INTRODUCTION

Tuberculosis (TB) has troubled humankind throughout history. It has been a leading cause of death throughout the world, and
still is in low-income and middle-income countries. The limitations of existing methods of prevention, diagnosis, and treatment
of tuberculosis have been emphasized by the increased susceptibility of HIV-infected people to develop the disease, and by the
emergence of drug-resistant strains¹. Multidrug-resistant (MDR) tuberculosis – resistant to at least isoniazid and rifampicin – is
an increasingly important public health and clinical issue,especially in countries with a high burden of HIV. Reports of MDR
tuberculosis isolates resistant to second-line drugs have amplified these concerns. In March 2006, the first data were published
on the world wide occurrence of tuberculosis with resistance to second-line drugs, termed extensively drug resistant (XDR)
tuberculosis¹. Outbreaks of nosocomial MDR tuberculosis have occurred in both poor and wealthy nations, typically in HIV-
infected patients. Transmission has been reduced in industrialized countries through a combination of infection control
strategies, including comprehensive treatment protocols and staff training programmes (administrative measures): ventilation,
isolation, air filtration, and ultraviolet germicidal irradiation (environmental controls); and the use of respiratory masks
(personal protection)¹.

Figure 1. Chest x-ray of Tuberculosis

Types of Tuberculosis

Tuberculous Lymphadenitis
Twenty-one percent of extra pulmonary TB may have typical or atypical presentations. Therefore, a high index of suspicion is
warranted. HIV infected individuals are more likely to have disseminated (miliary), abdominal, or mediastinal tuberculosis.
Diagnostic parameters such as an acid-fast smear and culture of specimens from extra pulmonary sites are often not sensitive
as those from pulmonary tuberculosis. Histological examination of lymph node biopsies shows reactive hyperplasia and
granulomata (with or without caseation). In 18% of TB adenitis, chest radiography revealed pulmonary change. Laboratory tests
such as adenosine deaminase level or polymerase chain reaction (PRC) can be helpful in suspected cases or to establish a
diagnosis of extra pulmonary tuberculosis². In India, children under 14 years of age have prevalence rates of 4.4 cases per 1000.
Tuberculous lymphadenitis in developed countries with low TB prevalence is more often seen in immigrants and in those who
travel to countries of higher prevalence. In recent years, lymphadenitis is common between 20 and 40 years of age and exhibits
female predominance. The infection of lymph nodes by my-cobacterium occurs either through hematogenous dissemination
following primary tuberculosis. Extra pulmonary tuberculosis in HIV infection is seen when CD4 counts are below 300/ml³.
Often in those patients tuberculous lymphadenitis can also occur in association with pulmonary and/or miliary disease.
Intrathoracic lymphadenitis may be the presenting feature of primary tuberculosis in HIV infection (Figure 2).
Figure 2. The subcutaneous nodules at the rick of this adolescent patient are swollen lymph nodes. They are not ulcerated. This
is a primary form of tuberculosis found mainly in adolescents, later accompanied by necrosis and formation of fistulae.

Pleural Tuberculosis
TB is the most common cause of pleural effusion worldwide (30-60%). The pathogenesis of Tuberculosis pleurisy can occur with
a primary infection, especially in young adults and adolescents. Merio et al ⁴ ,⁵ reported 22% of pediatric TB to be tuberculous
pleural effusion. It is seen within weeks or months from rupture of a sub pleural tuberculous focus resulting in inflammation by
mycobacterial antigens and T-cells previously sensitized of TB antigens with exudation of fluid due to a delayed hypersensitivity
reaction of M. tuberculosis. The fluid has very few organisms and pleural tissue has granulomata.

Tuberculous Emphysema
Tuberculous emphysema results from bronchopleural fistula following the rupture of cavitary pulmonary TB with frank pus in
the pleural space. TB emphysema contains a large number of M. tuberculosis. Rarely a spinal abscess may drain into the pleural
space. Tuberculous emphysema if untreated or inadequately treated can result in emphysema necessitatis, which often is a
bronchopleural cutaneous fistula. The emphysema may also drain into retroperitoneal space. TB emphysema needs drainage
with or without decortications in addition to chemotherapy.

