The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.

Understanding how differentiation programs originate from the gene-expression 'landscape' of hematopoietic stem cells (HSCs) is crucial for the development of new clinical therapies. We mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSCs and eight early progenitor populations. We found that transcriptional programs were extensively shared, extended across lineage-potential boundaries and were not strictly lineage affiliated. Elements of stem, lymphoid and myeloid programs were retained in multilymphoid progenitors (MLPs), which reflected a hybrid transcriptional state. By functional single cell analysis, we found that the transcription factors Bcl-11A, Sox4 and TEAD1 (TEF1) governed transcriptional networks in MLPs, which led to B cell specification. Overall, we found that integrated transcriptome approaches can be used to identify previously unknown regulators of multipotency and show additional complexity in lymphoid commitment.

Combined protection of vaccination and nirmatrelvir-ritonavir against hospitalization in adults with COVID-19.

Among U.S. adults at risk for severe COVID-19 in Epic Cosmos, the lowest rate of hospitalization was among those receiving three or more mRNA vaccine doses and nirmatrelvir-ritonavir (aHR 0.22, 95%CI: 0.19-0.24). Adults who are at high-risk of severe COVID-19 disease, including vaccinated persons, should be considered for antiviral treatment.

Antimicrobial-Resistant Nontyphoidal Salmonella Infection Following International Travel-United States, 2018-2019.

BACKGROUND: Antimicrobial resistance in nontyphoidal Salmonella (NTS) can limit treatment options. We assessed the contribution of international travel to antimicrobial-resistant NTS infections. METHODS: We describe NTS infections that were reported to the Foodborne Diseases Active Surveillance Network during 2018-2019 and screened for genetic resistance determinants, including those conferring decreased susceptibility to first-line agents (ciprofloxacin, ceftriaxone, or azithromycin). We used multivariable logistic regression to assess the association between resistance and international travel during the 7 days before illness began. We estimated the contribution of international travel to resistance using population-attributable fractions, and we examined reported antimicrobial use. RESULTS: Among 9301 NTS infections, 1159 (12%) occurred after recent international travel. Predicted resistance to first-line antimicrobials was more likely following travel; the adjusted odds ratio varied by travel region and was highest after travel to Asia (adjusted odds ratio, 7.2 [95% confidence interval, 5.5-9.5]). Overall, 19% (95% confidence interval, 17%-22%) of predicted resistance to first-line antimicrobials was attributable to international travel. More travelers than nontravelers receiving ciprofloxacin or other fluoroquinolones had isolates with predicted resistance to fluoroquinolones (29% vs 9%, respectively; P < .01). CONCLUSIONS: International travel is a substantial risk factor for antimicrobial-resistant NTS infections. Understanding risks of resistant infection could help target prevention efforts.

Point Prevalence Estimates of Activity-Limiting Long-term Symptoms Among United States Adults ≥1 Month After Reported Severe Acute Respiratory Syndrome Coronavirus 2 Infection, 1 November 2021.

BACKGROUND: Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021. METHODS: We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration. RESULTS: On 1 November 2021, at least 3.0-5.0 million US adults, or 1.2%-1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month's duration. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%-3.8%. CONCLUSIONS: Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Increased Multidrug-Resistant Salmonella enterica I Serotype 4,[5],12:i:- Infections Associated with Pork, United States, 2009-2018.

Reports of Salmonella enterica I serotype 4,[5],12:i:- infections resistant to ampicillin, streptomycin, sulphamethoxazole, and tetracycline (ASSuT) have been increasing. We analyzed data from 5 national surveillance systems to describe the epidemiology, resistance traits, and genetics of infections with this Salmonella strain in the United States. We found ASSuT-resistant Salmonella 4,[5],12:i:- increased from 1.1% of Salmonella infections during 2009-2013 to 2.6% during 2014-2018; the proportion of Salmonella 4,[5],12:i:- isolates without this resistance pattern declined from 3.1% to 2.4% during the same timeframe. Among isolates sequenced during 2015-2018, a total of 69% were in the same phylogenetic clade. Within that clade, 77% of isolates had genetic determinants of ASSuT resistance, and 16% had genetic determinants of decreased susceptibility to ciprofloxacin, ceftriaxone, or azithromycin. Among outbreaks related to the multidrug-resistant clade, 63% were associated with pork consumption or contact with swine. Preventing Salmonella 4,[5],12:i:- carriage in swine would likely avert human infections with this strain.

Trends in Laboratory-Confirmed SARS-CoV-2 Reinfections and Associated Hospitalizations and Deaths Among Adults Aged ≥18 Years - 18 U.S. Jurisdictions, September 2021-December 2022.

