Leishmaniasis By: Dr Osman Sadig
<ul><li>The leishmaniasis  are a group of diseases </li></ul><ul><li>with a variety of  clinical manifestations </li></ul>...
<ul><li>5- L tropica  6- L major  </li></ul><ul><li>7- L ethiopica  8- L braziliensis </li></ul><ul><li>9- L mexicana </li...
 
 
<ul><li>The outcome of the infection depends on : </li></ul><ul><li>1- Parasite invasiveness & pathogenicity </li></ul><ul...
<ul><li>Visceral leishmaniasis </li></ul><ul><li>VL is usually fatal disease without TR. </li></ul><ul><li>Epidemiology </...
<ul><li>-  Main endemic areas in Sudan are : </li></ul><ul><li>1-  Eastern Sudan along Atbara & Rahad </li></ul><ul><li>ri...
<ul><li>- More than  24 600  cases &  1193  deaths </li></ul><ul><li>had been reported in Sudan during </li></ul><ul><li>1...
<ul><li>Leishmania exists in 2 different forms : </li></ul><ul><li>1-  Promastigote  in the vector developing </li></ul><u...
 
 
<ul><li>The vector  is  Female sand fly  -  Phlebotomus orientalis </li></ul><ul><li>- Phl martini  (termite hill dweller)...
 
<ul><li>Transmission </li></ul><ul><li>Depends on the presence of suitable  reservoir ,  vector  and susceptible human  ho...
<ul><li>Out breaks </li></ul><ul><li>- Mellut town  1940 </li></ul><ul><li>- Southern Fung  1956 </li></ul><ul><li>- Jum j...
<ul><li>Immunity </li></ul><ul><li>Out come of infection depends on the </li></ul><ul><li>interplay between  protective CM...
<ul><li>Leishmania infection results in life long latent immunity. With immunoparesis leishmania can become opportunistic ...
<ul><li>Clinical manifestations </li></ul><ul><li>- Varies from  asymptomatic self limitting   </li></ul><ul><li>dis to  f...
<ul><li>2 - Probable case : suspect case +  leucopenia </li></ul><ul><li>3 - Confirmed case : suspect case +  positive par...
<ul><li>- Splenomegaly  (95%) </li></ul><ul><li>- Wt loss  (80%) & wasting later </li></ul><ul><li>- Anaemia  (75%):  chro...
<ul><li>-  skin pigmentation : The skin is dry, thin,  scaly with sparse hair. </li></ul><ul><li>Atypical cases  present w...
<ul><li>Differential diagnosis </li></ul><ul><li>- Malaria must be ruled out </li></ul><ul><li>- Enteric fever </li></ul><...
<ul><li>- Histoplasmosis  - infectious mononucleos </li></ul><ul><li>- Other causes of gross splenomegaly  - Malnutrition ...
<ul><li>Laboratory & diagnosis: </li></ul><ul><li>- CBC & ESR: </li></ul><ul><li>- anaemia (60-90%) </li></ul><ul><li>- le...
<ul><li>- Specific diagnosis depends on clinical  suspicion & either 1-  parasitology  OR  2-  serology . </li></ul><ul><l...
<ul><li>- rarely from puffy coat layer of blood  - Culture in NNN media </li></ul><ul><li>* Negative splenic aspirate does...
<ul><li>2- Serology : in clinically suspected cases </li></ul><ul><li>(FAT, DAT, ELIZA, Latex Agg test, PCR) </li></ul><ul...
<ul><li>-  Katex  detects Ag in urine, sensitive and  specific </li></ul><ul><li>-  ICT 3   LST:   measures  type 1V hyper...
<ul><li>Treatment of VL:  ( supportive/ specific) </li></ul><ul><li>- TR ideally given to  confirmed cases  in </li></ul><...
<ul><li>2- Specific TR :- </li></ul><ul><li>A- First line drugs: </li></ul><ul><li>1 - Sod stibogluconate  is pentaval  an...
<ul><li>-  CI : cardiac dis, liver dis, renal fail, </li></ul><ul><li>moribund pat & full blown AIDS. </li></ul><ul><li>2-...
<ul><li>TOC in day 21. It is reconstituted and  diluted in 5% dextrose and infused  over 30—6o min.  Main indications of a...
