Researchers are claiming a breakthrough in the battle against leishmaniasis, a potentially fatal disease affecting millions, many of them in Africa. The Centers for Disease Control in the USA includes Southern Africa in its list of regions affected by the lethal illness, which produces fever, weight loss, anaemia, and swelling of the spleen and liver. The disease is thought to have significant negative impacts on economic productivity.
Leishmaniasis is caused by a microscopic parasite related to the one that causes malaria. It is transmitted to humans by bites from tiny, blood-sucking sand flies. Three forms occur: one affects internal organs, one triggers skin ulcers, and one causes the membranes of the nose and mouth to erode away.
Describing their findings as ”a new picture” of how the disease is transmitted, the researchers say their work has important implications for developing drugs and vaccines. But the broader picture also underscores the many gaps between research and benefits for ordinary people, particularly given the lack of interest in so-called third-world illnesses by big pharmaceutical companies conscious of their fiduciary duty towards their shareholders. The good news is that these gaps are being filled in by researchers working in the developing world and in non-profit university laboratories.
The newest study, published in this week’s edition of the journal Nature, reveals that the average sand fly bite can vomit up more than 1,000 parasites, most at a stage in their life cycle when they are primed to cause infection.
By counting parasites in different parts of the sand flies’ digestive tract, the researchers have shown that the flies ”actively regurgitate” the parasite when they bite.
But the sand fly does more than just inject.
Animal testing showed that mice receiving a single infectious sand fly bite developed more severe skin lesions, and faster, than those injected with 1,000 infectious parasites from a syringe. This suggested that something else — dubbed an ‘exacerbation factor’ — was transmitted along with the parasites.
The exacerbation factor is in fact the main component of a gel released by the parasites while they are inside sand flies. The gel is known to block the sand fly gut, causing it to feed more often and for longer, which increases the chance of parasite transmission. Its additional role in enhancing infection was unknown until now.
The research also shows how the parasite has evolved a chemical that functions both in the insect that transmits it and in its dog, human or other host. This, say the scientists, highlights the importance of studying all three organisms simultaneously – an important issue in an era of increased specialisation.
”This is an excellent example of collaborative research bringing together biology and chemistry to unravel key questions,” says Mike Ferguson, one of the authors of the study, carried out by the Liverpool School of Tropical Medicine and the Wellcome Trust Biocentre at the University of Dundee, both in the United Kingdom, and the Max-Planck-Institut f?r Biologie in Germany.
Sometimes the problem is that information about third-world diseases is about as hard to come by as funding.
While infectious and parasitic diseases disproportionately wreak havoc in poor countries, authors and editors from these nations are significantly under-represented in journals that publish research in tropical medicine, according to work done by Jennifer Keiser of Princeton University’s Office of Population Research and her colleagues.
More than 70 per cent of editorial and advisory board members for the dozen leading journals that publish research on tropical medicine are from rich countries, with a high ranking in the United Nations human development index, which considers life expectancy, education levels and income. Just five per cent of the board members are from poor countries and five journals had only board members from rich countries.
For the six top-rated journals, the researchers fund that only 14 per cent of the authors who published recent research papers were from poor countries. These findings contrast with the relatively common occurrence of international research collaborations between scientists in rich and poorer countries.
But the research continues despite the difficulties in communicating about it.
Patients who cannot afford existing expensive medicines might benefit from a lower dose of the same drug, according to a pilot study carried out at the Kala-Azar Medical Research Centre at the Banaras Hindu University in Varanasi, India. The cost would not be astronomical but is still beyond the reach of many of the world’s poor.
So Médicins sans Frontières (Doctors Without Borders) launched an ambitious international effort to create a virtual industry driven by public needs rather than share price. The Drugs for Neglected Diseases Initiative began two years ago to create drugs for diseases that have poor commercial prospects because they affect mainly people in the developing world. (Not that the developed world is immune; most cases of leishmaniasis in the USA come from Mexico and Latin America.)
The Paris-based charity has put up an initial US$1 million for five pilot projects to develop and produce drugs for visceral leishmaniasis and sleeping sickness, both common in Africa. The parasites for both diseases can live inside the human body for months or even years, constantly dodging a gradually tiring immune system.
Pet dogs are a key source of the blood-sucking sand flies. But research from the Middle East recommends that children can be protected from potentially lethal leishmaniasis by fitting the animal with an insecticide-impregnanted collar. Work done by the Tabriz University of Medical Sciences in Iran found that dog collars can reduce the disease by 40 per cent.
The news should be of comfort to dog owners in at least 70 countries in Africa, Asia, Latin America and Europe where the disease is endemic and a common strategy in the war against the sand fly parasite has been to cull infected dogs.
This technique has been something of a failure because dog owners refuse to comply. In Brazil, animal-related visceral leishmaniasis has increased steadily over the past two decades despite spraying 200,000 houses with insecticide and killing 20,000 dogs a year.
The problem is that stray dogs must still be culled and collars are unlikely to be fitted on jackals, foxes and other wild animals who can also carry the sand fly.
So other researchers are investigating why some people infected with leishmaniasis sometimes manage to keep the disease at bay. A heavy first infection provokes an immune response that protects against re-infection, although the original pathogen may still be present.
Yasmine Belkaid and colleagues of the National Institute of Allergy and Infectious Diseases in the United States have studied this form of immunity in animal tests, using mice deliberately infected with a type of leishmaniasis. They reported that a certain type of immune cell is the key player.
These cells, known by the snappy title of CD4+CD25+ suppressor T cells, have been the focus of intense study because of their role in autoimmunity, when the immune system attacks the body. The findings raise the question of whether vaccine designers should avoid or target these cells – and will be important for other research into fighting other diseases, such as tuberculosis.
Other researchers have identified a mutant form of the leishmaniasis parasite that can remain indefinitely in host animals and people without making them ill. When the parasite is reactivated, this causes the most severe forms of the disease. But little is known about the factors that enable the parasite to persist in this way. So far it has been difficult to carry out such studies owing to the need for lengthy experiments. The findings could assist the development of effective vaccines and chemotherapy.
So far, vaccine developers have drawn a blank in the fight against the parasites that cause leishmaniasis and sleeping sickness. Part of the problem is that many parasites are masters of disguise, able to rapidly shuffle the surface proteins that the human immune system uses to recognise intruders.
Some scientists are now plotting an alternative, sweeter line of attack: they are trying to get the immune system to respond not to proteins, but to the complex sugars that parasites carry on their surfaces.
Neither politics nor war is being allowed to get in the way of the research. Investigations into leishmaniasis as well as significant genetic hearing loss problems continue in troubled Palestine, although many other joint cross-border science collaborations have crashed under America’s self-proclaimed ”Road Map” for the Middle East.
And on the other side of the world, in financially-embattled Argentina, leishmaniasis researchers are among the beneficiaries of July’s announcement of US $ 15 million in grants to replace decades-old scientific equipment. The Regional Medicines Institute in Resistencia in northern Argentina — which researches diseases of the poor such as leprosy and leishmaniasis — will receive special microscopes, portable ultrasound equipment and other instruments worth US$200,000. The equipment will assist disease diagnosis and allow researchers to analyse how environmental conditions affect human health.
”We have not had new equipment since the 1970s,” said director Jorge Gorodner. —SciDev.Net