Cysticercosis (Taenia Solium) • Spirometra Spp

DIAGNOSTIC TOOLS FOR PARASITES OF THE CNS

Hanspeter Marti Swiss Tropical and Public Health Institute Basel ESCMID / Switzerland eLibrary [email protected] August 8, 2017 © byTitle of Presentation author 1 Parasites in the Brain

Helminths • Alaria spp. • Paragonimus spp. • Angiostrongylus spp. • Schistosoma spp. • Baylisascaris procyonis • Strongyloides spp. • Cysticercosis (Taenia solium) • Spirometra spp. • Echinococcus spp. • Toxocara spp. • Fasciola hepatica • Trichinella spp • Gnathostoma spinigerum Amoeba • Acantamoeba spp. • Entamoeba histolytica • BalamuthiaESCMIDmandrillaris eLibrary• Naegleria fowlerii © by author 24 year old female Returned from Thailand 2 weeks earlier Severe frontal headache, vomiting Fully oriented, moderate stiffness of the neck

WBC: 8700/mm3 (18% eosinophil granulocytes) CSF differential count: all polynuclear cells were eosinophils CT scan of the brain was normal Diagnosis: EosinophilicESCMID meningitis eLibrary STI/TropMed © by author DD eosinophilic meningitis

Parasitic: - Echinococcosis Malignant: - Angiostrongyliasis - Anisakiasis - Glioblastoma - Gnathostomiasis Fungal: - Lymphoma - Toxocariasis - Aspergillosis - Acute leukaemia - Neurocysticercosis - Coccidioidomyciosis - Meningeal - Schistosomiasis Non-infectious: carcinomatosis - Strongyloidiasis - VP-shunt Drugs: - Paragonimiasis - Neurosarcoidosis - Ibuprofen - Fascioliasis - Wegener’s - Ciprofloxacin - Baylisascariasis granulomatosis - Intraventricular - Lagochilascariasis - Churg-Strauss syndrome Vancomycin - Ascaris - Eosinophilic CNS - Intraventricular - Trichinellosis vasculitis Gentamicin - Sparganosis ESCMID- Idiopathic eLibrary hyper- - Post -vaccination - Toxoplasmosis eosinophilic syndrome encephalitis © by author Diagnosis

• Clinical picture + suggestive food history

• Eosinophilia (blood, CSF)

• Serology

• Detection of larvae in CSF only rarely possible ESCMID eLibrary © by author CSF with eosinophilic pleocytosis (Giemsa stain).

ESCMID eLibrary © by author ELISA: Screening test

Controls Patients Patient_9

Trichinella Toxocara

Echinococcus done

Fasciola be Schisto adult ag Schisto egg ag Filaria

Strongyloides ESCMID eLibrary Confirmation to test Confirmation © by author Most frequent crossreactions: assess pattern!

Antigen Sm Sm Fh Eg Sr Av Tc Ts Parasitosis adult egg Schistosomiasis Fasciolosis Echinococcosis Strongyloidosis Filariosis Toxocarosis Trichinellosis

ESCMID eLibrary © by author Angoistrongylus Western Blot

ESCMID eLibrary August 8, 2017 © byTitle of Presentation author 9 Diagnosis

Findings on CT and MRI imaging of the brain are generally non-specific: there may be focal lesions)

ESCMID eLibrary © by author Findings in imaging procedure

2-4 Weeks after ingestion of larvae: Lung CT may show opaque, subpleural, round lesions

MRI Head

ESCMID eLibrary Li H, Am J Trop ©Med Hygby2008 author Transmission

Accidental Infection of human host by: - Contact with slugs/snails (faeces) - Eating salad (where slug/snails have been) Caesar Salad Jamaica (Slom TJ, NEJM 2002) - Eating un-/under-cooked Crustacea, frogs.. (parataenic ESCMIDhosts) eLibrary Wang Q et al. Lancet Infect Dis. © by author Epidemiology

ESCMID eLibrary

Distribution of A. cantonensis and human infections or outbreaks worldwide (modified from Wang Q© et al. Human by angiostrongyliasis author. Lancet Infect Dis. 2008;8:621-30) Angiostrongyloidosis

Eosinophilic meningitis • most frequent manifestation. • severity is determined by the number of invasive larvae. • most cases are mild and self-limiting with spontaneous resolution of symptoms after 1–8 weeks. • serious sequelae are rare.

