Tuberculosis is a contagious chronic granulomatous disease

Mycobacterium tuberculosis (doesn't retain gram dyes)

• This disease usually affects the lungs, but it may affect any other organ or tissue of the body

• Usually, the centers of tuberculosis granulomas undergo cheesy necrosis or CASEOUS

Epidemiology :-

It is estimated that 1.7 billion people are infected worldwide, with 8 to 10 million new cases and 1.5
million deaths per year.

• It decreased throughout the years of the 1800s and 1900s. However, in 1984 the decline in new cases
suddenly stopped, a change caused by the increased incidence of tuberculosis in people infected with
the human immunodeficiency virus (HIV).

• Poverty, overcrowding and debilitating chronic disease

Elderly people with weak immunity are also susceptible

• Increased risk of: diabetes mellitus, Hodgkin's disease, chronic lung diseases (especially silicosis),
chronic kidney failure, malnutrition, alcoholism and immunosuppression.

• In areas of the world where HIV infection is common, this infection has become the most important
risk factor for the spread of tuberculosis

It is important to distinguish infection from disease. Infection is the implantation of organisms in some
foci, which may or may not cause clinically significant tissue damage (ie, disease).

• Although organisms may be transmitted by other means, it is often transmitted directly from an
infected patient to a susceptible host through person-to-person transmission of airborne droplets
containing organisms.

Most of them, an asymptomatic center of pulmonary infection appears, which is self-limited.

Although uncommonly, primary tuberculosis may lead to fever and pleural effusion. Generally the only
evidence of infection, if any, is a small, fibrocalcified nodule at the site of infection.

Living organisms may remain latent in such foci for several decades or even for the entire life of the
host.

• Such people are infected but do not have an active disease, so they cannot transmit the organisms to
others

• Whenever their body's defense is reduced, the infection may reactivate and become a contagious and
potentially life-threatening door.

Mycobacterium tuberculosis infection usually leads to an increase in delayed sensitivity, which can be
detected by the tuberculin test (Manto) about 2 to 4 weeks after the beginning of the infection,
intradermal injection of 0.1 ml of purified protein derivatives (PPD) of a It creates visible and palpable
hardness (induration) (at least 5 mm in diameter) and reaches its maximum within 48 to 72 hours.
This test does not differentiate between infection and disease.

• False negative reactions (or skin test energy) may be caused by certain viral infections, sarcoidosis,
malnutrition, Hodgkin's disease, immunosuppression, and widespread active tuberculosis.

There is a possibility of false positive reactions due to infection Atypical bacteria are obtained

• About 80% of the population in some Asian and African countries are tuberculin positive. By
comparison, in 2012, 5-10% of the US population tested positive for tolucoline.

In total, 3-4% of people without previous exposure will develop active tuberculosis during the first year
of tuberculin positivity and less than 15% during the following years. Therefore, only a small fraction of
those who get an infection will develop an active disease.

Etiology :-

Mycobacteria are thin and pencil-shaped bacilli and resistant to acid (that is, they have large amounts of
complex lipids that easily bind to Zil-Nelson's dye and then stubbornly resist the loss of color).

• Mycobacterium tuberculosis hominis is responsible for most cases.

• The reservoir of infection is usually found in people with active lung disease.

Transmission is usually direct and is caused by inhalation of airborne organisms in droplets produced by
sputum excretion or by exposure to contaminated secretions of the patient.

Oral, pharyngeal and intestinal tuberculosis caused by drinking milk contaminated with Mycobacter
bovis is now rare in developed countries, but it is still seen in countries with unpasteurized dairy cows
and unpasteurized milk.

Other mycobacteria, especially Mycobacterium Avium-intracellular, are much less aggressive than
Mycobacterium tuberculosis and rarely cause disease in people with complete immunity. However,
these species are often found in AIDS patients and affect 10-30% of patients.

Pathogenesis :-

The pathogenesis of tuberculosis in people with healthy immunity and without previous exposure is
based on a cell-mediated immunity that creates resistance to the organism and leads to an increase in
tissue sensitivity to microbial antigens.

