Objective The evolution of antibiotic resistance is far outpacing the development of new antibiotics, causing global public health concern about infections that will increasingly be unresponsive to antimicrobials. This risk of emerging antibiotic resistance may be meaningfully altered in highly AIDS-immunocompromised populations. Such populations fundamentally alter the bacterial evolutionary landscape in two ways, which we seek to model and analyze. First, widespread, population-level immunoincompetence creates a novel host environment with disrupted selective pressures. Second, within AIDS-prevalent populations, the recommendation that antibiotics be taken to treat and prevent opportunistic infection raises the risk of selection for drug-resistant pathogens. Design To determine the impact of HIV/AIDS on the emergence of antibiotic resistance–specifically in the developing world where high prevalence and economic challenges complicate disease management. Methods We present an SEIR epidemiological model of bacterial infection, and parametrize it to capture HIV/AIDS-attributable emergence of resistance under conditions of both high and low HIV/AIDS prevalence. Results We demonstrate that HIV/AIDS-immunocompromised hosts can be responsible for a disproportionately greater contribution to emergence of resistance than would be expected based on population-wide HIV/AIDS prevalence alone. Conclusions As such, the AIDS-immunocompromised have the potential become wellsprings of novel, resistant, opportunistic pathogen strains that can propagate into the broader global community. We discuss how public health policies for HIV/AIDS management can shape the evolutionary environment for opportunistic bacterial infections.

Chemoprophylaxis (antibiotic prophylaxis) is a long relied-upon means of opportunistic infection management among HIV/AIDS patients, but its use represents an evolutionary tradeoff: Despite the benefits of chemoprophylaxis, widespread use of antibiotics creates a selective advantage for drug-resistant bacterial strains. Especially in the developing world, with combined resource limitations, antibiotic misuse, and often-poor infection control, the emergence of antibiotic resistance may pose a critical health risk. Extending previous work that demonstrated that this risk is heightened when a significant proportion of the population is HIV/AIDS-immunocompromised, we work to address the relationship between HIV/AIDS patients' use of antibiotic chemoprophylaxis and the emergence of resistance. We apply an SEIR compartmental model, parameterized to reflect varying percentages of chemoprophylaxis use among HIV/AIDS+ patients in a resource-limited setting, to investigate the magnitude of the risk of prophylaxis-associated emergence versus the individual-level benefits it is presumed to provide. The results from this model suggest that, while still providing tangible benefits to the individual, chemoprophylaxis is associated with negligible decreases in population-wide morbidity and mortality from bacterial infection, and may also fail to provide assumed efficacy in reduction of TB prevalence.

Despite the risk of emerging drug resistance that occurs with the frequent use of antimicrobial agents, targeted and prophylactic antibiotics have been considered crucial to opportunistic infection management among the HIV/AIDS-immunocompromised. As we recently demonstrated, the disrupted selective pressures that occur in AIDS-prevalent host populations increase the probability of novel emergence. This effect is concerning, given that bacterial strains unresponsive to first-line antibiotics can be particularly dangerous to hosts whose immune response is insufficient to fight infection in the absence of antibiotic support. While greater host susceptibility within a highly immunocompromised population may offer a fitness advantage to drug-resistant bacterial strains, this advantage could be mitigated by increased morbidity and mortality among the AIDS-immunocompromised. Using a Susceptible-Exposed-Infectious-Recovered (SEIR) epidemiological model parameterized to reflect conditions in an AIDS-prevalent host population, we examine the evolutionary relationship between drug-sensitive and -resistant strains of Mycobacterium tuberculosis. We explore this relationship when the fitness of the resistant strain is varied relative to that of the sensitive strain to investigate the likely long-term multi-strain dynamics of the AIDS-mediated increased emergence of drug resistance.

No abstract

We discuss a Red Team-Blue Team (RT-BT) study conducted to examine the formation and efficacy of social networks in self-organizing, ad hoc, or crowd-sourced intelligence and counter-intelligence operations in grassroots, improvised communities. Student volunteers were sorted into two teams: one team (Blue) was asked to find puzzle pieces using clues provided by the organizers, with the goal of reconstructing a message contained therein, while the opposing team (Red) was tasked with disrupting this process. While the Blue Team quickly organized into an efficient, centrally-governed structure, the Red Team instead adopted a decentralized, distributed operational network to hinder puzzle completion, using creative and diverse infiltration and disruption methods to interfere in the more centralized, hierarchical organization of their opponents. This exercise shows how untrained, unaffiliated individuals may self-organize into different types of social organizations to accomplish common tasks when aware of potential adversarial organizations, and how these choices may affect their efficacy in accomplishing collaborative clandestine goals.