The Ten-Thousand Year Fever

Rethinking Human and Wild-Primate Malarias

Loretta A Cormier

• Publisher: Routledge
• Year: 2016
• Print ISBN: 9781598744835
• eBook ISBN: 9781315417073
• Topic: Social Sciences
• Subtopic: Anthropology
• Index: Social Sciences

Malaria is one of the oldest recorded diseases in human history, and its 10,000-year relationship to primates can teach us why it will be one of the most serious threats to humanity in the 21st century. In this pathbreaking book Loretta Cormier integrates a wide range of data from molecular biology, ethnoprimatology, epidemiology, ecology, anthropology, and other fields to reveal the intimate relationships between culture and environment that shape the trajectory of a parasite. She argues against the entrenched distinction between human and non-human malarias, using ethnoprimatology to develop a new understanding of cross-species exchange. She also shows how current human-environment interactions, including deforestation and development, create the potential for new forms of malaria to threaten human populations. This book is a model of interdisciplinary integration that will be essential reading in fields from anthropology and biology to public health.

Chapter 1

INTRODUCTION: MALARIA AS A PRIMATE DISORDER

In this opening chapter, a case is made for the relevance of approaching malaria at the level of the primates. A broad overview of some of the key issues is provided here and is elaborated on in subsequent chapters. The phylogenetic relationships of the plasmodia infecting primates are described, including how recent advances in molecular genetics are changing our understanding of the relationship among the primate malarias. Humans are natural hosts to four species of malaria-causing plasmodia: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae.¹ These four parasites are not closely related to one another and separately colonized hominins² (humans and their ancestors). However, each of the four species is closely related to other plasmodia that infect nonhuman primates. For example, human P. falciparum and P. vivax are not closely related, but human P. falciparum is closely related to several great ape parasites, and P. vivax is closely related to several Old World monkey parasites.

Approximately 40 different species of malaria parasites have been identified in primates (see Appendix 1 for references). To date, genetic relationships have been established among about half of them, which can be divided into four main groups among the anthropoid³ primates. However, within these types, many of the plasmodia species are nonspecific according to particular host or have a history of host-switching across species. The malaria parasites as a whole are older than the emergence of the primates and even older than the emergence of mammals. The plasmodia responsible for malaria today are believed to be descendents of ancient protozoa (endocellular coccidian parasites) of the intestinal tract of the common ancestor of birds, reptiles, and amphibians (Cogswell 2000). The plasmodia affecting primates are differentiated here into four main groups: falciparum type, vivax type, malariae type, and ovale type. Analyses of the genetic relationships among the primate malaria parasites have revealed a complex history of human and wild-primate cross-infections, not only in the distant past but also in cases of relatively recent plasmodial host-switching. The terms “zoonosis” (transmission of disease from a nonhuman animal to a human) and “anthroponosis” (transmission of disease from a human to a nonhuman animal) are used in this work. However, arguably, cross-infections cannot be considered to be either zoonoses or anthroponoses in the conventional sense; rather anthropoid primates may be the most appropriate level of analysis for understanding the primate malarias.

OVERVIEW OF PRIMATE MALARIA

A disease consistent with the symptoms and ecology of malaria is recorded in numerous medical texts of the ancient world, including the writings of Greek, Roman, Ayurvedic, and Arabic physicians. In the 4th century b.c.e., frequent references are found in the works of the Greek physician Hippocrates describing an illness with symptoms that seem to suggest malaria, including cycling fevers, splenomegaly, and a relationship of the illness to habitats of low, marshy areas (Bruce-Chwatt and de Zulueta 1980). Similar descriptions of an illness characterized by periodic fevers can also be found in the works of Celsus, Pliny the Elder, and Galen (Dunn 1993) as well as in the works of Classical Roman physicians such as Martialis, Juvenal, Horace, and Livy (Stannard 1993). In South Asia, the Ayurvedic Hindu medical text Susruta (by 6–7th century c.e.) also describes a febrile disease with a relationship to mosquitoes that likely refers to a form of malaria (Chakravorty 1993). Arab physicians in the 11th and 12th centuries in Islamic Spain describe cyclical fevers linked to stagnant water sources (Bruce-Chwatt and de Zulueta 1980).

The earliest typology of malaria was based on the periodicity of the fever cycle. Beginning with Hippocrates, a distinction was made between “tertian” and “quartan.” Tertian malarias are characterized by occurring every third day, and quartan malarias occur every fourth day. In the ancient Greek description, both the day of onset and the day of crisis were included, so tertian cycles are actually 48 hours and quartan are 72 hours (Stannard 1993). These terms are still in use today with Plasmodium vivax, P. ovale, and P. malariae described as tertian malaria and P. falciparum described as quartan malaria. When malaria began to be documented in wild primates, early typologies also relied on periodicity for classification (Coatney et al. 1971). However, it is now known that such life history features can be plastic and are not a reliable way to determine the relationships among plasmodial forms. Human malarias are also classified frequently in contemporary research according to the severity of symptoms, contrasting “benign” malaria (P. vivax, P. ovale, and P. malariae) with “malignant” or “severe” malaria (P. falciparum).

