Prevalence and implications of multiple-strain infections

Infections by multiple strains of the same pathogen—coinfections or superinfections—raise interesting and challenging problems. From the perspective of the pathogen, superinfection is a trade-off: superinfecting strains will compete with resident strains for host resources but for many pathogens, coinfection or superinfection may be necessary for sexual recombination or genetic exchange and multiple pathogen strains may cooperate to share growth factors or to evade host defenses. For this reason, pathogen strains don’t resist superinfection completely and many infections are likely to be multiple-strain infections. Interactions between coinfecting or superinfecting strains may affect pathogen virulence, transmissibility, and evolution. But multiple-strain infections are difficult to study, especially in humans. Rare strains may be hard to detect and genetic diversity in pathogen populations—especially in pathogens with high mutation rates, such as HIV—may be due to within-host evolution rather than to multiple-strain infection. As a result, there is a paucity of studies of multiple-strain infections and—again with the exception of HIV—infections are often assumed to be due to genetically homogeneous pathogen populations. In a recent issue of Lancet Infectious Diseases, Oliver Balmer and Marcel Tanner have called much-needed attention to the prevalence and significance of multiple-strain infections (Balmer and Tanner 2011). They list more than 50 human pathogens for which multiple-strain infections have been documented and suggest that, with further study, multiple-strain infections are likely to be found for most pathogens. Most importantly, they discuss the implications of multiple-strain infections for clinical practice. In challenging the conventional wisdom about anti-pathogen treatment, Andrew Read and his colleagues have argued that, if there is competition between drug-sensitive and drug-resistant pathogen strains, elimination of the sensitive strains by aggressive chemotherapy may release the resistant strains from competitive suppression and so may promote the spread of drug resistance (Read, Day, and Huijben 2011). Balmer and Tanner make a similar argument: “contrary to common practice, non-treatment of asymptomatic multiple-strain infections might be better than treatment if parasite clearance reduces natural protection against more severe disease.” Clinical trials to determine the best approach to anti-pathogen chemotherapy should be informed by these evolutionary considerations. Balmer and Tanner call for better screening to identify multiple-strain infections and more empirical studies of the natural history of these infections. In conclusion they note, “An understanding of evolutionary processes can greatly benefit clinical medicine.” Lancet Infectious Diseases is a prominent journal and is read by many people in the infectious disease community. This valuable review should stimulate greater interest in multiple-strain infections and should lead to greater understanding of how multiple-strain infections may affect pathogen evolution and to better treatment strategies for patients who suffer from these infections.

References

Balmer, O., and M. Tanner. 2011. Prevalence and implications of multiple-strain infections. Lancet Infect Dis 11(11):868-78.

Read, A. F., T. Day, and S. Huijben. 2011. The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy. Proc Natl Acad Sci U S A 108 Suppl 2:10871-7.