Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
Occurrence of active tuberculosis in households inhabited
by patients with susceptible and multidrug- resistant
tuberculosis*
ELIZABETH CLARA BARROSO, ROSA Mª SALANI MOTA, VALÉRIA GÓES FERREIRA PINHEIRO, CREUSA LIMA CAMPELO, JORGE LUIS NOBRE RODRIGUES
Background: Since the first years of antituberculosis chemotherapy, there has been controversy regarding the transmissibility, infectiousness, virulence and pathogenicity of susceptible and drug- resistant strains of Mycobacterium tuberculosis.
Objective: To determine the incidence of active tuberculosis (TB) among individuals cohabiting with patients infected with susceptible and multidrug-resistant tuberculosis (MDR-TB).
Methods: A case- control study was conducted. Cases of MDR- TB were defined as those infected with M. tuberculosis
strains resistant to at least rifampin and isoniazid. Susceptible TB cases (controls) were defined as those first treated at approximately the same time as the first treatment of the MDR- TB cases - and cured by the time of the interview. Study cases were selected on the basis of the results of susceptibility tests, using the proportion method, carried out at the Central Laboratory of Public Health of the State of Ceará. The control group consisted of patients enrolled in the Tuberculosis Control Program between 1990 and 1999.
Results: We evaluated 126 patients and 176 controls. The number of individuals sharing the household with patients was 557 in the MDR- TB group and 752 in the controls. The average number of exposed individuals per index case was 4.42 and 4.27 among patients and controls, respectively. Of the 557 MDR- TB- exposed individuals, 4.49% (25) received antituberculosis treatment after the respective index case had begun treatment, compared to 5.45% (41/752) among the controls (p = 0.4468). Microepidemics of MDR- TB were confirmed in eight families.
Conclusion: Our results suggest that the incidence of active TB is comparable between households inhabited by MDR-TB patients and those inhabited by susceptible- MDR-TB patients.
Key words: Tuberculosis, multidrug- resistant/epidemiology. Tuberculosis/trasmission.
*St u dy carried ou t at t he Hospit al de Maracan aú / Min ist ério da Saú de (Maracan aú Hospit al/ Healt h Min ist ry) an d at t he Hospit al de Messejan a/ Secret aria da Saú de do Est ado do Ceará (Messejan a Hospit al/ Ceará St at e Depart men t of Healt h).
Co rresp o n d en ce t o : Elizab et h Clara Barro so - Ru a Fo n seca Lo b o 5 0 ap t o 4 0 2 , Ald eo t a. CEP - 6 0 .1 7 5 - 0 2 0 – Fo rt aleza, CE; p h o n e: 5 5- 8 5 - 2 6 7 1 5 5 7 ; e- m a il: vb a rro so @ fo rt a ln et .co m .b r
ST – Su scept ibilit y t est disease(1). Chemot herapy is t he most effect ive
weapon again st TB, leadin g t o a cu re in almost all cases. However, variou s fact ors may n egat ively e f f e c t o u t c o m e s (2 ). In a p p r o p r ia t e u s e o f medicat ion du rin g t reat men t is on e of t he most significant factors, creating resistant strains of the bact eria, or pat ien t s wit h “acqu ired resist an ce”. Pat ien t s who become ill aft er bein g in fect ed wit h s t r a in s t h a t h a ve d e ve lo p e d r e s is t a n t t o medicat ion s n ever admin ist ered (or admin ist ered fo r less t h a n a m o n t h ) t o t h o se p a t ien t s a re design at ed as cases of “primary resist an ce”(3). In t ern at ion ally, mu lt idru g- resist an t t u bercu losis (MDR- TB) is defined as those cases in which strains are resist an t t o (at least ) t h e co m b in at io n o f rifampin (RIF) an d ison iazid (INH)(3).
In t h e 1 9 6 0 s a n d 1 9 7 0 s, va rio u s st u d ie s co n d u ct ed in t h e USA sh o wed t h at , alt h o u g h st rain s resist an t t o an t it u bercu losis dru gs had appeared, t he expect ed in crease in t he in ciden ce of primary resist an ce du e t o acqu ired resist an ce did not occur. A possible explanation for this could be the fact that multidrug- resistant Mtb strains are eit her n ot as readily t ran smit t ed or do n ot cau se in fect ion or disease as easily as do su scept ible st rain s(4). Some au t hors have report ed t hat INH-resist an t st rain s presen t decreased pat hogen icit y in laborat ory an imals, especially in gu in ea pigs, leadin g t he scien t ific commu n it y t o believe t hat t hese st rain s were less likely t o cau se in fect ion or disease in hu man s(5).