Miliary, Central Nervous System and Genitourinary Tuberculosis

Tuberculomas are uncommon and may present as one or more parenchymal granulomata and may cause seizures, focal
neurologic deficits, or cognitive changes. Lesions are generally smaller than 2 cm and may not be visible on non contrast
computed tomographic (CT) images. Cerebral spinal fluid (CSF) may demonstrate lymphocyte predominant pleocytosis with an
elevated protein⁶. Meningitis may coexist in 10% of cases⁷. Miliary Tuberculosis (TBM) is not merely an extension of miliary
disease, but instead represents the extension of a caseous focus of TB in the brain cortex or meninges from which bacilli are
able to enter the subarachnoid space to cause diffuse meningitis. Hematogenous spread of bacilli, either during the primary
infection or at some point later during the infection, results in the establishment of a focus within the cortex, meninges, choroid
plexus or the walls of the ventricles⁸. This site of infection, also known as a Rich focus, may subsequently caseate and discharge
its contents into the subarachnoid space. The CNS may also become involved through direct extension from the middle ear or
vertebrae. The dense exudates that form around the spinal cord may obstruct cerebrospinal fluid at the ten-torial opening,
leading to hydrocephalus. Direct contact of the exudates with brain tissue may result in a hypersensitivity response. The most
serious complication is development of CNS vasculitis and subsequent infarction leading to hemiplegia or quadriplegia. Patients
may initially present with a prodromal period of fever, weight loss, headache, vomiting, or behavior changes. Delays in
diagnosis and treatment may result in neurologic changes, loss of consciousness, or convulsions. Typical CSF changes include a
low cell count <300 m⁹, predominately lymphocytic, low glucose <2.2 mmol per liter, and elevated protein >0.8 g per liter.
Nucleic acid amplification testing of CSF has high specificity (0.98) but low sensitivity (0.56) for TB, thus a negative test does not
necessarily support discontinuation of treatment in a patient suspected of having CNS TB⁸. Identifying AFB-positive organisms
may require repeated lumbar puncture. When TBM is suspected, anti-TB treatment should be considered early. Adjunctive
treatment with corticosteroids while providing a mortality benefit to those 14 years of age has not been shown to prevent
severe disability among survivors. Even with treatment, TBM is fatal in approximately 30% of cases. In a recent review of 545
patients with TBM¹⁰, 64.6% of HIV-infected patients died by 9 months after start of treatment versus 28.2% of non-HIV infected
patients. Patients with isolates resistant to both isoniazid and rifampicin had a significantly higher relative risk of death¹¹.

Paradoxical reactions have been reported in CNS TB where patients appear to have clinical deteri- oration several weeks into
therapy demonstrating an increase in CSF pleocytosis, usually lymphocytic, but occasionally polymorphonuclear predominant ¹².
Despite adequate medical and surgical treatment of tuberculomas or tuberculous brain abscesses, paradoxical enlargement and
development of new lesions are well described. Adjunctive therapy with thalidomide, a tumor necrosis factor alpha-modulating
drug, has been used successfully in four pediatric cases of in-tractable intracranial disease¹³. Further investigation of
thalidomide in the treatment of intractable intracranial tuberculous infection may be warranted (Figure 3).

Figure 3. Miliary tuberculosis in lung can occur when tuberculous lung lesions erode pulmonary veins or when extrapulmonary
tuberculosis lesion erodes systemic veins.

Pathophysiology of Tuberculous
Tuberculosis may occur in 3 stages:

Primary infection

Latent infection

Active infection

M. tuberculosis bacilli initially cause a primary infection, a small percentage of which eventually progress to clinical disease of
variable severity. However, most (about 95%) primary infections are asymptomatic. An unknown percentage of primary
infections resolve spontaneously, but the majority are followed by a latent (dormant) phase. A variable percentage (5 to 10%)
of latent infections subsequently reactivate with symptoms and signs of disease.

