Differentiating between acute febrile illnesses (AFIs) caused by arboviruses like dengue virus (DENV) and other pathogens is challenging, particularly in the case of coinfections, which often require comprehensive diagnostic testing for accurate identification. Recognizing DENV coinfections is important because they may contribute to increased disease severity, and their identification can aid in patient management decisions. Using data from the Sentinel Enhanced Dengue Surveillance System in Puerto Rico (2012-2024), we compared patients with DENV monoinfection to those coinfected with DENV and another pathogen. All pathogens were identified via nucleic acid detection by using real-time, reverse transcriptase-polymerase chain reaction or serology. We examined demographic and clinical features linked to coinfection using Mann-Whitney-Wilcoxon, χ2, or Fisher's exact tests. Among 50,189 participants tested for DENV, 1,218 (2.4%) had DENV infections, with 1,172 (96.2%) monoinfections and 46 (3.8%) coinfections. The most frequent coinfecting pathogens were adenovirus (17.4%), influenza A (15.2%), human metapneumovirus (15.2%), and respiratory syncytial virus (10.9%). Dengue virus coinfections were associated with younger age (median: 13 versus 16 years; P = 0.011) and symptoms of rhinorrhea (52.2% versus 27.3%; P <0.001) and cough (60.9% versus 36.4%; P = 0.001). Among 549 hospitalized dengue patients, 20 (3.6%) had coinfections. Five of seven participants with DENV/influenza A coinfection were hospitalized. Hospitalization, intensive care unit admission, the administration of blood products, and severe dengue indicators (plasma leakage, severe bleeding, and organ involvement) were not significantly associated with DENV coinfection. Overall, DENV coinfections were uncommon in AFI cases in Puerto Rico, and they primarily involved respiratory viruses. Overlapping symptoms may complicate clinical management, emphasizing the importance of comprehensive pathogen testing in settings where arboviruses and respiratory viruses cocirculate.

Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other poorly understood post-acute infection syndromes (PAIS) can present with unexplained symptoms or conditions that may be misunderstood by healthcare providers, causing delays in diagnosis and care. To address these issues, the Centers for Disease Control and Prevention (CDC) funded the Long COVID and Fatiguing Illness Recovery Program (LC&FIRP), initiated as a pilot project to assess whether providing tele-mentoring and other online education for primary care providers could help them improve the quality of life and support the recovery of their patients with these conditions. The LC&FIRP multi-disciplinary team-based care approach is built on the Extension for Community Healthcare Outcomes (ECHO) learning model, which is an evidence-based virtual learning framework developed by the University of New Mexico and designed to disseminate and implement best practices, especially in under-resourced areas. A distinctive feature of LC&FIRP was the inclusion of lived-experience experts. To explore the influence of lived-experience experts on the care patients received, we collected the educational recommendations provided by the lived-experience experts during webinar sessions (January 2022-March 2024) and grouped these by themes. The major themes that emerged included validation of patients' illness experience; attitudes and beliefs about Long COVID, ME/CFS, and PAIS; understanding patients' challenges and communicating with empathy; navigating referrals; recognizing and supporting disability; and supporting self-care. Investigators also interviewed patients of the Family Health Centers of San Diego (FHCSD) about their experiences receiving care from participating primary care providers and employed content analysis methods to code interview transcripts to identify themes among patients' perspectives. Positive comments from the patients about topics emphasized by the lived-experience experts provided evidence of providers' uptake and application of the experts' recommendations and support the value of involving lived-experience experts in medical education to improve health services.

Seroprevalence studies play an important role in estimating the number of children infected with SARS-CoV-2. We report SARS-CoV-2 seroprevalence in children seeking medical care for any reason at a free-standing pediatric hospital in Seattle, WA over a 2.5-year period and four distinct pandemic waves. We randomly selected residual serum samples from children and young adults seeking medical care as inpatients and outpatients at Seattle Children's Hospital between June 2020 and December 2022 to test for the presence of anti-nucleocapsid (N) antibodies. Samples were categorized into four distinct pandemic waves based on Washington State epidemiology: Wave 1 (June 2020-October 2020), Wave 2 (November 2020-June 2021), Wave 3 (July 2021-November 2021), and Wave 4 (December 2021-December 2022). Patient characteristics and COVID-19 vaccine status were obtained, and zip codes were used to ascertain the Social Vulnerability Index (SVI). Multivariable Poisson regression models with robust variance estimates were used to examine the relationship between patient characteristics and anti-N-positivity for each wave. Among 8,040 samples from 7,102 patients included in the analyses, seroprevalence rose from 2.4% (95% CI, 2.0%-3.1%) in Wave 1 to 25.5% (95% CI 23.3%-27.8%) in Wave 4 (following the Omicron surge). High SVI, Hispanic ethnicity, or use of government insurance was associated with increased anti-N positivity in most waves. We observed a steady increase in anti-N seroprevalence followed by a sharp increase after the Omicron surge in early 2022. Our data demonstrate the burden of COVID-19 on specific groups with health disparities within our region throughout the pandemic.IMPORTANCEOur results highlight the importance of seropositivity studies as essential tools to provide information on the incidence and prevalence of SARS-CoV-2 seropositivity. Our results also reinforce other reports demonstrating the inequitable burden of COVID-19 on groups with health disparities and that this inequitable burden continued to persist throughout the pandemic, even in a region with high adherence to COVID-19 mitigation efforts. It also highlights SVI's value in identifying communities that must be part of pandemic research, and public health and vaccination strategies.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative disease resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1-2 new individuals per million each year, and the sporadic type accounts for 90% of those cases. Though the median age at onset and disease duration vary depending on the subtype of sporadic CJD (sCJD), the disease typically affects middle-aged to elderly individuals with a median survival of 4-6 months. sCJD in younger individuals is extremely rare. Here, we present a 21-year-old female who died with a sporadic prion disease. She presented with psychiatric symptoms followed by a rapidly progressive neurocognitive and motor decline. EEG was negative for periodic sharp wave complexes; however, brain MRI was suggestive of prion disease. The cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) assay was indeterminate. Neuropathologic examination at autopsy revealed severe neuronal loss and gliosis with secondary white matter degeneration but minimal spongiform changes and PrP deposits in the cerebellum and neocortex by immunohistochemistry. Absence of pathogenic mutations and methionine/valine heterozygosity at codon 129 of the prion protein gene (PRNP), atypical type 1 protease-resistant PrP that lacks or shows underrepresentation of the diglycosylated PrP isoform by western blot analysis, and no acquired prion disease risk factors resulted in a final diagnosis of atypical sCJD. Very young onset sCJD often has atypical clinical presentations and disease progression, neuropathological examination results, and/or laboratory test results that may confound diagnosis. It is critical to perform thorough, comprehensive evaluations to make an accurate diagnosis, which includes autopsy confirmation with histology, prion protein typing and prion gene sequencing.

