TuberculoseUnivag 2017 1

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TUBERCULOSE PULMONAR 
Prof. Dr. Clovis Botelho / Univag
1
TB no Brasil 
Faixa Etária 
Casos
Incidência
(100.000 hab.)
0-4
1.585
9,7
5-9
875
5,3
10-19
7.686
1,8
20-39
42.519
98,8
40-59
28.827
90,7
>=60
10.980
75,5
Total 
92.472
48,4
Distribuição dos casos
Total 
de 
casos
15 anos 
ou + anos
Menores de
15 anos 
Pulmonar
Extra
pulmonar
Pulmonar
Extra
pulmonar
BK +
BK sem 
confirmação
BK +
BK sem 
confirmação
95%
5%
80%
20%
85%
15%
65%
35%
20%
80%
Fonte: Manual de Recomendações para o Controle da Tuberculose no Brasil – MS 2010
Smoking and Tuberculosis
8
8
Aumento do risco de TB infecção
Africa do Sul; N= 2.401; PPD (10mm) = 1.832 (76%)
den Boon et al. Thorax. 2005;60(7):555-557.
Pack/Years
5
5-15
15
Odds Ratio (95% CI)a
Never Smokers
Current Smokers
9
Key Point
Smoking may increase the risk of Mycobacterium tuberculosis infection.
This study by den Boon et al was designed to determine the association between smoking and M tuberculosis infection. 
A random sample of addresses in 2 urban communities in Cape Town, South Africa, was selected. Adults (N=2401) completed a questionnaire, including questions about smoking, and had a tuberculin skin test (TST) result recorded. 
Information on smoking and TST results were compared in a cross-sectional population survey.
Infection with M tuberculosis was defined as a TST of 10 mm or more. This was referred to as a positive TST.
 A total of 1832 (76%) subjects had a positive TST.
The number of pack/years smoked was calculated as the average number of cigarettes smoked per day multiplied by the duration of smoking divided by 20.
Five hundred fifty participants had 5-pack/year history of smoking. The adjusted OR for having a +TST in smokers with 5-pack/years was found to be 1.77 (95% CI, 1.33-2.35); 407 participants had a 5- to 15-pack/year history. The adjusted OR for having a +TST in smokers with 5 to 15 pack/years was found to be 1.77 (95% CI, 1.25-2.50); 288 participants had a 15-pack/year history. The adjusted OR for having a +TST in smokers with 15 pack/years was 1.90 (95% CI, 1.28-2.81).
den Boon noted that although the probability of a +TST seemed to increase slightly with the number of pack/years smoked, the differences among the various pack/year categories were not significant.
Reference
den Boon S, van Lill SWP, Borgdorff MW, et al. Association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area. Thorax. 2005;60(7):555-557. 
Slide 9
Smoking: TB-Related Mortality
India, Coorte 12 anos; 81.443 Homens acima de 35 anos de idade
Pednekar et al. Prev Med. 2007;44(6):496-498.
Never Smokers
Cigarette Smokers
Bidi Smokers
Relative Risk (95% CI)b 
10
Key Point
In India approximately 32% of TB deaths may be attributed to bidi smoking. 
Pednekar et al examined the association between smoking (mainly bidi smoking) and TB in Mumbai, India. Recruitment of a cohort of 81,443 men aged 35 years, began in 1991, and follow-up continued to the end of 2003. The most common form of smoking in India is bidi smoking. Bidi is a smoking stick made by rolling a dried, rectangular piece of temburni leaf (Diospyros melanoxylon) with about 0.2 g of sun-dried, flaked tobacco into a conical shape and securing the roll with a thread. The length of a bidi is usually about 4 to 8 cm.
A follow-up study was done 5 to 6 years after the initial survey with available subjects. If participants had died, the date of death was recorded. If subjects had moved out of the area the moving date was recorded.
Subjects were divided into ever smokers and never smokers. The adjusted risk of TB deaths among bidi smokers was 2.60 (95% CI, 2.02, 3.33) times higher than never smokers.
The adjusted risk of TB deaths among cigarette smokers was 2.12 (95% CI, 1.70, 2.66) times higher than never smokers.
