1st Medical Integrated Students, Research (MISR) Conference
Review of Vaccine Candidates for most
serious parasitic infections in Egypt
Hatem El-Sheemy
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Research Groupunder supervision of
Prof.Dr. Heba Abdel-Aaty Head of parasitology department
MUST College of Medicine
Hatem El-Sheemy, Mahmoud Mammdouh Gad Ahmed, Ahmad Ali
Essam Elkomy, Bola Amin, Abd El Rahman ElSadek
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How this work started?
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Systematic Reviews Importance
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Aim of the Work
• Review of the most recent publication for the prevalence of parasitic infections in Egypt.
• Selection of the most serious ones• Review of vaccine candidates and
Clinical Trials (if available) for most serious parasitic infections in Egypt.
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Our Selection Criteria
Based on1. Effect of the parasitic infection on Egyptians
health & economy
2. Re-emergence of parasitic infections specially those with a long history with Egypt (were endemic)
3. Availability of Vaccination clinical trials against this parasitic infection.
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• Fascioliasis (Trematode)
(Fasciola gigantica\Fasciola Hepatica)• Schistosomasis (Trematode)
Schistosoma Mansoni• Toxoplasmosis (Protozoa)
Toxoplasma gondii
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Vaccine DevelopmentPre-clinical development Antigen identification
Clinical development 4 phases Vaccine trials:
Phase I Small scale – to assess the safety of vaccine
Phase II Larger scale – to assess the efficacy and S\effects
Phase III Larger scale – to assess the efficacy and S\effect Phase IV Post-marketing surveillance to detect rare S\E
for the now Licensed vaccine
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Fascioliasis .. An old friend !Fasciolia hepatica was
identified in cattle represented in Egyptian
tombs (Esteban et al., 2003)
With the presence of liver fluke fragments
in an Egyptian mummy
(David, 1997).
History in Egypt
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1949, sheep (16%)
1988, 59.5% in Dakahlia 29.7% in Gharbia
2002, sheep 12.7% in North Sinai30% annual loss in milk and meat
2005, sheep 20.6% in Dakahlia
2006, 11.2% in Dakahlia 21.8% in Gharbia
2014 17.6% donkeys in Giza Zoo, 7.7% in Sharkia
Animal Fascioliasis Human Fascioliasis
Fascioliasis
1960 only sporadic human cases
1990, overall prevalence of 3%.
2003, 12.8% in Delta (5 villages)
2006 in Dakahlia, 4.8%
2014 Fasciola gigantica eggs in stool reached up to 6.02% in 1810 randomly collected human stool samples from Kafr El-Sheikh Governorate% Prevelance
Badawy et al 2014ElBahy et al
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Fascioliasis
Vaccination
Fasciola giantica Glutathione S-transferase (Purified GST Ag in Goats)
Egypt 200990% Reduction in eggs per gram faeces (EPG)66% Reduction in fluke burdenThis was the first report of protective vaccination of goats against F. gigantica with purified GST antigen.
Cathepsin B Antigen (Mice) France 2013
66% Reduction in parasite with Cathepsin B2 (rFgCatB2) 60% Reduction in parasite with Cathepsin B3 (rFgCatB3)
in 2010, the same group repeated study with larger sample (15 Goats)59.6% reduction of ova per gram32.6% reduction of worm burdenWithout immunopotentiator (Ferund's Adjuvant) usageDeghiedy et al 2008,2010
Chantree et al 2013
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Fascioliasis
Vaccination
Fasciola hepatica
Leucine aminopeptidase (FhLAP)75% reduction of worm Loads in rabbits
Cathepsin L protease (FhCB-1)50-55% reduction in worm burden and egg production72.4% with adding Freund's adjuvant
Acosta et al 2008
Rohbinson et al 2012
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Fascioliasis & Schistosomiasis
“Fascioliasis appears frequently associated to other detrimental diseases, especially Schistosomiasis “
Estebean 2003
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Schistosomiasis A never ending story?
schistosomiasis haematobium was endemic in Ancient Egypt. Infection was diagnosed in mummies 3000, 4000 and 5000 years old
History in Egypt
Deelder 1990
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1925 60% in North Delta1935, 32% in Nile Delta1983 16.4% in Nile Delta1996, 12% in Nile Delta2000 36.4% in National surv2003 12.3% in Delta2006, 5.3% in Dakahlia2009, 2.5% in Menoufia
Schistosoms Mansoni
Schistosomiasis
% Prevelance
All the three recent reports indicated1.Low-intensity of infection2.Development of PZQ Resistance
Barakat et al 2013
2013 0.8% (8\1000) students in Berket-ESabaa School
2014 26.7% 186\700 among fishermen in lake manzla
Aug. 2015 29% 433\1493 In Kafr El-Shiekh Gov.