<ul><li>4- Paromomycin  (aminosidine) 15mg/kg  for 17 days IM or IV diluted in NS  over 90 min. Usually used in combin  wi...
<ul><li>Follow up: </li></ul><ul><li>- gen condition, temp, spleen, Wt, CBC </li></ul><ul><li>- TOC  at 25—30 day  of TR t...
<ul><li>-  slow responder  = pat with no clinical  </li></ul><ul><li>response & low grade parasitaemia </li></ul><ul><li>a...
<ul><li>-  Relapse  (5%)   = pat with clinical and  parasitological confirmed case & past  history of TR of VL.  1 st  , 2...
<ul><li>Complications of VL </li></ul><ul><li>- Intercurrent infections  (Tb, otitis M, canc </li></ul><ul><li>oris, pyode...
<ul><li>PKDL   - grade 1 PKDL = rash on the face +/- </li></ul><ul><li>upper chest & arms </li></ul><ul><li>- grade 2 PJDL...
 
 
<ul><li>-  Parasites are scanty  in PKDL which may  serve as a reservoir of infection  - PKDL should be differentiated fro...
<ul><li>Causes of death in VL   -  intercurrent infection including HIV  - hepatic failure  - renal failure  </li></ul><ul...
<ul><li>VL & HIV Co infection </li></ul><ul><li>- Both are associated wz  immune suppres </li></ul><ul><li>and  potentiate...
<ul><li>-  VL may be rapidly progressive  & may  </li></ul><ul><li>have predominant GIT symptoms  -  CD4 < 200  &  associa...
<ul><li>and  drug SE are more severe .  -  Combined anti leish & anti retroviral  </li></ul><ul><li>drugs for TR.   </li><...
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Leishmaniasis

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Leishmaniasis

  1. 1. Leishmaniasis By: Dr Osman Sadig
  2. 2. <ul><li>The leishmaniasis are a group of diseases </li></ul><ul><li>with a variety of clinical manifestations </li></ul><ul><li>1- Visceral leishmaniasis VL/ PKDL </li></ul><ul><li>2- Cutaneous leishmaniasis CL </li></ul><ul><li>3- Mucocutaneous leishmaniasis MCL </li></ul><ul><li>4- Diffuse cutaneous leishmaniasis DCL </li></ul><ul><li>Over 20 pathogenic sp of leish parasites </li></ul><ul><li>are known: </li></ul><ul><li>1- L donovani 2- L infantum </li></ul><ul><li>3- L archibaldi 4- L chagasi </li></ul>
  3. 3. <ul><li>5- L tropica 6- L major </li></ul><ul><li>7- L ethiopica 8- L braziliensis </li></ul><ul><li>9- L mexicana </li></ul>
  4. 6. <ul><li>The outcome of the infection depends on : </li></ul><ul><li>1- Parasite invasiveness & pathogenicity </li></ul><ul><li>2- dose of inoculum </li></ul><ul><li>3- parasite tropism </li></ul><ul><li>4- genetically determined host immune </li></ul><ul><li>response A single leish sp can produce diff clinical syndromes and each of the syndromes can be caused by more than one sp e.g. Viscerotropic L tropica </li></ul>
  5. 7. <ul><li>Visceral leishmaniasis </li></ul><ul><li>VL is usually fatal disease without TR. </li></ul><ul><li>Epidemiology </li></ul><ul><li>- About 500 000 new cases annually, 90% </li></ul><ul><li>in India & Sudan </li></ul><ul><li>- Infection is endemic in India, China </li></ul><ul><li>Central Asia, East Africa, Middle east, </li></ul><ul><li>Medit region and Latin America </li></ul><ul><li>- VL is endemic in Sudan & has been </li></ul><ul><li>reported since early 19 th century. </li></ul>
  6. 8. <ul><li>- Main endemic areas in Sudan are : </li></ul><ul><li>1- Eastern Sudan along Atbara & Rahad </li></ul><ul><li>rivers </li></ul><ul><li>2- Sinnar & Blue Nile states </li></ul><ul><li>3- Upper Nile state </li></ul><ul><li>4- Eastern Equatoria around Kapoita </li></ul><ul><li>5- South Kordofan </li></ul><ul><li>6- South Darfor </li></ul><ul><li>- VL is caused by L. donovani (LDB), L. infantum, L. chagasi & L. tropica ( usually mild disease) </li></ul>
