Cholera: causative agent Vibrio cholera

Vaccine against cholera whole cell killed parenteral vaccine

This vaccine is still in use in many developing countries including India .The vaccine is prepared from classical V.cholera but it carrier equal protection against El Tor biotype .but not protect against classical V.cholera

Composition

The vaccine consists of a mixture in equal proportion of sterile suspension of cholera type Inaba and Ogawa so that each milliliter contains a total of 12000 million organisms .It is a head killed and phenol preserved vaccine

Dose and route of administration

The primary immunization consist of two doses injected subcutaneously at an interval of 4-6 weeks .the dose for an adult is 0.5 ml each injection ,for child between 2-10 years of age it is 0.3 ml and for children between 1-2 years of age 0.2 ml is injected .the vaccine is not recommended for use in children less than one years of age .the vaccine is injected intramuscularly or deep subcutaneously in deltoid region or anterolateral part of thigh .

Contraindication

1. patients with acute infections or chronic illness
2. children under one year of age
3. sever reaction to apreviously administrated cholera vaccine 
4. pregnancy ,though there is no information to suggest that cholera vaccine is unsafe during pregnancy .

Adverse reactions

a-local reactions transient swelling ,redness and pain

b-general reactions headache ,pyrexia and malaise usually lasting 1-2 days ,anaphylaxis reaction and neurological syndrome such as neuritis ,polyneuritis ,cerebral and meningeal irritation may occur very rarely .

Immunity

the protection value of vaccine is estimated to be around 50% for period of 3-6 months . booster are needed to be given every 6 months to subjects who are likely to be exposed to infection .A single booster will suffice even if longer than six months have elapsed since the last dose was administrated repeated vaccination over a period of three years may result in the development of hypersensitivity to protein constituent of the vaccine .

oral B whole cell cholera vaccine

composition : this vaccine is usually referred to as B subunit whole cell (BSWC ) VACCINE .It is consist of purified B subunit from cholera toxin of Inaba and Ogawa serotypes

 composition of one dose of BSWC cholera vaccine

Dose and route of administration

Because of acid sensitivity especially that of B subunit the vaccine is administered together with a sodium bicarbonate –citric acid buffer solution that is calculated to ensure adequate neutralization of stomach acidity for preservative of vaccine when passing through stomach the vaccine is given in three doses in a  liquid formulation .

Efficacy

The vaccine was found to be completely safe with no side effects .It also induced significant rise in serum vibriocidal antibodies in 89% individuals and antitoxin rise in 100%  volunteers .

In volunteers in the USA three doses of BSWC vaccine afforded 63% protection and the WC component alone 56% protection against a subsequent challenge with virulent V. cholera  O1 of the El-Tor biotype .Protection against diarrhea illness with a stool out put of at least 2 liters was 100 % for the BSWC vaccine and 56% for the WC vaccine .

BSWC was also associated with short term cross protection against diarrhea caused by E .coli that produced heat labile toxin presumably due to antigenic similarity of the B subunit of Cholera toxin and LT of enterotoxigenic E .coli 

 Disadvantage

Though the  results obtained with BS-WC vaccine in Bangladesh trial are extremely encouraging because of almost 85% protection for 6 months and 50% up to three years .this vaccine suffers from three disadvantages

• transient protection in children
• three dose schedule makes it difficult for community vaccination
• high cost of vaccine because of purified B subunit component

live attenuated DNA recombinant vaccines

with the advent of rDNA techniques it has become possible to attenuate pathogenic V .cholerae O1 by cloning genes encoding virulence factors and using these cloned genes to create  precise and no reverting deletion mutants .a large number of such strains have been formulated and it is hoped that soon we will have an effective ,safe and economical oral cholera vaccine with excellent efficacy .

typhoid fever

caused by Salmonella typhi : vaccines against typhoid fever

A- Parenteral killed whole cell vaccine

This vaccine is prepared from Ty2 strain of Salmonella typhi which has been found to be safe and effective in man it is grown in a liquid or a solid medium and killed by acetone heat –phenol or formalin treatment. The material is diluted so that the volume recommended as a single human dose contains the desired concentration of bacteria

Heat phenol killed vaccine

The heat phenol treated vaccine contains million S .typhi per ml .S.paratyphi A organisms may also be added in a concentration of 500 million organisms per ml .this vaccine is used in adults in dose of 0.5 ml ,two doses are given 4-6 weeks a part and annual boosters of same dose are recommended .for children between the age of 5-15 years ,the vaccine contains 33.3million organisms of S .typhi  and 16.7 million S.paratyphi A per ml

Acetone killed and dried vaccine

This vaccine typhoid –paratyphoid A for adults contain 2500 million S .typhi  and 1250 million S.paratyphi A organisms per ml .this vaccine can be given intradermally as well as subcutaneously

Contraindication

• patients with acute infections or chronic illnesses .
• sever reactions from previously administered  typhoid vaccine such as polyneuritis ,myelitis or various manifestation of cerebral and meningeal disease
• immunization of children under 12 years of age is not recommended.

Adverse reactions

a-local reactions transient swelling ,redness and pain

b-general reactions headache ,pyrexia and malaise may last for fours years

B: Ty21a live oral typhoid vaccine

With nitroso guanidine .mutant of S.typhi 21a strain has been obtained which has a mutation in the gal E gene of the bacteria .this strain also lacks vi polysaccharide

Composition

The vaccine contains lyophilized preparation of ty 21a organisms 10⁹ in gelatin capsule a long with two additional capsule of a sodium bicarbonate –citric acid buffer solution that is calculated to ensure adequate neutralization of stomach acidity for preservative of vaccine when passing through stomach the vaccine is given in three doses in a  liquid formulation are ingested in one week to complete the course no major side effects are noted with this vaccine .

C: purified Vi polysaccharide vaccine

Purify Vi polysaccaharide by a non denaturing technique so that it could be used as a parenteral vaccine

Recommendation

For  use of TY21a and Vi typhoid vaccineis to be stored in refrigerator .the freezing  is not recommended ,if done ,will not damage the vaccine the capsules are self administered with cold or Luke warm drink ,preferably one hour before food ,in three doses on alternate days .Significant side effect have not been  encountered but transient mild nausea ,vomiting ,abdominal cramps ,diarrhea and urticaria occur in less than 1% of vaccine

Future prospect

Vi polysaccharide –protein conjugated vaccines .

Conjugated vi polysaccharide to tetanus toxoid ,diphtheria toxoid and cholera toxoid ,thereby conferring T dependent properties on the polysaccharide and elicited higher levels of antibodies.