COVID-19 Epidemiology during Delta Variant Dominance Period in 45 High-Income Countries, 2020-2021.

The SARS-CoV-2 Delta variant, first identified in October 2020, quickly became the dominant variant worldwide. We used publicly available data to explore the relationship between illness and death (peak case rates, death rates, case-fatality rates) and selected predictors (percentage vaccinated, percentage of the population >65 years, population density, testing volume, index of mitigation policies) in 45 high-income countries during the Delta wave using rank-order correlation and ordinal regression. During the Delta-dominant period, most countries reported higher peak case rates (57%) and lower peak case-fatality rates (98%). Higher vaccination coverage was protective against peak case rates (odds ratio 0.95, 95% CI 0.91-0.99) and against peak death rates (odds ratio 0.96, 95% CI 0.91-0.99). Vaccination coverage was vital to preventing infection and death from COVID-19 during the Delta wave. As new variants emerge, public health authorities should encourage the uptake of COVID-19 vaccination and boosters.

Determining Gaps in Publicly Shared SARS-CoV-2 Genomic Surveillance Data by Analysis of Global Submissions.

Viral genomic surveillance has been a critical source of information during the COVID-19 pandemic, but publicly available data can be sparse, concentrated in wealthy countries, and often made public weeks or months after collection. We used publicly available viral genomic surveillance data submitted to GISAID and GenBank to examine sequencing coverage and lag time to submission during 2020-2021. We compared publicly submitted sequences by country with reported infection rates and population and also examined data based on country-level World Bank income status and World Health Organization region. We found that as global capacity for viral genomic surveillance increased, international disparities in sequencing capacity and timeliness persisted along economic lines. Our analysis suggests that increasing viral genomic surveillance coverage worldwide and decreasing turnaround times could improve timely availability of sequencing data to inform public health action.

Neutralizing and Neuraminidase Antibodies Correlate With Protection Against Influenza During a Late Season A/H3N2 Outbreak Among Unvaccinated Military Recruits.

BACKGROUND: Antibodies that inhibit hemagglutination have long been considered a correlate of protection against influenza, but these antibodies are only a subset of potentially protective antibodies. Neutralizing and neuraminidase antibodies may also contribute to protection, but data on their associations with protection are limited. METHODS: We measured preoutbreak hemagglutinin pseudovirus neutralization (PVN) and neuraminidase inhibition (NAI) antibody titers in unvaccinated military recruits who experienced an H3N2 influenza outbreak during training. We conducted a case-control study to investigate the association between titers and protection against influenza illness or H3N2-associated pneumonia using logistic regression. RESULTS: With every 2-fold increase in PVN titer, the odds of medically attended polymerase chain reaction-confirmed H3N2 infection (H3N2+) decreased by 41% (odds ratio [OR], 0.59; 95% confidence interval [CI], .45 to .77; P < .001). Among those who were H3N2+, the odds for pneumonia decreased by 52% (OR, 0.48; CI, .25 to .91; P = .0249). With every 2-fold increase in NAI titer, the odds of medically attended H3N2 infection decreased by 32% (OR, 0.68; 95% CI, .53 to .87; P = .0028), but there was no association between NAI titers and H3N2-associated pneumonia. There was also no synergistic effect of PVN and NAI antibodies. CONCLUSIONS: PVN and NAI titers were independently associated with reduced risk of influenza illness. NAI titers associated with protection had greater breadth of reactivity to drifted strains than PVN titers. These findings show that PVN and NAI titers are valuable biomarkers for assessing the odds of influenza infection.

Outbreak of Chlamydia pneumoniae Infections and X-ray-Confirmed Pneumonia in Army Trainees at Fort Leonard Wood, Missouri, 2014.

