Transcript Influenza Virulence Graph

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 However, this model is outdated and ignores undeniably relevant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.