Rev. lnst. Med. trop. São Paulo37 (5): 375-383, setembro/outubro, 1995

MYCOBACTER/UM AV/UM COMPLEX (MAC) ISOLATEO FROM AIOSPATIENTS ANO THE CRITERIA REQUIREO FOR ITS IMPLlCATION IN

OISEASE

David Jamil HADAD (1), Maria Cecília de Almeida PALHARES (2), Anna Luiza Nunes PLACCO (3), Carmem SilviaBruniera DOMINGUES (4), Adauto CASTELO FILHO (5), Lucilaine FERRAZOLI (6), Sueli Yoko Mizuka UEKI (6), Maria

Alice da Silva TELLES (6), Maria Conceição MARTINS (6) & Moisés PALACI (6)

SUMMARY

Before the AIOS pandemia, the Mycobacterium avium complex (MAC) was responsible in most casesfor the pneumopathies that attack patients with basic chranic pulmonary diseases such as emphysemaand chronic bronchitis ". ln 1981, with the advent of the acquired immunodeficiency syndrome(AIOS), MAC started to represent one of the most frequent bacterial diseases among AIOS patients,with the disseminated form of the disease being the major clinical manifestation of the infection".Between January 1989 and February 1991, the Section of Mycobacteria of the Adolfo Lutz Institute,São Paulo, isolated MAC frorn 103 patients by culturing different sterile and no-sterile processedspecimens collected frorn 2304 patients seen at the AIOS Reference and Training Center and/or EmilioRibas Infectology Institute, Oisseminated disease was diagnosed in 29 of those patients on the basis ofMAC isolation frorn blood and/or bone marraw aspirate. The other 74 patients were divided into cat-egories highly (5), moderately (26) and little suggestive of disease (43) according to the criteria ofOAVIOSON (1989)10. The various criteria for MAC isolation from sterile and non-sterile specimensare discussed.

KEYWORDS: Mycobacterium avium cornplex (MAC); Acquired immunodeficiency syndrame(AIOS); Oiagnostic cri teria.

INTRODUCTION

ApproximateJy 60 species are recognized todayin the genus Mycob acterium. Among them, particu-larly important in terms of human pathology arethose included in the Mvcob act erium tuberculo sis(M. tube rculo sis, M. bovis, M. africanum) complexand M. le p rae . However, at least 22 other speciesknown by the generic term Mycobacteria other than

tuberculosis (MOTT) may cause disease in humanbeings in the presence of certain host conditi ons".

Prior to the AIOS pandemia, MAC was mostly re-sponsible for pneumopathies mainly occurring in adultmales with some chronic basic lung disease such as pul-monary emphysema, bronchiectasia, pneumoconiosis or

(I) Holder of Master'x degree in Infectious and Parasitic Diseases, Escola Paulista de Medicina (EPM), and infectologist physician at lhe A/DSReterence and Training Center (CRTA).

(2) Head ofthe CRTA laboratory.(3) Holder of a degree in Biomedicine. CRTA laboratory.(4) Responsible for lhe AIOS Epidemiologic Alert Center (CVEJ of lhe Health Secrel~riat of lhe State of São Paulo.(5) Associare Professor, Discipline in lnfectious and Parasitic Diseases, EPM.(6) Scientifi c researcher, Sector of Mycobacteria, Adolfo Lutz Institute.·

Correspondence to: David Jamil Hadad, Rua Antonio Carlos 122, O I :109·01 O, São Paulo, SP, Brasil.

375

HADAD, D.1.; PALHARES, M.C de A., PLACCO, A.L.N.:DOMINGUES, CS.B.;CASTELO FILHO, A.;FERRAZOLl, L., UEKI, SYM;TELLES,M.A. da S.: MARTINS,M.C & PALACI. M. - Mycohacterium avium eomplex (MAC) isoluted from AIDS putients and lhe criteria required forits implication in disease. Rev, Inst, Med, trop. S,Paulo, 37 (5): 375-383, 1995.

cicatricial lesions due to tuberculosis': Until 1980, fewcases of disseminated disease had been reported in thelirerature", and most of them affected patients with ma-lignant hematologic disease such as hairy cell leukernia"and immunosuppressed by drugs or with other basic pa-thologies":

Over the last 14 years, with the advent of the ac-quired immunodeficiency syndrome (AIOS), severalMOTI have been reported to be responsible for opportu-nistic infections in these patients, with those belongingto the Mycobacterium avium-iruracellulare complex be-ing the most frequently reported. Disseminated MACdisease started to represent the major form of clinicalmanifestation 01' disease due to these mycobacteria=".

