Coverage From ID Week 2020

 such as Ebola virus, rabies, Zika virus, African swine fever (ASF), and 

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

 emerged into the human experience through an intricate and complex biological process known as spillover. Spillover of novel pathogens typically occurs through the intersection of the agent (eg, viruses, bacteria, parasites) with livestock, vectors, wildlife, or even the natural environment. 

To make matters more complicated and concerning for public health and health care professionals, the spillover event is almost always invisible. Detecting emerging pathogens relies on strong public health surveillance systems and astute clinicians. Without well-resourced public health and health care infrastructure, such as advanced molecular epidemiology techniques, emerging pathogens and strains or variants of known pathogens can go unnoticed for long periods, resulting in delays in treatment and prevention measures.

The characterization and prediction of spillover intersections are of global importance, and it is critical to develop understanding of how, when, and where spillover events occur. The coronavirus disease 2019 (COVID-19) pandemic has spotlighted this issue; it is imperative to be better prepared for future pandemics.

Can we predict the next pandemic spillover event?

The jump of animal and environmental pathogens into human populations or other hosts is an ongoing biological “long game” that dates back thousands of years. From the current version of SARS-CoV-2, Ebola virus, measles virus, and HIV to historical epidemics such as plagues (eg, smallpox, cholera, and bubonic plague, also called the Black Death), pathogens have consistently found a way to move into the human population.

 In contrast to newer threats, rabies is one of the oldest described infectious diseases, likely with an ancient pedigree that predates most historical accounts.

 Regardless of the pathogen, this ongoing and longstanding “dance” between pathogens and susceptible hosts is a natural process, with the outcome of pathogen emergence in human populations likely comprising only a small percentage of spillover events between all animals.

With so many variables, such as complex pathogen life cycles, modes of transmission, and random susceptible hosts’ interaction, an initial spillover event resulting in ongoing transmission into a new host is relatively rare and usually an imperfect process. Most mammalian viruses lack the ability to infect humans. Moreover, should a natural zoonotic virus spillover into a human host, subsequent human-to-human transmission is often not possible or unsustainable. However, with enough opportunities, pathogens can adapt themselves to broaden their host range or evolve to sustain transmission in a more suitable host. Experts in pathogen spillovers believe that the rate of novel infectious disease emergence has increased in recent history.

The dichotomy between host-range transmissibility bottlenecks and the increased rate of naturally occurring spillovers makes predicting what pathogen could trigger the next pandemic extremely difficult. Discovering an exact emerging pathogen within the global ocean of emerging and reemerging agents is a tall task, even for those equipped with advanced molecular diagnostics and epidemiologic technologies. That being said, there is a working knowledge of spillover events and how zoonotic and human intersections throughout the world can increase risk.

Most spillover events are dead ends, meaning that the infectious agent could infect a novel host but is not capable of sustaining a transmission cycle within that new host. This happens frequently, particularly in areas where human and zoonotic populations overlap. Avian influenza is an excellent example of this. High pathogenicity avian influenza (HPAI) strains such as H5N1 and H7N9 have repeatedly spilled over into human hosts. Luckily, to date, there has not been a subsequent sustained human-to-human transmission in the spillover events from the current strains of HPAI; when human-to-human transmission has occurred, it has been limited.

Unfortunately, viruses have an extensive history of learning to adapt to transmission within a new host. Occasionally a virus will acquire enough of the right mutations to infect a novel host and allow for subsequent and sustainable transmission in the host. HIV is an excellent example of this. The evolutionary ancestor of HIV is simian immunodeficiency virus (SIV), which has circulated in nonhuman primates for tens of thousands of years. Multiple independent spillover events of SIV occurred, but the virus was not fit to maintain transmission in a human host. That changed in the early 20th century when handling of bushmeat from an infected primate and blood-to-blood contact with the handler was believed to have occurred. This resulted in the initial spillover of a variant of SIV that could sustain itself in a novel host, humans, which led to the HIV pandemic.

What about emerging and reemerging pathogens?

