This document provides information on the treatment of Kala-azar (visceral leishmaniasis) and post-kala-azar dermal leishmaniasis (PKDL). It discusses the clinical features, case definitions, objectives of treatment, and drug treatment options for primary kala-azar, treatment failure, and relapse cases. The first-line drugs recommended are liposomal amphotericin B, miltefosine, and paromomycin. For PKDL, first-line treatment is oral miltefosine for 12 weeks, and second-line options include amphotericin B deoxycholate or sodium stibogluconate. Special considerations for treatment in pregnancy, co-

1. Treatment of Kala-
azar and PKDL
Dr Shahjada Selim
MBBS MD (EM)
Registrar (Medicine)
Shaheed Suhrawardy Medical College Hospital, Dhaka
email:selimshahjada@gmail.com

2. Clinical Features of
KASymptoms:
Fever-usually insidious, irregular, low
grade, associated with chills & rigor.
Classically the fever is biphasic.
Weight loss.
Abdominal swelling.
Pigmentation.
Bleeding manifestations.
Secondary infections.

3. ..............Clinical Features of KA
Signs:
Increased temperature
Anemia
Gum bleeding
Lymphadenopathy
Splenomegaly
Hepatomegaly
Ascites
Edema

4. Clinical Case Definition
Following clinical case definitions will be used for reporting
and follow up. The case definitions will be as follows:
Primary Kala-azar (PKA):
An individual who is diagnosed to have KA
with the above mentioned case definition
and no history of treatment for KA before
will be considered as primary Kala-azar (PKA).

5. ........Clinical Case Definition
Kala-azar Treatment Failure (KATF):
An individual, who is diagnosed to have KA with
the above mentioned case definition and history
of treatment for KA within last one year, will
be reported as KATF.
All efforts should be made to diagnose
KATF parasitologically by examination of
smear or bone marrow or PCR.

6. ........Clinical Case Definition
Relapse Kala-azar (RKA):
An individual who is diagnosed to have KA with
the above mentioned case definition and history
of treatment for KA anytime in the past but not
within last one year will be reported as RKA. All
efforts should be made to diagnose KATF
parasitologically by examination of splenic
smear or bone marrow or PCR.

7. Objectives of Treatment
 To cure the patient
 To prevent the complications of the disease and
minimize side effects of medicines
 To restrain drug resistance and reduce the risk of
spread of disease.
Complications and concomitant disease conditions (if
any) should also be diagnosed and treated accordingly.

8. Drug treatment of
Primary
Kala-azar (PKA):

9. 1st
line treatment for
PKADrug of choice
Liposomal Amphotericin B
(10 mg/kg body wt, single dose)
Alternative 1st
line choices
(Depending on availability in our country)
1.Miltefosine
2.Paromomycin
3.Combination treatment

10. 2nd
line treatment for PKA
(if the 1st
line drugs are not available or not
tolerated):
1.Amphotericin B deoxycholate
2.Sodium Stibogluconate (SSG)

11. …….1st
line treatment
Combination treatment
Combination of Miltefosine and Paromomycin
will be 1st
choice.
Other alternative combinations will be-
• Liposomal Amphotericin B*
+ Miltefosine
or
• Liposomal Amphotericin B*
+ Paromomycin
* LAmB 5 mg/kg body weight single dose .

12. Description of the drugs for
PKALiposomal Amphotericin B (LAmB)
 To improve the tolerance and widen the narrow therapeutic
window, a lipid formulation of Amphotericin B is formulated.
Amongst the three formulations liposomal Amphotericin B has the
best safety profile.
 Liposomal Amphotericin B should be given in a single
intravenous infusion at a dose of 10 mg/kg for a period not less than
2 hours duration. Please see annex XX for details.
 In special situations like children of less than 5 years, in
pregnancy, co-infection with HIV/ AIDS etc would be treated with
multiple dose of Liposomal Amphotericin B (5mg/kg body weight on
alternate days for 3 doses). Please see annex XX for details.

13. Indications for alternative 1st
line
drugs:
• When Liposomal Amphotericin B is not indicated
due to hypersensitivity, intolerance or
contraindication.
• When Liposomal Amphotericin B is not available.

14. Miltefosine:
Miltefosine is a relatively safe oral drug for the
treatment of Kala-azar.
Recommended 28 days dose schedule:
Age more than 12 years and weighing ≥25kg:
100 mg daily. (cap 50 mg in morning and 50 mg in
the evening with meal)
Age more than 12 years but weighing <25kg:
50 mg daily. (cap 50 mg in the morning with meal)
Age 2‑12 years:
2. 5 mg/ kg body weight daily in two divided doses
with meal (not exceeding 50mg/day)

15. In case of missed doses, the scheduled 28 doses may be
taken within a period of 35 days. The daily dose should
never exceed the recommended amount.
If an exact dose cannot be administered, the closest 10
mg increment will be chosen at the dose.
Rounding will be done as follows:
If the calculation comes to <5 ‑ to round dose down.
If the calculation comes to >5 ‑ to round the dose up.

