OPPORTUNISTIC INFECTIONS

AND LABORATORY DIAGNOSIS

AUGUSTINE BARNABA (MC/MLT/06/02)

LIMBIKANI CHAPONDA (MC/MLT/06/04)
EDSON MUMBA (MC/MLT/06/33)
WHAT IS AN OPPORTUNISTIC INFECTION?

 Infection with an organism that is common, but rarely

causes illness in person with strong immune system.

 Because these organisms are commonly found in the

environment but do not cause illness in healthy people,
they are not contagious. They do not pose a risk to
HIV negative people.
OPPORTUNISTIC INFECTIONS

 Vulnerability to opportunistic infections varies

depending on the extent of the immune system
damage.

 An opportunistic infection may affect different organ

systems with different levels of severity, depending on
the extent of immune system damage.
 NATURAL PROGRESSION OF HIV DISEASE
1000
900 Asymptomatic
Relative level of
800
CD4+ cell Count

Plasma HIV-RNA
700 CD4+ T cells TB
Acute HIV
600 infection
syndrome
500
HZV
400
300 OHL

200 OC
PCP
100 TB
CMV, MAC
0
0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11
Months Years After HIV Infection
OPPORTUNISTIC INFECTION PREVENTION

Primary Prophylaxis
 giving medication to prevent an opportunistic infection
from occurring
Secondary Prophylaxis (Maintenance therapy)
 giving medication after an opportunistic infection is
treated to prevent it from recurring.
COTRIMOXAZOLE PROPHYLAXIS

Can prevent:
 Pneumocystis carinii pneumonia
 Cerebral toxoplasmosis
 Malaria
 Parasitic diarrheas
 Disease caused by non-typhoid salmonella
 Disease caused by streptococcus pneumoniae
OI PROPHYLAXIS: PATIENT EDUCATION

 Maintain good personal and food preparation hygiene.

 Drink bottled or boiled water.
 Eat only well cooked meat, fish, poultry.
 Wash fruits and vegetables well.
 Do not eat raw eggs.
 Do not handle turtles, chicks, ducklings, or cat feces.
PATHOPHYSIOLOGY

 Impaired T-cell immunity and CD4+ T-cell depletion

in HIV disease are the key elements in the
pathophysiology of most OIs

 An impairment in the host defence mechanisms and

higher levels of plasma HIV RNA have been
associated with increased rates of mucocutaneous
candidiasis and colonisation with Candida
PATHOPHYSIOLOGY CONT…

 HIV infection is an independent risk factor for

acquisition of TB and rapid progression to disease.
Defects of cellular immunity and macrophage function
have been demonstrated in HIV-infected persons with
TB.

 Colonisation of the intestinal tract with mycobacterium

avium complex (MAC) is believed to be the primary
route of MAC infection in patients with AIDS, and
precedes the appearance of bacteraemia and
disseminated disease by several months
PATHOPHYSIOLOGY CONT…

 In patients with AIDS, progressive loss of cell-

mediated immunity permits CMV re-activation and
replication to begin and results in tissue necrosis in
association with non-specific inflammation.

 Increasing evidence suggests that lung damage

occurring during Pneumocystis jiroveci pneumonia
(PCP) is a result of the type and extent of the host
inflammatory response to P jiroveci rather than a result
of direct damage by the organism.
PATHOPHYSIOLOGY CONT…

 Cellular immunity, mediated by T cells, macrophages,

and activity of cytokines and interferon-alpha, is
necessary for maintaining quiescence of chronic T
gondii infection.

 In cryptococcal infection the microbes polysaccharide

capsule is thought to be the primary virulence factor
that elicits a local inflammatory response and the
increased production of prostaglandins and several
cytokines, particularly interferon-gamma.
LAB. DIAGNOSIS

CD4+ CELL COUNT

 TB can occur throughout the course of HIV disease but
the risk increases as the CD4+ count decreases.
 P jiroveci pneumonia (PCP) and candidiasis are more
likely when the CD4+ count is below 200 cells/µL.
 Toxoplasmosis occurs when the CD4+ count is below
100 cells/µL.
 CMV and mycobacterium avium complex (MAC) are
encountered with CD4+ count below 50 cells/µL.
RESULTS:
 Variable
LAB. DIAGNOSIS CONT..

