Lecture 53 - 3rd Asessment - Toxoplasma

Learning Objectives  Must      

know about:

Importance to Kuwait Modes of Transmission Pathogenesis & Symptoms Type of specimen AND Diagnosis Prevention Life Cycle

 Should 

(Toxoplasmosis)

know:

Treatment

4 November 2005 A 27 year-old Kuwaiti was admitted in Ibne-Sina Hospital with a 10-day history of headache and lethargy. On the day of his admission, he presented with seizures and became confused, disoriented, and irritated. He had no fever. The Pt. had renal transplant 5 Yrs ago and was on immunosuppressive maintenance therapy [Cyclosporin, steroid].

Physical Examination: He was lethargic and could not answer properly to questions.  His vital signs were all within normal limits  Chest examination and radiograph were normal. Investigative Protocol: Laboratory Investigation: Blood, Serum, CSF: Microscopy Biochemical & Electrolyte analysis Bacterial, Viral, Parasitic studies

Clinical Queries • What is your provisional diagnosis? • What’s the etiological agent of this • infection? How did he get the infection?

• What’s the significance of Immunosuppressive therapy? • How would you diagnose this infection? • How would you manage this patient? • How would you prevent this patient?

Clinical Case 2 A pregnant Syrian lady attended the clinic for her 1st antenatal check up. •

Her physical condition was normal

•

The ultrasound showed delayed fetal development

•

She was screened for ‘TORCH’ Toxo IgG: 1:360

IgM: 1:

Clinical Queries

• What is your provisional diagnosis? • What’s the etiological agent of this infection? • How would you detect this infection: i, in Mother ii, in the fetus? • What’s the significance of this infection in pregnancy? • How would you manage this case?

• Would you screen all pregnant ladies in Kuwait?

Toxoplasmosis gondii

Toxoplasma

Toxoplasmosis is a zoonotic infection 

It is a coccidian parasite Sexual stage in the intestinal mucosa of a carnivorous definitive host [cat]

Zoonotic Cycle [Cat]

Oocyst

Maturation 3-4 days

Cyst

Toxoplasmosis

Toxoplasma gondii

Toxoplasmosis is a zoonotic infection

Worldwide:

Kuwait, Syria, Lebanon

[20 – 75%]

  Congenital Toxoplasmosis: Pregnancies

Stages:

Tachyzoites Bradyzoites

1-5 / 1000

Toxoplasmosis

Epidemiology

20 – 75% of various population have Ab. to Toxoplasma gondii

Middle East: Year

Kuwait

34-75%

1983

Saudi Arabia

25-45%

1994

UAE

34%

1997

Egypt 1995

25-50%

Toxoplasmosis

Tachyzoites

Toxoplasma gondii

Bradyzoites

Toxoplasma Cyst

Zoonotic Cycle [Cat]

Oocyst

Maturation 3-4 days

Cyst

M O D E

s O F T R A N S M I S S I O N

Toxoplasmosis

Modes of

Transmission

1. Acquired:

i, Eating food contaminated with Oocyst ii, Eating uncooked infected meat (cysts) iii, Transfusion of contaminated blood

Rare

iv, Transplantation of infected organ

Rare

2. Opportunistic: Transplant Pts., Immunocompromized Pts. “Reactivation of Infection”

3. Congenital:

From infected mother to fetus

Never follow any emergency vehicle closer than:

100 feet. 500 feet. 800 feet. 250 feet.

Toxoplasmosis Pathogenesis 

Intracellular infection



Spread by destroying cells, bloodstream/lymphatics



Primary target sites: CNS, Eyes



In macrophage: blocks Phago-lysosome fusion

Toxoplasmosis Pathogenesis 

Intracellular infection



Spread by destroying cells, bloodstream/lymphatics



Primary target sites: CNS, Eyes



In macrophage: blocks Phago-lysosome fusion



Outside macrophage: killed by Ab + complement



Infection controlled by IL2 & interferon gamma

Toxoplasmosis

Clinical

Presentation

Clinical presentation depends on: i, Mode of Transmission ii, Immune Status of the Host

1. Acquired:

Self limiting & generally asymptomatic

2. Opportunistic: Encephalitis in Immunocompromized Pts 3. Congenital: Fetal damage depends on the time of infection acquired during pregnancy. Risk of fetal damage is highest in the 1st trimester Retinochoroiditis, Encephalitis, Abortion

Congemital Toxoplasmosis Rate of Transplacental

Congenital Sequele

Transmission

1st Trimester

14%

41%

2nd Trimester

29%

8%

3rd Trimester

59%

0%

Toxoplasmosis Infection in Pregnancy

Consequences of fetal infections  Premature labour  Still birth  Spontaneous abortion  Congenital malformations Risk of fetal damage is highest in the 1st trimester Eye, ear, brain, heart, liver, spleen

Clinical Presentation

Hydrocephalus

Chorioretini tis

Toxoplasmosis Clinical Presentation I.

A pregnant Syrian lady showed delayed fetal development on ultrasound during her 1st antenatal check up.

