Study suggests onsite monitoring at buildings or complexes could aid efforts against disease spread
Photo by Jan Antonin Kolar on Unsplash
In a new study, wastewater surveillance for multiple pathogens at five different sites—including an office and a museum—identified local trends that were not captured in larger surveillance programs, and some sites used the data to inform efforts to prevent disease spread. Jay Bullen of Untap Health in London, U.K., and colleagues present these findings in the open-access journal PLOS Global Public Health.
People with viral infections produce waste containing viral RNA that ends up in wastewater in sewage systems. Measuring viral RNA levels in wastewater at treatment plants can be a cost-effective way to monitor community health. For instance, this method has been useful for monitoring COVID-19 infection trends and tracking polio eradication efforts.
Prior research suggests that wastewater surveillance programs that track multiple diseases at once could be beneficial at the municipal level. However, few studies have assessed their potential value at smaller, site-specific scales.
To fill that gap, Bullen and colleagues monitored daily wastewater concentrations of multiple viruses at five different sites in the U.K.; an office, a charity center for elderly citizens, a museum, a university co-working space, and a care home. The community size of the sites ranged from 50 to 2,000 people, and the researchers measured wastewater levels of the viruses SARS-CoV-2, influenza A and B, RSV A and B, and norovirus GI and GII.
Analysis of trends captured in the wastewater measurements revealed links with site-specific reported events, including staff illness, cleaning practices, and holidays. At the care home, where the community had less contact with the larger regional community, wastewater data captured local events that were not seen in public health data. In larger, more open communities, such as the university space, wastewater data aligned more closely with public health data.
Some sites began using the wastewater data to help inform decisions about disease prevention efforts, such as enhanced cleaning routines and notices in bathrooms about washing hands with soap.
These findings suggest that near-source wastewater monitoring could benefit local communities and perhaps provide earlier warnings of wider trends. Further research is needed to refine understanding of these potential benefits.
The authors add: “Building-level wastewater surveillance enables detection of norovirus, influenza, RSV and COVID-19 in a local population not captured by national surveillance. We see a future with near-source wastewater surveillance scaled across different communities to provide tailored local infection prevention and control measures, reducing outbreaks.”
“It’s really sore,” my (Josh’s) five-year-old daughter said, cradling her broken arm in the emergency department.
“But on a scale of zero to ten, how do you rate your pain?” asked the nurse.
My daughter’s tear-streaked face creased with confusion.
“What does ten mean?”
“Ten is the worst pain you can imagine.” She looked even more puzzled.
As both a parent and a pain scientist, I witnessed firsthand how our seemingly simple, well-intentioned pain rating systems can fall flat.
What are pain scales for?
The most common scale has been around for 50 years. It asks people to rate their pain from zero (no pain) to ten (typically “the worst pain imaginable”).
This focuses on just one aspect of pain – its intensity – to try and rapidly understand the patient’s whole experience.
How much does it hurt? Is it getting worse? Is treatment making it better?
Rating scales can be useful for tracking pain intensity over time. If pain goes from eight to four, that probably means you’re feeling better – even if someone else’s four is different to yours.
But that common upper anchor in rating scales – “worst pain imaginable” – is a problem.
People usually refer to their previous experiences when rating pain. Photo by Rodnae Productions on Pexels
A narrow tool for a complex experience
Consider my daughter’s dilemma. How can anyone imagine the worst possible pain? Does everyone imagine the same thing? Research suggests they don’t. Even kids think very individually about that word “pain”.
People typically – and understandably – anchor their pain ratings to their own life experiences.
This creates dramatic variation. For example, a patient who has never had a serious injury may be more willing to give high ratings than one who has previously had severe burns.
“No pain” can also be problematic. A patient whose pain has receded but who remains uncomfortable may feel stuck: there’s no number on the zero-to-ten scale that can capture their physical experience.
In reality, pain ratings are influenced by how much pain interferes with a person’s daily activities, how upsetting they find it, their mood, fatigue and how it compares to their usual pain.
Other factors also play a role, including a patient’s age, sex, cultural and language background, literacy and numeracy skills and neurodivergence.
For example, if a clinician and patient speak different languages, there may be extra challenges communicating about pain and care.
Still, we work with the tools available. There is evidence people do use the zero-to-ten pain scale to try and communicate much more than only pain’s “intensity”.
So when a patient says “it’s eleven out of ten”, this “impossible” rating is likely communicating more than severity.
They may be wondering, “Does she believe me? What number will get me help?” A lot of information is crammed into that single number. This patient is most likely saying, “This is serious – please help me.”