SPUTUM STAIN AND CULTURE

 Three sputum specimens obtained on 3 consecutive
days should be examined for AFB and cultured for
mycobacteria.
 Toluidine Blue O (TBO) staining has an acceptable
sensitivity and very high specificity in expectorated
sputum samples for PCP.
RESULTS:
 Acid-fast bacilli (AFB) stain and mycobacterial culture
are positive in TB and MAC
 TBO staining is positive in PCP
LAB. DIAGNOSIS CONT..

Blood cultures
 Two blood cultures are usually sufficient for the
detection of disseminated MAC. One blood culture
identifies 91% of patients with MAC bacteraemia, while
a second blood culture increases the identification rate to
98%. However, up to 6 weeks of culture may be
required, which limits the clinical utility.
 Up to 75% of patients with HIV-associated cryptococcal
meningitis have positive blood cultures. Blood cultures
may be helpful if disseminated disease is suspected in
the absence of meningitis.
RESULTS:
 May be positive in MAC and cryptococcus infection
LAB. DIAGNOSIS CONT..
CMV cultures
 Blood, other body fluids or tissue specimens; the test can be
done using conventional tube cell culture or shell vial assay.
RESULTS
 presence or absence of cytopathic effects

CMV serology
 The test is done using ELISA. The utility of CMV serology is
modest since invasive disease is more commonly due to re-
activation than to primary infection
RESULTS:
 CMV-IgM titre is indicative of acute infection; CMV-IgG titre
suggests past infection
LAB. DIAGNOSIS CONT..

TOXOPLASMA GONDII SEROLOGY

 Presence of anti-T gondii IgM antibodies does not
necessarily indicate a recently acquired infection as
they can remain elevated for more than 1 year. Recent
T gondii infection is likely when serial specimens
obtained at least 3 weeks apart and tested in parallel
reveal at least a 4-fold increase in IgG titres.
RESULTS:
 Presence of anti-T gondii IgM and IgG suggest recent
and past infection, respectively
LAB. DIAGNOSIS CONT..

FULL BLOOD COUNT

 Anaemia is common in HIV-infected patients with
opportunistic infections. In disseminated MAC, the
anaemia is an important negative predictor for survival,
is usually profound, and is often accompanied by
leukopenia and thrombocytopenia.
RESULTS
 Anaemia often accompanied by leukopenia and

thrombocytopenia
LAB. DIAGNOSIS CONT..

CRYPTOCOCCAL POLYSACCHARIDE ANTIGEN

 Very specific; sensitivity is greater than 90%. High
initial CSF titres (≥1:1024) are a marker of poor
prognosis and correspond to a high organism burden.
CSF antigen titres fall with successful treatment.
RESULTS
 From serum or CSF; titre above 1:4
LAB. DIAGNOSIS CONT..

LIVER FUNCTION TESTS

 Alkaline phosphatase is elevated in HIV-infected
patients with MAC or CMV hepatobiliary disease. In
CMV hepatitis, it is usually accompanied by elevation
of AST and ALT.
RESULTS:
 Elevated
LAB. DIAGNOSIS CONT..

LACTATE DEHYROGENASE
 Elevated in MAC, and frequently elevated in PCP.
Serial determinations of LDH during successful
treatment for PCP show a gradual decline of LDH.
Thus it may serve as a prognostic indicator in PCP.

 However, elevated LDH should be interpreted with

caution, because it is also elevated in patients with
various other lung diseases, such as pulmonary TB and
other bacterial pneumonias
RESULTS:
 Elevated
THE OPPORTUNISTIC INFECTIONS INCLUDE:

Fungal infections
 Pneumocystis jiroveci pneumonia (PCP)
 Candidiasis
 Cryptococcosis
Bacterial infections
 Tuberculosis
 Mycobacterium avium complex (MAC) infections
Parasitic infections
 Toxoplasmosis
 Cryptosporidiosis
 Isospridiam
Viral infections
 Herpes simplex virus infection (HSV)
 Cytomegalovirus virus CMV
 Varicella Zoster Virus
FUNGAL INFECTIONS
P JIROVECI PNEUMONIA

 Pneumocystis microbes are classified in the fungus

kingdom on the basis of DNA analysis but also share
biologic characteristics with protozoa.

 The organism that infects humans and causes PCP is

now named Pneumocystis jiroveci.

