One example is hepatitis Delta virus, which cannot syn- thesize its own envelope protein and is thus dependent on coinfection by hepatitis B virus (Petney and Andrews, 1998). An ‘‘endopathocenosis’’ can exist within the indi- vidual host. In the digestive tract, the commensal bacte- rium Escherichia coli can produce an enterotoxin in certain microenvironments (pH variations), thus weakening the intestinal epithelium and facilitating massive invasion by potentially enteropathogenic viruses, such as rotavirus, picornavirus, and noroviruses (Lorrot and Vasseur, 2007). Several types of relationships between diseases have been identiﬁed since Grmek put forward his hypothesis in 1969: Antagonism One disease hinders the spread of another. For example, signiﬁcant anemia impedes thalassemia and plasmodial infection (Veenemans et al., 2008); latent infection of mice by herpes murine viruses confers resistance against Y. pestis (Barton et al., 2007) or confers a partially immunological protection against another antigenically related infectious agent, as observed in ﬂaviviruses. Indeed, antibodies against dengue virus strongly protect against experimental yellow fever virus infection (Brandiss et al., 1986), suggesting that the reason yellow fever appears never to have occurred in Asia maybe because of widespread immunity to dengue among Asian populations living in endemic areas (Monath, 2007). Synergy One disease facilitates the introduction or development of another disease, as illustrated by antibody-dependent enhancement (ADE). According to this hypothesis, two consecutive infections by different dengue serotypes could favor dengue hemorrhagic fever (Kliks et al., 1988, 1989). ‘‘Opportunistic’’ microorganisms take advantage of a weakened immune system that has been compromised by AIDS or other causes, such as malnutrition, antibiotic treatment, and cancer chemotherapy, eventually leading to the emergence of other dominant clinical pictures (e.g., cryptococcosis, pneumocystosis, toxoplasmosis, and Ka- posi’s sarcoma). Independence Two diseases have no inﬂuence on each other, and their spread within the population of a given territory is inde- pendent. Pathocenosis and Ecology 239 PATHOCENOTIC IMBALANCE AND DISEASE EMERGENCE The pathocenosis can be stable (‘‘endemic’’ or in equilib- rium) in a stable ecological situation where the density and behaviors of the different components are not subject to major changes. This equilibrium can be disturbed, how- ever, leading to sharp variations in the frequencies of cer- tain diseases and even to the emergence of new diseases in a particular population or territory. Thus, a succession of disturbances can lead to a dynamic sequence of pathoce- noses, one health state giving way to a new one after a period of upheaval. Such perturbations include the introduction of infec- tious agents and environmental changes of ‘‘natural’’ or human origin. For instance, Zinkernagel (2001) pointed out that better hygiene has shifted the average age of infection by certain pathogens; as a result, some diseases that are benign in childhood have become more frequent in adults, in whom they are generally more severe. The same phenomenon is observed following mass vaccination campaigns (e.g., measles). The arrival of a new infectious agent can disclose the existence of a previously silent or unnoticed agent through synergistic interaction. For example, coinfection by childhood viruses (Epstein-Barr virus [EBV], human herpesvirus type 6 [HHV6], or cyto- megalovirus [CMV]) could be a prerequisite for visceral leishmania onset following infection by Leishmania infan- tum (Louzir and Dellagi, 1999). Conversely, the emergence of an infectious agent can lead to the demise of another; although the mechanisms are controversial, tuberculosis may have had a role in the decline in leprosy in Europe during the 17th and 18th centuries (Lietman et al., 1997; Donoghue et al., 2005). Likewise, in an antagonistic inter- action, the disappearance of one disease can pave the way for the reemergence of another (see the above-mentioned assumed relationships between plague and smallpox or measles). Any change in the circulation of these interacting viruses would modify the conditions and frequency of infection by the others and, thus, the epidemiology of the diseases. PATHOCENOSIS: A HUMAN MEDICINE NEW PARADIGM FOR Currently, the emergence of an infectious disease is usually addressed from a monodisciplinary (i.e., biomedical) point