Health metrics for helminth infections

https://doi.org/10.1016/j.actatropica.201312001 Get rights and content

Highlights

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    Health-adjusted life years are standard units for comparing disease burden.
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    The DALY and the QALY are the most frequently used in cost-effect analyses.
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    While sometimes useful, both the DALY and QALY metrics have significant limitations.
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    This is particularly true for ‘neglected tropical diseases’ (NTDs).
  • •
    Interim approaches for disease burden assessment are discussed.

Abstract

Health metrics based on health-adjusted life years have become standard units for comparing the disease burden and treatment benefits of individual health conditions. The Disability-Adjusted Life Year (DALY) and the Quality-Adjusted Life Year (QALY) are the most frequently used in cost-effect analyses in national and global health policy discussions for allocation of health care resources. While sometimes useful, both the DALY and QALY metrics have limitations in their ability to capture the full health impact of helminth infections and other ‘neglected tropical diseases’ (NTDs). Gaps in current knowledge of disease burden are identified, and interim approaches to disease burden assessment are discussed.

Graphical abstract

Limitations of DALYs and QALYs (metrics commonly used to assess the health burden of helminth infections) are discussed and recommendations made to improve appraisals of their impact.
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Introduction

In a broad sense, health metrics are numbers assigned to quantify the impact of different diseases on personal health status. They are numerical judgments of the value of certain health states or treatment outcomes and, in the literature of the different disciplines that evaluate health outcomes, they can be referred to as ‘preferences’, ‘values’, or ‘utilities’ (Gold et al., 1996). In economics, the ‘utility’ of a transaction can be inferred from an informed, ‘rational’ consumer's willingness to pay for goods or services. By contrast, in health care, many personal factors can influence a person's valuation of a given health state. This makes it quite challenging to define health metrics that accurately reflect the value of individual health states to society-at-large.
The notion underpinning the use of such health ‘utilities’ is that they could allow us to compare the efficacy and effectiveness of different health interventions on a ‘like-is-like’ basis (Gold et al., 1996, Murray, 1996). If it is believed that if such metrics are applied to different diseases in a ‘fair’ manner, then the relative value of each intervention can be assessed in terms of the health utility gained, as captured by the health metric. The result is that decisions in favor of more ‘effective’ interventions can be made on a utilitarian basis across a broad range of health-related harms (Murray, 1996). The use of health metrics presupposes that the decision maker agrees with this unitization of health states, and that maximization of health utility is the right approach to allocation of limited health care resources.
The move to quantify disease impact of different health states comes from the greater implementation of health economics in evaluation of disease control initiatives. It springs from the efforts of policymakers to improve the efficiency of health care investments and health care delivery in all settings, including less-developed countries.
In standard cost-effectiveness analysis (CEA), the final outcome that is typically assessed is ‘cost per health-unit gained’, while in cost-benefit analysis (CBA) the outcome is in the form of ‘cost spent per costs saved or averted’ through the intervention program. To conduct either CEA or CBA, there must be an identifiable, measurable, scalable, unitized consequence that results from the proposed treatment (or preventive care) given by the health program under study. In sum, the gain can either be measured as non-monetary health effects, as is done in CEA, or as associated monetary benefits, as is done in CBA. Those who pay for health care (payors) may be most interested in CBA, whereas patients, social programs, and healthcare providers may be more interested in the outcomes that are included in CEA.
Early evaluations of helminth control programs used ‘cases prevented’ or ‘cases cured’ as the outcomes that were measured in their CEA (Guyatt, 1998). The drawback to this disease-centric approach was the outcomes could not then be compared among the different parasite infections, because each infection had its own pathogen-specific morbidities. Similarly, without a generalizable health metric, there was no meaningful comparison between deworming interventions and the many competing disease control programs implemented elsewhere in the health sector.
The cost effectiveness approach is fundamentally utilitarian in philosophy, encapsulating the belief that program impact can be potentially maximized at a minimum of cost (Gold et al., 2002). The assumption is that the expected outcomes of the program are scalable (i.e., retaining the same value at all locations and at all levels of aggregation), additive (i.e., two units gained are twice as valuable as one unit gained), and are fungible (i.e., interchangeable among different individuals in the same or different locations) (Murray, 1996). As discussed later in this paper, human health perception and health-seeking behavior diverge significantly from this assumed unitization of health. However, the creation of such health ‘units’ is essential to performing the sort of comparisons favored by health economists in their ‘league table’ rankings of health investments (Jamison, 1996, Jamison, 2006). It has long been recognized in economics that the value of a transaction is determined by the consumer's (not the seller's) perception of value. Because of this, the units of health or health burden employed in CEA must in some way incorporate patient preferences about the possible alternative health outcomes that are being compared (Gold et al., 1996).
