20 Leishmaniasis

Jo… 18/09/18

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1 billion people globally infected with parasitic diseases (roughly the same billion people who live on less than 1 dollar / day)

Is a flagellate protozoa - single celled, with a nucleus, kinetoplast, flagellum

Vector = Sand Fly

20.1 Lifecycle

Starts from bite of a female sandfly.

Injects a promastigote.

This infects macrophages.

Transforms to an amastigote within macrophage.

Taken up by sandfly for blood meal

Inside sandfly gut they transform back into promastigote.

20.2 Vector

Sandfly

30 known species

Different in “new world” and “old world”

20.3 Leishmania

There are at least 17 species that cause disease within humans (21 species overall)

What you want to know:

Is this visceral or cutaneous?

If it’s cutaneous: old world or new world?

If new world: viannia or non-viannia?

20.3.1 Cutaneous

All other species of leishmania (not donovani and infantum) cause cutaneous.

All the Viannia subgenus carry a risk of mucocutaneous disease (only known in new world), so needs a different treatment

20.3.1.1 Epidemiology

Main one’s in the old world are leishmania tropica and major

tropica - spread from person to person by sand fly

major - zoonotic, spread by sandflies from rodents

Lot’s of british soldiers got cutaneous leishmaniasis in iraq and afghanistan. Now loads of syrian citizens are getting it.

Main ones in new world are called after the country they’re from

They’re spread in a sylvatic cycle. Spread by sand flys from wild animals (sloths, dogs)

20.3.1.2 Clinical Features

Lesions after bitten by sand fly

Incubation after weeks-months

Lesions occur at the site of bite (so exposed parts)

Nodular lesion initially, then it breaks down in the middle to form an ulcer.

Nearly all the time these lesions will heal spontaneuoslly. They are large and disfiguring but they usually go away.

Thee genus cause characteristic lesions (look at the slides!)

Usually the infection is at the margin of the ulcers, not in the middle.

20.3.1.2.1 Unusual lesions

Lymphatic spread

Diffuse CL

Recidivans - after the lesion heals, you get a plaque that forms, that looks a lot like cuteanous tb

20.3.1.3 Mucocutaneous Leishmaniasis

Horrendous destructive lesions at nasal and oropharynx. This is not at the site of the original bite.

Half occur within two years of initial lesion

90% within ten years

Only occurs within viannia group

This is why we need to know if viannia or not

Occurs in roughly 15% of braziliensis type

20.3.1.4 Diagnosis

Find the amastogote

You base it on the local epidemiology

Scrape the lesion, or skin smear

The best way is a punch biopsy. At the raised red margin of the lesion. YOu’re looking inside the macrophage for amastogote

You can also do PCR. You might want to do this for american imported case, is it viannia or not?

20.3.1.5 Treatment

Local versus Systemic

20.3.1.5.1 Local Treatment

Only if no risk of mucocutaneous disease. All old world disease.

If been to americas either PCR or just assume they’re viannia and treat.

Intralesional pentavalent antimony (sodium stibogluconate) You’re injecting the dermis multiple points with this. You’ll need the lesion injected weekly until v clear resolution (any where between one week and two months)

20.3.1.5.2 Systemic Treatment

-If mucosal lesion, or lymph node mets. -If new world disease -If unresponsive to local rx

Now you’re giving same drug, sodium stibogluconate. But IV for three weeks (20 days)

This is a toxic drug though. Can cause pancreatitis, bone marrow suppression, conduction abnormalities. You need monitoring of amylase, lfts, fbc, regular ecgs.

20.3.1.5.3 Other
  • Cryotherapy
  • Curettage (not good evidence for this)
  • Thermotherapy - kill off amastogotes

Plenty of others but no good evidence for them.

Miltefosine, may be alright, its used for visceral (but no great evidence for it yet)

20.3.1.6 Prevention and Control

Difficult as multiple ways that things are being spread.

Depends on the local vector or resevoir.

