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THE TRAVEL OF THE WORM Míriam J. Álvarez-Martínez, M. D., Ph. D. Hospital Clinic, Barcelona (Spain) CRESIB (Barcelona Center for International Health Research) University of Barcelona [email protected] ESCMID Online Lecture Library © by author

THE TRAVEL OF THE WORM

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Page 2: THE TRAVEL OF THE WORM

CLINICAL CASE • 69y/ Spanish male, had lived in Dominican Republic (2000-2002) • Hypertension treated with enalapril

• DM-2 years of evolution without treatment and without known

chronic complications

• Bronchial asthma treated with salmeterol, ipratropium bromide and chronic oral glucocorticoids

• Vocal cord carcinoma intervened in 2003 (free from disease)

• Prostate adenocarcinoma treated with radical prostatectomy in 2003 (disease-free)

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February 1st, 2008 (Hospital 1):

• Left hemiparesis with partial remission

• MRI brain acute cerebral ischemic injury

CURRENT DISEASE

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15 days later (hospital 1): • Vomiting, headache and fever 38 º C • Physical exploration moderate neck stiffness without source

NRL standard ENT examination

• LP purulent CSF, 26000 Leukocyte (PMN 95%), Gram and cultures negative

• Cerebral CT not added lesions to the objectified in MRI performed during previous admission

• Broad spectrum ATB treatment good clinical outcome and normalization of CSF

CURRENT DISEASE

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• Blood cultures & urine culture (+) for Escherichia coli

• Discharge 1 month later (March 1st)

Since discharge: • Wife of patient reported a progressive malaise,

anorexia, weight loss and episodes of disorientation

CURRENT DISEASE

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March 15th, 2008 (Hospital 2, HC-BCN) • Suddenly worsening decreased level of consiousness, without

fever • Physical exploration cachectic appearance • LP 900 leukocytes (PMN 100%), Prot 320, Glu 0, ADA 13, CSF

cytocentrifuge abundant cellularity (PMN only), Gram- stain, no microorganism

• CT Brain unchanged from previous studies

CURRENT DISEASE

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• Diagnosis of Bacterial meningitis treatment meropenem 1g/12h, vancomycin 1 g/12h & ampiciline 1g/6h

• Due to reduced consiousness level ICU • At 48h of ATB treatment Control LP • CSF culture Gram negative rods

CURRENT DISEASE

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• ATB change to meropenem & ciprofloxacin • Urine culture Mixed bacteria • CSF culture E. coli susceptible to

amoxicilin-clavulanic, ampicilin, cefazoline, cefuroxime & gentamicine, & resistent to ciprofloxacine & cotrimoxazole

• Negative blood cultures

CURRENT DISEASE

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• ATB change to Ceftriaxone • Normal Abdominal Eco • TT Ecocardio none valvular vegetations

“…at that time a test was performed showing the diagnosis…”

CURRENT DISEASE

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Microbiology results • 28 April 2008 • 29 April • 30 April

• 8 May

• 9 May

• CSF: E. coli • BAS: E.coli

• CSF: E. coli • Traqueal aspirate :

larvaeStrongyloides stercoralis; Candida sp.

• Urine: Candida sp. • CSF: NO parasites or bacterias • Duodenal Aspirate : larvae

Strongyloides stercoralis • Negative faecal sample

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Rhadbitiforme Larva (L1) & Strongyloides stercoralis eggs in duodenal aspirate.

Larva: 250 x 20 µm. Egg: 50 µm . 40X

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Strongyloides

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Cestodostape worms

Trematodosflukes

Platyhelmintosgusanos planos

Nematodosround worms

Nematohelmintosgusanos redondos

Metazoa

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Nematodes characteristics

• Round worms • No segmented • Mouth, esophagus & anus • Separated sex (female > male) • Reproduction - oviparus - larviparus • Infection - ingestion eggs/ larvae

- penetration - larvae

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Strongyloides stercoralis

• Round worm • S. fülleborni chimpancees & limited

human infections. • World distribution • Tropical & subtropical areas • Microhabitats in rural areas in the

Mediterranean basin of Spain (La Safor)-rice fields

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Larva rhabditiforme

Larva filariforme

Rhabditiforme larva (L1)

Filariform larva (L3)

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Strongyloides’ travels

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Life cycle of Strongyloides

Chiodini et al., Atlas of helminthology,2006.

