Optimizing Disease Detection and Containment Through a Waste-Before-Case Approach

by Megan Diamond – Manager, Health Initiative, The Rockefeller Foundation & Aparna Keshaviah – Senior Statistician, Mathematica

When a new public health threat emerges – like the highly infectious Omicron variant of the SARS-CoV-2 virus – detecting the first case before there has been widespread community transmission can be like searching for the proverbial needle in a haystack.

Yet wastewater testing is a tool optimized to do just that. People infected with SARS-CoV-2 shed the virus when they go to the bathroom – including asymptomatic people who may not even know they are infected. The sewers then act like large magnets, aggregating the virus particles found in feces into centralized locations where researchers and public health officials can take samples and detect the virus, sometimes before a clinical case emerges. In fact, over the past week, multiple cities in the United States were able to detect Omicron in the wastewater before a clinical case was identified.

As vaccinations plateau and testing declines, public health officials are looking for alternative means to passively collect data that provides real-time insights for decision-making. Wastewater testing does exactly that, at the fraction of the cost of clinical testing.

Wastewater-based epidemiology (WBE) is not a new field. Decades of evidence have shown that WBE is an effective tool for detecting outbreaks of pathogens like poliovirus and typhoid, with the potential for much more. And although it has been used in several countries, including in the United States, to monitor for SARS-CoV-2, ongoing questions remain on how to best interpret and use data derived from wastewater for pandemic response.

For example, wastewater data is inherently messy, and more work is needed to reliably distinguish signal from noise in viral concentrations collected from wastewater to detect a rising threat. It’s also unclear how wastewater data should be synthesized with other local public health data—such as clinical case counts and reports of Covid-like symptoms—to provide officials with a more holistic measure of Covid-19 risk in their community. The potential of sequencing viral RNA in wastewater remains underexplored, too.

The creation of the Wastewater Action Group (WAG) – which includes leading researchers and public health officials in Atlanta (Emory University), Houston, Louisville, Tribal Nations (Arizona State University) and Tulsa  – is one of the ways that The Rockefeller Foundation and PPI are supporting cities across the US to translate wastewater data into action.  Together, this network of partners is refining wastewater sampling, testing, and sequencing protocols; developing metrics and strategies for wastewater-based risk communication; and expanding wastewater testing to underserved populations that are not connected to centralized wastewater treatment plants.

The impact of these efforts are being seen in real time:

  • In Houston, Texas, partners at the Houston Health Department and Rice University detected Omicron in the wastewater before a confirmed clinical case and subsequently sequenced positive samples from school children residing in the service areas of the wastewater treatment plan.
  • In Louisville, Kentucky, partners at the University of Louisville and Louisville Metro Dept. Public Health & Wellness detected Omicron in the wastewater before a confirmed case in Jefferson County. Through close collaboration with the State of Kentucky, they can now do targeted sequencing within the community.
  • In Tulsa, Oklahoma, partners at the Tulsa Health Department and University of Oklahoma saw an increase in influenza A virus concentration was detected in the wastewater, enabling quick communication to the public.

PPI recently met the growing need for rapid peer-to-peer learning by hosting an urgent meeting focused on wastewater sequencing in light of the emergence of Omicron. More than 30 wastewater testing leaders attended and since then, more than half have either reached out to someone they met on the call or adapted their response plans based on information shared during the session.

PPI is also dedicated to hearing from end users of public health data. Through a collaboration with Mathematica, The Rockefeller Foundation is fielding a nationwide survey among public health leaders.

The results of the survey could inform the development of decision-making tools for public health departments and help policymakers determine how they can best support wastewater surveillance across the country.

At present, no single data source provides a full picture of COVID-19. The most widely reported data—clinical case counts—overlook large swaths of the population that lack access to quality health care. As a result, the first signs of an outbreak are often detected weeks, if not months, after the emergence of a new threat. Wastewater testing is a way to fill this critical data gap.

The world can no longer wait for fragmented, delayed, and biased data. By supporting the development and scaling of wastewater-based epidemiologic tools and knowledge, PPI seeks to boost the capacity of public health officials to detect infectious disease outbreaks and prevent the next pandemic.

Omicron is the Grinch That Stole Christmas

The Center for Disease Control (CDC) is reporting that up to 90% of the infections with COVID-19 Sars 2 Coronavirus are the new Omicron strain. It replicates itself 70 times faster than the Delta strain and contact with an infected person within 12 feet for one or more seconds can result in infection. For those who have been vaccinated against COVID-19 with the Moderna or Pfizer Vaccine, and received a third shot or booster, the expectation is that if they become infected with Omicron, they will either have no symptoms or a mild case. By definition “mild COVID” means your respiratory system is not compromised enough to require hospitalization. Despite this, most of the current deaths in countries which are having a COVID surge are in people older than 65 years of age.

