Hepatitis A/Typhoid Fever

Although difficult to determine accurately, annual global figures for reported cases of hepatitis A and typhoid are estimated to be in the region of 1.5 million and at least 16 million, respectively. Moreover, typhoid fever accounts for up to 600,000 deaths worldwide each year. The two diseases are often found in partnership and have common routes of transmission, particularly where sanitation is poor. As a consequence of the overlap in mode of transmission and risk factors, individuals travelling to endemic regions are frequently advised to have a number of vaccinations in order to minimise their risk of infection. There is a real need to provide effective preventative vaccination against multiple infectious diseases in the most convenient way for the recipient.

Typhoid fever is caused by the organism Salmonella typhi, which is typically ingested with water or food contaminated with faeces. Similar syndromes of enteric fever are caused by S. paratyphi. In contrast, hepatitis A is caused by a picornavirus, but has a similar mode of transmission. Unlike typhoid, childhood infection with hepatitis A is often asymptomatic and confers lifelong immunity. Most children in developing countries will have been infected with hepatitis A infection in early childhood. In the , seropositivity rates for hepatitis A are low but increase with age, with estimates ranging from 4% in children to over 20% in those aged over 44 years. Cases are sporadic and may be associated with prolonged morbidity in adults. Mortality from fulminant hepatitis is low (1%), but increases to 3% in individuals over 44 years of age. Treatment is primarily supportive for infected individuals. Vaccination programmes in endemic countries are not required for hepatitis A, due to the fact that the majority of infections are usually acquired in early childhood, when they are mostly asymptomatic and confer lifelong immunity against further infection. However, individuals travelling from countries of low endemicity to those of moderate or high endemicity are likely to require vaccination.

In parts of the world such as South and , and , typhoid remains a significant problem, particularly in children, and this warrants the implementation of effective vaccination programmes. Despite this, epidemics of typhoid fever continue to occur in regions of high endemicity, and the situation is potentiated by widespread resistance to first-line antibiotics including an increasing resistance to the fluoroquinolones. Between 1980 and 1989, over 80% of the 1735 cases of typhoid fever in the were imported from abroad, primarily from . Unlike with hepatitis A, up to 10% of people with typhoid will die in resource-poor settings, although mortality from imported infection is usually much lower. Patients with typhoid are usually infectious for 6–8 weeks, but approximately 3–10% become chronic carriers and are a potential source of infection to others for some years. Appropriate treatment of typhoid with antibiotics not only treats the infected individual, but may reduce the future transmission of infection by preventing chronic carriage.

Vaccine prevention of hepatitis A is primarily centred on the industrialised world where public health measures, especially improvements in sanitation, have reduced the prevalence of food and water-borne diseases and hence also the development of natural immunity against infection. However, the speed and ease of worldwide travel means that populations within areas of low hepatitis A and typhoid endemicity are at risk not only of imported disease, but also when travelling to areas of moderate or high endemicity. Consequently, vaccine prevention of both diseases is becoming even more important as travellers become more adventurous, visiting increasingly exotic destinations. As discussed previously, the epidemiology of hepatitis A and typhoid is such that many travellers require protection from both diseases. However, travellers will often leave at short notice, with minimal time to seek travel health advice. In addition, individuals may be discouraged from visiting travel clinics by the inconvenience of receiving multiple injections and the discomfort that this causes. Therefore, combining vaccines in one syringe may improve travellers’ compliance with the multiple vaccines required for some destinations.

Monovalent vaccines currently available against hepatitis A and typhoid have seroconversion rates of greater than 90% and 70%, respectively. Immunogenicity studies of the combined inactivated hepatitis A vaccine and the capsular Vi polysaccharide vaccine (ViATIM^®) have shown similar seroconversion rates. Whilst local adverse reactions at the injection site are more common with ViATIM than with either of the individual vaccines, they are less frequent than when the monovalent vaccines are administered concurrently. In comparison with Hepatyrix^® (the other currently available combined typhoid and hepatitis A vaccine), ViATIM has shown more local reactions at the injection site. However, hepatitis A and typhoid seroconversion rates have proved to be more rapid with ViATIM. Rapid seroconversion is particularly beneficial for those travellers who present within days of travel to highly endemic countries. However, it should be remembered that ViATIM is not licensed for use in children aged under 16 years, and requires boosting for hepatitis A and typhoid at 6–36 months and 3 years, respectively. In common with other monovalent and combined vaccines, ViATIM it is not licensed for protection against infection with S. paratyphi.

Improving the acceptability of vaccines to an increasing population of last minute worldwide travellers is essential and is growing in importance. Rapid seroconversion to multiple vaccines with minimal local and systemic side-effects in one syringe is the major goal. Consequently, the development of ViATIM and other combined vaccines may reduce morbidity and mortality in the traveller and ultimately the burden of imported disease to countries of low endemicity.

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This Editorial has been written by the specialist opinion leaders, Dr Lisa Ford and Dr Nick Beeching, Liverpool School of Tropical Medicine, and published in the latest issue of the serial publication, Drugs in Context.

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