تشخیص

Urine 24 hours

Volume 600 cc

Calcium                   29mg/24hrs                             50-300

Phosphorus                  138 mg/24hrs                          40-100

 Na                      51meq/24hrs                          130-260

K                         36meq/24hrs                          40-80

Cl                        55mmol/24hrs                        110-250

Protein                 108mg/24hrs                          20-150

Citrate                 38mg/24hrs                           296.8 - 911.6

Oxalate                40mg/24hrs                               male=29-85    
      female=29-79

Creat.                     126 mg/24hrs                         600-1800

Bone marrow result

Diagnosis:

   Bone marrow aspiration

     Some leishman body organism       identified in the background

Bone marrow biopsy

  Visceral leishmaniasis

Closer view from previous image	Microscopic appearance of bone marrow aspiration * 40 Hyperplasic bone marrow full of precursors between bony spicles
Leishman bodies are in the macrophage and scattered in marrow field
	Atlas view of leishman bodies in macrophages

Differential diagnosis

Infectious causes

Subacute infectious endocarditis

Tuberculosis

Typhoid fever(prolonged salmonella bacteremia)

brucellosis

typhus

Chronic Malaria

Amebic liver abscess

Hepatosplenic schistosomiasis

Disseminated fungal infection:histoplasmosis

Infectious mononucleosis

Hematologic causes

Hodgkin disease

acute aleukemic leukemia

aplastic anemia

Etiology of stone formation

1- endemic stones(bladder stone)

2 – metabolic disorders

Hypercalciuria

Hyperoxaluria

Hyperuricosuria

Cystinuria

Xanthinuria,ect.

3- decrease of inhibitors

Citrate

Magnesium

Pyrophosphate

Glycosaminoglycan

Nephrocalcin

Osteopontine

Protrombin fragment-1

4- disease related

Prematurity

IBD

CF

RTA

MSK

ADPCK

GSD1

Cystinosis

antibiotics

5- infection

Urease positive

Corinebacterium urealiticum

6- anatomical disorders

Congenital anomalies

Foreign body

Surgical

7- medication

Drugs and metabolites

Metabolic effects

Treatment

Diet

Hydration

Medication

Surgery

Visceral leishmaniasis

Etiologic agents: leishmania donovani,leishmania infantum/leishmania chagasi

Sometimes cutaneous leishmaniasis / amazoneinsis and tropic can be visceral

Variation in intensity of involvement

One extreme

In apparent , self resolving

Ratio of 6.5/1 to 18/1

Classic (kala-azar)(dumdum – assam – infantile splenomegaly)

Fever,weight loss,hepatosplenomegaly, anemia ,leukopenia, trombocytopenia, hypergamaglobulinemia and in indian , hyperpigmentation

A small percentage of patients who have been treated for VL will have diffuse skin lesions called post kalaazar dermal leismaniasis

Hypopigmented,erythematous and nodular on face and troso and persists for several months and years.

Epidemiology

90% in india,bangladesh,sudan,brazil

L. donovani is responsible for visceral leishmaniasis in eastern india
and bangladesh

L. chagasi for Visceral leishmaniasis in latin america

L. lnfantum is endemic in mediterranean region

L. tropica in middle east

Transmission

Vector=sand fly   (phlebotomus argentipes)

Suitable reservoir= human , dogs , rats , gerbiles , small carnivores

Susceptible human

Other routes

Contaminated blood

Accidental needle stick

Sharing of contaminated needle

prenatal

Pathogenesis

Environmental and genetic characteristics of host determines

   severity of his disease

Components of immunity involvement in kala-azar

Leishman specific CD4 t CELLS ☻

T helper cells that secret INF GAMA and interleukin-2☻

IL10,IL4,TGF- BETA

INCUBATION PERIOD

3-8 months or longer than a year to 10 years

reactivation years after treatment may occur

Clinical manifestation

Fever( intermittent , twice daily )

weight loss, cachecsia

Abdominal enlargement due to hepatosplenomegaly and insidious

Rare cases with chill not rigor

Skin is dry and thin and scaly and hair may be lost and hyperpigmentation

Extremities edema is in malnourished children and echymosis

Epistaxis and gingival bleeding

hemorrage

Renal complications

microscopic hematuria usually mild

albuminuria

  albuminuria of leishmaniasis is due to focal leishmanial lesions, analogous to focal nephritis in bacteremias, and not to fever. In fatal cases, parasitized macrophages may be seen in the interstitial tissues of the kidneys.

 chronic renal insufficiency during convalescence from kala-azar, presumably from toxic effect of pentavalate antimonates.

renal involvement

The kidney lesions are characterized more by interstitial damage than glomerular or vascular damage.

nephrotic syndrome associated with heavy proteinuria 

The renal biopsy revealed a segmental necrotising glomerulonephritis with 70% crescents.

