Visceral leishmaniasis: successful vaccine trial in dogs

Visceral leishmaniasis, which is the most severe form of that group of diseases, affects 500 000 people in the world each year. It is caused by a protozoan, Leishmania infantum, transmitted by sand fly bites. There is no vaccine for this disease, which can rapidly lead to death if no treatment is given. In the most heavily affected areas, the dog population is hit heavily by infection. It acts as parasite reservoir for humans. Development of a vaccine for dogs could help brake transmission of the disease to humans, by reducing this reservoir. Such prevention treatment has just been tested successfully on dogs by an IRD team in Montpellier, in conjunction with the Rocher veterinary clinic (La Garde, Var) and the biopharmaceutical company Bio Véto Test (La Seyne-Sur-Mer, Var). The first results showed total lasting protection of these animals against the disease, could open the way towards the development of a human vaccine.

Visceral leishmaniasis, which is the most severe form of the leishmaniases, hits an annual total of 500 000 people, mostly in the developing countries. It is caused by the parasite Leishmania infantum. A flagellate protozoan, it uses as vector an insect resembling a midge, the sand fly, colonizing the intestine and then the salivary glands. The female insect feeds on mammals’ blood. It can thus pass the parasite on to humans by a single bite. Once in the blood stream, L. infantum passes into particular cells of the immune system, the macrophages. These eventually burst, releasing the parasites which move on to penetrate other cells. The infected subject suffers bouts of fever, anaemia, enlarged spleen and liver, and weight loss. In the absence of treatment, these clinical signs usually announce a fatal outcome.

The sand fly sucks blood from mammals other than humans. This is how, right around the Mediterranean rim, 5 million dogs, a proportion of from 1 to 42 % depending on the area, are affected by visceral leishmaniasis. These animals are thus a reservoir for these parasites, which continuously feed the mammal-sand fly-human cycle. In this context, development of a canine vaccine would help reduce the portion of the animal population infected. The risks of transmission of the disease to humans would in this way be indirectly reduced.

Up to now, several dog vaccines, mostly developed from whole dried parasites, have proved not to be really effective. A team from the IRD Montpellier research centre, working with the Rocher veterinary clinic (La Garde, Var, France) and the biopharmaceutical firm Bio Véto Test (La Seyne-Sur-Mer, Var), have recently produced and tested a new type of treatment, composed solely of antigen proteins excreted by the parasite. The first trials indicate that this would completely and lastingly protect dogs against the disease.

Twelve out of 18 dogs included in the study were treated with increasing doses of protein antigens excreted by the parasite (that is 50, 100, 200 micrograms) made up to a formula with an adjuvant. The other six received no treatment. Two injections at an interval of three weeks resulted in infection of all the animals with L. infantum. They were followed up for two years in order to monitor the progress of the disease. The mixture of parasite proteins proved to be especially effective, as 100% protection was obtained for the doses of 100 micrograms (six immunized dogs out of six) and 200 micrograms (three out of three).

The researchers also focused on the changes to the immune system brought on by the vaccination. Laboratory experiments showed that the effectiveness of the vaccine stems from the activation of certain cells of the immune system, the T lymphocytes of type Th1. These induce the infected macrophages to produce nitric oxide, highly toxic for cells. This process, which did not occur in the untreated dogs, thus enables macrophages to get rid of the parasites that are infecting them. The animal thus acquires long-term protection against visceral leishmaniasis.

Although this vaccine’s effectiveness has been shown only on a limited number of animals, it is a further step towards protection of dogs against this disease. These results, confirmed indeed by the first, highly encouraging, data from a large-scale clinical trial currently under way (phase III), are promising for efforts to reduce transmission of leishmaniasis to humans. They also point to new lines of investigation for elaborating a possible human vaccine. An integrated research project, involving several IRD groups, has just been set up in India, to work on this. It should lead to an assessment of the effectiveness of such a vaccine in humans.

