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Issue 36, September 6, 2022

CDC Science Clips: Volume 14, Issue 36, September 6, 2022

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention score to track social and mainstream media mentions.

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. Effect of biannual mass azithromycin distributions to preschool-aged children on trachoma prevalence in Niger: A cluster randomized clinical trial
        Arzika AM, Mindo-Panusis D, Abdou A, Kadri B, Nassirou B, Maliki R, Alsoudi AF, Zhang T, Cotter SY, Lebas E, O'Brien KS, Callahan EK, Bailey RL, West SK, Goodhew EB, Martin DL, Arnold BF, Porco TC, Lietman TM, Keenan JD.
        JAMA Netw Open. 2022 Aug 1;5(8):e2228244.
        IMPORTANCE: Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. OBJECTIVE: To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. INTERVENTIONS: Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. MAIN OUTCOMES AND MEASURES: Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens. RESULTS: At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07). CONCLUSIONS AND RELEVANCE: The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02048007.

      2. Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study
        Lo SW, Mellor K, Cohen R, Alonso AR, Belman S, Kumar N, Hawkins PA, Gladstone RA, von Gottberg A, Veeraraghavan B, Ravikumar KL, Kandasamy R, Pollard SA, Saha SK, Bigogo G, Antonio M, Kwambana-Adams B, Mirza S, Shakoor S, Nisar I, Cornick JE, Lehmann D, Ford RL, Sigauque B, Turner P, Moïsi J, Obaro SK, Dagan R, Diawara I, Skoczyńska A, Wang H, Carter PE, Klugman KP, Rodgers G, Breiman RF, McGee L, Bentley SD, Almagro CM, Varon E.
        Lancet Microbe. 2022 Aug 16.
        BACKGROUND: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. METHODS: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). FINDINGS: Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. INTERPRETATION: Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. FUNDING: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.

    • Chronic Diseases and Conditions
      1. Food sensitivities in a diverse nationwide cohort of veterans with interstitial cystitis/bladder pain syndrome
        Jarman A, Janes JL, Shorter B, Moldwin R, De Hoedt AM, Barbour KE, Kim J, Freedland SJ, Anger JT.
        J Urol. 2022 Aug 24:101097ju0000000000002938.

      2. Urban and rural differences in new onset type 2 diabetes: Comparisons across national and regional samples in the diabetes LEAD network
        McAlexander TP, Malla G, Uddin J, Lee DC, Schwartz BS, Rolka DB, Siegel KR, Kanchi R, Pollak J, Andes L, Carson AP, Thorpe LE, McClure LA.
        SSM Popul Health. 2022 Sep;19:101161.
        INTRODUCTION: Geographic disparities in diabetes burden exist throughout the United States (US), with many risk factors for diabetes clustering at a community or neighborhood level. We hypothesized that the likelihood of new onset type 2 diabetes (T2D) would differ by community type in three large study samples covering the US. RESEARCH DESIGN AND METHODS: We evaluated the likelihood of new onset T2D by a census tract-level measure of community type, a modification of RUCA designations (higher density urban, lower density urban, suburban/small town, and rural) in three longitudinal US study samples (REGARDS [REasons for Geographic and Racial Differences in Stroke] cohort, VADR [Veterans Affairs Diabetes Risk] cohort, Geisinger electronic health records) representing the CDC Diabetes LEAD (Location, Environmental Attributes, and Disparities) Network. RESULTS: In the REGARDS sample, residing in higher density urban community types was associated with the lowest odds of new onset T2D (OR [95% CI]: 0.80 [0.66, 0.97]) compared to rural community types; in the Geisinger sample, residing in higher density urban community types was associated with the highest odds of new onset T2D (OR [95% CI]: 1.20 [1.06, 1.35]) compared to rural community types. In the VADR sample, suburban/small town community types had the lowest hazard ratios of new onset T2D (HR [95% CI]: 0.99 [0.98, 1.00]). However, in a regional stratified analysis of the VADR sample, the likelihood of new onset T2D was consistent with findings in the REGARDS and Geisinger samples, with highest likelihood of T2D in the rural South and in the higher density urban communities of the Northeast and West regions; likelihood of T2D did not differ by community type in the Midwest. CONCLUSIONS: The likelihood of new onset T2D by community type varied by region of the US. In the South, the likelihood of new onset T2D was higher among those residing in rural communities.

    • Communicable Diseases
      1. Incidence of COVID-19 among persons experiencing homelessness in the US from January 2020 to November 2021
        Meehan AA, Thomas I, Horter L, Schoonveld M, Carmichael AE, Kashani M, Valencia D, Mosites E.
        JAMA Netw Open. 2022 Aug 1;5(8):e2227248.
        IMPORTANCE: A lack of timely and high-quality data is an ongoing challenge for public health responses to COVID-19 among people experiencing homelessness (PEH). Little is known about the total number of cases of COVID-19 among PEH. OBJECTIVE: To estimate the number of COVID-19 cases among PEH and compare the incidence rate among PEH with that in the general population. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from a survey distributed by the Centers for Disease Control and Prevention to all US state, district, and territorial health departments that requested aggregated COVID-19 data among PEH from January 1, 2020, to September 30, 2021. Jurisdictions were encouraged to share the survey with local health departments. MAIN OUTCOMES AND MEASURES: The primary study outcome was the number of cases of COVID-19 identified among PEH. COVID-19 cases and incidence rates among PEH were compared with those in the general population in the same geographic areas. RESULTS: Participants included a population-based sample of all 64 US jurisdictional health departments. Overall, 25 states, districts, and territories completed the survey, among which 18 states (72.0%) and 27 localities reported COVID-19 data among PEH. A total of 26 349 cases of COVID-19 among PEH were reported at the state level and 20 487 at the local level. The annual incidence rate of COVID-19 among PEH at the state level was 567.9 per 10 000 person-years (95% CI, 560.5-575.4 per 10 000 person-years) compared with 715.0 per 10 000 person-years (95% CI, 714.5-715.5 per 10 000 person-years) in the general population. At the local level, the incidence rate of COVID-19 among PEH was 799.2 per 10 000 person-years (95% CI, 765.5-834.0 per 10 000 person-years) vs 812.5 per 10 000 person-years (95% CI, 810.7-814.3 per 10 000 person-years) in the general population. CONCLUSIONS AND RELEVANCE: These results provide an estimate of COVID-19 incidence rates among PEH in multiple US jurisdictions; however, a national estimate and the extent of under- or overestimation remain unknown. The findings suggest that opportunities exist for incorporating housing and homelessness status in infectious disease reporting to inform public health decision-making.