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Larva Dermatitis in site of penetration

L3

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L1 intestinal lumen --- faeces ESCMID Online Lectu

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Free life cycle

Direct

L1 in faeces

L3 infects again

Rhabditiform larva

Filariform Larva L3

L3 L1

L1 ESCMID Online Lecture Library

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male-female adults

Filariform larva Rhabditiform

L3 L1

L1

L3

Free Life Cycle Indirect L3—Adults—eggs—L1—L3

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Direct cycle to other person External Autoinfection Internal Autoinfection

L1 L3

L3

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Diagnosis of Strongyloides • Identification of larvae (rhabditiforms-L1 & rarely

filariform larvae) in faeces or duodenal fluid. – Wet preparation – Hot water emergence technique – Faecal Concentration (formol-ether) – Culture (Charcoal, Agar) – Harada Mori – Enterotest o string test

• Detection of larvae in sputum (diseminated form) ESCMID Online Lectu

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Rhabditiform larva of Strogyloides stercolaris wet prep. Size 200-250 µm.

L1

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Detail esophagus Rhabditiform larva of Strongyloides

L1

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Rare worm’s travel

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Recurrent meningitis by E. coli caused by severe disseminated

Strongyloidosis

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• Acute Strongyloidiasis • Chronic Strongyloidiasis • Hyperinfection syndrome

– High acceleration autoinfection process within the life cycle.

– Larvae are confined to locations own cycle: intestines, lungs and skin.

– Motivated by alteration of the immune status of the host.

Igual Adell et al. Estrongiloidiasis. EIMC, 2007

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Genta et al., Disregulation of Strongyloidiasis: a new hipothesis. Clin Microb Rev, 1982.

Molting rate of lavae in the instestinal lumen

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Corticoids & Hiperinfection • Main factor in triggering hyperinfection.

– < 10 days after corticosteroids hiperinfection produced. – No hiperinfection after inmunosupression by non-

steroids drugs. – Even with subconjuntival/parenteral corticosteroids – VIH + Corticosteroids: Hiperinfection, but not in other

OI – HIPERINFECTION SYNDROME IS NOT associated

to the LEVEL of immunosuppression, but to the used IMMUNOSUPRESSED AGENT

Genta et al., Disregulation of Strongyloidiasis: a new hipothesis. Clin Microb Rev, 1982.

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Vadlamudi et al. Intestinal strongyloidiasis and hyperinfection syndrome. Clin Mol Allerg 2006, 4(8); 1-13.

1

2

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• Acute Strongyloidiasis • Chronic Strongyloidiasis • Hyperinfection syndrome • Disseminated Strongyloidosis

– In the context or not of hiperinfection – Larvae afecting different organs: Brain, liver, lymphatic, urinary & others.

• Severe Disseminated Strongyloidosis – Complicated with bacterial infection from intestine.

High Mortality. – Frequency 1,5 -2,5% – Due to alteration of intestinal wall because high

penetration of larvae from the intestinal lumen. Igual Adell et al. Estrongiloidiasis. EIMC, 2007

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Recurrent Meningitis by E. coli Form of Severe Disseminated Strongyloidosis

– Rare recurrence (5% of disseminated forms) – Theories of bacterial transportation (to brain)

• Disrruption of intestinal wall and pass fecal flora into the circulation.

• Bacteria adhered to the outer surface of the larvae are transported during migration .

• Excreted bacterial to circulation from the intestinal tract of the larva.

• Favored by a defect in the cranial valve system.

Smallman et al. Strongyloides stercoralis hyperinfestation syndrome with E.coli meningitis. J Clin Pathol, 1986. Somin et al. Fatal recurrent bacterial meningitis- A complication of chronic Strongyloides infection. Eur J Int Med, 2008.

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CHAGAS & STRONGYLOIDES COINFECTION

Screening S. stercoralis

218 patients

79 (36,2%)

S. stercoralis positive

39 (49%)

coinfected

S. stercoralis & T.cruzi

• High prevalence of co-infection

of St and CD in patients from Latin-America.

• Bolivian patients the most important group.

• At the presence of eosinophilia, the screening

for St and CD is strongly recommended.

• Taking into account the nature of these NTDs,

their burden could be underestimated

in non-endemic areas.

Bolivia

RD Congo

Ecuador

Guinea Ecualtorial

Honduras

India

Sierra Leona

Alvarez et al., Communication, SEIMC, 2012

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