Co-infection of individual hosts by multiple parasite species is a pattern that is very commonly observed in natural populations. Understanding the processes that generate these patterns poses a challenge. For example, it is difficult to discern the relative roles of exposure and susceptibility in generating the mixture and density of parasites within hosts. Yet discern them we must, if we are to design and deliver successful medical interventions for co-infected populations. Here, we synthesise an emergent understanding of how processes operate and interact to generate patterns of co-infection. We consider within-host communities (or infracommunities) generally, that is including not only classical parasites but also the microbiota that are so abundant on mucosal surfaces and which are increasingly understood to be so influential on host biology. We focus on communities that include a helminth, but we expect similar inferences to pertain to other taxa. We suggest that, thanks to recent research at both the within-host (e.g. immunological) and between-host (e.g. epidemiological) scales, researchers are poised to reveal the processes that generate the observed distribution of parasite communities among hosts. Progress will be facilitated by using new technologies as well as statistical and experimental tools to test competing hypotheses about processes that might generate patterns in co-infection data. By understanding the multiple interactions that underlie patterns of co-infection, we will be able to understand and intelligently predict how a suite of co-infections (and thus the host that bears them) will together respond to medical interventions as well as other environmental changes. The challenge for us all is to become scholars of co-infections.

Parasitism, aptly defined as one of the 'living-together' strategies (Trager, 1986), presents a dynamic system in which the parasite and its host are under evolutionary pressure to evolve new and specific adaptations, thus enabling the coexistence of the two closely interacting partners. Microsporidia are very frequently encountered obligatory intracellular protistan parasites that can infect both animals and some protists and are a consummate example of various aspects of the 'living-together' strategy. Microsporidia, relatives of fungi in the superkingdom Opisthokonta, belong to the relatively small group of parasites for which the host cell cytoplasm is the site of both reproduction and maturation. The structural and physiological reduction of their vegetative stage, together with the manipulation of host cell physiology, enables microsporidia to live in the cytosolic environment for most of their life cycle in a way resembling endocytobionts. The ability to form structurally complex spores and the invention and assembly of a unique injection mechanism enable microsporidia to disperse within host tissues and between host organisms, resulting in long-lasting infections. Microsporidia have adapted their genomes to the intracellular way of life, evolved strategies how to obtain nutrients directly from the host and how to manipulate not only the infected cells, but also the hosts themselves. The enormous variability of host organisms and their tissues provide microsporidian parasites a virtually limitless terrain for diversification and ecological expansion. This review attempts to present a general overview of microsporidia, emphasising some less known and/or more recently discovered facets of their biology.

The transmission of malaria across the Arabian Peninsula is governed by the diversity of dominant vectors and extreme aridity. It is likely that where malaria transmission was historically possible it was intense and led to a high disease burden. Here, we review the speed of elimination, approaches taken, define the shrinking map of risk since 1960 and discuss the threats posed to a malaria-free Arabian Peninsula using the archive material, case data and published works. From as early as the 1940s, attempts were made to eliminate malaria on the peninsula but were met with varying degrees of success through to the 1970s; however, these did result in a shrinking of the margins of malaria transmission across the peninsula. Epidemics in the 1990s galvanised national malaria control programmes to reinvigorate control efforts. Before the launch of the recent global ambition for malaria eradication, countries on the Arabian Peninsula launched a collaborative malaria-free initiative in 2005. This initiative led a further shrinking of the malaria risk map and today locally acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen, with the latter contributing to over 98% of the clinical burden.

Zoonotic parasites are important causes of endemic and emerging human disease in northern North America and Greenland (the North), where prevalence of some parasites is higher than in the general North American population. The North today is in transition, facing increased resource extraction, globalisation of trade and travel, and rapid and accelerating environmental change. This comprehensive review addresses the diversity, distribution, ecology, epidemiology, and significance of nine zoonotic parasites in animal and human populations in the North. Based on a qualitative risk assessment with criteria heavily weighted for human health, these zoonotic parasites are ranked, in the order of decreasing importance, as follows: Echinococcus multilocularis, Toxoplasma gondii, Trichinella and Giardia, Echinococcus granulosus/canadensis and Cryptosporidium, Toxocara, anisakid nematodes, and diphyllobothriid cestodes. Recent and future trends in the importance of these parasites for human health in the North are explored. For example, the incidence of human exposure to endemic helminth zoonoses (e.g. Diphyllobothrium, Trichinella, and Echinococcus) appears to be declining, while water-borne protozoans such as Giardia, Cryptosporidium, and Toxoplasma may be emerging causes of human disease in a warming North. Parasites that undergo temperature-dependent development in the environment (such as Toxoplasma, ascarid and anisakid nematodes, and diphyllobothriid cestodes) will likely undergo accelerated development in endemic areas and temperate-adapted strains/species will move north, resulting in faunal shifts. Food-borne pathogens (e.g. Trichinella, Toxoplasma, anisakid nematodes, and diphyllobothriid cestodes) may be increasingly important as animal products are exported from the North and tourists, workers, and domestic animals enter the North. Finally, key needs are identified to better assess and mitigate risks associated with zoonotic parasites, including enhanced surveillance in animals and people, detection methods, and delivery and evaluation of veterinary and public health services.

