Linking Decision Theory and Quantitative Microbial Risk Assessment: Tradeoffs Between Compliance and Efficacy for Waterborne Disease Interventions

Achieving health gains from the U.N. Sustainable Development Goals of universal coverage for water and sanitation will require interventions that can be widely adopted and maintained. Effectiveness—how an intervention performs based on actual use—as opposed to efficacy will therefore be central to evaluations of new and existing interventions. Incomplete compliance—when people do not always use the intervention and are therefore exposed to contamination—is thought to be responsible for the lower‐than‐expected risk reductions observed from water, sanitation, and hygiene interventions based on their efficacy at removing pathogens. We explicitly incorporated decision theory into a quantitative microbial risk assessment model. Specifically, we assume that the usability of household water treatment (HWT) devices (filters and chlorine) decreases as they become more efficacious due to issues such as taste or flow rates. Simulations were run to examine the tradeoff between device efficacy and usability. For most situations, HWT interventions that trade lower efficacy (i.e., remove less pathogens) for higher compliance (i.e., better usability) contribute substantial reductions in diarrheal disease risk compared to devices meeting current World Health Organization efficacy guidelines. Recommendations that take into account both the behavioral and microbiological properties of treatment devices are likely to be more effective at reducing the burden of diarrheal disease than current standards that only consider efficacy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/1/risa13381.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/2/risa13381-sup-0001-Appendix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/3/risa13381_am.pd

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

Abstract Background Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. Methods We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. Results Based on parameter estimates from the literature the reproductive number ( R 0 $\mathcal {R}_{0}$ ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, R 0 $\mathcal {R}_{0}$ for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. Conclusions Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower R 0 $\mathcal {R}_{0}$ for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ( R 0 > > 1 $\mathcal {R}_{0}>>1$ ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens.https://deepblue.lib.umich.edu/bitstream/2027.42/146145/1/12879_2018_Article_3425.pd

The dynamics of methicillin-resistant Staphylococcus aureus exposure in a hospital model and the potential for environmental intervention

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections. An important control strategy is hand hygiene; however, non-compliance has been a major problem in healthcare settings. Furthermore, modeling studies have suggested that the law of diminishing return applies to hand hygiene. Other additional control strategies such as environmental cleaning may be warranted, given that MRSA-positive individuals constantly shed contaminated desquamated skin particles to the environment. Methods We constructed and analyzed a deterministic environmental compartmental model of MRSA fate, transport, and exposure between two hypothetical hospital rooms: one with a colonized patient, shedding MRSA; another with an uncolonized patient, susceptible to exposure. Healthcare workers (HCWs), acting solely as vectors, spread MRSA from one patient room to the other. Results Although porous surfaces became highly contaminated, their low transfer efficiency limited the exposure dose to HCWs and the uncolonized patient. Conversely, the high transfer efficiency of nonporous surfaces allows greater MRSA transfer when touched. In the colonized patient’s room, HCW exposure occurred more predominantly through the indirect (patient to surfaces to HCW) mode compared to the direct (patient to HCW) mode. In contrast, in the uncolonized patient’s room, patient exposure was more predominant in the direct (HCW to patient) mode compared to the indirect (HCW to surfaces to patient) mode. Surface wiping decreased MRSA exposure to the uncolonized patient more than daily surface decontamination. This was because wiping allowed higher cleaning frequency and cleaned more total surface area per day. Conclusions Environmental cleaning should be considered as an integral component of MRSA infection control in hospitals. Given the previously under-appreciated role of surface contamination in MRSA transmission, this intervention mode can contribute to an effective multiple barrier approach in concert with hand hygiene.http://deepblue.lib.umich.edu/bitstream/2027.42/112924/1/12879_2013_Article_2936.pd

The joint effects of water and sanitation on diarrhoeal disease: a multicountry analysis of the Demographic and Health Surveys

