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Modern Plague

More than 60 million people are infected by


HIV the causative agent of AIDS 90% in
developing countries
In Israel 5000 HIV + cases 100 AIDS
)2003(
Acquired Immunodeficiency Syndrome

Retroviral Disease Characterized by profound


immunosuppression that leads to
,opportunistic infection
,secondary neoplasms
and neurologic manifestations
Epidemiology
 Homosexual and bisexual men
 Intravenous drug abusers
 Hemophilic and other blood recipients
 Heterosexual contacts of members of a high-
risk group
 2% transmission from mother to child
 6%of cases the risk factor can’t be
determined
Transmission

 Sexual :The virus is carried in the semen, or


vaginal secretions, both within the
lymphocytes and in the cell-free state. Enters
the recipient’s body through abrasions of
rectal, oral or vaginal mucosa.
 Viral transmission occurs in two ways: direct
inoculation into the blood vessels or into the
dentritic cells within the mucosa.
 In USA and Europe 20x1 M-F transmission in
Asia and Africa the risk of F-M transmission is
higher
Transmission

Parenteral: Drug abusers, Hemophilics, and


random recipients of blood

Mother to infant: Tran placental, Birth


canal, Breast milk

Health care workers: 0.3% of


seroconversion in case of accident
HIV I , II

 Protein p24 Target for Ab


used for Diagnosis )ELISA(
 Glycoproteins gp120,
gp41 Critical for HIV infection
of cells
 gag pol env genes
Targets in highly effective anti
HIV Tx.
 nef protein Essential for
progression of HIV infection
:Pathogenesis

 Cell mediated immunosuppression


 Viral tropism to CD4 receptor cells: )Macrophages Dentritic cells
and T lymphocytes( In addition to the CD4 receptors for HIV
,the virus must also bind to a second surface molecule )co-
receptors( for entry into the cell:

CCR5). ) in both Monocytes and T lymphocytes


CXCR4))in T lymphocytes
Individuals who inherit two defective copies
) homozygote( of CCR5 are resistant to develop AIDS(
)M-Tropic and T-tropic strain(
:Pathogenesis

Once internalized ,the viral genome there's two


possibilities
Latency )In “resting” T lymphocytes and in
macrophages for months to years
Transcription in activated T lymphocytes that result
in direct Cell Lysis ,Apoptosis induction, and loss of
immature precursors of Cd4Tcells
 B Cell function is also abnormal
:Pathogenesis

:CNS involvement
The mechanism of HIV induced damage in CNS is not
clear
Most workers believe that Neurologic deficit is caused
indirectly by viral products and soluble factors
produced by infected Microglia
Natural history

Early acute phase :


Represents the initial response of an
immunocompetent adult to HIV )high level of
viral production,viremia, and widespread
seeding of the lymphoid tissue
Nonspecific acute viral symptoms for 2 to
4 weeks )3 to 6 weeks after infection(
Natural history

Middle chronic phase

)not true microbiological latency(


The immune system is intact but there is
continuous HIV replication

Persistent generalized lymphadenopathy, minor opportunistic


infections, thrombocytopenia
Natural history

Final crisis:
Breakdown of host defense, dramatic
increase in plasma virus, and clinical disease
Opportunistic infections and neoplasms in HIV+

tozoal and Helminthic Infections


yptosporidiosis Neoplasms
eumocytosis Kaposi sarcoma
xoplasmosis B cell Lymphoma
Fungal Infections Helminths
Primary Ly. Brain
ongyloides Candidiasis Ca Cx
yptococcosis Stercoralis CNS Tumor
ccidioidomycosis
stoplasmosis

rial Viral
CMV Mycobacteriosis atypical
HSV,VZV .Nocardiosis
ella infections
Pneumocystic Carinii Pneumonia
PCP

(Reactivation of prior latent infection)


This opportunistic infection is the presenting
feature in 20% of AIDS patients, (Before HAART)
and approximately 50% of patients develop
this Infection
PCP
PCP
PCP Silver Stain
PCP SPUTUM
Cryptococcus
Mycosis of worldwide distribution present in
the soil and droppings of birds particularly
.pigeons .Infects patients when it is inhaled
The most feared lesion caused by
C.neoformans is in meninges and brain, that
can affect normal individuals, but is more
. frequently AIDS patients
Cryptococcus Neoformans

Occurs in about 10% of AIDS patients.

It is second in frequency only to Candidiasis


Among fungal infections.

Meningitis is the major clinical manifestation.