      2. Public health response to a case of paralytic poliomyelitis in an unvaccinated person and detection of poliovirus in wastewater - New York, June-August 2022
        Link-Gelles R, Lutterloh E, Schnabel Ruppert P, Backenson PB, St George K, Rosenberg ES, Anderson BJ, Fuschino M, Popowich M, Punjabi C, Souto M, McKay K, Rulli S, Insaf T, Hill D, Kumar J, Gelman I, Jorba J, Ng TF, Gerloff N, Masters NB, Lopez A, Dooling K, Stokley S, Kidd S, Oberste MS, Routh J.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1065-1068.
        On July 18, 2022, the New York State Department of Health (NYSDOH) notified CDC of detection of poliovirus type 2 in stool specimens from an unvaccinated immunocompetent young adult from Rockland County, New York, who was experiencing acute flaccid weakness. The patient initially experienced fever, neck stiffness, gastrointestinal symptoms, and limb weakness. The patient was hospitalized with possible acute flaccid myelitis (AFM). Vaccine-derived poliovirus type 2 (VDPV2) was detected in stool specimens obtained on days 11 and 12 after initial symptom onset. To date, related Sabin-like type 2 polioviruses have been detected in wastewater* in the patient's county of residence and in neighboring Orange County up to 25 days before (from samples originally collected for SARS-CoV-2 wastewater monitoring) and 41 days after the patient's symptom onset. The last U.S. case of polio caused by wild poliovirus occurred in 1979, and the World Health Organization Region of the Americas was declared polio-free in 1994. This report describes the second identification of community transmission of poliovirus in the United States since 1979; the previous instance, in 2005, was a type 1 VDPV (1). The occurrence of this case, combined with the identification of poliovirus in wastewater in neighboring Orange County, underscores the importance of maintaining high vaccination coverage to prevent paralytic polio in persons of all ages.

      3. Summary of guidance for minimizing the impact of COVID-19 on individual persons, communities, and health care systems - United States, August 2022
        Massetti GM, Jackson BR, Brooks JT, Perrine CG, Reott E, Hall AJ, Lubar D, Williams IT, Ritchey MD, Patel P, Liburd LC, Mahon BE.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1057-1064.
        As SARS-CoV-2, the virus that causes COVID-19, continues to circulate globally, high levels of vaccine- and infection-induced immunity and the availability of effective treatments and prevention tools have substantially reduced the risk for medically significant COVID-19 illness (severe acute illness and post-COVID-19 conditions) and associated hospitalization and death (1). These circumstances now allow public health efforts to minimize the individual and societal health impacts of COVID-19 by focusing on sustainable measures to further reduce medically significant illness as well as to minimize strain on the health care system, while reducing barriers to social, educational, and economic activity (2). Individual risk for medically significant COVID-19 depends on a person's risk for exposure to SARS-CoV-2 and their risk for developing severe illness if infected (3). Exposure risk can be mitigated through nonpharmaceutical interventions, including improving ventilation, use of masks or respirators indoors, and testing (4). The risk for medically significant illness increases with age, disability status, and underlying medical conditions but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments (3,5). CDC's public health recommendations change in response to evolving science, the availability of biomedical and public health tools, and changes in context, such as levels of immunity in the population and currently circulating variants. CDC recommends a strategic approach to minimizing the impact of COVID-19 on health and society that relies on vaccination and therapeutics to prevent severe illness; use of multicomponent prevention measures where feasible; and particular emphasis on protecting persons at high risk for severe illness. Efforts to expand access to vaccination and therapeutics, including the use of preexposure prophylaxis for persons who are immunocompromised, antiviral agents, and therapeutic monoclonal antibodies, should be intensified to reduce the risk for medically significant illness and death. Efforts to protect persons at high risk for severe illness must ensure that all persons have access to information to understand their individual risk, as well as efficient and equitable access to vaccination, therapeutics, testing, and other prevention measures. Current priorities for preventing medically significant illness should focus on ensuring that persons 1) understand their risk, 2) take steps to protect themselves and others through vaccines, therapeutics, and nonpharmaceutical interventions when needed, 3) receive testing and wear masks if they have been exposed, and 4) receive testing if they are symptomatic, and isolate for ≥5 days if they are infected.

      4. Surveillance for coccidioidomycosis, histoplasmosis, and blastomycosis -- United States, 2019
        Smith D, Williams S, Benedict K, Jackson B, Toda M.
        MMWR Surveillance Summaries. 2022 ;71(7):1-14.
        Problem/Condition: Coccidioidomycosis, histoplasmosis, and blastomycosis are underdiagnosed fungal diseases that often mimic bacterial or viral pneumonia and can cause disseminated disease and death. These diseases are caused by inhalation of fungal spores that have distinct geographic niches in the environment (e.g., soil or dust), and distribution is highly susceptible to climate changes such as expanding arid regions for coccidioidomycosis, the northward expansion of histoplasmosis, and areas like New York reporting cases of blastomycosis previously thought to be nonendemic. The national incidence of coccidioidomycosis, histoplasmosis, and blastomycosis is poorly characterized. Reporting Period: 2019. Description of System: The National Notifiable Diseases Surveillance System (NNDSS) tracks cases of coccidioidomycosis, a nationally notifiable condition reported to CDC by 26 states and the District of Columbia. Neither histoplasmosis nor blastomycosis is a nationally notifiable condition; however, histoplasmosis is voluntarily reported in 13 states and blastomycosis in five states. Health departments classify cases based on the definitions established by the Council of State and Territorial Epidemiologists. Results: In 2019, a total of 20,061 confirmed coccidioidomycosis, 1,124 confirmed and probable histoplasmosis, and 240 confirmed and probable blastomycosis cases were reported to CDC. Arizona and California reported 97% of coccidioidomycosis cases, and Minnesota and Wisconsin reported 75% of blastomycosis cases. Illinois reported the greatest percentage (26%) of histoplasmosis cases. All three diseases were more common among males, and the proportion for blastomycosis (70%) was substantially higher than for histoplasmosis (56%) or coccidioidomycosis (52%). Coccidioidomycosis incidence was approximately four times higher for non-Hispanic American Indian or Alaska Native (AI/AN) persons (17.3 per 100,000 population) and almost three times higher for Hispanic or Latino persons (11.2) compared with non-Hispanic White (White) persons (4.1). Histoplasmosis incidence was similar across racial and ethnic categories (range: 0.9-1.3). Blastomycosis incidence was approximately six times as high among AI/AN persons (4.5) and approximately twice as high among non-Hispanic Asian and Native Hawaiian or other Pacific Islander persons (1.6) compared with White persons (0.7). More than one half of histoplasmosis (54%) and blastomycosis (65%) patients were hospitalized, and 5% of histoplasmosis and 9% of blastomycosis patients died. States in which coccidioidomycosis is not known to be endemic had more cases in spring (March, April, and May) than during other seasons, whereas the number of cases peaked slightly in autumn (September, October, and November) for histoplasmosis and in winter (December, January, and February) for blastomycosis. Interpretation: Coccidioidomycosis, histoplasmosis, and blastomycosis are diseases occurring in geographical niches within the United States. These diseases cause substantial illness, with approximately 20,000 coccidioidomycosis cases reported in 2019. Although substantially fewer histoplasmosis and blastomycosis cases were reported, surveillance was much more limited and underdiagnosis was likely, as evidenced by high hospitalization and death rates. This suggests that persons with milder symptoms might not seek medical evaluation and the symptoms self-resolve or the illnesses are misdiagnosed as other, more common respiratory diseases. Public Health Action: Improved surveillance is necessary to better characterize coccidioidomycosis severity and to improve detection of histoplasmosis and blastomycosis. These findings might guide improvements in testing practices that enable timely diagnosis and treatment of fungal diseases. Clinicians and health care professionals should consider coccidioidomycosis, histoplasmosis, and blastomycosis in patients with community-acquired pneumonia or other acute infections of the lower respiratory tract who live in or have traveled to areas where the causative ungi are known to be present in the environment. Culturally appropriate tailored educational messages might help improve diagnosis and treatment. Public health response to these three diseases is hindered because information gathered from states' routine surveillance does not include data on populations at risk and sources of exposure. Broader surveillance that includes expansion to other states and more detail about potential exposures and relevant host factors can describe epidemiologic trends, populations at risk, and disease prevention strategies.

