Open access peer-reviewed chapter - ONLINE FIRST

Neurocysticercosis and the Central Nervous System: Advancements in Diagnosis, Treatment, and Future Prospects

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Nicholas Aderinto, Gbolahan Olatunji, Emmanuel Kokori, Ismaila Ajayi Yusuf, Chimezirim Ezeano, Muili Abdulbasit and Timilehin Isarinade

Submitted: 26 January 2024 Reviewed: 29 January 2024 Published: 10 June 2024

DOI: 10.5772/intechopen.1004554

Intestinal Parasites - New Developments in Diagnosis, Treatment, Prevention and Future Directions IntechOpen
Intestinal Parasites - New Developments in Diagnosis, Treatment, ... Edited by Nihal Dogan

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Intestinal Parasites - New Developments in Diagnosis, Treatment, Prevention and Future Directions [Working Title]

Prof. Nihal Dogan

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Abstract

Neurocysticercosis presents a formidable global health challenge. This parasitic infection induces cystic lesions, primarily in the brain and spinal cord, leading to neurological symptoms and complications. Global prevalence varies, driven by socioeconomic conditions, cultural practices, and dietary habits, particularly in low and middle-income countries. Diagnosis remains challenging, relying on clinical, serological, and neuroimaging findings, with advanced tools like CT and MRI scans enhancing accuracy. Treatment strategies involve antiparasitic medications, anti-inflammatory drugs, and surgical interventions. Ongoing research explores innovative diagnostics and treatments, emphasising a comprehensive, individualised approach. A One Health approach, integrating human, animal, and environmental health, is crucial for effective prevention. Exploring the socioeconomic impacts, ethical considerations, and technology integration, including telemedicine, is paramount. Understanding cultural factors influencing healthcare-seeking behaviour contributes to culturally sensitive interventions. Technology integration can improve diagnostic capabilities and healthcare access, especially in regions with limited resources.

Keywords

  • neurocysticercosis
  • Taenia solium
  • central nervous system
  • diagnosis
  • treatment
  • epidemiology

1. Introduction

Neurocysticercosis is a formidable intersection of parasitology and neurology, presenting a global health challenge [1]. This condition arises from the infestation of the central nervous system by the larval form of Taenia solium, the pork tapeworm [2]. Neurocysticercosis is a parasitic infection caused by the cysticerci of Taenia solium, primarily found in pork [3]. Upon ingesting undercooked or raw infected pork, humans become inadvertent hosts to the tapeworm larvae [4]. The larvae then migrate to various tissues, with the central nervous system being a prime target [5]. The resulting neurocysticercosis manifests as cystic lesions in the brain, spinal cord, or other neural tissues, leading to neurological symptoms and complications [6].

The impact of neurocysticercosis on the central nervous system cannot be overstated. Cysticerci in neural tissues triggers inflammatory responses and immune reactions, culminating in neurological symptoms such as seizures, headaches, and cognitive impairments [7]. The significance of this parasitic infection extends beyond its immediate clinical manifestations, as it poses substantial challenges to public health systems, particularly in regions where the disease is endemic [8]. Moreover, neurocysticercosis is a leading cause of acquired epilepsy worldwide. The burden of neurological sequelae resulting from this parasitic infection emphasises the necessity for advancements in diagnosis and treatment strategies [9]. Addressing neurocysticercosis not only requires a comprehensive understanding of its pathogenesis but also necessitates a holistic approach to mitigate the socio-economic impact on affected communities [10].

The link between the tapeworm Taenia solium and neurocysticercosis underscores the importance of studying this parasitic infection’s intestinal and neurological aspects [11]. The life cycle of T. solium involves a complex interplay between humans and pigs [12]. Understanding the dynamics of the tapeworm’s transmission from the intestines to the central nervous system sheds light on potential intervention points for preventing and treating neurocysticercosis [13]. This chapter explores the intestinal relationship between Taenia solium and neurocysticercosis, exploring the pathways of transmission, risk factors, and preventive measures.

