Virulence and Behavior Samantha Stewart, Tristan Dimmick, and Derek Waldron Faculty Advisor: Todd Livdahl Introduction The co-evolution of humankind and its afflicting diseases is a complex and progressive system that strives toward equilibrium in disease virulence and transmission relative to host immunity and fitness. The rapid genetic mutation and subsequent evolution of human-based bacterial and viral diseases combines with natural human immunity and genetic diversity through sexual recombination to create an ever-fluctuating system of host/parasite dynamics whose understanding is instrumental in active manipulation of disease characteristics through human intervention. As the world’s population density continues to grow, disease containment and prevention has become increasingly important to maintaining public health. Attempts at reducing disease virulence through intentional human behavioral changes have seen both success and failure, and have begun to establish a new avenue in disease management theory. In the scope of disease management, virulence is defined as the infectivity of a disease in a population and severity of the disease in individual hosts. The basic model of virulence evolution is called the Trade-Off Model, which states that disease virulence and transmission are negatively correlated- higher virulence causes a disease to proliferate in a host, increasing host incapacitation and therefore potentially decreasing transmission potential. Many current virulence management efforts utilize this model, attempting to force lower virulence by limited transmission of diseases. However, this model is outdated and ignores undeniably relevant factors such as disease transmission method and the existence of natural reservoirs. Vector-borne diseases benefit from higher virulence, as incapacitated hosts can still be reached by vectors, and higher disease levels in the host increase the chance of vector-based transmission. The highly virulent Ebola virus is seen in short bursts of human infections, as its transmission is severely limited by its virulence. However, strong evidence of a natural reservoir for Ebola shows that transmission reduction does not necessarily cause evolution of reduced virulence. In order to determine human behavior linked to virulence, common diseases plaguing humanity must be examined before action is taken. HIV and influenza, two nearly polar opposite diseases, are extremely prevalent and highly relevant to human disease control, making them ideal candidates for study. While HIV is a growing and deadly epidemic, with sexual transmission and no recovery factor, influenza has a high recovery rate and infects humanity seasonally. To understand how virulence can be reduced by active means, we must first witness how it has been evolving in natural settings. Moving Forward Confounding factors continue to limit our understanding of the relationship between virulence and transmission. This makes indirect attempts at forced virulence evolution through manipulation of transmission ineffective and largely futile. Modern approaches to disease intervention theory stress direct active selection against virulence. Evidence supporting this claim includes the eradication of virulent diphtheria in the US through an intensive anti-toxin vaccination program in the early 1920’s. Two strains of diphtheria had previously existed; one with a harmful toxin that attacked human throat cells, and one benign. Upon implementation of the anti-toxin vaccine, healthcare officials were able to select against the toxin-producing strain of diphtheria, favoring the benign. Currently, virulent diphtheria has all but disappeared from the scope of first-world countries, though it is still seen in areas and countries with relaxed vaccination efforts. This fully supports the theory of direct selection against virulence, as it has shown a complete reduction in virulence when performed correctly. Study Conclusions Influenza and HIV, two of the most important diseases in the scope of humanity, appear to evolve virulence on a level beyond our understanding and capability for direct action to have favorable results. A key factor involved is extremely rapid evolution, a characteristic found in many viruses. Bacterial infections and antibiotic treatments facilitate direct selection against virulence, but the rapid evolution of viral pathogens makes most attempts at active reduction in virulence redundant, as any changes made can easily be reversed in the natural course of evolution. For HIV, prevention appears to be the best answer to solve the epidemic, while influenza’s control will continue to rely on yearly vaccinations battling its frighteningly rapid evolutionary tendencies. Influenza Virulence Model This STELLA model incorporates two strains representing the influenza virus. One is mildly virulent while the other exhibits a higher virulence and lower recovery rate. Influenza Overall with the mutations in the influenza virus there are 3 main groups: the A, B, and C viruses. The two important groups that affect humans are the A and B viruses. Within the A group, its high mutation rate causes many serotypes such as H3N2 and H1N1. The B virus group has no serotypes mainly due to the fact that its mutation rate is approximately 3 times slower than the A virus. The mutations occurring within the viruses are one of the many reasons why the virulence of the influenza virus has been hard to control or reduce. There are approximately 10 different A virus strains and also mutation such as antigenic shifts prevent methods such as vaccinations from working effectively. Even though the vaccination efforts have reduced mortality of the influenza virus by approximately 70-80% lasting immunity is almost impossible. Further studies linking virulence to its correlated factors would help in determining the correct approach for human-mediated virulence shifts. Each pathogen is different and highly unique, necessitating individual analysis and consideration of each case, for an effective grasp of virulence management techniques and effectiveness. Once these have been established, disease control can tighten its grasp of pathogens and begin to even the odds in the evolutionary war. HIV HIV is a lentivirus that can lead to acquired immunodeficiency syndrome (AIDS). HIV infects vital cells in the human immune system. HIV infection leads to low levels of CD4+ T cells. When these cells decline below a certain level, cell immunity is lost, and the body progressively becomes susceptible to opportunistic infections. HIV has a very high genetic variability due to its fast replication cycle and high mutation rate. HIV Virulence Graph Influenza Virulence Graph The graph of the population exemplifies how the influenza A virus maintains a steady population through out time. However the influenza B virus moves to insubstantial numbers due to its low virulence. Both viruses however are ever present. This graph represents an indefinite cycle between Infected A , which is more virulent than infected B. Over time Infected B takes over suscseptibles from infected A, but infected B is not substantial enough to rule out infected A.