Emerging and reemerging pathogens occur and sustain themselves through a zoonotic vehicle. Zoonotic disease emergence arises as a consequence of transmission of a frequently multihost pathogen from an animal host (direct or indirect transmission) to a human, with or without onward human-to-human transmission and establishment. In most instances, a zoonotic reservoir is defined as 1 or more epidemiologically linked and intersecting animal populations or environments in which a pathogen can be maintained and transmitted to humans and, more broadly, domestic animals.

Some of the most-studied viruses are those that intersect with zoonotic and human populations. Studies of RNA viruses (eg, Ebola virus, influenza, Lassa fever, rabies, coronaviruses, HIV) have provided insight into how they might be evolutionarily predisposed to zoonoses due to a predisposition toward evolvability and host switching.

 Results of a study by Johnson et al demonstrated a number of key rules, perhaps most importantly that viruses with greater host plasticity in animal reservoirs are more likely to demonstrate human-to-human transmissibility.

Some virus families, such as arenaviruses (eg, Lassa fever) and filoviruses (eg, Ebola and Marburg viruses), are predisposed to human-to-human transmission. Correspondingly, some groups of mammals are common reservoirs of zoonotic viruses, including rodents (especially for arena- and bunyaviruses), primates (retroviruses), and bats (coronaviruses, paramyxoviruses, and rhabdoviruses).

 Spillover pathways also can vary. Hunting is a notable source of exposure to nonhuman primate viruses, and the proximity of homes to fields is a significant driver for exposure to rodent-borne viruses.

It is almost impossible to predict the next big emerging or reemerging pathogens. However, there are factors that can contribute to an infectious agent becoming problematic for humans. These drivers come from genetic influences, environmental influences, and sociological behaviors. Some examples of potential spillover drivers are:

An agent expanding to new geographic locations or new populations (eg, Vibrio populations and West Nile virus)

An infectious agent that exhibits broad host-ranges (eg, coronaviruses and influenza viruses)

A sustained zoonotic transmission cycle with nearby human population centers (eg, retroviruses and rhabdoviruses)

A previously known agent(s) whose role in specific diseases have previously gone unrecognized (eg, herpesviruses)

A family, genus, or species with a documented history of previous spillover events (eg, HPAI and 

Re-emerging infectious diseases with an incidence of disease that significantly declined in the past but have since reappeared (eg, measles).

As the recent COVID-19 pandemic and prior emergence of pathogens have shown, there will be a “next” pandemic (or at least epidemic) pathogen. Investigators feel strongly there will be a SARS-CoV-3 pathogen.

 Additionally, variants of SARS-CoV-2 have quickly spread, demonstrating that novel phenotypes from a singular virus can take hold when multicontinental transmission rates are high.

There are clues in recent history to what some of the more likely emergent pathogens will be. For example, 1 instance of a tropical disease that has spread recently into new areas due, at least in part, to changing climate is the chikungunya virus. As with dengue virus, it is transmitted by the 

 “tiger mosquito.” Chikungunya virus was previously confined to tropical regions around the Indian Ocean. However, in the past decade, the virus has been reported in countries in Europe, Asia, Africa, and the Americas, achieving sustained transmission. 

Another example is the Zika virus, which burst onto the international scene through its association with a birth defect known as microcephaly. The Ebola virus epidemic that emerged in 2014 in West Africa illustrates how a virus that previously affected only small groups of individuals, perhaps a few hundred, can sweep rapidly through an area to affect tens of thousands and become extremely difficult to contain. In February, health authorities in Guinea declared an outbreak of Ebola in the rural community of Gouéké in Nzérékoré prefecture after 3 cases of Ebola were confirmed by the national laboratory, marking the first time the disease has been reported in the country since an outbreak ended in 2016.

One of the more current worrisome emerging pathogens is the ASF virus. ASF is a highly contagious and deadly viral disease that affects domestic and wild pigs. Currently, ASF is not a threat to human health and cannot be transmitted from pigs to humans.

