Tuberculosis

የህዝብ በህዝብ ለህዝብ

Abyot ,2015
From Harrison, WHO 2013 ,jimma and others
handout
PREPARATION OF SPUTUM SMEARS

 Labeling Slides for Smears

 Take smear and put on slide at least 3 slides
 Drying :The prepared slides must dry in the air for about 15-30
minutes. Do not use flame for drying. Mycobacteria may lose the acid-
fastness by exposure extreme heat.
 Staining with 1% carbon fuchsin
 Heat very gently until steam appears.
 Decolorization : Rinse each slide individually in a gentle stream of
running water, until all free stain is washed away.
 Decolorize the smear using 3% acid-alcohol for 3 minutes or until the
solution runs clear.
 Wash the slide with a gentle stream of running water.
 Tilt the slide to drain off excess rinse water.
 Counterstaining : Flood smear with 0.1 % methylene blue counter
stain for 1 minute.
 Wash the slide with a gentle stream of running water.
 Tilt and place the slide on the rack to dry in the air.
 AFB observation
 AFB is stained in red with blue background by acid-fast or Ziehl-
Neelsen staining. AFB is usually rod-shaped but occasionally may
appear as coccoid (spherical,) or filaments (thread-like), or clumped (in
group).
 Reporting scale
 Follow the scale when reporting smears: Finding Reporting
 No AFB found in at least 100 Negative
 1 to 9 AFB per 100 fields Actual AFB count
 10 to 99 AFB per 100 fields 1+
 1 to 10 AFB per field (count at least 50 fields) 2+
 >10 AFB per field (count at least 20 fields 3+
EPIDEMIOLOGY

 probability of transmission depend on → exogenous

• intimacy & duration of contact
• Degree of infectiousness of the case
• Shared environment(poorly ventilated rooms)
– Degree of infectiousness depend on
• Positive sputum smear-highly infectious
• Cavitary-↑↑bacteria→↑infections
• Smear negative/culture +ve → less infectious
• Smear-ve and culture –ve,EPTB → noninfectious
• HIV+TB →less infectious (less cavities)
 Extrapulmonary TB are essentially noninfectious.
 Because persons with both HIV infection and TB are less
likely to have cavitations, they may be less infectious than
persons without HIV co-infection
 The most infectious patients have cavitary pulmonary
disease or, much less commonly, laryngeal TB.
 M. tuberculosis is most commonly transmitted from a person with
infectious pulmonary TB to others by droplet nuclei, which are
aerosolized by coughing, sneezing, or speaking. The tiny droplets
dry rapidly; the smallest (<5–10 m in diameter) may remain
suspended in the air for several hours and may reach the
terminal air passages when inhaled. There may be as many as
3000 infectious nuclei per cough.
 Other routes of transmission of tubercle bacilli (e.g., through
the skin or the placenta) are uncommon and of no epidemiologic
significance.
 The risk of developing disease after being infected depends
largely on endogenous factors, such as the individual's innate
immunologic and nonimmunologic defenses and level of
function of cell-mediated immunity.
 Clinical illness directly following infection is classified as
primary TB and is common among children in the first few
years of life and among immunocompromised persons.
Although primary TB may be severe and disseminated, it is
not generally associated with high-level transmissibility.
 When infection is acquired later in life, the chance is
greater that the mature immune system will contain it at
least temporarily. Dormant bacilli, however, may persist
for years before reactivating to produce secondary (or
postprimary) TB, which, because of frequent cavitation, is
more often infectious than is primary disease.
 Overall, it is estimated that up to 10% of infected persons
will eventually develop active TB in their lifetime, with half
of them doing so during the first year after infection. The
risk is much higher among HIV-infected persons.
 Age is an important determinant of the risk of disease after
infection. Among infected persons, the incidence of TB is
highest during late adolescence and early adulthood; the
reasons are unclear. The incidence among women peaks at
25–34 years of age. In this age group rates among women
may be higher than those among men, while at older ages the
opposite is true. The risk increases in the elderly, possibly
because of waning immunity and comorbidity.
 A variety of diseases and conditions favor the development
of active TB. In absolute terms, the most potent risk factor
for TB among infected individuals is clearly HIV co-
infection, which suppresses cellular immunity.
Risk factors for active TB among infected
• Late adolescence(women 25-34 yrs)
• Older age
• HIV infection
• Recent infection<1 year
• Fibrotic lesion
• Sillicosis
• CRF/hemodyalysis
• Diabeteis
• Iv drug use
• Immunosuppressive drugs
• Gastroctomy,Jujunoileal bypass
• Posttrasplantation
• Malnutrition/severe decrease in weight
Etiology of TB

– Mycobacteria: family of mycobacteriacea / order actinomycetale

– Common species mycobacteria tuberculosis complex is M.tuberculosis
– M .tuberculosis complex includes

• M.bovis,
• M.caprea,
• M.africanum,
• M.microti,
• M.pennipeddi,
• M.canneti
Etiology of TB

