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Presented by,
Shumaila Taskeen
M-5766, Division of VPH
Major credit seminar
Neglected Parasitic Infection-
Toxoplasmosis
Beware CATS are everywhere
DO YOU KNOW
Toxoplasma infection is:
– Capable of altering behaviour of I/H ( rat & mice) in order to favour transmission
( Joanne; 2007 )
In humans:
– Linked to Intermittent Explosive disorder ( IED)
– Decreased novelty seeking behavior, slower reactions, lower rule-consciousness &
greater jealousy (in men)
– Greater warmth, conscientiousness and moralistic behavior (in women)
– Associated with Schizophrenia, Obsessive compulsive disorder, bipolar illness,
suicidal attempts, self directed violence & memory loss in elderly.
(Jaroslav; 2007)
• Less attractive to global funding agencies and policy makers
• Mainly concerned with poorer of poor segment of society
• Less attention paid on surveillance, prevention and treatment
• Parasitic infections typically associated with poor and
marginalized communities in low income countries.
• CDC targeted 5 diseases as priorities for pubic health action:
– Cysticercosis
– Toxoplasmosis
– Chagas diseas
– Toxocariosis
– Trichomoniasis
Neglected parasitic infections(NPI)?
(CDC)
Neglected Parasitic
Infection
Etymology :-
- Toxo: arc/ bow shaped, plasma:form
• Obligatory I/C protozoan parasite
• Complex life cycle:
- Definitive host- Cat
• - I/H- 350 sp. of warm blooded
mammals including birds (Tenter et al., 2000)
• Pre-patent period: Cat sheds oocysts
(~100million)
- 3-10 days after ingesting tissue cyst
- 18 days after ingesting tachyzoites/oocysts
• Predilection site; intestinal epithelium, muscle,
brain tissue
Introduction
1908 1909 1939 19571948
Nicolle & Manceaux
discovered from
African rodent- C. gondii.
Identified in congenitally
infected infant died of
encephalitis.
Renamed as:
Toxoplasma gondii.
Found to cause abortion
storms in sheep.
T. gondii specific Ab-test:
Sabin- Feldman dye Test
1970
Dubey et al.,
discovered life cycle,
felids as D/H
Timeline
Transmission cycle & Host range
(Worth et al., 2013)
WILD-life Toxoplasmosis
Global Prevalence
• Globally- At least 1/3rd of the human population is infected.
(A review on human toxoplasmosis; 2012)
• ~ 30% of human population is chronically infected.
(Animals are key to human toxoplasmosis; 2014)
• Annually >1 million cases in the European region due to contaminated
food. (WHO factsheet ; 2015)
• Seroprevalence :
 S-E Asia, North America & Northern Europe ~10-30%
 Central & Southern Europe, Latin America & tropical
African countries ~ 30 & 50%
Global prevalence
(Shwab et al., 2013)
Genetic diversity
Multilocus PCR-RFLP genotyping
?
Genotypic distribution
Acute
toxoplasmosis
• Asymptomatic
• Flu like signs-lymphadenopathy, myalgia ,
fever
• Immunocompromised -Encephalitis,
Hydrocephalus & Retinochoroiditis
Congenital
Toxoplasmosis
Clinical forms
(A review of humanToxoplasmosis;
2014)
Conti..
Chronic
Toxoplasmosis/
Reactivation
In immunocompromised (HIV/
Cancer patients/ organ transplant
recipients.
Ocular
toxoplasmosis
Necrotising retinochoroiditis ,
strabismus etc.
(A review of human Toxoplasmosis;
2014)
Asymptomatic, respiratory,
ocular signs, I/U infection-
encephalitis, hepatitis,
ascites, perinatal death
Sheep& goat-abortion
Oppurtunistic pathogen,
respiratory & neuromuscular
signs
Pig-subclinical
Cattle-asymptomatic,
not usually abortion
Clinical signs in domestic
animals
North
N=203
West
N=250
East
N=499
South
N=512
• Overall prevalence: 22.40%
• Regional prevalence:
• Highest: South India (37.3%)  Climate favour sustenance &
proliferation of oocysts
• Lowest: West India (8.8%)
• Findings: Prevalence is
- High in married women (25.8%) than single women (4.3%)
- Increased with age: 18.1% in 18–25 yr.group  40.5% in > 40 yr. group
- 66% in those residing in mud houses
- More in socioeconomically backward and tribal populations, barefoot
workers & consuming contaminated water or vegetables
Conclusion
Diagnosis
• Isolation -body tissues/fluids – Tachyzoite- inoculation in lab
mice/tissue culture (Montoya; 2002)
-Fecal examination- Oocyst- sheather’s sugar solution
• Molecular technique- PCR - Prenatal diagnosis – for serologically
positive female, targets-B1, AF146527, p30 etc.
