Bottom-up regulation of malaria population dynamics in mice co-infected with lung-migratory nematodes.

When and how populations are regulated by bottom up vs. top down processes, and how those processes are affected by co-occurring species, are poorly characterised across much of ecology. We are especially interested in the community ecology of parasites that must share a host. Here, we quantify how resources and immunity affect parasite propagation in experiments in near-replicate 'mesocosms'' - i.e. mice infected with malaria (Plasmodium chabaudi) and nematodes (Nippostrongylus brasiliensis). Nematodes suppressed immune responses against malaria, and yet malaria populations were smaller in co-infected hosts. Further analyses of within-host epidemiology revealed that nematode co-infection altered malaria propagation by suppressing target cell availability. This is the first demonstration that bottom-up resource regulation may have earlier and stronger effects than top-down immune mechanisms on within-host community dynamics. Our findings demonstrate the potential power of experimental ecology to disentangle mechanisms of population regulation in complex communities.

The potential impact of coinfection on antimicrobial chemotherapy and drug resistance.

Across a range of pathogens, resistance to chemotherapy is a growing problem in both public health and animal health. Despite the ubiquity of coinfection, and its potential effects on within-host biology, the role played by coinfecting pathogens on the evolution of resistance and efficacy of antimicrobial chemotherapy is rarely considered. In this review, we provide an overview of the mechanisms of interaction of coinfecting pathogens, ranging from immune modulation and resource modulation, to drug interactions. We discuss their potential implications for the evolution of resistance, providing evidence in the rare cases where it is available. Overall, our review indicates that the impact of coinfection has the potential to be considerable, suggesting that this should be taken into account when designing antimicrobial drug treatments.

Analysis of a summary network of co-infection in humans reveals that parasites interact most via shared resources.

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. In addition, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite-resource links. Reported co-infection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in co-infected patients, but the compartmentalized structure of the network will limit how far these indirect effects are likely to spread.

Birth order and post-traumatic stress disorder.

OBJECTIVE: To compare the birth order of patients with post-traumatic stress disorder (PTSD) and adjustment disorder (AD) with population norms. METHOD: 83 PTSD patients and 104 AD control patients from a psychiatric trauma clinic were diagnosed according to DCR-10 guidelines. A family history was taken as to number of siblings, and their birth order. We compared the distribution of birth order for each patient group against birth order distributions expected by chance for the same years of birth using UK population-level birth order from the Office for National Statistics. RESULTS: Psychiatric patients with PTSD were more likely to be from a large family, specifically to be the fifth child or later (OR 4.78, p < .001) and less likely to be the eldest child (OR .65, p < .001) than the general population in England and Wales. There were no differences for birth order between AD patients and the general population. CONCLUSION: People with PTSD are more likely to be the youngest children from large families than expected from a random sample of people born in the same years. This association with birth order was not found for another psychiatric diagnosis AD from the same clinic. We discuss possible psychosocial and biological causes, and implications for further research.

The nature and consequences of coinfection in humans.

OBJECTIVE: Many fundamental patterns of coinfection (multi-species infections) are undescribed, including the relative frequency of coinfection by various pathogens, differences between single-species infections and coinfection, and the burden of coinfection on human health. We aimed to address the paucity of general knowledge on coinfection by systematically collating and analysing data from recent publications to understand the types of coinfection and their effects. METHODS: From an electronic search to find all publications from 2009 on coinfection and its synonyms in humans we recorded data on i) coinfecting pathogens and their effect on ii) host health and iii) intensity of infection. RESULTS: The most commonly reported coinfections differ from infections causing highest global mortality, with a notable lack of serious childhood infections in reported coinfections. We found that coinfection is generally reported to worsen human health (76% publications) and exacerbate infections (57% publications). Reported coinfections included all kinds of pathogens, but were most likely to contain bacteria. CONCLUSIONS: These results suggest differences between coinfected patients and those with single infections, with coinfection having serious health effects. There is a pressing need to quantify the tendency towards negative effects and to evaluate any sampling biases in the coverage of coinfection research.