The mainstream media has been reporting on this paper (open access at PNAS) on the hunt for the origin of HIV in the Americas.
The surprising result was the finding that HIV first came to the United States from Haiti (rather than the previous origin which was thought to be a flight attendant from Canada) between 1966 and 1972, and flew under the radar of public health authorities for over a decade. The infection, spread initially by heterosexuals from Haiti, went undetected from as early as 1966 until 1981 and then only because it had jumped into a highly susceptible population. This article is rather humbling, because in perhaps the medically advanced country in the world, it evaded detection for so long until it finally created an epidemic in the male homosexual population.
So how did they figure this out?
Basically, they used a combination of an evolutionary understanding of viral spread through populations (with the understanding that new mutations and new strains occur with time) combined with archival samples of blood from early victims of the disease which allowed the authors to track the virus down to Haiti.
Critically, the "group M, subtype B" of HIV, which though less frequent than the pandemic virus, indicated the original pattern of HIV spread, from Africa, to Haiti, and ultimately the US and the rest of the world. By testing the sequences of the essential env and gag genes, which encode envelope proteins and group-specific antigen structural proteins (the viral matrix, capsid and nucleoproteins) respectively, they could identify where exactly where they branched off from the original viral strain from Africa. If the "Haitian spread" hypothesis were correct, one would expect the subtype B virus to be present in these older samples, and more closely resemble the African subtype.
Sure enough, this is what they found:
In the above analysis of the branching of env genes, the green branches represent the Haitian genotypes and the bolded text represent the archival samples from early HIV cases in Haitian immigrants. Consistent with the hypothesis of a Haitian origin, they represent early branch points from the African subgroup. Based on the author's analysis, this spread of genotypes in Haiti makes the probability of a non-Haitian origin is less than one in a thousand. If the alternative hypothesis were correct, one would expect that early samples would represent the pandemic clade from the US, and it would be more closely related to the original African virus. The authors tested other models of phylogenetic analysis and they linked the viral origin to Haiti even more strongly.
Using molecular clock analyses to determine when would have expected these mutations to have evolved is what led the researchers to believe the new strains originated in the Americas in the late 60s to early 70s.
I'm less surprised by this, given the long incubation time of the virus, that it would ultimately evade detection by public health authorities for almost 12 years. Not only does the incubation time figure into making it difficult to link the virus to the illness, but if you think about it, the exposure that caused the illness is also in distant memory of the patients making it unlikely people would consider a link between sexual partners and the presence of the disease. In retrospect, a pandemic was almost inevitable, as it would have been nearly impossible to link the behavior with the illness without large numbers of sick patients to compare common experiences. The authors even hypothesize that the reason the virus took so long to be identified was that it initially spread from a heterosexual population, which was low risk for infection, allowing it to spread slowly and undetected throughout the US. However, once it spread to the male homosexual population, which was high-risk for transmission, there was a rapid increase in the number of cases which made it possible for doctors to link the cause to the effect.
It's a fascinating, and ultimately humbling story. HIV was spreading throughout one of the most advanced countries in the world for over a decade, undetected. Not until a highly-susceptible population acted as the canaries in the coal mine were we able to realize there was this subtle, deadly infection, capable of destroying one's immune system years after the initial exposure, which for most patients, would be nothing but a distant memory.
A final note, I apologize if I get details of this story incorrect, viral genetics and phylogeny are not my field, but it's such an interesting story to me as a med student that I felt I had to relate it. I am glad of any corrections to my interpretation of this paper and look forward to see the take of experts like Tara to see if they resemble my own.
M. Thomas P. Gilbert, Andrew Rambaut, Gabriela Wlasiuk, Thomas J. Spira, Arthur E. Pitchenik, and Michael Worobey The emergence of HIV/AIDS in the Americas and beyond PNAS published November 1, 2007, 10.1073/pnas.0705329104
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So we (Trinis) can claim the honour of having our own subtype?
