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Is this leash-mania? Who was Camberley Kate?

4/7/2017

 
A 3 year old boy had been referred to the Paediatricians with a history of intermittent fevers, weight loss and abdominal distension. On examination the child had an enlarged liver and spleen. The working diagnosis was lymphoma and a lymph node biopsy and bone marrow aspirate were planned. The child was discussed at the paediatric oncology multidisciplinary team meeting and the Microbiologist pricked up his ears when he heard the child was originally born in Brazil and came to the UK a year ago.
​
A discussion then took place about whether this might actually not be cancer at all but rather an infection. In particular, the Microbiologist suggested a diagnosis of leishmaniasis… everyone gave him “that” look… here we go again they thought! Another weird diagnosis from Microbiology!!
Leishmaniasis
Is this leash-mania?
So what is leishmaniasis?
Leishmaniasis is a parasitic disease transmitted via the bite of infected female sandflies of the Phlebotomus (Old World = Europe, Asia and Africa) and Lutzomyia (New World = The Americas) genera. Sandflies are those pesky blood sucking bugs that are only 2-3mm in size and don’t make any noise. They usually bite outdoors between dusk and dawn. They are like the stealth version of the mosquito and wreck an evening BBQ on the sand!
 
Leishmaniasis can occur in travellers to endemic countries as well as people who live there. In terms of parasitic diseases only malaria causes more deaths per year than leishmaniasis.
 
What are the different Leishmania spp. and where do they occur?
There are lots of different Leishmania spp. but they occur in different parts of the world. In Europe about 2,700 cases of leishmaniasis occur annually in Portugal, Spain, France, Italy, Greece, Malta, Cyprus, Croatia, Albania, Bulgaria and Turkey, although Turkey is the most common country (80%). However, I particularly like the names of the New World species as their name gives a more specific clue to where they occur.
​Old World
​New World
L. aethiopica
L. donovani
L. infantum
L. major
L. tropic
L. amazonensis
L. braziliensis
L. guyanensis
L. mexicana
L. panamensis
L. peruviana
How does leishmaniasis present?
Whilst leishmaniasis may be asymptomatic it can present in a number of other ways:
  • Visceral leishmaniasis
  • Post kala-azar dermal leishmaniasis
  • Cutaneous leishmaniasis
  • Mucocutaneous leishmaniasis
 
Visceral leishmaniasis is the most severe form and occurs mainly in children under 4 years old. Worldwide it is estimated that 200-400 thousand people a year develop visceral leishmaniasis (90% in Bihar state, India) and 10-20% of these people die. The incubation period varies from 10 days to over 1 year. The main clinical features are fever and anorexia with progressive weight loss, abdominal distension (with hepatosplenomegaly) and weakness. Untreated visceral leishmaniasis usually leads to death within 2 to 3 years. Even after treatment some patients relapse within a year and need retreating.
 
Post kala-azar dermal leishmaniasis occurs in up to 60% of patients with Old World (Europe, Asia and Africa) visceral leishmaniasis due to L. donovani and can occur before, during or after treatment. An immunological reaction to the parasite leads to skin lesions (macules, papules, nodules and/or plaques) on the face, trunk and limbs which can be severe and disfiguring.
 
Cutaneous leishmaniasis appears as a nodule at the site of the bite of an infected sandfly. There are an estimated 700 thousand to 1.2 million cases of cutaneous leishmaniasis (75% in Brazil, Syria and Afghanistan). Old World infections usually become a dry ulcer which eventually heals (after months or years) leaving a small scar; whereas New World lesions usually become a wet ulcer with localised painful lymphadenopathy.
 
There are 35,000 cases of mucocutaneous leishmaniasis worldwide. Mucocutaneous leishmaniasis occurs when New World parasites spread, via the blood stream or lymphatics, from the skin to the oral and upper respiratory tract mucosa. This causes gradual destruction of the nasal cartilage and septum, which if untreated eventually leads to destruction of the nose, pharynx, palate, upper lip and larynx resulting in terrible disfiguration.
 
