HIV’s “Patient Zero” was exonerated long ago

The news over the past 24 hours has exclaimed over and over:

HIV’s Patient Zero Exonerated

How scientists proved the wrong man was blamed for bringing HIV to the U.S.

Researchers Clear “Patient Zero” from AIDS Origin Story

H.I.V. Arrived in the U.S. Long Before ‘Patient Zero’

Gaetan Dugas: “patient zero” not source of HIV/AIDS outbreak, study confirms

HIV’s supposed “Patient Zero” in the U.S., Gaetan Dugas, is off the hook! He wasn’t responsible for our outbreak!

This is presented as new information.

Gaetan Dugas, from Wikipedia.

It is not, and I think by focusing on the “exoneration” of Dugas, a young flight attendant and one of the earliest diagnosed cases of AIDS in the U.S., these articles (referencing a new Nature paper) are missing the true story in this publication–that Dugas was really a victim of Shilts and the media, and remains so, no matter how many times the science evidence has cleared his name.

First, the idea that Dugas served to 1) bring HIV to the U.S. and 2) spark the epidemic and infect enough people early on that most of the initial cases could be traced back to him is simply false. Yes, this was the hypothesis based on some of the very early cases of AIDS, and the narrative promoted in Randy Shilts’s best-selling 1987 book, “And the Band Played On.” But based on the epidemiology of first symptomatic AIDS cases, and later our understanding of the virus behind the syndrome, HIV, we quickly understood that one single person in the late 1970s could not have introduced the virus and spread it rapidly enough to lead to the level of infections we were seeing by the early 1980s. Later understanding of the virus’s African origin and its global spread made the idea of Dugas as the epidemic’s originator in America even more impossible.

When we think of Dugas’s role in the epidemiology of HIV, we could possibly classify him as, at worst, a “super-spreader“–and individual who is responsible for a disproportionate amount of disease transmission. Dugas acknowledged sexual contact with hundreds of individuals between 1979 and 1981–but his numbers were similar to other gay men interviewed, averaging 227 per year (range 10-1560). And while Shilts portrayed Dugas as a purposeful villain, actively and knowingly spreading HIV to his sexual partners, that does not jibe with both our scientific knowledge of HIV/AIDS or with the assistance Dugas provided to scientists studying the epidemic. Dugas worked with researchers to identify as many of his partners as he could (~10% of his estimated 750), as the scientific and medical community struggled to figure out whether AIDS stemmed from a sexually-transmitted infection, as several lines of evidence suggested. There’s no evidence Dugas was maliciously infecting others, though that was the reputation he received. Dugas passed away from complications of AIDS in March of 1984–weeks before the discovery of HIV was announced to the general public.

Furthermore, the information in the new publication is not entirely novel. Molecular analyses carried out in part by Michael Worobey, also an author on the new paper, showed almost a decade ago that Dugas could not have been the true “Patient Zero.” The 2007 paper, “The emergence of HIV/AIDS in the Americas and beyond,” had the same conclusions as the new paper: HIV entered the U.S. from the Caribbean, probably Haiti, and was circulating in the U.S. by the late 1960s–when Dugas was only about 16 years old, and long before his career as a flight attendant traveling internationally. So this 2007 molecular analysis should have been the nail in the coffin of the Dugas-as-Patient-Zero ideas.

But apparently we’ve forgotten that paper, or other work that has followed the evolution of HIV over the 20th century.

What is unique about the new publication is that it included a sample from Dugas himself, via a plasma contribution Dugas donated in 1983, and other samples banked since the late 1970s. The new paper demonstrated that Dugas’s sample is not in any way unique, nor is it a “basal” virus–one of the earliest in the country, from which others would diverge. Instead, it was representative of what was already circulating among others infected with HIV at that time. In supplemental information, the authors also demonstrated how notation for Dugas in scientific notes changed from Patient 057, then to Patient O (for “Outside California”) to Patient 0/”Zero” in the published manuscript–which Shilts then named as Dugas and ran with in his narrative.

Graphic of sexual network of early AIDS cases, from Auerbach et al., Am J Med 1984.


The media then extended Shilts’s ideas, further solidifying the assertion that Dugas was the origin of the U.S. epidemic, and in fact that he was outright evil. The supplemental material notes that Shilts didn’t want the focus of the media campaign initially to be about Dugas, but was convinced by his editor, who suggested the Dugas/Patient Zero narrative would result in more attention than the drier critiques of policy and inaction in response to the AIDS epidemic by the Reagan administration.

