Background • Sore throats caused by Group A Streptococcal (GAS) bacteria require identification and treatment with correct antibiotics, or

they may lead to acute Rheumatic Fever (RF).• Most sore throat clinical prediction rules have been developed in first world settings, to reduce unneccessary antibiotic use.• The safety of these rules in high RF regions has not been well established. • The Pacific island group of New Zealand (NZ) has a high rate of RF. In 2014, per 100,000 of population there were 4.1 initial

attacks and 0.4 recurrent cases of RF. Initial attacks of RF were highest among school age children; Pacific peoples (35 per 100,000) and Māori (12.3 per 100,000000) (ESR 2015).

AimTo assess whether four GAS sore throat rules work well/safely enough to be recommended in the high RF setting of New Zealand.

Methods A subsection of data from a large previously published RCT (Lennon et al 2009) was subjected to further in-depth analysis. • Setting: four schools with sore throat clinics, South Auckland, NZ (a high RF region)• Year:2000-2001• Patients:children aged 5-18 years. • Protocol:All patients with self reported sore throats had throat swabs taken for culture and were examined (by trained lay

workers). • There were 12836 total sore throat encounters,12032 Group A Strep negative and 804 Group A Strep positive.

Analyses undertaken• Signs and symptoms of GAS positive and negative sore throat encounters compared using SAS.• Four sore throat prediction rules were applied to the data. Three were chosen as they are well known internationally (Wald et

al 1998, World Health Organization (WHO) 1991, McIsaac revised Centor 1998), one was chosen as it had been developed in NZ on the basis of expert opinion, but had not previously been validated/ tested (NZ Heart Foundation 2008). Their details are shown in Table 1.

Summary of results1. No signs and symptoms separately or in combination reliably predicted GAS sore throats. 2. Prediction rule performance:

• The most sensitive was the NZ Heart Foundation’s (54%) • The highest positive predictive value was 16%, (the McIssac revised Centor rule) • The highest specificity was found in the WHO and McIsaac revised Centor rules (both 99%) • Negative predictive value was 95-96% across all four rules.

Conclusions – In a word - No!1. No reliable predictors of GAS sore throat in these New Zealand children were found. 2. All four prediction rules tested, performed poorly on this data set.3. Rule and predictor failure may be due to differences in:

• Suboptimal examination/swab training of the lay staff • GAS prevalence (which may affect pre test probability)• High rates of other clinical comorbidities existing in this population which may blur the theoretical line

between bacterial and viral sore throat symptoms. In the NZ Māori and Pacific youth population, there are high rates of causes of chronic cough (including asthma, bronchiectesis (Twiss 2005, Singleton et al 2014), and parental and youth smoking (Ministry of Health 2014)); and lower socioeconomic status than the European population (Ministry of Health 2010; Ministry of Health 2012)

• Undeclared anti pyretic use (no patients/ parents were asked about this)4. ’First world’ derived guidelines may not necessarily be safely transferrable to high RF risk settings.

IDSA Poster Abstract 52790Session: Diagnostic Microbiology: StreptococciOctober 9, 2015San Diego

Are clinical prediction rules for a Group A Streptococcal sore throat safe in a population at very high risk of Rheumatic Fever?

Wald et al. 1998 McIsaac et al. 1998 Heart Foundation 2008 WHO 1991-4PPV % 1.86 15.79 5.75 11.11NPV % 95.09 95.04 95.65 95.04Sensitivity % 1.22 1.08 53.61 3.44Specificity % 96.74 99.70 53.74 98.55

Table 4: Performance of four GAS sore throat prediction rules on the data set

Results

Variable % of GAS positive sore throat encounters with this variable present

% of GAS negative sore throat encounters with this variable present

% GAS positive in those with this variable present

% GAS positive in those with this variable not present

TEMP > 38 C 1.1 0.3 15.8 4.0TEMP >= 38.3 C 0.53 0.2 10.7 5.0HEADACHE 43.0 54.4 4.0 6.2NAUSEA 40.0 43.4 4.6 5.3ABDOMINAL PAIN 49.5 55.3 4.5 5.6DIFFICULTY SWALLOWING 87.7 88.6 5.0 5.4COUGH 73.5 78.1 4.6 6.0RUNNY NOSE 67.4 72.9 4.6 6.0HOARSE VOICE 3.7 3.9 4.9 5.0SNEEZING 54.6 60.7 4.5 5.7RED THROAT 90.9 89.2 5.1 4.2PUS in the throat 9.7 6.9 6.8 4.8ULCERS on roof of mouth 3.7 2.4 7.4 4.9SWOLLEN neck glands 64.6 70.4 5.4 4.8SORE neck glands 36.9 34.4Red EYES 0.81 1.66 2.5 5.0

Table 3 – Signs and symptoms of self reported sore throat encounters

*Totals varied with approximate 4% of the 12836 missing for most symptoms, but 12% for temperature

Variable % in the data set No. of encounters in the data set GAS positive culture %SEXFemale 51% 5947 5.3%Male 49% 5772 6.9%AGE GROUP5 to < 8 yrs 35% 4109 5.6%8 to < 12 yrs 44% 5178 6.1%12 to < 15 yrs 18% 2158 7.1%15 to < 19 yrs 4% 319 7.5%ETHNICITYMāori 38% 6706 6.2%Other, including European 5% 590 4.2%Pacific 57% 4397 6.2%TOTAL* (n=12836) 6.3%

Table 2– Demographics of those who self presented with sore throat

*Totals varied with approximately 10% not reporting demographic variables

References

Centor R et al. (1981) The diagnosis of strep throat in adults in the emergency room, Medical Decision Making, 1, pp 239-246.