In everyday life, we use a range of other communication strategies. We might grimace, groan, move less or differently, use richly descriptive words or metaphors.
Collecting and evaluating this kind of complex and subjective information about pain may not always be feasible, as it is hard to standardise.
As a result, many pain scientists continue to rely heavily on rating scales because they are simple, efficient and have been shown to be reliable and valid in relatively controlled situations.
But clinicians can also use this other, more subjective information to build a fuller picture of the person’s pain.
Visual scales are one tool. For example, the “Faces Pain Scale-Revised” asks patients to choose a facial expression to communicate their pain. This can be particularly useful for children or people who aren’t comfortable with numeracy and literacy, either at all, or in the language used in the health-care setting.
A vertical “visual analogue scale” asks the person to mark their pain on a vertical line, a bit like imagining “filling up” with pain.
Listen for the story behind the number, because the same number means different things to different people.
Use the rating as a launchpad for a more personalised conversation. Consider cultural and individual differences. Ask for descriptive words. Confirm your interpretation with the patient, to make sure you’re both on the same page.
Patients
To better describe pain, use the number scale, but add context.
Try describing the quality of your pain (burning? throbbing? stabbing?) and compare it to previous experiences.
Explain the impact the pain is having on you – both emotionally and how it affects your daily activities.
Paediatric health professionals are trained to use age-appropriate vocabulary, because children develop their understanding of numbers and pain differently as they grow.
A starting point
In reality, scales will never be perfect measures of pain. Let’s see them as conversation starters to help people communicate about a deeply personal experience.
That’s what my daughter did — she found her own way to describe her pain: “It feels like when I fell off the monkey bars, but in my arm instead of my knee, and it doesn’t get better when I stay still.”
From there, we moved towards effective pain treatment. Sometimes words work better than numbers.
New research shows that the adult brain can generate new neurons that integrate into key motor circuits. The findings demonstrate that stimulating natural brain processes may help repair damaged neural networks in Huntington’s and other diseases.
“Our research shows that we can encourage the brain’s own cells to grow new neurons that join in naturally with the circuits controlling movement,” said Abdellatif Benraiss, PhD, a senior author of the study, which appears in the journal Cell Reports. “This discovery offers a potential new way to restore brain function and slow the progression of these diseases.” Benraiss is a research associate professor in the University of Rochester Medical Center (URMC) lab of Steve Goldman, MD, PhD, in the Center for Translational Neuromedicine.
Is neuron regeneration in the adult brain possible?
It is now understood that niches in the brain contain reservoirs of progenitor cells capable of producing new neurons. While these cells actively produce neurons during early development, they switch to producing support cells called glia shortly after birth. One of the areas of the brain where these cells congregate is the ventricular zone, which is adjacent to the striatum, a region of the brain devastated by Huntington’s disease.
The idea that the adult brain retains the capacity to produce new neurons, called adult neurogenesis, was first described by Goldman and others in the 1980s while studying neuroplasticity in canaries. Songbirds, like canaries, are unique in the animal kingdom in their ability to lay down new neurons as they learn new songs. The research in songbirds identified proteins—one of which was brain-derived neurotrophic factor (BDNF)—that direct progenitor cells to differentiate and produce neurons.
Further research in Goldman’s lab showed that new neurons were generated when BDNF and another protein, Noggin, were delivered to progenitor cells in the brains of mice. These cells then migrated to a nearby motor control region of the brain—the striatum—where they developed into cells known as medium spiny neurons, the major cells lost in Huntington’s disease. Benraiss and Goldman also demonstrated that the same agents could induce new medium spiny neuron formation in primates.
Rebuilding and reconnecting brain networks
The extent to which newly generated medium spiny neurons integrate into the brain’s networks has remained unclear. The new research, conducted in a mouse model of Huntington’s disease, demonstrates that the newly generated neurons connect with the complex networks in the brain responsible for motor control, replacing the function of the neurons lost in Huntington’s.
The researchers used a genetic tagging method to mark new cells as they were created, which allowed them to follow them over time as they developed new connections. This enabled the researchers to map the connections between the new neurons, their neighbours, and other brain regions. Employing optogenetics techniques, the researchers turned the new cells on and off, confirming their integration into broader brain networks important for motor control.
A new path for Huntington’s disease therapies
The study indicates that a possible treatment for Huntington’s disease would be to encourage the brain to replace lost cells with new, functional ones and restore the brain’s communication pathways. “Taken together with the persistence of these progenitor cells in the adult primate brain, these findings suggest the potential for this regenerative approach as a treatment strategy in Huntington’s and other disorders characterised by the loss of neurons in the striatum,” said Benraiss.