Because the effective cells in both processes are similar, the emergence of increased tissue sensitivity is
associated with the acquisition of immunity to the organism.

First, invading mycobacteria enter the endosomes of macrophages. This process is carried out by the
macrophage mannose receptor, which recognizes mannose capped glycolipids on the bacterial cell.

By manipulating the endosomal pH, organisms can inhibit the natural antimicrobial response and
prevent endosomal maturation. The final result of this "endosome manipulation " is the disruption in
the formation of effective phagolysosome and the continued multiplication of mycobacteria takes place.

Therefore, the earliest stage of primary tuberculosis (<3 weeks) in non-susceptible people is the
uncontrolled proliferation of bacilli inside the alveolar macrophages and air spaces, which results in
bacteremia ( unchecked bacilliary proliferation) and the cultivation of the organism in different parts of
the body, despite bacteremia, most patients are asymptomatic at this stage. They have a mild flu-like
illness.

Cell-mediated immunity is created approximately 3 weeks after the introduction of the microbe. The
processed mycobacterial antigens reach the lymph nodes and are presented by macrophages (in the
context of MHC class II) to CD4 + T cells with alpha beta receptor of T cells.

• Under the influence of IL-12 secreted from the Alveolar macrophage, these T cells turn into CD4+TH 1
cells that can produce interferon gamma.

Interferon gamma produced by CD4+ T cells plays an essential role in activating macrophages release
mediators that have effects

The following are important:

• TNF is responsible for calling monocytes (monocyte recruitment) which in turn are activated and
differentiated into "epithelioid histiocytes", which are the main cells in the granulomatous response.

Gamma interferon together with TNF activates the Inos gene, which increases the level of NO at the site
of infection. NO is a strong oxidizing agent and forms active nitrogen intermediates and other free
radicals that are capable of oxidative degradation of several mycobacterial components from cell wall to
DNA (Bactericidal activity).

In short, immunity against tuberculosis infection is mainly mediated by T cells and is characterized by
two parts: increased sensitivity and emergence of resistance to the organism.

• As increased sensitivity and resistance appear simultaneously, the loss of increased sensitivity (for
example, tuberculin negativity in a person who was previously tuberculin positive) is a dangerous sign
indicating the loss of resistance to the organism.

( TH-1 = Tuberculin positivity ( Hypersensitivity)

Image slide no. 15 check it.

Primary Tuberculosis :-

Primary tuberculosis is a type of disease that occurs in people who have not been exposed to it before
and therefore have not been sensitized.

. In primary tuberculosis, the source of the organism is exogenous. About 5% of people who are newly
infected develop an obvious disease.

Morphology :-

In countries where bovine and milk tuberculosis have been widely eradicated. Primary tuberculosis
starts in the lungs in the vast majority of cases

• Usually, inhaled bacilli are implanted in the distal air spaces of the lower part of the upper lobe or the
upper part of the lower lobe and usually adjacent to the side.
With the progress of sensitization, a 1 to 1.5 cm area of white-gray inflammatory density called Ghon
focus appears, and in most cases, the center of this focus undergoes cheesy necrosis.

In most cases, the center of this foci undergoes cheesy necrosis. Tuberculosis bacilli are either free or
inside phagocytes to the regional lymph nodes, which are often cheesy. The combination of
parenchymal lesion and lymph node involvement is called Ghon complex.

During the first few weeks, it spreads to other parts of the body through the lymphatic and blood
vessels.

In nearly 95% of the cases of cell-mediated immune formation, it inhibits infections. Therefore, the
Ghon complex undergoes progressive fibrosis followed by calcification. Despite being implanted in other
organs, no damage is caused.

Histologically, sites of active involvement appear with a characteristic granulomatous inflammatory

reaction, forming both cheesy and non-cheesy tubercles.

• Granulomas are usually surrounded by a fibroblastic rim marked with lymphocytes.

Secondary TB:- Secondary tuberculosis is a type of disease that occurs in a previously sensitized host.

This type may appear shortly after primary tuberculosis. But with more prevalence, it occurs several
decades after the initial infection due to the reactivation of the initial latent lesions. Especially when the
host's resistance decreases.