Ho w e ve r, s in c e t h e f irs t d e c a d e s o f chemot herapy, various st u dies have proven t hat st rain s resist an t t o INH, st rept omycin (SM) an d para- amino salicylic acid can indeed be transmitted an d lead t o developmen t of TB(4). In a st u dy in volvin g a gu in ea- pig model of t he disease, wide variation in virulence was observed among strains, alt hou gh resist an t st rain s were n ot shown t o be con sist en t ly less viru len t (6).
The combin ed prevalen ce of MDR- TB (primary + acqu ired) in t he st at e of Ceará in creased from 0.82% in 1994 to 1.48% in 1999(7). Between 1995
an d 1996, t he prevalen ce was 0.6% for primary MDR- TB an d 3.3% for acqu ired MDR- TB(8).
Chemoprophylaxis is one of the most efficacious r e s o u r c e s in TB t r e a t m e n t . Th e Br a z ilia n Department of Health recommends the use of INH as a prophylact ic agen t in order t o preven t t he development of active TB in individuals cohabiting wit h pat ien t s wit h TB. In t he case of in dex cases diagn osed wit h MDR- TB, t here is n o object ive re c o m m e n d a t io n , sin c e t h e re h a s b e e n n o con sist en t , con clu sive research t o ju st ify su ch a recommen dat ion (9).
Th e t h eo ry t h at resist an t st rain s were less pat hogen ic was highly accept ed du rin g t he first decades of an t it u bercu losis chemot herapy. In t he 1990s, institutional epidemics of MDR- TB in human immu n odeficien cy viru s (HIV)- posit ive pat ien t s were report ed(3), evokin g debat e regardin g t his t heory. Transmissibilit y of TB, especially MDR- TB, con t in u es t o be a cau se of great con cern amon g h ealt h p ro fessio n als, p at ien t fam ilies an d t h e gen eral popu lation .
The object ive of t his st u dy was t o det ermin e t h e in cid en ce o f act ive TB am o n g in d ivid u als cohabiting with patients infected with susceptible TB or MDR- TB
METHODS
The presen t st u dy was carried ou t in t he st at e of Ceará, where 41,073 TB cases were report ed between 1990 and 1999(7). The population of the st at e is 6,809,290(10), an d t he popu lat ion of it s capit al, Fort aleza, is 1,965,513(10). Of t he t ot al n u m b e r o f ca se s re p o rt e d , 5 0 % o ccu rre d in Fortaleza.
Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
Con t rols were defin ed as t hose cases t hat were in itially treated at approximately the same time as the first treatment of MDR- TB cases. Controls were requ ired t o have had act ive TB at t he begin n in g of t reat men t , have been cu red by t he t ime of t he in terview (su sceptible TB) u n der Regimen I, which con sist s of 2 mon t hs of RIF- INH- pyrazin amide (PZA), followed by 4 mon t hs of RIF- INH.
Case select ion was based on t he resu lt s of su sc e p t ib ilit y t e st s (STs) p e rf o rm e d a t t h e Laboratório Central do Estado do Ceará (Ceará State Central Laboratory), the only laboratory in the state t hat performs su ch t est s. The laborat ory operat es u n der t he au spices of t he Cen t ro de Referên cia Professor Hélio Fraga, a n at ion al referen ce cen t er for STs. Some cases were select ed from amon g pat ien t s examin ed at t he Hospit al de Maracan aú (a st at e referen ce hospit al for TB), locat ed in t he cit y of Maracan aú (n ear Fort aleza). Ot hers were pat ien t s from t he Hospit al de Messejan a (a st at e an d region al referen ce hospit al an d ou t pat ien t clinic for TB) located in Fortaleza, while still others were from t he Un idade San it ária Don a Libân ia (Dona Libânia Health Clinic), a reference clinic that is also locat ed in Fort aleza.
