imported schistosomiasis - saludentreculturas.esschistosomiasis in european travelers and migrants:...

Imported Schistosomiasis

Rogelio López-Vélez MD, DTM&H, PhDNational Referral Unit for Tropical Diseases

Infectious Diseases DepartmentRamón y Cajal University Hospital. Madrid. Spain

XVII JORNADA MEDICINA VIAJERO

BURDEN OF THE DISEASE

700 million people live in endemic areas

200 million people have schistosomiasis

90% of the cases occurring in sub-Saharan Africa

1.5 million disability-adjusted life years (DALYs) lost annually


Focal distribution of schistosomiasis in West Africa


Imported schistosomiasis diagnosed in 1-5% of the patients (travellers and migrants)

attending Tropical Diseases Units in Western countries


17,353 Ill Returned Tropical Travelers 1997-2004

Imported schistosomiasis in travellers and expatriates


4.5% in travelers to Sub-Saharan Africa


~20.000 patients

European series

4% in Sub-Saharan Africa


Nicols DJ; 2008

• Geosentinel 1997-2008• 401 cases• Male 59%, age <45 yold• Tourist 60%, expatriate 51%• Africa 83%, Asia 8%• Asymptomatic 34%


Coltart CE; 2015

• Hospital for Tropical Diseases, London1997-2012

• 1020 cases• Asymptomatic 36%• 42% eosinophilia

Field V; 2010

• EuroTravNet 2008• 129 cases (4% of all Dx from SSA)• Tourists 19.4%• Expatriate 48.8%• VFRs 14.0%• Africa 61.2%


Prevalence of strongyloidiasis and schistosomiasis among migrants: a systematic review and meta-analysis. Asundi A; Lancet 2019

• 88 studies of more than 78,000 migrants from endemic countries• Pooled schistosomiasis seroprevalence 18.4%• Sub-Saharan African migrants: seroprevalence 24.1·% (stool+ 1%, urine+ 6%)• The prevalence of Schistosome eggs in stool or antibodies in serum did not

differ between people with and without HIV

Imported schistosomiasis in immigrants


Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNetSurveillance Data. Lingscheid T. Am J Trop Med Hyg 2017

• 1997-2010 (14 years)• 1,465 cases of imported schistosomiasis• 486 (33%) travelers, 231 (16%) long-term expatriates, 748 (51%) immigrants. • 95% acquired in the African region. • S. mansoni was identified in 570 (39%) and S. haematobium in 318 (22%) cases• 57.5% of patients were symptomatic. • Acute symptoms reported in 27%, leading to earlier presentation within 3 m.• Praziquantel was used in all patients to treat schistosomiasis.

Imported schistosomiasis in travelers and migrants. European series


2,238 cases in 6 series

European series: places of adquisition


• LAKES– lake Malawi, Tanganyika, Kivu, Victoria– lake Kariba on the Zambesi; Volta lake in

Ghana; lake Nzilo in Katanga DR Congo;lake Muhazi in Rwanda

• RIVERS– the Senegal, the Volta and the Niger in

West Africa and the Zambesi (Zambesefalls) in southern Africa.

– Dogon country in Mali, Banfora falls inBurkina Faso and the Omo river in southEthiopia.

– The lower Nile does not constitute animportant source of contamination intravelers. The upper Nile basin in Uganda(Jinja District) is a risk area

Travellers and expatriates: places of acquisition

S. mekongi is endemic around the Mekong river rapidsstraddling the lao-cambodian border (Si Pan Don), anemerging travel destination


Schistosomiasis adquiered in Corsica

• 2012-2014• 12 cases in travelers to Corsica• Urinary schistosomiasis• S. haematobium / S. bovis hybridisation• Cavu river• Bulinus truncatus• ~100 additional cases described over 2 years among Corsica residents and visitors

from other parts of France

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 20, No. 9, September 2014


www.cdc.gov/eid

Pathogenesis

• Cercarial dermatitis (swimmers' itch) in zoonotic Schistosoma sp

• Acute schistosomiasis: serum sickness-like syndrome caused by immune-complexes:coincides with worm maturation and start of egg laying

• Haematuria is produced by passage of eggs through the bladder mucosa

• Granuloma and fibrosis around the ova, is cell-mediated and is regulated bothpositively and negatively by a cascade of cytokine, cellular, and humoral responses.

