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Title: Wastewater surveillance for infectious disease: a systematic review
Authors:
Pruthvi Kilaru MPH
1
, Dustin Hill PhD
1,2
, Kathryn Anderson MD/PhD
3
, Mary B. Collins PhD
4
,
Hyatt Green PhD
5
, Brittany L. Kmush PhD
1
, David A. Larsen PhD*
1
1. Department of Public Health, Syracuse University, Syracuse, NY, USA
2. Graduate Program in Environmental Science, SUNY ESF, Syracuse, NY, USA
3. Department of Medicine, SUNY Upstate, Syracuse, NY, USA
4. Department of Environmental Studies, SUNY ESF, Syracuse, NY, USA
5. Department of Environmental Biology, SUNY ESF, Syracuse, NY, USA
* Correspondence to: Dr. David Larsen, Department of Public Health, Syracuse University,
Syracuse, NY, 13244, USA
Abstract:
Wastewater surveillance of SARS-CoV-2 has shown to be a valuable source of information
regarding SARS-CoV-2 transmission and COVID-19 cases. Though the method has been used
for several decades to track other infectious diseases, there has not been a comprehensive
review outlining all of the pathogens surveilled through wastewater. The aim of this study is to
identify what infectious diseases have been previously studied via wastewater surveillance prior
to the COVID-19 Pandemic and identify common characteristics between the studies, as well as
identify current gaps in knowledge. Peer-reviewed articles published as of August 1, 2020 that
examined wastewater for communicable and infectious human pathogens on 2 or more
occasions were included in the study. Excluded from this list were all reviews and methods
papers, single collection studies, and non-human pathogens. Infectious diseases and
pathogens were identified in studies of wastewater surveillance, as well as themes of how
wastewater surveillance and other measures of disease transmission were linked. This review
did not include any numerical data from individual studies and thus no statistical analysis was
done. 1005 articles were identified but only 100 were included in this review after applying the
inclusion criteria. These studies came from 38 countries with concentration in certain countries
including Italy, Israel, Brazil, Japan, and China. Twenty-five separate pathogen families were
identified in the included studies, with the majority of studies examining pathogens from the
family Picornaviridae, including polio and non-polio enteroviruses. Most studies of wastewater
surveillance did not link what was found in the wastewater to other measures of disease
transmission. Among those studies that did compare wastewater surveillance to other measures
of disease transmission the value observed was dependent upon pathogen and varied by study.
Wastewater surveillance has historically been used to assess water-borne and fecal-orally
transmitted pathogens causing diarrheal disease. However, numerous other types of pathogens
have been surveilled using wastewater and wastewater surveillance should be considered as a
potential tool for many infectious diseases. Wastewater surveillance studies can be improved by
incorporating other measures of disease transmission at the population-level including disease
incidence and hospitalizations.
. CC-BY-NC 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
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NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
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Introduction:
Infectious disease surveillance is most commonly conducted at the health center or the
hospital,
1
either through passive reporting or active case finding.
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This type of event-based
infectious disease surveillance monitors trends in morbidity and mortality, alerting health
systems when a statistically improbable uptick of events occurs. In this way, the number of
cases, hospitalizations, and deaths from endemic infectious diseases such as malaria or
influenza are tracked and the effectiveness of interventions such as mosquito control or
vaccines can be monitored. Importantly, due to cost and non-representative access to molecular
diagnostics, many pathogens under surveillance are characterized by their symptoms or
syndromes, such as influenza-like illness. For emerging pathogens, event-based infectious
disease surveillance may note an odd increase in some symptom or condition, notably as
occurred with microcephaly and Zika,
3,4
or pneumonia cases without a known cause as
occurred with COVID-19.
5
Event-based infectious disease surveillance requires a health system
capable of observing an unexpected trend, a population with sufficient access to that health
system, and a sufficiently large trend or cluster of odd cases to alert officials.