Individuals with certain primary immunodeficiency disorders (PID) may be unable to clear poliovirus infection after exposure to oral poliovirus vaccine (OPV). Over time, vaccine-related strains can revert to immunodeficiency-associated vaccine-derived poliovirus (iVDPVs) that can cause paralysis in the patient and potentially spread in communities with low immunity. We reviewed the efforts for detection and management of PID patients with iVDPV infections and the epidemiology through an analysis of 184 cases reported to the World Health Organization (WHO) during 1962-2024 and a review of polio program and literature reports. Most iVDPV patients (79%) reported in the WHO Registry were residents in middle-income countries and almost half (48%) in the Eastern Mediterranean Region. Type 2 iVDPV was most frequently isolated (53%), but a sharp decline was observed after the switch to bivalent OPV in 2016, with only six cases reported during 2017-2024 compared to 63 during 2009-2016. Patients with common variable immunodeficiency have longer excretion of iVDPV than with other PID types. Implementation of sensitive sentinel surveillance to detect cases of iVDPV infection in high-risk countries and offer antiviral treatment to patients is challenged by competition with other health priorities and regulatory hurdles to the compassionate use of investigational antiviral drugs.

Before October 2024, the Advisory Committee on Immunization Practices (ACIP) recommended use of a pneumococcal conjugate vaccine (PCV) for all adults aged ≥65 years, as well as for those aged 19-64 years with risk conditions for pneumococcal disease who have not received a PCV or whose vaccination history is unknown. Options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals) or 21-valent PCV (PCV21; CAPVAXIVE; Merck Sharp & Dohme) alone or 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme). There are additional recommendations for use of PCV20 or PCV21 for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on expanding the age-based PCV recommendation to include adults aged 50-64 years. On October 23, 2024, ACIP recommended a single dose of PCV for all PCV-naïve adults aged ≥50 years. Recommendations for PCVs among adults aged 19-49 years with risk conditions and PCV13-vaccinated adults have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides updated clinical guidance for use of PCV.

BACKGROUND: A sharp increase in reported brucellosis incidence was observed in northwestern Tajikistan (from 1.0/100,000 people in January-May 2022 to 32.7/100,000 in January-May 2023). Most (82%) cases were from the same remote mountainous village (population = 10,712). The aim of this study was to identify risk factors for brucellosis infection and mitigate disease risk. METHODS: Using a case-control design, we conducted face-to-face interviews and collected blood samples during May-June 2023. Fifty-seven cases and 114 controls were recruited. Cases were the first person in a household diagnosed with brucellosis during February-June 2023 with positive serum agglutination test and antibody titers ≥1/160 from blood samples. Two controls were selected for each case (neighbors from different households matched by age and sex). Controls testing positive were excluded and replaced. We conducted conditional multivariable logistic regression to calculate adjusted odds ratio (AOR) and 95% confidence intervals (CI). RESULTS: Among the 87 brucellosis patients reported, 57 (66%) agreed to participate and didn't have secondary cases in the household. Of the 57 cases, 68% were 15-44 years old, and 44% were male. Cases peaked in May 2023. Common symptoms were joint pain (95%), fever (84%), weakness (72%), and night sweats (65%). Of selected controls, 13% tested positive and were excluded. All cases and 94% of controls owned livestock (mostly cattle, sheep, or goats); no animals had not been vaccinated in the past 5 years. Brucellosis was associated with consumption of both homemade kaymak (clotted cream) and home-raised meat compared with neither (AOR: 59 [95%CI: 4.3-798], p < 0.01), home-raised meat but not kaymak compared with neither (AOR: 54 [4.0-731], p < 0.01), and involvement in animal slaughter compared with no involvement (AOR: 36 [2.8-461], p < 0.01). CONCLUSION: Contact with unvaccinated livestock or consumption of their products was a key contributor to this outbreak in a remote village of Tajikistan. With 13% of controls testing positive, true incidence was likely greater than reported. Following our investigation, a brucellosis awareness education campaign and animal vaccination campaigns were carried out in the region and only one case was reported in September 2023.

