Pneumocystis Pneumonia—Los Angeles

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Pneumocystis Pneumonia—Los Angeles

Journal article excerpt

By: Michael S. Gottlieb, et al.

Date: June 5, 1981

Source: M. S. Gottlieb, et. al. "Pneumocystis Pneumonia—Los Angeles," Moridity and Mortality Weekly report (June 5, 1981): (30) 21, 1-3. Available online at 〈http://www.cdc.gov/mmwr/preview/mmwrhtml/june_5.htm〉 (accessed January 21, 2006).

About the Author: Michael S. Gottlieb was an assistant professor of medicine at the University of California at Los Angeles (UCLA) in 1981, when he submitted the featured report as its lead author. In 1985, Gottlieb co-founded the American Foundation for AIDS Research. He maintains a private medical practice in Los Angeles.

INTRODUCTION

Within an eight-month period in 1980–1981, five young men were hospitalized in the Los Angeles area with a rare, severe form of pneumonia caused by the pathogen (disease-causing microorganism) Pneumocystis carinii. In reporting the outbreak to the Centers for Disease Control and Prevention (CDC), the physician Michael S. Gottlieb and his colleagues first documented in medical literature (in the report below) the disease that was to become known as AIDS.

The report jarred physicians in New York and San Francisco, who noticed a handful of similar cases occurring at about the same time. In another unusual occurrence, eight young men in the New York area with Kaposi's sarcoma had recently died. Kaposi's sarcoma is a form of skin cancer that was usually seen mainly in elderly persons. Suspecting a new or emerging disease among young men, the CDC formed a task force to investigate the outbreaks.

All of the young men with both Pneumocystis pneumonia and Kaposi's sarcoma were actively homosexual, and early on, the task force considered the disease likely to be confined to the community of homosexual males. By the end of 1981, it became clear that that the newly recognized disease affected other population groups, when the first cases of Pneumocystis pneumonia were reported in drug users who injected their drugs. It also became clear that the disease was not confined to the United States, when similar cases were found within a year in the United Kingdom, Haiti, and in Uganda, where the disease was called "slim."

In 1982, scientists at the CDC linked the transmission of the disease to blood, and coined the term AIDS, describing the viral disease as an acquired immune deficiency syndrome. The CDC's editorial response to Gottlieb's report describing the initial assumption that the disease resulted in an alteration in the immune system proved to be correct. The infectious nature of AIDs, however, remained unconfirmed until 1984, when scientists at both the Pasteur Institute in Paris and the National Cancer Institute identified the virus eventually known as the Human Immunodeficiency Virus (HIV) that causes AIDS.

PRIMARY SOURCE

EPIDEMIOLOGIC NOTES AND REPORTS

In the period October 1980–May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died. All 5 patients had laboratory-confirmed previous or current cytomegalovirus (CMV) infection and candidal mucosal infection. Case reports of these patients follow.

Patient 1: A previously healthy 33-year-old man developed P. carinii pneumonia and oral mucosal candidiasis in March 1981 after a 2-month history of fever associated with elevated liver enzymes, leukopenia, and CMV viruria. The serum complement-fixation CMV titer in October 1980 was 256; in May 1981 it was 32. The patient's condition deteriorated despite courses of treatment with trimethoprim-sulfamethoxazole (TMP/SMX), pentamidine, and acyclovir. He died May 3, and postmortem examination showed residual P. carinii and CMV pneumonia, but no evidence of neoplasia.

Patient 2: A previously healthy 30-year-old man developed P. carinii pneumonia in April 1981 after a 5-month history of fever each day and of elevated liver-function tests, CMV viruria, and documented seroconversion to CMV, i.e., an acute-phase titer of 16 and a convalescent-phase titer of 28 in anticomplement immunofluorescence tests. Other features of his illness included leukopenia and mucosal candidiasis. His pneumonia responded to a course of intravenous TMP/SMX, but, as of the latest reports, he continues to have a fever each day.

Patient 3: A 30-year-old man was well until January 1981 when he developed esophageal and oral candidiasis that responded to Amphotericin B treatment. He was hospitalized in February 1981 for P. carinii pneumonia that responded to TMP/SMX. His esophageal candidiasis recurred after the pneumonia was diagnosed, and he was again given Amphotericin B. The CMV complement-fixation titer in March 1981 was 8. Material from an esophageal biopsy was positive for CMV.

Patient 4: A 29-year-old man developed P. carinii pneumonia in February 1981. He had had Hodgkins disease 3 years earlier, but had been successfully treated with radiation therapy alone. He did not improve after being given intravenous TMP/SMX and corticosteroids and died in March. Postmortem examination showed no evidence of Hodgkins disease, but P. carinii and CMV were found in lung tissue.

Patient 5: A previously healthy 36-year-old man with clinically diagnosed CMV infection in September 1980 was seen in April 1981 because of a 4-month history of fever, dyspnea, and cough. On admission he was found to have P. carinii pneumonia, oral candidiasis, and CMV retinitis. A complement-fixation CMV titer in April 1981 was 128. The patient has been treated with 2 short courses of TMP/SMX that have been limited because of a sulfa-induced neutropenia. He is being treated for candidiasis with topical nystatin.

The diagnosis of Pneumocystis pneumonia was confirmed for all 5 patients antemortem by closed or open lung biopsy. The patients did not know each other and had no known common contacts or knowledge of sexual partners who had had similar illnesses. Two of the 5 reported having frequent homosexual contacts with various partners. All 5 reported using inhalant drugs, and 1 reported parenteral drug abuse. Three patients had profoundly depressed in vitro proliferative responses to mitogens and antigens. Lymphocyte studies were not performed on the other 2 patients.

