Recommendations for empirical syndemics analyses: A stepwise methodological guide.

Syndemic theory posits that co-occurring diseases interact in a manner that increases disease transmission, progression, and negative health outcomes. And that adverse socioeconomic and environmental conditions promote this disease or health condition clustering and interaction. The concept offers two important contributions to the health sciences. First, it positions socioeconomic, structural, and environmental conditions as central to disease burdens. Second, as a portmanteau - 'syn' for synergy and 'demic' for disease epidemics - syndemic theory indicates that in some cases diseases do not merely co-occur but synergistically interact to affect an outcome that is more than the accumulation of the individual disease effects. The difficulty in operationalizing these central elements has resulted in a divergence of scholarship from the centralizing principles of the theory towards a simpler accumulation perspective in which more conditions equate to worse health outcomes. In addition, all empirical syndemic assessments should include robust qualitative assessments of the dynamics, however, much syndemic scholarship focuses only on quantitative analyses. To address these issues, a five-step approach to quantitative analyses of syndemic arrangements is proposed: (1) identifying disease clusters within a defined population; (2) determining the relevant social and structural factors that support disease clustering; (3) determining if clusters are distinct by social/demographic groups within the population; (4) evaluating if the identified disease cluster contributes to worse health outcomes; and (5) assessing for synergy between clustering diseases. This stepwise strategy ensures not only a rigorous assessment of hypothesized syndemic interactions but also presents a closer alignment of scholarship with syndemics theory. As an illustration, the approach is applied to an assessment of a hypothesized HIV/cardiovascular disease syndemic in South Africa. While syndemics theory has proven valuable in guiding public health interventions and policy, progressive improvement must be made in the application of the theory to ensure that it continues to effectively inform comprehensive practice.