A 10-year-old boy was brought to the ED because of abdominal pain. The family had arrived in the...

•A 10-year-old boy was brought to the ED because of abdominal pain. •The family had arrived in the United States from Yemen just the day before presentation•The boy had crampy abdominal pain for 1 month (mid-epigastric region). •Although there was intermittent abdominal distention, he had no fever, nausea, vomiting, diarrhea, constipation or gross blood in the stools. •The child had lost 20 pounds during this time.

PMH: •Received immunizations, but no documentation was available• No hospitalization or surgery•History of contact with cows and goats and a questionable consumption of unpasteurized milk. •The water supply was reportedly clean • No history of swimming in fresh water. •The patient walked barefoot outside. •No household members had similar symptoms.

Physical examination •A thin, cooperative boy in no acute distress. V/S were NL. •H&N: normal. No lymphadenopathy•Heart: regular rate and rhythm, with no murmurs.•The lungs were clear to auscultation bilaterally. •The abdomen was soft, but mildly distended, and bowel sounds were present. There was no rebound tenderness, guarding, ascites or masses. The liver was nontender and smooth, with the edge palpable 8 cm below the right costal margin. The spleen was not palpable. •The rest of the physical examination was unremarkable.

Labs• WBC: 15 000/mm3 (4% bands, 8%N, 41% L, 2% M, 44% E and 1% B). • HB 12.9 g/dl, platelet count was 494K• Serum electrolytes, coagulation profile, liver enzymes, bilirubin and urine analysis were normal. • Computed tomography of the abdomen showed hepatomegaly.• Esophagogastroduodenoscopy revealed esophagitis, but no varices.

•Hepatitis A and hepatitis B serology indicated past infection. •Hepatitis C IgG : negative. •Serum immunoglobulins:

•Normal IgM, •Slightly elevated IgA and IgG. •IgE was 23 010 IU/ml, 10 times the upper end of normal (normal 1 to 240 IU/ml).

•Serology for Toxocara species and Trichinella spiralis was negative. •Filariasis was excluded. •There were no ova or parasites in the stools on three separate occasions. •Stool and urine examinations were negative for schistosomiasis. •The diagnosis was made only after a more invasive study.

Because this boy had •Persistent gastrointestinal complaints •Came from an endemic area •Walked barefoot •Had eosinophilia •Extremely elevated serum IgE value, schistosomiasis was suspected and a rectal biopsy was done.

•The biopsy showed ellipsoid eggs, each with a lateral spine, characteristic of Schistosoma

mansoni . Pediatr Infect Dis J. 1999 Jun;18(6):556, 572-3

Schistosomiasis

Nahed Abdel-Haq, M.DDivision of Infectious DiseasesChildren’s Hospital of Michigan

What could they have in common? Akhnaton, was allegedly diagnosed with bilharziasis or schistosomiasis. Some also mentioned that Napoleon Bonaparte was infected with this parasite after swimming in Egypt. The famous Egyptian singer, Abdel Halim Hafez died with complications of this disease

Napoleon after coronation as Emperor of France

Abdel-Halim Hafez, the popular Arabic musician and singer

Schistosomiasis

•Described by Theodore Bilharz in Cairo in 1851 (Bilharzia)

•200 M people in 74 countries•120 M have symptoms•20 M have severe illness•Despite control programs:

continues to spread•Reports of R to praziquantilAllen GP et al. NEJM 2002, Volume 346:1212-1220

Schistosomiasis is second only to malaria in human impact among tropical diseases and is the third most prevalent parasitic disease in the world.