The authors suggest this approach could also be combined with other cell replacement therapies. Research in Goldman’s lab has shown that glial cells called astrocytes also play an important role in Huntington’s disease. These cells do not function properly in the disease and contribute to the impairment of neuronal function. The researchers have found that replacing the diseased glial cells with healthy ones can slow disease progression in a mouse model of Huntington’s. These glial replacement therapies are currently in preclinical development.
Immune molecules called cytokines play important roles in the body’s defence against infection, helping to control inflammation and coordinating the responses of other immune cells. A growing body of evidence suggests that some of these molecules also influence the brain, leading to behavioural changes during illness.
Two new studies from MIT and Harvard Medical School, focused on a cytokine called IL-17, now add to that evidence. The researchers found that IL-17 acts on two distinct brain regions — the amygdala and the somatosensory cortex — to exert two divergent effects. In the amygdala, IL-17 can elicit feelings of anxiety, while in the cortex it promotes sociable behaviour.
These findings suggest that the immune and nervous systems are tightly interconnected, says Gloria Choi, an associate professor of brain and cognitive sciences, a member of MIT’s Picower Institute for Learning and Memory, and one of the senior authors of the studies.
“If you’re sick, there’s so many more things that are happening to your internal states, your mood, and your behavioural states, and that’s not simply you being fatigued physically. It has something to do with the brain,” she says.
Jun Huh, an associate professor of immunology at Harvard Medical School, is also a senior author of both studies, which appear today in Cell. One of the papers was led by research scientists Byeongjun Lee and Jeong-Tae Kwon, and the other was led by postdocs Yunjin Lee and Tomoe Ishikawa.
Behavioral effects
Choi and Huh became interested in IL-17 several years ago, when they found it was involved in a phenomenon known as the fever effect. Large-scale studies of autistic children have found that for many of them, their behavioural symptoms temporarily diminish when they have a fever.
In a 2019 study in mice, Choi and Huh showed that in some cases of infection, IL-17 is released and suppresses a small region of the brain’s cortex known as S1DZ. Overactivation of neurons in this region can lead to autism-like behavioral symptoms in mice, including repetitive behaviours and reduced sociability.
“This molecule became a link that connects immune system activation, manifested as a fever, to changes in brain function and changes in the animals’ behaviour,” Choi says.
IL-17 comes in six different forms, and there are five different receptors that can bind to it. In their two new papers, the researchers set out to map which of these receptors are expressed in different parts of the brain. This mapping revealed that a pair of receptors known as IL-17RA and IL-17RB is found in the cortex, including in the S1DZ region that the researchers had previously identified. The receptors are located in a population of neurons that receive proprioceptive input and are involved in controlling behaviour.
When a type of IL-17 known as IL-17E binds to these receptors, the neurons become less excitable, which leads to the behavioural effects seen in the 2019 study.
“IL-17E, which we’ve shown to be necessary for behavioural mitigation, actually does act almost exactly like a neuromodulator in that it will immediately reduce these neurons’ excitability,” Choi says. “So, there is an immune molecule that’s acting as a neuromodulator in the brain, and its main function is to regulate excitability of neurons.”
Choi hypothesises that IL-17 may have originally evolved as a neuromodulator, and later on was appropriated by the immune system to play a role in promoting inflammation. That idea is consistent with previous work showing that in the worm C. elegans, IL-17 has no role in the immune system but instead acts on neurons. Among its effects in worms, IL-17 promotes aggregation, a form of social behaviour. Additionally, in mammals, IL-17E is actually made by neurons in the cortex, including S1DZ.
“There’s a possibility that a couple of forms of IL-17 perhaps evolved first and foremost to act as a neuromodulator in the brain, and maybe later were hijacked by the immune system also to act as immune modulators,” Choi says.
Provoking anxiety
In the other Cell paper, the researchers explored another brain location where they found IL-17 receptors — the amygdala. This almond-shaped structure plays an important role in processing emotions, including fear and anxiety.
That study revealed that in a region known as the basolateral amygdala (BLA), the IL-17RA and IL-17RE receptors, which work as a pair, are expressed in a discrete population of neurons. When these receptors bind to IL-17A and IL-17C, the neurons become more excitable, leading to an increase in anxiety.
The researchers also found that, counterintuitively, if animals are treated with antibodies that block IL-17 receptors, it actually increases the amount of IL-17C circulating in the body. This finding may help to explain unexpected outcomes observed in a clinical trial of a drug targeting the IL-17-RA receptor for psoriasis treatment, particularly regarding its potential adverse effects on mental health.
“We hypothesise that there’s a possibility that the IL-17 ligand that is upregulated in this patient cohort might act on the brain to induce suicide ideation, while in animals there is an anxiogenic phenotype,” Choi says.
During infections, this anxiety may be a beneficial response, keeping the sick individual away from others to whom the infection could spread, Choi hypothesises.
“Other than its main function of fighting pathogens, one of the ways that the immune system works is to control the host behaviour, to protect the host itself and also protect the community the host belongs to,” she says. “One of the ways the immune system is doing that is to use cytokines, secreted factors, to go to the brain as communication tools.”
The researchers found that the same BLA neurons that have receptors for IL-17 also have receptors for IL-10, a cytokine that suppresses inflammation. This molecule counteracts the excitability generated by IL-17, giving the body a way to shut off anxiety once it’s no longer useful.
Distinctive behaviours
Together, the two studies suggest that the immune system, and even a single family of cytokines, can exert a variety of effects in the brain.
“We have now different combinations of IL-17 receptors being expressed in different populations of neurons, in two different brain regions, that regulate very distinct behaviours. One is actually somewhat positive and enhances social behaviours, and another is somewhat negative and induces anxiogenic phenotypes,” Choi says.
Her lab is now working on additional mapping of IL-17 receptor locations, as well as the IL-17 molecules that bind to them, focusing on the S1DZ region. Eventually, a better understanding of these neuro-immune interactions may help researchers develop new treatments for neurological conditions such as autism or depression.
“The fact that these molecules are made by the immune system gives us a novel approach to influence brain function as means of therapeutics,” Choi says. “Instead of thinking about directly going for the brain, can we think about doing something to the immune system?”
The Gauteng Department of Health is appealing against a judgment by the Johannesburg High Court ordering it to provide radiation oncology treatment to a backlog of nearly 3000 cancer patients at Charlotte Maxeke Hospital and Steve Biko Hospital.
In April last year, activists from SECTION27, Cancer Alliance and the Treatment Action Campaign (TAC) joined cancer patients to march to the department’s provincial office, demanding that millions of rands set aside for radiation treatment be used.
The matter was then taken to court by the Cancer Alliance, represented by SECTION27, after years of attempts to engage with the department about radiation services. They said in a statement they wanted the court to compel the department to provide treatment to the backlog of cancer patients still waiting.
Some patients have been on the list for nearly three years, while others have died while waiting, according to the judgment by Acting Judge Stephen van Nieuwenhuizen. He noted that “irreparable harm” has occurred and continues to occur in the absence of treatment.
He said the backlog, of mostly Charlotte Maxeke patients, had grown due to a lack of radiation equipment at the hospital and a shortage of staff. This was in spite of an allocation of R784-million over three years, specifically ring-fenced for radiology oncology services. The allocation was also meant to help clear the backlog of patients.
Delays in finalising a tender for these services meant that R250-million was returned to National Treasury at the end of the fiscal year, he said.
The judge found that the provincial department had infringed on the rights of these cancer patients in that a high standard of professional ethics had not been maintained. “Efficient and effective use of resources were not promoted. Services were not provided impartially, fairly, equitably and without bias.”
Judge van Nieuwenhuizen said the provincial health department had done “nothing meaningful” since the money was allocated in March 2023 to actually provide radiation oncology treatment to the cancer patients. “On the other hand, the health and general well-being of cancer patients has significantly deteriorated. There is a clear, imminent and ongoing irreparable harm that cancer patients who are on the backlog list are suffering.”
The judge ruled that the department’s failure to provide radiation services to cancer patients on the backlog list was unconstitutional and unlawful.
He added that the provincial health officials “have conducted themselves as a law unto themselves” and ordered that measures be put in place to ensure officials are “held to account for their constitutionally imposed obligation to provide healthcare services … to cancer patients who are on the backlog list”.
He also ordered that the list of cancer patients still awaiting radiation treatment must be updated within 45 days and that a progress report and long-term plan must be submitted to the court within three months.
Salomé Meyer, director of the Cancer Alliance, told GroundUp the ruling would allow the court to get accurate information on the circumstances of each patient still waiting for treatment.
She said the judgment “confirms that civil society has a role to play to hold the government responsible for what it is supposed to do”.
In a statement on 2 April, the department confirmed that it had filed an application for leave to appeal against the ruling. The department said “there are several substantive grounds of appeal, which if left unchallenged will be greatly prejudicial to the patients undergoing radiation oncology services at the hospitals” and might set an “undesirable” precedent.