– M.tbc: road shaped, nonspore forming, thin ,aerobic bacterium, neutral on gram stain
– Acid fast due to mycolic acid, FA and lipids in cell wall
– Other organisms AFB positive

• Rhodococcus,
Nocardia,leigionella,isospora,cryptospordium
– Resistant to most antibiotics due to impermeable lipid and glycopeptide rich cell wall
– Lipoarabinomannon-helps M.O to live inside macrophages
Pathogenesis

 The interaction of M. tuberculosis with the human host

begins when droplet nuclei containing microorganisms from
infectious patients are inhaled. While the majority of inhaled
bacilli are trapped in the upper airways and expelled by
ciliated mucosal cells, a fraction (usually <10%) reach the
alveoli. There, alveolar macrophages that have not yet been
activated phagocytize the bacilli.
 If the bacilli are successful in arresting phagosome
maturation, then replication begins and the macrophage
eventually ruptures and releases its bacillary contents.
Other uninfected phagocytic cells are then recruited to
continue the infection cycle by ingesting dying macrophages
and their bacillary content, thus in turn becoming infected
themselves and expanding the infection.
 Bacille Calmette-Guérin (BCG)
 Ultimately, the chemo attractants and bacterial products
released during the repeated rounds of cell lysis and
infection of newly arriving macrophages enable dendritic
cells to access bacilli; these cells migrate to the draining
lymph nodes and present mycobacterial antigens to T
lymphocytes. At this point, the development of CMI and
humoral immunity begins. These initial stages of infection
are usually asymptomatic.
 About 2–4 weeks after infection, two host responses to M.
tuberculosis develop: a macrophage-activating CMI response
and a tissue-damaging response. The macrophage-activating
response is a T cell–mediated phenomenon resulting in the
activation of macrophages that are capable of killing and
digesting tubercle bacilli.
 The tissue-damaging response is the result of a delayed-type
hypersensitivity (DTH) reaction to various bacillary antigens;
it destroys unactivated macrophages that contain multiplying
bacilli but also causes caseous necrosis of the involved
tissues .
 it is the balance between the two that determines the form
of TB that will develop subsequently.
 With the development of specific immunity and the
accumulation of large numbers of activated macrophages at
the site of the primary lesion, granulomatous lesions
(tubercles) are formed. These lesions consist of
accumulations of lymphocytes and activated macrophages
that evolve toward epithelioid and giant cell morphologies..
 Although M. tuberculosis can survive, its growth is inhibited
within this necrotic environment by low oxygen tension and
low pH. At this point, some lesions may heal by fibrosis, with
subsequent calcification, whereas inflammation and necrosis
occur in other lesions.
 Delayed-Type Hypersensitivity
 In a minority of cases, the macrophage-activating response is
weak, and mycobacterial growth can be inhibited only by
intensified DTH reactions, which lead to lung tissue destruction.
The lesion tends to enlarge further, and the surrounding tissue is
progressively damaged. At the center of the lesion, the caseous
material liquefies. Bronchial walls as well as blood vessels are
invaded and destroyed, and cavities are formed. The liquefied
caseous material, containing large numbers of bacilli, is drained
through bronchi.
 Within the cavity, tubercle bacilli multiply, spill into the airways,
and are discharged into the environment through expiratory
maneuvers such as coughing and talking.
 In the early stages of infection, bacilli are usually transported by
macrophages to regional lymph nodes, from which they gain
access to the central venous return; from there they reseed the
lungs and may also disseminate beyond the pulmonary vasculature
throughout the body via the systemic circulation. The resulting
extrapulmonary lesions may undergo the same evolution as those
in the lungs, although most tend to heal.
 Skin Test Reactivity
 Coincident with the appearance of immunity, DTH to M.
tuberculosis develops. This reactivity is the basis of the
TST, which is used primarily for the detection of M.
tuberculosis infection in persons without symptoms. The
cellular mechanisms responsible for TST reactivity are
related mainly to previously sensitized CD4+ T lymphocytes,
which are attracted to the skin-test site. There, they
proliferate and produce cytokines.
 While DTH is associated with protective immunity (TST-
positive persons being less susceptible to a new M.
tuberculosis infection than TST-negative persons), it by no
means guarantees protection against reactivation. In fact,
cases of active TB are often accompanied by strongly
positive skin-test reactions.
Clinical manifestation

 Primary-result from initial infection with bacilli

– In high prevalent –children-middle and lower lobe
– Lesion usually peripheral + hilar or parathracheal LAP

– Majority heal –later calcification(Ghon focus)

– In children /HIV +ve→rapid progression to clinical
illness, increased size of lesion, pleural/pericardial
effusion

– Lymph node involvement → obstruction + collapse

→bronchoectasis/emphysema
– Hematogeneous spread →milliary +meningitis
– Hypersensitivity reaction →erythema nodosum,
phylectunar conjunctivitis
Clinical manifestation

 Post primary TB
– Also called 2⁰/adult type/reactivation
– Result from endogenous reactivation of latent infection or re infection

– Usually localized to apical & posterior segments of upper lobe(b/c ↑ O2 tension) & superior segment
of lower lobe.
– Lesion range- small infiltrate to large cavity