 HIV-infected patients with PCP have a similar

presentation to non-HIV immunosuppressed patients,
but the median duration of their symptoms before
diagnosis is much longer (28 v 5 days, respectively)
 Clinical features of PCP among HIV-infected children
are similar to those in adults (i.e., fever, tachypnea,
dyspnea, and cough).
LAB. DIAGNOSIS

 Serum Lactic dehydrogenase (LDH) is ↑ but serial determinations of

LDH during successful treatment for PCP show a gradual decline of
LDH.
 PCR
 Toluidine blue stains the cyst wall blue or lavender
 Gomori's methenamine-silver stains the cyst wall brown or black
 Giemsa or Wright's Stain, stains the trophozoites and intracystic
sporozoites pale blue with a punctate red nucleus
 Po2 >30 mm/Hg
CRYPTOCOCCUS INFECTION

 Usually presents as a sub-acute meningitis or

meningoencephalitis with fever, malaise and headache.
 However, disseminated disease can occur, with or
without concurrent meningitis.
 In such cases, pulmonary involvement or skin lesions
may be present.
LAB. DIAGNOSIS
CSF findings include:
 a mildly elevated protein,
 normal or slightly low glucose,
 a few lymphocytes and numerous organisms.
 India ink examination on the CSF should be performed.
 The cryptococcal antigen in the CSF is almost always positive
in patients with meningitis or meningoencephalitis.
 Evaluation of cryptococcal antigen in the serum should also be
considered.
Blood cultures:
 HIV-associated cryptococcal meningitis have positive blood
cultures for Cryptococcus neoformans.
Candidiasis

 Candida albicans is the most common cause of

mucosal and esophageal candidiasis.

 The condition is often associated with low CD4+ cell

count (<100/μl), high viral load, and neutropenia
(<500/μL)

 Patients may present with oral, oesophageal or vaginal

infection.
Candidiasis cont..

 Manifestations include pseudo-membranous

candidiasis (oral thrush) with altered taste sensation
and/or difficulty swallowing liquids and solids;
 odynophagia or dysphagia in oesophageal disease,
 In vaginal disease, erythema with adherent white
discharge, marked itching, and swelling of labia
LAB.DIAGNOSIS

 A scraping for microscopic examination for yeast

forms, using a 10% potassium hydroxide (KOH)
preparation, may show characteristic findings,
including pseudo-hyphae and budding yeast.

 Cultures are usually not necessary unless the lesions

fail to resolve on antifungal treatment.
TAKE HOME MESSAGE

 Opportunistic infections do not cause illness in healthy

people and are not contagious.
 Primary Prophylaxis prevents the first episode of an
opportunistic infection.
 Adherence to prophylactic medications is very
important, especially to INH.
 Good personal hygiene and careful food preparation
can reduce (but not eliminate) risk for some
opportunistic infections.
BACTERIAL INFECTIONS
TUBERCULOSIS (TB)

 TB is an infectious disease that affects mainly the

lungs (Pulmonary TB or PTB) but can also attack any
part of the body such as kidney, spine and brain (Extra-
pulmonary TB or EPTB).

 The most common transmission is human to human

although incidences of animal to human through
unpasteurized cow’s milk.
THE CAUSE OF TB

 Mycobacterium tuberculosis

 Mycobacterium bovis
 TB TRANSMISSION

Person to person
Via
Airborne transmission
In
Confined environment
RISK FACTORS FOR INFECTION

 Exposure to TB bacilli
 Duration of exposure to a person with PTB

 Intensity of exposure

Note:
 Untreated AFB smear positive cases are the most
infectious.
 Development of the disease depends on individual
susceptibility;
 HIV increases the risk of getting TB disease
EPIDEMIOLOGY
 1/3 of world’s population is infected with TB (WHO 2008 report).
 In 2007,there were 9.27million new cases of TB (139 per 100,000
population) worldwide.
 95% of TB cases and 98% of TB deaths are in the developing
countries.
 75% of TB cases in developing countries are in (15-50 years).
 14.8% (1.37 million) of the 9.27 million were HIV positive
 In 2005 Swaziland had highest incidence of TB with1262 cases per
100,000.
PATHOPHYSIOLOGY

 Infection with TB requires inhalation of droplet nuclei.

 Following deposition in the alveoli, M. tuberculosis is
engulfed by alveolar macrophages, but survives and
multiplies within the macrophages.
 Proliferating bacilli kill macrophages and are released; this
event produces a response from the immune system.
 Exposure may lead to clearance of M. tuberculosis,
persistent latent infection or progression to primary disease.
PATHOPHYSIOLOGY CONT..