Amira Taman et al 2014
El Morshedy et al 2015
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Why we selected Schistosomiasis
• A study was held in Nile delta indicates a PZQ resistance development ranging from 10% to 20% what makes us think about the availability and distribution of PZQ at pharmacies without prescription
• Amira Taman et al 2014, reported that some positive cases reported treatment with antischistosomal agents in the 6-8w
• Some Reports indicating that PZQ does not prevent reinfection nor does it reduce transmission in highly endemic areas.
Recent Re-emergence of Schistosomiasis mansoni in Egypt.Egypt’s long history with schistosomiasis and Liver diseasesPZQ resistance:
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Schistosomiasis
Vaccination WHO Report 2014
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Schist. Vaccines clinical trials
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Schistosoma Mansoni Vaccination
Sm-TSP-2 (Schistosoma mansoni Tetraspanin-2)
• In collaboration with researchers at the James Cook University The George Washington University, Passing now Phase I Clinical Trials at Texas Children's Hospital and Baylor College of Medicine,
@ USA
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Sm-TSP-2
• Sm-TSP-2 (Schistosoma mansoni Tetraspanin-2)
Sm-TSP2 is one of Schistosome Tegmunt membrane proteins
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Sm-TSP-2
• Preclinical: 57–64% protection in mice
Tran MH et al 2006
• Phase I: 83% reduction in adult worm survival rates.
After Knockdown of the Sm-tsp-2 gene in the immature human stage of the parasite,
the schistosomula.Tran MH et al 2010
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How long have you been in Egypt?
Toxoplasma Gondii was found in Egyptian Mummy from the Third
intermediate period (806-784 BC)Khairat R. et al 2013
So Long
Toxoplasmosis
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Toxoplasmosis Diagnosis
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Toxoplasmosis effect on…
Primary infection in Pregnancy Seroconversion: (1gG- \ IgM-)
(1gG+ \ IgM+)
In immunosuppressed people
EconomyInfection is not only acquired by contact with the definitive host, but also by ingestion of raw milk and milk products.
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Toxoplasmosis .. A Timeline..IgG+ \IgM+ among Pregnant Females
• 2001 Qalyoubya 58.1% - 6.5% Ah Hussein et al
• 2008 Alex 46.2% - 20.2% Awadallah HN et al
• 2010 Fayoum 45.8% - 30.5% N Ghonim et al
• 2012 Menoufia 67.5% - 2.8% eldeeb et al
• 2012 Sharkia 30% - 10% Amany, M et al
• 2013 Qena 46.8% - 18.4% Abdelaziz Tamam et al
• 2013 Gharbia 42.8% - X Gamea GA (MSc theisis) • 2014 Mansoura 44% - X eltantawy et al
• 2014 Sharkia 63% - 11% H Ahmed et al
• Aug 2015 Menoufia 52.2% - 9.78% Nassef NE et al
• Sept 2015 Cairo 31% - 20% Hassanin et al
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Toxoplasmosis .. In Pregnancy
Hassanain MA et al sept. 2015
57.5 %(61cases) were susceptible to primary infection (IgG-/IgM-).23.6 % (25 cases) of studied women (IgG+/IgM-) were immune.8.5% (9 cases) acute toxoplasmosis (IgG+/IgM+) 10.4% (11%) confirmed for recent infection (IgG-/IgM+)
Cairo (Kasr elainy) & Bani-Sueif GenHosp
Groups No. Cases with IgG+ cases
IgM+ cases
Group1 56 abortion in the 1st trimester 17 12
Group2 30 abortion in the 2nd trimester 8 5
Group3 15 intrauterine fetal death 7 2
Group4 5gave birth to babies with congenitalanomalies
2 1
Total 106 - 26 20 41 21 14One
Qena 2013
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Toxoplasma & infertility
After many reports in many countries
a Report from Egypt in 2013 indicated that:
El Tantawy N. et al
IgG+ in 193 (61.85%) of 312 infertile ladies attending
Gynecology clincat Mansoura University
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Toxoplasmosis .. In Chronic Liver diseases
Mansoura University Hospital, El Nahas et al April . 2014
“opportunistic T. gondii infection represents a serious risk for HCV patients.
