Tuberculosis and Nontuberculous Mycobacteriosis in Patients with AIDS

Tuberculosis and Nontuberculous Mycobacteriosis in Patients with AIDS* Arthur

M. Fournier,

Ha R. Erdfrocht, and Margaret

M.D.;

M.D.;

A. Fischl,

Gordon

Timothy

M. Dickinson,

Cleary,

M.D.;

Ph.D.;

M.D.

Thirty-six patients with A I D S and culture-proven nontuber-

syndrome of dyspnea, chills, hemoptysis, and chest pain was

culous mycobacteriosis were compared to 20 patients with

seen in a significant minority of patients with nontuber-

acquired immunodeficiency syndrome ( A I D S ) and tuber-

culous mycobacteriosis. Lymphadenopathy was seen almost

culosis with regard to clinical signs, symptoms, and diag-

exclusively in patients with tuberculosis. Pulmonary sources

nostic methods. Patients with nontuberculous mycobac-

(expectorated sputum or bronchoscopy specimens) were the

teriosis were more often younger and homosexuals, while

most common source of diagnosis in both groups. Patients in

patients with tuberculosis were usually Haitian-American

both groups in whom the diagnosis was obtained from

or users of intravenous drugs. A majority of patients with

pulmonary sources frequently had negative chest x-ray films

tuberculosis presented with fever and weight loss. These

on presentation. Cavitary disease was absent from both

symptoms were seen in approximately 50 percent of the

groups.

patients with nontuberculous mycobacteriosis. A distinct

l V / f vcobacterial infections have been recognized as important opportunistic infections in patients with the a c q u i r e d (AIDS).

14

immunodeficiency

syndrome

Nontuberculous mycobacteriosis is found in

about 10 percent

of patients with A I D S .

Overall,

tuberculosis is much less common, but the incidence is increasing,

3

and

among

Haitian-American

patients

with A I D S , it is approximately 50 percent." Distinguishing infection caused by

Mycobacterium

hominis from nontuberculous mycobacterial infections or from other opportunistic infections that cause wasting illness is a challenge to all clinicians dealing with A I D S . This is particularly true if initial acid-fast smears are negative. Accordingly, w e reviewed our experience

counts, differentials, "routine" chemistries, alkaline phosphatase, SGOT, SGPT, OKT3/OKT4 ratios, syphilis serologies, and admission chest x-ray films. Chest x-ray films were considered "abnormal" if they demonstrated hilar adenopathy or parenchyma] infiltrates. Also entered for each group was the source of the positive culture and whether or not initial acid-fast smears were positive. Each individual item in the protocol was compared between the two groups using Fisher's exact test or unpaired Student's t-tests. Clinical specimens from normally contaminated sources were treated with N-acetyl cysteine — 2 percent sodium hydroxide, and concentrated by centrifugation. The concentrated sediment was used to prepare fluorochrome acid-fast smears and to inoculate Lowenstein-Jensen medium. Normally sterile body fluids and minced tissue were not treated before inoculation to insolated media. All specimens were routinely incubated at 35°C for eight weeks. The identification of each isolate was confirmed by the State of Florida laboratory service. 7

with both nontuberculous mycobacteriosis and tuber-

RESULTS

culosis to identify differences in demographics, clinical presentation, and source of diagnosis, and to deter-

The demographic characteristics of patients with

mine what extent the clinical presentation of these

both nontuberculous mycobacteriosis and tuberculosis

infections is modified by A I D S .

are summarized in Table 1. Our demographic data document the predeliction for nontuberculous

METHODS The charts of 36 patients with AIDS and positive cultures for nontuberculous mycobacteria were identified, abstracted on a clinical research protocol, and compared to similar abstracts of 20 randomly selected AIDS patients with positive cultures for M hominis. This patient sample represented all cases of nontuberculous mycobacterioses in AIDS patients seen at Jackson Memorial Hospital from January 1980 through June 1985. The diagnosis of AIDS was made according to criteria of the Center for Disease Control. All patients with tuberculosis had at least one opportunistic infection which fulfilled the C D C criteria. The research protocol included demographic data, elements of a medical history, positive physical findings, admission, laboratory results including complete blood 6

*From the Division of General Medicine and Infectious Disease, University of Miami School of Medicine, Miami. Manuscript received July 13; revision accepted September 14. Reprint requests: Dr. Fournier, University of Miami, PO Box 01B9060-R103, Miami 33101 772

my-

cobacteriosis as an opportunistic infection in homosexuals and tuberculosis as an opportunistic infection in other risk groups. Although the C D C has removed "Haitians" as a risk factor for A I D S , we have elected to maintain

this category

for

demographic

purposes,

since Haitian-Americans form such a large group of patients with A I D S in Miami who do not fall into any other risk group, and since tuberculosis

is such a

common problem for these patients. Of the 36 cases of nontuberculous mycobacteriosis, 11 were caused by M kansasii, and 25 by M

avium-intracellulare.

