schistosomiasi - aisf · flukes. 0 20 40 60 80 100 0 1020 30405060 ... splenomegaly, normal hepatic...
TRANSCRIPT
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Schistosomiasi
M. Albonico, Fondazione Ivo de Carneri Organizzazione Mondiale della Sanita’
AISF Monothematic Conference 2011
Hepatic diseases related to migratory flows
Milano 13 – 14 Ottobre 2011
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1) Introduzione e epidemiologia (151) Introduzione e epidemiologia (15’’))
2) Clinica e diagnosi della schistosomiasi (202) Clinica e diagnosi della schistosomiasi (20’’))
4) Discussione (54) Discussione (5’’))
3) Terapia e controllo della schistosomiasi (53) Terapia e controllo della schistosomiasi (5’’))
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Italia: anno 2000-2010• Inversione di tendenza della prevalenza ed
incidenza delle malattie parassitarie per – migrazioni di italiani nei PVS per lavoro o
per turismo– migrazioni di popolazioni dall'Africa e da
altre aree endemiche– aumento di parassitosi opportunistiche in
soggetti immunocompromessi• Necessità di formazione ed aggiornamento di
personale sanitario su patologie riemergenti• Rivalutazione delle malattie parassitarie non
solo quale patologia d'importazione ma quale priorità sanitaria globale, prevenibile e curabile, alla quale sono esposte piu' di due miliardi di persone.
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Specie di SchistosomaSpecie di Schistosoma
•• Schistosoma haematobium Schistosoma haematobium (Africa, (Africa, urinariourinario))
•• Schistosoma mansoni Schistosoma mansoni (Africa/Sud (Africa/Sud America, America, intestinaleintestinale))
•• Schistosoma intercalatum Schistosoma intercalatum (Africa, (Africa, intestinaleintestinale))
•• Schistosoma japonicum Schistosoma japonicum (Asia, (Asia, intestinaleintestinale))
•• Schistosoma mekongi Schistosoma mekongi (Asia, (Asia, intestinaleintestinale))
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Prince William Hit by a rare tropical diseases
Daily Mirror 27 October 2003
His Royal Highness caught bilharzia during a rafting holiday in Uganda
but was promply diagnosed and treated in hospital
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Il problema
Totale infetti 200 milioni
Con malattia associata
70 milioni ematuria 30 milioni patologia renale 20 milioni patologia intestinale/epatica
Morti attribuibili
300,000
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Contaminazione fecale/urinaria di acqua dolce
Come ci si infetta ?
Bagnandosi in laghi, fiumi
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Life cycle of schistosomes
Paired adult flukes
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0
20
40
60
80
100
0 10 20 30 40 50 60
1 / 10 ml
>1000/10 ml
Prev
alen
ce %
Tipica distribuzione di intensità per età della
schistosomiasi ( S.haematobium )
Wilkins et al. (1979) R. Soc. Trop. Med. Hyg. (modified)
age
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Schistosomiasis- clinical featuresDifferent phases:
Acute
Chronic-subclinical
Severe-symptomatic
Clinical disease resulting from schistosomes usually occurs only in heavily infected individuals
1st symptoms: localized dermatitis after penetration through the skin (12-48 h)
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Acute schistosomiasis(4-10 weeks after infection)
The acute stage, Katayama fever, is normally found in young children or young adults with no previous exposure to the disease. It is due predominantly to S. mansoni infection.It is a response to the sudden high level of antigen exposure and is usually associated with the onset of egg deposition
Clinical symptoms consists of skin rashes, asthma-like episodes, daily fever, malaise, diarrhoea,swollen lymph nodes and aching joints and other non specific symptoms
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Chronic-subclinical schistosomiasis
(several months after infection) :
• Associated with diarrhoea or haematuriaand fevers
• In children the infection can depresstheir growth rate
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Severe- symptomatic Schistosomiasis(8-10% of the patients):
It is the consequence of many years of progressive injury resulting from chronic eggdeposition in the tissues and the resulting host granuloma formation
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Clinical features
• Intestinal schistosomiasis (granulomas --> polyps, protein loss, malabsorption, strictures)
• Hepatosplenic schistosomiasis (portal hypertension --> ascites, varices, splenomegaly, normal hepatic function)
• Urinary schistosomiasis (hematuria, chronic infection, obstruction)
• Other (cardiopulmonary, CNS, etc.)
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Intestinal schistosomiasisInfection
Heavy infection
Intestinal lesions DiarrhoeaBloody diarrhoeaBlood in stool
Liver involvement, peri-portal fibrosis Hepatomegaly (MSL)Splenomegaly
Portal hypertension
GI bleeding, haematemesis Ascites, liver failure
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Intestinal schistosomiasis(S. mansoni)
Granuloma formation around eggs that collect in the intestinal wall results in fibrosis. Erosion of the sub-mucosa and villous tissue also occurs, andgastrointestinal hemorrhage results from damage to the submucosa. Eggs are eliminated with feces
Children with intestinal schistosomiasis develop intermittent abdominal pain, sometimes accompanied with bloody diarrhea. The blood loss and ulceration of intestinal schistosomiasis may result in iron deficiency
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Egg in tissue of the smallintestine. Note intense granuloma.
