Asymptomatic Infections Drive Many Epidemics

Monkeypox, COVID, and polio: These three very different diseases have been dominating news cycles recently, but they share at least one common characteristic: some people can become infected — and in turn infect others — while showing no symptoms.

In 1883, the famous bacteriologist Friedrich Loeffler (1852–1915) recognized that an individual’s asymptomatic carriage of bacteria could lead to diphtheria in others. Now, as then, asymptomatically infected people present a conundrum: How do you fight the spread of a disease when you can’t identify some of the people who are spreading it?

“Typhoid Mary” is perhaps the quintessential example of asymptomatic transmission of infections leading to illness and death. At the turn of the 20th century, young Mary Mallon emigrated from Ireland to New York City, where she soon became a cook for wealthy Manhattan families.

George Soper, a sanitary engineer, was hired by a stricken family to investigate. After epidemiologic study, he suspected that Mary was a carrier of Salmonella typhi, the bacterial cause of typhoid fever. He persuaded the NY Department of Health to test her — against her will — for infection. After her stool was found to test positive for Salmonella, Mary was forcibly moved to North Brother Island, where she remained largely isolated from others for the next 2 years. In 1910, she was released by a new commissioner after promising not to work as a cook.

However, working under an assumed name, Mary resumed cooking at the Sloane Hospital for Women in Manhattan. Over the next 3 months, at least 25 staff members became ill. Having been found out, Mary was again exiled to the island, where she spent the rest of her life. She died in 1938 after having infected at least 122 people, five of whom died.


Asymptomatic infections are primary drivers of COVID. Earlier in the pandemic, a meta-analysis suggested a 40% rate of asymptomatic infections, although some early reports arrived at lower estimates. A 2021 JAMA Network Open modeling study indicated a 60% rate.

Those rates are changing with the Omicron variants, by which even more cases are asymptomatic. Is this from a mutation in the virus? Some suggest that it is most likely due to prior vaccination resulting in boosted immunity and infections being milder. Of concern is that, although people may be asymptomatic, they still have the same viral load in their nose and can readily transmit infection.

Dr Vincent Racaniello

Vincent Racaniello, PhD, a professor of virology at Columbia University in New York, told Medscape Medical News that “SARS-CoV-2 COVID is so effective at transmitting because it does this asymptomatic transmission. And so you’re out and about, you have no idea that you’re infected. You’re effectively doing what we call community transmission.”

This distinguishes SARS-CoV-2 from SARS-CoV-1. SARS-CoV-1 — which caused the SARS epidemic in 2002–2004 — had very little asymptomatic shedding. With COVID, on the other hand, “A lot of people are infected but never transmit,” Racaniello added. “I think 80% of transmissions are done by 20% of infected people because those are the ones who are shedding the most virus.”


The August case of paralytic polio in Rockland County, New York, is “the first case of polio reported in the United States in nearly 10 years, and only the second instance of community transmission identified in the US since 1979,” a spokesperson for the Centers for Disease Control and Prevention (CDC) told Medscape via email. “Although no additional cases of polio have been reported at this time, recent wastewater findings elevate concerns that poliovirus is present in these communities, posing a risk to those who are unvaccinated.”

Poliovirus has now been found in the wastewater of New York City and three surrounding counties: Rockland, Orange, and Sullivan.

Unlike COVID, which is spread through air and respiratory secretions, polio has primarily fecal-oral transmission, meaning it is spread by people ingesting food or water contaminated with stool.

According to the World Health Organization, up to 90% of infections are unrecognized because the person has no to minimal symptoms. Symptoms are nonspecific in the remainder. Only a small proportion of those infected go on to develop paralysis.

Dr Paul Offit

Paul Offit, MD, a virologist and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told Medscape that before widespread immunization, polio “caused 25,000 – 30,000 children every year to be paralyzed and 1500 to die. Roughly 1 of every 200 children who was infected was paralyzed. We had the inactivated vaccine followed by the oral polio vaccine (OPV). The price that we paid for the OPV was that rarely it could revert to the so-called neurovirulent type, a paralytic type.”

Use of the OPV was discontinued in 2000 in the US but is still widely used worldwide because it is inexpensive and easier to administer than injections. It appeared that we were close to completely eradicating polio, as we had smallpox, but then vaccine-derived polio virus (VDPV) started cropping up in Africa, the Middle East, and Asia. They are mainly from the type 2 virus, as is the NY case. There have been three other cases of VDPV in the US since 2000.

Now, Offit estimates that only 1 in 2000 of those infected become paralyzed. This is why the CDC and epidemiologists are so concerned about the Rockland patient — that one case of paralysis could represent a large pool of people who are infected with polio and are asymptomatic, continuing to shed infectious virus into the sewage.

The CDC confirmed that it began conducting wastewater testing for polio in August 2022. In their interviews with Medscape, Offit and Racaniello were both critical of this, stressing that it is essential to do wastewater testing nationally, since asymptomatic polio can be expected to crop up from international travelers who have received OPV.

Many countries conduct that kind of wastewater surveillance. Racaniello was particularly critical of the CDC. “We’ve been telling CDC for years, at least a decade, Why don’t you check the wastewater?,” Racaniello said “It’s been known for many years that we should be looking to monitor the circulation of these viruses. So we are using paralysis as a sentinel to say that this virus is in the wastewater, which is just not acceptable!”