      5. A primer on Monkeypox virus for obstetrician–gynecologists: Diagnosis, prevention, and treatment
        Meaney-Delman D, Galang R, Petersen B, Jamieson D.
        Obstet Gynecol. 2022 :391-397.

      6. Impact of age and symptom development on SARS-CoV-2 transmission in households with children-Maryland, New York, and Utah, August 2020-October 2021
        Sumner KM, Karron RA, Stockwell MS, Dawood FS, Stanford JB, Mellis A, Hacker E, Thind P, Castro MJ, Harris JP, Deloria Knoll M, Schappell E, Hetrich MK, Duque J, Jeddy Z, Altunkaynak K, Poe B, Meece J, Stefanski E, Tong S, Lee JS, Dixon A, Veguilla V, Rolfes MA, Porucznik CA.
        Open Forum Infect Dis. 2022 Aug;9(8):ofac390.
        BACKGROUND: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. METHODS: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. RESULTS: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). CONCLUSIONS: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

    • Community Health Services
      1. Intervening at the right level to improve student health: An analysis of levels of influence on sexual behavior of high school students
        Li J, Timpe Z, Suarez N, Ashley CL, Rasberry CN, Robin L.
        AIDS Educ Prev. 2022 Aug;34(4):300-310.
        This study adopts a socio-ecological framework and examines school- and district-level influences on sexual behaviors among high school students from 16 school districts that were federally funded to conduct a school-based, multilevel sexual health program. We drew cross-sectional data from the 2015 and 2017 Youth Risk Behavior Survey from funded school districts containing 648 schools and 101,728 students. We used multilevel modeling to determine the percentage of variance in sexual health outcomes explained at school and district levels, overall and by race/ethnicity and biological sex. We found protective behaviors such as using hormonal birth control had considerable district-level variance (10.1%) while sexual risk behaviors such as having multiple sex partners showed considerable school-level variance (12.7%). We also found significant subgroup heterogeneity in the variance. Findings indicate school-based interventions should address all levels of influences of the educational system to effectively improve a myriad of student sexual health outcomes.

    • Disaster Preparedness and Emergency Services
      1. Establishing a public health emergency operations center in an outbreak-prone country: Lessons learned in Uganda, January 2014 to December 2021
        Kayiwa J, Homsy J, Nelson LJ, Ocom F, Kasule JN, Wetaka MM, Kyazze S, Mwanje W, Kisakye A, Nabunya D, Nyirabakunzi M, Aliddeki DM, Ojwang J, Boore A, Kasozi S, Borchert J, Shoemaker T, Nabatanzi S, Dahlke M, Brown V, Downing R, Makumbi I.
        Health Secur. 2022 Aug 18.
        Uganda is highly vulnerable to public health emergencies (PHEs) due to its geographic location next to the Congo Basin epidemic hot spot, placement within multiple epidemic belts, high population growth rates, and refugee influx. In view of this, Uganda's Ministry of Health established the Public Health Emergency Operations Center (PHEOC) in September 2013, as a central coordination unit for all PHEs in the country. Uganda followed the World Health Organization's framework to establish the PHEOC, including establishing a steering committee, acquiring legal authority, developing emergency response plans, and developing a concept of operations. The same framework governs the PHEOC's daily activities. Between January 2014 and December 2021, Uganda's PHEOC coordinated response to 271 PHEs, hosted 207 emergency coordination meetings, trained all core staff in public health emergency management principles, participated in 21 simulation exercises, coordinated Uganda's Global Health Security Agenda activities, established 6 subnational PHEOCs, and strengthened the capacity of 7 countries in public health emergency management. In this article, we discuss the following lessons learned: PHEOCs are key in PHE coordination and thus mitigate the associated adverse impacts; although the functions of a PHEOC may be legalized by the existence of a National Institute of Public Health, their establishment may precede formally securing the legal framework; staff may learn public health emergency management principles on the job; involvement of leaders and health partners is crucial to the success of a public health emergency management program; subnational PHEOCs are resourceful in mounting regional responses to PHEs; and service on the PHE Strategic Committee may be voluntary.

    • Disease Reservoirs and Vectors
      1. The tropical lineage within the Rhipicephalus sanguineus species complex is cause for growing concern in the U.S. based on its prominent role in creating and perpetuating multiple recently identified outbreaks of Rocky Mountain spotted fever in the southwestern United States and northern Mexico. This lineage is undergoing a northward range expansion in the United States, necessitating the need for enhanced surveillance for Rh. sanguineus. To inform more focused surveillance efforts we use species distribution models (SDMs) to predict current (2015-2019) and future (2021-2040) habitat for the tropical lineage. Models using the MaxEnt algorithm were informed using geolocations of ticks genetically confirmed to be of the tropical lineage, for which data on 23 climatic and ecological variables were extracted. Models predicted that suitability was optimal where temperatures are relatively warm and stable, and there is minimal precipitation. This translated into habitat being predicted along much of the coast of southern states including California, Texas, Louisiana, and Florida. Although the endophilic nature of tropical Rh. sanguineus somewhat violates the assumptions of SDMs, our models correctly predicted known locations of this tick and provide a starting point for increased surveillance efforts. Furthermore, we highlight the importance of using molecular methods to distinguish between ticks in the Rh. sanguineus species complex.

      2. A new species of tick, Ixodes (Ixodes) mojavensis (Acari: Ixodidae), from the Amargosa Valley of California
        Backus LH, Foley JE, Hobbs GB, Bai Y, Beati L.
        Ticks Tick Borne Dis. 2022 Aug 5;13(6):102020.
        Ixodes (Ixodes) mojavensis, n. sp. (Acari: Ixodidae), is described from all parasitic stages collected from the endangered vole Microtus californicus scirpensis Bailey, 1900 (Rodentia: Cricetidae), Mus musculus L. 1758 (Rodentia: Muridae), and Reithrodontomys megalotis (Baird; 1857) (Rodentia: Cricetidae) in the Amargosa Valley of California. When first collected in 2014, this tick was tentatively identified as Ixodes minor Neumann, 1902 because the nucleotide similarity between its 16S rDNA sequence and a homologous GenBank sequence from an I. minor from the eastern U.S. was 99.51%. Nevertheless, adults of I. mojavensis differ morphologically from I. minor by hypostomal dentition, absence of a spur on palpal segment I, and punctation patterns; nymphs by the shapes of basis capituli, auriculae, cervical grooves and external files of hypostomal denticles; and larvae by the length of idiosomal setae and hypostomal dentition. DNA sequencing of fragments of 4 different genes, 12S rDNA, 16S rDNA, cytochrome c oxidase subunit I (COI), and intergenic transcribed spacer 2 (ITS2) of I. mojavensis and of closely related species of Ixodes shows that the mitochondrial gene sequences of the new tick species are almost identical to the I. minor homologous genes. Phylogenetically, the two species do not cluster in mutually exclusive monophyletic clades. However, ITS2 sequences of I. mojavensis and I. minor diverge deeply (≥ 5.74% maximum likelihood divergence) and are as different as homologous genes from other recognized species. The discrepancy between the two sets of genes is suggestive of past mitochondrial introgression or incomplete mitochondrial lineage sorting.