16. When to avoid the use of
Miltefosine:
Miltefosine is the preferred drug for the treatment of Kala-
azar/ PKDL in the elimination program except in the
following situations:
 Pregnancy
 Married women of child bearing age who are not using
contraceptives regularly.
 Women who are breast feeding.
 Children less than 2 yrs of age
Miltefosine may not be the ideal drug for patients of Kala-
azar
• With severe under nutrition
• Severe anemia and
• Patients with known history of kidney or liver disease

17. Adverse reactions of Miltefosine and
their treatment:
Adverse reactions to Miltefosine are mostly mild.
Mild to moderate vomiting is seen in 40%
patients and mild diarrhea in 15‑20% patients.
These usually occur during first week of
treatment.

18. Paromomycin:
Paromomycin is a promising and effective drug for
the treatment of Kala-azar. It has been registered
for use in India which is a parenteral
aminoglycoside.
Doses and administration:
Paromomycin sulphate should be given at a dose
of 15mg/kg/day. Each dose is to be taken from a
separate ampoule. It should be given I/M in the
gluteal muscle (alternative buttock, cheeks) once
a day for 21 days.

19. Combination therapy:
The 1st
choice of combination therapy will be
Miltefosine and Paromomycin.
The alternate choices-
Liposomal Amphotericin B + Miltefosine
or
Liposomal Amphotericin B + Paromomycin.

20. …..Combination therapy
Dose and administration:
1st
choice:
Cap. Miltefosine following the above
mentioned dose for 10 days
+
Inj. Paromomycin following the above
mentioned dose for 10 days

21. ……..Combination therapy
Alternate choice:
Inj. LAmB 5 mg/ kg body wt IV single dose on day 1
+
Cap. Miltefosine following the above mention dose
from day 2 to day 8.
Or
Inj. LAmB 5 mg/ kg body weight IV single dose on
day 1
+
Inj. Paromomycin following the above mention dose
from day 2 to day 11.

22. Treatment for KATF and RKA
KATF and RKA cases will be treated with
alternative 1st
line agent (eg. Patient who
received LAmB will be treated with Miltefosine or
Paromomycin or combination).
If alternative 1st line agents are not available,
then a 2nd
line agent should be used.

23. Indications of 2nd
line drugs:
When the first line drugs are not available
or not tolerated.

24. Amphotericin B deoxycholate:
Recommended second line drug for treatment of Kala-azar
and KATF is Amphotericin B deoxycholate.
Amphotericin B deoxycholate is also an effective drug. But it
has high toxicity profile and thus pushed to second line.
Amphotericin B deoxycholate 1 mg/kg daily or alternate day
is recommended in the form of infusion (in 5% Dextrose
solution 500 ml) for 15 doses having a cure rate of >90%. A
test dose should be given before administration of
Amphotericin B.
After preparation of solution 5 drops /min for 30 min, then 10
drops/min for another 30 min and if there is no reaction
occurs, then the infusion should be given slowly over a
period of 4-6 hours.

25. Sodium Stibogluconate
(SSG):
SSG is an effective and widely used drug for KA
and KATF. But the drug is pushed to second line
because of its cardiac toxicity and is recommended
by WHO to be phased out gradually.
SSG should be given at a dosage of 20mg/kg body
weight, daily IM injection for 30 days.
It is essential to weigh the patient before starting
treatment. Clinical cardiac monitoring should be
done throughout the treatment period.

26. Route of Administration of SSG:
The preferred route of administration
recommended is by deep intramuscular (IM)
injection. It is better not to give the drug
intravenously (IV) to avoid the risk of
cardiovascular collapse.

27. Assessment of cure after treatmentAssessment of cure after treatment
(Initial cure):
1 week after completion of treatment
 Improvement of all clinical parameters
including
 absence of fever
 Reduction of spleen size
 Gain in body weight.

28. Assessment of cure at 6Assessment of cure at 6
monthsmonths (Definitive cure):
 No fever
 Substantially reduced spleen size or not
palpable
 Feeling of general well being.

29. Drug treatment of PKDL

30. Treatment of PKDL
First line treatment:
Miltefosine
Longer duration of oral Miltefosine is recommended.
The treatment will be supervised. Patient will received
their drugs monthly after being followed up by the
respective physician.
Adult dose: 100 mg daily for 12 weeks in two divided
doses.
Children: 2.5 mg/kg body weight/ day in two divided
doses, not exceeding 50mg/day for 12 weeks.

