Bernard Bouteille

During the first week early phase of COVID-19, some patients exhibit symptoms that are mainly due to SARS-CoV-2 replication and the important pulmonary cytolysis that takes place. Thereafter, a progressive decrease in upper airway viral shedding ensues, which may result from the emergence of a cytokine storm [ 1]. Meanwhile, data regarding the involvement of the nervous system in relation to SARS-CoV-2 infection become progressively available [ 2]. Here, we consider sleep impairment potentially provoked by virus brain penetration and the nitric oxide (NO)-induced deleterious mechanisms that may emerge.

To study the anatomo-biochemical substrates of brain inflammatory processes, Wistar male rats were infected with Trypanosoma brucei brucei. With this reproducible animal model of human African trypanosomiasis, brain cells (astrocytes, microglial cells, neurons) expressing the inducible nitric oxide synthase (iNOS) enzyme were revealed. Immunohistochemistry was achieved for each control and infected animal through eight coronal brain sections taken along the caudorostral axis of the brain (brainstem, cerebellum, diencephalon and telencephalon). Specific markers of astrocytes (anti-glial fibrillary acidic protein), microglial cells (anti-integrin alpha M) or neurons (anti-Neuronal Nuclei) were employed. The iNOS staining was present in neurons, astrocytes and microglial cells, but not in oligodendrocytes. Stained astrocytes and microglial cells resided mainly near the third cavity in the rostral part of brainstem (periaqueductal gray), diencephalon (thalamus and hypothalamus) and basal telencephalon. Stained neurons were scarce in basal telencephalon, contrasting with numerous iNOS-positive neuroglial cells. Contrarily, in dorsal telencephalon (neocortex and hippocampus), iNOS-positive neurons were plentiful, contrasting with the marked paucity of labelled neuroglial (astrocytes and microglial) cells. The dual distribution between iNOS-labelled neuroglial cells and iNOS-labelled neurons is a feature that has never been described before. Functionalities attached to such a divergent distribution are discussed.

Within the genus Taenia, three species are human parasites: T. solium, T. saginata and a new uncommon species, T. asiatica, described recently in Asia. T. saginata and T. solium live as adult tapeworms in human intestines, where they cause taeniasis. T. saginata is widely present worldwide, in all regions where cattle are bred. T. solium is endemic in many countries where livestock and consumption of pigs are common. Cattle and pigs become infected by ingesting eggs emitted by humans into the environment and serve as the respective intermediate hosts of these helminths and host larval forms, or metacestodes or cysticerci. Cysticerci develop into adult worms in the human intestines after a person has eaten contaminated raw or undercooked meat. In the T. solium, eggs are also human contaminants. Humans, like swine, can develop cysticercosis after ingesting eggs with water or contaminated food, or via dirty hands. The clinical manifestations of cysticercosis are highly variable both in kind and in severity. The period between initial infection and the onset of symptoms can also vary. The clinical expression of cysticercosis is generally dependent on the number, size and location of the cysts, as well as the host immune response to the parasite. The preferred locations are the muscles, subcutaneous tissues, central nervous system (CNS), and eyes. Subcutaneous and muscular forms are often asymptomatic. Severe cysticercosis is due to larvae located in human CNS - neurocysticercosis. The World Health Organization (WHO) lists neurocysticercosis as a neglected tropical disease. It estimates that about 50 million people worldwide have neurocysticercosis in the world and that it causes about 50,000 deaths each year. Its most frequent clinical manifestations are seizures, intracranial hypertension, neurological deficits, and sometimes psychiatric manifestations. It is also responsible for more than 50% of the cases of late-onset epilepsy in developing countries. The T. solium taeniasis/cysticercosis complex is endemic in many developing countries in sub-Saharan Africa, Latin America, and Asia. Although T. solium had virtually disappeared in developed countries due to industrialization, improved methods of husbandry, and health checks, cysticercosis and neurocysticercosis are diagnosed anew in North America, Europe and Australia due to increased immigration from endemic areas. Cysticercosis is considered an eradicable disease. Although theoretically feasible, this concept has been replaced by projects to control and reduce the impact of cysticercosis on human health (through mass treatment of people, veterinary control of pigs, improved farming techniques, and health education).

Arginase serum levels were increased in human African trypanosomiasis patients and returned to control values after treatment. Arginase hydrolyzes l -arginine to l -ornithine, which is essential for parasite growth. Moreover, l -arginine depletion impairs immune functions. Arginase may be considered as a biomarker for treatment efficacy.

Human African trypanosomiasis (HAT) is caused by the injection of Trypanosoma brucei (T. b.) gambiense or T. b. rhodesiense by Glossina, the tsetse fly. Three historical eras followed the exclusive clinical approach of the 19th century. At the turn of the century, the “initial research” era was initiated because of the dramatic spread of HAT throughout intertropical Africa, and scientists discovered the agent and its vector. Two entities, recurrent fever and sleeping sickness, were then considered a continuum between hemolymphatic stage 1 and meningoencephalitic stage 2. Treatments were developed. Soon after World War I, specific services and mobile teams were created, initiating the “epidemiological” era, during which populations were visited, screened, and treated. As a result, by 1960, annual new cases were rare. New mass screening and staging tools were then developed in a third, “modern” era, especially to counter a new epidemic wave. Currently, diagnosis still relies on microscopic detection of trypanosomes without (wet and thick blood films) or with concentration techniques (capillary tube centrifugation, miniature anion-exchange centrifugation technique). Staging is a vital step.Stage 1 patients are treated on site with pentamidine or suramin. However, stage 2 patients are treated in specialized facilities, using drugs that are highly toxic and/or that require complex administration procedures (melarsoprol, eflornithine, or nifurtimox-eflornithine combination therapy). Suramin and melarsoprol are the only medications active against Rhodesian HAT. Staging still relies on cerebrospinal fluid examination for trypanosome detection and white blood cell counts: stage 1, absence of trypanosomes, white blood cell counts ≤ 5/µL; stage 2, presence of trypanosomes, white blood cell counts ≥ 20/µL; T. b. gambiense HAT intermediate stage, between these still controversial thresholds. Our group has proposed the use of noninvasive ambulatory polysomnography to identify sleep–wake abnormalities characteristic of stage 2 of the disease. Only patients with abnormal sleep–wake patterns would then undergo confirmative lumbar puncture.