[13,14] and leptospirosis [15] also occurred. These effects outlasted the immediate crisis period; today, some countries from central and Eastern Europe and former Soviet Union have not been able to achieve Millennium Development Goal (MDG) number 6, ‘to halt or reverse the spread of TB and HIV’ [16]. Even in the absence of economic crisis or downturn, infectious diseases disproportionately affect vulnerable groups. In a review of the European literature, this effect could be found in every single EU Member State [17]. A separate study comparing wealth distribution and TB rates across EU Member States demonstrated a strong correlation between income equality and lower TB rates [18]. Thus, health inequalities, whose importance has been thoroughly documented by the WHO Commission on the Social Determinants of Health [19], may be as relevant for communi- cable diseases as they are for non-communicable diseases. In order to gain a better understanding of the interrelationships between economic crises and infectious disease, we conducted a systematic literature review of studies examining the impact of previous economic crises on infectious disease burdens; findings from this analysis can inform communicable disease control research and activities during a time of economic turmoil. It is first important to define what we mean by ‘‘economic crisis’’. Commentators often adopt implicit definitions that may include falling GDP, drying up of liquidity and rising or falling prices due to inflation or deflation. Where quantitative measures are used they are applied inconsistently. There is greater clarity in respect of some related terms , which themselves are often treated synonymously with the term ‘‘economic crisis’’. Thus, a recession is conventionally considered by most politicians and media commentators to exist when there is decline in GDP in two successive quarters but this originated in a simple ‘‘rule of thumb’’ in an article in the New York Times, while others define a recession in terms of increases in unemployment. Academic researchers are more likely to use the National Bureau of Economic Research (NBER) definition of ‘‘a significant decline in economic activity spread across the economy, lasting more than a few months, normally visible in real GDP, real income, employment, industrial production, and wholesale-retail sales. A recession begins just after the economy reaches a peak of activity and ends as the economy reaches its trough’’ [20]. While this definition has considerable utility, these measures can be somewhat remote from ordinary people. Hence, for the purposes of this review we adopt a broader concept of ‘‘crisis’’ to include a number of situations in which individuals and households suffer marked falls in living standards as a consequence of external factors. Specifically, we looked at: a) b) events that were clearly identifiable from the papers as financial crises, measured in terms of rapid falls in GDP, increases in unemployment, or reductions in government spending that go beyond routine business-cycle fluctua- tions. This included events explicitly labelled as financial crises, such as that in East Asia in the 1990s, but also situations characterised by the rapid onset of the changes listed here. It also included situations where economic sanctions were imposed by the international community, as in Serbia, or where other events were worsened by sanctions, as in Cuba. major political crises or disruption, where this was known from other evidence, although not always referred to explicitly in the papers, to have led to a financial crisis as described above. Many of these studies captured the Transformational Depression in Eastern Europe in the early-1990s which has yielded considerable evidence [21]. Economic Crises and Infectious Diseases c) civil and military conflict, which like political crises are often not described in by researchers in terms of their economic consequences but are known to give rise to financial crises. Our use of this broad approach is justified by the need to capture as much of the relevant literature as possible as we inferred from an initial scoping review of the literature that we would miss important papers if we defined economic crisis in narrow terms. In our tabulated results we include information on the definition of crisis used in each paper. Since the definitions differed significantly across studies, we confined ourselves to a narrative synthesis of the evidence, and we were unable to carry out a quantitative meta- analysis. We are aware of the extensive literature on the association between economic fluctuations and mortality overall, and to a lesser extent from specific causes. This literature has produced conflicting results, identifying both pro- and counter-cyclic relationships [6,22,23,24,25,26,27,28,29,30,31]. However, while we have taken account of it in interpreting the findings we report, most of this research does not look specifically at infectious disease. Furthermore, as infectious diseases now comprise a small proportion of overall mortality in industrialised populations, this research, which has mostly examined changing death rates, would not be expected to find significant effects. Methods Although past economic crises, downturns and situations of major political turmoil (such as the collapse of the Soviet Union) are instructive, each event has its own unique characteristics and generalisations need to be made with caution. There is no a priori unit for analysis; a broad range of sweeping conjectures and observations can be made about economic circumstances, which might be seen as confusing, potentially contradictory, and without clear impetus for further research or clear intervention. Moreover, the risks are dynamic and complex, with potential non-linear effects as new infections can spark exponential rises in secondary cases; brief high-risk exposures in a susceptible sub- population could generate a subsequent wave of infections more generally; or singular cases may die out rather than provoking local epidemics, generating public disdain for ‘‘false alarms’’. These effects are also social in nature, and often deemed too difficult to attribute causality. Additionally, there are feedback loops arising from policies (such as whether to cut public health budgets), which are themselves dependent on institutional and economic circumstances as well as on the depth of the crisis at hand. The effects are likely to be disease-specific, as the agent- host-environment framework differs between, say, tick-borne encephalitis and tuberculosis. Finally, there are likely to be variable lag effects; in some cases the health consequences of a crisis will be apparent almost at once but in others the crisis may lead to changes in behaviour or material conditions that contribute to increased infections some years later. Clearly, the latter are much more difficult to identify and attribute to an economic event. i. Analytical Framework In order to structure the analysis of this study, a version of the classic framework for analyzing infectious disease risks, the susceptible-infected-removed (SIR) model (Figure 1), was em- ployed [32]. This model is a useful intuitive framework for the purpose of organizing our review since it breaks down complex processes into three key analytic parameters. It describes the progress of an infectious disease epidemic by defining those who PLoS ONE | www.plosone.org 2 June 2011 | Volume 6 | Issue 6 | e20724