And the media certainly talked about it. A 1987 edition of U.S. News and World Report included a dubious quote attributed to Dugas: “‘I’ve got gay cancer,’ the man allegedly told bathhouse patrons after having sex with them. ‘I’m going to die, and so are you.’” NPR’s story adds “The New York Post ran a huge headline declaring “The Man Who Gave Us AIDS. Time magazine jumped in with a story called ‘The Appalling Saga Of Patient Zero.’ And 60 Minutes aired a feature on him. ‘Patient Zero. One of the first cases of AIDS. The first person identified as the major transmitter of the disease,’ host Harry Reasoner said.”

This is the real scandal and lingering tragedy of Dugas. His story was used to stoke fear of HIV-infected individuals, and especially gay men, as predators seeking to take others down with them. His story was used in part to justify criminalization of HIV transmission. So while science has exonerated him again and again, will the public–and the media–finally follow?





Did Yersinia pestis really cause Black Plague? Part 5: Nail in the coffin

Despite its reputation as a scourge of antiquity, Yersinia pestis–the bacterium that causes bubonic plague–still causes thousands of human illnesses every year. In modern times, most of these occur in Africa, and to a lesser extent in Asia, though we have a handful of cases each year in the U.S as well.

When Y. pestis was first confirmed as the cause of bubonic plague during an 1894 outbreak in Hong Kong, most people assumed that we also now knew the cause of the 14th-century Black Death, and the later plague outbreaks that resurfaced periodically. However, there has been lingering resistance to the idea that Y. pestis actually caused the Black Death. I covered the reasoning behind this resistance in a series of posts back in 2008, so I’ll just give the Cliff notes version here. Basically, many of those advocating “not Y. pestis” pointed to differences in the epidemiology of the Black Death compared to modern outbreaks of Y. pestis. Today, people are much less likely to die of plague; the outbreaks aren’t nearly as big; and the pneumonic form (which infects the lungs and is therefore able to spread directly person-to-person) seems too rare to account for the number of cases that occurred during the Black Death. Also, they argue that transmission across Europe was much too fast, given that rodents (typically rats) are the disease vector. Instead of Yersinia, some authors have suggested that the Black Death was instead caused by a hemorrhagic fever virus, or perhaps by an unknown microbe that went extinct sometime in the last 600 years.

More recently, we’ve been able to test these claims, using paleomicrobiology to look for molecular evidence of Y. pestis in skeletons that presumably died of plague. Many of these come from mass graves that have been dated to the time of the Black Death–some also have parish or other town records to attest to the timing of the grave. In most cases, investigators found Y. pestis DNA. In a few cases, they didn’t, which led to controversy and charges of contamination in the positive samples.

However, the tide has turned. In 2010 and 2011, three papers came out which, um, put the nail in the coffin for the Y. pestis naysayers. At the time, the papers got press not necessarily because of what they explained, but because the ancient Y. pestis strains looked fairly ordinary–there was nothing obvious to suggest why, from the bacterial point of view, the Black Death was so deadly. However, I hadn’t had a chance to read these closely until now, and one of the punches never made it into the mainstream media. From the discussion section of this paper, the authors note:

Two of the authors (SW and JM) have previously argued that the epidemiology, virulence, and population dynamics of the Black Death were too different from those factors of modern yersinial plague to have been caused by Y. pestis (13). Given the growing body of evidence implicating this bacterium as responsible for the pandemic, we believe scientific debates should now shift to addressing the genetic basis of the epidemic’s unique characteristics.

The reference cited within is this paper, where the authors cast doubt on another group’s finding of Y. pestis DNA in ancient corpses. So it took them 10 years and probably a dozen or more papers, but two “Black Death doubters” have now come around. Score one for the weight of scientific evidence changing minds.

Works cited

Schuenemann VJ, Bos K, DeWitte S, Schmedes S, Jamieson J, Mittnik A, Forrest S, Coombes BK, Wood JW, Earn DJ, White W, Krause J, & Poinar HN (2011). Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. Proceedings of the National Academy of Sciences of the United States of America, 108 (38) PMID: 21876176

Bos KI et al. A draft genome of Yersinia pestis from victims of the Black Death. Nature, 2011.

Haensch, S et al. Distinct Clones of Yersinia pestis Caused the Black Death. PLoS Pathogens, 2010.

