I have written several articles on the coronavirus and on masks and healthcare issues. A series of links have been provided at the bottom of this article for your convenience. This article will, however address a different aspect of the virus or on healthcare issues in general.
I only just came up with the idea of writing this article while I was reading a book by Charles Kenny, entitled “The Plague Cycle: The Unending War Between Humanity and Infectious Disease.” I know I should get out more, or try reading a book of fiction. While you might be right on both accounts , I have found this book to be very inciteful and informative. While reading one of the later chapters, I came across a statement made by the author. He proposed a possible cause of the initial spread of HIV (Human Immunodeficiency Virus) which was the virus responsible for AIDS ( Acquired Immune Deficiency Syndrome). In order to make his proposition easier to understand I will have to give the reader a little background information. I am sure that my readers have heard of the disease called Smallpox. Well if you haven’t, it is a contagious, disfiguring and often deadly disease that has affected humans for thousands of years. Naturally occurring smallpox was wiped out worldwide by 1980–the result of an unprecedented global immunization campaign. Samples of the smallpox virus are kept for research purposes. Well what they neglected to tell people getting vaccinated was that due to a shortage of hypodermic needles, many needles were reused for these vaccinations. This was occurring mainly in the third world countries of you guessed it, Africa. We also need to discuss the origins of HIV.
HIV first emerged as a mutation from a simian version in the 1920s, probably somewhere in the Kinshasa district in the Democratic Republic of the Congo. However, the first epidemic only occurred fifty years later in Kinshasa, spread accidentally during the immunization campaign for smallpox, most assuredly related to the unfortunate practice of re-using hypodermic needles. This is the first time I came across this theory, but the time line for the eradication of smallpox and the spread of HIV correlates precisely. We all know that viruses are opportunistic, and it would not be the first time that man had caused more damage while trying to do good. I will give the reader a little refresher course on HIV and AIDS in the Addendum Section.
While compiling background information for HIV/AIDS and its origins, I discovered that the author is certainly in the minority on his theory of the initial spread. While there is no denying that the virus originally did come from monkeys and has been spread by sexual contact and sharing needles and even improperly screened blood products, we are talking of the fist few cases that started the initial spread. Remember not too long ago were we told that the COVID virus originated in a wet market in Wuhan China. The WHO and Dr. Fauci pushed that theory, even though none of the narrative being proposed fit any of the facts. We also need to remember a few things, Dr. Fauci was involved in the initial research and search for treatments of HIV/AIDS, HUMMM. I wrote an article on this subject, “Fauci and HIV and Now Coronavirus, Sounds Like DeJaVu.”President Trump said that the Wuhan Virology Center was the ultimate source of the viral pandemic. Yellow man has to be wrong. Well we all know that President Trump was right.
I have come across a government report entitled “The Origins of the COVID-19 Global Pandemic, Including the Roles of the Chinese Communist Party and the World Health Organization.” As expected it is lengthy. I will only cover a small portion of the article, the portion that discussed the Chinese cover-up.
THE CHINESE COMMUNIST PARTY’S COVER-UP
From the early stages of the pandemic, the CCP repeatedly acted to conceal vital information
about the virus from their own people, the WHO, and the world. The timeline above notes
• The failure of the CCP to notify the WHO about the outbreak of a novel disease within
• The repeated failure of the CCP to notify the WHO of cases meeting the WHO definition
• The decision not to immediately publish the WIV’s completed genetic mapping of
SARS-CoV-2, the virus that causes COVID-19, which would have shown its similarity to
SARS-CoV and confirmed it to be a novel coronavirus.
• The shuttering of the Shanghai lab that published the SARS-CoV-2 genome online.
• The lack of new case announcements during CCP political meetings between January 6th
and January 17th.
• The suppression of reports from medical doctors within the PRC providing evidence of
• The six days of undisclosed response during January, during which General Secretary Xi
and other senior CCP officials kept secret their knowledge that human-to-human
transmission was occurring and that a pandemic was likely
I have discussed the COVID-19 virus in depth in several articles, One article in particular covers all aspects of the virus in depth , “The Cornavirus Exposed,” which is now a two part article. I update the posting as new information becomes available. In this posting I have discussed in depth the origins of the virus in China, so I won’t rehash it here. However I will bring up a phrase, that I am sure you have heard before, Gain Of Function Research. This topic is the crux of this article. However, in case you are not familiar with the term, I will briefly explain it. “Gain-of-function” is the euphemism for biological research aimed at increasing the virulence and lethality of pathogens and viruses. GoF research is government funded; its focus is on enhancing the pathogens’ ability to infect different species and to increase their deadly impact as airborne pathogens and viruses. Ostensibly, GoF research is conducted for biodefense purposes.
So here we have it. I want to add that nowhere in this article did I mention that there was anything done for nefarious reasons. In both instances scientists and medical professionals were trying to do the right thing. Though in the second case it is a little iffy. We do however, know that the virus was not intentionally released by the Wuhan Virology Center, or least we hope that is the case. What we do know is that they most certainly covered it up and did nothing to contain it once it did escape. Which is just as bad. So many senseless deaths could have been prevented if they had acted appropriately or even more had never did the research to begin with. In the case of the small pox vaccinations, reusing the needles was total negligence. They had to know that no good would come of it. We can understand it being done in the early 1900s when the technology was not where it needed to be and needles were extremely expensive and difficult to make.
In an era when we’re racing toward eradication of some infections, we’re simultaneously abusing our existing weapons against communicable disease so badly that we create new threats. Millions will die prematurely from preventable diseases, in part because we’re underutilizing sanitation and vaccination while overusing antibiotics, and we’re intentionally developing new diseases as weapons.
Another road block for vaccinations, are the recurrent vaccine conspiracy theories, and there are many of them. The one most harmful and has cost untold deaths is the rumor that the Measles vaccine cause autism. This has bee soundly debunked. However it continues to cause parents to refuse to give child hood vaccines to their children. It has also caused a resurgence in polio cases. What are people thinking. Another instance is the case where the CIA were using phony Hepatitis Vaccines to try and catch Osama Bin Laden. This has caused untold hardship throughout the Middle East. Dozens of people who have been administering the real vaccines have been killed by radical Muslims. A recurrent theme continues to re-surfaces again and again, that of doing the wrong thing for the right reasons. What the hell was the CIA thinking? I have included information on both of these cases in the Addendum. In the last topic that I have included in the Addendum, is a brief monolog on the use of antibiotics in agriculture and the raising of farm animals. The vast majority of antibiotic use and abuse has taken place in these areas, and is also responsible for much of the antibiotic resistance so prevalent in our society today.
So in conclusion, we are not God, we don’t always know better and we certainly don’t have all the answers. So maybe we need to take a step back and evaluate the situation before we act? Because once the actions are taken, it is usually very difficult or impossible to undo the resulting damage. There is also no denying that millions of lives have been affected by these actions. If something seems like a bad idea, it most certainly is a bad idea. Unfortunately the more advanced our society becomes the more likely we are going to want to tinker with mother nature, we just never seem to learn from our mistakes. And yes, I believe that in all too many cases we are our own worst enemy.
“The Plague Cycle: The Unending War Between Humanity and Infectious Disease,” By Charles Kenny; cdc.gov, “About HIV;” hiv.gov, “What is AIDS;” spectrumlocalnews.com, “Doctor describes HIV/AIDS epidemic and COVID-19 pandemic parallels as ‘hauntingly similar’,” By Stacy Rickard; ncbi.nlm.nih.gov, “Origins of HIV and the AIDS Pandemic,” By Paul M. Sharp and Beatrice H. Hahn; pubmed.ncb.nlm.nih.gov, “The Origin of COVID-19 and Why It Matters,” By David M. Morens, Joel G. Breman and et.al.; gop-foreignaffairs.house.gov, “The Origins of the COVID-19 Global Pandemic, Including the Roles of the Chinese Communist Party and the World Health Organization,” By Michael T. McCaul; nlm.nih.gov, “smallpox: A Great and Terrible Scourge;” medium.com, “Why People Are Against Vaccinations,” By Ed Fernyhough; grunge.com, “THE TRAGIC TRUE STORY OF THE CIA’S FAKE VACCINATION CAMPAIGN,” By Marina Manoukian; asyousow.org, “antibiotics and factory farms;”
Why People Are Against Vaccinations
A culture of confusion and misinformation contributes to conspiracy theories
In 2020, NBC reported on a case where a woman from Colorado neglected to seek adequate medical attention for her four-year-old son, who was sick from the flu. The mother, rather than listening to medical advice, called on the opinions of 178,000 members of the Facebook group “Stop Mandatory Vaccination” instead. She was recommended homeopathic remedies by the group to treat her son, but unfortunately, her son died from his illness.
NBC explains that in this Facebook group and others like it, conspiracies about vaccines and other forms of conventional and effective modern medicines are spread. The sorts of myths spread by these groups include beliefs that “outbreaks of preventable diseases are ‘hoaxes’ perpetrated by the government”, that vaccines cause autism, and that the reason healthcare practitioners encourage vaccination is because they are colluding with pharmaceutical companies for profits. All of these theories are not only wrong, but also extremely dangerous for the public.
