Infectious Diseases

Viral Infections:TRANSIENT VIRAL INFECTIONS: are structurally heterogeneous. elicits an immune response that eliminates the virus

and may or may not confer lifelong protection. The mumps virus, for example, has only one

serotype and infects people only once. influenza viruses, can repeatedly infect the same

individual owing to antigenic variation. The immune response to respiratory syncytial virus

wanes with time, allowing even the same serotype of virus to infect repeatedly

Measles: single-stranded RNA virus of paramyxovirus family spread by respiratory droplets, initially multiplies within

upper respiratory epithelial cells. then spreads to lymphoid tissues, where it can replicate

in mononuclear cells, including T lymphocytes, macrophages, and dendritic cells.

then spreads by blood throughout the body. Measles may cause croup, pneumonia, diarrhea, keratitis

with scarring and blindness, encephalitis(SSPE), and hemorrhagic rashes ("black measles") in malnourished children .

Morphology: blotchy, reddish-brown rash on face, trunk, and

proximal extremities produced by dilated skin vessels, edema, and a moderate nonspecific mononuclear perivascular infiltrate.

Ulcerated mucosal lesions in oral cavity (the pathognomonic Koplik spots) are marked by necrosis, neutrophilic exudate, and neovascularization.

The lymphoid organs: marked follicular hyperplasia, large germinal centers, and randomly distributed multinucleate giant cells (Warthin-Finkeldey cells) which have eosinophilic nuclear and cytoplasmic inclusion bodies are pathognomonic of measles and are also found in lung and sputum

Mumps: member of paramyxovirus family. enter upper respiratory tract through inhalation

of respiratory droplets. spread to draining lymph nodes where they

replicate in lymphocytes (preferentially in activated T cells).

then spread through blood to salivary glands. Mumps virus also can spread to central nervous

system, testis, ovary, and pancreas. Aseptic meningitis is most common extra salivary

gland complication of mumps infection, occurring in about 10% of cases.

Morphology: mumps parotitis: bilateral in 70% of cases,

affected glands are enlarged, have a doughy consistency, and are moist, glistening, and reddish brown on cross-section.

On microscopic examination, the gland interstitium is edematous and diffusely infiltrated by macrophages, lymphocytes, and plasma cells, which compress acini and ducts.

mumps orchitis: testicular swelling caused by edema, mononuclear cell infiltration, and focal hemorrhages. swelling may compromise blood supply and cause areas of infarction.

Pancreas: lesions may be destructive, causing parenchymal and fat necrosis and neutrophil-rich inflammation.

Mumps encephalitis.

Poliovirus Infection: spherical, unencapsulated RNA virus of enterovirus

genus. like other enteroviruses, is transmitted by fecal-oral

route. It first infects tissues in oropharynx, is secreted into

saliva and swallowed, and then multiplies in intestinal mucosa and lymph nodes, causing a transient viremia and fever.

Although most polio infections are asymptomatic, in about 1 of 100 infected persons poliovirus invades central nervous system and replicates in motor neurons of spinal cord (spinal poliomyelitis), or brain stem (bulbar poliomyelitis).

Viral Hemorrhagic Fevers: VHFs are systemic infections characterized by fever

and hemorrhage. Caused by enveloped RNA viruses in four different

families: arena viruses, filo viruses, bunya viruses, and flavi viruses.

All depend on an animal or insect host for survival and transmission. Humans are infected when they come into contact with infected hosts or insect vectors.

human-to-human transmission can occur. There are no cures or effective drug therapy. VHF viruses are potential biologic weapons.

The pathogenesis of hemorrhagic manifestations are due to thrombocytopenia, or severe platelet or endothelial dysfunction.

there is increased vascular permeability. There may be necrosis and hemorrhage in many

organs, and often there is widespread hepatocellular necrosis.

CHRONIC LATENT VIRAL INFECTIONS (HERPES VIRUS INFECTIONS): Herpes viruses are large encapsulated viruses

that have a double-stranded DNA genome that encodes approximately 70 proteins.

Herpes viruses cause acute infection followed by latent infection in which the viruses persist in a noninfectious form with periodic reactivation and shedding of infectious virus.

There are nine types of human herpes viruses, belonging to three subgroups :

α-group viruses: including herpes simplex virus-1 (HSV-1), HSV-2, and varicella zoster virus (VZV), which infect epithelial cells and produce latent infection in neurons.

β-group viruses: including CMV, human herpesvirus 6 ( causes exanthem subitum which is a benign rash of infants),and human herpesvirus7 (not yet associated with a specific disease).

γ-group viruses: KSHV/HHV-8 ( cause Kaposi sarcoma).

Herpes Simplex Virus: HSV-1 and HSV-2 differ serologically but are genetically

similar and produce acute and latent infections. Both viruses replicate in skin and mucous membranes at

site of entrance of virus (usually oropharynx or genitals), and cause vesicular lesions of epidermis.