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2. Epidemiology

2.1 Global prevalence and distribution

Neurocysticercosis exhibits a notable global prevalence, with specific regions experiencing a disproportionately high incidence. According to the World Health Organisation, neurocysticercosis affects around 50 million people worldwide and is a major cause of epilepsy and seizures across the globe [14]. The disease is associated with poor sanitation and is highly prevalent in Sub-Saharan Africa, Latin America and Asia [15]. Endemic hotspots include areas with poor sanitation and limited access to healthcare, particularly in low and middle-income countries. Latin America, sub-Saharan Africa, Southeast Asia, and parts of India have been identified as regions with a high prevalence of neurocysticercosis [16]. Within these areas, the transmission dynamics of Taenia solium, the causative agent, play a crucial role in shaping the epidemiological landscape [16]. Various factors contribute to the variations in neurocysticercosis prevalence across different regions. Socioeconomic conditions, inadequate sanitation infrastructure, and limited resources for public health interventions create an environment conducive to transmitting the parasite [17]. Furthermore, cultural practices, dietary habits, and local customs can influence the risk of infection, adding complexity to the epidemiological profile of neurocysticercosis [17].

2.2 High-risk populations

Neurocysticercosis often disproportionately affects individuals in lower socioeconomic strata [3]. Limited access to clean water, sanitation facilities, and healthcare services heightens the risk of infection [6]. Poverty-driven practices such as backyard pig farming and consumption of undercooked pork contribute to the prevalence of T. solium infestation in these vulnerable populations [9].

Cultural practices, including open defecation and insufficient hygiene practices, can facilitate the spread of T. solium eggs [18]. Dietary habits, especially the consumption of raw or undercooked pork in traditional dishes, contribute significantly to the transmission of neurocysticercosis. Understanding the interplay between culture, lifestyle, and disease transmission is crucial for effective public health interventions.

The ingestion of contaminated food, particularly undercooked pork containing viable cysticerci, serves as the primary mode of transmission for neurocysticercosis [12]. Improperly cooked pork acts as a vehicle for the tapeworm larvae, initiating the cycle of infection when consumed by humans. While less common, person-to-person transmission of neurocysticercosis can occur in specific circumstances. Poor hygiene practices, particularly in settings with inadequate sanitation, may lead to the faecal-oral transmission of T. solium eggs, perpetuating the infection cycle within communities.

Neurocysticercosis places a considerable burden on healthcare systems, particularly in regions with high incidence. The complex nature of the disease, coupled with the neurological complications it induces, demands specialised medical attention. Diagnostic challenges and the long-term management of affected individuals contribute to the strain on healthcare resources. The economic implications of neurocysticercosis extend beyond healthcare costs. The disease can lead to productivity losses due to the chronic nature of neurological symptoms, impacting affected individuals’ ability to work. Additionally, public health interventions and preventive measures require substantial financial resources, emphasising the economic burden of neurocysticercosis.

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3. Life cycle of Taenia solium

Taenia solium follows a complex lifecycle primarily involving humans and pigs and, less commonly, direct transmission between humans. Upon excretion of gravid proglottids or eggs from humans contaminating food and water, these proglottids or eggs find their way into the pig intermediate host [19]. When pigs ingest the tapeworm eggs, the eggs hatch, releasing oncospheres – young organisms encased in an embryonic shell [20]. These oncospheres travel through the pig’s vasculature, spreading to various body parts, including viscera, skeletal muscles, subcutaneous tissues, and the cerebral parenchyma [19].

In the human host, the lifecycle continues with the consumption of raw or undercooked pork containing tapeworm larvae, known as cysticerci. These cysts adhere to the small intestine, initiating a multi-month developmental process [21]. Mature tapeworms, reaching lengths of up to 8 meters [22], are morphologically characterised by four muscular, circular suckers, an anterior scolex, and a rostellum with two rows of hooks [23]. These features enable them to adhere to the intestinal wall with minimal inflammation, often leading to mild or no symptoms.

The maturation process culminates in the release of tiny segmented proglottids, each containing thousands of eggs (up to 60,000) and exhibiting uteri with side branches resembling a “Christmas tree” [24]. These proglottids detach from the tapeworm, pass through the digestive tract, and exit the human host through excrement. Failure to observe proper hygiene during food preparation can contaminate various food sources, setting the stage for potential foodborne infections [19]. Notably, the subtle proliferation of these proglottids poses a serious threat, particularly in regions where pigs have access to human waste or lax cleanliness regulations. Alternatively, T. solium eggs can be ingested directly through the faecal route. Due to their sticky nature, these eggs can persist on hands and surfaces for several months under specific conditions [19, 25].

Crucial stages in the life cycle involve tissue invasion and migration, initiated when cysticerci mature within the human intestine [26]. The larvae’s first stage’s oncosphere hatches inside the intestine and penetrates the intestinal wall. Subsequently, these larvae enter the bloodstream, migrating across different organs and tissues. The ability of cysticerci to spread throughout the body, including the central nervous system (CNS), introduces a range of possible clinical outcomes [25]. Once in the bloodstream, these larvae have the potential to migrate to various tissues and organs, with a higher likelihood of reaching the central nervous system. This migration to the CNS is particularly significant, presenting a spectrum of clinical consequences and potential complications [25].