31. Second line treatment of PKDL
Amphotericin B deoxycholate
Dose: 1 mg/kg body wt daily or alternative IV (in
5%Dextrose solution) for 60-80 doses over 4 months.
Route: IV
Sodium Stibogluconate (SSG)
SSG should be given at a dosage of 20‑mg/kg/day in
intramuscular route. It is essential to weight the
patient every time, before starting a new cycle. Total 6
cycles of treatment should be given. Each cycle
consists of 20 days of treatment and there should be
an interval of 10 days in between two cycles.

32. Treatment of Cutaneous Leishmaniasis
(CL):
The treatment approach largely depends in part on
the Leishmania species/ strain and the geographic
area in which infection was acquired. In general, the
first sign of a therapeutic response to adequate
treatment is decreasing indurations (lesion flattening).
The healing process for large, ulcerative lesions often
continues after the end of therapy.

33. First line choice:
Sodium stibogluconate:
The standard daily dose will be 20 mg/kg/day, IM for 20
days (10 days may suffice based on clinical judgment).
Or
Cap. Miltefosine
The doses should be calculated as follows:
Age more than 12 years and weighing ≥25kg: 100 mg.
(cap 50 mg in morning and 50 mg in evening with meals)
Age more than 12 years but weighing <25kg: 50 mg. (cap
50 mg in the morning with meals)
2‑12 years: 2.5 mg/kg body weight. in two divided dose,
not exceeding 50mg/day with meals.

34. Second line choice for CL:
Ketoconazole: 600 mg daily for 28 days
or,
Itraconazole: 200 mg twice daily for 28
days or,
Fluconazole: 200 mg daily for 6 weeks
(for adult).

35. Treatment of Kala-azar in specialTreatment of Kala-azar in special
situations:situations:The treatment of Kala-azar in special situations is
recommended in centers where appropriate expertise and
facilities are available. The following conditions can be
considered as special situations:
 Pregnancy
Risk of treatment should be weighed against benefit.
Treatment should be prioritized according to the severity. If a
pregnant mother is diagnosed as KA during 1st
trimester she
should be treated at 2nd
trimester or if she diagnosed as KA
during 3rd
trimester then she should be treated after delivery.
Drug of choice is Liposomal Amphotericin B (5 mg/kg body
weight on alternate days for 3 doses). Miltefosine and Sodium
stibogluconate is contraindicated in case of pregnancy.

37.  Kala-azar with TB
Treatment of both diseases should be continued and KA will
be treated as PKA.
 Kala-azar HIV/AIDS co-infection
It will be treated with Liposomal Amphotericin B with multiple
doses. ARV should be continued for HIV/AIDS.
 Kala-azar in a patient suffering from another
serious disease
All the case of Kala-azar with serious co-morbidities should
be treated under specialized supervision. Liposomal
Amphotericin B will be the drug of choice and treatment
should be given in a tertiary care facility.

38. Complete Treatment of Kala-Complete Treatment of Kala-
azar:azar:
All efforts should be made to ensure the complete
treatment. The following measures are
recommended to complete the treatment:
 Every patient should be counseled so that the
patient/family fully understands the importance of
complete treatment and the consequences of the
incomplete treatment.
 All treatment should be provided free of cost to
eliminate the economic constraint as a reason for
discontinuation of treatment

39.  Each patient should have a separate treatment
box at the health facility that contains the full dose of
drugs labeled with the name and individual identification
of the patient. A treatment card with a unique
identification number showing the number of days the
treatment taken should be provided to patients.
 It is advisable to follow up the patients during
treatment, immediately after completion of treatment
and up to 1 year (at 1st
, 5th
, 9th
, 12th
month)
 The treatment should be directly observed as per
SOPs.
 There should be coordination amongst the public
and private sector providers and a follow up plan should
be developed for each patient.

40. Monitor the patient regularly for signs and symptoms
(indicative of adverse events of drugs) and should be reported
as major & minor events (Ref. Training module for Kala-azar
elimination program).
Perform the tests if clinically indicated in treatment sites and
monitor the results. This can help to take timely measures even
before the signs appear.
Periodic meetings should be organized to review the reports of
major and minor adverse events obtained from the different
levels. This will help to guide the program in recommending the
tests that should be done to monitor the patients on treatment.
 Regularly report the adverse events on the reporting
formats to higher levels once in a month for a review and
feedback.

41. Pharmacovigilance:
Pharmacovigilance is important to ensure the safety of the
medicines used in the treatment of Kala-azar and PKDL. It
should be the responsibility of the national program to
ensure pharmacovigilance. The program can provide very
useful information regarding efficacy of treatment options
and related adverse events during follow up of the patients.
The program must encourage health facilities and personals
to ensure regular reporting of major and minor adverse
events. The following measures will help to recognize early
the occurrence of adverse events.