The ultimate factor driving the move toward CEA is the knowledge that resources are limited for investment in health care and the efficient allocation of scarce resources would be an ethical ‘good’ for the world community. The salient policy discussion in setting disease control priorities has been, "How much health can we buy for 1 million dollars?" (Jamison, 1996) Unfortunately the basic cost-effect algorithm is an essentially linear approach that is often not well suited to the realities of health care, and not well suited to the non-linear economic features of low-income life (Banerjee and Duflo, 2011, King and Bertino, 2008).
In defining the health burden of developing countries, there is a new appreciation of the role of chronic parasitic diseases in the perpetuation of disability, particularly in the setting of rural poverty (Engels and Savioli, 2006). In highly developed regions such as Europe and North America where parasites are now infrequent, we tend to conceptualize infectious diseases predominantly as ‘acute’ health problems that will respond rapidly to appropriate antimicrobial therapy and leave the treated patient with only minimal or no lasting disability. While there is an increasing realization that a number of major chronic diseases are caused by infection, including those caused by human papilloma virus (HPV), Helicobacter pylori, HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV), in high-income countries, the impact of communicable diseases is often considered to be minimal compared to the impact of chronic non-communicable diseases (Gwatkin et al., 1999, Murray et al., 2012c).
By contrast, in the developing world, parasitic infections are common, recurrent, and long-lasting health problems that represent an ongoing inflammatory challenge and a significant health threat to the populations who are at continuing daily risk for reinfection (Jia et al., 2012, Satayathum et al., 2006, Wang et al., 2012). Also, in the context of health burden assessment, it is important to realize that parasite-related disease outlasts the period of parasitic infection (Giboda and Bergquist, 1999)—in the typical endemic setting, active infection represents only a major risk factor for parasite-associated disease. Although past Global Burden of Disease Program assessments (Mott, 2004, Murray and Lopez, 1996) have assumed that patients with helminth infections are ‘mostly asymptomatic’, this is not true—meta-analysis of available clinical evidence has shown that helminth infections are associated with many significant morbidities and chronic/permanent disabilities (Carabin et al., 2011, Chan, 1997, Furst et al., 2012a, King et al., 2005, Quattrocchi et al., 2012).
There is a severe lack of information on the long-term outcomes of patients exposed to chronic parasitic infections during their childhood or young adulthood. Risk of advanced pathology over time has often only been inferred via cross-sectional studies (e.g., King et al., 1988), in which patient age serves as a proxy for duration of exposure among long-term residents of an endemic area.
Formal decision analysis for health care resource allocation is often based on Markov-type models that project the expected outcomes of an intervention based on the probabilities of disease, its proper diagnosis, and its response to different treatments over time (King et al., 2011, Petitti, 2000). For helminth diseases, such a life-path analysis approach has suffered from a lack of well-measured longitudinal data inputs. Conditional probabilities for transition from mild to more severe health states are mostly unknown (Kirigia, 1997, Kirigia, 1998). It has been demonstrated that both patients and ‘disease experts’ have a poor ability to prognosticate on the risk of transition between health states associated with the various conditions associated with helminth infection (Kirigia, 1997, Kirigia, 1998). By the same token, most formal treatment studies have typically provided outcomes and follow-up of therapy for only 1–2 years’ duration (Richter, 2003).
While it is true that there are many highly effective anthelminthics for treating these parasitic infections (e.g., praziquantel, albendazole, mebendazole; Anonymous, 2010), within a resource-challenged region, access to effective treatment is still not generally available. Furthermore, even after successful therapy, environmental factors can strongly favor the process of reinfection (Jia et al., 2012, Satayathum et al., 2006). As a result, for the majority of local residents, the worm infections will frequently recur, and disease will persist for most of their lives. In fact, worm infections are so common that chronic manifestations of infection-associated disease are often mistaken as normal for health status in endemic areas (Amazigo et al., 1997, Danso-Appiah et al., 2004, Mekheimar and Talaat, 2005, Ukwandu and Nmorsi, 2004). This makes it difficult for people in endemic areas to provide a valid comparison of their infected health state to a ‘full-health’ state, which is understood to be the expected norm in the cultures of high-income, highly developed economies, such as Europe, Japan, or North America. As discussed later in the article, this places limitations on the use of standard health metric valuation approaches for diseases of developing countries.