  7. 9. <ul><li>- More than 24 600 cases & 1193 deaths </li></ul><ul><li>had been reported in Sudan during </li></ul><ul><li>1996—2001. This is only reported cases </li></ul><ul><li>and does not reflect actual dis transmiss </li></ul><ul><li>- The dis affects mainly children & young </li></ul><ul><li>adults and is commoner among poor people, farmers, labourers, malnourished, people visiting endemic areas for the 1 st time and in the immunosuppressed </li></ul><ul><li>- Leishmania exists in 2 different forms: </li></ul>
  8. 10. <ul><li>Leishmania exists in 2 different forms : </li></ul><ul><li>1- Promastigote in the vector developing </li></ul><ul><li>from amastigotes through series of </li></ul><ul><li>intermediate stages in the digestive tract </li></ul><ul><li>eventually migrating to the proboscis and </li></ul><ul><li>inoculated to the skin of the host with the blood meal. It is pearl or spindle shaped 10—15 mc with flagellum . </li></ul><ul><li>2- Amastigote : develops in the human- being from promastigote & proliferate </li></ul><ul><li>in the R/E system within macrophages. It is oval in shape. </li></ul>
  9. 13. <ul><li>The vector is Female sand fly - Phlebotomus orientalis </li></ul><ul><li>- Phl martini (termite hill dweller) </li></ul><ul><li>- Phl lutzomyia in new world leishma </li></ul><ul><li>The reservoir </li></ul><ul><li>- Depends on the leish sp & the vector </li></ul><ul><li>- Rodents, dogs, wild animals & patients </li></ul><ul><li>with VL (PKDL) </li></ul>
  10. 15. <ul><li>Transmission </li></ul><ul><li>Depends on the presence of suitable reservoir , vector and susceptible human host </li></ul><ul><li>1- H uman to human ( anthroponotic) e.g. India (causing epidemics) </li></ul><ul><li>2- A nimal reservoir to human ( zoonotic transmission) e.g. dogs in the ME and Mediterranean where the dis. is sporadic in children and opportunistic in immunosuppressed – HIV patients </li></ul><ul><li>3- Congenital, sexual & BT are rare. </li></ul>
  11. 16. <ul><li>Out breaks </li></ul><ul><li>- Mellut town 1940 </li></ul><ul><li>- Southern Fung 1956 </li></ul><ul><li>- Jum jum tribe 1958 (Satti) </li></ul><ul><li>- Western Upper Nile 1984—1994 </li></ul><ul><li>- Gedarif state 1996—200- </li></ul>
  12. 17. <ul><li>Immunity </li></ul><ul><li>Out come of infection depends on the </li></ul><ul><li>interplay between protective CMI respon </li></ul><ul><li>at one hand & dis enhancing immune </li></ul><ul><li>response on the other hand </li></ul><ul><li>1- Th1 CD4 cells are protective by </li></ul><ul><li>producing IL2 & INF gamma which </li></ul><ul><li>stimulate macrophage to inhibit the </li></ul><ul><li>growth of amastigotes </li></ul><ul><li>2- Th2 CD4 cells produce IL4,5 which </li></ul><ul><li>enhance disease progression </li></ul>
  13. 18. <ul><li>Leishmania infection results in life long latent immunity. With immunoparesis leishmania can become opportunistic pathogen through reactivation or new infection . </li></ul>
  14. 19. <ul><li>Clinical manifestations </li></ul><ul><li>- Varies from asymptomatic self limitting </li></ul><ul><li>dis to frank VL which is fatal if untreated , </li></ul><ul><li>with mild dis in between. </li></ul><ul><li>1- Clinically suspect case is any pat who </li></ul><ul><li>lives or had traveled to an endemic area </li></ul><ul><li>presenting with fever of > 2/52 + spleenomegaly and/or Lymphadenopathy in whom malaria is ruled out or treated </li></ul>
