Leishmaniasis

By

Raghda El-Sayed Farag

Assistant prof. of Tropical Medicine

Leishmania(Haemo-somatic flagellates)

• These are flagellated protozoa transmitted by insect bite (sand flies)

• They infect blood and tissues of human and reservoir hosts.

• Three species infecting man, with the same morphology and L. cycle in insect, but differ in geographical distribution, vector, C/P and culture characteristics.

Leishmaniasis

- Leishmaniasis is a parasitic disease transmitted by the bite of sand flies. (Pholobotomus or Lutzomyia)

- Found in parts of at least 88 countries including the Middle East

- Different species of Leishmania cause different forms of disease

Clinical Types Of Leishmaniasis

1-Visceral leishmaniasis:A) Old world visceral leishmaniasis: L. donovani complex (L.

donovani, L. infantum)B) New world visceral leishmaniasis : L. chagasi L. amazonensis.

2-Cutaneous leishmaniasis:L. tropica complex (L. major, L. tropica)

3-Mucocutaneous leishmaniasis:L. braziliensis complex

Prevalence

• About 1.5 million new cases of cutaneous leishmaniasis occur in the world each year

• 500,000 new cases of visceral leishmaniasis estimated to occur each year

Endemic Areas for Leishmaniasis

BMJ 2003;326:378

• Some species tend to cause cutaneous leishmaniasis (e.g., L. major and L.tropica), whereas some species tend to cause visceral leishmaniasis (e.g., L. infantum and L donovani)

Morphology

• Promasitogte– Motile– Midgut– Insect

• Amastigote– Non-motile– Intracellular– Mammalian stage

Digenetic Life Cycle

• Morphology :

1-In RECs all over the human body & reservoir

hosts, it takes amastigote forms (intracellular in

macrophages).

2- In insect vector and culture, it takes the promastigote form.

Promastigote

LIFE CYCLE

Visceral Leishmaniasiskala-azar, black fever, Dumdum fever

• 1903• 1920• 1931

William Leishman

Pentavalent antimony

Experimental transmission

A) Old world visceral leishmaniasis:

L. donovani complex (L. donovani, L. infantum)

B) New world visceral leishmaniasis :

L. chagasi

L. amazonensis.

Life cycle:

• Habitat:

1. In R.E.Cs of viscera, mainly cells of spleen, Kupffer cells

of liver, bone marrow, intestinal mucosa of large

intestine& mesenteric L.N.

2. In endothelial cells of kidney , suprarenal capsules, lungs,

meninges and in CSF.

3. In macrophages of the intestinal wall, circulating blood,

heart and in nasal secretions.

Definitive host: Man.Reservoir hosts: Dogs, rodents and desert gerbils.

Insect vectors: are female sand flies; Phelobotomus or Lutzomyia.

• Infective stage: Promastigotes in buccal cavity and pharynx of sand fly.

• Mode of infection: 1. Bite of infected vector. 2.Blood transfusion or organ transplantation. 3.Direct in epidemics from man to man by nasal secretions. 4. Congenital. 5. Accidental in laboratory.

Geographical distibution:

• L. donovani: the disease is endemic in India, Pakistan,

Indonesia, Thailand, Central Africa and Sudan.

• L. infantum: Mediterranean areas (North Africa, Southern

Europe).

• L. chagasi: in the Central and South America.

Initial Infection• Similar in all species

start by Inoculation of promastigotes

↓

Inflammation & chemotaxis

↓

Receptor mediated phagocytosis by macrophage

Promastigote Amasitgote Transformation

Parasite SpreadMacrophage lysis & parasite release

Lymphatic spread

Blood spread

↓

Target organs

REC in Skin/lymph nodes/spleen/liver/kidneys

bone marrow

Pathogenesis & Symptomatology:• Incubation period: 1-3 ms, may be short as 2 wks.

• A primary lesion at the site of infection is rarely

observed, but minute papules have been described in

infants, and in Africa dermal lesions of the legs or

arms can occur (dermal leishmaniomas).