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4. Transmission to the central nervous system

Rather than solely serving as the definitive host, humans can also act as the intermediate host for T. solium through feco-oral transmission [19]. Following ingestion, the eggs hatch into larvae within the human gastrointestinal tract [19]. This larval stage traverses the gastrointestinal tract walls, migrating to the tissues and causing tissue cysticercosis [19]. Host factors, including the immune system and specific genetic factors, influence the potential migration from the gastrointestinal tract to tissues [27]. Cysticercosis often exhibits a predilection for the brain, subcutaneous tissue, and the eye, although migration to other organs is possible [27]. Migration to the brain results in neurocysticercosis [27].

The encysted larva (cysticercus) gains access to the brain by disrupting the protective blood–brain barrier (BBB) and blood-cerebrospinal fluid barrier [28]. Studies in animal models of neurocysticercosis reveal increased expression of markers for BBB destruction, such as the endothelial barrier antigen and immunoglobulin G [28]. Upon entering the brain, the cysticercus may form either a parenchymal lesion within the brain substance or an extra-parenchymal lesion in the cerebrospinal fluid (CSF), subarachnoid space, ventricles, and cisterns [28].

Cysticerci exhibit remarkable longevity within the brain, often surviving for several years, achieved through modulation of the host immune system and the induction of immune tolerance [29]. This modulation involves the secretion of compounds such as prostaglandins and cytokines, including paramyosin and taenia-statin [29]. The cellular immune system is influenced by the induction of immunoregulatory cytokines like IL-10 and TGF-B [30]. Suppressed by the cysticercus, the immune system shifts to a Th2 response, facilitating the formation of a granuloma in the brain [30]. The granuloma comprises parasites, multinucleated giant cells, a surrounding fibrous collagen layer, CD68 macrophages, and various T cell subtypes [30].

While the cysticercus can inhibit the host system for extended periods, its modulatory effects eventually diminish [30]. Albendazole or Praziquantel initiates a switch to a Th1 immune response, leading to an inflammatory response and cyst degeneration [3, 30]. However, the degeneration of the cyst and the inflammatory response during treatment may exacerbate symptoms [3]. Therefore, anti-inflammatory medications such as corticosteroids are often prescribed with Praziquantel and Albendazole [31, 32]. Moreover, treating immunodeficiency states contributes to the reconstitution of the immune system against brain cysts [33]. Patients with neurocysticercosis (NCC) and human immunodeficiency virus (HIV) co-infections typically remain asymptomatic initially. However, after initiating antiretroviral therapy (ART), these patients develop robust cellular and humoral immune responses [33]. Following CNS access, the manifestations of neurocysticercosis vary, with clinical presentations determined by factors such as the number, location, size of cysts, cyst viability, and the host immune response [3].

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5. Diagnosis

Neurocysticercosis (NCC) presents a diagnostic challenge due to the difficulty in histologically confirming the presence of the parasite in most cases. As a result, the diagnosis is primarily based on a combination of clinical, serological, and neuroimaging findings. Recognising the ongoing difficulty of proper diagnosis, this section delves into a review of advanced diagnostic approaches used in identifying NCC.

5.1 Imaging

5.1.1 Computed tomography (CT) scan findings in neurocysticercosis diagnosis

CT is valuable for identifying calcifications in NCC. Calcifications resembling buckshot-shaped nodules, especially in endemic areas, indicate NCC. Well-defined, round cystic lesions with smooth walls, presenting a “Swiss cheese” appearance, are characteristic. CT also reveals pericyst inflammation through enhancement, indicating the degenerative process of cysts [34, 35, 36].

5.1.2 MRI in neurocysticercosis diagnosis

MRI improves soft tissue resolution and provides enhanced details. Viable cysts appear hypointense on T1 and FLAIR MRI scans. Contrast-enhanced MRI reveals unique enhancement patterns, aiding in differentiating cysticerci phases. MRI is superior at detecting meningeal involvement, offering extensive information on the central nervous system’s inflammatory response and disease severity [343637]. Despite advances in neuroimaging, diagnosing NCC remains challenging. Developed in 1996 and subsequently reviewed, diagnostic criteria include absolute major and minor neuroimaging criteria. These criteria aid in standardising the diagnosis [38, 39, 40].

