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Neurocysticercosis—More Than a Neglected Disease

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Neurocysticercosis—More Than a Neglected Disease Editorial Neurocysticercosis—More Than a Neglected Disease Theodore E. Nash1*, Siddhartha Mahanty1, Hector H. Garcia2,3 1 Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Department of Microbiology, School of Sciences, and Center for Global Health - Tumbes, Universidad Peruana Cayetano Heredia, Lima, Peru´, 3 Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru´ Neurocysticercosis (NCC) is the most penetrate the intestinal mucosa and are es most basic research cannot be performed common cause of adult-acquired epilepsy carried to the muscles, brain, and other in developed, non-endemic countries. The worldwide and one the most frequent tissues of the pig and establish as cysts high cost of the logistics to establish and parasitic infections associated with chronic which, when ingested by humans in poorly maintain the stages of the life cycle required morbidity in the United States. Despite its cooked pork, develop into tapeworms for basic experiments is compounded by importance [1–4], worldwide morbidity (taeniasis). Humans become infected with the difficult challenge of obtaining financial due to NCC is underappreciated and cysts (cysticercosis) following the accidental support for a neglected disease. Research- research is underfunded, and therefore ingestion of ova-contaminated hands, ers have naturally turned to imperfect researchers are unable to capitalize on food, or water. Because the life cycle of models of cestode infections that are recent advances that hold great promise to the parasite is complex and exacting, it is employed to understand immune host prevent millions of cases of epilepsy and to particularly susceptible to interruption, response and host–parasite interactions, to effectively treat viable brain infections. and simple interventions such as corralling develop in vitro and in vivo assays to Similar to most neglected tropical pigs, preventing indiscriminate defecation, understand how effective drugs work, and diseases, assessing the global burden of and fully cooking pork can potentially to discover safer and better drugs for use in disease for NCC is very imprecise, and is prevent human infection. humans. Controlled human treatment tri- particularly burdensome because of the Advancements in our knowledge of the als and observational studies are difficult to insensitivity of serology as a diagnostic tool importance of NCC, the means to estab- conduct because of their cost, need for and the need for brain imaging to establish lish the diagnosis, and the re-purposing frequent imaging, and requirement for long presence of infection and/or disease. and use of drugs to treat disease has been periods of follow up. As a consequence, a These limitations are particularly evident phenomenal. It is easy to forget that a few relatively small cadre of persons and in Africa, where infrastructure and avail- decades ago the diagnosis of NCC was laboratories are devoted to understanding ability of CT and/or MRI facilities are made infrequently, medical treatments the parasite and its disease manifestations. limited. NCC is common in many coun- were unavailable, and its role as a primary Despite these impediments, there have tries of Central and South America, Haiti, cause of adult onset epilepsy unknown. been a number of notable advances in India, most of Africa, Southeast Asia, and Despite these advances, the study of NCC recent years that could lead to better parts of China. Estimates of the burden of lags behind most other major infections of treatments and control of disease. As cysticercosis and NCC, based upon de- the tropics, and further progress requires examples, a potentially useful avenue of tailed studies of endemic communities, improved and more effective approaches research has been the development of were recently published [2], and the as well as an increased and balanced highly effective vaccines to the invading burden of disease is substantial [3]. Some commitment of resources. oncosphere larva in pigs, which are based communities showed a prevalence of The study of NCC is inherently difficult. on high levels of immunity that normally greater than 35% for infection with The life cycle is near impossible to maintain develops to the migrating larva [7]. cysticercosis by serology and brain imag- in the laboratory, and for practical purpos- Strategic use of vaccines could potentially ing, and intracerebral calcifications indic- ative of NCC in 10%–20% of randomly Citation: Nash TE, Mahanty S, Garcia HH (2013) Neurocysticercosis—More Than a Neglected Disease. PLoS studied individuals. Studies of persons with Negl Trop Dis 7(4): e1964. doi:10.1371/journal.pntd.0001964 epilepsy in well-characterized communi- Published April 25, 2013 ties found that 29% of epilepsy in endemic This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, communities is attributable to NCC [5], modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under which in some communities amounted to the Creative Commons CC0 public domain dedication. 