Mitigating a COVID-19 Outbreak Among Major League Baseball Players - United States, 2020.

Mass gatherings have been implicated in higher rates of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), and many sporting events have been restricted or canceled to limit disease spread (1). Based on current CDC COVID-19 mitigation recommendations related to events and gatherings (2), Major League Baseball (MLB) developed new health and safety protocols before the July 24 start of the 2020 season. In addition, MLB made the decision that games would be played without spectators. Before a three-game series between teams A and B, the Philadelphia Department of Public Health was notified of a team A player with laboratory-confirmed COVID-19; the player was isolated as recommended (2). During the series and the week after, laboratory-confirmed COVID-19 was diagnosed among 19 additional team A players and staff members and one team B staff member. Throughout their potentially infectious periods, some asymptomatic team A players and coaches, who subsequently received positive SARS-CoV-2 test results, engaged in on-field play with teams B and C. No on-field team B or team C players or staff members subsequently received a clinical diagnosis of COVID-19. Certain MLB health and safety protocols, which include frequent diagnostic testing for rapid case identification, isolation of persons with positive test results, quarantine for close contacts, mask wearing, and social distancing, might have limited COVID-19 transmission between teams.

Public Health Emergency Preparedness System Evaluation Criteria and Performance Metrics: A Review of Contributions of the CDC-Funded Preparedness and Emergency Response Research Centers.

OBJECTIVES: The US Centers for Disease Control and Prevention (CDC)-funded Preparedness and Emergency Response Research Centers (PERRCs) conducted research from 2008 to 2015 aimed to improve the complex public health emergency preparedness and response (PHEPR) system. This paper summarizes PERRC studies that addressed the development and assessment of criteria for evaluating PHEPR and metrics for measuring their efficiency and effectiveness. METHODS: We reviewed 171 PERRC publications indexed in PubMed between 2009 and 2016. These publications derived from 34 PERRC research projects. We identified publications that addressed the development or assessment of criteria and metrics pertaining to PHEPR systems and describe the evaluation methods used and tools developed, the system domains evaluated, and the metrics developed or assessed. RESULTS: We identified 29 publications from 12 of the 34 PERRC projects that addressed PHEPR system evaluation criteria and metrics. We grouped each study into 1 of 3 system domains, based on the metrics developed or assessed: (1) organizational characteristics (n = 9), (2) emergency response performance (n = 12), and (3) workforce capacity or capability (n = 8). These studies addressed PHEPR system activities including responses to the 2009 H1N1 pandemic and the 2011 tsunami, as well as emergency exercise performance, situational awareness, and workforce willingness to respond. Both PHEPR system process and outcome metrics were developed or assessed by PERRC studies. CONCLUSIONS: PERRC researchers developed and evaluated a range of PHEPR system evaluation criteria and metrics that should be considered by system partners interested in assessing the efficiency and effectiveness of their activities. Nonetheless, the monitoring and measurement problem in PHEPR is far from solved. Lack of standard measures that are readily obtained or computed at local levels remains a challenge for the public health preparedness field. (Disaster Med Public Health Preparedness. 2019;13:626-638).

Overview of the Translation, Dissemination, and Implementation of Public Health Preparedness and Response Research and Training Initiative.

We provide an overview of a Centers for Disease Control and Prevention-funded public health preparedness and response (PHPR) research and training initiative to improve public health practice. Our objectives were to accelerate the translation, dissemination, and implementation (TDI) of promising PHPR evidence-based tools and trainings developed by the Preparedness and Emergency Response Research Centers (PERRC) or the Preparedness and Emergency Response Learning Centers (PERLC) between 2008 and 2015. Nine competitive awards were made to seven academic centers to achieve predetermined TDI objectives. The outputs attained by the initiative included: user-friendly online repositories of PERRC and PERLC tools and trainings; training courses that addressed topics; a community resilience manual to synthesize, translate, and implement evidence-based programs; and Web applications that supported legal preparedness, exercise evaluation, and immunization education. The evaluation identified several best practices and potential barriers to implementation. As illustrated by the work in this supplement, the broader awareness and implementation of PERRC preparedness products and PERLC trainings and the continued evaluation of their impact could enhance the PHPR capacity and capability of the nation, which could lead to improved health security.

