Highlights June 2023 from EID, Nature Communications, Clinical Microbiology Reviews

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Overview and links to articles mentioned this month.

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June 2024, Emerging Infectious Diseases: Noelle M. Cocoros details the development of the RAVIOLI algorithm, a new method using electronic health records to enhance surveillance of respiratory viruses beyond traditional influenza-like illness methods. This approach notably improved detection of respiratory illnesses including SARS-CoV-2 and RSV, providing early warnings of emerging respiratory infection trends. https://wwwnc.cdc.gov/eid/article/30/6/23-0473_article

• June 2024, Emerging Infectious Diseases: Park et al. explore severe Human Parainfluenza Virus pneumonia in adults at a tertiary hospital in Seoul, highlighting its prevalence and severe impact, especially in the immunocompromised. The study emphasizes the significant role of fungal co-infections in mortality rates. https://wwwnc.cdc.gov/eid/article/30/6/23-0670_article

• June 2024, Emerging Infectious Diseases: A study on Chronic Wasting Disease (CWD) finds no transmission to human cerebral organoids, suggesting a strong species barrier, which is crucial for understanding the zoonotic potential of CWD. https://wwwnc.cdc.gov/eid/article/30/6/23-1568_article

• June 2024, Emerging Infectious Diseases: Marta Zlotnick examines foodborne disease outbreaks in the U.S. linked to foods eligible for irradiation. The findings suggest a significant prevention potential through irradiation, which is currently underutilized. https://wwwnc.cdc.gov/eid/article/30/6/23-0922_article

• June 2024, Emerging Infectious Diseases: Katrine Finderup Nielsen's follow-up study on the 23-valent pneumococcal polysaccharide vaccine in Denmark shows moderate and persistent effectiveness against invasive pneumococcal disease, except for serotype 3. https://wwwnc.cdc.gov/eid/article/30/6/23-0975_article

• May 2024, Clinical Microbiology Reviews: Trisha Greenhalgh and colleagues provide a comprehensive review on masks and respirators, affirming their effectiveness in reducing transmission of respiratory infections and outlining future research directions for improving their use and public acceptance. https://journals.asm.org/doi/10.1128/cmr.00124-23

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• June 2024, Nature Communications: Research by Haddrell et al. discusses the correlation between ambient CO2 levels and SARS-CoV-2 stability, revealing that increased CO2 concentrations can significantly enhance the virus's survival in aerosols, emphasizing the importance of ventilation in public health strategies. https://www.nature.com/articles/s41467-024-47777-5

• June 2024 BMJ Public Health - a paper alleging that much of the excess mortality associated with the pandemic is actually due to COVID vaccines. This paper is flawed - perhaps it did not receive the usual BMJ review? https://bmjpublichealth.bmj.com/content/2/1/e000282

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Podcast text below:

Electronic Health Record–Based Algorithm for Monitoring Respiratory Virus–Like Illness, by Noelle M. Cocoros, in June 2024 Emerging Infectious Diseases

Multiple respiratory viruses circulate and cause significant illness and death, but public health has traditionally focused surveillance efforts on influenza and influenza-like illness (ILI). Syndromic surveillance systems provide little information on which pathogens are circulating and often require fever, lowering sensitivity.

Using electronic health record data from 3 large practice groups in Massachusetts the authors developed the RAVIOLI algorithm for respiratory virus-like illness surveillance. They used virus illness syndromes and associated pathogens using historical data to identify diagnosis codes and other characteristics of healthcare visits most predictive of confirmed respiratory viral illnesses. Specifically, RAVIOLI uses a combination of health record diagnosis codes, laboratory results and measured fever with ≥10% positive predictive value for any respiratory virus or specific viruses to estimate the incidence of total and pathogen specific viral respiratory disease.

Key findings and public health implications:

• RAVIOLI identified 2-3 times more respiratory illness than ILI surveillance, which missed important increases in SARS-CoV-2 and RSV.

