The Anglo-Ethiopian Society
Lecture - Thursday 16th June 2011
Leishmaniasis in Ethiopia
Given by - Dr Pascale Kropf
Reviewed by - Anne Parsons
Dr Pascale Kropf is an immunologist who for the last few years has been studying leishmaniasis in Ethiopia.
Leishmaniasis is a parasitic disease spread by the bite of the sandfly. It causes serious and significant public health problems. There are different forms of leishmaniasis and the disease has been reported on all continents except Australia and Antarctica.
The cutaneous form affects the skin and mucus membranes. Skin sores usually start at the site of the sandfly bite and can last for months or years before healing on their own. It is the more common type of presentation and although self healing can result in disfiguring scars. Patients tend to develop immunity to further leishmaniasis infection. As an aside, Pascale mentioned that in the middle-east parents may deliberately expose a child to be bitten on their bottom to provoke immunity thus avoiding the possibility of facial scarring.
Systemic, or visceral, leishmaniasis affects the entire body. This form generally develops 2 to 8 months after a person is bitten by the sandfly and it can lead to deadly complications. The parasites damage the immune system by decreasing the numbers of disease-fighting cells. However, only 1 person develops overt disease out of 30 to 100 subclinical cases where there are no overt symptoms. Risk factors include malnutrition, HIV, and use of immunosuppressant drugs.
Ethiopia has the highest rate anywhere of co-infection with leishmaniasis and HIV. Leishmaniasis must be treated first before antiretrovirals for the HIV can be started. There are several drugs that can be used to treat visceral leishmaniasis. Antimony-containing compounds are the main ones and are provided free in Ethiopia. The drawback is that these drugs have to be given for 20 to 30 days as injections (causing severe inconvenience) and are also extremely toxic - most patients with leishmaniasis who die in Ethiopia die as a result of drug treatment rather than the disease. Liposomal amphotericin is the drug usually preferred in developed countries and although a good response is obtained in southern Ethiopia, for some reason it is not effective in the north. Compliance with the oral drug miltefosine is poor.
Sandflies, unlike mosquitoes, are extremely small (less than 3mm), hairy, hop around, live on land in cracked soil or the surface of huts rather than near water, and are silent. Only the female sandfly needs blood. Because the sandflies are so small, they can usually penetrate the mesh of the bednets used against mosquitoes. The most effective preventative measure that can be taken is wearing protective clothing and liberal use of an insect repellent such as 50% DEET.
As an immunologist Pascale's work has focussed on the study of such parameters as Tcell counts and interferon levels. In people who do not develop overt visceral disease, Tcells (which belong to a group of white blood cells) produce and release a protein called interferon-gamma; this in turn activates nitric oxide synthase, an enzyme that catalyses the production of nitric oxide from the essential amino acid arginine; it is this nitric oxide that is believed to be toxic to the leishmania parasite at a cellular level. However, those patients who do suffer overt and non-healing disease have been found to have very low levels of arginine and thus production of the killer nitric oxide is diminished. Why are the arginine levels low and what can be done? These patients seem to have excessive levels of an enzyme called arginase which just breaks down the arginine. Enzyme inhibitor drugs in many other fields of medicine are well known but research in this area for leishmaniasis is unlikely to be effective. Pascale believed one easy step forward may be to boost arginine levels naturally - food supplementation was a distinct possibility with peanuts (and Spanish peanuts in particular) having an exceedingly high content. She did note though that this was not an endorsement for healthy people to start adopting faddy diets!
Pascale noted with pleasure the improvements and enthusiasm she has seen in hospitals and medical schools (such as Gondar) during her time in Ethiopia. Whilst there is still a massive gap in public knowledge concerning this deadly disease research indicates that the situation for leishmaniasis generally may be slowly, slowly changing.
We thank Pascale enormously for this presentation and for setting out complex scientific and medical facts so clearly.