5.2 Laboratory tests

5.2.1 Serological tests

Serum Western blot with a specific proportion of T. solium cysts is a successful method, confirming exposure or sickness precisely. Monoclonal antibody-based antigen detection assays are useful for verifying continued infection. The enzyme-linked immunoelectrotransfer blot test (EITB) is an effective serological technique, particularly for patients with multiple brain cysts [41, 42, 43, 44, 45].

5.2.2 Cerebrospinal fluid analysis

Serological tests in CSF, including ELISA, remain feasible options, especially in individuals with viable neurocysticercosis infections. Antigen detection in serum and CSF is a cyst viability biomarker crucial for monitoring anthelmintic medication effectiveness [45, 46, 47].

Clinical/exposure criteria, such as identifying specific antibodies or antigens, extraneural cysticercosis, evidence of household contact, and clinical signs, provide circumstantial evidence to support the diagnosis. Symptomatic NCC patients often present with seizures, headaches, focal neurologic abnormalities, and cognitive deterioration [40]. Definitive and probable diagnoses have evolved, incorporating neuroimaging criteria, clinical/exposure criteria, and additional evaluations. Criteria for definitive and probable diagnoses involve various combinations of neuroimaging and clinical/exposure criteria [40].

5.3 Advanced diagnostic tools

The widely accepted LLGP-EITB test is the standard for antibody detection, demonstrating remarkable diagnostic performance in clinical settings. Monoclonal antibody-based techniques, such as B158/B60 Ag-ELISA and HP10 assays, have emerged as effective tools for establishing the presence of live parasites. Recent research proposes innovative techniques, including urine assays for T. solium DNA and portable fluorescence sensors for on-the-spot diagnostics. Continued progress in neuroimaging, exemplified by portable MRI machines, enhances accessibility, particularly in low- and middle-income countries (LMICs) [18, 48, 49, 50, 51, 52, 53, 54, 55].

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6. Treatment

The therapeutic management of neurocysticercosis aims to alleviate symptoms, treat the parasitic infection, combat the inflammatory process, and manage complications. It is best approached from an individualised, patient-specific perspective [56]. The treatment approaches vary based on factors such as the viability of cysts, age (children or adults), location, number, and size of the cysts, among others. There are two major components to managing neurocysticercosis: pharmacological and surgical approaches.

6.1 Antiparasitic treatment

Antiparasitic treatment is recommended, and its use alone is reserved for patients without complications like untreated hydrocephalus, cerebral oedema, and other causes of raised intracranial pressure. The recommended antiparasitic regimen for cases with ≤2 viable parenchymal cysticerci is a monotherapy of oral Albendazole at 15 mg/kg/day divided into 2 daily doses for 10–14 days with food, up to a maximum dose of 1200 mg/day.

In cases with >2 viable cysticerci, combination therapy of albendazole (15 mg/kg/day PO in two divided doses) with Praziquantel (50 mg/kg/day in 3 divided doses) for 10–14 days is recommended [57, 58]. Albendazole impairs glucose uptake by the larvae and adult stages, depletes glycogen stores, and decreases adenosine triphosphate (ATP) production, leading to parasite death [59, 60]. Praziquantel causes rapid, sustained muscular contraction and tegumental disruption, exposing the parasite antigens to the immune system [59, 60].

6.2 Anti-inflammatory drugs

The inflammatory response against parasites is a significant pathological mechanism seen in neurocysticercosis. Anti-inflammatory treatment is indicated for parenchymal neurocysticercosis with Vesicular neurocysticercosis, solitary cysticercus granuloma, or cysticercotic encephalitis, and all cases of extra-parenchymal neurocysticercosis. Corticosteroids are the anti-inflammatory agents of choice, recommended in patients with different forms of neurocysticercosis [57, 58].

Some corticosteroids in use include Prednisone, Prednisolone, methylprednisolone, and dexamethasone. High intravenous doses (e.g., dexamethasone 0.2–0.4 mg/kg/day) are used in significant inflammatory responses, and the dosage is adjusted based on the size and number of parasites. The corticosteroids are gradually tapered off after the end of the cysticidal treatment or as long as inflammation persists [61]. For children and adolescents, dexamethasone dosage is 0.1 to 0.2 mg/kg/dose PO daily in oral solution, while for adults, it is 6 to 8 mg PO daily in 3 divided doses. Prednisolone and prednisone are also prescribed at 1 to 2 mg/kg/dose PO daily [57].

Other drugs used in managing neurocysticercosis include Anti-Epileptic Drugs such as carbamazepine, phenytoin, phenobarbital, and valproic acid, as epilepsy is a major symptom of neurocysticercosis. The treatment of epilepsy in neurocysticercosis follows the standard management for epilepsy from other causes [59].

