Associate Professor Fiona Russell

Principal Research Fellow,

Centre for International Child Health,

WHO Collaborating Centre for Research and Training in Child and Neonatal Health,

Department of Paediatrics, The University of Melbourne

Pneumococcal Group, Murdoch Childrens Research Institute

CPMG Travel Clinic, Flemington Road

Typhoid

• Typhoid fever is a serious, systemic infection

• Salmonella enterica serotype Typhi

• ~22 million cases & 216,500 deaths annually, primarily in Asia

• Mainly affect low income areas of the world, where sanitation & clean water are lacking

• Epidemics & high endemic disease rates have occurred in the Central Asian Republics, India, Bangladesh, Pakistan, Asia & the Pacific Islands

• Recent African data shows high burden ≥ Asia (spread of H58 lineage from Asia)

• Growing evidence of previously unrecognised disease in children aged <5 years

• Increasing resistance to available antimicrobial agents, including fluoroquinolones

Source: Crump, J., Luby, S., & Mintz, E. (2004). The global burden of typhoid fever. Bulletin of the World Health Organization, 82(5), 346-353. Retrieved from http://www.who.int/bulletin/volumes/82/5/346.pdf?ua=1

Who is at risk?

• Humans are the only carriers of S. Typhi

• Anyone who has not been immunised, in particular:• Australian residents who travel to areas where typhoid is widespread

• Australian residents who visit friends & relatives in areas where typhoid is widespread

• People who come to visit or live in Australia from areas where typhoid is widespread

• Anyone who has had close contact with an infected person

• Young children, who are at greater risk of infection than adults

2016:Zimbabwe

NigeriaSouth Africa

Fiji

Transmission

• Ingestion of food or water heavily contaminated

• Faecal: from persons who are acutely ill or chronic carriers, if personal hygiene and general sanitation is inadequate.

• Oral: vegetables fertilised with human waste and eaten raw; shellfish harvested from sewage-contaminated beds; contaminated milk products

Signs and symptoms• Quite insidious, not specific, and

mimic those of other infectious diseases

• Severity is variable, but nearly all have fever and headache

• Incubation period 7-14 days, but can be shorter or longer

• Symptoms: • low-grade fever, chills, headache,

myalgia, malaise, anorexia and nausea

• Abdominal discomfort and constipation, and diarrhoea can occur early in the illness

• In some cases, a macular rash (rose spots) on the trunk

• Enlargement of the liver and/or spleen occurs in 50%

• Symptoms increase over days

Outcomes

• Complications in 10-15%: • more likely in those who are not treated or are late seeking medical• Include: intestinal haemorrhage and perforation, toxic myocarditis, pneumonia,

seizures, typhoid encephalopathy, and meningitis (usually in young children)

• <1% CFR if treated promptly with antibiotics

• If untreated, CFR as high as 20%

• Following recovery, convalescing patients may continue to excrete in their faeces (+/- urine):• 1-3% (10%) become long-term carriers, excreting the organism for >1 year • More common in women & those with biliary tract abnormality• Chronic carriers require prolonged courses of antibiotics to clear the organism

Treatment

• Since 1948, chloramphenicol was the drug of choice

• In 1970s, chloramphenicol-resistant strains emerged & became endemic in many countries of South & South-East Asia

• Ampicillin and co-trimoxazole have been used, but resistance to multiple antibiotics has developed since 1987 in China, South-East Asia, India, Bangladesh, & Pakistan

• In 1997, a large outbreak of multi-drug resistant typhoid was reported in Tajikistan involving 8,901 cases and 95 deaths

• Drug-resistant strains have been seen in the UK in returned travellers

• Treatment is usually with fluoroquinolones (ciprofloxacin), cephalosporins, or azithromycin when there is resistance to fluoroquinolones

Prevention

• Avoid risky foods & drinks "Boil it, cook it, peel it, or forget it“

• Hand washing

• Vaccination

Vaccine Contraindications Side effects

TYPHIM Vi

TYPHERIX

Nb. 2w pre-travel

• < 2 y • Anaphylaxis to a previous dose• Anaphylaxis to any component of this vaccine

Fever (3%)Headache (~3%)Redness or swelling at injection site (10-20%)

VIVAXIM (Hep A & Typhoid)

Nb. 2w pre-travel

• < 16 y• Anaphylaxis to a previous dose• Anaphylaxis to any component of this vaccine

Fever (3%)Headache (~3%)Redness or swelling at injection site (10-20%)

VIVOTIF

(nb. Proguanil should be administered only if 10+ days elapsed since the final dose of Vivotif)

• < 6 y• Anaphylaxis to a previous dose• Anaphylaxis to any component of this vaccine• Acute febrile illness, wait until recovered• Immunocompromised• Should not be given until at least 3 days after taking antibiotics• Pregnancy

Fever or headache (5%)Stomach pain, nausea, vomiting, rash (rare)

Vaccines in the pipeline

• Conjugates• provide higher efficacy

• earlier administration to infants & young children at risk

• longer duration of protection

• administered in combination with other routine childhood vaccines

• A 2-dose Vi-rEPA conjugate vaccine developed by US NIH

• Vi-PS conjugated to a novel carrier protein consisting of recombinant exotoxin of Pseudomonas aeruginosa

• 91.5% VE among preschool children aged 2–5 years in Vietnam

• vaccine has not yet been licensed internationally

Questions?