 Active TB typically occurs through a process of re-activation.

 Approximately 10% of individuals with latent infection will
progress to active disease over their lifetime.
 The risk is greatest within the 2 years following initial acquisition
of M. tuberculosis.
 A number of conditions can alter this risk, particularly HIV
infection, in which the annual risk of developing active TB is 8%
to 10%.
 Immunocompromised conditions and treatment with
immunosuppressing medicines, including systemic
corticosteroids also contribute to re-activation.
PATHOPHYSIOLOGY CONT…

 Successful containment of TB is dependent on the cellular

immune system, mediated primarily through T-helper cells
(TH1 response).
 T cells and macrophages form a granuloma with a centre that
contains necrotic material (caseous centre), M. tuberculosis
and peripheral granulation tissue consisting primarily of
macrophages and lymphocytes; the granuloma serves to
prevent further growth and spread of M. tuberculosis.
 These individuals are non-infectious and have latent TB
infection; the majority of these patients will have a normal
CXR and be tuberculin skin test (TST) -positive.
PATHOGENESIS
 Active TB typically occurs through a process of re-activation.
 Approximately 10% of individuals with latent infection will
progress to active disease over their lifetime.
 The risk is greatest within the 2 years following initial acquisition
of M. tuberculosis.
 A number of conditions can alter this risk, particularly HIV
infection, in which the annual risk of developing active TB is 8%
to 10%.
 Immunocompromised conditions and treatment with
immunosuppressing medicines, including systemic corticosteroids
and TNF-alpha antagonists, also contribute to re-activation.
PATHOGENESIS CONT..

Pulmonary TB
 Occurs when the primary infection does not heal completely and
there is continued multiplication of organisms in the lung several
months or years later due to poor health, malnutrition and
defective immune responses.
 An inflammatory reaction leads to a liquefied destruction of the
lung tissue with caseation (a cheese like mass).
 Erosion through the wall of a bronchus leads to the discharge of
the liquefied tissue and the formation of a cavity.
 Bacilli multiply in the wall of the cavity and can be found in the
sputum (‘open’ infectious stage).
PATHOGENESIS CONT..

Tuberculous Meningitis
 Tubercle bacilli reach the meninges in the blood.

 Occurs more frequently in non-immune infants and young children

as a complication of primary tuberculosis.
 Condition is often fatal unless treated an early stage.

Miliary tuberculosis
 Occurs if the site of primary infection ruptures through a blood
vessel and bacilli are disseminated throughout the body.
 Many small granulomata are formed which on a chest X-ray look
like millet seeds (hence name miliary TB).
 Pts are often acutely ill with fever. The liver, spleen and lymph
glands may be enlarged .
PATHOGENESIS CONT…

Renal and Urogenital TB

 Tubercle bacilli reach the kidneys and genital tract by way of the
blood circulation usually some years following primary infection.
 Renal infection is often suspected when repeated urine specimens
are found to contain pus cells but no organisms isolated by routine
culture.
 There may be frequency in passing urine, haematuria and usually
a recurring fever.
Note
 Tuberculosis of the genital tract (epididymitis in males,
endometrial tuberculosis in females) can cause infertility and
pelvic inflammatory disease.
PATHOGENESIS CONT….

Bone and Joint TB/Spinal TB

 A commonly infected site is the spine which may lead to collapse
of vertebrae and the formation of a ‘cold’ abscess in the groin.
 TB starts in an intervertebral disc and spreads along the and
longitudinal ligaments before involving adjacent vertebral bodies
NOTE
 Diagnosis of PTB in children is more difficult because there is
rarely a cough with sputum production.
 A diagnosis is usually made from a positive tuberculin reaction
and X-ray.
 There is weight loss and failure to thrive.
REMEMBER

 The diagnosis of TB can be overlooked, as it may present with

signs and symptoms (such as fevers, weight loss and malaise) that
may be attributed to HIV itself
 The clinical manifestations of pulmonary TB may be different
depending on the level of immunosuppression in HIV-infected
persons
 A high index of suspicion must be maintained when evaluating an
HIV-infected patient with symptoms suggestive of TB, as chest x-
rays may appear normal in 7% to 14% of cases
 Depending on the involved site, TB may present with shortness of
breath, cough, lymphadenopathy, headache, meningism,
abdominal pain, dysuria or abscess formation.
LABORATORY DIAGNOSIS