Infection is usually not transmissible in the primary stage and is never contagious in the latent stage.

1.Primary Tuberculous infection

Infection requires inhalation of particles small enough to traverse the upper respiratory defenses and deposit deep in the
lungs, usually in the subpleural airspaces of the middle or lower lobes. Larger droplets tend to lodge in the more proximal
airways and typically do not result in infection. Infection usually begins from a single droplet nucleus, which typically carries few
organisms. Perhaps only a single organism may suffice to cause infection in susceptible people, but less susceptible people may
require repeated exposure to develop infection.

To initiate infection, M. tuberculosis bacilli must be ingested by alveolar macrophages. Bacilli that are not killed by the
macrophages actually replicate inside them, ultimately killing the host macrophage (with the help of CD8 lymphocytes);
inflammatory cells are attracted to the area, causing a focal pneumonitis that coalesces into the characteristic tubercles seen
histologically.
In the early weeks of infection, some infected macrophages migrate to regional lymph nodes (eg, hilar, mediastinal), where
they access the bloodstream. Organisms may then spread hematogenously to any part of the body, particularly the apical-
posterior portion of the lungs, epiphyses of the long bones, kidneys, vertebral bodies, and meninges. Hematogenous
dissemination is less likely in patients with partial immunity due to vaccination or to prior natural infection with M. tuberculosis
or environmental mycobacteria.

Latent TB infection occurs after most primary infections. In about 95% of cases, after about 3 weeks of uninhibited growth, the
immune system suppresses bacillary replication, usually before symptoms or signs develop. Foci of bacilli in the lung or other
sites resolve into epithelioid cell granulomas, which may have caseous and necrotic centers. Tubercle bacilli can survive in this
material for years; the balance between the host’s resistance and microbial virulence determines whether the infection
ultimately resolves without treatment, remains dormant, or becomes active. Infectious foci may leave fibronodular scars in the
apices of one or both lungs (Simon foci, which usually result from hematogenous seeding from another site of infection) or
small areas of consolidation (Ghon foci). A Ghon focus with lymph node involvement is a Ghon complex, which, if calcified, is
called a Ranke complex. The tuberculin skin test and interferon-gamma release blood assays (IGRA) become positive during the
latent stage of infection. Sites of latent infection are dynamic processes and are not entirely dormant as was once believed.

Less often, the primary focus progresses immediately, causing acute illness with pneumonia (sometimes cavitary), pleural
effusion, and marked mediastinal or hilar lymph node enlargement (which, in children, may compress bronchi). Small pleural
effusions are predominantly lymphocytic, typically contain few organisms, and clear within a few weeks. This sequence may be
more common among young children and recently infected or reinfected immunosuppressed patients.

Extrapulmonary TB at any site can sometimes manifest without evidence of lung involvement. TB lymphadenopathy is the most
common extrapulmonary manifestation; however, meningitis is the most feared because of its high mortality in the very young
and very old.

2.Secondary Tuberculous disease

Healthy people who are infected with tuberculosis have about a 5 to 10% lifetime risk of developing active disease, although
the percentage varies significantly by age and other risk factors.

In 50 to 80% of those who develop active disease, TB reactivates within the first 2 years, but it can also reactivate decades later.

Any organ initially seeded may become a site of reactivation, but reactivation occurs most often in the lung apices, presumably
because of favorable local conditions such as high oxygen tension. Ghon foci and affected hilar lymph nodes are much less likely
to be sites of reactivation.

Conditions that impair cellular immunity (which is essential for defense against TB) significantly facilitate reactivation. Thus,
patients coinfected with HIV and not receiving appropriate antiretroviral therapy (ART) have about a 10% annual risk of
developing active disease.

