Chagas disease in Australia and New Zealand: risks and needs for public health interventions
Chagas disease is a chronic protozoan infection caused by Trypanosoma cruzi that is endemic in Mexico, Central and South America (Latin America) (WHO 2010a,b). Twenty to forty per cent of infected persons develop long-term complications such as potentially fatal cardiomyopathy and disabling upper or lower digestive tract involvement requiring long-term medical care (Rassi et al. 2010). Immunosuppressed patients, including those infected with HIV or receiving immunosuppressive treatments, risk severe cardiac and toxoplasmosis-like cerebral damages with devastating consequences. A key feature is the decades-long asymptomatic period before symptoms occur, which means most chronic carriers are unaware of their infection and their potential for transmission. The long-lasting and severe consequences requiring long-term and complex medical care mean that Chagas disease entails consequent economic costs. The total annual and lifetime costs to society of an infected individual in Australia have been estimated to amount to $15 762 ($13 249–17 442) and $91 531 ($42 992–149 333), respectively (Lee et al. 2013); this costing does not include patients who go on to receive a heart transplant for Chagas cardiomyopathy when the costs sharply escalate. This substantial human and economic burden makes Chagas disease a prominent parasitic infection in endemic countries (Lee et al. 2013).
Trypanosoma cruzi infection is primarily a zoonosis affecting mammalian species including native wildlife, domestic cats and dogs. Humans are accidental hosts. Vectorial transmission predominates in endemic regions. The Western Pacific region harbours several vectors able to transmit T. cruzi, including seven species of triatomines (WHO 2011). Triatoma leopoldi occurs in northern parts of Australia and native wildlife has been infected with various species of Trypanosoma, which highlights the potential for local vectorial transmission (Monteith 1974). It is noteworthy that unlike the human infection, the animal form of Chagas disease is notifiable in Australia (Department of Agriculture Fisheries & Forestry 2013).
In non-endemic countries, non-vectorial routes are responsible for infection. These include transplacental (vertical), through contaminated blood transfusion or tissue and organ transplantation, and during laboratory accidents (Bern et al. 2008; Rassi et al. 2010; Carlier et al. 2011). Mother-to-child infection occurs in 5–10% of pregnancies, whereas the risk related to transfusion of contaminated blood products reaches 20–40% (WHO 2002). Recipients of platelet concentrate transfusions incur the highest risk of infection. The persistence of low-grade parasitemia during the asymptomatic phase of the infection accounts for a sustained risk of transmission even in the absence of re-exposure to the infectious agent (Leiby et al. 2008).
Chagas disease affects 8–10 million people, predominantly in Latin America (WHO 2010a,b). Due to increasing population movements both within and outside of Latin America in the 1990s, the disease has spread to at least 19 non-endemic countries in Western Europe, North America and Asia-Pacific (Schmunis & Yadon 2009; WHO 2010b). It is estimated that more than 16 million persons at risk left their country and migrated to non-endemic regions since 2000 (WHO 2009). Moreover, the booming tourism industry in Latin America means that a rising number of travellers from non-endemic countries visit endemic areas and thus face risks of infection (World Tourism Organisation 2013). Yet, so far Chagas disease has been only exceptionally reported in travellers. Currently, the United States have an estimated 300 000–500 000 cases and Europe has 70 000–120 000 cases. Active transmission has been identified in several non-endemic countries (WHO 2009; Basile et al. 2011; Bern et al. 2011). Chagas disease-related deaths have been reported in both immigrants and local populations. The majority of cases in non-endemic countries affect adult Latin American immigrants; 20–30% suffer from cardiac complications at time of diagnosis (Munoz et al. 2009; WHO 2009; Jackson et al. 2010). Children born to an infected mother comprise the second most affected group, whereas blood transfusion and organ transplant recipients account for a minority of cases. In Europe, only 10–20% of screened individuals who tested positive for the infection were aware of their status, which highlighted the risk of silent transmission in the absence of efforts to actively identify those at risk (Jackson et al. 2010).
In 2011, WHO reported that Chagas disease was an emerging health issue in the Western Pacific region in the context of growing population movements from endemic countries with an increasing number of cases being reported (WHO 2011). WHO warned against the risks pertaining to the ongoing silent transmission and the insufficient attention given to people carrying the infection, and raised the issue of the lack of ongoing research and data collection in the region, most notably in countries likely to be prominently affected such as Australia and Japan. Insufficient attention might prevent effective public health measures.