INTRODUCTION: Chlamydia pneumoniae (Cp) is a bacterium that causes pneumonia and other respiratory diseases. Fever may be present early but absent by time of presentation to clinic. Increases in X-ray-confirmed pneumonia (XCP) and laboratory-confirmed Cp infections were observed in new soldiers in training at Fort Leonard Wood (FLW), Missouri, early in 2014. These findings prompted a site assistance visit from the U.S. Army Public Health Command, Aberdeen Proving Ground, Maryland, with a review of available data and information to describe the outbreak, and inspections of barracks and training facilities and review of training practices to identify opportunities for interventions to reduce the risk of respiratory disease agent transmission. MATERIALS AND METHODS: The study population was trainee soldiers at FLW in 2013-2014. Data from two acute respiratory disease surveillance systems were studied. A local surveillance system operated by the FLW General Leonard Wood Army Community Hospital Preventive Medicine Department tracked weekly chest X-rays taken and the numbers positive for pneumonia. A Naval Health Research Center, San Diego, California, laboratory-based Febrile Respiratory Illness Surveillance Program collected clinical data and nasal, or nasal and pharyngeal swabs, for nucleic acid amplification testing from up to 15 trainees/week with fever and either cough or sore throat. Up to 4 of the 15 specimens could be from afebrile patients with XCP. Specimens were tested for a variety of agents. RESULTS: Monthly rates of XCP rose quickly in 2014 and peaked at 0.9/100 trainees in May. The percentage of the San Diego surveillance system specimens that were positive for Cp also increased quickly in 2014, peaking at 54% in May. During the first half of 2014, the San Diego program studied specimens from 141 ill trainees; 37% (52/141) were positive for Cp, making it the most common organism identified, followed by rhinoviruses (8%), influenza viruses (4%), Mycoplasma pneumoniae (2%), and adenoviruses (1%). The remaining specimens (48%) were negative for all respiratory pathogens. Only 12% (6/52) of Cp positive patients were febrile. Facilities inspections and review of training practices failed to identify variables that might be contributing to an increased risk of respiratory agent transmission. CONCLUSION: The XCP rate and the percentage of specimens positive for Cp increased in early 2014, peaking in May. Only 12% of trainees with laboratory-confirmed Cp were febrile. Historically, acute respiratory disease surveillance at military training centers focused on febrile diseases, particularly those caused by adenoviruses. With introduction of an adenovirus vaccine in late 2011, respiratory disease rates dropped with only sporadic occurrences of adenovirus-associated disease. In 2012, the San Diego surveillance program began providing data on multiple respiratory disease agents, in addition to adenoviruses and influenza viruses. Since then, Cp, rhinoviruses and Mycoplasma pneumoniae have frequently been detected in trainees with acute respiratory disease. Respiratory surveillance programs supporting Army training centers should be re-evaluated in this post-adenovirus vaccine era, to include assessment of the fever criterion for selecting patients for study, the value of chest X-ray surveillance and the value of rapidly providing laboratory results to inform provider decisions regarding antibiotic use.

Chemoprophylaxis against group A streptococcus during military training.

Chemoprophylaxis with intramuscular benzathine penicillin G has been used widely by the U.S. military to prevent epidemics of group A streptococcus infections during basic training. The recent global shortage of benzathine penicillin prompted a detailed analysis of this issue in 2017 by military preventive medicine and infectious disease authorities in San Antonio, Texas, and San Diego, California, USA. This paper explores the history of group A streptococcus and chemoprophylaxis in the U.S. military training environment, current policy and practice, and challenges associated with widespread chemoprophylaxis. In light of the history presented, preventive medicine authorities at basic training centers should be extremely cautious about discontinuing benzathine penicillin chemoprophylaxis.

Outbreak of influenza and rhinovirus co-circulation among unvaccinated recruits, U.S. Coast Guard Training Center Cape May, NJ, 24 July-21 August 2016.