Also, this condition may be caused by re-infection due to the reduction of the immunity obtained in the
primary disease by inoculation of large amounts of invasive bacilli. Reactivation of endogenous
tuberculosis is more common in areas with low prevalence, while re-infection It plays an important role
in areas with high prevalence.

Whatever the source of the organism. Only a fraction of patients (less than 5%) with primary disease
later develop secondary tuberculosis.

Secondary pulmonary tuberculosis is classically limited to the apex of one or both upper lobes, the cause
is unknown, but it may be due to high oxygen pressure in the apexes.

Because of the increased sensitivity that already exists. The bacilli induce a rapid and intense tissue
response, which tends to slough off the wall of the foci, the infection spreads

• Regional lymph nodes are less involved in the initial stages compared to primary tuberculosis

On the other hand, cavitation, which occurs easily in the secondary type, leads to the spread through
airways.

Regional lymph nodes are less involved in the early stages compared to primary tuberculosis

In all HIV positive patients who refer due to lung disease. Secondary tuberculosis should be considered.

Disease manifestations depend on the severity of immune suppression, for example, patients with mild
triimmune (check) suppression (number of CD4+T cells more than 300 per cubic millimeter) suffer from
common secondary tuberculosis (cavity formation).
In contrast, patients with severe immune suppression (T cell count less than 200) present with a clinical
picture similar to progressive tuberculosis (congestion of the middle and lower lobes, umbilical
lymphadenopathy, lack of cavity formation)

Also, the severity of immunosuppression determines the possibility of extrapulmonary involvement,

which is 10-15% in mild immunosuppression to more than 50% in severe immunosuppression.

Other atopic manifestations in HIV positive people that make the diagnosis of tuberculosis difficult. They
include the increase of extensive negative cases of sputum compared to HIV negative people, false
negative PPD due to tuberculin anergy, and lack of tissue granulomas (in the final stages of HIV
infection).

Morphology :-

The primary lesion is usually a small, dense focus that is less than 2 cm in diameter and is located 1 to 2
cm near the apex.

Such foci are in the form of areas with specific borders, hard and grayish white to yellow, which have
variable amounts of central cheesiness and peripheral fibrosis.

In favorable cases, the primary parenchymal center undergoes progressive fibrous encapsulation that
leaves only fibroblastic foci.

From the histological point of view, active lesions show characteristic interconnected tubercles with
central cheesiness. Tuberculosis bacilli can be shown with appropriate methods in the primary exudate
and cheesy stages of granuloma formation.

Peak and localized secondary pulmonary tuberculosis may improve by creating fibrosis or after
treatment.

The disease may progress and spread from one of the different paths

Progressive Pulmonary TB:-

The peak lesion becomes larger with the expansion of the cheesiness ( CASEOUS NECROSIS) zone.
Corrosion into a bronchus empties the cheesy center and leaves an irregular cavity lined with cheesy
material, that it is weakly limited by fibroous tissue.

Corrosion of blood vessels may lead to hemoptysis.

Miliary lung disease :-

It happens when the organisms are drained through the lymphatics to the lymphatic channels, which are
also emptied into the venous circulation and return to the right half of the heart and from there reach
the pulmonary arteries.

Each of the microscopic lesions or visible and small foci (with a diameter of 2 mm) were formed from
yellowish-white density and spread throughout the lung parenchyma.
(The term miliary is derived from the similarity of these wastes to miliary grains). Miliary lesions may
spread and coalesce to cause almost complete occlusion of large areas or even entire lung lobes

• In progressive pulmonary tuberculosis, the pleural cavity is invariably involved, and pleural serous
effusions, tuberculous empyema, or obstructive fibrotic pleuritis are possible.

Intrabronchial, intratracheal and laryngeal tuberculosis:-

• It is when the infectious substance spreads either through the lymphatic channels or through the
infectious sputum

• The mucous membrane may be torn by small granulomatous lesions, sometimes alone

It is revealed in microscopic examination.