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19-64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose of PCV21 as an option for adults aged ≥19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21.

mRNA-based COVID-19 vaccines have played a critical role in reducing severe outcomes of COVID-19. Humoral immune responses against SARS-CoV-2 after vaccination have been extensively studied in blood; however, limited information is available on the presence and duration of SARS-CoV-2 specific antibodies in saliva and other mucosal fluids. Saliva offers a non-invasive sampling method that may also provide a better understanding of mucosal immunity at sites where the virus enters the body. Our objective was to evaluate the salivary immune response after vaccination with the COVID-19 Moderna mRNA-1273 vaccine. Two hundred three staff members of the U.S. Centers for Disease Control and Prevention were enrolled prior to receiving their first dose of the mRNA-1273 vaccine. Participants were asked to self-collect 6 saliva specimens at days 0 (prior to first dose), 14, 28 (prior to second dose), 42, and 56 using a SalivaBio saliva collection device. Saliva specimens were tested for anti-spike protein SARS-CoV-2 specific IgA and IgG enzyme immunoassays. Overall, SARS-CoV-2-specific salivary IgA titers peaked 2 weeks after each vaccine dose, followed by a sharp decrease during the following weeks. In contrast to IgA titers, IgG antibody titers increased substantially 2 weeks after the first vaccine dose, peaked 2 weeks after the second dose and persisted at an elevated level until at least 8 weeks after the first vaccine dose. Additionally, no significant differences in IgA/IgG titers were observed based on age, sex, or race/ethnicity. All participants mounted salivary IgA and IgG immune responses against SARS-CoV-2 after receiving the mRNA-1273 COVID-19 vaccine. Because of the limited follow-up time for this study, more data are needed to assess the antibody levels beyond 2 months after the first dose. Our results confirm the potential utility of saliva in assessing immune responses elicited by immunization and possibly by infection.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

PROBLEM/CONDITION: A 2019 report quantified the higher percentage of potentially excess (preventable) deaths in U.S. nonmetropolitan areas compared with metropolitan areas during 2010-2017. In that report, CDC compared national, regional, and state estimates of preventable premature deaths from the five leading causes of death in nonmetropolitan and metropolitan counties during 2010-2017. This report provides estimates of preventable premature deaths for additional years (2010-2022). PERIOD COVERED: 2010-2022. DESCRIPTION OF SYSTEM: Mortality data for U.S. residents from the National Vital Statistics System were used to calculate preventable premature deaths from the five leading causes of death among persons aged <80 years. CDC's National Center for Health Statistics urban-rural classification scheme for counties was used to categorize the deaths according to the urban-rural county classification level of the decedent's county of residence (1: large central metropolitan [most urban], 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore [most rural]). Preventable premature deaths were defined as deaths among persons aged <80 years that exceeded the number expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Preventable premature deaths were calculated separately for the six urban-rural county categories nationally, the 10 U.S. Department of Health and Human Services public health regions, and the 50 states and the District of Columbia. RESULTS: During 2010-2022, the percentage of preventable premature deaths among persons aged <80 years in the United States increased for unintentional injury (e.g., unintentional poisoning including drug overdose, unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall) and stroke, decreased for cancer and chronic lower respiratory disease (CLRD), and remained stable for heart disease. The percentages of preventable premature deaths from the five leading causes of death were higher in rural counties in all years during 2010-2022. When assessed by the six urban-rural county classifications, percentages of preventable premature deaths in the most rural counties (noncore) were consistently higher than in the most urban counties (large central metropolitan and fringe metropolitan) for the five leading causes of death during the study period.During 2010-2022, preventable premature deaths from heart disease increased most in noncore (+9.5%) and micropolitan counties (+9.1%) and decreased most in large central metropolitan counties (-10.2%). Preventable premature deaths from cancer decreased in all county categories, with the largest decreases in large central metropolitan and large fringe metropolitan counties (-100.0%; benchmark achieved in both county categories in 2019). In all county categories, preventable premature deaths from unintentional injury increased, with the largest increases occurring in large central metropolitan (+147.5%) and large fringe metropolitan (+97.5%) counties. Preventable premature deaths from CLRD decreased most in large central metropolitan counties where the benchmark was achieved in 2019 and increased slightly in noncore counties (+0.8%). In all county categories, preventable premature deaths from stroke decreased from 2010 to 2013, remained constant from 2013 to 2019, and then increased in 2020 at the start of the COVID-19 pandemic. Percentages of preventable premature deaths varied across states by urban-rural county classification during 2010-2022. INTERPRETATION: During 2010-2022, nonmetropolitan counties had higher percentages of preventable premature deaths from the five leading causes of death than did metropolitan counties nationwide, across public health regions, and in most states. The gap between the most rural and most urban counties for preventable premature deaths increased during 2010-2022 for four causes of death (cancer, heart disease, CLRD, and stroke) and decreased for unintentional injury. Urban and suburban counties (large central metropolitan, large fringe metropolitan, medium metropolitan, and small metropolitan) experienced increases in preventable premature deaths from unintentional injury during 2010-2022, leading to a narrower gap between the already high (approximately 69% in 2022) percentage of preventable premature deaths in noncore and micropolitan counties. Sharp increases in preventable premature deaths from unintentional injury, heart disease, and stroke were observed in 2020, whereas preventable premature deaths from CLRD and cancer continued to decline. CLRD deaths decreased during 2017-2020 but increased in 2022. An increase in the percentage of preventable premature deaths for multiple leading causes of death was observed in 2020 and was likely associated with COVID-19-related conditions that contributed to increased mortality from heart disease and stroke. PUBLIC HEALTH ACTION: Routine tracking of preventable premature deaths based on urban-rural county classification might enable public health departments to identify and monitor geographic disparities in health outcomes. These disparities might be related to different levels of access to health care, social determinants of health, and other risk factors. Identifying areas with a high prevalence of potentially preventable mortality might be informative for interventions.

OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥ 90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and they resembled T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

Lyme disease, a tickborne zoonosis caused by certain species of Borrelia spirochetes, is the most common vectorborne disease in the United States. Approximately 90% of all cases are reported from 15 high-incidence jurisdictions in the Northeast, mid-Atlantic, and upper-Midwest regions. After the implementation of a revised surveillance case definition in 2022, high-incidence jurisdictions report cases based on laboratory evidence alone, without need for additional clinical information. In 2022, 62,551 Lyme disease cases were reported to CDC, 1.7 times the annual average of 37,118 cases reported during 2017-2019. Annual incidence increased most in older age groups, with incidence among adults aged ≥65 years approximately double that during 2017-2019. The sharp increase in reported Lyme disease cases in 2022 likely reflects changes in surveillance methods rather than change in disease risk. Although these changes improve standardization of surveillance across jurisdictions, they preclude detailed comparison with historical data.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Background Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children and young adult HAI titers against the 2019-2020 LAIV4 and ccIIV4.Methods Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n =100) or LAIV4 (n=98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.Results GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p&lt;0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p&lt;0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p&lt;0.05) than cell-grown GMTs [ccIIV4 day 28: egg=205 (95% CI: 178-237); cell=136 (95% CI:113-165); LAIV4 day 28: egg=96 (95% CI: 83-112); cell=63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.Conclusion The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. For both vaccines, the A/H3N2 cell-grown antigen levels were lower than egg-grown, but the GMFR for cell-grown and egg-grown did not differ significantly within vaccine type.Clinical Trials No NCT03982069Competing Interest StatementConflict of Interest: RKZ has received funding by Sanofi for an unrelated study. MPN has research funding from Merck &amp; Co., Inc. for an unrelated study. JMM has received funding from Merck, Sharp and Dohme for an unrelated study.Clinical TrialClinical Trials No.: NCT03982069Funding StatementThis work was supported by the Centers for Disease Control and Prevention (CDC) [5U01IP001035] and by National Institutes of Health (NIH) [UL1TR001857], [KL2 TR001856], and/or [TL1 TR001858]. This work represents the views of the authors and not the CDC or NIH. Pennsylvania Statewide Immunization Information System (PA-SIIS) vaccine registry was used to verify vaccination status. These data were supplied in part by the Bureau of Health Statistics &amp; Registries, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. REDCap and the Department of Biomedical Informatics grant support (Clinical and Translational Sciences Institute at the University of Pittsburgh Grant Number UL1-TR-001857). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Pittsburgh. 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:The Institutional Review Boards at the University of Pittsburgh and the Centers for Disease Control and Prevention (CDC) approved this study. Written informed consent and assent, where appropriate, were obtained from all participants and/or their parents/legal guardians prior to beginning study procedures.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.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 expla ning 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.YesData can be made available upon request.HAIhemagglutination inhibition assayIIVinactivated influenza vaccineccIIV4cell-culture-based inactivated influenza vaccine quadrivalentLAIV4Egg-based live attenuated influenza vaccine quadrivalentEMRElectronic medical recordRDEReceptor-destroying enzymePBSPhosphate-buffered salineCDCCenters for Disease Control and PreventionFDAFood and Drug AdministrationGMTGeometric mean titersGMFRGeometric mean fold riseACIPAdvisory Committee on Immunization PracticePA-SIISPennsylvania Statewide Immunization Information System