Slide 10
References
Altet M, Alcade J, Plans P. Passive smoking and risk of pulmonary tuberculosis in children immediately following infection: A case contol study. Tuber Lung Dis. 1996;77(6):537-544.
Pednekar MS, Gupta PC. Prospective study of smoking and tuberculosis in India. Prev Med. 2007;44(6):496-498.
Aumento da TB doença
Kolappan et al. Thorax. 2002;57(11):964-966; 
Odds Ratio (95% CI)a 
Nonsmokers
India, 1993-1996; Casos (85 TB) – Controles (459 NTB)
Current Smokers
TB – 74,1% Fumantes; NTB – 55,2% Fumantes
11
Key Point
There is an association between tobacco smoking and the development of pulmonary tuberculosis (TB).
In India the prevalence of pulmonary TB is higher among men aged 15 years than in women of the same age. In children aged 10 to 14, however, there is no difference in the prevalence of TB between males and females. Although the cause of this is unclear, it has been noted that in India men start smoking around the age of 15. The prevalence of smoking in women is very low. Kolappan et al undertook this case-control study to determine if there was an association between tobacco smoking and pulmonary TB.
The source of cases and controls for the Kolappan et al study was a TB survey carried out between 1993 and 1996 in 30 villages from 2 areas of the Tiruvallur district of Tamil Nadu in South India. The disease status of cases and controls was determined during the survey period. Exposure to smoking was ascertained for cases and controls at the time of study in 1998.
Men aged 20 to 50 years who were sputum smear and/or culture positive for pulmonary TB defined the case group, and men aged 20 to 50 who were screened and determined not to have TB became the control group.
Eighty-five men aged 20 to 50 years with TB (smear and/or culture positive) were selected as cases and 459 age-matched men without TB were selected randomly as controls. 
The survey included questions such as smoking status, type of tobacco smoked, quantity of tobacco smoked, duration of tobacco smoking, and age at which participant started smoking.
There were 64 smokers among the 85 cases and 253 smokers among the 459 controls.
The estimated crude OR of the association between tobacco smoking and pulmonary TB was 2.48 (95% CI, 1.42-4.37); P<.001. The age-adjusted OR (Mantel-Haenszel estimate) was 2.24 (95% CI, 1.27-3.94); P<.05.
Reference
Kolappan C, Gopi PG. Tobacco smoking and pulmonary tuberculosis. Thorax. 2002;57(11):964-966. 
Slide 11
Tabagismo Passivo X TB doença
Barcelona; 93 crianças (após contato domiciliar com TB) = casos; 95 controles
Altet et al. Tuber Lung Dis. 1996;77(6):537-544.
Exposed 
to Smoking
Odds Ratio (95% CI)a 
P.00005
Not Exposed 
to Smoking
12
Key Point
There is an increased risk of developing pulmonary tuberculosis (TB) immediately following infection in children exposed to ETS. 
In 1992 Altet et al evaluated the effect of ETS on the development of active pulmonary TB in children following infection of a family member with TB.
A person exposed to ETS was defined as a nonsmoker exposed to the combustion products of tobacco smoked by others, not only at the time of the survey, but also during the 6 months prior to the study. A questionnaire was used to obtain information on participants’ exposure to ETS .
Children in Barcelona 15 years of age who were household contacts of a new pulmonary TB case were studied in this unmatched case-control study.
Ninety-three contacts who became cases were included. These were pulmonary TB cases in whom M tuberculosis complex was isolated from their bronchopulmonary specimens (sputum, bronchial washings, or bronchoalveolar lavage), or gastric aspirates. An individual with clinical and radiological evidence of active disease and a positive tuberculin skin test (TST), even in the absence of a positive culture, was also included.
Ninety-five +TST contacts without clinical, radiological, and or/bacteriological evidence of active pulmonary TB were chosen as controls.
TSTs were considered positive if the diameter ofthe induration was at least 
5 mm.
Bacille Calmette-Guérin (BCG) vaccinated individuals were excluded.
In this study, exposure to ETS was associated with an increased risk for developing active pulmonary TB in children when a child was exposed to a family member with active TB. 
The OR for developing pulmonary TB in a child exposed to ETS was 5.29 (95% CI, 2.33-12.82; P<.00005).