Mucicarmin stain is characteristically positive


Cryptococcus Neoformans
Cryptococcus Neoformans
The polysaccharide prevent phagocytosis
CSFCryptococcus Neoformans
CSFCryptococcus Neoformans

MUCICARMIN
Histoplasmosis Infection is acquired by inhalation of
Spores of Histoplasma Capsulatum an intracellular fungi,
parasite unstimulated Macrophages, and are controlled
By helper T cells and activated Macrophages

Clinically resemble Tb:


1) Self limited lung involvement often latent.
2) Chronic secondary lung progression.
3) Extra pulmonary dissemination.

In healthy adults epithelioid granulomas with necrosis


and cavities are seen.
In AIDS patients granulomas are not formed and
macrophages are filled by yeasts
Histoplasmosis
Histoplasmosis
Histoplasmosis
Coccidioidomycosis

 Coccidiodes immitis is a highly contagious fungi. In


endemic areas 80% of the population have a positive
skin test reaction West USA and Mexico
 As is the case of Histoplasmosis most primary
infections are asymptomatic but in 10% have
pulmonary lesions 1% meningeal and skin inf.
 Immunocompromised patients frequently develop
meningitic or disseminated infection
Coccidiodes immitis

The primary and secondary lung lesions of Coccidioides


Immitis are very similar to the granulomatous lesions
of Histoplasmosis.

C. immitis is a thick-walled no budding spherules 20 to


60 microns in diameter filled with small endospores.

A pyogenic reaction appear when the spherules rupture.


Coccidiodes immitis
Coccidiodes immitis
Cryptosporidium parvum

Protozoal parasite, cause a transient watery diarrhea in children


and a chronic debilitating diarrhea in AIDS.

Sporozoites adhered to the intestinal and colonic epithelium


causing malabsorption.
Secretory diarrhea occurs when Sporozoites disrupt the
microvilli and enter the cytoplasm of epithelial cells.

Cryptosporidia shed in the stool and is stained with modified acid


Fast In tissue the parasite lined the edges of colonic epithelial cells
Cryptosporidium parvum
Acid Fast in Coproparasitoscopy
Strongyloides Stercoralis

Free-living female measure 1 mm by 50 microns


Eggs are oval 50 to 60 microns
Life Cycles: Direct, Indirect and Autoinfection
,Once filariform larvae penetrate skin, travel to lungs
migrate up and are swallowed. In proximal GIT mature
.into adult and produce viable eggs
Autoinfectio occurs, when larvae penetrate the bowel
.wall or peri-anal skin and reach the lymphatics
Strongyloides Stercoralis
Strongyloides Stercoralis
Strongyloides Stercoralis
Mycobacteria

Mycobacterial infections are frequently seen with AIDS


Mycobacterium tuberculosis has been increasing in frequency
since the start of the AIDS epidemic.The appearance of
M. tuberculosis with AIDS is similar to that of non-AIDS patients,
with granulomatous pulmonary disease, though the infection
may be more extensive or may be disseminated to other organs.
Mycobacterium Avium Complex (MAC) infection is more unique
to AIDS .Is characterized by involvement mostly of the
organs of the mononuclear phagocyte system (lymph node,spleen,
liver, marrow).
MAC infections are less likely to produce visible granulomas,
and the lesions often consist of clusters of macrophages filled with
numerous Mycobacteria. Definitive diagnosis of mycobacterial
disease is made by culture.
Mycobacterium Tuberculosis
Lung infection showing histio-
cytes containing bacilli

Mycobacterium Avium
Macrophages filed mycobacteria
Progressive Multifocal Leukoencephalitis

JC Polyomavirus infect Oligodendrocytes and demyelination


is the principal pathology
The JC virus infects 80% of the human population
before adulthood without producing overt illness .

The virus typically remains latent,


unless there is reactivation due to immunodeficiency .

PML appears to have a strong association with AIDS


Kaposi Sarcoma

 Vascular tumor rare in immunocompetents,


but the most common neoplasm in AIDS
 May arise early before the immune system. is
compromised.
 The tumor cells are primitive mesenchymal cells that
can form vascular channels
 HHV type 8 is all wise present in tumor but the
causation role of virus is not clear.
 Clinically HIV associated KS differ from the sporadic
form
AIDS related Lymphoma

 6% of AIDS patients develop lymphoma 120-fold


greater than in the general population
 In contrast to KS immunodeficiency is firmly
implicated as the central predisposing factor
 Three groups on the basis of location: Systemic 80%
/ CNS 20% )EBV related( / Body cavity-based
lymphoma )rare()HHV8 related(
 Aggressive B cell Lymphoma
GIT Lymphoma
CNS and AIDS

 In addition to infections and neoplasms, several


neuropathologic changes occur
 Self limited meningoencephalitis at the time of
seroconversion
 Aseptic meningitis
 Vacuolar myelopathy
 Peripheral neuropathies
 AIDS dementia complex )progressive encephalopathy(
Giant Cell Encephalitis in Aids
! I'mDiego , andI paint what I see

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