Schistosomiasis/Etiology

• Human disease: caused mainly by 3 species of flat worms

• S. mansoni: most common (Africa), intestinal disease

• S. japonicum: Asia, Pacific, intestinal disease

• S. haematobium: affects 54 countries in Africa and the Middle East, urinary disease

Schistosomiasis/Unusual species

• S. mekongi: disease mainly in the Mekong river basin,

•Related to S. japonicum•Disease is similar, milder

• S. intercalatum: in central Africa•Similar to S. manosoni but milder

• S. mattheei and S. bovis: mainly animals

Schistosomiasis/Distribution

• Schistosoma haematobium, S. mansoni and S. intercalatum infections: in sub-Saharan Africa

• S. mansoni remains endemic in parts of Brazil, Venezuela and the Caribbean

• S. japonicum still occurs in China, Indonesia & the Philippines

• S. makongi: Cambodia & Laos (Mekong River)

Schistosomiasis/Epidemiology

• Humans are principal hosts for major species

• Intermediate host is the snail• Appropriate snail is required for

maintaining the cycle• Eggs excreted in stools: S. mansoni,

S. japonicum• Eggs excreted in urine: S.

haematobium• Eggs hatch in fresh water into

motile miracidia which infect snails

Life Cycle of the Schistosome

Allen GP et al. NEJM 2002, Volume 346:1212-1220

Cercariae: infectious stage

Adult worms: males/females

In endemic areas, most at risk are school-age children, women, and those involved in occupations such as irrigation, farming and fishing.

Epidemiology/travelers

• Most in travelers to Africa• Swimming, wading, bathing in fresh

water in areas of poor sanitation, snail hosts

• Most cases are in swimmers in•Lake Malawi•Lake Kariba•Zambezi River

• Present with acute schsitosomiasis• Common early symptoms:

hematurea, diarrhea• Rare: transverse myelitis

Epidemiology/Immigrants

• Immigrants from endemic areas: may remain infected for 30-40 yrs

• Average life span of schistosome is 5 yrs

• Adult worms may live for decades

• Not notifiable disease in US• True incidence in immigrants,

returned travelers is unknown

Epidemiology/Animals

•Various animals, such as dogs, cats, rodents, pigs, horses and goats, serve as reservoirs for S. japonicum, and

•Dogs for S. mekongi •Variants in birds

Susceptibility• HLA class I and II antigens : more

severe manifestations of the disease

• HLA-B16 and Cw2: S. haematobium associated bladder CA in Egypt

• HLA-DR, DQ, DP: protection from hepatic fibrosis

• Advanced fibrosis is related to gamma-interferon receptor gene on chromosome 6

• Resistance to re-infection: 5q31-q35

Schistosomiasis/clinical manifestations

•Maculopapular eruption at site of penetration of cercariae

•Develops few hours after infection

•May develop up to one week later

•Similar but less severe than swimmer’s itch

Schistosomiasis/clinical manifestations

• Swimmer’s itch: sensitized individuals exposed to non-human schistosomes

• Various avian and mammalian schistosomes cause the reaction

• Mild-moderate pruritus at penetration site in few hours

• Intermittent pruritus, papular eruption in 5-14 d

• The cycle of infection is not completed in humans: no systemic complications

Acute Schistosomiasis/Katayama Fever

•Areas with high transmission rates

• Immune complex-mediated reaction

•Deposition of eggs in tissues•Contaminated water exposure

14-84 days earlier•All patients have eosinophilia•Not all shed eggs

Acute Schistosomiasis/Katayama Fever

• Fever, headache, generalized myalgias

• Right upper quadrant pain, tender hepatomegaly

• Bloody diarrhea• Respiratory symptoms: 70% S.

mansoni• Interstitial pneumonia (radiologic)• Splenomegaly: 30%• Aseptic meningitis

Chronic Schistosomiasis

• A results of host immune response to schistosome eggs

• Granulomatous reaction to secreted Ag/fibrosis

• Severity depends on: – Amount of Ag release (severity &

duration)– Intensity of fibro-obstructive disease

• Granulomas at sites of maximum egg deposition

• S. mansoni & S. japonicum: intestine & liver• S. haematobium: genitourinary tract

Chronic Schistosomiasis

• Granulomas may develop in other organs:

