Implications of Nano-Biosensors in the Early Detection of Neuroparasitic Diseases

Abstract

Parasitic diseases affecting millions of people globally cause fatalities and incapacitating conditions. It is, therefore, essential to detect parasitic diseases by looking for the parasite/s or their specific proteases that they produce at different phases of their life cycles. Numerous symptoms and indicators can result from a parasitic infection of the neurological system, but it is still challenging to diagnose an infection because the symptoms are frequently vague or minor. It is more likely that a parasite infection of the nervous system will be identified and treated well if one is familiar with fundamental epidemiological traits and distinctive radiography findings. For accurate diagnosis of these neurological disorders, proper identification and adoption of acceptable public health measures for the management of epidemic outbreaks are required. For numerous diseases, conventional in vitro techniques are time-consuming and need centralized facilities. So, the development of biosensor technology could lead to point-of-care diagnostics that are as accurate, fast, and affordable as or better than current standards. Modern biosensors include varied sensing techniques, such as optical, electrical, and mechanical transducers, as well as micro- and nanofabrication technologies. Only a handful of well-known biosensor examples have successfully transitioned from laboratory research to clinical applications despite the need for the medical community. Biosensor-based diagnosis of protozoan diseases like malaria, leishmaniasis, American trypanosomiasis (Chagas disease), and toxoplasmosis has been accomplished but is still in the infancy stage. In addition to the advancements in biosensors for the diagnosis of parasitic infections, we highlight the considerable challenges that must be overcome in order to bring integrated diagnostic biosensors into use in real-world scenarios.

Full text

43
© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2023
A. Gautam, V. Chaudhary (eds.), Theranostic Applications of Nanotechnology in
Neurological Disorders, https://doi.org/10.1007/978-981-99-9510-3_3
3
Implications ofNano-Biosensors
intheEarly Detection ofNeuroparasitic
Diseases
ShabirAhmadRather, RashaidAliMustafa,
MohammadVikasAshraf, M.A.HannanKhan,
ShoebAhmad, andZahoorAhmadWani
Abstract
Parasitic diseases affecting millions of people globally cause fatalities and inca-
pacitating conditions. It is, therefore, essential to detect parasitic diseases by
looking for the parasite/s or their specic proteases that they produce at different
phases of their life cycles. Numerous symptoms and indicators can result from a
parasitic infection of the neurological system, but it is still challenging to diag-
nose an infection because the symptoms are frequently vague or minor. It is more
likely that a parasite infection of the nervous system will be identied and treated
well if one is familiar with fundamental epidemiological traits and distinctive
radiography ndings. For accurate diagnosis of these neurological disorders,
proper identication and adoption of acceptable public health measures for the
management of epidemic outbreaks are required. For numerous diseases, con-
ventional invitro techniques are time-consuming and need centralized facilities.
So, the development of biosensor technology could lead to point-of-care diag-
nostics that are as accurate, fast, and affordable as or better than current stan-
dards. Modern biosensors include varied sensing techniques, such as optical,
electrical, and mechanical transducers, as well as micro- and nanofabrication
technologies. Only a handful of well-known biosensor examples have success-
S. A. Rather · R. A. Mustafa · M. A. HannanKhan
Department of Zoology, School of Biosciences and Biotechnology, Baba Ghulam Shah
Badshah University,
Rajouri, Jammu and Kashmir, India
M. V. Ashraf · S. Ahmad
Department of Biotechnology, School of Biosciences and Biotechnology, Baba Ghulam Shah
Badshah University,
Rajouri, Jammu and Kashmir, India
Z. A. Wani (*)
Division of Veterinary Parasitology, SKUAST-K, Shuhama, Jammu and Kashmir, India

44
fully transitioned from laboratory research to clinical applications despite the
need for the medical community. Biosensor-based diagnosis of protozoan dis-
eases like malaria, leishmaniasis, American trypanosomiasis (Chagas disease),
and toxoplasmosis has been accomplished but is still in the infancy stage. In
addition to the advancements in biosensors for the diagnosis of parasitic infec-
tions, we highlight the considerable challenges that must be overcome in order to
bring integrated diagnostic biosensors into use in real-world scenarios.
Keywords
Biosensors · Neurological diseases · Parasites · Diagnosis · Applications
3.1 Introduction
Infections of the central nervous system (CNS) are crucial because they compro-
mise central nervous system health (Sundaram etal. 2011). It has been estimated
that 25% of people worldwide are parasite-infected, with infections being more
common in developing rural areas and agriculture of subtropical and tropical coun-
tries (Youssef and Uga 2014).
It’s possible for human parasites to live in the CNS or another unusual area of the
body. Globally, CNS parasite infections are regarded as major causes of morbidity
and mortality. There are several distinct species that can be categorized as parasites,
including metazoans, which are multicellular organisms, and protozoa, which are
single-celled organisms (Carpio et al. 2016), which can be either free-living or
obligatory in nature (Walker and Zunt 2005). The majority of eukaryotic cells on
earth are protozoa, which are vital pathogens for humans as well as animals
(Zarlenga and Trout 2004), where they can cause extremely minor to serious, life-
threatening illnesses Lim etal., 2016).
Helminths wreak physical havoc on the tissues they inhabit, triggering a strong
inammatory reaction (Graeff-Teixeira etal. 2009). Humans are infected by a wide
variety of parasites, and occasionally a substantial number of these parasites move
to the central nervous system and cause illness (Nash 2014). Diseases caused by
soil-transmitted helminths, Toxoplasma gondii, Schistosoma, Taenia solium, and
Plasmodium can all result in neurological impairments (John et al. 2015; Abdel
Razek etal. 2011).
Molecular recognition of a target analyte is converted into a quantiable signal
by a transducer in a biosensor. The glucose sensor, which was rst introduced
30years ago in its current form and is still in use today, is the most well-known
example. It has completely changed how diabetes is managed. Assays using lateral
ow, such as those used in home pregnancy tests, are other prevalent examples
(Luong etal. 2008). Biosensors have the potential to provide a user-friendly, sensi-
tive, and affordable technology platform for infectious disease diagnosis and ther-
apy prediction (Foudeh et al. 2012). Low energy consumption, short test times,
multiplexing capability, and high portability are some benets, including small uid
S. A. Rather etal.

45
volume manipulation (cheaper cost and less reagent) (Whitesides 2006). Biosensors
that can carry out the intricate molecular tests necessary for many infectious dis-
eases have recently been developed as a result of recent advancements in micro- and
nanotechnology. Parallel to this, important strides have been achieved in our under-
standing of pathogen genomes, proteomics, and interactions with the host (Mairiang
et al. 2013). While biosensor-based immunoassays may boost the sensitivity of
pathogen-specic antigen detection, multiplex detection of host immune response
antibodies (serology) may increase overall specicity. Additional system integra-
tion might make it easier to build assays that incorporate both pathogen-specic
targets and indicators of host immune responses at various phases of infection
(Mohan etal. 2011).
The rst-ever Global Neglected Tropical Disease Day was founded in 2020 (on
January 30) to commemorate the recent advancements in the battle against diseases,
to inspire businesses and nations to take action in remembrance of the challenges
yet ahead, and to celebrate the achievements. Despite joint efforts to develop effec-
tive and safe treatments and remove vectors, precise and early identication is the
initial action needed to speed up the therapy. Some diseases can be quickly identi-
ed through clinical evaluation or pattern recognition of the physical symptoms,
while asymptomatic disorders and diseases that are just beginning to manifest are
more challenging to identify. The most common course of action, utilizing knowl-
edge of the pathogen genome and the host’s immunologic response, is a molecular
and serological diagnosis using techniques like enzyme-linked immunosorbent
assay (ELISA) and reverse transcription-polymerase chain reaction (RT PCR)
(Lammie etal. 2011).
The downsides of these and other tests include the need for high-quality person-
nel, pricey tools and chemicals, and time-consuming procedures along with inade-
quate infrastructure and resources. Furthermore, these tests continue to exhibit
cross-reactivity, such as with the arboviruses, dengue, and Zika (Zaidi etal. 2020),
as well as false-negative and false-positive results, as is seen in the case of SARS-
CoV-2 pandemic (Lorentzen etal. 2020). The creation of diagnostic systems that
can identify diseases in their earliest stages with high specicity, cheap cost, sensi-
tivity, and robustness while also being simple to use becomes of vital importance.
These benets of biosensors are in addition to the potential for the creation of min-
iature loco determination systems, which meet the needs of low-income nations and
remote areas like conict zones or native tribes.
With an emphasis on the differences between various signal transducer tech-
niques and their potential for clinical translation, this chapter focuses on develop-
ments in biosensor technology for neuro-parasitic disorders. Labelled and label-free
assays are the two types of detection techniques, among which label-free assays
directly detect the presence of an analyte through biochemical processes on a trans-
ducer surface (Rapp etal. 2010).
A biosensor is a sensing device or a measurement system that is specially created
for the estimation of a substance using biological interactions and then interprets
these interactions into a readable form using transduction and electromechanical
methods (Chaudhary etal. 2023). Figure 3.1 gives us information about the three
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

46
Fig. 3.1 Block diagram of biosensor
main components of a biosensor. These parts are the bioreceptor, the transducer, and
the detector in terms of the conceptual and fundamental manner of functioning. A
biosensor’s primary job or objective is to detect a substance with a biologically
specied composition. These substances frequently consist of proteins, immuno-
logical compounds, antibodies, enzymes, etc.
It is accomplished by utilizing a different physiologically delicate substance that
contributes to the creation of the bioreceptor. In other words, a bioreceptor is the
part of a biosensor that acts as a template for the substance to be detected.
Bioreceptors can be made from a variety of materials.
For instance, a protein is screened using its equivalent selective substrate, while
an antibody is screened using antigen and vice versa. The transducer system is the
second element. This device’s primary job is to electrically represent the interaction
between a bioanalyte and the appropriate bioreceptor. “Trans” signies change, and
“ducer” implies energy, according to the name itself.
Transducers, then, essentially change one kind of energy into another. The rst
form, which is produced by a particular interaction between the bioanalyte and bio-
receptor, is biochemical in nature, whereas the second form is typically electrical in
character. Transducers are used to convert the biological response into an electrical
signal. The detection system is the third element.
It does this by receiving the electrical signal from the transducer component and
amplifying it appropriately so that the related response can be correctly read and
analyzed. The availability of immobilization schemes that may be utilized to immo-
bilize the bioreceptor in order to increase the feasibility and efciency of its reaction
with the bioanalyte is a crucial necessity for nano-biosensors in addition to these
components. The performance of the systems based on this technique is also
impacted by changes in temperature, pH, interference with pollutants, and other
physicochemical uctuations, which makes immobilization the overall process of
biological sensing more affordable (Kissinger 2005).
In essence, nano-biosensors are nanomaterial-based sensors that are interestingly
not specialized sensors that can detect tiny events and occurring (Gautam 2022).
Nanomaterials, or materials with one of their dimensions between 1 and 100nm, are
a special gift that nanotechnology has given to humanity. These materials are
S. A. Rather etal.

47
extremely unique due to their size limitations. They differ greatly from the same
materials at the bulk scale in all signicant physicochemical aspects and have the
majority of their constituent atoms localized at or near their surface. They can per-
form extremely effective functions in the biosensor technology’s sensing mecha-
nism. Nanoelectromechanical systems (NEMS), which are highly active in their
electrical transduction mechanisms, are created when devices made of nanomateri-
als are integrated with electrical systems. On the basis of their electrical and
mechanical characteristics, a number of nanomaterials have been investigated for
use in enhanced biological signaling and transduction pathways.
Nanowires, nanotubes, nanoparticles, thin lms, and nanorods comprised of
nanocrystalline matter are a few examples of these materials that are frequently
used (Jianrong etal. 2004). Among these, the usage of nanoparticles has received
the most attention and analysis to date. The miracles of nanotechnological implica-
tions of the matter have made it feasible for nano-biosensors to play a very impor-
tant role in the development of biosensor technology (Chaudhary 2022).
Numerous studies throughout the world have looked into a wide range of bio-
sensing tools that use nanoparticles or nanostructures. These can range from
employing amperometric tools for the enzyme-based detection of glucose to using
quantum dots as uorescent agents for the binding detection to even using biocon-
jugated nanomaterials for targeted biomolecular detection. For use in immunosens-
ing and immunolabelling, they include colloidal nanoparticles that can bind to
antibodies. These components can also be employed to improve electron micros-
copy-based detections.
Additionally, metal-based nanoparticles are particularly good materials for elec-
tronic and optical applications. By utilizing their optoelectronic capabilities, these
nanoparticles can be effectively exploited for the detection of nucleic acid sequences.
The primary categories of nanomaterials used to improve upon the sensing mecha-
nisms now in use in biosensor technology are listed in Table3.1. It emphasizes the
potential benets of a number of nanomaterials used and some proof of their use
thus far.
Table 3.1 An overview of nanomaterial used for improving biosensor technology
Nanomaterial
used Benets References
Nanoparticles Aid in immobilization, enable better loading of bioanalyte,
and also possess good catalytic properties
Luo etal.
(2006)
Nanorods Good plasmonic materials which can couple sensing
phenomenon well and size-tunable energy regulation, can be
coupled with MEMS, and induce specic eld responses
Kabashin etal.
(2009)
Carbon
nanotubes
Improved enzyme loading, higher aspect ratios, ability to be
functionalized, and better electrical communication
Davis etal.
(2003)
Nanowires Highly versatile, good electrical and sensing properties for
bio- and chemical sensing; charge conduction is better
MacKenzie
etal. (2009)
Quantum dots Excellent uorescence, quantum connement of charge
carriers, and size-tunable band energy
Huang etal.
(2005)
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

48
In keeping with this theme, carbon nanotubes have also been employed to
enhance biosensing processes through their capacity to enable quick detection and
much-improved interactions between the analyte and the bioreceptor molecule. For
the detection of glucose (Chen et al. 2008) and insulin (Qu et al. 2006), carbon
nanotube-based biosensors have been in use. The text that follows discusses the
benets and results of using various nanomaterials, as well as their inherent advan-
tages and the crucial factors that can greatly affect their effectiveness.
3.2 Echinococcosis (Hydatid Disease)
Echinococcus granulosus and Echinococcus multilocularis are the two cestode spe-
cies that infect humans most frequently (Algros etal. 2003). Cystic hydatid disease
caused by endemic parasite E. granulosis is more frequently occurring in Latin
America, the Middle East, and the Mediterranean region (Al zain et al. 2002).
Alveolar echinococcosis (also known as alveolar hydatid disease) that is native to
China, Turkey, Alaska, and central Europe is caused by E. multilocularis. The para-
site can infect household dogs and cats, although its primary hosts are red and Arctic
foxes. According to epidemiological evidence, rodents and dogs or foxes can trans-
mit the E. multilocularis to each other as they come into contact with infected ani-
mals. More frequently, females and children suffer disproportionately in endemic
nations (Kern etal. 2003).
Canids like dogs and wolves have E. granulosus adults in their intestines (Bouree
2001). Following ingestion of egg by ungulates, the oncospheres swiftly move from
the small intestine to the liver before moving by lymphatic vessels or blood to the
lung, kidney, pericardium, vertebrae, periorbital tissue, and brain, where it develops
into hydatid cyst. Hydatid cysts, which are lled with a serous uid containing sco-
lices, also develop in infected humans (Garret etal. 1977). Solitary hydatid cysts
form in the liver as a result of the majority of infections. However, unlike E. granu-
losus, E. multilocularis mostly affects the liver. It can also spread by blood or lym-
phatic channels to other organs. Hydatid cysts are usually taken up by canids along
with infected offals, where multiple scolices get released, and they penetrate deeply
between villi into the crypts of Liberkuhn and develop to maturity in about 47days.
Echinococcosis patients frequently have elevated erythrocyte sedimentation rate
(ESR) and serum eosinophilia. Eosinophilia in the cerebrospinal uid (CSF) is nor-
mally absent because echinococcal infections are encapsulated. A veterinarian
ought to be consulted when echinococcal infection in humans is identied because
farm animals or domestic pets, particularly dogs, are frequently the source of the
infection. Serum indirect hemagglutination (IHA), indirect uorescent antibody
(IFA), and enzyme-linked immunosorbent assay (ELISA) can all be used to conrm
the diagnosis of E. granulosus infection, approximately 98% for patients with
hepatic cysts, while the test sensitivity values range from 50% to 60% in patients
with pulmonary cysts. Serum assays to identify E. multilocularis are more accurate
and non-cross-reactive than those to identify E. granulosus (Jiang etal. 2001). A
negative antibody detection test does not rule out the diagnosis of Echinococcosis
S. A. Rather etal.

