June 5, 1981. Pneumocystis Pneumonia. Los Angeles.

The Pump Handle, an online “water cooler for the public health crowd”, have been publishing a series of articles on Public Health Classics, “exploring some of the classic studies and reports that have shaped the field of public health.” From lead poisoning to the Surgeon General’s 1964 report on the implications of cigarette smoking, the series makes for engrossing material about how our health and standards of living have radically changed due to pivotal research and medical findings.

The front page of the MMWR's June 5, 1981 report that included the first report on what would later be discovered to be AIDS.

The front page of the MMWR’s June 5, 1981 report that included the first report on what would later be discovered to be AIDS.

I’m very grateful that the ladies that blog at The Pump Handle, Liz Borkowski and Celeste Monforton, have given me an opportunity to submit my own interpretation of a Public Health Classic. I focused on a succinct report published in 1981 in the CDC’s Morbidity and Mortality Weekly Report (MMWR) reporting a very unusual outbreak of Pneumocystic pneumonia in Los Angeles among young gay men, which the public health world would later  discover to be the first ever published report on the HIV/AIDS epidemic. This fungal pneumonia is now known as a common opportunistic infection in people with HIV/AIDS but at the time it was rare infection among many other odd fungal and viral infections, blood cancers and strange symptomatology afflicting scores of gay men across the country and physicians were baffled as to the underlying culprit. As Liz wrote in an email in our back and forth correspondence, “it’s so chilling to think back to 1981 and how these physicians had no idea they were witnessing the start of [a] horrific global pandemic.”

As I write in the article,

“In just a decade, AIDS would be the second leading cause of death in young men 25 to 44 years in the United States and would have infected over 8 to 11 million people worldwide. The most recent estimate for the number of people worldwide living with HIV/AIDS is 34 million in 2011, with 68% residing in sub-Saharan Africa. That year, there were 2.5 million new HIV infections and 1.7 million AIDS-related deaths … The June 5th report is a symbol of a time before HIV/AIDS became ubiquitous, before it became a pandemic, before a small globular virus became mankind’s biggest global public health crisis.”

Check out my article “Public Health Classics: The First Report of AIDS” at The Pump Handle and see the original 1981 report here.

 

The Immunological Blitzkrieg That Is HIV Infection

It can be hard to comprehend the damage that pathogenic viruses and microbes can inflict on the human body, especially if you have scientists prattling on about cells, using multi-syllabic acronyms and tossing around – god forbid! – actual numbers. It’s helpful to have easily understood images to help put diseases into perspective, to understand that viruses like HIV have tangible and real effects. That’s why I’m so happy to have stumbled upon an incredible image from a 2004 paper that is a pictorial testament to the immunological blitzkrieg that is HIV infection.

A well-known hallmark of HIV infection is the loss of lymphocytic CD4+ T-cells, otherwise known as “helper T-cells”, that hunt and destroy invading bacteria, viruses and fungi. In this paper, the investigators were studying the underlying mechanisms that hasten the loss of these vital CD4+ T-cells from the gastrointestinal tract and the lymph nodes of HIV infected individuals.

Though we often think that the gastrointestinal tract has one job – to digest the meals that we organize our day around – it is, in fact, much more than just a digesting tube. The large intestine houses bacteria that produce vitamin K as well as a slew of water-soluble vitamins belonging to the B family, including folic acid, biotin and riboflavin. Serotonin factories in the stomach and small intestine, known as enterochromaffin cells, produce 90% of this vital neurotransmitter that modulates our emotions and moods, which might explain why a stomach bug can leave us emotionally depleted, why our stomach “flutters” with anxiety or love or why we might get a certain “gut instinct” about future events.

The intestine also houses immune cells in groups known as Peyer’s patches that are sown along the tail-end of the GI tract known as the ileum, that abuts the large intestine. These cells lie in wait for that one moment when you go against your physician’s recommendations and chow down on a microbe-laced ceviche on your vacation south of the equator. They serve as the “immune sensors of the intestine” (1). The gut has so many immune cells housed in its crevices – including at least 70% of the body’s lymphocytes – that it is technically the body’s largest lymphoid organ (1)!

In short, our intestine is not only the heart and soul of our body, but it is also its immunological epicenter. Perhaps we should consider being a little kinder to this spectacular wonder-organ.

Representative endoscopic photographs of the terminal ileum in the small intestine of a healthy patient on the left and a HIV-infected patient on the right. Arrows point to Peyer’s patches, areas of lymphoid tissue housing CD4+ T-cells.