ObjectivesTo assess whether the joint effects of water and sanitation infrastructure, are acting antagonistically (redundant services preventing the same cases of diarrhoeal disease), independently, or synergistically; and to assess how these effects vary by country and over time.MethodsWe used data from 217 Demographic and Health Surveys conducted in 74 countries between 1986 and 2013. We used modified Poisson regression to assess the impact of water and sanitation infrastructure on the prevalence of diarrhoea among children under 5.ResultsThe impact of water and sanitation varied across surveys, and adjusting for socio‐economic status drove these estimates towards the null. Sanitation had a greater effect than water infrastructure when all 217 surveys were pooled; however, the impact of sanitation diminished over time. Based on survey data from the past 10 years, we saw no evidence for benefits in improving drinking water or sanitation alone, but we estimated a 6% reduction of both combined (prevalence ratio = 0.94, 95% confidence limit 0.91–0.98).ConclusionsWater and sanitation interventions should be combined to maximise the number of cases of diarrhoeal disease prevented in children under 5. Further research should identify the sources of variability seen between countries and across time. These national surveys likely include substantial measurement error in the categorisation of water and sanitation, making it difficult to interpret the roles of other pathways.ObjectifsEvaluer les effets conjoints des infrastructures de l'eau et d'assainissement afin de voir si elles sont des services redondants prévenant les mêmes cas de maladies diarrhéiques, si elles agissent indépendamment ou en synergie et d’évaluer comment ces effets varient selon les pays et au fil du temps.MéthodesNous avons utilisé les données de 217 enquêtes démographiques et santé menées dans 90 pays entre 1986 et 2013. Nous avons utilisé la régression de Poisson modifiée pour évaluer l'impact des infrastructures de l'eau et d'assainissement sur la prévalence de la diarrhée chez les enfants de moins de cinq ans.RésultatsL'impact de l'eau et de l'assainissement variait dans toutes les enquêtes et l'ajustement pour le statut socioéconomique conduisait ces estimations vers le néant. L'assainissement avait un effet plus important que l'infrastructure de l'eau lorsque toutes les 217 enquêtes ont été poolées. Toutefois, l'impact de l'assainissement a diminué au fil du temps. Basé sur des données d'enquêtes des dix dernières années, nous n'avons vu aucune preuve pour les bénéfices de l'amélioration de l'eau potable ou de l'assainissement seuls, mais nous avons estimé une réduction de 6% pour la combinaison des deux (rapport de prévalence = 0,94; IC95%: 0,91 à 0,98).ConclusionsLes interventions sur l'eau et l'assainissement devraient être combinées pour maximiser le nombre de cas de maladies diarrhéiques prévenus chez les enfants de moins de cinq ans. Des recherches supplémentaires devraient identifier les sources de variabilité observées entre les pays et dans le temps. Ces enquêtes nationales comportent probablement une erreur importante de mesure dans la catégorisation de l'eau et de l'assainissement, ce qui rend difficile l'interprétation des rôles des autres voies.ObjetivosEvaluar el efecto conjunto del agua e infraestructura sanitaria, y determinar si son servicios redundantes que previenen los mismos casos de enfermedad diarreica, actúan de forma independiente o actúan de forma sinérgica; y evaluar como dichos efectos varían según el país y a lo largo del tiempo.MétodosHemos utilizado los datos de 217 Censos Demográficos y de Salud realizados en 90 países entre 1986 y 2013. Hemos realizado una regresión de Poisson modificada para evaluar el impacto del agua y de la infraestructura sanitaria sobre la prevalencia de la diarrea en niños menores de cinco años.ResultadosEl impacto del agua y del saneamiento variaba a lo largo de los censos, y el ajustar según el estatus socioeconómico llevaba los resultados a cero. El saneamiento tenía un mayor efecto que la infraestructura para el agua si se agrupaban los 217 censos; sin embargo, el impacto del saneamiento disminuía a lo largo del tiempo. Basado en los datos censales de los últimos diez años, no encontramos evidencia de los beneficios de la mejora del agua para consumo o del saneamiento por sí solos, pero hemos estimado una reducción del 6% de las dos intervenciones combinadas (tasa de prevalencia = 0.94, IC 95% 0.91‐0.98).ConclusionesLas intervenciones en el agua o el saneamiento deberían combinarse para maximizar el número de casos de enfermedad diarréica prevenidas en niños menores de cinco años. Estudios futuros deberían identificar las fuentes de variabilidad observada entre países y a lo largo del tiempo. Es posible que los censos nacionales incluyan un error sustancial en la medición de las categorías de agua y saneamiento, lo cual complica la determinación del papel de vías alternativas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110633/1/tmi12441.pd