Eosinophilic encephalitis Rare, mostly fatal manifestation resulting from massive infection. Ocular Larva Migrans syndrome Ectopic migration of the parasite into the eye causes severe ESCMIDocular inflammation with permanenteLibrary visual impairment. © by author Angiostrongylus: key points

Severe headache, nausea, vomiting, paraesthesia Stiffness of the neck Peripheral eosinophilia Liquor pleocytosis and eosinophilia

ESCMID eLibrary STI/TropMed © by author Angiostrongylus Diagnosis

History of travel / consumption of undercooked food  peripheral eosinophilia

CSF: 500-2000 leukocytes/mm3  25-75% eosinophil granulocytes

CSF protein elevated in 2/3 of the cases CSF pressure elevated; can be relieved by lumbar puncture ESCMID eLibrary STI/TropMed © by author Angiostrongylus: Diagnosis

Exclusion of bacterial or viral meningitis  Tuberculosis

Exclusion of other parasitic infection  Toxocara, Trichinella, Strongyloides (serology)  Paragonimus (radiology of the lung, serology)  Gnathostoma (serology) ESCMID eLibrary STI/TropMed © by author ESCMID eLibrary © by author 18 DIAGNOSTIC TOOLS FOR PARASITES OF THE CNS

Hanspeter Marti Swiss Tropical and Public Health Institute Basel ESCMID / Switzerland eLibrary [email protected] August 8, 2017 © byTitle of Presentation author 19 Cysticercosis

ESCMID eLibrary © by author ESCMID eLibrary August 8, 2017 © by author 21 Life cycle – T. solium

ESCMID eLibrary © by author(from Manson’s Tropical Tropical Diseases, 23rd edition, 2014) ESCMID eLibrary © by author ESCMID eLibrary © by author Diagnosis

Intestinal infection • Detection of eggs or proglottids in faeces • Coporantigen stool assays • Stool PCR ESCMID eLibrary © by author Taenia solium or T. saginata?

Eggs cannot be distinguished

Proglottids

T.solium T. saginata 7-12 14-32

Cysticercosis • CT / MRI imaging • Serology (Western Blot)

ESCMID eLibrary © by author ESCMID eLibrary Cyst Scolex © by author But not only in the brain: (calcified) cysticerci in sceletal muscles

• neurocysticercosis is the worldwide leading cause of late-onset epilepsy. • the clinical picture varies widely according to the location of the cysticerci and their stage of evolution ESCMID eLibrary © by author How do epileptic seizures happen?

• Cysts of 1-2 cm do not cause symptoms as long as they are viable. • Dying cysts lead to inflammatory reactions which cause clinical symptoms (e.g. headache, epileptic seizures). • Calcifications occur after the inflammation and can be epileptogenic foci.

Multiple subarachnoidal cysts in spine Thoracic and cervical spine, blocking the liquor circulation

 WB for cysticercosis both positive in serum and CSF ESCMID PCR of spinaleLibrary fluid positive for T. solium © by author Cysticercosis Antigen (Ag) ELISA

 Enzyme Immunoassay that indicates the presence of viable cysticerci of Taenia spp. in serum 2-6 weeks p.i.  The assay is genus specific, based on detection of ES glycoprotein antigens from T.saginata cysticerci.  As T. solium is the only Taenia species causing cysticercosis in humans, the test is specific.  Antigen levels are generally higher in extraparenchymal neurocysticercosis (particularly subarachnoid NCC) than in intraparenchymal NCC; ESCMID eLibrary August 8, 2017 ©A synthetic peptideby for the diagnosis author of visceral leishmaniasis 34 Cysticercosis Antigen (Ag) ELISA

 Antigen levels correlate with the number and size of lesions  Infections with only one viable cyst are often not detectable.  The ELISA does not detect degenerated or calcified cysticerci  Well suited for serological monitoring of therapy as antigen levels drop rapidly after successful anthelminthic treatment

ESCMID eLibrary August 8, 2017 ©A synthetic peptideby for the diagnosis author of visceral leishmaniasis 35 Antigen levels and brain images of the subarachnoid lesions

ESCMIDCirculating antigen level follow eLibrary post-treatment evaluation of subarachnoid neurocysticercosis, Garcia HH, J Neuroparasitol 2010 © by author Thank you