Infectious Disease (Intro, Viral, Fungal Infection)

What is the general principles of microbial pathogenesis?

Entry

Adhesion

Invasion

Propagation

Damage

Exit

How are most pathogens transmitted?

From person to person by:

• Respiratory

• Fecal-oral

• Sexual routes

What are some examples of respiratory (aerosolized) viruses/bacteria?

Influenza virus

M. tuberculosis and varicella-zoster virus

What are some examples of enteric pathogens: fecal-oral route?

Hepatitis A and E virus (HAV, HEV)

Poliovirus

Rotavirus

V. Cholera

Shigella spp.

C. jejuni

S. enterica

Hookworm, schistosomes

What are some examples of sexually transmitted: mucosal contact?

Virus → Herpes simplex virus (HSV), HIV, human papillomavirus (HPV)

Bacteria → Treponema pallidum, Neisseria gonorrhoeae

Protozoa → Trichomonas vaginalis

Arthropods → Phthisis pubic, lice

What is virulence?

A pathogen’s relative capacity or degree to overcome a host’s immune defense and cause disease

What does virulence relate to?

To the ability to adhere to:

• Host cells

• Invade cells and tissues

• Deliver toxins

What is bacteremia?

Bacteria in the blood

What is the difference between bacteremia and septicemia?

One is bacteria in the blood

The other is sustained bloodstream invasion and dissemination of pathogens

How does septicemia manifest?

Fever

Low arterial pressure

Other signs/symptoms of sepsis

What are some examples of septicemia?

Viremia

Bacteremia

Fungemia

Parasitemia

What will happen if septicemia is allowed to progress?

The organism may multiply and cause DIC with widespread hemorrhage and thrombi

What are the major categories of infectious agents?

Virus

Bacteria

Fungi

Parasites (protozoa and helminths)

Which patients are most susceptible to severe opportunistic infections?

HIV/AIDS

Transplant recipients

Chemotherapy patients

Steroid users

Congenital immunodeficiency

What are opportunistic organisms?

Organisms that can cause disease in immunocompromised individuals but not in people with an intact immune system

• The most devastating immunodeficiency is that caused by infection with HIV

What are some examples that can increase the susceptibility to opportunistic organisms?

Leukemia – suppresses bone marrow function

Immunosuppressive drugs

• Aspergillus spp. and Pseudomonas spp.

Decline in immune response – reactivation of latent infection

• Herpesviruses and M. tuberculosis

Cystic fibrosis

• Pseudomonas aeruginosa and Burkholderia cepacian

Sickle cell disease

• P. aeruginosa

Age-related decline and malnutrition

What is the mechanisms of injury of a virus?

Directly damage host cells by entering them and replicating at the hosts expense

Direct cytopathic effects, antiviral immune responses, and transformation of infected cells

What is tropism?

Predilection for viruses to infect certain cells and not others

What is a major determinate of tissue tropism?

The presence of viral receptors on host cells

What is the mechanisms of injury of bacteria?

Pathogenic bacteria have virulence genes that encode proteins responsible for key bacterial properties

• Adhesins and pili

• Bacterial endotoxin and exotoxins delivery

What does it mean when a patient is more virulent?

They have less chance for transmission

What is a common pathogenesis for a suppurative (purulent) infection?

Formation of “pus”

What highlighted viral species affect the digestive system?

Mumps

Hepatitis B

What highlighted viral species is systemic with skin eruptions?

Measles

Rubella

Varicella-zoster

HSV 1/2

What highlighted viral species is systemic with hematologic disorders

Cytomegalovirus

EBV

HIV 1/2

What highlighted viral species inflict arboviral and hemorrhagic fevers?

Dengue virus 1-4

Yellow fever

What highlighted viral species affects the central nerve system?

Poliovirus

Which viral species is associated with skin/genital warts?

Human papillomavirus

Which virus is the leading cause of vaccine-preventable death and illness worldwide?

Measles

What type of individuals often experience severe cases of measles?

Immunocompromised individuals

How does the T-cell immune system respond to measles?