So it should be considered in their investigations and follow-up”
76.9%12.8%
Early
stage
92.6%13.6%
Late Stag
eIgG +
30\39
5\30 11\75
75\81
Control Group: IgG: 6\40 IgM: 3\6
IgG +
IgM + IgM +
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Toxoplasmosis .. Prevalence Studies
180 Healthy
22.2%
180 HCV\HBV
32.8%
Mansoura University Hospital,
IgG + IgG +
40\180 59\180
El Henawy et al Sept. 2015
“opportunistic T. gondii infection represent a potential significant risk for chronic HCV patients.”
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Toxoplasmosis .. In Renal diseases
Hamza H et al April. 2015
30 Healthy control
60 hemodialysis 30SLE
30 Renal transplant recipients
61.7%
60%
70% 30%
“No significant association could be found between T. gondii seropositivity and the clinical manifestations of CKD patients.”
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Toxoplasmosis .. Source of InfectionIN Animals:• Definitive Host: Cat 2010: Giza 153\158 stray cat were IgG + reported high environmental contamination with oocysts in Egypt.
Yara ElKapany et al
DOGS: 50\51 Stray dogs in Giza ElBehairy et al 2013
Anti-Toxoplasma anti-bodies were found in:-• 59.5% of Domestic turkeys, • 47.2% of Chickens • 50% of Ducks ElMasry et al
2003• 11.8% Chickens 36\304 in 4 different governorates with sample from each season in the year.
Hani Ibrahim et al 2014
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Economical effect
Ahmed Elsify et al
• Giza 2008: 35.6 in sheep and 43.7% in goats• Delta 2013: 31.01% in sheep 17.11% in
goats. • Animals had previous case history of reproductive disorders and births of weak lambs and kids.
• Several cats were observed moving in and out of the farm.
• Serological examinations of all aborted ewes and does revealed positive reaction for Toxoplasma gondii infection.
• Infection represents a serious impact on the fertility and overall production of the involved animals.
• Fetal death is likely caused by the multiplication of T. gondii in the placenta rather than invasion of the fetus by the parasite
Abortion Due to Toxoplasmosis in Sheep and goats
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Toxoplasmosis .. Vaccination
Autoclaved Toxoplasma Vaccine (ATV) Egypt• Significant increase in the percentage of splenic CD8+TL • death of mice vaccinated with ATV was delayed for nine days while control
group mice died in the fifth day.• significant decrease in parasite density in different organs, and a marked
reduction of pathological changes in liver suggesting that significant immune responses were mounted following vaccination.
• Further studies are needed to evaluate the efficacy of vaccine with larger sample size
The S48 strain Toxovax Intervert Schering Netherlands
• a live vaccine originally developed for use in sheep, but when used in cats inhibits sexual development of T. gondii (Cat intestine).
• However it causes many side effects and expensive Kur et al 2009
Eissa M et al 2012
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Limitations
• The huge cost of vaccine trials where Still no vaccine licensed for human use.
• Absence of recent prevalence studies for some parasitic infections in Egypt specially those reported highly prevalent before.
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Conclusion
Absence of proper vaccines against parasitic infections ,development of drug-resistance ,
re-emergence and high prevalence of some parasitic infections are putting the control of
Parasitic infections in Egypt at a risk.
This increases the need for further screening and mass eradication of parasitic diseases
before its too late.
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Recommendations
• Intense need for Infection control awareness campaigns against parasitic infections especially in rural areas and among school students.
• More studies and national wide surveys about prevalence of parasitic infection in Egypt.
• To encourage vaccine trials projects in Egypt• Careful consideration for reports about
development of PZQ resistance in Egypt.
Thank You All
Review of Vaccine Candidates for the most serious parasitic
infections in Egypt(( ))