1% or greater of the population. By Funding: Funded in part by the Intramural Research Program of NIAID/NIH. HHG is supported by a Wellcome conservative estimates, greater than 5 Trust Senior International Fellowship on Tropical Medicine and Public Health. The funders had no role in study, million cases of epilepsy worldwide, which design, data collection and analysis, decision to publish or preparation in the manuscript. are all preventable, are caused by NCC. Competing Interests: The authors have declared that no competing interests exist. The life cycle of the pork tapeworm * E-mail: [email protected] Taenia solium is complicated [1,6]. The Hector H. Garcia, MD, PhD, is a coordinating member of the Cysticercosis Working Group in Peru. He directs the tapeworm lives in the human small Center for Global Health - Tumbes of the Universidad Peruana Cayetano Heredia in Lima, Peru, where he is also intestine and sheds multiple proglottids, a Professor at the Department of Microbiology, and is Head of the Cysticercosis Unit of the Instituto Nacional each containing 30,000–50,000 infectious de Ciencias Neurologicas of the Peruvian Ministry of Health. Siddhartha Mahanty, MD, is a Staff Physician in the Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of ova. Proglottids may retain ova as they are Health (NIH), Bethesda, MD. He is an infectious diseases specialist with a long-standing interest in clinical excreted in feces, or liberate ova in the tropical medicine and the immunology of human helminth infections. He co-directs the Clinical Parasitology feces or around the anus. When free- Unit at the National Institutes of Health Clinical Center. Theodore Nash, MD, is a Principal Investigator and Head of the Gastrointestinal Parasite Section in the Laboratory of Parasitic Diseases, National Institute of Allergy and roaming pigs ingest human stools with Infectious Diseases, NIH, Bethesda, MD. He has a long-term interest in neurocysticercosis and directs studies at infectious ova, the liberated oncospheres the Clinical Center NIH as well as in Lima, Peru. PLOS Neglected Tropical Diseases | www.plosntds.org 1 April 2013 | Volume 7 | Issue 4 | e1964 prevent infection in the obligate interme- fective and safer alternatives are needed. require the development of easy to use in diate host, eliminating taeniasis and NCC. The natural history and prognosis of vitro and in vivo drug screening methods Sensitive methods to diagnose tapeworm single enhancing degenerating lesions [12]. infections have been developed and are has been well defined. NCC is a chronic A number of intervention strategies to likely to play an important role in control inflammatory infection of the brain and control infection have also been realized. of infection. Recombinant and/or synthe- much of morbidity is directly or indirectly The introduction of oxfendazole as a single sized antigens have been identified to caused by inflammation. Corticosteroids dose therapy for porcine cysticercosis, replace T. solium–harvested antigens in have traditionally been used to control coproantigen detection for improved diag- antibody detection assays [8]. The T. parasite-induced inflammation. How to nosis of taeniasis, and as already men- solium genome, which has recently been use corticosteroids effectively is being tioned, a highly efficacious TSOL18 pig published [9], offers an expanded arma- studied and preliminary results indicate vaccine, have made control of transmission mentarium of tools to interrogate the that rational use leads to decreased a potentially achievable goal. Other vac- biology of the parasite, identify molecules seizures [10]. Most persons with epilepsy cines also look promising. A series of involved in host–parasite interactions, and due to NCC only have calcified granulo- attempts at control of human infections discover more effective and safer cysticidal mas that, in many cases, are the foci of using mass chemotherapy with praziquan- drugs. Complicated subarachnoid infec- seizures; half of such lesions develop tel or niclosamide as well as many inter- tion previously carried a dismal prognosis, sporadic episodes of perilesional edema ventions at the same time have been which has now improved, most likely around the calcifications
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