Severe immunodeficiency characterized by a CD4lymphocyte number of less than 100/mm3 has been con-sidered the major risk factor for disseminated MAC dis-ease, whose clinical manifestations are quite nonspecific:fever, night sweating, adynamia and weight loss 19, re-quiring a differential diagnosis from other opportunisticinfection.

Although the differential diagnosis assumes the iso-lation and identification of MAC frorn sterile specimenssuch as blood, bone marrow, Iymphonode, and liver orspleen tissue, some investigators tend to place a highervalue on the isolation of these micraorganisms frorn non-sterile sites both for a predictive indication of dissemina-tion and for the diagnosis of infection7,IO,33 However, inpractice there are rnany difficulties in differentiating thethree types of"relationship between MAC and lhe humanhost: colonization, infection and disease ", especiallywhen these mycobacteria are isolated frorn non-sterilespecimens.

The objectives of the present report are to presentthe results obtained by us with mycobacteriologic exami-nation of the different specimens collected from HIV -in-fected patients or patients with AIDS, determine the fre-quency of MAC isolation and, finally, analyze and dis-cuss the cri teria available in the literature for the determi-nation of the diagnostic value of the isolation of thesemycobacteria frorn different sterile and non-sterile speci-mens.

MATERIALS AND METHODS

PATIENTS AND SOURCE OF SPECIMENS

From January 1989 to February 1991 a total of 6537clinical specimens were processed in the Section of My-cobacteria, Department of Bacteriology, of Adolfo LutzInstitute, The specimens were obtained from patients

376

with suspected ar diagnosed HIV/AIDS seen at theEmilio Ribas Infectology Institute and/or AIOS Refer-ence and Training Center - São Paulo (CRTA-SP).

A total of 5484 specimens collected fiam 2304 pa-tients were selected frorn the above total on the basis 01'notification of the confirmed presence of AIOS. This se-lectión was made using no. III Epidemiologic Notifica-tion Cards/ AIOS of Sexually Transmissible Diseases/AIDS of the Epidemiological Surveillance Center of De-partrnent of Health of São Paulo State.

The specimens were collected according to the sus-pected involvement of various sites, except cerebrospinalfluid (CSF), which was collected from several patientsfor the contraI of tuberculous meningoencephalitis, andbrain toxoplasmosis and cryptococcosis.

Search for mycobacteria in the different clinical speci-mens:

Culture: specimens of sputum, bronchial wash, gas-tric wash, feces, urine, biopsies, and pleural and perito-neal secretions and fluids were decontaminated by themethod of Petroff and later inoculated (0.2 ml) intoLowenstein-Jensen rnedium'".

Blood specimens (5 ml) were directly inoculatedinto biphasic culture medium consisting of Middlebrook7H9 liquid medium (Difco) containing lhe anticoagulantsodium polyanethol sulfonate (0.25 g/rnl), polymyxin B(200 U/ml), amphotericin B (10 mg/m!), carbenicillin(50 mg/ml) and trimetoprim (20 mg/ml), and 01'Lowenstein-Jensen solid medium. Bane marrow aspi-rates and CSF samples were directly inoculated intoLowenstein-Jensen medium (appraximately 0.2 ml).

After inoculation, the culture media were incubatedat 37°C and inspected weekly until the occurrence of my-cobacteria colonies or for a period of up to 60 days whenthey were considered negative because of the absence argrowth. Biopsies and skin secretions were also incubatedat 28°C and 37°C.