Military and Coast Guard recruits are particularly susceptible to respiratory infections. Although seasonal influenza vaccinations are mandatory for recruits, the vaccine expires annually in June. On 29 July 2016, the U.S. Coast Guard Training Center Cape May, NJ, identified an increase in febrile respiratory illness (FRI) among recruits. During 24 July-21 August, a total of 115 recruits reported symptoms. A total of 74 recruits tested positive for respiratory infections: influenza A (H3) (n=34), rhinovirus (n=28), influenza/rhinovirus co-infection (n=11), and adenovirus/rhinovirus co-infection (n=1), while 41 recruits had no laboratory-confirmed specimen but were considered suspected cases. Only one recruit reported receiving the seasonal influenza vaccine within the previous 12 months. Influenza predominated during 24 July-6 August, whereas rhinovirus predominated during 7 August-20 August. Most (92.2%) cases were identified in four of 10 recruit companies; incidence rates were highest among recruits in weeks 2-4 of an 8-week training cycle. Key factors for outbreak control included rapid detection through routine FRI surveillance, quick decision-making and streamlined response by using a single chain of command, and employing both nonpharmaceutical and pharmaceutical interventions.

Department of Defense end-of-season influenza vaccine effectiveness estimates for the 2017-2018 season.

The Department of Defense (DoD) generates influenza vaccine effectiveness (VE) estimates each season. The Armed Forces Health Surveillance Branch Air Force (AFHSB-AF) satellite, Naval Health Research Center Operational Infectious Disease Directorate at the Naval Health Research Center (NHRCOID), and the Armed Forces Health Surveillance Branch (AFHSB) all conduct influenza surveillance and perform test-negative case-control analyses to estimate seasonal influenza VE for DoD populations. The mid-season estimates contribute to the aggregate data utilized by the Food and Drug Administration's Vaccine and Related Biological Products Advisory Committee to select the composition of the influenza vaccine for the next influenza season. The full season data provide DoD with direct estimates for force health protection decisions. The 2017-2018 DoD influenza season was predominated by influenza A(H3N2) with varying levels of adjusted overall VE estimates. AFHSB-AF satellite's VE for dependents was moderate at 49% (95% confidence interval [CI]: 42%-55%) for all strains. NHRC-OID's VE among dependents was moderate-high at 63% (95% CI: 50%-73%) for all strains. AFHSB service member VE was low at 18% (95% CI: 4%-30%). These estimates highlight the need for continued influenza surveillance and VE estimate calculations each season among the different DoD populations as circulating strains and VE may change annually.

Acute Respiratory Disease in US Army Trainees 3 Years after Reintroduction of Adenovirus Vaccine 1.

The 1999 cessation of vaccination against adenovirus types 4 and 7 among US Army trainees resulted in reemergence of acute respiratory disease (ARD) outbreaks. The 2011 implementation of a replacement vaccine led to dramatic and sustained decreases in ARD cases, supporting continuation of vaccination in this population at high risk for ARD.

Frequency of influenza H3N2 intra-subtype reassortment: attributes and implications of reassortant spread.

BACKGROUND: Increasing evidence suggests that influenza reassortment not only contributes to the emergence of new human pandemics but also plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. We studied this process within 2091 H3N2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses. RESULTS: We found that the amount of H3N2 intra-subtype reassortment depended on the number of sampled genomes, occurred with a steady frequency of 3.35%, and was not affected by the geographical origins, evolutionary patterns, or previous reassortment history of the virus. We identified both single reassortant genomes and reassortant clades, each clade representing one reassortment event followed by successful spread of the reassorted variant in the human population. It was this spread that was mainly responsible for the observed high presence of H3N2 intra-subtype reassortant genomes. The successfully spread variants were generally sampled within one year of their formation, highlighting the risk of their rapid spread but also presenting an opportunity for their rapid detection. Simultaneous spread of several different reassortant lineages was observed, and despite their limited average lifetime, second and third generation reassortment was detected, as well as reassortment between viruses belonging to different vaccine-associated clades, likely displaying differing antigenic properties. Some of the spreading reassortants remained confined to certain geographical regions, while others, sharing common properties in amino acid positions of the HA, NA, and PB2 segments, were found throughout the world. CONCLUSIONS: Detailed surveillance of seasonal influenza reassortment patterns and variant properties may provide unique information needed for prediction of spread and construction of future influenza vaccines.

