Microbial causes of

Opportunistic Infection
Definitions

• OIs are infections more frequently and are more severe in people
with weakened immune systems, including people with HIV.

• considered as AIDS-defining conditions

• caused by bacteria, fungi, and parasites

Some of the most common OIs are:
Herpes simplex virus
Candidiasis (thrush)
Tuberculosis (TB)
Salmonella infection(GIT)
Toxoplasmosis—a parasitic infection that
can affect the brain
 Herpesviruses
chronic/latent/recurrent infections
 General feature

• Enveloped dsDNA, icosahedral symmetry.

• Contain many important human pathogens

• Establish lifelong persistent infections

• Latency infections in neurons is its specialty

• Periodic reactivation

• Herpes: the lesions are creeping in nature

Gingivitis (swollen, tender gums)
 Herpes virus types that infect
humans
• Herpes simplex I & II: (oropharynx and cold sores, genital
herpes)
• CMV , EBV and HHV-6 : persist in lymphocytes
• Varicella zoster : (chicken pox, shingles)
• CMV: (microcephaly, infectious mononucleosis)
• Epstein-Barr virus: (mononucleosis, Burkitt’s lymphoma)
• Human herpesvirus 6 & 7 (Roseola)
• Human herpesvirus 8 (Kaposi’s sarcoma)
Classification of Human Herpesviruses
• Family Herpesviridae
Sub family –herpesvirinae
Sub family Genus Official name Common
Alpha simplex HHV 1 Herpes simplex type 1
HHV 2 Herpes simplex type 2
________________________________________
Varicello HHV 3 Varicella Zoster virus
_________________________________________________________
Beta herpevi Cytomegalo HHV 5 Cytomegalovirus
Roseolo HHV 6 HHV 6
HHV 7 HHV 7
____________________________________________________________
Gamma her Lymhocrypto HHV 4 Epstein-Bar virus
Rhadino HHV 8 Kapossi’s sarcoma associated
herpes virus
 Herpes Simplex
Viruses
• Extremely widespread in the human population.

• Broad host range, being able to replicate in many types of

cells and to infect many different animals.

• They grow rapidly and are highly cytolytic.

• Responsible for a spectrum of diseases, ranging from

gingivostomatitis to keratoconjunctivitis,
encephalitis, genital disease, and infections of
newborns.
 Properties of the HSV 1
and 2
• There are two distinct HSVs: type 1 and type 2 (HSV-1, HSV-2).

• Their genomes are similar in organization

• They can be distinguished by sequence analysis.

• The two viruses cross-react serologically, but some unique proteins

exist for each type.

• They differ in their mode of transmission

• HSV-1 is spread by contact, usually by infected saliva.

• HSV-2 is transmitted venereal or congenitally

Characteristics HSV-1 HSV-2
Clinical
Primary infection:
• Gingivostomatitis + -
• Pharyngotonsillitis + -
• Keratoconjunctivitis + -
• Neonatal infections ± +
Recurrent infection:
• Cold sores, fever blisters + -
• Keratitis + -
Primary or recurrent infection:
Cutaneous herpes
• Skin above the waist + ±
• Skin below the waist ± +
• Hands or arms + +
• Herpetic whitlow + +
• Eczema herpeticum + -
• Genital herpes ± +
• Herpes encephalitis + -
 Characteristics
HSV causes cytolytic infections

Lesions induced in the skin and mucous membranes

by HSV-1 and HSV-2 resemble those of VZV.

Characteristic histopathologic changes include

 ballooning of infected cells

 Cowdry type A inclusion bodies

 formation of multinucleated giant cells.

 Clinical findings
• Oropharyngeal Disease

• Primary (pharyngitis and tonsillitis) usually asymptomatic.

• Symptomatic disease occurs most frequently in small children

<5

• The incubation period is about 3–5 days.

• Symptoms include fever, sore throat, lesions, gingivostomatitis,

and malaise.

• Primary infections in adults

 Skin Infections
Intact skin is resistant to HSV, uncommon in healthy
persons.
It occur abrasions that become contaminated with the
virus (traumatic herpes).
These lesions are seen on the fingers of dentists and
hospital personnel (herpetic whitlow) and on the bodies
 Neonatal Herpes
• Acquired in utero, during birth, or after birth.

• The mother is the most common source of

infection.
• The newborn infant seems to be unable to limit
the replication and spread of HSV and has a
propensity to develop severe disease.
DP Monga-DMIP
 Laboratory diagnosis
• Cytopathology

• A rapid cytologic method is to stain scrapings obtained

from the base of a vesicle (E.g., with Giemsa's stain)

• The presence of multinucleated giant cells indicates

that herpesvirus (HSV-1, HSV-2, or varicella-zoster) is
present= Inclusion bodies
Isolation and identification of virus

• Inoculation of tissue cultures is used for viral

isolation.

• Then identified immunofluorescence staining with

specific antiserum.

• Typing of HSV isolates may be done using antibody

• Polymerase Chain Reaction (PCR) used to detect

 Serology
• Antibodies appear in 4–7 days after infection and
reach a peak in 2–4 weeks.

• They persist with minor fluctuations for the life of the

host.