Although we may very well have a historical record of malaria going back to the time of Hippocrates in the 4th century b.c.e., the causative agent for malaria was discovered less than 150 years ago in 1880 by the military physician Alphonse Laveran, which he named Oscillaria malariae (Sherman 2005). The transmission of malaria by mosquitoes was discovered by Ronald Ross, a surgeon-major in the Indian medical service, who published his finding in 1897 (Sherman 2005). The genetic relationships among the primate malarias have begun to be elucidated only within the last 25 years.

Historically, it has been common in the literature to make a distinction between the human and the nonhuman primate (or simian) malarias. From a public health perspective, the separation is logical, because the primary focus is in understanding the malaria parasites that have been identified as significant agents of human disease. Such a division can be problematic, because it prioritizes the host over the parasite. Some species of plasmodia infect both human and nonhuman primates. Also, the division of primates into the categories of human and nonhuman is not taxonomically valid for the order Primates. For example, humans, bonobos, chimpanzees, gorillas, and orangutans (hominids) are far more closely related to one another than any are to New World monkeys. However, in this text, I do frequently make the distinction between human and nonhuman (or wild) primates. The rationale is more anthropological than public health oriented, in making our traditional distinction in gradistic differences among the primates, particularly regarding relevance of factors related to the elaboration of human culture. Nonetheless, such a distinction is expository rather than taxonomic.

As previously stated, four species of plasmodia are responsible for human malaria infections: P. falciparum, P. vivax, P. malariae, and P. ovale. Genetically, these four plasmodia are not closely related, with P. falciparum being the most distant. Each of the four has undergone separate evolutionary histories and has closer genetic relatives among the wild-primate parasites than any have to one another. For that reason, the primate malarias will be distinguished as four broad types that manifest across human and nonhuman primate species: falciparum type, vivax type, malariae type, and ovale type. This typology is consistent with the basic classification scheme developed by the first synthetic overview of the primate malarias (Coatney et al. 1971). However, in the original work of Coatney and associates (1971), classification was based on gross morphology and periodicity, which has proven to have been misleading in light of recent advances in the molecular phylogeny of plasmodia. For example, P. fragile was judged to be closely related to P. falciparum, and P. simiovale was thought to be closely related to P. ovale (hence the now erroneous name “simiovale”), but both P. fragile and P. simiovale are now known to be more closely related to human P. vivax than to P. falciparum.

Less than two years ago only two falciparum-type primate malarias had been identified: human P. falciparum and African ape P. reichenowi. The picture has become much more complicated now in that at least three new falciparum-type lines have been identified in chimpanzees (P. billcollensi, P. billbrayi, and P. gaboni) and two in gorillas (P. GorA and P. GorB). In addition, P. falciparum has been identified in bonobos, chimpanzees, and gorillas. The vivax type includes human P. vivax and at least 10 related forms that infect New World monkeys, Old World monkeys, and Asian apes. The malariae type includes human P. malariae, New World monkey P. brasilianum (affecting at least 35 species), and chimpanzee P. rodhaini, which may be the same parasite as P. malariae. The ovale type includes human P. ovale and possibly P. schwetzi.⁴ Very recently, P. ovale and has been found in chimpanzees in Cameroon (Duval et al. 2009, 2010) which the researchers believe to represent natural cross-infections.

Primates appear to be particularly vulnerable to the malaria parasites. Sinden and Gilles (2002) estimate that malaria parasites infect approximately 120 living species of mammals, reptiles, and birds. A review of the literature (see Appendix 1) found malaria parasites documented in 65 primate species; thus species infecting primates represent half of all identified malaria parasites. As is described in depth in this work, within the four major types of plasmodia specific to primates, some have demonstrated an ability to laterally transfer, or “host-switch,” across primate species, genera, and even families. Others appear to be more host-specific.

I propose that the most appropriate grouping for the four types of parasites (falciparum, vivax, ovale, and malariae) is as primate malaria and that the level of anthropoid primate is the most appropriate level of analysis for understanding these four types of plasmodia. At this time, the grouping can be applied only to the anthropoid primates (monkeys, apes, and humans). The prosimians remain an open question. These so-called “lower primates” are small-bodied, primarily nocturnal species that include tarsiers, lemurs, lorises, galagos, and bushbabies.⁵ Although eight species of malaria parasites have been identified in prosmians (see references in Appendix 1), insufficient research has been done at this time to be able to determine their genetic relationships to the anthropoid primate plasmodia.

The four types of parasites appear to be specific to anthropoid primates. Thus far, we do not have evidence that any of these plasmodia naturally parasitize taxa outside the primates. However, within the primates, species within each of the four types infect a variety of primate species. Many of the specific plasmodia species infect more than one species of primate, some of which are as distantly related as humans and platyrrhine (New World) monkeys. In addition, many primate species are infected by more than one species of plasmodia. Most of these multiple infections occur within the vivax group in Asian macaques. However, some New World monkeys are infected with both malariae and vivax type, chimpanzees have demonstrated mixed infections of falciparum and malariae type (and also the unclassified P. schwetzi), and humans can also have mixed infections.