Environmental surveillance, on the other hand, is a broad category for systems that
monitor the presence or absence of a pathogen in the environment. Their defining characteristic
is the circumvention of human behavior and health systems, which reduces bias, while still
providing information regarding risks to human health. For example, environmental surveillance
may routinely test known vectors for pathogens,
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alerting the public to the detection of, or an
increase in, the pathogen in the vector population.
Wastewater surveillance is a type of environmental surveillance that has historically
been utilized to track water-borne or fecal-orally transmitted pathogens. The origins of
wastewater surveillance hail back to the London cholera epidemic of the mid-1800’s, John
Snow, and the Broad Street Pump, when a cesspool near a house with multiple cholera deaths
was excavated and found to be leaking into the pump’s water supply.
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With the scientific
evidence supporting germ theory, scientists began hunting sewage not only for cholera but also
for other pathogens including salmonella typhi bacteria (typhoid),
8,9
coxsackie viruses,
10
and
poliovirus.
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From the 1970’s onward, wastewater surveillance formed a critical component of
the worldwide initiative to eradicate polio,
12
and perhaps polio provides the best contrast
between event-based and environmental surveillance systems. Whereas event-based polio
surveillance relies on an unexpected increase in acute flaccid paralysis which occurs in only
0.5% of polio cases,
13
wastewater surveillance can detect poliovirus circulating in a community
before any paralysis occurs.
14
The COVID-19 pandemic saw the broad adaptation of wastewater surveillance across
the globe,
15
as the limitations of event-based surveillance systems for an emerging pathogen
were laid bare. Most interestingly, COVID-19 is a respiratory-transmitted pathogen, suggesting
that a pathogen’s mode of transmission need not be fecal-oral or waterborne for wastewater
surveillance to be useful. Could wastewater surveillance be a more widely applied tool, not only
monitoring trends in waterborne or fecal-orally transmitted pathogens but also pathogens of
pandemic potential and those causing the greatest burden of disease? SARS-CoV-2 is certainly
the pathogen du jour, but as wastewater surveillance systems are erected should they also be
incorporating other pathogens into their surveillance? Herein we present a systematic review of
. CC-BY-NC 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 29, 2021. ; https://doi.org/10.1101/2021.07.26.21261155doi: medRxiv preprint
3
wastewater surveillance for infectious disease, reporting the documented successes of testing
wastewater for infectious disease pathogens that circulate primarily in humans.
Methods:
Systematic Literature Review
Following PRISMA guidelines
16
, we searched PubMed, SCOPUS, Science Direct and
Google Scholar for studies looking at wastewater-based surveillance of infectious diseases
(both viral and bacterial) in human populations and published before August 1st, 2020. For the
databases (PubMed, SCOPUS, and Science Direct), search terms included Mesh headings,
MeSH terms, and text words and synonyms, including “Wastewater”, “Waste water”, “Sewage”,
“Sewer”, “Environmental”, “Surveillance”, “Disease”, “Feces”, "wastewater-based epidemiology",
"Environmental surveillance", “Environmental Epidemiology “, “Wastewater Surveillance “,
"Environmental Monitoring", "Wastewater Monitoring", “Virus”, “Bacteria”. These terms were
combined using the boolean terms “AND” and “OR” when applicable. Similar terms were used
but with filters on Google Scholar to limit the search to material of interest. The filters included
the inclusion of the characters “doi” to look for a Digital Object Identifier to ensure that it was a
published work, and the exclusion of the terms "systematic review", "literature review", "meta-
analysis", and "review" in the title. The boolean term “NOT” was used to aid in excluding these
terms. All sources, databases and Google Scholar, were filtered to look for texts in the English
language. The search string used for each individual database and Google Scholar, as well as
the filters used, can be found in Appendix 1.
Once article lists were pulled from their respective sources, duplicates were removed,
using Microsoft Excel’s built-in remove duplicated function, using both title and authors as the
reference for removal. Reviewers (Pruthvi Kilaru and Dustin Hill) screened titles and abstracts
for remaining articles, retrieved articles for full-text review, and assessed full-text articles based
on eligibility criteria.
Eligibility Criteria
We included published studies which tested wastewater for communicable and/or
infectious human diseases on more than one occasion and during two or more time periods.
