The central nervous system (CNS) and peripheral nervous system are increasingly recognized as relevant and also preferential targets for a wide range of parasites, i.e. protozoa (including free-living amoebae), helminths, arthropods and fungi, both in human and veterinary medicine (Carpio et al., Reference Carpio, L, Parkhouse, Short and Dua2016; Idro et al., Reference Idro, Ogwang, Barragan, Raimondo and Masocha2022). Parasitic infections of the nervous system may result in different, clinically significant and often underdiagnosed neurological manifestations, ranging from rapid encephalitis and obstructive hydrocephalus to epilepsy, cognitive decline and behavioural changes, through a wide range of pathogenetic mechanisms (Del Brutto, Reference Del Brutto2012; Singh et al., Reference Singh, Angwafor, Njamnshi, Fraimow and Sander2020). The Special Issue (SI), titled ‘Current advances in neuroparasitology in human and veterinary medicine: from pathogenesis to clinical management’, provides an interdisciplinary overview of the different ways in which parasites may invade, persist within and affect the nervous system in humans and animals. The contributions highlight the pathological pattern shared across different parasite species and hosts (e.g. vascular and perivascular involvement, chronic granulomatous neuroinflammation and latency). Additionally, it explores how these parasites damage neural circuits which are relevant for behaviour and cognition, interact with cerebrospinal fluid (CSF) pathways, and how antiparasitic treatments can themself affect the CNS. These studies have clear implications for clinical practice, for the surveillance and control of parasitic diseases, and for our understanding of how infections can influence brain function over both short and long time scales. At the same time, neuroparasitic infections provide biologically informative models for investigating CNS immunobiology, vascular pathology and circuit-level modulation (Singh et al., Reference Singh, Angwafor, Njamnshi, Fraimow and Sander2020; Idro et al., Reference Idro, Ogwang, Barragan, Raimondo and Masocha2022).

The SI comprises 11 peer-reviewed contributions (Table 1), including narrative reviews (4), neuropathological studies (3), clinical and epidemiological investigations (2), experimental research on neural cells (1) and case studies (1).

Table 1.

Overview of the manuscripts included in this SI on Current advances in neuroparasitology in human and veterinary medicine: from pathogenesis to clinical management, with indication of their primary contribution field

Table 1 Long description

Columns list papers, title, first author, study type, parasite or parasite group, and host for 11 entries. Toxoplasma gondii appears in five entries: an eco epidemiological sero epidemiological study in Alpine game species, a cross sectional clinical study in humans with HIV, a narrative review on clinical toxoplasmosis risk factors in humans, a narrative review of major human brain parasites that includes Toxoplasma gondii, and a neuropathological study in red foxes from Italy and Australia. Two comparative neuropathological studies cover free living amoebae across species, one for Acanthamoeba spp. and one for Balamuthia mandrillaris, both listing humans and animals as hosts. Plasmodium vivax is covered in a narrative review focused on cerebral malaria in humans, and Plasmodium falciparum appears within the major human brain parasites narrative review. Taenia solium neurocysticercosis appears in a case report with literature review in humans and also within the major human brain parasites narrative review. Leishmania infantum appears in an in vitro experimental study using murine astrocytes in a cell culture model. One narrative review on neurotropic parasites of small companion animals lists multiple parasite groups and examples, with dogs and cats as hosts.

The contribution by Contini et al. (Reference Contini, De Giorgio, Guarino, Maritati and Bruschi2026) offers a broad clinical and public health overview of the major human parasites affecting the CNS, synthesizing the current knowledge on cerebral malaria, neurocysticercosis, cerebral hydatidosis, toxoplasmic encephalitis and less frequent infections like schistosomiasis, toxocariasis and amoebiasis. The authors emphasized that the most severe examples of CNS parasitism occur in neglected populations with limited diagnostic and therapeutic resources. Cerebral malaria, caused by Plasmodium falciparum, is explored in depth, as it remains a leading cause of childhood mortality; the authors also discuss how advanced tools like magnetic resonance imaging and retinal fluorescein angiography may help to assess the severity of brain damage. Meanwhile, neurocysticercosis, the most common helminthic CNS infection and a major cause of acquired epilepsy in developing countries, is discussed with a focus on neuroimaging supported by immunodiagnostics as primary tools. The authors also stress the need to combine antiparasitic treatments with antiepileptics, anti-inflammatories and, in cases of obstructive hydrocephalus, neurosurgical procedures. They review cerebral hydatidosis and opportunistic toxoplasmic encephalitis in advanced HIV patients and also the primary amoebic meningoencephalitis caused by Naegleria fowleri, which may cause a rapid fatal condition with limited therapeutic options. Finally, the potential of nanotechnology to improve the blood–brain barrier penetration of the drugs commonly used is explored.

