Moreover the tendency for positive effects on pathogen abundance corroborates the negative effects on host health because larger infections are a mechanism by which disease can be exacerbated. The consistency of these detrimental coinfection effects across a wide range

of pathogens suggests a general incidence of interactions between coinfections. The long-term effects among survivors of coinfections can be varied and in some cases severe, including blindness, chronic diarrhoea, chronic inflammation, carcinoma, immunosuppression, liver fibrosis, meningitis, renal failure, rheumatic fever, etc. 31 The direction of reported coinfection effects could have at least two explanations. GSK2118436 mouse The first is that coinfection may be more likely in individuals of poor health, which in turn leads to poorer prognosis among coinfected cases. The relative paucity of experimental studies of coinfection in humans means sampling biases towards people of poorer health is possible, but impossible to

account for in our analyses. The second explanation is that coinfecting pathogens interact synergistically with each other, for example via the host’s immune system, so that the presence of one enhances the abundance and/or virulence of the other. A clear example of this is HIV, which causes immunosuppression, increasing the likelihood of additional infections and occurred in two fifths Cytoskeletal Signaling inhibitor of reported coinfections (Fig. 4). Differences between reported coinfections and global mortality figures may also suggest important interactions between coinfecting pathogens. Coinfections that were more commonly reported than their relative contribution to global mortality may involve particular synergistic pathogen–pathogen interactions, such as among herpes viruses like CMV or HSV infection enhancing the risk of HPV coinfection.32 Conversely, infections that cause high mortality 2-hydroxyphytanoyl-CoA lyase but had relatively few reports of coinfection could result from antagonistic interactions, reducing the likelihood of such coinfections occurring and being reported, like P. aeruginosa exoproduct limiting S. aureus colony formation.

33 An alternative and possibly more likely explanation of the discrepancies between reported coinfections and global mortalities from infections could be greater funding availability (e.g. HIV/AIDS research), higher interests of virologists in coinfection and/or easier observations or more routine screening compared with other pathogens, for instance the greater difficulty of detecting intestinal helminths in coinfection research. The lack of coinfection publications reporting on major infectious causes of childhood mortality remains unexplained. While some publications do study childhood coinfection and find coinfection to be more common in children, 34 current coinfection research does not include the infections that kill the most infants globally.