Diplôme Universitaire d’ Antibiologie
14 janvier 2015
HELMINTHIASES D’IMPORTANCE MÉDICALE
Parasitoses d’ici et d’ailleurs
PARTIE 1: RAPPELS ÉPIDÉMIOLOGIQUES ET PHYSIOPATHOLOGIQUES
Dr Danièle Maubon
Faculté de médecine – CHU de Grenoble
Laboratoire de Parasitologie-Mycologie
[email protected]
PLAN
Partie 1: Rappels épidémiologiques/cycles/pathogénèse/prévention
 NEMATODES
= vers ronds
 Oxyure
 Soil Transmitted
Helminths




Anguillulose
Ascardiose
Trichocéphalose
Ankylostomose
 CESTODES
= vers plats segmentés

Cestodoses
ADULTES
 Taeniases


TREMATODES
= vers plats foliacés


Bilharziose
Distomatose
Cestodoses
LARVAIRES


Cysticercose
Echinococcoses
Partie 2: Prise en charge thérapeutique individuelle et focus molécules antiparasitaires
 Dr MP Brenier-Pinchart
NEMATODES
ENTEROBIASIS - EPIDEMIOLOGY – LIFE CYCLE





Enterobius vermicularis: pinworm
Humans are the only natural host.
Fecal-oral contamination
Maturation: 2 weeks
Adult worms





Migrates to the perineum (often at night)
Infectious in the environment : 3 weeks.
Worldwide distribution
Prevalence


terminal ileum, cecum, appendix
5-15%
Children < 18 +++
CLINICAL SIGNS AND DIAGNOSTIC TOOLS




Asymptomatic
Pruritus ani and pruritus vulvae
Abdominal pain (can mimic acute appendicitis)
Biological diagnostic


Not systematic
Scotch-test: transparent tape is pressed against the perineum
PREVENTION
 Thorough and regular handwashing
 Bathe in the morning
 NO control strategy…
STH- PATHOGENS
Roundworm
 Ascaris lumbricoides

Whipworm
 Trichuris trichiura

Hookworms
 Necator americanus
Ancylostoma duodenale

Strongyloides
 Strongyloides stercoralis

STH- EPIDEMIOLOGY
 1.5 billion people=24% of the world's population infected with STH
 Wide distribution: tropical and subtropical areas +++
 Especially sub-Saharan Africa, the Americas, China and east Asia.
 Over 1 billion of children : need of treatment and preventive
interventions.
STH - GENERAL TRANSMISSION
Infection happens in different ways
INGESTION (eggs)
 Vegetables are not carefully cooked, washed or peeled
 Contaminated water source
 Accidental ingestion or geophagia (children)
SKIN PENETRATION (larvae)
 Hookworm eggs  soil  mature larvae
 Mature hookworm larvae as Strongyliodosis larvae can actively
penetrate the skin.
 People become infected by walking barefoot on the contaminated
soil.
 THREE WEEKS TO 2 MONTHS OF MATURATION are needed
 No direct person-to-person transmission
 No infection from fresh faeces
 Adults worms do not multiply in the human host
 Reinfection occurs only through the environment.

GENERALIZED LIFE CYCLE OF INTESTINALS
NEMATODES
Ascaris
Hookworm
Strongyloides
Larvae through lungs
Risk of Loeffler syndrom
INGESTION (Eggs)
SKIN PENETRATION (Larvae)
Medical Microbiolgy; Ch 86; 4th edition
STH – CLINICAL SYMPTOMS


Morbidity and symptoms
Related to the number of worms harbored.






Nutritional effects







Light infections
 Poor symptoms.
Heavy infections
General malaise, weakness
Intestinal manifestations (diarrhea, abdominal pain)
Impaired cognitive and physical development.
STH impair the nutritional status of infected people .
The worm feeds on host tissues, including blood
Loss of iron and protein.
Increase malabsorption of nutrients.
Loss of appetite
Reduction of nutritional intake and physical fitness.
Impact on growth and physical development +++
STH - SPECIFIC CLINICAL SIGNS
Hookworms (Ancylostoma)
 chronic intestinal blood
loss
 ANAEMIA.
Whipworm (T. trichiura)
 dysentery
 GASTRO-INTESTINAL
BLEEDING, anemia
Roundworm (A. lumbricoides)
 Compete for vitamin A
 OBSTRUCTION syndrome (highly
infected)
Strongyloides (S. stercoralis)
 autoinfestation: larva currens,
DISSEMINATION
 chronic infection of extended
duration
STRONGYLOIDES HYPERINFECTION SYNDROME
(ANGUILLULOSE DISSÉMINÉE)