6.3 Surgical management

Surgery is reserved for selected cases, playing a minor role in the overall management since most cases can be effectively managed with antiparasitic and anti-inflammatory drugs [60, 62]. Indications for surgical treatment include extraparenchymal neurocysticercosis with intraventricular cysts, hydrocephalus due to racemose cysts, or hydrocephalus due to ependymitis caused by neurocysticercosis. Surgical intervention is also considered for intramedullary and extramedullary spinal cysticercosis, large parenchymal colloidal cysts, subarachnoid racemose cysts causing mass effect, confirmation of the diagnosis of an atypical Solitary Cysticercus Granuloma, or in the case of surgery for intractable epilepsy associated with neurocysticercosis [63].

Surgical excision of cysts is the recommended treatment for intraventricular neurocysticercosis, especially lateral and third ventricular cysts. Endoscopic excision is minimally invasive, reducing the risk of complications associated with open craniotomy and minimising brain manipulation. The procedure involves placing a single burr hole in the pre-coronal region for access, grasping the cyst with forceps, and removing the entire scope assembly through the burr hole to prevent cyst loss or rupture in the ventricle [62, 63].

For managing hydrocephalus due to neurocysticercosis, surgical interventions such as fenestration of the anterior wall of the third ventricle and ventriculo-peritoneal shunt placement are considered. Hydrocephalus in neurocysticercosis arises from inflammation and mechanical obstruction from cysts or scars, affecting cerebrospinal fluid flow. Surgical excision of cysts usually relieves obstruction, but inflammatory reactions may persist, necessitating a ventriculo-peritoneal shunt to alleviate raised intracranial pressure and associated symptoms [59].

An alternative for managing hydrocephalus in neurocysticercosis is Endoscopic Third Ventriculostomy (ETV), providing an alternative route for cerebrospinal fluid flow directly from the third ventricle to the subarachnoid space, bypassing the fourth ventricle [64]. Combining cyst removal and ETV is less invasive than conventional craniotomies and avoids shunt-related complications [65].

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7. Challenges in management

7.1 Drug resistance

The management of neurocysticercosis involves addressing various factors, such as the severity of symptoms, extent of cyst involvement, stage of cyst degeneration, and accompanying inflammation, while also considering potential future complications. Treatment typically includes the administration of anthelmintic medications, such as albendazole and praziquantel, alongside anti-epileptic drugs to manage seizures and corticosteroids to reduce inflammation. Surgical procedures may be necessary for cases resistant to conventional treatment methods. While some treatments lack robust randomised studies, anecdotal evidence supports the use of anthelmintics with corticosteroids for viable cysts. The emergence of drug resistance remains a significant concern in the management of neurocysticercosis. However, reports of drug resistance in neurocysticercosis have not been widely reported. Resistance to first-line drugs of choice like albendazole is therefore subject to ongoing research.

7.2 Surgical complications

Surgical intervention plays a crucial role in managing neurocysticercosis, particularly in cases of intraventricular cysts or giant cysts unresponsive to medical treatment. The shift towards endoscopic procedures, performed through a single burr hole, has become preferable due to its minimally invasive nature [1]. Experienced surgeons can achieve good outcomes with minimal side effects, and concerns about anaphylactic reactions to cyst rupture during surgery have not been substantiated [66]. The complications usually seen in patients with neurocysticercosis are common to other neurosurgical procedures, such as wound infection, fistula formation, and reported cases of intraoperative or postoperative haemorrhage. Ventricular bleeding can be seen after neuroendoscopy. Rupture of interventricular or cisternal cysticercus during surgery is not associated with disease dissemination [1, 66].

The management of hydrocephalus stemming from subarachnoid neurocysticercosis often necessitates CSF drainage or shunt placement. Ventriculocisternostomy with third ventricle fenestration offers a potential alternative, potentially averting the need for a shunt device and improving prognosis. Common complications associated with shunts, such as malfunction or infection, contribute to morbidity. Surgical complications leading to patient mortality correlate with the frequency of shunt revisions, although corticosteroids may mitigate the risk of shunt dysfunction [67].

The management of large cysts within the lateral fissure is a topic of debate, typically necessitating surgical intervention when conservative treatments prove unsuccessful. Surgical resection may be considered following ineffective medical management. Overall, surgical management tends to yield positive outcomes in most cases [66]. Surgeons play a crucial role in assessing the patient’s clinical and radiographic features, customising the surgical approach to the specific characteristics and location of the cyst.