Two papers by Siddiqui and colleagues (Siddiqui et al., Reference Siddiqui, Maciver, Lloyd and Khan2026a, Reference Siddiqui, Maciver, Lloyd and Khan2026b) focus on the aggressive and life-threatening infections caused by free-living amoebae. The first paper examines Balamuthia mandrillaris, a free-living amoeba, which spreads through the bloodstream, causing a subacute or chronic granulomatous amoebic encephalitis, contrasting with the rapid and devastating impact of primary amoebic meningoencephalitis caused by N. fowleri. The comparison across the lesions observed in humans and animals allows us to identify a shared pathological pattern of blood vessel invasion, granulomatous inflammation, necrotizing vasculitis and multifocal tissual damage, with both trophozoites and cysts within the neural tissue. Their second paper (Siddiqui et al., Reference Siddiqui, Maciver, Lloyd and Khan2026b), however, provides a cross-species analysis of granulomatous amoebic encephalitis caused by Acanthamoeba species. They show that, also in this case, the histopathological features are remarkably consistent across humans and animals (e.g. haematogenous spread, pronounced perivascular tropism, granulomatous neuroinflammation and progressive tissue destruction, with coexistence of trophozoites and cysts). Together, these 2 contributions demonstrate that different genera of free-living amoebae use similar strategies to colonize the CNS and to persist in the brain, targeting vascular and perivascular niches and triggering chronic granulomatous inflammation, and highlight the relevance of animal models for therapeutic developments in human medicine.

The SI also includes articles on the insidious effects of latent CNS infections, specifically Toxoplasma gondii and Malaria vivax, including the fascinating ability for T. gondii to influence behaviour and ecosystem dynamics. Severance and Xiao (Reference Severance and Xiao2026) try to clarify, through a comprehensive review, which conditions allow the latent infection of T. gondii to remain subclinical and which are, however, the triggers allowing the active clinical disease. They highlight a striking paradox: despite the high worldwide prevalence of T. gondii exposure, clinical toxoplasmosis remains relatively rare, and reliable predictors of progression from latent infection to neurological disease are still lacking. Putting together data from obstetrics, ophthalmology, transplantation, oncology and HIV/AIDS care, the authors map out a complex multifactorial risk profile in which immunodeficiency, in utero exposure, host genetic susceptibility, age, antibody levels, parasite strain virulence, parasite burden and infectious stage could modulate the likelihood of the disease becoming active.

On the same theme of subclinical infections, Rovito et al. (Reference Rovito, Zanet, Trunfio, Calcagno and Ferroglio2026) investigate the infections of T. gondii in immunocompromised patients. In a cross-sectional cohort of patients with HIV infection, the authors investigated a link between T. gondii IgG antibodies, neurocognitive performance across 6 key areas (including depressive and anxiety symptoms, educational attainment) and a panel of CSF biomarkers of nerve damage, Alzheimer’s-like pathology, macrophage-derived inflammation and glial activation. Overall, latent T. gondii infection was not associated with overt neurocognitive impairment or detectable CNS pathophysiological alterations, even in patients with HIV and low CD4 counts. These findings underscore just how complex host–parasite interactions are, pointing to the need for long-term studies to see if these subtle infections have hidden, long-term consequences.

Expanding the perspective from the clinical and biological complexity of latent infection to its ecological determinants, Vada et al. (Reference Vada, Zanet, Carpignano, Perrone and Ferroglio2026) investigate the epidemiology of T. gondii exposure in alpine game species from northern Italy. By integrating serological data with geospatial analyses, the authors show that wild boar density, age and proximity to human settlements are key predictors of T. gondii seropositivity. These findings emphasize the importance of wildlife ecology and anthropogenic interfaces in shaping the epidemiology of this zoonotic parasite and demonstrate how reliable wildlife density estimates can contribute to the assessment of zoonotic risk associated with free-ranging wild game animals. Together with the studies on latent toxoplasmosis and neuropathology included in this SI, this work illustrates how understanding neuroparasitic diseases requires an integrated approach spanning environmental exposure, host ecology, infection dynamics and disease expression.

The contribution of Mahlangu and Van Zyl (Reference Mahlangu and Van Zyl2026) gave a spotlight on cerebral malaria caused by Plasmodium vivax, focusing on both how the infection damages the CNS and how properties of antimalarial drugs used for the treatment interact with the nervous system. Plasmodium vivax is traditionally considered less severe than P. falciparum; however, it is increasingly linked to serious neurological symptoms. The authors outline a multifactorial pathophysiology of the brain injuries, including microvascular obstruction, systemic inflammation, cytokine-mediated neurotoxicity and oxidative stress. They also review the pharmacological profiles of commonly used drugs like chloroquine, primaquine and tafenoquine, looking at how well they cross the blood–brain barrier, how they are metabolized and how they interact with brain receptors. Notably, primaquine carries the highest risk of neurological side effects, while tafenoquine is generally safer, and chloroquine has distinct neurological and cardiac risks. These differences highlight the vital importance of screening patients for G6PD deficiency and psychiatric history before starting treatment, and tailoring therapies to individual risk profiles.

