Vaccine candidates for the most serious parasitic infections in Egypt

1st Medical Integrated Students, Research (MISR) Conference
Review of Vaccine Candidates
for most serious parasitic
infections in Egypt
Hatem El-Sheemy

Research Group
under 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

How thiswork started?

SystematicReviews Importance

Aim of theWork
• Review of themost recent publication for the prevalence of
parasitic infectionsin Egypt.
• Selection of themost serious ones
• Review of vaccine candidates and ClinicalTrials (if available)
for most serious parasitic infectionsinEgypt.

Our SelectionCriteria
Based on
1. Effect of the parasitic infection onEgyptianshealth & economy
2. Re-emergence of parasitic
infections specially those with
a long history with Egypt (were endemic)
3. Availabilityof Vaccination clinical
trials against this parasitic infection.

• Fascioliasis (Trematode)
(Fasciola giganticaFasciola Hepatica)
• Schistosomasis (Trematode)
Schistosoma Mansoni
• Toxoplasmosis (Protozoa)
Toxoplasma gondii

Vaccine Development
Pre-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 Seffects
Phase III Larger scale – to assess the efficacy and Seffect
Phase IV Post-marketing surveillance to detect rare SE
for the now Licensed vaccine

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

1949, sheep (16%)
1988, 59.5% in Dakahlia
29.7% in Gharbia
2002, sheep 12.7% in North Sinai
30% annual loss in milk and meat
2005, sheep 20.6% 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 2014
ElBahy et al

Fascioliasis
Vaccination
Fasciola giantica
 Glutathione S-transferase (Purified GST Ag in Goats) Egypt 2009
90% Reduction in eggs per gram faeces (EPG)
66% Reduction in fluke burden
This 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 gram
32.6% reduction of worm burden
Without immunopotentiator (Ferund's Adjuvant) usage
Deghiedy et al 2008,2010
Chantree et al 2013

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 production
72.4% with adding Freund's adjuvant
Acosta et al 2008
Rohbinson et al 2012

Fascioliasis & Schistosomiasis
“Fascioliasis appears frequently
associated to other detrimental
diseases, especially Schistosomiasis “
Estebean 2003

Schistosomiasis A neverending story?
schistosomiasis haematobium was endemic in
Ancient Egypt. Infection was diagnosed in mummies
3000, 4000 and 5000 years old
History in Egypt
Deelder 1990

1925 60% in North Delta
1935, 32% in Nile Delta
1983 16.4% in Nile Delta
1996, 12% in Nile Delta
2000 36.4% in National surv
2003 12.3% in Delta
2009, 2.5% in Menoufia
Schistosoms Mansoni
Schistosomiasis
% Prevelance
All the three recent reports indicated
1.Low-intensity of infection
2.Development of PZQ Resistance
Barakat et al 2013
2013 0.8% (81000) students
in Berket-ESabaa School
2014 26.7% 186700 among fishermen
in lake manzla
Aug. 2015 29% 4331493
In Kafr El-Shiekh Gov.
Amira Taman et al 2014
El Morshedy et al 2015

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 diseases
PZQ resistance:

Schistosomiasis
Vaccination
WHO Report 2014

Schist. Vaccines clinical trials

Schistosoma MansoniVaccination
 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,
@ US

Sm-TSP-2
• Sm-TSP-2 (Schistosoma mansoni Tetraspanin-
2)
Sm-TSP2 is one of Schistosome Tegmunt membrane proteins

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

How long have youbeen in Egypt?
Toxoplasma Gondii was found in
Egyptian Mummy from the Third
intermediate period (806-784 BC)
Khairat R. et al 2013
Toxoplasmosis

Toxoplasmosis Diagnosis

Toxoplasmosis effecton…
Primary infection in Pregnancy
Seroconversion: (1gG- IgM-)  (1gG+ IgM+)
In immunosuppressed people
Economy
Infection is not only acquired by contact with the definitive host,
but also by ingestion of raw milk and milk products.

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

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 5
gave birth to babies
with congenital
anomalies
2 1
Total 106 - 26 20
41
21
14
One
Qena 2013

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 clinc
at Mansoura University

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
Stage
IgG +
3039
530 1175
7581
Control Group: IgG: 640 IgM: 36
IgG +
IgM + IgM +

Toxoplasmosis .. Prevalence Studies
180
Healthy
22.2%
180
HCVHBV
32.8%
Mansoura University Hospital,
IgG + IgG +
40180 59180
El Henawy et al Sept. 2015
“opportunistic T. gondii infection represent
a potential significant risk for chronic HCV patients.”

Toxoplasmosis .. In Renaldiseases
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.”

Toxoplasmosis .. Source of Infection
IN Animals:
• Definitive Host: Cat
2010: Giza 153158 stray cat were IgG +
reported high environmental contamination with oocysts in Egypt.
Yara ElKapany et al
DOGS: 5051 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 36304
in 4 different governorates with sample from each season in the year.
Hani Ibrahim et al 2014

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

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

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.

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.

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
Hatem45132@student.must.edu.eg
Review of Vaccine Candidates for the
most serious parasitic infections in Egypt
(( ))

Vaccine candidates for the most serious parasitic infections in Egypt

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