Background Triatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. When these blood-sucking bugs adapt to new microhabitats, their phenotypes may change. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood.Methods/Findings We combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrial cytb and nuclear ITS2 DNA-sequence analyses to study Rhodnius ecuadoriensis populations from across the species’ range. We found three major, naked-eye phenotypic variants. Southern-Andean bugs (SW Ecuador/NW Peru) from house and vertebrate-nest microhabitats are typical, light-colored, small bugs with short heads/wings. Northern-Andean bugs (W Ecuador wet-forest palms) are dark, large bugs with long heads/wings. Finally, northern-lowland bugs (coastal Ecuador dry-forest palms) are light-colored and medium-sized. Wing and (size-free) head shapes are similar across Ecuadorian populations, regardless of habitat or naked-eye phenotype, but distinct in Peruvian bugs. Bayesian phylogenetic and multispecies-coalescent DNA-sequence analyses strongly suggest that Ecuadorian and Peruvian populations are two independently-evolving lineages, with little within-lineage structuring/differentiation.Conclusions We report sharp naked-eye phenotypic divergence of genetically similar Ecuadorian R. ecuadoriensis (house/nest southern-Andean vs. palm-dwelling northern bugs; and palm-dwelling Andean vs. lowland); and sharp naked-eye phenotypic similarity of typical, yet genetically distinct, southern-Andean bugs from house and nest (but not palm) microhabitats (SW Ecuador vs. NW Peru). This remarkable phenotypic diversity within a single nominal species likely stems from microhabitat adaptations possibly involving predator-driven selective pressure (yielding substrate-matching camouflage coloration) and a shift from palm-crown to vertebrate-nest microhabitats (yielding smaller bodies and shorter heads and wings). These findings shed new light on the origins of phenotypic diversity in triatomines, warn against excess reliance on phenotype-based triatomine-bug taxonomy, and confirm the Triatominae as an informative model-system for the study of phenotypic change under ecological pressure.Author summary Triatomine bugs feed on the blood of vertebrates including humans and transmit the parasite that causes Chagas disease. The bugs, of which 150+ species are known, are highly diverse in size, shape, and color. Some species look so similar that they are commonly confused, whereas a few same-species populations look so different that they were thought to be separate species. Despite the crucial role of naked-eye phenotypes in triatomine-bug identification and classification (which are essential for vector control-surveillance), the origins of this variation remain unclear. Here, we describe a striking case of phenotypic divergence, with genetically similar bugs looking very different from one another, and phenotypic convergence, with bugs from two genetically distinct populations (likely on their way to speciation) looking very similar – and all within a single nominal species, Rhodnius ecuadoriensis. Phenotypically divergent populations occupy different ecological regions (wet vs. dry) and microhabitats (palm-crowns vs. vertebrate nests), whereas convergent populations occupy man-made and nest (but not palm) microhabitats. These findings suggest that triatomines can ‘respond’ to ecological novelty by changing their external, naked-eye phenotypes as they adapt to new microhabitats. We therefore warn that phenotypic traits such as overall size or color may confound triatomine-bug species identification and classification.

Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, as seen with the Zika virus (ZIKV) epidemic where large proportions of infection were asymptomatic. However, multiple imperfect indicators of infection provide an opportunity to estimate the underlying incidence of infection. We developed a modeling approach that integrates a generic Time-series Susceptible-Infected-Recovered epidemic model with assumptions about reporting biases in a Bayesian framework and applied it to the 2016 Zika epidemic in Puerto Rico using three indicators: suspected arboviral cases, suspected Zika-associated Guillain-Barré Syndrome cases, and blood bank data. Using this combination of surveillance data, we estimated the peak of the epidemic occurred during the week of August 15, 2016 (the 33rd week of year), and 120 to 140 (50% credible interval [CrI], 95% CrI: 97 to 170) weekly infections per 10,000 population occurred at the peak. By the end of 2016, we estimated that approximately 890,000 (95% CrI: 660,000 to 1,100,000) individuals were infected in 2016 (26%, 95% CrI: 19% to 33%, of the population infected). Utilizing multiple indicators offers the opportunity for real-time and retrospective situational awareness to support epidemic preparedness and response.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe author(s) received no specific funding for this work.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:Exemption was obtained from the CDC Human Subjects Research Office as the data were collected as part of regular surveillance activities.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.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.YesAll relevant data are within the manuscript and its Supporting Information files.

INTRODUCTION: The first outbreak of dengue in American Samoa was reported in 1911. Sporadic outbreaks have been reported since, as were outbreaks of other pathogens transmitted by Aedes species mosquitoes including Ross River, chikungunya, and Zika viruses. During an outbreak of dengue virus-type 2 (DENV-2) in 2016-2018, we conducted household-based cluster investigations to identify population-specific risk factors associated with infection and performed entomologic surveillance to determine the relative abundance of Ae. aegypti and Ae. polynesiensis. METHODS AND FINDINGS: We contacted dengue patients who had tested positive for DENV infection and offered them as well as their household members participation in household-based cluster investigations. For those that accepted participation, we also offered participation to residents of households within a 50-meter radius of each case-patient's home. Questionnaires were administered and serum specimens collected for testing by RT-PCR and anti-DENV IgM ELISA. Adult female mosquitoes were aspirated from inside and outside participating households and tested by RT-PCR. We analyzed characteristics associated with DENV infection in bivariate analyses. A total of 226 participants was enrolled from 91 households in 20 clusters. Median age of participants was 34 years (range: <1-94), and 56.2% were female. In total, 7 (3.2%) participants had evidence of DENV infection by IgM ELISA (n = 5) or RT-PCR (n = 2). Factors significantly associated with DENV infection were reporting a febrile illness in the past three months (prevalence ratio: 7.5 [95% confidence interval: 1.9-29.8]) and having a household septic tank (Fisher's Exact Test, p = 0.004). Of 93 Ae. aegypti and 90 Ae. polynesiensis females collected, 90% of Ae. aegypti were collected inside homes whereas 83% of Ae. polynesiensis were collected outside homes. DENV nucleic acid was not detected in any mosquito pools. Sequencing of the DENV-2 from patient specimens identified the Cosmopolitan genotype of DENV-2 and was most closely related to virus detected in the Solomon Islands during 2016. CONCLUSIONS: This investigation demonstrated that dengue is a continuing risk in American Samoa. Increased frequency of infection among residents with a septic tank suggests a need to investigate whether septic tanks serve as larval habitats for mosquito vectors of DENV in American Samoa. Future efforts should also evaluate the role of Ae. polynesiensis in DENV transmission in the wild.