Control patients were matched to study patients for gen der, age, an d year of first t reat men t . The mean period between first treatment and MDR- TB d ia g n o sis wa s 6 .5 ± 3 yea rs. Th e st u d y wa s con du ct ed in t he year 2000, alt hou gh t he median was extended an extra year into the past. All active TB pat ien t s were select ed from t he records of t he TB control program (at the Hospital de Maracanaú and Hospital de Messejana) from 1993 on. Patients were n ot ified by mail an d in vit ed t o part icipat e. Pa rt icip a t in g p a t ien t s g a ve writ t en in fo rm ed con sen t , an d t he st u dy design was approved by t he Comit ê de Ét ica em Pesqu isa da Un iversidade Federal do Ceará (Et hics- in - Research Commit t ee o f t h e Fe d e ra l Un ive rsit y o f Ce a rá ). At t h e phthisiology clinic, patients were screened through chest X- rays and routine blood tests (including HIV serology if con sen t was given ), as well as spu t u m smear an d cu lt u re for acid- fast bacilli if t here was expectoration. If the patient was considered cured, a questionnaire was filled out and the data entered in t o t he con t rol dat abase.
Variou s charact erizat ion s were made t hrou gh applying the questionnaire. Cured TB, TB treatment non- compliance and contact with TB were defined
accordin g t o t he crit eria est ablished by t he 1st Brazilian Tu bercu losis Con sen su s(9). The au t hors defined a micro- epidemic of MDR- TB as 2 or more cases of MDR- TB in the same household, confirmed by ST. Number of previous treatments was defined as t he n u mber of t reat men t s prior t o MDR- TB d ia g n o sis (st u d y g ro u p ) o r a s t h e n u m b er o f t reat m en t s p rio r t o p at ien t in t erview (co n t ro l grou p).
Löwenstein- Jensen culture media was used. The proport ion met hod on solid media was u sed for t he ST. Resist an ce was defin ed as at least 1% colon y growt h in crit ical con cen t rat ion s of INH (0.2 µ g/ mL), et hambu t ol (2 µ g/ mL) or RIF (40 µ g/ mL), or at least 10% colon y growt h in crit ical con cen t rat ion s of et hion amide (20 µ g/ mL), PZA (100 µ g/ mL) or SM (4 µ g/ mL).
The chi- squ are t est was u sed in t he st at ist ical an alysis an d valu es of p < 0.05 were con sidered statistically significant. Statistical evaluations were performed wit h t he aid of t he Excel for Win dows an d Word for Win dows programs.
RESULTS
Of t he 1500 STs evalu at ed at t he Laborat ório Cen t ral do Est ado do Ceará in t he 1990s, 266 st rain s were resist an t t o at least t h e RIF- INH combination. Of the 266 patients from whom those samples were obt ain ed, 153 were locat ed an d a standard questionnaire was filled out. Of those 153 pat ien t s, 27 were exclu ded for variou s reason s: 5 were in fect ed wit h at ypical mycobact eria, 2 did not meet the criteria for a diagnosis of MDR- TB, 6 had had no contact, 4 belonged to families already in clu d ed in t h e st u d y (o n ly in d ex ca ses were exempted from exclu sion ), an d 10 did n ot provide relia b le in fo rm a t io n o n t h e t rea t ed co n t a ct s. Therefore, t he st u dy grou p comprised a t ot al of 126 pat ien t s.
TABLE 1
Distribution of index cases and contacts treated in three reference centers for tuberculosis in the state of Ceará between 1 9 9 0 and 1 9 9 9 . Two g roups of are represented: active susceptible tuberculosis
(control g roup) and multidrug - resistant tuberculosis patients (study g roup)
Group Index cases Con t act s Con t act s/ in dex cases
Control 176 752 4.27
Study 126 557 4.42
Total 302 1309 4.33
TABLE 2
Dist ribu t ion of families in t he con t rol an d st u dy grou ps in relat ion t o t he n u mber of pat ien t s per family t reat ed in t hree referen ce cen t ers for t u bercu losis in t he st at e of Ceará bet ween 1990 an d 1999
Nu mber of t reat ed Families in Families in Tot al n u mber
pat ien t s per family con t rol grou p study group of families
N % N % N %
0 149 84.7 109 86.5 258 85.4
1 19 10.8 12 9.5 31 10.3
2 5 2.8 3 2.4 8 2.6
3 1 0.6 1 0.8 2 0.7
4 1 0.6 1 0.8 2 0.7
5 1 0.6 1 0.3
Total 176 100.0 126 302 100.0
± 3 years. In t he con t rol grou p, t he mean period bet ween first t reat men t an d t he in t erview was 6.5 ± 5 years. Con siderin g all st u dy part icipan t s, t he mean period bet ween diagn osis of MDR- TB an d t he st u dy on set was 4.1 years.