Anti-Vax and Science Scepticism
Conspiracy theories are not only limited to issues of healthcare. In reality, the proliferation of conspiracy theories throughout contemporary societies, which are supposedly advanced, are enabled by a few fundamental factors.
Other recent, popular conspiracy theories include the belief that Huawei 5G has somehow been responsible for the transmission of coronavirus, that the current vaccination drive is an attempt that has been made by Bill Gates to microchip humanity, and that Meghan Markle is a robot.
To account for the presence and the underground popularity of conspiracy theories like these, some understanding of human psychology, and some comprehension of how information flows throughout our societies, is required. Indeed, paranoid political thinking, online echo chambers, trolls, and the dissemination of misinformation on unregulated social media platforms, are all relevant dynamics to consider, to understand the circulation of conspiracy theories in our contemporary societies.
There are two other related dynamics which must also be factored in, especially to understand conspiracy theories that neglect scientific knowledge. First of all, many conspiracy theories demonstrate considerable ignorance of basic science. Take, for example, flat earth theory. Flat earth theory can be disproven by a simple experiment involving sticks placed on a piece of bendable cardboard, and light. When the cardboard is bent, the length of the shadows will diverge. This divergence is caused by the different angles at which the light strikes the sticks. The sticks emulate objects on the earth such as buildings, trees, or people, cardboard emulates the surface of the earth, and bending it emulates the curvature of the earth.
However, a second dynamic confounds the efforts of those who wish to use science as a tonic to dispel conspiracy theories. Conspiracy theorists often build scepticism of science into the theories they defend, in an effort to disarm any appeal to accuracy. These attempts are often very muddled and confused, but they can nevertheless easily be de-riddled.
Take, for example, the anti-vax conspiracy theory suggesting the current vaccination drive has been orchestrated by Bill Gates, who allegedly wishes to microchip humanity. Scepticism of science is here displayed by the mistrust of conventional medicine. A prominent figure within the scientific community, Bill Gates, is ascribed a sinister yet incoherent motive for wanting people vaccinated, which functions to portray science not as a force that can do good, but as a malicious tool the rich and powerful use as a means of social control. It is, however, obviously nonsense.
In reality, vaccinations have been one of the most important healthcare breakthroughs and innovations in modern history. The first vaccinations were developed towards the end of the 18th century, while more sophisticated methods of production, commercialisation, and vaccinations against a wider range of diseases, has enabled greater protection.
Vaccination is a vital example of biomedical know-how and technology which has saved hundreds of millions of lives worldwide. It is a brutal truth that without vaccinations, life would be very different from how we know it now. One significant problem, however, is the current fact that many people refuse to accept that vaccines are an honest tool produced by science to improve public health. Tackling anti-vax conspiracies must therefore focus on the roots that enable misinformation and science scepticism to spread.
Education and Online Regulation
One of the biggest problems with the view that people should be free to choose whether or not they and their children will get vaccinated against various diseases has to do with the risk this puts children of anti-vax parents at. An anti-vax parent who withholds access to vaccines from their child firstly forces their worldview onto that child, precluding them from accessing information about vaccinations themselves and forming their own views.
Secondly and more importantly, anti-vax parents who withhold vaccine access from their children puts them at the objective risk of catching the diseases vaccines protect against, and suffering the consequent risks of harm and even death. The risks to people’s health that accrue as consequences of anti-vax attitudes are not matters of opinion — they are factual.
It is defensible that in some instances, adults should have the legal right to reject vaccination, however unwise, since autonomy is integral for free societies. However, when the facts of the matter have been established about the risks of abdicating vaccination, parents should be denied the right to choose whether or not their children should receive vaccines, due to the objective threats this places their children’s health under.
Whether anti-vax misinformation should be regulated online is a more precarious issue. This would no doubt be a form of censorship, and in my view, it is better to combat misinformation with abundant truth, rather than by placing constraints on freedom of speech. The optimal method of tackling science scepticism, conspiracy theories, and anti-vax misinformation, is therefore through improving people’s access to high-quality and easy-to-understand resources explaining the fundamentals of the subjects in question, not through the regulation and restriction of echo chambers and content.
Anti-vax opinions and conspiracy theories put people at objective risk of disease and harm. It is the duty of people who understand the factual efficacy of vaccines against terrible diseases to combat misinformation about vaccines when they see or hear it. It is the responsibility of educators to incorporate teaching about vaccinations into national curricula, to reduce the appeal of anti-vax conspiracy theories and science skepticism in the future.
THE TRAGIC TRUE STORY OF THE CIA’S FAKE VACCINATION CAMPAIGN
Although the CIA isn’t entirely to blame for the fact that wild polio remains endemic in Pakistan, they certainly didn’t help the situation when they tried to use a fake hepatitis B vaccination program to capture Osama bin Laden. And even though their plan didn’t exactly work as intended, it was effective enough to lead to a distrust of healthcare workers working to administer polio vaccines, per National Geographic.
As The Poynter Institute tells it, the situation was first reported by Saeed Shah, a Pakistani journalist, who claimed that the CIA and the State Department tried to stop him from publishing the story. The operation even reportedly used the “Save the Children” charity as a front, which goes against the CIA regulation that prohibits it from using American companies as fronts, although foreign companies are considered “fair game.”
In the end, bin Laden was killed roughly one month after the CIA attempted to utilize their fake vaccination program. But was it worth it to give some children less than the adequate number of vaccine doses for hepatitis B and to sow distrust of health care workers? This is the tragic true story of the CIA’s fake vaccination campaign
WHO IS DR. SHAKIL AFRIDI?
Dr. Shakil Afridi worked as a senior health official in the Khyber Pakhtunkhwa Province in Pakistan during the late 1990s and early 2000s. After Afridi was kidnapped and ransomed in 2008, National Geographic reports that he and his family left Pakistan and moved to California. They didn’t stay long, however, for a variety of reasons, including the fact that Afridi’s medical license wasn’t considered valid in the United States and he was unable to practice medicine as he had in Pakistan.
After returning to Pakistan, Afridi claims that he met an American woman named Kate after attending an event hosted by the “Save the Children” charity. And in January, 2011, Afridi was asked by Kate to start a hepatitis B vaccination campaign near Abbottabad.
But according to Scientific American, the aim of the vaccination program was not actually to vaccinate people, but instead to collect DNA from the neighborhood where it was believed that Osama bin Laden was hiding. After the used vaccination needles were collected for disposal, the CIA handlers planned to pass the needles on to the CIA, who would then test the DNA on the needles to see if any of the vaccinated children were related to bin Laden.
The CIA had been tipped off that bin Laden may have been hiding in Bilal Town, a suburb of Abbottabad, but there were a number of risks involved with launching a raid, so they wanted to be certain of his whereabouts beforehand.
FAKE HEPATITIS B VACCINES
In March, 2011, Afridi went to Abbottabad, claiming he had the funds to provide free hepatitis B vaccines. Afridi put up posters advertising the campaign around Abbottabad and, according to The Guardian, the vaccination project was even begun in Nawa Sher, “a poorer part of town to make it look more authentic.”
A hepatitis vaccine is typically given over the course of three doses. The second dose comes one month after the first, and the final dose comes six months after the first dose, as confirmed by the Hepatitis B Foundation. But after administering the first dose in March, in April, Afridi and the nurses working on the vaccination program moved to Waziristan Kothi in Bilal Town, a three-story house where it was believed that bin Laden was living.
National Geographic reports that in his testimony, Afridi claimed that he had “no suspicions that his employer had another motive for launching a vaccination campaign in Abbottabad beyond health care and research.” But when Afridi got to Waziristan Kothi, he was informed that none of the residents were home. However, the visit wasn’t entirely futile for the CIA. They found out that Ibrahim Saeed Ahmed lived at the compound, who the CIA knew was bin Laden’s “trusted courier.”
One month later, bin Laden was killed by U.S Navy SEALs in a raid. Three weeks later, reports Radio Free Europe, Afridi was arrested by Pakistan’s Inter-Services Intelligence for the role he played in the vaccination drive.
AFFECTING THE POLIO VACCINATION EFFORTS
Daniel Berehulak/Getty Images
After Afridi was convicted in Pakistan, the United States cut Pakistan’s aid by $33 million, $1 million “for each of the 33 years of a prison sentence given to [Afridi],” per The Guardian. But the fake vaccination program ended up having another detrimental effect.
National Geographic reports that in 2012, polio flared up in Pakistan, partly due to the distrust towards health care workers after news of the fake vaccination campaign spread. Even before bin Laden’s death, there was a negative view of polio vaccines, “where some village imams had claimed that the polio vaccines were part of a Western plot to sterilize Pakistani Muslims.”
The revelation of the CIA’s fake vaccination program only made it more difficult to administer vaccines. According to WIRED, the CIA’s fake vaccination program feeds into conspiracy theories about vaccines and exacerbates the existing distrust directed toward health care workers. Unfortunately, as has been seen during polio vaccination rejections in the past, polio cases always rise when polio vaccination efforts are rejected. The BBC reports that as of 2020, Pakistan and Afghanistan are the last two countries where wild polio is known to occur.
HIV (human immunodeficiency virus) is a virus that attacks the body’s immune system. If HIV is not treated, it can lead to AIDS (acquired immunodeficiency syndrome). Learning the basics about HIV can keep you healthy and prevent HIV transmission. You can also download materials to share or watch videos on basic information about HIV.
