Opportunistic parasitic infections

1. OPPORTUNISTIC
PARASITIC
INFECTIONS Dr.T.V.Rao MD
09/26/14 Dr.T.V.Rao MD 1

2. OPPORTUNISTIC INFECTIONS AND
THEIR RELATIONSHIP TO HIV/AIDS
• OIs are signs of a declining
immune system. Most life-threatening
OIs occur when your
CD4 count is below 200
cells/mm3. OIs are the most
common cause of death for
people with HIV/AIDS.
12/04

3. Opportunistic parasitic infections
in Immunosuppressed patients
• Infections with opportunistic pathogens
were the leading cause of diarrhoea in
HIV infectedindividuals, especially, in
subjects with advanced disease.
C. partum and I.belli,were the most
commonpathogens.
• Among the non opportunistic pathogens
E. histolytica/
• E. dispar seemed to contribute significantly
has shown
12/04

4. Parasitic Infections
Toxoplasma gondii
encephalitis (TE)
•Cryptosporidiosis
•Microsporidiosis
•Isospora belli
12/04

5. Toxoplasma gondii Encephalitis:
Epidemiology
• Caused by the T gondii, a protozoan
• Disease usually caused by reactivation of latent
tissue cysts
• Primary infection may be associated with acute
cerebral or disseminated disease
• Seroprevalence varies widely: 15% in the United
States, 75% in some European countries, higher
in some developing countries
12/04

6. Toxoplasmosis
• Toxoplasmosis is caused by the parasite
Toxoplasma gondii that can cause encephalitis
and neurological disease in patients with low
CD4 counts. The parasite is carried by cats,
birds, and other animals and is also found in
soil contaminated by cat feces and in meat,
particularly pork.
12/04

7. Toxoplasma gondii
Encephalitis: Epidemiology
• In advanced AIDS, 12-month incidence of TE
was 33% in toxoplasma seropositive patients not
on prophylaxis or ART
• Incidence and mortality lower in United States
and Europe since widespread use of prophylaxis
and potent ART
• Occurs primarily in patients with CD4 count
<200 cells/μL, especially <50 cells/μL
12/04

8. Toxoplasma gondii Encephalitis:
Epidemiology
• Primary infection acquired from
tissue cysts in undercooked meat
or ingestion of sporulated oocysts
(from cat feces) in soil, water, or
food
• No transmission by person-to-person
contact
12/04

9. Toxoplasma gondii
Encephalitis: Clinical Manifestations
• Focal encephalitis with headache, confusion,
or motor weakness and fever
• Focal neurological abnormalities, may
progress to seizures, altered mental status,
coma
• Dissemination may occur, with
retinochoroiditis, pneumonia, other organ
involvement
12/04

10. 12/04

11. 12/04

12. Toxoplasma gondii Encephalitis:
Diagnosis
• Serum antitoxoplasma
IgG
(positive in almost all
patients with TE)
• IgM usually negative
12/04

13. Toxoplasma gondii Encephalitis:
Diagnosis
• Imaging
– CT, MRI of brain: often
multiple contrast-enhancing
lesions,
often with edema
– PET or SPECT may
help distinguish TE
from lymphoma
• Detection of organism
(brain biopsy)
• CSF PCR not sensitive
12/04
Credit: P. Volberding, MD, UCSF Center
for HIV Information Image Library

14. Toxoplasma gondii Encephalitis:
• Imaging Diagnosis
–CT, MRI of brain: multiple contrast-enhancing
lesions, often with edema
–PET or SPECT may help distinguish TE
from lymphoma
• Detection of organism (brain biopsy)
• CSF PCR not sensitive
12/04

15. Toxoplasma gondii
Encephalitis: Diagnosis
• Definitive diagnosis: clinical syndrome +
imaging + detection of organism (brain
biopsy)
• May initially make empiric diagnosis on
basis of clinical and radiographic
improvement to TE therapy, in absence of
a likely alternative diagnosis
– Brain biopsy if failure to respond to therapy
12/04

16. Toxoplasma gondii Encephalitis:
Diagnosis
• Differential diagnosis
–CNS lymphoma,
mycobacterial infection
(TB), fungal infection,
Chagas disease, abscess,
PML
12/04

17. • Toxoplasmosis is treatable with aggressive
therapy, and prophylaxis is recommended for
patients with low CD4 counts (usually less
than 200). Diagnosis of this condition often
requires imaging studies (CT or MRI) of the
brain and a blood test. For more information,
see CDC’s Toxoplasmosis and You Can Prevent
Toxo.
12/04

18. Toxoplasmosis is treatable
• Toxoplasmosis is treatable with aggressive
therapy, and prophylaxis is recommended for
patients with low CD4 counts (usually less
than 200). Diagnosis of this condition often
requires imaging studies (CT or MRI) of the
brain and a blood test. For more information,
see CDC’s Toxoplasmosis and You Can Prevent
Toxoplasmosis .
12/04