But we are always watching for the next emerging human pathogen (

Rodney E. Rohde, PhD, SM(ASCP), SVCM, MBCM, is professor and chair of the Clinical Laboratory Science Department, College of Health Professions, at Texas State University in San Marcos and an associate adjunct professor of biology at Austin Community College in Texas. He is a board certified specialist in virology, microbiology, and molecular biology with the American Society for Clinical Pathology.

Ryan P. McNamara, PhD, is a virologist and research associate at the University of North Carolina at Chapel Hill School of Medicine.

Alexander KA, Carlson CJ, Lewis BL, et al. The ecology of pathogen spillover and disease emergence at the human-wildlife-environment interface. In: Hurst CJ, (eds). 

The Connections Between Ecology and Infectious Disease

. Cham Springer; 2018:267-298. doi:10.1007/978-3-319-92373-4_8

Rohde RE, Rupprecht C. Update on lyssaviruses and rabies: will past progress play as prologue in the near term towards future elimination? 

Jones KE, Patel NG, Levy MA, et al. Global trends in emerging infectious diseases. 

. 2008;451(7181):990-993. doi:10.1038/nature06536

Johnson CK, Hitchens PL, Pandit PS, et al. Global shifts in mammalian population trends reveal key predictors of virus spillover risk. 

. 2020;287(1924):28720192736. doi:10.1098/rspb.2019.2736

McNamara R, Rohde RE. The imminence of the next SARS outbreak. Smerconish. January 14, 2021. Accessed February 17, 2021. https://www.smerconish.com/exclusive-content/the-imminence-of-the-next-sars-outbreak

Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. 

. 2011;1(1):a006841. doi:10.1101/cshperspect.a006841

Johnson CK, Hitchens PL, Evans TS, et al. Spillover and pandemic properties of zoonotic viruses with high host plasticity. 

Dearing MD, Dizney L. Ecology of hantavirus in a changing world. 

. 2010;1195:99-112. doi:10.1111/j.1749-6632.2010.05452.x

What are emerging infectious diseases? Baylor College of Medicine. Accessed February 17, 2021. https://www.bcm.edu/departments/molecular-virology-and-microbiology/emerging-infections-and-biodefense/emerging-infectious-diseases

Emerging SARS-CoV-2 variants. Centers for Disease Control and Prevention. Updated January 28, 2021. Accessed February 17, 2021. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html

New Ebola outbreak declared in Guinea. World Health Organization. February 14, 2021. Accessed February 17, 2021. https://www.afro.who.int/news/new-ebola-outbreak-declared-guinea

African Swine Fever (ASF). US Department of Agriculture. November 5, 2020. Accessed February 17, 2021. https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/swine-disease-information/african-swine-fever/seminar

Articles

Infectious diseases are emerging at an alarmingly rapid pace, faster than any other time in human history.

Virus Spillover and Emerging Pathogens Pick Up Speed

Carbapenems and third- and fourth-generation cephalosporin were the antibiotic classes most strongly associated with

 infection arising in healthcare facilities, in a new 

The review and analysis of studies of hospitalized patients publishedin English between January 2013 and April 2020 was conducted by Claudia Slimings, PhD, School of Pathology and Laboratory Medicine, The University of Western Australia, Crowley, Western Australia, Australia, and Thomas Riley, PhD, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia.

 of studies of antibiotic usage linked to iatrogenic 

 infection published in 2014, Slimings and Riley had found that use of cephalosporings or clindamycin were the most likely antibiotics to precede 

 infection (CDI).In that earlier review, the investigators suggested that concern with fluoquinolones might have been overemphasized, particularly if fluoroquinolone-resistant epidemic strains of 

In the current review, Slimings and Riley find that iatrogenic 

 infection is more than twice as likely after recent exposure to carbapenems or third- and fourth-generation cephalosporins; and that there are "modest" associations with fluoroquinolones, clindamycin andß-lactamase inhibitor combination penicillin antibiotics.