Preparedness Training Programs for Working With Deaf and Hard of Hearing Communities and Older Adults: Lessons Learned From Key Informants and Literature Assessments.

OBJECTIVES: The objectives of this study were to (1) identify available training programs for emergency response personnel and public health professionals on addressing the needs of Deaf and hard of hearing individuals and older adults, (2) identify strategies to improve these training programs, and (3) identify gaps in available training programs and make recommendations for addressing these gaps. METHODS: A literature review was conducted to identify relevant training programs and identify lessons learned. Interviews were conducted by telephone or email with key informants who were subject matter experts who worked with Deaf and hard of hearing persons (n=11) and older adults (n=11). RESULTS: From the literature, 11 training programs targeting public health professionals and emergency response personnel serving Deaf and hard of hearing individuals (n=7) and older adults (n=4) were identified. The 4 training programs focused on older adults had corresponding evaluations published in the literature. Three (43%) of the 7 training programs focused on Deaf and hard of hearing persons included individuals from the affected communities in the development and implementation of the training. Key informant interviews identified common recommendations for improving training programs: (1) training should involve collaboration across different emergency, state, federal, and advocacy agencies; (2) training should involve members of affected communities; (3) training should be more widely accessible and affordable; and (4) training should teach response personnel varied communication techniques relevant to the Deaf and hard of hearing and older adult communities. CONCLUSIONS: Developing effective, accessible, and affordable training programs for emergency response personnel working with Deaf and hard of hearing persons, some of whom belong to the older adult population, will require a collaborative effort among emergency response agencies, public health organizations, and members of the affected communities. (Disaster Med Public Health Preparedness. 2018;12:606-614).

Preparedness and emergency response research centers: using a public health systems approach to improve all-hazards preparedness and response.

In 2008, at the request of the Centers for Disease Control and Prevention (CDC), the Institute of Medicine (IOM) prepared a report identifying knowledge gaps in public health systems preparedness and emergency response and recommending near-term priority research areas. In accordance with the Pandemic and All-Hazards Preparedness Act mandating new public health systems research for preparedness and emergency response, CDC provided competitive awards establishing nine Preparedness and Emergency Response Research Centers (PERRCs) in accredited U.S. schools of public health. The PERRCs conducted research in four IOM-recommended priority areas: (1) enhancing the usefulness of public health preparedness and response (PHPR) training, (2) creating and maintaining sustainable preparedness and response systems, (3) improving PHPR communications, and (4) identifying evaluation criteria and metrics to improve PHPR for all hazards. The PERRCs worked closely with state and local public health, community partners, and advisory committees to produce practice-relevant research findings. PERRC research has generated more than 130 peer-reviewed publications and nearly 80 practice and policy tools and recommendations with the potential to significantly enhance our nation's PHPR to all hazards and that highlight the need for further improvements in public health systems.

Ancient, independent evolution and distinct molecular features of the novel human T-lymphotropic virus type 4.