Science Daily
September 13, 2005

Original web page at Science Daily


A vaccine to kill tapeworm

A vaccine for pigs could help save the 50,000 people a year in poor countries killed by a gruesome parasite. Initial trials suggest it is nearly 100 per cent effective. The vaccine, developed by a team at the University of Melbourne, Australia, targets a tapeworm called Taenia solium. The adult form, caught from eating undercooked pork, grows only inside the human intestine, stealing nutrients from the host.

This can be debilitating. But far worse is what can happen if people swallow any of the microscopic eggs shed in vast numbers in the faeces of those carrying the adult form. The eggs hatch in the intestine and the immature parasites, known as oncospheres, burrow through the gut wall. They then migrate through the body and lodge themselves in muscles, the eyes and the brain, causing a disease called cysticercosis. Its symptoms vary depending on the location and number of what are called cysticerci. Many people have no serious symptoms, but some go blind, become confused, suffer difficulty with balance or have epileptic seizures. Heavy infections can kill, often as a result of inflammation after the parasites die. The parasite has been virtually eliminated in developed countries, but even in the US there are around 1000 cases each year, mainly among immigrants. In central and South America, Asia and Africa, millions of people have symptoms of the disease.

While humans are the main host for T. solium, pigs are the intermediate host, and an essential step in the tapeworm’s life cycle. If a pig eats the eggs then, as in humans, the eggs hatch in the intestine, burrow through the gut wall and travel to muscles, where they form cysticerci. The infection rarely causes symptoms in pigs. Only cysticerci- not eggs- can develop into the adult form, so if you prevent infection in pigs, you can break the life cycle, says team member Charles Gauci. The Australian group has created a vaccine based on two proteins found on the oncosphere. The vaccine triggers the production of antibodies by the immune system that cause oncospheres to burst.

Small-scale trials, in which eggs isolated from adult tapeworms were fed to up to 30 pigs, have already been conducted in Mexico, Peru, Cameroon and Honduras. The vaccine provided between 99.5 and 100 per cent protection in every trial. The Melbourne researchers, together with collaborators in Lima, Peru, now have plans for larger field trials in which the pigs will be allowed to forage as normal, they reported at a conference on parasitology in Melbourne last week. At the moment, two vaccinations about one month apart provide several months of immunity. The team’s aim is to provide lifelong immunity with one or two shots, though they say the vaccine will still be beneficial even it has to be given yearly. There is no reason why the vaccine would not work in people too. But safety issues make it much more costly to develop a human vaccine, and it should not be necessary, says Gauci. “An effective control programme would involve treating people with existing drugs to remove tapeworm from a population and preventing the reinfection of the human population by vaccinating pigs,” he says.

Source: New Scientist Boston office
August 2, 2005

Original web page at


Liver flukes in China

The infection rate of food-borne parasitic diseases has climbed dramatically in the country in the past 10 years, health officials said. The incidence of liver flukes, the leading food-borne parasitic worm, has increased by 75 percent over the period, according to a survey conducted by the Ministry of Health throughout China’s 31 provinces and autonomous regions from June 2001 to 2004.It is estimated that more than 12 million Chinese have been infected with liver flukes through food, and have gone on to develop hepatic distomiasis, a liver disorder.

South China’s Guangdong Province, the Guangxi Zhuang Autonomous Region and Northeast China’s Jilin Province have the highest rates of hepatic distomiasis, recording a 182, 164 and 630 percent growth compared with a similar survey conducted from 1988 to 1990. Guangdong is home to almost half of the nation’s hepatic distomiasis patients. “Food-borne parasitic disease is a growing threat to public health and an outstanding issue for food safety,” said Hao Yang, an official with the Disease Control and Prevention Division of the Ministry of Health. The survey attributed the increasing incidence of liver fluke-caused disease to people’s growing penchant for raw food. More and more people have developed a taste for raw seafood, especially those living in coastal regions. For example, raw fish salad, a kind of sashimi, is a common food for people living on the coast.