Acid-fast bacilli (AFB) stain: Ziel-Neelsen or Auramine-phenol

 3 sputum specimens should be obtained on 3 consecutive days,
examined for AFB.
 Specimens obtained through bronchoscopy with bronchoalveolar
lavage and trans-bronchial biopsy may be useful in the evaluation
of an abnormal chest x-ray when sputum smears are negative.
 In extra-pulmonary TB, specimens from other sites should be also
examined for AFB.
Culture
 Lowenstein Jensen egg medium.

Molecular tests: nucleic acid amplification (NAA); PCR

 Can detect nucleic acid sequences unique to organisms in the
Mycobacterium tuberculosis complex, allowing for a rapid
diagnosis.
LABORATORY DIAGNOSIS CONT..

Tuberculin Skin Test

 Tuberculin is a purified protein derived from tubercle bacilli. Also
known as PPD (purified protein derivative).
 Following infection with M. tuberculosis, a person develops
hypersensitivity to tuberculin.
 Tuberculin injected into the skin of an infected person produces a
delayed local reaction after 24-48 hours.
 This reaction is quantified by measuring the diameter of skin
induration (thickening) at the site of the reaction.
Note
 The test does not measure immunity. By it itself, it does not indicate
the presence or extent of TB disease; it only indicates infection with
M. tuberculosis.
ACID FAST PRINCIPLE

 Primary stain penetrates cell wall.

 Intense decolorization does not release primary stain
from the cell wall of AFB.
 Color of AFB based on primary stain.
 Counter stain provides contrasting background
SMEAR PREPARATION AND STAINING
STAINING CHARACTERISTICS

oMycobacteria are called Acid

Fast Bacilli (AFB) due to their
microscopic appearance after
decolorizing.

oOrganisms appear red on a

blue background
MALAWI DIAGNOSIS SET UP
Reference Laboratory CHSU
 Microscopy (ZN and Auramine-phenol)
 Culture (Lowenstein Jensen egg-medium)
Central Hospitals
 Microscopy (ZN and Auramine-phenol)
 Tuberculin Skin test (PPD)
District Hospitals
 Microscopy (ZN /Auramine-phenol)
Health Centre
 Microscopy (ZN)
MALAWI DIAGNOSIS SET UP CONT..

Culture is done only at the Reference Lab

 To manage treatment failures and patients that have
relapsed.
 To monitor multi-drug resistance

 To identify M. tuberculosis variants and strains e.g.

M. bovis.
MYCOBACTERIUM AVIUM COMPLEX
 Mycobacterium avium complex refers to multiple
related species of non-tuberculous mycobacteria (e.g.,
M. avium, M. intracellulare, M. paratuberculosis)
 Typically occurs in AIDS patients who have CD4+
counts below 50 cells/µL
 Clinical presentation may include symptoms and signs
(e.g., persistent fever, night sweats, fatigue, weight loss
and anorexia).
 More unusual presentations include palatal and
gingival ulceration,septic arthritis and osteomyelitis,
endophthalmitis, pericarditis and GI bleeding.
LAB. DIAGNOSIS
 FBC may show anaemia (often severe) and leukopenia.
 Abnormal LFTs, including elevated alkaline phosphatase and
LDH, and low albumin.
 Bacteraemia: blood cultures should be drawn from all patients.
The most sensitive method for the detection of
mycobacteraemia is by a lysis-centrifugation blood culture
system.Biopsy of bone marrow (or colon in colitis) with
culture from tissue obtained may be useful, although blood
cultures are more sensitive.
 In patients with CD4+ count of 50 cells/microlitre or greater, a
history of fever for more than 30 days, a haematocrit below
30% or a serum albumin level below 30 g/L (<3.0 g/dL) are
sensitive predictors of MAC bacteraemia.
VIRAL OI
Opportunistic Infections
61
 Clinical Latency

 At CD4 cell counts over 500 cells/uL many complications

overlap with conditions found in uninfected populations (bacterial
pneumonia, tuberculosis, minor skin conditions), but they may be
more frequent.

 At CD4 counts between 200 and 500 cells/uL other conditions

and opportunistic infections may begin to appear (Kaposi’s
sarcoma, oral candidiasis, herpes zoster, etc.).