  15. 20. <ul><li>2 - Probable case : suspect case + leucopenia </li></ul><ul><li>3 - Confirmed case : suspect case + positive parasitology </li></ul><ul><li>Presentation </li></ul><ul><li>- IP : 1—2/12 (2/52—10 years) </li></ul><ul><li>- Onset : insidious , but may be acute </li></ul><ul><li>- Fever (95%) : prolonged fever without rig </li></ul><ul><li>It may be intermittent, remittent wz doubl </li></ul><ul><li>spike or contin. Fever is well tolerated. </li></ul>
  16. 21. <ul><li>- Splenomegaly (95%) </li></ul><ul><li>- Wt loss (80%) & wasting later </li></ul><ul><li>- Anaemia (75%): chronic dis, bleeding, </li></ul><ul><li>hemolysis, BM infilt wz parasites, hypresp </li></ul><ul><li>haemodilution. </li></ul><ul><li>- Hepatomegaly (60%) - LN (75%) </li></ul><ul><li>- cough (75%) - anorexia (70%) </li></ul><ul><li>- epistaxis (50%) - diarhoea (40%) </li></ul><ul><li>- vomiting (15%) - jaundice (5%) </li></ul><ul><li>- edema (5%) - ascites. </li></ul>
  17. 22. <ul><li>- skin pigmentation : The skin is dry, thin, scaly with sparse hair. </li></ul><ul><li>Atypical cases present with: - mild symptoms and/or isolated splenomegaly </li></ul><ul><li>- lymphadenopathy may be the sole </li></ul><ul><li>presentation in India </li></ul><ul><li>- Some present with PKDL </li></ul><ul><li>- Some show sub clinical sero conversion </li></ul><ul><li>- In immunosuppressed (e.g AIDS) fever and spleenomegaly may be absent </li></ul>
  18. 23. <ul><li>Differential diagnosis </li></ul><ul><li>- Malaria must be ruled out </li></ul><ul><li>- Enteric fever </li></ul><ul><li>- H/S schistosomiasis - African trypansom </li></ul><ul><li>- Miliary Tb </li></ul><ul><li>- Brucellosis & relapsing fevers </li></ul><ul><li>- AIDS </li></ul><ul><li>- Liver abscess </li></ul>
  19. 24. <ul><li>- Histoplasmosis - infectious mononucleos </li></ul><ul><li>- Other causes of gross splenomegaly - Malnutrition </li></ul>
  20. 25. <ul><li>Laboratory & diagnosis: </li></ul><ul><li>- CBC & ESR: </li></ul><ul><li>- anaemia (60-90%) </li></ul><ul><li>- leucopenia (84%) </li></ul><ul><li>- thrombocytopenia (73%) </li></ul><ul><li>- high ESR </li></ul><ul><li>- Liver biochemstry: </li></ul><ul><li>albumin < 30 g/l (88%), globulin >30 g/l (78%), elevated ser bilirubin, transaminases and ALP </li></ul><ul><li>- Renal profile & ECG </li></ul>
  21. 26. <ul><li>- Specific diagnosis depends on clinical suspicion & either 1- parasitology OR 2- serology . </li></ul><ul><li>1- Parasitology : specimen obtained from: </li></ul><ul><li>- Gland puncture is easy & safe with </li></ul><ul><li>50—65% sensitivity </li></ul><ul><li>- BM aspirate require trained person, </li></ul><ul><li>painful & require sp needle wz </li></ul><ul><li>64—92% sensitivity </li></ul><ul><li>- Splenic puncture : invasive & hazardous </li></ul><ul><li>with 90—95% sensitivity </li></ul>
  22. 27. <ul><li>- rarely from puffy coat layer of blood - Culture in NNN media </li></ul><ul><li>* Negative splenic aspirate does not </li></ul><ul><li>exclude diagnosis </li></ul><ul><li>* Parasitology is the only diagnostic method in relapse, HIV pat & infants < 6/12 </li></ul>
  23. 28. <ul><li>2- Serology : in clinically suspected cases </li></ul><ul><li>(FAT, DAT, ELIZA, Latex Agg test, PCR) </li></ul><ul><li>- DAT is sensitive, specific, simple and </li></ul><ul><li>can be easily performed under field </li></ul><ul><li>conditions, but needs trained staff. </li></ul><ul><li>Not useful for relapse diagn or TOC. Positive DAT (>1:64000) combined with negative LST in a clinical suspect is diagnostic. Positive LST rules out active VL even if DAT is positive. </li></ul>
