Schistosomiasis (Bilharzia)

Types

Hepatic-intestinal

Liver fibrosis, portal hypertension, varices, pancytopenia, colitis, appendicitis, cor pulmonale

  • Schistosoma mansoni: Pipe-Stem fibrosis

  • Schistosoma japonicum

  • Schistosoma mekongi

  • Schistosoma intercalatum

Urogenital

Haematuria, haematospermia, postrenal renal failure, chronic lower abdominal pain, infertility

  • Schistosoma haematobium: Sandy patches (bladder)

Lifecycle

  1. Eggs excreted in urine or stool

  2. Egg releases miracidia, which penetrates into snail

  3. Develops into cercariae in the snail, then released into water

  4. Cercaria burrow into skin

  5. Male and female, 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

Clinical features

Katayama-Syndrome

  • 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:..... (Rothe lecture)

  • Serology (e.g. EIA/IFAT) may be negative

  • Nucleic acid detection: PCR of blood should be positive (stool/urine may be negative)

  • Treat

Diagnosis

  • 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)

Antigen

  • detection not sensitive enough

Antibody detection

  • (serological (immuno) assays). Antibody to soluble egg antigen. ELISA 96% sensitive (mansoni), 92% (haematobium). Takes approx. 6 weeks to seroconvert.

  • Circumoval precipitation test (COPT):

  • Haematological: Eosinophilia (acute)

  • Radiological: Ultrasound (liver

Treatment

  • Praziquantel kills adult flukes (not young worms), therefore repeat at 3 months

  • Prednisolone

References

Schistosoma mansoni egg (with miricidium inside)

Haematobium

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

schistosomiasis."


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

African countries.


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

endemic countries.


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

website: https://www.pediatricpraziquantelconsortium.org


3. GHIT's investment in the Pediatric Praziquantel Consortium

https://www.ghitfund.org/investment/portfoliodetail/detail/27/en

https://www.ghitfund.org/investment/portfoliodetail/detail/60/en

https://www.ghitfund.org/investment/portfoliodetail/detail/103/en

https://www.ghitfund.org/investment/portfoliodetail/detail/138/en

https://www.ghitfund.org/investment/portfoliodetail/detail/179/en


--

Communicated by:

ProMED

promed@promedmail.org


[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.

- Mod.EP