• Obstructive uropathy

• Presinusoidal portal hypertension (Symmer´s fibrosis)


Acute schistosomiasis (Katayama fever)

§ In travelers (infected for the first time)§ Usually occur 2-6 (1-12) weeks after exposure and last for days-weeks§ ++ S. mansoni and S. japonicum

Symptoms§ Fever (1.6-1.7 % of all febrile travelers)§ Dry cough, Asthma§ Arthralgia, myalgia§ Rash, urticaria§ Abdominal pain, diarrhoea§ Mild hepatosplenomegaly§ Seizures, spinal cord pressure§ Miocarditis§ Relapsing acute schistosomiasis has been observed 2 weeks after the

primary episode in some patients

Life-threatening complications1-neurological2-cardiac3-pulmonary


Acute schistosomiasis (Katayama fever)

Diagnosis

§ RISK OF EXPOSURE + FEVER + EOSINOPHILA

§ Ova detection usually negative (+ 10 weeks of exposure)§ PREPATENT PERIOD: 4-6 weeks in S. mansoni, up to 12 weeks in S. haematobium, but in rare

cases acute pase might develope up to 5 months

§ Serology 35% negative initially (positive at +3-4 weeks after exposure)

§ The absence of eosinophilia togheter with a negative serology does not ruleout acute schistosomiasis

§ PCR is an emerging diagnostic tool for acute schistosomiasis


Chronic schistosomiasis

§ Genitourinay: 10% in enedemic areas, 5% in imported cases

§ S. haematobium§ Haematuria (urine dipstick +), haematospermia§ Disuria, recurrent UTI (Salmonella)§ Obstructive uropathy§ Stones§ Glomerular disease§ Bladder cancer (unlikely in travelers)

§ Female genital pain or bleeding and infertility§ Vulvovaginal ulcera, fibrotic nodules “Sandy patches”

§ Eosinophilia: travellers ~50%; migrants~15-30%

§ May occasionally cause hepatic complications as well

§ S. haematobium increase the likelihood of contracting HIV/AIDS


Genito-urinary schistosomiasisXVII JORNADA MEDICINA VIAJERO

Chronic schistosomiasis

§ Hepato-intestinal 10% in enedemic areas, 5% in imported cases

§ S. mansoni, S. guineensis, S. intercalatum, S. mattheei§ S. japonicum, S. mekongy, S. malayensis§ Abdominal pain, chronic diarrhoea, rectal bleeding§ Hepatosplenomegaly, portal hypertension, liver fibrosis, ascites, variceal

bleeding (unlikely in travelers), § Hepatic function is nornal (fibrosis rather tan cirrhosis)§ HBV/HCV worsens the prognosis

§ Intestinal schistosomiasis with polyps (Egypt) or without polyps (Brazil)§ Pulmonary schistosomiasis: dypsnea, nodules, fibrosis, cor pulmonale§ Neuro schistosomiasis: seizures, transverse myelitis§ Ectopic granulomas: lungs


S. mansoni


Ultrasound / Rx

US GenitourinaryBladder wall lesions: focal or diffuseHydronephrosisStones

US LiverHepatosplenomegalyPeriportal fibrosisDilatation of portal/splenic veinsCollateral veins

Plain abdominal X-RayBladder calcificationsUreteric stones

IV UrographyHydroureterHydronephrosis

Barium meal / enemaEsophageal varicesIntestinal polyps

CT SCAN / MR

EndoscopyCystoscopy

Sandy patchesHyperemiaGranulesNodulesUlcersPolypsCarcinoma

ColonoscopyPolyps

Upper gastrointestinal endoscopyOesophageal varices

Laparoscopy (with liver biopsy)GranulomasFibrosisPortal hypertension


Richter J et al. Ultrasound assessment of… Z Gastroenterol 2016; 54: 653–660

Ultrasound classification of hepatic/periportal fibrosis associated with chronic hepatointestinal schistosomiasis


CNS schistosomiasis

Arch Neurol 2005


Pulmonary nodules in African migrantscaused by chronic schistosomiasis.

F Gobbi, Lancet Infectious diseases 2017


1. Egg detection in urine / stools

2. Egg detection in biopsy

3. PCR in urine / stools

4. Serology

5. Circulating antigen (CCA, CAA) in urine / blood

Parasitological diagnosis of schistosomiasis


DIAGNOSIS 1. Egg detection in urine & stool samplesPerform urine and stool samples in every case to exclude double infections

Microscopy in urine samples– Urine collected from 10:00 AM to 2:00 PM as circarian variation of ova excretion;

exercise urine is questioned– Centrifugation OR Filtration : 10 mL of urine filtered through Nucleopore filters– Sensitivity of single sample: 3 eggs per mL– Intensity of infection expressed as number of eggs / 10 mL– Ejaculation