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Hepatosplenic schistosomiasis(S. mansoni)
Eggs swept back into the liver induce granulomas whic causes tissue fibrosis. This leads to obstruction of the hepatic vasculature. Fibrosisof the liver can result in portal hypertension,hepatosplenomegaly, ascites formation,oesophageal varices leading to fatal hematemesis (vomiting blood).
Parenchymal liver cells remain unaffected by granulomas, and, hence, liver function remains normal
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Fibrosis in liver due to heavy infection with S. mansoni. Note normal liver tissue next to fibrotic vessels.
Granuloma in liver surrounding eggs of S. mansoni. Note the lateral spine (arrow)
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A doctor palpates the spleen of a young boy suffering from schistosomiasis.
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Cirrhosis with portal hypertension and ascytes (fluidaccumulation in the abdominal cavity)
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Urinary schistosomiasisInfection Heavy infection Bladder lesions Haematuria Dysuria Calcified bladder Hydroureter Hydronephrosis Non-functioning kidney (uni-, or bilateral) Bladder cancer = =
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SchistosomiasiSchistosomiasi(Centro Malattie Tropicali, Negrar)(Centro Malattie Tropicali, Negrar)
203 187
39
60
50
100
150
200
250Sierologia
S.mansoni
S.haematobium
S.intercalatum
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• Un architetto italiano si presenta con febbre elevata, brividi, dopo un soggiorno in Ghana senza profilassi antimalarica
• Lamenta anche tosse secca persistente• Ricerca plasmodio: negativa• Emocromo: leucociti 11.000 con
eosinofili, 25%• Ricerche parassitologiche: negative• Diagnosi?
Febbre e brividi al rientro dal Ghana
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SchistosomiasiSchistosomiasi(Centro Malattie Tropicali, Negrar)(Centro Malattie Tropicali, Negrar)
Sindrome di Katayama12 casi
• Febbre
• Tosse (Rx torace negativo o con infiltrato interstiziale)
• Eosinofilia >15%
• Anamnesi positiva per rischio
NB= la sierologia e l’esame diretto possono essere negativi
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• Senegalese, “vu’ cumpra?’...• Si presenta perchè da circa due anni
soffre di dolori addominali ricorrenti ed episodi di rettorragia
• Lieve eosinofilia, >> IgE totali• Ricerche parassitologiche negative• Sierologia (IFAT): positività 1/160 per S.
mansoni
Addominalgie e rettorragia
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• Senegalese maschio 34 anni.• Da 6 anni in Italia torna periodicamente al villaggio. • Accesso PS per epigastralgie. • Ematici citolisi 2N e lieve aumento GGT.• HBsAg+ antiHCV-.• Eco: fegato disomogeneo, VBI non dilatate con netto rinforzo
periduttale. Milza omogenea diametro 15cm. Porta 11.5mm. Non ascite.
• EGDscopia: varici esofagee F2 con punti rossi. Inizia terapia con betabloccante.
• Invio parassitologico feci in lab con quesito specifico. Positivo per rare uova di S mansoni.
• Praziquantel solo per uso veterinario, non somministrabile in H.Perso al follow up.
Epatite B e schistosomiasi
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• Segni ecografici suggestivi ?• Discrepanza tra ipertensione portale (+++) e danno
epatico (+)• Pensare alla schistosomiasi e chiedere esame
parassitologico al laboratorio con quesito specifico • Accesso al Praziquantel ?
Epatite B e schistosomiasi – discussione
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Ematemesi ricorrente• Nigeriano, 45 anni• Si presenta al PS perché ha avuto un episodio di
ematemesi franca;• Splenomegalia, lieve epatomegalia;• Eco epatica esclude cirrosi; non ascite• All’EGDS, varici esofagee sanguinanti• Riferiva tre altri episodi negli ultimi 12 mesi;• Coproparassitologico: rarissime uova di
S.mansoni in 1/5 campioni
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DIAGNOSIDIRETTAI) ricerca delle uova:
- dimostrazione delle uova vitali in: feci, urine, biopsia rettale ed epatica, pezzo operatorio
- hatching test: dimostrazione di vitalità infezione attiva
- esame definito come negativo con 3 campioni ( feci, urine)
- il numero di uova correla con la carica infestante
- ricerca su urine: alta sensibilità per S. H.-urofiltrazione- ricerca su feci: scarsa sensibilità , tecniche di concentrazione
II) biopsia mucosa rettale : usato in associazione con esame feci (S. M.)