Distinct skin exanthem

• Diffuse, blotchy reddish-brown rash

  • Face, trunk, proximal extremities

Ulcerated mucosal lesions (oral cavity)

• Necrosis

• Exudate

How is measles transmitted?

Via respiratory droplets

What are the major surface cell receptors in measles?

CD46

SLAM

Nectin

What is the life cycle of measles?

Initially multiples in respiratory tract

Spreads to local lymphoid tissue

Later disseminates:

• Lymphoid

• Blood vessels

What cells are commonly seen in measles?

Warthin-Finkeldey (WF) cells

What virus causes measles?

Measles virus (a paramyxovirus)

What are the 3 C’s of measles?

Cough

Coryza (runny nose)

Conjunctivitis

What are Koplik spots?

Small white lesions on the buccal mucosa that appear before the rash and are pathognomonic for measles

What serious CNS complication can occur years after measles infection?

Subacute sclerosing panencephalitis (SSPE)

What vitamin deficiency worsens measles severity?

Vitamin A deficiency

What virus causes mumps?

Mumps virus (a paramyxovirus)

• Acute, systemic viral infections

What is the classic clinical manifestation of mumps?

Parotitis (painful swelling of the parotid gland)

• Usually bilateral (70%)

• Infect salivary gland epithelial cells

What salivary gland is most commonly affected?

Parotid gland

How is mumps transmitted?

Via respiratory droplets

What are the gross features of affect glands in mumps?

Enlarged

Doughy

Moist

Glistening

Reddish-brown

What is the life cycle of mumps?

Spread to draining LNs

Replicate in lymphocytes

Spread in blood to other organs/glands

Which organs/glands are commonly affected by mumps?

Testis → Atrophy,, infertility

Ovary → Infertility

Pancreas

CSN (aseptic meningitis)

What histologic findings may be seen in mumps parotitis?

Mononuclear inflammatory infiltrates

Edema

Acinar cell necrosis

How is poliovirus transmitted?

Fecal-oral route (CD155)

How does polio manifest?

Mild, self-limited infection to paralysis of limb and respiratory muscles

What cells cause paralysis in poliomyelitis?

Motor neurons of the spinal cord and brainstem

What is the life cycle of poliovirus?

Replicates in mucosa (pharynx, tonsil, Peyer’s patches)

Spreads via lymphatics → LNs → Blood

Replicates in motor neurons (spinal cord, brainstem)

What type of virus is West Nile virus?

Arbovirus (Flavivirus)

Most patients with West Nile virus develop what type of illness?

Asymptomatic or mild self-limited infection

Maculopapular rash, petechiae

What type of complications make but 1.5% of West Nile virus cases?

CNS complications

• Meningitis

• Encephalitis

• Meningoencephalitis

What is the life cycle of West Nile Virus?

Replicates in skin dendritic cells

Migrate to LNs

Enter bloodstream and cross blood-brain barrier

How is West Nile Virus transmitted?

Arthropod-borne virus (mosquito vector, bird amplifier host)

Who are the discussed “dead end” hosts of West Nile virus?

Horses

Humans

How is viral hemorrhagic fever transmitted?

Via animal or insect host

• Mosquitoes

• Person-to-person common with Ebola

How does the mild acute form of viral hemorrhagic fever present?

Fever

Headache

Myalgia

Rash

Neutropenia

Thrombocytopenia

How does the severe and life-threatening form of viral hemorrhagic fever present?

Sudden hemodynamic deterioration and shock

Petechiae

Hemorrhage

Necrosis

What are the different types of enveloped RNA viruses of viral hemorrhagic fever and their associated illnesses?

Adenoviridae → Lassa

Filoviridae → Ebola

Flaviviridae → Dengue, Yellow yellow

Bunyaviridae → Hantavirus

How is zika virus transmitted?

Transmission via mosquitoes

• Perinatal transmission

• Infect through blood and sexual contact

How does zika virus manifest in adults?

Mild and nonspecific

Fever

Myalgia

Arthralgia

Conjunctivitis

Maculopapular rash lasting a few days to 1 weeks

What kind of complication can a small number of zika virus infected adults develop?

Neurologic complications

• Guillain-Barre syndrome

How does zika virus manifest in prenatal cases?