– Highly infectious.
Clinical Manifestations

 Pulmonary TB
 Pulmonary TB can be conventionally categorized as primary
or postprimary (adult-type, secondary).
 Primary Disease
 Primary pulmonary TB occurs soon after the initial infection with
tubercle bacilli.
 Often seen in children.
 Because most inspired air is distributed to the middle and lower
lung zones, these areas of the lungs are most commonly involved
in primary TB. The lesion forming after initial infection (the Ghon
focus) is usually peripheral and accompanied by transient hilar or
paratracheal lymphadenopathy.
 Some patients develop erythema nodosum in the legs or
phlyctenular conjunctivitis.
 In young children with immature CMI and in persons with impaired
immunity, it may progress rapidly to clinical illness.
 Pleural effusion, which is found in up to two-thirds of cases, results
from the penetration of bacilli into the pleural space from an adjacent
subpleural focus.
 In severe cases, the primary site rapidly enlarges, its central portion
undergoes necrosis, and cavitation develops (progressive primary TB).
 Enlarged lymph nodes may compress bronchi, causing total obstruction
with distal collapse, partial obstruction with large-airway wheezing, or
a ball-valve effect with segmental/lobar hyperinflation
 Lymph nodes may also rupture into the airway with
development of pneumonia, often including areas of necrosis
and cavitation, distal to the obstruction.
 Bronchiectasis may develop in any segment/lobe damaged by
progressive caseating pneumonia. Occult hematogenous
dissemination commonly follows primary infection.
 Post primary (Adult-Type) Disease
 Also referred to as reactivation or secondary TB, post primary
TB is probably most accurately termed adult-type TB, since it
may result from endogenous reactivation of distant latent
infection or recent infection (primary infection or reinfection).
 It is usually localized to the apical and posterior segments of the
upper lobes, where the substantially higher mean oxygen tension
favors mycobacterial growth. The superior segments of the lower
lobes are also more frequently involved.
 The extent of lung parenchymal involvement varies greatly,
from small infiltrates to extensive cavitary disease.
 With cavity formation, liquefied necrotic contents are
ultimately discharged into the airways and may undergo
bronchogenic spread.
 Massive involvement of pulmonary segments or lobes, with
coalescence of lesions, produces caseating pneumonia.
– Early in the coarse Sx / Sn non specific & insidious
– Fever , night sweats ,wt loss , anorexia, general malaise, weakness

– Cough – productive purulent haemoptysis

– Massive haemoptysis →blood vessel erosion (Rasmussen’s Aneurism)

– Dyspenia & ARDS

– Physical findings-normal, rales, ronki, amphoric,fever,wasting, clubbing, pale
 Early in the course of disease, symptoms and signs are often
nonspecific and insidious, consisting mainly of diurnal fever
and night sweats , weight loss, anorexia, general malaise, and
weakness.
 Cough eventually develops—often initially nonproductive and
subsequently accompanied by the production of purulent
sputum, sometimes with blood streaking.
 Massive hemoptysis may ensue as a consequence of the
erosion of a blood vessel in the wall of a cavity. Hemoptysis,
however, may also result from rupture of a dilated vessel in a
cavity (Rasmussen's aneurysm) or from aspergilloma
formation in an old cavity.
 Pleuritic chest pain sometimes develop.Extensive disease may
produce dyspnea and, in rare instances, adult respiratory
distress syndrome.
 No abnormalities detectable by chest examination.
 Occasionally,rhonchi due to partial bronchial obstruction and
classic amphoric breath sounds in areas with large cavities
may be heard.
 fever (often low grade and intermittent) and wasting.
Absence of fever does not exclude TB.
 In some cases, pallor and finger clubbing develop. The most
common hematologic findings are mild anemia, leukocytosis,
and thrombocytosis with a slightly elevated erythrocyte
sedimentation rate and/or C-reactive protein level.
Extrapulmonary TB

 In order of frequency, the extrapulmonary sites most

commonly involved in TB are the lymph nodes, pleura,
genitourinary tract, bones and joints, meninges, peritoneum,
and pericardium. However, virtually all organ systems may be
affected.
Tuberculous Lymphadenitis

 The most common presentation of extrapulmonary TB in both

HIV-seronegative and HIV-infected patients
 35% in general
 lymph node disease is common in HIV-infected patients and in
children.
 Presents as painless swelling of the lymph nodes, most commonly
at posterior cervical and supraclavicular sites (referred to as
scrofula).
 Lymph nodes are usually discrete in early disease but develop
into a matted nontender mass over time and may result in a
fistulous tract draining caseous material.
 ↑ ed with HIV infection
 TB lymphedenitis
 Most common EPT>25%
 Common in HIV

 scrolofula carvical/supraclavicular LN
 LN painless/discrete→flactuate →drain
 Systemic symptoms+/_
 Dx-FNA,BX of LN,
 50% AFB +ve, 70-80% culture +ve
 Associated pulmonary disease is present in <50% of cases,
and systemic symptoms are uncommon except in HIV-
infected patients.
 The diagnosis is established by fine-needle aspiration biopsy
(with a yield of up to 80%) or surgical excision biopsy.
 cultures are positive in 70–80% of cases.
Pleural TB