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DIAGNOSIDIRETTA
III) ricerca degli antigeni: Circulating Anodic Antigen (CAA)Circulating Catodic Antigen ( CCA)
ELISA su glicoproteina sia nel siero che su urineCCA siero + CCA urine 98% sensibilitàStrisce reattive per CCA nelle urine per S. mansoni*
alta sensibilità e specificità
costosi
usati per ricerca
* Stothard et al., ACTA Tropica, 2006, 97, 219-228
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DIAGNOSIINDIRETTANon differenzia tra infezione passata e recente
I) SIERODIAGNOSI (sensibilità > 90%):Ig anti vermi: positivi già in fase acutaIg anti uova: si positivizzano in fase recente/cronicascarsa utilità nella clinica pratica ???????IFAT (Ab contro antigeni intestinali)
III) STRUMENTALE:- ecografia addominale (tipiche bande iperecogene epatiche- Rx-addome in bianco (calcificazioni vescicali)- TAC, urografia, scintigrafia renale - cistoscopia, colonscopia
II) Biomolecolare:-PCR-ELISA for S. mansoni (Gomes et al., PLoS NTD, 2010, 4, e604)
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Schistosoma haematobium• Segno tipico?
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Esame feci:
Kato-Katz
Esame urine:
filtrazione
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Ecografia
http://apps.who.int/tdr/svc/publications/training-guideline-publications/ultrasound-in-schistosomiasis
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3 criteria
• 1. Image pattern of Liver parenchima (IP score)• 2. Periportal thickening (PT score)• 3. Portal Hypertension (PH score)
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Interpretation of the final score
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Fibrosis of portal vein (S. mekongi)
‚Network‘: interlobular structures
(S. japonicum)
Ultrasound findings
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Asymptomatic Hepatic Schistosomiasis Detected byUltrasonograpy and Confirmed by Liver Biopsy
liver network echogenic pattern and portalvein dilatation with thickening of the portal vein wall in the liver
atrophy and band-like linear calcification in the right lobe of the liver
Inter Med 48: 1109-1110, 2009
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Ultrasound „in the field“
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controllo della Schistosomiasi nel mondo
Quasi eradicatoProgammi di controllo su larga scala in attoControllo limitato o assente
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LATRINE
EDUCAZIONE SANITARIA
ACQUA SICURA
CONTROLLO MOLLUSCHI:
Molluschicidi
Gestione risorse idriche
FARMACI
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Evoluzione casi in Marocco 1982-1999
6582
10645
5165
37432588
3887 3705
23581137
2310
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
Controllo
Eliminazione
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In ragazzi in età scolare 90% della patologia dovuta sia a schistosomiasi urinaria che intestinale può essere guarita dalla terapia già dopo 6 mesi dopo il trattamento.
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• Regression of ascites and hepatomegaly in 50-60 % of patients with advanced disease.*
• Healing of colonic ulcers and reduction in size of the colonic polyps.**
Impact of periodic chemotherapy on Schistosomiasis morbidity
* Foster, 1987, Trans Roy Soc Trop Med Hyg 81, 55-59** Abaza et al., 1978, Trans Roy Soc Trop Med Hyg 72, 602-604
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0%
10%
20%
30%
40%
50%
60%
70%
80%
negativi 4,50% 7,20% 11,00%
intermedi 13,60% 37,60% 70,60%
malattia 63,60% 42,90% 25,90%
gravi 18,30% 12,10% 11,60%
prevalenza 79% 11,50% 11%
1997 1998 1999
Regression of liver pathology after treatment
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Oxamniquina (capsule 250 mg, sosp. 250 mg/100 ml)
• Efficace per S. mansoni (CR 60-90%).
• Dagli anni 80 fallimenti terapeutici riportati in Brasile e ceppi resistenti isolati in laboratorio da Porto Rico, Brasile and Liberia.
* Foster, 1987, Trans Roy Soc Trop Med Hyg 81, 55-59** Abaza et al., 1978, Trans Roy Soc Trop Med Hyg 72, 602-604
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Praziquantel (compresse 600 mg)
• Efficace per S. mansoni (CR 60-90%) S. haematobium (CR 80-95%) e S. intercalatum (CR 60-80%) a 40 mg/kg in dose unica.
• Efficace per S. japonicum e S. mekongi (CR 60-80%) a 60 mg/kg in due dosi .
• Scarso effetto su schistosomi immaturi
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EFFICACIA - Praziquantel (compresse 600 mg)
• In 1995, bassi tassi di cura per S. mansoni suscettibile alla oxaminiquina sono stati riportati dal Senegal . In Egitto 46 pazienti non sono guariti dopo 3 dosi ripetute.
• Un ceppo resistente in laboratorio di S. mansoni è stato selezionato dopo dosi ripetute di praziquantel a basso dosaggio. Un ceppo isolato dai molluschi in Senegal èstato dimostrato resistente in animali di laboratorio.
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Distribuzione farmaci• Dose calcolata in base
all’altezza invece che al peso
• Validato su 25.000 bambini
• 98.6% bambini tra 30 e 60 mg/kg e 84.7% bambini tra 40 e 60 mg/kg
Montresor et al., (2001)Trans Roy Soc Trop Med Hyg, 95, 1-3
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1 ½
2
2 ½
4
--110 cm
--125 cm
--138 cm
--150 cm
--178 cm
--160 cm3
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Glance at the recent past
Series of international publications
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Questions ?