Key messages

• Compared to a control (no vaccine, placebo ('dummy') or vaccine for another disease), typhoid conjugate vaccines (TCVs) may result in a large decrease in acute typhoid fever cases.

• We are uncertain whether TCVs, compared to other typhoid vaccines, decrease acute typhoid cases.

• There may be little to no difference in death from any cause, and unwanted effects, when TCVs are compared to a control, a non-conjugated typhoid vaccine or a different TCV. There is a slight decrease in serious unwanted effects when TCV is compared to a control, but may be little to no difference when compared to other TCVs.

• More robust research in typhoid-endemic countries (countries where typhoid occurs regularly) in this area is needed.

What are TCVs?

Typhoid conjugate vaccines (TCVs) are designed to protect against typhoid fever, sometimes known as enteric fever, caused by the bacteria Salmonella typhi (S typhi). The bacteria have an outer layer of sugar molecules (called the Vi polysaccharide). To help the body make a strong immune response, the Vi polysaccharide is attached to a protein. This helps the immune system recognise and fight S typhi more effectively. The TCVs assessed include Vi tetanus toxoid (Vi-TT), Vi diphtheria toxoid (Vi-DT), Vi-CRM₁₉₇ and Vi-rEPA.

Why are TCVs important?

Typhoid fever causes sickness and death in people in low- and middle-income countries (LMICs) - mostly sub-Saharan Africa, South- and Southeast Asia. It is passed from person-to-person through faecal-oral transmission (germs spread through contact with human faeces). People with typhoid may have a high fever, body aches, headache, nausea and vomiting, poor appetite and, later, stomach ache. Typhoid should be diagnosed with a laboratory test but is often diagnosed based on symptoms. It can be treated with antibiotics, but there is growing antibiotic resistance. Vaccination, together with interventions like access to clean water, handwashing and improved hygiene, helps to prevent typhoid fever. The World Health Organization (WHO) recommends typhoid vaccination in routine immunisation programmes for children in high-risk areas. Unlike other typhoid vaccines, TCVs can be given to children under two years old.

What did we want to find out?

We wanted to find out how well typhoid conjugate vaccines prevent acute typhoid fever and death from any cause, and how safe they are.

What did we do?

We searched for studies that compared TCVs to a control (no vaccine, a placebo or a vaccine for another disease), other typhoid vaccines and other TCVs. We summarised the results and rated our confidence in the evidence.

What did we find?

We found 19 studies with 395,650 participants and included 394,790 in our analysis. Participants were aged between six weeks and 60 years. The smallest study included 75 participants and the largest 326,794. The studies were conducted mostly in LMICs with most in Asia.

Main results

Compared to no vaccine, placebo or vaccine for another disease, TCV vaccination may result in a large decrease in typhoid fever and probably results in little to no difference in deaths from any cause. TCV vaccination results in little to no difference in unwanted effects and in a slight decrease in serious unwanted effects. TCV vaccination compared to control likely results in a longer duration of protection, with one study showing lower rates of acute typhoid fever for up to four years.

Compared to non-conjugated typhoid vaccines, TCVs may result in little to no difference in acute typhoid fever and likely result in little to no difference in unwanted effects. There is a slight decrease in serious unwanted effects when TCV is used instead of non-conjugate typhoid vaccines. None of the studies reported deaths for this comparison.

Compared to other TCVs, no studies reported on typhoid fever. There is little to no difference in deaths from any cause when comparing one TCV (Vi-TT) to another. Vaccination with Vi-TT likely results in little to no difference in unwanted effects and may result in little to no difference in serious unwanted effects compared to another TCV.

Our confidence in some of the evidence was decreased because it was not always precise, did not always fully apply to our question and there were potential biases.

What are the limitations of the evidence?

Death was not always reported and, when it was, the number was low. This may have led to fewer deaths being reported than occurred. No studies compared the effectiveness of one TCV to another in preventing typhoid fever. Unwanted effects are not defined identically by study authors. We reported these as a combined outcome instead of as specific effects like nausea or rash, which may limit the use of these results by healthcare practitioners.

How up-to-date is this evidence?

The review is current to 19 April 2024.