This article is more than 5 years old. Information may no longer be current.
HIV/AIDS – the discovery of an unknown, deadly virus
Click Here to Manage Email Alerts
This is the second EIStories, a series of articles about outbreak investigations conducted by CDC EIS officers.
The EIS is a training ground for many infectious disease folks, and most look back on that time with fondness for what they learned, the people they met and the service they gave. Epidemiology is an important part of infectious diseases, and we think a look at some of the more important cases may be interesting and informative. For this series, we begin in Los Angeles in 1981; an outbreak of Pneumocystis carinii pneumonia among five, young homosexual men.
Twenty-five years ago this month, the CDC published the first official Morbidity and Mortality Weekly Report of a then-nameless, deadly syndrome that is now a global epidemic, one of the deadliest in human history: AIDS.
In the beginning the syndrome only affected a handful of gay men; however, the disease quickly grabbed attention as cases rapidly increased and the death toll mounted.
James W. Curran, MD, MPH, dean of Emory University’s Rollins School of Public Health, led the CDC’s HIV prevention programs for more than a decade, including efforts to investigate the first known AIDS cases in the early 1980s.
![EIStories [logo]](images/content/idn/200606/eistorieslogo.gif)
“It is sometimes difficult to reflect 25 years, going back to five cases of pneumocystis in gay men in June of 1981, to understand how something that began so slowly and so quietly, can now be the number four cause of death in the entire world, something that we thought was a small problem back then,” he said at a CDC press teleconference. “Even in the early 1980s, we were always greatly concerned that we would underestimate the burden and impact of AIDS on the population. I think we still have to consider that we may be underestimating the burden and impact of this insidious global epidemic, and that perhaps silence does still equal death in the worldwide scene, and that denial and complacency are still the greatest enemies to progress.”
Unusual cases in LA
In January of 1981, Michael S. Gottlieb, MD, a young assistant professor of medicine at the University of California at Los Angeles School of Medicine, met Michael — the man who would become the AIDS index case. Michael was in his early 30s, homosexual and very thin because of recent weight loss, according to Gottlieb, now assistant clinical professor of medicine at UCLA.
“I first saw him in the medical ward, he had been admitted to the emergency room several days before complaining of fever, dramatic weight loss and thrush. Within a week, infiltrates blossomed on his chest X-ray and the bronchosopy confirmed pneumocystis,” he said.
Physicians used a then-experimental assay and determined that Michael had very few CD4 cells, fewer than 50.
“He was treated with Bactrim [trimethoprim-sulfamethoxazole, Roche]. We followed him for about a year at which time he died with widespread Kaposi’s sarcoma,” he said.
What grabbed Gottlieb’s attention was not only his extremely low T-cell count, but also the presence of Pneumocystis carinii pneumonia (PCP), a condition that is uncommonly seen among otherwise healthy young men such as Michael. P. carinii is a rare form of pneumonia, usually exclusively found in severely immunocompromised patients.
“In all of my training I had only seen one case of pneumocystis,” he said. “When we first saw Michael, as immunologists our gut feeling was T-cell immune deficiency. We really thought it was interesting and might be an example of a known condition, maybe a slowly evolving leukemia of some kind.”
Little did he know that this initial case would be the brink of an epidemic.
Word of this unique case spread to local physicians though the medical grapevine and physicians referred three more patients with fever, weight loss and unknown diagnosis in Los Angeles to UCLA.
“We admitted them all to UCLA and diagnosed them with PCP and found the characteristic CD4 depletion,” he said. “All four were gay and so we began to think their illness may have some association with sexual preference because that was the only commonality these patients had. They did not know each other and had no prior contact, sexual or otherwise, with each other.”
He oversaw the care of the second patient, then the third and fourth patients; all had the same symptoms: fatigue, fever and pneumocystis. By the spring of 1981, the researchers dubbed the disease GRID — Gay-Related Immune Deficiency, according to Gottlieb.
“No disrespect to the gay community was intended, it was simply what we saw and all that we knew,” he said.
CDC becomes aware
Unsure if something larger may be on his hands, Gottlieb took precautions to inform the medical community and called Arnold Relman, MD, at the time editor of The New England Journal of Medicine, to ask him for publishing advice.
“He gave me very good advice and said to call the CDC and write the cases up for the MMWR,” Gottlieb said.
He then reached out to Wayne Shandera, MD, a CDC EIS officer in Los Angeles, who Gottlieb had known at Stanford during his immunology fellowship. He asked if Shandera had heard of anything out of the ordinary affecting gay men in Los Angeles, or for that matter, anywhere in the country. Shandera responded that he would look into it.
A few days later, however, Shandera noted a critically ill patient in a Santa Monica hospital. This patient was diagnosed with pneumocystis and was also homosexual.
“With relatively little effort he turned up the fifth patient, which began to give me a feeling that this was not going to be rare,” Gottlieb said. “At this point I was thinking ‘one case, OK it may be just an isolated case’. But then three more came in from local physicians and then the health officer finds one within a couple of days. I thought ‘there is something brewing out there.’”