Previous posts in the series

Part 1

Part 2

Part 3

Part 4

Hemolytic uremic syndrome (HUS) in history–part 3

I left off yesterday with the initial discovery of “Vero toxin,” a toxin produced by E. coli (also called “Shiga toxin” or “Shiga-like toxin”). Though this may initially seem unconnected to hemolytic uremic syndrome (HUS), the discovery of this cytotoxin paved the way for a clearer understanding of the etiology of this syndrome, as well as the mechanisms by which disease progressed. By the early 1980s, several lines of research pointed toward E. coli, and particularly O157:H7, as the main cause of HUS.

A 1982 Centers for Disease Control and Prevention MMWR report found a rare E. coli serotype, O157:H7, associated with hemorrhagic colitis following consumption of hamburgers. Similar results were reported in a 1983 Lancet paper, which found serotype O157 among their collection of verotoxin-producing strains. Another paper that same year from a Canadian group showed that O157:H7 was the second most common cytotoxic strain in their collection of over 2,000 E. coli isolates. The most common was serotype O26–more on that below. This paper also discussed an outbreak of hemorrhagic colitis that had occurred at a nursing home, with O157 identified as the cause. The evidence was mounting, but these were small studies and not always associated with HUS. Still, these papers collectively were suggestive of a connection between E. coli infection (especially with strains that produced the shiga/vero toxin), hemorrhagic colitis, and HUS.

In 1985, a new study came out which really helped to seal the deal. Rather than look only at cases in isolation, the authors designed a case-control study looking at patients with “idiopathic HUS” (in other words, HUS of unknown origin which started with diarrhea, rather than the other variant lacking this symptom). They ended up with 40 patients who qualified. They then picked a single control for each patient, matching them on age, sex, and season of the year. The controls were children either diagnosed with Campylobacter enterocolitis (and therefore, enterocolitis of a known cause) or were healthy children either from a local daycare center, or kids coming in for elective surgeries. Stools were collected from each group and tested for a variety of organisms, including vero toxin-producing E. coli (VTEC, also known as STEC for the shiga-like toxin nomenclature). They also tested for activity of the toxin itself in fecal samples. Finally, in the case patients, attempts were made to collect what are called “acute” and “convalescent” blood samples. These are samples taken when the patient is actually sick (“acute”), and then ones taken a few weeks later (“convalescent), to look at the presence of antibodies in the blood. If it was an infection by the suspected organism (in this case, STEC/VTEC), you should see a rise in antibodies the host produces that target the organism–for these kids, they were looking for antibodies to the shiga/vero toxin.

They found either vero toxin or VTEC in 60% of the case patients, but in none of the controls. Of the VTEC isolated, serotypes included O26, O111, O113, O121, and O157. For the latter, it was the most common type isolated (25% of the VTEC found). Of the patients who were negative for both VTEC and vero toxin, from those who had paired blood samples (12/16 of the remaining cases), 6 did show a rise in antibody titer against the vero toxin–suggesting they had been exposed and were producing antibodies to neutralize the toxin. So, for those keeping score, 75% of the cases had evidence of VTEC infection either by culture or serological techniques. It may not have been the nail in the coffin and there are certainly some flaws (the diversity of controls and lack of analysis of blood titers for the controls being two that pop out at me), but this paper went a long way toward establishing VTEC/STEC as the cause of HUS, which has been subsequently confirmed by many, many studies worldwide.

The most common vehicles of transmission of these organisms have also come into clearer focus since the 1950s, with almost all HUS/STEC outbreaks associated with food products; most common is still the O157:H7 serotype. O157 is a bit unique, in that this strain typically doesn’t ferment sorbitol–as such, this is often used as a diagnostic feature that sets it apart from “normal” E. coli. However, as I mentioned above (and as the current outbreak has shown), a number of other serotypes besides O157:H7 can also cause HUS. Most of these don’t appear to be as commonly associated with outbreaks–rather, they may more commonly cause sporadic disease where fewer people may become sick. Because these don’t have the unique sorbitol-non-fermenting feature, these may be overlooked at a diagnostic lab. There are assays that can detect the Shiga-like toxin directly (actually, we now know there are multiple families of related toxins), but not all labs use these routinely, so it’s likely that the incidence of infection due to non-O157 STEC is higher than we currently know.

HUS was once a mysterious, “complex” disease whose perceived etiology shifted almost overnight, as scientific advances go. What implications does this have for other diseases whose etiology is similarly described as HUS was 50 years ago? More on that tomorrow.