The Effect of Ongoing Exposure Dynamics in Dose Response Relationships

Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens

Phenotypic variations in persistence and infectivity between and within environmentally transmitted pathogen populations impact population-level epidemic dynamics

Abstract Background Human pathogens transmitted through environmental pathways are subject to stress and pressures outside of the host. These pressures may cause pathogen pathovars to diverge in their environmental persistence and their infectivity on an evolutionary time-scale. On a shorter time-scale, a single-genotype pathogen population may display wide variation in persistence times and exhibit biphasic decay. Methods We use a transmission modeling framework to develop an infectious disease model with biphasic pathogen decay. We take a differential algebra approach to assessing model identifiability, calculate basic reproduction numbers by the next generation method, and use simulation to explore model dynamics. Results For both long and short time-scales, we demonstrate that epidemic-potential-preserving trade-offs have implications for epidemic dynamics: less infectious, more persistent pathogens cause epidemics to progress more slowly than more infectious, less persistent (labile) pathogens, even when the overall risk is the same. Using identifiability analysis, we show that the usual disease surveillance data does not sufficiently inform these underlying pathogen population dynamics, even when combined with basic environmental monitoring data. However, risk could be indirectly ascertained by developing methods to separately monitor labile and persistent subpopulations. Alternatively, determining the relative infectivity of persistent pathogen subpopulations and the rates of phenotypic conversion will help ascertain how much disease risk is associated with the long tails of biphasic decay. Conclusion A better understanding of persistence–infectivity trade-offs and associated dynamics can improve our ecological understanding of environmentally transmitted pathogens, as well as our risk assessment and disease control strategies.https://deepblue.lib.umich.edu/bitstream/2027.42/149181/1/12879_2019_Article_4054.pd

Disease transmission models for public health decision making: analysis of epidemic and endemic conditions caused by waterborne pathogens.

Developing effective policy for environmental health issues requires integrating large collections of information that are diverse, highly variable, and uncertain. Despite these uncertainties in the science, decisions must be made. These decisions often have been based on risk assessment. We argue that two important features of risk assessment are to identify research needs and to provide information for decision making. One type of information that a model can provide is the sensitivity of making one decision over another on factors that drive public health risk. To achieve this goal, a risk assessment framework must be based on a description of the exposure and disease processes. Regarding exposure to waterborne pathogens, the appropriate framework is one that explicitly models the disease transmission pathways of pathogens. This approach provides a crucial link between science and policy. Two studies--a Giardia risk assessment case study and an analysis of the 1993 Milwaukee, Wisconsin, Cryptosporidium outbreak--illustrate the role that models can play in policy making

Dengue Serotype Differences in Urban and Semi-rural Communities in Ecuador

Dengue is a major vector-borne infection causing large outbreaks in urban communities in tropical regions. During the period 2010- 2014; 434 serum samples from febrile patients were collected from a  semi-rural community hospital located in the norwestern region of Ecuador. Dengue virus (DENV) was investigated by reverse transcriptase PCR; a total of 48 samples were positive for dengue. During our study we detected  DENV-2 and DENV-3 from 2010 to 2013 and the four  DENV  serotypes during the period 2013-2014.  Surprisingly, our results contrasted with surveys carried out in urban centers throughout the  Ecuadorian Coast in which  DENV-1, DENV-2 and DENV-4 were prevalent during years 2010-2013 and only 2 serotypes  (DENV-1 and DENV-2) in 2014.These results suggest  that dengue viruses in semi-rural communities didn’t  originate in the Ecuadorian cities.  &nbsp

The Water Quality in Rio Highlights the Global Public Health Concern Over Untreated Sewage

Water quality issues in Rio have been widely publicized because of the 2016 Olympics. Recent concerns about polluted waters that athletes may be exposed to highlights the conditions that more than a billion people globally are exposed to daily. Despite these unhealthy conditions, much is unknown about the risks and exposure pathways associated with bathing in or drinking untreated or partially treated sewage. Beyond acute illness, we are learning more about the chronic sequelae that arise from repeated exposure to pathogens found in sewage. Additionally, we do not know enough about how to measure water quality, especially in developing countries. A consequence of these knowledge gaps is that data from developed countries are used to guide public health approaches in low- and middle-income settings. More data that are locally specific are needed to inform guidelines for improving sanitation and water quality in Rio and other cities in developing countries