In the past, when patients in this area became infected with COVID-19, we arranged for them to go to the local hospitals to receive an infusion of a monoclonal antibody solution made either by Regeneron or by Eli Lilly. The infusion prevented the infection from becoming severe enough to progress to a severe state requiring inpatient hospital respiratory care. These monoclonal antibodies do not work against Omicron. For this reason, the FDA and CDC have removed the Emergency Use Authorization and ended the administration of these drugs nationwide.

There is a third monoclonal antibody made by Glaxo and Var called Sotrovimab which effectively throttles Omicron, but it is in limited supply. As of today, the State of Florida has received 1050 dosages. Production has been accelerated and hopefully the drug will be available in mid to late January for infusion. There are two new antiviral pills which should work as well. The Pfizer product received FDA approval today and, with production acceleration, some should be available by mid-January. Until these drugs are locally available the medical community has no medications to offer patients who contract the COVID-19 Delta or Omicron variant to limit the severity of the disease.

My advice to my patients and loved ones is to reintroduce distancing and masking. Wear a good N95 mask when you will be around others – especially indoors. If you must be indoors with others, make sure the windows and doors are open and the ventilation is excellent. If there is an air filtration system with HEPA Merv 13 level filters and ultraviolet light that adds protection. Distancing with the aggressive Omicron variant will require 12 feet not six feet.

This is a heartbreaking restrictive change in scheduling and behavior we are asking for at a time of the year when families and friends travel to gather to celebrate. Younger and leaner healthier individuals who are vaccinated will survive this. The real questions are who they will transmit this infection to unknowingly, who is too young to be vaccinated or too old to have a robust immune system?

Our office staff will be reassessing the risk to patients and staff daily. With the local testing positivity rate >10% in Palm Beach County, our contacts will be by phone and telehealth. When the Pfizer anti-viral pill Paxlovid is available, and or Sotrovimab for infusion, we will return to regular in-office patient visits.

I apologize for the inconvenience. Stay safe and call if you have questions.

COVID-19 & Public Health Departments

I received an email from the Florida Department of Public Health saying a Federal Judge from Missouri had struck down the necessity for health care workers to be vaccinated against COVID or risk losing their jobs. The suit was brought by several states and, while Florida was not part of this particular lawsuit, was part of other lawsuits which are ongoing.  My immediate thought is that the Florida Department of Public Health should have more important things to do such as providing public health! 

I contrast this with a story told to me by a reliable source – a 66-year-old New Yorker. He lives in the Upper West Side of Manhattan with his 63-year-old wife and spends winters at a home on the West Coast of Florida. 

They packed up their car and, for the first time, hired a professional driver to transport it plus some belongings down to their Florida winter home . They were scheduled to board a flight to Sarasota on December 2nd until the husband received a text message from the NY City Department of Health.  The message said that using cell phone location tracking data they have discovered that the husband was within six feet of an individual who tested positive for COVID-19.  They provided contact information and requested he call the number to receive precautionary recommendations.

When he called, they advised that if he was vaccinated and had no symptoms of COVID he should be tested in four to seven days but remain masked and quarantined until then. The husband stays home most days, except for a daily morning bicycle ride along the Hudson River down to Battery Park where he rents out a gym for a private 90-minute workout with a vaccinated masked trainer who is the only other individual in the facility.  He then bikes home along the Hudson River stopping at a food truck on sunny days to purchase a cup of coffee which he drinks alone on a bench overlooking the river. He and his wife mask, maintain safe distances from others and avoid indoor facilities.

The couple decided to follow the advice of the Health Department. They separated within their home staying masked indoors. They rescheduled their flights for the following week. They have appointments to have nasal PCR tests on day 7 after exposure.

Wouldn’t it be lovely if we had a public health department in Florida that actually practiced public health along with citizens who respected the health of others by following recommendations to prevent transmission of the disease?

Dementia – Multiple Trials & Interventions to Delay Cognitive Decline

There have been multiple studies presented at scientific meetings recently that look at what influences the development of dementia and what may delay it. We have known for years that anything that interferes with sensory input to the brain can lead to increased risk of dementia. Improving hearing with hearing aids was found long ago to improve your chances to avoid dementia as you age.

A recent study published by Cecelia Lee, MD MS in JAMA Internal Medicine revealed that individuals undergoing improvement of vision with cataract surgery reduced their risk of dementia significantly. The study looked at over three thousand patients undergoing cataract surgery and or glaucoma treatment between the years 1994 and September 2018. Patients were evaluated every two years during the study with Cognitive Abilities Screening Instrument (CASI) and those with scores indicating a cognitive decline were referred for more detailed testing. Although having cataract surgery reduced your risk of dementia treating glaucoma, it did not provide the same risk reduction for dementia. There were numerous theories on why cataract repair helped based on the type and quality of light reaching the retina and brain, but it was an improvement to normal in another of our senses.

