Prophylaxis & Treatment Of Typhoid Fever

(Highest incidence occurs in 30-40 years age group)

Typhoid Incubation period 10-14 days
Typhoid cause a typhoid ulcer, in the lower ileum and the risk of perforation is highest in 3rd week of typhoid fever. If the muscle sheath is intact, sarcolemmal tubes containing histiocytes appear along the endomysial tube which, in about 3 months, restores properly oriented muscle fibres e.g. in Zenker’s degeneration of the abdominal musculature in typhoid.

Ampicillin

Ciprofloxacin is the drug of choice for Enteric fever and Cotrimaxazole is used as an alternative drug for the treatment of Enteric fever and Ceftriaxone is used for treatment of multi-drug resistant enteric fever.
Amikacin is not used for the treatment of enteric fever.
Other recommended drugs in the treatment of enteric fever are Ceftriaxone, Azithromycin, Amoxycillin, and chloramphenicol.

Ref: Lippincott’s Illustrated Reviews: Pharmacology, 4th Edition, Page 378 ; Harrison’s Principles of Internal Medicine, 17th Edition, Page 959

The Ty21a vaccine is licensed for use in individuals > 5 years.
A three dose regimen is recommended.
Vaccine is administered on alternate days: 0n days 1, 3 and 5.

Vi polysaccharide vaccine for typhoid is recommended in children more than 2 years of age.
It is administered as a single dose subcutaneously or intramuscularly.

Ans. is ‘a’ i.e., Amikacin 

Ans. is ‘b’ i.e., Water can transmit the disease; ‘c’ i.e., Type 21 ya is an oral vaccine

TYPHOID VACCINE

1. Heat killed phenol extracted, whole cell vaccine

a)Monovalent anti typhoid vaccine

b)Bivalent antityphoid vaccine

c) TAB vaccine

. Since S. typhi is the major cause of typhoid fever in India, the vaccine of choice is the monovalent typhoid vaccine.

. It is given subcutaneously.

. Efficacy is up to 3 years and after that booster is required.

1. Ty2 la oral vaccine (typhoral)

. It is a live oral vaccine

. It is a stable mutant of S. typhi strain

. Ty2 1 a, lacking the enzyme UDP-galactose -4-epimerase (Gal E mutant).

1. Typhim – Vi (ViCPS)

. Contains purified Vi polysaccharide antigen

. It is given subcutaneously or intramuscularly.

1. Vi-rEPA

. Vi polysaccharide bound to a nontoxic recombinant protein that is identical to pseudomonas aeruginosa exotoxinA

Features of vaccines

. 3 year efficacy is maximum with whole cell vaccine.

. 1 year efficacy is same with all these three vaccines.

. Whole cell vaccine is associated with a much higher incidence of adverse effects.

. The only recommondation for domestic vaccination include people who have intimate or house hold contact with a chronic carrier or laboratory workers who frequently work with S. typhi

. Because of their similar short term efficacy and low incidence of side effects, the current bias is toward the use of Ty2 la or ViCPS for vaccination of travellers.

Ans. is ‘d’ i.e., Vi polysaccharide of bacterial cell used for vaccination 

Ans. is `d’ i.e., Ciprofloxacin

Treatment of Typhoid fever

o Empirical treatment                  —>             Ceftriaxone, Azithromycin.

o Fully susceptible                      —>            Ciprofloxacin (First line), Amioxicil lin (second line), Chloramphenicol, Trimethoprim – Sulfamethoxazole.

o Multidrug resistant                   —>            Ciprofloxacin, Ceptriaxone, Azithromycin.

o Nalidixic acid resistant               —>            Ceftriaxone, Azithromycin, high dose ciprofloxacin.

Note : For susceptible organism ciprofloxacin is the DOC in typhoid fever.

Treatment of carrier

o Amoxicillin or ciprofloxacin with or without cholecystectomy.

Ans. is ‘c’ i.e., 2 years

o The Vi polysacchiride vaccine is licensed for individuals aged 2 years because it does not elicit immune response in children less than 2 years.

Ans. is ‘c’ i.e., Typhoid 
o Chronic carriers are seen in typhoid fever, hepatitis B, dysentery, meningitis, malaria, gonorrhea and diphtheria.

Ans. is ‘a’ i.e. Typhoid Vi, ‘b’ i.e. H. influenza vaccine (Hib), ‘c’ i.e. Hepatitis B vaccine

Subunit vaccines (cellular fraction)

• Subunit vaccines are defined as those containing one or more pure or semipure antigens.

o Instead of entire microbe, subunit vaccine include only the antigens that best stimulate the immune system.