In some cases larvae can directly reinvade




The intestine
Perianal skin (larva currens)
Perpetuate the infection (“autoinfection cycle”).
In cases of immunodeficiency: risk of
HYPERINFECTION SYNDROME
 Life-threatening infection


Risk factors for SHS







Pulmonary involvement +++
Corticosteroids - even short duration
Hematologic malignancy, hematopoietic cell
transplantation
Immunosuppressive drug therapy
Solid organ transplantation
Human T-cell leukemia virus type 1 (HTLV-1)
infection
Hypogammaglobulinemia, and malnutrition
Important to suspect, diagnose and treat the infection.
LOFFLER (OR LOEFFLER) SYNDROM
Passage of helminth larvae through the lungs
 Eosinophilic pulmonary infiltrates and respiratory
symptoms
Mainly with ROUNDWORM +++ (Ascaris)
 More uncommon: Strongyloides & hookworm
 8 to 15% of infected individuals respiratory
symptoms
 9 to 12 days after the ingestion of eggs
 Lasting 5 to 10 days
Symptoms: cough, dyspnea, wheeze, and hemoptysis
and may progress to frank respiratory distress

Biology
• Peripheral eosinophilia (> 0,5G/L)
• Respiratory secretions or gastric lavage can show Ascaris larvae
• Eggs will not be detectable in the stool (early stage)
Radiography
• Transient bilateral infiltrates
STH - DIAGNOSIS


Intermittent shedding of parasite in stools ++++
An accurate diagnosis needs




Microscopic examination of multiple stool samples (x3)
Use of different techniques are recommended (x2)
A walnut-sized sample
A direct examination AND a concentration technique
BAILENGER CONCENTRATION
To search for parasites
in stool please ask for
« Examen
parasitologique des
selles » and not for
« coproculture »
(mainly used for the
detection of bacteria)
STH - SPECIFIC TECHNIQUE FOR STRONGYLOIDES
Baermann technique
 Based on the active migration
of Strongyloides larvae and
their attraction to warm
temperatures.


Alternative tests
 Serology
+++
 Stool culture: rarely used
 Polymerase chain reaction
Faeces are
suspended in
warm water.
Larvae move
into the warm
water.
Larvae are
collected for
identification
STH - STRATEGY FOR CONTROL

Control morbidity


Children: schools +++








Without previous diagnosis to all at-risk people
Once or twice a year
Health and hygiene education


Good entry point for deworming activities
Promotion of hand washing
Improved sanitation.
Childbearing age, pregnant & breastfeeding women
Adults with high-risk occupations
WHO recommendations
Deworming  control worm burden  Periodic drug treatment


Periodic treatment of at-risk people
Provision of adequate sanitation
Health information for travelers


Food and water precautions
Avoiding walking barefoot on soil
CESTODES
HUMAN TAENIASIS - CYSTICERCOSIS

TAENIASIS
 Intestinal infection caused by adult TAPEWORMS



CYSTICERCOSIS
 Tissue infected by cystercerci TAPEWORMS





Taenia solium
Taenia saginata
Taenia solium
Worldwide
 45 million with adult T. saginata
 2-3 million with adult T. solium
 50 million with T. solium cysticerci.
 In areas where pigs and cattle come into contact with
human faeces
Acquisition
 Taeniasis: Inadvertent ingestion of tapeworm larval
cysts (cysticerci) in undercooked pork or beef.
 Cysticercosis: Inadvertent ingestion of eggs
T. saginata
 Minor impact on human health
T. solium
 Major impact
 50,000 people die annually from the CNS or cardiac
complications.
Generalized life cycle of tapeworms
Medical Microbiolgy; Ch 86; 4th edition
HUMAN TAENIASIS – LIFE CYCLE

Strictly human TAPEWORM species
T. saginata  beef tapeworm
Taeniasis
T. solium  pork tapeworm
Taenisasis
Cysticercosis
Infective stage
Cysticerci
Infective
stage eggs
TAENIASIS - SYMPTOMS

Prepatent period
8 to 14 weeks
 Mild and non-specific symptoms.
 Abdominal pain
 Nausea, diarrhea, constipation
 Decreased/increased appetite
 Weight loss


Passage of proglottids in the stool
T. saginata: active migration of the proglottids through the
anus/aberrant locations
 T. solium proglottids are less active

TAENIASIS - DIAGNOSTIC TESTS
Proglottids

Stool sample analysis


Taenia proglottids or
eggs
near the anus
eggs

eggs
Adhesive tape preparations
 Taken

Eggs
Repeated sampling
Morphology of proglottids
 Eggs
of T. saginata and T.
solium are identical
T. saginata
T. solium
CYSTICERCOSIS