DIAGNOSIS 1. Egg detection in urine & stool samplesPerform urine and stool samples in every case to exclude double infections

Microscopy in stool samples– 3 stool samples collected in different days– Sedimentation / Flotation standard techniques– Kato-Katz tick smear: 40-50 mg of feces is placed on a slide and stained (covered by

cello strip 24h soaked in glycerol-malachite or glycerol-methylene blue before use)– Sensitivity of single sample: 50 eggs per gr– Intensity of infection expressed as number of eggs / 1 gr

stool concentration as Kato-Katz tick smear


Morphology of Schistosoma sp. eggs

S. haematobium (urine): ~140 mm, with a terminal spine.

S. intercalatum (fecal): ~190 mm, with a long, sharply pointed terminal spine

S. mansoni (fecal): ~150 mm, with a thin shell and lateral spine

S. japonicum (fecal): ~90 mm, with a small spine or hooklike structure

S. mekongi (fecal): ~65 mm, similar to that of S. japonicum


Rectal snips

§ With proctoscope, mucosa crushed under a coverslipand viewed at low power without staining

Biopsy samples§ Bladder mucosa: cystoscopy§ Rectal: fiberoptic sigmoidoscopy or colonoscopy§ Liver: needle, open§ Other places

S. mansoni

S. mansoni S. haematobium S. japonicum

DIAGNOSIS 2. Egg detection in biopsy


DIAGNOSIS 3. PCR in urine / stools

§ Detects parasite DNA in stool, urine, blood and tissue samples§ Very sensitive in acute schistosomiasis§ Can be used to confirm neuroschistosomiasis§ Identification of the infecting species possible§ Remains+ time after treatment (parasite-DNA persistence)

S EPCR 97,4% 85,1%

S EPCR 100% 100%

Low endemic area in Brazil; N= 206S. mansoni in feces

High endemic area in Nigeria; N= 400S. haematobium in urine

2010 2012


DIAGNOSIS 4. Serology

§ Detect IgG, IgM or IgE

§ IHA, ELISA, IFAT: Soluble Worm Antigen or Soluble Egg Antigen or Crude Wormextract. A cercarial antigen-ELISA is promising

§ Sensitivity and specificity: up to >90% when combining IHA and ELISA

§ Does not correlate with intensity of infection§ Does not discriminate between current and past infection§ Does not discriminate especies. Species-specific monoclonal antibodies have been

developed

§ Seroconversion within 4-8 weeks (3-14 w) after infection, but may take longer.§ Most assays remain positive for at least two years after effective treatment, and

often much longer.

§ Western blot antibody test for confirmation


Commercial IHA kitDiagnosis: Serology

with 2 different assays


DIAGNOSIS 5. Antigen detection

§ ICT-Circulating cathodic antigen (CCA) with labeled Mab in urine

§ Sensitivity 70-100% (but lacks sensitivity in light infections)

§ More sensitive for S. mansoni than for S.haematobium

§ Specificity 95%

§ False + in UTI, haematuria and pregnancy (always perform the test together withurine dipstick)

§ Indicative of active infection or treatment failure (serology remains + for years)

§ Useful in acute schistosomiasis. Potential of being used as a single screening testfor African migrants. Sensitivity in traveles is nuclear when parasite load is low

Positive Trace Negative


Practical approach to migrants and travellers for schistosomiasis

STEP 1§ serology: with two different assays (not <2 months after exposure in travelers)§ blood eosinophile count§ urine for WBC/RBC

STEP 2§ urine/stool microscopy for O&P§ (urine CCA antigen)§ blood PCR: mainly in acute schistosomiasis§ ultrasound (liver & kidney)


§ Repeatedly reported in screened immigrants and refugees§ S. mansoni/S. haematobium: very frequent in African immigrants/refugees§ S. mekongi: frequent among Cambodian and Laotian refugees§ S. japonicum and S. intercalatum: exceptional

§ Eosinophilia in 15-30%§ Many (20-60%) are asymptomatic§ Acute schistosomiasis syndrome is almost non-existent§ Present with chronic disease manifestations mainly related to urinary

schistosomiasis

Screen to every immigrant from endemic area

ECDC assessment: Public health guidance on screening and vaccination for infectious disease in newly arrived migrants

Offer serological screening (ELISA, IHA, ICT) and treatment (to those found to bepositive) to all migrants from countries of high endemicity in Sus-Saharan Africa andfocal areas of transmisión in Asia, South America and North Africa.

