1. Leishmania Treatment Center Walter Reed Army Medical Center
Leishmaniasis
MAJ Mark Polhemus
Leishmania Treatment Center
Walter Reed Army Medical Center

2. Introduction
Leishmaniasis is a parasitic disease transmitted by the bite of sand flies.
Found in parts of at least 88 countries including the Middle East
Three main forms of leishmaniasis
Cutaneous: involving the skin at the site of a sandfly bite
Visceral: involving liver, spleen, and bone marrow
Mucocutaneous: involving mucous membranes of the mouth and nose after spread from a nearby cutaneous lesion (very rare)
Different species of Leishmania cause different forms of disease

3. Introduction
In the Middle East L. major and L. tropica are the most common species
L. major causes skin infection
L. tropica causes skin and visceral infection and rarely causes mucocutaneous infection
About 1.5 million new cases of cutaneous leishmaniasis in the world each year
500,000 new cases of visceral leishmaniasis estimated to occur each year also
20 cases of cutaneous leishmaniasis from L. major/ L tropica and twelve cases of visceral infection caused by L. tropica were reported in soldiers from Desert Storm

4. Endemic Areas for Leishmaniasis
Highlighted areas are parts of the world where leishmaniasis has been reported.
Taken from British Medical Journal :378
BMJ 2003;326:378

5. Leishmaniasis in the Middle East
90% of cutaneous leishmaniasis occurs in Afghanistan, Iran, Saudi Arabia, Syria, Brazil and Peru
8,779 cases were reported in Iraq in 1992
Sore is commonly called the Baghdad boil
At least 20 cases of cutaneous leishmaniasis were reported in Americans from Desert Storm
90% of all visceral leishmaniasis occurs in Bangladesh, Brazil, India, and the Sudan
2893 cases were reported in Iraq in 2001
12 visceral leish cases were reported in Americans in Desert Storm
90% of mucocutaneous leishmaniasis occurs in Bolivia, Brazil and Peru
Rarely associated with L tropica which is found in Middle East
Data on leishmaniasis is based on voluntary reporting by countries so true incidence may be higher in countries that are not likely to report.
Numbers of cases in Iraq come from recent Promed messages (authors Desjeux and Deresinki)

6. Life Cycle
1- Sandfly bites animal and ingests blood infected with Leishmania
2- Sandfly bites human and injects Leishmania into skin
Reservoir: Small animals – including dogs, rats, gerbils, sloths.
Vector: Sandflies which become infected by ingesting blood from these small animals. The sandfly is very small and does not make noise when it flies. They are most active at night (from dusk to dawn) and less active during the hottest part of the day. About 1/3 the size of a mosquito, they can fly through the mesh of mosquito nets unless the bed nets are treated with Permethrin. Their mouthparts are too small, however, to bite through clothing.
Lifecycle:
Leishmaniasis is spread to humans by the bite of some types of sand flies. Sand flies become infected by biting an infected animal (for example, a rodent or dog) or person. When the sandfly bites an infected animal it ingests blood (specifically white blood cells) infected with Leishmania. The Leishmania changes form inside the gut of the sandfly – from amastigote to promastigote.
At night, the sandflies slip through untreated bed nets or land on skin without repellent and bite. Leishmania from the gut of the sandfly are are injected into the skin of the human. In the human the Leishmania again change form – back to amastigote.
If another sandfly bites the infected human, the sandfly ingests blood infected with Leishmania, becomes infected, and flys off to infect another human or animal. The life cycle continues.
Leishmaniasis also can be spread by blood transfusions or contaminated needles.
4- Cycle continues when sandfly bites another human or animal reservoir
3- Another sandfly bites human and ingests blood infected with Leishmania

7. Cutaneous Leishmaniasis

8. Photograph provided by COL Naomi Aronson

9. Photograph provided by COL Naomi Aronson

10. Cutaneous Leishmaniasis
Most common form
Characterized by one or more sores, papules or nodules on the skin
Sores can change in size and appearance over time
Often described as looking somewhat like a volcano with a raised edge and central crater
Sores are usually painless but can become painful if secondarily infected
Swollen lymph nodes may be present near the sores (under the arm if the sores are on the arm or hand…)
Some sores are covered by a scab or have not yet ulcerated so they may look like red raised plaques- sometimes with dry crust/scale

11. Cutaneous Leishmaniasis
Most sores develop within a few weeks of the sandfly bite, however they can appear up to months later
Skin sores of cutaneous leishmaniasis can heal on their own, but this can take months or even years
Sores can leave significant scars and be disfiguring if they occur on the face
If infection is from L. tropica it can spread to contiguous mucous membranes (upper lip to nose)