Although reinfections with SARS-CoV-2 have occurred in the United States with increasing frequency, U.S. epidemiologic trends in reinfections and associated severe outcomes have not been characterized. Weekly counts of SARS-CoV-2 reinfections, total infections, and associated hospitalizations and deaths reported by 18 U.S. jurisdictions during September 5, 2021-December 31, 2022, were analyzed overall, by age group, and by five periods of SARS-CoV-2 variant predominance (Delta and Omicron [BA.1, BA.2, BA.4/BA.5, and BQ.1/BQ.1.1]). Among reported reinfections, weekly trends in the median intervals between infections and frequencies of predominant variants during previous infections were calculated. As a percentage of all infections, reinfections increased substantially from the Delta (2.7%) to the Omicron BQ.1/BQ.1.1 (28.8%) periods; during the same periods, increases in the percentages of reinfections among COVID-19-associated hospitalizations (from 1.9% [Delta] to 17.0% [Omicron BQ.1/BQ.1.1]) and deaths (from 1.2% [Delta] to 12.3% [Omicron BQ.1/BQ.1.1]) were also substantial. Percentages of all COVID-19 cases, hospitalizations, and deaths that were reinfections were consistently higher across variant periods among adults aged 18-49 years compared with those among adults aged ≥50 years. The median interval between infections ranged from 269 to 411 days by week, with a steep decline at the start of the BA.4/BA.5 period, when >50% of reinfections occurred among persons previously infected during the Alpha variant period or later. To prevent severe COVID-19 outcomes, including those following reinfection, CDC recommends staying up to date with COVID-19 vaccination and receiving timely antiviral treatments, when eligible.

Effectiveness of COVID-19 mRNA Vaccination in Preventing COVID-19-Associated Hospitalization Among Adults with Previous SARS-CoV-2 Infection - United States, June 2021-February 2022.

Previous infection with SARS-CoV-2, the virus that causes COVID-19, has been estimated to confer up to 90% protection against reinfection, although this protection was lower against the Omicron variant compared with that against other SARS-CoV-2 variants (1-3). A test-negative design was used to estimate effectiveness of COVID-19 mRNA vaccines in preventing subsequent COVID-19-associated hospitalization among adults aged ≥18 years with a previous positive nucleic acid amplification test (NAAT) or diagnosis of COVID-19.† The analysis used data from Cosmos, an electronic health record (EHR)-aggregated data set (4), and compared vaccination status of 3,761 case-patients (positive NAAT result associated with hospitalization) with 7,522 matched control-patients (negative NAAT result). After previous SARS-CoV-2 infection, estimated vaccine effectiveness (VE) against COVID-19-associated hospitalization was 47.5% (95% CI = 38.8%-54.9%) after 2 vaccine doses and 57.8% (95% CI = 32.1%-73.8%) after a booster dose during the Delta-predominant period (June 20-December 18, 2021), and 34.6% (95% CI = 25.5%-42.5%) after 2 doses and 67.6% (95% CI = 61.4%-72.8%) after a booster dose during the Omicron-predominant period (December 19, 2021-February 24, 2022). Vaccination provides protection against COVID-19-associated hospitalization among adults with previous SARS-CoV-2 infection, with the highest level of protection conferred by a booster dose. All eligible persons, including those with previous SARS-CoV-2 infection, should stay up to date with vaccination to prevent COVID-19-associated hospitalization.

Antigen Test Positivity After COVID-19 Isolation - Yukon-Kuskokwim Delta Region, Alaska, January-February 2022.

Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for ≥24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR] = 6.39) or after symptomatic infection (aOR = 9.63), and less likely after previous infection (aOR = 0.30), receipt of a primary COVID-19 vaccination series (aOR = 0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR = 0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days.

Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 - United States, April-September 2022.

Nirmatrelvir-ritonavir (Paxlovid), an oral antiviral treatment, is authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness. However, real-world evidence on the benefit of Paxlovid, according to vaccination status, age group, and underlying health conditions, is limited. To examine the benefit of Paxlovid in adults aged ≥18 years in the United States, a large electronic health record (EHR) data set (Cosmos†) was analyzed to assess the association between receiving a prescription for Paxlovid and hospitalization with a COVID-19 diagnosis in the ensuing 30 days. A Cox proportional hazards model was used to estimate this association, adjusted for demographic characteristics, geographic location, vaccination, previous infection, and number of underlying health conditions. Among 699,848 adults aged ≥18 years eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within 5 days of COVID-19 diagnosis. Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] = 0.49), among those who had received ≥3 mRNA COVID-19 vaccines (aHR = 0.50), and across age groups (18-49 years: aHR = 0.59; 50-64 years: aHR = 0.40; and ≥65 years: aHR = 0.53). Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19-associated hospitalization.

COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis - California and New York, May-November 2021.