    • Environmental Health
      1. In vivo and in vitro toxicity of a stainless-steel aerosol generated during thermal spray coating
        Kodali V, Afshari A, Meighan T, McKinney W, Mazumder MH, Majumder N, Cumpston JL, Leonard HD, Cumpston JB, Friend S, Leonard SS, Erdely A, Zeidler-Erdely PC, Hussain S, Lee EG, Antonini JM.
        Arch Toxicol. 2022 Aug 19.
        Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague-Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m(3) × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0-200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days.

      2. Metabolism of 3-chlorobiphenyl (PCB 2) in a human-relevant cell line: Evidence of dechlorinated metabolites
        Zhang CY, Li X, Flor S, Ruiz P, Kruve A, Ludewig G, Lehmler HJ.
        Environ Sci Technol. 2022 Aug 22.
        Lower chlorinated polychlorinated biphenyls (LC-PCBs) and their metabolites make up a class of environmental pollutants implicated in a range of adverse outcomes in humans; however, the metabolism of LC-PCBs in human models has received little attention. Here we characterize the metabolism of PCB 2 (3-chlorobiphenyl), an environmentally relevant LC-PCB congener, in HepG2 cells with in silico prediction and nontarget high-resolution mass spectrometry. Twenty PCB 2 metabolites belonging to 13 metabolite classes, including five dechlorinated metabolite classes, were identified in the cell culture media from HepG2 cells exposed for 24 h to 10 μM or 3.6 nM PCB 2. The PCB 2 metabolite profiles differed from the monochlorinated metabolite profiles identified in samples from an earlier study with PCB 11 (3,3'-dichlorobiphenyl) under identical experimental conditions. A dechlorinated dihydroxylated metabolite was also detected in human liver microsomal incubations with monohydroxylated PCB 2 metabolites but not PCB 2. These findings demonstrate that the metabolism of LC-PCBs in human-relevant models involves the formation of dechlorination products. In addition, untargeted metabolomic analyses revealed an altered bile acid biosynthesis in HepG2 cells. Our results indicate the need to study the disposition and toxicity of complex PCB 2 metabolites, including novel dechlorinated metabolites, in human-relevant models.

      3. Topical Collection: Advancements in hydrogeological knowledge of Haiti for recovery and development
        Adamson JK, Gutierrez A, Perez-Monforte S, Rodriquez-Vera M, LaVanchy GT, Jean-Baptiste G, Emmanuel E, Moliere E, Gelting R, Miner WJ, Dykstra S.
        Hydrogeol J. 2022 .
        Haiti’s groundwater resources are poorly understood and scarcely researched, despite their importance as the principal source for water supply. The knowledge gap and its role of inhibiting informed relief, recovery and investments in development are described, along with an update on progress towards the UN Sustainable Development Goals. This essay leads a topical collection of seven articles that advance hydrogeological knowledge of Haiti. Additional data, research and monitoring are identified as urgently needed for the nation’s sustainable development. © 2022, The Author(s).

    • Epidemiology and Surveillance
      1. The clinical and genomic epidemiology of seasonal human coronaviruses in congregate homeless shelter settings: A repeated cross-sectional study
        Chow EJ, Casto AM, Rogers JH, Roychoudhury P, Han PD, Xie H, Mills MG, Nguyen TV, Pfau B, Cox SN, Wolf CR, Hughes JP, Uyeki TM, Rolfes MA, Mosites E, Shim MM, Duchin JS, Sugg N, Starita LA, Englund JA, Chu HY.
        Lancet Reg Health Am. 2022 Nov;15:100348.
        BACKGROUND: The circulation of respiratory viruses poses a significant health risk among those residing in congregate settings. Data are limited on seasonal human coronavirus (HCoV) infections in homeless shelter settings. METHODS: We analysed data from a clinical trial and SARS-CoV-2 surveillance study at 23 homeless shelter sites in King County, Washington between October 2019-May 2021. Eligible participants were shelter residents aged ≥3 months with acute respiratory illness. We collected enrolment data and nasal samples for respiratory virus testing using multiplex RT-PCR platform including HCoV. Beginning April 1, 2020, eligibility expanded to shelter residents and staff regardless of symptoms. HCoV species was determined by RT-PCR with species-specific primers, OpenArray assay or genomic sequencing for samples with an OpenArray relative cycle threshold <22. FINDINGS: Of the 14,464 samples from 3281 participants between October 2019-May 2021, 107 were positive for HCoV from 90 participants (median age 40 years, range: 0·9-81 years, 38% female). HCoV-HKU1 was the most common species identified before and after community-wide mitigation. No HCoV-positive samples were identified between May 2020-December 2020. Adults aged ≥50 years had the highest detection of HCoV (11%) among virus-positive samples among all age-groups. Species and sequence data showed diversity between and within HCoV species over the study period. INTERPRETATION: HCoV infections occurred in all congregate homeless shelter site age-groups with the greatest proportion among those aged ≥50 years. Species and sequencing data highlight the complexity of HCoV epidemiology within and between shelters sites. FUNDING: Gates Ventures, Centers for Disease Control and Prevention, National Institute of Health.

    • Global Health
      1. High-risk US international travelers seeking pretravel consultation during the COVID-19 pandemic
        Hyle EP, Le MH, Rao SR, Mulroy NM, Walker AT, Ryan ET, LaRocque RC.
        Open Forum Infect Dis. 2022 Aug;9(8):ofac399.
        BACKGROUND: To assess the implications of coronavirus disease 2019 (COVID-19)-related travel disruptions, we compared demographics and travel-related circumstances of US travelers seeking pretravel consultation regarding international travel at US Global TravEpiNet (GTEN) sites before and after the initiation of COVID-19 travel warnings. METHODS: We analyzed data in the GTEN database regarding traveler demographics and travel-related circumstances with standard questionnaires in the pre-COVID-19 period (January-December 2019) and the COVID-19 period (April 2020-March 2021), excluding travelers from January to March 2020. We conducted descriptive analyses of differences in demographics, travel-related circumstances, routine and travel-related vaccinations, and medications. RESULTS: Compared with 16 903 consultations in the pre-COVID-19 period, only 1564 consultations were recorded at GTEN sites during the COVID-19 period (90% reduction), with a greater proportion of travelers visiting friends and relatives (501/1564 [32%] vs 1525/16 903 [9%]), individuals traveling for >28 days (824/1564 [53%] vs 2522/16 903 [15%]), young children (6 mo-<6 y: 168/1564 [11%] vs 500/16 903 [3%]), and individuals traveling to Africa (1084/1564 [69%] vs 8049/16 903 [48%]). A smaller percentage of vaccine-eligible travelers received vaccines at pretravel consultations during the COVID-19 period than before, except for yellow fever and Japanese encephalitis vaccinations. CONCLUSIONS: Compared with the pre-COVID-19 period, a greater proportion of travelers during the COVID-19 period were young children, were planning to visit friends and relatives, were traveling for >28 days, or were traveling to Africa, which are circumstances that contribute to high risk for travel-related infections. Fewer vaccine-eligible travelers were administered travel-related vaccines at pretravel consultations. Counseling and vaccination focused on high-risk international travelers must be prioritized during the COVID-19 pandemic.

