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Typhoid in the modern era

The microbiology laboratory has made great strides in introducing clinically useful diagnostics over the past couple of decades, particularly in recent years with the development of molecular assays that ‘narrow the gap’ and provide early diagnoses.

While introducing new tests, it has also been important to evaluate and discard old tests that may not contribute greatly to patient outcomes. One such test that has come under the spotlight is the classic Widal agglutination test in the diagnosis of typhoid.

The Widal test, developed by George Fernand Widal in 1896, uses a suspension of killed Salmonella typhi as antigen to detect agglutinating antibodies to somatic O antigens and flagellar H antigens present in serum of typhoid patients. There are many reasons for its lack of clinical utility.

Antibodies are not present in the acute illness and take time to develop.

Significant cross reactivity can occur with other infectious agents that mimic typhoid including malaria, dengue, endocarditis, tuberculosis and chronic liver disease.

Other limitations are of a technical nature and include non-standardisation of the antigen preparation used in the assay, interference with serological responses following typhoid vaccination commonly provided to travellers, and prior exposure and antibodies in patients most susceptible to typhoid, especially those from endemic areas visiting friends and relatives (VFRs).

Unless multiple antigens are included, it generally does not detect the other causes of enteric fever, S. Paratyphi A, B and C.

It is now time to discontinue this simple agglutination test for typhoid in modern medicine and consider more appropriate diagnostic tests.

Typhoid fever

Typhoid fever is a life-threatening illness caused by the bacterium Salmonella Typhi. Whereas Salmonellae which cause gastroenteritis are zoonoses, humans are the only reservoir for S.Typhi and S. Paratyphi which cause enteric fever.

Typhoid fever is still common in the developing world where it affects about 21.5 million people each year but is much less common in the Lucky Country such as ours where good sanitation prevails. About 100 cases are notified each year in Australia. In 2014, 92% of cases were acquired overseas. India continues to be the most common country of acquisition and in 2014 accounted for more than half of cases.

Most transmission occurs through contaminated drinking water or food. Large epidemics are most often related to faecal contamination of water supplies or street-vended foods.

A chronic carrier state – excretion of the organism for more than one year – occurs in about 5% of infected persons. Where no travel history is present, the likely source of infection is contaminated food or water from a human carrier akin to ‘Typhoid Mary’. Such an outbreak was reported in Auckland, New Zealand, this year where 20 local cases and one death occurred when a carrier from Samoa helped prepare food at a church community gathering.

The incubation period is typically eight to 14 days but may be much longer.

Without therapy, the illness may last for three to four weeks and death rates range between 12% and 30%. Increasing resistance to available antimicrobial agents, including fluoroquinolones, has occurred in recent years. Resistance to antimicrobials including amoxycillin, and trimethoprim+sulfamethoxazole has limited the options for treatment; reduced susceptibility to quinolones is common in infections acquired on the Indian subcontinent and in Southeast Asia.

While awaiting the results of susceptibility testing, azithromycin or ceftriaxone should be used for initial therapy for infections acquired in these regions.

Diagnosis of enteric fevers

Two sets of blood cultures are the single most useful diagnostic procedure for diagnosis of enteric fever. Other bodily fluids and tissues may yield positive cultures including faeces, urine, and if seeded, bones and joints, liver and gall bladder.

Food handlers, healthcare workers, carers of children, and carers of the elderly, and others who are not able to maintain their own personal hygiene, should further be excluded from working with food or caring for people until two consecutive stool specimens – collected at least 48 hours apart and the first specimen collected not sooner than 48 hours post-cessation of antibiotics – are culture negative.

Prevention

Both an oral live attenuated multi-dose vaccine and a killed vaccine are available. Booster doses after 3-5 years are generally required if continued exposure occurs.

Vaccine efficacy is of the order of only 80%.

What to order

Blood culture x 2 (Salmonella Typhi and Salmonella Paratyphi)

Faeces for Bacterial PCR and MCS;

Urine MCS

Collection Centres: Faeces and urine samples are accepted at all collection centres. Blood cultures are collected only at designated collection centres.

Sample

Blood (use blood culture bottles), faeces, urine

Transportation

Ambient

Costs

Medicare rebate applies

Typhoid Mary

Mary Mallon, better known as Typhoid Mary, was an Irish immigrant to New York and the first person in the United States identified as an asymptomatic carrier of the pathogen associated with typhoid fever.

Over the course of her career as a cook, she was presumed to have infected 51 people, three of whom died. She was twice forcibly isolated by public health authorities and died after a total of nearly three decades in isolation.

 

General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs.

The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.