Toxoplasmosis Presentation  History of abortions ??  Fetal abnormality on ultrasound during antenatal check up Birth of a the sickpregnant baby In  most cases mother is asymptomatic

 Screening: TORCHS

Toxoplasmosis

Investigation

TORCHS  TO R C H S

Toxoplasma gondii Rubella CMV HSV Syphilis

Toxoplasmosis

Investigation

I. Serology: 1. IgG antibodies 2. IgM antibodies 3. IgA antibodies

II. PCR III. Sabin & Feldman Dye Test IV. Culture V. Animal inoculation

Toxoplasmosis

Treatment

Acute acquired toxoplasmosis in Immunocompetent hosts is self limiting However,

Infection acquired during pregnancy does require treatmen to reduce fetal infection. Spiramycin

50-100 mg/Kg/day x 4 wks

 Pyrimethamine

1-2 mg/Kg/day

Sulfadiazine wks Folinic acid

x 4 wks

100-200 mg/Kg/day x 4

Toxoplasmosis

Prevention

I. Primary Prevention Prevention

II.

Secondary

Primary Prevention: 1. Avoid contact with materials contaminated with cat feces 2. Wear gloves during gardening 3. Cook meat to 65 0C 4. Wash fruits & vegetables before use 5. Premarital screening Secondary Prevention: Identification and treatment of acquired acute infection

6th December 2003 A 35 year-old Kuwaiti was admitted in Ibne-Sina Hospital with a 10-day history of headache and lethargy. On the day of his admission, he presented with tonic clonic seizures and became confused, disoriented, and irritated. He had no fever. The Pt. had renal transplant 13 Yrs ago and was on immunosuppressive maintenance therapy [Cyclosporin, steroid].

Clinical Queries • What is your provisional diagnosis? • What’s the etiological agent of this • infection? How did he get the infection?

• What’s the significance of Immunosuppressive therapy? • How would you diagnose this infection? • How would you manage this patient? • How would you prevent this patient?

Toxoplasmosis Clinical Presentation I.

A pregnant Syrian lady showed delayed fetal development on ultrasound during her 1st antenatal check up.

Clinical Queries

• What is your provisional diagnosis? • What’s the etiological agent of this infection? • How would you detect this infection: in Mother in the fetus? • What’s the significance of this infection in pregnancy? • How would you manage this case?

• Would you screen all pregnant ladies in Kuwait?

Toxoplasmosis in Pregnancy Guidelines for Serologic Screening

IgG >512 ; IgM +ive

* Recent

Infection IgG >512 First Trimester Recent Inf. Confir or Early 2nd Trimester * Infected near

IgM >80 IgG +ive [repeat after 3 wks] IgM –ive

conception

*

IgG 4-fold rise

Toxoplasmosis in Pregnancy Guidelines for Serologic Screening

Each Subsequent Trimester [repeat at delivery] Seroconverted

IgG+ive

Pt. Baby at Risk Confirm by IgM

Check baby for Congenital Infection

At Time of Delivery

IgG +ive

Check baby

Infections in Pregnancy Important Pathogens I. Viral pathogens: CMV; HBV;

Cong. Rubella; VZV

HIV HSV

II. Bacterial pathogens: Listeria monocytogenes

Cl. Perfringens

Treponema pallidum

Brucella sp.

III. Parasitic pathogens: Toxoplasma gondii

IV. Fungal pathogens: Candida albicans

Malaria

Health Education • • • • • • • • •

What is Toxoplasmosis? How the infection is transmitted? Who are at high risk? How common it is in Kuwait? Why the pregnant women must know about it? Does it do any harm (damage) to the fetus? Can a pregnant women find out if she is immune? How it is diagnosed during pregnancy? Is there any vaccination against it?

Amoebiasis

(E. histolytica)

Prevalence very high in tropics

•Mode of Transmission: –

Feco-oral

- Contaminated food/ water

Cyst is the infective stage •Pathogenesis: –

Proteolytic enzymes/ Toxins

- Lysis of macrophages

•Pathology: –

Flask shaped ulcers in large intestine

–

Amoeboma,

Peritonitis,

Hepatic abscess

•Presentation: - Carriers

- Mild diarrhoea

- Bloody mucoid diarrhoea

- Abscess

•Diagnosis: - Microscopy [Trichrome staining] •Prevention: Improved personal hygiene

- Serology

Giardiasis

G. lamblia

Prevalence very high in tropics

Mode of transmission – Feco-oral route – Infective stage:

Pathogenesis:

- Contaminated food/ water Cyst

secreting proteolytic enzymes/ toxins ?

mechanical damage of villi

Pathology: Presentation: Diagnosis: Prevention:

Microvilli damage, Carriers, Microscopy

Malabsorption

Fatty diarrhoea [Trichrome staining]

Improved personal hygiene

Trichomoniasis

T. vaginalis

Prevalence high in young women Mode of transmission: sexual intercourse NO cyst stage is present

Pathogenesis: Pathology: Presentation:

Proteolytic enzymes/ toxins ? Multiple small ulcers on vagina/urethra Frothy foul smelling vaginal discharge Itching/ irritation,

Diagnosis: Prevention:

Males are asymptomatic

Microscopy; Motile trophozoites Treat both partners

Cryptosporidiosis

Immunocompromised patients: 

Mode of transmission:



Pathogenesis:

C. parvum associated with AIDS

Feco-oral, contaminated food/ water

Proteolytic enzymes/ toxins ? Cellular infiltration of lamina propria



Pathology:

Villous atrophy



Presentation:

Majority asymptomatic,

Outbreaks

Profuse greenish watery diarrhoea 

Diagnosis:

Microscopy of stool smear with SMB stain IFA

(Oocysts)



Management:

Rehydration, Paromomycine



Prevention:

Good personal hygiene