    • Health Behavior and Risk
      1. Characteristics associated with US adults' self-reported COVID-19 protective behaviors when getting food from restaurants, winter 2021
        Wittry BC, Hoover ER, Pomeroy MA, Dumas BL, Marshall KE, Yellman MA, St Louis ME, Garcia-Williams AG, Brown LG.
        Public Health Rep. 2022 Aug 24:333549221116360.
        OBJECTIVES: Visiting restaurants and bars, particularly when doing so indoors, can increase transmission risk of SARS-CoV-2, the virus that causes COVID-19, among people who are not fully vaccinated. We aimed to understand US adults' self-reported protective behaviors when getting food from restaurants during the COVID-19 pandemic when vaccines were not widely available. METHODS: We used online nationwide survey data from January 2021 to assess self-reported restaurant-related behaviors of respondents (n = 502). We also used multiple logistic regression models to examine associations between respondents' characteristics and these restaurant-related behaviors. RESULTS: Half (49.7%) of respondents reported eating indoors at a restaurant at least once in the month before the survey. Respondents most likely to report eating inside restaurants were in the youngest age category (18-34 y), had personal COVID-19 experience, or indicated they felt safe eating inside a restaurant. Among respondents who had gotten food from a restaurant, more than 65% considered each of the following factors as important in their restaurant dining decision: whether the restaurant staff were wearing face masks, the restaurant requires face masks, other customers are wearing face masks, seating was spaced at least 6 feet apart, someone in their household was at risk for severe COVID-19 illness, and the restaurant was crowded. The most common protective behavior when eating at a restaurant was wearing a face mask; 44.9% of respondents who had eaten at a restaurant wore a face mask except when actively eating or drinking. CONCLUSION: The need for practicing prevention strategies, especially for those not up to date with COVID-19 vaccines, will be ongoing. Our findings can inform COVID-19 prevention messaging for public health officials, restaurant operators, and the public.

    • Immunity and Immunization
      1. Safety monitoring of Pfizer-BioNTech COVID-19 vaccine booster doses among children aged 5-11 years - United States, May 17-July 31, 2022
        Hause AM, Baggs J, Marquez P, Myers TR, Su JR, Hugueley B, Thompson D, Gee J, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1047-1051.
        On May 17, 2022, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine to authorize a homologous* booster dose for children aged 5-11 years ≥5 months after receipt of the second primary series dose(†) (1) based on findings from a clinical trial conducted among 401 children aged 5-11 years (2). To further characterize the safety of booster vaccination in this age group, CDC reviewed adverse events and health impact assessments after receipt of a Pfizer-BioNTech third dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events occurring after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system comanaged by CDC and FDA. During May 17-July 31, 2022, approximately 657,302 U.S. children aged 5-11 years received a third Pfizer-BioNTech dose (either a third primary series dose administered to immunocompromised children or a booster dose administered to immunocompetent children)(§); 3,249 Pfizer-BioNTech third doses were reported to v-safe for children in this age group. Local and systemic reactions were reported to v-safe after a second dose and a third dose with similar frequency; some reactions (e.g., pain) were reported to be moderate or severe more frequently after a third dose. VAERS received 581 reports of adverse events after receipt of a Pfizer-BioNTech third dose by children aged 5-11 years; 578 (99.5%) reports were considered nonserious, and the most common events reported were vaccine administration errors. Three (0.5%) reports were considered serious; no reports of myocarditis or death were received. Local and systemic reactions were common among children after Pfizer-BioNTech third dose vaccination, but reports of serious adverse events were rare. Initial safety findings are consistent with those of the clinical trial (2).

      2. Progress toward measles elimination - South-East Asia Region, 2003-2020
        Khanal S, Kassem AM, Bahl S, Jayantha L, Sangal L, Sharfuzzaman M, Bose AS, Antoni S, Datta D, Alexander JP.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1042-1046.
        In 2013, member states of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goal of measles elimination and rubella and congenital rubella syndrome control(†) by 2020 (1). In 2014, to provide impetus toward achieving this goal, the Regional Director declared measles elimination and rubella control one of the Regional Flagship Priorities. In 2019, SEAR member states declared a revised goal of eliminating both measles and rubella(§) by 2023 (2). The recommended strategies to achieve elimination include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities(¶) (SIAs); 2) developing and sustaining a sensitive and timely case-based surveillance system that meets recommended performance indicators**; 3) developing and maintaining an accredited laboratory network; 4) achieving timely identification, investigation, and response to measles outbreaks; and 5) collaborating with other public health initiatives to achieve the preceding four strategies. This report updates a previous report and describes progress toward measles elimination in SEAR during 2003-2020 (3). In 2002, coverage with the first dose of a measles-containing vaccine in routine immunization (MCV1) was 70%, and only three countries in SEAR had added a second routine dose of measles-containing vaccine in routine immunization (MCV2). During 2003-2020, all countries introduced MCV2, and estimated coverage with MCV1 increased 35%, from 65% to 88%, and coverage with MCV2 increased 1,233% from 6% to 80%. Approximately 938 million persons were vaccinated in SIAs. Annual reported measles incidence declined by 92%, from 57.0 to 4.8 cases per 1 million population, and estimated deaths decreased by 97%; an estimated 9.3 million deaths were averted by measles vaccination. By 2020, five countries were verified as having achieved measles elimination. To achieve measles elimination in the region by 2023, additional efforts are urgently needed to strengthen routine immunization services and improve measles-containing vaccine (MCV) coverage, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory capacity.