Influenza vaccine effectiveness: Maintained protection throughout the duration of influenza seasons 2010-2011 through 2013-2014.

BACKGROUND: Factors, such as age, comorbidities, vaccine type, herd immunity, previous influenza exposure, and antigenic shift may impact the immune response to the influenza vaccine, protection against circulating strains, and antibody waning. Evaluating vaccine effectiveness (VE) is important for informing timing of vaccine administration and evaluating overall vaccine benefit. METHODS: VE was assessed using febrile respiratory illness surveillance among Department of Defense non-active duty beneficiaries from influenza seasons 2010-2011 through 2013-2014. Respiratory specimens were taken from participants meeting the case definition and tested by polymerase chain reaction for influenza. VE was calculated using logistic regression and by taking 1 minus the odds ratio of being vaccinated in the laboratory confirmed positive influenza cases versus laboratory confirmed negative controls. RESULTS: This study included 1486 participants. We found an overall adjusted VE that provided significant and fairly consistent protection ranging from 54% to 67% during 0-180days postvaccination. This VE dropped to -11% (95% confidence interval: -102% to 39%) during 181-365days. CONCLUSIONS: Our study found moderate VE up to 6months postvaccination. Since the influenza season starts at different times each year, optimal timing is difficult to predict. Consequently, early influenza vaccination may still offer the best overall protection.

Performance of the Quidel Sofia rapid influenza diagnostic test during the 2012-2013 and 2013-2014 influenza seasons.

The Quidel Sofia Influenza A+B Fluorescent Immunoassay was used to test nasal swab specimens from patients with influenza-like illness at US-Mexico border-area clinics in the 2012-2013 and 2013-2014 influenza seasons. Compared with real-time reverse transcription polymerase chain reaction, the overall sensitivities and specificities were 83% and 81%, and 62% and 93%, respectively.

Seroprotective antibodies to 2011 variant influenza A(H3N2v) and seasonal influenza A(H3N2) among three age groups of US Department of Defense service members.

BACKGROUND: In 2011, a new variant of influenza A(H3N2) emerged that contained a recombination of genes from swine H3N2 viruses and the matrix (M) gene of influenza A(H1N1)pdm09 virus. New combinations and variants of pre-existing influenza viruses are worrisome if there is low or nonexistent immunity in a population, which increases chances for an outbreak or pandemic. METHODS: Sera collected in 2011 were obtained from US Department of Defense service members in three age groups: 19-21 years, 32-33 years, and 47-48 years. Pre- and post-vaccination samples were available for the youngest age group, and postvaccination samples for the two older groups. Specimens were tested using microneutralization assays for antibody titers against H3N2v (A/Indiana/10/2011) and seasonal H3N2 virus (A/Perth/16/2009). RESULTS: The youngest age group had significantly (p<0.05) higher geometric mean titers for H3N2v with 165 (95% confidence interval [CI]: 105-225) compared with the two older groups, aged 32-33 and 47-48 years, who had geometric mean titers of 68 (95% CI: 55-82) and 46 (95% CI: 24-65), respectively. Similarly, the youngest age group also had the highest geometric mean titers for seasonal H3N2. In the youngest age group, the proportion of patients who seroconverted after vaccination was 12% for H3N2v and 27% for seasonal H3N2. DISCUSSION: Our results were similar to previous studies that found highest seroprotection among young adults and decreasing titers among older adults. The proportion of 19- to 21-year-olds who seroconverted after seasonal vaccination was low and similar to previous findings. Improving our understanding of H3N2v immunity among different age groups in the United States can help inform vaccination plans if H3N2v becomes more transmissible in the future.

