Emerging Neurological Infections PDF

Preface

Infections of the nervous system are among the most vivid of all diseases because of their dramatic clinical presentations and ominous prognoses. Over the past 20 years, there has been remarkable progress in the recognition, understanding and treatment of neurological infections. As new infections have arisen, an appreciation has developed of factors influencing neurovirulence and the spread of different agents. The fields of microbiology and neuroscience have experienced revolutionary developments, ranging from seminal molecular and epidemiological advances to unforeseen neurological infections in humans and other species. Hence, it is timely to provide a book that merges these two disciplines, as we face new neurological infections due to microbial evolution (Enterovirus 71, drug resistant bacteria and viruses), a change in host (variant Creutzfeld-Jacob disease, Nipah Virus, HIV/AIDS), or expanding geographic locations of different infectious agents (Lyme disease, Japanese encephalitis Virus, West Nile virus). Infections of the nervous system have had a long and colorful history in terms of epidemics throughout the world including poliomyelitis, rabies, bacterial meningitides, arbovirus encephalitides together with those infections with prominent neurological complications such as measles, influenza, leprosy, tuberculosis, and most recently HIV/AIDS.

The underlying determinants of these past epidemics apply to today's emerging epidemics including changes in human demographics and behavior, technology and industry, economic development and land use, international travel and commerce, microbial adaptation with increased microbial virulence, and breakdown or absence of public health resources due to political priorities or poverty. However, the accelerated rate of appearance of new neurological infections in the last decade lies in several current global circumstances, not the least of which is the exponential rise in the global human population size, now 6.2 billion but expected to reach 10 billion by 2050. Indeed, as the population rises, there has been an increase in environmental pollution, trafficking of humans and animals and their products across international borders together with new food production practices. Major social upheavals also contribute to emerging infections including famine and war coupled with poverty or social inequality. Prime examples of burgeoning and emerging neurological infections include the HIV/AIDS epidemic, which has influenced most biomedical fields and exhibits a wide range of neurological manifestations, and the increased frequency of transmissible spongiform encephalopathies, such as vCJD. These two diseases reflect changing social and economic milieus respectively, which resulted in the emergence of diseases previously unknown in humans. Both diseases are zoonoses, likely contracted by humans through eating contaminated foods; simian immunodeficiency virus-infected bush meat was likely the source of HIV infection in humans while consumption of bovine spongiform encephalopathy-infected cattle tissues represents the most plausible explanation for vCJD in humans. However, other mechanisms of zoonotic infection have recently been shown to cause new or re-emerging neurological infections in humans including Nipah virus transmission from pigs to humans with fruit bats serving as the primary reservoir and West Nile virus from a mosquito or a bird transported from warmer climates.

Increased quantity and speed of travel by humans and the exportation of animals globally has provided ripe opportunities for neurotropic pathogens to spread across continents. Fifty years ago it would have taken months for livestock to be shipped across oceans during which time sick human, or animals would have died or been culled while today's movements across continents occur in a matter of hours. Social developments over the past two decades have also contributed to the appearance of new diseases including increased global urbanization and changing trends in the workforce, with more women now working and subsequently greater dependence on day care. Similarly, select regions of the world, coping with increased population size, poverty, and war and already beset with other diseases, are now faced with the ever increasing HIV/AIDS epidemic and its accompanying opportunistic infections of the brain. These regions have few or diminishing resources to cope with the associated economic and social burdens.

Neurological infections are unique among infections because they are usually evolutionary cul-de-sacs for many pathogens, frequently resulting in the host being unable to support further pathogen replication and spread or, worse still, death. Unlike systemic infections, pathogens in the brain also pose a more ominous predicament for clinicians because of the brain's enhanced vulnerability due to its limited host defense mechanisms, which are largely dependent on innate immunity. In addition, delivery of drugs across the blood–brain barrier remains an obstacle, even when highly specific and

effective drugs are available. Moreover, drug resistance has also become a pressing issue among neurological infections just as it is for systemic infections, including methacillin-resistant Staphylococcus aureas and drug-resistant tuberculosis and herpes virus infections. Other treatment strategies may also yield new infections including the proposed use of stem cells from human embryos or animal organs in xeno-transplantation. Nonetheless, we are in an era of hitherto unimagined tools for the diagnosis and treatment of diseases. The use of molecular tools for infectious disease epidemiology was barely in its infancy a decade ago, yet today it is the cornerstone of controlling disease outbreaks and monitoring ongoing epidemics. Indeed, a greater understanding of host susceptibility to infection has arisen through the identification of specific host genotypes associated with disease including single nucleotide polymorphisms. Neurological diagnostics and therapeutics have also evolved with the advent of improved neuroimaging, neurocognitive testing, and a wider availability to specific drugs for neurological infections. The approach taken herein is one of emphasizing the basis for emergence or resurgence of neurological infections together with recognition of the disease and its pathogenesis and finally, implementing the appropriate therapeutic and public health measures.

The present monograph contains chapters from authors who were selected for their internationally recognized expertise in areas related to emerging diseases and specific neurological infections. Thus, the spectrum of topics covered by the authors of each chapter ranges widely from determinants of emerging infections to new pathogens, new locations and disease manifestations of infectious neurological disease, drug resistance, and finally, potential interventions. The book begins with a chapter devoted to the origins of new infections that focuses on microbial evolution in relation to disease while in the second chapter, environmental factors that contribute to emerging infections are addressed. In Part II, new human pathogens are examined, concentrating on Nipah virus, prion diseases and neurotropic viruses causing hemorrhagic fevers. The spread of pathogen into new geographic domains is reviewed in Part III in respective chapters dealing with cerebral malaria, rabies, neurocysticercosis, borrelial infections, flaviviruses including West Nile and Japanese encephalitis viruses and African trypanosomias. New human diseases caused by previously recognized pathogens is the spotlight of Part IV in which enterovirus 71 encephalitis, campylobacter infection, and Guillain-Barré syndrome, and putative brain pathogens including human herpes virus-6, endogenous retroviruses, and other microbes linked to multiple sclerosis are considered. In view of the increased impact of drug resistant pathogens, Part V reviews the clinical aspects and mechanisms of drug resistance of herpes simplex virus, HIV-1, and nosocomial infections among neurological diseases. Finally, potential interventions including vaccine development and priority strategies are addressed in Part VI.

We anticipate that this book will provide a perspective of emerging neurological infections for those working or training in neurology, neurosurgery, infectious diseases, public health, pediatrics, and in related basic science disciplines. We hope, however, that this book will also contribute to the early identification and enhanced care of patients afflicted with neurological infections.