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8. Advancements in research

8.1 Emerging diagnostic technologies

Confirming neurocysticercosis (NCC) histologically is often not feasible, necessitating reliance on neuroimaging and immunological tests. Despite advancements in these diagnostic methods, identifying neurocysticercosis remains challenging due to the limited specificity of clinical and neuroimaging findings and the less-than-ideal predictive values of immunodiagnostic tests, particularly in regions where the disease is endemic [67]. This diagnostic challenge has, therefore, necessitated the need to develop universal diagnostic criteria for neurocysticercosis.

In 1993, criteria were proposed and later validated in a 1997 study involving 401 patients with seizures and a solitary brain mass on CT scans. In 2001, an international expert group introduced neurocysticercosis diagnostic criteria. Despite some criticism, these criteria remain essential for clinicians worldwide when dealing with suspected NCC cases [62]. In 2017, Del Brutto et al. updated the diagnostic criteria for NCC, emphasising neuroimaging to reduce false positives in endemic regions and enhance detection in non-endemic areas where NCC is often overlooked [1, 18]. The revised criteria state that definitive NCC diagnosis requires visible tapeworm scolex on neuroimaging. However, challenges such as limited access to neuroimaging, radiologist training issues, and high imaging costs pose obstacles, particularly in developing countries.

Simple, affordable, and efficient diagnostic tools are required to detect infections and at-risk populations. Research indicates the possibility of isolating T. solium DNA from patients’ urine, validated by positive Enzyme-linked immunoelectrotransfer blot (EITB) outcomes for anti-T. solium antibodies in individuals with subarachnoid and viable parenchymal cysts [67]. Using portable fluorescent sensors, capable of detecting antibodies and providing results for later examination on mobile devices, offers significant benefits in diagnosis and surveillance. Nonetheless, the sensitivity of urine tests is contingent upon the infection load. Similar to serological tests, they cannot pinpoint the location of cysts, whether in the central nervous system (CNS) or elsewhere in the body.

The real-time quantitative polymerase chain reaction (qPCR) test, targeting the repetitive Tsol13 sequence in the T. solium genome, demonstrates high sensitivity and specificity for Neurocysticercosis (NCC). This test serves as a marker for “cure” in cerebrospinal fluid (CSF) and offers a definitive diagnosis of NCC from plasma samples. Notably, all 18 CSF samples from patients with active NCC tested positive for T. solium DNA using the TsolR13 qPCR method [18]. Ongoing advances in neuroimaging are enhancing the early diagnosis and treatment of NCC. In a population study in Mexico, 9.1% of 155 asymptomatic, healthy patients revealed calcified lesions through MRI scanning. The approval of a portable MRI machine by the Food and Drug Administration (FDA) opens possibilities for increased accessibility to MRIs in hospitals and clinics, especially in Low- and Middle-Income Countries (LMIC) [68].

8.2 Novel treatment approaches

The search for innovative drug targets in treating neurocysticercosis and taeniasis is essential, considering the absence of recent clinical trials establishing specific indications, doses, and treatment durations for antihelminthic drugs. Despite debates on the safety and usefulness of anticysticercal treatment, there is a lack of vaccines or new drugs in the pipeline for clinical trials. Exploring tapeworm-specific detoxification pathways, non-canonical heat shock proteins, and their uniquely tailored proteome and metabolism could offer promising avenues for future drug intervention studies in neurocysticercosis [40].

Genome sequencing and mapping of parasitic tapeworms have unveiled approximately 250 to 300 novel protein kinases. These kinases, integral to major metabolic pathways of the parasite, emerge as potential targets. Notably, the mitogen-activated protein kinase (MAPK) family, including evolutionarily conserved extracellular signal-regulated kinases (ERK 1/2), plays a role in oestrogen-dependent reproduction of helminth parasites. Although the exact involvement of ERK 1/2 in host–parasite interaction remains unclear, the demonstrated role of an ERK-like protein suggests it could be considered a target for antihelminthic drug design [69].

In the same vein, sequences associated with a progesterone receptor have been detected in T. solium through RT-PCR and Western blotting, and an mRNA with sequence similarity to an oestrogen receptor has been demonstrated [69]. If steroidal hormone receptors exist in Taenia cysticerci, oestrogen receptor antagonists could significantly affect parasite transmission and development. Exploring the cysticidal effects of tamoxifen in T. solium may contribute to developing novel therapeutic agents for controlling cysticercosis in humans and livestock in future studies.

