Opportunistic Infections

Shelbay G. Blanco, MD, MPH

Preventive and Social Medicine II
 Objectives

• Discuss basic factors regarding Opportunistic infections (OIs)

• See the frequency with which these OIs occur & clinical features,
Diagnosis & treatment of some OIs.
• Discuss patient education messages for preventing OIs.
PATHOGEN
“A pathogen is a microbe or microorganism
such as a virus (such as HIV), bacterium
(such as staph), prion, or fungus (such as
yeast) that causes disease in its animal or
plant host”.
First devised in 1880.
Patients are susceptible
to bacterial, fungal,
parasitic and viral
infections

HIV, Cancer
chemotherapy, bone
marrow transplantation,
immune deficiency
disorder or blood
disorders . 22
 The basics of OIs

• HIV infects a type of WBC called CD4 cells

• When the immune system loses too many CD4
cells OIs are more likely to develop
• Different type of OIs develop at different levels of
CD4 count, depending on the microbes or
pathogens endemic in that particular region
 PATHOGENESIS
“The pathogenesis of a disease is the
mechanism by which the disease is
caused. The term can also be used to
describe the origin and development
of the disease and whether it is
acute, chronic or recurrent”.
 OPPORTUNISTIC PATHOGEN
 “An infectious microorganism that is
normally a commensal or does not harm its
host but can cause disease when the host’s
resistance is low”.

OPPORTUNISTIC INFECTION
 “An opportunistic infection is an infection
caused by pathogens, particularly
opportunistic pathogens”.
OPPORTUNISTIC CONDITIONS
 When the immune system isn’t working
properly, normal flora can overpopulate or
move into areas of the body where they do
not normallyoccur.
 When the balance of normal microbes is
disrupted, for example when a person takes
broad spectrumantibiotics.
 Disease can result when normal flora are
traumatically introduced to an area of the
body that is axenic or that they do not
normally occur in.
 Causes of Immunodeficiency
 Malnutrition
 Chemotherapy forcancer
 Skin damage
 Medical procedures
 Pregnancy
 Immunosuppressing agents for organ transplant
recipients
 The concomitant presence of certain underlying
diseases such as cancer, diabetes, cystic fibrosis
 Side effects of certain medical therapies and drugs
such as corticosteroids
 Infection with immunity-destroyingmicroorganisms
 Age, both old and young
 Definition

• An infection by a microorganism when

the body's immune system is impaired
and unable to fight off infection, as in
AIDS, Infants, neutropenia, and
congenital
GENERAL INTRODUCTION OF AIDS

 Acquired immunodeficiency syndrome(AIDS)

 Humanimmunodeficiency virus (HIV)
 Retrovirus
 CD4 T cells, macrophages and dendrite cells.
 Cellular immunity islost.
 leaves individuals susceptible to various
opportunistic infections
 AIDS Definition

• CDC definition of an HIV +ve person as having AIDS

-- Has had at least one of over 21 AIDS defining OIs
and/or
--Has had a CD4 cell count of 200 or less