 accounts for 20% of extrapulmonary cases

 Isolated pleural effusion usually reflects recent primary
infection, and the collection of fluid in the pleural space
represents a hypersensitivity response to mycobacterial
antigens. Pleural disease may also result from contiguous
parenchymal spread, as in many cases of pleurisy accompanying
postprimary disease.
 symptoms such as fever, pleuritic chest pain, and dyspnea.
 Physical findings are those of pleural effusion: dullness to
percussion and absence of breath sounds.
 A chest radiograph reveals the effusion and, in up to one-
third of cases, also shows a parenchymal lesion.
 The fluid is straw colored and at times hemorrhagic; it is an
exudate with a protein concentration >50% of that in serum
(usually 4–6 g/dL), a normal to low glucose concentration, a
pH of 7.3 (occasionally <7.2), and detectable white blood
cells (usually 500–6000/L).
 Neutrophils may predominate in the early stage, but
lymphocyte predominance is the typical finding later.
 AFB are seen on direct smear in only 10–25% of cases, but
cultures may be positive for M. tuberculosis in 25–75% of
cases; positive cultures are more common among postprimary
cases.
 Determination of the pleural concentration of adenosine
deaminase (ADA) is a useful screening test: tuberculosis is
virtually excluded if the value is very low.
 Tuberculous empyema is a less common complication of
pulmonary TB. It is usually the result of the rupture of a
cavity, with spillage of a large number of organisms into the
pleural space. This process may create a bronchopleural
fistula with evident air in the pleural space. A chest
radiograph shows hydropneumothorax with an air-fluid level.
 The pleural fluid is purulent and thick and contains large
numbers of lymphocytes. Acid-fast smears and
mycobacterial cultures are often positive. Surgical drainage
is usually required as an adjunct to chemotherapy.
 May result in severe pleural fibrosis and restrictive lung
disease
TB of the Upper Airways

 Nearly always a complication of advanced cavitary pulmonary

TB, TB of the upper airways may involve the larynx, pharynx,
and epiglottis. Symptoms include hoarseness, dysphonia, and
dysphagia in addition to chronic productive cough. Findings
depend on the site of involvement, and ulcerations may be
seen on laryngoscopy. Acid-fast smear of the sputum is
often positive, but biopsy may be necessary in some cases to
establish the diagnosis. Carcinoma of the larynx may have
similar features but is usually painless.
Genitourinary TB

 Genitourinary TB, which accounts for 10–15% of all

extrapulmonary cases may involve any portion of the
genitourinary tract.
 Local symptoms predominate, and up to 75% of patients have
chest radiographic abnormalities suggesting previous or
concomitant pulmonary disease. Urinary frequency, dysuria,
nocturia, hematuria, and flank or abdominal pain are common
presentations.
 Urinalysis gives abnormal results in 90% of cases, revealing
pyuria and hematuria.
 Culture-negative pyuria in acidic urine raises the suspicion of
TB. IV pyelography, abdominal CT, or MRI may show
obstructions, and calcifications and ureteral strictures are
suggestive findings.
 Severe ureteral strictures may lead to hydronephrosis and
renal damage. Genital TB is diagnosed more commonly in
female than in male.
 In females, it affects the fallopian tubes and endometrium
and may cause infertility, pelvic pain, and menstrual
abnormalities. Diagnosis requires biopsy or culture of
specimens obtained by dilatation and curettage.
 In male patients, genital TB preferentially affects the
epididymis, producing a slightly tender mass that may drain
externally through a fistulous tract; orchitis and prostatitis
may also develop.
 Genitourinary TB responds well to chemotherapy.
Extra Pulmunary TB

 TB of upper airways
– Larynx,pharynx,epiglottis,hoarseness/dysphagia
– Dx laryngoscopy(ulcer),AFB+culture

 Genitourenary TB-15 % of EPTB

– Due to hematogenuos seeding
– Local sx-dysuria,hematuria,frequency,flank pain
– Urine abnormal in 90%
– Culture -ve pyuria---→ TB
– IVP
– Calcification and urethral strictures →hydronephrosis and renal damage
Skeletal TB

 responsible for 10% of extrapulmonary cases.

 pathogenesis is related to reactivation of hematogenous
foci or to spread from adjacent paravertebral lymph
nodes.
 Weight-bearing joints (the spine in 40% of cases, the hips
in 13%, and the knees in 10%) are most commonly affected.
 localized pain and/or swelling of insidious onset, discharge
of pus, muscle weakness, paralysis, and stiffness of joints
 While the upper thoracic spine is the most common site of spinal
TB in children, the lower thoracic and upper lumbar vertebrae
are usually affected in adults.
 With advanced disease, collapse of vertebral bodies results in
kyphosis (gibbus). A paravertebral "cold" abscess may also form.
 In the upper spine, this abscess may track to and penetrate the
chest wall, presenting as a soft tissue mass; in the lower spine, it
may reach the inguinal ligaments or present as a psoas abscess.
 Aspiration of the abscess or bone biopsy confirms the
tuberculous etiology,
 A catastrophic complication of Pott's disease is paraplegia,
which is usually due to an abscess or a lesion compressing the
spinal cord.
 Diagnosis requires examination of the synovial fluid, which is
thick in appearance, with a high protein concentration and a
variable cell count. Although synovial fluid culture is positive
in a high percentage of cases, synovial biopsy and tissue
culture may be necessary to establish the diagnosis.
Extra Pulmunary TB

