Key Findings

Combined hepatitis A and typhoid vaccines have been widely used globally and proven to be safe, well tolerated and efficacious in adults. 2 The combined hepatitis A and typhoid vaccine (Vivaxim) available in Australia is licensed for use from age 16 years, but the monovalent components are approved for use from age 2 years. 2 Advantages of a single injection have led to widespread 'off-label' use of Vivaxim in children. 2 This study aimed to investigate the tolerability of Vivaxim in children aged 2-16 years. 2

Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents and adults at increased risk of meningococcal disease. 11 In 2011, MenACWY-CRM (Menveo, GSK, Siena, Italy) was approved for children 2-10 years of age in the United States. 11 Although no safety concerns arose from clinical trials, it remains important to monitor its safety in routine clinical settings. 11

The possibility of using pharmacological tests to determine side effects produced by adsorbed DPT vaccine and chemical typhoid vaccine was studied. 7 Both vaccines were shown to be capable of prolonging sleep induced by hexenal or thiopental in experimental animals. 7 The following difference in the action of these two preparations was revealed on the model of “chemical convulsions” induced by the injection of thiosemicarbazide: while immunization with DPT vaccine activated thiosemicarbazide-induced convulsive syndrome in mice, no such stimulating effect was observed after the injection of typhoid, vaccine. 7 The study of pharmacological effects allowed to evaluate some aspects of the side effects produced by prophylactic preparations. 7

Typhoid fever continues to be a major public health problem in developing countries with about 33 million cases per year. 1 Protective efficacy of traditional acetone/phenol killed vaccines is similar to newer typhoid vaccines (Ty21A and Vi antigen vaccine) but side effects of these newer vaccines are considerably less. 1 Though the mortality is low, typhoid fever causes considerable morbidity and loss of working days. 1 Problems during treatment are increasing due to emergence and spread of multidrug resistant S. typhi. 1 Hence to decrease the incidence of typhoid fever in addition to ensuring safe water supply and excreta disposal a typhoid vaccine needs to be introduced in the National Immunization Schedule. 1

The clinical and immunological responses to typhoid vaccination with parenteral and oral vaccines in two groups of 30 adult male subjects were studied. 5 Specific anti-Salmonella typhi cell-mediated immunity and total or specific anti-lipopolysaccharide faecal immunoglobulin (Ig) A titres in vaccinated subjects were monitored. 5 Cellular antibacterial activity was significantly increased only in orally vaccinated subjects. 5 Serum arming activity and inhibition experiments suggested an IgA-dependent cellular cytotoxicity in those orally vaccinated. 5 In these subjects, a total and anti-lipopolysaccharide faecal IgA increase was observed lasting up to 8 months after completion of the vaccination schedule. 5 In parenteral vaccinated subjects, an early onset transitory increase of IgM rheumatoid factor was observed. 5 Oral vaccine was well tolerated and free of side effects, whereas 65% of parenterally vaccinated subjects reported side effects such as fever, headache, malaise and local tenderness in the injection site. 5

A mutant (Ty21a) of Salmonella typhi, which lacks the enzyme uridine 5'-diphosphate-glucose-4-epimerase, was evaluated in volunteers for use as a live attenuated oral typhoid vaccine. 10 Five to eight doses of vaccine (containing 3-10(10) viable organisms per dose) were given to 155 men without significant side effects. 10 The rate of excretion of the vaccine strain in stools was low, and the majority of isolations occurred on day 1 after vaccination. 10 Revertants able to ferment galactose were not found in any of 958 stool isolates tested. 10 The mutant, strain Ty21a, grown in brain-heart infusion broth (BHIB) with 0.1% galactose, produces more O side chain than the same vaccine strain cultivated without galactose. 10 Volunteers vaccinated with strain Ty21a grown in galactose and then challenged with 10(5) virulent S. typhi were significantly protected from disease and also had decreased stool carriage of S. typhi as compared with controls. 10 Strain Ty21a grown without galactose did not provide vaccinees significant protection nor decrease fecal excretion of S. typhi as compared with controls. 10 Strain Ty21a, when grown in BHIB with 0.1% galactose, results in a safe, stable and protective oral vaccine that warrants further study in field trials. 10

One hundred fifty-seven travelers who received the new oral typhoid vaccine strain Ty21a between April 1990 and February 1992 were surveyed by questionnaire to assess compliance and toxicity. 3 The four-dose vaccine should be taken every other day before meals, and kept refrigerated between doses. 3 Noncompliance with one or more of these instructions was seen in approximately 30% of travelers. 3 Thirty-four (21.6%) took one or more doses after meals, 13 (8.3%) did not take all four doses, 10 (6.4%) failed to take the dose every other day, and five (3.2%) did not keep the vaccine refrigerated. 3 The vaccine was well-tolerated and only 14 (8.9%) had one or more minor side effects. 3 Of 59 (38%) who had received injectable typhoid vaccine previously, all preferred oral versus injectable vaccine, and reported moderate-to-severe side effects with the injectable form. 3 Until a single-dose, oral typhoid vaccine is available, Ty21a is an attractive option. 3 To achieve maximum efficacy, the importance of compliance should be emphasized. 3