• NACO Definition: AIDS has been defined as the occurrence of life

threatening opportunistic infections, malignancies, neurological
diseases and other specific illnesses in patients with HIV infection
and/or with CD4 count less than 200/cmm
Opportunistic infections association with
HIV and AIDS
 HIV does not kill anybody directly.
 People with HIV can get many infections called
opportunistic infections.
 Many of these illnesses are very serious, and they need to be
treated and some can be prevented.
 People with advanced HIV infections are vulnerable to
infections and malignancies.
 Opportunistic Infections are caused by various pathogenic
microorganisms such as
bacteria, fungi, virus and parasites.
OI (CDC GUIDELINE 2011) • BACTERIA
• PARASITES • Mycobacterium avium
• Isosporiasis, chronic complex
intestinal (greater • Tuberculosis
• Pneumonia -recurrent
than 1 month's • Progressive
duration) multifocal
leukoencephalopat
• Toxoplasmosis of hy
brain • Salmonella septicemia-
recurrent
• Cryptosporidiosis,
• Neurosyphilis Syphilis
chronic intestinal • Bartonellosis
(greater than 1
month's duration) • OTHERS
• Wasting syndrome due to
• Leishmaniasis HIV
• Chagas Disease • Invasive cervical cancer
• Kaposi's sarcoma
• Malaria • Lymphoma, multiple forms
• Isosporiasis • Encephalopathy, HIV-related
OI (CDC GUIDELINE 2011)
• VIRUS
• Cytomegalovirus • Fungal
disease (particularly
CMV retinitis) • Candidiasis of bronchi, trachea,
• Herpes simplex 1,2 : esophagus, or lungs oral thrush,
chronic ulcer(s) vaginitis
(greater than 1 month's • Coccidioidomycosis
duration); or bronchitis,
pneumonitis, or • Cryptococcosis(Meningitis)
esophagitis
• Histoplasmosis
• Herpes zoster
• Human papilloma virus • Pneumocystis carinii
• Hepatitis B • pneumonia
• HHV-6 and HHV-7 Disease • Aspergillosis
• Varicella-Zoster Virus
Disease • Penicilliosis(P. marneffi)
• Human Herpesvirus-8
Disease
 AIDS (Acquired Immune Deficiency Syndrome)

• AIDS (Acquired Immune

Deficiency Syndrome) is the final
stage and natural progression of
HIV (Human Immunodeficiency
Virus.)
• These infections usually occur
when the CD4 cells drop below 200
cells/ul, i.e. immunocompromised
state.
• It is estimated that as many as 40
million people worldwide suffer
from AIDS
 HIV Related infections and illnesses
BACTERIAL VIRAL FUNGAL PARASITIC OTHER
ILLNESSES
Tuberculosis Varicella zoster Candidiasis Isosporiasis AIDS -
dementia

Bacterial Oral leukoplakia Cryptococcosis Microsporidi-osis Invasive

respiratory cervical
infections cancer
Bacterial enteric HSV Penicilliosis Cryptosporidiosis Non-
infections Hodgkin's
CMV lymphoma
Pneumocystis Human herpes Giardiasis Kaposi's
jiroveci pneumonia virus type 8 sarcoma
Toxoplasmosis
Atypical Human papilloma Strongyloidiasis
mycobacteriosis virus
Opportunistic Infections
 Respiratory Infections
• Bacterial pneumonias
(LRTI) can be very
serious & recurrent
• As Cell Mediated
Immunity depletes,
opportunistic infections
such as Pneumocystis ,
severe fungal and viral
pneumonias may occur.
 Respiratory Infections
Bacterial: Fungal:
Pneumococcal, Cryptococcosis
Klebsiella, E.coli, ,
Heamophilus, Histoplasmosis,
Staphylococcal Pneumocystis jiroveci
pneumonias, Aspergillosis,
Tuberculosis, MAC.
Viral: Other: Kaposi’s sarcoma,
Cytomegalovirus
Herpes simplex virus
Lymphocytic interstitial
pneumonitis
OPPORTUNISTIC BACTERIAL PATHOGENS
 Bacterial pathogens are associated with the
significant proportion of morbidity and mortality.
The following genera of pathogens are most
common in person infected with

 Campylobacter  Salmonella
 Flavobacterium  Shigella
 Haemophilus  Staphylococcus
 Mycobacterium  Streptococcus
 Nocardia  Treponema
 Pseudomonas  Yersinia
 Rhodococcus
 OPPORTUNISTIC BACTERIA
There are two main references to study opportunistic bacteria:
1. Opportunistic bacteria with reference to the site change.
 Example: E.coli
2. Opportunistic bacteria with reference to the immunocompromised
condition.
 Example: AIDS and its related opportunistic bacteria.
Pseudomonas aeruginosa:
as an opportunistic pathogen
 member of the Gamma Proteobacteria
 Gram-negative, aerobicrod
 Belongsto family Pseudomonadaceae.
 Oxidase-positive
 Infections by Pseudomonas aeruginosa

 urinary tract infections,

 respiratory system infections,
 dermatitis,
 bacteremia,
 bone andjoint infections,
 gastrointestinal infections
Infections are caused particularly in:

 Patients with severeburns

 cystic fibrosis
 cancer
 AIDS

• Pseudomonas aeruginosa is primarily a

nosocomial pathogen.
 Characteristics contributing to its
success as opportunistic pathogen

 Ubiquitous in soil and water, and on surfaces in contact with soil or water
 Actively swimming by means of its flagellum
 Respiratory andnever fermentative
 Can grow in the absence of O 2 if NO 3 is available as a acceptor of
respiratory electron


Pathogenesis of Pseudomonas aeruginosa

Composed of three distinct stages

 bacterial attachment andcolonization;

 local invasion;
 disseminated systemic disease.
 Invasion
Attachment and Produce extracellular enzymes and toxins that
colonization  Break down physical barriers
It uses:  Damage host cells and immune defense.
 Flagella
 Pilli Two exocellular proteases involved are:
 Exopolysaccharide  Elastase
(alginate orslime)  Alkaline protease

Some more proteins are; hemolysins and

cytotoxins
Dissemination

 Involves spread of infection to other parts

 Mediated by same extracellular products that

produce localizedinfection
E.coli
 Infections:
• Virulent strains of E. coli can cause:
 Gastroenteritis (inflammationof stomach and
small intestine)
 Urinary tract infections
 Neonatal meningitis (colonisation of newborn’s
intestine)
Classification of E .coli
 Enterotoxigenic E. coli (ETEC)
diarrhea (without fever) in humans, pigs, sheep,
goats, cattle, dogs, and horses
 Enteropathogenic E.coli(EPEC)
diarrhea in humans, rabbits, dogs, cats and
horses
 Enteroinvasive E. coli (EIEC)
found onlyin humans
 Enterohemorrhagic E.coli (EHEC)
found in humans, cattle, and goats
 Enteroaggregative E.coli (EAEC)
found onlyin humans
 Causesof infection
 E. coli infood
 During meatprocessing.
 Meat is not cooked to 160°F (71°C).
 Food come in contact with raw meat

 E. coli from person-to-personcontact

When an infected person does not wash his hands well

after a bowel movement.
• E. coli inwater
• Human or animal feces infected with E. coli
sometimes get into lakes, pools, and water supplies.
People can become infected when contaminate city
or town water supply has not been properly treated
with chlorine or when people accidentally swallow
contaminated water.
 Precautions:
 Cook all types of beef to at least 160°F (71°C).
 Wash any tools or kitchen surfaces that have touched
rawmeat.
 Wash your hands properly after using washroom.
 Use only pasteurized milk, dairy, and juice products.
 Use only treated, or chlorinated, drinking water.
 Campylobacter
 Campylobacter is a genus that belongs to Family
Campylobacteraceae of KingdomBacteria.
 Twisted bacteria with spiral or corkscrew
appearance.
 These are motile with either unipolar or bipolar
flagella
 Gram-negative.
 Microaerophilic
 Oxidase positivetest.
 Campylobacter &AIDS
 Campylobacter infections are among the most common bacterial
infections in humans.
 Diarrhoea
 Bacteremia
 C. jejuni is usually the most common cause of community-
acquired inflammatory enteritis.
 Symptoms Includesabdominal pain, cramping, dehydration and
fever.
 Flavobacterium

 Flavobacterium is agenus that

belongs to Family
Flavobacteriaceae.
 Gram-negative bacteria.
 Rod shapedbacteria
 They maybe motile or non-motile
 Found in soil and fresh water
 Flavobacterium &AIDS

 Flavobacterium spp. may play a pathogenic role in

patients with advanced HIV disease
 Endocarditis
 Pneumonia
 Bacteremia
 F.meningosepticum is the most imp example of this
genus.
 Haemophilus
 Haemophilus is a genus that belongs to
the Pasteurellaceae family
 Gram-negative bacteria.
 Pleomorphic bacteria (wide range of shapes
they occasionally assume)
 Aerobic or facultativelyanaerobic.
 The genusincludes commensal
and pathogenicorganisms
 Haemophilus & AIDS
 Meningitis is one of the most common bacterial infections
occurring in persons infected with HIV caused by
Haemophilus influenzae,
 Pneumonia
 Upper respiratory tract infections, such as otitis and
sinusitis
 Genital infections.
 Recently HIV infection increases the risk of acquiring
invasive H. influenza infection.
 Nocardia

• Nocardia is a gram positive actinomycete.