Can try and control vector with mosquito nets (need to be insecticide treated)

Can put mosquito repellent impregnated collars on dogs.

What about a vaccine? It should be possible. In afghanistan, traditional practice is to attempt inocculation against babies, and it seems to work!

20.3.1.7 Summary

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20.3.2 Visceral

Species causing disease:

Africa and Asia - donovani

infantum (chagasi, really the same thing as infantum) - mediterranean and south america

20.3.2.1 Epidemiology

Two main types:

donovani - india, bangladesh, nepal, east africa

infantum - medittaranean basin, americas

Infantum is a zoonotic infection, dogs, to sandflies, to people

donovani is a person to person infection (so it occurs as an outbreak: in civil war, disaster, etc. You can have very large outbreaks)

20.3.2.2 Clinical Features

Infected macrophages spread to liver, spleen, lymphatics and bone marrow

Incuabate 2-4 months, up ot 2 years

Not all infected patients progress to disease

1:30 - 1:100 infantum infections cases progress to full disease. Same with donovani.

Once you’ve got the disease though IT IS ALMOST UNIVERSALLY FATAL! (?if left untreated)

  • fEVER
  • splenomegaly (massive)
  • pancytopenia
  • lymphadenopathy
  • profound weakness
  • wasting syndrome

Superimposed bacterial infection and TB are very common

20.3.2.2.1 Post Kala Azar Dermal Leishmaniasis

Kala Azar - the black fever

A secondary cutaneous manifestation of disease. Hypopigmented macules/papules/rash

Occurs up to 20 years after cure. These nodules are packed with amastogotes!

There are higher rates in some part of the world than others. Up to 30% of cases in south sudan get this!

20.3.2.3 Diagnosis

Microscopy: of splenic or bone marrow aspirate

Difficult to do this in resource poor setting! Green needle and ten ml syringe into splenic tip! Apparently risk of bleeding is about 1:1000.

But you can also do blood tests with serology, and dipstick tests,

and PCR in high resource setting

20.3.2.4 Treatment

Not easy, not widely available, not cheap!

First Line:

  • Sodium stibogluconate - up to a 28 day IV high dose course of this quite toxic drug. There is a major problem with resistance, almost useless on indian subcontinent, and 1/4 of patients in east africa also have resistance
  • Amphotericin B - 15 day course, 4hrly infusion. causes average drop in hb of ~3 grams over fortnight. causes aki, can be cardiotoxic, raised potassium
  • Ambisome - safer but way more expensive. $5000 for treatment course

  • Paromomycin - used in combination

  • AmBisome 10mg/kg single dose (very high dose). That trial in india got a 96% cure rate. This is cheaper at $160 per treatment course. The data from africa is less reassuring

  • Miltefosine oral drug (only oral drug) - initially developed as chemotherapy, but dropped as too toxic for chemo. But one month has a 93.4% cure rate

20.3.2.5 Prevention and Control

If dogs are resevoir (infantum) - culling of dogs, insecticide treated collars of dogs, vaccines of dogs

If it’s human to human (donovani) - treat cases, vector control

20.3.2.6 Summary

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20.3.2.7 HIV and Visceral Leishmaniasis

Both diseases potentiate the effect of other disease.

20.3.2.7.1 Epidemiology

There are 6 main countries with visceral leishmaniasis, all of these countries have HIV infected populations.

6% coinfection in india and brazil (VL patients having HIV) 50% of VL patients in ethopia now also have HIV

Clinical presentation is usually similar, sometimes weirder.

But the mortality rate with treatment is much higher, as is the relapse rate (extremely high)

The relapse rate is the really high thing. VL can become practically untreatable.

20.3.2.7.2 Diagnostics

Higher pathogen burden, so easier to see parasites.

But immune based tests (like DAT and rK39) are much less sensitive. If you use the two together you can push the sensitivity up again.

20.3.2.7.3 Treatment

Miltefosine + L-AmB (lower failure and mortality rate)