Identification of mycobacteria: non-pigmentedmycobacteria colonies with a rough aspect, growing inLowenstein-Jensen medium only at 37°C for a period ofmore than seven days (slow growth), niacin producing,nitrate reducing, sensitive to paranitrobenzoic acid andresistant to 2-thiophenocarboxylic acid were identifiedas M. tuberculosis'F Strains characterized as Mycobac-teria other than M. tuberculosis (MOTI) were identifiedby the methods of KENT & KUBICA (1985)22 andOAVID et a!. (1989)9

HADAD, DJ .. PALHARES, M.C. de A., PLACCO, A.LN.;DOMINGUES, C.S.B;CASTELO FILHO. A.;FERRAZOLl. L; UEKI, SY-M.;TELLES,M.A. da 5 .. MARTINS.M.C. & PALACl, M. - Mycobacrer;um aV;lIm complex (MAC) isolated from AIDS patients and lhe criteriu required forits irnplication in disease. Rev. Inst. Med, trop, S,Paulo, 37 (5); 375-383,1995.

Clinical and laboratory data:

The clinical signs and symptoms that permitted thediagnosis of disseminated disease were obtained fromCRTA medical records and from the following regionalhospitaIs: Sul, Mauá, Franco da Rocha, Brigadeiro,Ferraz de Vasconcelos, Mandaqui, Ipiranga, andHeliópolis, and frorn the Municipal ltaquera Hospitaland the Santa Marcelina Health House.

Date of AIDS diagnoses and date of deaths for cases01' disseminated MAC disease were obtained from lheepidemiologic notification cards.

Data about hemoglobin, total leucocyte and Iympho-cyte and serum glutamic oxaloacetic transaminase(GOT), glutamic-pyruvic transaminase (GPT) and alka-line phosphatase (AP) determinations performed on lheoccasion of the specimen collection that led to thediagnosis of disseminated MAC disease were also ob-tained from these medical records.

Definition of disseminated MAC disease and díagnos-tic categories:

AIJ patients with MAC strains identified from blood,bone marrow aspirate, Iymphonode and/or ganglionar se-cretions were considered to be cases of disseminatedMAC disease?".

Patients with MAC strains isolated from other siteswere distributed into the following diagnostic categories,defined on the basis of isolation sites:

HIGHLY SUGGESTIVE OF DISEASE: when MACstrains were isolated from two or more CSF specimens;

MODERATELY SUGGESTIVE OF DISEASE:when the strains were isolated frorn the sarne non-sterilespecimen two or more times,from two non-sterile speci-mens regardless of the number of specimens positive foreach type, and from a single CSF specimen;

LITTLE SUGGESTIVE OF DISEASE: when lhestrains were isolated from a single non-sterile specimen.

RESULTS

MAC was isolated from the different specimens of103 (4.5%) of the 2304 patients whose specimens werecultured (Table l ). ProportionaLJy, there was a higher fre-quency of isolation of these rnicroorganisms from blood(14.8%) and bone marrow aspirate (25.7%) samples. Thetable also shows the isolation 01' MAC from only one pa-tient among those whose lyrnphonode and/or ganglionarsecretions were cultured.

Table 2 shows the classification of these 103 pa-tients into four diagnostic categories according to previ-ously established criteria. We emphasize that MAC wasisolated from non-sterile specimens collected from 60(58.2%) of these patients.

The clinical signs and symptoms of 18 of the 29cases 01' disseminated MAC disease are presented inTable 3. This analysis could not be extended to ali pa-tients because 01' lack of access to their data. It is interest-ing to mention that ali of these 15 patients had fever.

TABLE 1

Frequency of MAC isolation frorn different specirnens obrained frorn 2304 patientswith processed cultures.

Specimen Number of No. of patients (%)processed with MACcultures

Sputum 899 36 4.0

Bronchial lavage 566 30 5.3

Gastric lavage 56 1.8

Feces 20 1 5.0

Urine 81 2 2.5

Cerebrospinal fluid 1372 16 1.2Blood 122 18 14.8

Bone marrow aspirare 74 19 25.7

Ganglionary secretion 30 3.3Others 150 O 0.0

377

.' ''; ..~'~.'.