Liver fluke found in seafood can cause severe distomiasis in human beings, said Xu Longqi, a researcher with the National Institute of Parasitic Disease under the Chinese Centre for Disease Control and Prevention. Symptoms of the disease include diarrhea, malnutrition and hepatocirrhosis, he added. Eating raw or semi-raw pork and beef can also trigger parasitic diseases, proven by the high infection rate in Southwest China’s Yunnan Province, where such food abounds. Local residents in Dali and Simao in Yunnan, for example, enjoy eating raw pork, which is a source of such diseases, said Xu. However, land-borne parasitic diseases that infect human beings are well under control, said Hao. On a national level, the infection rate of this kind of parasitic disease is 63.65 percent lower, compared with the 1st survey. In 1990, there were 536 million patients with verminosis. By the end of 2004, this figure had dropped to 136 million. Hookworm, roundworm and whip worm, the most common land-borne parasitic diseases, are in sharp decline, said Xu. “Rural hygiene campaigns have helped eliminate the worms, and lower the infection rate,” said Hao. He also called for vigilance against diseases passed to humans through pets, and suggested pregnant women stay away from domesticated animals.

ProMed Mail
June 7, 2005

Original web page at ProMed Mail


Veterinarians’ comment on the news “Salmon from farms bred sea lice” (Vetscite News 12 April, 2005)

Aquaculture vets in BC counter critics and confirm that sea lice levels are ‘properly controlled’.

The Association of Aquaculture Veterinarians in Canada’s British Columbia has outlined concerns over a mathematical scenario of how sea lice might be transmitted from farmed salmon to wild salmon, referring to a study widely publicised worldwide last week which gave birth to headlines such as ‘Parasite on farmed salmon threatens wild species: study’ or ‘Farm sea lice plague wild salmon’ in some major international media.

Under provincial regulation the British Columbia Ministry of Agriculture, Food and Fisheries (BC MAFF) requires all salmon farms to have a comprehensive Fish Health Management Plan (FHMP) as a condition of license. These plans include mandatory monthly or more frequent sea lice monitoring for Atlantic salmon at all marine net pen sites. This monitoring is done and paid for by the farms.

Periods of juvenile salmon out-migration have been determined by Fisheries and Oceans Canada (DFO). During these periods BC MAFF requires mandatory action if sea lice levels exceed 3 mobile lice/fish. In the Broughton area lice levels must be at these low levels before March 1st. To ensure that sea lice numbers are being sampled and reported properly, BC MAFF audits sampling by the farms on a random basis. For example, in 2005 during the peak smolt out migration 50% of the active salmon farms in BC will be sampled by BC MAFF fish health staff. During the first two weeks in March 2005 the BCMAFF Fish Health Veterinarian attended a number of farms in the Broughton area and confirmed that the lice levels on the farms were being properly sampled and controlled as per the management agreement between BCMAFF and the industry.

BC Salmon Farmers Association
10 May, 2005

Original web page at BC Salmon Farmers Association


Salmon from farms breed sea lice

Salmon farms help stock supermarkets but also breed parasitic sea lice that infect young wild salmon and could endanger other important ocean species such as herring, scientists said Tuesday. Even a single farm can have far-reaching effects, Canadian researchers Martin Krkosek, Mark Lewis and John Volpe found. The study adds fuel to the clamor over farmed versus wild salmon, a debate that extends along Pacific Northwest coastlines. “We know that the lice do infect other species,” said Krkosek, a University of Alberta mathematical biologist. “The transmission from farmed fish to wild fish is much larger than what was previously believed.” Adult salmon can survive such infections, but the younger salmon are more vulnerable. “Normally, juvenile salmon have time to build resistance and put on body mass before they encounter these parasites,” Krkosek said.

The Canadian government has found that salmon farms effectively control sea lice. But citing concerns over declining populations of native juvenile salmon off northern Vancouver Island, the government announced plans last week to do more research on the matter. The study, being published Wednesday in the London-based Proceedings of the Royal Society B, contradicts the government’s conclusion on the danger posed by sea lice from salmon farms.

Ransom A. Myers, a marine biology professor at Dalhousie University in Canada, called it “a very thorough analysis” that relies on an enormous data set. But Robert Scott McKinley, a University of British Columbia professor of aquaculture, was unconvinced. “I think it hints of fear-mongering,” he said. In the published study, the researchers looked at 5,514 juvenile pink and chum salmon as they swam up two narrow fjords in British Columbia, past a salmon farm.