Apparently there was some concern that the public would not understand. Offit viewed it as one more piece of necessary education: “You shouldn’t be alarmed about this as long as you’re vaccinated. If you’re not vaccinated, realize that this is a risk you’re taking.”


Monkeypox cases have been skyrocketing in the US in recent weeks. More than 18,000 cases have been reported since the first case in Boston on May 19, 2022.

Dr Stuart Isaacs

“Monkeypox was such a rare zoonotic disease, and the disease always historically was introduced through animal contact,” Stuart Isaacs, MD, a pox virologist at the University of Pennsylvania, told Medscape. “And then the infected person would have potential spread within the household as the most common human-to-human spread, The sexual transmission is driving a lot of this infection and potentially allowing this to efficiently spread from person to person.”

A recent study from Belgium, available only as a preprint, created concerns about potential asymptomatic transmission of monkeypox Three men had undergone testing for anogenital chlamydia and gonorrhea but showed no clinical signs of monkeypox. The same samples were later tested by polymerase chain reaction (PCR), and their viral load in anorectal swabs was similar to or slightly lower than that of symptomatic patients. While no cultures were done, the patients seroconverted by later antibody testing, confirming infection.

Via email, a CDC spokesperson told Medscape, “At this time, CDC does not have enough data to support transmission from aerosolized virus for the ongoing monkeypox outbreak, or to assess the risks for transmission from asymptomatic people. The data supports the main source of transmission currently as close contact with someone who is infected with monkeypox.”

Isaacs agreed, saying studies of smallpox, a related orthopox virus, also suggested this.

In the UK, the Institute of Tropical Medicine is offering PCR testing for monkeypox to all patients who come for gonorrhea/chlamydia screening. Racaniello said, “I think that would be great to get a sense of who is infected. Then you could look at the results and say what fraction of people go on to develop lesions, and they give you a sense of the asymptomatic rate, which we don’t know at this point.”

Unfortunately, to be tested for monkeypox in the US requires that the patient have a lesion. “This is part of the dropped ball of public health in the US,” Racaniello said. “We’re not thinking about this…. We need to be doing [infectivity] experiments. So then the question is, how much infectious virus do you need to transmit?”


We’ve seen that asymptomatic carriage of bacteria and viruses occurs readily with typhoid, COVID, diphtheria, and polio (among many other organisms, such as methicillin-resistant Staphylococcus aureus or group A strep) and is far less likely with monkeypox.

Two common denominators emerged from these interviews. The first and biggest hurdle is identifying asymptomatic carriers, which is hampered by the politicization of the CDC and funding cuts to public health. “It used to be the CDC was all about public health, and now it’s administrators, unfortunately,” said Racaniello, citing science writer Laurie Garrett, author of the influential 1994 book, The Coming Plague.

We don’t conduct proper surveillance, he pointed out. Wastewater surveillance has been neglected for more than a decade. It has been used for SARS-CoV-2 but is only now being initiated for polio and monkeypox. Norovirus testing would also be especially helpful in reducing foodborne outbreaks, Racaniello suggested.

The second common denominator is the need to increase the availability and uptake of vaccines. As Racaniello said about COVID, “The virus is here to stay. It’s never going to go away. It’s in humans. It’s in a lot of animals. So we’re stuck with it. We’re going to have outbreaks every year. So what do you do? Get vaccinated.” And he added, “Vaccination is the most important strategy to go on with our lives.”

Isaacs was a bit more tempered, not wanting to oversell the vaccine. He said, “The vaccine is just part of the toolkit,” which includes education, testing, isolation, and reducing risk, all of which decrease the transmission cycles.

Speaking of how anti-vaxxers had specifically targeted the Hasidic community in New York State’s Rockland County, Offit noted, “I don’t think it’s a knowledge deficit as much as a trust deficit.” He said officials should identify people in communities such as these who are trusted and have them become the influencers.

The final major hurdle to controlling these outbreaks remains global disparities in care. Monkeypox has been endemic in Nigeria for decades. It was only when it spread to Europe and America that it received attention. Polio has been actively circulating in Africa and the Middle East but is only getting attention because of the New York case.

Africa was unable to afford COVID vaccines until recently. While many in the US are on their fourth booster, as of December 2021, more than 80% of people in Africa had not yet received a single dose, according to an article by Munyaradzi Makoni in The Lancet Respiratory Medicine.

Echoing Peter Hotez’s long-standing plea for “vaccine diplomacy,” Racaniello concluded, “My philosophy has always been we should give [vaccines] to them. I mean, we spend trillions on guns. Can’t we spend a few hundred million on vaccines? We should give away everything in terms of medicine to countries that need it, and people would like us a lot better than they do now. I think it would be such a great way of getting countries to like us…. So what if it costs a billion dollars a year? It’s a drop in the bucket for us.”

Given globalization, an infectious outbreak anywhere is a risk to all.

Racaniello and Offit report no relevant financial relationships. Isaacs receives royalties from UpToDate.

Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. You can find her at or on Twitter @drjudystone.

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