49
because some cyst carriers do not produce detectable antibody levels. Serological
testing is not advised as a way to gauge treatment effectiveness because it cannot
predict CNS involvement (Gottstein 1992).
3.2.1 Biosensor Application forDiagnosis ofEchinococcosis
A dreadful parasitic disease that affects millions of people worldwide is echinococ-
cosis and has had disastrous impacts on animal husbandry because it has been
neglected. Recent studies have focused on a number of characteristics of E. granu-
losus, including its global distribution, pathology, diagnostic techniques, and inno-
vative therapeutics for both humans and animals (Wen et al. 2019; Eckert and
Thompson 2017). Despite the fact that this zoonotic parasite can be diagnosed in a
number of ways, many of these tests are expensive, complicated, and call for spe-
cialized training. The imaging techniques, like ultrasonography and radiography
(X-ray), are among the popular methods used to screen the population at a fair price
(Wen etal. 2019). According to McManus etal. (2012) and Gottstein etal. (2014),
serology tests are also frequently used to identify indicators from the host (markers
of inammation, cytokines, or chemokines) and parasite (circulating antigens or
DNA). For the diagnosis and management of echinococcosis, practitioners can now
adhere to precise manuals and algorithms (Wen etal. 2019; Brunetti etal. 2010).
Cystic echinococcosis (CE) is diagnosed in the lab using a variety of substances,
including antibodies, antigens, and cytokines. The lack of sensitivity and/or insuf-
cient specicity of these methods, however, make them unsuitable as reliable diag-
nostic tools (Siles-Lucas et al. 2017). Furthermore, they call for particular
infrastructure congurations and qualied employees. Due to the advancement of
nanotechnology, the creation of biosensors for the diagnosis of echinococcosis has
currently achieved signicant advancements. Using the near-infrared transmission
angular spectra of porous silicon microcavities, an efcient method for an optical
biosensor for the diagnosis of cystic hydatid disease was developed by Li etal. in
2017. A more recent study (Darabi etal. 2019) found that in silico design and evalu-
ation was an effective way to identify the antigens present in hydatid cysts. To
swiftly, precisely, and effectively detect parasites, viruses, etc., researchers have
been creating portable electroanalytical biosensing equipment or analyzers. More
straightforward and quick methods are still desperately needed despite recent sig-
nicant advancements. Because of their mechanical and chemical characteristics,
which are useful in both veterinary and human health, nanoparticle-based biosen-
sors are greatly desired (Cesewski and Johnson 2020; Moulick etal. 2017).
The use of nanometal products has brought attention to the need for efcient
parasite management techniques, but the nanoparticles will likely contaminate the
environment (Lin etal. 2010), necessitating the establishment of safe use proce-
dures and toxicity thresholds to reduce the impact on helpful bacteria, animals,
and the food chain (Kahru and Dubourguier 2010). Gold, silver, chitosan, and
oxidized metals have been shown to have antiparasitic and inhibitory effects on
protoscolices in a number of studies. Mahmoudvand et al. (2014) employed
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

50
different quantities (50–500mg/mL) of selenium nanoparticles (in the size range
of roughly 80–220nm) for 10–60min. According to the ndings (Mahmoudvand
etal. 2014), biogenic Se-NPs at all concentrations have strong scolicidal effects,
particularly at concentrations of 500 and 250mg/mL after 10 and 20min of appli-
cation, respectively.
Ag-NPs had the most powerful scolicidal effects, according to the results of
Norouzi (2017), and can therefore be employed in CE surgery. Malekifard (2017)
looked at the effectiveness of gold nanoparticles on hydatid cyst scolices and found
that all concentrations of gold nanoparticles had substantial scolicidal effects. All
protoscoleces were killed within 60min by gold nanoparticles at a concentration of
1mg/mL (Malekifard 2017). Previous research (Rahimi etal. 2015) looked into the
scolicidal effects of green-produced silver NPs at various concentrations (0.025,
0.05, 0.1, and 0.15mg/mL) and exposure times (10, 30, 60, and 120min) against
protoscolices of CHD.The results demonstrated that Ag NPs had signicant scoli-
cidal effects at all doses. After 120min of exposure, the doses of 0.1 and 0.15mg/
mL indicated mortality rates of 83% and 90%, respectively. Ag-NPs produced by
biosynthesis had a 40% scolicidal activity at 0.025mg/mL for 10min. According to
a report, because they are more affordable, safe, and nontoxic than the commonly
utilized chemical materials, biogenic Ag-NPs may be taken into consideration as a
viable scolicidal agent for CHD surgery.
The study by Safarpour etal. (2021) suggests an easy, reliable, and useful
method for echinococcosis diagnosis. This procedure is based on the develop-
ment of a sandwich complex between chitosan-gold nanoparticle protein A and
an anti-Ag B antibody-bound hydatid cyst antigen (Ag B). By observing a
change in color that does not change in the absence of an Ag B biosensor, quick
colorimetric results can be obtained. Notably, it also describes a eld-applicable
method based on blood samples for the prompt detection of infected cases with-
out the need for expert staff or sophisticated equipment. Gold nanoprobes have
a long history of usage in biosensing, notably when used to detect DNA, which
has been well established.
The detection of the microorganisms that cause tuberculosis and malaria was
accomplished in a beautiful work by multiplex non-cross-linking colorimetric tech-
nology (Veigas etal. 2015). Chitosan has reportedly been used in the past to improve
the production of gold nanoparticles and cause observable color changes, according
to Mohan etal. (2019). It has been suggested that chitosan-capped gold nanoparti-
cles or gold nanoparticles functionalized or stabilized with organic polymers, such
as chitosan nanocomposites, are the best delivery systems since they do not have the
toxicity like that of other chemical reagents (Abrica-Gonzalez etal. 2019; Saeed
etal. 2020).
As a matter of fact, chitosan-based biosensors have shown good sensitivity, sta-
bility, and selectivity for the detection of a variety of targets, proteins, DNAs, bac-
teria, glucose, and a number of tiny biomolecules (Jiang and Wu 2019; Shrestha
et al. 2016). Unexpectedly, colorimetric biosensors and gold nanoparticles have
demonstrated considerable uses in diagnostics (Chang et al. 2019; Aldewachi
etal. 2017).
S. A. Rather etal.

51
3.3 Schistosomiasis (Bilharzia)
The ve species of blood ukes (digenetic trematodes), Schistosoma mekongi,
Schistosoma japonicum, Schistosoma haematobium, Schistosoma intercalatum, and
Schistosoma mansoni are responsible for schistosomiasis, which affects up to 300
million people annually globally (El-Garem 1998). Three of the ve species
S. japonicum, S. haematobium, and S. mansoni have been implicated for their role
in the pathology of the central nervous system (CNS) (Pittella 1997). At least 30
other mammals are similarly susceptible to infection, but humans are the only
known hosts.
Schistosomiasis is considered a “man-made disease” by some specialists since it
gets transmitted when one comes in contact with water as endemicity necessitates
the presence of an intermediate mollusk host (aquatic or amphibious snails) (Zheng
etal. 2002).
In general, endemicity rates are greater in nations with inadequate sanitary
infrastructure and access to clean water. Unfortunately, by damming up or irrigat-
ing with contaminated diseased water in impoverished nations in an effort to
enhance inadequate sanitary conditions and water supplies, endemicity is fre-
quently increased (Babiker etal. 1985). Moreover, travelers who are cautioned to
avoid drinking tap water in countries where the schistosome is prevalent fre-
quently ignore less obvious ways to contract it, such as washing clothes, going
barefoot, and bathing.
The furcocercous cercariae pierce human skin and cause the rst infection. The
larva migrates into the venous system, preferring venules and venous plexi, after
shedding its tail. Schistosomiasis’s clinical signs can appear at various phases of the
parasite’s life cycle and vary depending on the species that is infected.
The preferred locations in the human body for each of their distinct species are
peribladder veins (S. haematobium), superior mesenteric veins (S. japonicum), or
mesenteric veins (S. mansoni), (Pollner etal. 1994). Sixty percent of all schisto-
somal brain infections are caused by S. japonicum eggs, which are smaller than
eggs from other schistosomal species. In contrast, S. mansoni eggs, which are
larger, typically only cause spinal cord infections (Pittella 1994). According to
Scrimgeour and Gajdusek (1985), S. haematobium can infect either the spinal
cord or brain.
The CNS is not believed to be a place where adult worms travel, nor is it believed
that worm eggs develop into worms there. It is hypothesized that Batson’s plexus
serves as a route for entry into the central nervous system. Once within, eggs cause
a granulomatous reaction as tissues work to enclose the invading parasite.
Granulomas have exudative and necrotic characteristics after persistent infection.
Vascular walls and nearby tissue can both have severe necrosis (File 1995).
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

52
3.3.1 Biosensor-Based Diagnosis ofSchistosomiasis
The Schistosoma genus of trematodes worms causes the neglected tropical disease
known as schistosomiasis. It is the second-most common parasitic disease globally.
S. mansoni, S. japonicum, and S. haematobium are the principal disease-causing
species. In Mediterranean Europe, Southeast Asia, sub-Saharan Africa, South
America, and the Middle East, 779 million people are at risk of catching HIV, and
it has the potential to affect up to 300 million people annually. Non-endemic areas
are also susceptible to it. Schistosomiasis in humans is one of the most common
parasite illnesses. Particular freshwater snails act as intermediary hosts in the trans-
mission cycle, which involves the contamination of surface water with excrement
(de Albuquerque et al. 2020; Gryseels et al. 2006; McManus et al. 2020).
Schistosomiasis can be managed by both prevention and treatment. The two most
important ways to avoid schistosomiasis are to improve cleanliness and get rid of
snail hosts. To assess the success or failure of schistosomiasis control programs and
to ascertain whether control efforts have led to elimination, precise and sensitive
diagnostic tests are needed.
Diagnoses for schistosomiasis are crucial for identifying and treating infections
in both prevalent and non-prevalent locations because they inform case detection,
morbidity estimations, and control strategies (Ajibola et al. 2018; Odundo
etal. 2018).
Schistosomiasis can currently be diagnosed by molecular, immunological, and
conventional parasitological techniques (Katz etal. 1972). Utilizing a microscope to
identify parasitic eggs in the urine and feces or using an immunological method
(antibody or antigen detection) are two common classical parasitological techniques
(van Etten etal. 1994; Odundo etal. 2018). According to Caldeira etal. (2012), the
Kato-Katz approach is affordable and practical and gives a high level of specicity.
The sensitivity of the test depends on the severity of the sickness, the method, and
the post-infection host’s perception.
According to Odundo etal. (2018), only 65–86% of existing antibody analyses
are fully understood. Recently, clinical sciences and food and drug analysis process
control have given screen printing electrode biosensors a lot of attention. These sen-
sors are capable of measuring extremely small concentrations of analytes by identi-
fying changes in potential, current, and conductance brought on by an immunological
response (Taleat etal. 2014). According to Lin etal. (2008) and Yang etal. (2009),
nanotechnology has been utilized to improve and increase the correctness of exist-
ing procedures as well as unexpectedly produce new ones. The creation of extremely
sensitive, adaptable diagnostic care devices has shown signicant promise when
using NPs in immunosensing (Dequaire etal. 2000; Baptista etal. 2008; Wan etal.
2013). Table3.2 lists a variety of nanosensors that have been utilized to improve the
detection of schistosomal infections.
In order to identify the S. mansoni genome, Santos et al. (2019) created an
impedimetric biosensor. Using cyclic voltammetry and electrochemical impedance
spectroscopy, the biosensor was identied. With a limit of detection of 0.6pg/L, the
created genosensor could identify minute amounts of S. mansoni DNA.
S. A. Rather etal.

53
Table 3.2 List of nanosensor/nano-material used in improving the diagnostic ability against
schistosomal infections
Nanosensor
nano-materials
used Efcacy
Schistosomes
spp. References
GICA GICA identication strips of S. japonicum in
mice, rabbits, buffaloes, and goats show high
sensitivity (100% in each spp.) and specicity
(100%, 100%, 94.23%, and 88.64%,
respectively). When compared with ELISA, the
GICA strips exhibited similar sensitivity and
specicity in the diagnosis of schistosomiasis in
mice, rabbits, buffaloes, and goats. Besides,
only 5μL of serum is required for the test, and
the detection can be completed within 5min
S. japonicum Xu etal.
(2017)
AuNPs-Mab/
ELISA
ELISA’s sensitivity and specicity for detecting
circulating schistosomal antigen (CSA) using
AuNPs-Mab was 100% and 97.8%. A more
signicant positive correlation was detected on
the use of AuNPs-Mab/ELISA (r=0.882).
Loading AuNPs with Mab (6D/6F) improved
the precision of sandwich ELISA for the
determination of CSA, allowing active and mild
infections to be identied easily
S. mansoni Kame etal.
(2016)
MPTS-
AuNPs-DNA
probe system
The proposed biosystem detected the S.
mansoni genome sequence in urine samples,
cerebrospinal uid system, and serum in
varying amounts. It measured concentrations in
urine (27–50pg/L), cerebral uid (25–60pg/L),
and serum (27–42pg/L). The limit detection
(LOD) of the biosensor was 0.6pg/μL.The
developed labeled free genosensor was able to
detect small concentrations of S. mansoni DNA
in complex biological uids
S. mansoni Santos
etal.
(2019)
AuNP-IgG
nanosensor
Immobilized AuNPs combined with bilharzia
antibodies proved their diagnostic potential.
The detection range of bilharzia antigen in stool
samples was 1.13×10−1ng/mL to 2.3×103ng/
mL, with a detection limit of 8.3887×10−2ng/
mL, showing the ability of the nano biosensor
for detection of bilharzia antigen in stool
samples
S. mansoni Odundo
etal.
(2018)
(continued)
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

54
Table 3.2 (continued)
Nanosensor
nano-materials
used Efcacy
Schistosomes
spp. References
MBA-Fe3O4-
NPsAuNPs-
DNA probe
system
On the changed surface of the electrode, the
probe system exhibits an efcient
electrochemical response. At varied DNA
quantities in the genome, the proposed
biosystem was capable of identifying S.
mansoni unique nucleotide sequences in
cerebrospinal uid (CFS) and blood samples.
At higher DNA concentrations, bio-recognition
caused an increase in electron transfer
resistance and a decrease in current peaks
during electrochemical testing. The established
platform had detection limits of 0.781 and
0.685pg/L DNA for serum and CFS,
respectively
S. mansoni Santos
etal.
(2017)
AuNP-IgG
conjugate
Conjugate was tested as the analyte with a
differing concentration of conjugate soluble egg
antigen (SEA). The single response was directly
proportional to the SEA concentration. A SEA
concentration plot against the current change
was obtained. The detection limit of
3.31×10−5ng/mL was obtained with formula
3σ/slope, where σ is the standard deviation of
three blank solutions
S. mansoni Naumih
etal.
(2016)
NCE-AGs The proposed NCE electrode’s quantitative
response and great sensitivity to Abs of S.
mansoni are as low as 38pg, indicating that it
may be developed as a site-user, low-cost, and
rapid electrochemical immuno-sensor
S. mansoni Shohayeb
etal.
(2016)
Table 3.3 provides an overview of a number of biosensors developed for the
detection of schistosomiasis. Schistosomiasis is the second most common parasite
disease in the world, yet little is being done to create biosensors for early detection
of the condition. There aren’t many articles on this topic that have been published,
and the ones that have are often lacking in gures of worth and terms of optimiza-
tion. The only study that described a genosensor for S. haematobium detection using
RNA isolated from adult worms as the analyte was by Mach etal. (2015). However,
various study teams have sought to demonstrate the viability of such a development
because the systems testing shows no differences from those seen for other disor-
ders that are obviously present. When contrasted, the detection systems were even
more adaptable, allowing for the development of novel and improved devices. These
techniques included AP, DPV, ASV, QCM, and EIS, as well as specialized electro-
chemical markers like silver, tetramethylbenzidine, ferrocene, and ferro/
ferricyanide.
S. A. Rather etal.