62
Herpes Simplex infection
 Caused by two closely related viruses, identified as
type 1 and type 2. They cause a wide variety of
primary and recurrent mucocutaneous infections.
 Following a 1 0 infection, the virus maintains a latent
state, and recurrent disease is caused by reactivation of
the latent viral infection.
 Primary genital herpes is the most common cause of
genital ulceration. The typical incubation period is 3 to
14 days after sexual exposure. The primary lesion
begins as a small group of painful, pruritic vesicles,
which break down to form ulcerating, pustular lesions
in 2 to 4 days..
HSV cont…
 By the time the patient sees a physician, the lesions are usually in
the ulcerative phase. Painful, enlarged inguinal lymph nodes are
common. New lesions will continue to form during the first week of
the primary illness in about 75% of patients
 About 2/3 of patients will have systemic symptoms including fever
and headache. Fewer than 10 % of patients will develop aseptic
meningitis or urinary retention. The duration of the illness may total
14 to 21 days..
 In the immunocompromised patient, herpetic infections may be
associated with progressive mucocutaneous ulcerations of the face,
mouth, or anogenital regions. Lesions may coalesce, forming large,
superficial ulcers that last for weeks or months.
Herpes Simplex
HSV cont…

Herpes Simplex
 Lesions begin as painful, pruritic grouped vesicles
 Vesicles break down to form an ulcer
 Lesions are located in the anogenital area
Cutaneous anthrax
 Ulcer is painless
 Lesion is located on exposed parts of the body
 Ulcer and eschar are surrounded by characteristic non-
pitting edema
Cytomegalovirus (CMV)
 Member of the herpes virus family
(EBV, varicella-zoster, herpes simplex)
 Worldwide seroprevalence 30-100%
 Found in body fluids
 Blood, saliva, urine, breast milk

 Most people are infected with CMV at some point in life

Types of CMV Infection

 Primary infection
(asymptomatic to mononucleosis like syndrome in immune
competent individuals)
 Latent infection
(presence of viral genome in mononuclear leukocytes,
endothelial cells, and organs in the absence of active
replication of infectious virus)
 Reactivation during a period of immunosuppression 20 to drugs
or intercurrent infection (eg, HIV).
 Reinfection
(new strain of CMV)
CMV continue..
 is usually an asymptomatic infection. Clinically significant
CMV disease frequently develops in patients
immunocompromised by HIV, solid-organ transplantation,
and bone-marrow transplantation.
 congenital transmission from a mother with acute infection
during pregnancy is a significant cause of neurological
abnormalities and deafness in newborns
CMV
CMV diseases
 CMV retinitis is a common opportunistic infection in
late-stage AIDS, typically with CD4+ lymphocyte
counts of less than 50 cells/µL. Typically, patients
exhibit a progressive decrease in visual acuity, which
may progress to blindness if untreated.
 Gastritis and Colitis-CMV may infect the
gastrointestinal tract from the oral cavity through the
colon. The typical manifestation of disease is
ulcerative lesions.
CMV disease cont..
 Pneumonia -Adults manifesting CMV infection as a
mononucleosis syndrome may occasionally have
pneumonia.
 Hepatitis
Detection of CMV Infection
 Immune status: serology (IgG)
 Active infection (viremia)
 Histology

 Viral culture

 Shell vial culture

 Antigenemia assay

 CMV PCR (qualitative/quantitative)