BACKGROUND: Human T-lymphotropic virus type 4 (HTLV-4) is a new deltaretrovirus recently identified in a primate hunter in Cameroon. Limited sequence analysis previously showed that HTLV-4 may be distinct from HTLV-1, HTLV-2, and HTLV-3, and their simian counterparts, STLV-1, STLV-2, and STLV-3, respectively. Analysis of full-length genomes can provide basic information on the evolutionary history and replication and pathogenic potential of new viruses. RESULTS: We report here the first complete HTLV-4 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocyte DNA from an HTLV-4-infected person. The HTLV-4(1863LE) genome is 8791-bp long and is equidistant from HTLV-1, HTLV-2, and HTLV-3 sharing only 62-71% nucleotide identity. HTLV-4 has a prototypic genomic structure with all enzymatic, regulatory, and structural proteins preserved. Like STLV-2, STLV-3, and HTLV-3, HTLV-4 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains unique c-Myb and pre B-cell leukemic transcription factor binding sites. Like HTLV-2, the PDZ motif important for cellular signal transduction and transformation in HTLV-1 and HTLV-3 is missing in the C-terminus of the HTLV-4 Tax protein. A basic leucine zipper (b-ZIP) region located in the antisense strand of HTLV-1 and believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-4. Detailed phylogenetic analysis shows that HTLV-4 is clearly a monophyletic viral group. Dating using a relaxed molecular clock inferred that the most recent common ancestor of HTLV-4 and HTLV-2/STLV-2 occurred 49,800 to 378,000 years ago making this the oldest known PTLV lineage. Interestingly, this period coincides with the emergence of Homo sapiens sapiens during the Middle Pleistocene suggesting that early humans may have been susceptible hosts for the ancestral HTLV-4. CONCLUSION: The inferred ancient origin of HTLV-4 coinciding with the appearance of Homo sapiens, the propensity of STLVs to cross-species into humans, the fact that HTLV-1 and -2 spread globally following migrations of ancient populations, all suggest that HTLV-4 may be prevalent. Expanded surveillance and clinical studies are needed to better define the epidemiology and public health importance of HTLV-4 infection.

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

BACKGROUND: In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. METHODS AND FINDINGS: We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. CONCLUSIONS: This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis.

Human T-lymphotropic virus type 3 (HTLV-3) is a new virus recently identified in two primate hunters in Central Africa. Limited sequence analysis shows that HTLV-3 is distinct from HTLV-1 and HTLV-2 but is genetically similar to simian T-lymphotropic virus type 3 (STLV-3). We report here the first complete HTLV-3 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocytes from an HTLV-3-infected person. The HTLV-3(2026ND) genome is 8,917 bp long and is genetically equidistant from HTLV-1 and HTLV-2, sharing about 62% identity. Phylogenetic analysis of all gene regions confirms this relationship and shows that HTLV-3 falls within the diversity of STLV-3, suggesting a primate origin. However, HTLV-3(2026ND) is unique, sharing only 87% to 92% sequence identity with STLV-3. SimPlot and phylogenetic analysis did not reveal any evidence of genetic recombination with either HTLV-1, HTLV-2, or STLV-3. Molecular dating estimates that the ancestor of HTLV-3 is as old as HTLV-1 and HTLV-2, with an inferred divergence time of 36,087 to 54,067 years ago. HTLV-3 has a prototypic genomic structure, with all enzymatic, regulatory, and structural proteins preserved. Like STLV-3, HTLV-3 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains a unique activator protein-1 transcription factor upstream of the 21-bp repeat elements. A PDZ motif, like that in HTLV-1, which is important for cellular signal transduction and transformation, is present in the C terminus of the HTLV-3 Tax protein. A basic leucine zipper region located in the antisense strand of HTLV-1, believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-3. The ancient origin of HTLV-3, the broad distribution of STLV-3 in Africa, and the propensity of STLVs to cross species into humans all suggest that HTLV-3 may be prevalent and support the need for expanded surveillance for this virus.

A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma.