HADAD. D.1.: PAlHARES. M.C. de A.: PlACCO, A.l.N.:DOMINGUES, C.S.B.;CASTELO FilHO. A.:FERRAZOLl. L.; UEKI. S.Y.M.;TELLES.M.A. da S.: MARTINS.M.C. & PAlACI. M. - Mvcobocteriun, lIviUI11 complex (MAC) isolated from AIOS patients and the cri teria required forits implication in disease. Rev. Inst. Med. trop, S.Paulo, 37 (5); 375-383. 1995.

TABLE 2

Distribution of patients frorn whom the Mycobacterium avium complex was isolatedaccording to the diagnostic categories established and isolation sites.

Diagnostic categorySite of isolation

No. of patients (%)(n=103)

Diagnosis of disseminated disease

Blood

Blood and sputum

Blood and bronchial lavage

Blood and ganglionary secretion

Bone rnarrow

Bone marrow and sputurn

Bone rnarrow and gastric lavage

Bone marrow and cerebrospinal tluid

Blood and bone rnarrow

Blood, bone maITOW feces

Blood, bone rnarrow and cerebrospinal tluid

Highly suggestive of disease

Cerebrospinal tluid (3 sarnples)

Cerebrospinal tluid (2 samples)

Moderately suggestive of dísease

Sputum (2 samples)

Sputum (2 samples ) and bronchiallavage

Sputurn (3 sarnples) and bronchial lavage

Sputum (4 samples)

Sputurn and Bronchiallavage

Bronchial Iavage (2 sarnples)

Urine (2 sarnples)

Cerebrospinal fluid

Little suggestive of disease

Sputum

Bronchiallavage

Urine

29(27.9)

7(6.6)

1(1.0)

1(1.0)

1(1.0)

8(7.6)

1(1.0)

1(1.0)

1(1.0)

6(5.7)

l( 1.0)

1(1.0)

5(4.8)

4(3.8)

1(1.0)

26(25.0)

8(7.6)

2(1.9)

2(1.9)

1(l.0)1(1.0)

2( 1.9)

1(1.0)

9(8.7)

43(41,3)

20(19.2)

22(21.1 )

1(1.0)

The chemical and cytologic analysis of the bloodof these 15 patientsis presented in Table 4. Eleven ofthem had hemoglobin levels lower than 10 g/dl and amean number of totallymphocytes of 787.9/mmJ

DISCUSSION

Although the pathogenic potential of MAC and amarked degree of irnmunodeficiency represent preponder-

378

ant factors for the development of the disease, the interpre-tation of MAC isolation from different specimens requirescaution, especially because this is an environmental micro-organism with the ability to contaminate specimens ar tocolonize the mucosal surfaces of human beings in a tran-sitory manner without any harm to the host6.II.J4.15.;!6.2M.

Thus, what are the criteria used to attribute a patho-genic role to this complex in a given patient?

HAOAO, 0.1.; PALHARES, M.C. de A.; PLACCO, A.L.N.;OOMINGUES, C.S.B.;CASTELO FILHO, A.;FERRAZOLI, L.; UEKI, S.Y.M.;TELLES.M.A. da S.; MARTINS,M.C. & PALACI, M. - Mvcobucterium avium complex (MAC) isolated trem AIOS pauents and lhe criteria required forits implication ;11 disease. Rev. Inst. Med. trop. S.Paulo, 37 (5): 375-383, 1995 ..

In 1967, YAMAMOTO et al.", in Japan, praposed:a) major cri teria: I) isolation of MOTT four times armore with a number of colonies of more than 100 assoei-ated with the presence of clinical symptoms that might beattributed to these bacilli, and 2) presence of a lesioncontaining MOTT and histopathological alterations pos-sibly due to these bacilIi; b) minor criteria: I) MOTTisolation more than four times ar a number of coloniesexceedi ng 100, 2) MOTT elimination during the courseof the disease, 3) MOTT isolation from an organ or tis-sue whose histopathological characteristics are notknown, and 4) intradermal reaction halo to tuberculinobtained from MOTT larger than that in response to thetuberculin protein derivative obtained from M. tubercu-losis, or an increase in the halo in response to tuberculinobtained frorn MOTT coinciding with the course of thedisease. The diagnosis of the disease is established whenat least-one of the major criteria or alleast three of thefour minor cri teria are satisfied.