Maciel et al. (Reference Maciel, Gomes Dos Santos, Silva, Arantes, Carlotti Junior and Pinto2026) examine the consequences of the intraventricular neurocysticercosis migration in CSF pathways and hydrocephalus onset, describing an illustrative case in which a free-floating cyst moved from the left lateral ventricle to the foramen magnum region after external ventricular surgical drainage. Reviewing 29 similar cases in the medical literature, the authors found that in over half of these instances, the cyst’s movement was triggered by medical interventions, like drainage or shunts, that may alter the natural flow of CSF.

The last contribution of human concern is by Islek et al. (Reference Islek, Ozeken, Uraz, Ucisik, Reis, Taskan and Sahin2026), which explores cerebral leishmaniasis from a cellular perspective, focusing on the role of astrocytes in the neuroimmune response to Leishmania infantum infection. Although Leishmania has traditionally been regarded as a macrophage-resident parasite, growing evidence indicates that it can invade the CNS and induce neurological manifestations. Using an in vitro model of infected murine astrocytes, the authors demonstrate that sodium perborate tetrahydrate reduces intracellular parasite persistence while modulating oxidative stress and inflammatory responses towards a host-protective phenotype. Their findings highlight the active contribution of astrocytes to the control of cerebral leishmaniasis and identify these cells as promising targets for future neuroimmune-based therapeutic strategies.

The CNS parasitism of veterinary concern is examined in 2 contributions beyond that of Vada et al. (Reference Vada, Zanet, Carpignano, Perrone and Ferroglio2026). In particular, Morganti et al. (Reference Morganti, Mandara, Tamponi, Varcasia, Scala, Zanet, Brustenga, Diaferia and Veronesi2026) reviewed neurotropic parasites of small companion animals. Beyond T. gondii and Neospora caninum, well-recognized causes of neurological disease, the authors considered a broad spectrum of protozoa, helminths, fungi and arthropods that can affect the nervous system of dogs and cats. Parasites with intrinsic neurotropism, such as Encephalitozoon cuniculi and Gurltia paralysans, but also agents that impair neurological function through ectopic migration of larvae, eggs or adult stages (Baylisascaris procyonis, Angiostrongylus cantonensis, Dirofilaria immitis, Spirocerca lupi, Cuterebra spp., Cryptococcus spp.), immune-mediated mechanisms (L. infantum), coagulation disorders (Angiostrongylus vasorum), electrolyte modifications (Toxocara canis) or neurotoxins (i.e. Ixodes holocyclus venom). Neurological complications related to antiparasitic treatment, including direct drug neurotoxicity and possible post-treatment neuroinflammatory reactions, are also discussed.

Brustenga et al. (Reference Brustenga, Giglia, Liyanage, Rigamonti, Loukopoulos, Fisher, Haining, Lucentini, Morganti, Moretta, Diaferia, D’avino, Gobbi, Ranucci, Passamonti, Jabbar, Hufschmid, Mandara and Veronesi2026), however, examined the neuroanatomical distribution of T. gondii in naturally infected red foxes (Vulpes vulpes) from Italy and Australia. Latent T. gondii infection has been associated with altered risk-taking and predator avoidance in several host species, but data on the localization of parasitic elements and lesions in free-living carnivores have been scarce. The study was conducted on brains from 100 foxes investigated through serology, histopathology, PCR and immunohistochemistry. The lesions detectable were distributed across the prefrontal and frontal cortex, basal ganglia, thalamus, amygdala, hippocampus and midbrain, regions involved in emotion, motivation, executive control and threat assessment. The pattern parallels that described in experimental murine models and is compatible with largely stochastic seeding of the brain rather than strict region-specific tropism. Nonetheless, the consistent involvement of key behavioural circuits provides a plausible neuropathological substrate for previously reported behavioural modifications in foxes and other intermediate hosts, with potential implications for predator–prey interactions and the eco-epidemiology of T. gondii.

It is hoped that the research and reviews conducted in the 11 papers published in this SI will encourage further multidisciplinary research and strengthen collaboration among parasitologists, neurologists, psychiatrists, veterinarians, immunologists, ecologists and public health professionals, reflecting the One Health perspective that underlies much of the work presented here.