55
Table 3.3 Electrochemical biosensors for Schistosomiasis disease diagnosis
Sensor Electrode Analyte Technique Modication Sample Reference
Immunosensor GQC Rabbit anti- S. japonicum SEA QCM MPA/ME/SjAg Rabbit serum Wang etal.
(2012)
Immunosensor MPPCPE Rabbit anti-Schistosome
labelled with colloidal gold
ASV Fe3O4/Au/MCH/EDC/NHS/SEA Rabbit
antibodies
Xu etal. (2010)
Immunosensor NCE Anti-S. mansoni DPV GA/CS/schistosomiasis antigen Synthetic
antibodies
Shohayeb etal.
(2016)
Immunosensor GQC SjCAg QCM ImRS/NRS or SPA/InRS Rabbit and
human serum
Wen etal.
(2011)
Immunosensor SPCE-16 Anti- S. japonicum SEA CV EDC/NHS/SEA/SjE16 Human serum Deng etal.
(2013)
Immunosensor SPCE Inhibitor of S. japonicum DPV GA/SEA Human serum Zeng etal.
(2012)
Immunosensor NCE Anti S. mansoni DPV GA/CS/schistosomiasis antigen Synthetic
antibodies
Shohayeb etal.
(2016)
Genosensor Au Schistosoma DNA and genomic
material
EIS MBA/EDC/NHS/Fe3O4NPs/AuNPs/
thiolated oligonucleotide probe
Human
specimens
Santos etal.
(2017)
Genosensor Au RNA extracted from S.
haematobium eggs
AP Thiol/capture probe Human urine Mach etal.
(2015)
Genosensor Au S. mansoni DNA EIS
CV
AuNPs/MPTS/oligonucleotide probe Human
specimens
Santos etal.
(2019)
Immunosensor SPGE Mouse Schistosome SEA DPV
CV
AuNP-rabbit anti-schistosome Stool sample Odundo etal.
(2018)
MPA mercaptopropionic acid, MCH 6-mercapto-1-hexanol, ME mercaptoethanol, SjAg Schistosoma japonicum antigen, NHS N-hydroxysuccinimide, EDC
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide, SPA Staphylococcal protein A, SEA native soluble egg antigen, ImRS immunized rabbit’s sera, InRS infected
rabbit’s sera, GA glutaraldehyde, MBA mercaptobenzoic acid, SjE16 Schistosoma japonicum calcium-binding protein, Fe3O4 AuNP-IgG gold nanoparticle-anti-
bilharzia conjugate, NP magnetite nanoparticles, SjCAg Schistosoma japonicum circulating antigens, MPTS mercaptopropyltrimethoxysilane, AuNPs gold
nanoparticles, MPPCPE magnetic porous pseudo-carbon paste electrode, GQC gold quartz crystal, SPCE-16 16-channel screen-printed carbon electrode array,
NCE nanocarbon-screen-printed electrode, SPCE screen-printed carbon electrode, Au gold, SPGE screen-printed gold electrode, QCM quartz crystal microbal-
ance, ASV anodic stripping voltammetry, EIS electrochemical impedance spectroscopy, DPV differential pulse voltammetric, CV cyclic voltammetry, AP
amperometry
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

56
3.4 The Role ofBiosensors intheEarly Detection
ofCerebral Malaria
Malaria, spread by the female Anopheles mosquitoes, is still a signicant parasite
disease that affects humans globally. The disease is mostly prevalent in tropical and
subtropical regions around the world (Jain etal. 2014; WHO 2018). The endemic
countries, which are primarily malaria, spread by the female Anopheles mosquitoes,
is still a signicant parasite disease that affects humans globally. The disease is
mostly prevalent in tropical and subtropical regions around the world (Jain etal.
2012; WHO 2018). The endemic countries, which are primarily developing nations,
bear a heavy economic cost from the disease. A parasitic alveolate protozoan
belonging to the genus Plasmodium is the causative agent of malaria. There are six
species in this genus, which are known to infect humans: Plasmodium vivax,
Plasmodium cynomolgi, Plasmodium malariae, Plasmodium falciparum,
Plasmodium ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri), and
Plasmodium knowlesi. Considering the World Health Organization’s (WHO) target
of eradicating malaria by 2030, the goal can only be reached if every case is cor-
rectly diagnosed and handled (Feachem etal. 2019). Routine testing in suspected
cases is still unavailable to some of the endemic communities. For instance, in pub-
lic health institutions in 2018, only 74% of individuals who had malaria suspicions
had access to testing procedures (WHO 2018). During this time, there were 228
million cases worldwide, with 405,000 fatalities (WHO 2018).
Various control measures have been successful, but they have been constrained
by inadequate early diagnostic techniques for identication, particularly in low par-
asitemia conditions. The identication of asymptomatic people has a signicant
impact on the malarial dynamics including its spread, control, and perhaps treat-
ment. Diagnostic procedures may aid medical professionals in pursuing additional
research into other febrile illness etiologies, preventing severe illness and likely
death, and minimizing the presumed usage of antimalarial medications and their
related side effects (White 1991).
Numerous technologies have up to now tried to get around the difculties in
diagnosing malaria by focusing on rapid diagnostic requirements and early-stage
detection of cerebral malaria. Therefore, the chapter thoroughly reviews the most
current developments in biosensor technology in this area, with an emphasis on
analytical performances, development, and applicability for rapid diagnosis of the
most targeted biomarkers of malaria.
3.4.1 Role ofCerebral Malaria-Related Complications
inNeurodegenerative Diseases
Cerebral malaria is a severe and potentially life-threatening complication of malaria
caused by the parasite Plasmodium falciparum (Fig.3.2). It occurs when infected
red blood cells adhere to the blood vessel walls in the brain, leading to inamma-
tion, impaired blood ow, and the accumulation of infected cells, causing cerebral
S. A. Rather etal.

57
Fig. 3.2 Life cycle of Plasmodium spp. (Adapted from Krampa etal. 2020)
edema and increased intracranial pressure. In some cases, this can result in seizures,
coma, and death if not promptly treated. While the immediate consequences of cere-
bral malaria are primarily related to acute brain injury, there may be long-term neu-
rological consequences, potentially linking it to neurodegenerative diseases.
Persistent immune responses triggered by the parasite or residual parasites in the
brain could create a pro-inammatory environment that leads to neuronal dysfunc-
tion and degeneration, similar to what is observed in certain neurodegenerative dis-
orders. Chronic inammation and neuronal damage associated with cerebral malaria
may contribute to the development or exacerbation of neurodegenerative conditions
such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis
(ALS). However, further investigation is needed to establish a direct causative rela-
tionship between cerebral malaria and these neurodegenerative diseases, as various
factors can inuence their development and progression. Understanding the poten-
tial long-term neurological implications of cerebral malaria could aid in developing
targeted therapies to mitigate its impact on brain health.
3.4.2 Biosensors-Based Detection ofMalarial Biomarkers
With numerous analytical advantages and cost-effectiveness, biosensors and immu-
nosensors have emerged as promising sensing instruments in recent years (Perkins
and Bell 2008; Turner 2013). This development has been inuenced by the rising
demand for point-of-care diagnostic devices. Electrochemical biosensors are one of
the sensor types that have drawn a lot of attention in diagnostics due to pivotal
design benets, ease of handling and better performance over traditional laboratory
methods (Belluzo etal. 2008; Wang 2008). As attempts are made to improve and
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

58
miniaturize sensor systems to make them easily operable, these properties make
them suitable for point-of-care use. Table3.4 summarizes different biosensor-based
detection methods for malarial parasites.
Table 3.4 Biosensor detection of various malaria biomarkers
Analytes Sensing technique Transducer Biomarker
Receptor
molecule Reference
Antigens Colorimetric – pLDH
(PvLDH,
PfLDH)
pL1 aptamer Jeon etal.
(2013)
EIS Gold
electrode
pLDH pL1 aptamer Lee etal.
(2014)
EIS GCE pLDH P38 aptamer
(90 mer
ssDNA)
Jain etal.
(2016)
EIS GCE HRP-2 Anti-HRP-2
antibody
Brince etal.
(2016)
Chemiresistive
(electrical
conductance)
– PfHRP-2 Anti-HRP-2
antibody
Paul etal.
(2017)
– – PfHRP-2 Anti-PfHRP-2 Gikunoo
etal. (2014)
EIS Gold disc
electrodes
PfGDH ssDNA
aptamer
(NG3)
Singh etal.
(2018)
Potentiometric
(FET)
Gold
micro-
electrodes
Pf GDH ssDNA
aptamer
(NG3)
Singh etal.
(2019)
Amperometric Gold-SPE PfHRP-2 Anti-PfHRP 2
mAb
Hemben
etal. (2017)
Amperometric Gold-SPE pLDH pLDH capture
antibody
Hemben
etal. (2017)
Spectrophotometric
indicator
displacement
medium
– PfHRP-2 NA Chakma
etal. (2016)
Colorimetric – PfLDH 2008s-biotin
DNA aptamer
Dirkzwager
etal. (2016)
Colorimetric – PfLDH 2008s aptamer Fraser etal.
(2018)
Amperometric SPE PfHRP-2 Mouse
anti-PfHRP-2
antibody
Sharma
etal. (2008)
FRET – pLDH Fluorescently-
labeled
aptamer (36
mer ssDNA)
Kenry etal.
(2016)
Amperometric
magneto
Immunosensor
– PfHRP2 Anti-HRP2
IgM antibody
De Souza
Castilho
etal. (2011)
(continued)
S. A. Rather etal.

59
Table 3.4 (continued)
Analytes Sensing technique Transducer Biomarker
Receptor
molecule Reference
Antibodies SPR Gold disc Antibodies of
Pf
PfHRP2 Sikarwar
etal. (2014)
Nucleic
acids
Quartz crystal
microbalance
–Pf msp2 gene Biotinylated
probe
Potipitak
etal. (2011)
Droplet
microuidic
platform
–Pf
topoisomerase
I
ds DNA
substrate
Hede etal.
(2015)
SERS
Nanoplatform
– Pf DNA
sequences
Magnetic
bead and
nanorattle
Ngo etal.
(2016)
Quartz crystal
microbalance
Silver
electrode
18s rRNA
gene (Pf and
Pv)
Immobilized
probe
Wangmaung
etal. (2014)
Infected
red blood
cells
EIS SPE Pf infected
RBCs
Monoclonal
antibody
Kumar etal.
(2016)
Microuidic
separation and
MRR
– Infected
RBCs
– Kong etal.
(2015)
EIS electrochemical impedance spectroscopy, FRET uorescence resonance energy transfer, GCE
glassy carbon electrode, SPE screen-printed electrode, SERS surface-enhanced Raman spectros-
copy, SPR surface plasmon resonance
3.4.2.1 Detection ofPlasmodium falciparum Histidine-Rich Protein 2
(PfHRP-2)
Plasmodium falciparum-specic histidine-rich protein 2 (PfHRP-2) is secreted during
parasite growth and development and is involved in the detoxication of heme. The
antigen’s high levels of expression throughout the parasite life cycle can be credited
for its widespread use in electrochemical and optical immunosensors. Although
largely present in the blood, trace levels can also be detected in the patient’s saliva,
urine, and cerebrospinal uid, providing a chance for noninvasive testing (Rodriguez-
del Valle etal. 1991; Parra etal. 1991). In the case of the detection techniques, elec-
trochemical techniques have been found to perform better than optical methods.
Amperometric immunosensors have utilized nanoparticles, particularly gold (AuNP),
for signal amplication (Cao etal. 2011; Liuetal. 2013; Ju etal. 2011). Because of
their small size and simplicity in immobilizing bioconjugate probes, there is a larger
surface concentration of detecting antibodies that are enzyme-tagged, leading to
stronger indicators from the reaction between substrate and enzyme.
Magnetic nanoparticles (MNPs) have been used to create a malaria immunosen-
sor that is incredibly sensitive. A monoclonal antibody that binds a specic epitope
of the target antigen was tagged with horse radish peroxidase in order to provide an
electrochemical signal, while anti-HRP-2 was coupled to magnetic nanoparticles as
catch components (De Souza Castilho et al. 2011). The anti-HRP-2 magnetic
nanoparticles were trapped on a magnetic graphite-epoxy composite electrode in a
sandwich assay conguration and treated with anti-HRP-2-HRP and
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

60
HRP-2-stimulated serum. According to amplitude measurements, the limit of detec-
tion was signicantly more than what has been reported in earlier studies (Sharma
etal. 2008). However, this technique would need magnetic electrode supports to be
applied in the eld (De Souza Castilho etal. 2011).
Even though antibodies are typically used as capture molecules in biosensing
platforms for disease indicators, antibody stability is a challenge for immunoassays.
Genetic modications that increase the permanency of antibodies, as well as the
usage of articial substitutes like aptamers, have been some attempts to get around
these disadvantages (Ravaoarisoa etal. 2010). The parental monoclonal antibodies
(mAb) and the recombinant Fab fragments had similar binding properties. This
technology suggests a nancially advantageous substitute to large-scale antibody
manufacture for diagnostic purposes by offering the choice of individual antibody
fragments with better stability, resistance to denaturation even with prolonged expo-
sure, and afnities.
Further, some diagnostic procedures examine the close receptor and target recog-
nition by themselves in addition to adding molecular labels and nanoparticles for
enhanced diagnosis (Thukral etal. 2023). Since there are no potentially confusing
chemical labels, utilizing such label-free formats reduces the complexity of the
assay, the amount of time needed for preparation, and the cost of the analysis.
Various other techniques have been designed and utilized to detect PfHRP-2in
patients’ blood, such as indicator displacement assay (IDA) and electrochemical
impedance spectroscopy (EIS)-based methods, which have various advantages for
the use a detection models in point-of-care testing.
3.4.2.2 Detection ofPlasmodium Lactate Dehydrogenase (pLDH)
Lactate dehydrogenase is produced by Plasmodium during its intraerythrocytic
stages. The glycolytic pathway benets greatly from the catalytic activity of the
enzyme. It is generated by parasites within infected red blood cells that are meta-
bolically active. It serves as a telltale sign of a recent infection. As a result, it is more
accurate inlocating recent and untreated infections.
Aptamer-based sensors that target pLDH appear to be on the rise (Jeon etal.
2013; Lee etal. 2012; Figueroa-Miranda etal. 2018). Aptamers have several advan-
tages over antibodies, including reduced size, thermostability, a longer shelf life
without functional degradation, affordability, simplicity of synthesis, and
adaptability.
Single-stranded DNA aptamers (pL1 aptamers) have been utilized to target
recombinant Plasmodium falciparum LDH (PfLDH) and Plasmodium vivax LDH
(PvLDH) in buffer and real samples as a potential method for asymptomatic and
early diagnosis of malaria. Impedance measurements are used to identify the inter-
action between pL1 and the target proteins with great sensitivity and specicity. A
colorimetric test was used to measure the intrinsic enzymatic activity of LDH utiliz-
ing microbeads that were functionalized with aptamers. Due to the beads’ large
surface area for analyte binding, the aptamer-tethered enzyme capture (APTEC)
assay produced a LoD for recombinant PfLDH of 4.9ng/mL (Dirkzwager et al.
2016; Fraser etal. 2018).
S. A. Rather etal.