 Skeletal TB
– 10% of all extrapulmonary case
– Reactivation of hematogenous foci or adjacent LN
– Weight bearing joints(spine,hip,knee)
– Spinal tbc(Pott”s Dx)= adjacent vertebrae thoracic/lumbar

• Collapse of vertabrae –kyphosis (gibbus)

• Paravertebral”cold”abcess
• Psoas abcess
• Paraparesis/paraplegia
Tuberculous Meningitis and Tuberculoma

 Accounts for 5% of extrapulmonary cases.

 Tuberculous meningitis results from the hematogenous spread of
primary or postprimary pulmonary TB or from the rupture of a
subependymal tubercle into the subarachnoid space.
 In more than half of cases, evidence of old pulmonary lesions or a
miliary pattern is found on chest radiography.
 The disease often presents subtly as headache and slight mental
changes after a prodrome of weeks of low-grade fever, malaise,
anorexia, and irritability.
 Typically, the disease evolves over 1–2 weeks, a course longer
than that of bacterial meningitis. Since meningeal
involvement is pronounced at the base of the brain, paresis
of cranial nerves (ocular nerves in particular) is a frequent
finding, and the involvement of cerebral arteries may
produce focal ischemia. The ultimate evolution is toward
coma, with hydrocephalus and intracranial hypertension.
 Examination of CSF reveals a high leukocyte count (up to
1000/L), usually with a predominance of lymphocytes but
sometimes with a predominance of neutrophils in the early stage;
a protein content of 1–8 g/L (100–800 mg/dL); and a low glucose
concentration. However, any of these three parameters can be
within the normal range. AFB are seen in up to one-third of
cases.
 Culture of CSF is diagnostic in up to 80% of cases and remains
the gold standard. PCR has a sensitivity of up to 80%, but rates
of false-positivity reach 10%. Imaging studies (CT and MRI) may
show hydrocephalus and abnormal enhancement of basal cisterns
or ependyma.
 Tuberculoma, an uncommon manifestation of central nervous
system TB, presents as one or more space-occupying lesions
and usually causes seizures and focal signs.
 CT or MRI reveals contrast-enhanced ring lesions, but biopsy
is necessary to establish the diagnosis.
Extra Pulmunary TB

 TB meningitis/Tuberculoma
 5% extrapulmonary
 Children/HIV-adult
 Hematogenuos -primary/post primary or ependymal rupture
 50% CXR-miliary /old lesion
 Presentation
 Subtle→headache,mental change or acute confusion ,lethargy, change in sensorium, neck rigidity
 Cranial nerve palsy
 Hydrocephalus, space occupying lesion- tuberculoma
 CSF protein, WBC / lymphocyte, glucose

 AFB yield by increased volume, repeated LP

 CT/MRI
 Anti TB + steroids
Gastrointestinal TB

 Accounts for 3.5% of extrapulmonary cases.

 The pathogenetic mechanisms: swallowing of sputum with direct
seeding, hematogenous spread, or ingestion of milk from cows
affected by bovine TB.
 Although any portion of the gastrointestinal tract may be affected,
the terminal ileum and the cecum are the sites most commonly
involved.
 Abdominal pain (at times similar to that associated with appendicitis)
and swelling, obstruction, hematochezia, and a palpable mass in the
abdomen are common findings at presentation. Fever, weight loss,
anorexia, and night sweats are also common.
 With intestinal-wall involvement, ulcerations and fistulae may
simulate Crohn's disease; the differential diagnosis with this
entity is always difficult. Anal fistulae should prompt an
evaluation for rectal TB. As surgery is required in most
cases, the diagnosis can be established by histologic
examination and culture of specimens obtained
intraoperatively.
 Tuberculous peritonitis follows either the direct spread of
tubercle bacilli from ruptured lymph nodes and
intraabdominal organs (e.g., genital TB in women) or
hematogenous seeding. Nonspecific abdominal pain, fever,
and ascites should raise the suspicion of tuberculous
peritonitis.
 paracentesis reveals an exudative fluid with a high protein
content and leukocytosis that is usually lymphocytic.
Extra Pulmunary TB
 Gastrointestinal tuberculosis
 Any part
 Source-swallowing sputum, unpasteurized milk, hematogenous
 Common- cecum/ileum
 Clinical picture
 Depend on the organ
 Hepatobilliary-jaundice,hepatomegaly
 Splenomegaly
 Abdominal pain, diarrea,constipation
 Hematochezia
 Fever, wt loss, night sweat, anal fistula
 Ascites,(peritonitis),lymph node
 U/S,C/T/MRI / peritoneal fluid analysis-AFB +culture
Tuberculous Pericarditis

