Free Medical Study

Leishmaniasis:

Leishmaniasis is one of the complexes of disease caused by an obligate intracellular protozoa of the genus Leishmania and transmitted by sandfly of Phlebotomas genus.

Types of Leishmaniasis:

There is another form which is known as 

→Diffuse cutaneous leishmaniasis

CUTANEOUS LEISHMANIASIS

Species causing leishmaniasis

INCIDENCE

All over the world 1-1.5 million cases of CL and 500000 cases of VL are found. Of all the VL cases more than 90℅ are from India,Bangladesh,Southern Sudan,northeast Brazil.

VECTORS OF LEISHMANIASIS

Phlebotomus argentips ,Phlebotomus papatasi 

     vector in Bangladesh

Lutzomiya longipalpis

Sergentomyia babu

 Sergentomyia barudii

 Sergentomyia shortii    

KALA AZAR IN BANGLADESH

This is most common form of leishmaniasis found in Bangladesh.

In late 1970, kala azar emerged sporadically.

During 1981-85,only 8 upazilas reported kala azar.

Number of reported cases increased from 3978 (Three Thousand Nine hundred Seventy Eight) in1993 to 8505 (Eight Thousand Five Hundred Five) in 2005.

Annually 10000 cases are treated.

LIFE CYCLE

                Mode of transmission

Infected animal/mammal

↓

Bite by female sandfly

↓

Amastigote form ingested in stomach

↓

Transformation and multiplication

↓

Promastigote(transmission to pharynx)

↓

Regurgitational transmission to mammalian host during bite.

Period of transmission

As Phlebotomas argentypes is a wet zone species the highest risk of transmission in bangladesh is between april to september when the relative humidity remains as75-80%

Pathogenesis

Micro wound  produced by sandfly bite

↓

Promastigote form acts against body's defense mechanism

↓

Invade the RES by attaching on the surface of macrophage through receptor

↓

Formation of phagosome & fution with lysosome

↓

Phagolysosome

↓

Whether multiply or die

↓

If multiplication make the environment  of the RES suitable by proton pump mechanism

contd

↓

Detoxification of metabolites

↓

Scavange the oxidative free radicles

↓

Multiply by binary fission & form amastigote

↓

Amastigotes are taken up by new cells & the cycle is repeated

↓

Formation of granulomatous tissue (Dermal lesion) or hyperplastic  lesion(visceral lesion)...

↓

-Bone Marrow dysfunction-pancytopenia

-Loss of defense mechanism

-Macrophage infiltrates spleen,liver,lymphnodes

Clinical feature

Fever :Initially high fever usually accompanied by rigor and chills. Fever intensity decreases over time and patients may become afebrile for weeks to months followed by a relaps, usually lesser intensity, intermittent, double quotadian and usually without sign of toxaemia.

contd

Weight loss

Pallor

Bleeding

Splenomegaly

Hepatomegaly with or without mild jaundice

Blackening of skin

DIFFERENTIAL DIGNOSIS

Malaria

Typhoid

Miliary tuberculosis

Leukaemia

Lymphoma

Hepatitis

INVESTIGATION

Direct evidences(Parasitological confirmation):

→Demonstration of parasite(Amastigote/LD bodies)  on microscopy

→Demonstration of parasite(promastigotes) in culture done on NNN (Neil Nicole Novy) media

   →Specimens(as per frequency of the population of macrophages):

-splenic aspirate

-bone marrow aspirate

-blood buffy coat

-lymph node aspirate

-liver biopsy

-peripheral blood

contd

Indirect evidence:

Sero immunology:

→ICT by rk39 strip

→Direct agglutination test

→ELISA

→Indirect fluroscent antibody test(IFAT)

→Complement fixation test

Haematological

→CBC,ESR,HB%

→Platelet count

→Blood film

Biochemical

→Aldehyde test(not done)

→Liver enzymes, total protein, AG ratio

→Serum bilirubin

TREATMENT

1st line treatment-

Miltefosine:-

 Dose:

˃12 years and weighing≥25 kg: 100mg(cap 50 mg in morning and 50 mg in evening with meals)

˃12 years but weighing˂25 kg: 50mg(cap 50 mg in the morning with meals)

2-12 years: 2.5mg/kg body weight in two divided oral dose not exceeding 50 mg/day with meals.