61
The aptamer-tethered enzyme capture assay was then integrated into a transport-
able microuidic biosensor. The platform addressed some of the assay’s original
issues with large sample and reagent volumes while identifying P. falciparum in
clinical samples and culture samples with excellent specicity and sensitivity
(Dirkzwager etal. 2016; Fraser etal. 2018).
3.4.2.3 Detection ofGlutamate Dehydrogenase (GDH)
In Plasmodium parasites, glutamate dehydrogenases (GDH) are involved in ammo-
nium assimilation and catabolism of glutamate. Signicantly soluble amounts of the
enzyme are present during parasite’s development, thus a potent target to detect the
presence of the parasite in a patient’s body (Li etal. 2005). By grafting a gold elec-
trode with a thiolated ssDNA aptamer (NG3) particular to P. falciparum (PfGDH), a
label-free capacitive aptasensor was created. The sensor has a range of 100fM–100nM
and produced a limit of detection in serum of 0.77pM.To create a sensitive and trust-
worthy miniaturized aptaFET biosensor, the NG3 aptamers were immobilized on
interdigitated gold microelectrodes (IDE) and coupled to the eld effect transistor
(FET). FET-type devices offer the benet of permitting straightforward and sensitive
electrochemical measurements without the requirement of a traditional redox marker.
In the presence of similar plasmodial and human proteins, the FET-based potentio-
metric sensor was highly selective, making it suitable for real-world sample analysis
for the detection of malaria (Park etal. 2012; Singh etal. 2018, 2019).
3.4.2.4 Detection ofHemozoin
The malaria parasites consume between 60% and 80% of erythrocytic hemoglobin
at this stage of their life cycles, resulting in the production of heme and polymeriza-
tion into insoluble hemozoin crystals (Chugh etal. 2013). Since hemozoin is only
found in the digestive vacuoles of parasites, its presence in the blood is a reliable
indicator of Plasmodium parasites that are actively engaged in metabolism. It has
been demonstrated that surface-enhanced Raman spectroscopy (SERS) has the abil-
ity to multiply the hemozoin’s Raman signal by several orders of magnitude (Pagola
etal. 2000). Uninfected lysates do not exhibit a Raman shift when exposed to a
gold-coated buttery wing as a SERS substrate, but parasitized RBCs do.
When parasitemia levels were between 0.0005% and 0.005% in the early ring
stage, the spectrum markers of hemozoin from infected RBC could be detected. A
different SERS method that used synthesized silver nanoparticles inside parasites to
achieve close contact with hemozoin demonstrated an ultrasensitive hemozoin
detection at 0.00005% parasitemia level in the ring stage (2.5 parasites/L), whereas
enhancements of Raman signals occur when hemozoin crystals are in direct contact
with metal surfaces (Chen etal. 2016). Although Raman spectrometers are expen-
sive, especially those with high spectral resolutions, several SERS techniques have
demonstrated promising results. Magnetic resonance relaxometry (MRR) has been
utilized to achieve label-free detection using the paramagnetic characteristics of
hemozoin crystals. The MRR technology has achieved early parasitemia detection
at a level of 0.0005% when used in conjunction with a microuidic setup (Krampa
etal. 2020).
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

62
There aren’t many known malaria biomarkers; hence, the collection of parasit-
ized RBCs has been suggested as a workaround. In order to nd a diverse range of
aptamers that specically bind various epitopes found on parasitized RBC surfaces,
a unique microuidic SELEX (I-SELEX) was used. Monoclonal antibodies were
used as capture elements for cells infected with malaria after being immobilized on
an AuNP-modied screen-printed electrode. The interaction of monoclonal anti-
bodies with parasitized RBCs resulted in impedimetric changes that allowed
infected RBCs to be distinguished from healthy, uninfected RBCs (Garcia 2007;
Birch et al. 2015). In addition to the protein and antibody-dependent detection
methods in malaria, various nucleic acid markers have also been explored as an
alternative.
Additionally, parallel testing may be the best method for delivering healthcare
because of its higher throughput, decreased reagent/assay setup, and reduced labor
requirements. A multitargeted diagnostic approach between different parasitic spe-
cies is the main goal of multiplexed malaria testing. To differentiate between pas-
sive/resolved or active infections and to discriminate between falciparum and
non-falciparum malaria, the most widely used techniques combine PfHRP-2/LDH
or PfHRP-2/aldolase (Jepsen et al. 2012; Iqbal et al. 2004; Laeur et al. 2012;
Deraney etal. 2016).
3.5 Applications ofBiosensors intheEarly Detection
ofHuman African Trypanosomiasis (HAT)
Human African trypanosomiasis (HAT), also referred to as sleeping sickness, is a
disease that only affects sub-Saharan Africa. The parasite was discovered for the
rst time in humans in 1902. A trypanosome parasite-group protozoan is responsi-
ble for HAT. Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense
are the two distinct subspecies. Around 90% of cases are caused by the Trypanosoma
brucei gambiense, which causes a persistent infection in patients asymptomatically
and increases the likelihood that the disease will progress to an advanced state.
When a person is sick, their central nervous system is impacted, which makes it
more difcult to treat or control the illness (Büscher et al. 2017; Bottieau and
Clerinx 2019).
On the other hand, Trypanosoma brucei rhodesiense infections manifest symp-
toms weeks or months after rst coming into touch with the parasite. This species
quickly damages the neurological system by causing an acute infection. The
patient’s medical history and course of treatment inuence the symptoms in both
species (Bottieau and Clerinx 2019). Intermittent fever, pruritus, headaches,
lymphadenopathy, anemia, and hepatosplenomegaly are a few typical traces. The
meningoencephalitis stage, which manifests as neuropsychiatric and sleep disor-
ders, aberrant movement, limb paralysis, hemiparesis, violent behavior, or psy-
chotic behaviors, is said to start when the parasite penetrates the blood-brain
barrier (BBB) (Bonnet et al. 2015; Masocha and Kristensson 2019;
Radwanska 2010).
S. A. Rather etal.

63
One of the neglected tropical illnesses is human African trypanosomiasis (HAT),
and early detection is just as crucial to therapy as it is to prevention. The biosensor-
based detection assays have also been attempted for its point-of-care diagnosis. The
development of the HAT identication system from human blood samples was
reported by Tweed-kent etal. in 2012 (Tweed-kent etal. 2012). The assay’s meth-
odology was based on a glassy carbon cylindrical rod electrode (GCCRE) that has
been enhanced with carboxylated single-walled carbon nanotubes (CSWCNT), and
the assay’s approach was based on an immobilized aptamer created by a Trypanosoma
brucei RNA.It is crucial to emphasize the 4.0 fmol/L limit of detection that was
attained in actual samples. The hybrid aptasensor that the authors describe is a
quicker and more affordable alternative to current commercial tests for diagnosing
HAT.It represents a development in the usage of modied ion-selective electrodes
(Cordeiro etal. 2021). The diagnosis of HAT is quite challenging due to differences
in reactivity toward different parasite species, the symptoms, and affordability of
the conventional tests. The current tests include the following:
1. Antibody detection using Card-Agglutination Trypanosomiasis Test (CATT)
(Penchenier etal. 2003).
2. Parasite Detection by Lymph Node Examination (WHO 2013), Mini Anion
Exchange Centrifugation Technique (mAECT) (Lutumba etal. 2006; Buscher
etal. 2009), and Capillary Tube Centrifugation (CTC) (WHO 2013).
3. Stage diagnosis, which involves the use of microscopic techniques to detect try-
panosomes in cerebrospinal uid (Brun etal. 2010; Sekhar etal. 2014).
Existing diagnostic techniques require specialized mobile teams that are skilled in
doing quick testing utilizing invasive methods, making them difcult and time-
consuming to apply. The goal is to provide straightforward tests that make it possi-
ble to incorporate HAT diagnosis-related activities into the public health
infrastructure. Some of the novel HAT staging biomarkers are under investigation
and are discussed as follows:
Antibody levels such as that of intrathecal IgM, particularly in Trypanosoma
brucei gambiense patients, are preferable over WBC counting as a measure for HAT
staging (Courtioux etal. 2006).
Another area of research being looked into is the modication of immune effec-
tors, such as cytokines and chemokines, for the development of new diagnostic
techniques for HAT staging. Early macrophage and astrocyte activation, a rise in
inammatory cytokines, and the appearance of Mott cells (plasma cells expressing
IgM) are some characteristics of late-stage HAT neuroinammation. Two signi-
cant sources of inammatory cytokines and chemokines in the brain are activated
astrocytes and macrophages. Both Trypanosoma brucei gambiense and Trypanosoma
brucei rhodesiense levels of these cytokines and chemokines have been tested to
investigate their diagnostic potential (Cordeiro etal. 2021).
The measurement of the differences in protein expression between infected and
noninfected settings is a different strategy that is currently being researched. Only a
few studies have dened the CSF protein patterns for the rst and second stages of
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

64
HAT illness. For stage 2 patients, there is a signicant increase in immunoglobulin
levels (Courtioux etal. 2006; Tiberti etal. 2013), but there are also 73 proteins that
differ in expression between the two stages. Osteopontin and beta-2-microglobulin
have both been shown to be reliable indicators of patients in the rst and second
stages (Tiberti etal. 2010). It is now possible to study new protein biomarkers, par-
ticularly for differentiating between stages 2 and 1 of the disease, thanks to the
development of new tools for protein and peptide analysis (Geiger etal. 2011).
Recent research has focused on the alteration of the typical sleep-wake cycle, the
most common clinical sign of HAT (Brun etal. 2010). For these studies, polysom-
nography has been employed.
A polysomnography can be used to investigate sleep disorders and includes tests
such as an electroencephalogram, electromyogram, and electrooculogram. Other
physiological measurements like heart rate and respiratory rate are also recorded.
According to studies, stage 2 patients have a high number of SOREMPs during the
course of their sleep, not just at night but also during the day (Buguet etal. 2012).
For illness staging, it has been suggested to use PCR to amplify particular para-
site DNA sequences found in blood, CSF, urine, or saliva samples. For staging HAT
illness, the loop-mediated isothermal amplication (LAMP) technique exhibits
great specicity and sensitivity. Additionally, this technique amplies the target
DNA at a constant temperature, allowing for the use of the test in low-tech labora-
tories or in the eld in HAT-endemic areas with little equipment (Cordeiro
etal. 2021).
3.5.1 American Trypanosomiasis (Chagas Disease)
The majority of the nations in South and Central America are endemic to
Trypanosoma cruzi (Moncayo 2003). Reduviid bug bites are the most common way
to contract the infection, although they can also spread transplacentally, through
eating infected guinea pigs, through blood transfusions, or through organ trans-
plants (Busch etal. 2003). Infection has migrated from rural Latin America to the
United States and other countries due to rising urbanization and emigration (Dias
etal. 2002). Endemicity is at its highest level wherever Triatoma spp. is present. The
reduviid bug usually lives in damp environments; however, it has evolved to live in
cities (Leiby etal. 2002).
When migrants from rural areas with high endemicity donate infected blood to
blood banks, transmission via transfusion happens more frequently in urban settings
(Sanchez-Guillen et al. 2002). However, trypanosome-infected transfusions con-
tinue to be widespread in many South American nations (Busch 2003). The preva-
lence of contaminated blood products has decreased in some locations due to
increased blood product screening. Immune-suppressed patients have replaced tour-
ists and immigrants as the group in the United States with the highest risk of con-
tracting an infection (Leiguarda etal. 1990).
The vector excretes feces containing T. cruzi stages while consuming a blood
meal from a potential host, and these stages are then left behind on mucous
S. A. Rather etal.

65
membranes or skin (Kirk and Schoeld 1987). During scratching at the site of an
insect bite, skin breaches occur that allow stages to enter the human host. These then
reproduce by binary ssion. These cells shed into the bloodstream, where they
travel to distant regions and grow into adult intracellular organisms. Unlike African
trypanosomes, T. cruzi only divides after infecting a new cell or after unintention-
ally ingesting a host. Infected cells burst, releasing infectious parasites as well as
potent inammatory parasitic chemicals that strongly induce a host response (Hall
and Joiner 1993).
A trypanosome can be seen in serum or CSF, which is required for a conclusive
diagnosis (CDC 2003). Blood can reveal intracellular motile creatures when exam-
ined under a microscope. Direct visualization of the parasite is unusual during per-
sistent infection. Both chronic and acute forms of infection can be detected by
serum antibody detection tests, which are specic and sensitive (Matsumoto etal.
1993). When deciding on a course of treatment, clinical history plays a more signi-
cant role than diagnostic tests in identifying how chronic the illness is. Leishmaniasis-
related cross-reactivity can happen (Umezawa etal. 2001).
3.5.2 Advances inBiosensors fortheDetection
ofChagas Disease
The two types of biosensors that have been studied for Chagas disease diagnosis are
electrochemical and optical. Amperometric and impedimetric sensors are involved
in electrochemical sensors (Erdmann etal. 2013), but only surface plasmon reso-
nance (SPR) transducers are documented for optical sensors (Luz etal. 2015).
Pumpin-Ferreira etal. released a study in 2005 about a biosensor for the detec-
tion of Chagas disease. The amperometric immunosensor requires an electrochemi-
cal contact; hence, the measurements were performed with a potentiostat-galvanostat.
Potentiostats are strong pieces of machinery, but they are too huge and heavy to be
used as a portable biosensing system. Because these biosensors offer greater minia-
turization and integration possibilities for portable systems, further electronics for
readout systems need to be created for them. Salinas etal. also published a study on
an amperometric immunosensor in the same year (Salinas etal. 2005) with an anal-
ysis time of no more than 23min. In comparison to the ELISA approach, this group
achieved a higher level of sensitivity.
For the diagnosis of Chagas disease, Luz etal. (2015) created the rst biosensor
based on SPR transducers. They collected the parameter relating to the presence of
antibodies against T. cruzi shown in human serum in around 20min. In 2016, the
same group of researchers found that their immunoassay distinguished Chagas dis-
ease from other infectious diseases with a higher percentage of accuracy compared
to ELISA and also displayed a higher sensitivity of 100% compared to other diag-
nostic methods, such as PCR, which has a sensitivity of 90% and an acceptable
specicity of 97.2% (Luz etal. 2016). However, because the integration of a light
source is necessary for the laser generation and light detectors, the SPR transducing
principle now results in high volume and hefty commercial apparatus. The only
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

66
applications for this technology at the moment are lab tests. Additionally, SPR
equipment costs more than $50,000 USD, even though optical biosensors can be
quite sensitive. This makes it difcult for many researchers to afford such systems
(Coltro etal. 2014). In order to diagnose viral diseases using magnetic microbeads,
Corina etal. created a portable electrochemical biosensor platform. A mini-portable
potentiostat with eight channels that the group created and produced was used to
make this platform portable. With assay reading durations of 20s, they were able to
successfully show the platform’s application for the diagnosis of Chagas disease,
and the ndings they got in terms of sensitivity and selectivity were comparable to
those of ELISA.But the system isn’t currently offered in stores. In order to conduct
the tests, the technique also necessitates the detection of electrochemical processes,
which results in indirect steps. These procedures might be avoided in the future by
using different detecting methods, including sound sensors.
Additionally, Regiart etal. (2016) reported the development of an electrochemi-
cal immunosensor detecting anti-IgM Trypanosoma cruzi antibodies. By boosting
the sensor’s active surface area, they used gold nanoparticles to raise its limit of
detection. In this study, a detection limit of 3.03ng/mL was attained. In the same
year, Janissen etal. used a nanowire biosensor based on eld-effect transistor (FET)
technology for the CD protein marker IBMP8-1, achieving a limit of detection of
about 6fM (Janissen etal. 2017). This study illustrates the potential of this highly
sensitive biosensor for the management of this condition.
Table 3.5 summarizes various nanomaterials that have been used for drug deliv-
ery in preclinical studies of Chagas disease.
S. A. Rather etal.