• Before March 2020, influenza and nonspecific codes dominated RAVIOLI. SARS-CoV-2 then predominated until fall 2021 when RSV and influenza reemerged.

• The highest rates of RAVIOLI were in children 0-4 years old (up to 25% during RSV and influenza peaks), followed by ages 5-24.

• Most RAVIOLI patients were identified by diagnosis codes, then positive tests, then fever. 33% or fewer in the nonspecific RAVIOLI category had fever.

• RAVIOLI provides early indication of emerging respiratory infection trends and prevailing pathogens beyond traditional ILI surveillance focused on influenza and requiring fever.

• Broader pathogen monitoring informs testing guidance, health communication, targeted prevention like vaccination, infection control measures, and policies to minimize population health impacts.

• The system provides users with granular insight into evolving trends in respiratory viral illness rates that both retains the best features of traditional syndromic surveillance (capacity to monitor changes in disease incidence in near real time regardless of whether persons get tested) and simultaneously broadens the scope of surveillance to include multiple pathogens, not just influenza and SARS-CoV-2.

• The data provide insight into the relative proportions of con¬tributing pathogens across multiple clinical facilities using both test results and diagnosis codes to iden¬tify organisms.

• We recommend reviewing Figure 1 and Figure 2 for insights into this analysis. Figure 1 shows the significant higher and variable viral disease estimates from the RAVIOLI algorithm versus clinical cases meeting the case definition for influenza-like illness cases.

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In summary, in this paper describing the development of RAVIOLI, an electronic health record-based algorithm integrating lab tests and syndromic data for surveillance of multiple respiratory viruses, the major finding was that this approach identified 2-3 times more respiratory illness than traditional methods and important trends in SARS-CoV-2, RSV, and influenza that influenza-like illness surveillance missed and provide pathogen specific estimates of illness.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010–2019, by Park et al., in June Emerging Infectious Diseases.

https://wwwnc.cdc.gov/eid/article/30/6/pdfs/23-0670.pdf

Background: Human parainfluenza virus (HPIV) is a major cause of acute respiratory tract infections, such as croup in children and pneumonia in immunocompromised patients. However, the characteristics of severe HPIV-associated pneumonia in adults have not been well evaluated.

The study investigated the epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010–2019 at a tertiary hospital in Seoul, South Korea. The study was conducted as part of a prospective, observational cohort study of patients with severe virus-associated pneumonia admitted to the intensive care unit (ICU).

Key findings and implications for public health:

• HPIV was found to be the leading cause of severe virus-associated hospital-acquired pneumonia (HAP) at 25.2% and the third most common for community-acquired pneumonia (CAP) at 15.7%.

• Most patients were elderly and common underlying conditions in patients with severe HPIV-associated pneumonia included: hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%).

• Co-infections with other pathogens occurred in 54.5% of patients admitted to the ICU, with bacterial co-infections being more common than viral and fungal co-infections.

• The 90-day mortality rate for HPIV-associated pneumonia was 55.2%, comparable to that for severe influenza virus–associated pneumonia (48.4%).

• Ribavirin treatment was not associated with lower mortality rates.

• Fungal co-infections, mainly Aspergillus species, were associated with 82.4% of deaths and were significantly more common in the HAP group (20.6%) than in the CAP group (5.0%).

In summary, in this paper investigating severe HPIV-associated pneumonia in adults, the major findings were the high prevalence of HPIV in severe HAP and CAP cases, the high mortality rate comparable to severe influenza, and the significant impact of fungal co-infections on mortality. The paper highlights the importance of considering the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia and that contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Lack of Transmission of Chronic Wasting Disease Prions to Human Cerebral Organoids by Bradley R. Groveman and others in June Emerging infectious Diseases.

