LEISHMANIASISLEISHMANIASIS

MAJ Mark Polhemus Leishmania Treatment CenterWalter Reed Army Medical Center

INTRODUCTIONINTRODUCTION

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

INTRODUCTIONINTRODUCTION

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

ENDEMIC AREAS FOR ENDEMIC AREAS FOR LEISHMANIASISLEISHMANIASIS

BMJ 2003;326:378

LEISHMANIASIS IN THE MIDDLE LEISHMANIASIS IN THE MIDDLE EASTEAST

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

LIFE CYCLELIFE CYCLE

3- Another sandfly bites human and ingests blood infected with Leishmania

2- Sandfly bites human and injects Leishmania into skin

1- Sandfly bites animal and ingests blood infected with Leishmania

4- Cycle continues when sandfly bites another human or animal reservoir

CUTANEOUS CUTANEOUS LEISHMANIASISLEISHMANIASIS

CUTANEOUS LEISHMANIASISCUTANEOUS 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…)

CUTANEOUS LEISHMANIASISCUTANEOUS 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)

VISCERAL VISCERAL LEISHMANIASISLEISHMANIASIS

VISCERAL LEISHMANIASISVISCERAL 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

VISCERAL LEISHMANIASIS IN VISCERAL LEISHMANIASIS IN DESERT STORMDESERT 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

Magill et al, NEJM 1993:328(19)

VISCERAL LEISHMANIASISVISCERAL 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.

MUCOCUTANEOUS MUCOCUTANEOUS LEISHMANIASISLEISHMANIASIS

MUCOCUTANEOUS MUCOCUTANEOUS LEISHMANIASISLEISHMANIASIS

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

PREVENTIONPREVENTION 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

DIAGNOSISDIAGNOSIS

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

DIAGNOSIS: DIAGNOSIS: CUTANEOUS CUTANEOUS LEISHMANIASISLEISHMANIASIS

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

DIAGNOSIS:DIAGNOSIS:CUTANEOUS LEISHMANIASISCUTANEOUS LEISHMANIASIS

Patients with any of the following Patients with any of the following findings should be referred early to findings should be referred early to avoid long term complications:avoid long term complications:

Big lesions (greater than an inch in size)Many lesions (3 or more)Sores on the faceSores on the hands and feetSores over joints

DIAGNOSIS:DIAGNOSIS:VISCERAL VISCERAL LEISHMANIASISLEISHMANIASIS

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

DIAGNOSISDIAGNOSISMUCOCUTANEOUS LEISHMANIASISMUCOCUTANEOUS 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

DIAGNOSISDIAGNOSIS 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: 301-319-7155/9956

DSN 285-7155/9956

Return kit and specimen to:Commander, WRAIRAttn: Leishmania Diagnostics LaboratoryDivision of Experimental Therapeutics503 Robert Grant AvenueSilver Spring, MD 20910-7500

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.

TREATMENTTREATMENTCUTANEOUS AND MUCOCUTANEOUSCUTANEOUS 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

TREATMENTTREATMENTVISCERAL LEISHMANIASISVISCERAL 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

POINTS OF POINTS OF CONTACTCONTACT

POINTS OF CONTACTPOINTS OF CONTACT

Clinical questions or patient referralLTC Glenn Wortmann, COL Naomi Aronson, COL Charles

OsterLeishmania Treatment CenterInfectious Disease ServiceWalter Reed Army Medical CenterComm: 202-782-1663/8695/8691DSN: 662-1663/8695/8691

To request Diagnostic KitsCPT Eric Fleming, LTC Peter Weina, CAPT Philip CoyneWalter Reed Army Institute of ResearchComm: 301-319-9206/9956/7155DSN: 285-9206/9956/7155

Email for all is first.lastname@na.amedd.army.mil