To fill this gap, we investigated evidence, practices and policies pertaining to Chagas disease in Australia and New Zealand. To better illustrate the risk, we calculated an estimated prevalence for both countries.
A search in the literature was conducted using the MEDLINE database and Google Scholar to identify epidemiological and clinical evidence and policy documents pertaining to Chagas disease in the Western Pacific region. To complement this strategy, experts were consulted in Australia and New Zealand about the clinical management of the disease and of its risk management in blood banks.
To estimate the population at risk, we extracted the latest demographic data available in Australia and New Zealand from the respective national statistics websites (Australian Bureau of Statistics 2013; New Zealand Statistics 2013). This allowed for determining the number of permanent residents originating from endemic countries. Following previous models, we multiplied these numbers by the country of origin average infection rate (Basile et al. 2011).
Epidemiological evidences and estimation of prevalence
So far, there has been no epidemiological study about the real burden of Chagas disease in Australia, New Zealand or any Western Pacific country. Therefore, estimations rely on modelling (Schmunis & Yadon 2009). Australia hosts a growing number of residents of Latin American origin. Whereas there were 79 510 residents born in an endemic country in 1997, this figure rose to 116 430 in 2011, a 46% increase (Australian Bureau of Statistics 2013). New Zealand data from 2006 showed that 6315 residents were born in an endemic country (New Zealand Statistics 2013). Overall, Chile and Brazil were the predominant countries of birth, followed by Argentina and Colombia (Table 1). Of note, these data do not include temporary residents from endemic countries, whose number is likely to be important, undocumented immigrants, travellers or Australian or New Zealander citizen born of a mother originating from Latin America. There are no available data about long-term Australian and New Zealander travellers and expatriates who have lived in endemic countries. Therefore, our estimations based on residency registries underestimate the real magnitude of the populations at risk. In Europe, for example, undocumented immigrants and non-permanent residents accounted for a substantial proportion of cases (Jackson et al. 2010; Basile et al. 2011).
Table 1. Residents originating from Chagas disease endemic countries living in Australia (2011) and New Zealand (2006) and estimated number of infected residents
|El Salvador||3.37||10 850||366||57||1|
|Total|| ||116 430||1928||6315||82|
According to our estimation, Australia hosted 1928 infected residents in 2011 and New Zealand 82 in 2006. The Australian estimate is higher than previously published given the increased population at risk (Schmunis & Yadon 2009). An important limitation of this method pertains to the use of average infection rates at country level, which may obscure important variation among regions of origin and may differ from infection rates found among immigrants outside of Latin America. Of importance, the median age of Latin American immigrants in Australia was 39 years in 2011, highlighting the fact that a substantial proportion of women are of childbearing age and thus at risk of vertically transmitting T. cruzi (Australian Bureau of Statistics 2013).
In Europe, only 5–10% of estimated cases have been diagnosed and reported, reflecting the insufficient public health interventions in place (WHO 2009; Basile et al. 2011). In Australia and New Zealand, a single case has been reported so far (Sooklim et al. 2011). In Japan, a country with a large population of Brazilian and Peruvian origin and an estimated 3000 cases, only 17 cases, all in immigrants, have been reported since 1976 (WHO 2011). No other country from the Western Pacific region has reported any case to date.
Policy and practice
A few non-endemic countries have policies and programs aiming at identifying cases and preventing transmission (WHO 2009; Requena Mendez et al. 2013). Spain, the UK, France and Switzerland test blood donors with risk factors. While no non-endemic country has a national policy about screening for congenital transmission, it is practised in several regions and local institutions in Spain, Italy and Switzerland, where populations at risk reside.
No country in the Western Pacific region has any health policy designed to systematically identify individuals at risk of T. cruzi infection. There is no programme to screen pregnant women at risk, their children and the rest of the family in case of positive results as shown effective elsewhere (Zulantay et al. 2013). No national recommendation pertains to testing blood and organ donors or persons with current or foreseen immunosuppression at risk of reactivation of the infection. The Australian Red Cross Blood Service and the New Zealand Blood Service follow the Guide to the Preparation, Use and Quality Assurance of Blood Components published by the Council of Europe as external reference standard. Both institutions screen donors with a questionnaire applied every time they donate blood, but do not routinely test blood for Chagas disease in persons at risk. Any donor with a personal history of Chagas disease is permanently deferred from donation, and individuals born in endemic areas or transfused with fresh blood components in an endemic areas are permanently restricted to donate plasma for fractionation only until a serologic test proves the donor is negative (P. Flanagan, personal communication) (WHO 2011). Since 2003, the Australian Red Cross has identified and tested 154 past donors at risk of Chagas disease, with an estimated risk of blood-borne transmission of 0.04% (Australian Red Cross Blood Service 2010). As this procedure does not operate as a systematic mechanism of identification of infected individual, it only entails very limited impact on the identification and management of active infections.
