Leishmaniasis is caused by protozoa of the genus Leishmania transmitted by sandfly bites. It presents as visceral, cutaneous, or mucosal disease. Visceral leishmaniasis (VL), also known as kala-azar, affects the spleen, liver, bone marrow and lymph nodes and is fatal without treatment. It is most common in India, Nepal, Brazil and East Africa. The parasite is transmitted when an infected sandfly bites and transmits amastigotes, which multiply within macrophages. Pentamidine antimonials are first-line treatment but resistance is growing. Amphotericin B and miltefosine are also used. Control relies on vector control and

1. LEISHMANIASIS

2. Introduction
• Caused by unicellular flagellate intracellular
protozoa belonging to the genus Leishmania
• Several diverse clinical syndromes
– visceral leishmaniasis (VL, kala-azar)
– cutaneous leishmaniasis (CL)
– mucosal leishmaniasis (ML).
• Zoonotic transmission
• Reservoirs -Chiefly canine and rodent, Human- in
India and Sudan
• Vector-phlebotomine sandfly

3. Distribution of Visceral leishmaniasis

4. VISCERAL LEISHMANIASIS (KALA-AZAR)
• Leishmania donovani complex
• Vector Phlebotomine sandfly
• Common in India , Bangaladesh , Nepal ,Brazil,
Sudan and humid climate of Mediterranean
sea
• Disease can present unexpectedly in
immunosuppressed patients-after renal
transplantation and in AIDS

5. Transmission

6. Transmission
Feeding Female phlebotomine sandfly bite - saliva ( Flagellate promastigote)
Promastigote taken by macrophage and lost their flagella(Amastigote)
Invade immunity and lysis of macrophage and infection of other cell
Bite of sand fly –amstigote transforms into promastigote in the gut of vector ready to
infect new host

7. Life cycle

8. Pathogenesis
• The great majority of people infected with
flagellar promastigotes remain asymptomatic
and control the infection
• Those unable to do so develop clinical disease
• In visceral diseases the spleen, liver, bone
marrow and lymph nodes are primarily
involved

9. Clinical features
• On the Indian subcontinent both adults and
children are equally affected
• On other continents it is predominantly a
disease of small children and infants, except in
HIV co-infection (adult disease)
• Malnutrition increases susceptibility to the
visceral disease
• The incubation period ranges from weeks to
months (occasionally several years)

10. Clinical features
• The first sign -fever -rigor and chills
• Fever intensity decreases over time and patients
may become afebrile for intervening periods
ranging from weeks to months
• Splenomegaly
• Hepatomegaly occurs later, to a lesser degree
than splenomegaly.
• Lymphadenopathy in Africa, the Mediterranean
and South America but is rare on the Indian
subcontinent

11. Clinical features
• Blackish discoloration of the skin -in advanced
illness
• Moderate to severe anemia, Thrombocytopenia
to Pancytopenia common feature.
• Congestive cardiac failure
• Hepatic dysfunction
• Bleeding from retina, gastrointestinal tract and
nose.
• In progressive disease, hypoalbuminaemia may
manifest as pedal oedema, ascites and anasarca

12. Clinical features
• In Advances disease, there is profound
immunosuppression
• Secondary infections are very common.
– Tuberculosis, pneumonia, severe amoebic or bacillary
dysentery, gastroenteritis, herpes zoster and
chickenpox infections, boils, cellulitis and scabies are
common occurrences.
• Without adequate treatment most patients with
clinical VL are likely to die
• Death mostly due to sepsis

13. Investigations
• CBC--Pancytopenia is the most dominant feature,
with granulocytopenia and monocytosis.
• Polyclonal hypergammaglobulinaemia, chiefly IgG
followed by IgM, and hypoalbuminaemia
• Serology-
– Immunofluorescence antibody test-- specific
– Direct agglutination test
– Rapid immunochromatographic k39 strip test
– Formal gel (aldehyde) or other similar tests based on
the detection of raised globulin

14. Investigations
• PCR
• Culture –NNN media
• ELISA
• Buffy coat-demonstration of parasite in
immunosupressed
• Bone marrow-LD bodies
• Splenic aspirate-98% sensitive

15. Splenic smear showing amastigote

16. Diagnosis
• Patient from Endemic area
• History of fever
• Features of pancytopenia
• Moderate to huge splenomegaly
• K39 positive or demonstration of LD bodies in
Bone marrow or splenic aspirate

17. Differential diagnosis
• Malaria
• CML
• Myelofibrosis
• Disseminated TB
• Typhoid
• Many other neoplastic and infectious
conditions

18. Treatment
• Pentavalent antimonials- Stibogluconate
• Pentamidine isetionate
• Antifungal –Amphotericine B
• An aminoglycoside-Paromomycin
• Alkyl phospholipid-Miltefosin, oral
preparation