  24. 29. <ul><li>- Katex detects Ag in urine, sensitive and specific </li></ul><ul><li>- ICT 3 LST: measures type 1V hypersensitivity . </li></ul><ul><li>It is negative in active VL, but becomes </li></ul><ul><li>positive in 80% 3—6 months after TR </li></ul><ul><li>It is valuable in epidemiological studies and augments DAT in the diagnosis if it is negative. </li></ul>
  25. 30. <ul><li>Treatment of VL: ( supportive/ specific) </li></ul><ul><li>- TR ideally given to confirmed cases in </li></ul><ul><li>hospital settings under med supervision </li></ul><ul><li>- Trial of TR is only considered if there are </li></ul><ul><li>no lab. facilities & after exclusion of </li></ul><ul><li>other infections and occasionally in </li></ul><ul><li>highly suspected cases despite –Ve lab. </li></ul><ul><li>1- Supportive TR include nutritional care, </li></ul><ul><li>oral hygiene, Fe, folic acid, multivit, TR </li></ul><ul><li>of infections, BT & correction of flu & E </li></ul>
  26. 31. <ul><li>2- Specific TR :- </li></ul><ul><li>A- First line drugs: </li></ul><ul><li>1 - Sod stibogluconate is pentaval antimony (SSG) in 100mg/ml. Dose 20 mg/kg/d IV or IM for 30 days. </li></ul><ul><li>- SE: include A,N,V, fatigue, headache arthralgia myalgia, cough, cardiotoxicity, renal damage </li></ul><ul><li>pancreatitis, elevated ser amylase and transaminases, and local pain </li></ul>
  27. 32. <ul><li>- CI : cardiac dis, liver dis, renal fail, </li></ul><ul><li>moribund pat & full blown AIDS. </li></ul><ul><li>2- Meglumine antimoniate is similar to SSG </li></ul><ul><li>but in 85 mg/ ml </li></ul><ul><li>B- Second line drugs : </li></ul><ul><li>1- Amphotericin B 1mg/kg EOD for 30 days Nephrotoxic. 2 nd line drug. 2 - Ambisome (amphotericin B lipid complex) is alternative 1 st line drug. 50 dollars for 50 mg vial & 600 dollars total TR. Dose 20—30 mg/kg over 2/52 in doses of 3—5 mg/ kg with </li></ul>
  28. 33. <ul><li>TOC in day 21. It is reconstituted and diluted in 5% dextrose and infused over 30—6o min. Main indications of ambisome are: - unresponsiveness to SSG - 3 rd relapse </li></ul><ul><li>- cardiac disease - hepatic & renal impairment </li></ul><ul><li>- moribund patients . 3- Pentamidine 3—4 mg/kg EOD for 10 doses 2 nd line drug </li></ul>
  29. 34. <ul><li>4- Paromomycin (aminosidine) 15mg/kg for 17 days IM or IV diluted in NS over 90 min. Usually used in combin with SSG. Oto/ Nephrotoxic. </li></ul><ul><li>5- Miltefosine : anti neoplastic. Oral, sp </li></ul><ul><li>used in India </li></ul><ul><li>6- Allopurinol 7- ketoconazole 8- INF gamma </li></ul>
  30. 35. <ul><li>Follow up: </li></ul><ul><li>- gen condition, temp, spleen, Wt, CBC </li></ul><ul><li>- TOC at 25—30 day of TR to asses the parasitological cure. GP in routine use. - Initial cure = clinical cure + parasitologic </li></ul><ul><li>cure by the end of TR </li></ul><ul><li>- Definite cure = absence of symptoms </li></ul><ul><li>and signs 6/12 after initial cure </li></ul><ul><li>- Follow up at 3, 6, 12 M & if symptoms rec </li></ul>
  31. 36. <ul><li>- slow responder = pat with no clinical </li></ul><ul><li>response & low grade parasitaemia </li></ul><ul><li>after 30/d of TR. Extend TR to 60 days or </li></ul><ul><li>until 2 consecutive –ve TOC - Non responder = patient with no clinical </li></ul><ul><li>response & high grade parasitology after </li></ul><ul><li>30 days TR with SSG. Combine SSG + paramomycin OR go to ambisome for TR. </li></ul>
