Tag: Respiratory

Has a decade of maternal pertussis vaccination reduced its effectiveness?
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In a recent modeling and meta-analysis study published in the journal Nature Communications, researchers evaluated if maternal immunization against pertussis, a highly contagious bacterial respiratory infection, experienced reduced efficacy (‘blunting’) due to prolonged use. They reviewed four studies with up to six years of follow-up and designed a novel mathematical model to evaluate immunization’s short- and long-term effects on disease transmission dynamics. While incapable of ruling out minor reductions in vaccine effectiveness (VE), their findings highlight that maternal immunizations are (and will continue to be) essential in preventing pertussis transmission and, more importantly, saving the lives of unvaccinated newborns.

Study: Maternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study. Image Credit: Kateryna Kon / Shutterstock

Pertussis and the results of global immunization efforts

Pertussis, colloquially called ‘whooping cough,’ is a highly contagious respiratory illness caused by the bacteria Bordetella pertussis. Its symptoms included chronic or severe cough, general fatigue and fever, nausea, and difficulty breathing. It is characterized by its severe hacking cough from which the name “whooping” is obtained. Pertussis infections are most severe in children, especially newborns, and were a significant cause of childhood mortality before the 1940s.

Thankfully, pertussis is easily preventable via vaccines. Global large-scale immunization efforts in the 1940s reduced transmission rates by 90% in most countries. Unfortunately, for reasons hitherto unknown, pertussis has been staging a comeback over the past two decades. This has prompted a resurgence into pertussis-centric research aimed at evaluating the mechanisms underpinning rising transmission rates.

Infants, especially newborns, are the cohort most vulnerable to the disease, given their suboptimal immune development and lack of immunization. To counter this, numerous nations (since 2012) and the World Health Organization (since 2015) have recommended and initiated maternal immunization programs. Vaccinating women during the gestation period has been clinically revealed to transfer its protective effects to their unborn infants, resulting in an estimated 70% reduction in newborn mortality.

“However, the downstream consequences of maternal immunization, when infants receive their routine pertussis vaccines, are poorly understood. Specifically, there has been long-standing concern regarding potential immunological blunting, i.e., the interference of maternally transferred antibodies with the infant immune response.”

Understanding if current vaccination protocols are resulting in immunization blunting, and if so, to what extent, will allow for the revision of present immunization policies and may require an overhaul of the vaccines used or the process itself.

About the study

In the present study, researchers conducted a meta-analysis to investigate if prolonged (2012 to 2023) maternal immunization has reduced vaccine effectiveness (VE). The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Data collection was initiated by collating relevant publications from three online databases (PubMed, Web of Science, and Scopus) from database initiation till August 25, 2023. This search revealed 374 articles across databases, 146 of which were duplicate records. Of the 228 remaining publications, abstract screening revealed 69 potential articles, which full-text screening further narrowed down to the final sample set – four.

“To be included in our review, studies had to provide an estimate of the relative risk (RR) of pertussis in infants having received at least one dose of their primary immunization from vaccinated vs. unvaccinated mothers. We selected only those studies that used laboratory-confirmed diagnosis of pertussis.”

Each of the four included studies reported at least five pertussis relative risk estimates in comparing vaccinated and unvaccinated mothers. Study analyses were carried out using two steps – Firstly, to account for different metrics used in the included studies, standard relative risks were calculated and applied to each included metric. Secondly, the meta-analyses were carried out. The meta-regression used herein was corrected to account for ‘population’ as a random intercept.

Finally, researchers devised a novel mathematical model based on the Susceptible-Exposed-Infected-Recovery (SEIR) model, explicitly testing for VE accounting for immunization blunting. The model had two outcome measures – 1. failure in “take” (if the primary vaccine failed), and 2. failure in duration (loss or reduction of vaccine protection). The model works in a hierarchical compartmentalization framework comprising three levels, each with their own ‘paths.’

Level 1: “These three possible paths or compartments start from their mother’s immunization status during pregnancy, followed by an infant immunization schedule that resembles that of the empirical studies.” Level 2: “…newborns can be born in three possible compartments: from vaccinated mothers whose immunization succeeded, mothers whose immunization failed (i.e., who received the vaccine but whose infant remained unprotected), or unvaccinated mothers.” Level 3: “Each of the three compartments is followed by a compartment for successful primary infant immunization and a compartment for failed primary infant immunization, thereby becoming susceptible, or no immunization thereby also becoming susceptible.”