https://wwwnc.cdc.gov/eid/article/30/6/23-1568_article

Chronic wasting disease henceforth referred to as CWD, is a cervid fatal neurodegenerative prion disease with unknown zoonotic potential that might pose a risk to humans who are exposed. CWD affects cervids, such as moose, elk, and several species of deer, across much of North America, South Korea, and certain countries in northern Europe, including Norway, Finland, and Sweden CWD is the most transmissible of the prion disease family; transmission between cervids is highly efficient. Another member of the prion disease family, bovine spongiform encephalopathy (BSE), has transmitted to humans and caused the emergence of variant Creutzfeldt-Jakob disease. That transmission is widely believed to have occurred through ingestion of contaminated food. Subsequently, concern is ongoing as to whether CWD prions could likewise infect humans because of the high likelihood of CWD-tainted meat entering the human food chain.

To assess the potential of CWD to infect human neural tissue, we used human cerebral organoids with 2 different prion genotypes, 1 of which has previously been associated with susceptibility to zoonotic prion disease. We exposed organoids from both genotypes to high concentrations of CWD inocula from 3 different sources for 7 days, then screened for infection periodically for up to 180 days. No de novo CWD propagation or deposition of protease-resistant forms of human prions was evident in CWD-exposed organoids. Some persistence of the original inoculum was detected, which was equivalent in prion gene knockout organoids and thus not attributable to human prion propagation. Overall, the unsuccessful propagation of CWD in cerebral organoids supports a strong species barrier to transmission of CWD prions to humans.

The need for models that are more closely related to humans has been partially addressed using nonhuman primates. Transmission of CWD to squirrel monkeys has been readily demonstrated but, to date, transmission studies in cynomolgus macaques (a closer laboratory animal model to humans than squirrel monkeys) have not shown evidence of prion disease. In those studies, no markers of prion infection were found in macaques euthanized as many as 13 years after inoculation with CWD. In contrast, BSE readily transmitted to macaques, causing behavioral and cerebellar signs and progressing to extremely severe ataxia within a few weeks of initial clinical signs. For adult animals, euthanasia was required at about 160 weeks after inoculation. This encouraging difference between BSE and CWD supports a strong species barrier against CWD infecting humans.

So the main reason for reviewing this article, was to explore a case study in exploring species barriers in the case of the highly transmissible CWD disease, finding that at at this time, transmission of CWD to human is unlikely.

Foodborne Disease Outbreaks Linked to Foods Eligible for Irradiation, United States, 2009–2020, by Marta Zlotnick, in June Emerging Infectious Diseases.

Food irradiation is a safe and effective way to reduce foodborne pathogens, sterilize insects, delay ripening, and extend shelf life. However, it has not been widely adopted in the United States, with estimates suggesting only around one third of spices and less than 0.1% of imported produce and meats are irradiated. Its adoption in the U.S. has been limited due to high costs and consumer perceptions.

Methods: The authors searched the Foodborne Disease Outbreak Surveillance System (FDOSS) for outbreaks caused by Campylobacter, Salmonella, E. coli, or Listeria from 2009-2020 where the food source was known. They categorized the implicated foods by whether they were eligible for irradiation and tallied the number of illnesses, hospitalizations and deaths in outbreaks linked to irradiation-eligible foods. They also conducted a literature review to identify any additional relevant outbreaks.

Key findings and public health implications:

Of 2,153 outbreaks caused by the 4 pathogens of interest, 482 (22.4%) had a known food source. None of these outbreaks had irradiation listed as a processing method.

155 (32.2%) of the 482 outbreaks with a known source were linked to an irradiation-eligible food. These outbreaks caused 3,512 illnesses, 463 hospitalizations, and 10 deaths.

The most common irradiation-eligible food sources were chicken (52 outbreaks), beef (31 outbreaks), and eggs (29 outbreaks), comprising 72% of the total.

The illnesses, hospitalizations and deaths in outbreaks linked to irradiation-eligible foods may have been prevented if those foods had been irradiated.

Irradiation typically eliminates a large proportion of pathogenic microorganisms, though its efficacy depends on factors like temperature and water content.