• Human infection is rare and contracted throughinhalation.
• Infection is more common amongimmunocompromised patients,
especially those with impaired cell mediated immunity.
• The patient may have other infections e.g tuberculosis.
Rhodococcus

 Pneumonia is the most common manifestation of

Rhodococcusinfection.
 Very most of cases originally reported were in patients who were
immunocompromised due to malignancies, immunosuppressive.
 Pulmonary infection occurs by the inhalation of the Rhodococcus
 Streptococcuspneumoniae
 Taxonomy
 Genus Streptococcus
 family Streptococcaceae.
 Morphology
 Cocci
 0.5-1.2um
 often Arranged in Pairs or
Chains
 Gram-positive
 General characteristics
 Non motile
 Carbohydrates fermenters

 Infection
 spontaneously cause disease in humans,
monkeys, rabbits, horses, mice and guinea pigs.
 Patients with HIV infection are at increased risk
for bacterial pneumonia
 Pneumocystis carinii Pneumonia

• Occurs in advanced HIV disease, when CD4

falls below 250
• Clinical features:-fever,
-dry cough,
-chest pain,
-shortness of breath.
• Diagnosis- C/F, sputum tests, X-ray
• Treatment-TMP-SMZ (co-trimoxazole)
 Gastrointestinal Infections
Causes:
Direct HIV infection
Bacterial/viral/protozoal/parasitic
infection
Presentations
• Watery/loose Diarrhoea,+/-
malabsorption due to villous
atrophy
• loss of appetite, nausea &
vomiting, progressive weight loss
N.B. bloody stool indicates
shigellosis/amoebic dysentery
 Diarrhoea
Acute Chronic
- Bacterial - CMV
• Salmonella - Mycobacterium avium
• Shigella complex
• Campylobacter - Parasites
• Clostridium difficile • Microsporidia
- Enteric viruses • Cryptosporidia
• adenovirus • Cyclospora
cayetanensis
• astrovirus
• Giardia lamblia
• Isospora belli
 Salmonella

 Salmonella infection has an increased incidence in HIVinfected

populations.
 Salmonellosis and bacteremia are occurring at an increased rate
in person with HIV.
 A characteristic feature of Salmonellosis inAIDS is the relapses
that occur during appropriate antibiotic therapy.
 S. typhimurium and S. enteridis are the two most common
serotypes isolated from the blood of patients withAIDS in the
United States
 Yersinia

 Yersinia is responsible for causing plague in peoplesinfected

with AIDS
 Y. pestis is a gram-negative, facultatively aerobic rod it is
primarily a rodent pathogen.
 The vector for this bacterium is a rat flea, Xenopsylla cheopis.
 Rat flea is actually an insect which transmits that bacterium
between two hosts.
 Shigella

 Taxonomy
• Family Enterobacteriaceae
• Four species:
• Shigella dysenteriae:
• Shigella flexneri:
• Shigella sonnei:
• Shigella boydii

• Morphology: rod-shaped, gram negative

 General characteristics
 facultatively anaerobic
 Non-lactose fermenting
 non-motile
 Infection
 spread from human to human via the fecal-oral route
 major cause of diarrheal disease
 HIV-infected persons are at increased risk for infection
 Staphylococcus

Taxonomy
 Genus Staphylococcus
 Family Staphylococcaceae
Morphology
 spherical
 1 µm in size
 thick cell wall
 Gram-positive
 General characteristics
 facultative anaerobe
 immobile
 Coagulase Positive
 Are resistant to
 122 °F temperatures
 high salt concentrations (<10%)
 drying
 Infection
 common flora: skin, nasal cavity, pharynx, gastrointestinal
tract, genitourinary tract
 A bacteremia may result in seeding
other internal abscesses, other skin
lesions, or infections in the lung,
kidney, heart, skeletal muscle or
meninges.

 common cause of community-

acquired (CA) or hospital-acquired
(HA) bacterial skin and soft- tissue
infections among patients with HIV
infection.
 Cryptosporidiosis

• Found in about 35% of AIDS diarrheal cases.