19. Pentavalent antimonials
• First drug / Remain the main stay of treatment
• Upcoming resistant in Indian subcontinent
• Sodium stibogluconate (100 mg/ml)
• Meglumine antimoniate (85 mg/ml)
• Daily dose is 20 mg/kg body weight, IV/IM for 28-30 days
• Side-effects -common
– Arthralgias, myalgias, raised hepatic transaminases, pancreatitis
– Severe cardiotoxicity--prolongation of QTc > 0.5 msec,
ventricular ectopics, runs of ventricular tachycardia
– Torsades de pointes, ventricular fibrillation and sudden death

20. Amphotericine B
• Conventional Amphotericin B /liposomal
• Amphotericin B deoxycholate given once daily or on
alternate days at a dose of 0.75-1.00 mg/kg for 15-20
doses, is used in patients with Sb failure or as a first-line
drug in regions with a significant level of Sb
unresponsiveness
• Liposomal-10-15 mg/kg is adequate,100% cure rate
• Side-effects-
– Infusion-related- high fever with rigor, thrombophlebitis,
diarrhoea and vomiting,
– Renal or Hepatic toxicity, hypokalaemia, thrombocytopenia,
myocarditis and occasional sudden death

21. Miltefosine
• Approved in India, Germany and Colombia for the
treatment of VL
• A daily dose of 50 mg (patient's body weight < 25 kg)
to 100 mg (≥ 25 kg), or 2.5 mg/kg body weight for
children, for 28 days
• Cures over 90% of patients
• Side-effects include
– Mild to moderate vomiting and diarrhoea,
– Skin allergy or Nephrotoxicity.
– Teratogenicity --C/I in pregnancy
– Female patients are advised not to become pregnant for
the duration of treatment and another 2 months

22. Paromomycin /An aminoglycoside
• Recent drug
• Undergone trials in India and Africa
• Approved by FDA
• Highly effective
• IM at 15 mg/kg body weight daily for 3 weeks
• No significant auditory or renal toxicity is seen

23. Pentamidine isetionate
• This was used to treat Sb-refractory patients
with VL
• Abandoned-
• Declining efficacy
• Serious side effects
• Side-effects
– Type 1 diabetes mellitus,
– Hypoglycaemia
– Hypotension

24. Response to treatment
• A good response results in abatement of fever
• Feeling of well-being,
• Gradual decrease in splenic size,
• Weight gain and recovery of blood counts.
• Follow for at least 6 months to detect relapse
• Relapse is indicated by enlargement of the spleen,
return of fever, weight loss and decline in blood
counts.
• Depending upon the geographical location, patients
can be retreated either with Sb or conventional or lipid
amphotericin B.

25. HIV-visceral leishmaniasis co-infection
• HIV-induced immunosuppression increases
the risk of contracting VL 100-1000 times.
• Most cases of HIV-VL co-infection have been
reported from Spain, France, Italy and
Portugal, although the numbers are increasing
in Africa (mainly Ethiopia) and Brazil and on
the Indian subcontinent

26. HIV VL-coinfection

27. HIV-VL Presentation
• Atypical clinical presentations of VL in patients co-infected
with HIV pose a diagnostic challenge.
• Clinical triad of fever, splenomegaly and hepatomegaly
<50% the patients with a CD4 count under 50 cells/mm3
.
• VL may present with gastrointestinal involvement
(stomach, duodenum or colon), ascites, pleural or
pericardial effusion, or involvement of lungs, tonsil, oral
mucosa or skin.
• Diagnostic principles remain the same as those in non-HIV
patients.
• Parasites are numerous and easily demonstrable, even in
buffy coat preparations, Bronchial fluid, other body fluid

28. Treatment in VL-HIV coinfection
• Essentially the same as in immunocompetent
patients
• Conventional amphotericin B (0.7 mg/kg/day for
28 days) may be more effective in achieving
initial cure than Sbv
(20 mg/kg/day for 28 days)
• Co-infected patients-tendency to relapse within
1 year.
• Prevention of relapse, the role of maintenance
chemotherapy is debatable.
• Highly active antiretroviral therapy (HAART)

29. VL-Prevention and control
• A multipronged approach is needed.
• Vector control -insecticide spray is very
important.
• Mosquito nets or curtains treated with
insecticides will keep out the tiny sandflies.
• In endemic areas with zoonotic transmission,
infected or stray dogs should be destroyed.

30. VL-Prevention and control
• In areas with human to human transmission,
early diagnosis and treatment of human
infections
• Reduce the reservoir and control epidemics
of VL
• Serology is useful for screening of suspected
cases in the field
• No vaccine is currently available.