Background Acute rheumatic fever ( ARF) and rheumatic heart disease (RHD) remain an unequal cause of preventable suffering and premature death in many countries, including among indigenous Māori and Pacific populations in New Zealand. There is a lack of strong evidence on interventions to prevent ARF. This study aimed to identify modifiable risk factors , with the aim of producing evidence to support policies and programs to decrease ARF rates. Methods A case-control study was conducted in New Zealand using hospitalized first-episode cases of ARF who met a standard case definition. Population controls (3:1 ratio) were matched for age, ethnicity, socioeconomic deprivation, location, sex, and month of recruitment. A comprehensive, pretested questionnaire was personally administered by trained interviewers. Results The study included 124 cases and 372 controls. Multivariate analysis identified strong associations between ARI and household overcrowding (OR 3·88; 95% CI 1·68-8·98) and barriers to accessing primary health care (OR 2·07; 95% CI 1 ·08-4·00), as well as a high intake of sugary drinks (OR 2·00; 1·13-3·54). There was a marked five-fold increased risk of ARF for those with a family history of ARF (OR 4.97, 95% CI 2.53-9.77). The risk of ARF was elevated after self-reported skin infection (aOR 2.53; 1.44-4.42) and sore throat (aOR 2.33; 1.49-3.62). Interpretation These globally relevant findings draw attention to the critical importance of household crowding and access to primary health care as strong modifiable causal factors in the development of ARF. They also support an increased focus on the role of management of skin infections in the prevention of ARF. |
Causal pathway from group A streptococcus (GAS) exposure to rheumatic fever (RAF) and rheumatic heart disease (RHD) showing major hypothetical clusters of risk and protective factors
Comments
Research led by the University of Otago in New Zealand has uncovered the strongest evidence yet that household crowding is a major risk factor for acute rheumatic fever and streptococcal skin infections.
Their research is published in two companion articles in the international medical journal The Lancet Regional Health – Western Pacific .
Lead researcher Professor Michael Baker, from the University of Otago, Wellington, says it is the first time researchers have investigated the risk factors for group A streptococcal infections of the throat (strep throat ) and skin ( skin streptococcal ) that can cause rheumatic fever.
The studies found that both rheumatic fever and streptococcal skin infections were linked to barriers to accessing primary health care and a family history of rheumatic fever and rheumatic heart disease, a serious illness that can develop if rheumatic fever is left untreated. .
Professor Baker says it is a big step forward to have identified a key pathway that drives the risk of rheumatic fever.
“Finding a strong association between skin infection and rheumatic fever adds to the evidence of other research carried out by our group on the importance of streptococcal skin in the triggering of this disease. These results suggest that treating skin infections in young children may provide a way to prevent them from developing rheumatic fever.
“Our findings reinforce the central role that good-quality , uncrowded housing plays in protecting children during the period when they are vulnerable to rheumatic fever and other infectious diseases. It is also a reminder of the importance of having good access to primary health care .”
An unexpected finding from the rheumatic fever risk factors study was that drinking sugary drinks was twice as common among rheumatic fever cases compared to healthy controls, even after adjusting for all other risk factors.
“There are several ways in which sugary drinks could increase the risk of rheumatic fever. We are planning further research to test some of these hypotheses. In the meantime, this is another reason for children to switch to healthy alternatives, such as water or plain milk,” says Professor Baker.
Associate Professor Jason Gurney (Ngā Puhi), who played a leading role in the study of risk factors for rheumatic fever, also emphasized the importance of the research findings.
“Rheumatic fever is an important example of the stark inequalities that exist in terms of health outcomes in New Zealand. Rheumatic fever rates are around 20 times higher for Māori and 44 times higher for Pacific peoples than for non-Māori and non-Pacific peoples.
“It is vital that new incoming health organisations, particularly the Māori Health Authority, Public Health Agency and Health New Zealand, act on these research findings as a high priority. “It is also crucial that we look deeper into the social determinants of this disease and continue to address inequalities in access to things like healthy, high-quality housing and primary care.”