Diagnosis
• Serology-
-ELISA- IgM , IgG , IgA
-Sabin Feldman test (1948)
-Indirect fluorescent assay
-Modified agglutination
-Latex agglutination
-IgG avidity test
Immunofluorescence
assay (Courtesy-CDC)
Identification of
parasite
Ultrasonography
MRI, CT scan
PCR-amniotic
fluid
MICE
CELL
CULTURE
Hydrocephalus,
intracerebral
calcification
Congenital
Toxoplasmosis
B1 GENE
Fetal diagnosis
Treatment
• Pregnant women- Spiramycin @ (2-3 tablets) daily * 3 weeks repeated
after a 2-week interval till parturition.
• Congenital & Acquired Toxoplasmosis- Pyrimethamine, Sulfadiazine
& folinic acid.
• Tissue cyst- Atovaquone & Clindamycin.
• AIDS patients- Clarithromycin, pyrimethamine, sulfadiazine
• Treatment in cats- Clindamycin
Prevention & control
Wear gloves while
gardening.
Cats should not be
fed raw meat.
Surfaces in contact
with raw meat be
washed with soap
and scalding hot
water.
Disinfect litter
pans daily with
scalding water.
Conti..
• Cook meat- internal temperature of 66 °C,
• Do not drink untreated water.
• Dogs kept out of the cat litter and vaccinated
for Distamper
• Pregnant & immunocompromised patients-
blanch ground vegetables
Advanced researches
• Parasite strictly depends on a key protein – ACTIN to form a
communication network and communicate.
• Protein depletion-network collapse-asynchronised replication- parasite
trapped inside the host cell- halt infection.
(University of Glasgow center)
Toxoplasmosis: novel
target to prevent
transmission
• TgSAG1 -major immune-dominant antigen - ideal candidate for recombinant
vaccine
• Conclusion-Et-TgSAG1 elicits TgSAG1-specifc Humoral and CMI in chickens.
• Et-TgSAG1 elicits a Th 1-dominant immune response in mice and a prolonged
survival time compared with wild-type E. tenella and non-immunized mice
• Toxoplasmosis is one of the most common causes of infectious
retinitis, accounting for 30–50% of posterior uveitis in Brazil.
(Commodaro et al., 2009)
Case Adult -Trimethoprim
(160mg)+ Sulfamethoxazole
(800mg) every 3 days * 20 months
Children-Trimethoprim (40mg/5ml)
/ Sulfamethoxazole (200mg/5ml)
every 3 days
Control No treatment No treatment
Conti..
• Initial study ended in yr.2000 and 116 /124 original patients followed
from 2000-2010 ;
- 59 (50.86%) from treated group &
- 57(49.13%) from control group
• Result -After 10 years, recurrence rate -same in both groups (22 each)
• Conclusion-
• Long term intermittent treatment with (Trimethoprim/
Sulfamethoxazole ) can reduce rate of recurrence only for the
duration when the patient is being treated
• Without prolonged suppressive treatment~ 80% of cases relapse &
20%–30% of patients on suppressive therapy relapse.
• Side effects of drugs have led to discontinuation of therapy in up to
40% of patients.
(Boothroyd et al., 2008)
• Nanoparticles of gold, silver- antimicrobial & antiparasitic activity.
• Develop a cost effective vaccine for cats- prevent shedding of
organism in feces.
• Determine number of children infected congenitally to guide
screening & treatment of Congenital Toxoplasmosis.
• Improve ways to prevent contamination of meat especially field raised
meat.