Study findings

Exploring the historical landscape of VE in infant pertussis via the novel model revealed that infant (maternal) immunization substantially decreased disease incidence. However, consistent with global reports, this was followed by a gradual rebound in pertussis persistence. This is consistent with the previously described “end-of-honeymoon” effect and is expected in most diseases managed using imperfect yet highly efficient vaccines. These results validate model reliability.

Analyzing the sample dataset using this model revealed that the first vaccine dose in infants following maternal immunization is highly effective against pertussis contraction, but the second and third doses are much more uncertain, consistent with previous uncertainty regarding blunting effects. The model demonstrated the presence of a decade-long lag phase following the introduction of maternal immunization, during which time blunting effects are liable to be underestimated in trial studies.

Encouragingly, quantifying the blunting effects suggests that they are minor and pale compared to the infant mortality-saving that maternal immunization provides. These findings support the public health decisions of many countries (55 as of 2021) to continue maternal immunization efforts and recommend that other nations follow suit.

Conclusions

The present study conducted a meta-regression analysis of four epidemiological publications to investigate the potential blunting effect of decade-long maternal immunization efforts. They further devised and implemented a mathematical model to interpret pertussis relative risk while explicitly accounting for vaccine efficacy blunting.

Their findings reveal the presence of a transient decade-long lag phase following maternal immunization, characterized by the masking and underestimation of blunting effects, thereby explaining previous inconsistencies in the literature. More importantly, the study highlights that while moderate levels of VE loss via blunting do exist, they are far outweighed by the infant mortality savings that maternal vaccination provides.
Journal reference:

Briga, M., Goult, E., Brett, T. S., & Rohani, P. (2024). Maternal pertussis immunization and the blunting of routine vaccine effectiveness: A meta-analysis and modeling study. Nature Communications, 15(1), 1-11., DOI – 10.1038/s41467-024-44943-7, https://www.nature.com/articles/s41467-024-44943-7
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February 4, 2024
Are urban green spaces beneficial to air quality?

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A study published in the journal PNAS claims that urban green space has only a moderate effect on air pollution control and that street-level vegetation can actually increase air pollution by restricting ventilation.

Study: Reassessing the role of urban green space in air pollution control. Image Credit: taka1022 / Shutterstock

Background

Air pollution is a leading cause of respiratory diseases and premature death globally. Among various air pollutants, small-diameter (2.5 µm) particulate matter (PM) is estimated to cause approximately ten million excess deaths worldwide. The World Health Organization (WHO) considers air pollution as the most significant environmental threat to human health.

About 70% of all health complications arising from air pollution can be attributed to greenhouse gases emitted by human activities (anthropogenic emissions). Major strategies that have been taken into consideration for reducing anthropogenic emissions include cleaner energy production, efficient discharging of industrial smoke, reduced dependency on fossil fuel vehicles, and sustainable agriculture practices.

The literature has given immense attention to the utilization of vegetation as a passive abatement method for outdoor air pollution and the installation of physical-chemical filters as an active abatement method for indoor air pollution.

In this study, scientists have investigated the effect of urban green space on ambient air pollution.

Study design

The scientists utilized 2,615 air quality monitoring stations over Europe and the United States to derive annual concentrations of major air pollutants (NO₂, PM₁₀, PM_2.5, and O₃) between 2010 and 2019. They determined the changes in urban green space around each air quality station using moderate-resolution satellite data and very high-resolution aerial imagery.

They conducted a series of appropriate statistical analyses to determine the association between urban green space and air quality after adjusting for changes in anthropogenic emissions and climate.

Important observations

Air quality station-derived data showed a decline in NO₂(nitrogen dioxide), PM₁₀, and PM_2.5between 2010 and 2019, which was relatively consistent across the United States and Europe. In contrast, an induction in O₃concentration in the ambient air was observed during the same period. Overall, these observations indicate that recent strategies to reduce anthropogenic emissions might be useful in controlling air pollution.

Distribution of the air quality–monitoring stations across biomes in Europe (n = 2,127) and the United States (n = 488) (A). Inset histograms show the proximity of stations to roads and the building footprint within 30 m. Air pollutant time series along with linear trends are shown in (B).

Considering biome-specific vegetation types, the study found that stations situated within the forest biome exhibit the highest decline in air pollutants, especially PM, compared to those situated in the Mediterranean shrubland and savanna/grassland biomes. This might be due to higher pollutant deposition and dispersion capacity of forest vegetation than Mediterranean shrubland. Another possibility could be that dry environments in Mediterranean shrublands may facilitate long-range aerosol transport of dust and smoke.