The bulk of the early work on the wild-primate malarias was done in the 1960s and 1970s by researchers including Robert G. Coatney, William E. Collins, Peter Contacos, Leonidas Deane, Don Eyles, P. C. C. Garnham, and McWilson Warren. In 1971, Coatney and associates published, The Primate Malarias. Although nearly 40 years have passed since its original publication, it remains the most comprehensive source of data on nonhuman primate malarias. Their typology of the primate plasmodia derived from morphological analysis and life history traits. Much of our knowledge about the specific phylogenetic relationships among the primate malarias has come to light only quite recently with advances in molecular genetics. Although this research has revolutionized our understanding of the relationships among these plasmodia, it is still a relatively new field, and many questions remain. Differing methods of analysis of genetic markers have sometimes produced differing phylogenetic trees of relatedness, particularly among the complicated relationships of members of the vivax group. Some relationships have been consistent across analyses, the closest relative of human P. vivax being, surprisingly, New World monkey P. simium (implicating a lateral transfer).

The molecular research that has been conducted on the relationships among the malaria plasmodia is biased toward falciparum and vivax types, primarily because these are the most significant in causing disease in human populations. Falciparum malaria, as stated, is the most severe form of malaria to humans and has been the best studied. Human vivax malaria, while being less severe, is the most frequently occurring type of malaria outside tropical Africa. Relatively less research has been done on the milder malariae types and ovale types, which appear to be less common worldwide. However, as is discussed later, the prevalence of P. malariae may be seriously underestimated in the New World tropics. Many of the wild-primate malarias remain molecularly uncharacterized, and their relationship to the others remains to be fully understood.

One of the most important early relationships that was identified was between two falciparum-type malarias: human P. falciparum and African ape P. reichenowi. Up until 2010, P. falciparum was thought to be a uniquely human parasite. However, as is discussed in Chapter 3, it has recently been discovered that bonobos (Pan paniscus), chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla) harbor P. falciparum and several additional falciparum-type plasmodia, previously unknown. Among the four types of malaria parasites in primates falciparum type is an outgroup (Chapter 3). The vivax, malariae, and ovale types are all more closely related to one another than any of the three are to the falciparum malaria.

Early hypotheses about the origin of falciparum malaria included it arising as a zoonosis from domesticated birds with the advent of agriculture. Some of the early genetic studies seemed to support this view. However, subsequent molecular studies demonstrated the close genetic relationship between P. reichenowi and P. falciparum, ruling out the avian hypothesis (McCutchan et al. 1984; Waters, Higgins, and McCutchan 1991, 1993). The prevailing view then became that the two forms of falciparum malaria separated with the divergence of the humans, chimpanzees, and gorillas 5 to 10 million years ago and that the two plasmodial forms co-evolved in humans and African apes.⁶ In 2010 that view was upended several times by research suggesting that chimpanzees, bonobos, or gorillas were the original source of falciparum in humans (Chapter 3).

The relationships among the vivax-type malarias are extremely complicated and far from being definitively resolved for several reasons. One involves the state of development of genetic research. As previously stated, differing methods of genetic analysis have not produced identical phylogenetic trees. Although molecular studies have consistently placed the same plasmodia within the vivax group, there is controversy regarding the precise relationships among many of the plasmodia in the vivax group. Three factors make sorting out these relationships complicated: in some cases, the same primate host harbors multiple closely related vivax species, the same vivax species can infect multiple primate hosts, and vivax-type malarias are prone to host-switching. Thus co-evolutionary processes can be taking place in one plasmodia species across multiple hosts, and a single host can be involved with simultaneous co-adaptation to multiple plasmodia. And genetic relationships can be difficult to differentiate from convergent evolution when one is dealing with such closely related primate species and closely related plasmodia species. The possibility of potentially multiple lateral transfers during a given plasmodium’s evolutionary history makes these relationships even more difficult to disentangle.

The vivax group includes at least 11 plasmodia, most of which occur in Southeast Asian primates. Included are seven closely related plasmodia of Asian monkeys, one occurring in gibbons (Hylobates). At least three forms exist outside Asia. One is the e...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• 1. Introduction: Malaria as a Primate Disorder
• 2. Co-Evolution: Parasites, Vectors, and Hosts
• 3. Falciparum Type: The Great Ape Malaria
• 4. Vivax Type: The Macaque Malaria
• 5. Migration: Malaria in the New world
• 6. Rhesus Factor: Experimental Studies in wild Primates
• 7. Ethics: Human Experimentation
• 8. Future: The Primate Malaria Landscape
• Appendix 1 Plasmodia Parasites and Their Natural Primate Hosts
• Appendix 2 Experimentally Induced Plasmodium cross-Infections into Novel Hosts
• Appendix 3 Naturally Acquired cross-Infections with Novel Malaria Parasites
• Appendix 4 Primate Species and All Infections with Plasmodium Parasites
• References
• Index
• About the Author