Another study looked at the effect of taking a daily multivitamin on the risk of developing dementia. This study funded in part by Centrum Silver and called the COSMOS trial looked at 2262 men and women all older than sixty-five with a mean age of seventy-three. They were evaluated before entry into the study with cognitive tests and again every year for three years. Those taking a multivitamin exhibited a “slowing of cognitive aging by 60%”. Taking a multivitamin seems like an easy inexpensive intervention to preserve cognitive function and hopefully these results will be confirmed and reproduced in future studies.

Recent studies looked at the benefits in maintaining brain volume and cognitive function when drinking coffee and tea containing caffeine. The studies showed that coffee drinkers benefitted more than tea drinkers but they both benefitted in reducing the risk of cognitive decline. A recent publication took the research a step further by having test subjects drink several cups of coffee and several cups of tea per day. The benefits of drinking both beverages on the same day were far greater than drinking individually.

    Last but not least , a study executed by the Cleveland Clinic Genomic Medicine Institute under the direction of F. Cheng, PhD, looked at insurance data to determine if taking Viagra (Sildenafil) modified your risk of developing Alzheimer’s disease (one form of dementia)  The study over a 6-year period suggested that Viagra users were 69% less likely to develop Alzheimer’s disease than non-Sildenafil users. This study, which was announced and covered extensively on television news and the print media, resulted in more phone calls to my office than the other studies. This was an observational type of study and further research is needed before prescribing this medication for this preventive reason.

Of interest to me was the fact that most of the men who called asking for Viagra after reading this article were on other medications for other medical illnesses that prevented them from safely using Sildenafil products.

Phthalates and Early Death

Environmental Health is an online journal that printed the research of Leonardo Trasande, M.D. who practices and works at the NYU Grossman School of Medicine in New York City. His teams’ research found that the death toll and lost working time due to illness from phthalates were far higher than previously thought.

Their study examined middle aged adults between 55 and 64 years during the years 2013 and 2014. The analysis used the data of 5303 adults participating in the U.S. National Health and Nutrition Examination Survey who provided urine samples as part of the study. Phthalates can be measured in the urine and there are known reference ranges of normality. Their research, when extrapolated to the middle-aged population, estimates about 100,000 deaths and forty billion dollars or more lost in economic productivity among 55-64 year old Americans during 2013 and 2014.

Phthalates are a group of chemicals used to make plastics more durable. They are called “ plasticizers” and can be found in personal care products such as soaps, shampoos, hair sprays, fragrances. They are additionally seen in vinyl flooring , lubricating oils and in polyvinyl chloride plastics. These polyvinyl plastic products are seen in food wrappings, garden hoses, medical tubing ( IV tubing). Some of them get into our foods and we eat them and drink them. Some of them are aerosolized and we inhale them. In human beings we see damage to the lungs, liver, kidneys and reproductive organs from phthalate exposure.

Women apparently have a higher urinary phthalate content than men because there are so many of these chemicals in personal care products. There have even been reports of phthalates in infant diapers. Limiting exposure to these chemicals is important but learning where they are and what your risk is remains difficult. This is an area that requires far more timely research and far more transparency.

Alcohol & Gastrointestinal Cancer

For many years now we have been taught that adult consumption of alcohol in moderation is an acceptable life practice. We have been told that women can safely drink one alcoholic beverage per day, if not pregnant, while men can drink two per day. Of course, driving a car or handling machinery while under the influence is not acceptable. We were also taught that our alcoholic beverages were highly caloric and that they, in fact, were considered “empty” calories providing little if any nutritional benefit.

Unfortunately, the purchase and consumption of alcoholic beverages during the COVID-19 Pandemic has markedly increased as a result of isolation, stress and quarantine.  We have also seen individuals binge drink large quantities of alcohol and even seen individuals become toxic with alcohol poisoning. Moderation and being responsible are always stressed with regard to alcohol consumption.

A study in JAMA Network Open may make us reconsider those ideas. This study looked at the adult South Korean population from 2009- 2017 who did not have a gastrointestinal cancer diagnosed. They followed almost 12,000 adults aged 40 or older with 40% agreeing they drank alcohol. Participants were divided into mild, moderate and heavy drinkers based on the volume of alcohol consumed. They were then followed and compared to the non-drinking portion of the group for the development of GI cancers.