•Skin•Lungs•Brain•Adrenal glands•Skeletal muscles

• The inflammatory response assist in migration of the eggs to the lumen (GI,UB)

• Egg output is low in immundeficient pts

Chronic SchistosomiasisGI

• Gut wall: inflammation, hyperplasia, ulcers, microabscesses, polyposis

• Colicky pain: lower abdomen, left iliac fossa

• Diarrhea: common, + constipation• Blood: occult, gross• Colonic, rectal stenosis• Colonic polyposis:protein-losing

enteropathy• Colorectal CA risk: small; if any

Chronic SchistosomiasisLiver

• Embolization of eggs to the liver• S. mansoni and S. japonicum• Presiusoidal inflammation, periportal

fibrosis• Incidence: 4-8% of pts• Takes yrs, heavy infection• Hepatomegaly: granulomatous inflamm.,

early • Periportal collagen:

• Obstruct blood flow• Portal hypertension• Varices, bleeding, splenomegaly


• Periportal fibrosis seen by US, CT, MRI• Liver synthetic function is preserved

until late• Lobular architecture is retained• No nodular regenerative hyperplasia• Quantification of hepatosplenic

disease: clinical, US criteria by WHO• S. haematobium: occasional colonic,

hepatic disease


• Coinfection with HBV, HCV may occur• S. mansoni: accelerated deterioration• Higher risk of hepatocellular CA (HBV)• S. japonicum: no significant

interaction• EGYPT:• Mass campaign of parenteral therapy

for schstosomiasis• High prevalnce of HCV in the country:

widespread reuse of needles

The abdomen of an 11-year-old boy with intestinal schistosomiasis with the size and extent of the liver and spleen marked, indicating the severity of infection. The disease has caused a stunting of the boy's growth, he is only 120cms tall and weighs 22 kg. WHO

Lancet Infect Dis. 2004 Aug;4(8):498.

Clinical picture

Schistosomal appendicitis Eric Adehossi and Philippe Parola

,

Service des Maladies Infectieuses et Tropicales, CHU Nord,

Marseille, France

A 24-year-old African man recently emigrated to France from Sierra Leone was admitted to the department of surgery of our hospital for a 2-day history of acute abdominal pain. Physical examination of the abdomen revealed right iliac fossa tenderness and guarding, and peritonism. Standard blood haematology and chemistry values were within normal limits, except an increased C-reactive protein (30mg/L). Increased abdominal pain without any fever was noticed during the first 2 days of hospitalisation. Abdominal computed tomography scan showed calcifications from the initial to the distal part of both ureters, in the appendix (figure A), in the seminal vesicles, and within the ureteral wall of the bladder. This presentation is typical of genitourinary schistosomiasis due to Schistosoma haematobium, which is endemic in Sierra Leone, with schistosomial appendicitis. Neither eggs nor other parasites were detected in the urine and stools.

Histological examination of the appendix showed numerous S haematobium eggs in submucosa of the appendix

Abdominal CT scan showed calcifications from the initial to the distal part of both ureters and in the appendix

Chronic SchistosomiasisGenitourinary

•Specific for S. haematobium

•Hematurea: first sign (10-12wks after infection)

•Graulomatous response: eggs in tissue

•Dysurea: early and late in disease

GenitourinaryLate manifestations

• Proteinurea (nephrotic)• Bladder calcification• Obstruction of ureter• Renal colic• Hydronephrosis• Renal failure• secondary bacterial infection• Cystoscopy: areas of rough mucosa

(eggs)• Structural urinary tract abnormalities

GU Schstosomiasis. Plain radiograph showing: Calcification of the distal two thirds of both ureters and Bladder calcifications. (The Encyclopaedia of Medical Imaging Volume VII.)

Bladder Schstosomiasis. IVP showing Filling defects in the urinary bladder secondary to granulomas. (The Encyclopaedia of Medical Imaging

Vol.VII.)