For non-ß-lactam antibiotic classes, the strongest evidence for association with healthcare facility-associated (HCFA)-CDI infections was found for quinolones (fluoroquinolones) and lincosamides (clindamycin).Overall, quinolones were associated with 34% increased odds of HCFA-CDI (OR 1.34; 95% CI 1.13-1.60).Lincosamides were associated with 56% increased odds of HCFA-CDI (OR 1.56; 95% CI 1.13-2.14).The reviewers also found associations for antibiotics used to treat CDI, particularly vancomycin(OR 1.91; 95% CI 1.32-2.78).

The incidence rates of HCFA-CDI have been increasing, according to Slimings and Riley.They suggest several factors for the increase, including increased testing and more sensitive diagnostic tests, increased use of broad-spectrum antibiotics, inadequate prevention measures, aging populations, and emergence of community strains.

"Antibiotic use is the most important modifiable risk factor for CDI," Slimings and Riley assert."Other important risk factors include advanced age, increased number of comorbidities or severe underlying diseases and duration of healthcare exposure."

The multiple contributing factors and the different methodologies and populations of the 21 studies that met inclusion criteria posed challenges for the current meta-analysis. Slimings and Riley found that a more diverse range of patient populations had been studied since 2013, with increased focus on particular patient subgroups such as surgical and ICU patients and patients with particular conditions, rather than the general inpatient populations of the earlier studies.

"Studies using patient subgroups tended to have weaker associations," they observed."A potential explanation is that studies of patient subgroups had shorter periods of antibiotic exposure measurement."

The reviewers found that few studies marked dose-response relationships, or examined HCFA-CDI in relation to timing and duration of antibiotic exposure.They noted the substantial increase in computing power that has become available since their last review, and urged investigators to apply that to their patient cohort studies to clearly report surveillance definitions, criteria and laboratory methods for diagnosis of CDI in their institutions, and how these align with relevant current guidelines.

"Future studies should clearly report the parameters of exposure measurement, including all sources of information on exposure, as it was often unclear," Slimings and Riley indicated."Particularly in studies with a longer exposure window, when in-hospital prescription only was recorded, or whether prescription in the community setting was included."

Updated review and meta-analysis identifies the classes of antibiotics most strongly linked to healthcare facility-associated Clostridioides difficile infection.

Meta-Analysis Links Classes of Antibiotics to Latrogenic C difficile Infections

In the United States, 50% of the adult population is expected to have received at least 1 dose of a vaccine for COVID-19 by the end of this week, if the current pace is continued. The past week saw over 3.1 million vaccinations administered, according to the latest data from the US Centers for Disease Control and Prevention. Nearly 46% of adults have received at least 1 dose, with 28% having been fully vaccinated.

In Japan, prime minister Yoshihide Suga announced on Monday that the country will secure 100 million doses of COVID-19 vaccines by the end of June, enough to cover both the elderly and the medical worker populations. Japan has so far only administered vaccines to just 1.1 million people, which equates to less than 1% of the country’s population.

In Pakistan, cases are surging and hospital beds are quickly reaching capacity amidst a third wave of the COVID-19 pandemic. The country’s inoculation campaign is moving at a very slowly pace, and because of this the government has allowed the private sector to import and sell doses of vaccines. Sales saw the Russian vaccine, Sputnik V, sell out in the first weekend of April, as crowds waited at vaccination centers for hours in the hopes of receiving a shot.

World Vaccines

Data Table per Our World in Data (April 11, 2021, 12 AM EST)

In New York City, mayor Bill de Blasio announced on Monday that the city has administered over 5 million doses of COVID-19 vaccines, which he says will keep them on pace to meet their goal of fully vaccinating 5 million people by June.

US Vaccines

Data Table per CDC COVID-19 Tracker (April 11, 2021, 6 AM EST)

For more information on COVID-19 vaccination research, distribution, and assessment, check out some of these recent Contagion stories:

Looking at mRNA COVID-19 Vaccine Reactions

Pfizer Requests COVID-19 Vaccine Availability in Younger Pediatric Population

AstraZeneca COVID-19 Vaccine Linked to Rare Thrombosis, Thrombocytopenia Events

Despite a growing number of cases, millions gather in India for Hindu festival.