Zidovudine and other nucleoside analogue reverse transcriptase inhibitors (NRTIs), like zalcitabine and didanosine used for treatment of individuals infected with HIV-1, can select for viruses with Q151M and other associated mutations (for example, A62V, S68G, V751, F77L, F116Y) in the reverse transcriptase (RT) enzyme. These mutations confer resistance to multiple nucleoside analogues, and thereby compromise the efficacy of this class of drugs. Presently available phenotypic assays for detection of multiple nucleoside analogue resistant (MNR) HIV-1 require testing for each NRTI individually. Here we report an enzymatic RT assay that uses resistance to zidovudine triphosphate (zidovudine-TP) as a diagnostic biochemical marker of MNR HIV-1. This assay exploits the different biochemical mechanisms for zidovudine-resistance conferred by either Q151 M or T215Y/F mutations and the inability of conventional RT assays to detect T215Y/F-associated zidovudine resistance. The assay detects RT activity directly in plasma by using Amp-RT, an ultra-sensitive PCR-based RT assay. We show that enzymatic resistance to zidovudine-TP is specific to MNR RT and is distinguishable from both wild-type (WT) and RT containing classical zidovudine-resistant mutations (D67N, K70R, T215Y/F, K219Q). Compared to WT, MNR HIV-1 RT had 5- to 36-fold increases in the concentration of drug required to inhibit 50% (IC50) of RT activity, depending on the presence of Q151 M alone or with additional MNR mutations. A screening assay utilizing 1 microM zidovudine-TP was developed and validated on 14 reference isolates, 37 plasma specimens, and seven patient-derived viruses. Twenty-three specimens were found to have reduced susceptibility to zidovudine-TP, and all had Q151 M. In contrast, 21 specimens were sensitive to zidovudine-TP, of which 12 had WT genotypes, four had T215Y/F, and five had T69S-insertions along with T215Y/F mutations. This RT-based phenotypic assay provides a specific and rapid tool for the direct identification and monitoring of Q151M-associated MNR HIV-1 in plasma.

Comparative analysis of two commercial phenotypic assays for drug susceptibility testing of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) isolates from 50 plasma specimens were analyzed for phenotypic susceptibility to licensed reverse transcriptase inhibitors and protease inhibitors by the Antivirogram and PhenoSense HIV assays. Twenty of these specimens were from recently seroconverted drug-naïve persons, and 30 were from patients who were the sources of occupational exposures to HIV-1; 16 of the specimens in the latter group were from drug-experienced patients. The phenotypic results of the Antivirogram and PhenoSense HIV assays were categorized as sensitive or reduced susceptibility on the basis of the cutoff values established by the manufacturers of each assay. Data for 12 to 15 drugs were available by both assays for 38 specimens and represented a total of 529 pairs of results. The two data sets had a 91.5% concordance by phenotypic category. The discordant results (n = 45) were distributed randomly among 26 specimens and included 28 results (62.2%) which were within a twofold difference of the assay cutoff values. None of the discordant results were associated with primary resistance mutations that predicted high-level (>20-fold) resistance. Discordant results were distributed equally among specimens from drug-experienced and drug-naïve individuals and were slightly higher for protease inhibitors than for nonnucleoside reverse transcriptase inhibitors or nucleoside reverse transcriptase inhibitors. The findings of the present study demonstrate that the results of the Antivirogram and PhenoSense HIV assays correlate well, despite the use of different testing strategies.

Use of glass beads and CF 11 cellulose for removal of leukocytes from malaria-infected human blood in field settings

Passage of malaria infected blood through a two-layered column composed of acid-washed glass beads and CF 11 cellulose removes white cells from parasitized blood. However, because use of glass beads and CF 11 cellulose requires filtration of infected blood separately through these two resins and the addition of ADP, the procedure is time-consuming and may be inapropriate for use in the field, especially when large numbers of blood samples are to be treated. Our modification of this process yields parasitized cells free of contaminating leukocytes, and because of its operational simplicity, large numbers of blood samples can be processed. Our procedure also compares well with those using expensive commercial Sepacell resins in its ability to separate leukocytes from whole blood. As a test of usefulness in molecular biologic investigations, the parasites obtained from the blood of malaria-infected patients using the modified procedure yield genomic DNA whose single copy gene, the circumsporozite gene, efficiently amplifies by polymerase chain reaction

Polymorphism in the circumsporozoite protein of the human malaria parasite Plasmodium vivax

The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B-and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have le to the emergence of the variant CS repeat sequence ANGA (G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P.vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-dept study of parasite population dynamics is required before field trials for vaccine formulations based on polymorphic immunodominant determinants are conducted.