The viruses then spread to sensory neurons that innervate these primary sites of replication, where viruses establish latent infection.

Morphology: All HSV lesions are marked by formation of large pink to

purple intranuclear inclusions (Cowdry type A) that contain intact and disrupted virions and push darkly stained host cell chromatin to edges of nucleus.

Gingivostomatitis: caused by HSV-1. Genital herpes: usually by HSV-2, but also HSV-1. Herpesvirus (usually HSV-2) can be transmitted to

neonates through birth canal of infected mothers.

HSV-1 is the major infectious cause of corneal blindness.

Herpes simplex encephalitis: by HSV-1 and HSV-2 KSHV/HHV8 : Kaposi sarcoma.

Cytomegalovirus: β-group herpesvirus, can produce a variety of diseases

depending on age of host, and more important on host's immune status.

CMV causes a symptomatic or mononucleosis-like infection in healthy individuals ,but devastating systemic infections in neonates and in immunocompromised patients.

As its name implies, cytomegalovirus produces enlargement of infected cells. Infected cells exhibit gigantism of both entire cell and its nucleus. Within the nucleus is a large inclusion surrounded by a clear halo (owl's eye).

Transmission of CMV can occur by several mechanisms :

• Transplacental transmission ("congenital CMV")• Transmission of virus through cervical or vaginal

secretions at birth ("perinatal CMV")• Transmission through saliva.• Transmission by venereal route .• Iatrogenic transmission through organ transplants

or by blood transfusions.

Varicella-Zoster Virus : Acute infection with VZV causes chickenpox( Varicella );

reactivation of latent VZV causes shingles ( zoster). In contrast to HSV, VZV is transmitted in epidemic

fashion by aerosols, disseminates hematogenously, and causes widespread vesicular skin lesions.

VZV infects neurons in dorsal root ganglia and may recur many years after the primary infection, causing shingles.

In contrast to numerous recurrences of HSV, VZV usually recurs only once, most frequently in immunosuppressed or elderly persons.

Morphology: The chickenpox rash occurs approximately 2 weeks

after respiratory infection and travels in multiple waves centrifugally from the torso to head and extremities.

On histologic examination, chickenpox vesicles contain intranuclear inclusions in epithelial cells like those of HSV-1 .

Shingles occurs when VZVs that have long remained latent in dorsal root ganglia after a previous chickenpox infection are reactivated and infect sensory nerves

CHRONIC PRODUCTIVE VIRAL INFECTIONS: The immune system is unable to eliminate the

virus, and viral replication leads to persistent viremia.

The high mutation rate of viruses such as HIV and hepatitis B may allow them to escape control by immune system.

Hepatitis B Virus: significant cause of acute and chronic liver disease

worldwide. HBV is a DNA virus that can be transmitted

percutaneously (e.g., intravenous drug use or blood transfusion), perinatally, and sexually.

in chronic hepatitis: lymphocytic inflammation, apoptotic hepatocytes and progressive destruction of liver parenchyma.

Long-term viral replication can lead to cirrhosis of liver and an increased risk for hepatocellular carcinoma.

In some patients, immune response resulting in establishment of a "carrier" state without progressive liver damage.

TRANSFORMING VIRAL INFECTIONS: includes viruses that causing human cancer: Epstein-Barr virus (EBV), human papilloma virus (HPV), HBV, and human T-cell leukemia virus-1 (HTLV-1). Epstein-Barr Virus (EBV): causes infectious mononucleosis ( a benign self-limited

lympho proliferative disorder). Also hairy leukoplakia , certain lymphomas , and

nasopharyngeal carcinoma. Infectious mononucleosis is characterized by fever,

generalized lymphadenopathy, splenomegaly, sore throat, and atypical T - lymphocytes (mononucleosis cells) in blood .

EBV is transmitted by close human contact( saliva ).

Morphology: peripheral blood : absolute lymphocytosis .

Many of these are large atypical lymphocytes with an oval indented or folded nucleus, and scattered cytoplasmic azurophilic granules .

lymph nodes: discrete and enlarged throughout the body principally in posterior cervical, axillary, and groin regions.

On histologic examination expansion of paracortical area ( T-cell area ).

Human Papillomaviruses (HPVs): Non- enveloped DNA viruses that are members

of papova virus family. Based on DNA sequence, papillomaviruses are

classified into over 100 types. Some HPVs cause warts, benign tumors of

squamous cells on skin ( papillomas ). Other HPVs are associated with warts that can

progress to malignancy, particularly squamous cell carcinoma of cervix and anogenital area.

Papillomaviruses are mainly transmitted by skin or genital contact.

HPVs infect squamous epithelial cells, but their life cycle is not well understood since these viruses cannot be cultured in vitro.

In upper layers of stratified epithelium, HPV leads to a characteristic perinuclear vacuolization in epithelial cells (koilocytosis).

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