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 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


How this work started?


Systematic Reviews Importance


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.


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.


• Fascioliasis (Trematode)

(Fasciola gigantica\Fasciola Hepatica)• Schistosomasis (Trematode)

Schistosoma Mansoni• Toxoplasmosis (Protozoa)

Toxoplasma gondii


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


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 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


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


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


Fascioliasis & Schistosomiasis

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

Estebean 2003


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


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


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:


Schistosomiasis

Vaccination WHO Report 2014


Schist. Vaccines clinical trials


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


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 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


Toxoplasmosis Diagnosis


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.


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 5gave birth to babies with congenitalanomalies

2 1

Total 106 - 26 20 41 21 14One

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 clincat 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 Stag

eIgG +

30\39

5\30 11\75

75\81

Control Group: IgG: 6\40 IgM: 3\6

IgG +

IgM + IgM +


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.”


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.”


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


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

[email protected]

Review of Vaccine Candidates for the most serious parasitic

infections in Egypt(( ))

Health & Medicine

Vaccine candidates for the most serious parasitic infections in Egypt