67
Table 3.5 List of different nanomaterials with varying composition that have been used for drug delivery in preclinical studies of Chagas disease
Nanomaterial Preparation method Active agent Composition Size (nm) References
Polymeric nanoparticles Simple emulsication Bis-triazole
D0870
PLA-PEG 100–200 Molina etal. (2001)
Nanoprecipitation Ursolic acid Poly-εcaprolactone 172.2 Abriata etal. (2017)
Nanoprecipitation LYC NC-PCL-PLAPEG 105.3 Branquinho etal. (2014)
Nifurtimox PAC A ≤200 Gonzalez-Martin etal. (1998)
Nanoprecipitation LYC PCL-PLA-PEG 100–250 Branquinho etal. (2017)
Self-emulsifying R AV SEDDSs 100–250 Sposito etal. (2017)
Ionotropic gelation Nitric oxide RSNO 270–500 Contreras Lancheros etal. (2018)
Nanoprecipitation and
freeze-drying
BNZ Multiparticulate
benzonidazole
polymers
233 Seremeta etal. (2019)
Quantum dots Colloidal chemistry CdTe – NI Vieira etal. (2011)
Liposomes Extrusion ETZ pH-sensitive
liposomes
379 Morilla etal. (2005)
Mesoporous–silica
nanoparticles
Hydration BNZ Mesoporous silica
nanoparticle and
chitosan coating
3.3 Hu etal. (2014)
Nanoemulsions Emulsication Clove oil Sulfonamides 35–100 Vermelho etal. (2018)
Ursolic acid 57.3 Vargas De Oliveira etal. (2017)
Solid lipid nanoparticles High-pressure
homogenization and
microemulsion
S-Benzyldith-
iocarbazate
H2bdtc-SLNs 127.4 Carneiro etal. (2014)
mv millivolt, SEDDSs self-emulsifying drug delivery systems, BNZ benznidazole, R AV ravuconazole, PAC A poly(alkyl cyanoacrylate) nanoparticles, nm nano-
meter, PN nanoparticles with poly-ε-caprolactone, ZP zeta potential, NC nanocapsules, PEG polyethylene glycol-polylactide, PCL poly-ε-caprolactone
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

68
3.6 Advances inBiosensors fortheDetection
ofToxoplasmosis
Toxoplasmosis are caused by the protozoan parasite Toxoplasma gondii (Berger-
Schoch etal. 2011). Even though many infections only cause minor symptoms like
weariness, fever, and enlarged lymph nodes, they can cause serious disease and even
death in people with compromised immune systems or when the parasite is passed on
genetically (Xiao and Yolken 2015). The identication of certain antibodies against
the Toxoplasma parasite is frequently required for the diagnosis of toxoplasmosis. To
get around the shortcomings of traditional methods, poor sensitivity, low specicity,
and device complexity, a number of tools have been developed, including electro-
chemical, optical, and piezoelectric devices. According to Nambiar and Yeow (2011),
biosensors have a number of benets over traditional analytical techniques, including
excellent selectivity and sensitivity, the potential for miniaturization and portability,
quick response, small sample quantities, real-time detection, and low cost.
Electrochemical sensors have been utilized to detect specic IgG anti-T. gondii
antibodies, which serve as important markers for the determination and conrma-
tion of toxoplasmosis infection (Li etal. 2017). Another detection method involves
the use of an electrochemical immunosensor based on T. gondii IgM antibodies
(Tg-IgM) to verify the presence of toxoplasma infection (Jiang etal. 2013). The
majority of biosensors described in the literature for toxoplasmosis rely on immu-
noassays to detect anti-T. gondii antibodies.
In one approach, an agglutination-based piezoelectric immunoassay was devel-
oped to directly detect anti-T. gondii immunoglobulins in infected rabbit serum and
blood. This method utilizes antigen-coated gold nanoparticles that undergo specic
agglutination in the presence of the corresponding antibody, leading to a frequency
change detected by a piezoelectric device. The system demonstrated sensitivity to
anti-T. gondii antibody dilution ratios as low as 1:5500 (Wang et al. 2004; Ding
etal. 2005) developed an electrochemical biosensor employing enzyme-catalyzed
amplication. The surface of a gold electrode was immobilized with T. gondii anti-
gen to capture anti-Toxoplasma IgG, followed by the addition of anti-Toxoplasma
IgG horseradish peroxidase conjugate. Transduction methods such as quartz crystal
microbalance, electrochemical impedance spectroscopy, and cyclic voltammetry
were employed, achieving a detection limit of 1:9600in dilution ratio.
Luo etal. (2013) utilized two aptamers with high afnities to antitoxoplasma
IgG in the development of a quantum dots-labeled dual aptasensor. The presence of
anti-toxoplasma IgG leads to the formation of an aptamer-protein-aptamer sand-
wich complex, which is captured on a multi-well microplate. The uorescence emit-
ted by quantum dots is then measured, allowing for quantitative analysis. The
aptasensor demonstrated linearity within the range of 0.5–500IU, with the lowest
detection limit of 0.1IU.Another detection method, described by He etal. (2015),
utilized magnetic uorescent nanoparticles in the development of a genosensor for
the detection of T. gondii DNA oligonucleotides. This uorimetric method achieved
a limit of detection of 8.339nM.
S. A. Rather etal.

69
Alves etal. (2019), developed an immunosensor for detecting anti-Toxoplasma
antibodies, which can distinguish various stages of infection. Although IgM is com-
monly used as a marker for toxoplasmosis, it is not detectable in some patients,
making the measurement of IgG a more reliable diagnostic tool (Medawar-Aguilar
etal. 2019). Glyco-sylphosphatidylinositol glycolipid-anchored proteins (GPI-Aps)
are important for cell signaling and communication during infectious diseases and
are present on the surface of T. gondii, T. brucei, and P. falciparum (Tsai etal.
2012). GPI-Aps can be used for detecting anti-GPI IgG and IgM antibodies in sero-
positive patients (Echeverri et al. 2020). A simple colorimetric method based on
gold nanoparticles has been developed using synthetic polymorphic peptides
derived from the GRA6 antigen, specic for type II T. gondii, which can efciently
detect anti-GRA6II antibodies in serum samples. This biosensor-based immunoas-
say using AuNPs conjugated with polymorphic synthetic peptides can be used as a
serotyping device (Sousa etal. 2021).
3.7 Application ofBiosensor inEarly Detection
ofNeurocysticercosis
Taenia solium, commonly known as the pork tapeworm, is a helminth parasite that
is responsible for causing a condition called cysticercosis (Fig.3.3). Cysticercosis
occurs when animals and humans become infected with the eggs of T. solium, often
through the consumption of contaminated pork. Neurocysticercosis is a parasitic
infection of the central nervous system caused by the metacestode of the tapeworm
T. solium (Garcia etal. 2003). It is a leading cause of acquired epilepsy worldwide,
especially in developing countries. Early detection of neurocysticercosis is critical
for effective treatment and prevention of seizures and other neurological complica-
tions. The eggs of T. solium hatch and release oncospheres that have the ability to
invade the nervous system of humans. This invasion can lead to the development of
adult-acquired epilepsy and other neurological complications. Ingesting raw or
undercooked meat from pigs infected with cysticercosis can result in the develop-
ment of a tapeworm infection known as taeniasis in humans.
Patients with taeniasis may experience various symptoms including epigastric
discomfort, nausea, insomnia, anorexia, irritability, diarrhea, and weight loss.
Detecting T. solium infection is crucial for early diagnosis and effective manage-
ment of the disease. Different immunoassays have been developed to detect T. solium
infection in both infected humans and livestock animals. However, these methods
often require centralized laboratory facilities and are time-consuming, labor-
intensive, and have longer turnaround times. This can delay the diagnosis and treat-
ment of infected individuals.
To overcome these limitations, there is a need for innovative diagnostic
approaches that are rapid and sensitive and can be performed at the point of care.
Biosensors offer a promising solution in the early detection of T. solium infection.
These analytical devices utilize bioreceptors to recognize and interact with specic
molecular targets, producing a detectable signal that indicates the presence of the
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70
Cysticerci develop
in pig muscles
Pigs by coprophagia and
humans by contaminated
food/water or autoinfection
acquire parasite
Soil contamination by open
defecation
Contaminated
food ingested
by humans
Cysticerci can lodge in
human tissues such as
brain, eyes, muscles
Humans acquire T.solium
infection by ingesting raw or
undercooked pig/dog meat with
cysticerci
T. solium adult worm
lodges in human intestine,
discharges proglottics full
of eggs into the
environment via feces
Fig. 3.3 Lifecycle of Taenia solium. (Adapted from Siddiqua and Habeeb 2020)
infection. Biosensors can provide several advantages in the diagnosis of these infec-
tions, including rapid results, minimal sample requirements, portability, and poten-
tial for on-site testing. By utilizing biosensors, healthcare providers can obtain
real-time information about the infection status, enabling timely intervention and
appropriate treatment (Zhao etal. 2019; Kulkarni and Goel 2020).
Biosensors have emerged as a promising tool for the early detection of this disease.
Biosensors are analytical devices that combine a biological recognition element (such
as an enzyme or antibody) with a transducer to convert a biological signal into a mea-
surable signal. Biosensors offer several advantages for the early detection of neuro-
cysticercosis, including their high sensitivity, specicity, and selectivity. They can
detect the presence of the parasite’s antigens or antibodies in various biological sam-
ples, such as serum, cerebrospinal uid, and saliva. One type of biosensor that has
been developed for the early detection of neurocysticercosis is the electrochemical
biosensor. This biosensor consists of a working electrode, a reference electrode, and a
counter electrode. The biological recognition element is immobilized on the working
electrode, and the transducer measures the electrochemical signal generated by the
interaction between the recognition element and the target antigen or antibody. The
electrochemical biosensor can detect the presence of the parasite’s antigens or anti-
bodies in biological samples with high sensitivity and specicity.
Another type of biosensor that has been developed for the early detection of
neurocysticercosis is the optical biosensor. This biosensor utilizes light to measure
the interaction between the biological recognition element and the target antigen or
antibody. The optical biosensor can detect the presence of the parasite’s antigens or
antibodies in biological samples with high sensitivity and selectivity.
S. A. Rather etal.

71
Biosensors offer several advantages for the early detection of neurocysticercosis
over conventional diagnostic methods, such as ELISA and PCR. Biosensors are
portable, simple, and rapid, and they can provide real-time results. They can also
detect low levels of the parasite’s antigens or antibodies in biological samples,
which may not be detectable by conventional methods.
The detection of neurocysticercosis, caused by the infection of T. solium (pork
tapeworm) can be facilitated by various biosensor-based approaches. One such
method involves the use of a lateral ow test utilizing nano-sized up-converting
phosphor (UCP) reporter particles and a portable analyzer. This test detects antibod-
ies in serum samples that react with bacterial-expressed recombinant T24H, a spe-
cic marker for neurocysticercosis cases (Corstjens etal. 2014). The UCP-LF assay
incorporates TSOL18 and GP50 antigens, which are known to be highly protective,
immunogenic, and specic for the early diagnosis of cysticercosis (Gomez-Puerta
etal. 2019). Compared to ELISA, the UCP-LF assay demonstrates higher sensitiv-
ity (93.59% for TSOL18 and 97.44% for GP50) and specicity (100% for both
antigens), providing a rapid, small-volume and reliable method for cysticercosis
diagnosis (Zhang etal. 2021).
Another approach involves the use of a localized surface plasmon resonance
(LSPR) biosensor utilizing colloidal gold nanoparticles (AuNPs). This biosensor
detects T. solium antigens and demonstrates the ability to differentiate between pos-
itive and negative human serum samples, representing diseased and non-diseased
individuals with neurocysticercosis (Arcas et al. 2021). The LSPR biosensor,
employing AuNPs synthesized through a specic protocol, exhibits improved sta-
bility during biofunctionalization and offers potential for the diagnosis of neurocys-
ticercosis (Soares etal. 2018).
In addition, a biosensor based on quantum dot aptasensor (Q-DAS) technology
has been developed for the detection of antitoxoplasma IgG, which is relevant in
Toxoplasma screening. This biosensor employs specic aptamers as coating and
detection probes, enhancing sensitivity compared to conventional antibody-based
assays (Luo etal. 2014).
Peptides have also gained interest in biosensing for their unique characteristics,
such as biocompatibility, stability, ease of synthesis, and sequence versatility.
Peptide-based biosensors have been explored for the enhanced detection of patho-
gens, including T. solium. These biosensors offer advantages over antibody-based
assays in terms of resistance to harsh conditions and suitability for on-eld applica-
tions (Karimzadeh etal. 2018).
Among various transduction systems used in biosensors, electrochemical
and optical platforms are the most prevalent, followed by mass-based systems.
Bioreceptors such as antibodies, nucleic acids, aptamers, peptides, and bacte-
riophages have been employed to construct these biosensors, with the choice
of bioreceptor being crucial for achieving reliable detection with high sensi-
tivity and specificity (Bhardwaj etal. 2017; Wu etal. 2014, 2015; Vidic etal.
2019; Vizzini etal. 2021; Bruno 2014; Islam et al. 2022; Karimzadeh et al.
2018; Qiao etal. 2020; Tertis etal. 2021; Karoonuthaisiri etal. 2014; Anany
etal. 2018).
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72
3.8 Conclusion
Despite numerous efforts from committed individuals, the number of new cases and
fatalities from neuro-parasitic diseases continue to be frightening. Neuroparasitic
diseases have a severe inuence on the entire world. The challenges are enormous,
ranging from accessing isolated and unsafe regions to having treatments available to
help entire communities. To expedite the right diagnosis and, consequently, the
treatment, low-cost and miniature equipment like biosensors can be used in these
conditions.
In order to diagnose neuroparasitic disease early on, biosensors have become a
viable tool. In comparison to traditional diagnostic techniques, they have a number
of advantages and have excellent levels of specicity, selectivity, and sensitivity for
detecting the presence of the parasite’s antibodies or antigens in a variety of biologi-
cal samples. Biosensors have the potential to improve the diagnosis and treatment
of neuro-parasitic disease and reduce the burden of this disease worldwide.
References
Abdel Razek AA, Watcharakorn A, Castillo M (2011) Parasitic diseases of the central nervous
system. Neuroimaging Clin N Am 2:815–841
Abriata JP, Eloy JO, Riul TB, Campos PM, Baruf MD, Marchetti JM (2017) Poly-epsilon-
caprolactone nanoparticles enhance ursolic acid in vivo efcacy against Trypanosoma
cruzi infection. Mater Sci Eng C Mater Biol Appl 77:1196–1203. https://doi.org/10.1016/j.
msec.2017.03.266
Abrica-Gonzalez P, Zamora-Justo JA, Sotelo-Lopez A, Vazquez-Martinez GR, Balderas-Lopez JA,
Munoz-Diosdado A, Ibanez-Hernandez M (2019) Gold nanoparticles with chitosan, N-acylated
chitosan, and chitosan oligosaccharide as DNA carriers. Nanoscale Res Lett 14:258
Ajibola O, Gulumbe BH, Eze AA, Obishakin E (2018) Tools for detection of schistosomiasis
in resource limited settings. Med Sci (Basel) 6(2):39. https://doi.org/10.3390/medsci6020039
Al Zain TJ, Al-Witry SH, Khalili HM, Aboud SH, Al Zain FT Jr (2002) Multiple intracranial hyda-
tidosis. Acta Neurochir 144(11):1179–1185
Aldewachi H, Chalati T, Gardiner P, Woodroofe N (2017) Gold nanoparticle-based colorimetric
biosensors. Nanoscale 10:18–33
Algros MP, Majo F, Bresson-Hadni S etal (2003) Intracerebral alveolar echinococcosis. Infection
231:63–65
Alves LM, Barros HLS, Flauzino JMR, Guedes PHG, Pereira JM, Fujiwara RT, Mineo TWP,
Mineo JR, de Oliveira RJ, Madurro JM, Brito-Madurro AG (2019) A novel peptide-based sen-
sor platform for detection of anti-Toxoplasma gondii immunoglobulins. J Pharm Biomed Anal
175:112778
Anany H, Brovko L, El Dougdoug NK, Sohar J, Fenn H, Alasiri N, Jabrane T, Mangin P, Monsur
Ali M, Kannan B etal (2018) Print to detect: a rapid and ultrasensitive phage-based dipstick
assay for foodborne pathogens. Anal Bioanal Chem 410:1217–1230
Arcas AS, Jaramillo L, Costa NS, Allil RCS, Werneck MM (2021) Localized surface plasmon
resonance-based biosensor on gold nanoparticles for Taenia solium detection. Appl Opt
60(26):8137–8144
Babiker SM, Blankespoor HD, Wassila M etal (1985) Transmission of Schistosoma haematobium
in North Gezira, Sudan. J Trop Med Hyg 88:65–73
Baptista P, Pereira E, Eaton P, Doria G, Miranda A, Gomes I et al (2008) Gold nanoparticles for
the development of clinical diagnosis methods. Anal Bioanal Chem 391(3):943–950. https://
doi.org/10.1007/s00216-007-1768-z
S. A. Rather etal.