In reply to Sánchez-Montalvá and colleagues: in contrast to dengue, which has a well-defined spectrum of severe disease, most cases of noncongenital ZIKV disease are mild, except for rare complications such as Guillain–Barré syndrome.1 In the participants in our study, the signs and symptoms were consistent with uncomplicated ZIKV disease. Furthermore, with respect to the duration of detectable ZIKV RNA, we saw no difference between the 35% of participants who were enrolled at outpatient clinics and those who were enrolled at emergency departments (P = 0.22). We agree that it is not known whether humans can be reinfected with ZIKV; however, studies in mice have shown protection from reinfection, including an absence of detectable viremia.2 In vitro evidence of antibody-dependent enhancement can occur in flaviviruses in the absence of in vivo evidence.3 A study from Colombia showed no evidence of in vivo enhancement of ZIKV in patients with previous dengue virus infection.4 Moreover, findings in men from the continental United States, where dengue virus rarely circulates, were similar to those of our study.5 Finally, sexual transmission contributes to a small percentage of ZIKV infections and would not affect our findings.

BACKGROUND: The COVID-19 pandemic disrupted healthcare in the United States and raised concerns about certain antihypertensives, and may have impacted both prescribing practices and access to blood pressure (BP) medications. METHODS: We assessed trends in BP prescription fills before and during the first year of the COVID-19 pandemic, using cross-sectional data for BP fills and tablets in the IQVIA (IMS Health) National Prescription Audit® database. Drugs filled via retail (92% coverage), mail-order (78% coverage), and long-term care (72% coverage) channels from January 2018 through December 2020 were included. Data were projected nationally and by state. RESULTS: Between 2.9 to 3.4 billion BP tablets were dispensed monthly until February 2020, increasing sharply to 3.8 billion in March 2020 and declining to 3.4 billion in April, then increasing at three-month intervals until December 2020. The number of tablets per fill increased slightly over time, with the largest increase (from 66.7 to 68.6) during February-March, 2020. Tablets were dispensed through retail channels (99.7 billion), mail-order (14.7 billion), and long-term care (5.3 billion). Rates of patients initiating new medications decreased during 2020 compared to prior years. Fills did not vary significantly by drug class. CONCLUSIONS: A sharp increase in BP fills occurred with COVID-19 emergence, suggesting patients may have secured medications in preparation for potential access limitations. A decrease in new fills, indicating decreased initiation and/or modification of treatment regimens, suggests need for efforts to re-engage patients in the healthcare system and provide alternative ways to obtain medication refills and adjustments.

INTRODUCTION: Most e-cigarettes contain highly addictive nicotine. This study assessed trends in nicotine strength in e-cigarettes sold in the United States during January 2017-March 2022. AIMS AND METHODS: We obtained January 2017-March 2022 national retail e-cigarette sales data from NielsenIQ. We assessed monthly average nicotine strength overall, by e-cigarette product and flavor type, and manufacturer. A Joinpoint regression model assessed the magnitude and significance of changes in nicotine strength. RESULTS: During January 2017-March 2022, monthly average nicotine strength of e-cigarette products increased from 2.5% to 4.4%, an average of 0.8% per month (p < .001). Monthly average nicotine strength of disposable e-cigarettes increased the most (average monthly percentage change [AMPC] = 1.26%, p < .001) as compared to prefilled pods (AMPC = 0.6%, p < .001) and e-liquids (AMPC = 0.5%, p = .218). Monthly average nicotine strength for all flavors of e-cigarette products increased except for mint-flavored products. Increases were greatest for beverage-flavored products (AMPC = 2.1%, p < .001), followed by menthol-flavored products (AMPC = 1.2%, p < .001). Among the top 10 e-cigarette manufacturers assessed, monthly average nicotine strength decreased for Juul Labs products from 5% to 4.7% (AMPC = -0.1%, p < .001) but increased significantly for five manufacturers' products and remained unchanged at 5%-6% for four manufacturers' products. CONCLUSIONS: Monthly average nicotine strength of e-cigarette products increased overall, for most product and flavor types, and for some manufacturers in the United States during the study period. Imposing maximum limits on nicotine strength of e-cigarettes together with other evidence-based tobacco control strategies can help reduce the use of e-cigarettes among youth and increase tobacco product cessation among adults. IMPLICATIONS: From January 2017 to March 2022, the monthly average nicotine strength of disposable e-cigarettes increased substantially and exceeded prefilled pods since May 2020. E-cigarettes with menthol flavor and youth-appealing flavors, like fruit, also had sharp increases in monthly average nicotine strength. Among the top 10 e-cigarette manufacturers, monthly average nicotine strength increased or remained unchanged at a high nicotine level for all manufacturers' products, except Juul Lab's products. Comprehensive strategies including restricting sales of all flavored e-cigarettes, restricting youth tobacco product access, and imposing maximum limits on nicotine strength may help reduce youth e-cigarette use and increase tobacco cessation.

