The fever fight

In 2013 there were 205 notified cases of rheumatic fever in New Zealand - the highest total in more than 20 years and almost all (95 per cent) were Māori and Pacific children. This rate of 4.6 per 100,000 people compares with rates of less than one per 100,000 across the rest of the developed world. Rheumatic fever is an acute illness that can progress to more serious rheumatic heart disease, each year hospitalising some 600 New Zealanders and killing around 150.

A government target to reduce the incidence of rheumatic fever by two thirds – to 1.4 cases per 100,000 people by 2017 – has seen more than $40 million of extra budget spending, mainly allocated to fund sore-throat treatment programmes.

Alongside this work, we need much greater understanding of what causes the disease and what interventions are likely to be effective at preventing it, says Professor Michael Baker (above left), from the University of Otago, Wellington's (UOW) Department of Public Health.

Funded by the Rheumatic Fever Research Partnership (Health Research Council of New Zealand, Heart Foundation, Cure Kids, Te Puni Kokiri and the Ministry of Health), he and his colleague Professor Julian Crane (above right), from UOW's Department of Medicine, are leading two ground-breaking projects to help meet this knowledge gap.

One, led by Baker, aims to identify important modifiable risk factors for rheumatic fever. The other, led by Crane, will investigate the effect of the oral probiotic S. salivarius K12, produced by BLIS Technologies, as a way of reducing the strep throat infections that can cause rheumatic fever.

The projects are two of four currently funded by the Rheumatic Fever Research Partnership to tackle the disease. UOW is making a substantial contribution to another one of the four – a study looking at the role of echocardiography in the early diagnosis of rheumatic heart disease.

A further project, funded by the Health Research Council of New Zealand and the Ministry of Health, called Housing Effects About Rheumatic fever (HEART), is being led by UOW's Professor Philippa Howden-Chapman and Dr Ramona Tiatia.

Identifying risk factors, particularly those that are modifiable, is a key part of the puzzle, Baker says. This is the impetus behind the project he is leading, a national case-control study which began recruiting cases on 1 September.

Over the next two years this study aims to recruit 200 children and teenagers with rheumatic fever and compare them with 400 young people who do not have the disease, to identify important risk factors. Initially in Auckland, the study will extend to Northland and the Waikato and, possibly, to other parts of the North Island, depending on disease incidence and recruitment rates. Results will be available towards the end of 2016.

“The entire research team is aware of the urgent need for the results of this study to be made available to the Ministry of Health and other agencies who are directing our national response to this disease,” Baker says.

The study has been designed to investigate a full set of potentially modifiable factors, with a particular focus on household crowding, sleeping arrangements, home heating, washing facilities, tobacco smoke exposure, dental health, health-care access and nutrition, including plausible risk factors such as vitamin D deficiency.

Because rheumatic fever virtually vanished from the US and Europe in the 1960s, it has received surprisingly little attention from researchers, despite remaining an important disease across the developing world, Baker says.

“There have been very few high-quality case-control studies of the type we are conducting. Consequently, results of this New Zealand study have the potential to support global efforts to control rheumatic fever.”

He does admit, however, to feeling a bit anxious about the study.

“Case-control studies are unforgiving. You have to identify all of your hypotheses and risk factors at the start and build them in to your data collecting and testing. There are no second chances. Fortunately, we have a brilliant group of co-investigators, and Māori and Pacific advisory groups who have given us expert guidance about the study design and questions that we need to focus on.”

The study team includes paediatricians, microbiologists, immunologists and geneticists, as well as experts in epidemiology, oral health and housing. In what Baker describes as “very much a national effort to try to understand the disease”, team members are based at the University of Auckland, Environmental Science and Research (ESR) and the Auckland District Health Board, as well as the University of Otago.

The research team is also grateful for the high level of support it is getting from doctors, nurses and laboratory scientists.

“This support is critical for the success of this study. There is a lot of good will towards this research because of the recognition that we currently don't know how to stop this disease.”

Baker and his public health colleagues are also calling for better surveillance of rheumatic fever to clarify the true rate of the disease and the effect of current interventions on that rate.

A recent UOW review showed that New Zealand cannot accurately track rheumatic fever incidence over time and the impact of the major interventions, he says.

“New Zealand has such wonderful health information resources, it would be relatively easy to organise these data to give us comprehensive surveillance of rheumatic fever. A critical need is for a national rheumatic fever register to combine different data sources to give us a single, robust total for rheumatic fever incidence in this country.”

Meanwhile, both he and Crane are excited about the potential to make a difference for vulnerable populations through the probiotic currently being tested in a community trial in Porirua, Wellington.

Crane notes that probiotics have, until recently, been on the fringe, but there is growing recognition of their potential and, recently, considerable interest in understanding the mechanisms by which they can modify disease and how they interact with the bacteria that normally, and usually happily, live with us.

The probiotic is a naturally-occurring bacterium that lives in the mouths of some children which produces bacteriocin-like inhibitory substances (BLIS) to kill the bacteria causing Group A Streptococcal (GAS) sore throat – often referred to as strep sore throat – that can cause rheumatic fever.

Around 2,000 children and their families from 11 Porirua schools are involved in this first-ever large random, double-blind human clinical trial of BLIS – all of whom are already taking part in the government throat swabbing programme.

Crane hopes that if the study shows BLIS reduces strep sore throats, the lozenges will be made available to all children at risk of developing rheumatic fever and would provide a temporary respite from the risk.

Children in the trial will be given a throat and tongue swab at the beginning of the trial, which runs for three school terms. They will also be swabbed at the end of the trial to see whether BLIS has changed the bugs in their throats.

Working collaboratively with public health nurses and trained staff in the schools, researchers will also count how many sore throats the children get during the year to see any differences between children taking the probiotic and those taking the placebo.

A small pilot study in Italy has already shown a 90 per cent reduction in GAS sore throat in high-risk populations, but no formal blinded randomised trial has previously been undertaken, Crane says.
“BLIS is a New Zealand invention, so it would be fitting if we can demonstrate that it is effective at reducing a major New Zealand health problem like rheumatic fever.”

KARYN AMMUNDSEN