But back to this paper and this great image! On the left, we can see a snapshot of the ileum in a HIV-negative person. The endoscope – an expensive tube with a camera on its end exploring your nether regions – shows a rocky, Mars-like terrain in the ileum. This is healthy, all around A-plus stuff – those bumps scattered throughout are the Peyer’s patches filled with immunological cells.

On the right, we see an incredibly smooth, denuded ileum in a HIV-positive individual. There are no lymphocytic bumps to be seen and the researchers attest to the subject’s “almost complete absence of discernible lymphoid tissue” (2). In this patient, HIV has infected and destroyed many of the CD4+ cell clusters in the ileum. It’s a rather grim sight; the difference between this HIV-infected ileum and the healthy one is striking in its austerity.

Now, a few caveats. These two pictures could be the only suitable images that the researchers found in both of the participants, though they do state that they are representative of their findings in all of the studied participants. But it could be the case that there exists ileum in healthy people that looks very much like our desolate AIDS ileum above, just as there could be ileum in AIDS patients that resemble pebbly, healthy ileum. Or these images could be confounded by age – younger individuals have far more Peyer’s patches than older people – just another one of the innumerable upshots to getting old and wise (1). Or these pictures could represent just a momentary “snap shot” in time of a section of the gut whose immunological landscape is liable to change from week to week.

The researchers acknowledge that the images “could be considered anecdotal in isolation” but the endoscopic findings weren’t an aberration. They found that certain CD4+ T-cells, bearing the very receptor that HIV uses to infect these cell, were preferentially depleted from the gastrointestinal tract; the frequency of these particular T-cells in the GI tract were far lower relative to other T-cells, indicating that HIV is selectively infecting and killing these cells and resulting in a diminished population in the gut. This depletion was only found in the GI tract, not in the blood or in other lymph nodes.

Other studies have confirmed this gut-focused assassination by the HIV virus, finding that HIV delivers a devastating blow to the immune system by killing up to 60% of CD4+ T-cells within 2 to 4 weeks of infection, and that this depletion can last for up to five years even with the use of retroviral therapy (3). HIV is truly a wrecking-ball of a virus, systematically destroying cells and tissues beginning with the very organ that takes such good care of us, physically and emotionally – our gut.

Resources

“Two brains are better than one”. A great 2011 article from the New York Times on our “second brain”, the gut and its nervous system. Check out The Other Brain Also Deals With Many Woes.

Find out more about Peyer’s patches and their role in the intestine in this 2010 article, Peyer’s Patches: The Immune Sensors of the Intestine.

References

(1) C. Jung et al. (2010) Peyer’s Patches: The Immune Sensors of the Intestine. Int J Inflam. 2010: 823710.

(2) JM. Brenchley et al. (2004) CD4 T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract. J Exp Med. 200(6):749–759

(3) Evering TH et al (2012) Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection. PLoS Pathog. 8(2): e1002506.

ResearchBlogging.org
Brenchley, J. (2004). CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract Journal of Experimental Medicine, 200 (6), 749-759 DOI: 10.1084/jem.20040874

The Sea Has Neither Sense Nor Pity: the Earliest Known Cases of AIDS in the Pre-AIDS Era

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This is the story of a sailor and a pirate, and the two different types of oceans that they traversed. There are seven on Earth but only one courses through man. This ocean contains no mysterious and pale sea creatures, bottomless depths or brightly-flashing predators, but it does brim with industrious cells, with dissolved carbon dioxide and occasionally with unwanted parasites.

In August of 1961, a Norwegian teenager sailed from a fjord in Oslo through the North Sea and the Atlantic Ocean to Douala, Cameroon, a port tucked under the outward slab that makes up West Africa. He was a freshly turned fifteen year old and was working as a kitchen hand on a Norwegian merchant vessel. From Cameroon, he and his crew on the Hoegh Aronde sailed northwesterly from port to port, docking at Nigeria, Ghana, Cote D’Ivoire, Liberia, Guinea and Senegal over a period of 10 months before returning to his homeland (1).

The route of the Norwegian sailor’s initial trip abroad on the Hoegh Aronde, from Oslo, Norway to Doula, Cameroon from August 1961 to May 1962. Image: Edward Hooper, 1997 (See References). Click for source.

It was an exotic start to what would be a short but wide-ranging career as a sailor – over a period of four years, he would call at ports in Asia, Europe, Canada and throughout the Caribbean. Though he would never find himself in West Africa again, he would always carry a souvenir of his visit to this incredibly diverse and ecologically rich niche of the world.