Reference
Altet MN, Alcaide J, Plans P, et al. Passive smoking and risk of pulmonary tuberculosis in children immediately following infection: a case-control study. Tuber Lung Dis. 1996;77(6):537-544. 
Slide 12
Odds Ratioa (95% CI)
Dose dependente
The risk of developing active pulmonary TB following infection increases with the number of cigarettes smoked daily by household adults
 
Altet et al. Tuber Lung Dis. 1996;77(6):537-544.
None
21-40
40
1-20
P.01
P.001
Cigarettes/Day
13
Key Point
The risk of developing active pulmonary tuberculosis (TB) following infection increases with the number of cigarettes smoked daily by household adults.
In 1992 Altet et al evaluated the effect of environmental tobacco smoke (ETS) on the development of active pulmonary TB in children following infection of a family member with TB.
A person exposed to ETS was defined as “a nonsmoker exposed to the combustion products of tobacco smoked by others, not only at the time of the survey, but also during the 6 months prior to the study.” A questionnaire was used to obtain information on participants’ passive exposure to tobacco smoke.
Children in Barcelona 15 years of age who were household contacts of a new pulmonary TB case were studied in this unmatched case-control study.
Ninety-three contacts who became cases were included. These were pulmonary TB cases in whom 
M tuberculosis complex was isolated from their bronchopulmonary specimens (sputum, bronchial washings, or bronchoalveolar lavage), or gastric aspirates. An individual with clinical and radiological evidence of active disease and a positive tuberculin skin test (TST), even in the absence of a positive culture, was also included. 
Ninety-five +TST contacts without clinical, radiological, and or/bacteriological evidence of active pulmonary TB were chosen as controls.
TSTs were considered positive if the diameter of the induration was at least 5 mm.
Bacillus Calmette-Guérin (BCG)-vaccinated individuals were excluded.
Altet et al analyzed the relationship between the number of cigarettes smoked daily by household members and the risk of developing active pulmonary TB following infection.
The risk of developing active disease immediately following infection increased with exposure to increasing amounts of cigarette smoke. 
The adjusted OR for developing active disease immediately following infection in children exposed to the smoke of 1 to 20 cigarettes/day was found to be 1.61 (95% CI, 0.66-2.63). The adjusted OR for developing active disease immediately following infection in children exposed to the smoke of 21 to 40 cigarettes/day was found to be 3.95 (95% CI, 1.59-9.80). The adjusted OR for developing active disease immediately following infection in children exposed to the smoke of >40 cigarettes/day was found to be 7.76 (95% CI, 3.40-17.60). 
Reference
Altet MN, Alcaide J, Plans P, et al. Passive smoking and risk of pulmonary tuberculosis in children immediately following infection: a case-control study. Tuber Lung Dis. 1996;77(6):537-544. 
Slide 13
Berg et al., 2016, Cell 165, 139–152
14
Infect.17
Tuberculose - Tratamento
Infecção - uma transmissão bem sucedida 
Nidação do bacilo no alvéolo
Fagocitose pelo macrófago alveolar
Diagnóstico clínico
Tosse seca ou com catarro, hemoptoicos ou hemoptise, emagrecimento e febre baixa vespertina ou noturna, sudorese noturna, astenia e anorexia.
Diagnóstico da tuberculose
Sintomas
Exames:
Baciloscopia Cultura 
 
Exames complexos nos casos de difícil diagnóstico
PPD
Raios X
intracelular
(macrófago)
crescimento
lento
extracelular
(granuloma)
crescimento
intermitente
Populações bacilíferas e aerobiose
intra
cavitária
crescimento
geométrico
 
 bacilos persistentes 
 BACILOSCOPIA
Escarro: volume 5 a 10 ml/ 3 amostras 
Escarro induzido: nebulização /hipertônica a 3%
Lavado gástrico: paciente deitado, em jejum.
		
Outras amostras: LBA, líquido pleural, ascítico, LCR etc.
	Para que o BAAR seja (+) > 104 bacilos/ml amostra
	(Cavidade de 2cm ~ 109 bacilos/ml de escarro)
Bacilos álcool-ácido resistentes (BAAR ou BK)
tecido pulmonar
escarro
23
O “Mycobacterium tuberculosis” é um bacilo álcool-ácido resistente, estritamente aeróbio, que tem um tempo de geração prolongado, chegando a 20 horas.