73
Belluzo M, Ribone M, Lagier C (2008) Assembling amperometric biosensors for clinical diagnos-
tics. Sensors 8:1366–1399
Berger-Schoch AE, Herrmann DC, Schares G, Müller N, Bernet D, Gottstein B, Frey CF (2011)
Prevalence and genotypes of Toxoplasma gondii in feline faeces (oocysts) and meat from
sheep, cattle and pigs in Switzerland. Vet Parasitol 177(3–4):290–297
Bhardwaj J, Devarakonda S, Kumar S, Jang J (2017) Development of a paper-based electrochemi-
cal immunosensor using an antibody-single walled carbon nanotubes bio-conjugate modied
electrode for label-free detection of foodborne pathogens. Sens Actuators B Chem 253:115–123
Birch CM, Hou HW, Han J, Niles JC (2015) Identication of malaria parasite-infected red blood
cell surface aptamers by inertial microuidic SELEX (I-SELEX). Sci Rep 5:11347
Bonnet JC, Boudot B, Courtioux B (2015) Overview of the diagnostic methods used in the eld
for human African trypanosomiasis: what could change in the next years? Biomed Res Int
2015:583262
Bottieau E, Clerinx J (2019) Human African trypanosomiasis: progress and stagnation. Infect Dis
Clin 33:61–77
Bouree P (2001) Hydatidosis: dynamics of transmission. World J Surg 25:4–9
Branquinho RT, Mosqueira VC, De Oliveira-Silva JC, Simoes-Silva MR, Saude-Guimaraes DA,
De Lana M (2014) Sesquiterpene lactone in nanostructured parenteral dosage form is efca-
cious in experimental Chagas disease. Antimicrob Agents Chemother 58:2067–2075. https://
doi.org/10.1128/aac.00617-13
Branquinho RT, Roy J, Farah C, Garcia GM, Aimond F, Le Guennec JY et al (2017) Biodegradable
polymeric nanocapsules prevent cardiotoxicity of anti-trypanosomal lychnopholide. Sci
Rep 7:44998
Brince PK, Kumar S, Tripathy S, Vanjari SRK, Singh V, Singh SG (2016) A highly sensitive self
assembled monolayer modied copper doped zinc oxide nanober interface for detection of
Plasmodium falciparum histidine-rich protein-2: targeted towards rapid, early diagnosis of
malaria. Biosens Bioelectron 80:39–46
Brun R, Blum J, Chappuis F, Burri C (2010) Human African trypanosomiasis. Lancet
375(9709):148–159
Brunetti E, Kern P, Vuitton DA, Vuitton DA (2010) Expert consensus for the diagnosis and treat-
ment of cystic and alveolar echinococcosis in humans. Acta Trop 114:1–16
Bruno JG (2014) Application of DNA aptamers and quantum dots to lateral ow test strips for
detection of foodborne pathogens with improved sensitivity versus colloidal gold. Pathogens
3:341–355
Buguet A, Bisser S, Josenando T, Chapotot F, Cespuglio R (2012) Sleep structure: a new diagnos-
tic tool for stage determination in sleeping sickness. Acta Trop 93(1):107–117
Busch MP, Kleinman SH, Nemo GJ (2003) Current and emerging infectious risks of blood transfu-
sions. JAMA 289:959–962
Buscher P, Ngoyi DM, Kabor J etal (2009) Improved models’ of mini anion exchange centrifu-
gation technique (mAECT) and modied single centrifugation (MSC) for sleeping sickness
diagnosis and staging. PLoS Neglect Trop Dis 3(11):e471
Büscher P, Cecchi G, Jamonneau V, Priotto G (2017) Human African trypanosomiasis. Lancet
390(2017):2397–2409
Cao X, Ye Y, Liu S (2011) Gold nanoparticle-based signal amplication for biosensing. Anal
Biochem 417:1–16
Caldeira K, Teixeira CF, Silveira MB, Fries LCC, Romanzini J, Bittencourt HR et al (2012)
Comparison of the Kato-Katz and Helmintex methods for the diagnosis of schistosomiasis in a
low-intensity transmission focus in Bandeirantes, Paraná, southern Brazil. Mem Inst Oswaldo
Cruz 107(5):690–692. https://doi.org/10.1590/s0074-02762012000500019
Carpio A, Romo ML, Parkhouse RME, Short B, Dua T (2016) Parasitic diseases of the central
nervous system: lessons for clinicians and policy makers. Expert Rev Neurother 16(4):401–414
Carneiro ZA, Maia PI, Sesti-Costa R, Lopes CD, Pereira TA, Milanezi CM et al (2014) In vitro and
in vivo trypanocidal activity of H2bdtc-loaded solid lipid nanoparticles. PLoS Negl Trop Dis
8:e2847. https://doi.org/10.1371/journal.pntd.0002847
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

74
CDC (2003) DPDx laboratory diagnosis of parasites of public health concern. Centers for Disease
Control and Prevention
Cesewski E, Johnson BN (2020) Electrochemical biosensors for pathogen detection. Biosens
Bioelectron 159:112214
Chakma B, Jain P, Singh NK, Goswami P (2016) Development of an indicator displacement based
detection of malaria targeting HRP-II as biomarker for application in point-of-care settings.
Anal Chem 88:10316–10321
Chang CC, Chen CP, Wu TH, Yang CH, Lin CW, Chen CY (2019) Gold nanoparticle-based colori-
metric strategies for chemical and biological sensing applications. Nanomaterials 9:861
Chaudhary V (2022) Prospects of green nanotechnology for efcient management of neurodegen-
erative diseases. Front Nanotechnol 4:1055708
Chaudhary V, Rustagi S, Kaushik A (2023) Bio-derived smart nanostructures for efcient biosen-
sors. Curr Opin Green Sustain Chem 42:100817
Chen L, Gu B, Zhu G, Wu Y, Liu S, Xu C (2008) Electron transfer properties and electrocatalytic
behavior of tyrosinase on ZnO nanorod. J Electroanal Chem 617(1):7–13
Chen K, Yuen C, Aniweh Y, Preiser P, Liu Q (2016) Towards ultrasensitive malaria diagnosis using
surface enhanced Raman spectroscopy. Sci Rep 6:20177
Chugh M, Sundararaman V, Kumar S, Reddy VS, Siddiqui WA, Stuart KD, Malhotra P (2013)
Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum. Proc
Natl Acad Sci U S A 110:5392–5397
Coltro WKT, Neves RDS, Motheo ADJ, Da Silva JAF, Carrilho E (2014) Microuidic devices
with integrated dual-capacitively coupled contactless conductivity detection to monitor binding
events in real time. Sensors Actuators B Chem 192:239–246
Contreras Lancheros CA, Pelegrino MT, Kian D, Tavares ER, Hiraiwa PM, Goldenberg S et al
(2018) Selective antiprotozoal activity of nitric oxide-releasing chitosan nanoparticles against
Trypanosoma cruzi: toxicity and mechanisms of action. Curr Pharm Des 24:830–839. https://
doi.org/10.2174/1381612824666180209105625
Cordeiro TAR, de Resende MAC, Moraes SCS, Franco DL, Pereira AC, Ferreira LF (2021)
Electrochemical biosensors for neglected tropical diseases: a review. Talanta 234:122617.
https://doi.org/10.1016/j.talanta.2021.122617
Corstjens PL, de Dood CJ, Priest JW, Tanke HJ, Handali S, Cysticercosis Working Group in Peru
(2014) Feasibility of a lateral ow test for neurocysticercosis using novel up-converting nano-
materials and a lightweight strip analyzer. PLoS Neglect Trop Dis 8(7):e2944. https://doi.
org/10.1371/journal.pntd.0002944. PMID: 24992686; PMCID: PMC4080996
Courtioux B, Boda C, Vatunga G etal (2006) A link between chemokine levels and disease severity
in human African trypanosomiasis. Int J Parasitol 36(9):1057–1065
Darabi E, Motevaseli E, Khorramizadeh MR, Mohebali M, Rokni MB, Zahabiun F, Kia EB (2019)
Design and construction of a fusion peptide containing B1, B2, B4, and EPC1 epitopes for
diagnosis of human cystic echinococcosis. Iran J Public Health 48:1671–1680
Davis JJ, Coleman KS, Azamian BR, Bagshaw CB, Green MLH (2003) Chemical and biochemical
sensing with modied single walled carbon nanotubes. Chemistry 9(16):3732–3739
de Albuquerque RDDD, Mahomoodally MF, Lobine D, Suroowan D, Rengasamy KRR (2020)
Botanical products in the treatment and control of schistosomiasis: recent studies and distribu-
tion of active plant resources according to affected regions. Biology 9:1–26
De Oliveira EC, Carneiro ZA, De Albuquerque S, Marchetti JM (2017) Development and evalua-
tion of a nanoemulsion containing ursolic acid: a promising trypanocidal agent : nanoemulsion
with ursolic acid against T. cruzi. AAPS PharmSciTech 18:2551–2560
De Souza Castilho M, Laube T, Yamanaka H, Alegret S, Pividori MIM (2011) Immunoassays for
Plasmodium falciparum histidine-rich protein 2 related to malaria based on magnetic nanopar-
ticles. Anal Chem 83:5570–5577. https://doi.org/10.1021/ac200573s
Deng D, Xu B, Hu H, Li J, Hu H, Song S, Feng Z, Fan C (2013) Diagnosis of schistosomiasis
japonica with interfacial co-assembly-based multi-channel electrochemical immunosensor
arrays. Sci Rep 3(1–6):1789
S. A. Rather etal.

75
Deraney RN, Mace CR, Rolland JP, Schonhorn JE (2016) Multiplexed, patterned-paper immuno-
assay for detection of malaria and dengue fever. Anal Chem 88:6161–6165
Dequaire M, Degrand C, Limoges B (2000) An electrochemical metalloimmunoassay based on a
colloidal gold label. Anal Chem 72(22):5521–5528. https://doi.org/10.1021/ac000781m
Dias JC, Silveira AC, Schoeld CJ (2002) The impact of Chagas disease control in Latin America:
a review. Mem Inst Oswaldo Cruz 97:603–612
Ding Y, Wang H, Shen G, Yu R (2005) Enzyme-catalyzed amplied immunoassay for the detec-
tion of Toxoplasma gondii-specic IgG using Faradaic impedance spectroscopy, CV and
QCM.Anal Bioanal Chem 382(7):1491–1499
Dirkzwager RM, Liang S, Tanner JA (2016) Development of aptamer-based point-of-care diag-
nostic devices for malaria using three-dimensional printing rapid prototyping. ACS Sensors
1:420–426
Echeverri D, Garg M, Silva DV, Orozco J (2020) Phosphoglycan-sensitized platform for specic
detection of anti-glycan IgG and IgM antibodies in serum. Talanta 217:121117
Eckert J, Thompson RCA (2017) Chapter 1—Historical aspects of echinococcosis. In: Thompson
RCA, Deplazes P, Lymbery AJ (eds) Advances in parasitology, vol 95. Academic, Cambridge,
MA, pp1–64
El-Garem AA (1998) Schistosomiasis. Digestion 59:589–605
Erdmann CA, Kovalczuk E, Inaba J, Viana AG, Pessoa CA, Wohnrath K, Garcia JR (2013)
Development of a Nano-particle enhanced impedimetric biosensor for Chagas’ disease diagno-
sis. In: Proceedings of the XLII annual meeting of SBBq, Parana, Brazil, 18–21 May
Feachem RGA, Chen I, Akbari O, Bertozzi-Villa A, Bhatt S, Binka F, Boni MF, Buckee C,
Dieleman J, Dondorp A et al (2019) Malaria eradication within a generation: ambitious,
achievable, and necessary. Lancet 394:1056–1112
Figueroa-Miranda G, Feng L, Shiu SCC, Dirkzwager RM, Cheung YW, Tanner JA, Schöning MJ,
Offenhäusser A, Mayer D (2018) Aptamer-based electrochemical biosensor for highly sensi-
tive and selective malaria detection with adjustable dynamic response range and reusability.
Sensors Actuators B Chem 2018(255):235–243
File S (1995) Interaction of schistosome eggs with vascular endothelium. J Parasitol 81:234–238
Foudeh AM, Fatanat Didar T, Veres T, Tabrizian M (2012) Microuidic designs and techniques
using labon-a-chip devices for pathogen detection for point-of-care diagnostics. Lab Chip
12(18):3249–3266
Fraser LA, Kinghorn AB, Dirkzwager RM, Liang S, Cheung YW, Lim B, Shiu SCC, Tang MSL,
Andrew D, Manitta J etal (2018) A portable microuidic Aptamer-Tethered Enzyme Capture
(APTEC) biosensor for malaria diagnosis. Biosens Bioelectron 100:591–596
Garcia LS (2007) Diagnostic medical parasitology, 5th edn. ASM Press, Washington, DC,
pp130–140
García HH, Gonzalez AE, Evans CA, Gilman RH, Working Group in Peru (2003) Taenia solium
cysticercosis. Lancet (London, England) 362(9383):547–556
Garret M, Herbsman H, Fierst S (1977) Cytologic diagnosis of echinococcosis. Acta Cytol
21:553–554
Gautam A (2022) Towards modern-age advanced sensors for the management of neurodegenera-
tive disorders: current status, challenges and prospects. ECS Sensor Plus 1:042401
Geiger A, Simo G, Grebaut P, Peltier GB, Cuny G, Holzmuller P (2011) Transcriptomics and
proteomics in human African trypanosomiasis: current status and perspectives. J Proteome
74(9):1625–1643
Gikunoo E, Abera A, Woldesenbet E (2014) A novel carbon Nanobers grown on glass micro-
balloons immunosensor: a tool for early diagnosis of Malaria. Sensors (Switzerland)
14:14686–14699
Gomez-Puerta L, Vargas-Calla A, Castillo Y, Lopez-Urbina MT, Dorny P, Garcia HH etal (2019)
Evaluation of cross-reactivity to Taenia hydatigena and Echinococcus granulosus in the
enzyme-linked immunoelectrotransfer blot assay for the diagnosis of porcine cysticercosis.
Parasit Vectors 12:57
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

76
Gonzalez-Martin G, Merino I, Rodriguez-Cabezas MN, Torres M, Nunez R, Osuna A
(1998) Characterization and trypanocidal activity of nifurtimox-containing and empty
nanoparticles of polyethylcyanoacrylates. J Pharm Pharmacol 50:29–35. https://doi.
org/10.1111/j.2042-7158.1998.tb03301.x
Gottstein B (1992) Molecular and immunological diagnosis of echinococcosis. Clin Microbiol
Rev 192(5):248–261
Gottstein B, Wang J, Blagosklonov O, Grenouillet F, Millon L, Vuitton DA, Müller N (2014)
Echinococcus metacestode: in search of viability markers. Parasite 21:63
Graeff-Teixeira C, Da Silva AC, Yoshimura K (2009) Update on eosinophilic meningoencephalitis
and its clinical relevance. Clin Microbiol Rev 22:322–348
Gryseels B, Polman K, Clerinx J, Kestens L (2006) Human schistosomiasis. Lancet 368:1106–1118
Hall BF, Joiner KA (1993) Developmentally-regulated virulence factors of Trypanosoma cruzi and
their relationship to evasion of host defences. J Eukaryot Microbiol 40:207–213
He L, Ni L, Zhang X, Zhang C, Li R, Xu S (2015) Fluorescent detection of specic DNA sequences
related to Toxoplasma gondii based on magnetic uorescent nanoparticles Fe3O4/CdTe biosen-
sor. Int J Biochem Res Rev 6(3):130
Hede MS, Okorie PN, Fruekilde SK, Fjelstrup S, Thomsen J, Franch O, Tesauro C, Bugge MT,
Christiansen M, Picot S etal (2015) Rened method for droplet microuidics-enabled detec-
tion of Plasmodium falciparum encoded topoisomerase I in blood from malaria patients.
Micromachines 6:1505–1513
Hemben A, Ashley J, Tothill I (2017) Development of an immunosensor for PfHRP 2 as a bio-
marker for malaria detection. Biosensors 7:28. https://doi.org/10.3390/bios7030028
Hu X, Wang Y, Peng B (2014) Chitosan-capped mesoporous silica nanoparticles as pH-responsive
nanocarriers for controlled drug release. Chem Asian J 9:319–327. https://doi.org/10.1002/
asia.201301105
Huang Y, Zhang W, Xiao H, Li G (2005) An electrochemical investigation of glucose oxidase at a
CdS nanoparticles modied electrode. Biosens Bioelectron 21(5):817–821
Iqbal J, Siddique A, Jameel M, Hira PR (2004) Persistent histidine-rich protein 2, parasite lactate
dehydrogenase, and panmalarial antigen reactivity after clearance of Plasmodium falciparum
monoinfection. J Clin Microbiol 42:4237–4241
Islam MA, Karim A, Ethiraj B, Raihan T, Kadier A (2022) Antimicrobial peptides: promising
alternatives over conventional capture ligands for biosensor-based detection of pathogenic bac-
teria. Biotechnol Adv 55:107901
Jain P, Chakma B, Patra S, Goswami P (2014) Potential biomarkers and their applications for rapid
and reliable detection of malaria. Biomed Res Int 2014:1–20
Jain P, Das S, Chakma B, Goswami P (2016) Aptamer-graphene oxide for highly sensitive dual
electrochemical detection of Plasmodium lactate dehydrogenase. Anal Biochem 514:32–37
Jain K, Gowthamarajan K, Sood S, Elango K, Suresh B (2012) Olfactory drug delivery of arte-
mether-curcumin combination for management of cerebral malaria. Malar J 11(Suppl 1):P51.
https://doi.org/10.1186/1475-2875-11-S1-P51
Janissen RPK, Santos CA, da Silva AM, von Zuben AAG, Souto DEP, Costa ADT, Celedon P,
Zanchin NIT, Almeida DB etal (2017) InP nanowire biosensor with tailored biofunctionaliza-
tion: ultrasensitive and highly selective disease biomarker detection. Nano Lett 17:5938–5949
Jeon W, Lee S, Dh M, Ban C (2013) A colorimetric aptasensor for the diagnosis of malaria based
on cationic polymers and gold nanoparticles. Anal Biochem 439:11–16
Jepsen MPG, Röser D, Christiansen M, Larsen SO, Cavanagh DR, Dhanasarnsombut K, Bygbjerg
I, Dodoo D, Remarque EJ, Dziegiel M etal (2012) Development and evaluation of a multiplex
screening assay for Plasmodium falciparum exposure. J Immunol Methods 384:62–70
Jiang Y, Wu J (2019) Recent development in chitosan nanocomposites for surface-based biosensor
applications. Electrophoresis 40:2084–2097
Jiang L, Wen H, Ito A (2001) Immunodiagnostic differentiation of alveolar and cystic echinococ-
cosis using ELISA test with 18-kDa antigen extracted from Echinococcus protoscoleces. Trans
R Soc Trop Med Hyg 95:285–288
S. A. Rather etal.