It makes sense really. HIV was big in Trinidad in the early 80s. Granted, I always figured that it had to do with the regaularity of travel back and forth (the latest fashions seem to make it from NY to TT or Miami to TT faster than they made it to the Mid West), but I always wondered about my impression that AIDS started out on the West Coast.
The overall picture makes a lot of sense - I remember when I first heard about AIDS (in the early or mid 80s) it was a disease of gay men and Haitians.
...where tens of millions have no health insurance, and consequently don't necessarily go to the doctor as often as they should...
BTW, in the second sentence, please remove the comma behind "and then" and put it in front of that phrase. I had to read the sentence three times to understand it.
Fixed, I changed that sentence a lot because I was worried about being insensitive.
I think another important issue in understanding why HIV could spread for over a decade in a population in America without being noticed is reduced consumption of mainstream medical services. If infected Haitians were not seeing mainstream doctors, or other professionals that would know that the symptoms of AIDS were a unique disease that required immediate public health intervention, then even a large epidemic might go unnoticed. Gay men might have been more likely to see a doctor (for whatever reason) than Haitian or Haitian-decedent men at that time. Then the increased growth rate in gay populations and the increased interface of gay men with mainstream doctors is what lead to a more rapid identification of HIV/AIDS as a sexually transmitted disease.
This post also illustrates the (often ignored) public health concept that no population is an island. Passively ignoring a group of people can have negative consequences for them, but it can have even worse consequences for the population in total.
I thought the origin of HIV is Affrica. Just read this news on pozcupid. Maybe knowing the origin of HIV is helpful to fight against HIV.
I've been considering writing something on this on my blog ever since these finding were released. Considering, because I still haven't had a response to several questions I posed to two of the authors at UCLA.
Here's the thing:
The basic assumptions are flawed. They found what they were looking for because it was the only thing in the place they looked.
From the mid-60's to the mid-70's tuberculosis was under aggressive attack in the U.S. while rampant through many places in the Caribbean, including Haiti. It was also well entrenched in most of the west coast and central plains of Africa.
From the mid-60's through the late-70's U.S. tourism of the Caribbean, very much including Haiti was growing geometrically as were the length of stays and penetration of areas outside of the vacation resorts. Hippies and love children were all about gettin' real with the people. The geometric growth of recreational travel into the region was geometric because it was a combination of new tourists combined with repeat and repeat visitors.
A similar pattern in emerged during reconstruction in several African countries involving business and engineering management personal from the U.S. Again, repeat and repeat and repeat travel.
Are you getting the picture yet?
This study was almost entirely based on sampling preserved blood of Haitian immigrants to the U.S. Their blood was preserved because they died of TB from a country where lots and lots of people died of TB.
The question is how many blood samples were preserved by the CDC of Americans that died of TB? Then, how many of those samples were tested for HIV GM-B? There's no evidence that the answer is anything but 0.
To assume that there was a linear progression from Africa to Haiti to the U.S. is not only flawed, it's unsupported.
The likelihood that Haitian workers, who were housed in company barracks, were out having the type of unsafe sex required for infection is arguably much less than the likelihood that white-collar and blue-collar workers from the U.S. who took multiple trips back and forth and stayed in the cities were the ones infected.
This is the problem and stupidity of executing a forensic study of this nature without an anthropologist and cultural historian in key positions on the research team.
I think this is a lot of hoopla over an incomplete study rushed to conclusion in order to meet the ever draconian publication requirements at most major research universities in the U.S.
David B.
www.theskinofmyteeth.com
@Simon,
The virus did originate in Africa, this is a description of the virus traveling to the Americas and becoming pandemic.
@ David B.
From the article:
Does that address your concerns or do you still feel there is a sampling bias? Again, I'm not an expert in this field. I have no opinion.
Here's something that the findings did not make relatively available. People with progressive HIV (who now would be diagnosised with AIDS because of HIV's advanced state in their body) are highly susceptible to contracting and dieing of tuberculosis.