In 1970, EDWARDS13, in Australia, adopted as acriterion for MOTT disease the presence of tissue lesionsindistinguishable from active tuberculosis and the cul-ture of the bacillus at least once frorn lhe same tissue inthe absence of M. tuberculosis.

In 1981, the AMERICAN THORACIC SOCIETy2

adopted as a criterion for MOTT-induced pulmonary dis-ease the presence of an infiltrate on the chest X-ray of apatient whose pathology could not be determined bycareful clinical and laboratory investigation, but inwhose specimens lhe same mycobacterium species couldbe detected in the absence of other pathogens.

In 1982, AHN et al.', in the U.S., in a reanalysis ofthe above cri teria, proposed the following ones for thediagnosis of pulmonary disease caused by M. kansasii arM. iniracellulare: a) positive sputum bacilIoscopies fortwo weeks ar more after the beginning of chemotherapyin the presence of cavitation not explained by any otherdisease; b) absence of reduction in the number of colo-nies within one month ar absence of negativity of sputumwithin 2 to 4 months after branchial hygiene in the pres-ence of infiltration without cavitation that could not beexplained by any other associated disease, ar c) isolationof mycobacteria from tissue biopsies in association withhistopathological alterations compatible with the disease.

In 1986, TSUKAMURA33, in Japan, praposed diag-nosis of the disease based on the isolation of the samemycobacterium species from two or more cultures ofsputum samples collected over a period of seven days arseveral isolations at two to three month intervals in thepresence of a cavitary ar caseo-infiltrative pulmonary le-

sion. He also suggested the diagnostic importance of acavity with a sclerotic wall ar cavities inside a sele-rotic lesion associated with three or more cultures ofmonthly sputum samples collected over a period of sixmonths with isolation of more than 100 monthly of thesame mycobacterium species.

In 1989: DAVIDSON'O in the U.S. proposed that lhelarger the nurnber of positive culture and the number ofcolonies present in them, and the longer the periodof ob-servation of these findings, the greater the chance of theisolated mycobacterium being lhe agent responsible forthe disease,

In 1990 the AMERICAN THORAC1C SOC1ETY"in a reevaluation of the criteria established in 1981, pro-posed that the diagnosis of MOIT -induced lung diseaseshould be based on the presence of AFB in two ar moresputum samples (ar a sputum sample and bronchiallavage) and/or abundant MOTT growth associatedwith the exclusion of another morbid entities thatmight justify the pulmonary disease, such as fungaldisease, malignant disease or tuberculosis.

However, it is important to point out that most of theabove cri teria still need validation.

In 1985, KIEHN et al24 and in 1986 HAWK1NS etal. ", in New York (U.S.A.), validated the isolation 01'MAC from blood, bane marrow, Iymphonode ar liver forthe diagnosis 01' disseminated disease in HIV -infectedpatients by documenting this clinical form of the diseaseat autopsy in alI AIDS patients studied and by isolatingMAC frorn these specimens.

In view of the above information, in our series wedefined as cases of disseminated disease the 29 patientsfrorn whose blood and/or bane marrow aspirate MACwas isolated in association ar no! with MAC isolationfrorn non-sterile specimens.

Analysis of clinical signs andsymptorns was per-formed in only 15 of the 29 cases. The presence of feverin all of the 15 patients .agreed with data reported formost series in the literature'P-". However, analysis of lheother clinical signs and symptoms among the present pa-tients with this disease (table 3) was harnpered oy the factthat these clinical parameters were obtained from medi-cal records and not by prospective patient evaluation.With respect to the laboratory data, a mean hemoglobinconcentration of 9.0 g/dl and a mean total Iymphocytenumber of 787.9/mmJ were the most frequent alterations.These data are similar to those reported by others+".