POSITIVIDADE DO ESCARRO
POSITIVIDADE NO LAVADO GÁSTRICO
 TB: BAAR -
Lesão pauci-bacilar
 Tratamento baseado no quadro clínico-radiológico sugestivo
Teste Tuberculínico – PPD
 Medida correta 
 Radiologia da tuberculose
Objetivos do controle da tuberculose
Reduzir as fontes de infecção
(sintomáticos respiratórios - bacilíferos)
Reduzir o número de casos
(declínio da prevalência)
Reduzir a morbimortalidade
(óbitos - agravos - seqüelas)
42
 TB no Brasil - Tratamento (71%)
43
Abandono do Tratamento (12%)
44
Distribuição da frequência do mês de ocorrência do abandono do tratamento, Cuiabá/MT
J Bras Pneumol. 2005;31(5):427-35
2,3
2,3
17,4
21,2
36,4
15,9
6,8
0
10
20
30
40
1º mês
2º mês
3º mês
4º mês
5º mês
6º mês
%
DEMORA 
Demora atribuída
principalmente
ao paciente
Demora atribuída
principalmente
ao médico 
INÍCIO DO
TRATAMENTO
INSTALAÇÃO
DOS SINTOMAS
PRIMEIRO ATENDIMENTO
MÉDICO
 Tempo médio entre a instalação dos sintomas de TB até o início do tratamento (demora total): 13,4 semanas, Longo demais!!!
 Período médio da demora atribuída ao paciente foi de 9,4 semanas, Muito Longo 
 Tempo médio da demora atribuída ao médico foi de 4,2 semanas, Longo
			Demora em Cuiabá
Esquema básico (EB) para o tratamento da TB 
(adultos e adolescentes)
Regime
Fármacos
Faixa de peso
Unidades/dose
Meses
2RHZE
Fase intensiva
RHZE
150/75/400/275 mg
comprimido
em dose fixa combinada
20 a 35kg
2 comprimidos
2
36 a 50 kg
3 comprimidos
> 50kg
4 comprimidos
4RH
Fase de manutenção
RH
300/200ou
150/100 mg
comprimido ou cápsula
20 a 35kg
1 comp. ou cáps.
300/200 mg
4
36 a 50 kg
1 comp. ou cáps.
300/200 mg + 1 comp. ou cáps. 150/100 mg
> 50kg
2 comp. ou cáps.
300/200 mg
Fonte: Nota Técnica PNCT/DEVEP/SVS/MS
	
 	Retratamento: recidiva (*) ou retorno após abandono
(*) Adoecimento por TB após tratamento anterior com Esquema I ou EB com cura, independentemente do tempo em que esse primeiro episódio ocorreu.
Fonte: Nota Técnica PNCT/DEVEP/SVS/MS
Indicações do Esquema Básico (EB)
Caso novo: (*) de todas as formas de TB pulmonar e extrapulmonar (exceto meningoencefalite), infectados ou não pelo HIV 
(*) Paciente que nunca usou medicamentos anti-TB ou usou por menos de 30 dias.
Associação Medicamentosa
Rifampicina
1:108 bacilos resistentes
Isoniazida
1:106 bacilos resistentes
Pirazinamida
1:104 bacilos resistentes
Etambutol
1:106 bacilos resistentes
“Fogo cruzado”
1 bacilo resistente
 em
 1024 bacilos
+
+
+
Crescimento bacilar e fases do tratamento
1om 
2om 
Transmissibilidade
 Morbidade
 Resistência
Crescimento
geométrico
Fase de ataque 
Tratamento prolongado e bifásico
3om 
4om 
5om 
6om 
Fase de manutenção 
Crescimento lento 
Cura efetiva
e duradoura da doença.
Importante no tratamento
3º - Isolamento, alimentação, repouso, etc
2º Gravidade da doença 
1º - Uso correto da medicação
53
Muito obrigado!
clovisbotelho8@gmail.com
*
*
*
“Controle da Tuberculose – Integração Ensino Serviço”
CARACTERÍSTICAS INDIVIDUAIS
ASSOCIADAS A TUBERCULOSE