Editorial Note: Pneumocystis pneumonia in the United States is almost exclusively limited to severely immunosuppressed patients (1). The occurrence of pneumocystosis in these 5 previously healthy individuals without a clinically apparent underlying immunodeficiency is unusual. The fact that these patients were all homosexuals suggests an association between some aspect of a homosexual lifestyle or disease acquired through sexual contact and Pneumocystis pneumonia in this population. All 5 patients described in this report had laboratory-confirmed CMV disease or virus shedding within 5 months of the diagnosis of Pneumocystis pneumonia. CMV infection has been shown to induce transient abnormalities of in vitro cellular-immune function in otherwise healthy human hosts (2,3). Although all 3 patients tested had abnormal cellular-immune function, no definitive conclusion regarding the role of CMV infection in these 5 cases can be reached because of the lack of published data on cellular-immune function in healthy homosexual males with and without CMV antibody. In 1 report, 7 (3.6%) of 194 patients with pneumocystosis also had CMV infection' 40 (21%) of the same group had at least 1 other major concurrent infection (1). A high prevalence of CMV infections among homosexual males was recently reported: 179 (94%) had CMV viruria; rates for 101 controls of similar age who were reported to be exclusively heterosexual were 54% for seropositivity and zero fro viruria (4). In another study of 64 males, 4 (6.3%) had positive tests for CMV in semen, but none had CMV recovered from urine. Two of the 4 reported recent homosexual contacts. These findings suggest not only that virus shedding may be more readily detected in seminal fluid than urine, but also that seminal fluid may be an important vehicle of CMV transmission (5).

All 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.

SIGNIFICANCE

From the relative obscurity of a handful of cases among the male homosexual community in the early 1980s, AIDS has mushroomed to become a pandemic involving ever-increasing millions. The disease, now accepted as being the result of the effects of infection by one of several types of the Human Immunodeficiency Virus (HIV), is suspected to have originated in Central Africa, where a similar strain of the virus was present in a sub-group of chimpanzees. AIDS knows no boundaries of sexual orientation, gender, or age.

In 2004, more than three million people world-wide died from AIDS. As of 2005, nearly forty million people are infected with HIV; approximately double the population of Australia. Nearly two-thirds (approximately twenty-five million) live in sub-Saharan Africa. The increase in the number of cases in this region has been particularly marked, as has the involvement of women, who now comprise nearly half all infected adults worldwide.

The Joint United Nations Program on HIV/AIDS (UNAIDS) and the World Health Organization regard AIDS in Africa as not one single epidemic, but of a series of outbreaks. Beginning in the late 1970s, HIV spread across the breadth of the continent from West Africa to the Indian Ocean. The epidemic then spread southward, where it is now most pronounced.

According to 2004 figures from UNAIDS, South Africa is the world's hotbed of AIDS, representing almost 65 percent of the world's cases. The prevalence of the disease has remained fairly stable. However, this may reflect the near equal number of new cases (3.1 million in 2004) and deaths (2.3 million in 2004).

The Caribbean is the second-worst-affected region. The prevalence of HIV in the population is at or above 3 percent in the Bahamas, Trinidad and Tobago, and Haiti.

Over 400,000 Latin American women are infected with HIV. However, the bulk of those who are infected are men who have sex with men and those who inject illicit drugs. A particularly grim example is provided by Brazil, where some 60 percent of drug users in major cities are estimated to be infected.

As of 2005, the HIV infection rate is growing most quickly in Asia. From 2002 to 2004, there was a 50 percent increase in infections in East Asia, with 56 percent of these being in women. This sharp increase was fueled by epidemics in China, Indonesia, and Vietnam. Epidemics are also erupting in several states in India.

Affluence is no guarantee of safety from HIV/AIDS. In both the United States and Europe, the number of HIV infections is increasing. However, the wider affordability of antiretroviral therapy is decreasing the overall death rate from the disease. The increasing numbers of people who are surviving longer with HIV is proving taxing to many local health care systems. In developed countries, unprotected sex between heterosexuals is now a major cause of AIDS.

In the 1980s and 1990s researchers proved that the principle target for AIDS-related maladies is the immune system. Much research has since focused on clarifying the changes in the infected human immune system, and in trying to prevent, slow or even reverse these changes.

A type of T cell called the CDC4+ T cell aids in the destruction of virus-infected host cells. But, in HIV infection the number of CDC4+ cells declines over time, allowing the viral infection to proceed. The resulting decline in the immune system impairs a person's ability to fight off foreign organisms leaves the person vulnerable to life-threatening illnesses that normally would be routinely dispatched.

If the reasons for the accelerated loss of the T cells can be determined, perhaps the loss can be prevented. This would better equip patients to fight the infection.

In the 1990s, the use of Highly Active Anti-Retroviral Therapy (HAART), consisting of a "cocktail" of drugs targeted to the AIDS virus, has shown promising results in delaying the onset of symptoms. The drug mixture typically contains a nucleoside analog, which blocks genetic replication, and inhibitors of two enzymes that are critical enzyme in the making of new virus (protease and reverse transcriptase).

The benefits achieved by HAART comes at the expense of side effects that can often be severe. Also, the treatment is expensive, which blunts the use of this approach in the areas of the world most at need. Research published toward the end of 2001 indicates that the use of HAART in a systematic but periodic fashion achieves the benefits but lessens the occurrence of side effects and decreases treatment cost.

What lies ahead? Estimates of the number of people living with HIV in 2020 vary from approximately forty million, according to UNAIDS, to 200 million, according to the International AIDS society. As the majority of those affected of young to middle aged adults, the economic consequences of the removal of the vital part of the work force could be catastrophic.