379

HADAD. D.J.; PAlHARES, M.C. de A.; PlACCO, A.L.N.;DOMINGUES, C.S.B.;CASTElO FILHO. A.;FERRAZOLl. L.; UEKI. S.Y.M.;TEllES.M.A. da S.: MARTINS,M.C. & PAlACI, M. - Mvcobacterium avium complex (MAC) isolated from AlDS patients and the cri teria required forits irnplication in disease, Rev. Inst. Med. trop. S.Paulo, 37 (5): 375-383,1995.

Mean GOT, GPT and AP values were within normallevels although high serum AP levels of these patientsare commonly reported'"-".

To establish a sure diagnosis for the remaining 74patients it would be obligatory to isolate MAC fromblood or bone marrow. However, since this was a retro-spective study, these specimens unfortunately were notcollected and .cultured for mycobacteria. Consequentlywe opted for the stratification of these patients into threediagnostic casegories (Table 2) mainly on the basis of thepostulates of DAVIDSONlo.

In the second group, categarized as highly sugges-tive af the disease, we included the patients with MACisolation from one or more CSF specimens (sterile speci-mens). In this respect, little has been reported on thepathogenicity of MAC for the central nervaus system andthe possible relationship between MAC isalation framthe CSF only and the existence of disseminated dis-ease1r..2UO.J5.J6 Considering that CSF is a sterile speci-

men, MAC isolatian from it shauld signify disseminateddisease in view ar the fact that MAC access to the centralnervous system would be preceded by hematogenic dis-semination. On the other hand, anatomopathologicalsubstrates relating MAC isolation from CSF to diseases

involving the central nervous system are still quitescarce". Among the few reports citing the pathogenicityof MAC for the central nervous system is that 01'CHAPMAN (1960)5, in Texas, who reported granulo ma-tous meningitis detected at autopsy in a IJyear old boywith disseminated MAC disease and MAC isolation frornthe CSF before death.

Recently, lACOB et a1.21, in New York (U.S.A.), re-ported MAC isolation frorn the CSF of 15 patients andM. fortuitum isol~tion from another, all of them ÀIDSpatients. Autopsy was perfarmed in three of these 16cases, revealing extensive involvement of the liver, gas-trointestinal tract, bone marrow, lymphonode and centralnervous systern, with discrete inflarnmatory activity andpoorly farmed granulomas without giant Langhans cells.Although the material obtained at autopsy was not cul-tured, AFB were visualized by direct inspection ar mostsites, Thus, if, on the one hand this study presented thefirst substantial evidence in the AIOS pandemia thatMAC isolation from the CSF may represent a marker ofits hematogenic dissemination, on the other hand we can-not base aurselves on this finding as a reference of thepathogenicity of MAC for the central nervous systemsince there are no reports of the detection of AFB in thecentral nervous system 01' 01' the isolation of mycobacte-ria from brain tissue cultures.

TABLE 3

Signs anel symptorns

Clinical signs and syrnptoms of 15 patients with disseminated disease caused by Mycobacterium avium complex.

No. of cases (%)

Fever

Night sweating

Generalized maiaise

Adynamia

Anorexia

Weight loss

Generalized pain

RespiratoryCoughDyspneaRetrosternal pain

GastrointestinalDiarrheaEpigastric pain

LymphadenopathyLocalizedGeneralized

Hepatosplenomegaly

[5(1000)

4(367)

1(6.7)

[(6.7)

1(6.7)

1(6.7)

1(67)

4(26.7)2( 13.3)[(6.7)

2( 13.3)1(67)

[(6.7)1(6.7)

1(6.7)

380

HAOAO, 0.1.; PALHARES, M.C. de A.; PLACCO, A.L.N.;OOMINGUES. C.S.B.:CASTELO FILHO. A.;FERRAZOLl. L.; UEKI. S.Y.M.;TELLES.M.A. da S.; MARTINS.M.C. & PALACI. M. - Mvcobacterium avium complex (MAC) isolated from AIOS pauents and the criteria required forits implication in disease Rev. Inst. Med. trop. S.Paulo, 37 (5): 375-383. 1995.

TABLE 4

Chernical and cytologic analysis of blood frorn 15 patients with disseminated disease caused by Mycobucterium avium cornplex.