• Subunit vaccines are obtained from extracted cellular fraction which is the major antigenic constituent of organism. o Examples are:

(i)     Meningococcal vaccine from cell wall polysacchlaride

(ii)    Pneumococccal vaccine from Capsular polysaccharide

(iii)   Hepatitis B polypeptide vaccine

(iv)   Typhoid vaccine from Vi polysaccharide

(v) H. Influenza vaccine from capsular polysaccharide.

Ans. is ‘a’ i.e., Typhoid & ‘b’ i.e., Chicken pox 

Ans. is ‘a’ i.e., Typhoid 

Ans. is ‘b’ i.e., Typhoid 

Ans. is ‘d’ i.e., Pertussis 

Ans. is ‘c’ i.e., Typhoid 

Ans. is ‘d’ i.e., Highest incidence occur in 30-40 years age group 
Typhoid fever

o Typhoid fever is the result of systemic infection mainly by S.typhi found only in man.

o The term enteric fever include both typhoid fever (caused by S. typhi) and paratyphoid fever (caused by S. Paratyphi ‘A’, ‘B’, & ‘C’).

o Reservoir -4 Man is the only reservoir. Carriers are more important than cases.

o Source of infection

           Primary —> Feces, Urine

           Secondary —> Water, food, fingers, flies.

o Age      Highest incidence occurs in the 5-19 years of age group.

o Sex Males > Females

o Incubation period —> 10-14 days.

• Treatment

Cases –> Ciprofloxacin is the DOC.

Carriers -4 Amoxicillin or ampicillin with cholecystectomy.

Ans. is ‘a’ i.e., 1, 3, 5 days 

ANTI-TYPHOID VACCINES

o The old parenteral killed whole-cell vaccine was effective but produced strong side-effects.

o So, they are not used now.

o Two safe and effective vaccines are now licensed and available : ‑

1. The Vi polysachharide vaccine

                       It is composed of purified Vi capsular polysaccharide from the Ty2 strain of S.Typhi.

                       It is administered subcutaneously or intramuscularly.

                       Only one dose is required.

                       The vaccine confers protection 7 days after injection.

                       To maintain protection, re-vaccination is recommended every 3 years.

                       The vaccine is licensed for individuals aged 2 years. -4 It does not elicit immune response in children < 2 years.

                       The vaccine is stable for 6 months at 37° C and for 2 years at 20°C. The recommended storage temprature is 2-8°C.

                       The Vi polysaccharide vaccine can be co-administered with other vaccines relevant for international travellers-such as yellow fever and hepatitis A

                       Acyclovir is given to prevent the development of systemic disease in varicella infected immunosuppresed patients & can halt the progression of zoster in adults.

                       Varicella zoster immunoglobulin given within 72 hrs of exposure can prevent chicken pox and is recommended in exposed immunocompromised persons.

                       A live attenuated varicella vaccine is recommended for children between 12-18 months. It is effective even if given within 3-5 days after exposure.

2. The Ty 21 a oral vaccine

                       It is an orally administered, live attenuated Ty2 strain of S.Typhi in which multiple genes (including for Vi Capsular polysaccharide) have been mutated chemically.

                       This lyophilized vaccine is available in 2 preparations : ‑

1. Enteric coated capsules —> Used for travellers to developing countries. It is used in individuals 5 years of age.

2. Liquid suspension –> Used by public health programmes for young children in developing countries. It can be administered from the age of 2 years.

               Vaccine is administered on 1, 3 and Sthe day, i.e., a 3-dose regimen is recommended.

                       Vaccine confers protection 7 days after the last dose.

                       The recommendation is to repeat this series (3 doses) every 3 years for people living in endemic areas, and every year for individuals travelling from non-endemic to endemic countries.

                       Ty 21 a requires storage at 2-8°C, it retains potency for approximately 14 days at 25°C.

                       Proguanil and antibacterial drugs should be stopped from 3 days before until 3 days after giving Ty 21a, as these drugs may harm live bacteria.

                       The vaccine is not efficacious if administered at the time of ongoing diarrhea.

                       Avoided during diarrhoea as efficacy will reduce.

                       Can be given to HIV +ve, asymptomatic persons with CD4 cell count of > 200/mm3

                       Well tolerated and has low rates of adverse events.

Not recommended in congenital or acquired immunodeficiency, acute febrile illness, acute intestinal infection and in patients on antimitotic drugs

May be given simultaneously with live vaccines of polio, cholera, yellow fever and MMR.