Patients with tuberculosis and A I D S were significantly older than those with nontuberculous mycobacteriosis. There were no differences

with regard to

whether the infection was an initial or subsequent

Mycobacteriosus in AIDS Patients (Fournier

et at)

Table 1—Demographic Comparison of Nontuherculous Mycobacteriosis vs Tuberculosis in Patients with AIDS Nontuberculous M ycobacteriosis (n = 36) Black White Male Female First opportunistic infection Risk factor for AIDS: 1. Homosexual 2. Drug User 3. Haitian Age, yr Duration of symptoms, days

%

Tuberculosis (n = 20)

%

p-Value

19 17 27 9

52 48 75 25

19 1 15 5

95 5 75 25

<0.001

25

69

10

50

NS

27 3 6 32 + 5.5

75 8 16

1 5 14 45+18.5

5 20 70

<0.001 NS <0.001 <0.002

42.5 + 61

NS

62 + 61

opportunistic infection.

NS

no significant differences between the two groups in

The clinical features of A I D S patients with mycobac-

the following: hematocrit; hemoglobin; total white

terioses are displayed in Table 2. The presence of pneumonia is a possible con-

blood cell count; differential; absolute lymphocyte count; or helper to suppressor cell ratios. Elevated

founder of our results. Patients were not routinely

liver enzymes were found commonly in both groups,

screened for P carinii

pneumonia. Rather, the diag-

but there were no differences in the degree of elevation

nosis was made by bronchoscopic lavage or biopsy when indicated by the clinical circumstances. Nine out

or in the pattern of elevation (transaminase vs alkaline phosphatase).

Pneumocystis

carinii

of 36 patients with nontuberculous mycobacteriosis

T h e source of culture-confirmed diagnosis and

and five out of 20 with tuberculosis had concomitant

whether or not initial acid-fast smears were positive are

Pneumocystis infection.

summarized in Table 3. A positive initial smear was

Because these cases are

equally distributed between both groups, represent a

more likely with tuberculosis,

minority of cases in each group, and because we were

sputum samples (p<0.01). Lymph node and bone

particular ly from

interested in defining not the natural history of my-

marrow biopsies proved u seful in the diagnosis of

cobacterioses but the natural history of these infections

tuberculosis. Stool and urine smears and cultures were

in patients with A I D S , w e elected not to exclude these

underutilized sources or positive smears and cultures

cases from analysis. In addition, we felt that finding

in both types of infections.

that 25 percent of patients in both groups

discovered to have a second infection with Pneu-

Table 4 summarizes the value of pulmonary sources in diagnosing nontuberculous mycobacteriosis and

mocystis was worthy of reporting.

tuberculosis in patients with A I D S . T h e most common

were

Both nontuberculous mycobacteriosis and tuber-

x-ray abnormality in both groups was bilateral in-

culosis most often presented with fever, weight loss,

terstitial infiltrates. Cavitary disease was absent from

and cough, although fever and weight loss were seen

both groups.

more often in patients with tuberculosis. There were

Concomitant Pneumocystis infection may have

Table 2—Clinical Features of Nontuberculous Mycobacteriosis and Tuberculosis in Patients with AIDS

Symptoms/Signs

Nontuberculous Mycobacteriosis (n = 36)

%

Tuberculosis (n = 20)

%

p-Value

Fever Weight loss Cough Diarrhea Night sweats Weakness Dyspnea Chills Hemoptysis Chest pain Lymphadenopathy*

20 18 24 10 9 8 11 9 6 7 1

56 50 67 28 25 22 31 25 17 19 2

16 15 11 2 5 3 2 1 0 0 9

80 75 55 10 25 15 10 5 0 0 45

.06 .07 NS NS NS NS .075 .075 .06 <0.05 <0.001

:

Lymph nodes > 2 cm. CHEST / 93 / 4 / APRIL. 1988

773

Table 3—Sources o f Positive Acid-Fast Smears and Cultures in 20 Patients with Tuberculosis and 36 Patients with Nontuberculous Mycobacteriosis* Nontuberculosis Mycobacteriosis

Tuberculosis AFB Smear

Pos/Culture

AFB Smear

Pos/Culture Pos

3 1 4 ... 11 ... 1

6 2 9 ... 11 ...