 Due either to direct extension from adjacent mediastinal or

hilar lymph nodes or to hematogenous spread
 The onset may be subacute, although an acute presentation,
with dyspnea, fever, dull retrosternal pain, and a pericardial
friction rub, is possible.
 symptoms and signs of cardiac tamponade may ultimately
appear.
 A definitive diagnosis can be obtained by pericardiocentesis
under echocardiographic guidance.
 The effusion is exudative in nature, with a high count of
lymphocytes and monocytes. Hemorrhagic effusion is common.
Direct smear examination is very rarely positive. Culture of
pericardial fluid reveals M. tuberculosis in up to two-thirds of
cases, while pericardial biopsy has a higher yield. High levels of
ADA, lysozyme, and IFN- may suggest a tuberculous etiology.
 Complications
 chronic constrictive pericarditis with thickening of the
pericardium, fibrosis, and calcification
Extra Pulmunary TB

 Pericardial TB
– Hematogenous
– Reativationof latent focus
– Rupture of lymph node
– Increased with HIV
– High mortality

 Acute presentation-fever,pain,firiction rub,effusion,sn of

tamponade
 ECHO strands→pericardiocentesis
 Exudative+lymphocytic→AFB+culture
Miliary or Disseminated TB

 Miliary tuberculosis (TB) refers to clinical disease resulting from

the hematogenous dissemination of Mycobacterium tuberculosis.
 Although in children it is often the consequence of primary
infection, in adults it may be due to either recent infection or
reactivation of old disseminated foci. The lesions are usually
yellowish granulomas 1–2 mm in diameter that resemble millet
seeds.
 Fever, night sweats, anorexia, weakness, and weight loss are
presenting symptoms in the majority of cases.
 Physical findings include hepatomegaly, splenomegaly, and
lymphadenopathy. Eye examination may reveal choroidal
tubercles, which are pathognomonic of miliary TB.
 Meningismus occurs in <10% of cases. A high index of
suspicion is required for the diagnosis of miliary TB.
 Chest radiography reveals a miliary reticulonodular pattern.
 Other radiologic findings include large infiltrates,
interstitial infiltrates (especially in HIV-infected patients),
and pleural effusion. Sputum smear microscopy is negative in
80% of cases.
 Various hematologic abnormalities including anemia with
leukopenia, lymphopenia, neutrophilic leukocytosis and
leukemoid reactions, and polycythemia.
Extra Pulmunary TB

 Milliary or disseminated TB
 Hematogenous spread/ local spread(pleura,hilar ln)
 Child primary/adult-recent infection/reactivation of disseminated foci
 Small granuloma 1-2 mm-millet size
 Clinical feature
 Nonspecific/protean(fever,wt loss,sweating)
 Fever of unknown origin, organomegaly, lymph node
 Choroidal tubercle(pathognomonic)-30%
 +/_ Cough, menigismus(<10%)

 Dx high index of suscipicion

 CXR typical
 Sputum _ve(80%)
 Pancytopenea,DIC,abnormal liver test
 Granuloma on biopsy(BM,Liver)
HIV-Associated TB

 TB can appear at any stage of HIV infection, and its

presentation varies with the stage.
 When CMI is only partially compromised, pulmonary TB
presents in a typical manner, with upper-lobe infiltrates and
cavitation and without significant lymphadenopathy or pleural
effusion.
 In late stages of HIV infection, a primary TB–like pattern,
with diffuse interstitial or miliary infiltrates, little or no
cavitation, and intrathoracic lymphadenopathy, is more
common.
 Extrapulmonary TB is common among HIV-infected patients.
The most common forms are lymphatic, disseminated, pleural,
and pericardial.
 Atypical radiographic findings, a lack of classic granuloma
formation in the late stages, and a negative TST.
HIV associated TB

 Important OI in HIV/AIDS
 70-80% TB patients-HIV +ve(Africa)
 15% annual risk of TB disease if infected(10Xnormal) in HIV
infected
 TB-all spectrum immunity status

 Pictures depend on level of immunity

– CD4>200-same as other patients
 CD4<200-atypical presentation
– Primary type ,disseminated, lower lobe, LAP, pleural effusion,+EPTB, milliary, no cavitary

• Atypical lung involvement

• Atypical CXR
• Diagnosis difficult
• Negative PPD
HIV associated TB

 Less cavitary-less infectious

 Less smear positivity
 High burden of bacilli in body –high Blood culture positivity
(mycobacterium)

 EPTB is common >30%(40-60%)-

lymphatic,DTB,pleura,percardium,meninges
 Dx-difficult ”atypical granuloma”
Drug-resistant tuberculosis (MDR- and
XDR-TB)
 Multi-drug resistant tuberculosis (MDR-TB) is defined as TB
that is resistant at least to INH and RMP.
 Isolates that are multiply-resistant to any other combination
of anti-TB drugs but not to INH and RMP are not classed as
MDR-TB.
 "Extensively drug-resistant tuberculosis" (XDR-TB) is defined
as MDR-TB that is resistant to quinolones and also to any one
of kanamycin, capreomycin, or amikacin.
 The principles of treatment for MDR-TB and for XDR-TB are
the same.
 The mortality is higher in XDR
Terminology