Definition: Tissue infected by cystercerci
Secondary to T. solium EGG ingestion

Cysticerci : muscles, subcutaneous tissues, eyes and brain

Neurocysticercosis





Severe form
 Major cause of EPILEPSY in low-income countries
Africa, Asia, Latin America
Sometimes asymptomatic for years.
Symptoms




Depending on number, size, stage and location of the cysticerci
Subcutaneous palpable nodules
Spontaneous degeneration: inflammatory reaction
Chronic headaches, blindness, seizures, hydrocephalus, meningitis, dementia etc.
Cysticercosis - Diagnostic
 Both
imaging AND serological
testing
Brain computed tomography (CT) scan
or MRI
 Serologic tests / serum or CSF
 X-ray: inactive (calcified) cysts in muscle
or brain
 Biopsies of nodules

Warning: Serology = crossreactions may occur with other
parasites.
PREVENTION AND CONTROL

T. saginata



Individual approach
Cook or freeze beaf meat
T. solium








Individual approach AND public health interventions
Access to preventive chemotherapy
Identification and treatment of taeniasis cases
Health education
Improved sanitation
Improved pig husbandry
Anthelmintic treatment of pigs
Improved meat inspection
HUMAN ECHINOCOCCOSIS

Zoonotic disease

TAPEWORMS of the genus Echinococcus.

Two most important forms

Cystic echinococcosis (CE) = hydatidosis = hydatid
disease


Entire adult worm
Echinococcus granulosus
Alveolar echinococcosis (AE)

E. multilocularis
Scolex showing hooks
LIFE CYCLE
Alveolar echinococcosis
 Wildlife cycle
 Foxes, other carnivores (dogs and cats)
 Small mammals (rodents).
Cystic echinococcosis
 dog–sheep–dog cycle +++
Infective stage:
embryophores
Humans
Accidental intermediate hosts
Intermediate hosts:
herbivorous and
omnivorous animals
Humans
accidental intermediate hosts
not able to transmit the disease
DISTRIBUTION
More than 1 million people affected with echinococcosis worlwilde.
Cystic echinococcosis (CE)


Global distribution
Endemic regions


Incidence > 50 per 100 000
person-years
Prevalence 5–10%
Alveolar echinococcosis (AE)
• Northern hemisphere +++
• China
• Russian Federation
• Continental Europe
• North America
• France
• Eastern regions
CLINICAL SIGNS
E. granulosus
 Cystic echinococcosis (CE)

Prepatent period
years
 Linked to hydatid cysts growth
E. Multilocularis
 Alveolar echinococcosis (AE)

X
Prepatent period


Primary tumour-like lesion


Development of HYDATIDS
LIVER +++

Abdominal pain, nausea and
vomiting
 Lungs

++
Chronic cough, chest pain and
short breath
 Bones,
kidneys, spleen,
muscles, central nervous
system, and eyes





LIVER +++
Larval metastases


5 -15 years
Spleen, lungs, brain
Weight loss
Abdominal pain
General malais
Hepatic failure.
If untreated, progressively
fatal
DIAGNOSTIC TOOLS
CE

Computed tomography (CT) scans




MRI
Ultrasonography
Radiography






Thin rim of calcification
Serological tests


Visualisation of mother and daughter cysts
Specific antibodies
Screening + confirmation test
Follow-up / recurrence
Liver involvement
Eosinophilia (25%)
NO Biopsies or other guided punctures!
AE

CT scan





Heterogeneous lesion
Necrotic area (N) and a calcified area (C)
Can mimic carcinoma.
Serological tests
Histopathology for AE +++
SURVEILLANCE, PREVENTION AND CONTROL
CE

Cycle: domestic animal  preventable
disease








Wash hands + avoid contact with dog
faeces
Prevent dogs from soiling immediate
environment.
Prevent access to raw sheep meat or
viscera.
Improved hygiene in the slaughtering of
livestock
Deworming of dogs
Vegetables: thoroughly washed before
consumption
Public education campaigns
Eradication program



Vaccination of lambs
Deworming of dogs
Culling of older sheep
AE

Cycle: Wild animal species 
more complex




Regular deworming of
domestic animals
Culling of foxes …quite
inefficient.
Deworming of definitive hosts
with anthelminthic baits
Cost–benefit effectiveness:
controversial.
TREMATODES
SCHISTOSOMIASIS (OR BILHARZIA)
Caused by a trematode (blood
fluke)
 Genus Schistosoma






Mummies’ parasite
200 millions of people
infected worldwide




Schistosoma haematobium +++
Schistosoma mansoni +++
Other species (S. intercalatum,
S. japonicum, S. mekongi, etc.)
3rd most common parasitic
infection
Poor sanitation
Socioeconomic consequences
Neglected Tropical Disease
PATHOGENIC AGENT