Molecular Epidemiology of Adenovirus Type 21 Respiratory Strains Isolated From US Military Trainees (1996-2014).

BACKGROUND: The circulation of human adenovirus type 21 (HAdV21) in the United States has been documented since the 1960s in association with outbreaks of febrile respiratory illness (FRI) in military boot camps and civilian cases of respiratory disease. METHODS: To describe the molecular epidemiology of HAdV21 respiratory infections across the country, 150 clinical respiratory isolates obtained from continuous surveillance of military recruit FRI, and 23 respiratory isolates recovered from pediatric and adult civilian cases of acute respiratory infection were characterized to compile molecular typing data spanning 37 years (1978-2014). RESULTS: Restriction enzyme analysis and genomic sequencing identified 2 clusters of closely related genomic variants readily distinguishable from the prototype and designated 21a-like and 21b-like. A-like variants predominated until 1999. A shift to b-like variants was noticeable by 2007 after a 7-year period (2000-2006) of cocirculation of the 2 genome types. US strains are phylogenetically more closely related to European and Asian strains isolated over the last 4 decades than to the Saudi Arabian prototype strain AV-1645 isolated in 1956. CONCLUSIONS: Knowledge of circulating HAdV21 variants and their epidemic behavior will be of significant value to local and global FRI surveillance efforts.

Epidemiology of pathogen-specific respiratory infections among three US populations.

BACKGROUND: Diagnostic tests for respiratory infections can be costly and time-consuming. Improved characterization of specific respiratory pathogens by identifying frequent signs, symptoms and demographic characteristics, along with improving our understanding of coinfection rates and seasonality, may improve treatment and prevention measures. METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US-Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Clinical and demographic questionnaire data and respiratory swabs were collected from participants, tested by PCR for nine different respiratory pathogens and summarized. Age stratified characteristics of civilians positive for influenza and recruits positive for rhinovirus were compared to other and no/unknown pathogen. Seasonality and coinfection rates were also described. RESULTS: A total of 1444 patients met the FRI or SARI case definition and were enrolled in this study. Influenza signs and symptoms varied across age groups of civilians. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. Coinfections were found in 6% of all FRI/SARI cases tested and were most frequently seen among children and with rhinovirus infections. Clear seasonal trends were identified for influenza, rhinovirus, and respiratory syncytial virus. CONCLUSIONS: The age-stratified clinical characteristics associated with influenza suggest that age-specific case definitions may improve influenza surveillance and identification. Improving identification of rhinoviruses, the most frequent respiratory infection among recruits, may be useful for separating out contagious individuals, especially when larger outbreaks occur. Overall, describing the epidemiology of pathogen specific respiratory diseases can help improve clinical diagnoses, establish baselines of infection, identify outbreaks, and help prioritize the development of new vaccines and treatments.

Retrospective analysis of demographic and clinical factors associated with etiology of febrile respiratory illness among US military basic trainees.

