2 The diagnostic tests

Clinical need and practice

2.1

Sore throat is usually a self-limiting condition that lasts about a week. In most cases it is caused by a virus but, in a few people, sore throat is caused by bacterial infection, usually group A streptococcus (strep A). Sore throat usually does not need antibiotic treatment, regardless of the cause (viral or bacterial). Most people get better without antibiotics and withholding antibiotics rarely leads to complications.

2.2

Unnecessary use of antibiotics can contribute to antimicrobial resistance. This is microorganisms' ability to withstand antimicrobial treatments such as antibiotics (that is, the antimicrobial treatments become ineffective). Addressing antimicrobial resistance is one of the key NHS priorities, described in the NHS 5‑year plan for how the UK will contribute to containing and controlling antimicrobial resistance by 2040.

2.3

NICE's guideline on antimicrobial prescribing for acute sore throat was developed to help limit antibiotic use and reduce antimicrobial resistance. The guidance advises that sore throat is self-limiting. Also, it recommends using clinical scoring criteria such as Centor or FeverPAIN to help identify people who are more or most likely to benefit from an antibiotic. However, the guidance does not cover the potential use of rapid tests for strep A to increase diagnostic confidence of strep A infection and guide antimicrobial prescribing.

2.4

The purpose of this assessment is to evaluate the clinical and cost effectiveness of using rapid tests to detect strep A infection in people with a sore throat aged 5 and over, to help appropriate prescribing of antibiotics. These tests are only intended for people who are identified as more or most likely to benefit from antibiotics by clinical scoring tools such as FeverPAIN or Centor.

The condition

2.5

Sore throat is characterised by inflammation of the pharynx (pharyngitis) or inflammation of the tonsils (tonsillitis). Symptoms of a sore throat include pain in the throat, fever and a headache. Other symptoms could also include nausea, vomiting, abdominal pain, muscle pain, and rashes.

2.6

The most common cause of bacterial infection is strep A, accounting for about 80% of bacterial infections. The remaining 20% of bacterial infections are usually caused by group C and G streptococcus. Strep A throat infections are more common in children than adults and the incidence of strep A infections is highest in winter and spring.

2.7

Most cases of strep A infection resolve without complications. However, rarely complications can develop, such as rheumatic fever (affecting the heart), post-streptococcal glomerulonephritis (affecting the kidneys), or necrotising fasciitis (a severe infection of soft tissue). Strep A can also cause scarlet fever and invasive group A strep infections. Invasive group A strep infections happen when the bacteria move from the throat into other parts of the body. This can lead to sepsis or streptococcal toxic shock syndrome. The risk of invasive group A strep infections is usually very low, but is higher in older people (aged over 75 years), in whom the risk of associated mortality is also higher.

The care pathway

2.9

Antibiotic prescribing for sore throat should be guided by the FeverPAIN or Centor clinical risk scoring tools, unless the patient is systemically very unwell, has symptoms and signs of a more serious illness or condition, or is at high risk of complications.

  • People with a FeverPAIN score of 0 or 1, or a Centor score of 0, 1 and 2 are unlikely to benefit from an antibiotic. They should be offered advice on self-care without an antibiotic prescription.

  • People with a FeverPAIN score of 2 or 3 might benefit from an antibiotic. They may be offered advice on self-care or a back‑up antibiotic prescription (to use if symptoms do not start to improve within 3 to 5 days or worsen rapidly or significantly at any time).

  • People with a FeverPAIN score of 4 or 5, or a Centor score of 3 or 4 are most likely to benefit from an antibiotic. For these people either an immediate or a back-up antibiotic prescription should be considered. This should take into account the risk of possible complications of untreated strep A and of possible adverse effects of antibiotics.

2.10

The purpose of the rapid tests is to increase diagnostic confidence of a suspected strep A infection and guide antimicrobial prescribing decisions. The tests are for people identified as more or most likely to benefit from antibiotics by clinical scoring tools. They have a faster turnaround time than laboratory culture of throat swabs. This could allow a prescribing decision in the initial consultation (but some tests might need confirmation of negative test results by laboratory culture). This may contribute to improved antimicrobial stewardship. The tests are suitable for all settings where patients present with an acute sore throat. This includes both primary and secondary care, and community pharmacies.

The interventions

The assessment included 21 rapid tests for strep A, of which 17 tests use immunoassay detection methods (rapid antigen detection tests) and 4 use molecular methods (polymerase chain reaction [PCR] or isothermal nucleic acid amplification).