Systemic millet tuberculosis:-

• It occurs when the infectious foci in the lungs return to the heart through the pulmonary veins; The
organisms then spread through the systemic arterial system

• Almost any organ in the body can be infected. These lesions are similar to pulmonary lesions. Millet
tuberculosis mainly in the liver, bone marrow, spleen, adrenal glands, meninges and kidneys Fallopian
tubes and epididymis can be seen.

Organ-specific tuberculosis:-

• It is revealed in any of the organs or tissues in which the microbe is implanted through the blood, and
it may be a single manifestation of tuberculosis.

The organs that are usually affected are: meninges (tuberculous meningitis), kidneys (renal
tuberculosis), adrenal glands (which used to be an important cause of Addison's disease), bones
(osteomyelitis) and fallopian tubes (salpingitis).

When the vertebrae are affected, it is called PAT disease. Cold abscesses near the vertebra may spread
along the tissue plates and create an abdominal mass with the pelvis.

TB lymphadenitis :-

• The most common type of extrapulmonary tuberculosis is usually formed in the neck area

(scrofula)

• In HIV negative people, lymphadenopathy is unifocal and in most cases there is no evidence of
extranodal disease.

• In people with HIV, it is probably a multifocal disease in almost all cases. There are systemic symptoms
and active tuberculosis is seen in the lungs and other organs.

Intestinal tuberculosis

In the past years, intestinal tuberculosis, which was caused by drinking contaminated milk, was one of
the centers
Relatively common cases were primary tuberculosis:-

.Today, in developed countries, intestinal tuberculosis is often an advanced complication of secondary

tuberculosis, which occurs secondary to the ingestion of an infectious substance.

Usually, the organisms are trapped in the lymphoid accumulations of the small and large intestinal
mucosa, which then undergo inflammatory enlargement and ulceration of the covering mucosa,
especially in the ileum.

Clinical :-

Localized secondary tuberculosis may be asymptomatic

Systemic symptoms are probably related to cytokines released by activated macrophages (such as IL-1,
TNF)

They often appear at the beginning of the disease and include malaise, anorexia, weight loss, and fever.
Generally, mild and recurring fever and night sweats are seen.

It happens following progressive pulmonary involvement, the amount of sputum increases, which is
initially mucoid then its purulent.

When pitting is revealed. Sputum contains tuberculosis bacilli. Some degree of hemoptysis is present in
nearly half of all people with pulmonary tuberculosis.

Pleuritic pain may be caused by the spread of infection to the lateral surfaces.

Extrapulmonary manifestations of tuberculosis are diverse and depend on the organ involved (for
example, tuberculous salpingitis with infertility, tuberculous meningitis with headache and neurological
disorders, Pots disease with paraplegia.

The diagnosis of lung disease is determined to some extent based on the history and physical and
radiographic findings of density or pitting in the tops of the lungs. However, in the end, some
tuberculosis bacilli should be identified

Fast acid smears and cultures should be prepared from the sputum of suspected tuberculosis patients.

Older culture methods may take up to 10 weeks to become positive, but new radiometric methods that
track mycobacterial metabolism determine the response within 2 weeks.

• Using the PCR method for DNA amplification in M. Tuberculosis allows rapid diagnosis.

However, culture remains the gold standard because it also allows drug sensitivity to be tested.

• Multidrug resistance is more common today, so now all newly diagnosed cases in the United States
are treated with multidrug therapy.

• Prognosis is generally good if the infection is limited to the lungs

Except when the causative agent is a drug-resistant species or the disease occurs in the elderly, disabled
people or patients with weak immunity, who are at high risk of contracting miliary tuberculosis.

• In stable cases, amyloidosis may appear.

Non-tuberculous mycobacterial disease:-

Non tuberculosis Mycobacterium disease in persons with normal immune :.

Chronic lung disease in people with healthy immunity is the most common local clinical disease caused
by non-tuberculous mycobacteria.

• In the United States, the most important strains are M. Avium-intracellulare or ( M. Avium complex)
M. Kansasii, M. Abscessus.

• In some cases, non-tuberculous mycobacteria cause cavitary disease of the upper lobe of the lung,
which looks similar to tuberculosis (especially in people with a history of long-term smoking or alcohol
consumption).