- HIV (human immunodeficiency virus) is a virus that attacks the body’s immune system. If HIV is not treated, it can lead to AIDS (acquired immunodeficiency syndrome).
- There is currently no effective cure. Once people get HIV, they have it for life.
- But with proper medical care, HIV can be controlled. People with HIV who get effective HIV treatment can live long, healthy lives and protect their partners.
+++Where did HIV come from?
- HIV infection in humans came from a type of chimpanzee in Central Africa.
- The chimpanzee version of the virus (called simian immunodeficiency virus, or SIV) was probably passed to humans when humans hunted these chimpanzees for meat and came in contact with their infected blood.
- Studies show that HIV may have jumped from chimpanzees to humans as far back as the late 1800s.
- Over decades, HIV slowly spread across Africa and later into other parts of the world. We know that the virus has existed in the United States since at least the mid to late 1970s.
To learn more about the history of HIV in the United States and CDC’s response to the epidemic, see CDC’s HIV and AIDS Timeline.How do I know if I have HIV?
The only way to know for sure whether you have HIV is to get tested. Knowing your HIV status helps you make healthy decisions to prevent getting or transmitting HIV.Are there symptoms?
Some people have flu-like symptoms within 2 to 4 weeks after infection (called acute HIV infection). These symptoms may last for a few days or several weeks. Possible symptoms include
- Night sweats,
- Muscle aches,
- Sore throat,
- Swollen lymph nodes, and
- Mouth ulcers.
But some people may not feel sick during acute HIV infection. These symptoms don’t mean you have HIV. Other illnesses can cause these same symptoms.
See a health care provider if you have these symptoms and think you may have been exposed to HIV. Getting tested for HIV is the only way to know for sure.What are the stages of HIV?
When people with HIV don’t get treatment, they typically progress through three stages. But HIV medicine can slow or prevent progression of the disease. With the advancements in treatment, progression to Stage 3 is less common today than in the early days of HIV.
Stage 1: Acute HIV Infection
- People have a large amount of HIV in their blood. They are very contagious.
- Some people have flu-like symptoms. This is the body’s natural response to infection.
- But some people may not feel sick right away or at all.
- If you have flu-like symptoms and think you may have been exposed to HIV, seek medical care and ask for a test to diagnose acute infection.
- Only antigen/antibody tests or nucleic acid tests (NATs) can diagnose acute infection.
Stage 2: Chronic HIV Infection
- This stage is also called asymptomatic HIV infection or clinical latency.
- HIV is still active but reproduces at very low levels.
- People may not have any symptoms or get sick during this phase.
- Without taking HIV medicine, this period may last a decade or longer, but some may progress faster.
- People can transmit HIV in this phase.
- At the end of this phase, the amount of HIV in the blood (called viral load) goes up and the CD4 cell count goes down. The person may have symptoms as the virus levels increase in the body, and the person moves into Stage 3.
- People who take HIV medicine as prescribed may never move into Stage 3.
Stage 3: Acquired Immunodeficiency Syndrome (AIDS)
- The most severe phase of HIV infection.
- People with AIDS have such badly damaged immune systems that they get an increasing number of severe illnesses, called opportunistic infections.
- People receive an AIDS diagnosis when their CD4 cell count drops below 200 cells/mm, or if they develop certain opportunistic infections.
- People with AIDS can have a high viral load and be very infectious.
- Without treatment, people with AIDS typically survive about three years.
+++Remember that I stated this was the first time it was proposed that HIV was spread by immunization needles. Do you honestly believe that it was from eating infected monkey meat? I don’t know about you but this doesn’t sound very likely. Not very many viruses or bacteria can survive the strong acids of the GI tract. I have never heard of HIV doing so. It kind of reminds you of the misinformation being spread on the origins of COVID-19. This is kind of why I included the background information of HIV, so you could judge for yourself.
What is AIDS?
AIDS is a set of symptoms (or syndrome) caused by the HIV virus. A person is said to have AIDS when their immune system is too weak to fight off infection, and they develop certain symptoms and illnesses (known as ‘opportunistic infections ’). This is the last stage of HIV, when the infection is very advanced, and if left untreated will lead to death.
Basic facts about AIDS
- AIDS stands for acquired immune deficiency syndrome. It’s also called advanced HIV infection or late-stage HIV.
- AIDS is a set of symptoms and illnesses that develop when an advanced HIV infection has destroyed the immune system.
- Fewer people develop AIDS now, as more people are on treatment for HIV and staying well.
Although there is no cure for HIV, with the right treatment and support, people living with HIV can enjoy long and healthy lives. To do this, it’s especially important to commit to taking treatment correctly.
Doctor describes HIV/AIDS epidemic and COVID-19 pandemic parallels as ‘hauntingly similar’
DALLAS — Forty years since the HIV/AIDS epidemic hit the nation on June 5, 1981, HIV/AIDS survivors and people living with HIV report seeing similarities between the epidemic and the COVID-19 pandemic.
What You Need To Know
Prism Health North Texas CEO Dr. John T. Carlo notes numerous parallels between the HIV/AIDS crisis that appeared in the ’80s and the COVID-19 pandemic
Carlo says both health crises created a stigma among patients; another similarity, he said, is a reluctance to take preventative measures
In both instances, Carlo says, health inequities inhibited effective treatment
“The first thing was that the fear that living with HIV would put you at high risk for more severe COVID-19 infection. And many people I talked to talked about the fact that they’ve lived for 40 years with the past epidemic of HIV only to experience potentially dying over a weekend from COVID-19,” said Prism Health North Texas CEO Dr. John T. Carlo.
Prism Health North Texas has four health centers in Dallas and has been providing care for people living with HIV since 1986, around the height of the HIV/AIDS epidemic. Most of Dr. Carlo’s career has been focused on public health emergencies like HIV/AIDS, Ebola, H1N1, West Nile Virus, and the community’s response to them. He says the unknowns of the HIV/AIDS epidemic are hauntingly similar to those associated with the COVID-19 pandemic.
“I think it really reminded us back when, in the early ’80s, when we had this unknown virus, we didn’t know where it came from and we had no treatment, and we barely had a way to test for it. So as you remember from coronavirus, it was very, very similar. You know, and now thankfully the vaccine came out, but that’s another piece where we’re just still waiting from the HIV and AIDS epidemic to have a vaccine like we’ve seen with the coronavirus,” Carlo said.
“It may be as a part of our evolution as human beings, but I do think it was extremely apparent, not only during HIV and AIDS but also during the coronavirus pandemic where we really were internalizing stigma by looking at who became infected and who did not. And oftentimes using, I think, what would be our innate fear of infectious diseases as a way to subdivide populations, which again is extremely dangerous, especially when you’re looking at the tremendous health inequities that we have in this country,” Carlo said.
While developed countries had access to effective antiretrovirals in the late ’90s, in places that were hard-hit like Sub-Saharan Africa and Haiti, the deaths continued to climb until at least a decade later.
“We may visualize from our history, you know, that those that were suffering from HIV and AIDS were white, male, gay men, and really this was not the case and is not the case,” Carlo said. “It’s just it’s interesting that that the fact that African Americans, Latinos, Hispanics, men and women were suffering from HIV and AIDS and yet even today we still see only this visible group of people that were affected. So, I think even back during our early ’80s period, there was still this inequity of awareness that there were many populations that were more seriously affected.”
Dr. Carlo says the health inequities that existed during the AIDS crisis, once therapies became available, mirror how COVID-19 treatments and vaccine rollouts have been.
“Even early on with the coronavirus pandemic, we recognized that there were systemic inequities in terms of having available treatments. There were some early indications that certain medications might be effective for preventing severe coronavirus infections. These drugs were experimental but were being run at very specific hospitals. And what we found is even with that limited scope, there were still inequities within that system. And I think it just continued to perpetuate into what we saw with the vaccines initially as they came out,” Carlo said.
The biggest struggle with both HIV/AIDS and COVID is complacency. Despite the advances in technology, he wants to remind everyone there’s still a ways to go with both HIV/AIDS as well as COVID-19.
“We’re certainly not done with HIV and AIDS after 40 years and we’re certainly not done with coronavirus at this point with all the variants,” Carlo said. “With HIV/AIDS, many people who are becoming infected are not taking the precautions of prevention that really do work and could work. I think the same thing is happening with coronavirus today. I think many people are believing that it’s not a problem anymore and that we’re done, we’ve declared the victory. And we know we’re not done yet. So I think there’s a lot of parallels unfortunately, and it’s back to our sense of complacency and wanting to perhaps move on from a terrible crisis that we’ve been under, but I think we’ve got to have that perspective that we’re not done yet.”
Dr. Carlo believes we all need to celebrate the successes that we’ve had with COVID-19 treatments and vaccines, and the therapies created to control HIV. But he says there is still much to learn with these diseases.
“We are at our very best when we created vaccines that work incredibly well and are incredibly safe. And it’s remarkable that we have these great vaccines so quickly and are able to move into this direction and we should celebrate that. But we are not at our best when we look at the health inequities and who suffered the most during this pandemic,” Carlo said. “And, as we know, that was a structured issue related to your socioeconomic background, your race and ethnicity, as well as your underlying medical conditions, which were not treated. So I think again, HIV and AIDS is very similar to this because these are the same successes and challenges that we continue to face.”