By November 30, 2021, approximately 130,781 COVID-19-associated deaths, one in six of all U.S. deaths from COVID-19, had occurred in California and New York.* COVID-19 vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19), associated severe illness, and death (1,2); among those who survive, previous SARS-CoV-2 infection also confers protection against severe outcomes in the event of reinfection (3,4). The relative magnitude and duration of infection- and vaccine-derived protection, alone and together, can guide public health planning and epidemic forecasting. To examine the impact of primary COVID-19 vaccination and previous SARS-CoV-2 infection on COVID-19 incidence and hospitalization rates, statewide testing, surveillance, and COVID-19 immunization data from California and New York (which account for 18% of the U.S. population) were analyzed. Four cohorts of adults aged ≥18 years were considered: persons who were 1) unvaccinated with no previous laboratory-confirmed COVID-19 diagnosis, 2) vaccinated (14 days after completion of a primary COVID-19 vaccination series) with no previous COVID-19 diagnosis, 3) unvaccinated with a previous COVID-19 diagnosis, and 4) vaccinated with a previous COVID-19 diagnosis. Age-adjusted hazard rates of incident laboratory-confirmed COVID-19 cases in both states were compared among cohorts, and in California, hospitalizations during May 30-November 20, 2021, were also compared. During the study period, COVID-19 incidence in both states was highest among unvaccinated persons without a previous COVID-19 diagnosis compared with that among the other three groups. During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; 7.2-fold (California) and 9.9-fold lower (New York) among unvaccinated persons with a previous COVID-19 diagnosis; and 9.6-fold (California) and 8.5-fold lower (New York) among vaccinated persons with a previous COVID-19 diagnosis. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These relationships changed after the SARS-CoV-2 Delta variant became predominant (i.e., accounted for >50% of sequenced isolates) in late June and July. By the week beginning October 3, compared with COVID-19 cases rates among unvaccinated persons without a previous COVID-19 diagnosis, case rates among vaccinated persons without a previous COVID-19 diagnosis were 6.2-fold (California) and 4.5-fold (New York) lower; rates were substantially lower among both groups with previous COVID-19 diagnoses, including 29.0-fold (California) and 14.7-fold lower (New York) among unvaccinated persons with a previous diagnosis, and 32.5-fold (California) and 19.8-fold lower (New York) among vaccinated persons with a previous diagnosis of COVID-19. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These results demonstrate that vaccination protects against COVID-19 and related hospitalization, and that surviving a previous infection protects against a reinfection and related hospitalization. Importantly, infection-derived protection was higher after the Delta variant became predominant, a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning (2,5,6). Similar cohort data accounting for booster doses needs to be assessed, as new variants, including Omicron, circulate. Although the epidemiology of COVID-19 might change with the emergence of new variants, vaccination remains the safest strategy to prevent SARS-CoV-2 infections and associated complications; all eligible persons should be up to date with COVID-19 vaccination. Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change.

Survey of Adherence with COVID-19 Prevention Behaviors During the 2020 Thanksgiving and Winter Holidays Among Members of the COVID-19 Community Research Partnership.

Prevention behaviors represent important public health tools to limit spread of SARS-CoV-2. Adherence with recommended public health prevention behaviors among 20000 + members of a COVID-19 syndromic surveillance cohort from the mid-Atlantic and southeastern United States was assessed via electronic survey following the 2020 Thanksgiving and winter holiday (WH) seasons. Respondents were predominantly non-Hispanic Whites (90%), female (60%), and ≥ 50 years old (59%). Non-household members (NHM) were present at 47.1% of Thanksgiving gatherings and 69.3% of WH gatherings. Women were more likely than men to gather with NHM (p < 0.0001). Attending gatherings with NHM decreased with older age (Thanksgiving: 60.0% of participants aged < 30 years to 36.3% aged ≥ 70 years [p-trend < 0.0001]; WH: 81.6% of those < 30 years to 61.0% of those ≥ 70 years [p-trend < 0.0001]). Non-Hispanic Whites were more likely to gather with NHM than were Hispanics or non-Hispanic Blacks (p < 0.0001). Mask wearing, reported by 37.3% at Thanksgiving and 41.9% during the WH, was more common among older participants, non-Hispanic Blacks, and Hispanics when gatherings included NHM. In this survey, most people did not fully adhere to recommended public health safety behaviors when attending holiday gatherings. It remains unknown to what extent failure to observe these recommendations may have contributed to the COVID-19 surges observed following Thanksgiving and the winter holidays in the United States.

Outbreak of Foodborne Botulism Associated with a Commercially Produced Multipack Potato Product, Colorado: September 2019.