In t h e s t u d y g ro u p , 7 9 (6 2 .7 % ) o f t h e participants were male, compared to 110 (62.5%) in the control group. Mean age was 39 ± 25 in the study group and 41 ± 14 years in the control group. In the study group, 78 (62%) of the 126 were tested for HIV, as were 97 (55%) of the 176 patients in the control group. All HIV test results were negative. As can be seen in Table 1, the total number of index cases was 302 and the total number of patients having contact with those cases was 1309. The distribution of families in relation to the number of treated patients is shown in Table 2.
w i t h a c t i v e t u b e r c u l o s i s , t h e r e w a s a st a t ist ica lly sig n ifica n t d ifferen ce b et ween t h e t wo g ro u p s in t h e p ercen t a g e o f t h o se t rea t ed p r i o r t o t h e t r e a t m e n t o f i n d e x c a s e s , p re d o m in a n t ly wh e n t h e y co h a b it e d wit h t h e M DR- TB in d e x c a s e s . No s u c h d if f e r e n c e b e t we e n t h e t wo g ro u p s wa s fo u n d fo r t h o se p a t ie n t s wh o we re t re a t e d a ft e r t re a t m e n t o f t h e in d e x ca se s.
Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
TABLE 3
In ciden ce of pat ien t s per grou p t reat ed prior t o/ aft er, prior t o, or aft er in dex cases in t hree referen ce cen t ers for t u bercu losis in t he st at e of Ceará bet ween 1990 an d 1999
Treat ed pat ien t s Con t rol grou p St u dy grou p P*
Prior t o/ aft er in dex case (70/ 752) 9,3% (86/ 557) 15,4% 0,0010
Prior t o in dex case (29/752) 3,95% (61/557) 10,9% <0,0001
Aft er in dex case (41/752) 5,45% (25/557) 4,49% 0,4468
*Chi- squ are t est .
TABLE 4
Dist ribu t ion of MDR- TB micro- epidemics in relat ion t o t he n u mber of MDR- TB cases per family t reat ed in t hree referen ce cen t ers for t u bercu losis in t he st at e of Ceará bet ween 1990 an d 1999
Nu mber of MDR- TB cases Nu mber of MDR- TB Total
(in t he same hou sehold) micro- epidemics*
N N
2 6 1 2
3 1 3
5 1 5
Total 8 2 0
*MDR- TB micro- epidemic is defin ed as t he exist en ce of 2 or more n ew MDR- TB cases in t he same hou sehold, con firmed by su scept ibilit y t est s. MDR- TB: mu lt idru g- resist an t t u bercu losis.
Of t h e 1 2 6 c a s e s o f MDR- TB, 11 4 h a d developed acqu ired mu lt idru g resist an ce an d 12 had primary mu lt idru g resist an ce. Eleven of t hese pat ien t s were u n likely t o have gen erat ed n ew TB cases. For 1 pat ien t , t here was n o in format ion on in dividu als who may have come in t o con t act .
DISCUSSION
The t ot al n u mber of TB cases report ed in t he st at e of Ceará decreased from 43,508 du rin g t he 1980s t o 41,073 du rin g t he 1990s an d has been st eadily decreasin g du rin g t his decade as well(8). This might reflect underreporting of TB cases, since t he n u mber of MDR- TB cases act u ally in creased du rin g t he 1990s(7).
Befo re co m m en t in g o n t h e resu lt s, we wo u ld like t o h ig h lig h t se ve ra l lim it a t io n s o f t h e p resen t st u d y. First , t h is wa s a ret ro sp ect ive s t u d y. In a d d i t i o n , d a t a w e r e c o l l e c t e d e xc lu s ive ly f ro m m e d ic a l re c o rd s , w it h o u t co n d u ct in g p a t ien t in t erviews, in 2 5 % o f t h e ca se s e va lu a t e d . Ho we ve r, sin ce t h e se we re c h ro n ic c a se s, a d m it t e d va rio u s t im e s a n d
g en era t in g m u lt ip le m ed ica l ch a rt s, t h ere wa s a n a b u n d a n ce o f d a t a , a n d t h ese p a t ien t s were well kn o wn t o t h e h o sp it a l st a ff, in clu d in g t h e a u t h o r o f t h is st u d y. In o rd er t o a vo id b ia s d u e t o la ck o f in fo rm a t io n o r u n relia b ilit y o f t h e d a t a , n u rses a n d so cia l ca sewo rkers, wh o were resp o n sib le fo r t h e m a jo rit y o f t h e in fo rm a t io n e n t e r e d i n t h e m e d i c a l r e c o r d s , w e r e in t erviewed . Th e o t h er 7 5 % o f p a t ien t s h a d b een t rea t ed b y t h e a u t h o r fo r t h e la st d eca d e an d an swered t h e q u est io n n aire in p erso n . Dat a o n co n t ro l g ro u p su b ject s were co llect ed fro m pat ien t in t erviews an d m edical records, allowin g f o r c o m p a r is o n a n d ve r if ic a t io n o f d a t a . Fu rt h erm o re, o win g t o t h e fa ct t h a t t h is wa s a ret rospect ive st u dy, we were u n able t o det ermin e t h e t ra n sm issio n t im e o f eit h er su scep t ib le o r MDR- TB.