At Prism Health North Texas, people living with HIV are connected to care and services in the area. The organization strives to remove barriers that may prevent people from getting quality health care.
“We are very, very intentional, as we’re looking at HIV as a virus that is treatable and preventable. And what we do from there is to really stage our resources so that we can reach as many people as effectively as possible. And to reach that end, we don’t take the conditions of health insurance or how much money you have or how much money you make or what resources you have as a condition of whether or not we will see you. You know, we see everybody regardless of the ability to pay,” Carlo said. “The other part, though, is this is not a charitable clinic. This is a clinic that you can receive the very best HIV treatment in this area. So we’re not here to just provide services for the for the low income, this is really a place for everybody. And that I think is the health equity model that I think is what makes this organization successful. We look at every individual as really somebody that really has a right to receive the best health care, and we strive to do the very best and make sure that we are supplying that health care and meeting those individual needs.”
Beyond just treatment, Prism Health North Texas addresses other unmet medical needs like behavioral health, depression, anxiety, substance abuse, even high blood pressure.
“We see it every day, and if we don’t do that treatment, we can’t be successful in HIV treatment and prevention. So we really have set the stage to supply the health care in a comprehensive manner, and really take it as a patient centered approach so that we can do the very best for our patients,” Carlo said.
Origins of HIV and the AIDS Pandemic
Acquired immunodeficiency syndrome (AIDS) of humans is caused by two lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2). Here, we describe the origins and evolution of these viruses, and the circumstances that led to the AIDS pandemic. Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates. Most of these transfers resulted in viruses that spread in humans to only a limited extent. However, one transmission event, involving SIVcpz from chimpanzees in southeastern Cameroon, gave rise to HIV-1 group M—the principal cause of the AIDS pandemic. We discuss how host restriction factors have shaped the emergence of new SIV zoonoses by imposing adaptive hurdles to cross-species transmission and/or secondary spread. We also show that AIDS has likely afflicted chimpanzees long before the emergence of HIV. Tracing the genetic changes that occurred as SIVs crossed from monkeys to apes and from apes to humans provides a new framework to examine the requirements of successful host switches and to gauge future zoonotic risk.
Ever since HIV-1 was first discovered, the reasons for its sudden emergence, epidemic spread, and unique pathogenicity have been a subject of intense study. A first clue came in 1986 when a morphologically similar but antigenically distinct virus was found to cause AIDS in patients in western Africa (Clavel et al. 1986). Curiously, this new virus, termed human immunodeficiency virus type 2 (HIV-2), was only distantly related to HIV-1, but was closely related to a simian virus that caused immunodeficiency in captive macaques (Chakrabarti et al. 1987; Guyader et al. 1987). Soon thereafter, additional viruses, collectively termed simian immunodeficiency viruses (SIVs) with a suffix to denote their species of origin, were found in various different primates from sub-Saharan Africa, including African green monkeys, sooty mangabeys, mandrills, chimpanzees, and others (Fig. 1). Surprisingly, these viruses appeared to be largely nonpathogenic in their natural hosts, despite clustering together with the human and simian AIDS viruses in a single phylogenetic lineage within the radiation of lentiviruses (Fig. 2). Interestingly, close simian relatives of HIV-1 and HIV-2 were found in chimpanzees (Huet et al. 1990) and sooty mangabeys (Hirsch et al. 1989), respectively. These relationships provided the first evidence that AIDS had emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species (Sharp et al. 1994). Indeed, subsequent studies confirmed that SIVmac was not a natural pathogen of macaques (which are Asian primates), but had been generated inadvertently in US primate centers by inoculating various species of macaques with blood and/or tissues from naturally infected sooty mangabeys (Apetrei et al. 2005, 2006). Similarly, it became clear that HIV-1 and HIV-2 were the result of zoonotic transfers of viruses infecting primates in Africa (Hahn et al. 2000). In this article, we summarize what is known about the simian precursors of HIV-1 and HIV-2, and retrace the steps that led to the AIDS pandemic.
Lentiviruses cause chronic persistent infections in various mammalian species, including bovines, horses, sheep, felines, and primates. The great majority of lentiviruses are exogenous, meaning that they are transmitted horizontally between individuals. However, it has recently become clear that, on several occasions in the past, lentiviruses have infiltrated their hosts’ germlines and become endogenous, vertically transmissible, genomic loci (Fig. 2). Examples include the rabbit endogenous lentivirus type K (RELIK), which became germ-line embedded approximately 12 million years ago (Katzourakis et al. 2007; van der Loo et al. 2009), and two prosimian endogenous lentiviruses, which independently invaded the germ-lines of both the grey mouse lemur (pSIVgml) and the fat-tailed dwarf lemur (pSIVfdl) about 4 million years ago (Gifford et al. 2008; Gilbert et al. 2009). These “viral fossils” are of particular interest because they provide direct evidence of the timescale of lentivirus evolution. Molecular clocks derived from extant SIV sequences suggested that ancestral SIVs existed only a few hundreds of years ago (Wertheim and Worobey 2009), but it has long been suspected that such analyses may grossly underestimate deeper evolutionary timescales (Sharp et al. 2000; Holmes 2003). Recent studies of SIV-infected monkeys on Bioko Island, Equatorial Guinea, partly substantiated this conclusion, showing that geographically isolated subspecies have been infected with the same type of SIV for at least 30,000 years and probably much longer (Worobey et al. 2010). The endogenous viruses in lemurs reveal that the span of evolutionary history of primate lentiviruses as a whole is at least two orders of magnitude greater still. Thus, it is possible that at least some SIVs, such as those infecting four closely related species of African green monkeys (Chlorocebus species), have coevolved with their respective hosts for an extended period of time, perhaps even before these hosts diverged from their common ancestor (Jin et al. 1994a). So far, SIV infections have only been found in African monkeys and apes, and so it seems likely that primate lentiviruses emerged in Africa sometime after the splits between lineages of African and Asian Old World monkeys, which are believed to have occurred around 6–10 million years ago (Fabre et al. 2009). However, because neither Asian nor New World primates have been sampled exhaustively, the conclusion that SIVs are restricted to African primates must remain tentative, especially because none of these primate species has been examined for endogenous forms of SIV (Ylinen et al. 2010). Thus, our understanding of the evolutionary history of primate lentiviruses is still incomplete.
To date, serological evidence of SIV infection has been reported for over 40 primate species, and molecular data have been obtained for most of these (also see Klatt et al. 2011). The latter studies have shown that the great majority of primate species harbor a single “type” or “strain” of SIV. That is, viral sequences from members of the same species form a monophyletic clade in evolutionary trees. This host-specific clustering indicates that the great majority of transmissions occur among members of the same species; however, there are also numerous documented instances when SIVs have crossed between species. Examples range from incidental “dead-end” infections (e.g., SIVver infections of baboons) (Jin et al. 1994b; van Rensburg et al. 1998) to the generation of new SIV lineages with substantial secondary spread (e.g., SIVgor infection of gorillas) (Van Heuverswyn et al. 2006). In addition, cross-species transmissions have generated mosaic SIV lineages through superinfection and recombination in species that already harbored an SIV (e.g., SIVsab infection of sabaeus monkeys) (Jin et al. 1994a). In both mandrills (Mandrillus sphinx) and moustached monkeys (Cercopithecus cephus), such recombination events have led to the emergence of a second SIV strain that cocirculates with the original virus (Souquiere et al. 2001; Aghokeng et al. 2007). Thus, it is clear that in addition to more long-standing virus/host relationships, a number of naturally occurring SIVs have emerged more recently as a result of cross-species transmission and recombination. What remains unknown is when and how often these cross-species transfers have occurred, what impact they had on virus and host biology, and whether AIDS is a frequent consequence of SIV host switching. The prevalence of naturally occurring SIV infections varies widely, ranging from 1% in some species to over 50% in others (Aghokeng et al. 2010), and it is tempting to speculate that less ubiquitous SIVs were acquired more recently and/or may be more pathogenic.Go to:
ORIGIN AND DISTRIBUTION OF SIVcpz
Of the many primate lentiviruses that have been identified, SIVcpz has been of particular interest because of its close genetic relationship to HIV-1 (Fig. 2). However, studies of this virus have proven to be challenging because of the endangered status of chimpanzees. The first isolates of SIVcpz were all derived from animals housed in primate centers or sanctuaries, although infection was rare in these populations. Collective analyses of nearly 2,000 wild-caught or captive-born apes identified fewer than a dozen SIVcpz positive individuals (Sharp et al. 2005). Because other primate species, such as sooty mangabeys and African green monkeys, are much more commonly infected, both in captivity and in the wild (Fultz et al. 1990; Phillips-Conroy et al. 1994; Santiago et al. 2005), this finding raised doubts about whether chimpanzees represented a true SIV reservoir. To resolve this conundrum, our laboratory developed noninvasive diagnostic methods that detect SIVcpz specific antibodies and nucleic acids in chimpanzee fecal and urine samples with high sensitivity and specificity (Santiago et al. 2003; Keele et al. 2006). These technical innovations, combined with genotyping methods for species and subspecies confirmation as well as individual identification, permitted a comprehensive analysis of wild-living chimpanzee populations throughout central Africa.