      3. Implementation of an outbreak response vaccination campaign with typhoid conjugate vaccine - Harare, Zimbabwe, 2019
        Poncin M, Marembo J, Chitando P, Sreenivasan N, Makwara I, Machekanyanga Z, Nyabyenda W, Mukeredzi I, Munyanyi M, Hidle A, Chingwena F, Chigwena C, Atuhebwe P, Matzger H, Chigerwe R, Shaum A, Date K, Garone D, Chonzi P, Barak J, Phiri I, Rupfutse M, Masunda K, Gasasira A, Manangazira P.
        Vaccine X. 2022 Dec;12:100201.
        INTRODUCTION: Typhoid fever is a public-health problem in Harare, the capital city of Zimbabwe, with seasonal outbreaks occurring annually since 2010. In 2019, the Ministry of Health and Child Care (MOHCC) organized the first typhoid conjugate vaccination campaign in Africa in response to a recurring typhoid outbreak in a large urban setting. METHOD: As part of a larger public health response to a typhoid fever outbreak in Harare, Gavi approved in September 2018 a MOHCC request for 340,000 doses of recently prequalified Typbar-TCV to implement a mass vaccination campaign. To select areas for the campaign, typhoid fever surveillance data from January 2016 until June 2018 was reviewed. We collected and analyzed information from the MOHCC and its partners to describe the vaccination campaign planning, implementation, feasibility, administrative coverage and financial costs. RESULTS: The campaign was conducted in nine high-density suburbs of Harare over eight days in February-March 2019 and targeted all children aged 6 months-15 years; however, the target age range was extended up to 45 years in one suburb due to the past high attack rate among adults. A total of 318,698 people were vaccinated, resulting in overall administrative coverage of 85.4 percent. More than 750 community volunteers and personnel from the MOHCC and the Ministry of Education were trained and involved in social mobilization and vaccination activities. The MOHCC used a combination of vaccination strategies (i.e., fixed and mobile immunization sites, a creche and school-based strategy, and door-to-door activities). Financial costs were estimated at US$ 2.39 per dose, including the vaccine and vaccination supplies (US$ 0.79 operational costs per dose excluding vaccine and vaccination supplies). CONCLUSION: A mass targeted campaign in densely populated urban areas in Harare, using the recently prequalified typhoid conjugate vaccine, was feasible and achieved a high overall coverage in a short period of time.

    • Informatics
      1. Recent changes to virus taxonomy ratified by the International Committee on Taxonomy of Viruses (2022)
        Walker PJ, Siddell SG, Lefkowitz EJ, Mushegian AR, Adriaenssens EM, Alfenas-Zerbini P, Dempsey DM, Dutilh BE, García ML, Curtis Hendrickson R, Junglen S, Krupovic M, Kuhn JH, Lambert AJ, Łobocka M, Oksanen HM, Orton RJ, Robertson DL, Rubino L, Sabanadzovic S, Simmonds P, Smith DB, Suzuki N, Van Doorslaer K, Vandamme AM, Varsani A, Zerbini FM.
        Arch Virol. 2022 Aug 23.
        This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2022. The entire ICTV was invited to vote on 174 taxonomic proposals approved by the ICTV Executive Committee at its annual meeting in July 2021. All proposals were ratified by an absolute majority of the ICTV members. Of note, the Study Groups have started to implement the new rule for uniform virus species naming that became effective in 2021 and mandates the binomial 'Genus_name species_epithet' format with or without Latinization. As a result of this ratification, the names of 6,481 virus species (more than 60 percent of all species names currently recognized by ICTV) now follow this format.

    • Injury and Violence
      1. Suicide among males across the lifespan: An analysis of differences by known mental health status
        Fowler KA, Kaplan MS, Stone DM, Zhou H, Stevens MR, Simon TR.
        Am J Prev Med. 2022 Sep;63(3):419-422.
        INTRODUCTION: Suicide among males is a major public health challenge. In 2019, males accounted for nearly 80% of the suicide deaths in the U.S., and suicide was the eighth leading cause of death for males aged ≥10 years. Males who die by suicide are less likely to have known mental health conditions than females; therefore, it is important to identify prevention points outside of mental health systems. The purpose of this analysis was to compare suicide characteristics among males with and without known mental health conditions by age group to inform prevention. METHODS: Suicides among 4 age groups of males were examined using the 3 most recent years of data at the time of the analysis (2016-2018) from the Centers for Disease Control and Prevention's National Violent Death Reporting System. Decedents with and without known mental health conditions were compared within age groups. The analysis was conducted in August 2021. RESULTS: Most male suicide decedents had no known mental health conditions. More frequently, those without known mental health conditions died by firearm, and many tested positive for alcohol. Adolescents, young adults, and middle-aged males without known mental health conditions more often had relationship problems, arguments, and/or a crisis as a precipitating circumstance than those with known mental health conditions. CONCLUSIONS: Acute stressors more often precipitated suicides of males without known mental health conditions, and they more often involved firearms. These findings underscore the importance of mitigating acute situational stressors that could contribute to emotionally reactive/impulsive suicides. Suicide prevention initiatives targeting males might focus on age-specific precipitating circumstances in addition to standard psychiatric markers.

      2. BACKGROUND: Concussion education for parents/guardians (hereafter referred to as parents) has the potential to play an important role in youth athlete concussion safety. The goal of this study was to evaluate the impact of the Centers for Disease Control and Prevention's (CDC) HEADS UP handout on parent-child communication about concussion. METHODS: YMCA branches from 15 associations from across the United States were randomized to CDC HEADS UP intervention condition or education as usual control condition using a cluster randomization strategy. In the intervention condition, coaches shared parent- and athlete-specific handouts with parents and asked parents to share and discuss the athlete-specific handouts with their child. Generalized estimating equations, with repeated measures to account for the correlation among matched participants and YMCA associations, were employed. RESULTS: Multivariable analyses exploring the relationship between time (pre- and post-intervention) and communication showed that the percent of parents who talked to their child about concussion increased in the intervention group (aRR=1.33, 95% CI=1.22, 1.44), but not in the control group. CONCLUSION: CDC HEADS UP handouts help families talk about concussion safety. Sports organizations seeking to educate parents of athletes about concussion should consider using CDC HEADS UP handouts and following a similar dissemination strategy.

    • Laboratory Sciences
      1. The performance of using dried blood spot specimens for HIV-1 viral load testing: A systematic review and meta-analysis
        Vojnov L, Carmona S, Zeh C, Markby J, Boeras D, Prescott MR, Mayne AL, Sawadogo S, Adje-Toure C, Zhang G, Perez Gonzalez M, Stevens WS, Doherty M, Yang C, Alexander H, Peter TF, Nkengasong J.
        PLoS Med. 2022 Aug 22;19(8):e1004076.
        BACKGROUND: Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies. METHODS AND FINDINGS: Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify virological failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended virological failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes. CONCLUSIONS: This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml virological failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.

    • Maternal and Child Health
      1. Time to shunt failure in children with myelomeningocele: an analysis of the National Spina Bifida Patient Registry
        Rocque BG, Hopson B, Shamblin I, Liu T, Ward E, Bowman R, Foy AB, Dias M, Heuer GG, Smith K, Blount JP.
        J Neurosurg Pediatr. 2022 Aug 19:1-6.
        OBJECTIVE: Hydrocephalus is common among children with myelomeningocele and is most frequently treated with a ventriculoperitoneal shunt (VPS). Although much is known about factors related to first shunt failure, relatively less data are available about shunt failures after the first one. The purpose of this study was to use a large data set to explore time from initial VPS placement to first shunt failure in children with myelomeningocele and to explore factors related to multiple shunt failures. METHODS: Data were obtained from the National Spina Bifida Patient Registry. Children with myelomeningocele who were enrolled within the first 5 years of life and had all lifetime shunt operations recorded in the registry were included. Kaplan-Meier survival curves were constructed to evaluate time from initial shunt placement to first shunt failure. The total number of children who experienced at least 2 shunt failures was calculated. A proportional means model was performed to calculate adjusted hazard ratios (HRs) for shunt failure on the basis of sex, race/ethnicity, lesion level, and insurance status. RESULTS: In total, 1691 children met the inclusion criteria. The median length of follow-up was 5.0 years. Fifty-five percent of patients (938 of 1691) experienced at least 1 shunt failure. The estimated median time from initial shunt placement to first failure was 2.34 years (95% confidence interval [CI] 1.91-3.08 years). Twenty-six percent of patients had at least 2 shunt failures, and 14% of patients had at least 3. Male children had higher likelihood of shunt revision (HR 1.25, 95% CI 1.09-1.44). Children of minority race/ethnicity had a lower likelihood of all shunt revisions (non-Hispanic Black children HR 0.74, 95% CI 0.55-0.98; Hispanic children HR 0.74, 95% CI 0.62-0.88; children of other ethnicities HR 0.80, 95% CI 0.62-1.03). CONCLUSIONS: Among the children with myelomeningocele, the estimated median time to shunt failure was 2.34 years. Forty-five percent of children never had shunt failure. The observed higher likelihood of shunt revisions among males and lower likelihood among children of minority race/ethnicity illustrate a possible disparity in hydrocephalus care that warrants additional study. Overall, these results provide important information that can be used to counsel parents of children with myelomeningocele about the expected course of shunted hydrocephalus.