Since SARS-CoV-2 was first identified, the world has witnessed more than 641 million confirmed cases of COVID-19, resulting in more than 6.6 million deaths (1). The global spread of the virus and the resulting destruction of lives and livelihoods brought into sharp focus the interconnectedness of local, domestic, and global public health infrastructure and the global need for a trusted, resilient public health workforce to overcome systemic inequities. | | As the public health agency for the United States, the Centers for Disease Control and Prevention (CDC) invests in global and domestic public health to improve core public health capabilities. CDC collaborates with partners in the interdependent global public health ecosystem to strengthen the systems needed for disease surveillance and reporting, diagnostic testing, outbreak and pandemic responses, and clinical service delivery, including treatment, immunizations, and infection prevention and control.

Anthrax is caused by, Bacillus anthracis, a soil-borne bacterium that infects grazing animals. Kenya reported a sharp increase in livestock anthrax cases from 2005, with only 12% of the sub-counties (decentralised administrative units used by Kenyan county governments to facilitate service provision) accounting for almost a third of the livestock cases. Recent studies of the spatial extent of B. anthracis suitability across Kenya have used approaches that cannot capture the underlying spatial and temporal dependencies in the surveillance data. To address these limitations, we apply the first Bayesian approach using R-INLA to analyse a long-term dataset of livestock anthrax case data, collected from 2006 to 2020 in Kenya. We develop a spatial and a spatiotemporal model to investigate the distribution and socio-economic drivers of anthrax occurrence and incidence at the national and sub-county level. The spatial model was robust to geographically based cross validation and had a sensitivity of 75% (95% CI 65-75) against withheld data. Alarmingly, the spatial model predicted high intensity of anthrax across the Northern counties (Turkana, Samburu, and Marsabit) comprising pastoralists who are often economically and politically marginalized, and highly predisposed to a greater risk of anthrax. The spatiotemporal model showed a positive link between livestock anthrax risk and the total human population and the number of exotic dairy cattle, and a negative association with the human population density, livestock producing households, and agricultural land area. Public health programs aimed at reducing human-animal contact, improving access to healthcare, and increasing anthrax awareness, should prioritize these endemic regions.

Vaccination is the main means for preventing measles, mumps, and rubella virus infections and their related complications (1,2). Achieving and maintaining high 2-dose measles, mumps, and rubella vaccination coverage in the United States has led to elimination of endemic measles in 2000, rubella and congenital rubella syndrome in 2004, and a sharp decrease in mumps cases. However, measles and rubella remain endemic in many countries, leading to importations of cases and occasional local transmission within the United States (3). Reported U.S. mumps cases declined >99% from the prevaccine period (4); however, mumps is endemic worldwide, and since 2006, the number of mumps cases and mumps outbreaks has increased in the United States, with wider geographic spread since 2016 (4). Given the risk for importation of measles and rubella and the resurgence of mumps, maintaining high measles, mumps, and rubella (MMR) vaccination coverage is important. Since 1978, only one MMR vaccine, M-M-R II (Merck and Co., Inc.), has been available in the United States. On June 6, 2022, the Food and Drug Administration approved a second MMR vaccine, PRIORIX (GlaxoSmithKline Biologicals), for the prevention of measles, mumps, and rubella in persons aged ≥12 months. The three live attenuated viruses contained in PRIORIX are genetically similar or identical to the corresponding components in M-M-R II (Table) (5-7). On June 23, 2022, the Advisory Committee on Immunization Practices (ACIP) unanimously recommended PRIORIX as an option to prevent measles, mumps, and rubella according to the existing recommended schedules and for off-label uses (i.e., indications not included in the package insert)* (1,2). ACIP considered PRIORIX to be safe, immunogenic, and noninferior to M-M-R II. Both PRIORIX and M-M-R II are fully interchangeable for all indications for which MMR vaccination is recommended. This report contains ACIP recommendations specific to PRIORIX and supplements the existing ACIP recommendations for MMR use (1,2).

The clinical presentation of varicella in unvaccinated persons, with skin vesicles and scabs, has facilitated the use of rapid diagnostic methods for confirming disease. Polymerase chain reaction (PCR) assays are the diagnostic method of choice. The sharp decline in unmodified cases of varicella due to the US varicella vaccination program has led to fewer healthcare providers being familiar with varicella presentation and an increased reliance on laboratory diagnosis to confirm suspected cases. The mild, atypical presentation of the disease in vaccinated persons (fewer skin lesions, mostly maculopapular) has made it more challenging for providers to recognize and also to collect samples to detect the virus. Nonetheless, PCR is highly sensitive and specific in confirming modified disease if adequate samples are provided. While a positive PCR result is confirmatory, interpreting a negative result can prove to be more challenging in determining whether suspected varicella is falsely negative or attributable to other causes. Enhanced education of healthcare providers is critical for adequate specimen collection from modified varicella cases. In addition, more sensitive commercial serologic assays are needed in the United States for varicella immunity testing in the vaccine era.

