3.3 Clinical manifestations and
diagnosis
In most cases for patients suffering from neuroangiostrongyliasis, a
presumptive diagnosis has to be made by using several observations such
as; symptoms, history of travel and diet, analysis of CSF or serum
samples, and serological tests (Ansdell et al., 2021). Nevertheless, in
regions where the rat lungworm is not endemic or it has been very
recently introduced, there may be a delay in considering
neuroangiostrongyliasis as diagnosis by the medical practitioners, which
may hinder treatment effectiveness (Cowie et al., 2022; Luo et al.,
2023).
Generally, the incubation period of Angiostrongylus cantonensisis 1-2 weeks; however it may vary. The symptoms associated withAngiostrongylus cantonensis may also vary; nevertheless, some
common indicators are headache, neck stiffness, Brudzinski’s sign/
Kernig’s sign, hyperesthesia/paresthesia, fever, muscle weakness, facial
palsy and paralysis of the external muscles (Cowie et al., 2022; Tseng
et al., 2011). The symptoms and severity of the disease may be dependent
on parasite strain (Lee et al., 2014), parasite load, and the patient’s
tolerance level towards their immune response (Watthanakulpanich et al.,
2021). For example, severe headache was the most common symptom in
Thailand, fever and neck stiffness in China, and headache and fever in
Taiwan (Khamsai et al., 2020). Whether the variation in symptoms sheds
light on the severity of the infection is unclear; the majority of cases
resolve spontaneously, though more serious cases may result in death
(McAuliffe et al., 2019). Nevertheless, given that none of the symptoms
are distinctive enough to be diagnostic, most cases require laboratory
testing to obtain a definitive diagnosis.
In Taiwan, a study by Lee et al. (2014) investigated the genetic
differences among Angiostrongylus cantonensis populations, and
discovered the presence of two primary strains showing infectivity in
non-permissible hosts such as humans. The more common strain showed low
genetic diversity and high infectivity, whereas the new strain isolated
from Hualien showed considerable genetic difference from the other
strains, and much lower infectivity in their mouse models. This is
corroborated by another metagenomic study concluding that there is low
genetic diversity in infective invasive Angiostrongylus
cantonensis strains globally (Červená et al., 2019). Hence, the large
variety of symptoms may possibly arise from other factors such as larval
development in the human host, and interaction with the individual
immune systems.
Definitive diagnosis is possible with visual confirmation ofAngiostrongylus cantonensis larvae in the blood or cerebrospinal
fluid (CSF); however it is rarely successful (Ansdell et al., 2021).
Detection of blood eosinophilia, and studying CSF characteristics e.g.,
high CSF pressure, CSF white blood cell count (especially eosinophils),
and CSF proteins are often used as initial indicators (Wang et al.,
2011). Radiography such as magnetic resonance imaging (MRI) and computed
tomography (CT) scans are also used as supplementary tests, particularly
MRI of the brain where lesions, leptomeningeal enhancement, or increased
signal intensity in the subcortical white matter may be detected after
the first few weeks of infection (Ansdell et al., 2021). MRI of the
spine is recommended for patients with myeloradicular symptoms.
Furthermore, CT scans of the chest have shown nodular lesions,
indicative of migratory larvae or young adult parasites, but is
ineffective in most cases. Nevertheless, it is recommended to undergo a
chest CT scan only if there are respiratory symptoms (Ansdell et al.,
2021).
Serological methods such as dot immunogold filtration assay (DIGFA)
developed by Eamsobhana et al. (2021), are already in use in hospitals
of endemic regions, such as Thailand. The disadvantage of serological
methods is the delay in formation of antibodies; however serological
tests are still a common procedure, both as a method of diagnosis, as
well as to rule out the presence of other parasites (Carvalho et al.,
2022).
Detection of parasite DNA in CSF or serum of patient by polymerase chain
reaction (PCR) is currently used for conclusive results (Carvalho et
al., 2022). Molecular techniques have a number of benefits over other
methods (e.g., visual detection or serological methods) where early
detection can be done from parasite fragments without need of antibody
formation (Qvarnstrom et al., 2016). There are a number of molecular
assays that are currently in use or under development which can be used
for high sensitivity or specificity (Carvalho et al., 2022). There is a
possibility of a negative PCR result despite strong clinical suspicion
if the sample is taken from early infection stages, however it is
recommended that the test be repeated in 5-10 days in such a scenario
(Ansdell et al., 2021). Recently, a novel method, metagenomic
next-generation sequencing (mNGS) used for the presence of multiple
parasites simultaneously, has also been used to detectAngiostrongylus cantonensis in some case studies (Carvalho et
al., 2022). Additionally, the AcanR3990 qPCR assay developed by Sears et
al. (2021), shows potential for success as a diagnostic tool for
neuroangiostrongyliasis, with greater accuracy and sensitivity than
conventional PCR with ITS primers (Jarvi et al., 2023). Genetic
characterization of the obtained A. cantonensis larvae as done by
Dumidae et al. (2023) provides substantial reference data for more
robust molecular identification methods.
In Taiwan, the current method of Angiostrongylus cantonensisdetection is by use of PCR on CSF samples (Luo et al., 2023). In
addition, alternative markers for easier detection ofAngiostrongylus cantonensis infection are being tested, such as
IgE antibody levels in Angiostrongylus cantonensis infected mouse
models (Lee et al., 2023), and microRNA upregulation in
meningoencephalitis caused by Angiostrongylus cantonensisinfection (Chen and Lai, 2023).