Section snippets

Commonly used health metrics: DALYs and QALYs

This section reviews the approaches most commonly used to quantify disease-related health burden in policy discussions. The metrics used most often are generically referred to as Health-Adjusted Life-Years (HALYs) (Carabin et al., 2005). Disability-Adjusted Life Years, or DALYs, and Quality-Adjusted Life Years, or QALYs, are the two formulations most frequently seen in the literature (Gold et al., 2002).

Concerns about the DALY

Despite the widespread use of the DALY metric in public policy discussions, is it the right metric for low mortality conditions that occur uniquely in certain sub-populations of the world? There is no doubt that the DALY has become a ‘norm’ for ranking health states (Gold et al., 2002), and many policymakers and funding agencies unquestioningly accept the DALY values as accurate and valid for all ranked health conditions. As a result it is important to consider what the DALY actually can and

General concerns about the use of health-adjusted life years (HALYs)

The impetus for the development of time-based health metrics has been their use in cost-utility and CEA of health care interventions (Gold et al., 1996). The goal of CEA is to find means to maximize the ‘good’ for populations in a cost-efficient manner, in which expenditures can have the greatest impact. The approach is based on utilitarian philosophy, but the implementation can be flawed, leaving individuals or sub-populations significantly disadvantaged in the analysis (Gold et al., 2002).
The

The neglected tropical diseases movement

Since the promulgation of the initial DALY assessments in 1996 (Murray and Lopez, 1996), many workers who were active in control of diseases of developing countries, including helminth infections, have responded to the apparent undervaluation of these diseases in the DALY system. The neglected tropical disease (NTD) initiatives began by drawing attention to the flaws of the DALY system, while aiming to mobilize increased efforts for NTD control. Beginning in 2002, the Global Fund to Fight AIDS,

Remaining problems with health burden assessments for helminth infections

Helminth infections are mostly diseases of poverty in resource-poor areas, and consequently, resources have often been quite limited for their study. In areas where vital statistics are not collected, populations at risk can only be estimated. Our standard diagnostics for helminths (eggs counts) are insensitive (Colley et al., 2013, Knopp et al., 2008, Knopp et al., 2009), particularly for young children (Verani et al., 2011). This leads to serious misclassification bias in health outcomes

Conclusion

Health metrics are a commonly used system of estimating the impact of health care interventions in policy planning. While they serve a useful role in CEA, they are flawed in their estimation of the impact of diseases on individual and community well-being. While many decision-makers have assumed that the DALY is an accurate measure of the impact of parasitic diseases on global health, the limitations of the DALY system mean that major aspects of helminth disease are overlooked in most burden

Acknowledgements

This work is supported in part by National Institutes of Health research grant R01 TW008067 (funded by the Fogarty International Center) and by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) at the University of Georgia. The funders had no role in the data collection and analysis, decision to publish, or preparation of the manuscript. Special thanks to Dr. Amaya Bustinduy, Ms. Maria King, and members of the Regional Network for Research, Surveillance and Control

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