Chimpanzees are classified into two species, the common chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Common chimpanzees have traditionally been further subdivided into a number of geographically differentiated subspecies (Groves 2001). Four subspecies were defined on the basis of mitochondrial DNA sequences (Gagneux et al. 1999), namely western (P. t. verus), Nigeria-Cameroonian (P. t. ellioti, formerly termed P. t. vellerosus), central (P. t. troglodytes), and eastern (P. t. schweinfurthii) chimpanzees. To determine the distribution of SIVcpz among these populations, fecal (and in some cases urine) samples were collected at different field sites and tested for the presence of virus specific antibodies. Antibody positive fecal specimens were then subjected to RNA extraction and reverse transcriptase polymerase chain reaction (RT-PCR) amplification to molecularly characterize the infecting virus strain. At select field sites, mitochondrial and microsatellite analyses of host DNA were also used to confirm sample integrity and to determine the number of tested individuals. Figure 3A summarizes current molecular epidemiological data derived from the analysis of over 7,000 chimpanzee fecal samples collected at nearly 90 field sites (Santiago et al. 2002, 2003; Worobey et al. 2004; Keele et al. 2006; Van Heuverswyn et al. 2007; Li et al. 2010; Rudicell et al. 2010). These studies have identified common chimpanzees as a natural SIVcpz reservoir, but also revealed important differences between the epidemiology of SIVcpz and that of other primate lentiviruses. First, only two of the four chimpanzee subspecies were found to harbor these viruses. SIVcpz was detected at multiple sites throughout the ranges of both central and eastern chimpanzees in an area ranging from Cameroon to Tanzania, but there was no evidence of infection in western and Nigeria-Cameroonian chimpanzees, nor in bonobos, despite testing of multiple communities. In addition, SIVcpz prevalence rates among central and eastern chimpanzees varied widely, ranging from 30% to 50% in some communities to rare or absent infection in others. In contrast, other SIVs, such as those of sooty mangabeys and African green monkeys, are much more widely and evenly distributed and infect their hosts at generally higher prevalence rates (Phillips-Conroy et al. 1994; Santiago et al. 2005). Nonetheless, the puzzle of why SIVcpz was so scarce among captive chimpanzees was finally resolved: As it turned out, most of these apes were imported from West Africa and thus were members of the P. t. verus subspecies, which does not harbor SIVcpz (Prince et al. 2002; Switzer et al. 2005).
The absence of SIVcpz from two of the four subspecies suggested that chimpanzees had acquired this virus more recently, after their divergence into different subspecies. Indeed, phylogenetic analyses of full-length proviral sequences revealed that SIVcpz represents a complex mosaic, generated by recombination of two lineages of SIVs that infect monkeys (Bailes et al. 2003). In the 5′ half of the genome, as well as the nef gene and 3′ LTR, SIVcpz is most closely related to SIVrcm from red-capped mangabeys (Cercocebus torquatus); however, in the vpu, tat, rev, and env genes, SIVcpz is most closely related to a clade of SIVs infecting several Cercopithecus species, including greater spot-nosed (C. nictitans), mustached (C. cephus), and mona (C. mona) monkeys (Bailes et al. 2003). Chimpanzees are known to hunt and kill other mammals, including monkeys (Goodall 1986), suggesting that they acquired SIV in the context of predation. The current range of the central chimpanzee overlaps those of red-capped mangabeys and the various Cercopithecus species, and so it is likely that the cross-species transmission events that led to the emergence of SIVcpz occurred in that area, and that SIVcpz later spread to eastern chimpanzees, although it is unclear whether this occurred during or subsequent to their divergence from the central subspecies. Importantly, all of more than 30 sequenced SIVcpz strains show an identical mosaic genome structure. Moreover, there is no evidence that chimpanzees harbor any other SIV, although they, as well as bonobos, are routinely exposed to SIVs through their hunting behavior (Mitani and Watts 1999; Surbeck and Hohmann 2008; Leendertz et al. 2011).Go to:
NATURAL HISTORY OF SIVcpz INFECTION
Initially, SIVcpz was thought to be harmless for its natural host. This was because none of the few captive apes that were naturally SIVcpz infected suffered from overt immunodeficiency, although in retrospect this conclusion was based on the immunological and virological analyses of only a single naturally infected chimpanzee (Heeney et al. 2006). In addition, SIV-infected sooty mangabeys and African green monkeys showed no sign of disease despite high viral loads in blood and lymphatic tissues (Paiardini et al. 2009), leading to the belief that all naturally occurring SIV infections are nonpathogenic. However, the sporadic prevalence of SIVcpz, along with its more recent monkey origin, suggested that its natural history might differ from that of other primate lentiviruses. To address this, a prospective study was initiated in Gombe National Park, Tanzania, the only field site where SIVcpz infected chimpanzees are habituated and so can be observed in their natural habitat.
Gombe is located in northwestern Tanzania on the shores of Lake Tanganyika. The park is home to three communities, termed Kasekela, Mitumba, and Kalande, which have been studied by Goodall and colleagues since the 1960s, 1980s, and 1990s, respectively (Pusey et al. 2007). Prospective studies of SIVcpz in Gombe began in 2000 (Santiago et al. 2002). By 2009, infections were documented in all three communities, with mean biannual prevalence rates of 13%, 12%, and 46% in Mitumba, Kasekela, and Kalande, respectively (Rudicell et al. 2010). Analysis of epidemiologically linked infections revealed that SIVcpz spreads primarily through sexual routes, with an estimated transmission probability per coital act (0.0008–0.0015) that is similar to that of HIV-1 among heterosexual humans (0.0011) (Gray et al. 2001; Rudicell et al. 2010). SIVcpz also appears to be transmitted from infected mothers to their infants, and in rare cases, possibly by aggression (Keele et al. 2009). Migration of infected females constitutes a major route of virus transmission between communities (Rudicell et al. 2010).
Behavioral and virological studies also provided insight into the pathogenicity of SIVcpz. Age-corrected mortality analyses revealed that infected chimpanzees had a 10- to 16-fold increased risk of death compared to uninfected chimpanzees (Keele et al. 2009). SIVcpz-infected females were less likely to give birth and had a much higher infant mortality rate than uninfected females. Postmortem analyses revealed significant CD4+ T-cell depletion in three infected individuals, but not in either of two uninfected individuals. One infected female, who died within 3 years of acquiring the virus, had histopathological findings consistent with end-stage AIDS. Taken together, these findings provided compelling evidence that SIVcpz was pathogenic in its natural host. Subsequent studies of both wild and captive chimpanzees confirmed these findings. By the end of 2010, the Kasekela and Mitumba communities had experienced three additional deaths, all SIVcpz related. One case concerned an infant born to an infected mother, whereas the other two were adult females, one of whom died with severe CD4+ T cell depletion within 5 years of acquiring SIVcpz (KA Terio et al., submitted). Moreover, demographic studies revealed that the Kalande community, which showed the highest SIVcpz prevalence rates (40%–50%), had suffered a catastrophic population decline, whereas the sizes of the Mitumba and Kasekela communities, which were infected at a much lower level (12%–13%), remained stable (Rudicell et al. 2010). It has been suggested that only members of the P. t. schweinfurthii subspecies, or more particularly the chimpanzees of Gombe, are susceptible to SIVcpz-associated pathogenicity (Weiss and Heeney 2009; Soto et al. 2010). However, a prospective study of orphaned chimpanzees in Cameroon identified an SIVcpz infected P. t. troglodytes ape that suffered from progressive CD4+ T cell loss, severe thrombocytopenia, and clinical AIDS (Etienne et al. 2011). Thus, it seems likely that SIVcpz has a substantial negative impact on the health, reproduction, and lifespan of all chimpanzees that harbor SIVcpz in the wild.Go to:
ORIGIN AND DISTRIBUTION OF SIVgor
Noninvasive testing also led to the unexpected finding of a new SIV lineage in wild-living gorillas (Fig. 4). Analysis of ∼ 200 fecal samples from southern Cameroon identified several HIV/SIV antibody positive gorillas, and amplification of viral sequences revealed the existence of a new SIV lineage, termed SIVgor (Van Heuverswyn et al. 2006). This lineage fell within the radiation of SIVcpz, clustering with strains from P. t. troglodytes apes, suggesting that gorillas had acquired SIVgor by cross-species infection from sympatric chimpanzees (Fig. 4). Phylogenetic analyses of full-length SIVgor sequences confirmed this conclusion, indicating that SIVgor resulted from a single chimpanzee-to-gorilla transmission event estimated to have occurred at least 100 to 200 years ago (Takehisa et al. 2009). Subsequent screening of over 2500 fecal samples from 30 field sites across central Africa uncovered additional SIVgor infections, but only in western lowland gorillas (Gorilla gorilla gorilla) and not in eastern gorillas (Gorilla beringei). Although virus-positive apes were present at field sites more than 400 km apart, only four such sites were identified, and prevalence rates in these communities did not exceed 5% (Fig. 3B). Thus, SIVgor appears to be much less common in gorillas than SIVcpz is in chimpanzees (Neel et al. 2010). Whether SIVgor is more prevalent in communities in parts of west central Africa that have not yet been tested is not known. It is also unclear whether SIVgor is pathogenic for its host, because there has been no opportunity to study the natural history of this infection in either captive or wild-living gorillas. Finally, it remains a mystery how gorillas acquired SIVgor, because they are herbivores and do not hunt or kill other mammals. Nonetheless, gorillas and chimpanzees feed in the same forest areas, which must have led to at least one encounter that allowed transmission.