BACKGROUND: Basic trainees in the US military have historically been vulnerable to respiratory infections. Adenovirus and influenza are the most common etiological agents responsible for febrile respiratory illness (FRI) among trainees and present with similar clinical signs and symptoms. Identifying demographic and clinical factors associated with the primary viral pathogens causing FRI epidemics among trainees will help improve differential diagnosis and allow for appropriate distribution of antiviral medications. The objective of this study was to determine what demographic and clinical factors are associated with influenza and adenovirus among military trainees. METHODS: Specimens were systematically collected from military trainees meeting FRI case definition (fever ≥38.0°C with either cough or sore throat; or provider-diagnosed pneumonia) at eight basic training centers in the USA. PCR and/or cell culture testing for respiratory pathogens were performed on specimens. Interviewer-administered questionnaires collected information on patient demographic and clinical factors. Polychotomous logistic regression was employed to assess the association between these factors and FRI outcome categories: laboratory-confirmed adenovirus, influenza, or other FRI. Sensitivity, specificity, positive and negative predictive value were calculated for individual predictors and clinical combinations of predictors. RESULTS: Among 21,570 FRI cases sampled between 2004 and 2009, 63.6% were laboratory-confirmed adenovirus cases and 6.6% were laboratory-confirmed influenza cases. Subjects were predominantly young men (86.8% men; mean age 20.8 ± 3.8 years) from Fort Jackson (18.8%), Great Lakes (17.1%), Fort Leonard Wood (16.3%), Marine Corps Recruit Depot (MCRD) San Diego (19.0%), Fort Benning (13.3%), Lackland (7.5%), MCRD Parris Island (8.7%), and Cape May (3.2%). The best multivariate predictors of adenovirus were the combination of sore throat (odds ratio [OR], 2.94; 95% confidence interval [CI], 2.66-3.25), cough (OR, 2.33; 95% CI, 2.11-2.57), and fever (OR, 2.07; 95% CI, 1.90-2.26) with a PPV of 77% (p ≤ .05). A combination of cough, fever, training week 0-2 and acute onset were most predictive of influenza (PPV =38%; p ≤ .05). CONCLUSIONS: Specific demographic and clinical factors were associated with laboratory-confirmed influenza and adenovirus among military trainees. Findings from this study can guide clinicians in the diagnosis and treatment of military trainees presenting with FRI.

Dramatic decline of respiratory illness among US military recruits after the renewed use of adenovirus vaccines.

BACKGROUND: In late 2011, after a 12-year hiatus, oral vaccines against adenovirus types 4 (Ad4) and 7 (Ad7) were again produced and administered to US military recruits. This study examined the impact of the new adenovirus vaccines on febrile respiratory illness (FRI) and adenovirus rates and investigated if new serotypes emerged. FRI rates and their associated hospitalizations had markedly risen since vaccine production ceased in 1999. METHODS: From 1996 to 2013, the Naval Health Research Center conducted FRI surveillance at 8 military recruit training centers in the United States. During this period, 58 103 FRI pharyngeal swab specimens were studied, yielding 37 048 adenovirus-positive cases, among which 64% were typed. RESULTS: During the 2 years after reintroduction of the vaccines, military trainees experienced a 100-fold decline in adenovirus disease burden (from 5.8 to 0.02 cases per 1000 person-weeks, P < .0001), without evidence that vaccine pressure had increased the impact of adenovirus types other than Ad4 and Ad7. Although the percentage of type 14 increased following reintroduction of the vaccination, the actual number of cases decreased. We estimate that the vaccines prevent approximately 1 death, 1100-2700 hospitalizations, and 13 000 febrile adenovirus cases each year among the trainees. CONCLUSIONS: These data strongly support the continued production and use of Ad4 and Ad7 vaccines in controlling FRI among US military trainees. Continued surveillance for emerging adenovirus subtypes is warranted.

Outbreak of Group A beta hemolytic Streptococcus pharyngitis in a Peruvian military facility, April 2012.

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a common cause of acute pharyngitis as well as other diseases. Closed populations such as those living on military bases, nursing homes, and prisons are particularly vulnerable to GAS outbreaks due to crowding that facilitates person-to-person transmission. This report details a large outbreak of GAS pharyngitis at a Peruvian military training facility near Lima, Peru, in April 2012. Initial findings showed 145 cases. However, as the investigation continued it was revealed that some trainees may have concealed their illness to avoid real or perceived negative consequences of seeking medical care. A subsequent anonymous survey of all trainees revealed at least 383 cases of pharyngitis among the facility's 1,549 trainees and an attack rate of 34 percent among the 1,137 respondents. The epidemic curve revealed a pattern consistent with routine person-to-person transmission, although a point-source initiating event could not be excluded. Laboratory results showed GAS emm type 80.1 to be the culprit pathogen, an organism not commonly implicated in outbreaks of GAS in the Americas. Barious unique and illustrative features of outbreak investigation in military facilities and populations are discussed.