The presence of simultaneous chronic lung disease (COPD and cystic fibrosis pneumoconiosis) is an
important risk factor for non-tuberculous mycobacterial infection.

Non tuberculosis Mycobacterial infection in immune suppressed persons :-

In immunosuppressed people (especially HIV positive people) M. Avium complex is seen as a diffuse
disease and Show systemic symptoms (fever, night sweats, weight loss).

• Liver and spleen enlargement, lymphadenopathy and digestive symptoms (such as diarrhea and
malabsorption) indicative of reticuloendothelial system involvement with pathogen

• In most patients with AIDS, pulmonary involvement can be distinguished from tuberculosis

• Diffuse M. Avium infection in AIDS patients

The advanced stages of the disease are seen (when the number of CD4+ T cells reach less than 100
numbers per cubic millimeter) Therefore, in histological examination, granuloma is not seen and
instead, foamy histiocytes with atypic

Al mycobacteria are observed.

Slide number : 40 Shown Ghon complex (check it urselves)

Reactivation or secondary TB more typically seen in adults.

Slide number 41 :- CASEOUS NECROSIS shown

The granuloma have areas of CASEOUS NECROSIS, this pattern of multiple caseating granulomas
primarily in the upper lobes is most characteristic of secondary tuberculosis.

Slide 42:- Granuloma shown

Granuloma composed of transformed macrophages called epitheliod cells along with lymphocytes,
occasional PMNs, plasma cells and fibroblasts.

Slide 43:- CASEOUS material composed of necrotic elements of the granuloma as well as the infectious
organisms.
Slide 44 : Typical Giant cell for infectious granulomas is called a Langhans giant cell and has the nuclei
lined up along one edge of the cell. ( see picture on slide)

Slide 45: To find Mycobacterium on tissue section, a stain acid fast bacilli is done (AFB stain). The
Mycobacterium stain as red rods.

Slide 46 :- This is miliary pattern of granulomas because there are the multitude of small tan granulomas
about 2-4 mm in size, scattered throughout the lung parenchyma.

Slide 47:- Miliary pattern is shown

Fungi may produce same pattern in lung

Fungal diseases :-

Fungi are divided into two groups: “yeasts” and “molds”. Yeasts are round or oval and divide by
budding. • Molds form tubular structures called hyphae and grow by branching and longitudinal
expansion.

These two groups overlap because some fungi (such as Histoplasma capsulatum, Coccidioides immitis,
and Blastomyces dermatitis ) are dimorphic (that is, they grow in the tissues as yeast and in the culture
medium as mold).

Human mycoses can be divided into superficial, subcutaneous, and deep types Opportunistic

• Superficial and subcutaneous fungi (such as dermatophytes or chromoblastomycoses) are limited to

the skin and subcutaneous tissues in almost all cases.

Deep mycoses :-

• They are caused by very invasive organisms (especially dimorphic fungi) that can cause systemic
disease by penetrating deep tissues and organs. While immunocompromised hosts may develop
pulmonary disease after inhaling infectious forms of the organism

• Deep mycoses cause more severe disease in immunosuppressed individuals.

Opportunistic fungi :-

They are organisms with low aggressiveness

Which cause local or systemic infections in immunocompromised patients or people who have had
intravascular catheters for a long time.

• Examples of opportunistic fungi include molds “Aspergillus and Mucormycosis” and yeast-like fungi
(Candida and Cryptococcus neoformans).

• All systemic fungi (opportunistic or deep mycoses) can infect the lung, although extrapulmonary
disease may be more common and clinically important with some fungi.

Candidiasis :-

• Candida albicans is the most common pathogenic fungus. This fungus is a natural organism living in the
oral cavity of the digestive system and the mouth of many people
• Morphology

• False hyphae and true hyphae can be seen in the tissue sections of C. Albicans in yeast-like forms
(blastoconidia).