In human VL, glomerulosclerosis, mesangial cell proliferation, and interstitial nephritis have been reported

Advanced visceral leishmaniasis

Secondary bacterial infection

Pneumonia

Septicemia

Tuberculosis

Dysentery

measles

Visceral leishmaniasis in HIV

Splenomegaly may be absent

Patients may  have involvement of lung , pleura ,oral mucosa , esophagus , stomach , small intestine , skin , bone marrow , aplastic anemia

Diagnosis:

Clinical

The diagnosis of leishmaniasis is suggested by a history of possible exposure in endemic areas and by such clinical manifestations as

(1) prolonged intermittent fever, frequently with double daily peaks;

 (2) enlargement of the spleen or lymph nodes or both with, in some cases, enlargement of the liver;

(3) leukopenia;

 (4) anemia; and

 (5) elevation of serum globulin

Confimation

Splenic and lymph node aspiration and biopsy and wright-giemsa stain

Culture of splenic and bone marrow aspiation or blood in N.N.N media

Serum antibody

ELISA using recombinant k39 a kinesin-like antigen

Leishmanin skin test(montenegro)

Is negative in visceral leishmaniasis and has epidemiologic importance

laboratory

Anemia may be sever

Hemolysis,marrow replacement,splenic sequestration of erythrocytes,hemodilution,TNF ALFA

Leukopenia

Hypergamaglobulinemia(Alb<3 and IgG >5 or 5-10bg/dl)

ESR usually elevated

Elevated liver transaminases

Mostly Kidney shows immune complex deposition (mild glomerulonephritis)

Treatment:

Liposomal amphotericin (ambisome) can be the choice

3mg kg /1,5,14,21 days

Adverse effect:fever,loss of appetite,hypokalemia,azotemia,renal tubular acidosis trombophlebitis,weight loss ,hearing loss,diplopia,seizure, peripheral neuropathy,anaphylactic reaction

Amphotericine B deoxycolate is another choice

Pentavalent antimony can still be used but is not recommended in india because of 40% resistance

Adverse effects are abominal pain,anorexia,vomiting,nausea,myalgia,arthralgia,headache,malaise,pancreatitis,renal failure,ECG abnormalities

Pentamidine isethionate

2-4mg/kg for 15 days

Adverse effects:Life threatening hypoglycemia by pancreatic beta cell injury

Miltefosine (phosphocoline analogue)

2.5 mg/kg/day for 4 weeks

Parenteral parmomycin

Ketoconazole,imidazole,itraconazole

Prevention of renal damage

Use of allopurinol in cannine leishmaniasis prevented the progression of renal damage by improvement of proteinuria and azoemia

It is used with pentavalent antimonials

Response to therapy

Return of temperature to normal

Brisk reticulocytosis

Gradual reduction of spleen size

Reappearance of eosinophiles in peripheral blood smear

Follow up:

Monitor every 6 months for 2 years

Antibody is absent 1 year later

If post kala_azar dermal leishmaniasis occur treatment should be reinstituted

Thank you any comments

Fuadin (stibophen). All were ultimately treated with Neostam (stibamine glucoside), Neostibosan (ethylstibamine), or stibanose (sodium antimony gluconate, 20 mg. antimony per centimeter) in one or more courses of one or more of these pentavalent compounds. Two failures were re-treated, successfully, with stilbamidine (4, 4’-diamidinostilbene isethionate).

tartar emetic (potassium or sodium antimony tartrate) may be attempted. A satisfactory dose schedule is as follows: First day, 10 cc. of freshly prepared 0.5 percent solution; third day, 20 cc.; fifth day, 30 cc., and this repeated every other day until a total of 360 cc. (1.8 gm.) has been given.

Neostam 5.0 and

Neostibosan 10.0 gm

stilbamidine 4.0 gm.