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Mycobacterial
Infections

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Jeffrey R. Starke, MD

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Pediatrics

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Slide 2

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TUBERCULOSIS IS A SOCIAL
DISEASE WITH MEDICAL
IMPLICATIONS

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Slide 3

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MYCOBACTERIOLOGY
non-motile, nonspore - forming, weakly Grampositive rods; often appear slightly bent or beaded
obligate aerobes; simple growth requirements
cell wall: 20 to 60 percent lipids
generation time of 12 to 48 hours (except rapid
growers)
acid-fastness: form stable mycolate complexes with
arylmethane dyes (carbolfuchsin, crystal violet,
auramine, rhodamine)

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Slide 4

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GROWTH MEDIA FOR MYCOBACTERIA
Blood agar - rapid growers - M. fortuitum,
M. chelonae, M. abscessus; 5-10 days
Classic - egg yolk and glycerin
(Lowenstein - Jensen, Dorset); 3-6 weeks
Synthetic - glycerol and ammonium salts
(Middlebrook, Tween - albumin); 2-6 weeks
Liquid-Radiometric (Middlebrook variant);
10-21 days

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Slide 5

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SPECIATION OF MYCOBACTERIA
Growth characteristics: colony shape and
color, rate, temperature (33- 40)
Chemical tests: niacin (M. tuberculosis)
DNA probes
HPLC - unique patterns of mycolic acids
Drug susceptibility - eg. M. bovis resistant to
pyrazinamide

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Slide 6

EPIDEMIOLOGY OF
TUBERCULOSIS
IN THE WORLD 1990s

10 million cases per year

2-3 million deaths per year
600,000 cases dual TB/HIV
2 billion infected individuals
$30 $50 billion per year direct impact

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Slide 7

EPIDEMIOLOGY OF TUBERCULOSIS
U.S.A. 1990S
Average 20,000 cases per year (26K 18K)
Contributed to 2,000 deaths per year
10-20 million infected individuals
Pool of infected individuals grew by
400,000 per year due to legal immigration
$1-2 billion per year in direct economic
impact
2011: slightly more than 11,000 cases

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Slide 8

U.S. Pediatric TB Cases (0-14 years

old)

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1,800
1,600
1,400
1,200
1,000

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800
600
400
200
0
1980

2000

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Slide 9

SOME REASONS WHY

TUBERCULOSIS RESURGED IN
THE U.S. 1984-92

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HIV co-epidemic

Immigration and visitation

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Transmission in congregate

settings
Poor tuberculosis control

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Slide 10

IMMIGRATION-RELATED TUBERCULOSIS
IN THE UNITED STATES
About 1 million annual legal immigrants
30 - 40% have latent tuberculosis infection
(LTBI)

Pool of infected individuals increases by 300400K per year

2% - 5% risk of disease: 6,000 20,000 future
cases per year

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Slide 11

MONOCLONAL ANTIBODIES & TUBERCULOSIS

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Remicade (Infliximab)
monoclonal antibody against tnf alpha
black box warning for tuberculosis 84 cases by 10/01
severe pulmonary, G-I and disseminated tuberculosis
must do at least A TB risk assessment and TST prior
to use

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Humira (adalimumab), Enbrel (etanercept)

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less information known

strong warning to assess for TB risk and place a TST

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TRANSITIONS IN TUBERCULOSIS

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Susceptible
Exposed

Infected

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Diseased

Sick
Diagnosed

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Treated
Cured
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Slide 13

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RISK FACTORS FOR TUBERCULOSIS
Increased risk of acquiring or having infection
Foreign born from high prevalence country
Intravenous drug or crack cocaine user
Family history of TB (2-3 generations)
Contact with HIV- infected individuals
Contact with inmates of prison or jail (past or present)
Some nursing homes, residential living
Some healthcare workers
Increased risk of developing disease after infection
HIV infected
Immune suppression - drugs or disease
Recent (<3 years) infection
Certain diseases: silicosis, diabetes mellitus
Extremes of ages: infants, elderly

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Slide 14

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STAGES OF TUBERCULOSIS
Exposure
Defined by contact investigation - recent (< 3
months) contact with an infectious case
Negative ST, physical exam and chest radiographs
Period during which the skin test may be negative in
an infected person
Children < 5 years old should be treated (usually
INH) because they may develop disease rapidly
Older children and adults often not treated, but
repeat skin test 3 months after exposure over

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STAGES OF TUBERCULOSIS
Infection
Hallmark is a positive skin test
Germs in the body
Chest radiograph is normal or shows only one or more
granulomas or fibrotic lesions
No symptoms, physical exam is normal
Anyone with infection should be treated when the risk of
disease outweighs the risk of serious adverse reactions to
the medication

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Slide 16

SKIN-TESTING, INFECTION AND

DISEASE
TST takes 3 weeks to 3 months to turn positive
after infection has occurred
Risk of disease after untreated infection
Normal adults: 5-10 percent in lifetime (half of risk in
first 2-3 years)
HIV-infected adults: 5-10 percent per year
Infants: 40 percent in 1-2 years
Older children: 5-10 percent (delayed)

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STAGES OF TUBERCULOSIS
Disease
Clinical and/or radiographic manifestations of
progressive tuberculosis infection
Primary: complication of initial infection
Reactivation: disease occurs after period of
dormancy of the infection
TST is negative in 10% of disease cases (50% of
meningeal or miliary disease)

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Slide 19

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TIMETABLE OF PEDIATRIC
TUBERCULOSIS
Type

Timetable

Miliary, Meningeal

1-12 months

Segmental adenopathy

2-12 months

Cervical adenopathy

2-12 months

Pleural effusion

3-9 months

Skeletal

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6 months 2 years

Renal

1-5 years

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Slide 22

ARE CHILDREN WITH

TUBERCULOSIS
EVER CONTAGIOUS?

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Difficult to answer in the community

Orphanages caretaker with TB led to
transmission; a child with TB did not
Schools only 2 reported epidemics caused by
children <13 years old
Childrens Hospitals rare case reports of
transmission, all with special circumstances, none
has been patient -to - patient

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FEATURES OF CONTAGIOUS
PEDIATRIC TUBERCULOSIS
Cavitary lung lesion

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Sputum production

Positive acid-fast stain of sputum smear

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Bronchoscopy
Draining lesions or surgical drainage of
an abscess

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CLINICAL AND RADIOGRAPHIC

MANIFESTATIONS OF CHILDHOOD
PULMONARY TUBERCULOSIS
Paucity of signs and symptoms relative to chest radiograph
findings
Infants more symptomatic: fever, cough, focal wheezing,
respiratory distress
Predominance of hilar and/or mediastinal adenopathy (not
always discernable on plain radiographs)
Any lobe of lung involved; 25% multilobar
Local pleural reaction/effusion is common
Collapse-consolidation or segmental pattern most common
Obstructive signs/symptoms with endobronchial lesions
Not contagious

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TUBERCULOUS AND
NONTUBERCULOUS
MYCOBACTERIAL LYMPHADENITIS

Age (years)
Residence
Risk factors for TB
TST on family
Chest xray
TST (mm)
Response to anti-TB drugs

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NTM

TB

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1-5
rural, suburban
no
negative
usually negative
0-15 usual
no

any
urban
yes
often positive
+ in 10-20%
>10; many >15
yes but slow

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