A considerable number of travelers receive multiple travel vaccinations before going on holiday. 4 Here, we present a case report of a 56-year-old male traveler. 4 On day 1, he received vaccinations against influenza, Tdab (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), MMR (measles, mumps, and rubella), yellow fever, and cholera. 4 On days 1, 3, 5, and 7, he self-administered an oral vaccine against typhoid. 4 Treatment comprised the combination of 220 mg naproxen and 180 mg fexofenadine (SJP-003), to be taken 4 h before and 6 h after the vaccinations on day 1, and every 12 h thereafter until the end of day 7. 4 Side effects were noted daily, and their severity was scored on a scale ranging from 0 (absent) to 10 (severe). 4 These reports revealed that, except from a slight bruising at the injection site, no side effects were experienced from day 1 to day 4. 4 After the second dose on day 3, treatment was discontinued. 4 Two hours after taking the typhoid vaccine on Day 5, various flu-like symptoms were reported of moderate to high severity, including fever, muscle aches (both with severity score of 8), headache (severity score 7), and nausea (severity score 6). 4 Therefore, at 2 h after typhoid vaccination on day 5, naproxen and fexofenadine were self-administered. 4 At 4 h thereafter, all symptoms were resolved. 4 Treatment was continued at the 12 h schedule. 4 On day 6 and 7, no side effects were reported. 4 Taken together, this case study suggests that the combination of naproxen and fexofenadine was effective in preventing or reducing vaccination side effects. 4 Therefore, more research is warranted to further evaluate the efficacy of SJP-003. 4

Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. 9 We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. 9 There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.5 x 10(8) CFU), lower-dose vaccine (5 x 10(7) CFU), or placebo in the 21 days after vaccination, although recipients of high-dose vaccine (8%) had more frequent diarrhea than placebo recipients (0%) in the first 7 days. 9 Seventy-seven percent and 46% of recipients of high- and lower-dose vaccines, respectively, briefly excreted vaccine organisms in their stools. 9 All blood cultures were negative. 9 Antibody-secreting cells producing antilipopolysaccharide (LPS) immunoglobulin A (IgA) were detected in 100 and 92% of recipients of high- and lower-dose vaccines, respectively. 9 Almost half the volunteers developed serum anti-LPS IgG. 9 Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees. 9 This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens. 9

Reasons for Side Effects

Side effects of typhoid vaccine are a result of the body’s reaction to the components in the vaccine. 7 The vaccine is designed to help the body’s immune system build a defense against the disease. 7 This process involves activating, or “stimulating,” the immune system. 7 As a result, some people who are vaccinated may experience side effects. 7 This is because the immune system is working in response to the vaccine, and that can affect other parts of the body. 7

Common Side Effects

Fever

Some people may experience fever after receiving the typhoid vaccine. 5 This is a result of the body’s immune response to the components in the vaccine. 5

Headache

Some people may experience headache after receiving the typhoid vaccine. 5 This is a result of the body’s immune response to the components in the vaccine. 5

Malaise

Some people may experience malaise after receiving the typhoid vaccine. 5 This is a result of the body’s immune response to the components in the vaccine. 5

Local tenderness at the injection site

Some people may experience pain at the injection site after receiving the typhoid vaccine. 5 This is a result of the body’s immune response to the components in the vaccine. 5

Diarrhea

Some people may experience diarrhea after receiving the typhoid vaccine. 9 This is a result of the body’s immune response to the components in the vaccine. 9

Nausea

Some people may experience nausea after receiving the typhoid vaccine. 4 This is a result of the body’s immune response to the components in the vaccine. 4

Muscle aches

Some people may experience muscle aches after receiving the typhoid vaccine. 4 This is a result of the body’s immune response to the components in the vaccine. 4

Side Effects Management

Fever

If you are concerned about fever, talk to your doctor. 5 Taking over-the-counter pain relievers and fever reducers can help alleviate the symptoms. 5

Headache

If you are concerned about headache, talk to your doctor. 5 Taking over-the-counter pain relievers can help alleviate the symptoms. 5

Malaise

If you are concerned about malaise, talk to your doctor. 5 Getting plenty of rest can help alleviate the symptoms. 5

Local tenderness at the injection site

If you are concerned about pain at the injection site, talk to your doctor. 5 Applying a cold compress can help alleviate the symptoms. 5

Diarrhea

If you are concerned about diarrhea, talk to your doctor. 9 Staying hydrated and taking an antidiarrheal medication can help alleviate the symptoms. 9

Nausea

If you are concerned about nausea, talk to your doctor. 4 Taking an anti-nausea medication can help alleviate the symptoms. 4

Muscle aches

If you are concerned about muscle aches, talk to your doctor. 4 Applying a warm compress can help alleviate the symptoms. 4

Comparing Studies

Similarities

The similarities between these studies are that they all indicate that typhoid vaccines are generally safe and well-tolerated. 2 They also show that some people may experience side effects. 2

Differences

The differences between these studies are the types of vaccines investigated and the populations used in the studies. 2 For example, some studies examined the safety of a specific typhoid vaccine (Ty21a). 10 While other studies examined the safety of a variety of typhoid vaccines. 1 Likewise, some studies focused on children while other studies focused on adults. 2

Real-Life Considerations

It is important to be aware of possible side effects after receiving a typhoid vaccine. 2 If you experience side effects, talk to your doctor. 2 Also, typhoid vaccines do not always prevent all cases of typhoid fever. 1 Therefore, in addition to vaccination, it is important to consume safe water and food to prevent typhoid fever. 1

Limitations of Current Research

There are some limitations to research on side effects of typhoid vaccine. 2 For example, some studies are small and their results may not be generalizable. 2 Also, some studies have focused on the side effects of specific typhoid vaccines. 2 Therefore, their findings may not apply to other typhoid vaccines. 2

Future Research Directions

Further research is needed on side effects of typhoid vaccines. 2 It needs larger studies with more participants that compare the incidence and severity of side effects among different types of typhoid vaccines and in different populations. 2 This information will help us to better understand the safety of typhoid vaccines and improve how these vaccines are administered. 2

Conclusion

Typhoid vaccines are generally safe, well-tolerated, and effective preventive measures. 2 However, some people may experience side effects. 2 Before receiving a typhoid vaccine, it is important to talk to your doctor to discuss the risks and benefits, and be prepared for the possibility of side effects. 2