12. Small, raised lesion on trunk without significant oozing or scab.
Photograph provided by COL Naomi Aronson

13. Multiple lesions on arm with a variety of appearances.
Photograph provided by COL Naomi Aronson

14. Both lesions are leishmaniasis
Note the raised border and wet appearance of the sore on the back of the hand.
Sores over joints are very concerning as scarring with healing can lead to limited movement of joint.
Photograph provided by COL Charles Oster

15. Back of hand.
Note raised border and wet appearance. Patient has bacitracin ointment applied to lesion.
Photograph provided by COL Naomi Aronson

16. Upper Eyelid.
Note the dry, crusted/scabbed appearance which is different than previous sores shown.
Photograph provided by COL Naomi Aronson

17. Close up of another dry, crusted lesion with concentric surrounding scale. This is a typical appearance for Old World Leishmaniasis.
Photograph provided by COL Charles Oster

18. Three lesions on face.
Raised and dry but not scabbed. Another different presentation. This was Leishmania tropica.
Photograph provided by COL Charles Oster

19. Visceral Leishmaniasis

20. Two children with visceral leishmaniasis
Two children with visceral leishmaniasis. The size of the spleen is marked on the abdomen. Normally the spleen does not protrude below the bottom rib.
Photograph provided by COL Charles Oster

21. Visceral Leishmaniasis
Most severe form of the disease, may be fatal if left untreated
Usually associated with fever, weight loss, and an enlarged spleen and liver
Anemia (low RBC), leukopenia (low WBC), and thrombocytopenia (low platelets) are common
Lymphadenopathy may be present
Visceral disease from the Middle East is usually milder with less specific findings than visceral leishmaniasis from other areas of the world
Based on our experience with Desert Storm, well nourished American soldiers generally have a less symptomatic, relatively oligoparasitic infection that was not life threatening but posed some diagnostic challenges

22. Visceral Leishmaniasis in Desert Storm
The following symptoms were found in eight visceral leishmaniasis patients returning from Desert Storm
Fevers: 6 of 8
Weight loss: 2 of 8
Nausea, vomiting, low-grade watery diarrhea: 2 of 8
Lymphadenopathy: 2 of 8
Hepatosplenomegly: 2 of 8
Anemia: 3 of 8
Leukopenia or thrombocytopenia: 0 of 8
Elevated liver enzymes: 6 of 8
No symptoms: 1 of 8
Summary of the presenting symptoms of eight soldiers with visceral leishmaniasis from Desert Storm. The summary is from an New England Journal of Medicine article by COL Alan Magill and others from the Walter Reed Army Medical Center Infectious Disease Service.
Magill et al, NEJM 1993:328(19)

23. Visceral Leishmaniasis
Symptoms usually occur months after sandfly bite
- Soldiers from Desert Storm presented up to five months after leaving the Persian Gulf
Because symptoms are non-specific and often start after redeployment there is usually a delay in diagnosis
Visceral leishmaniasis should be considered in any chronic FEVER patient returning from an endemic area.
From the Desert Storm experience, would also consider visceral leishmaniasis in patients with low grade elevated temperature, chronically elevated liver function tests and mild anemia

24. Mucocutaneous Leishmaniasis

25. Mucocutaneous Leishmaniasis
Occurs with Leishmania species from Central and South America
Very rarely associated with L. tropica which is found in the Middle East
- This type occurs if a cutaneous lesion on the face spreads to involve the nose or mouth
- This rare mucosal involvement may occur if a skin
lesion near the mouth or nose is not treated
May occur months to years after original skin lesion
Hard to confirm diagnosis as few parasites are in the lesion
Lesions can be very disfiguring
Much of the destruction is from a hyperimmune reaction to the Leishmania infection. There are not many parasites in the affected tissue so confirming the diagnosis can be difficult. This form of leishmaniasis would be unusual in soldiers infected in South West Asia.

26. Photograph provided courtesy of COL Donald Skillman

27. Prevention
Suppress the reservoir: dogs, rats, gerbils, other small mammals and rodents
Suppress the vector: Sandfly
Critical to preventing disease in stationary troop populations
Prevent sandfly bites: Personal Protective Measures
Most important at night
Sleeves down
Insect repellent w/ DEET
Permethrin treated uniforms
Permethrin treated bed nets
Sandflies bite dusk to dawn so personal protection is most important during these times.
Even light clothing covering skin is sufficient to prevent the bite of the sandfly.
DEET is the most effective insect repellent.
Sandflies are small enough to fly through bed netting unless it is treated with permethrin.