The study further analyzed how changes in total urban green space and tree cover can impact air quality at the street, borough, and city levels. The analysis revealed a weak and highly variable effect of green space changes on air pollution, particularly at the street level. This could be because of the fact that planting vegetation, especially tall vegetation, near emission sources, such as across streets, can reduce microscale ventilation and subsequently increase the concentrations of pollutants in the air.

Considering the changes in tree cover, the analysis revealed a negative association with air pollution at both the borough level and city level. This association was particularly evident for O₃and PM. Overall, the study found that an induction in tree cover has a significantly higher effect in reducing air pollution than total green space augmentation.

Furthermore, the study found that the effect of urban green space on air quality was negligible in magnitude than climatic drivers, including wind speed, precipitation, and humidity. These climatic drivers showed a negative association with all types of air pollutants except for O_3.

Example of an extreme increase (A−C) and decrease (D−F) in green space within a 60-m buffer (street-level) of two air quality–monitoring stations. Aerial photographs from Google Earth Pro shown for reference.

Study significance

The study finds that urban green space is not always a good strategy to improve air quality and reduce air pollution. According to the findings, the effect of green space on air quality can widely vary depending on the type of green space (total green space vs. tree cover), spatial scale (street-level versus borough-level versus city-level), and biome (forest versus Mediterranean shrubland).

One interesting finding of the study is that increased vegetation along roadsides can actually increase air pollution by restricting the ventilation of vehicle-emitted pollutants. The aerodynamic effects of green space can be effective in channeling pollutants away from pedestrians. However, in areas with unfavorable aerodynamic conditions, the pollutant dispersion effect of green space can overshadow its pollutant deposition effect.

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February 2, 2024
Mechanically ventilated patients in intermediate care units of rural hospitals have higher death rates

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A new National Institutes of Health-supported study finds that patients receiving ventilator life support in the intermediate care units – a potentially less costly alternative for people not sick enough for the intensive care units (ICUs) but too ill for the general ward – of rural hospitals had significantly higher death rates than patients in the same type of unit at urban hospitals. The study also found that patients with respiratory failure in the ICUs at rural and urban hospitals fare similarly. Published in the journal Annals of the American Thoracic Society, this study highlights the need for more careful evaluations of patients with breathing problems who are assigned to intermediate care units.

This study has important implications for rural hospitals when determining how to care for their sickest patients on mechanical ventilation, as rural hospitals tend to be smaller and less resourced. It emphasizes the need to assess whether rural intermediate care units can meet the complex demands of critically ill patients, and the importance of carefully evaluating the processes designed to care for them.”

Gustavo Matute-Bello, M.D., deputy director for the Division of Lung Diseases at the National Heart, Lung, and Blood Institute (NHLBI), NIH

The research team, led by Emily Harlan, M.D., a pulmonary and critical care physician at the University of Michigan, Ann Arbor, collected data from 2010 to 2019 on 2.75 million hospitalizations of Medicare patients (65 years or older) who were on respiratory support at rural and urban hospitals across the country. The researchers conducted separate analyses for patients admitted to the general, intermediate, and ICU wards, and another analysis of patients in all the wards combined.

When they compared patients in all the wards, they found that those receiving mechanical ventilation in rural hospitals had significantly higher 30-day death rates than those in urban hospitals. However, when the researchers broke down the data by level of care, patients in the ICUs of rural and urban hospitals had a similar chance of dying. The difference in outcomes, the researchers discovered, was singularly explained by the higher mortality rates for patients in the rural intermediate care units – 37% died within 30 days compared to 31.3% in urban hospitals.

When patients are admitted to a hospital, the least sick are taken to the general ward and the sickest go to the ICU. However, U.S. hospitals are increasingly shifting toward a model that incorporates intermediate care units, which use fewer resources and can be less expensive to operate than ICUs. While these units may help a rural hospital’s financial bottom line how rural patients fared in them compared to their urban counterparts, was largely unknown.

“This study underscores the importance of learning more about how to best use intermediate care units and highlights the need to continue investing in rural hospitals to make sure all who need it have access to life-saving care,” said Harlan. “There is a common belief that rural hospitals may have a lower quality of care, but that’s not what we saw for the ICU patients in our study.”

Source:

NIH/National Heart, Lung and Blood Institute

Journal reference:

Harlan, E. A., et al. (2024) Rural-Urban Differences in Mortality among Mechanically Ventilated Patients in Intensive and Intermediate Care. Annals of the American Thoracic Society. doi.org/10.1513/AnnalsATS.202308-684OC.

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January 31, 2024