The Epidemic: Typhoid at Cornell

In the United States, we tend to take our clean drinking water for granted. Even though there are periodic concerns which bubble up about pharmaceuticals or other chemicals in our water supply, we typically believe–with good reason–that we have little to fear when it comes to contamination from microbes. Our drinking water, while far from perfect, is heads and shoulders above what it once was–something many of us forget or have never realized. There have been notable breakdowns, such as the 1993 outbreak of Cryptosporidium in Milwaukee that sickened over 400,000 individuals, but these days such events are few and far between.

This hasn’t always been the case. In the early 1900s, the safety of the water supply even in many large U.S cities wasn’t monitored, and there were no standards in place to guarantee that individuals receiving pumped water wouldn’t be made ill by it. This is the setting for David DeKok’s new book, “The Epidemic,” detailing a 1903 outbreak of typhoid fever (caused by Salmonella enterica serovar Typhi) in Ithaca, New York, that hit at least 512 homes in the town and left 82 dead, including 29 Cornell students. It’s estimated that 10 percent of the populace was sickened, one of the last of the major typhoid outbreaks in the U.S.

The book begins with a description of those behind Ithaca’s water supply back in the day. It was an ugly mess of local businessmen and members of Cornell’s Board of Trustees, who unwittingly set the outbreak in motion with the 1901 sale of Ithaca Water Works to local businessman William Morris. Morris was a Cornell alum, a lawyer and entrepreneur who had previously invested in power companies. He had agreed to buy the Water Works only as a side deal that provided him with his main interest, Ithaca Gas Light Company. The deal was financed in part by Cornell University, with some of Morris’s buddies on the Board of Trustees greasing the deal.

Morris had never run a water company before and while others in town had suggested adding in a filtration plant upon Morris’s purchase of the company, Morris ultimately refused, and began construction on a huge new dam. For this, he hired Italian workers–from an area of Italy where typhoid was still endemic. This was prior to the discovery of the carrier state for typhoid, so while the workers appeared to be quite healthy, at least one of them was unwittingly spreading the deadly organism. Coupled with the atrocious state of the dam construction site–including limited access to outhouses, so workers urinated and defecated near the creek where they were working–this assured that Six Mile Creek would be contaminated, and a good portion of Ithaca’s water supply along with it.

Soon, the cases started to roll in. From January 1903 until May of that year, they piled up even as students began to flee the campus, sometimes unknowingly taking their infection home with them to family members. What followed was a mess of blame-gaming and politicking, with no one taking responsibility and officials contending that the very victims of the outbreak were responsible by being careless about what they ate and drank. Even well into the epidemic, the need for boiling contaminated water was debated and put aside as students and townfolk were dying. Indeed, a letter from late February 1903–well into the epidemic–shows that university officials were still denying they carried any blame, or even that their students were drinking contaminated water.

DeKok uncovers a story that will make anyone interested in public health seethe in anger, and yet it’s one that can–and does–still happen today, as the good ol’ boys’ network and corporate interests trump the health of the populace. Our drinking water is much improved, but corporations are still allowed to pollute with little more than a slap on the wrist. Sadly, DeKok recounts how Morris’ wealthy friends ended up protecting him from any kind of fallout, while Andrew Carnegie came through and donated enough funds to cover medical and funeral bills for the affected students. Finally, in an ironic turn of events, DeKok also notes how Morris’ companies evolved over the years into the General Public Utilities Corporation, which ran the Three Mile Island nuclear power plant.

“The Epidemic” is a story of an outbreak that, with just a bit of foresight and concern for the public good over private profits, could have been prevented entirely. It sadly mirrors many public health controversies that still thrive today. For instance, one passage notes that any government funding for the water works was fear-mongered as “socialism,” a platform that could have come from our current Republican leadership. It’s a tragic reminder that we don’t always learn from our mistakes, and while our water may be safer today than in 1903, public health still gets trampled on by private industry. Will we ever learn?

“Pox” by Michael Willrich

Next to Ebola, my favorite virus would probably be smallpox (Variola virus). I mean, now that it’s eradicated in nature, what’s not to love about the mysteries it’s left us–where it came from, why it was so deadly (or, not so deadly, as in the emergence of the “mild” form, variola minor), and will a new poxvirus emerge to take its place? The topic is particularly germane since the debate still rages on about the fate of the world’s smallpox stocks. Smallpox has killed untold millions and influenced the destiny of societies; and as Michael Willrich details in his new book, Pox: An American History, the legacy smallpox has left us is still alive and well today.
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