Varicella- zoster virus (VZV)
 commonly causes chicken-pox in children and both
shingles and postherpetic neuralgia in adults.
 10 infection results in chickenpox (varicella), which
may rarely result in complications including
encephalitis or pneumonia.
 VZV remains dormant in the nervous system of the
infected person (virus latency), in the trigeminal and
dorsal root ganglia. In about 10-20% of cases, VZV
reactivates later in life producing a disease known as
herpes zoster or shingles. Serious complications of
shingles include postherpetic neuralgia, zoster
multiplex, myelitis, or herpes ophthalmicus.
Pathogenesis
 Replication of the virus occurs in the respiratory and
viremia follows.
 Virus is taken up by endothelial cells where it
undergoes replication.
 Immumne sytem is overwhelmed and during 2nd
viremia chills and fever becomes evident.
 Virus lodges in capillary endothelial cells of the skin
and then spread to the epithelial cells followed by rash
development and vesicle formation confine in facial,
lumbar and thoracic areas.
Pathogenesis contin..
 Vesicles fall off become crusted and fall off within
1wk ( chicken pox)
 During vesicle development, virus is transported to
cranial nerves and dorsal root ganglion by movement
along the sensory nerve.
 During immunosupresion, latent virus in posterior root
or cranial sensory nerve ganglion is reactivated.
 Virus moves down to the skin and produce lesions
 Lesions heal 3-4wks and subsides
Pathogenesis cont
 Posthepatic neuralgia frequently occurs in adults
>60yrs old. (Due to scarring of in the ganglia and
afferent portions of the sensory nerves.
 Zoster develops early in the course of disease in
immunocompromised patients.
PARASITIC OI
Toxoplasmosis
 Etiological agent-T gondii
 Acquired by both immunocompetent and immunocompromised
individuals.
 Human get infected by ingestion of infected warm blooded
animals or ingestion of contaminated food with cat feces.
 Trophozoites 1st invade the intestinal mucosa and may invade
any organ where they develop into tissue cysts
 Cysts remain dormant in immunocomptent person but are
reactivated when immune system is impaired
Toxoplasmosis cont…
 10 site of infection is the brain followed by
lungs.
 In pregnant woman T. gondii infection may
result to congenital toxoplasmosis.
 Congenital toxoplasmosis may lead to:
 Mental retardation
 Chorioretinitis

 Cerebral calcifition
LABORATORY DIAGNOSIS
 Seropositivity for anti-toxoplasma IgG antibodies
makes the diagnosis more likely; however, absence of
these antibodies does not exclude it

 CSF shows mild mononuclear pleocytosis and elevated

protein. Giemsa staining can show tachyzoites. DNA
amplification can be useful in detecting T gondii in the
CSF.
Cryptosporidiosis
 A highly infectious intestinal parasite found most
commonly among farm and domesticated animals. It is
transmitted through contaminated food and water.
 Results in watery diarrhea which resolves < 1 months
but becomes unreletented in immunocompromised.
Other symptoms include; weight loss, abdominal
cramps, nausea, vomiting, fever, and headache.
 In immunocompromised patients fluid loss may reach
up to 3 to 6 liters per day.
LABORATORY DIAGNOSIS
 acid-fast stain is traditionally
used to most reliably and
specifically detect the presence
of cryptosporidial oocysts .
 Immunologically, anti-
cryptosporidial IgM, IgG, and
IgA can be detected by ELISA
or by the antibody
immunofluorescence assay
(IFA).
acid-fast stain
 genetic methods of detecting C.
parvum PCR (Polymerase Chain
Reaction) or other DNA-based
detection methods.
Isospra belli
 Infection with I. belli begins when the mature oocyst is
ingested in water or food.
 In the immunocompetent, infection is generally
asymptomatic or a self-limiting gastro-enteritis.
 Infection in immunocompromised individuals ranges
from a self-limiting enteritis to severe diarrhoeal illness
resembling that of cryptosporidiosis.
LABORATORY DIAGNOSIS
 Oocytes can be demonstrated
in faeces after formal ether
concentration where they
appear as translucent, oval
structures measuring 20-33m
by 10-19m.
 oocysts can be seen in a
faecal smear stained by a
modified Ziehl-Neelsen
method , where they stain a
granular red colour against a
green background, or by
phenol-auramine. Oocyte stained by MZN
REFERENCES:
 www.aids-etc.org
 www.aidsinfo.nih.gov
 CDC. Guidelines for the prevention of opportunistic infections in persons infected
with human immunodeficiency virus: a summary. MMWR 1995;44(No. RR-8).
 CDC. Guidelines for the prevention of opportunistic infections in persons infected
with human immunodeficiency virus. MMWR 1997;46(No. RR-12).
 CDC. Guidelines for the prevention of opportunistic infections in persons infected
with human immunodeficiency virus. MMWR 1999;48(No. RR-10).
REFERENCES CONT..

 CDC. Guidelines for the prevention of opportunistic

infections among HIV-infected persons–-
recommendations of the U.S. Public Health Service
and the Infectious Disease Society of America.
MMWR 2002;51(No. RR-8).
 TB/HIV A clinical Manual 2nd ED WHO
 Monica Cheesebrough Part II
 Basic Medical Microbiology Robert boy F.Boyd 5th ED
pages 411- 417, 515 - 517