• Clinical features: -watery diarrhea,
-Abdominal bloating,
-profound weight loss .
• Diagnosis: Microscopy
• Treatment: Paromomycin/ Azithromycin.

Response is poor with all available therapies.

Prevention of malnutrition & symptomatic
relief vital in management.
 Cytomegalovirus

• Never occurs unless CD4 cell count less than 50

• Most typically affects the eyes
• Clinical features:-Blurry vision,
- Respiratory, CNS &
Gastrointestinal complications.
• Diagnosis: specialist (ophthalmologist)
examination
• Treatment: Gancyclovir, Foscarnet.
 Neurological Infections
Cryptococcal Meningitis

• Most frequent systemic

fungal infection in HIV
infected persons
• Symptoms: headache,
n.eB.ck stiffness, cranial
nerve palsies,+/- coma;
fever is rare
• Prognosis is poor with
no treatment. :Raised skin lesions resulting
from dissemination of the yeast
in an imunocompromised patien
 Cryptococcal meningitis

• Most common cause of meningitis in AIDS

• Clinical features:
-headache, fever,
-nausea and vomiting,
-confusion and impaired consciousness,
-signs of meningism (only in about 40%)
• Diagnosis: CSF examination (Indian ink staining,
Ag Titre)
• Treatment: Amphotericin B/Fluconazole with or
without 5-flucytosine.
 Treponema
pallidum
 Taxonomy
 genus Treponema
 family Spirochaetaceae.
 Morphology
 spiral-shaped
 0.2 µm in diameter and 6- 15 µm
in length
 Gram negative
General characteristics
 endoflagella
 Infection
 transmitted by direct contact
 Infection is initiated when T. pallidum penetrates dermal micro
abrasions or intact mucous membranes.
 Neurosyphilis is most common in patients with HIV infection.
 headache, meningeal irritation and nerve abnormalities.
 Toxoplasmal meningitis

CNS infection of T gondii is an

AIDS indicator
CD4 cells >50 cells/ml
Meningitis
Diagnosis
Serology-Ab detection
PCR
 Toxoplasmosis

• Commonest cause of focal cerebral lesions in

HIV/AIDS
• Clinical features:
-focal neurological deficit (FND),
-Seizures, intracranial hemorrhage,
-altered mental state and coma
• Diagnosis: CT Brain
• Treatment: Sulfadiazine or Clindamycin,
plus Pyrimethamine & Folinic acid.
 Mycobacterium

 Tuberculosis is an unquestionably, the most potent opportunistic

bacterial infection complicating HIV infection caused by Mycobacerium
tuberculosis.
 It is responsible for more than 2 million deaths and 8 million new cases
annually
 Tuberculosis is the most common opportunistic infection.
 About a third of the HIV positive population worldwide is coinfected with
M. tuberculosis.
 Tuberculosis

• Major world wide co-infection.

• Clinical features:-cough,
-hemoptysis,
- weight loss,
-evening rise of temp.
• Diagnosis: sputum for AFB, chest X-ray, culture
of specimen from the site (in case of extra
PTB), Skin test (PPD)
• Treatment: DOTS as per RNTCP
 Mycobacterium Avium Complex

• Usually occurs only if the CD4 count is less than 75

• Clinical features:-Flu like fever,
-chills, sweats,
-anemia, fatigue.
• Treatment-Clarithromycin, ethambutol
• Note: certain infections like
Histoplasmosis, Blastomycosis, Mycobacterium
Avium intra cellular (MAC) have not been reported
from our country so far
 Mycobacterium avium Complex
• Appear as isolated lymphadinitis
• Recurrent fever, weight loss, failure to thrive,
neutropenia, night sweats, chronic diarrhea,
malabsorption, abdominal pain
• Lymphadenopathy, hepatomegaly,
splenomegaly
• Respiratory symptoms
• Diagnosis-Biopsy,AFB stain,Blood culture,PCR
A Patient with HIV Wasting
Syndrome
This can be clinically indistinguishable
from advanced TB
 Candidiasis
Causative organism:
Candida species
Sites of colonisation
– Gastrointestinal tract
–Genital tract women
–Typical presentations :
Oral/vulvovaginal thrush
Balanitis
+/- oesophageal
candidiasis
 Candidiasis

• Oral Candidiasis may be the initial sign of HIV infection.

