Liver fibrosis, portal hypertension, varices, pancytopenia, colitis, appendicitis, cor pulmonale
Schistosoma mansoni: Pipe-Stem fibrosis
Haematuria, haematospermia, postrenal renal failure, chronic lower abdominal pain, infertility
Schistosoma haematobium: Sandy patches (bladder)
Eggs excreted in urine or stool
Egg releases miracidia, which penetrates into snail
Develops into cercariae in the snail, then released into water
Cercaria burrow into skin (several hundred required to develop infection??not all cercariae that penetrate the skin can successfully migrate to the liver, survive, and reach the veins to reproduce. Additionally, the parasites have evolved mechanisms to evade the host's immune system, and a single cercariae is less likely to overcome the host's defense mechanisms and establish an infection. If only male cercariae penetrate the skin without any female cercariae, the male worms are unlikely to find suitable partners for reproduction within the host's bloodstream)
Mature to male and female, take up long-term residence and lay eggs
Note re transmission: Although schistosomiasis is not transmitted by swallowing contaminated water, if your mouth or lips come in contact with water containing the parasites, you could become infected. Because water coming directly from canals, lakes, rivers, streams, or springs may be contaminated with a variety of infectious organisms, you should either boil water for 1 minute or filter water before drinking it. Boiling water for at least 1 minute will kill any harmful parasites, bacteria, or viruses present. Iodine treatment alone WILL NOT GUARANTEE that water is safe and free of all parasites.
Lifecycles of Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum (A) Paired adult worms (larger male enfolding slender female). (B) Eggs (left to right, S haematobium, S mansoni, S japonicum). (C) Ciliated miracidium. (D) Intermediate host snails (left to right, Oncomelania, Biomphalaria, Bulinus). (E) Cercariae. Source: https://www.thelancet.com/clinical/diseases/schistosomiasis
When to consider
Travel, endemic area
Immune reaction to immature parasite (not a reaction to egg laying)
Fever, eosinophilia, urticarial rash (may not have this classic triad)
Complications during acute phase: neuro (encephalitis), pulmonary, cardiac...
Signs and symptoms of chronic schistosomiasis include: abdominal pain, enlarged liver, blood in the stool or blood in the urine, and problems passing urine. Chronic infection can also lead to increased risk of liver fibrosis or bladder cancer.
Patients can present with portal hypertension (increased BP in the portal system due to resistance to blood flow) due to peri-portal fibrosis; signs and symptoms, including hepato-splenomegaly (increased pressure within the portal system can cause enlargement of the spleen. As blood flow through the liver is impeded, the spleen acts as a filter, leading to congestion and enlargement), gastrooesophageal varices (re-routing of blood to systematic circulation to reduce portal pressure), haematemesis, and ascites (Increased pressure in the portal system impairs the liver's ability to regulate fluid balance, leading to fluid leakage into the abdominal space). Hepatic function is commonly preserved until late stages
Rarely, eggs are found in the brain or spinal cord and can cause seizures, paralysis, or spinal cord inflammation.
Parasitological: direct visualisation of ova: urine (sedimented), faecal concentrate, biopsies (rectal snips, liver, bladder). 45% sensitive
The principle behind the Kato-Katz technique is straightforward: people infected with STH or intestinal schistosomes pass the eggs of the worms through their faeces. By examining a stool sample under a microscope it is possible to count the number and the type of eggs that are present
It was developed in 1954 by the Japanese physician, Dr. Kan Kato (1913–2011), together with his adviser, Dr. Momoshige Miura (1891–1989), a renowned Japanese medical researcher and psychiatrist. The technique was modified for use in field studies in 1972 by a Brazilian team of researchers led by the Brazilian Parasitologist, Naftale Katz (b.1940)
detection not sensitive enough
(serological (immuno) assays). Antibody to soluble egg antigen. ELISA 96% sensitive (mansoni), 92% (haematobium). Takes approx. 6 weeks to seroconvert therefore for Katayama serology (e.g. EIA/IFAT) may be negative
Circumoval precipitation test (COPT): a serological test used for diagnosis of schistosomiasis, detects serum antibodies to Schistosoma. Schistosoma japonicum egg as antigen (freeze-dried in the reagent). Soluble egg antigens of Schistosoma japonicum block the formation of the circumoval precipitin by serum from infected humans. IgM/IgG, doesn't distinguish current from previous infection (can stay + 1 year after treatment). Not recommended for routine diagnosis in endemic areas.
For Katayama, nucleic acid detection: PCR of blood should be positive (stool/urine may be negative)
Haematological: Eosinophilia (acute)
Radiological: Ultrasound (liver): Living in the bowel lumen, Schistosomes lay eggs in the mesenteric veins and, thus, these eggs can reach the portal vein. Species S. mansoni and S. japonicum are most common. Within the portal venules, an inflammatory reaction and consequent granulomatous response will lead to periportal fibrosis as a healing process. Due to the difference in the size of the eggs, S. mansoni infection has its eggs deposited along the large portal veins of the hepatic hilum, whereas the S. japonicum infection has the eggs laying within the small peripheral portal veins.
Praziquantel kills adult flukes (not young worms), therefore repeat at 3 months
Katayama fever: steroids, praziquantel? (1/3 cases already shed eggs)
Schistosoma mansoni egg (with miricidium inside)
SCHISTOSOMIASIS: CHILDREN, ARPRAZIQUANTEL
A ProMED-mail post
Today [16 Nov 2021], the GHIT-invested Pediatric Praziquantel Consortium, a public-private partnership dedicated to the development of arpraziquantel, a potential new treatment option for schistosomiasis in preschool-aged children, announced the completion of its pivotal phase III trial in Côte d'Ivoire and Kenya.
The results of the trial, co-funded by the Global Health Innovative
Technology (GHIT) Fund and the European & Developing Countries
Clinical Trials Partnership (EDCTP), confirm a favorable efficacy and
safety profile for arpraziquantel in children 3 months to 6 years of
age, affected by this neglected tropical disease. This allows the
program to progress towards regulatory file submission to the European
Medicines Agency (EMA).
Schistosomiasis is one of the most damaging parasitic diseases,
affecting the lives of around 240 million people, and is highly
prevalent in sub-Saharan Africa. The drug praziquantel -- the current
standard treatment developed in the 1970s -- is safe, effective, and
available for school-aged children and adults. At present, around 50
million preschool-aged children have been left untreated in public
health programs primarily due to the lack of an appropriate
child-friendly formulation of the drug.
Derived from praziquantel, arpraziquantel is an orally dispersible
tablet (dissolves in the mouth). It was developed by Astellas Pharma
Inc. in Japan, subsequently optimized by Merck in Germany, and
transferred for clinical manufacturing to Farmanguinhos in Brazil. The
new tablet is small, has appropriate taste properties, can be taken
with or without water, and withstands the hot and humid challenges
presented by a tropical climate.
Kio Yamabe, Acting CEO of the GHIT Fund said: "Having partnered with
the Pediatric Praziquantel Consortium since 2013, we believe that
international collaborations like this are key to addressing the
burden of major infectious diseases in the developing world. The
successful joint development of arpraziquantel by Consortium partners
Astellas, Merck, and Farmanguinhos embodies our unwavering commitment
to drive Japanese innovation and technology through global
partnerships. This remarkable achievement would not have been possible
without the tireless efforts of the consortium, which was directly
involved in the clinical trials, as well as the engagement of the
children who participated in the trials and their families and
communities that supported the trials. I would also like to thank our
stakeholders, including the Japanese government, private companies,
the Bill & Melinda Gates Foundation, Wellcome, council members, board
members, selection committee members, and external reviewers, for
their generous support over the years."
The successful completion of the phase III trial has been a
consolidated effort of strong and experienced in-country partners --
the Kenya Medical Research Institute and Université Félix
Houphouet-Boigny -- with the Swiss Tropical and Public Health
Institute overseeing the trial management. Merck acted as trial
sponsor, ensuring that the necessary quality standards and regulatory
requirements from authorities such as EMA were addressed. Expert
input, including from the World Health Organization, has supported the
development of the program.
Dr Michael Makanga, Executive Director, EDCTP said: "With the
completion of the phase III trial, the Pediatric Praziquantel
Consortium demonstrates that balanced North-South collaboration with
complementary expertise, bidirectional knowledge sharing, and mutual
trust, is a key success factor to develop and deliver safe and
affordable treatments for neglected tropical diseases, such as
The rationale for the study was based on data gathered from the
clinical Phase I study in adult volunteers, a taste study in children
6-11 years of age, and a phase II dose-finding study in _Schistosoma
mansoni_-infected children 3 months to 6 years of age, conducted in
In the completed phase III trial, children aged 3 months to 6 years
infected with _S. mansoni_ or _S. haematobium_ were enrolled in
different age groups and treated with a single dose of arpraziquantel.
High efficacy was observed with cure rates close to or above 90% for
_S. mansoni_ (at a dose of 50 mg/kg) and _S. haematobium_ (at a dose
of 60 mg/kg). The primary endpoint of clinical cure, defined as no
parasite eggs in the stool (_S. mansoni_) 17 to 21 days after
treatment or urine (_S. haematobium_) 17 to 21 days and additionally
35 to 40 days after treatment, met the pre-specified success criteria.
Arpraziquantel treatment at both doses demonstrated favorable safety,
tolerability, and improved palatability among preschool-aged children.
No new potential risks or safety concerns were identified.
With the full clinical development phase successfully completed, the
program has entered the regulatory filing stage, while preparing for
the potential delivery of arpraziquantel through the Consortium's
dedicated access program, ADOPT.
On behalf of the Consortium, Merck intends to apply for a scientific
opinion by EMA under the EU-M4all procedure for high-priority
medicines for human use intended for markets outside the European
Union. A positive opinion by EMA would facilitate the inclusion of
arpraziquantel in the World Health Organization (WHO) list of
prequalified medicinal products, as well as regulatory approvals in
Peter Guenter, Member of the Executive Board of Merck and CEO of
Healthcare, said: "With this milestone, we continue our commitment to
eliminating schistosomiasis and ensuring all people affected by this
neglected tropical disease have access to a life-saving therapy.
Together with our Consortium partners, we are steadfast in our vision
to bring new hope to the world's most vulnerable populations."
1. About schistosomiasis
Schistosomiasis (also known as bilharzia) is one of the most prevalent
parasitic diseases in sub-Saharan Africa, caused by parasitic
flatworms called schistosomes, of which _S. mansoni_ and _S.
haematobium_ are the 2 major species. The disease affects almost 240
million people, mainly in communities without access to safe drinking
water and with poor sanitation, with an estimated number of deaths of
about 200 000 per year. The parasites live within freshwater snails
and infect humans by penetrating the skin. The disease can lead to
chronic inflammation of the organs, which can be fatal but also to
anemia, stunted growth, and impaired learning ability with devastating
consequences for the lives of young children.
2. About the Pediatric Praziquantel Consortium
The Pediatric Praziquantel Consortium is an international
not-for-profit partnership that aims to reduce the global disease
burden of schistosomiasis by addressing the medical needs of infected
preschool-age children. Its mission is to develop, register, and
provide access to a suitable pediatric praziquantel formulation for
treating schistosomiasis in this age group. The pediatric formulation
under investigation has been designed to be smaller, exhibit improved
palatability, and be orally dispersible compared with the current
commercial formulation. For more information, visit the Consortium
3. GHIT's investment in the Pediatric Praziquantel Consortium
[The new formulation of praziquantel is a major advancement. According
to the press release, the new formulation dissolves in the mouth
whereas previously praziquantel tablets needed to be crushed before
being administered to children. See the comments on the treatment of
schistosomiasis in children in the ProMED post from 2019 listed below.