      2. BACKGROUND: COVID-19-disrupted schools, including shifts to virtual learning which may have impacted academic progress. This study assessed characteristics associated with changes in academic grades (before and during the pandemic) for different learning modalities for US students ages 13-19. METHODS: Students (N = 2152) completed a web survey on school-related experiences during the 2020-2021 school year. County social vulnerability and SARS-CoV-2 transmission data were merged with survey data. Multivariable logistic regression analysis for grade change was conducted with student and school characteristics for each learning modality, controlling for community characteristics. RESULTS: Greater proportions of remote/virtual (34.4%) and hybrid (30.1%) learning students reported grade decline compared to in-person students (19.9%). Among in-person students, odds of reporting same/improved grades were 65% lower among non-Hispanic black students and 66% lower among non-Hispanic students from other races, compared to non-Hispanic white students. Among hybrid students, odds of reporting same/improved grades for students reporting anxiety were 47% lower than students without anxiety, and odds of reporting same/improved grades among students reporting substance use were 40% lower than students not reporting substance use. Among remote/virtual students, odds of reporting same/improved grades among students with depression were 62% lower than odds of students not reporting depression symptoms. Remote/virtual students who received school-provided educational services also had 1.55 times the odds of reporting same/improved grades, compared to remote/virtual students not receiving these services. CONCLUSIONS: Academic grades were negatively impacted during COVID-19 and learning mode may have contributed. Understanding these impacts is critical to student health and academic achievement.

      3. Donor human milk use in advanced neonatal care units - United States, 2020
        Boundy EO, Anstey EH, Nelson JM.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1037-1041.
        Approximately 50,000 infants are born in the United States each year with very low birthweight (VLBW) (<1,500 g).* Benefits of human milk to infants with VLBW include decreased risk for necrotizing enterocolitis, a serious illness resulting from inflammation and death of intestinal tissue that occurs most often in premature infants, especially those who are fed formula rather than human milk; late-onset sepsis; chronic lung disease; retinopathy of prematurity; and neurodevelopmental impairment (1). When mother's own milk is unavailable or insufficient, pasteurized donor human milk (donor milk) plus a multinutrient fortifier is the first recommended alternative for infants with VLBW (2). CDC's 2020 Maternity Practices in Infant Nutrition and Care (mPINC) survey was used to assess practices for donor milk use in U.S. advanced neonatal care units of hospitals that provide maternity care (3). Among 616 hospitals with neonatal intensive care units (level III or IV units),(†) 13.0% reported that donor milk was not available for infants with VLBW; however, approximately one half (54.7%) reported that most (≥80%) infants with VLBW do receive donor milk. Donor milk availability for infants with VLBW was more commonly reported among hospitals with a level IV unit, higher annual birth volume, location in the Midwest and Southwest regions, nonprofit and teaching status, and those designated Baby-Friendly.(§) Addressing hospitals' barriers to providing donor milk could help ensure that infants with VLBW receive donor milk when needed and help reduce morbidity and mortality in infants with VLBW (1,4).

    • Nutritional Sciences
      1. Folic acid and the prevention of birth defects: 30 years of opportunity and controversies
        Crider KS, Qi YP, Yeung LF, Mai CT, Head Zauche L, Wang A, Daniels K, Williams JL.
        Annu Rev Nutr. 2022 Aug 22;42:423-452.
        For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify (n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B(12) as well as expanded biomarker testing.

    • Occupational Safety and Health
      1. Individual-level permethrin exposure biomarkers in U.S. army soldiers: comparison of two treatment formulations for military uniforms
        Proctor SP, Nguyen VT, Hebert AA, Taylor KM, McClung HL, Heaton KJ, Ospina M, Calafat AM.
        J Expo Sci Environ Epidemiol. 2022 Aug 23.
        BACKGROUND: Evidence suggests that wearing permethrin-treated military uniforms is not associated with current adverse health conditions. However, exposure through this route results in permethrin biomarker concentrations considerably higher than those in the U.S. POPULATION: The U.S. Army is exploring different methods of uniform treatment that reduce exposure while maintaining effective protection from insect vector-borne diseases. OBJECTIVE: To compare permethrin exposure when wearing two types of permethrin-treated military uniforms. METHODS: Eight male soldiers participated in a 32-day crossover design study to compare permethrin exposure when wearing the current Army uniform (CurrU) and a uniform with a new applied fabric treatment (NewU). Each soldier wore the uniforms for designated 8 h/day time periods over 3 consecutive days separated by a 'wash-out' week of no exposure. Permethrin exposure was assessed from the urinary concentrations of 3-phenoxybenzoic acid (3-PBA) and of the sum of cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (∑DCCA). Estimated dose was determined based on ∑DCCA concentrations. RESULTS: Permethrin exposure biomarkers were 21% (3-PBA, p = 0.025) and 35% (∑DCCA, p < 0.001) lower when wearing the NewU compared to the CurrU; the dose was 33% lower (p = 0.05). SIGNIFICANCE: Findings suggest the new treatment reduces human permethrin exposure biomarkers resulting from wearing-treated military uniforms.

      2. Hierarchy of contamination control in the fire service: Review of exposure control options to reduce cancer risk
        Horn GP, Fent KW, Kerber S, Smith DL.
        J Occup Environ Hyg. 2022 Aug 5:1-20.
        The international fire service community is actively engaged in a wide range of activities focused on development, testing, and implementation of effective approaches to reduce exposure to contaminants and the related cancer risk. However, these activities are often viewed independent of each other and in the absence of the larger overall effort of occupational health risk mitigation. This narrative review synthesizes the current research on fire service contamination control in the context of the National Institute for Occupational Safety and Health (NIOSH) Hierarchy of Controls, a framework that supports decision making around implementing feasible and effective control solutions in occupational settings. Using this approach, we identify evidence-based measures that have been investigated and that can be implemented to protect firefighters during an emergency response, in the fire apparatus and at the fire station, and identify several knowledge gaps that remain. While a great deal of research and development has been focused on improving personal protective equipment for the various risks faced by the fire service, these measures are considered less effective. Administrative and engineering controls that can be used during and after the firefight have also received increased research interest in recent years. However, less research and development have been focused on higher level control measures such as engineering, substitution, and elimination, which may be the most effective, but are challenging to implement. A comprehensive approach that considers each level of control and how it can be implemented, and that is mindful of the need to balance contamination risk reduction against the fire service mission to save lives and protect property, is likely to be the most effective.

