Pharmacotherapy/Treatment Of Typhoid Fever

Typhoid fever is a systemic infection caused by salmonella enterica serotype typhimurium (salmonella typhi). Symptoms are non-specific and clinically non-distinguishable from other febrile illnesses. Some people (3-5 percent) can be carriers without exhibiting any symptoms. Clinical severity varies and severe cases can lead to complications or even death.

The disease affects about 11-21 million people worldwide. It is estimated to cause between 128000-161000 typhoid related deaths annually around the world. A similar but less severe disease, paratyphoid fever is caused by paratyphi A, B and uncommonly C.

The number of infections in many European countries has dropped significantly. This is as a result of improved hygienic conditions. There is hardly any case of death. However, India, Pakistan and many parts of Africa especially Egypt and Nigeria have a significant burden.

Typhoid fever

Symptoms

1. Prolong fever (39-40°c)

2. Headache

3. Nausea

4. Vomiting

5. Loss of appetite

6. Constipation

7. Confusion

8. Diarrhea

9. Weakness and pain in the body

10. Cough

11. Stomach pain

Paratyphi may develop a rash of flat, nose coloured spots.

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Severe cases can lead to septicemia (infection of the blood) perforation of the bowel or intestine. Perforation can lead to leaking blood in the body. Death occurs from pneumonia, intestinal bleeding, septicemia or perforation.

Cause

1. Poor hygiene

2. Eating contaminated food

3. Drinking contaminated water

After entering the digestive tract through infected food, it goes to the small intestine where it may stay for 1-3 week. It enters the bloodstream and attaches to white blood cells. This is the reason they say it travels with the body immune system. It goes to the liver, spleen and bone marrow where they multiple and re enter the bloodstream. Again they invade the gallbladder, biliary system, lymphatic tissue of the bowel where they multiply in high numbers. They finally enter the intestinal tract. The disease can last between 3-4 weeks without treatment. Majority of people can recover without treatment.

Diagnosis

1. Antibody test

2. Blood, stool or faeces test for Salmonella

Pharmacotherapy/Treatment

Drug

Treatment is the use of antibiotics. However, the bacteria is now resistant to many of the available antibiotics. Antibiotics of choice are based on region. There have been records of resistance to chloramphenicol ampicillin and trimethoprim/sulfamethoxazole. Current drugs of choice are the fluoroquinolones such as norfloxacin, sparfloxacin, ciprofloxacin and ofloxacin (excluding pregnant women and children). Others are azithromycin, amoxicillin and clavulanic acid, ceftriaxone, etc. Many antibiotics are still effective against it in Nigeria.

Surgery

Severe cases will require surgery to seal up perforated places. Gallbladder removal can significantly reduce infection burden.

Vaccines

There are three vaccines approved for typhoid fever. An injectable typhoid conjugate vaccine (TCV) consists of Vi polysaccharide antigen linked to tetanus toxoid (TT) protein. This shot is given to 6 months old to 45 years old.

The injectable Vi capsular unconjugated polysaccharide vaccine (ViCUPS vaccine) based on the purified Vi antigen (known as Vi-PS vaccine is given intramuscularly in a single dose. Protection is induced about 7 days after the injection. In countries or areas at risk, the protective efficacy 1.5 years after vaccination is about 72%; after 3 years it is about 50%. The vaccine is licensed for individuals aged >2 years. To maintain protection, revaccination is recommended every 3 years.

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The last is an oral vaccine based on the live, attenuated mutant strain of S. typhi Ty21a (Ty21a vaccine), is supplied in enteric coated capsules given to children 6 years and above. It consists of 4 capsule one to be taken every second day, the last which is to be taken one week before travel. The immunization will take effect from a week after the last dose and can last for three years. A booster dose can be given in 5 years. This programme varies from country to country. Some use three capsule and booster doses at 3 years. Proguanil, mefloquine and antibiotics should be stopped from 3 days before until 3 days after the administration of Ty21a

Of all the vaccines, TCV is better because of its safety and efficacy profile. It has better immunological properties with long duration of action. It can also be used on young children. 1 dose of TCV has an efficacy of 81.6 percent after a one year follow up. Seroconversion 4 fold increase in ViIgG level under 28 days after vaccination was reported by 99 percent positive recipients with 2 percent positive for the control group.

Vaccines are not 100 percent effective. This includes even TCV. Vaccines are contraindicated in persons currently positive for typhoid fever. Oral typhoid vaccines should be avoided in person living with human immunodeficiency virus (HIV). Side effects of typhoid vaccines are fever, gastrointestinal tract problems like nausea and headache. Oral vaccines have more side effects.