ORIGINS OF HIV-1
HIV-1 has long been suspected to be of chimpanzee origin (Gao et al. 1999); however, until recently, the perceived lack of a chimpanzee reservoir left the source of HIV-1 open to question. These uncertainties have since been resolved by noninvasive testing of wild-living ape populations. It is now well established that all naturally occurring SIVcpz strains fall into two subspecies-specific lineages, termed SIVcpzPtt and SIVcpzPts, respectively, that are restricted to the home ranges of their respective hosts (Figs. 3 and and4).4). Viruses from these two lineages are quite divergent, differing at about 30%–50% of sites in their Gag, Pol, and Env protein sequences (Vanden Haesevelde et al. 1996). Interestingly, population genetic studies have shown that central and eastern chimpanzees are barely differentiated, calling into question their status as separate subspecies (Fischer et al. 2006; Gonder et al. 2011). However, the fact that they harbor distinct SIVcpz lineages suggests that central and eastern chimpanzees have been effectively isolated for some time. In addition, molecular epidemiological studies in southern Cameroon have shown that SIVcpzPtt strains show phylogeographic clustering, with viruses from particular areas forming monophyletic lineages, and the discovery of SIVgor has identified a second ape species as a potential reservoir for human infection (Van Heuverswyn et al. 2006). Collectively, these findings have allowed the origins of HIV-1 to be unraveled (Keele et al. 2006; Van Heuverswyn et al. 2007).
HIV-1 is not just one virus, but comprises four distinct lineages, termed groups M, N, O, and P, each of which resulted from an independent cross-species transmission event. Group M was the first to be discovered and represents the pandemic form of HIV-1; it has infected millions of people worldwide and has been found in virtually every country on the globe. Group O was discovered in 1990 and is much less prevalent than group M (De Leys et al. 1990; Gurtler et al. 1994). It represents less than 1% of global HIV-1 infections, and is largely restricted to Cameroon, Gabon, and neighboring countries (Mauclere et al. 1997; Peeters et al. 1997). Group N was identified in 1998 (Simon et al. 1998), and is even less prevalent than group O; so far, only 13 cases of group N infection have been documented, all in individuals from Cameroon (Vallari et al. 2010). Finally, group P was discovered in 2009 in a Cameroonian woman living in France (Plantier et al. 2009). Despite extensive screening, group P has thus far only been identified in one other person, also from Cameroon (Vallari et al. 2011). Although members of all of these groups are capable of causing CD4+ T-cell depletion and AIDS, they obviously differ vastly in their distribution within the human population.
Figure 4 depicts a phylogenetic tree of representative HIV-1, SIVcpz, and SIVgor strains. It shows that all four HIV-1 groups, as well as SIVgor, cluster with SIVcpzPtt from central chimpanzees, identifying this subspecies as the original reservoir of both human and gorilla infections. HIV-1 groups N and M are very closely related to SIVcpzPtt strains from southern Cameroon, indicating that they are of chimpanzee origin. It has even been possible to trace their ape precursors to particular P. t. troglodytes communities. HIV-1 group N appears to have emerged in the vicinity of the Dja Forest in south-central Cameroon, whereas the pandemic form, group M, likely originated in an area flanked by the Boumba, Ngoko, and Sangha rivers in the southeastern corner of Cameroon (Keele et al. 2006; Van Heuverswyn et al. 2007). Existing phylogenetic data support a gorilla origin of HIV-1 group P, but too few SIVgor strains have been characterized to identify the region where this transmission might have occurred. In contrast, the immediate source of HIV-1 group O remains unknown, because there are no ape viruses that are particularly closely related to this group (Fig. 4). Thus, HIV-1 group O could either be of chimpanzee or gorilla origin. Nonetheless, the fact that group O and P viruses are more closely related to SIVcpzPtt than to SIVcpzPts suggests that both groups originated in west central Africa, which is consistent with their current distributions.
How humans acquired the ape precursors of HIV-1 groups M, N, O, and P is not known; however, based on the biology of these viruses, transmission must have occurred through cutaneous or mucous membrane exposure to infected ape blood and/or body fluids. Such exposures occur most commonly in the context of bushmeat hunting (Peeters et al. 2002). Whatever the circumstances, it seems clear that human–ape encounters in west central Africa have resulted in four independent cross-species transmission events. Molecular clock analyses have dated the onset of the group M and O epidemics to the beginning of the twentieth century (Korber et al. 2000; Lemey et al. 2004; Worobey et al. 2008). In contrast, groups N and P appear to have emerged more recently, although the sequence data for these rare groups are still too limited to draw definitive conclusions.
Eastern chimpanzees are endemically infected with SIVcpzPts throughout central Africa (Fig. 3A). Although prevalence rates have not been determined for all field sites, the P. t. schweinfurthii communities that have been studied show infection rates that are very similar to those found in P. t. troglodytes (Keele et al. 2006, 2009; Rudicell et al. 2010). Given that SIVcpzPtt strains have been transmitted to gorillas and humans on at least five occasions, it is striking that evidence of similar transmissions from eastern chimpanzees is lacking. There are a number of possible explanations. First, the risk of human exposure to SIVcpzPts may be lower, perhaps because of differences in the frequencies or types of human–ape interactions in central and east Africa. Second, SIVcpzPts infections of humans may have occurred, but gone unrecognized, because of limited human sampling and a lack of lineage-specific serological tests. Finally, as discussed below, SIVcpzPtt has evolved to overcome human restriction factors, such as tetherin, which may pose a barrier to cross-species transmission; because SIVcpzPts is highly divergent from SIVcpzPtt, viruses from this lineage may not have been able to adapt in the same way. Although SIVcpzPtt and SIVcpzPts strains replicate with similar kinetics in human CD4+ T cells in vitro (Takehisa et al. 2007), such cultures are unlikely to accurately recapitulate the conditions of viral replication and transmission in vivo.Go to:
ORIGINS OF HIV-2
Since its first discovery, HIV-2 has remained largely restricted to West Africa, with its highest prevalence rates recorded in Guinea-Bissau and Senegal (de Silva et al. 2008). However, overall prevalence rates are declining, and in most West African countries HIV-2 is increasingly being replaced by HIV-1 (van der Loeff et al. 2006; Hamel et al. 2007). Viral loads tend to be lower in HIV-2 than HIV-1 infected individuals, which may explain the lower transmission rates of HIV-2 and the near complete absence of mother-to-infant transmissions (Popper et al. 2000; Berry et al. 2002). In fact, most individuals infected with HIV-2 do not progress to AIDS, although those who do, show clinical symptoms indistinguishable from HIV-1 (Rowland-Jones and Whittle 2007). Thus, it is clear that the natural history of HIV-2 infection differs considerably from that of HIV-1, which is not surprising given that HIV-2 is derived from a very different primate lentivirus.
A sooty mangabey origin of HIV-2 was first proposed in 1989 (Hirsch et al. 1989) and subsequently confirmed by demonstrating that humans in West Africa harbored HIV-2 strains that resembled locally circulating SIVsmm infections (Gao et al. 1992; Chen et al. 1996). SIVsmm was found to be highly prevalent, both in captivity and in the wild, and to be nonpathogenic in its natural host (Silvestri 2005). In a wild-living sooty mangabey community, SIVsmm was primarily found in higher-ranking females, suggesting that virus infection had no appreciable negative effect on reproductive behavior or success (Santiago et al. 2005). Finally, the fact that sooty mangabeys are frequently hunted as agricultural pests in many areas of West Africa provided plausible routes of transmission.
Since its first isolation, at least eight distinct lineages of HIV-2 have been identified, each of which appears to represent an independent host transfer (Fig. 5). By analogy with HIV-1, these lineages have been termed groups A–H, although only groups A and B have spread within humans to an appreciable degree. Group A has been found throughout western Africa (Damond et al. 2001; Peeters et al. 2003), whereas group B predominates in Cote d’Ivoire (Pieniazek et al. 1999; Ishikawa et al. 2001). All other HIV-2 “groups” were initially identified only in single individuals, suggesting that they represent incidental infection with very limited or no secondary spread. Of these, groups C, G, and H have been linked to SIVsmm strains from Cote d’Ivoire, group D is most closely related to an SIVsmm strain from Liberia, and groups E and F resemble SIVsmm strains from Sierra Leone (Gao et al. 1992; Chen et al. 1996, 1997; Santiago et al. 2005). Because of their sporadic nature, groups C–H have been assumed to represent “dead-end” transmissions. However, a second divergent HIV-2 strain has recently been placed in group F (Fig. 5). This virus was identified in an immigrant in New Jersey, who came from the same geographic area in Sierra Leone where this lineage was first discovered (Smith et al. 2008). Unlike the original index case, the newly identified group F infection was associated with reduced CD4 T cell counts and high viral loads (Smith et al. 2008). It is presently unknown whether group F has been spreading cryptically in humans, or whether the two group F viruses represents independent transmissions from sooty mangabeys.