0 0 4 0 39 0 0

1 2 12 I 49 1 2

Lymph node bx Bone marrow bx Bronchoscopy Liver bx Sputum Stool Urine

2

*Several patients had more than one positive culture result, and more than one positive source.

slightly increased the number of patients in both

infection

groups with abnormal x-ray films. However, in 40

intravenous drugs in our study population. Only one of

percent of patients with tuberculosis and 14 percent of

our cases of tuberculosis was in a homosexual. Others

patients with nontuberculous mycobacteriosis with a

have observed this low incidence of tuberculosis

pulmonary source of diagnosis, the initial chest roent-

among homosexuals with A I D S . Socioeconomic fac-

1213

and a relatively high percentage of users of

3

tors partially explain this. Thirty percent of our Hait-

genogram was normal.

ian-American patients with A I D S and mycobacteriosis

DISCUSSION

Since our initial report of immunodeficiency in Haitian-American patients,

8

our experience with

A I D S has grown to include patients in all risk groups. Original estimates of the incidence of tuberculosis in non-Haitians and nontuberculous mycobacteriosis in 5

Haitians were probably low. T h e ultimate diagnosis of 4

mycobacterial infections was straightforward, since

had nontuberculous infection. Seventeen percent of non-Haitians with A I D S and mycobacteriosis had M hominis grow on culture. Thus, although the incidence of tuberculosis in Haitian-Americans and nontuberculous mycobacteriosis in non-Haitians is statistically significant, it lacks sufficient predictive value to warrant empiric treatment.

these organisms grow well on culture media. A rapid

In patients with A I D S and both tuberculosis and

initial diagnosis is more problematic, particularly if

nontuberculous mycobacteriosis, the most common

acid-fast smears are negative. Patients frequently dete-

presenting complaints were fever, weight loss, and

riorate waiting for culture results to return, and much

cough. The incidence of these symptoms in our

time and money are lost pursuing other diagnoses

patients with A I D S was higher than a recent report of

while cultures are pending. Accurate diagnosis is

disseminated tuberculosis in a community hospital

necessary since treatment and prognosis of the two

and a group of patients with disseminated M avium-

diseases were different: Patients with tuberculosis,

intracellulare

even with A I D S , respond well to therapy.

infection but without A I D S .

15

14

The

Nontuber-

higher incidence of these symptoms may be due, in

culous mycobacteriosis does not respond well to con-

part, to the fact that our patients have A I D S , and in

ventional therapy, and newer agents have given mixed

part by the confounding effect of Pneumocystis

results. '

and other opportunistic infections.

33

9 11

In Miami, the relatively high incidence of tuberculosis among non-Haitians with A I D S may be explained by the overall high incidence of M

hominis

Table 4—Chest X-Ray Films in Tuberculosis and Nontuberculous Mycobacteriosis with a Pulmonary Source of Diagnosis (Expectorated Sputum or Bronchoscopy Specimen) Tuberculosis Chest roentgenogram abnormal Chest roentgenogram normal Percent with normal roentgenograms and positive cultures

774

Nontuberculosis Mycobacteriosis

carinii

Dyspnea, chills, hemoptysis, and chest pain were present in a significant minority of patients with nontuberculous mycobacteriosis, but were virtually absent from patients with tuberculosis. Conversely, significant adenopathy was seen much more commonly in the tuberculosis group. Chills in patients with nontuberculous mycobacteriosis may correlate with bacteremia. The gastrointestinal manifestations of nontuberculous mycobacteriosis in A I D S patients have recently

12 8

31 5

been emphasized and a possible gastrointestinal portal of entry has been proposed.

1617

While our data support

diarrhea as a prominent symptom, they also demonstrate the disseminated, multisystem nature of this disease.

40%

14%

Since our numbers are small, we cannot comment Mycobacteriosus in AIDS Patients (Fournier

et at)

on the value of stool and urine acid-fast smears and cultures. Reports of nontuberculous

mycobacteria

growing from blood cultures in patients with A I D S

1 8 1 9

are encouraging and should facilitate diagnosis. Only one blood culture grew nontuberculous mycobacteria out of hundreds from our patients. T h e poor recovery of organisms from blood samples was probably due to the procedure used in our laboratory. Special procedures using the lysis-centrifugation (Isolator) system and the blood culture (Bactec 12A) were

not per-

formed. A recent publication demonstrated the efficiency of these systems for the isolation of mycobacteria from blood samples.

20

W e confirm the finding that cavitary disease is rare in patients with A I D S and tuberculosis.

21,22

W e orig-

inally intended to exclude patients with cavitary disease to simplify comparison with the nontuberculous mycobacterial

group.

In

actuality,

no patient

who

otherwise met study criteria was excluded because of cavitary disease. A pulmonary source (expectorated sputum or bronchoscopy-obtained specimens) was the most frequent source of diagnosis in both patient groups. W e were surprised by the high yield of expectorated sputum, both in terms of positive smears and cultures, considering that we had no patient with cavitary disease and that the yield of expectorated sputum in patients with noncavitary tuberculosis without A I D S is generally felt to be low. This finding may be a consequence of immunodeficiency. Given the high percentage of diagnoses made from pulmonary sources even when the admission

chest

x-ray

film

was

normal,

clinicians

should collect sputum specimens and consider bronchoscopy in any case of suspected mycobacterial infection. ADDENDUM Many patients with evolving immunodeficiency develop tuberculosis before the criteria for A I D S

are

met, but because of the design of this study, such patients were not identified. This study does document that both tuberculosis and atypical

mycobacteriosis

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