AIDS patients with ARF treated for wrong infection
AIDS patients with ARF treated for wrong infection
Cryptococcus seen in immunodeficient patients
Houston researchers have shown through a retrospective study that clinicians sometimes attribute acute respiratory failure (ARF) in AIDS patients to Pneumocystis carinii pneumonia, when the true culprit is Cryptococcus neoformans meningo-encephalitis.1
Pneumocystis is so common among people who come into hospitals to be treated for ARF that clinicians often assume AIDS patients with ARF symptoms have this disease, says Richard J. Hamill, MD, associate professor of medicine, microbiology and immunology at Baylor College of Medicine in Houston, and staff physician of the Section of Infectious Diseases of the VA Medical Center in Houston. Hamill co-wrote an article on the study, published in Clinical Infectious Diseases.1
The study showed that the incidence of ARF in AIDS patients who have cryptococcosis is underestimated in the literature and sometimes overlooked by clinicians. Hamill’s research confirms anecdotal evidence that cryptococcal disease is often seen in people with compromised immune systems.
John Perfect, MD, professor of medicine at Duke University Medical Center in Durham, NC, says he’s seen cryptococcal infection relatively commonly in HIV patients and others with compromised immune systems.
"In our situation and in our location, cryptococcus is still a major opportunistic fungal pathogen in patients with HIV and organ transplants, and occasionally in normal individuals," says Perfect, who is co-author of a book called Cryptococcus Neoformans (Washington, DC: ASM Press; 1998).
Raising cryptococcosis awareness
Perfect says he has spoken and written about cryptococcal disease to raise clinicians’ awareness of it. If physicians thought about cryptococcal disease when they are presented with ARF symptoms, pulmonary lesions, and chronic meningitis, they could easily test patients for it and make a correct diagnosis.
The problem is that when physicians assume ARF patients have pneumocystis, they treat them with a sulfa antibiotic called trimethoprim/sulfamethoxazole, which works for pneumocystis but has no effect on cryptococcal disease, Hamill says.
"For cryptococcus, we usually give patients amphotericin B, which is an antifungal drug," he adds.
Only 11 of 19 case patients in the study had been given the antifungal drug. All of these patients had died, and most within four weeks of diagnosis with cryptococcal disease.
The cryptococcosis study also showed there is a significantly higher incidence of cryptococcal disease in black AIDS patients than in other races. Hamill speculates one reason for this higher incidence may be that black AIDS patients fail to access the health care system as early in their disease as do white AIDS patients.
"We didn’t look at socioeconomic levels or anything like that," Hamill says. "They may have had the same level of CD4 as someone else, but they waited until their cryptococcal became worse before coming in for treatment."
There also is the possibility that cryptococcal disease is worse in blacks for genetic reasons, although this theory has not been studied.
Consider other etiologies
Hamill says it would be easy for physicians and clinics to find cryptococcal disease in AIDS patients if they would simply think of etiologies other than pneumocystis when they’re presented with a case of ARF.
The serum antigen test to identify cryptococcal disease is simple and inexpensive and can be done in a few minutes, Hamill says. "It’s a little slide test where you look for a clumping of latex beads."
ARF patients often have been on prophylaxis for pneumocystis, and this prophylaxis is very effective.
"So if a patient who is taking prophylaxis comes in for treatment, physicians should consider the possibility of other etiologies," Hamill says. "They should do other tests to make a diagnosis, and one of those tests is serum cryptococcal antigen."
Patients with cryptococcal disease sometimes experience cranial pressure that can cause brain damage. If a clinician suspects the patient is experiencing this symptom, the clinician could do a spinal tap that would immediately show whether the patient has meningitis due to cryptococcal infection, Hamill suggests.
"If I have an AIDS patient with a low CD4 count and a fever and no obvious source of infection, I do the serum cryptococcal antigen test," he adds.
Hamill has suspected for years that cryptococcal disease has a higher incidence rate than most clinicians think. Since 1992, he has been involved with a project sponsored by the Centers for Disease Control and Prevention that involves collecting cryptococcus fungal isolates mostly from AIDS patients in Houston. So far, his research group has collected 500 to 600 isolates of cryptococcal pathogens from different patients, 95% of whom have AIDS.
The ARF and cryptococcosis study offers some proof that this incidence rate is underestimated. Here are some of the study’s findings and methodology:
Researchers conducted a case-control, referent study, selecting 210 HIV-positive patients from existing databases from January 1993 to May 1996 at four major teaching hospitals in Houston. Researchers identified cases by active surveillance of positive cryptococcal antigen tests and/ or recovery of C. neoformans from any body site in 14 microbiology laboratories.
Twenty-nine of the 210 patients (13.8%) had acute respiratory failure. Ten patients were excluded from analysis, leaving 19 cases that met the case definition of acute respiratory failure due to cryptococcal disease. Among the 19 cases, 100% died, with a median survival time of only two days. More than 50% of referents had been alive for more than a year, and 25% of referents had died.
When patients had neurological manifestations, they were more likely to have their disease diagnosed and treated. This finding emphasized how clinicians often failed to recognize the respiratory syndrome associated with cryptococcal disease.
Researchers postulate that cases had a fulminant course due to acute dissemination shortly after acquisition of a primary pulmonary infection. They base this belief on the lack of cryptococcal disease in all except for one case; respiratory symptoms that often preceded neurological manifestations; common systemic symptoms that suggest dissemination; and the detection of fungemia in at least two patients more than a week before onset of neurological signs and symptoms.
Variables independently predictive of ARF in patients with cryptococcal disease were black race, a lactate dehydrogenase level of greater than or equal to 500 IU/L, the presence of interstitial infiltrates, and the presence of cutaneous lesions.
Reference
1. Visnegarwala F, Graviss E, et al. Acute respiratory failure associated with cryptococcosis in patients with AIDS: Analysis of predictive factors. Clin Infect Dis 1998; 27:1,231-1,237.
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