Haitian's died of TB. Americans didn't because the likelihood of being exposed to TB in the U.S. was infinitesimally small.
MarkH:
I understand why that paragraph seems to offer irrefutable proof that this went down exactly as their fancy graphics propose. Expressions like "little doubt", "information implies", and "statistically significant" are cover words for leaps of reason. The flaw in the central line of logic is that the CDC was not preserving samples of U.S. citizen's death by TB because Americans weren't dieing of TB in statistically significant numbers (so 0).
If Americans with the HIV strain cited had died of TB at the same point in time, then there'd be preserved samples to now test for HIV GM-B. But there weren't, and the question I've been waiting for an answer on is how many did the study assume - my guess is zero. That's a massive hole in the formula.
Their study was premised on testing blood samples with death due to TB and all the CDC had was samples from Haitians. This does not, as they assume, prove anything more than Haitian immigrants that died of TB during that time also were infected with HIV GM-B.
The likelihood of the linear progression of Africa-Haiti-U.S. is never proven and is an overly broad assumption to be the basis of their conclusion.
The inference that Americans with HIV GM-B (with access to far superior medical care for opportunistic infections than Haitian immigrants) didn't die and therefore didn't exist is ridiculously flawed. Americans tourists infected with HIV GM-B (that had not yet progressed to what we now call AIDS) could easily have been the source of infection in Haiti.
Ultimately, my point is that the distribution logic here is as flawed and filled with leaps to conclusions as the study in the 80's that declared an Air Canada steward as "patient zero" and the source of HIV in the U.S. _My complaint_ is that this study and it's findings is flawed for the same reasons as the "patient zero" craze - and the outlets that promoted this study should know better by now.
I certainly don't feel this deserves the Peer Review stamp as no one has reviewed the mechanics behind their summary claims at this point. And it's very difficult to do so because one would essentially have to recreate the forensic research before the medical data from the blood samples will have an conclusive properties.
Again, I say, it is beyond ridiculous that a study committee approved this project and awarded money to it without an anthropological and cultural historian in key positions on the research team.
Interesting David. I look forward to other people who specialize in this more providing commentary - like Tara. I don't think your criticism of this being peer-reviewed is correct, PNAS is a peer-reviewed journal, however lax they tend to be towards members.
I get what you're saying, but at the same time they had valid sequences to compare these samples too that represent the bulk of the genetic analysis in the paper. While it seems to me the origin that you describe is possible, traveling from the US to Haiti and then back, is that still consistent with the data showing the variation in strains present in Haiti but not in the US? This part seems strange to me. It seems as though the distribution seen in Haiti should have been seen in the US samples, if it indeed had been here first. Does this seem unreasonable? or am I misunderstanding the assumptions?
Fascinating? Why? Wouldn't it still go undetected weren't it for PCR? And even, what does PCR detect? HIV? No! Undefined debris. As a matter of fact, the way I see it, the only fascinating thing about this nonsense story is that it's backed up by the term peer reviewed.
depp=true
notiz=[disemvoweled for HIV/AIDS denialism and idiocy]
Ultimately what I'm pointing out is that people with HIV in developed countries, regardless of the point in time that HIV enters the population, overwhelmingly have not died of TB. That is because, until recently, TB was under very tight control and the opportunity of exposure very small.
In developing and non-developing countries TB was and is so widespread, that people infected with HIV quickly succumbed to it.
It is unlikely the CDC has any preserved blood samples of any Americans that died of TB from that time, much less samples infected with HIV. It is, however, certain that they have vast stores of samples from immigrants that died of any conditions other than physical trauma as that is one of their primary occupations - looking for diseases entering the country via immigration and activating appropriate local and regional responses, especially for something like TB.
It is very safe to assume that the CDC has blood samples of something approaching 100% of people dieing of TB. But that's not what HIV infected people from North America were dieing of - they were dieing of uninteresting things like pneumonia and unlikely and aggressive cancers/wasting. As I said, in the area the researchers were looking, they found the only thing that was there.