There is no clinical guideline in general practice or other medical speciality dealing specifically with Chagas disease in Australia. In Australia and New Zealand, access to and turnaround time for test results is limited by the very few laboratories performing serological testing. The ICPMR laboratory at Westmead Hospital in Sydney performs an ELISA test and processes samples from New Zealand. Confirmatory tests have to be performed overseas. Finally, none of the two antiparasitic drugs is registered or available in both countries. Currently, doctors have to order them through special access schemes, which results in long delays before being able to initiate treatment.
Strategies to consider in Australia and New Zealand
In the absence of a vaccine and other primary prevention measures, WHO advocates a two-pronged strategy to tackle Chagas disease emergence and transmission in non-endemic countries (WHO 2002, 2009, 2011). The first pertains to interrupting transmission. The second relates to facilitating access to treatment for infected persons as early as possible to prevent complications. Overall, these strategies should aim at multiplying opportunities for persons at risk to enter in contact with detection and caring programmes.
Despite a theoretical risk of vectorial transmission in Western Pacific countries, no case has ever been recorded, thus limiting the need to address this route of transmission in priority. Experiences in Europe and North America rather support focussing efforts to identify vertical and blood/organ routes of transmission. Given the likely emergence of Chagas disease in Australia and to a lesser extent in New Zealand, this public health approach should be given attention.
The rationale for screening blood donors is supported by evidence showing that infected Latin American immigrants unaware of their infection are willing to donate blood (Jackson et al. 2010). The current strategy of identifying and discarding donors at risk in Australia and New Zealand is in line with guidelines from countries with low risk of transmission. Improved epidemiological evidence may lead to consider a systematic testing strategy of donors at risk such as adopted in Spain and Switzerland, where routine donation testing allowed for identifying blood-borne transmission (Castro 2009). Moreover, the current system could be better connected to clinical practice in Australia by ensuring that all donors identified as at risk undergo full testing and follow-up to enhance the capacity of identifying infected individuals.
Given the rising number of organ donors and recipients at risk and the identification of tissue-borne transmission in Europe and the United States, guidelines about donors and receivers testing have been recently published (Chin-Hong et al. 2011; Pinazo et al. 2011). Considering similar trends in population movement to Australia and New Zealand, these guidelines merit accrued attention among specialists and testing should be recommended in donors at risk until more data are available about the risk. These guidelines also discuss rational for testing donors at risk while balancing the risks and benefits of using contaminated organs in a context of chronic organ shortage.
Screening pregnant women and their infants at risk does not aim at preventing transmission stricto sensu but rather at identifying those susceptible to benefit from early treatment and at protecting women before future pregnancies. Moreover, extending the screening to the whole family of a seropositive pregnant woman provides additional opportunities to identify cases and potential sources of transmission (Zulantay et al. 2013). The available antiparasitic treatments are contra-indicated during pregnancy, and infected mothers identified by prenatal screening programmes are treated after terminating breastfeeding (Carlier et al. 2011). Of note, breastfeeding is not contra-indicated given its favourable risk–benefit ratio (Norman & Lopez-Velez 2013). Most infected neonates are asymptomatic and treatment is highly effective when given during the first 2 years of life (WHO 2002; Rassi et al. 2010). Screening pregnant women at risk is a cost-effective intervention in non-endemic countries, and evidence lends support to a protective effect of treatment against subsequent T. cruzi transmission (Sicuri et al. 2011; Murcia et al. 2013).