Imported schistosomiasis in immigrants


§ Travelers are almost exclusively infected while visiting Sub-Saharan Africa.§ S. mansoni/S. haematobium: low worm burden, and often does not allow to

determine the Schistosoma sp in feces or urine. Diagnosis is made by serology§ S. mekongi and S. japonicum only occasionally reported

§ Many (>60%) are symptomatic§ Acute schistosomiasis syndrome is reported in 27% of patients. Is a cause of

fever in 1-2% of all returned travelers§ Eosinophilia in 50-60%§ Urinary schistosomiais is the most frequent reported§ Terminal hematuria (micro or macro): starting 10-12 weeks after infection; Haematospermia

§ Chronic schistosomiasis is rare

>1/3 with unapparent disease: investigate to every exposed traveler


Attack rates in exposed tourists is about 65% (from 32% in Malawi lake to 97%in Dogon country Mali). Attack rate is co-related to the number and theduration of the exposures


TREATMENT: acute schistosomiasis

Prednisolone• 1-1.5 mg/Kg po for 3-6 days• corticosteroids decreases plasma levels of PZQ by 50%

Artemisinins + Praziquantel• Artemether-lumefantrine or Dihydroartemisinin-piperaquine

Praziquantel• Remains controversial as is ineffective on young (7-28 days) schistosomule• 60 mg/kg/d (divided in 2-3 doses) po on day 3 after initiation of treatment• Associated with paradoxical reactions in 40-59% of acute schistosomiasis• Complete course once the chronic phase has been reached (~about 3 months after

exposure or detection of eggs in urine/stools)

ivermectin• 200 ug/kg po when given steroids for possible strongyloidiasis in migrants


TREATMENT: chronic schistosomiasis

Praziquantel (Biltricide® 600 mg tablets)• 40 mg/Kg po (single dose): CR= 60-90%. Failures of 40 mg/Kg are well-documented• 60 mg/Kg po (in 2-3 doses): for Sh, Sm, Si• 75 mg/Kg po (in 2-3 doses): for Sj, Sme, Smal• 120 mg/Kg po: 40 mg/Kg/d for 3 consecutive d or 60 mg/Kg/d for 2 consecutive d • Repeat second dose on day 21-30 if (re)exposure in the past 3 months• Can be used in pregnancy (human data are limited) and in small children• Racemic mixture of R and S enantiomers (R-PZQ is the effective molecule)• Same response in HIV+• Few side effects: nausea, vomiting, malaise and abdominal pain

Steroids• for 2 months in case of neurochistosomiasis


TREATMENT: chronic schistosomiasis

Oxamniquine (Vansil®)• Only for Sm• 60 mg/Kg po divided in 3 doses one day• CR= 80%, resistance reported in Brazil and Kenya• Repeat second dose on day 21-30 if (re)exposure in the past 3 months

Metrifonate (Bilarcil®)• For Sh• I no longer produced

Albendazole• may be effective in sh (Ben SA. Int Health 2017)

Mefloquine

Silymarin• can reverse experimental hepatic fibrosis


FOLLOW UP after treatment

• if eggs were found initially– repeat urine/stool samples for O&P at 3, 6, 12 months– PZQ is not ovicidal: eggs can persist for some time– vitality of eggs (hatching test+) >3 moths indicates treatment failure or reinfection

• if eosinophilia was initially present– repeat at 3, 6 moths– eosinophilia should be cleared at 6 months

• if eosinophilia was not initially present– repeat at 7 days (as may rise just after PZQ treatment) and if positive repeat as above

• if CCA was initially +– repeat testing at 3 months

• if serology was positive– remain positive for years, with fluctuating pattern over time– no major role in port-treatment monitoring

Regression over weeks to months of intestinal and vesical lesions, reactive hepatomegaly, and even severe upper urinary tract lesions and liver fibrosis (more so in children)


FOLLOW UP after treatment


§ behavioural changes: information

§ providing a safe water supply for bathing§ filtering with fine-mesh filters, heating to 50°C (122°F) for 5 minutes,

allowing water to stand for ≥24 hours before exposure and chlorinatingadequately the water

§ vigorous towel-drying after accidental exposure to water

§ topical applications of 50% DEET to the skin immediately after exposure

§ prophylaxis§ a single dose of artesunate at 6 mg/kg just after exposure, followed by a

single dose of praziquantel at 40 mg/kg at 6-8 weeks post-exposure???

§ malaria chemoprophylaxis with mefloquine does prevent travelers toacquire a significant parasite burden???

Prevention in travelers


provide pre-travel information

suspect, diagnose and treat successfully


imported schistosomiasis - saludentreculturas.esschistosomiasis in european travelers and migrants:...

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