During September 2019, public health authorities in El Paso County, Colorado, were notified of four patients who had presented to nearby hospitals with clinical features consistent with botulism, a paralytic illness caused by botulinum neurotoxin. One patient died soon after presentation; the other three patients required intensive care but recovered after receiving botulism antitoxin. Botulinum toxin type A was detected in serum from all patients. On further investigation, all four patients had shared a meal that included commercially prepared roasted potatoes from an individual package without refrigeration instructions that had been left unrefrigerated for 15 d. Storage of the product at ambient temperature likely allowed botulism spores to produce botulinum toxin, resulting in severe illness and death. The manufacturer improved labeling in response to this outbreak. Public health officials should consider unrefrigerated potato products as a potential source of botulism; clinicians should consider botulism as a possible cause of paralytic illness.

Vaccination Status of Alaska Native Persons With Hepatitis A Virus Infection-Alaska, 1996-2018.

Following increases in reported cases of hepatitis A, we assessed the impact of hepatitis A vaccine in Alaska Native persons. During 1996-2018, only 6 cases of hepatitis A were identified, all in unvaccinated adults. Populations can be protected against hepatitis A by achieving sufficient vaccination coverage over time.

Epidemiology of Invasive Haemophilus influenzae Serotype a Disease-United States, 2008-2017.

BACKGROUND: Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008-2017. METHODS: Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. RESULTS: From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. CONCLUSIONS: Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development.

Use of Pfizer-BioNTech COVID-19 Vaccine in Persons Aged ≥16 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2021.

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside 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. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,† and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.§ In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation¶ for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.

The risk of morbidity and mortality following recurrent malaria in Papua, Indonesia: a retrospective cohort study.

BACKGROUND: An acute episode of malaria can be followed by multiple recurrent episodes either due to re-infection, recrudescence of a partially treated parasite or, in the case of Plasmodium vivax or P. ovale, relapse from the dormant liver stage of the parasite. The aim of this study was to quantify the impact of recurrent malaria episodes on morbidity and mortality in Papua, Indonesia. METHODS: We undertook a retrospective analysis of routinely collected data from malaria patients attending the primary referral hospital in Papua, Indonesia, between April 2004 and December 2013. Multi-state modelling was used to estimate the effect of recurring malaria episodes on re-presentation and admission to hospital and death. The risks of early (≤ 14 days) and late (15 to 365 days) hospital admission and death were estimated separately in our study to distinguish between the direct and indirect effects of malaria recurrence on adverse outcomes. RESULTS: A total of 68,361 patients were included in the analysis, of whom 37,168 (54.4%) presented initially with P. falciparum, 22,209 (32.5%) with P. vivax, and 8984 (13.1%) with other species. During 12 months of follow-up after each of the first four malaria episodes, 10,868 (15.9%) patients were admitted to hospital and 897 (1.3%) died. The risk of re-presenting to the hospital with malaria increased from 34.7% (95% CI 34.4%, 35.1%) at first episode to 58.6% (57.5%, 59.6%) following the third episode of malaria. After adjusting for co-factors, infection with P. vivax was a significant risk factor for re-presentation (hazard ratio (HR) = 1.48 (95% CI 1.44, 1.51)) and late admission to hospital (HR = 1.17 (1.11, 1.22)). Patients infected with P. falciparum had a greater overall rate of mortality within 14 days (HR = 1.54 (1.25, 1.92)), but after multiple episodes of malaria, there was a trend towards a higher rate of early death in patients infected with P. vivax compared to P. falciparum (HR = 1.91 (0.73, 4.97)). CONCLUSIONS: Compared to patients initially infected with P. falciparum, those infected with P. vivax had significantly more re-presentations to hospital with malaria, and this contributed to a high risk of inpatient admission and death. These findings highlight the importance of radical cure of P. vivax to eliminate the dormant liver stages that trigger relapses.

Outbreak of Salmonella Newport Infections with Decreased Susceptibility to Azithromycin Linked to Beef Obtained in the United States and Soft Cheese Obtained in Mexico - United States, 2018-2019.

In September 2018, CDC identified Salmonella enterica serotype Newport (Newport) infections that were multidrug resistant (MDR), with decreased susceptibility to azithromycin, a recommended oral treatment agent. Until 2017, decreased susceptibility to azithromycin had occurred in fewer than 0.5% of Salmonella isolates from U.S. residents. This report summarizes the investigation of a multistate MDR Salmonella outbreak conducted by CDC, state and local health departments, and the U.S. Department of Agriculture's Food Safety and Inspection Service. During June 2018-March 2019, 255 cases of infection with the outbreak strain were identified in 32 states; 43% of patients (89 of 206 with information on travel) reported recent travel to Mexico. Infections were linked to consumption of soft cheese obtained in Mexico and beef obtained in the United States. Consumers should avoid eating soft cheese that could be made from unpasteurized milk, regardless of the source of the cheese. When preparing beef, a food thermometer should be used to ensure that appropriate cooking temperatures are reached. When antibiotic treatment is needed for a patient, clinicians should choose antibiotics based on susceptibility testing wherever possible.