There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis, including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955-1958, followed to 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiograph. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9 cm (IQR: 2-2.9 cm - 4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (IQR 1-1.9 cm - 2-2.9 cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM. | Coccidioidomycosis (CM), also known as San Joaquin Valley Fever, causes a variety of symptoms including pneumonia. This historical study investigates CM of the lungs in American soldiers with CM in the 1950s, prior to modern antifungals, to better understand the natural history. | eng

The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck Sharp & Dohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged <19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)(†) approach to guide its deliberations regarding use of these vaccines. Risk-based recommendations on use of PPSV23 for persons aged 2-18 years with certain underlying medical conditions(§) that increase the risk for pneumococcal disease have not changed.

Error rates that have been published in recent open black box studies of forensic firearms examiner performance have been very low, typically below one percent. These low error rates have been challenged, however, as not properly taking into account one of the categories, "Inconclusive", that examiners can reach in comparing a pair of bullets or cartridges. These challenges have themselves been challenged; how to consider the inconclusives and their effect on error rates is currently a matter of sharp debate. We review several viewpoints that have been put forth, and then examine the impact of inconclusives on error rates from three fresh statistical perspectives: (a) an ideal perspective using objective measurements combined with statistical algorithms, (b) basic sampling theory and practice, and (c) standards of experimental design in human studies. Our conclusions vary with the perspective: (a) inconclusives can be simple errors (or, on the other hand, simply correct or at least well justified); (b) inconclusives need not be counted as errors to bring into doubt assessments of error rates; (c) inconclusives are potential errors, more explicitly, inconclusives in studies are not necessarily the equivalent of inconclusives in casework and can mask potential errors in casework. From all these perspectives, it is impossible to simply read out trustworthy estimates of error rates from those studies which have been carried out to date. At most, one can put reasonable bounds on the potential error rates. These are much larger than the nominal rates reported in the studies. To get straightforward, sound estimates of error rates requires a challenging but critical improvement to the design of firearms studies. A proper study-one in which inconclusives are not potential errors, and which yields direct, sound estimates of error rates-will require new objective measures or blind proficiency testing embedded in ordinary casework.

BACKGROUND: The preventive and curative strategies of malaria are based on promoting the use of long-lasting insecticidal nets (LLINs) and treating confirmed cases with artemisinin-based combination therapy. These strategies have led to a sharp decline in the burden of malaria, which remains a significant public health problem in sub-Saharan countries. The objective of this study was to determine and compare the residual efficacy of LLINs recommended by the World Health Organization. METHODS: The study was conducted in six villages in two sites in Senegal located in the Sahelo-Sudanian area of the Thiès region, 70 km from Dakar and in Mbagame, a semi-urban zone in the Senegal River Valley. A census was conducted of all sleeping places in each household to be covered by LLINs. Five brands of LLIN were distributed, and every six months, retention rates, net use, maintenance, physical integrity, insecticide chemical content, and biological efficacy were examined for each type of LLIN. RESULTS: A total of 3012 LLINs were distributed in 1249 households in both sites, with an average coverage rate of 94% (95% CI 92.68-95.3). After 36 months, the average retention rate was 12.5% and this rate was respectively 20.5%, 15.1%, 10%, 7%, and 3% for Olyset Net(®), Dawa Plus(®) 2.0, PermaNet(®) 2.0, NetProtect(®) and Life Net(®), respectively. The proportion of LLINs with holes and the average number of holes per mosquito net increased significantly during each follow-up, with a large predominance of size 1 (small) holes for all types of LLINs distributed. During the three-year follow-up, bioassay mortality rates of a susceptible strain of insectary reared Anopheles coluzzii decreased in the following net types: in Dawa Plus(®) 2.0 (100% to 51.7%), PermaNet(®) 2.0 (96.6% to 83%), and Olyset Net(®) (96.6% to 33.3%). Mortality rates remained at 100% in Life Net(®) over the same time period. After 36 months, the average insecticide content per brand of LLIN decreased by 40.9% for Dawa Plus(®) 2.0, 31% for PermaNet(®) 2.0, 39.6% for NetProtect(®) and 51.9% for Olyset Net(®) and 40.1% for Life Net. CONCLUSIONS: Although some net types retained sufficient insecticidal activity, based on all durability parameters measured, none of the net types survived longer than 2 years.

BACKGROUND: We evaluated clinical and laboratory findings among patients with non-severe or severe dengue in Puerto Rico to examine whether clinical manifestations vary by age. METHODS: During 2012-2014, we enrolled patients who arrived at the emergency department with fever or history of fever within 7 days of presentation. Serum samples were tested for dengue virus (DENV) by RT-PCR and IgM ELISA. Severe dengue was defined as severe plasma leakage or shock, severe bleeding, or organ involvement at presentation, during hospitalization, or follow-up. RESULTS: Of 1089 dengue patients identified, 281 (26%) were severe. Compared to those with non-severe dengue, patients with severe dengue were more often aged 10-19 years (55% vs. 40%, p < 0.001) and hospitalized (87% vs. 30%, p < 0.001). Severe plasma leakage or shock was more common among children aged 0-9 (59%) or 10-19 years (86%) than adults (49%) (p < 0.01). Severe bleeding was less common among 10-19 year-olds (24%) compared to 0-9 year-olds (45%) and adults (52%; p < 0.01). CONCLUSIONS: Severe plasma leakage was the most common presentation among children, highlighting important differences with adults. Vaccination against dengue could help prevent severe dengue among children in Puerto Rico.