The study found that as the fish migrated past the farm — about one-eighth of a mile long — clouds of lice infected the juvenile wild salmon at unnaturally high rates for nearly 19 miles around the farm. Normally, sea lice are rarely found on wild juvenile salmon. “Conservatively, this means that the parasite footprint of the farm is 150 times larger than the farm itself,” said Volpe, a University of Victoria marine ecologist. The study also found that the lice bred as they infected the migrating juvenile salmon, allowing them to re-infect the fish and potentially endanger other marine species.

Some European countries, where salmon farming is popular, use chemicals to control the parasites and dye to turn the salmon flesh pink. The use of those chemicals has led some environmentalists to hold demonstrations run ads urging consumers to boycott farmed salmon. Some grocery stores carry labels saying farmed fish contain dye. And a major study in the journal Science last year found more cancer-causing PCBs in farmed fish over wild fish.

April 12, 2005

Original web page at Yahoo


Reemergence of canine Echinococcus granulosus infection

As a consequence of large-scale outdoor slaughter of sheep during the 2001 foot and mouth disease (FMD) outbreak in the United Kingdom and the possibility of increased risk for transmission of Echinococcus granulosus between sheep and dogs, a large survey of canine echinococcosis was undertaken in mid-Wales in 2002. An Echinococcus coproantigen-positive rate of 8.1% (94/1,164) was recorded on 22% of farms surveyed, which compares to a rate of 3.4% obtained in the same region in 1993. Positivity rates between FMD-affected properties and unaffected ones did not differ significantly. Significant risk factors for positive results in farm dogs were allowing dogs to roam free and the infrequent dosing (>4-month intervals) of dogs with praziquantel. When these data are compared to those of a previous pilot hydatid control program in the area (1983–1989), an increase in transmission to humans appears probable.

Echinococcus granulosus infection in sheep and dogs has been known to be endemic in parts of Wales and the English borders for many decades. An analysis of national hospital records for the period 1974–1983 showed that the incidence of human cystic echinococcosis was 0.2 cases per million in England and 2 cases per million population in Wales, with highest rates (5.6 cases per million) occurring in southern Powys County. To reduce the incidence of human cystic echinococcosis (also called cystic hydatid disease), a voluntary hydatid control program of supervised dog dosings at weekly intervals with praziquantel was introduced in south Powys in 1983 and continued until 1989. Ovine hydatidosis rates in the intervention area dropped from 23.5% to 10.5% after that period, and experimental use of sentinel lambs confirmed that transmission of E. granulosus was significantly reduced by this regime. Trend analyses of hospital admissions of human hydatid disease showed that, by 1993, clinical cystic echinococcosis disease in children (<15 years old) had ceased in the intervention area.
However, a new focus of human cystic echinococcosis was identified for the period 1984–1990 in an area bordering south Powys, namely, the northern parts of the counties of Gwent and mid-Glamorgan. Furthermore, canine echinococcosis rates, measured indirectly with an Echinococcus-specific coproantigen enzyme-linked immunosorbent assay (ELISA), reflected the clinical data for intervention and nonintervention areas.

In 1989, the supervised dog-dosing program was stopped and replaced by a health education program. A follow-up abattoir and dog coproantigen survey in 1995 to 1996, however, indicated that E. granulosus infection had reemerged in sheep and dogs in the previous hydatid-control intervention areas. In 2001, the foot and mouth disease (FMD) epidemic in sheep in England and Wales affected some farms in both the former hydatid-intervention and nonintervention areas. Concern was raised that dog access to carcasses of sheep, euthanized as part of the FMD control program and awaiting incineration, could amplify the prevalence of infection in dogs and thereby the subsequent risk for humans. A third coproantigen survey of farm dogs in south Powys and north Gwent was therefore undertaken in 2002 to determine the prevalence of canine echinococcosis in the former hydatid-intervention and nonintervention areas.

Emerging Infectious Diseases
April 12, 2005

Original web page at Emerging Infectious Diseases