Fetal death

Moderate severe brain defects

• Fetus

• Newborn child

Calcification

Atrophy

Hypoplasia

Which receptor does SARS-CoV-2 use to enter cells?

ACE2 receptor

What inflammatory cytokines are strongly associated with severe COVID-19?

IL-6

TNF-α

What pediatric syndrome is associated with COVID-19?

MIS-C (Multisystem Inflammatory Syndrome in Children)

How is COVID-19 transmitted?

Respiratory droplets

Aerosolization

How does COVID-19 manifest as?

Fatigue

Weakness

Dyspnea

Chest pain

Cough

What phycological symptoms present with COVID-19?

PTSD

Memory or concentration problems

Anxiety

Depression

How are poxvirus transmitted?

Transmitted via:

• Bodily fluids

• Mucosal membranes

• Respiratory droplets

• Infected animals

• Contaminated objects

• Vertical transmission transplacentally or during birth

What are some animal reservoir for poxvirus?

Squirrels

Gambian rats

Dormice

Monkeys

What variola virus is poxvirus 96% similar to?

Smallpox (Orthopoxvirus)

What are common histologically presentations of poxvirus?

Guarnieri bodies

Ground glass keratinocyte nuclei with basophilic halo and multinucleation

What is the common progression of poxvirus lesion?

Macules → Papules → Vesicles → Pustules → Ulcers

What are classic clinical manifestations of HSV?

Fever blisters, cold sores

Gingivostomatitis

Genital herpes

Corneal lesions

Disseminated

• Herpes esophagitis

• Herpes bronchopneumonia

• Herpes hepatitis

Where does HSV establish latency?

Sensory neurons

How is HSV-1 and HSV-2 distinguished?

Genetically similar

Serologically different

Where does HSV replicate?

The skin and the mucous membranes

• Usually, oropharynx or genitals

What histologic findings are classic for HSV?

Cell fusion → Inclusion-bearing multinucleated syncytia

Glassy pink to purple coloration

Chromatin margination

What form of HSV is commonly associated with oral herpes?

HSV-1

What form of HSV is commonly associated with genital herpes and vertical transmission through the birth canal?

HSV-2

What disease results from primary varicella zoster virus infection?

Chickenpox (varicella)

Which group is affect by chickenpox (varicella)?

Mild in children

Severe in adults and immunocompromised

What disease results from varicella zoster virus reactivation?

Shingles (herpes zoster)

What lesion description is classic for chickenpox?

"Dewdrop on a rose petal"

• Macules to papules

What are common presentations of shingles (herpes zoster)?

Vesicular lesions

Itching, burning, and sharp pain

How is varicella zoster virus transmitted?

Via aerosols, disseminates hematogenously, causes widespread vesicular lesions

• Infects skin/mucous membranes and associated neurons

What histologic finding is pathognomonic for cytomegalovirus?

Owl-eye inclusions

What determines the severity of disease manifestation of cytomegalovirus?

Host immune status and age

What cells are infected in cytomegalovirus?

Monocytes and their bone marrow progenitors

Congenital CMV causes what triad?

Microcephaly

Periventricular calcifications

Hearing loss (high-yield addition)

How is cytomegalovirus transmitted?

Via transplacental, neonatal, saliva, genital, organ transplants, and blood transfusion

What are the clinical presentation for congenital: in-utero transmission CMV?

Cytomegalic inclusion disease

IUGR

Jaundice

Hepatosplenomegaly

Anemia

Thrombocytopenia

Encephalitis

Microcephaly with foci of calcification (fatal)

What are the clinical presentation for perinatal (vertical or breast milk transmission) CMV?

Mostly asymptomatic by shed virus for month the years

Interstitial pneumonitis

What are the clinical presentation for mononucleosis CMV?

Fever

Atypical lymphocytosis, lymphadenopathy

Hepatitis, marked hepatomegaly

What are the clinical presentation for immunosuppressed (HIV, transplant) CMV?

Severe primary infections

Severe latent infections

• Primarily effects lung, can progress to ARDS

• Necrosis of intestine and lung

What disease is classically associated with EBV?

Infectious mononucleosis