Ans. is ‘b’ i.e., 3
o To maintain protection, revaccination is recommended every 3 years.

Ans. is ‘b’ i.e., Typhoral 21 A oral vaccine 

o When this question was framed (2001), the old parenteral killed vaccine (Heat killed phenol extracted, whole cell vacine) was used.

• Since S. typhi is the major cause of typhoid fever in India, the vaccine of choice was the monovalent typhoid vaccine.
• So, at that time option ‘c’ was the correct answer.

o But due to strong side effects, this vaccine is not used now.

o Two vaccines now recommended are : ‑

1. The Vi polysaccharide vaccine.

2. The Ty 2Ia vaccine (Typhoral).

Ans. C i.e. Clindamycin

Clindamycin

• It is used primarily to treat anaerobic infections caused by susceptible anaerobic bacteria, including dental infections, and infections of the respiratory tract, skin, and soft tissue, and peritonitis.
• In patients with hypersensitivity to penicillins, clindamycin may be used to treat infections caused by susceptible aerobic bacteria, as well.
• It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus.
• Topical application of clindamycin phosphate can be used to treat mild to moderate acne

Ans. is ‘d’ i.e., Cefixime

Ans. is ‘d’ i.e., Typhoid

Post-exposure immunization

Post exposure immunization is prophylactic immunization immediately after exposure to a pathogen, in order to prevent infection by the pathogen and the development of disease.

Post exposure immunization is given for –

1. Varicella (chicken pox)
2. Measles
3. Rabies 
4. Tetanus
5. Hepatitis
6. Meningococcal meningitis

Ans. is ‘a’ i.e., 1, 3, 5 days

ANTI-TYPHOID VACCINES

• The old parenteral killed whole-cell vaccine was effective but produced strong side-effects.
• So, they are not used now.
• Two safe and effective vaccines are now licensed and available : –

1.The Vi polysachharide vaccine

1. It is composed of purified Vi capsular polysaccharide from the Ty2 strain of S.Typhi.
2. It is administered subcutaneously or intramuscularly.
3. Only one dose is required.
4. The vaccine confers protection 7 days after injection.
5. To maintain protection, re-vaccination is recommended every 3 years.
6. The vaccine is licensed for individuals aged 2 years. → It does not elicit immune response in children < 2 years.
7. The vaccine is stable for 6 months at 37° C and for 2 years at 20°C. The recommended storage temprature is 2-8°C.
8. The Vi polysaccharide vaccine can be co-administered with other vaccines relevant for international travellers-such as yellow fever and hepatitis A
9. Acyclovir is given to prevent the development of systemic disease in varicella infected immunosuppresed patients & can halt the progression of zoster in adults.

• Varicella zoster immunoglobulin given within 72 hrs of exposure can prevent chicken pox and is recommended in exposed immunocompromised persons.
• A live attenuated varicella vaccine is recommended for children between 12-18 months. It is effective even if given within 3-5 days after exposure.

2.The Ty 21a oral vaccine

• It is an orally administered, live attenuated Ty2 strain of S.Typhi in which multiple genes (including for Vi Capsular polysaccharide) have been mutated chemically.
• This lyophilized vaccine is available in 2 preparations : ‑

1. Enteric coated capsules → Used for travellers to developing countries. It is used in individuals 5 years of age.

2.Liquid suspension → Used by public health programmes for young children in developing countries. It can be administered from the age of 2 years.

1. Vaccine is administered on 1, 3 and 5the day, i.e., a 3-dose regimen is recommended.
2. Vaccine confers protection 7 days after the last dose.
3. The recommendation is to repeat this series (3 doses) every 3 years for people living in endemic areas, and every year for individuals travelling from non-endemic to endemic countries.
4. Ty 21 a requires storage at 2-8°C, it retains potency for approximately 14 days at 25°C.
5. Proguanil and antibacterial drugs should be stopped from 3 days before until 3 days after giving Ty 21 a, as these drugs may harm live bacteria.
6. The vaccine is not efficacious if administered at the time of ongoing diarrhea.
7. Avoided during diarrhoea as efficacy will reduce.
8. Can be given to HIV +ve, asymptomatic persons with CD4 cell count of > 200/mm3
9. Well tolerated and has low rates of adverse events.
10. Not recommended in congenital or acquired immunodeficiency, acute febrile illness, acute intestinal infection and in patients on antimitotic drugs
11. May be given simultaneously with live vaccines of polio, cholera, yellow fever and MMR.

Ans. is ‘d’ i.e., Typhoral vaccine cannot be given with other live vaccines