His journeys were lonesome, solitary. In Cameroon the sailor unburdened himself of his loneliness and slept with at least one woman, catching gonorrhea – this much is known. Perhaps it was the same woman or another that infected him with an unfamiliar virus simmering away in West Africa just waiting to travel foreign oceans and lands. A viral hitchhiker with a proclivity for the horizon, a pirate if you will. This virus, a certain strain of HIV included in the rare outlier group O that is genetically and immunologically distinct from the main group M that is plaguing the world today, a HIV group that native to West Africa and to Cameroon in particular but found itself in a Norwegian man who would travel the world.

When he returned to his homeland in 1965, he married and became a father to two children in a short two-year span. In spite of his exciting new role as  husband and father, he often felt unwell and his family was plagued with strange illnesses. His muscles ached, a red rash covered his body and he found himself often besieged by respiratory ailments (2). In 1967, his wife became ill with fevers, an omnipresent yeast infection as well as the same respiratory infections that lurked in her husband. The next year, the sailor would see his youngest daughter developing unusual diseases not often seen in toddlers – arthritis, blood and bone infections, along with the same yeast and respiratory infections afflicting her family.

Despite his poor health, the sailor found himself crossing the sea again to Europe. From 1969 to 1973, he worked as a long-distance truck driver delivering cargo as he traversed Belgium, the Netherlands, France, Germany, Austria, Switzerland and Italy (1).

With his ailing family far away across the North Sea, the sailor would seek refuge again in Europe. His coworkers would later say that he slept with many women and prostitutes along his long and lonely lorry routes. Often beginning his route in Wesseling, Germany, he would deliver to Liége and Lyons in France, occasionally stopping in Reims between the two cities (1). Investigators in this part of France would later find cases of HIV group O in individuals that had died in the late 1970s and early 1980s but had never visited verdant Cameroon.

In 1974, the sailor fell deeply ill. He died two years later, at the age of 29, his body riddled by bizarre diseases and was followed quickly in death by his wife and his youngest daughter. Autopsies would find puzzling results – overwhelming systemic infections not often seen except in the severely immunocompromised. The pathologist conducting the autopsy would save the sailor’s lymph node, liver, kidney and lung, the mother’s leg muscle and the daughter’s lymph node, spleen and liver and, years later, the family’s serum samples would test positive for HIV antibodies. This unfortunate family, to this day unidentified, represent the first recorded cluster of confirmed HIV/AIDS infections in the pre-AIDS era, before the AIDS pandemic sparked in the late 1970s and early 1980s. The sailor’s daughter is the earliest known case of pediatric AIDS (3).

“The sea has neither sense nor pity,” wrote Anton Chekov in his short story “Gusev”. Blood churns, dark liquids pumped through the valves by the stalwart heart, all the while feeding our bodies oxygen. A corrosive virus pirates the sea, hijacking cells and visiting the ports of our body, our brain, muscles, spleen and liver. Why infect that one person, at that moment in time? There is no meaning or sense to it. The tides rise, the tides fall. The earth spins, blood spills. A ship makes its port on schedule, becomes lost or is brought to the bottom of the sea. A man dies from an infection caught 15 years earlier in a distant port, a salty partner that he introduced to his family. There is no meaning, little salvation and only grief.

Resources

If you’d like to read the “Gusev” story by Chekhov, you can do so here.

Shortly after the researchers’ work into the Norwegian AIDS cluster, researchers from Tulane discovered evidence that a St. Louis teenager, Robert Rayford, was infected and died of AIDS in 1969. His case is troubling – a 15 year old succumbing to an infection that typically takes year before progression to AIDS and death. Some sources claim he was a gay prostitute while others say that he was sexually abused as a child. Whichever may be tragic alternative it is, the fact remains that this boy had never traveled outside of St. Louis, someone had infected him and that AIDS was most certainly circulating in a limited fashion in the United States before the 1970s. Read more about him in this 1988 New York Times article.

A few months back, I created a playlist of hip hop and R&B artists singing about the HIV/AIDS crisis and admonishing safe sex to their listeners. Check out the playlist and accompanying article “Let’s Talk About Sex: Hip Hop on HIV” here.

References

1) Hooper E. (1997) Sailors and star-bursts, and the arrival of HIV. BMJ. 315(7123): 1689-91

2) Lindboe CF et al. (1986) Autopsy findings in three family members with a presumably acquired immunodeficiency syndrome of unknown etiology. Acta Pathol Microbiol Immunol Scand A. 94(2):117-23

3) Frøland, SS et al. (1988) HIV-1 infection in Norwegian Family before 1970. Lancet. 1(8598): 1344-5

ResearchBlogging.org
Frøland SS, Jenum P, Lindboe CF, Wefring KW, Linnestad PJ, & Böhmer T (1988). HIV-1 infection in Norwegian family before 1970. Lancet, 1 (8598), 1344-5 PMID: 2897596