Rapid antigen detection tests

2.11

Of the rapid antigen detection tests, 16 use lateral flow (immunochromatographic and immunofluorescence) technology and 1 test (QuikRead Go Strep A test) is a turbidimetric immunoassay (see table 1). Depending on the technology, the results of the lateral flow tests are read by visual inspection or by using a test reader device.

2.12

Several manufacturers recommend that negative rapid antigen detection test results are confirmed by microbiological culture of a throat swab.

Table 1 Summary of rapid antigen detection tests
Product (manufacturer) Test format Limit of detection Time to result (minutes) Results Confirmation of negative result?

Clearview exact Strep A cassette (Abbott)b

Cassette

5×104 organisms/test

5

Qualitative

Yes

Clearview exact Strep A dipstick (Abbott)c

Test strip

5×104 organisms/test

5

Qualitative

Yes

BD Veritor plus system group A Strep (Becton Dickinson)

Cassette

1×105 to 5×104 CFU/ml

5

Qualitative

Yes

Strep A rapid test (Biopanda reagents)

Cassette

1E+05 organisms/swab

5

Qualitative

Yes

Strep A rapid test (Biopanda reagents)

Test strip

1E+05 organisms/swab

5

Qualitative

Yes

NADAL Strep A (nal von minden GmbH)

Test strip

1.5×105 organisms/swab

5

Qualitative

No

NADAL Strep A (nal von minden GmbH)

Cassette

1.5×105 organisms/swab

5

Qualitative

No

NADAL Strep A plus (nal von minden GmbH)

Cassette

1.5×105 organisms/swab

5

Qualitative

No

NADAL Strep A plus (nal von minden GmbH)

Test strip

1.5×105 organisms/swab

5

Qualitative

No

NADAL Strep A scan test (nal von minden GmbH)d

Cassette

1.5×105 organisms/swab

5

Qualitative

No

OSOM Strep A test (Sekisui diagnostics)

Test strip

Not known

5

Qualitative

Yes

QuikRead Go Strep A test kit (Orion Diagnostica)e

N/A

7×104 CFU/swab

Less than 7

Qualitative

Not known

Alere TestPack Plus Strep A (Abbott)

Cassette

Not known

5

Qualitative

Yes (if symptoms persist)

Bionexia Strep A plus (Biomerieux)

Cassette

1×104 organisms/swab

5

Qualitative

Not known

Bionexia Strep A dipstick (Biomerieux)

Test strip

Not known

5

Qualitative

Not known

Biosynex Strep A (Biosynex)

Cassette

1×105 bacteria/swab

5

Qualitative

Not known

Sofia Strep A FIA (Quidel)f

Cassette

1.86×104 to 9.24×103 CFU/test

5 to 6

Qualitative

Yes

Abbreviations: CFU, colony forming units; N/A, not applicable.

Notes:

Time to result (minutes) does not include sample preparation time.

b, Replaced by Clearview Strep A cassette 2.

c, Replaced by Clearview Strep A dipstick 2.

d, Needs BD Veritor Plus analyser.

e, Needs QuikRead go instrument.

f, Needs Sofia analyser.

Molecular tests

2.13

Of the molecular tests, 2 use isothermal nucleic acid amplification (Alere i Strep A and Alere i Strep A 2 tests) and 2 use PCR (Cobas Strep A assay and Xpert Xpress Strep A); see table 2.

Table 2 Summary of molecular tests for rapid strep A detection
Product Analyser Limit of detection Time to result (minutes) Result Confirmation of negative result?

Alere i Strep A (Abbott)2

Alere i instrument

4 to 42 CFU/ml

Less than 8

Qualitative

Yes

Alere i Strep A 2 (Abbott)3

Alere i instrument

Not known

Less than 6

Qualitative

No

Cobas Strep A assay (Roche Diagnostics)

Cobas Liat analyser

5 to 10 CFU/ml

Less than 15

Qualitative

No

Xpert Xpress Strep A (Cepheid)

GeneXpert system

Not known

18 or more

Not known

Not known

Abbreviation: CFU, colony forming units.

Notes:

Time to result (minutes) does not include sample preparation time.

2, Replaced by ID NOW Strep A 2 test.

3, Rebranded to ID NOW Strep A 2.

The comparator

2.14

Antibiotic prescribing decisions using clinical judgement and a clinical scoring tool such as FeverPAIN or Centor, outlined in section 2.9.

Reference standard

2.15

The reference standard for assessing the accuracy of the rapid strep A tests is microbiological culture of throat swabs.

2.16

The reference standard is unlikely to be 100% accurate. Its accuracy may depend on the culture media and swabbing technique used to collect the sample.