of t he pat ien t s in t he st u dy grou p were n ot t est ed fo r HIV. Th is wa s b eca u se t h is t est is n o t p a rt o f o u r ro u t in e, esp ecia lly fo r o u t p a t ien t s. Mo st o f t h e h o s p it a liz e d p a t ie n t s w e r e t e s t e d . All volu n t eers in t he con t rol grou p were ou t pat ien t s, an d all were o ffered HIV t est s, b u t 4 5 % refu sed . Alt h o u g h we m a y h a ve m issed a p o sit ive ca se a m o n g t h ese, t h ere wa s n o evid en ce o f HIV risk fa ct o rs a m o n g t h ese p a t ien t s
Due to discrepancies found in the literature(12,13),
we believed t hat variat ion s in gen der or age cou ld lead t o m isin t erp ret at io n s. Th erefo re, g en d er-matched and age- er-matched controls were selected. In 1 9 7 9 , Sim in el et a l. p u b lish ed a st u d y co m p risin g 31 8 9 ch ild ren wh o h a d h a d clo se con t act wit h TB cases(14). Of t he 931 in dex cases,
676 were infected with INH- susceptible strains and 255 wit h INH- resist an t st rain s. In order t o avoid bias, t he au t hors in vest igat ed several variables, in clu din g t he ages of t he children , du rat ion of exposure, and severity of the index cases. Statistical analysis confirmed the hypothesis that the sources of INH- resistant Mtb were less pathogenic, not only t o laborat ory an imals bu t t o hu man s as well. This study involving children was very important because adu lt s are more likely t o become in fect ed ou t side t heir homes, especially in cou n t ries su ch as Brazil, where there is a high prevalence of TB. The present study shows that the percentage of patients treated aft er su scept ible an d MDR- TB in dex cases are st at ist ically similar bet ween t he st u dy grou p an d con t rol grou p (Table 3). If du rat ion of exposu re had been st rat ified, we might have fou n d similar resu lt s, t hat is, a smaller percen t age of pat ien t s t reat ed amon g t hose who had MDR- TB.
In 1 9 8 5 , Sn id e r e t a l. p u b lish e d a st u d y com prisin g 1352 con t act s, of which 398 were in fect ed wit h st rain s resist an t t o INH or SM. The au t hors mat ched t hese 398 pat ien t s for age, race, g en d er a n d g eo g ra p h ic lo ca t io n t o t h e sa m e n u m b e r o f p a t ie n t s d ia g n o se d wit h st ra in s su scept ible t o 9 dru gs. No eviden ce of lower risk of in fect ion was fou n d amon g pat ien t s exposed
individuals were family members and therefore were exposed for lon ger periods.
From 1994 to 1998, Teixeira et al. carried out a case- control study in Vitória (in the state of Espírito Santo) on the prevalence of infection and active tuberculosis in households inhabited by patients wit h su scep t ib le TB a n d MDR- TB. Th is st u d y comprised 408 individuals cohabiting with 78 TB patients, 26 infected with resistant strains and 52 with susceptible strains. The authors concluded that the prevalence of infection and the progression to a ct ive t u b ercu lo sis a m o n g t h o se exp o sed t o susceptible and MDR- TB was similar, despite the longer duration of exposure in individuals with MDR- TB in d ex cases(1 5 ). Th e au t h o rs in clu d ed
d u ra t io n o f e xp o su re in t h e ir a n a lysis a n d hypot hesized t hat lon ger du rat ion of exposu re compensates for the lower pathogenicity of resistant strains, resulting in the percentage of new TB cases from contact with susceptible TB cases being equal to that from contact with MDR- TB cases.
All t hree of t hese (Simin el et al., Sn ider et al. an d Teixeira et al.) were case- con t rol st u dies, determining the prevalence of infection and disease in in d ivid u a ls co h a b it in g wit h p a t ien t s wit h suscept ible- TB an d MDR- TB pat ien t s. However, each was carried o u t d u rin g d ifferen t p erio d s wit hin t he past 3 decades an d employed differen t chemotherapeutic drugs. Nevertheless, they can be compared. Det ermin in g t he du rat ion of exposu re was a common difficu lt y faced by all of t hese authors.
Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
corresponded to the duration of symptoms plus 15 days after the beginning of the appropriate therapy(16).
In contrast, there is no therapy that has proven highly effica cio u s in ca ses o f MDR- TB. It h a s b een demonstrated that conversion of sputum smear microscopy and culture to negative occurs in only 65% of properly treated cases, and the incidence of recurrence is quite high(17), thereby increasing the
likelihood of transmission.
In a su rvival st u dy carried ou t in t he st at e of Ceará, the 5- year survival of MDR- TB patients who had not adhered to treatment was 73%, compared t o 32% for t hose who had n o access t o proper treatment(8). This gives an indication of the duration
of exposu re amon g in dividu als cohabit in g wit h MDR- TB patients. However, the incidence of active TB resu lt in g from close con t act wit h MDR- TB pat ien t s is similar t o t hat resu lt in g from su ch co n t a ct w it h su sce p t ib le - TB p a t ie n t s. Th is su ggest s t hat t he pat hogen icit y of m u lt idru g-resistant strains is actually lower. Nevertheless, this does n ot lessen ou r con cern regardin g t his t ype of exposu re sin ce t he proport ion s of act ive TB wit hin t he t wo grou ps con verges aft er some t ime, creat in g a cu mu lat ive risk for t he developmen t of primary MDR- TB.
We studied the proportion of individuals having close contact with a TB patient and receiving treatment prior to treatment of the corresponding index case (Ta b le 3 ). We o b served t h is wa s sig n ifica n t ly predomin an t in t he st u dy grou p, leadin g u s t o speculate that MDR-TB patients are the real victims and are less able to transmit the disease. This was reinforced by the fact that, for 11 of the 12 patients with primary MDR-TB, there was little evidence that these patients generated new cases of TB.
Melo et al., in a cohort study conducted from 1995 to 1998 at a reference clinic in the city of São Paulo, reported 4 MDR- TB outbreaks (3 or more individuals) within families(18). Vidal et al. carried out
a prospective study from 1989 to 1994 in a general hospital in Barcelona, Spain, with the objective of studying the increased risk of TB transmission during micro- epidemics within families. They considered 3 or more individuals with TB in one household a micro-epidemic, since 2 or more new TB cases within a family is a greater number than expected(19). Since
the proportion of MDR- TB to TB was, on average, 1.48% in 1999 in the state of Ceará(7), we considered 2 cases of MDR- TB in the same household to be
greater than expected. This definition allows us call attention to MDR-TB, a disease that represents a very serious health threat.
In our study, a discordance of 33% was found between the susceptibility profiles of Mtb strains isolated from new MDR-TB cases and those of Mtb strains isolated in the index cases from the same households. This has also been reported in other studies.
Kritski et al. reported that 54% of the 13 strains isolat ed from pat ien t s who had had con t act wit h 1 2 in d ex p a t ien t s h a d d ifferen t su scep t ib ilit y profiles, and that 3 (23%) of them were susceptible t o all dru gs t est ed(20). Mean age in t he grou p st u died by t he au t hors was 35.6 years.
Teixeira et al. report ed a discordan ce of on ly 17% in t he su scept ibilit y profiles of 6 st rain s isolat ed from pat ien t s who cohabit ed wit h MDR-TB in dex cases(15). The st rain was su scept ible t o t he dru gs t est ed, bu t it s DNA fin gerprin t was identical to that isolated from the respective index patient. Mean age of the patients studied was 39.5 years.
In a follow- up to a previous study, Schaaf et al. conducted a prospective study involving children younger than 5 years of age cohabiting with adult pulmonary MDR-TB patients and monitored (between 1994 and 2000) for 30 months. They authors reported that 25% of the clinically isolated strains presented different resistance profiles, although also multidrug resistant. The DNA fingerprinting confirmed that the isolated strains were not the same as those of the in dex cases. No other sou rce of con tagion was identified, although the multidrug- resistant strains isolated were prevalent in the community in which the children lived(21, 22 ).
We conclude that the incidence of treatment of TB patients is similar between those cohabiting with susceptible-TB patients and those cohabiting with MDR- TB patients. This is extremely serious and demands that, as soon as possible, protective measures and proper chemoprophylaxis be made available to individuals cohabiting with patients with MDR-TB.
ACKNOWLEDGMENTS
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