19. Toxoplasma gondii
Encephalitis: Treatment
• Preferred:
–Pyrimethamine 200 mg PO first dose,
then 50 mg (weight <60 kg) to 75 mg
(≥60 kg) PO QD + sulfadiazine 1,000
mg (<60 kg) to 1,500 mg (≥60 kg) PO Q
6 hours, + leucovorin 10-20 mg PO QD
• Duration: ≥6 weeks, longer if
extensive disease or incomplete
response 12/04

20. Toxoplasma gondii Encephalitis:
Prevention of Recurrence
• Lifelong chronic maintenance therapy
(secondary prophylaxis) after completion
of initial therapy, unless immune
reconstitution on ART
– Preferred: TMP-SMX 1 DS PO QD
– Alternative: dapsone 100 mg PO QD, or
dapsone + pyrimethamine + leucovorin +/-
aerosolized pentamidine, or atovaquone
12/04

21. Toxoplasma gondii Encephalitis:
Considerations in Pregnancy
• Perinatal transmission usually occurs only with
acute maternal infection, but in advanced HIV
may occur with reactivation of chronic infection
• If primary T gondii infection during pregnancy,
consult with maternal-fetal specialist
• If symptomatic toxoplasmosis during pregnancy:
– Detailed ultrasound of fetus
– Infant should be treated
12/04

22. Cryptosporidiosis
• Cryptosporidiosis is a diarrheal disease
caused by the protozoa Cryptosporidium,
and it can become chronic for people
with low CD4 counts. Symptoms include
abdominal cramps and severe chronic
diarrhea. Treatment and antiretroviral
therapy are important. For more
information, see CDC’s Cryptosporidiosis
and You Can Prevent Cryptosporidiosis. 12/04

23. 12/04

24. Cryptosporidiosis
• Infection with this parasite can occur
through: swallowing water that has been
contaminated with fecal material (in
swimming pools, lakes, or public water
supplies); eating uncooked food (like
oysters) that are infected; or by person-to-
person transmission, including
changing diapers or exposure to feces
during sexual contact. 12/04

25. Cryptosporidiosis: Epidemiology
• Caused by Cryptosporidium
species
–Protozoan parasites
–Infect small intestine mucosa; in
immunosuppressed patients,
also infect large intestine and
other sites 12/04

26. Cryptosporidiosis: Epidemiology
• Infection results from ingestion of oocysts
excreted in feces of infected humans or animals
– Water supplies and recreational water sources
(oocysts may withstand standard chlorination)
– Person-to-person transmission via oral-anal contact,
from infected children to adults (eg, during diapering)
• Risk greatest with CD4 count <100 cells/μL
• Incidence dramatically lower in areas with
widespread use of effective ART
12/04

27. Cryptosporidiosis:
Clinical Manifestations
• Acute or subacute onset of profuse
watery, nonbloody diarrhea, often with
nausea, vomiting, and abdominal
cramping
• Fever in 1/3 of patients
• Malabsorption is common; dehydration,
malnutrition may result
• Biliary tract and pancreatic duct may be
infected, causing cholangitis and
12/04
pancreatitis

28. Cryptosporidiosis
12/04

29. Cryptosporidiosis: Diagnosis
• Microscopic identification of oocysts in
stool or tissue
– Modified acid-fast and other stains
– Consider repeat stool sampling
• DFA or ELISA
• Small intestine biopsy with identification of
Cryptosporidium organisms
• Cannot be cultured
12/04

30. Cryptosporidiosis: Treatment
• ART with immune restoration (to CD4
count >100 cells/μL) results in complete
resolution
• No consistently effective antimicrobial
therapy
– Consider nitazoxanide or paromomycin
• Symptomatic treatment: antidiarrheals (eg,
loperamide, tincture of opium)
• Supportive care: hydration, nutritional
support 12/04 (IV therapies may be needed)

31. Cryptosporidiosis:
Treatment Failure
•Supportive
treatment
•Optimal ART
12/04

32. Cryptosporidiosis:
Prevention of Recurrence
•No effective
prevention, other than
immune restoration
with ART
12/04

33. Microsporidiosis
12/04

34. Microsporidiosis: Epidemiology
• Protists,
• Many species, including Enterocytozoon
bieneusi, Encephalitozoon cuniculi,
Encephalitozoon intestinalis
• Ubiquitous, may be zoonotic and/or
waterborne
• Risk greatest with CD4 count <100 cells/μL
• Incidence dramatically lower in countries
with widespread use of effective ART 12/04

35. Microsporidiosis: Epidemiology
• Ubiquitous, may be zoonotic
and/or waterborne
• Risk greatest with CD4 <100
cells/μL
• Incidence dramatically lower in
countries with widespread use of
effective ART
12/04