77
Jiang ST, Hua EH, Liang M, Liu B, Xie GM (2013) A novel immunosensor for detecting
Toxoplasma gondii-specic IgM based on goldmag nanoparticles and graphene sheets. Colloid
Surface B 101:481–486
Jianrong C, Yuqing M, Nongyue H, Xiaohua W, Sijiao L (2004) Nanotechnology and biosensors.
Biotechnol Adv 22(7):505–518
John CC, Carabin H, Montano SM, Bangirana P, Zunt JR, Peterson PK (2015) Global research
priorities for infections that affect the nervous system. Nature 2015(527):S178–S186
Ju H, Zhang X, Wang J (2011) Biological and medical physics, biomedical engineering. In: Signal
amplication for nanobiosensing. Springer, NewYork
Kabashin AV, Evans P, Pastkovsky SW etal (2009) Plasmonic nanorod metamaterials for biosens-
ing. Nat Mater 8(11):867–871
Kahru A, Dubourguier C (2010) From ecotoxicology to nanoecotoxicology. Toxicology
269:105–119
Kame M, Elbaz H, Demerdash Z, Elmoneem E, Hendawy M, Bayoumi I (2016) Nano-immunoassay
for diagnosis of active schistosomal infection. World J Med Sci 13:27
Karimzadeh A, Hasanzadeh M, Shadjou N, de la Guardia M (2018) Peptide based biosensors.
TrAC Trends Anal Chem 107:1–20
Karoonuthaisiri N, Charlermroj R, Morton MJ, Oplatowska-Stachowiak M, Grant IR, Elliott CT
(2014) Development of a M13 bacteriophage-based SPR detection using Salmonella as a case
study. Sensors Actuators B Chem 190:214–220
Katz N, Chaves A, Pellegrino J (1972) A simple device for quantitative stool thick-smear technique
in schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 14(6):397–400
Kenry GA, Zhang X, Zhang H, Lim CT (2016) Highly sensitive and selective aptamer-based uo-
rescence detection of a malarial biomarker using single-layer MoS2 nanosheets. ACS Sensors
1(11):1315–1321
Kern P, Bardonnet K, Renner E etal (2003) European echinococcosis registry: human alveolar
echinococcosis, Europe, 1982–2000. Emerg Infect Dis 9:343–349
Kirk ML, Schoeld CJ (1987) Density-dependent timing of defaecation by Rhodnius prolixus,
and its implications for the transmission of Trypanosoma cruzi. Trans R Soc Trop Med Hyg
81:348–349
Kissinger PT (2005) Biosensors—a perspective. Biosens Bioelectron 20(12):2512–2516
Kong TF, Ye W, Peng WK, Hou HW, Preiser PR, Nguyen NT, Han J (2015) Enhancing malaria
diagnosis through microuidic cell enrichment and magnetic resonance relaxometry detection.
Sci Rep 5:1–12
Krampa FD, Aniweh Y, Kanyong P, Awandare GA (2020) Recent advances in the development
of biosensors for malaria diagnosis. Sensors (Basel) 20(3):799. https://doi.org/10.3390/
s20030799. PMID: 32024098; PMCID: PMC7038750
Kulkarni MB, Goel S (2020) Microuidic devices for synthesizing nanomaterials—a review. Nano
Express 1:032004
Kumar B, Bhalla V, Suri CR, Varshney GC, Kumar B, Bhalla V, Singh Bhadoriya RP, Suri C,
Varshney GC, Looareesuwan S etal (2016) Label-free electrochemical detection of malaria-
infected red blood cells. RSC Adv 6:1–5
Laeur L, Stevens D, McKenzie K, Ramachandran S, Spicar-Mihalic P, Singhal M, Arjyal A,
Osborn J, Kauffman P, Yager P etal (2012) Progress toward multiplexed sample-to-result detec-
tion in low resource settings using microuidic immunoassay cards. Lab Chip 12:1119–1127
Lammie P, Solomon A, Secor E, Peeling R (2011) Diagnostic needs for NTD programs. In: Causes
impacts neglected tropical and zoonotic diseases, pp346–356
Lee S, Manjunatha DH, Jeon W, Ban C (2014) Cationic surfactant-based colorimetric detection of
Plasmodium lactate dehydrogenase, a biomarker for malaria, using the specic DNA aptamer.
PLoS One 9(7):e100847
Lee S, Song KM, Jeon W, Jo H, Shim YB, Ban C (2012) A highly sensitive aptasensor towards
Plasmodium lactate dehydrogenase for the diagnosis of malaria. Biosens Bioelectron
35:291–296
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

78
Lei J, Ju H (2012) Signal amplication using functional nanomaterials for biosensing. Chem Soc
Rev 41:2122. https://doi.org/10.1039/c1cs15274b
Leiby DA, Herron RM Jr, Read EJ etal (2002) Trypanosoma cruzi in Los Angeles and Miami
blood donors: impact of evolving donor demographics on seroprevalence and implications for
transfusion transmission. Transfusion 42:549–555
Leiguarda R, Roncoroni A, Taratuto AL etal (1990) Acute CNS infection by Trypanosoma cruzi
(Chagas’ disease) in immunosuppressed patients. Neurology 40:850–851
Li Y, Ning YS, Li L, Peng DD, Dong WQ, Li M (2005) Preparation of monoclonal antibodies
against Plasmodium falciparum glutamate dehydrogenase and establishment of colloidal gold
immunochromatographic assay. Di Yi Jun Yi Da Xue Xue Bao 25:435–438
Li P, Jia Z, Lü G (2017) Hydatid detection using the near-infrared transmission angular spectra of
porous silicon microcavity biosensors. Sci Rep 7:44798
Lim CZF, Bhantooa D, Balgobin D, Bissoonauth N, Ramburran DK, Lu F (2016) Parasitic enceph-
alitis caused by plasmodium falciparum, trypanosoma brucei and toxoplasma gondii. Ann
Infect Dis Epidemiol 1(1):1005
Lin CC, Chen LC, Huang CH, Ding SJ, Chang CC, Chang HC (2008) Development of the multi-
functionalized gold nanoparticles with electrochemical-based immunoassay for protein A
detection. J Electroanal Chem 619:39–45. https://doi.org/10.1016/j.jelechem.2008.03.014
Lin D, Tian X, Fengchang W, Xing B (2010) Fate and transport of engineered nanomaterials in the
environment. J Environ Qual 39:1896–1907
Lorentzen HF, Beneld T, Stisen S, Rahbek C (2020) COVID-19 is possibly a consequence of the
anthropogenic biodiversity crisis and climate changes. Dan Med J 28(5):67
Luo X, Morrin A, Killard AJ, Smyth MR (2006) Application of nanoparticles in electrochemical
sensors and biosensors. Electroanalysis 18(4):319–326
Luo Y, Liu X, Jiang T, Liao P, Fu W (2013) Dual-aptamer-based biosensing of toxoplasma anti-
body. Anal Chem 85(17):8354–8360. https://doi.org/10.1021/ac401755s
Luong JH, Male KB, Glennon JD (2008) Biosensor technology: technology push versus market
pull. Biotechnol Adv 26(5):492–500. [PubMed: 18577442]
Lutumba P, Robays J, Miaka C et al (2006) Validity, cost and feasibility of the mAECT and
CTC conrmation tests after diagnosis of African of sleeping sickness. Trop Med Int Health
11:470–478
Luz JGG, Souto DEP, Machado-Assis GF, de Lana M, Kubota LT, Luz RCS, Damos FS, Martins
HR (2015) Development and evaluation of a SPR-based immunosensor for detection of anti-
Trypanosoma cruzi antibodies in human serum. Sensors Actuators B Chem 212:287–296
Luz JGG, Souto DEP, Machado-Assis GF, de Lana M, Luz RCS, Martins-Filho OA, Damos FS,
Martins HR (2016) Applicability of a novel immunoassay based on surface plasmon resonance
for the diagnosis of Chagas disease. Clin Chim Acta 454:395
Mach KE, Mohan R, Patel S, Wong PS, Hsieh M, Liao JC (2015) Development of a biosensor-
based rapid urine test for detection of urogenital schistosomiasis. PLoS Neglected Trop Dis
9:e0003845
MacKenzie R, Auzelyte V, Olliges S etal (2009) Nanowire development and characterization for
applications in biosensing. In: Nanosystems design and technology, pp143–173
Mahmoudvand H, Harandi MF, Shakibaie M etal (2014) Scolicidal effects of biogenic selenium
nanoparticles against protoscolices of hydatid cysts. Int J Surg 12:399–403
Mairiang D, Zhang HM, Sodja A etal (2013) Identication of new protein interactions between
dengue fever virus and its hosts, human and mosquito. PLoS One 8(1):e53535
Malekifard F (2017) Scolicidal effect of the gold nanoparticle on protoscoleces of hydatid cyst
invitro. J Urmia Univ Med Sci 28(2):130–137
Masocha W, Kristensson K (2019) Human African trypanosomiasis: how do the parasites enter
and cause dysfunctions of the nervous system in murine models? Brain Res Bull 145:18–29
Matsumoto TK, Hoshino-Shimizu S, Nakamura PM etal (1993) High resolution of Trypanosoma
cruzi amastigote antigen in serodiagnosis of different clinical forms of Chagas’ disease. J Clin
Microbiol 31:1486–1492
S. A. Rather etal.

79
McManus DP, Gray DJ, Zhang W, Yang Y (2012) Diagnosis, treatment, and management of echi-
nococcosis. BMJ 344:e3866
McManus DP, Bergquist R, Cai P, Ranasinghe S, Tebeje BM, You H (2020) Schistosomiasis—
from immunopathology to vaccines. Semin Immunopathol 42:355–371
Medawar-Aguilar V, Jofre CF, Fernández-Baldo MA, Alonso A, Angel S, Raba J, Messina GA
(2019) Serological diagnosis of Toxoplasmosis disease using a uorescent immunosensor with
chitosan-ZnO-nanoparticles. Anal Biochem 564:116–122
Mohan CO, Gunasekaran S, Ravishankar CN (2019) Chitosan-capped gold nanoparticles for indi-
cating temperature abuse in frozen stored products. NPJ Sci Food 3:2
Mohan R, Mach KE, Bercovici M et al (2011) Clinical validation of integrated nucleic acid and
protein detection on an electrochemical biosensor array for urinary tract infection diagnosis.
PLoS One 6(10):e26846
Molina J, Urbina J, Gref R, Brener Z, Rodrigues Junior JM (2001) Cure of experimental Chagas’
disease by the bis-triazole DO870 incorporated into ‘stealth’ polyethyleneglycol-polylactide
nanospheres. J Antimicrob Chemother 47:101–104. https://doi.org/10.1093/jac/47.1.101
Moncayo A (2003) Chagas disease: current epidemiological trends after the interruption of vecto-
rial and transfusional transmission in the Southern Cone countries. Mem Inst Oswaldo Cruz
98:577–591
Morilla MJ, Montanari J, Frank F, Malchiodi E, Corral R, Petray P et al (2005) Etanidazole in
pH-sensitive liposomes: design, characterization and in vitro/in vivo anti-Trypanosoma cruzi
activity. J Control Release 103:599–607. https://doi.org/10.1016/j.jconrel.2004.12.012
Moulick A, Richtera L, Milosavljevic V, Cernei N, Haddad Y, Zitka O, Kopel P, Heger Z, Adam
V (2017) Advanced nanotechnologies in avian inuenza: current status and future trends—a
review. Anal Chim Acta 983:42–53
Nambiar S, Yeow JT (2011) Conductive polymer-based sensors for biomedical applications.
Biosens Bioelectron 26(5):1825–1832. https://doi.org/10.1016/j.bios.2010.09.046. Epub 2010
Oct 1. PMID: 21030240
Nash TE (2014) Parasitic diseases that cause seizures. Curr Rev Clin Sci 14:29–34
Naumih JO, Noah N, Andala D, Janet K, Ndikau M, Kimani G et al (2016) Spectroelectrochemical
characterization of anti-schistosoma-gold nanoparticle conjugate for use in immunoassays.
J.Kenya Chem, Soc, p 9
Ngo HT, Gandra N, Fales AM, Taylor SM, Vo-Dinh T (2016) Sensitive DNA detection and SNP
discrimination using ultrabright SERS nanorattles and magnetic beads for malaria diagnostics.
Biosens Bioelectron 81:8–14
Norouzi R (2017) A review on most nanoparticles applied against parasitic infections. J Biol
Todays World 6(10):196–203
Odundo J, Noah N, Andala D, Kiragu J, Masika E (2018) Development of an electrochemical nano-
biosensor for rapid and sensitive diagnosis of bilharzia in Kenya. S Afr J Chem 71:127–134
Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK (2000) The structure of malaria pigment
β-haematin. Nature 404:307–310
Park SJ, Kwon OS, Lee SH, Song HS, Park TH, Jang J (2012) Ultrasensitive exible graphene
based eld-effect transistor (FET)-type bioelectronic nose. Nano Lett 12:5082–5090
Parra ME, Evans CB, Taylor DW (1991) Identication of Plasmodium falciparum histidine-rich
protein 2in the plasma of humans with malaria. J Clin Microbiol 29:1629–1634
Paul B, Panigrahi AK, Singh V, Singh SG (2017) A multi-walled carbon nanotube-zinc oxide
nanober based exible chemiresistive biosensor for malaria biomarker detection. Analyst
142:2128–2135
Penchenier L, Grebaut P, Njokou F, Eyenga VE, Buscher P (2003) Evaluation of LATEX/
T.b.gambiense for mass screening of Trypanosoma brucei gambiense sleeping sickness in
Central Africa. Acta Trop 85(1):31–37
Perkins MD, Bell DR (2008) Working without a blindfold: the critical role of diagnostics in
malaria control. Malar J 7:S5
Pittella JE (1994) The relation between involvement of the central nervous system in schistoso-
miasis mansoni and the clinical forms of the parasitosis. A review. J Trop Med Hyg 94:15–21
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