Blastocystis is a common parasite of the human large intestine but has an uncertain role in disease. In this review, we appraise the published evidence addressing this and its weaknesses. Genetic diversity studies have led to the identification of numerous subtypes (STs) within the genus Blastocystis and, recently, methods for studying variation within STs have been developed, with implications for our understanding of host specificity. The geographic distribution of STs is summarised and the impact this may have on investigations into the role of the organism in disease is discussed. Finally, we describe the organelle and nuclear genome characteristics and look to future developments in the field.

From the early 1920s until the advent of penicillin in the mid 1940s, a clinical course of malaria was the only effective treatment of general paresis, a common manifestation of tertiary syphilis that was nearly always fatal. For a number of reasons, Plasmodium vivax became the parasite species most often employed for what became known as malariotherapy. This provided an opportunity, probably unique in the annals of medicine, to observe and investigate the biology, immunology and clinical evolution of a dangerous human pathogen in its natural host. There is little doubt that the lessons learned from these studies influenced the malaria research and control agendas. It is equally true that over the last 40 years, the insights afforded by malariotherapy have remained largely undisturbed on the dusty shelves of institutional libraries. In this chapter, we broadly review the published data derived from malariotherapy, and discuss its relevance to current challenges of P. vivax epidemiology, immunology and pathology.

Plasmodium vivax is part of a highly diverse clade that includes several Plasmodium species found in nonhuman primates from Southeast Asia. The diversity of primate malarias in Asia is staggering; nevertheless, their origin was relatively recent in the evolution of Plasmodium. We discuss how humans acquired the lineage leading to P. vivax from a nonhuman primate determined by the complex geological processes that took place in Southeast Asia during the last few million years. We conclude that widespread population genomic investigations are needed in order to understand the demographic processes involved in the expansion of P. vivax in the human populations. India represents one of the few countries with widespread vivax malaria. Earlier studies have indicated high genetic polymorphism at antigenic loci and no evidence for geographic structuring. However, new studies using genetic markers in selectively neutral genetic regions indicate that Indian P. vivax presents complex evolutionary history but possesses features consistent with being part of the ancestral distribution range of this species. Such studies are possible due to the availability of the first P. vivax genome sequences. Next generation sequencing technologies are now paving the way for the sequencing of more P. vivax genomes that will dramatically increase our understanding of the unique biology of this species.

Glucose-6-phosphate dehydrogenase (G6PD) is a potentially pathogenic inherited enzyme abnormality and, similar to other human red blood cell polymorphisms, is particularly prevalent in historically malaria endemic countries. The spatial extent of Plasmodium vivax malaria overlaps widely with that of G6PD deficiency; unfortunately the only drug licensed for the radical cure and relapse prevention of P. vivax, primaquine, can trigger severe haemolytic anaemia in G6PD deficient individuals. This chapter reviews the past and current data on this unique pharmacogenetic association, which is becoming increasingly important as several nations now consider strategies to eliminate malaria transmission rather than control its clinical burden. G6PD deficiency is a highly variable disorder, in terms of spatial heterogeneity in prevalence and molecular variants, as well as its interactions with P. vivax and primaquine. Consideration of factors including aspects of basic physiology, diagnosis, and clinical triggers of primaquine-induced haemolysis is required to assess the risks and benefits of applying primaquine in various geographic and demographic settings. Given that haemolytically toxic antirelapse drugs will likely be the only therapeutic options for the coming decade, it is clear that we need to understand in depth G6PD deficiency and primaquine-induced haemolysis to determine safe and effective therapeutic strategies to overcome this hurdle and achieve malaria elimination.

Population studies show that individuals acquire immunity to Plasmodium vivax more quickly than Plasmodium falciparum irrespective of overall transmission intensity, resulting in the peak burden of P. vivax malaria in younger age groups. Similarly, actively induced P. vivax infections in malaria therapy patients resulted in faster and generally more strain-transcending acquisition of immunity than P. falciparum infections. The mechanisms behind the more rapid acquisition of immunity to P. vivax are poorly understood. Natural acquired immune responses to P. vivax target both pre-erythrocytic and blood-stage antigens and include humoral and cellular components. To date, only a few studies have investigated the association of these immune responses with protection, with most studies focussing on a few merozoite antigens (such as the Pv Duffy binding protein (PvDBP), the Pv reticulocyte binding proteins (PvRBPs), or the Pv merozoite surface proteins (PvMSP1, 3 & 9)) or the circumsporozoite protein (PvCSP). Naturally acquired transmission-blocking (TB) immunity (TBI) was also found in several populations. Although limited, these data support the premise that developing a multi-stage P. vivax vaccine may be feasible and is worth pursuing.