42. fever>2weeks &
Residing/travelling
in endemic areas
fever>2weeks &
Residing/travelling
in endemic areas
YesYes Evidence of another
disease other than KA?
Evidence of another
disease other than KA?
Diagnosis And Management
Chart
NoNo
Splenomegaly, weight
loss, anemia
Splenomegaly, weight
loss, anemia
Is the patient
pregnant?
Is the patient
pregnant?
PKDL and choice of drugs
1st
line- Miltefosine:
2nd
line
a)Amphotericin-B Deoxycholate
b)LAmB
c) SSG
PKDL and choice of drugs
1st
line- Miltefosine:
2nd
line
a)Amphotericin-B Deoxycholate
b)LAmB
c) SSG
Record as KATF and use:
1.Alternative First line Treatment:
a. Miltefosine b. Paromomycin c. Combination
2. Second line drugs
a. Amphotericin B deoxycholate b. SSG
Record as KATF and use:
1.Alternative First line Treatment:
a. Miltefosine b. Paromomycin c. Combination
2. Second line drugs
a. Amphotericin B deoxycholate b. SSG
Had complete treatment
with Miltefosine or any
other drugs given within
last year?
Had complete treatment
with Miltefosine or any
other drugs given within
last year?
YesYes
PKA and choice of drugs:
LAmB
Alternate choice-
1. Miltefosine 2. Paromomycin
3. Combination of alternative
choice
PKA and choice of drugs:
LAmB
Alternate choice-
1. Miltefosine 2. Paromomycin
3. Combination of alternative
choice
KA with pregnancy and
choice of drugs
LAmB
Alternative:
a. Amphotericin-B
b.Paromomycin c.
SSG
KA with pregnancy and
choice of drugs
LAmB
Alternative:
a. Amphotericin-B
b.Paromomycin c.
SSG
Hypo pigmented patches (macule)
without loss of sensation with or
without
Erythematous patch (papule)
Subcutaneous nodule
fever or h/o KA
Hypo pigmented patches (macule)
without loss of sensation with or
without
Erythematous patch (papule)
Subcutaneous nodule
fever or h/o KA
If yes & rk39
(+)
If yes & rk39
(+)
If yes & rk39
(+)

43. Chart for Kala-azar treatmentChart for Kala-azar treatment
1st
line treatment for Kala-azar
Drug of choice-
1. LAmB
2. Alternative 1st
line choices
• Miltefosine
• Paromomycin
• Combination of Miltefosine and
Paromomycin - 1st
choices
Alternative combinations will be-
LAmB + Miltefosine
Or,
LAmB+ Paromomycin.
*
LAmB 5 mg/kg body weight on
2nd
line treatment for Kala-azar
1. Amphotericin-B deoxycholate
2. Sodium stibogluconate (SSG)
Weight (kg) SAG (ml)
up to 3 0.6
4-5 0.8-1
6-8 1.2-1.6
9-10 1.8-2
11-13 2.2-2.6
14-15 2.8-3.0
16-18 3.2-3.6
19-20 3.8-4.0
21-23 4.2-4.6
24-25 4.8-5.0
26-28 5.2-5.6
29-30 5.8-6.0
31-35 6.2-7.0
36-40 7.2-8.0
41-45 8.2-9.0
46-50 9.2-10
51-55 10.2-11
56-60 11.2-12

44. Treatment ChartTreatment Chart
When LAmB is not available or
contraindicated or in KATF
1st
line drugs:
1. Miltefosine
2. Paromomycin
3. Combination of 1st
choice
2nd
line drugs
a. Amphotericin-B deoxycholate
b. Sodium stibogluconate (SSG)
When LAmB is not available or
contraindicated or in KATF
1st
line drugs:
1. Miltefosine
2. Paromomycin
3. Combination of 1st
choice
2nd
line drugs
a. Amphotericin-B deoxycholate
b. Sodium stibogluconate (SSG)
Rx for RKA
1.Combination 1st
line drugs
cap. Miltefosine + inj.
Paromomycin
2. Alternate combination-
Inj. LAmB + Cap. Miltefosine
Or,
Inj. LAmB + Inj. Paromomycin
Rx for RKA
1.Combination 1st
line drugs
cap. Miltefosine + inj.
Paromomycin
2. Alternate combination-
Inj. LAmB + Cap. Miltefosine
Or,
Inj. LAmB + Inj. Paromomycin
Rx for PKDL
1st
line- Miltefosine:
2nd
line
a.Inj. Amphotericin B Deoxycholate
b.b. Inj. Sodium stibogluconate (SSG)
Rx for PKDL
1st
line- Miltefosine:
2nd
line
a.Inj. Amphotericin B Deoxycholate
b.b. Inj. Sodium stibogluconate (SSG)

45. THANK
YOU