Reducing the burden of group A streptococcal disease in the Northern Territory: the role of chemoprophylaxis for those at greatest risk

The unacceptably high prevalence among Indigenous people and people who need dialysis warrants a clinical trial of prophylactic antibiotics

Relatively little is known about the epidemiology of invasive group A streptococcal (iGAS) disease in Australia. In this issue of the MJA, Birrell and colleagues report that the iGAS disease burden in the Northern Territory continues to fall largely on Indigenous Australians and people undergoing haemodialysis.1 This raises the question of whether antibiotic prophylaxis should be provided to those at greatest risk. Their report is timely, as national public health guidelines are being developed following the listing of iGAS disease as nationally notifiable in July 2021.2

Birrell and her colleagues analysed ten years (2011–21) of iGAS surveillance data from the NT, where iGAS has been notifiable since 2011. Using multiple data sources, they also report its wet season incidence among haemodialysis patients according to whether they had received trimethoprim–sulfamethoxazole (TMP/SMX) as melioidosis prophylaxis.

The iGAS disease burden in the NT reported by Birrell and colleagues is staggering. In the sparsely populated desert regions of Central Australia, the annual incidence was 82.2 cases per 100000 population (95% confidence interval [CI], 71.8–92.7 per 100000), 3.5 times as high as for the tropical Top End (23.2 [95% CI, 20.6–25.8] cases per 100000 population),1 and 26 times as high as the recently reported incidence in Victoria (3.1 [95% CI, 2.4–5.2] cases per 100000 population).3 The incidence among Indigenous people was more than seven times as high as for non‐Indigenous Territorians,1 consistent with Australian and overseas literature on iGAS disease in First Nations peoples.4,5,6 Further, the annual incidence among Indigenous people in Central Australia (172 [95% CI, 148–197] cases per 100000) was more than twice that in the Top End (71.5 [95% CI, 61.3–81.7] cases per 100000) or Western Australia (79.9 [95% CI, 62.6–97.2] cases per 100000).6

Impetigo, associated with extensive scabies infestation, is an important precursor of iGAS disease,7 and the prevalence of GAS impetigo among Australian Indigenous children is the highest documented rate in the world.4 Social determinants of health, particularly overcrowded living conditions, underlie this health inequity and indicate that both primordial and primary disease prevention are needed.

The high annual incidence of iGAS disease among NT haemodialysis patients (1643 [95% CI, 1374–1950] cases per 100000)1 is consistent with earlier reports.8 This finding reflects the multiplicative impact of several risk factors for iGAS disease in the NT: lower socio‐economic status and, in particular, poor housing; being Indigenous; chronic kidney disease and associated comorbid conditions, particularly diabetes; and widespread skin disease facilitating entry of GAS bacteria.

Birrell and colleagues found that no people receiving haemodialysis developed iGAS disease while receiving TMP/SMX as melioidosis prophylaxis during the wet season, whereas the incidence among those not receiving antibiotics was 1122 (95% CI, 412–2441) cases per 100000 population.1 NT Health iGAS guidelines recommend long term secondary antibiotic prophylaxis for people requiring dialysis who have experienced iGAS infections, recognising the 16% recurrence rate for these patients.9

Given the findings of Birrell and her colleagues, the question is whether antibiotic prophylaxis should be routinely offered throughout the year to NT people undergoing haemodialysis to prevent first episode iGAS disease. The proportion of dialysis patients receiving melioidosis prophylaxis during the wet season increased after routine prescribing was introduced in November 2014. Problems of bias and confounding, concerns in any uncontrolled observational study, could be overcome by a randomised controlled trial (RCT) of antibiotic prophylaxis during the period when patients are not routinely receiving antibiotics (ie, not during the wet season). Such a trial would be challenging despite the extraordinarily high incidence of iGAS disease among NT people receiving dialysis and the apparent 100% effectiveness of antibiotic prophylaxis.1 If prophylaxis achieves an 90% reduction in the annual incidence of iGAS disease (from 1643 to 164 cases per 100000 population), about 770 person‐years of observation would be required in each trial arm to achieve 80% power (with 1:1 enrolment; α = 0.05). As the number of people receiving dialysis in the NT is expected to reach 1000 in 2023,10 the trial would need to run over several years to achieve the required sample size.

The 30‐day risk of iGAS infection for contacts of someone with an index infection is about 2000‐fold as high as the background risk, and even higher for mother–neonate pairs and couples over 75years of age.11 While some authorities recommend antibiotic prophylaxis for close contacts, others do not,12 and no RCT assessments of short term prophylaxis have been reported. Given the high incidence of iGAS disease in the NT,1 a trial of contact prophylaxis is worth considering, and would provide evidence for informing Australian and overseas public health guidelines.

At a time when Australian public health guidelines for iGAS disease are being developed, the study by Birrell and colleagues provides important insights into who is at greatest risk and the possible role of antibiotic prophylaxis. It also highlights the importance of future clinical trials for generating evidence to inform iGAS infection prevention activities.