50% of US Adults Expected to be Partially Vaccinated by End of Week

The United States just surpassed 31 million cases of COVID-19 and is inching towards 559,000 deaths since the pandemic first began. It’s been a long and exhaustive 15 months since we began responding to this novel disease and a pandemic that shook the world. In this time though, multiple efficacious vaccines have been developed and approved through the Federal Drug Administration (FDA) Emergency Use Authorization (EUA) process. 

Vaccines are easily one of the best tools we have against COVID-19. Equitable vaccine distribution coupled with continued community infection prevention efforts, like masks, can help us get ahead of transmission and end the pandemic.

Currently in the United States, there have been over 237 million vaccine doses delivered and 187 million administered. The Centers for Disease Control and Prevention (CDC) 

 that 119 million people have received at least one dose and 72 million are fully vaccinated. This represents roughly 22% of the U.S. population and 61.4% of the population aged 65 years or older. As we work to improve vaccine distribution and address hesitancy, question surrounding vaccine reactions (reactogenicity) both local and more systemic also arise and should be assessed.

 discusses reactions following mRNA-based COVID-19 vaccines. The authors reviewed data from the CDC’s v-safe program, which is an active surveillance system for collecting self-reported information from vaccine recipients. V-safe is a voluntary system that utilizes smart phone text messages and a web-based survey. 

The authors reported that as of February 21, 2021, a total of 3,643,918 individuals had enrolled in v-safe and completed at least one health survey. The authors noted that, “most v-safe participants reported an injection site reaction (dose 1: 70.0%; dose 2: 75.2%) or a systemic reaction (dose 1: 50.0%; dose 2: 69.4%) during days 0 to 7 after vaccination. The most frequently reported solicited local and systemic reactions after the first dose of COVID-19 vaccine were injection site pain (67.8%), fatigue (30.9%), headache (25.9%), and myalgia (19.4%). Reactogenicity was substantially greater after the second dose for both vaccines, particularly for systemic reactions, including fatigue (53.9%), headache (46.7%), myalgia (44.0%), chills (31.3%), fever (29.5%), and joint pain (25.6%).”

Virologist Dr. Angela Rasmussen noted that the “vaccines are fairly reactogenic according to participants in v-safe, but that’s actually a pretty bit limitation. It’s [v-safe] voluntary and people are more likely to report if they are experiencing side effects. While side effects are common, they generally are fairly minor and have no lasting impact. I’d still rather have the full spread of these side effects than COVID-19!”

The authors noted that a larger percentage of individuals who received the Moderna vaccine, reported through v-safe some reactions. These were worse after the second dose and in the case of both vaccines individuals who reported local and systemic reactions stated that day 1 after the vaccine was the worst. Overall, this information and insight into reactions for the two most common vaccines being deployed in the United States is important and vital information.

With millions of people vaccinated for COVID-19, A new study, collecting data from CDC's v-safe program, discusses reactions following mRNA-based vaccines. 

It has been well-documented that racial disparities exist in the incidence rates of people diagnosed with HIV. And separately, with the emergence of the COVID-19 pandemic, the prevalence of the Non-Hispanic (NH) Black and Hispanic people being disproportionately diagnosed with the virus, and suffering higher mortality rates has also been a disturbing trend.

A new study looked at the potential conflation of HIV and COVID-19, and if there were racial disparities to be discovered within the combination of these two health issues.

Jessica Islam PhD, MPH, assistant member of Cancer Epidemiology at Moffitt Cancer Center, was part of a team of investigators who looked at racial disparities of COVID-19 in people living with HIV (PLWH) in the United States. They reviewed COVID-19 positive data and HIV status by using the US National COVID Cohort Collaborative (N3C).

“We were able to look specifically into people living with HIV and racial disparities in COVID-19 positivity across racial and ethnic groups,” Islam stated.

