Associate Professor Masaaki Kitajima from the Water Quality Control Engineering Laboratory at Hokkaido University discusses the importance of wastewater-based epidemiology in detecting and preventing further disease outbreaks.
Wastewater-based epidemiology is the process of analysing wastewater to determine the consumption of, or exposure to, chemicals or pathogens in a population.
Associate Professor Masaaki Kitajima from the Water Quality Control Engineering Laboratory at Hokkaido University has worked in the area of wastewater-based epidemiology for some time and the recent COVID-19 pandemic has accelerated his research efforts significantly.
The Innovation Platform spoke with Associate Professor Kitajima to find out more about his recent achievements and wastewater-based epidemiology in general.
What is wastewater-based epidemiology and what is its potential for use in healthcare research? Has its importance been accelerated by the COVID-19 pandemic?
Wastewater-based epidemiology (WBE) is a field of study that involves analysing wastewater samples to gather information about the health status of a population. By monitoring the presence and levels of specific pathogens, such as viruses, researchers can gain insights into the prevalence and trends of diseases in a community.
WBE has the potential to be a valuable tool in healthcare research for multiple reasons.
Firstly, wastewater analysis can provide early warning signs of disease outbreaks in a population. This is particularly useful for infectious diseases like COVID-19, as infected individuals shed the virus in their faeces even before symptoms appear. By monitoring wastewater, health authorities can identify viral RNA fragments and estimate the prevalence of the virus in a community, potentially allowing for early intervention and control measures.
In addition, WBE can provide a broader understanding of the infectious disease prevalence of a population by analysing the presence of various pathogens in wastewater. It can help to identify infection trends and the overall burden of infectious diseases within a community. This information can aid in public health planning, resource allocation, and policymaking.
Thirdly, WBE can complement traditional healthcare surveillance methods, which rely on clinical data and individual testing. It provides a population-level perspective, covering a larger segment of the population, including asymptomatic individuals who may not seek medical care. WBE can fill gaps in data and provide a more comprehensive picture of public health.
The importance of WBE has indeed been accelerated by the COVID-19 pandemic. During the pandemic, researchers and public health agencies recognised the potential of monitoring wastewater for SARS-CoV-2, the virus causing COVID-19.
WBE has been utilised as a tool to track the presence and spread of the virus in communities, estimate infection rates, monitor the effectiveness of control measures, and provide early warnings of outbreaks. It has proven useful in identifying viral hotspots, including in asymptomatic individuals, and has acted as a complementary surveillance method alongside individual testing.
The pandemic has highlighted the value of WBE as an additional tool for monitoring and responding to infectious diseases.
Can you outline your key research focuses/ projects currently? What are the aims and objectives of your research?
My current research focuses on wastewater-based epidemiology concerning viral diseases with the following key projects:
- Detection and monitoring of viral outbreaks: We aim to detect and monitor the presence of viral pathogens in wastewater to provide early warning signs of outbreaks. This includes the detection of viruses causing diseases, such as SARS-CoV-2, influenza virus, RS virus, norovirus, monkeypox virus, and others. We focus on developing sensitive methods to detect viruses in wastewater samples.
- Estimating disease prevalence and dynamics: We seek to estimate the prevalence and dynamics of viral diseases within a population. By quantifying viral nucleic acids in wastewater samples, we can track changes in disease patterns over time and predict the number of cases in the next several days. This information can help in understanding transmission dynamics, evaluating the impact of control measures, and guiding public health interventions.
- Identification of emerging viral threats: Our WBE research focuses on early detection and identification of emerging viral threats. By actively monitoring wastewater for novel or known viruses, we can potentially identify new viral strains or variants before they cause significant outbreaks. This early detection can help public health agencies prepare and respond effectively to emerging viral diseases.
- Spatial and temporal tracking of viral transmission: WBE allows for spatial and temporal tracking of viral transmission patterns within a community. By analysing wastewater samples from different locations or over time, we can gain insights into the geographic distribution of viral infections, monitor the spread of viruses between different areas, and identify potential hotspots or clusters of infection.
- Integration with clinical data and individual testing: We aim to integrate wastewater surveillance with clinical data and individual testing to provide a more comprehensive understanding of viral diseases. Combining data from different sources can enhance the accuracy of disease surveillance, identify asymptomatic cases, and provide a population-level perspective on viral transmission and prevalence.
These research projects demonstrate the potential of WBE in monitoring, tracking, and responding to viral diseases. By leveraging wastewater analysis, we aim to contribute to early detection, prediction of cases, and overall public health planning for viral outbreaks.
What have been the most standout achievements from your recent research?
I worked with researchers from Shinogi, a major pharmaceutical company in Japan, to develop a highly sensitive and practically usable method for the detection of viral RNA in wastewater.
We devised this method as a response to the COVID-19 pandemic, and to the challenge of finding SARS-CoV-2 in wastewater in areas where there are low infection rates. In such countries, including Japan, it was hard to detect the presence of the virus in wastewater using existing detection methods.
The method, known as Efficient and Practical virus Identification System with ENhanced Sensitivity for Solids (EPISENS-S), employs direct RNA extraction from wastewater pellets formed via low-speed centrifugation. The results demonstrated that the sensitivity of the EPISENS-S method was two orders of magnitude higher than that of the conventional method (PEG precipitation, followed by regular RT-qPCR; PEG-QVR-qPCR).1
Following on from the success of the EPISENS-S method, we went on to develop a more sensitive and robust method (EPISENS-M) employing adsorption-extraction to detect SARS-CoV-2 RNA in wastewater.