  32. 37. <ul><li>- Relapse (5%) = pat with clinical and parasitological confirmed case & past history of TR of VL. 1 st , 2 nd and 3 rd relapse - For 1 st relapse: SSG for 60 days or till </li></ul><ul><li>2 consecutive –ve TOC OR SSG + paramomycin </li></ul><ul><li>- For 2 nd relapse: SSG + parmomycin OR </li></ul><ul><li>go to ambisome </li></ul><ul><li>- For 3 rd relapse ambisome Screen for HIV for non resp and relapse cases </li></ul>
  33. 38. <ul><li>Complications of VL </li></ul><ul><li>- Intercurrent infections (Tb, otitis M, canc </li></ul><ul><li>oris, pyoderma, viral) </li></ul><ul><li>- Malnutrition & anaemia </li></ul><ul><li>- Bleeding, hepatic failure </li></ul><ul><li>- Neurological (P. neuropathy, GB, ataxia </li></ul><ul><li>myelopathy, deafness) </li></ul><ul><li>- PKDL : usually follows TR but can occur </li></ul><ul><li>during TR or wz out history of clinical VL. </li></ul>
  34. 39. <ul><li>PKDL - grade 1 PKDL = rash on the face +/- </li></ul><ul><li>upper chest & arms </li></ul><ul><li>- grade 2 PJDL = dense rash most of the </li></ul><ul><li>face, on the trunk, arm & legs. </li></ul><ul><li>When extensive & black nodule = grade </li></ul><ul><li>2 severe </li></ul><ul><li>- grade 3 = dense rash most of the body </li></ul><ul><li>including hands & feet. Ulceration, crust </li></ul><ul><li>scaling & mucosal spread (PKML) can </li></ul><ul><li>occur. </li></ul>
  35. 42. <ul><li>- Parasites are scanty in PKDL which may serve as a reservoir of infection - PKDL should be differentiated from L. leprosy, measels, fungal infections, syphilis, yaws & T versecolor </li></ul><ul><li>- TR is given for grade 3 & 2 severe. Dose 20 mg/k SSG daily till clinical cure up to 2/12 </li></ul>
  36. 43. <ul><li>Causes of death in VL - intercurrent infection including HIV - hepatic failure - renal failure </li></ul><ul><li>- bleeding - malnutrition - severe anaemia </li></ul><ul><li>- cancrum oris - HF or cardiac arrest (SSG) </li></ul>
  37. 44. <ul><li>VL & HIV Co infection </li></ul><ul><li>- Both are associated wz immune suppres </li></ul><ul><li>and potentiate each other - Suspected in VL pat wz high parasitaemia , non responders & in relapsers </li></ul><ul><li>- Clinical diagn may be diff . Fever, spleno </li></ul><ul><li>and pancytopenia may not be present </li></ul><ul><li>and clinical suspicion may be obscured by opportunistic infections . Presentation may be atypical . </li></ul>
  38. 45. <ul><li>- VL may be rapidly progressive & may </li></ul><ul><li>have predominant GIT symptoms - CD4 < 200 & associated opportunistic </li></ul><ul><li>infections are common - Serology is –ve in up to 50% due to </li></ul><ul><li>depressed immune response </li></ul><ul><li>- Diagn by parasitology . Parasites are </li></ul><ul><li>abundant in LN or BM aspirates. It is +ve in 50% in the buffy coat of blood </li></ul><ul><li>- TR is diff. Relapse rate & mortality high </li></ul>
  39. 46. <ul><li>and drug SE are more severe . - Combined anti leish & anti retroviral </li></ul><ul><li>drugs for TR. </li></ul><ul><li>- Response to anti leishmanial TR is poor </li></ul><ul><li>due to depressed immune resp & increas </li></ul><ul><li>parasite load. Relapse in 50% & relapses </li></ul><ul><li>should only be treated if symptoms are </li></ul><ul><li>severe </li></ul>

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