Other risk factors that facilitate reactivation, but to a lesser extent than HIV infection, include

Diabetes

Head and neck cancer

Gastrectomy

Jejunoileal bypass surgery

Dialysis-dependent chronic kidney disease

Significant weight loss

Use of drugs that suppress the immune system

Patients who require immunosuppression after solid organ transplantation are at the highest risk, but other
immunosuppressants such as corticosteroids and tumor necrosis factor (TNF) inhibitors also commonly cause reactivation.
Tobacco use also is a risk factor.

In some patients, active disease develops when they are reinfected rather than when latent disease reactivates. Reinfection is
more likely to be the mechanism in areas where TB is prevalent and patients are exposed to a large inoculum of bacilli.
Reactivation of latent infection predominates in low-prevalence areas. In a given patient, it is difficult to determine whether
active disease resulted from reinfection or reactivation.

TB damages tissues through delayed-type hypersensitivity (DTH), typically producing granulomatous necrosis with a caseous
histologic appearance. Lung lesions are characteristically but not invariably cavitary, especially in immunosuppressed patients
with impaired DTH. Pleural effusion is less common than in progressive primary TB but may result from direct extension or
hematogenous spread. Rupture of a large tuberculous lesion into the pleural space may cause empyema with or without
bronchopleural fistula and sometimes causes pneumothorax. In the prechemotherapy era, TB empyema sometimes
complicated medically induced pneumothorax therapy and was usually rapidly fatal, as was sudden massive hemoptysis due to
erosion of a pulmonary artery by an enlarging cavity.

The course of TB varies greatly, depending on the virulence of the organism and the state of host defenses. The course may be
rapid in members of isolated populations (eg, Native Americans) who, unlike many Europeans and their American descendents,
have not experienced centuries of selective pressure to develop innate or natural immunity to the disease. The course is often
more indolent in these European and American populations.

Acute respiratory distress syndrome (ARDS), which appears to be due to hypersensitivity to TB antigens, develops rarely after
diffuse hematogenous spread or rupture of a large cavity with spillage into the lungs.

Diagnosis of Tuberculous
Chest x-ray

Acid-fast stain and culture

Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)

When available, nucleic acid amplification test (NAAT)

MSD.
 Figure 4. Chest x ray of tuberculosis

2.Acid fast strain and culture

Figure 5.Microphotograph of TB bacillus, Mycobacterium tuberculosis on an oil-immersion smear slide stained with
Ziehl-Neelsen or acid-fast staining of a clinical sample. Bacilli are long and rod-shaped; a bacillus is indicated by a
black arrow; magnification, X 2250.
6.PREVENTIONS
.Latest studies conducted in 2018

1.The BCG vaccination is a live vaccine against tuberculosis.

2.If you’re traveling to a place where TB is common, avoid spending a lot of time in crowded places with sick people
3.Limit contact with other people. If you live with others, sleep in a separate room and isolate yourself as much as possible.
4.Cover your mouth when you laugh, sneeze, or cough.
Wear a surgical mask when you’re around other people.
5.Keep your space ventilated. Open windows, if possible, and use a fan. Germs spread more easily in poorly ventilated places
6. getting a diagnosis and treatment early

7. staying away from other people until there is no longer a risk of infection

8. wearing a mask, covering the mouth, and ventilating rooms

7. RISK FACTORS
People with weakened immune systems are most likely to develop active TB. The following are some issues that can weaken
the immune system:

1. HIV- For people with HIV, doctors consider TB to be an opportunistic infection. This means that a person with HIV has a
higher risk of developing TB and experiencing more severe symptoms than a person with a healthy immune system.
2. Smoking- Tobacco use and second-hand smoke increase the risk of developing TB.
These factors also make the disease harder to treat and more likely to return after treatment.
3. Other conditions-
1.low body weight
2.substance abuse disorders
3.diabetes
4.Silicosis
5.severe kidney disease
6 .head and neck cancer

TREATMENT
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