• Further access impact of toxoplasmosis on health, including mental
health.
• Improve preventive health education for public.
(Neglected parasitic infections in U.S, CDC)
Future prospects

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Toxoplasmosis- a neglected tropical disease

  • 1. Presented by, Shumaila Taskeen M-5766, Division of VPH Major credit seminar Neglected Parasitic Infection- Toxoplasmosis Beware CATS are everywhere
  • 2. DO YOU KNOW Toxoplasma infection is: – Capable of altering behaviour of I/H ( rat & mice) in order to favour transmission ( Joanne; 2007 ) In humans: – Linked to Intermittent Explosive disorder ( IED) – Decreased novelty seeking behavior, slower reactions, lower rule-consciousness & greater jealousy (in men) – Greater warmth, conscientiousness and moralistic behavior (in women) – Associated with Schizophrenia, Obsessive compulsive disorder, bipolar illness, suicidal attempts, self directed violence & memory loss in elderly. (Jaroslav; 2007)
  • 3. • Less attractive to global funding agencies and policy makers • Mainly concerned with poorer of poor segment of society • Less attention paid on surveillance, prevention and treatment • Parasitic infections typically associated with poor and marginalized communities in low income countries. • CDC targeted 5 diseases as priorities for pubic health action: – Cysticercosis – Toxoplasmosis – Chagas diseas – Toxocariosis – Trichomoniasis Neglected parasitic infections(NPI)? (CDC)
  • 4. Neglected Parasitic Infection Etymology :- - Toxo: arc/ bow shaped, plasma:form • Obligatory I/C protozoan parasite • Complex life cycle: - Definitive host- Cat • - I/H- 350 sp. of warm blooded mammals including birds (Tenter et al., 2000) • Pre-patent period: Cat sheds oocysts (~100million) - 3-10 days after ingesting tissue cyst - 18 days after ingesting tachyzoites/oocysts • Predilection site; intestinal epithelium, muscle, brain tissue Introduction
  • 5. 1908 1909 1939 19571948 Nicolle & Manceaux discovered from African rodent- C. gondii. Identified in congenitally infected infant died of encephalitis. Renamed as: Toxoplasma gondii. Found to cause abortion storms in sheep. T. gondii specific Ab-test: Sabin- Feldman dye Test 1970 Dubey et al., discovered life cycle, felids as D/H Timeline
  • 6. Transmission cycle & Host range (Worth et al., 2013)
  • 8. Global Prevalence • Globally- At least 1/3rd of the human population is infected. (A review on human toxoplasmosis; 2012) • ~ 30% of human population is chronically infected. (Animals are key to human toxoplasmosis; 2014) • Annually >1 million cases in the European region due to contaminated food. (WHO factsheet ; 2015) • Seroprevalence :  S-E Asia, North America & Northern Europe ~10-30%  Central & Southern Europe, Latin America & tropical African countries ~ 30 & 50% Global prevalence
  • 9. (Shwab et al., 2013) Genetic diversity Multilocus PCR-RFLP genotyping ?
  • 11. Acute toxoplasmosis • Asymptomatic • Flu like signs-lymphadenopathy, myalgia , fever • Immunocompromised -Encephalitis, Hydrocephalus & Retinochoroiditis Congenital Toxoplasmosis Clinical forms (A review of humanToxoplasmosis; 2014)
  • 12. Conti.. Chronic Toxoplasmosis/ Reactivation In immunocompromised (HIV/ Cancer patients/ organ transplant recipients. Ocular toxoplasmosis Necrotising retinochoroiditis , strabismus etc. (A review of human Toxoplasmosis; 2014)
  • 13. Asymptomatic, respiratory, ocular signs, I/U infection- encephalitis, hepatitis, ascites, perinatal death Sheep& goat-abortion Oppurtunistic pathogen, respiratory & neuromuscular signs Pig-subclinical Cattle-asymptomatic, not usually abortion Clinical signs in domestic animals
  • 16.