• The phagocytosed parasites are present in small

numbers in the blood, but are numerous in the R.E.Cs

of the affected organs with marked hyperplasia.

• The most important sign is fever (twice-daily rise),

mailase, headache, sweating, weakness, weight loss,

emaciation, non-productive cough, oedma,

abdominal discomfort, hepatosplenomegaly,

bleeding of mucous membrane of gums and nose.

• Diarrhea and dysentry are common (parasites in

lymphoid macrophages in the intestinal

submucosa).

• Anemia, thrombocytopenia and neutropenia due to

bone marrow infiltration.

- Types of anemia:1. Aplastic: extensive multiplication of the parasite in bone marrow.

2. Microcytic: lack of iron absorption from intestine.

3. Macrocytic: hepatic damage and fatty infiltration of liver causing deficient storage of

Vit.B12.

• Mucopurulent discharge containing leishmanial bodies.

• In human hosts, response to infection by L. donovani varies, by the type of the patient’s immune reaction

• Of particular concern, according to the World Health Organization (WHO), is the emerging problem of HIV/VL co-infection

• Pneumonia, tuberculosis, and dysentery are common in regions where leishmaniasis and, AIDS co infection present.

• These opportunistic infections are common cause of death

Post Kala Azar Dermal Leishmanoid

• Normally develops < 2 years after recovery

• Due to incomplete treatment Or as a Relapse

• Restricted to skin• Rare but varies geographically (high

incidance in India , Sudan)

• Manifests first as small hypo-pigmented macules, papules, nodules, or facial erythema, measle-like lesions on the face, which gradually increase in size and spread over the body.

• Eventually the lesions may coalesce to form disfiguring, swollen structures resembling leprosy, or disseminated cutaneous leishmaniasis.

• occasionally causing blindness if they spread to the eyes.

• Any type causing VL( Kala-azar) can lead to PKDL, so, it is commonly associated with L. donovani in India and Sudan.

Post Kala-Azar dermal leishmaniasis

• Dermal lesions may contain parasites in great numbers.

Diagnosis of Visceral Leishmaniasis

Clinical: in endemic areas, leishmaniasis may be suspected in a patient who has:

- Persistent, irregular or remittent fever (double daily peak).

- Hepato-splenomegaly. - Pain from perisplenism.

- Anaemia, leucopenia & emaciation.

Laboratory:

A- Direct:

-1. Demonstration of amastigote in a smear stained by Leishman. Material is

obtained from blood, bone marrow, L.N., splenic or liver biopsy, or nasal

secretions.

2.Culture on NNN media: showing promastigotes in the form of rosette grouping.

B-Indirect:

• Montenegro (leishmanin) test: 0.1-2.0 ml. of antigen

strains of human L.donovani or L. tropica is injected I.D. and the

result read after 72 hrs. A delayed reaction develops in cured

individuals.

-The test is -ve in early cases due to depression of cellular immunity

by the parasites, but becomes +ve 6-8 wks after completion of ttt.

• ELISA, or direct agglutination test

• High level of specific serum IgG is indicator of visceral leishmaniasis.

Diagnosis

- Living in or travelling to endemic area

- Clinical signs & symptoms

- Hypergammaglobulinemia

ELISA/Formol gel

- Bone marrow biopsy

- Spleen or liver biopsy

- Culture & Histology

Due to Similar morphology of all types we can need:

• Isoenzyme profiles - Zymodemes• Monoclonal antibodies• DNA detection by PCR

Treatment

Supportive: -Good nursing.

-Diet rich in vitamins, iron and liver support.

-Proper antibiotics for 2ry bacterial infection.

-Blood transfusion in case of sever anemia or bleeding.

