This disease is typical of the twentieth century (Fig. 2): sizable epidemics appeared at the beginning of the century and were close to elimination at the end of the century. Before Karl Landsteiner (1868–1943) discovered in 1909, in cooperation with Erwin Popper (1879–1955), its causative pathogen, poliovirus, the paralytic aspects of the disease were considered to be its characteristic feature and the disease was denominated “infantile paralysis”.

With the introduction of mass vaccinations, this severe, disabling, disease has almost completely disappeared. This illustrates that results obtained from experimental basic research, i.e. isolation of the virus in cell culture, can be translated into the elimination of a severe nervous system disorder. However, the elimination of polio left a number of interesting problems concerning its pathogenetic mechanisms unsolved (Nathanson 2008).

This disease is also called von Economo disease after Constantin von Economo (1876–1931; a disciple of Wagner-Jauregg), who presented his studies on this new nosological entity in 1929.

Lethargic encephalitis appeared in 1916 and disappeared as mysteriously as it had appeared 10 years later after sweeping three times around the world infecting millions of people and killing one-third of them. It caused severe sleep disturbances: most patients were lethargic, others were insomniac, and some developed narcolepsy-like sleep episodes. Survivors could, with a late onset, develop severe behavioral disturbances, or a Parkinson-like disorder, or both.

Neuropathological studies of victims of lethargic encephalitis heralded the localization of sleep-wakefulness regulating areas in the brain (Triarhou 2006; Bentivoglio and Kristensson 2007). The pathogen was never isolated, but the disease highlights that we should remember that infectious diseases causing severe mental disturbances and neurodegenerative disorders can suddenly become a real threat and be spread rapidly over the world.

With discoveries and progress of vaccines and antibiotic therapy, the infectious diseases of the nervous system have, during the past 50–60 years, fallen more or less out of favor in the neurological community, and are currently handled mostly by health authorities and infectious disease clinics. Since the early 1970s, the rapidly growing field of neuroscience has focused on other important areas of clinical and basic research. Thus, with the exception of HIV infection, infectious diseases of the nervous system have become a relatively neglected area of research.

As mentioned previously, the NTD do not include “the big three” infections (malaria, tuberculosis, HIV-AIDS). It is, however, frequently forgotten that important sequels may follow or may appear as late-onset disorders caused by cerebral malaria and HIV infections in infancy, namely epilepsy and cognitive disturbances (Newton and Wagner 2014; Kihara et al. 2014). These also represent an area of investigation up till now neglected in neuroscience. Importantly, the occurrence of seizures increases misunderstandings, stigmatization, social isolation caused by NTD, though epilepsy can be often managed by treatment with anti-epileptic drugs (Scorza et al. 2013).

Infections with worms affect annually hundreds of millions of people worldwide and some are often accompanied by complications of the central nervous system (CNS), e.g. cysticercosis (Fig. 3), causing neurocysticercosis (Carpio 2014). Others spread more rarely to the CNS, e.g. schistosomiasis (Fig. 4) (Ferrari 2014), onchocerciasis (Njamnshi and Zoung-Kanyi Bissek 2014) and other nematode infections (Intapan et al. 2014). As these infections are very common and causative pathogens are widely spread, the CNS is under a constant threat for millions of people. For example, over 230 million people are estimated to require treatment for schistosomiasis yearly (WHO 2012), and the blood flukes of the genus Schistosoma can cause neuroschistosomiasis in a proportion of cases (Ferrari 2014).

Among protozoa targeting the nervous system, infections with Toxoplasma gondii are common in high-income countries and are not included in the NTD group, while infections by Trypanosoma (T.) brucei in Africa and T. cruzi in Latin America represent severe NTD.

T. brucei, the causative agent of human African trypanosomiasis or sleeping sickness, is an example of a parasite that has predilection for the brain (Buguet et al. 2014; Masocha et al. 2014). This parasite caused large epidemics in sub-Saharan Africa at the turn of the twentieth century (Fig. 5). Two-thirds of the population in Uganda died during the 1896–1906 epidemic. African trypanosomiasis, which also causes infections of livestock (nagana), probably severely impeded the pre-colonial social and economic development of sub-Saharan Africa. With surveillance and better control of the T. brucei vector, the tsetse fly, the prevalence of human African trypanosomiasis rapidly declined in the second part of the twentieth century. However, the disease then re-emerged as control measures were neglected due to political unrest and civil wars, and was reported to affect >300,000 persons in 1998. Continued control measures have now brought the number of reported cases down to below 10,000 (WHO 2013), although this is probably an underestimate.

Chagas disease is the human infection caused by T. cruzi (Coura 2014). The infection, which affects primarily rural populations, has serious consequences for public health in Latin America, where it is estimated to have killed 10,000 people in 2008 (WHO 2012). It is an infection probably as old as mankind, as T. cruzi DNA was found in mummified bodies of 9,000 years ago. Carlos Chagas (1879–1933) in Brazil, in 1909, not only described the disease but also discovered the new Trypanosoma species he would prove to be the pathogen, and identified an insect vector, the triatomines (Fig. 6). Charles Darwin (1809–1899) is described to have been attacked by a triatomine bug during his expedition in 1835, and developed much later symptoms compatible with Chagas disease (Adler 1997). Triatomines are called “kissing bugs” because they bite near the lips and the eyes (the so-called kiss of death).

About 30 % of chronically infected people develop after a very long clinical latency the cardiac and/or gastrointestinal forms of Chagas disease, with progressive denervation of viscera which makes of this disease a major disorder of the autonomic nervous system. The pathogenesis of neurodegenerative events in Chagas disease is still enigmatic. Spread of T. cruzi to the brain, with reactivation of the acute form of Chagas disease, is of increasing concern in immunosuppressed individuals, including HIV-AIDS patients.

Leprosy can serve as an example of a NTD caused by bacteria. This chronic infection attacks the peripheral nervous system (Masaki and Rambukkana 2014), and is a severe social stigmatizing condition due to the accompanying conspicuous damages to the skin and extremities that are the result of sensory disturbances.

Disfigurement caused by leprosy has fired imagination in all cultures (Fig. 7). There are accounts of leprosy throughout recorded history, in ancient civilizations in Egypt (leprosy was probably described in an Egyptian papyrus written around 1550 B.C.), China, and India (where the earliest certain account of leprosy was reported between 600 and 400 B.C.). Leprosy may also represent a travel medicine disease, believed to have been brought from India to Greece by the soldiers of Alexander the Great in the fourth century B.C. (Sherman 2006). Segregation and even harsh punishment of lepers (up to burning them alive), the use of a leper clapper or bell to make them manifest and isolate lepers are well documented not only in Europe in the Middle Ages, but also elsewhere and throughout centuries. The renowned parable of the “healing-miracle” of Jesus encountering the ten lepers on the road to Galilee (Gospel of Luke 17:11–19) presented leprosy in the context of faith and salvation (Fig. 8).

Medical salvation of leprosy had, however, to wait for many centuries. The causative pathogen, Mycobacterium leprae, was discovered in 1873 by Gerhard Armauer Hansen (1841–1912) through his work in the Norwegian seaport Bergen. Hansen was sued and lost his post at the hospital when trying to prove his discovery by infecting a patient suffering from the anesthetic form of leprosy (Jay 2000). However, his efforts lead to a marked decline of the disease in Norway, and represented an obvious turning point in the fight against leprosy.