36. Microsporidiosis:
• In the gut of the host the spore
germinates, it builds up osmotic
pressure until its rigid wall ruptures
at its thinnest point at the apex. The
posterior vacuole swells, forcing the
polar filament to rapidly eject the
infectious content into the
cytoplasm of the potential host..
12/04

37. 12/04

38. Microsporidiosis:
Clinical Manifestations
• Most common: diarrheal illness
• Other manifestations: cholangitis,
hepatitis, encephalitis, ocular
infection, sinusitis, myositis,
disseminated infection
• Clinical syndromes may vary by
species
12/04

39. Microsporidiosis: Diagnosis
• Some species cannot be cultured
• Microscopic identification of stool or
tissue samples
–Selective stains
– Evaluate 3 stool samples
–Small bowel biopsy if stool studies are
negative and suspicion is high
12/04

40. Microsporidiosis
• Human microsporidiosis
represents an important and
rapidly emerging opportunistic
disease, occurring mainly, but not
exclusively, in severely
immunocompromised patients
with AIDS.
12/04

41. Microsporidiosis in
Immunocompromised persons
• Additionally, cases of microsporidiosis in
immunocompromised persons not
infected with HIV as well as in immune
competent persons also have been
reported. The clinical manifestations of
microsporidiosis are very diverse, varying
according to the causal species with
diarrhoea being the most common.
12/04

42. Microsporidiosis: Treatment
• ART with immune restoration
(to CD4 count >100 cells/μL)
–Results in resolution of
symptoms of enteric
microsporidiosis; but does not
eliminate the microsporidia
12/04

43. Microsporidiosis: Treatment
• E bieneusi infection: no specific
antimicrobial; consider fumagillin 60 mg
PO QD (not available in United States) or
nitazoxanide
• Non-E bieneusi microsporidial infection
(other than ocular): albendazole 400 mg
PO BID
– Treat until CD4 count >200 cells/μL
• Ocular infection: fumagillin (Fumidil B) eye
drops 70 mcg/mL (indefinitely) +
12/04albendazole 400 mg PO BID

44. Microsporidiosis: Treatment
• Supportive care: hydration, nutritional
support (IV therapies may be needed)
12/04

45. Microsporidiosis:
Adverse Events
• Albendazole: hypersensitivity,
neutropenia, CNS effects,
nausea, vomiting, diarrhea,
hair loss, elevated liver
enzymes
• Oral fumagillin:
12/04 thrombocytopenia

46. Microsporidiosis:
Treatment Failure
• Supportive treatment
• Optimal ART
12/04

47. Microsporidiosis:
Prevention of Recurrence
• Ocular: indefinite treatment
–May consider discontinuing
maintenance therapy in
asymptomatic patients on ART
with sustained increase in CD4
count to >200 cells/μL for ≥6
months (no data to support this
approach)
12/04

48. Microsporidiosis:
Considerations in Pregnancy
• Not recommended in
pregnancy:
–Albendazole: embryotoxic and
teratogenic in animals
–Systemic fumagillin: growth
retardation in rats
12/04

49. Isosporiasis
• Isosporiasis is a human intestinal disease
caused by the parasite Isospora belli. It is
found worldwide, especially in tropical and
subtropical areas. Infection often occurs in
immuno-compromised individuals, notably
AIDS patients, and outbreaks have been
reported in institutionalized groups in the
United States. The first documented case was
in 1915.
12/04

50. Isospora belli
• The coccidian
parasite Isospora
belli infects the
epithelial cells of the
small intestine, and
is the least common
of the three
intestinal coccidia
that infect human
12/04

51. Isospora belli
• Infection causes acute, non-bloody
diarrhea with crampy abdominal pain,
which can last for weeks and result in
malabsorption and weight loss. In
immunodepressed patients, and in
infants and children, the diarrhea can be
severe. Eosinophilia may be present
(differently from other protozoan
infections) 12/04

52. Isospora belli
12/04

53. Isospora belli
• Microscopic demonstration of the
large typically shaped oocysts is the
basis for diagnosis. Because the
oocysts may be passed in small
amounts and intermittently,
repeated stool examinations and
concentration procedures are
recommended.
12/04

54. . Isospora belli.
• The oocysts can be visualized on
wet mounts by microscopy with
bright-field, differential
interference contrast (DIC), and
epifluorescence. They can also be
stained by modified acid-fast
stain.
12/04

55. Isospora belli
• Trimethoprim
sulfamethoxazole is the usual
treatment choice. See
recommendations in The
Medical Letter (Drugs for
Parasitic Infections) for
complete information.
12/04

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57. • Programme Created by Dr.T.V.Rao MD
for Medical and Paramedical Students in
the Developing world
• Email
• doctortvrao@gmail.com
12/04