HIV opportunistic infections

1. TOXOPLASMOSIS
OLUM HERBERT
MBChB

2. Introduction
• Toxoplasmosis is an infection with protozoa Toxoplasma gondii, an
obligate intracellular parasite
• It’s a major cause of neurologic disease & deaths among patients with
advanced HIV disease.
• It a zoonosis, T. gondii infects warm blooded animals including
humans, but the primary host is the cat family.

3. Epidemiology
• Toxoplasmosis occurs world wide
• Sero-prevalence varies with different geographical locations &
nationality
• Paris, 90% of adults sero-positive
• US, 10 to 50%
• Uganda, 50% general population at Entebbe
58% HIV infected adults in Mulago

4. Forms of Toxoplasma gondii
It exists in 3 forms;
• Tachyzoites (fast dividing asexual form)
• Tissue cysts
- contains bradyzoites, slow dividing form of the parasites
- serve as a reservoir of tachyzoites,
- are responsible for disease transmission & latent infection.
- commonly occur in the brain, heart and skeletal muscle
• Oocysts
- infective oocysts contain sporozoites
- only form in cats, & are excreted in a non infectious form
- Sporulate after 2 to 21 days after excretion

5. Life Cycle
• T. gondii lifecycle takes place in cats, the definitive host
• A cat becomes infected with T. gondii(bradyzoites) by eating contaminated
raw meat.
• Sexual reproduction occurs in cat’s GIT where macrogametes and
microgametes develops from the ingested bradyzoites and fuse to form
zygote.
• Zygote gets encapsulated with a rigid cell wall
• The zygote sporulates and divides to form sporozoites within the oocysts

6. Con’t
• The Sporozoites become infectious after 24hrs after the cat sheds
oocysts in feaces
• Human infection results from ingestion of oocysts e.g soil or water
contaminated with cat faeces, ingestion of tissue cysts in
undercooked meat or vertically
• Asexual reproduction occurs in mammals including humans and birds

7. Life cycle

8. Transmission in humans
• Ingestion of undercooked infected containing Toxoplasma tissue cysts
• Ingestion of the oocysts from faecally contaminated hands, water or
food
• Organs transplantation
• Blood transfusion
• Trans-placental transmission
• Accidental inoculation of tachyzoites

9. Pathogenesis
• Ingestion of the tissue cysts or infective oocytes
• Tissue cysts are lysed by digestive enzymes & tachyzoites are released
• Sporozoites released from infective oocysts, penetrate epithelial cell &
transform into tachyzoites
• Tachyzoites invade intestinal epithelial cells & disseminate
haematogenously
• Tachyzoites actively invade nucleated cells, rapidly proliferate & destroy
host cells

10. Con’t
• Tissue invasion, destruction & parasite secretions result in activation
of host defense mechanisms (Humoral & Cell mediated immunity).
- Specific Ab mediated lysis of the tachyzoites
- Activation of macrophages resulting in intracellular killing
- Direct action of cytotoxic cells
• Evasion of the host immune response
• Intracellular sequestration
• Formation of parasitophorous vacuole and Inhibition lysosomal
fusion

11. Clinical presentation
• Acquired toxoplasmosis in Immuno-competent host
• Congenital toxoplasmosis
• Immuno-compromised host

12. Acquired toxoplasmosis
Acute infection
• Asymptomatic in 80 to 90% of cases
• Most common symptom is cervical lymphadenopathy
• Fever
• Muscle pain
• Sore throat
• Rash
• Hepatomegaly
• Splenomegaly
Latent infection
• No symptoms
• It has been associated with behavioral changes in animals

13. Congenital Toxoplasmosis
• Ocular disease(Most common presentations of congenital toxoplasmosis)
• Chorio-retinitis(posterior uveitis) causing visual loss
• Mild disease may consist of slightly diminished vision
• Severely disease may have full tetrad of signs;
-retinochoroiditis,
-hydrocephalus (least common but most dramatic)
-convulsions,
-Intracerebral calcification
• Encephalitis
• Hydrocephalus
NB; symptoms occurs 5-20days after exposure

14. Immuno-compromised host
• Disseminated toxoplasmosis, serious disease manifests as
Fever, encephalitis or brain abscess
• The most notable manifestation in patients with advanced HIV is
Toxoplasma encephalitis

15. Clinical manifestations of toxoplasmosis in
patients with AIDS
• Brain involvement
• Altered mental status
• Seizures
• Weakness
• Cranial nerve disturbances
• Sensory abnormalities
• Cerebellar signs
• Movement disorders
• Neuropsychiatric manifestations
• Meningismus
• Pulmonary toxoplasmosis
• Spinal cord involvement
• Extra-pulmonary toxoplasmosis
• Ocular toxoplasmosis

16. Diagnosis
• Clinical assessment / evaluation
- History
- Physical examination
• Investigations
Serology tests for detection of IgM/IgG: IgM positive in 1 week, IgG
positive in 2 weeks
Ocular disease: ophthalmoscopy showing iritis, vitritis and
chorioretinitis(white retinal lesions)
Encephalitis:
• MRI; shows ring-enhancing lesions
• CT Scan
• CSF PCR sensitivity

17. Treatment
• Acute infection usually does not require treatment
• Ocular or CNS disease: pyrimethamine plus sulfadiazine plus leucovorin
to prevent sulfadiazine bone marrow toxicity for 6 weeks
Acute / Reactivated
Pyrimethamine / Sulfadiazine
Trimethoprim / Sulfamethoxazole
Clindamycin
Spiramycin
Latent toxoplasmosis
Atovaquone
Clindamycin
Atovaquone / Clindamycin

18. Prevention and control
Persons at high risk
• Foetus (Pregnant mothers)
• Newborn babies
• Immunocompromised
• HIV / AIDS
• Organ transplant patients
• Patients on cancer treatment

19. Prevention
• Proper handling of food
- thorough cooking >66oC
- Good food handling practices
- Freeze storage
• High risk patients especially pregnant women should avoid cats.
• Screening of mothers during pregnancy
• Screening of Organ and blood donors
• Safe laboratory practices

20. Control
• Treatment of pregnant women with acute toxoplasmosis (Spiramycin)
• Prophylaxis of HIV / AIDS latent cases (SP)

21. Prognosis
• Immunocompetent patients have an excellent prognosis,
lymphadenopathy and other symptoms resolves within weeks of
infections
• Prognosis is poor in immunocompromised individuals like HIV
patients with a high viral load and poor adherence

22. Complications
• Ophthalmic complications
• Intraocular inflammation
• Posterior uveitis
• Cataracts
• Branch retinal vein occlusion
• Branch retinal artery occlusion
• Tractional retinal detachment
• Posterior synechiae
• Cystoid macular edema
• Optic atrophy

23. END
Questions?