Irradiation could be a useful complementary tool alongside existing food safety practices to improve food safety, especially if consumer demand increases through education.

In summary, in this United States study investigating foodborne disease outbreaks from 2009-2020, the major finding was that nearly one third of outbreaks with a known food source were caused by foods that could have been irradiated, suggesting irradiation could play an important role in preventing foodborne disease.

Masks and respirators for prevention of respiratory infections: a state of the science review, by Trisha Greenhalg and others, from the May issue of Clinical Microbiology Reviews

Masks have been used for centuries to reduce transmission of respiratory diseases. However, the efficacy, acceptability, and safety of masks and other face coverings have been among the most important and contested scientific questions of the COVID-19 pandemic. The need for a new review on masks following the polarising findings in the masks section of a 2023 Cochrane review of non-pharmaceutical interventions (9) which was, controversially, limited to randomized controlled trials only. Many clinicians and members of the media and public interpreted the Cochrane review as proving that “masks don’t work”.

The authors conducted a narrative review and meta-analysis to summarize the evidence base from multiple disciplines and study designs on the benefits, practicalities, disbenefits, and harms of masks and masking. They synthesized evidence from over 100 published reviews and selected primary studies, including re-analyzing contested meta-analyses of key clinical trials.

The review produced seven key findings. First, there is strong and consistent evidence for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Second, masks are, if correctly and consistently worn, effective in reducing transmission of respiratory diseases and show a dose-response effect. Third, respirators are significantly more effective than medical or cloth masks. Fourth, mask mandates are, overall, effective in reducing community transmission of respiratory pathogens. Fifth, masks are important sociocultural symbols; non-adherence to masking is sometimes linked to political and ideological beliefs and to widely circulated mis- or disinformation. Sixth, while there is much evidence that masks are not generally harmful to the general population, masking may be relatively contraindicated in individuals with certain medical conditions, who may require exemption. Furthermore, certain groups (notably deaf people) are disadvantaged when others are masked. Finally, there are risks to the environment from single-use masks and respirators.

One important feature of this review can be found in Table 1, where the different study designs contributing to mask research are described including their strengths and limitations, and going beyond RCTs, – such as laboratory aerosol studies, modelling, and real world observational studies – not all evidence is found in RCTs.

The authors recommend that future research should focus on improved characterization of situations in which masking should be recommended or mandated; attention to comfort and acceptability; communication support in settings where masks are worn; and development and testing of novel materials and designs for improved filtration, breathability, and environmental impact. Future reviews of mask and other nonpharmaceutical interventions should recognise that reviewing only RCTs is a significant limitation on evidence review.

Follow-Up Study of Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against All-Type and Serotype-Specific Invasive Pneumococcal Disease, Denmark, by Katrine Finderup Nielsen, in June 2024 Emerging Infectious Diseases

Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae can lead to serious illnesses like meningitis and bacteremia, especially in older adults. Denmark initiated a vaccination program with the 23-valent pneumococcal polysaccharide vaccine, henceforth referred to as P-P-S-V-twenty-three, for people over 65 years old from April 2020 to January 2023. P-P-S-V-twenty-three covers 23 pneumococcal serotypes, but its effectiveness against specific serotypes varies. This study follows up on a previous Danish study to assess the vaccine effectiveness, henceforth referred to as VE, of P-P-S-V-twenty-three against both all-type IPD and serotype-specific IPD, including the impact of serotype 3.

The researchers conducted a cohort study using nationwide data from various Danish registries. The study included just over one million, two hundred and fifty thousand individuals over 65 years old living in Denmark. They used a Cox regression model to estimate VE, adjusting for age, sex and underlying conditions. In the main analysis, individuals were censored for the first 14 days after vaccination. A sensitivity analysis included these individuals as unvaccinated during that period.

Key findings and public health implications:

P-P-S-V-twenty-three vaccination provided 32% protection against all-type IPD and 41% against IPD caused by the 23...