Antioxidant enzymes are vital for shielding parasites from host-induced oxidative stress (ROS) and are integral to numerous physiological functions. These enzymes, utilised by parasites for immune evasion, have been investigated in T. solium. The crystal structure of recombinant T. solium Cu/Zn-SOD was this organism’s first reported protein structure. T. solium expresses cytosolic Cu, Zn superoxide dismutase, a 2-Cys peroxiredoxin, and two glutathione transferase isoforms, all proven to protect mice against cysticercosis [70]. Their presence throughout developmental and adult stages highlights the pivotal role of antioxidant enzymes in T. solium physiology, suggesting potential for novel drug development.

Yan et al. [70] conducted a study identifying 197 novel proteases in T. solium, belonging to 37 families [69, 70]. These proteases were classified based on the active site amino acid residue into categories like aspartic, cysteine, serine, metallo-serine, and threonine proteases. This contrasts with a previous study [71] identifying only three putative proteases in T. solium [71]. The newly discovered proteases have potential implications for drug development, as they are believed to play crucial roles in various aspects of the parasite’s biology and interaction with the host immune system. Further exploration in this field is warranted.

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9. Future prospects

9.1 Potential vaccines

Vaccination is one of the most effective methods of treating various parasitic and infectious diseases and has successfully prevented major epidemics worldwide. Vaccines have been developed for infectious diseases such as malaria and typhoid, aiding in their treatment. In Addition, potential vaccines have also been developed for achieving herd immunity against pandemic diseases such as Ebola and coronavirus. No vaccines have been developed for treating neurocysticercosis or used in various clinical trials. However, some vaccines have been developed for pigs, which are being used in preclinical trials to pre-eliminate the parasite by preventing the transmission of the parasite from pigs to man since pigs are known to be an intermediate host of the diseases. Various vaccines, such as the recombinant oncosphere antigen, SP3VAC, pcDNA 3-B, and HP6/TSOL18, have been used in preclinical trials.

Recombinant oncosphere antigens are proteins cloned from Taenia solium oncosphere mRNA used to diagnose and manage Taenia solium-related diseases such as taeniasis and cysticercosis [72]. It has been found to be used as a vaccine through the development of proteins such as TSOL16, TSOL18, TSOL45-1A, and TSOL45-1B. these proteins have been used in various preclinical trials in pigs to evaluate their efficacy in protecting pigs against porcine cysticercosis (PCC). Of these vaccines, TSOL18 has been identified as the most effective candidate for protecting Pigs against PCC with a protection rate of 99.5% [1]. TSOL18, also known as Cysvax is a novel vaccine that was developed by Indian Immunological Limited and GALVmed and has been commercially available for sale and distribution in India since its formal licencing in 2016 [73]. Before it is licencing, it has been evaluated in various studies. For instance, Flisser et al [74] conducted a study evaluating the prevention of Pigs from PCC by vaccinating them with recombinant antigens TSOL18 and TSOL45-1A [74]. The study, which was conducted in Mexico and Cameroon showed a 100% protection rate from PCC through the use of these recombinant antigens. Other studies have also evaluated the combination of Cysvax with oxfendazole in the vaccination of pigs in Cameroon, Nepal, Uganda, and Tanzania, with a protection rate of>99% in these locations [75, 76, 77, 78].

SP3VAC is a synthetic vaccine composed of three peptides (GK1, KETc1, and KETc12) expressed in taenia solium larva and adult stages. This vaccine was developed and evaluated in pigs in Mexico by Huerta et al., [79]. Results from the study showed a reduction in the prevalence of cysticercosis by 52.6% and helped protect against PCC by 98.7%. Results from a further evaluation by Sciutto et al. in 2007 also supported the efficacy of SP3VAC on the protective effects of the vaccine against PCC [80]. However, the study concluded that a single vaccination dose is ineffective in preventing the transmission of taenia solium in endemic regions [80]. Other clinical trials have also shown the efficacy of SP3VAC in the vaccination of pigs though there are limited clinical trials conducted presently on the use of this vaccine in the last decade [80, 81, 82].

Other vaccines, such as pcDNA 3-B, and HP6/TSOL18 have been used in some studies to vaccinate pigs. A notable example is the study by Guo in 2007, which used pcDNA3-B, a DNA vaccine, in contrast to the common mRNA vaccines that are currently widely used [83]. This vaccine was developed by integrating Taenia solium B antigen with the pcDNA3.1 plasmid. Immunisation of the pigs with this vaccine showed a 92.6% protection rate, showing the effectiveness of this vaccine [84]. No studies have been conducted using this vaccine to date. HP6/TSOL18 is also an effective vaccine for protecting pigs against PCC. Just like the pcDNA-3B, this vaccine has also been evaluated in only one study to date, which was conducted by Parkhouse in 2008, [84]. However, further improvements in the vaccine from an intramuscular administration to an oral administration were shown in a study conducted by Monreal-Escalante et al., [85]. The study also showed its potential as an effective vaccine against PCC.

