Seroprevalence as an Indicator of Undercounting of COVID-19 Cases in a Large Well-Described Cohort.

Introduction: Reported confirmed cases represent a small portion of overall true cases for many infectious diseases. The undercounting of true cases can be considerable when a significant portion of infected individuals are asymptomatic or minimally symptomatic, as is the case with COVID-19. Seroprevalence studies are an efficient way to assess the extent to which true cases are undercounted during a large-scale outbreak and can inform efforts to improve case identification and reporting. Methods: A longitudinal seroprevalence study of active duty U.S. military members was conducted from May 2020 through June 2021. A random selection of service member serum samples submitted to the Department of Defense Serum Repository was analyzed for the presence of antibodies reactive to SARS-CoV-2. The monthly seroprevalence rates were compared with those of cumulative confirmed cases reported during the study period. Results: Seroprevalence was 2.3% in May 2020 and increased to 74.0% by June 2021. The estimated true case count based on seroprevalence was 9.3 times greater than monthly reported cases at the beginning of the study period and fell to 1.7 by the end of the study. Conclusions: In our sample, confirmed case counts significantly underestimated true cases of COVID-19. The increased availability of testing over the study period and enhanced efforts to detect asymptomatic and minimally symptomatic cases likely contributed to the fall in the seroprevalence to reported case ratio.

Immune regulation of a chronic bacteria infection and consequences for pathogen transmission.

BACKGROUND: The role of host immunity has been recognized as not only playing a fundamental role in the interaction between the host and pathogen but also in influencing host infectiousness and the ability to shed pathogens. Despite the interest in this area of study, and the development of theoretical work on the immuno-epidemiology of infections, little is known about the immunological processes that influence pathogen shedding patterns. RESULTS: We used the respiratory bacterium Bordetella bronchiseptica and its common natural host, the rabbit, to examine the intensity and duration of oro-nasal bacteria shedding in relation to changes in the level of serum antibodies, blood cells, cytokine expression and number of bacteria colonies in the respiratory tract. Findings show that infected rabbits shed B. bronchiseptica by contact up to 4.5 months post infection. Shedding was positively affected by number of bacteria in the nasal cavity (CFU/g) but negatively influenced by serum IgG, which also contributed to the initial reduction of bacteria in the nasal cavity. Three main patterns of shedding were identified: i- bacteria were shed intermittently (46% of individuals), ii- bacteria shedding fell with the progression of the infection (31%) and iii- individuals never shed bacteria despite being infected (23%). Differences in the initial number of bacteria shed between the first two groups were associated with differences in the level of serum antibodies and white blood cells. These results suggest that the immunological conditions at the early stage of the infection may play a role in modulating the long term dynamics of B. bronchiseptica shedding. CONCLUSIONS: We propose that IgG influences the threshold of bacteria in the oro-nasal cavity which then affects the intensity and duration of individual shedding. In addition, we suggest that a threshold level of infection is required for shedding, below this value individuals never shed bacteria despite being infected. The mechanisms regulating these interactions are still obscure and more studies are needed to understand the persistence of bacteria in the upper respiratory tract and the processes controlling the intensity and duration of shedding.

Epidemiology of Serious Bacterial Infections in Infants Less Than 90 Days in a Military Health System Cohort.

BACKGROUND: Management of suspected serious bacterial infections (SBIs) in infants less than 3 months old is challenging. Understanding the epidemiology of SBI is necessary to inform management decisions. Recent publications have challenged the previously accepted distribution of infections by specimen source and pathogen. We sought to describe the burden of SBIs in previously healthy infants less than 90 days old. METHODS: We conducted a retrospective analysis of the Military Health System database to identify SBI cases among term infants less than 90 days of age from 2005 to 2015. We defined an SBI case as any previously healthy infant with positive cultures for a likely pathogen from blood, urine or cerebrospinal fluid. RESULTS: Of 467,462 live births between January 2005 and September 2015, 3421 infants had positive cultures. After excluding 1781 episodes with isolates considered nonpathogenic or ICD-9 codes for chronic conditions, the overall incidence of SBI was 3.1 cases/1000 live births. The SBI rate dropped from 5.0 cases/1000 live births in 2005 to 2.0 cases/1000 live births in 2015 (P < 0.001 for trend). The most common pathogen was Escherichia coli (51.3%). CONCLUSIONS: In this retrospective review of 467,462 live births, the incidence of SBI decreased from 5.0/1000 to 2.0/1000 live births over time. We identified no cases of Listeria monocytogenes. These data can help inform decisions related to treatment and management of infants with suspected bacterial infections.

The Rapid Escalation of Fentanyl in Illicit Drug Evidence in Allegheny County, Pennsylvania, 2010-2016.

Opioid overdose deaths in the United States quadrupled from 1999 (n = 8050 deaths) to 2015 (n = 33 091 deaths), and the number of deaths associated with synthetic opioids, such as fentanyl, increased from 3105 deaths in 2013 to nearly 20 000 deaths in 2016. Given this rapid increase, timely surveillance for drugs in circulation is crucial. However, current surveillance systems used to track drug overdoses do not detect new drugs in circulation quickly. We studied the change in the presence of fentanyl in "stamp bag" drug evidence in Allegheny County, Pennsylvania, from 2010 through 2016. Stamp bags are small wax packets with individual stamps that contain mixtures of drugs, most commonly heroin, that law enforcement officers seize and retain as legal evidence. The proportion of stamp bags determined to contain fentanyl or a fentanyl analog was 2.1% in 2014 and rose sharply to 17.1% in 2016. Monitoring the chemical makeup of drug evidence items could help public health authorities identify drug use trends in their jurisdictions.

Characteristics of self-inflicted drug overdose deaths in North Carolina.

BACKGROUND: Drug overdose mortality is a major public health concern in the United States, with prescription opioids contributing substantially to recent increases in drug overdose deaths. Compared to unintentional drug overdose deaths, relatively little data describes intentional self-inflicted drug overdose deaths (i.e., suicide by drug overdose). The aim of this study was to examine the characteristics of self-inflicted drug overdose deaths, overall and in comparison to unintentional drug overdose deaths. METHODS: We linked vital statistics, prescription drug monitoring program, and toxicology data for self-inflicted and unintentional drug overdose deaths among North Carolina residents in 2012. RESULTS: Most self-inflicted (79.2%) and unintentional (75.6%) drug overdose decedents had a prescription for a controlled substance within one year of death. Toxicology results revealed that antidepressants contributed to a significantly higher percent of self-inflicted compared to unintentional drug overdose deaths (45.0% vs. 8.1%). Among deaths in which commonly prescribed opioids (oxycodone, hydrocodone) or benzodiazepines (alprazolam, clonazepam) contributed to death, a significantly higher percent of self-inflicted drug overdose decedents had a prescription for the substance within 30days of death compared to unintentional drug overdose decedents. CONCLUSIONS: The results highlight the use of prescription opioids, benzodiazepines, and antidepressants among self-inflicted drug overdose decedents. Importantly, the results indicate that self-inflicted drug overdose decedents were more likely than unintentional drug overdose decedents to have potential contact with the health care system in the weeks preceding death, offering an opportunity for professionals to identify and intervene on risk factors or signs of distress and potential for self-harm.