 TB SUSPECT: is any person with cough of two weeks or

more duration.
 A Definite/proven case of tuberculosis: A patient with two
sputum smears (one sputum positive is enough for HIV
positive patients) or culture positive for Mycobacterium
tuberculosis. OR
 Mycobacterium tuberculosis complex identified from a
clinical specimen, either by culture or by a newer method
such as molecular line probe assay
Classification of TB

1. Anatomical site of disease

2. Bacteriological results
3. History of previous treatment
4. HIV status
Anatomical site of TB disease

In general, recommended treatment regimens are similar,

irrespective of site.
 Pulmonary tuberculosis (PTB) refers to a case of TB involving
the lung parenchyma. Miliary tuberculosis is classified as
pulmonary TB because there are lesions in the lungs.
 Tuberculous intrathoracic lymphadenopathy (mediastinal and/or
hilar) or tuberculous pleural effusion, without radiographic
abnormalities in the lungs, constitutes a case of extrapulmonary
TB.
 A patient with both pulmonary and extrapulmonary TB should be
classified as a case of pulmonary TB
 Extrapulmonary tuberculosis (EPTB) refers to a case of TB
involving organs other than the lungs such as pleura, larynx.
 Diagnosis should be based on at least one specimen with
confirmed M. tuberculosis or histological or strong clinical
evidence consistent with active EPTB.
Bacteriologic classification

 Bacteriology refers to the smear status of pulmonary cases

and the identification of M. tuberculosis for any case by
culture or newer methods.
 Smear-positive pulmonary TB (PTB+)
 A patient with at least two initial sputum smear examinations
positive for AFB by direct microscopy, Or
 A patient with one initial smear examination positive for
AFB by direct microscopy and culture positive, Or
 A patient with one initial smear examination positive for AFB
by direct microscope and radiographic abnormalities
consistent with active TB as determined by a clinician.
 Smear-negative pulmonary TB (PTB-)
1. No response to a course of broad-spectrum antibiotics, And
2. Three negative smear examinations by direct microscopy, And
3. Radiological abnormalities consistent with pulmonary
tuberculosis, And
4. Decision by a clinician to treat with a full course of anti-
tuberculosis
 Extra-pulmonary TB (EPTB)
 TB in organs other than the lungs, proven by one culture-
positive specimen from an extra-pulmonary site or histo-
pathological evidence from a biopsy, Or
 TB based on strong clinical evidence consistent with active
EPTB and the decision by a physician to treat with a full
course of anti-TB therapy.
History of previous treatment

 New case (N): A patient who never had treatment for TB, or has been on
anti-TB treatment for less than four weeks in the past.
 Relapse (R): A patient declared cured or treatment completed of any form
of TB in the past, and is now found to be AFB smear-positive or culture
positive.
 Treatment after Failure (F): A patient who, while on treatment, is smear-
positive at the end of the fifth month or later, after commencing. or
patient who was initially sputum smear-negative but who becomes smear-
positive during treatment at two months or later.
 Return after default (D): pt coming smear +ve after at least 2 months of
interruption of Tx.
 Transfer in (T): A patient who is transferred-in to continue treatment in a
given treatment unit after starting treatment in another treatment unit for
at least four weeks.
 Other (O): A patient who does not fit in any of the above mentioned
categories. e.g. Smear negative PTB case who returns after default, EPTB
case returning after default, previously treated TB patients with an
unknown outcome of that previous treatment and who have returned to
treatment with smear-negative PTB or bacteriologically negative EPTB.
HIV status

Smear-positive PTB:
 One sputum smear examination positive for AFB and
 Laboratory confirmation of HIV infection
Smear Negative PTB:
 At least three sputum specimens negative for AFB, and
 Radiologic abnormalities consistent with active tuberculosis, and
 Laboratory confirmation of HIV infection, and
 Decision by a clinician to treat with full course of Anti-TB
chemotherapy or
 A patient with AFB smear-negative sputum which is culture-positive
for MTB.
 Extra pulmonary TB:
 One specimen from an extrapulmonary site culture or smear
Positive for AFB, or
 Histological or strong clinical evidence consistent with active
extrapulmonary TB.
 Laboratory confirmation of HIV infection, and
 Decision by a clinician to treat with full course of Anti-TB
chemotherapy
Diagnostic Methods

 AFB Microscopy
– Sputum(3X,spot,morning,spot)
– Tissue
– Urine/ gastric lavage- limited by the presence of commensal mycobacteria that can cause false-
positive results.

 Day 1: the first "on-the-spot" sample is collected.