As an epidemiologist, Islam’s previous research has focused on the prevention of cancers caused by infection, and treatment outcomes and disparities among PLWH.

Within the N3C, over 2.1 million patients were captured by the end of November 2020. Of those included in this cohort, 292,226 had been diagnosed with COVID-19, 11,011 people living with HIV (PLWH) and of them 1341 had tested positive for COVID-19.

As part of their comparison, Islam et al looked at HIV-negative patients with COVID-19 and also PLWH who had COVID-19. The investigators found the latter cohort were more likely to be 45+ years of age (62.3% vs.43.8%, p<0.001), male (70% vs. 46%, p<0.001), treated on an outpatient basis (9% vs. 5%, p<0.001). They also had a modified Charlson comorbidity index score ≥3 (80% vs. 10%,p<0.001).

The investigators also found that Non-Hispanic Blacks who had COVID-19 were more likely to have HIV (51% vs. 17%, p<0.001), as opposed to NH Whites who were less likely (24% vs. 47%, p<0.001).

“When comparing to PLWH without COVID-19, PLWH with COVID-19 were less likely to have a modified Charlson comorbidity index score of 3 or above (27% vs. 32%, p<0.001), with no significant differences in age or sex. COVID-19 positive PLWH were more likely to be NH-Black (51% vs. 45%, p<0.001) and Hispanic (8% vs. 5%, p<0.001), and, conversely, less likely to be NH-White (24% vs. 36%, p<0.001 ) when compared to PLWH without COVID-19,” the investigators reported.

“Certainly, racial disparities persist among people living with HIV and COVID-19 positivity, even after we adjusted for covariates such as age, sex, and comorbidity index…after we adjusted for all those cofactors, which could explain these disparities, we continued to see that Non-Hispanic Black, Hispanic and Asian people living with HIV have higher odds of COVID-19 positivity when compared to Non-Hispanic White adults.” 

Part of the issue Islam says is the existing structural barriers in place for minorities that make it more difficult to adhere completely to preventative behaviors when it comes to COVID-19.

 spoke to Islam recently about the importance of the N3C data base, further insights into this study, as well as her other research looking at structural barriers as it relates to preventative behaviors related to COVID-19. 

Videos

A recent study looked at the racial disparities amongst people living with HIV and COVID-19 positivity rates.  

Examining a Connection Between HIV, COVID-19, and Race

A retrospective comparative effectiveness study looked at time to clinical improvement or time to death among hospitalized patients who were treated with or without remdesivir.

Trends in COVID-19 Hospitalized Patients and the Impact of Remdesivir

This prognostic marker might not be an adequate reason to test for Clostridium difficile in hospitalized patients. 

Is an Elevated White Blood Cell Count Enough for C Diff Testing?

The company asked the Food and Drug Administration (FDA) to amend their Emergency Use Authorization (EUA) to include 12-15 year olds.

The newest research of rare adverse events among patients administered the vaccine highlights that venous or arterial thrombosis can develop in unexpected regions, including the brain or abdomen, 5-20 days after administration.

Overall, more than half a million more people died between March 2020 and the end of the year, suggesting the pandemic may have been indirectly involved in more deaths than previously realized.

Report: COVID-19 Cannot Directly Account for Jump in All-Cause Mortality Last Year

A new commentary from experts highlight the evolving understanding of antibody response in vaccinated transplant patients.

How Do COVID-19 Vaccines Benefit Transplant Recipients?

Even with just a mild case of COVID-19, many of the participants reported long-term symptoms that had a negative impact on their life.

1 in 10 COVID-19 Survivors Experience Symptoms 8 Months After Infection

While patients who developed a severe case of COVID-19 were at the highest risk, it was not limited to them.

COVID-19 Linked With Subsequent Mental and Neurological Conditions

Letters to legislators call for increased funding to address ongoing crisis.

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Face masks protect from COVID-19, but multilayered ones made of certain materials perform better than others.

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