From what I've learned of the study from the study summary and other sources, this is no more an appropriate set of assumptions as a foundation for a conclusion than were the assumptions for the patient zero study. It took quite some time for the patient zero study to be properly peer reviewed and discredited. There is every indication that the same is in store for this study.
Oh, I forgot to address your conclusion:
I'm not satisfied that that they've shown that a population such as Haiti's, filled with immune systems already ravaged by TB, poor nutrition, and poor medical resources would not be fertile ground for unusually accelerated variations of HIV. That combined with an inadequate number of "American" samples doesn't supply them with an adequate foundation for their conclusions.
Ok, I kind of get what you're saying. You think that TB is a confounding variable that prevents the American pandemic strains from people who died of other illness from serving as an adequate control.
I'm confused though about one logical leap. What about dying from TB or having poor nutrition would accelerate formation of more variants of the virus? On the one hand you have a sexually-transmitted disease, on the other, a respiratory disease. What about their interaction would make it more likely to have more strains? I don't see how their poor public health infrastructure and high disease rates would make the Haitian population more likely to spread an asymptomatic STD more efficiently than the US. I could see why it would be worse for something symptomatic - less healthcare and monitoring would mean worse spread - but since HIV is largely asymptomatic during the incubation period, why would that make Haiti any different from the US as neither patient population would be even bothering with medical care until they were at death's door?
HIV isn't categorized just as an STD because of the varied possible avenues of infection. It was just as likely to have spread via intravenous drug use, accidental needle sticks, and through blood products as through sexual contact. In places like Haiti (and even places like USSR) re-use of needles in medical facilities was a significant source of infection.
When you have a large number of people with impacted immune systems due to TB combined with poor nutrition HIV is able to spread quickly and efficiently. Because the medical infrastructure in Haiti was hardly able to treat TB, they had no resources to treat the opportunistic infections associated with HIV. This gave HIV a very available, large population of human "petri dishes" to work with. Statistically, of course, it provides more opportunity for successful mutation in a very short amount of time.
Then, there's also the significant societal opportunity. Few Haitians went to Africa and usually only once via slow boats. American's were going back and forth in very short amounts of time to both areas over and over again in the same amount of time it took the Haitians to make one round trip. That is a critical fact to overlook, which is what they've done. The Haitian population had repeated exposures to a variety of external visitors. The odds that a second strain was introduced rather than emerged are very high in favor of introduction when you consider the web of travel opportunities.
There has also been much discussion over the years of how this process of differentiation may have been aided by what to us seem to be bizarre, insane, and desperate local remedies to illness. Western medicine really doesn't pay enough attention to what opportunities are opened for successful mutations aided by an immune system pummeled by horrific herbal, petroleum, and compound remedies from societies around the world.
www.theskinofmyteeth.com
David
I agree with David B. There was a big flow of tourism from US to Haiti from the mid 50's to the 80's (not the opposite until the Haitians migrations to US). In addition, is it documented that there were Haitians traveling to Africa in the 60's? I have never heard of it but I may be mistaken. Africans were brought to Haiti by French in the 1500's to work on the sugar cane fields and sugar production, this is how Haiti was born. Initially, when I read about this study in a Newsweek article, I was confused, I thought that the HIV virus was brought from Africa to Haiti from that time (1500's). I am really puzzled about the actual travel of Haitians to Africa in the 1960's.
Also, besides the reasons that David B. suggests as how the HIV virus spread in Haiti (poor nutrition and medical care, re-use of needles, poverty), socially, Haitians are sexually promiscuous, and Haiti is a small country, only a 3rd of the Hispaniola island, with a large population. In any case, these are my two cents of logic.
There were large rebuilding projects after war and civil war (in the late '50's through mid '60's) in the region of Africa in question. Some Haitians were brought to Africa as workers on those projects. They did not travel to and fro, however, it was just a single long-winded round trip.
www.theskinofmyteeth.com
David B.