Not long after, Gottlieb, Shandera and colleagues reported their five patients to the CDC’s MMWR .
Around the same time, in the spring of 1981, Curran, then chief of Venereal Disease Research Department at the CDC, indicated that colleagues had noticed unusual requests for a drug called pentamidine, a back-up drug used to treat PCP. Requests were coming in from California and New York for people who had no underlying cancer or other conditions, according to Curran.
“Patients were having severe shortness of breath and pneumonia, weight loss, diarrheal disease, some had both skin manifestations and systemic manifestations of Kaposi’s sarcoma, a cancer which sometimes affected internal organs as well as the skin,” said Curran, now dean and professor of epidemiology and medicine at the Rollins School of Public, Emory University and director of the Emory Center for AIDS Research.
First MMWR report
The MMWR report, titled “Pneumocystis pneumonia — Los Angeles,” was published on June 5, 1981 and detailed the cases, which spanned from October 1980 to May 1981. Gottlieb and colleagues detailed the five case studies, noting the commonalities among the cases, such as sexual preference and quick development of this rare form of pneumonia. All five patients were previously healthy individuals who had laboratory-confirmed cytomegalovirus (CMV) infection within five months of PCP diagnosis and candidal mucosal infection, according to the report.
The following are summarized excerpts of the patient’s symptoms written in the original MMWR case reports:
- Patient 1: A 33-year-old man developed PCP and oral mucosal candidiasis in March 1981, after two months of fever that was associated with elevated liver enzymes, leucopenia and CMV viruria. The patient’s condition declined despite treatment with trimethoprim-sulfamethoxazole (TMP-SMX), pentamidine and acyclovir. He died on May 3.
- Patient 2: A 30-year-old man developed PCP in April 1981 after five months of fever associated with elevated liver enzymes, CMV viruria and seroconversion to CMV. In addition, he had leucopenia and mucosal candidiasis. PCP responded to treatment with intravenous TMP-SMX, however he continued to have fevers.
- Patient 3: A 30-year-old man developed esophageal and oral candidiasis around January 1981. He was treated with amphotericin B and responded well. In February, he was hospitalized for PCP that responded to treatment with oral TMP-SMX. Esophageal candidiasis reoccurred and he was retreated with amphotericin B. Biopsy showed he was positive for CMV.
- Patient 4: A 29-year-old man developed PCP in February 1981. Three years prior he had Hodgkin’s disease; however, was successfully treated with radiation therapy. PCP did not improve after administration of intravenous TMP-SMX and corticosteroids. He died in March. Postmortem examination showed PCP and CMV in lung tissue.
- Patient 5: A 36-year-old man visited his physician in April 1981 after a four-month history of fever, dyspnea and cough. He had been clinically diagnosed with CMV in September 1980. He was diagnosed with PCP, oral candidiasis and CMV retinitis. He was administered two short courses of TMP-SMX and was treated for candidiasis with topical nystatin.
The researchers concluded in the report: “all of the above observations suggest the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections, such as pneumocystosis and candidiasis. Although the role of CMV infection in the pathogenesis of pneumocystosis remains unknown, the possibility of P. carinii infection must be carefully considered in a differential diagnosis for previously healthy homosexual males with dyspnea and pneumonia.”
The MMWR circulated across Curran’s desk in the month prior to publication, in May 1981.
“Initially, this was thought to be a very small problem, but my reaction when I saw the report was this was something very serious, since the cases were often fatal,” he said, “and so we thought it was very important to look into it further to see if it was occurring more widely.”
Common threads
![Anthony S. Fauci, MD [photo]](images/content/idn/200606/fauci.jpg)
There was no indication of a common thread among these patients, besides sexual orientation, and the pattern of how cases evolved was unusual from the very first report, according to Anthony S. Fauci, MD, who was chief of Laboratory Immunoloregulation and an infectious diseases and immunology researcher at the NIH. Today, he is the director of the National Institute of Allergy and Infectious Disease.
“I had been involved as an infectious disease person and an immunologist who saw infectious diseases complications in immunosuppressed patients, particularly cancer patients, and to see otherwise previously healthy people who all had the common denominator of being gay men develop this disease that was virtually never seen in healthy’ people, was the first big clue right from the get go that this was something extremely unusual,” he said.
Raised awareness
Nationally, the MMWR prompted an awareness of these unique cases, which unbeknownst to many had been occurring in various pockets across the nation, with similar and dissimilar symptoms.
“It was sort of a mystery story that unfolded before our very eyes,” Fauci said.
Next month: More cases reported nationwide; the CDC investigates. – by Tara Grassia
For more information:
- Fenton K, Curran JW, et al. CDC 25 years of AIDS. CDC teleconference. May 5, 2006.
- Gottlieb MS, Schanker HM, Fan PT, et al. Pneumocystis pneumonia – Los Angeles. MMWR. 1981;30:250-252.
- Also, additional information is available at http://aidshistory.nih.gov.