Helminth parasites, trematode (flukes)
Adults : 10 to 20mm
S. mansoni : adults inferior mesenteric veins
S. hematobium : adults venous plexus of
bladder
Longevity :  10 years
 Intermediate host
Specific snail/ Schistosoma species

SCHISTOSOMIASIS : LIFE CYCLE
(2) Eggs
transit through tissues
Granuloma = Pathogenicity
Excreted in feces or urine
Release miracidium in freshwater
(3) Miracidium
Invade specific snails (intermediate hosts(4))
Multiplication in snails
Production of furcocercaires
(5) Furcocercaires
Released in fresh water
Penetrate human skin = infective stage
Maturation in portale hepatic circulation (7) - copulation
Survival
~ 48h
Survival
~ 18h
25°C
500µM
(1) Gravid female worms
deposit eggs in small venules

Bladder venoux plexus

S hematobium

Eggs in urine

Eggs + granulomas in bladder tissue, ureters…

Inferior mesenteric venous plexus

S mansoni

Eggs in feces

Eggs + granulomas in intestinal and rectal tissues
GEOGRAPHIC DISTRIBUTION

S. haematobium



Urogenital schistosomiasis
Africa only
 Endemic foci
 Uniformly distributed in endemic areas
S. mansoni



Intestinal schistosomiasis
Africa
South America (Brazil +++ , Caribbean)
Depends on the presence of the intermediate host

Bulinus

Biomphalaria
CLINICAL SIGNS

Contamination



Invasion stage variable intensity



fever, chills, asthenia, anorexia, headache: KATAYAMA fever
allergic symptoms : pruritus, cough, arthralgia, hepatosplenomegaly, myalgia
S. haematobium




No symptoms
Rash or itchy skin : furcocercaire penetration
Urogenital schistosomiasis
Hematuria
Pollakiuria, dysuria

S. mansoni

Intestinal schistosomiasis
abdominal pains +/diarrhea, tenesmus and anal
pain…
Complications

Complications
 Bladder and ureteral fibrosis
 Hepatic schistosomiasis
 Calcified bladder
 Cirrhosis
 Hydronephrosis
 Portal hypertension
 Bladder cancer
 Genital lesions
 hypersplenism
 In women
 genital schistosomiasis increaese HIV transmission
 infertility
DIAGNOSTIC TOOLS
Eosinophilia : invasion phase +++
 Anemia +/ Microscopic analysis of stool or
urine: eggs
 Antibody testing

Seroconversion : 4-8 weeks after
infection
 Positive for both active and past
illness
 ELISA + WB for confirmation


Biopsy (rectal, bladder, liver)
PREVENTION

Individual
 Avoid

swimming or wading in freshwater
Collective control of schistosomiasis
 Population-based
preventive chemotherapy - for
at-risk populations in endemic areas
 Safe water supply
 Snail control
 Improved sanitation
 Health education
SCHISTOSOMIASIS HAEMATOBIUM, CORSICA
March 2014: index case
 Focus for transmission of
schistosomiasis
haematobium.
 Still under investigation

Bulinus truncatus snails were found at sites 1, 2, 3, 5, and 6.
Berry A, EID, 2014
HUMAN FASCIOLIASIS



Sheep liver fluke ( all herbivores!)
Humans are incidental hosts
Major risk factor


Worldwide





consumption of contaminated water plants or waterwatercress
Regions with intensive sheep or cattle production
2,5 million cases reported worldwide
Several million at risk
Incidence has apparently increased since 1980
Temperate regions





Prevalence +++ Specific regions
Bolivia (65-92%)
Ecuador (24-53%)
Egypt (2-17%)
Peru (10%)
Adultes de Fasciola hepatica dans les voies biliaires d’un foie de bovin
CLINICAL SYMPTOMS


Subclinical
Acute phase




Fever
Hepatomegaly
Abdominal pain.
Chronic phase






Intermittent painJaundice
Anaemia
Pancreatitis
Gallstones
Bacterial super-infections
Chronic infections  fibrosis
DIAGNOSTIC TOOLS
Eosinophilia
 Antibody detection
 Chronic phase: Stool examination for ova and
parasites

 Multiple

specimens
Imaging: CT scans, MRI
PREVENTION - PUBLIC HEALTH INTERVENTIONS

Information - education - communication
Cultivation of vegetables in water free from faecal
pollution
 Cooking of vegetables before consumption


Veterinary public health measures
Treating domestic animals
 Separation between husbandry and humans


Environmental measures

Containment of the snail
TO BE CONTINUED…