In Australia and New Zealand, interventions designed to identify pregnant women at risk of transmission would represent a rational complement to the identification of blood donor with similar risk. Yet, in the absence of evidence about the real prevalence of T. cruzi infection in pregnant women, the cost–benefit ratio of such interventions cannot be assessed and it might be argued that New Zealand may host a too limited number of women at risk to afford favourable ratios. Criteria and strategies for screening pregnant women differ among non-endemic countries and need to be adapted to the local epidemiology (Flores-Chavez et al. 2011). Community-based studies conducted in Europe showed that major risk factors for infection, in addition to being born in Latin America, were Bolivian origin, a maternal infection with T. cruzi, and being older than 35 years (Munoz et al. 2009; Jackson et al. 2010). WHO has recently recommended screening pregnant women of Latin American origin who were born or had lived in Latin America; had received a blood transfusion in Latin America; or have a mother who had lived in Latin America (Carlier et al. 2011). The use of similar criteria has yielded good results in different European countries (WHO 2010a,b). Programme monitoring and evaluation would allow for adjusting these criteria to the Australian and New Zealand setting.
Ensuring that infected persons receive appropriate care makes full sense as a public health measure when all efforts are deployed to identify all those who need such interventions. If there are no active efforts to identify patients, diagnosed cases are restricted to individuals presenting with end-stage complications that are less amenable to curative interventions and have a generally poor prognosis (WHO 2002; Jackson & Chappuis 2011). But if programmes for early identification are in place, the majority of patients are at an early stage with more chance of benefiting from treatment (Jackson & Chappuis 2011; Navarro et al. 2012). The availability of accurate diagnostic tests and the benefit of treatment over the advent of cardiac complications when applied during the chronic asymptomatic phase support the rational for proposing screening to persons at risk (Viotti et al. 2006; Rassi et al. 2010).
Providing effective care in Australia and New Zealand will require addressing several challenges. At the community level, the lack of patients' mobilisation reinforces the fact that it remains a silent disease with poor visibility in the social and political arena. This neglected health issue also affords poor awareness from health professionals and public health officers in non-endemic countries. Therefore, there is high chance that diagnostic and treatment opportunities are missed during health care encounters (Jackson et al. 2009; Verani et al. 2010). In Europe, efforts have been put on enhancing awareness and education among health professionals in addition to ensuring the availability of tests and drugs (Jackson et al. 2009). To maximize the opportunities to detect cases, efforts should be made to inform and support specialists likely to attend patients with end-stage complications (infectious diseases specialists, cardiologists and gastroenterologists) as well as primary care physicians, including paediatricians and obstetricians, likely to see the largest share of persons at risk at an earlier stage, when more effective interventions are possible. Although WHO can provide drugs upon request, a national supply system might prove more straightforward for clinicians and patients, thus minimising the delays and risk of loss to follow-up. As a minimum, the availability of treatments for cases of emergencies (reactivation and acute phase) should be secured. Travel clinics have also a role to play by informing travellers and those visiting friends and relatives in endemic countries about the risks. Moreover, interventions to enhance awareness in communities at risk may facilitate demands for screening in asymptomatic persons (Navarro et al. 2011).
The limited evidence suggests that Chagas disease is an emerging health issue in Australia and New Zealand likely to increase in importance given the rapid rise of the population at risk. The problem may extend well beyond these two countries and potentially impacts on other countries in the Western Pacific region, as exemplified by the extent of the issue identified in Japan. In contrast to other parasitic infections with a low burden of disease in Australia and New Zealand, such as malaria, Chagas disease receives only minimal public health attention, which is likely to have significant consequences. The scarcity of data warrants using models whose assumptions, such as considering uniform and stable infection rates in each country of origin, have only limited accuracy. It is likely that clinicians, through lack of familiarity for what until recently was a geographically restricted infection, might not make the diagnosis even when faced with a patient with end-stage Chagas disease. The absence of strategy to identify infected individuals – with the exception of blood donors in Australia and New Zealand – means that T. cruzi infection will further spread unnoticed, putting individuals and communities at risk of suffering avoidable morbidity with potentially important costs for society.
In summary, the passive approach to tackling Chagas disease should be addressed as a matter of urgency for public and individual health reasons. We believe that Australia and New Zealand should align with some European non-endemic countries in putting in place: (i) epidemiological studies to better understand the context and risks; (ii) selective screening programmes for persons at risk; (iii) awareness programmes for clinicians in different sectors likely to meet with persons at risk, including travel clinics; (iv) improved access to diagnostic tools and treatment; and (v) links with Latin American communities to share information and education materials.
We thank Dr Peter Flanagan and John Dagger from the New Zealand Blood Service and Dr Helen Faddy from the Australian Red Cross Blood Service for their valuable contribution in providing information.