The Institute of Environmental Science and Research Ltd (ESR) (2015) Notifiable Diseases in New Zealand: Annual Report 2014 , Porirua, New Zealand.

Lennon DL et al. (2009) School-based prevention of acute rheumatic fever: A group randomized trial in New Zealand. Pediatr Infect Dis J. 2009; 28: 787-794.

McIsaac W et al. (1998) A clinical score to reduce unnecessary antibiotic use in patients with sore throat, Canadian Medical Association Journal, Jan 13, 1998, 158, 1, pp 75-83. This was validated by McIsaac in McIsaac W, Kellner J, Aufricht P et al. (2004) Empirical validation of guidelines for the management of pharyngitis in children and adults, Journal of the American Medical Association, April 7 2004, vol 291, no 13, pp 1587-595.

Ministry of Health (2010) Tatau Kahukura: Māori Health Chart Book 2010, 2nd Edition. Wellington, New Zealand: Ministry of Health. http://www.health.govt.nz/publication/tatau-kahukura-maori-health-chart-book-2010-2nd-edition

Ministry of Health (2012) Tupu Ola Moui Pacific Health Chart Book 2012. Wellington, New Zealand: Ministry of Health. http://www.health.govt.nz/publication/tupu-ola-moui-pacific-health-chart-book-2012

Ministry of Health (2014) Annual Update of Key Results 2013/14: New Zealand Health Survey. Wellington, New Zealand: Ministry of Health. http://www.health.govt.nz/publication/annual-update-key-results-2013-14-new-zealand-health-survey

New Zealand Heart Foundation (2008) Evidence-based, best practice New Zealand guidelines, 2. Group A Streptococcal sore throat management, Auckland, Heart Foundation.

Singleton RJ. et al (2014) Indigenous children from three countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis. Pediatr Pulmonol. 2014 Feb;49(2), p189-200. doi: 10.1002/ppul.22763.

Twiss, J. et al (2005) New Zealand national incidence of bronchiectasis ‘‘too high’’ for a developed country. Arch Dis Child 2005;90, pp 737–740. doi: 10.1136/adc.2004.066472

Wald E et al. 1998) Wald E, Green M, Schwartz B, et al. (1998) A streptococcal score card revisited, Pediatric Emergency Care, vol 14, no 2, pp 109-111.

World Health Organization (WHO) (1991, reprinted 1994) Acute respiratory infections in children case management in small hospitals in developing countries. A manual for doctors and other senior health care workers.

Table 1 – Sore throat prediction rules tested

*Dr Melissa Kerdemelidis, MPH MBChB, (Affiliations: Canterbury District Health Board, & Department of Paediatrics, University of Auckland, New Zealand)*Prof Diana Lennon, MBChB FRACP, (Affiliation: Department of Paediatrics, University of Auckland, New Zealand, and Starship Children’s Hospital and Kidz First Hospital, Auckland.) Mrs Joanna Stewart, MSc. (Affiliation: Department of Epidemiology and Biostatistics, University of Auckland, New Zealand)Mr Henare Mason, (Affiliation: National Hauora Coalition, Auckland, New Zealand)Ms Elizabeth Farrell, MHSc (Affiliation: Kidz First, Auckland, New Zealand)

Contact details: melissa.kerdemelidis@cdhb.health.nz; d.lennon@Auckland.ac.nz

Rule WHO 1991 rule Wald et al. 1998 rule Modified Centor criteria by McIsaac et al (1998). (Based on Centor et al 1981)

Heart Foundation 2008 rule

Criteria 1. pharyngeal exudate and2. tender, and enlarged cervical lymph nodes

6 factors, giving one point for the presence of each1. Age 5-15 years 2. Season (November to May) [To approximate this, the months of June to November were used in our New Zealand analysis]3. Fever greater than or equal to 38.3 C 4. Adenopathy (cervical lymph nodes greater than or equal to 1 cm or tender to palpation) 5. Pharyngitis (erythema, swelling or exudate of pharynx or tonsils) 6. No upper respiratory symptoms (no rhinorrhea, no cough, no conjunctivitis)

Five criteria1. temperature > 38 – 1 point2. no cough - 1 point3. tender anterior cervical adenopathy – 1 point4. tonsillar swelling or exudate – 1 point5. age 3-14 years - 1 point6. age 15-44 years – 0 point7. age greater than or equal to 45 years – minus 1 point

1. First step is to assess risk factors for GAS sore throat and rheumatic fever. These score one point each and are: • Māori or Pacific peoples – 1 point• aged 3-45 years – 1 point• living in lower socioeconomic areas of the North

Island of NZ [specified]• Past history of rheumatic fever For a score of 2-4 risk factors, and 0-1 risk factors, there are two separate arms of the algorithm.In this data set, the children were already in the appropriate age range (3-45 years), and living in a lower socioeconomic area of the North Island (South Auckland).So for these patients the Centor 1981 criteria were applied next.These are: • Temperature > 38 C – 1 point• No cough - 1 point• Swollen tender anterior cervical lymph nodes – 1

point• Tonsillar swelling or exudate – 1 point

What was considered ‘positive’ for this analysis

All criteria needed to be present.

A score of 5 or 6. A score of 4 or higher. The presence of any of these Centor criteria in this data set was then considered positive for the Heart Foundation rule, as any of these would then lead to medium or high risk categories in the HF algorithm.