80
Pittella JE (1997) Neuroschistosomiasis. Brain Pathol 7:649–662
Pollner JH, Schwartz A, Kobrine A, Parenti DM (1994) Cerebral schistosomiasis caused by
Schistosoma haematobium: case report. Clin Infect Dis 18:354–357
Potipitak T, Ngrenngarmlert W, Promptmas C, Chomean S, Ittarat W (2011) Diagnosis and geno-
typing of Plasmodium falciparum by a DNA biosensor based on quartz crystal microbalance
(QCM). Clin Chem Lab Med (CCLM) 49(8):1367–1373
Qiao Z, Fu Y, Lei C, Li Y (2020) Advances in antimicrobial peptides-based biosensing methods for
detection of foodborne pathogens: a review. Food Control 112:107116
Qu F, Yang M, Lu Y, Shen G, Yu R (2006) Amperometric determination of bovine insulin based on
synergic action of carbon nanotubes and cobalt hexacyanoferrate nanoparticles stabilized by
EDTA.Anal Bioanal Chem 386(20):228–234
Radwanska M (2010) Emerging trends in the diagnosis of human African trypanosomiasis.
Parasitology 137:1977–1986. https://doi.org/10.1017/S0031182010000211
Rahimi MT, Ahmadpour E, Rahimi Esboei B etal (2015) Scolicidal activity of biosynthesized
silver nanoparticles against Echinococcus granulosus protoscolices. Int J Surg 19:128–133
Rapp BE, Gruhl FJ, Lange K (2010) Biosensors with label-free detection designed for diagnostic
applications. Anal Bioanal Chem 398(6):2403–2412
Ravaoarisoa E, Zamanka H, Fusai T, Bellalou J, Bedouelle H, Mercereau-Puijalon O, Fandeur T
(2010) Recombinant antibodies specic for the Plasmodium falciparum histidine-rich protein
2. MAbs 2:416–427
Regiart M, Pereira SV, Bertolino FA, Garcia CD, Raba J, Aranda PR (2016) An electrochemical
immunosensor for anti-T. cruzi IgM antibodies, a biomarker for congenital Chagas disease,
using a screen-printed electrode modied with gold nanoparticles and functionalized with shed
acute phase antigen. Microchim Acta 183:1203–1210
Rodriguez-del Valle M, Quakyi IA, Amuesi J, Quaye JT, Nkrumah FK, Taylor DW (1991)
Detection of antigens and antibodies in the urine of humans with Plasmodium falciparum
malaria. J Clin Microbiol 29:1236–1242
Saeed RM, Dmour I, Taha MO (2020) Stable chitosan-based nanoparticles using polyphosphoric
acid or hexametaphosphate for tandem ionotropic/covalent crosslinking and subsequent inves-
tigation as novel vehicles for drug delivery. Front Bioeng Biotechnol 8:4
Safarpour H, Majdi H, Masjedi A, Pagheh AS, Pereira MdL, Rodrigues Oliveira SM, Ahmadpour
E (2021) Development of optical biosensor using protein A-conjugated chitosan–gold nanopar-
ticles for diagnosis of cystic echinococcosis. Biosensors 11:134
Salinas E, Torriero A, Battaglini F, Sanz M, Olisina R, Raba J (2005) Continuous-ow/stopped-
ow system for enzyme immunoassay using a rotating bioreactor: determination of Chagas
disease. Biosens Bioelectron 21:313–321
Sanchez-Guillen MC, Barnabe C, Guegan JF etal (2002) High prevalence anti-Trypanosoma cruzi
antibodies, among blood donors in the State of Puebla, a non-endemic area of Mexico. Mem
Inst Oswaldo Cruz 97:947–952
Santos GS, Andrade CAS, Bruscky IS, Wanderley LB, Melo FL, Oliveira MDL (2017)
Impedimetric nanostructured genosensor for detection of schistosomiasis in cerebrospinal uid
and serum samples. J Pharmaceut Biomed Anal 137:163–169
Santos GS, Caldas RGSC, Melo FL, Bruscky IS, Silva MAIL, Wanderley LB, Andrade CAS,
Oliveira MDL (2019) Label-free nanostructured biosensor for Schistosoma mansoni detection
in complex biological uids. Talanta 204:395–401
Scrimgeour EM, Gajdusek DC (1985) Involvement of the central nervous system in Schistosoma
mansoni and S. haematobium infection. A review. Brain 108:1023–1038
Sekhar GN, Watson CP, Fidanboylu M, Sanderson L, Thomas SA (2014) Delivery of antihuman
African trypanosomiasis drugs across the blood-brain and blood-CSF barriers. Adv Pharmacol
71:245–275
Seremeta KP, Arrua EC, Okulik NB, Salomon CJ (2019) Development and characterization of
benznidazole nano- and microparticles: a new tool for pediatric treatment of Chagas disease?
Colloids Surf B: Biointerfaces 177:169–177. https://doi.org/10.1016/j.colsurfb.2019.01.039
S. A. Rather etal.

81
Sharma MK, Rao VK, Agarwal GS, Rai GP, Gopalan N, Prakash S, Sharma SK, Vijayaraghavan R
(2008) Highly sensitive amperometric immunosensor for detection of plasmodium falciparum
histidine-rich protein 2in serum of humans with malaria: comparison with a commercial kit. J
Clin Microbiol 46:3759–3765
Shohayeb M, Arida H, Mersal GAM, El-badawy M (2016) Development of a nanotechnol-
ogy-based screen-printed biosensor for detection of schistosoma mansoni antibodies. Int J
Electrochem Sci 11:1337–1344
Shrestha BK, Ahmad R, Mousa HM, Kim IG, Kim JI, Neupane MP, Park CH, Kim CS (2016)
High-performance glucose biosensor based on chitosan-glucose oxidase immobilized poly-
pyrrole/Naon/functionalized multi-walled carbon nanotubes bio-nanohybrid lm. J Colloid
Interface Sci 482:39–47
Siddiqua T, Habeeb A (2020) Neurocysticercosis. Saudi J Kidney Dis Transpl 31(1):254–258
Sikarwar B, Sharma PK, Srivastava A, Agarwal GS, Boopathi M, Singh B, Jaiswal YK (2014)
Surface plasmon resonance characterization of monoclonal and polyclonal antibodies of
malaria for biosensor applications. Biosens Bioelectron 60:201–209
Siles-Lucas M, Casulli A, Conraths FJ, Müller N (2017) Chapter 3—Laboratory diagnosis of
Echinococcus spp. In: Thompson RCA, Deplazes P, Lymbery AJ (eds) Human patients and
infected animals, Advances in parasitology, vol 96. Academic, Cambridge, MA, pp159–257
Singh NK, Arya SK, Estrela P, Goswami P (2018) Capacitive malaria aptasensor using Plasmodium
falciparum glutamate dehydrogenase as target antigen in undiluted human serum. Biosens
Bioelectron 117:246–252
Singh NK, Thungon PD, Estrela P, Goswami P (2019) Development of an aptamer-based eld
effect transistor biosensor for quantitative detection of Plasmodium falciparum glutamate
dehydrogenase in serum samples. Biosens Bioelectron 123:30–35
Sposito PA, Mazzeti AL, De Oliveira FC, Urbina JA, Pound-Lana G, Bahia MT et al (2017)
Ravuconazole self-emulsifying delivery system: in vitro activity against Trypanosoma cruzi
amastigotes and in vivo toxicity. Int J Nanomedicine 12:3785–3799
Soares LMB, Costa NS, Peralta RHS, Peralta JH, Allil RCSB, Werneck MM, Carvalho ICS, Costa
KB (2018) Nanoparticles based plasmonic biosensor. In: Latin America optics and photonics
conference. OSA Technical Digest (Optica Publishing Group, 2018). Paper Tu2C.1
Sousa S, Castro A, Correia da Costa JM, Pereira E (2021) Biosensor based immunoassay: a new
approach for serotyping of toxoplasma gondii. Nanomaterials 11(8):2065
Sundaram C, Shankar SK, Thong K, Pardo-Villamizar CA (2011) Pathology and diagnosis of
central nervous system infections. Pathol Res Int 21:1–4
Taleat Z, Khoshroo A, Mazloum-Ardakani M (2014) Screen-printed electrodes for biosens-
ing: a review (2008–2013). Microchim Acta 181(9-10):865–891. https://doi.org/10.1007/
s00604-014-1181-1
Tertis M, Hosu O, Feier B, Cernat A, Florea A, Cristea C (2021) Electrochemical peptide-based
sensors for foodborne pathogens detection. Molecules 26:3200
Thukral P et al (2023) Sustainable green synthesized nanoparticles for neurodegenerative dis-
eases diagnosis and treatment. Mater Today Proc 73(2):323. https://doi.org/10.1016/j.
matpr.2022.10.315
Tiberti N, Hainard A, Lejon A etal (2010) Discovery and verication of osteopontin and beta-
2-microglobulin as promising markers for staging human African trypanosomiasis. Mol Cell
Proteomics 9(12):2783–2795
Tiberti N, Hainard A, Sanchez JC (2013) Translation of human African trypanosomiasis biomark-
ers towards eld application. Transl Proteomics 1(1):12–24
Tsai YH, Liu X, Seeberger PH (2012) Chemical biology of glycosylphosphatidylinositol anchors.
Angew Chem Int Ed 51(46):11438–11456
Turner APF (2013) Biosensors: sense and sensibility. Chem Soc Rev 42:3184
Tweed-kent A, Niemann M, Ulrich HG, Zelada-guille GA, Riu J, Rius FX (2012) Ultrasensitive
and real-time detection of proteins in blood using a potentiometric carbon-nanotube aptasensor
C.Biosens Bioelectron 41:366–371
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases

82
Umezawa ES, Nascimento MS, Stolf AM (2001) Enzyme-linked immunosorbent assay with
Trypanosoma cruzi excreted secreted antigens (TESA-ELISA) for serodiagnosis of acute and
chronic Chagas’ disease. Diagn Microbiol Infect Dis 39:169–176
van Etten L, Folman CC, Eggelte TA, Kremsner PG, Deelder AM (1994) Rapid diagnosis of schisto-
somiasis by antigen detection in urine with a reagent strip. J Clin Microbiol 32(10):2404–2406.
https://doi.org/10.1128/jcm.32.10.2404-2406.1994
Veigas B, Pedrosa P, Carlos FF, Mancio-Silva L, Grosso AR, Fortunato E, Mota MM, Baptista
PV (2015) One nanoprobe, two pathogens: gold nanoprobes multiplexing for point-of-care. J
Nanobiotechnol 13:48
Vermelho AB, Da Silva CV, Ricci Junior E, Dos Santos EP, Supuran CT (2018) Nanoemulsions of
sulfonamide carbonic anhydrase inhibitors strongly inhibit the growth of Trypanosoma cruzi. J
Enzyme Inhib Med Chem 33:139–146
Vidic J, Vizzini P, Manzano M, Kavanaugh D, Ramarao N, Zivkovic M, Radonic V, Knezevic N,
Giouroudi I, Gadjanski I (2019) Point-of-need DNA testing for detection of foodborne patho-
genic bacteria. Sensors 19:1100
Vieira CS, Almeida DB, De Thomaz AA, Menna-Barreto RF, Dos Santos-Mallet JR, Cesar CL et
al (2011) Studying nanotoxic effects of CdTe quantum dots in Trypanosoma cruzi. Mem Inst
Oswaldo Cruz 106:158–165
Vizzini P, Manzano M, Farre C, Meylheuc T, Chaix C, Ramarao N, Vidic J (2021) Highly sensitive
detection of Campylobacter spp. in chicken meat using a silica nanoparticle enhanced dot blot
DNA biosensor. Biosens Bioelectron 171:112689
Walker MD, Zunt JR (2005) Neuroparasitic infections: cestodes, trematodes, and protozoans.
Semin Neurol 25(3):262–277
Wan Y, Su Y, Zhu X, Liu G, Fan C (2013) Development of electrochemical immunosensors
towards point of care diagnostics. Biosens Bioelectron 47:1–11. https://doi.org/10.1016/j.
bios.2013.02.045
Wang J (2008) Electrochemical sensors, biosensors and their biomedical applications. In:
Electrochemical glucose biosensors. Elsevier, Amsterdam, pp57–69
Wang H, Lei C, Li J, Wu Z, Shen G, Yu R (2004) A piezoelectric immunoagglutination assay for
Toxoplasma gondii antibodies using gold nanoparticles. Biosens Bioelectron 19(7):701–709
Wang S, Yin S, Zeng H, Che F, Yang X, Chen G, Shen Z, Wu A (2012) Piezoelectric immunosen-
sor using hybrid self-assembled monolayers for detection of Schistosoma japonicum. PLoS
One 7:e30779
Wangmaung N, Chomean S, Promptmas C, Mas-oodi S, Tanyong D, Ittarat W (2014) Silver quartz
crystal microbalance for differential diagnosis of Plasmodium falciparum and Plasmodium
vivax in single and mixed infection. Biosens Bioelectron 62:295–301
Wen Z, Wang S, Wu Z, Shen G (2011) A novel liquid-phase piezoelectric immunosensor for
detecting Schistosoma japonicum circulating antigen. Parasitol Int 60:301–306
Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang W, McManus DP (2019) Echinococcosis:
advances in the 21st century. Clin Microbiol Rev 32(2):e00075
White NJ (1991) Sulfadoxine-pyrimethamine for the treatment of malaria. Trans R Soc Trop Med
Hyg 85:556–557
Whitesides GM (2006) The origins and the future of microuidics. Nature 442(7101):368–373
WHO (2013) Control and surveillance of human African trypanosomiasis. In: Report of a WHO
Expert Committee 984. WHO
WHO (2018) The World malaria report 2018. World Health Organization, Geneva, Switzerland
Wu W, Li J, Pan D, Li J, Song S, Rong M, Li Z, Gao J, Lu J (2014) Gold nanoparticle-based
enzyme-linked antibody-aptamer sandwich assay for detection of Salmonella typhimurium.
ACS Appl Mater Interfaces 6:16974–16981
Wu W, Zhao S, Mao Y, Fang Z, Lu X, Zeng L (2015) A sensitive lateral ow biosensor for
Escherichia coli O157:H7 detection based on aptamer mediated strand displacement ampli-
cation. Anal Chim Acta 861:62–68
S. A. Rather etal.

83
Xiao J, Yolken RH (2015) Strain hypothesis of Toxoplasma gondii infection on the outcome of
human diseases. Acta Physiol (Oxf) 213(4):828–845. https://doi.org/10.1111/apha.12458.
Epub Jan 28. PMID: 25600911; PMCID: PMC4361247
Xu L, Du J, Deng YN (2010) Fabrication of magnetic porous pseudo-carbon paste electrode elec-
trochemical biosensor and its application in detection of schistosoma egg antigen. Electrochem
Commun 12:1329–1332
Xu R, Feng J, Hong Y, Lv C, Zhao D, Lin J et al (2017) A novel colloidal gold immunochromatog-
raphy assay strip for the diagnosis of schistosomiasis japonica in domestic animals. Infect Dis
Poverty 6(1):84. https://doi.org/10.1186/s40249-017-0297-z
Yang M, Kostov Y, Bruck HA, Rasooly A (2009) Gold nanoparticlebased enhanced chemilumines-
cence immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food. Int J Food
Microbiol 133(3):265–271. https://doi.org/10.1016/j.ijfoodmicro.2009.05.029
Youssef AI, Uga S (2014) Review of parasitic zoonoses in Egypt. Trop Med Health 42(1):3–14
Zaidi MB, Cedillo-Barron L, Almeida MHG, Garcia-Cordero J, Campos FD, Perez F (2020)
Serological tests reveal signicant cross-reactive human antibody responses to Zika and
Dengue viruses in the Mexican population. Acta Trop 201:105201
Zarlenga DS, Trout JM (2004) Concentrating, purifying and detecting waterborne parasites. Vet
Parasitol 126:195–217
Zeng S, Tian Z, Che H, Yang H, Chen X, Feng X, Zhou Y, Zhang S, Wu S, Wang S (2012)
Novel printed electrode immunosensors for Schistosoma japonicum. J Cent S Univ Med Sci
37:541–548
Zhang D, Qi Y, Cui Y, Song W, Wang X, Liu M, Cai X, Luo X, Liu X, Sun S (2021) Rapid detection
of Cysticercus cellulosae by an up-converting phosphor technology-based lateral-ow assay.
Front Cell Infect Microbiol 11:762472
Zhao X, Li M, Liu Y (2019) Microuidic-based approaches for foodborne pathogen detection.
Microorganisms 7:381
Zheng J, Gu XG, Xu YL etal (2002) Relationship between the transmission of schistosomiasis
japonica and the construction of the Three Gorge Reservoir. Acta Trop 82:147–156
3 Implications ofNano -Biosensors intheEarly Detection ofNeuroparasitic Diseases