  • 17. • Overall prevalence: 22.40% • Regional prevalence: • Highest: South India (37.3%)  Climate favour sustenance & proliferation of oocysts • Lowest: West India (8.8%) • Findings: Prevalence is - High in married women (25.8%) than single women (4.3%) - Increased with age: 18.1% in 18–25 yr.group  40.5% in > 40 yr. group - 66% in those residing in mud houses - More in socioeconomically backward and tribal populations, barefoot workers & consuming contaminated water or vegetables Conclusion
  • 18. Diagnosis • Isolation -body tissues/fluids – Tachyzoite- inoculation in lab mice/tissue culture (Montoya; 2002) -Fecal examination- Oocyst- sheather’s sugar solution • Molecular technique- PCR - Prenatal diagnosis – for serologically positive female, targets-B1, AF146527, p30 etc.
  • 19. Diagnosis • Serology- -ELISA- IgM , IgG , IgA -Sabin Feldman test (1948) -Indirect fluorescent assay -Modified agglutination -Latex agglutination -IgG avidity test Immunofluorescence assay (Courtesy-CDC)
  • 20. Identification of parasite Ultrasonography MRI, CT scan PCR-amniotic fluid MICE CELL CULTURE Hydrocephalus, intracerebral calcification Congenital Toxoplasmosis B1 GENE Fetal diagnosis
  • 21. Treatment • Pregnant women- Spiramycin @ (2-3 tablets) daily * 3 weeks repeated after a 2-week interval till parturition. • Congenital & Acquired Toxoplasmosis- Pyrimethamine, Sulfadiazine & folinic acid. • Tissue cyst- Atovaquone & Clindamycin. • AIDS patients- Clarithromycin, pyrimethamine, sulfadiazine • Treatment in cats- Clindamycin
  • 22. Prevention & control Wear gloves while gardening. Cats should not be fed raw meat. Surfaces in contact with raw meat be washed with soap and scalding hot water. Disinfect litter pans daily with scalding water.
  • 23. Conti.. • Cook meat- internal temperature of 66 °C, • Do not drink untreated water. • Dogs kept out of the cat litter and vaccinated for Distamper • Pregnant & immunocompromised patients- blanch ground vegetables
  • 25. • Parasite strictly depends on a key protein – ACTIN to form a communication network and communicate. • Protein depletion-network collapse-asynchronised replication- parasite trapped inside the host cell- halt infection. (University of Glasgow center) Toxoplasmosis: novel target to prevent transmission
  • 26. • TgSAG1 -major immune-dominant antigen - ideal candidate for recombinant vaccine • Conclusion-Et-TgSAG1 elicits TgSAG1-specifc Humoral and CMI in chickens. • Et-TgSAG1 elicits a Th 1-dominant immune response in mice and a prolonged survival time compared with wild-type E. tenella and non-immunized mice
  • 27. • Toxoplasmosis is one of the most common causes of infectious retinitis, accounting for 30–50% of posterior uveitis in Brazil. (Commodaro et al., 2009) Case Adult -Trimethoprim (160mg)+ Sulfamethoxazole (800mg) every 3 days * 20 months Children-Trimethoprim (40mg/5ml) / Sulfamethoxazole (200mg/5ml) every 3 days Control No treatment No treatment
  • 28. Conti.. • Initial study ended in yr.2000 and 116 /124 original patients followed from 2000-2010 ; - 59 (50.86%) from treated group & - 57(49.13%) from control group • Result -After 10 years, recurrence rate -same in both groups (22 each) • Conclusion- • Long term intermittent treatment with (Trimethoprim/ Sulfamethoxazole ) can reduce rate of recurrence only for the duration when the patient is being treated
  • 29. • Without prolonged suppressive treatment~ 80% of cases relapse & 20%–30% of patients on suppressive therapy relapse. • Side effects of drugs have led to discontinuation of therapy in up to 40% of patients. (Boothroyd et al., 2008) • Nanoparticles of gold, silver- antimicrobial & antiparasitic activity.
  • 30. • Develop a cost effective vaccine for cats- prevent shedding of organism in feces. • Determine number of children infected congenitally to guide screening & treatment of Congenital Toxoplasmosis. • Improve ways to prevent contamination of meat especially field raised meat. • Further access impact of toxoplasmosis on health, including mental health. • Improve preventive health education for public. (Neglected parasitic infections in U.S, CDC) Future prospects