The EPISENS-M, which was modified from the EPISENS-S, allowed SARS-CoV-2 RNA detection from wastewater at a 50% detection rate when newly reported COVID-19 cases exceed 0.69/100,000 inhabitants in a sewer catchment.
Using the EPISENS-M, a longitudinal study was conducted and revealed a strong correlation between SARS-CoV-2 RNA concentration in wastewater and the new COVID-19 cases reported by intensive clinical surveillance. Based on this dataset, a mathematical model was developed based on viral shedding dynamics to estimate the newly reported cases using wastewater SARS-CoV-2 RNA concentration data and recent clinical data prior to sampling day.
Collectively, our results highlighted the potential of WBE to predict the number of COVID-19 cases in a community when fully notifiable clinical surveillance is not practiced.2
I also worked on a cross-sectional study which investigated the association of SARS-CoV-2 load in wastewater with the numbers of confirmed COVID-19 cases and tests for close contacts at the Tokyo 2020 Olympic and Paralympic Games. Here, daily testing of both athletes and support staff, along with sampling and testing of the wastewater in the sewage system, was carried out.
The results of these tests were reported to the Tokyo 2020 Organising Committee. Links were found between clinically reported cases and viral loads in wastewater. Overall, the study showed that WBE and clinical tests can can complement each other.3
In a further study, we applied the EPISENS-M method to detect influenza and RS viruses in addition to SARS-CoV-2, and investigated their concentrations in wastewater samples that had been stored since 2018 October (before the beginning of the COVID-19 pandemic).
The results demonstrated that infection of influenza and RS viruses was suppressed because of the countermeasure for COVID-19 and that ‘wastewater banking’ is useful in revealing the impact of the pandemic on other pathogens, such as influenza and RS viruses.4
What are the challenges facing epidemiology research and how can these be overcome?
Wastewater-based epidemiology research faces the following challenges that need to be addressed to maximise its potential and overcome limitations:
- Standardisation: Currently, WBE research lacks standardised protocols and methods, making it difficult to compare and integrate data from different studies or locations. Establishing standardised sampling, analysis, and data reporting procedures can enhance the comparability and reliability of WBE data. Collaborative efforts and international frameworks can facilitate the harmonisation of WBE practices.
• Quantitative interpretation: Interpreting quantitative data from wastewater samples can be challenging due to factors like dilution, degradation, and variations in sampling and analysis methods. Developing robust models and algorithms that account for these factors can improve the accuracy and precision of estimating viral loads and disease prevalence. Calibratio with clinical data and validation studies can further enhance the reliability of quantitative interpretations.
• Sensitivity and detection limits: The sensitivity of viral detection in wastewater can vary depending on the viral load, the efficiency of sample concentration, and the analytical methods used. Enhancing sample processing techniques, optimising detection methods, and developing more sensitive and specific assays can improve the detection limits of WBE, enabling the detection of low viral concentrations and early-stage infections.
• Integration with traditional epidemiological surveillance: Integrating WBE with traditional epidemiological surveillance systems and individual testing is essential for comprehensive disease monitoring and response. Establishing effective communication channels and collaborations between wastewater researchers, public health agencies, and clinical professionals can facilitate the exchange of information, data sharing, and co-ordinated actions.
• Cost-effectiveness and scalability: WBE research may require significant investments in laboratory infrastructure, sample collection, and analysis. Finding cost-effective approaches, optimising sampling strategies, and leveraging automation and high-throughput methods can enhance the scalability and affordability of WBE.
By addressing these challenges through collaboration, standardisation, technological advancements, and stakeholder engagement, WBE research can overcome limitations and realise its potential as a valuable tool for public health surveillance, monitoring, and response.
Can wastewater-based epidemiology detect multiple viruses at one time?
Yes, wastewater-based epidemiology (WBE) has the capability to detect multiple viruses at one time. A wastewater sample can contain multiple types of viruses shed from different infected individuals, and WBE involves analysing wastewater samples for the presence of viral genetic material, such as viral RNA or DNA.
Various molecular techniques, such as quantitative PCR (qPCR), digital PCR (dPCR), microfluidics-based high-throughput qPCR (MFQPCR/HT-qPCR), and next-generation sequencing (NGS), can be employed to detect and identify different viruses simultaneously.
By targeting specific genetic regions unique to different viruses, we can design assays that allow for the detection and quantification of multiple viral targets in a single wastewater sample. These assays can be customised to include a panel of viruses of interest, including both known viral pathogens and emerging viral threats.
The advantage of detecting multiple viruses simultaneously in wastewater is that it provides a comprehensive overview of viral presence and diversity within a community or population. This approach enables researchers to monitor and track multiple viral infections, estimate the prevalence of different viruses, identify co-circulation patterns, and detect the emergence of new viral strains or variants.
However, it is important to note that the simultaneous detection of multiple viruses in wastewater does require careful assay design and optimisation. The sensitivity, specificity, and dynamic range of the assays should be considered to ensure accurate and reliable results for each targeted virus. Additionally, data analysis methods need to be developed to interpret the presence and relative abundance of multiple viral targets in complex wastewater samples.
References
- https://www.sciencedirect.com/science/article/pii/S0048969722041985
- https://www.sciencedirect.com/science/article/pii/S0160412023000168
- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2795496
- https://www.sciencedirect.com/science/article/pii/S0048969723013104
Please note, this article will also appear in the fifteenth edition of our quarterly publication.
