of COVID-19 vaccines (3). The ACIP recommendation for the use of the Moderna COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

BACKGROUND: Aztreonam/avibactam is a combination agent that shows promise in treating infections caused by highly antibiotic-resistant MBL-producing Enterobacterales. This combination can be achieved by combining two FDA-approved drugs: ceftazidime/avibactam and aztreonam. It is unknown whether ceftazidime in the combination ceftazidime/aztreonam/avibactam has a synergistic or antagonistic effect on the in vitro activity of aztreonam/avibactam by significantly increasing or decreasing the MIC. OBJECTIVES: To determine whether increasing ceftazidime concentrations affect the MICs of aztreonam/avibactam alone. METHODS: A custom 8 × 8 chequerboard broth microdilution (BMD) panel was made using a digital dispenser (Hewlett-Packard, Corvallis, OR, USA). The panel included orthogonal 2-fold dilution series of aztreonam and ceftazidime ranging from 0.5 to 64 mg/L. Avibactam concentration was kept constant at 4 mg/L throughout the chequerboard. Thirty-seven Enterobacterales isolates from the CDC & FDA Antibiotic Resistance Isolate Bank or CDC's internal collection with intermediate or resistant interpretations to aztreonam and ceftazidime/avibactam were included for testing. All isolates harboured at least one of the following MBL genes: blaIMP, blaNDM or blaVIM. RESULTS: Regardless of the concentration of ceftazidime, aztreonam/avibactam with ceftazidime MICs for all 37 isolates were within one 2-fold doubling dilution of the aztreonam/avibactam MIC. CONCLUSIONS: Ceftazidime, in the combination ceftazidime/avibactam/aztreonam, did not affect the in vitro activity of aztreonam/avibactam in this sample of isolates. These findings can help assure clinical and public health laboratories that testing of aztreonam/avibactam by BMD can act as a reliable surrogate test when the combination of ceftazidime/avibactam and aztreonam is being considered for treatment of highly antibiotic-resistant MBL-producing Enterobacterales.

BACKGROUND: Continued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants. METHODS: We did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1-4 years) and infants (aged 18-22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ClinicalTrials.gov, NCT02521974 and NCT03554798. FINDINGS: The control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medical events in any group. Solicited and unsolicited adverse events were overwhelmingly mild or moderate irrespective of vaccine or dose. Nearly all children were seroprotected at baseline, indicating high baseline immunity. In children, the seroprotection rate 28 days after one dose was 100% for monovalent OPV2 and both novel OPV2 candidates. In infants at day 28, 91 (94% [95% CI 87-98]) of 97 were seroprotected after receiving monovalent OPV2, 134 (94% [88-97]) of 143 after high-dose novel OPV2-c1, 122 (93% [87-97]) of 131 after low-dose novel OPV2-c1, 138 (95% [90-98]) of 146 after high-dose novel OPV2-c2, and 115 (91% [84-95]) of 127 after low-dose novel OPV2-c2. Non-inferiority was shown for low-dose and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 despite monovalent OPV2 recipients having higher baseline immunity. INTERPRETATION: Both novel OPV2 candidates were safe, well tolerated, and immunogenic in children and infants. Novel OPV2 could be an important addition to our resources against poliovirus given the current epidemiological situation. FUNDING: Fighting Infectious Diseases in Emerging Countries and Bill & Melinda Gates Foundation.

On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (Pfizer, Inc; Philadelphia, Pennsylvania), a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 doses (30 μg, 0.3 mL each) administered intramuscularly, 3 weeks apart. On December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,(†) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(§) The recommendation for the Pfizer-BioNTech COVID-19 vaccine should be implemented in conjunction with ACIP's interim recommendation for allocating initial supplies of COVID-19 vaccines (2). The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

The emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has led to a global pandemic that has disrupted all sectors of society. Less than 1 year after the SARS-CoV-2 genome was first sequenced, an application* for Emergency Use Authorization for a candidate vaccine has been filed with the Food and Drug Administration (FDA). However, even if one or more vaccine candidates receive authorization for emergency use, demand for COVID-19 vaccine is expected to exceed supply during the first months of the national vaccination program. The Advisory Committee on Immunization Practices (ACIP) advises CDC on population groups and circumstances for vaccine use.(†) ACIP convened on December 1, 2020, in advance of the completion of FDA's review of the Emergency Use Authorization application, to provide interim guidance to federal, state, and local jurisdictions on allocation of initial doses of COVID-19 vaccine. ACIP recommended that, when a COVID-19 vaccine is authorized by FDA and recommended by ACIP, both 1) health care personnel(§) and 2) residents of long-term care facilities (LTCFs)(¶) be offered vaccination in the initial phase of the COVID-19 vaccination program (Phase 1a**).(††) In its deliberations, ACIP considered scientific evidence of SARS-CoV-2 epidemiology, vaccination program implementation, and ethical principles.(§§) The interim recommendation might be updated over the coming weeks based on additional safety and efficacy data from phase III clinical trials and conditions of FDA Emergency Use Authorization.