Genital schistosomiasis

• 1/3 of infected women• Isolated internal genital

disease is rare• Vulva, perinium: ulcers,

fistulas, hypertrophic, wart-like lesions

• Tubular infertility: rare, late• May facilitate transmission of

HIV

Schistosomiasis/Neurologic

• Egg deposits in the CNS: aberrant migration of worms, embolization

• Not all are symptomatic• Focal or generalized seizures

are typical for S. japonicum CNS involvement

• Focal neurologic deficits• 4.3% of hospitalized Chinese

adults have CNS disease

Schistosomiasis/Neurologic

• Transverse myelitis: most common neurologic complication of S. mansoni and S. haematobium

Treatment• Supportive • Steroids• Anticonvulsants: long term use

rarely needed

Schistosomiasis

• In childhood: growth retardation, anemia

• Cognitive impairment, memory deficits

• May affect maternal and fetal health

• Praziquantel: category B (safe in animals, not tested in humans)

• Risk:benefit: treat esp. after 4th month of gestation

Two boys, victims of schistosomiasis showing typical distension of the abdomen. WHO

GenitourinaryLate manifestations

• S. haematobium has role in some bladder CA

• Squamous cell carcinoma (SCC)• In Egypt: SCC 18-28% of all CA• Mainly male, smokers• The finding is not consistent in

all countries with endemic S. haematobium

Schistosomiasis/Differential diagnosis

• Toxocara infection• Trichinella spiralis infection• Filariasis• Hepatitis B, C virus infection• Tuberculosis• Amebiasis• Leishmaniasis • Myeloproliferative disease• Peptic ulcer disease• Cancer (GI, GU)

Schistosomiasis/diagnosisgeneral lab tests

•CBC with diff.: eosinophilia•Anemia:

•Fe-deficiency•Anemia of chronic disease•Marocytic

•Hypoalbuminemia•Elevated BUN/Cr•Hypergammaglobulinemia

Diagnosis

• Detection of eggs in stools or urine: Diagnostic

• 3 specimens may be needed: intermittent shedding

• Miracidium hatching test: • Concentration of ova on nylon bag, suspend in

distilled water• Miracidia hatch from ova: microscope

• Kato-Katz thick stool smear: rapid, simple, 40-50 mg of feces, used in field studies

Morphology of the Eggs of the 3 Key Schistosomes That Infect Humans

Allen GP et al. NEJM 2002, Volume 346:1212-1220

S. manosni egg: prominent lateral spineOvoid (140X61µ)

S. haematobium egg: prominent terminal spine, ovoid (150X62µ)

S. japonicum egg: lateral spine obscured, round (100X60µ)

Diagnosis/biopsy

•The most sensitive diagnostic test for schistosomiasis is Rectal or bladder biopsy

•Perform on patients with typical clinical findings but negative feces and urine samples

Eggs in the venules of the intestinal mucosa :shed into the intestinal lumen and the environment where they release their miracidia to parasitize the snails. The eggs are about 150 microns in max diameter. The lateral spine cannot be seen in this section..

Schistosomiasis/Serology

• Useful in specific circumstances• Antibodies persist after parasitologic cure• Useful in pts with no eggs: Katayama

fever• Helpful in field studies• Commercially available assays: Less

sensitive and specific than multiple stool sample exams

• Immunoblot assays to detect circulating egg or worm Ag: highly sensitive and specific

Hepatic fibrosis markers

• Serum procollagen peptide III, IV• P1 fragment of laminin• Hyaluronic acid• Fibrosin• Markers may decrease with

prazequantel treatment• Persistent elevation after parasitlogic

cure: R/out HBV, HCV• Liver biopsy may be needed

Calcified schistosome eggs leading to florid granulomatous reaction in tissue

Schistosomiasis/Treatment

• Praziquantel: mainstay of treatment and control programs

• Used since 1970s• Causes tetanic contractions in the worm:

detach from the vein and die• Safe, effective• Absorbed well, extensive 1st pass

metabolism• Secreted in breast milk• Metabolized by the liver• Antibodies by host are critical for efficacy

