LEISHMANIASIS / MedUrgent
LEISHMANIASIS
Leishmaniasis is
caused by leishmania species which are obligate intracellular flagellated
protozoa parasites. The disease is transmitted to man by the black female sand
fly phlebotomus which breeds in cool, shady places, on top of houses and in
hills. During a blood feed, the promastigotes are inoculated intradermal where
they transform into amastigotes and either proliferate locally to form a nodule
that ulcerate later (cutaneous Leishmaniasis) or disseminate into the midline
facial structures e.g. nose and mouth (espundia) or spread through macrophages
into the spleen, liver, lymphatics and bone marrow (visceral Leishmaniasis). In
humans the disease presents as granuloma with lymphocytes and macrophages
engulfing organisms. Amastigotes (Leishman Donovan Bodies - LD bodies) are the
only stage found in man. Clinically the disease is classified into three types:
1. Visceral
Leishmaniasis : Leishmania Donovan
2. Cutaneous Leishmaniasis : L.tropica.
A) Old world Leishmaniasis: Leishmania T. major and leishmania T. minor, l.aethiopica
B) New world Leishmaniasis : Leishmania Braziliansis and Leishmania Mexicans 3. Mucocutaneous Leishmaniasis (Espundia) - leishmania braziliansis It is caused by infection of the reticuloendothelial cells throughout the body by Leishmania donovani; a parasite that divides into three major biological forms. These species are morphologically similar and can only be differentiated clinically or by biochemical differences.
VISCERAL LEISHMANIASIS (kala-azar)
This is a chronic disease caused by one of the
sub-species of L.donovani that are widely distributed throughout the tropics
(L. Donovani found in India; L. Donovani infantum mainly in the Mediterranean
and Middle Eastern countries, Africa and China; L. Donovani Chagasi in South
America). The disease is usually transmitted by sand fly; however, blood
transfusion, sexual contact; nasal discharge and needle pricks are all
implicated.
Clinical manifestations
The incubation period varies from 9 to
10 months, but it could be short or as long as some years (an average of 3-6
months). Onset of the disease may be acute (high grade fever not associated
with rigors) or gradual (prolonged intermittent fever). The fever is
characteristically double peaked during the day. There is marked splenomegaly
due to hyperplasia of the reticuloendothelial cells that are filled with
parasites. Kupffer cells in the liver and the lymph nodes are similarly
affected and are filled with the amasigotes. In the nasopharyngeal mucosa,
granuloma and ulcerations may appear and extend down to the duodenum and
jejunum. Bone marrow, skin, heart muscles, kidneys, adrenals and parotids may
all be parasitized.
The patient does not look ill but
anemic, anxious and wasted. The appetite is good with protuberant abdomen and
dragging pain due to the presence of significant hepatosplenomegaly although
liver enlargement is of a lesser degree. Lymphadenopathy, hypopigmented hair,
black discoloration of the face (black sickness) and epistaxis secondary to
hypersplenism and associated thrombocytopenia. Jaundice is considered as a bad
prognostic sign. Anemia
Complications
include lobar
pneumonia or bronchopneumonia, secondary bacterial infection, dysentery
(bacterial or amoebic) which are considered serious complications, pulmonary
T.B., Cancrum oris, liver cirrhosis Uveitis DIC, glomerulonephritis and
amyloidosis affecting mainly the kidneys and nephrotic syndrome. Occular
complications including retinal hemorrhage and papiloedema. Some of these
complications could be the initial pretention symptoms especially chest
infections. Relapses may occur between 6 months to two years. Causes of death
are exhaustion, bacillary or amoebic dysentery pneumonia or coma.
If untreated, some
patients may undergo spontaneous cure while others may die due to intercurrent
infection. The mortality rate is high and death usually follows within 2 years
of onset.
Post-kala-azar Dermal Leishmaniasis
The skin lesions
appear within few months or longer following treatment of the African visceral
Leishmaniasis. The macules and papules affect the face, extremities and
sometimes involve the trunk. They start as hypopigmented macules, then change
into papules that look like lepromatous leprosy and parasites are usually found
in these lesions. Hepatosplenomegaly and marked ill health are not recognized
features of this condition. The diagnosis depends time of appearance of the
lesions and recovery of LD bodies from skin lesions. For Post-Kala-azar Dermal
Leishmaniasis it usually does not respond to treatment with diamidine and is
more refractory to antimonials.
Diagnosis
Visceral leishmaniasis
with splenomegaly should be differentiated from other conditions such as
typhoid, brucellosis, tuberculosis, chronic malaria, myelofibrosis, lymphomas
and viral diseases
Laboratory
Investigations
A number of specific
tests can be done, but confirmation is by isolation of the organism.
• CBC: anemia,
leucopenia with high eosinophil count, and thrombocytopenia
• Splenic aspirate
(not advisable in children <5 yrs old or those with thrombocytopenia) stained
for L.D bodies using Leishman or Gemsa stain
• Liver and lymph node
biopsy and bone marrow punctures for detection of L.D. bodies
• Monoclonal antibody
staining of tissue smears
• Serology: rk39 -
ICT, Formol Gel Aldehyde, Direct Agglutination Test, Polymerase Chain Reaction,
• Complement Fixation
Test, Indirect Fluorescent Antibody Titer and ELISA
• Fluorescent Antibody
Technique which is positive in early infection.
• Hamagglutination
test.
• Culture in NNN media
or inoculation of the tissue aspirate into hamsters
• Leishmanin Skin Test
(Montenegro test): It measures delayed hypersensitivity to the antigen prepared
from promastigotes. It is positive in cutaneous and mucocutaneous leishmaniasis
and negative in visceral leismaniasis and diffuse cutaneous leishmaniasis where
it indicates present or past infection and depressed cellular immunity.