9.2 Collaborative research initiatives

Collaborative research initiatives, whether locally or internationally, have been significant in managing a disease since, through proper clinical research, novel initiatives for the diagnosis and treatment of diseases can be generated. In addition, Challenges facing the management of a disease can also be identified with proper recommendations to tackle the challenges provided. International collaborative research has also helped improve the stage of scientific research in low-income countries Regarding neurocysticercosis, there have been up to 7860 papers published from 1928 up till 2021, with a rate of 200 papers per year since 2010 [86]. Most of the literature published on neurocysticercosis is case studies, while the least are systematic reviews. The USA stands as the country that produces the highest number of publications on neurocysticercosis to date. Many publications are also produced by endemic regions such as India, Peru, and Brazil [85].

The level of collaborative research initiatives locally is high while the level of international collaboration is uneven, with large countries such as India and Brazil having 9.9 and 18.7% in international collaborations, while low-income countries like Peru, Tanzania, and Kenya showing heavy international collaboration in 80% of their papers generated from these countries [87] income countries (HICs) and low- and middle-income countries (LMICs).

In addition to diagnosing and treating the disease, collaborative research should focus more on developing vaccines to eliminate the parasite in humans. More focus should also be placed on vaccines such as pcDNA-18 and HP6/TSOL18, as they can potentially be a vaccine source for humans. A planetary and one health approach is also a significant area of focus for collaborative research through the dynamics of transmission of the disease between humans, animals, and the environment. This approach involves the integration of human, animal, and environmental health, which will enable the generation and implementation of policies that will help prevent the transmission rate of the parasite [87].

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10. Conclusion

This exploration of neurocysticercosis has uncovered critical insights into its complexities and offered a roadmap for future research and intervention. The understanding of T. solium’s intricate life cycle, particularly its neurological aspects, emphasises the need for a holistic approach considering both human and porcine dimensions. The global prevalence, shaped by diverse socioeconomic, cultural, and dietary factors, underscores the necessity for targeted interventions tailored to specific regions.

Diagnostic challenges persist, urging the continuous development of advanced tools such as CT, MRI scans, and serological tests. Treatment strategies, though in place, face challenges of drug resistance and surgical complications, necessitating ongoing research into innovative solutions. The significance of a One Health approach cannot be overstated, emphasising collaborative efforts across human, animal, and environmental health.

Socioeconomic impacts and ethical considerations highlight the broader implications of neurocysticercosis on communities, urging research to delve into economic burdens, productivity loss, and social stigmatisation. Integrating technology, particularly telemedicine, stands as a promising avenue for improving access to healthcare, especially in underserved regions.

Capacity building and training programs emerge as pivotal components, empowering healthcare workers and community health workers for more effective disease control. The collaboration of diverse stakeholders, including healthcare professionals, veterinarians, environmental scientists, and policymakers, is essential for a comprehensive and sustainable approach.

In envisioning the future of neurocysticercosis research, addressing these dimensions will not only enhance our understanding of the disease but also contribute to the development of practical, culturally sensitive, and globally applicable strategies for prevention, diagnosis, and treatment. As the scientific community collectively advances towards these goals, the potential for meaningful global health impact in the realm of neurocysticercosis becomes increasingly tangible.

List of abbreviations

NCC

neurocysticercosis

CT

computed tomography

MRI

magnetic resonance imaging

CNS

central nervous system

LMIC

low- and middle-income countries

FDA

food and drug administration

qPCR

quantitative polymerase chain reaction

CSF

cerebrospinal fluid

MAPK

mitogen-activated protein kinase

ERK

extracellular signal-regulated kinase

ROS

reactive oxygen species

EITB

enzyme-linked immunoelectrotransfer blot

SP3VAC

synthetic vaccine composed of three peptides (GK1, KETc1, and KETc12)

PCC

porcine cysticercosis

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Written By

Nicholas Aderinto, Gbolahan Olatunji, Emmanuel Kokori, Ismaila Ajayi Yusuf, Chimezirim Ezeano, Muili Abdulbasit and Timilehin Isarinade

Submitted: 26 January 2024 Reviewed: 29 January 2024 Published: 10 June 2024