False hyphae are an important diagnostic criterion for C. Albicans and since the germinating yeast cells
are joined end to end, they imitate the true hyphae of fungi. The organisms can be stained with
hematoxylin and eosin and specific staining PAS

• Clinical course: candidiasis can involve the mucous membranes of the skin and deep organs (invasive
candidiasis).

The most common form of candidiasis is a superficial infection on the mucosal surfaces of the oral
cavity.

• This type of candidiasis is seen in infants, diabetics, children who receive oral corticosteroids, disabled
patients and people treated with broad-spectrum antibiotics that destroy the competing bacterial flora.
. Another group at risk are HIV positive patients; If oral thrush develops without an obvious cause, the
patient should be evaluated for HIV infection.

Candida vaginitis is a very common type of vaginal infection in women, especially diabetic or pregnant
women or OCP users. This disorder is usually accompanied by severe itching and a thick, curd-like
discharge.

Candidal esophagitis is common in patients with AIDS or blood-lymphatic malignancies. These patients
present with dysphagia (painful swallowing) and pain behind the sternum; In endoscopy, white plaques
and false membranes (similar to oral thrush) are seen in the esophageal mucosa.

Cutaneous candidiasis can be seen in different ways including nail body onychomycosis, nail bed, hair
follicles (folliculitis), skin folds such as armpits with intertrigo between fingers or toes, and penile skin
(balanitis). ((baby diaper rash)) is a candidal skin infection that occurs in the area of contact with wet
diapers on the perineum of breastfeeding infants.

Chronic mucocutaneous candidiasis is a chronic resistant disease that affects the mucous membranes,
skin, hair and nails; This disease is associated with the background disorder of T cells.

Means the spread of organisms through the blood to different tissues or organs

• Renal abscesses 2- Myocardial abscesses and endocarditis 3- Brain involvement (often in the form of
meningitis, but small parenchymal abscesses may occur) 4- Endophthalmitis 5- Liver abscesses

• Candida pneumonia that appears as bilateral nodular infiltrates

It is similar to pneumocystis pneumonia

The group of patients with acute leukemia who suffer from severe neutropenia after chemotherapy are
exposed to systemic disease.

The most common endocarditis is fungal endocarditis, which usually occurs in patients with artificial
heart valves or injection drug addicts.
Cryptococcosis :-

Cryptococcosis caused by C.neoformans • Rarely reported in healthy people

This disorder is seen in almost all cases as an opportunistic infection in immunocompromised patients
(especially in people with AIDS or blood-lymphatic malignancies).

• It is a 5-10 micron long yeast with a thick gelatinous capsule that reproduces by budding.

However, unlike Candida, false hyphae or true hyphae are not seen. The capsule plays an essential role
in diagnosis.

The capsule is colored with Indian ink or PAS.

Polysaccharide antigen capsule is the substrate for the latex axonalization test, which is positive in more
than 95% of patients with this disease.

Clinical syndromes:-

• Human cryptococcosis is usually seen as pulmonary disease involving the central nervous system or
disseminated disease

• The most common way of transmission is inhalation of the organism from soil or bird droppings

• The fungus first grows in the lungs and then spreads to other areas of the body (especially) the
meninges. The involvement of body tissues is associated with different responses.

. From the proliferation of gelatinous organisms with little or no infiltration of inflammatory cells (in
infected people) to the granulomatous reaction (in people with a stronger reaction).

• In immunocompromised people, fungi grow in the form of gelatinous masses in the meninges

Opportunistic fungi :-

• Murcormycosis and invasive aspergillosis are rare infections that occur in almost all cases in
immunocompromised people (especially people with hematologic malignancies, severe neutropenia,
corticosteroid administration, or allogeneic bone marrow transplantation).

Mucormycosis morphology is caused by a group of fungi called Zygomycetes.

Their hyphae are without septum and branch at right angles; On the other hand, Aspergillus hyphae
have a septum and branch in the acute angles

Mucor, Rhizopus, two fungi of clinical importance in the group of zygocyte

• Zygocytes and Aspergillus produce a purulent reaction and (sometimes granuloma); In most cases,
they attack the wall of blood vessels and cause vascular necrosis and infarction.