    • Parasitic Diseases
      1. Drug utilization and payment estimates for standard-of-care treatment of schistosomiasis have not been reported previously in the United States. This study estimates the utilization of praziquantel (standard-of-care drug) among patients with schistosomiasis and outpatient payments among those who were treated with praziquantel, and investigates the factors associated with praziquantel use from 2013-19 using IBM's MarketScan® Commercial Claims and Encounters database. Claims data showed that only 21% of patients with schistosomiasis diagnoses were treated with praziquantel. The mean total drug payments per patient treated with praziquantel increased from $110 in 2013-14 to $612 in 2015-18 (P < 0.01), and use decreased. These factors, including residing in a rural area, having a documented Schistosoma haematobium infection, or having a first schistosomiasis diagnosis in 2015-16, were associated with a decreased likelihood of patients receiving standard-of-care treatment. Policy solutions to exorbitant drug pricing, and better awareness and education among healthcare providers about schistosomiasis-especially those practicing in rural areas with high immigrant populations-are needed.

      2. Identification of factors associated with residual malaria transmission using school-based serological surveys in settings pursuing elimination
        Rakotondramanga JM, Vigan-Womas I, Steinhardt LC, Harimanana A, Ravaoarisoa E, Rasoloharimanana TL, Razanatsiorimalala S, Wesolowski A, Randrianarivelojosia M, Roche B, Garchitorena A.
        Malar J. 2022 Aug 21;21(1):242.
        BACKGROUND: Targeted research on residual malaria transmission is important to improve strategies in settings pursuing elimination, where transmission reductions prove challenging. This study aimed to detect and characterize spatial heterogeneity and factors associated with Plasmodium falciparum infections and exposure, P. falciparum apical membrane antigen 1 (PfAMA1) antibody (Ab) response, in the Central Highlands of Madagascar (CHL). METHODS: From May to July 2014, a cross-sectional school-based survey was carried out in 182 fokontany (villages) within 7 health districts of the CHL. Rapid diagnostic tests (RDTs) and a bead-based immunoassay including PfAMA1 antigen biomarker were used to estimate malaria prevalence and seroprevalence, respectively. Local Moran's I index was used to detect spatial "hotspots". Remotely sensed environmental data-temperature, vegetation indices, land covers, and elevation-were used in multivariable mixed-effects logistic regression models to characterize factors associated with malaria infection and cumulative exposure. RESULTS: Among 6,293 school-children ages 2-14 years surveyed, RDT prevalence was low at 0.8% (95% CI 0.6-1.1%), while PfAMA1 Ab seroprevalence was 7.0% (95% CI 6.4-7.7%). Hotspots of PfAMA1 Ab seroprevalence were observed in two districts (Ankazobe and Mandoto). Seroprevalence increased for children living > 5 km from a health centre (adjusted odds ratio (OR) = 1.6, 95% CI 1.2-2.2), and for those experiencing a fever episode in the previous 2 weeks (OR 1.7, 95% CI 1.2-2.4), but decreased at higher elevation (for each 100-m increase, OR = 0.7, 95% CI 0.6-0.8). A clear age pattern was observed whereby children 9-10 years old had an OR of 1.8 (95% CI 1.2-2.4), children 11-12 years an OR of 3.7 (95% CI 2.8-5.0), and children 13-14 years an OR of 5.7 (95% CI 4.0-8.0) for seropositivity, compared with younger children (2-8 years). CONCLUSION: The use of serology in this study provided a better understanding of malaria hotspots and associated factors, revealing a pattern of higher transmission linked to geographical barriers in health care access. The integration of antibody-assays into existing surveillance activities could improve exposure assessment, and may help to monitor the effectiveness of malaria control efforts and adapt elimination interventions.

    • Zoonotic and Vectorborne Diseases
      1. Knowledge, attitudes, and practices on Rocky Mountain Spotted Fever among physicians in a highly endemic region-Mexicali, Mexico
        Bestul N, Padilla R, Montaño T, Márquez A, Fierro M, Zazueta OE, Armstrong PA.
        Am J Trop Med Hyg. 2022 Aug 22.
        Rocky Mountain spotted fever (RMSF) is a potentially fatal tickborne disease caused by the bacterium, Rickettsia rickettsii and transmitted primarily by the brown dog tick (Rhipicephalus sanguineus) in the southwestern United States and Mexico. RMSF can be rapidly fatal if not treated early with doxycycline, making healthcare worker awareness and education critical to reduce morbidity and mortality. During 2008-2019, Mexicali experienced a RMSF epidemic with 779 confirmed cases, and an 11-year case-fatality rate of 18% (N = 140). A cross-sectional study was conducted with 290 physicians and physicians-in-training across 12 medical facilities in Mexicali. They were asked to complete a 23-item questionnaire to assess knowledge, attitudes, and practices for clinical, epidemiologic, and preventive aspects of RMSF. Half of participants were female, the largest age group was aged 25 to 44 (47%), and median time in practice was 6 years (interquartile rate: 1-21.5). Less than half (48%) surveyed were confident where diagnostic testing could be performed, and two-thirds did not regularly order serology (67%) or molecular diagnostic (66%) tests for RMSF when a patient presented with fever. Sixty-four percent knew doxycycline as first-line treatment of children < 8 years with suspected RMSF. When comparing healthcare workers with < 6 years of experience to those with ≥ 6 years, more experience was associated with greater confidence in where to have diagnostic testing performed (prevalence odds ratio [prevalence odds ratios [pOR]] = 2.3; P = 0.004), and frequency of ordering laboratory tests (serology, pOR = 3.3; P = 0.002; polymerase chain reaction, pOR = 3.9; P = 0.001). Continued education, including information on diagnostic testing is key to reducing morbidity and mortality from RMSF.

      2. Chapare hemorrhagic fever and virus detection in rodents in Bolivia in 2019
        Loayza Mafayle R, Morales-Betoulle ME, Romero C, Cossaboom CM, Whitmer S, Alvarez Aguilera CE, Avila Ardaya C, Cruz Zambrana M, Dávalos Anajia A, Mendoza Loayza N, Montaño AM, Morales Alvis FL, Revollo Guzmán J, Sasías Martínez S, Alarcón De La Vega G, Medina Ramírez A, Molina Gutiérrez JT, Cornejo Pinto AJ, Salas Bacci R, Brignone J, Garcia J, Añez A, Mendez-Rico J, Luz K, Segales A, Torrez Cruz KM, Valdivia-Cayoja A, Amman BR, Choi MJ, Erickson BR, Goldsmith C, Graziano JC, Joyce A, Klena JD, Leach A, Malenfant JH, Nichol ST, Patel K, Sealy T, Shoemaker T, Spiropoulou CF, Todres A, Towner JS, Montgomery JM.
        N Engl J Med. 2022 Jun 16;386(24):2283-2294.
        BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).


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