Protocol to Test Hypothesis That Streptococcal Infections and Their Sequelae Have Risen in Incidence Over the Last 14 Years in England



Streptococcal respiratory tract disease was a scourge of high-income countries (HICs) in the pre-antibiotic era. The sequelae were local (e.g. peritonsillar abscesses [Quinsy], mastoiditis, and even brain abscesses) or distant (rheumatic fever, childhood glomerulonephritis). The incidence of these diseases has reduced dramatically in HICs in the last 50 years, at least in part as a result of (liberal) use of antibiotics. However, strong pressure has been placed on doctors to reduce antibiotic prescribing. The evidence from RCTs has shown that the mean duration of diseases, such as tonsillitis, sinusitis and acute middle ear infection, is only slightly (about 20%) reduced by antibiotic therapy. The actual drop in prescriptions has been modest.[1] However, we plan to establish a trend line, and then continue to observe the incidence so that any upturn in serious disease can be detected early. We shall therefore observe the trends in craniofacial disorders that are often the result of local spread of Streptococcal infections and also the above mentioned autoimmune diseases. We will also track a condition that may tell us something about the underlying ecology of Streptococcal infections – scarlet fever. We will attempt to obtain data on actual antibiotic prescribing (overall and for the above infections) by year. A previous study based on primary care records [2 found that general practices with the greatest reductions in antibiotic prescribing experienced an increase in peritonsillar abscesses compared to baseline control patients. They did not examine for autoimmune disease.


  1. Database: We will search the Hospital Episode Statistics database for England, which contains information on all NHS-funded admissions to hospitals in England. All admissions are given ICD 10 (International Classification of Disease, 10th Revision) Diagnosis Codes and OPCS-4 (Office of Population Censuses and Surveys Classification of Interventions and Procedures) Procedure Codes. The HES database is linked to the Indices of Multiple Deprivation database and we will thus be able to obtain the socioeconomic status of patients.
  2. Date: 1st January 2001 to 31st December 2015 [to be confirmed]
  3. Search terms: See table 1.

Table 1: Disease Classes and Specific Search Terms

Broad Disease Type Disease Search terms
[to be completed]
Local spread Peritonsillar abscess (quinsy)
Temporal lobe abscess
Lemierre’s syndrome
Autoimmune Glomerulonephritis (under age 16)
Rheumatic fever
Scarlet fever

If a patient on a single admission has more than one disease, then the most serious condition (lowest on the list) will be recorded. Patients may have more than one admission.

  1. Additional information collected: See table 2.

Table 2: Additional Information to be Collected from Each Patient

Social class
Urban / rural residence
Number of admissions before first admission for one of the above diseases
  1. Analysis:
    We shall produce descriptive statistics for the mean values for numbers and proportions of admissions by disease and by disease category for age, sex, social class, and residence. At this stage we do not plan to use number of previous admissions in the analysis. We shall carry out the following analyses in pursuit of our hypothesis:

    1. We shall plot the number of cases of each of the above conditions by year. We shall also plot proportions of all admissions by condition.
    2. We shall make similar plots for people 16 and below, and for older people.
    3. We will group conditions into: 1) local spread, 2) auto-immune, and 3) scarlet fever for analysis.
    4. We shall generate age-standardised incidence rates and test whether there is a trend over time using joinpoint regression models. We will also look at age-specific incidence rates in a similar manner.

If there is a trend, we shall compare this across urban and rural residence, using the ONS classification. Likewise we will examine trends by the lowest social class versus all other social classes.


  1. Peterson I, Johnson AM, Islam A, Duckworth G, Livermore DM, Hayward AC. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ. 2007; 335: 982.
  2. Gulliford MC, Moore MV, Little P, Hay AD, Fox R, Prevost AT, Juszczyk D, Charlton J, Ashworth M. Safety of reduced antibiotic prescribing for self limiting respiratory tract infections in primary care: cohort study using electronic health records. BMJ. 2016; 354: i3410.

3 thoughts on “Protocol to Test Hypothesis That Streptococcal Infections and Their Sequelae Have Risen in Incidence Over the Last 14 Years in England”

  1. Dear Richard
    I think this idea of pre-publication of iterative protocols for studies based on analysis of routine data is potentially really helpful. Finding a feasible approach that promotes transparency but doesn’t become a frustrating straightjacket is something that I have struggled with. Like all protocol sharing, it relies on a degree of trust (in that another team could think ‘That’s a good idea, let’s pinch it’) which hopefully is warranted.
    On the specific topic of antibiotic stewardship, you may be interested in a recent development within NHS Scotland Information Services Division to create an Infection Intelligence Platform based on linked prescribing, lab, and admission data for the whole population of Scotland. See This may offer an additional data source when considering infection related questions.
    Rachael Wood

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