HIV and SIV must interact with a large number of host proteins to replicate in infected cells (Fu et al. 2009; Ortiz et al. 2009). Because the common ancestor of Old World monkeys and apes existed around 25 million years ago, the divergence of these host proteins may pose an obstacle to cross-species infection. In addition, primates (including humans) encode a number of host restriction factors, which have evolved as part of their innate immune response to protect against infection with a wide variety of viral pathogens (Malim and Emerman 2008; Neil and Bieniasz 2009; Kajaste-Rudnitski et al. 2010). Although viruses have, in turn, found ways to antagonize these restriction factors, these countermeasures are frequently species-specific. Thus, a number of adaptive hurdles have to be overcome before primate lentiviruses can productively infect a new species.
The first evidence of host-specific adaptation of HIV-1 came from an analysis of sites in the viral proteome that were highly conserved in the ape precursors of HIV-1, but changed—in the same way—each time these viruses crossed the species barrier to humans (Wain et al. 2007). This analysis identified one site in the viral matrix protein (Gag-30) that encoded a Met in all known strains of SIVcpzPtt and SIVgor but switched to an Arg in the inferred ancestors of HIV-1 groups M, N, and O, and has subsequently been conserved as a basic amino acid (Arg or Lys) in most strains of HIV-1. The fact that the same nonconservative amino acid substitution occurred on each of the three branches involving cross-species transmission to humans suggested that this matrix residue was under strong host-specific selection pressure. This conclusion was subsequently confirmed by two additional observations. First, it was found that a reciprocal transmission, in which a chimpanzee was experimentally infected with HIV-1, led to the reversion of this host-specific signature; that is, a basic residue at Gag-30 in HIV-1 changed back to a Met on in vivo propagation in a chimpanzee (Mwaengo and Novembre 1998). Second, it was found that in chimpanzee CD4+ T lymphocytes, a virus with a Met at position 30 replicated more efficiently that an otherwise isogenic virus with a Lys at the same position, whereas the opposite was true in human cells (Wain et al. 2007). Interestingly, only one of the two recently discovered HIV-1 group P strains has switched from a Met to a Lys at Gag-30 (Vallari et al. 2011). Although the structure of the HIV-1 matrix protein has been determined (Hill et al. 1996), the function of the amino acid at position 30 is not known, and it remains to be determined why this site is under such strong selection pressure.
The potential of an SIV to infect a new primate species is also influenced by its ability to counteract different host restriction factors. Three classes of restriction factors have been shown to constitute barriers to SIV cross-species transmission. These include (1) APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G), which interferes with reverse transcription (Sheehy et al. 2002); (2) TRIM5α (tripartite motif 5α protein), which interferes with viral uncoating (Stremlau et al. 2004); and (3) tetherin (also termed BST-2 and CD317) which inhibits the budding and release of virions from infected cells (Neil et al. 2008). Of these, tetherin appears to have had the greatest impact on the precursors of HIV-1 and HIV-2 (Fig. 6). Tetherin is comprised of a cytoplasmic amino-terminal region, a trans-membrane domain, a coiled-coiled extracellular domain, and a carboxy-terminal glycosylphosphatidylinositol (GPI) anchor (Fig. 6B). Recent studies have shown that most SIVs use their Nef protein to remove tetherin from the cell surface by targeting its cytoplasmic domain (Jia et al. 2009; Zhang et al. 2009). In contrast, HIV-1 (Neil et al. 2008; Van Damme et al. 2008) as well as SIVs from greater spot-nosed, mona, moustached, and Dent’s monkeys (Sauter et al. 2009; Schmokel et al. 2011) use their Vpu protein to degrade tetherin by binding to its membrane-spanning domain (Iwabu et al. 2009; Rong et al. 2009). Still other viruses use their envelope glycoprotein to interfere with tetherin, by interacting with either its extracellular or its cytoplasmic domain (Bour et al. 1996; Gupta et al. 2009; Le Tortorec and Neil 2009; Serra-Moreno et al. 2011). These various antitetherin responses appear to have emerged as a direct result of host-specific selection pressures following cross-species transmission (Sauter et al. 2009; Evans et al. 2010; Lim et al. 2010).
Because of the constant onslaught of viral pathogens, host restriction factors evolve rapidly (Sawyer et al. 2004, 2005; McNatt et al. 2009; Lim et al. 2010). Most notably, the human tetherin gene differs from that of other apes by a five-codon deletion in the region encoding the cytoplasmic domain (Sauter et al. 2009). Because Nef interacts with the cytoplasmic domain of tetherin, this deletion rendered the SIVcpz Nef protein inactive on transmission to humans. Gorilla tetherin does not have this deletion, and thus Nef continued to function as a tetherin antagonist on transmission of SIVcpz to gorillas (Fig. 6C). Thus, to facilitate replication in humans, SIVcpz and SIVgor had to find alternative routes to overcome tetherin. One option was to switch back to using Vpu, as in their monkey ancestors (Fig. 6C). However, this required that the SIVcpz and SIVgor Vpu proteins regained this function because neither has antitetherin activity in chimpanzee or humans cells. Not surprisingly, this was not successful in all instances (Fig. 6C). When representatives of each of the HIV-1 groups were analyzed, only the Vpu proteins of group M viruses showed potent antitetherin activity (Sauter et al. 2009). Group O and P Vpu proteins were completely inactive, whereas the group N Vpu showed only marginal activity (Sauter et al. 2009; Kirchhoff 2010). Moreover, even the latter adaptation came at a cost, because the group N Vpu lost its ability to down-modulate CD4. Thus, of the four transmitted ape viruses, only the precursor of HIV-1 group M succeeded in mounting a full antitetherin defense in human cells. It may thus not be a coincidence that only HIV-1 group M resulted in a global epidemic (Gupta and Towers 2009; Sauter et al. 2009).
Like many other SIVs, SIVsmm does not encode a vpu gene and uses its Nef protein to combat tetherin. Thus, on transmission to humans, SIVsmm had to overcome the same hurdle of a cytoplasmic tail deleted human tetherin. In this case, the envelope glycoprotein (gp41) was recruited as an alternative tetherin antagonist (Le Tortorec and Neil 2009). However, this escape mechanism has thus far only been observed for epidemic HIV-2 group A, and it will be interesting to determine which, if any, of the other HIV-2 groups have acquired a similar antitetherin activity. It seems likely that the cytoplasmic domain deletion in human tetherin has represented a significant barrier to SIV zoonoses, including those viruses that have succeeded in infecting humans.Go to:
ORIGIN OF THE AIDS PANDEMIC
HIV-1 evolves around one million times faster than mammalian DNA (Li et al. 1988; Lemey et al. 2006), because the HIV-1 reverse transcriptase is error prone and the viral generation time is short (Ho et al. 1995; Wei et al. 1995). This propensity for rapid genetic change has provided a unique opportunity to gain insight into when and where the AIDS pandemic had its origin. Phylogenetic and statistical analyses have dated the last common ancestor of HIV-1 group M to around 1910 to 1930, with narrow confidence intervals (Korber et al. 2000; Worobey et al. 2008). This indicates that after pandemic HIV-1 first emerged in colonial west central Africa, it spread for some 50 to 70 years before it was recognized. The probable location of the early epidemic has also been identified. Molecular epidemiological studies have indicated that most, if not all, of the early diversification of HIV-1 group M likely occurred in the area around Kinshasa, then called Leopoldville. All of the known HIV-1 group M subtypes were identified there, as well as additional lineages that have remained restricted to this area (Vidal et al. 2000). Leopoldville was also the place where the earliest strains of HIV-1 group M were discovered (Zhu et al. 1998; Worobey et al. 2008). Genetic analysis of infected blood and tissue samples collected from residents of Kinshasa in 1959 and 1960, respectively, revealed that HIV-1 had already diversified into different subtypes by that time (Worobey et al. 2008). Finally, demographic data indicate that pandemic HIV-1 emerged at a time when urban populations in west central Africa were expanding (Worobey et al. 2008). Leopoldville was the largest city in the region at that time and thus a likely destination for a newly emerging infection. Moreover, rivers, which served as major routes of travel and commerce at the time, would have provided a link between the chimpanzee reservoir of HIV-1 group M in southeastern Cameroon and Leopoldville on the banks of the Congo (Sharp and Hahn 2008). Thus, all current evidence points to Leopoldville/Kinshasa as the cradle of the AIDS pandemic.