These doses are scheduled for 28 days.

In case of missed doses,the scheduled 28 dose may be taken within a period of 35 days.

2.Liposomal amphhotericin B:-

Dose:

A total dose of 10-15mg/kg divided into 3 to 5 doses given either daily or alternative days through I/V infusion with 5% dextrose 500ml solution.

3.Paromomycin:

Dose:11mg/kg body weight of paromomycin base for 21 days.

contd

2nd line treatment:-

Sodium stibo gluc: Dose: 20 mg/kgbody weight I/M for 30 days.            

2.  Amphotericine B deoxycolate:

                                Dose: 1 mg/kg body weight daily or alternative days I/V (in 5% dextrose solution 500 ml) for 15 days.

Miltefosine

Adverse effect:

                              -mild to moderate vomiting

                              -mild diarrhoea

                              -oedema

                              -jaundice

                              -decreased urine

contd

Contra indication of miltefosine:

-pregnancy

-married women of child bearing age who are not using contraceptive regularly and are at risk of being pregnant

-women who are breast feeding

-children less than 2 years of age.

Sodium stibogluconate

Adverse effect:

                             -arthralgia

                             -myalgia

                             - raised hepatic transamminase

                             -severe cardiotoxicity

Response to therapy

Clinical improvement

Reduction in the size of spleen

Laboratory findings include improved Hb%, total count of WBC, increased albumin.

Complication of kala azar

Bleeding:

                  -epistaxis

                  -gum bleeding

                  -skin patichae

                  -GI bleeding

Severe opportunistic infections:

                  -amoebic/ bacillary dysentary

                  -pneumonia

                  -tuberculosis

                  -chicken pox

                  -herpes infection

cntnd

Cancrum oris

Post KA splenomegaly

Renal:NS, CKD

CLD

Outcome of kala azar

Kala azar treatment failure(KATF)

Post kala azar dermal leishmaniasis(PKDL)

Kala azar treatment failure
 

A case earlier diagnosed as kala azar, took complete treatment within one year, reappearance of symptom of kala azar and any positive lab evidence of parasite from bone marrow or splenic aspirate.

KATF can be treated by first line agents other than previously used 1st line therapy or any 2nd line drug(if 1st line is not available)

PKDL

A syndrome that developes at variable times after resolution of VL, manifested by skin lesions that can be of various types and initially are most prominent on the face.

Clinical types:

Erythomatous indurated lesions on the butterfly area of face

contd

2.Multiple symmetrical hypo pigmented macules or papules with irregular margins those may coalesce, having extensive distribution to the extremities and trunk.

3.Infiltrated plaques and nodules

4.Combination of papules, nodules and macular form.

PKDL

PKDL

Diagnostic tests for PKDL

Microscopy of slit skin smear using leishman or giemsa’s stain

Microscopy of skin biopsy matter using immuno histochemical stain

Culture of skin biopsy specimen in NNN media

Sero immunological tests

                       -rk39 ICT strip test

                       -DAT

PCR

Treatment for PKDL

Duration:

      6 cycles with 10 days interval between cycles.

Sodium stibo gluconate: 20mg/ kg body weight for 20 days per cycle.

Amphotericin B deoxycholate: 1mg/ kg body weight daily or alternative days I/V (in dextrose solution 500 ml) for 15 days per cycle.

Amphotericin B (liposomal): total dose of 10-15mg/ kg body weight divided into 3 to 5 doses per cycle.

HIV-VL Co infection

HIV induced co immunosuppression increases the risk of contacting VL 100-1000 times.

The clinical triad of fever, splenomegaly and hepatomegaly is found in fewer than half of patients with a CD4 count <50 cells/ mm3.

VL may present with gastrointestinal involvement, ascites, pleural or pericardial effusion or involvement of lungs, tonsils, oral mucosa or skin.

Treatment: Conventional Amphotericin B (0.7 mg/kg/ day for 28 days) may be more effective than Sb (20 mg/ kg/day for 28 days).