Knowledge to Predict Pathogens: <i>Legionella pneumophila</i> Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell

Legionella pneumophila (L. pneumophila) is a pathogenic bacterium of increasing concern, due to its ability to cause a severe pneumonia, Legionnaires’ Disease (LD), and the challenges in controlling the bacteria within premise plumbing systems. L. pneumophila can thrive within the biofilm of premise plumbing systems, utilizing protozoan hosts for protection from environmental stressors and to increase its growth rate, which increases the bacteria’s infectivity to human host cells. Typical disinfectant techniques have proven to be inadequate in controlling L. pneumophila in the premise plumbing system, exposing users to LD risks. As the bacteria have limited infectivity to human macrophages without replicating within a host protozoan cell, the replication within, and egress from, a protozoan host cell is an integral part of the bacteria’s lifecycle. While there is a great deal of information regarding how L. pneumophila interacts with protozoa, the ability to use this data in a model to attempt to predict a concentration of L. pneumophila in a water system is not known. This systematic review summarizes the information in the literature regarding L. pneumophila’s growth within and egress from the host cell, summarizes the genes which affect these processes, and calculates how oxidative stress can downregulate those genes

Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Critical Review Part I Uptake into Host Cells

Legionella pneumophila (L. pneumophila) is an infectious disease agent of increasing concern due to its ability to cause Legionnaires’ Disease, a severe community pneumonia, and the difficulty in controlling it within water systems. L. pneumophila thrives within the biofilm of premise plumbing systems, utilizing protozoan hosts for protection from disinfectants and other environmental stressors. While there is a great deal of information regarding how L. pneumophila interacts with protozoa and human macrophages (host for human infection), the ability to use this data in a model to attempt to predict a concentration of L. pneumophila in a water system is not known. The lifecycle of L. pneumophila within host cells involves three processes: uptake, growth, and egression from the host cell. The complexity of these three processes would risk conflation of the concepts; therefore, this review details the available information regarding how L. pneumophila invades host cells (uptake) within the context of data needed to model this process, while a second review will focus on growth and egression. The overall intent of both reviews is to detail how the steps in L. pneumophila’s lifecycle in drinking water systems affect human infectivity, as opposed to detailing just its growth and persistence in drinking water systems

An Advanced Risk Modeling Method to Estimate Legionellosis Risks Within a Diverse Population

Quantitative microbial risk assessment (QMRA) is a computational science leveraged to optimize infectious disease controls at both population and individual levels. Often, diverse populations will have different health risks based on a population's susceptibility or outcome severity due to heterogeneity within the host. Unfortunately, due to a host homogeneity assumption in the microbial dose-response models' derivation, the current QMRA method of modeling exposure volume heterogeneity is not an accurate method for pathogens such as Legionella pneumophila. Therefore, a new method to model within-group heterogeneity is needed. The method developed in this research uses USA national incidence rates from the Centers for Disease Control and Prevention (CDC) to calculate proxies for the morbidity ratio that are descriptive of the within-group variability. From these proxies, an example QMRA model is developed to demonstrate their use. This method makes the QMRA results more representative of clinical outcomes and increases population-specific precision. Further, the risks estimated demonstrate a significant difference between demographic groups known to have heterogeneous health outcomes after infection. The method both improves fidelity to the real health impacts resulting from L. pneumophila infection and allows for the estimation of severe disability-adjusted life years (DALYs) for Legionnaires' disease, moderate DALYs for Pontiac fever, and post-acute DALYs for sequela after recovering from Legionnaires' disease.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Legionella pneumophila as a Health Hazard to Miners: A Pilot Study of Water Quality and QMRA

Legionella pneumophila (L. pneumophila), the causative agent of legionellosis, is an aquatic bacterium that grows in warm water. Humans are only presented with a health risk when aerosolized water containing L. pneumophila is inhaled. In mining operations, aerosolized water is used as dust control and as part of the drilling operations, a currently ignored exposure route. This study characterized L. pneumophila concentrations in the mine's non-potable water and the relationship between L. pneumophila and chlorine concentrations. These concentrations informed a quantitative microbial risk assessment (QMRA) model to estimate the infection risk to miners exposed to aerosolized water containing L. pneumophila. Fourteen water samples were collected from seven locations at a mine and analyzed for temperature, pH, chlorine, and L. pneumophila serogroup. Most samples (93%) tested positive for L. pneumophila cells. The faucet from the sprinkler system on the adit level (entrance to the underground mine levels) showed the highest concentration of L. pneumophila (8.35 x 10(4) MPN/L). Disability adjusted life years (DALYs) were estimated in the QMRA model and showed that the risk for all miners was significantly lower (p < 0.0001) with the ventilation system on than when the system was off. Our study showed that the use of a ventilation system at the adit level of the mine reduced the risk of infection with aerosolized L. pneumophila.Southwest Environmental Health Sciences Center [NIEHS P30 ES006694]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Why pathogens matter for meeting the united nations’ sustainable development goal 6 on safely managed water and sanitation

Water and wastewater utilities, water and sanitation hygiene (WASH) practitioners, and regulating bodies, particularly in developing nations, rely heavily on indicator microorganisms, as opposed to pathogens, for much of their regulatory decisions. This commentary illustrates the importance of considering pathogens and not relying only on indicator organisms when making decisions regarding water and sanitation, especially with respect to meeting the current targets of the Sustainable Development Goal (SDG) 6. We use quantitative microbial risk assessment (QMRA) to present three common scenarios that WASH and public health practitioners encounter to illustrate our point. These include 1) chlorination of surface water for drinking, 2) land application of latrine waste as a fertilizer, and 3) recreation/domestic use of surface waters impacted by wastewater discharge. We show that the calculated probabilities of risk of infection are statistically significantly higher when using treatment/survival information for pathogens versus using indicator species data. Thus, demonstrating that relying solely on indicators for sanitation decision making is inadequate if we truly want to achieve the SDG6 targets of safely managed water and sanitation services

Research gaps and priorities for quantitative microbial risk assessment (QMRA)

The coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose-response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co-exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source-to-outcome continuum. Cross-cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies