Product characteristics for anthelmintics

In farm animals, several herd/pasture management strategies have been identified that could help to delay the development of antiparasitic resistance. The elaboration of standard general advice encouraging appropriate pasture or habitat management, as a direct way to favour refugia, and/or as the necessary adjunct to targeted and less frequent use, should be considered.

 

 

In relation to this area of parasitology, the European Medicines Agency has issued new guidance (“Concept paper for the revision of the guideline on the summary of product characteristics for anthelmintics”, see: https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-revision-guideline-summary-product-characteristics-anthelmintics_en-0.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Ancient feces reveal how 'marsh diet' left Bronze Age Fen folk infected with parasites

New research published today in the journal Parasitology shows how the prehistoric inhabitants of a settlement in the freshwater marshes of eastern England were infected by intestinal worms caught from foraging for food in the lakes and waterways around their homes.

The Bronze Age settlement at Must Farm, located near what is now the fenland city of Peterborough, consisted of wooden houses built on stilts above the water. Wooden causeways connected islands in the marsh, and dugout canoes were used to travel along water channels.

The village burnt down in a catastrophic fire around 3,000 years ago, with artefacts from the houses preserved in mud below the waterline, including food, cloth, and jewellery. The site has been called "Britain's Pompeii."

Also preserved in the surrounding mud were waterlogged "coprolites" -- pieces of human faeces -- that have now been collected and analysed by archaeologists at the University of Cambridge. They used microscopy techniques to detect ancient parasite eggs within the faeces and surrounding sediment.

Very little is known about the intestinal diseases of Bronze Age Britain. The one previous study, of a farming village in Somerset, found evidence of roundworm and whipworm: parasites spread through contamination of food by human faeces.

The ancient excrement of the Anglian marshes tells a different story. "We have found the earliest evidence for fish tapeworm, Echinostoma worm, and giant kidney worm in Britain," said study lead author Dr Piers Mitchell of Cambridge's Department of Archaeology.

"These parasites are spread by eating raw aquatic animals such as fish, amphibians and molluscs. Living over slow-moving water may have protected the inhabitants from some parasites, but put them at risk of others if they ate fish or frogs."

Disposal of human and animal waste into the water around the settlement likely prevented direct faecal pollution of the fenlanders' food, and so prevented infection from roundworm -- the eggs of which have been found at Bronze Age sites across Europe.

However, water in the fens would have been quite stagnant, due in part to thick reed beds, leaving waste accumulating in the surrounding channels. Researchers say this likely provided fertile ground for other parasites to infect local wildlife, which -- if eaten raw or poorly cooked -- then spread to village residents.

"The dumping of excrement into the freshwater channel in which the settlement was built, and consumption of aquatic organisms from the surrounding area, created an ideal nexus for infection with various species of intestinal parasite," said study first author Marissa Ledger, also from Cambridge's Department of Archaeology.

See:

Marissa L. Ledger, Elisabeth Grimshaw, Madison Fairey, Helen L. Whelton, Ian D. Bull, Rachel Ballantyne, Mark Knight, Piers D. Mitchell. Intestinal parasites at the Late Bronze Age settlement of Must Farm, in the fens of East Anglia, UK (9th century B.C.E.). Parasitology, 2019; 1 DOI: 10.1017/S0031182019001021

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

High risk of malaria transmission after blood transfusions in sub-Saharan Africa

A new study suggests that in certain areas of sub-Saharan Africa, nearly one in four blood bank supplies contain the parasites that cause malaria. Another study, focusing on the blood supply of Equatorial Guinea’s capital, Malabo, found much higher levels of latent malaria infection, most of it—more than 89 percent—at a level that commonly-used diagnostic technology cannot detect. Both studies were presented at the 7th Multilateral Initiative on Malaria (MIM) Pan African Malaria Conference in Dakar, Senegal.

Sub-Saharan Africa carries the highest burden of malaria in the world. According to the World Health Organization (WHO), 90 percent of all malaria cases are located in the region. In the quest for elimination of malaria, all sources of disease transmission, including the region’s blood banks, need to be addressed.

The first study, “A systematic review and meta-analysis of the risk of transfusion-transmitted malaria from blood donors in sub-Saharan Africa,” conducted by Dr Selali Fiamanya and colleagues from the Worldwide Antimalarial Resistance Network (WWARN),gathered results from 24 studies to assess malaria prevalence among 22,508 blood donors. Pooled prevalence of malaria parasitemia was 23.46 percent (95%CI: 19.7% – 27.2%), ranging from 6.5 percent to 74.1 percent, including more than 10 studies from Nigeria, Africa’s most populous country.

Half of all children receiving blood transfusions need the procedure to address malaria-induced anemia, the failure to keep these blood banks safe puts children and their parents at risk. Dr. Fiamanya’s study shows that without better vigilance, children receiving transfusions to address malaria’s impacts risk exposure to more malaria-causing parasites.

“Malaria is one of the primary infections that can be transmitted through a blood transfusion in sub-Saharan Africa,” said Dr. Fiamanya at WWARN. “Our research is only the first line of inquiry needed to address this risk. Pregnant women and children receive the majority of transfusions in this region. The technical challenges of diagnosing and removing the Plasmodium parasites from the blood banks requires further analysis, but we know already that these findings threatens the next generation—our future.”

The second study, “Prevalence of Malaria Parasites at the Malabo Blood Bank on Bioko Island, Equatorial Guinea,” conducted by Dr. Claudia Daubenberger, colleagues at the Swiss Tropical and Public Health Institute, and Dr. Tamy Robaina at the Malabo Blood Bank, with support from Marathon Oil Corporation and the Equatoguinean Ministry of Health and Social Welfare, used a more sensitive diagnostic test—quantitative polymerase chain reaction (qPCR) assays—to examine 200 blood samples collected in the country’s capital, Malabo.

Typically, rapid diagnostic tests (RDTs) and thick blood smear microscopy are used to diagnose malaria as these tests are much easier to deploy and use in the field. Neither diagnostic test can detect latent malaria infection, however, and low-level or asymptomatic infections can hide reservoirs of parasites that fuel future malaria outbreaks.

Using the qPCR assays, which are currently too expensive and unsuitable for most field conditions, Dr. Daubenberger and colleagues found that 29.5 percent of the blood samples were contaminated. All of the samples thought to be free of the malaria parasite held very low concentrations of the parasites—under 100 parasites per microliter of blood.

“With better screening technology and practices in place, blood banks in sub-Saharan Africa can be well placed to serve as a surveillance system, helping to monitor malaria and other transfusion-transmitted infectious diseases,” said Dr. Daubenberger. “Our findings clearly reinforce World Health Organization recommendations that all transfusion recipients receive preventive malarial treatments. This disease is a treatable and preventable burden that few patients needing blood transfusions can afford.”

The Pan African Malaria Conference is organized every three-to-four years by the MIM secretariat in collaboration with a group of African institutions. This year’s meeting falls four months after the release of the WHO’s 2017 World Malaria Report, which found there is a dire need for new malaria interventions, particularly in sub-Saharan Africa. The report found that despite recent advances, overall progress against global malaria control has stalled. In 2016, there were an estimated 216 million cases of malaria, about 5 million cases more than in 2015. Ninety percent of these cases occurred in sub-Saharan Africa.



This year’s malaria conference in Dakar is running parallel to The Malaria Summit, Ready to beat malaria, which is taking place alongside the Commonwealth Heads of Government Meeting (CHOGM) in London on 18th April 2018. This will bring together business leaders, philanthropists, scientists, Heads of States and civil society to announce significant new commitments to mobilize domestic resources, increase investment and develop new innovation and approaches towards beating malaria. The commitments sit alongside a call to action urging the Commonwealth as a whole—who represent citizens making up six out of ten malaria cases globally—to commit to accelerating progress against malaria, the world’s oldest and deadliest disease.

Posted by Dr. Tim Sandle

Mosquito bite avoidance for travellers

In many tropical countries, mosquitoes can spread diseases such as dengue, chikungunya, West Nile, malaria, yellow fever and Zika. Here are five simple rules you should follow to reduce your risk of infections spread by mosquitoes.

Public Health England have produced an information leaflet:

Mosquito Advice Sheet

Posted by Dr. Tim Sandle

World's First Malaria Vaccine

RTS has won approval in Europe as the world's first malaria vaccine. This is a major step towards prevention of a disease that kills more than half a million people worldwide every year. This week, the EMA concluded that the vaccine should be used for immunization of children in Africa of age 6 weeks to 17 months along with other protective measures against malaria such as insecticides and bed nets. Later this year, the WHO is going to review evidence for the vaccine and decide whether to recommend its use. The deadliest of the malarial parasite is the Plasmodium falciparum which is what the RTS,S vaccine targets. It works by inducing an immune response in the body. However, one point to be noted is that in clinical trials, the vaccine has not proved effective enough to be used alone.

Source: Science Alert.

Posted by Tim Sandle

Promising Malaria and Dengue Vaccines Alone Will Not Defeat Diseases

From Sanofi Pasteur:

Despite the optimism surrounding two first-in-class products, Sanofi Pasteur’s live-attenuated dengue vaccine, CYD-TDV, and GlaxoSmithKline’s (GSK’s) adjuvanted subunit malaria vaccine, RTS,S/AS01, vaccination alone is not a viable long-term solution for combatting these infectious diseases, says an analyst with research and consulting firm GlobalData.

According to Christopher J. Pace, Ph.D., GlobalData’s Managing Analyst covering Infectious Diseases, some industry pundits rightfully question the modest protective efficacies of CYD-TDV and RTS,S/AS01. Immunization must therefore be leveraged alongside vector control strategies, national and international surveillance programs, and public awareness campaigns as part of integrated disease prevention and control initiatives.

Pace explains: “Upon their anticipated approvals in late 2015, both Sanofi Pasteur’s CYD-TDV and GSK’s RTS,S/AS01 have the potential to begin providing long-awaited relief to billions of people living under the constant threat of dengue and malaria. At the very least, they represent landmark advances in the development of vaccines against these serious arthropod-borne illnesses.

“Nevertheless, GlobalData expects that while vaccines will be an essential component of future dengue and malaria prevention and control efforts, immunization cannot succeed as a ‘silver bullet’ solution for either disease.”

The analyst adds that renewed vector control efforts, from established methods such as mosquito nets and insecticides, to emerging microbiological and genetic techniques, are especially important to curtailing dengue and malaria transmission.

Pace continues: “There are a number of novel tools on the horizon that will complement vaccines, most notably improved insecticides and innovative microbiological (Walbachia, Chromobacterium [Csp_P]) and genetic (sterile male) vector control technologies, as well as more potent antivirals for dengue and antiparisitics for malaria.

“The cost of these vaccines will also emerge as a key issue, as both dengue and malaria primarily affect the developing world. Ultimately, GSK and Sanofi Pasteur must work with other stakeholders to champion innovative pricing strategies and encourage vaccine uptake as part of integrated surveillance, prevention, and control programs to maximize each product’s public health benefit and commercial potential,” the analyst concludes.

Posted by Tim Sandle

Chagas Disease Vaccine Promise

Chagas disease (or American trypanosomiasis) causes fever, fatigue, body aches, headache, rash, loss of appetite, diarrhoea, and vomiting. As well as growing in cases in the U.S. (particularly in Texas), it is a major cause of heart disease and gastrointestinal dysfunction in widespread areas throughout Latin America.

Chagas disease is caused by the tiny worm-like parasite Trypanosoma cruzi, which is carried by so-termed Kissing Bugs (the insects tend to leave bites around the mouth, specially while people are sleeping at night). Additionally, there is some evidence that bed bugs can also carry the parasite.

Currently there is no vaccine available. Treatment tends to be with anti-parasitic drugs (for those fortunate enough to be able to afford them).

In a new study, researchers report on success in developing the vaccine in mice infected with the disease causing parasite. Research has been led by scientists based at the University of Texas Medical Branch in Galveston, USA.

For more details, see TLN.

Posted by Tim Sandle

Malaria cells produce odors that attract mosquitoes

Malaria causing parasites produce chemical compounds that give off odors. These odors attract mosquitoes to come and bite an infected animal, thereby ensuring the cycle of infection continues.

Scientists have discovered that one malaria causing parasite Plasmodium falciparum produces chemical compounds called terpenes. Terpenes are a large and diverse class of organic compounds. In the chemical industry, they are the major components of resin, and of turpentine produced from resin.

These chemicals are key to producing the odors that attract mosquitoes. These chemicals have been detected in the sweat and breath of people who have malaria.

The researchers detected the chemical traces by infecting human blood cells with the parasites and holding them, with growth media, in air-tight bags. The gas produced by the respirating cells was then sampled and send for chemical analysis.

Further investigation showed that the parasite uses a chemical pathway (termed MEP) to produce the terpenes. Two terpenes were dominant: one called limonene (which has a slight lemon-y smell) and pinanediol (which has a slight pine-like odor). These smells appeal to mosquitoes and the insects are equipped to pick these out from distance.

It is hoped that the discovery will lead to the development of a breathalyzer test to determine if someone has malaria. Such tests would be far easier, and more pleasant for the patient to endure, than a blood test.

The information should also help scientists to understand why one person becomes infected with malaria and another does not, or why some people are more prone to being bitten by mosquitoes that others.

The research has been published in the journal mBio. The paper is titled “Malaria Parasites Produce Volatile Mosquito Attractants.”

In related news, mosquitoes carrying "tropical diseases" could become widespread across the U.K. over the next 20 or 30 years. This is assuming that European temperatures continue to rise.

Posted by Tim Sandle

Dracunculiasis and the Long Decline of an Ancient Disease

The disease dracunculiasis (guinea worm disease) has ravaged human populations for thousands of years (reference to the disease is documented in the Egyptian medical Ebers Papyrus, dating from around 1550 BC.) Current indications suggest that global incidences of the disease have been rapidly declining due to the concerted efforts of national and international health agencies. Here, only 148 dracunculiasis cases were reported worldwide in 2013 (which represents the lowest annual total ever recorded) and only four endemic countries remain: Chad, Ethiopia, Mali and South Sudan. With these countries, the majority of the cases occur in South Sudan . Nonetheless across these regions the number of endemic villages has declined from the peak of 23,735 in 1991 to 79 in 2013.

Guinea-worm disease is caused by the parasitic worm Dracunculus medinensis or "Guinea-worm". This worm is the largest of the tissue parasite affecting humans. The adult female, which carries about 3 million embryos, can measure 600 to 800 mm in length and 2 mm in diameter. The parasite migrates through the victim's subcutaneous tissues causing severe pain especially when it occurs in the joints. The worm eventually emerges (from the feet in most of the cases), causing an intensely painful oedema, a blister and an ulcer accompanied by fever, nausea and vomiting.
To find out more about this disease and why a decline has occurred, Tim Sandle has written a review paper for the journal Journal of Ancient Diseases & Preventive Remedies.

The reference is:

To view a copy, please contact Tim Sandle.

Drug-resistant malaria threatens to spread from Burma

Malaria with total resistance to the antimalarial drug artemisinin has taken hold in Burma and spread close to the border with India, threatening to render crucial medicines useless, scientists have warned.

If the resistant parasite reached India it would pose a serious threat to the chances of global control and eradication of the killer mosquito-borne disease, said Charles Woodrow of the Mahidol-Oxford tropical medicine research unit.

And if resistance spread from Asia to Africa, or emerges in Africa independently – as has been seen before with previously effective but now powerless antimalarials – “millions of lives will be at risk”, they said in a report.

For more details, see: The Guardian.

Posted by Tim Sandle

Dracunculiasis and the Long Decline of an Ancient Disease

The disease dracunculiasis has ravaged human populations for thousands of years (reference to the disease is documented in the Egyptian medical Ebers Papyrus, dating from around 1550 BC.) Current indications suggest that global incidences of the disease have been rapidly declining due to the concerted efforts of national and international health agencies. Here, only 148 dracunculiasis cases were reported worldwide in 2013 (which represents the lowest annual total ever recorded) and only four endemic countries remain: Chad, Ethiopia, Mali and South Sudan. With these countries, the majority of the cases occur in South Sudan. Nonetheless across these regions the number of endemic villages has declined from the peak of 23,735 in 1991 to 79 in 2013.

The disease is the basis of a new editorial by Tim Sandle. The reference is:

Sandle, T. (2015) Dracunculiasis and the Long Decline of an Ancient Disease, Journal of Ancient Diseases & Preventive Remedies, 2 (3): 1-2

For a copy, please contact Tim Sandle

Posted by Tim Sandle

Oldest ever parasite egg found

The discovery of a schistosomiasis parasite egg in a 6200-year-old grave could provide the first evidence that agricultural irrigation systems in the Middle East contributed to disease burden.

The egg has been found in a grave at a prehistoric town by the Euphrates river in Syria. The egg was found in the pelvic area of the burial where the intestines and bladder would have been during life.

Schistosomiasis is a disease caused by several species of flatworm parasites that live in the blood vessels of the bladder and intestines. The parasite spends part of its life cycle in snails that live in warm fresh water, before leaving the snail to burrow through the skin of people wading or swimming in the water. Today it is estimated that over 200 million people around the world are infected.

Read more...

Dwarf spiders try to keep paternity against rivals

How do lemurs fight infection?

The research suggests that the parasite may have been spread by the introduction of crop irrigation in ancient Mesopotamia, the region along the Tigris-Euphrates river system that covers parts of modern-day Iraq, Iran, Kuwait, Syria, and Turkey. Irrigation systems were starting to be introduced in Mesopotamia around 7,500 years ago. It is possible that these irrigation systems, that distributed water to crops, may have triggered the beginning of the disease burden of schistosomiasis some 6,000 years ago.

The finding also means that the parasite infected humans there at least a thousand years earlier than previously thought.

The finding has been published in the journal The Lancet Infectious Diseases. The paper is titled “Prehistoric schistosomiasis parasite found in the Middle East.”

Posted by Tim Sandle