Praziquantel

• Dose: 20 mg/kg/dose X 2-3 doses• Give Q 6-8hrs with food• Community-based programs:

single dose of 40 mg/kg• Use higher doses for S.

japonicum: 60 mg/kg total• Reexamination of stool or urine

one month after treatment to assess efficacy

Praziquantel

Cure rates• Parasitologic cure rate: 80%• Decrease in egg count: 95-99% • If cont. to shed eggs: retreat with

same dose• Causes regression of

hepatomegaly, reversal of pathology

• Chronic complications: no reversal

Praziquantel/Resistance•Rare but may be emerging•Not so far a significant

clinical or public health issue

•Reports of failed treatment from Egypt & Kenya: heavy use

•Altered tegumental structure of the worm

Praziquantel/alternatives

•Oxaminiquine: only alternative for S. mansoni infection

•Metrifonate: S. haematobium

•May have role in emerging Praziquantel resistance

Schistosomiasis/Treatment

•Steroids: – Cerebral disease associated with

surrounding edema– Severe Katayama fever

• Supportive care: chronic disease• Standard medical and surgical

therapy for chronic liver disease, varices

• Pts tolerate several episodes of hematemesis w/out encephalopathy

Schistosomiasis/prophylaxis

•Praziquantel is a poor choice

•Short ½ life (1-1.5h) •Cannot kill schistosomula (migrating larvae: 3-21 d old)

•Artemether: •Antimalarial•Kill schistosomula during first 21d in body

•Effective if given Q 2 weeks

Artemether• Not used in malaria endemic

areas: resistance may emerge• Have been used against S.

japonicum transmission in China• Dose: 6 mg/kg Q 15 days• Praziquantel+Artemether:

synergistic killing of adult worms• Target groups: in endemic areas

•Flood relief workers•Tourists•fishermen

Scistosomiasis/vaccine

• Target: Ag’s of schistosomula• Animal studies in mice, pigs,

buffalos: protective levels• Bith type 1,2 T-cell responses are

involved• Human studies: schistosome

derived molecule (S. haematobium glutathione S-transferase): Bilhvax

• Safe, immunogenic

Scistosomiasis/vaccine

•Other vaccines: S. japonicum antigens paramyosin (Sj-97) and Sj-GST-26

•Future: recombinant, synthetic peptide, DNA vaccines

•Vaccines to target transmitting hosts

•Vaccines will only be effcetive with control programs

Control programs

•Large scale population based chemotherapy

•Environmental modification•Controlling snail habitat•Use of molluscicides

•Behavioral modification•Difficult and costly to sustain

How can I prevent schistosomiasis?

•Avoid swimming or wading in fresh water when you are in countries in which schistosomiasis occurs. •Swimming in the ocean and in chlorinated swimming pools is generally thought to be safe.Center for Disease control and prevention


• Drink safe water. There is no way to make sure that water coming directly from canals, lakes, rivers, streams or springs is safe, • Either boil water for 1 minute or filter water before drinking it.• Boiling water: will kill any parasites, bacteria, or viruses present. • Iodine treatment alone will not guarantee that water is safe and free of all parasites. Centers for Disease Control and Prevention


•Bath water should be heated for 5 minutes at 150°F. Water held in a storage tank for at least 48 hours should be safe for showering. Centers for Disease Control and Prevention


• Vigorous towel drying after an accidental, very brief water exposure may help to prevent the Schistosoma parasite from penetrating the skin. • However, you should NOT rely on vigorous towel drying to prevent schistosomiasis. Centers for Disease Control and Prevention

Thank You

A 10-year-old boy was brought to the ED because of abdominal pain. The family had arrived in the...

Documents

Transcript of A 10-year-old boy was brought to the ED because of abdominal pain. The family had arrived in the...