How is leishmaniasis diagnosed?
There are two main methods for diagnosing leishmaniasis however the sample type varies between the clinical presentations. For visceral leishmaniasis the best sample type is a bone marrow biopsy whereas for cutaneous, mucocutaneous and post kala-azar dermal leishmaniasis the preferred sample type is a slit skin biopsy.
 
Microscopy of the biopsy allows identification of the parasites with a sensitivity of around 60-85%. In the developed world this can be supplemented by PCR with sensitivity and specificity of 98-99%; in the UK this is available at the London Hospital for Tropical Diseases.
 
There is also serology and skin sensitivity tests for Leishmania spp. antibodies but these are rarely used for diagnosing leishmaniasis as they cannot tell the difference between active disease and past exposure.
 
How is leishmaniasis treated?
Visceral, mucocutaneous and post kala-azar dermal leishmaniasis are treated with Amphotericin B or its lipid formulations (yes… it is an antifungal that is used to treat this parasitic disease!). There is no standardised regime, dosing of lipid formulations at 3 mg per kg daily, by IV infusion, for a total of 6 to 10 days is a recognised treatment. The main drawbacks to the use of these drugs are that they are expensive and require intravenous administration, although attempts have been made to make them cheaper in resource poor countries. An alternative treatment is Miltefosine (an alkylphosphocholine analogue) which is available orally. However, Miltefosine causes gastrointestinal disturbance and therefore compliance can be an issue; resulting in increasing parasite resistance.
 
Cutaneous leishmaniasis occurring in the Old World (Europe, Asia and Africa) is usually self-limiting and does not typically require treatment unless it is extensive or there are lots of lesions. However, New World (The Americas) lesions are treated, as these rarely resolve spontaneously.  Various topical treatments are available as well as oral and intravenous if necessary.
 
Pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate were the treatments of visceral leishmaniasis from the 1940s but these are pretty unpleasant and toxic compounds (causing pancreatitis, bone marrow suppression, cardiac dysfunction and hepatitis) and are no longer used routinely.
 
Can leishmaniasis be prevented?
Travellers and people living in endemic areas should try to avoid being bitten by sandflies which might be infected with Leishmania spp. This involves covering up skin with long trousers and a long sleeved top as well as avoiding being outdoors as much as possible between dusk and dawn when sandflies are active and feeding. People should also sleep under repellent impregnated mosquito nets to prevent the flies from biting the person while they are asleep.
 
A possible strategy to control leishmaniasis is to vaccinate dogs, who are the main host. Vaccinating dogs disrupts the transmission from dogs via sandflies to humans thereby preventing human disease. In 2011 a dog vaccine against L. infantum became available in Europe however I am doubtful about whether this strategy will have much of an effect on the incidence of leishmaniasis. One of the main problems is feral dogs being exposed rather than pet dogs and a trap and vaccinate policy will be expensive and unlikely to achieve adequate coverage.
 
Why is there no vaccination for humans? This is almost certainly due to the fact that leishmaniasis is seen as a disease of poverty in poor countries and there is no impetus to produce a human vaccine even though it is likely to be very effective and provide lifelong immunity, as having had and being treated for leishmaniasis provides lifelong protection from reinfection.
 
So what happened to our young boy? He underwent bone marrow biopsy and the haematologists saw parasites. The sample was sent to the London Hospital for Tropical Diseases and leishmaniasis was confirmed. Following 10 days of IV treatment with liposomal Amphotericin B he made a full recovery and remained well at follow up a year later. Everyone was relieved that he didn’t have cancer. The Paediatrician called the Microbiologist after follow up clinic to inform him of the outcome and the Microbiologist went home feeling rather smug.

​And who was Camberley Kate? She certainly had leash-mania!
Jamie
8/7/2017 03:47:24 am

Hey David, I really enjoy your medical based blogs, thanks for sharing!

David
9/7/2017 12:02:57 pm

Hi Jamie
Really please you enjoy the blogs, knowing people like you read them and value them makes it worthwhile.
Let me know if there are particular topic you think I should cover and I'll do my best to write about it.
David


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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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