 Day 2: the early morning sample (Sample 2) is submitted,
and then the second "on-the-spot" sample (Sample 3) is
collected.
 Mycobacterial Culture
 Definitive diagnosis depends on the isolation and
identification of M. tuberculosis.
 Because most species of mycobacteria,grow slowly, 4–8
weeks may be required before growth is detected.
 Culture remains the gold standard in mycobacterial detection
because of its higher sensitivity and specificity.
 Culture with Drug Susceptibility Testing (DST) is used for
the diagnosis and management of drug-resistant TB.
 Nucleic Acid Amplification
 performed on at least one respiratory specimen from
patients being evaluated for suspected pulmonary TB.
 Radiographic Procedures
 The "classic" picture is that of upper-lobe disease with
infiltrates and cavities.
 In the era of AIDS, no radiographic pattern can be
considered pathognomonic.
 Drug Susceptibility Testing
 The initial isolate of M. tuberculosis should be tested for
susceptibility to isoniazid and rifampin to detect MDR-TB,
 In addition, expanded susceptibility testing for second-line
anti-TB drugs (especially the fluoroquinolones and the
injectable drugs) is mandatory when MDR-TB is found.
 Molecular Tests for TB Diagnosis
 Line Probe Assay
 Gene Xpert MTB/RIF: indicated for the diagnosis of TB in
high MDRTB and TB/HIV settings.
 Histo-pathological examination
 Fine needle aspiration from accessible mass
 Aspiration of effusions
 Tissue biopsy from any body tissues
granuloma
Treatment of TB
Principles of antiTB chemotherapy

 Combination-
– ↓resistance(mutants will be killed by one of the drugs)
– Bacteria of different population

 Given for several months(>6 months)

– To kill slow growing organisms/semi dormant bacilli
– To prevent relapse

 Resistance low probability-even lower when drugs combined

– MDR
– XDR
 First line drugs for the treatment of TB in Ethiopia include:
 Rifampicin(R);
 Ethambutol (E);
 Isoniazid (H);
 Pyrazinamide (Z) and
 Streptomycin (S).
 The fixed dose combination (FDC) drugs available
 RHZE 150/75/400/275 mg
 RHZ 150/75/400 mg
 RH 150/75 mg
 EH 400/150mg
TB drugs available as loose form:
 Ethambutol 400 mg;
 Isoniazid 300 mg;
 Streptomycin sulphate vials 1 gm.
 Streptomycin is administered by injection while the other anti TB drugs are
to be taken orally.
 All the drugs should be taken together as a single, daily dose, preferably on
an empty stomach.
 First line essential drugs bactericidal- R,H,Z,S; bacteriostatic-E,T
 Do not give streptomycin to a pregnant woman because it can cause
permanent deafness in the baby.
 Pyridoxine supplementation is recommended for all pregnant women taking
INH.
 A breastfeeding woman who has TB
 the baby should continue to breastfeed in the normal way. Give
the infant a course of preventive therapy (INH). When
preventive therapy is completed, give the infant BCG if not yet
immunized.
 Pyridoxine supplementation is recommended for all breast
feeding women taking INH.
 Treatment of patient with renal failure
 avoid Streptomycin & Ethambutol; therefore the
recommended regimen is 2RHZ/4RH
 Patients with liver disorder
 Most anti-TB drugs can cause liver damage. Do not give
Pyrazinamide because this is the most hepatotoxic anti-TB
drug. for TB patients with liver disease, recommended
regimens are: 2SERH/6RH, 9RHE or 2SEH/10EH.
 Treatment Extrapulmonary TB
 Pulmonary and EPTB should be treated with the same
regimens.
 a total duration of 9 to 12 months for TB meningitis and TB
of bones or joints.
 Adjuvant corticosteroid treatment is recommended for TB
meningitis and pericarditis.
 In TB meningitis Ethambutol should be replaced by
Streptomycin.
 Tuberculous meningitis
 Chemotherapy should be initiated with RHZS in an initial
phase for 2 months and RH should be continued for 7 to 10
months in the continuation phase.
 Adjunctive corticosteroid therapy with dexamethasone is
recommended for all patients.
 N: 2RHZE/4RH
 F:2RHZES/RHZE/5RHE:send DST
 R:2RHZES/RHZE/5RHE:send DST
 T: same treatment
N(new), F(failure), R(Relapse), T(Transfer), O(Others)
 O:
 Defaulted patients coming with smear negative TB, EPTB,
or previously treated patients with unknown treatment
outcome:Treat as retreatment: 2RHZES/RHZE/5RHE
 Previously successfully treated patients coming with PTB-
ve or EPTB :Treatment as new: 2RHZE/4RH
Monitoring

 Drug side effects

– INH: hepatitis, peripheral neuropathy

– RIFA:GI reaction, hepatitis

– PZA: hepatitis,arthralgia

– STM: hypersensitivity, vestibular/ fetal auditory damage

– ETM: optic neuritis

Prevention of TB

– BCG-Milliary/meningitis prevented

– IPT-high risk –HIV/contact child with mother, prisoners

• 1st rule out active TB

• Contraindication-CLD/alcoholic
ለሳንባ ነቀርሳ በቂ ሃንዳውት ነው፣ከኤድስ ጋር ስላለው ዝምድና ሌላ
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