• Clinical features: -oral thrush,
-dysphagia
• Diagnosis: C/F, KOH preparation of the scrapings
• Treatment: Gentian
violet, Clotrimazole, Miconazole in mild cases (Oral Can.)
& Fluconazole in severe cases (esophageal Can.)
 Oral Hairy leukoplakia
• Common in HIV immunosuppressed
• Characterised by fine linear, warty
growths on edge of tongue.
• Can be mistaken for candidiasis
• Caused by Epstein Barr virus/?HPV
• No specific treatment; good oral
hygeine
 Oral Herpes
Causative organism:
Herpes simplex virus

Infection:
superficial painful ulcers;

Site:
mouth , around lips and
nose

Treatment:
5 days acyclovir 200mg
 Skin Conditions
• Herpes Zoster
• Reactivation of previous
varicella (chicken pox)
• Very common
• Can occur early in HIV disease
• Multi-dermatomal, recurrent
Causes acute, severe pain
• Risk of debilitating post herpetic
neuralgia (PHN more common in
older aptient)
• Disfiguring keloid formation
• Diagnosis clinical
 HIV and Genital Herpes
• More extensive disease
• Frequent recurrences
• Chronicity
• Associated high genital
viral load
• Important cofactor for
transmission of HIV
• Treatment of fist episode as
standard however higher
doses may be required for
longer periods especially in
chronic cases
 Infective Dermatoses
• Scabies
• Seborrheic
dermatitis
 Giant granulomatous leishmanial ulceration
Visceral Leishmaniasis

Has become more

Prevalent
Unusual presentations
Often occur
e.g.
Leishmania species
Normally causing only
Cutaneous disease, Can
present with
 HIV Related Malignancies

• Kaposi’s sarcoma
• Primary CNS lymphoma
• Carcinoma of the cervix
• Other lymphomas
 This is the
person living with
HIV/AIDS
 Patient Education

• Best way to prevent OIs is to keep immune

system strong
• Appropriate medication at certain CD4 cell levels
can prevent many OIs (prophylaxis)
• Treatment options available if OIs develop
• After recovery from OIs on-going maintenance
treatment is still needed
• Can stop prophylaxis or maintenance treatment
if CD4 cell count goes up
• Should not discontinue any treatment without
discussing first with Doctor
 General preventive measures:

• Prevent exposure to ill patients.

• Personal hygiene (washing hands etc.)
• Avoid contact with raw food, soil, cats, bird excreta, litter boxes
etc.
• Wash vegetables before cooking, avoid raw meat intake, drink
boiled water.
• Use condoms during sexual contact.
 Thus….

• OIs develop in an HIV infected individual

depending on the CD4 count & microbial
environment
• Most common OIs are TB, Candidiasis,
Cryptosporidiosis, Herpes zoster, Toxoplasmosis,
PCP
• Patient education plays vital role in preventing OIs
The Role of ARVs in Opportunistic Infections
• Antiretroviral therapy(ARV)
• ARVs improve the immune status, and therefore,
enhance how the host fights disease – keeping it free
from infections that might otherwise have taken the
opportunity to occur.

• Widespread use of Highly Active Anti Retroviral

Therapy (HAART) has been associated with
considerable

– Reduction in mortality
– Reduction in morbidity
– Reduction in social isolation
HIV/AIDS is one of the
greatest worldwide public
health challenges of the
modern age, and as future
health care workers, it is of
the utmost importance that
we maintain awareness and
continuing knowledge of this
heartbreaking and deadly
scourge.
 Exercise

• What are the basic factors that contribute to occurrence of

opportunistic infections?
• If you are the physician, what will you do so that you will not lose your
patient to follow-up? Write a narrative of not more than 250 words.
• Give 3 patient education messages for preventing OIs.
Discuss in 10 sentences the importance of such education
messages.
Thank you