Specific :

- Liposomal amphotericin-B (AmBisome® or Amphocil ) is the drug of choice 3 mg/kg per day on days 1-5, day 14 and day 21

- Antimony as Sodium stibogluconate (SSG) (Pentostam®) ) is an alternative therapy 20 mg/kg / day for 28 days repeated for 3 times

- Patients suffering from both HIV and visceral leishmaniasis (VL) may be treated with acyclovir or pentamidine in conjunction with first-line antileishmanial therapies such as miltefosine and amphotericin-B (AmBisome)

- Antimony as Sodium stibogluconate (SSG) alone or in combination with

rifampicin is used for the treatment of PKLD for a long course of up to 4 months

- Miltefosine , is a new drug for visceral and cutaneous leishmaniasis

Prevention:

- Control of sand flies by destruction of their breeding grounds

near human habitations and by the use of DDT

(dichlorodiphenyltrichloroethane).

- Avoid and destroy infective dogs ( reservior).

- Treatment of infected persons.

- Human beings can be protected by building houses with fine

mesh screening (40 meshes / inch2) and by use of repellents

Cutaneous Leishmaniasis

Cutaneous Leishmaniasis

A- Old world cutaneous leishmaniasis (Oriental Sore)

Causative parasite: Leishmania tropica, L. major and L.ethiopica.

Distribution: affects people in Middle and Far East,

Mediterranean region, Asia and Africa.

B- New world cutaneous and mucocutaneous

leishmaniasisCausative parasite: L. mexicana complex and L. braziliensis

complex.

Geographical distribution: Central and South America.

Reservoir host: forest rodents, cats and dogs.

Insect vector: Lutzomyia species.

• Infection remains restricted to the initial site of infection (the bite site)

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

Cutaneous Leishmaniasis

• I.P:• 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)

- Mucosal leishmaniasis might not be noticed until years after the original cutaneous sores healed.

- The best way to prevent mucosal leishmaniasis is to ensure adequate treatment of the cutaneous infection especially where L. tropica is prevalent .

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• Cutaneous infection where L. tropica is prevalent

Mucocutaneous Leishmaniasis

Mucocutaneous Leishmaniasis (Espundia)

• Occurs with Leishmania species from Central and South America: L. braziliensis

• Rarely associated with L. tropica in the Middle East- This type occurs if a cutaneous lesion on the face

near the mouth or nose is not treated• May occur months to years after original skin lesion• Hard to confirm diagnosis (few parasites in the lesion).• Lesions can be very disfiguring

Mucocutaneous Leishmaniasis

• The ulcers are painful, chronic, destructive and

resistant to treatment.

• Greater deformity , erosion of the nasal septum,

palate, larynx with loss of voice may occur.

• Death may develop from aspiration pneumonia, or

septicemia ( 2 ry bacterial infection).

Diagnosis:

I.Clinical: typical lesion, with elevated and indurated margin of the ulcer.

II.Laboratory:

1- Direct:• Examination of material aspirated or scraped

from the edge of the lesion and stained with Giemsa stain.

• Culture of the material on NNN media to see promastigotes.

• Animal inoculation.

2- Indirect:• Montenegro test (leishmanin reaction): is an

intradermal test using antigen from cultured promastigotes.

-It is positive within several months after appearance of the lesion and remains +ve for years.

-Generally 95% of cases show tests with induration and erythema of 4-5 mm or more in diameter, with delayed reaction after 3 days.

TreatmentCutaneous type

1. Local measures:• Surgical excision especially if single lesions.

• Scraping (curettage).

• Heating of lesion to 50°C with infra red rays.

• Freezing therapy, using carbon dioxide snow.

• Chemical methods, by using topical preparations as 2% atebrine

sulphate or 10% atebrine solution.

• I.D. injection of interferon gamma around lesions promotes

ulcer healing.

• Cleanliness to prevent secondary bacterial infection.

• Secondary infection needs local or systemic antibiotic

medication particularly in muco-cutaneous type.

2. specific:• Antimony (Pentostam) as topical ointment.

• Mucocutaneous type

• Antimony (Pentostam) is the drug of choice. Two or three courses may be needed.

-20 days of intravenous therapy in case of mucocutaneous type

- Fluconazole may decrease healing time in L. major infection

- If the sores are 1-3 in number, treatment may be facilitated by local infiltration of the drug into the edges of the ulcers.

• Amphotricin B: in severe resistant mucocutaneous type