Mucormycosis – Eyes Brain Lungs

Zygomycetes can form colonies in the nasal cavity or sinuses and then spread to the eyeball brain and
other structures of the head and neck.

The greatest risk of fulminant nasopharyngeal mucormycosis is in diabetic ketoacidosis patients.

Pulmonary disease may be limited (for example, cavity formation) or associated with diffuse miliary
involvement.

Invasive Aspergillus:-

• It is almost completely limited to immunocompromised patients. • The fungus preferentially resides in

the lungs and often causes a necrotizing pneumonia. As mentioned, Aspergillus types tend to invade
blood vessels and Therefore, systemic spread (especially brain) is often a fatal complication.

Allergic bronchial-pulmonary aspergillosis :-

• It occurs in patients with asthma

• Increased sensitivity type | Against the fungus that grows in the bronchi, the symptoms of the disease
intensifies

• These patients often have circulating IgE antibodies against Aspergillus and environmental

Aspergillum (fungal ball):-

• With the formation of a fungus colony in already existing lung cavities (for example, dilated bronchi,
lesions Tuberculosis cavity) is created

These may act as ball valves to block the cavity and the field Prepare for infection and hemoptysis

Dimorphic fungi:-

Dimorphic fungi, including B.dermatitidis, C.immitis, and H.Capsulatum, create deep mycoses
(Histoplasma capsulatum, Coccidioides immitis, and blastomyces in Matidis).

• Lung involvement (alone) is seen in people with healthy immunity, while people with weak immunity
present with widespread disease. In this section, due to the common manifestations of these infections,
all three are described together.

Acute pulmonary infection (primary) :-

Primary pulmonary nodules (consisting of accumulations of macrophages full of organisms) are

associated with similar lesions in regional lymph nodes.

With the addition of giant cells, these lesions turn into small granulomas, central necrosis may occur,
and later fibrosis and classification may occur.

Their similarity to primary tuberculosis is very high, and to differentiate these two lesions, observation
of yeasts (with the help of PAS staining with silver) is necessary. Clinical manifestations are similar to
influenza and are often self-limiting.

Chronic perforated lung disease

• It occurs in patients prone to chronic cavitary lung disease (often in the upper lobe), which is similar to
secondary tuberculosis.

These fungi may create a mass in the navel of the lung, which is similar to bronchogenic carcinoma in
radiography.
• At this stage, cough, hemoptysis and even shortness of breath, chest pain are possible to be seen.

Disseminated miliary disease:-

In infants or people with weak immunity (especially due to HIV infection), disseminated disease
(equivalent to millet tuberculosis) may occur. In these conditions, when T cell-mediated immunity is
severely impaired Granuloma is not formed.

Instead, foci of phagocytes full of yeast forms are found inside the cells of the phagocytic apparatus,
such as in the liver, spleen, lymph nodes, lymphoid tissue of the digestive tract, and bone marrow.

Adrenal glands and meninges may also be involved. Be; Rarely, sores develop in the nose, mouth,
tongue, or larynx.

Disseminated disease is associated with severe fever, enlarged liver and spleen, anemia, leukopenia, and
thrombocytopenia. Skin infections in disseminated blastomyces are often associated with
pseudoepitheliomatous hyperplasia and may be misdiagnosed as squamous cell carcinoma.

By using skin tests (equivalent to increased delayed sensitivity in tuberculin), it is possible to diagnose
infection with histoplasma (histoplasmin) and coccidioidin (coccidioidin).

There is no reliable skin test for blastomyces. The best way to diagnose an active infection is direct
observation of the organism in tissue sections and culture of sputum, bone marrow or liver biopsy.

• There are serological methods for detecting anti-fungal antibodies, but they are not sensitive and
specific.

Slide 74:- shows fungal granuloma produced by Aspergillus

Slide 75- also shows fungal granuloma

Slide 76- Hyphae of Aspergillus are seen and Aspergillus has a propensity to invade blood vessels.

Slide 77- Granuloma having a large Langhans gaint cell in center. Two small spherules of coccidioides
immitis are seen.

Slide 78:- The spherule contains endospores and In US C.Immitis is endemic to southwest.

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