As HIV-1 group M spread globally, its dissemination involved a number of population bottlenecks—founder events, which led to the predominance of different group M lineages, now called subtypes, in different geographic areas. HIV-1 group M is currently classified into nine subtypes (A–D, F–H, J, K), as well as more than 40 different circulating recombinant forms (CRFs), which were generated when multiple subtypes infected the same population (Taylor et al. 2008). It has been possible to trace the migration pathways of some of these subtypes and CRFs. For example, subtypes A and D originated in central Africa, but ultimately established epidemics in eastern Africa, whereas subtype C was introduced to, and predominates in, southern Africa from where it spread to India and other Asian countries. Subtype B, which accounts for the great majority of HIV-1 infections in Europe and the Americas, arose from a single African strain that appears to have first spread to Haiti in the 1960s and then onward to the US and other western countries (Gilbert et al. 2007). The recombination event that created CRF01 probably occurred in Central Africa, but this viral lineage was first noted in the late 1980s causing a heterosexual epidemic in Thailand, contemporary with subtype B viruses spreading among intravenous drug users (Taylor et al. 2008). CRF01 has gone on to dominate the AIDS epidemic in southeast Asia. Although the initial distribution of these subtypes and CRFs may have been largely caused by chance events, recent studies have suggested that viruses of different subtypes vary in their biological properties, which may influence their epidemiology (Taylor et al. 2008). For example, subtype D has been associated with greater pathogenicity (Kiwanuka et al. 2010) and an increased incidence of cognitive impairment and AIDS dementia (Sacktor et al. 2009). It thus appears that not only the genetic but also the biological diversity of HIV-1 group M subtypes and CRF is increasing.Go to:
Although primate lentiviruses were first identified in the late 1980s, it is only very recently that the complexities of their evolutionary origins, geographic distribution, prevalence, natural history, and pathogenesis in natural and nonnatural hosts have been appreciated. The preceding sections summarize what is known about the origins and evolution of the simian relatives of HIV-1 and HIV-2, their propensity to cross species barriers, and the host factors that govern such transmissions. Given that there are numerous additional primate species that harbor SIV, the question arises what to expect from future zoonoses? Host-specific restriction factors play a major role in preventing cross-species transmission, and they may well be responsible for the fact that only two types of SIV have thus far succeeded in colonizing humans. However, as exemplified by the various HIV-1 and HIV-2 outbreaks, they are certainly not insurmountable. Determining the entire spectrum of host restriction factors and their mechanisms of action will be required to gauge the likelihood of future zoonoses. In this regard, the role of tetherin should be examined further. Because this protein “tethers” virions to the cell surface, a lack of effective antitetherin measures may result in reduced titers of infectious virus in genital secretions. This may explain why the precursors of the rare groups of HIV-1 and HIV-2 were able to infect humans but unable to establish epidemic infections.
From the above, it is also clear that any newly introduced SIV must replicate to some extent to accumulate the necessary mutations that are required to adapt to divergent host proteins and restriction factors. Circumstances that enhance human-to-human passage would thus be expected to increase the chance of such adaptation. It has been suggested that large-scale injection campaigns conducted in west central Africa at the beginning of the twentieth century (Pepin et al. 2006, 2010; Pepin and Labbe 2008), together with the destabilization of social structures (Chitnis et al. 2000), the rapid growth of cities (Worobey et al. 2008), and an increased prevalence in sexually transmitted diseases, including genital ulcers (de Sousa et al. 2010), may have facilitated the early dissemination and adaptation of both HIV-1 and HIV-2. The fact that HIV-1 groups M and O as well as HIV-2 group A all emerged around the same time is consistent with this hypothesis (Korber et al. 2000; Lemey et al. 2003, 2004; Worobey et al. 2008; de Sousa et al. 2010). However, whether these medical interventions and/or social factors really played a role in the emergence of HIV-1 and HIV-2, and more importantly, whether such “jump-starts” were required to spawn the AIDS pandemic, will remain unknown.
Finally, it is important to view the pathogenesis of simian and human AIDS viruses in the context of their evolution (Kirchhoff 2009). One feature of pathogenic HIV-1 and HIV-2 infection that distinguishes them from nonpathogenic SIV infections is a high level of chronic immune activation, which is a strong predictor of disease progression. In HIV-1 infection, this immune activation is fueled, at least in part, by the inability of the Nef protein to down-modulate TCR-CD3, a function that is conserved in most nonpathogenic SIV infections (Schindler et al. 2006; Arhel and Kirchhoff 2009). Lack of this Nef function is associated with increased T-cell activation and apoptosis in vitro and loss of CD4+ T cells in natural SIV infection in vivo (Schindler et al. 2008). A higher state of T- cell activation is associated with enhanced levels of proviral transcription and viral replication, but also with increased expression of interferon-induced restriction factors, such as tetherin. In HIV-1, Vpu compensates for this by providing potent antitetherin activity. It has thus been proposed that to overcome the barriers of cross-species transmission, primate lentiviruses must induce an inflammatory milieu to increase their ability to replicate and accumulate mutations necessary for more adaptation (Kirchhoff 2009). If this were indeed the case, AIDS would be an inevitable consequence of SIV cross-species transmission.
The Origin of COVID-19 and Why It Matters
The COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a β-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia. Scientists have warned for decades that such sarbecoviruses are poised to emerge again and again, identified risk factors, and argued for enhanced pandemic prevention and control efforts. Unfortunately, few such preventive actions were taken resulting in the latest coronavirus emergence detected in late 2019 which quickly spread pandemically. The risk of similar coronavirus outbreaks in the future remains high. In addition to controlling the COVID-19 pandemic, we must undertake vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself.
Smallpox: A Great and Terrible Scourge
Campaign to Eradicate
Headed by D.A. Henderson of the United States Public Health Service, the WHO Smallpox Eradication Unit needed to ascertain levels of smallpox, arrange for the cost-effective production of vaccine and finally vaccinate large populations—many of whom were nomadic or lived in politically unstable regions.
Vaccinating for smallpox can be so difficult that even experienced vaccinators waste vaccine or fail to achieve an adequate “take.”
Jet injectors gave subcutaneous injections (injections under the skin) and delivered vaccine more efficiently than traditional methods of vaccination. To enable vaccinators to bring the jet injector into the field, Aaron Ismach, a civilian in the U.S. Defense Department, developed a foot-powered injector called the “ped-o-jet” which was not dependent on electricity.
Here King Tauf-Ahau Tupou III of Tonga demonstrates a jet-injector.
In 1961, two researchers developed a better method of delivery; the bifurcated needle was easy to use and required only one-quarter of the amount of vaccine previously needed. “Vaccine takes” were now nearly 100 percent and the procedure could be done quickly and easily.
+++The bifurcated needle was easy to carry into the field. After sterilization, the needle could be re-used up to 100 times, making it extremely cost-effective. Ultimately, the bifurcated needle came to be preferred over the jet injector.
In 1967, WHO workers vaccinated 25 million people but large segments of the population were still being missed. To address this, William Foege developed Eradication Escalation or E2. E2 entailed an all-out attack to contain smallpox outbreaks during October, the natural seasonal low point of smallpox transmission. Prevention of just one case during this critical period could permanently destroy a smallpox chain. In 1968, E2 was initiated on a trial basis in Sierra Leone, the world’s most smallpox infested country. Within nine months, Sierra Leone reached zero-pox.
Because many people are nomadic, WHO workers worried that large populations might go unvaccinated. E2 which attacked smallpox at the chain of transmission enabled WHO workers to eradicate smallpox—even when segments of the population were not vaccinated.
+++You tell me how the sterilized the needles in third world countries, where there wasn’t even drinkable water in many areas? I am sorry this practice was totally unconscionable and unethical, no matter what their best intentions were.
Antibiotics and factory farms
The overuse and misuse of antibiotics in the meat industry is contributing to the rise of antibiotic-resistance in the U.S. and across the world. This serious public health issue is estimated to kill 10 million people a year worldwide by 2050. In the U.S., antibiotic-resistant infections cause over two million illnesses and 23,000 deaths each year, costing society between $55 billion to $70 billion each year.
The majority of antibiotics in the U.S. are given to animals that are not sick; they are mixed into animals’ food and water to make them grow bigger or to prevent illness in cramped and unhealthy environments. As You Sow engages companies to promote responsible antibiotics policies throughout their supply chain. We advise that companies phase out the routine use of antibiotics in livestock, especially in classes of drugs important for human health. We also advocate for strong animal welfare policies certified by third-party organizations, which can decrease illness rates in livestock and improve brand reputation.
Antibiotic resistance occurs when an antibiotic loses its ability to effectively control or kill bacterial growth; in other words, the bacteria are “resistant” and continue to multiply in the presence of therapeutic levels of an antibiotic. Resistant microbes may require other medications or higher doses – often with more side effects, some of which may be life-threatening on their own. Some infections become completely untreatable due to resistance.
One of the main causes of antibiotic-resistant bacteria, sometimes referred to as superbugs, is the overuse and misuse of antibiotics in the meat industry. Antibiotic resistance is projected to kill 10 million people a year worldwide by 2050. In the U.S., these infections cause over two million illnesses and 23,000 deaths each year, costing society $55-70 billion.
This crisis is a global issue. The World Health Organization states that, “A post-antibiotic era – in which common infections and minor injuries can kill – far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century.”
In 2011, livestock consumed 80% of all antibiotics sold in the United States, and more than half of these antibiotics are considered important for human medicine.
The meat industry uses antibiotics in 3 ways:
- To make animals grow at faster rates
- To prevent illness (or control the spread of illness) in cramped and unhealthy confined living conditions
- To treat disease (the least common use by far)
The U.S. Department of Agriculture has determined that much of the antibiotics use in animal feed provides little therapeutic benefit to the animals. Nevertheless, the Food and Drug Administration permits extensive use of antibiotics in animals, including the same or similar antibiotics as those used for the treatment of humans.
covid-19 and Healthcare Postings