Non-communicable diseases, such as diabetes and obesity, were excluded. As we defined
surveillance as having the requirement of testing over time, all articles which tested wastewater
only once and/or on a single day were excluded. Articles which discussed diseases not related
to humans or not in the context of humans (e.g. influenza virus in pigs), were also excluded.
Peer-reviewed journal articles were included as long as they were not reviews, systematic
reviews, literature reviews, or meta-analyses. Non-peer reviewed journal articles such as
research notes, research letters, and short communications were excluded. Methods papers
that looked purely at and compared different techniques of drawing and sampling wastewater
were also excluded if they did not offer analysis of pathogens naturally present in the
wastewater. This included studies that spike wastewater with a pathogen only to look at
recovery in the context of comparing methods of sampling. Lastly, we excluded all papers which
reported the surveillance of SARS-CoV0-2. This determination was made to support the utility of
environmental surveillance outside of emergency/pandemic situations, to determine what and
. CC-BY-NC 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 29, 2021. ; https://doi.org/10.1101/2021.07.26.21261155doi: medRxiv preprint
4
where disease surveillance has been conducted in the past, and to support expansion and
extension of surveillance to other pathogens and regions.
Data Extraction
We initially extracted the following information from the articles meeting the eligibility
criteria: period of sampling, country the sampling occurred in, pathogen(s)/disease(s) being
monitored, number of samples pulled, amount of sample pulled, sample type (grab, composite,
other), method of detection, overall findings, was genetic typing done, and did the researchers
connect their findings to population health. The primary information of interest were the
disease(s) being monitored, method of detection, and if the authors connected their findings to
population health.
Role of the funding source
There was no funding source for this study.
Results
Literature searches initially identified 1005 entries (after removing duplicates), of which
159 abstracts met the inclusion criteria. After review of the articles, 100 scientific papers were
included (Figure 1, Table 1).
4
. CC-BY-NC 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 29, 2021. ; https://doi.org/10.1101/2021.07.26.21261155doi: medRxiv preprint
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Figure 1. PRISMA flow chart of articles included in the review. Reasons for exclusion include:
hypothetical Models – the experiment was hypothetical and no data were collected; methods
comparison – the paper compared multiple recovery methods; not pathogen –
paper focused on
non-communicable diseases (e.g. diabetes); not surveillance – sampled only once or for non-
surveillance purposes; not WW-based – wastewater was not directly tested; pathogen removal
– paper looked at removal techniques of pathogens in wastewater; not relevant* - e.
g. diseases
not tied to human population, effect on other species/animals
Across the 100 included articles, studies were conducted in 38 countries with the most
studies conducted in Italy (10 studies), China (8 studies), Japan (7 studies), Israel (7 studies),
and Brazil (7 studies). These 5 countries accounted for 39% (39/100) of the studies conducted
across all articles.
Figure 2. Global distribution of studies of wastewater surveillance for infectious disease.
Within the included articles, the most prevalent pathogens found were viruses from the
families Picornaviridae, Calciviridae, Adenoviridae, Reoviridae, and Hepeviridae (Figure 3). Of
the most prevalent families, three of them are known to have pathogens contributing to diarrheal
diseases (Picornaviridae, Caliciviridae, and Reoviridae) and make up 57.5% of the pathogens
studied across all articles. Within the Piconaviridae family, the most prevalent genus studied
was enteroviruses, with poliovirus being the most popular among that genus. Enteroviruses
made up 32.5% (52 instances) of pathogens found in all of the articles. Additionally, there were
20 other families of pathogens that appeared between 1 - 9 times within our literature review,
with a mean of 2.2 appearances and a median of 2 appearances each. Considering the global
burden of disease (Figure 4), diarrheal diseases were the most represented among studies of
wastewater surveillance, with other infectious diseases with a great burden not found in this
systematic review. Infectious diseases of international concern were better represented, with
5
on
es
al
. CC-BY-NC 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 29, 2021. ; https://doi.org/10.1101/2021.07.26.21261155doi: medRxiv preprint