28. Diagnosis
Heightened awareness of individuals, small unit leaders, and medical personnel is critical
Sores that will not heal have to be referred for evaluation – even if not “typical” for leishmaniasis
Individuals with fevers, weight loss, gastrointestinal complaints, anemia, abnormal liver tests should be referred for evaluation
When soldiers present to medical personnel they should volunteer that they were in South West Asia

29. Diagnosis: Cutaneous Leishmaniasis
Biopsy is required for diagnosis
Biopsy can be done locally if trained medical personnel are available AND Leishmania diagnostic capability present
If trained personnel and diagnostic capability are not available, patient should be referred to Walter Reed Army Medical Center
Biopsy specimens should be sent to Walter Reed (WRAIR) for diagnosis -Leishmania Diagnostics Laboratory
- Special laboratories will do microscopy, culture and PCR
- Mail out kits/instructions available
Preliminary results should be ready in less than two weeks
On occasion, a deep scraping of a skin lesion can be sufficient when the tissue scraping is subjected to giemsa stain, Leishmania culture and/or PCR.

30. Diagnosis: Cutaneous Leishmaniasis
Patients with any of the following findings should be referred early to avoid long term complications:
Big lesions (greater than an inch in size)
Many lesions (3 or more)
Sores on the face
Sores on the hands and feet
Sores over joints

31. Diagnosis:Visceral Leishmaniasis
Must be considered if diagnosis is to be made
Presentation is usually very non-specific and should be considered in febrile patients in / returned from SWA
Antibodies to Leishmania may be present in patient’s serum but this will not confirm or exclude the diagnosis
Diagnosis requires finding Leishmania on biopsy of bone marrow, liver, enlarged lymph node, or spleen
Patients should be referred to a Medical Center, for referral on to Walter Reed Army Medical Center for definitive diagnosis and management if other etiologies excluded
Methods available in the US for antibody detection in the serum
- IFA test
- rk39 dipstick (Kalazar DetectTM)

32. Diagnosis Mucocutaneous Leishmaniasis
Early diagnosis and treatment is critical to avoid disfigurement
Patients should be referred to Walter Reed Army Medical Center
Biopsies should be done but require special training to avoid further disfigurement
Biopsies will be evaluated by the same methods and special laboratories as for cutaneous lesion
Because few parasites are present, PCR may be particularly useful

33. Diagnosis
Mail-out diagnostic kits with instructions are available upon request from the Walter Reed Army Institute of Research
Limited to CONUS facilities and Landstuhl
POC: Dr Coyne/ Dr Weina Phone: / DSN /9956
Return kit and specimen to:
Commander, WRAIR
Attn: Leishmania Diagnostics Laboratory
Division of Experimental Therapeutics
503 Robert Grant Avenue
Silver Spring, MD
If kit is not available, place biopsy samples in formalin and send for histopathology review. This may be a less sensitive diagnostic method than above.
For expert second level review, slides of potential leishmaniasis cases can be forwarded to Armed Forces Institute of Pathology, AFIP, Geographic Pathology Division, Washington DC
Patient may be referred to Walter Reed Army Medical Center for assistance with diagnosis.

34. Treatment Cutaneous and Mucocutaneous
Antimony (Pentostam®, Sodium stibogluconate) is the drug of choice
Given under an experimental protocol at Walter Reed Army Medical Center (WRAMC)
20 days of intravenous therapy
Available at WRAMC for all branches of the military
Requires patient to come to WRAMC
Fluconazole may decrease healing time in L. major infection
Biopsy and culture to determine species is required
Six weeks of therapy is needed
Since L tropica is of more concern in the SWA theatre (because of potential visceralizing infection, rare mucocutaneous involvement, and chronic (recidivans) skin infection) , would not advocate use of azoles routinely as there is not data to support their use in L.tropica and speciation can not be reliably made using clinical appearance.
Mucocutaneous infection is treated with a longer treatment course (28 days)

35. Treatment Visceral Leishmaniasis
Liposomal amphotericin-B (AmBisome®) is the drug of choice
3 mg/kg per day on days 1-5, day 14 and day 21
Pentostam® is an alternative therapy
28 days of therapy is required
Although AmBisome® is widely available, the difficulty of accurate diagnosis and the potential severity of visceral infection suggest possible patients be referred to the Leishmania Treatment Center at WRAMC for maximal diagnostic efficiency
It is not known what species of visceral leishmaniasis is present in Iraq – WHO reports that children have L. infantum. During Desert Storm some of American soldiers were found to have visceral infection with L. tropica. Published studies of liposomal amphotericin for visceral leishmaniasis have not included patients with L. tropica so it is not known for sure that it would be effective but it is expected likely.

36. Points of Contact

37. Points of Contact Clinical questions or patient referral
LTC Glenn Wortmann, COL Naomi Aronson, COL Charles Oster
Leishmania Treatment Center
Infectious Disease Service
Walter Reed Army Medical Center
Comm: /8695/8691
DSN: /8695/8691
To request Diagnostic Kits
CPT Eric Fleming, LTC Peter Weina, CAPT Philip Coyne
Walter Reed Army Institute of Research
Comm: /9956/7155
DSN: /9956/7155
for all is