Normal values' Values obtained No. of cases (%)(n=15)

<10 11(786)

10-12 2(14.3)

> 12 1 (7.1)

NO" 1

X=9.05

<4,000 5(357)

4,000- J0,000 9(643)NO I

X=4514.3

<200 2(143)200-600 4(286)

600-1,000 4(28.6)>1,000 4(28.6)

NO 1X=787.9

<40 9(81.8)

>40 2(18.2)

NO 4X=37.7

=<50 12(85.7)

>50 2(14.3)

ND 1X=30.3

<220 7(636)>220 4(364)

NO 4

X=J80.7

Hemoglobin

(>=12g/dl)

Total white cells

(5,000- JO,OOO/mm')

Total Lymphocytes

(1,000-4,200/mm')

Glutamic oxaloacetic

transarninase(14-31 UIII)

Glutamic pyruvic

transarninase

(8-46UIII)

Alkaline phosphatase(80-220UI/l)

"According (o Kjeldberg (1993)"ND = nOI determined

ln relation to the third diagnostic category, classi-fied as moderately suggesti ve of the disease, accord-ing to the cri teria praposed by DAVIDSON'o, the rein-cidence of MAC isolation from non-sterile specimenswith a moderate number of colonies represents the ma-jor bacteriologic basis for the assignment of patientsto this category. We also decided to assign to this cat-egory those patients with a single MAC isolation frornthe CSF by considering the probability of disease

among them to be lower compared to the categoryhighly suggestive of disease.

We assigned to the last category the 43 patients withthe least prabability of disseminated disease as indicatedbya single isolation ofMAC frorn a non-sterile specimen.

1n summary, the present results indicate the need forfurther studies to determine the incidence and predictive

381

- -- - ---- -.--- - __ o _ .•••. - • __ - _

HADAD, OJ., PALHARES, M.C. de A.; PLACCO, A.L.N.;OOMINGUES, C.S.B.;CASTELO FILHO, A.;FERRAZOLl, L.; UEKI, S.Y.M.;TELLES,M.A. da S.; MARTINS,M.C. & PALACI, M. - Mycobacterium avium cornplex (MA C) isolated from AIOS patients and the criteria required forits implication in disease. Rev. Inst. Med. trop. S.Paulo, 37 (5): 375-383, 1995.

value of MAC-induced disease in each category, espe-ciaJly by culruring blood and/or bone marrow aspirateand by submitting to autopsy subjects suspected to havedisseminated MAC disease.

RESUMO

Complexo Mycobacterium avium (MAC) isolado depacientes com AIDS e os critérios exigidos para sua

implicação em doença.

Anterior a pandemia de AIDS, o ComplexoMycobacterium avium (MAC) era responsável pela mai-oria das vezes, por pneumopatias acometendo pacientescom doença pulmonar crônica de base como enfisema ebronquite crônica". Em 1981, com o advento dasíndrome de imunodeficiência adquirida (SIDA), o MACpassou a representar uma das doenças bacterianas maisfrequentes em pacientes com esta síndrome, sendo a do-ença disseminada a principal forma de manifestação clí-nica da infecção",

Entre Janeiro de 1989 e Fevereiro de 1991, no Setorde Micobactérias do Instituto Adolfo Lutz em São Paulo,o MAC foi isolado de 103 pacientes a partir do cultivo dediferentes espécimes estéreis e não estéreis processados,coletados de 2.304 pacientes atendidos no Centro de Re-ferência e Treinamento AIDS e/ou Instituto de Infectolo-gia Emilio Ribas. A doença disseminada foi diagnostica-da em 29 destes, com base no isolamento do MAC a par-tir do sangue e/ou aspirado de medula óssea. Os outros74 pacientes foram agrupados nas categorias altamente(5), moderadamente (26) e pouco sugestiva de doença(43) de acordo com os postulados de DAVIDSON(1989)10. Os diferentes critérios para valorizar o seu iso-lamento de espécimes estéreis e não estéreis são discuti-dos.

ACKNOWLEDGEMENTS

We are grateful to Prof. Dr. Gildo DeI Negro from"Disciplina de Moléstias Infecciosas da Faculdade deMedicina da Universidade de São Paulo" for his criticalreview 01' the manuscript.

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