The study found that the frequency of drinking is more of a risk factor for developing GI cancers than the actual volume consumed. In fact, among mild drinkers, those who had an alcoholic drink 3-4 nights a week had a greater chance of developing a GI cancer than those who drank heavily but less frequently.

In life nothing comes without a price. The question I raised and have not received an answer to is “Just how high is this risk?” Is the risk of developing a GI cancer with a cocktail with dinner equivalent to the risk of being killed in an auto accident on a major highway? Is a cocktail with dinner riskier than smoking a pack of cigarettes per day, or sky diving?

Until someone can present the data in a manner that I understand the true risk, it’s difficult to develop a health recommendation. Were these results an outlier unique to the Korean population? When I know based on evidence, I will let you know. Until then “cheers.”

Should I Measure My COVID Antibodies?

On a daily basis I get asked by patients to please add an antibody test to their necessary blood work monitoring chronic conditions and medications to see if they have immunity against COVID-19. Some want the information just to feel comfortable that they have responded to their vaccine administration. Some have had COVID-19 and want to see if their immunity is sufficient to avoid taking a COVID-19 vaccine or booster shot? Some who have not been vaccinated and have been ill recently but not tested just want to know if the illness was COVID-19.

The topic was just reviewed in the online journal MedPage Today. First of all, the test you order to determine if you developed immunity based on receiving the vaccine is different than the test you order to measure antibodies arising from a previous infection. Nathan Landau, PhD, a virologist with the NYU Grossman School of Medicine believes we do not yet have the data to determine if antibodies we develop from infection or vaccination are appropriate to provide immunity. “The real answer is we just don’t know. It takes time to gather that data, to know what titers people have and what their chance of getting infected is.”

To determine the level of antibody that is needed to prevent infection scientists must first perform neutralization assays or tests. These are not performed in the commercial labs that do antibody tests for COVID-19. The neutralization assay is the Gold Standard . The test is performed by taking the blood of an infected individual, isolating the blood serum and then diluting it into different strengths. The different strengths are then mixed with the live Sars2 Coronavirus in a set amount. They then observe if the virus is killed off.

 In order to kill the virus you must have neutralizing antibodies. The commercial labs only measure the total antibody not specifying how much of that is actually successful in neutralizing the live virus. The neutralization assay looks to see what dilution of the antibody kills off 50% of the virus.

For example a dilution of 1:100 means 1 milliliter of serum was mixed with 99 milliliter of saline. At this point we do not know what dilution is necessary to prevent infection. This data is known for diseases such as measles, German measles and different strains of hepatitis.

There has just not been enough time yet to make this determination but the research is ongoing and conclusions should be released soon. What is known is that the mRNA vaccines produce more immunity than the non mRNA vaccines. They also know that the antibody produced from a vaccine is superior to the immunity from infection against new variants and reinfection. The commercial tests are expensive, time consuming and use reagents affected by supply chain problems.

Relief From Migraine Headaches Erenumab (Aimovig) versus Topiramate

Patients with frequent migraine headaches, which disabling symptoms, were in the past treated with oral medications called beta blockers such as propranolol or metoprolol to prevent recurrences. Drugs such as amitriptyline (Elavil) and other antidepressants were used as well. Triptans, caffeine, acetaminophen, narcotics, and Ergot alkaloids rounded out the therapy. The headaches could be crippling and disabling for suffering patients. In recent years, physicians have added topiramate (Topamax) and injectable Aimovig (Erunumab) to the regimen.

Recently a double blinded controlled research project looked at 777 adults with at least four migraine headache days per month. To be in the study these individuals needed to have never been treated with migraine medications. Patients were randomly assigned to receive either Aimovig 70 mg, the 140 mg injection monthly or topiramate at a dosage of 50- 100 mg per day.

The study ran for twenty-four weeks. This was a phase 4 head-to-head study of the efficacy of one versus the other (Clinical Trials.gov Identifier: NCT03828539. The endpoints were at least a 50% reduction in monthly migraine days plus ability to remain in the study without leaving due to side effects from the medication.

The results and conclusion were that Aimovig injections resulted in fewer migraine headache days per month and less discontinuation due to side effects of the medication. Only about 11% of the Aimovig patients stopped the drug due to side effects (fatigue, nausea, disturbance in attention and dizziness) versus almost 40% in the Topiramate group (parasthesias, disturbance in attention, fatigue, and nausea).  The Aimovig group had a 55.4% of its participants achieve at least a 50% reduction in monthly migraine days compared with 31% in the topiramate group.

Patients with recurrent and severe headaches need a full neurological evaluation to determine the exact cause and type of headache they are experiencing. Once the cause and type of the headache are known, it is wonderful to have this calcitonin gene-related peptide receptor antagonist available to prevent migraines in sufferers of these severe headaches.