Dr Julie Bennett, who took a leading role in studying risk factors for strep infection, says the research provides a way forward for Aotearoa New Zealand to apply the general findings and test specific interventions that were highlighted in the investigation.
“The findings from these two studies and other related research suggest that skin infection is a key target for better treatment. It would be useful to conduct suitable trials to see how better access to effective treatment of skin infections could be provided and how this could reduce the subsequent risk of rheumatic fever. “Any intervention will need to be co-designed with Māori and Pacific peoples.”
Professor Jonathan Carapetis, director of the Telethon Kids Institute in Perth, Western Australia and professor at the University of Western Australia, is one of the world’s leading researchers on rheumatic fever and other streptococcal diseases. He describes the studies as a breakthrough in the global fight against these diseases.
“This is by far the most rigorous study ever conducted to identify risk factors for rheumatic fever. The study of risk factors for streptococcal skin and throat infections is a world first. Together, these studies provide a very strong foundation that can help guide our collaborative goal to eliminate rheumatic heart disease as a global health problem.”
Rheumatic fever is an inflammatory reaction to bacterial infection of the throat and skin by group A Streptococcus. One or more attacks of rheumatic fever can cause permanent damage to the heart valves, resulting in rheumatic heart disease that may require major surgery and can result in a lower quality of life and premature death. The indigenous and Pacific populations of New Zealand and Australia have some of the highest rates of rheumatic heart disease in the world. In 2015, an estimated 34 million people were living with rheumatic heart disease, with around 233,000 deaths per year.
Evidence before this study We conducted a structured review of the published literature focusing on risk factors for ARF, RHD, and GAS infections (with full results reported in the published study protocol). We restricted it to studies that used robust epidemiological designs (cohort, case-control, cross-sectional, controlled trials). This scope included studies referenced in Medline and Embase plus those found through a manual search of references identified in these studies. We also relied on a recently published systematic review on the social determinants of ARF, RHD, and GAS infection. This search found an almost complete lack of high-quality studies with none covering a full range of host and environmental risk factors and no intervention studies. The modifiable risk factors consistently identified were exposure to poverty and household overcrowding. The literature identified group A streptococcal pharyngitis as a known trigger of ARF. There was a recent record linkage study supporting the role of GAS skin infections. There was also some evidence that susceptibility has a familial and genetic component. Added value of this study Our study has identified important modifiable risk factors for Acute Rheumatic Fever (ARF), particularly household crowding and barriers to accessing primary health care. It used strict adjustment to control for the effects of established sociodemographic risk factors and family history, allowing the contribution of specific modifiable environmental exposures and health service factors to disease risk to be identified. The findings also demonstrated that a previous skin infection was associated with an increased risk of ARF. Implications of all available evidence The findings of this study show the importance of minimizing household crowding as an intervention to reduce the incidence of ARF in the many countries where this disease remains an endemic public health problem. The results also support the importance of access to primary health care and strengthen the evidence for effective treatment of skin infections to reduce ARI. The findings also show that there are likely benefits to targeting prevention interventions to populations with the highest rates of rheumatic fever (ARF) and rheumatic heart disease (RHD) and potentially incorporating family history of the disease into this process. The identified association between ARF and the amount of sugary drinks consumed each day requires further investigation. |
The rheumatic fever risk factors study was funded by the New Zealand Health Research Council (HRC) Rheumatic Fever Research Partnership (supported by the New Zealand Ministry of Health, Te Puni Kōkiri, Cure Kids , Heart Foundation and the HRC itself). The study of risk factors for streptococcal infection was funded by the HRC.
The researchers thank the many participants and their families for sharing their time and experiences to make these studies possible, as well as Māori and Pacific advisors, doctors, medical health officers, nursing staff, support staff at DHB, staff laboratory technicians in diagnostic and ESR laboratories and interviewers employed by CBG Health Research Limited.