• The diagnostic is limited by the multiple antigens

shared by HSV-1 and HSV-2.
 Cytomegalovirus(HHV-5)
• The largest of the Herpesviruses, genome ~240kbp

• CMV infection are 'slow' - 7-14 days

• More than 50 % population experienced infection by the age of

40

• Most infections are asymptomatic except people with immune

defects (T-cell defects) /pregnancy / newborns (congenital)

• Reactivations or re-infections are common throughout life.

 Immunocompromised individuals
• Both primary and recurrent infection may lead to
symptomatic disease.

• Primary CMV infection is usually more severe

than recurrent infection, with the exception of
bone marrow transplant recipients, where both
are just as severe.
Clinical Manifestations
• Fever
• Pneumonitis
• Hepatitis
• Gastrointestinal manifestations eg. colitis
• Encephalopathy
• Retinitis
• Poor graft function
 AIDS Patients
• CMV disease is present in 7.4% to 30% of all AIDS
patient.

• Sight-threatening retinitis, colitis, and encephalopathy

are the most common manifestations of CMV disease
in AIDS patients.

• Pneumonitis is extremely rare.

 Solid organ transplant
recipients
• Most common infection, leading cause of morbidity and
mortality.

• Occurs 1 - 3 months following transplant.

• Primary infection more severe than recurrent infection

Except Bone marrow transplanted.

• Does not appear to be associated with organ rejection.

 Congenital CMV Infection
• Mother infected in pregnancy : fetus at high risk

• Maternal infection usually asymptomatic

• Fetal infection asymptomatic to severe and disseminated

• Fetus damaged at any stage

• Severe developmental defects

• Mental retardation / deafness

Laboratory Diagnosis (CMV)

1 Cytology / histology : large cytomegalic 25-35 um intranuclear

inclusions-”owl’s eye”

2 Culture -Gold standard

4-6 weeks

3 Nucleic acid antigen detection IFA, IE

4 Serology

5 PCR
Cytopathic Effect of CMV

(Courtesy of Linda Stannard, University of Cape Town, S.A.)

Treatment (CMV)

• Ganciclovir - is the drug of choice

• Forscarnet - can be used as the 2nd line drug.

• Cifofovir (HPMCC) - approved for the treatment of CMV retinitis.

Fomivirsen - intravitreal fomivirsen is approved for the treatment
of CMV retinitis.

• CMV hyperimmune globulin - found to be effective against CMV

pneumonitis.
Epstein-Barr Virus(HHV-
4)

DP Monga-DMIP
Epstein-Barr Virus
• Ubiquitous

• Acute infectious mononucleosis / nasopharyngeal carcinoma

• Burkitt’s Lymphoma

• Dual cell tropism for human B-lymphocytes (generally non-

productive infection) and epithelial cells (productive infection).

• Highly host specific-No suitable animal host

Epstein-Barr Virus
• DNA genome about 172 kbp

• Two viral types: EBV1 and EBV2

• Depending on:

• Variation in genome
• Structure
• Antigen expression
• Biologic properties
Epstein-Barr Virus-clinical……
• Primary infection-infected saliva

• Incubation period30-50 days

• Initiate infection in oropharynx

• Replication in B cells or epithelial cells

• Sore throat, head ache

• Fever, malaise, fatigue

• Enlarged Lymphnode
Epstein-Barr Virus-clinical……
Young adults:

• Infectious mononucleosis: Autoantibodies

Self limiting lasts 2-4 weeks

Symptoms like primary infection

• Oral Hairy Leukoplakia: Wart like growth on tongue of some HIV

persons and transplant patients.

• It is an epithelial focus of EBV replication

• Burkitt’s lymphoma: B cell lymphoma

Hairy leukoplakia
Often presents as white plaques or warts on the
lateral surface of the tongue and is associated
with EBV infection.
 Burkitt's lymphoma

• Tumor of jaw

• African children

• Contain EBV DNA

• Genetic and environmental factors

• High levels of antibody to HBV

 Summary :Human Herpesviruses

Virus Subfamily Disease Site of Latency

Herpes Simplex Virus I a Orofacial lesions Sensory Nerve Ganglia
Herpes Simplex Virus II a Genital lesions Sensory Nerve Ganglia
Varicella Zoster Virus a Chicken Pox Sensory Nerve Ganglia
Recurs as Shingles

Cytomegalovirus b Microcephaly/Mono Lymphocytes

Human Herpesvirus 6 b Roseola Infantum CD4 T cells
Human Herpesvirus 7 b Roseola Infantum CD4T cells

Epstein-Barr Virus g Infectious Mono B lymphocytes, salivary

Human Herpesvirus 8 g Kaposi’s Sarcoma Kaposi’s Sarcoma Tissue
 Opportunistic Mycoses

• The opportunistic mycoses caused by fungi

that can’t infect healthy humans but can
cause serious often fetal mycoses in
people whose resistance has been lowered
(immunocompromised patients).

40
• The highly susceptible groups for
opportunistic fungal infection are
• AIDs patients,
• Leukemic patients,
• individuals on chemotherapy for
treatment of cancer,

41
• Although there is an ongoing list of opportunistic
mycosis, some are seen more often and includes:

• Candidousis (candidiasis),

• Cryptococcosis,

• Aspargillosis,

• Zygomycosis

• Trichosporonsis

42
Thank u

43