TREATMENT
1- Admission to
hospital with absolute bed rest
2- Management of fever
and complications including anemia, pneumonia and other infections.
3- Chemotherapy and
drugs available are:
A) Antimony compounds:
Sodium stibogluconate (Pentostam) is a Sodium Antimony compound and is the drug of choice. It is prepared in an isotonic neutral solution having 40% of the active substance and each ml of solution has 100mg of the active drug. The drug should be initially administered in a dose of 100mg and then increased by 100mg on daily basis until the total full dose of 600mg/day is reached. 30 injections are recommended for the Sudanese type. As for Indian kala-azar 6 injections are enough. In children aged 3-4 years the total dose is 400mg and those less than 2 years are given 200mg. The drug is given in a dose of 10-20 mg/kg/day IV slowly for 30 days and may be repeated twice. Contra-indications include jaundice, liver cirrhosis and nephritis.
• Ethyl stibamine (Neostam) may be given starting with a small dose of 100mg IV. This is increased daily by 100mg to a maximuin of 300mg/day, which is then continued for 8 days.
B) Diamidines:
i) Pentamidine
isoethionate IV diluted in %5 dextrose in a dose of 2 4mg/ kg/day or every
other day IM for a total of 14 doses. The dose may be repeated after 10 days.
ii)
Hydroxystilbamidine Isoethionate IV in a dose of 250mg /day mixed in 5%
dextrose to be given slowly for a period of 10 days. The course is repeated in
three occasions with a 10 day gap between each course, (a total of 30
injections).
C) Others
• Meglumin antimonite:
20mg/kg/day IV for 20 - 28 days
• Amphotericin B: (used in antimony resistant cases of kala- azar) 0.5 -1 mg/kg/day IV diluted in 5% glucose infusion or normal saline given IV over 3 - 6 hours. The treatment is with a dose of 0.25mg / kg that may be gradually increased to 1mg/kg on alternate days until 1-2 am have been given. It is administered on alternate days for 3-8 weeks depending on the severity of the infection. It is extremely nephrotoxic
• Relapasers can be treated with Pentostam or Amphotercin B
• Splenectomy may be
done in resistant cases
Old World Cutaneous leishmaniasis (Baghdad boil. Delhi boil)
This form of the
disease is characterized by nodular and ulcerative skin lesions caused by L.
tropica major, L. tropica minor and Laethiopica. tropica inoculation in human
tissue induces cell-mediated immune response that include lymphocytes, plasma
cells and macrophages leading to granuloma formation and ulceration that heal
with fibrosis and scar formation. The lesions tend to be multiple, have scales
over an ulcerating center and end up with severe disfiguring scars especially
on the face and extremities. Local lymphadenopathy may occur. Urban or Dry type
is also caused by L tropica major. Its reservoirs are dogs and man and it is
transmitted by the sandfly. It is common in the Middle East where 80% of the
affected individuals live in the big cities. The lesions occur on the exposed
part of the body, and begin as a small itchy nodule, which grow very slowly.
Leishmaniasis recidivans presents with large ulcers on the face with active
peripheries and healing from the center leaving severe scarring. Leishmanin
Skin Test is positive. Diffuse Cutaneous Leishmaniasis is caused by L.tropica
aethiopica and start as a small single and non-ulcerating nodule on the face
and then multiple nodules appear covering all body. Lesions do not ulcerate but
coalesce to form plaques. Leishmanin Skin Test is negative. Diagnosis is based
mainly on the identification of the parasites in the smears taken from the edge
of the ulcers and not the center.
Treatment
• Sodium
stibogluconate
• Meglumin antimoniate
(systemic or local infiltration)
• Mepacrine (local
infiltration)
• Heat therapy (local
application) Petamidine (4mg/kg/week)
New World Cutaneous Leishmaniasis (Espundia)
This type of leishmaniasis is caused by the
species L. Mexicana and Lbraziliensis. It is transmitted by the sand fly
lutzomyia and characterized by ulcerative skin lesions and destructive
mucocutaneous lesions in the mouth, nose and pharynx called Espundia. Cutaneous
lesions start as a small papule at the site of inoculation, gradually enlarge
to become an indurated ulcer. It is painless and usually heals spontaneously
within 6 - 18 months. Mucosal lesions appear after the cutaneous lesions have
healed by months or years, or they may develop as metastatic spread from the
cutaneous lesion. There is often progressive mutilating destruction of the
nasal septum, palate, lips, pharynx and larynx. Diagnosis is by identification
of the parasite in aspirates of tissue juice from biopsy of the lesions and
scrapings from the nasal mucosa. It is usually resistant to pentavalent
antimonies although at times it could respond to treatment when given in
maximum dosage.
Treatment
• Meglumine
antimoniate: 14 mg/kg/day for 10 – 15 days to be repeated after 15 days if
there is no healing. Local infiltration may be added
• Amphotericin B:
starting with small dose (0.1mg/kg/2 days) up to a total of 2-3 gm
• Pentamidine
• Nifurtimox
• Paromomycin: topical and parenteral
• Cryotherapy
• Radiofrequency or heat pads
may be used locally.
PREVENTION AND CONTROL
• Health education to
explain to people the life-cycle of the parasite, mode of infection, means of
protection, avoiding regions where the sand fly is known to live and breed,
destroying the sand fly by spraying homes with insecticides and removing breeding
areas
• Supplying protection
in the form of screening, use of safety nets, repellants, and wearing clothes
that cover all the body.
• Vaccination which is derived from L. tropica and is only useful for cutaneous leishmaniasis.
Comments
Post a Comment