leishmaniasis.pptx
TRANSCRIPT
WEC
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3 mo: 3 mo: double rise F., wt. double rise F., wt. loss, fatigue, severe pallorloss, fatigue, severe pallor
gross non-tender HSMgross non-tender HSM
pancytopeniapancytopenia
A.A. 63y M: 63y M: paronychia: paronychia: ulcerated ulcerated warty, at warty, at base of R. base of R. thumb. thumb. B.B. AsymptomaAsymptomatic 7 crusty, tic 7 crusty, ulcers on ulcers on limbs (1 on L limbs (1 on L ankleankle
Smear: LD Smear: LD bodies. Rx bodies. Rx with with antimoniateantimoniate
Severe Severe disfigurementdisfigurement
Seve
re d
isfigu
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Seve
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Phlebotomus
The VectorThe Vector
BM findingsBM findings
LEISHMANIASISLEISHMANIASIS
At the end of this session you will learnAt the end of this session you will learn Leishmaniasis affects the poorest with Mn, displacement, Leishmaniasis affects the poorest with Mn, displacement,
poor housing, resources, weak immunitypoor housing, resources, weak immunity A A spectrum disease:spectrum disease:• TheThe commonest commonest is ~ is ~ self-healing self-healing skin lesion skin lesion ((75%)75%)
• The worst/The worst/severest is severest is visceral d.visceral d. Kala Azar (Kala Azar (25%)25%) 60% in our60% in our Sub-continent Sub-continenta neglected ID, a neglected ID, should have been controlledshould have been controlled 1 of the important c/of 1 of the important c/of PUOPUO
L. & HIV/TB augments each otherL. & HIV/TB augments each other It is It is curablecurable
Our country is leading to control itOur country is leading to control it
Neglected Tropical Diseases (NTD)Neglected Tropical Diseases (NTD)
Disabling/DisfiguringDisabling/Disfiguring– DALYs vs. mortalityDALYs vs. mortality
StigmaStigma Diseases of PovertyDiseases of Poverty Biblical DiseasesBiblical Diseases Economic tollEconomic toll
– Poverty-promotingPoverty-promoting
• AscariasisAscariasis• TrichuriasisTrichuriasis• HookwormHookworm• SchistosomiasisSchistosomiasis• L. filariasisL. filariasis• OnchocerciasisOnchocerciasis• TrachomaTrachoma• LeprosyLeprosy• Buruli ulcerBuruli ulcer
• Chagas diseaseChagas disease• HATHAT• LeishmaniasisLeishmaniasis• Dengue FeverDengue Fever
WormsWorms
BacteriaBacteria
TissueTissueprotozoaprotozoa
VirusVirus
Prevalence: Prevalence: 12 mln12 mln. . 1.31.3 mln/y mln/y; 30k death; 30k death 350 million at risk350 million at risk
– Cutaneous L (CL)Cutaneous L (CL): : 90% in Afghanistan, Iran, Syria, KSA, 90% in Afghanistan, Iran, Syria, KSA, S S Lanka, Peru, BrazilLanka, Peru, Brazil
– MCLMCL: : 90% in S America90% in S America– Visceral L (VL) Visceral L (VL) (Kala Azar)(Kala Azar)
60% in BD, India, Nepal. 30% in Brazil, Sudan60% in BD, India, Nepal. 30% in Brazil, Sudan
EndemicEndemic in 88 countries (16 western) in 88 countries (16 western) Affects the Affects the rural poorest:rural poorest:
– have little knowledge about it have little knowledge about it – unlikely to seek early Rx., cannot afford Rxunlikely to seek early Rx., cannot afford Rx
Depth of the ProblemDepth of the Problem
1.5 million globally
WORLD DISTRIBUTION OF VLWORLD DISTRIBUTION OF VL
109 districtsof BD, India& Nepal
Bangladesh ScenarioBangladesh Scenario A A re-emerging IDre-emerging ID since 1990; disappeared during since 1990; disappeared during
‘Malaria Eradication Pgm’ ‘Malaria Eradication Pgm’ (1961-70)(1961-70)– poor control of vectorpoor control of vector– lack of access to Rxlack of access to Rx
139 Upazillas: 139 Upazillas: 45 districts45 districts PrevalencePrevalence 45k. 45k. IncidenceIncidence 10k/y10k/y
– 55% in 55% in MymensinghMymensingh– 25% in 25% in Pabna, Tangail, JamalpurPabna, Tangail, JamalpurBD has committed to eliminate kA/2015 (<1/10k popn. at BD has committed to eliminate kA/2015 (<1/10k popn. at
Upazila level). Upazila level). Now it is almost controlled!Now it is almost controlled!
Districts Affected in BangladeshDistricts Affected in Bangladesh
SynonymsSynonyms
Kala-azar, visceral L (VL), black fever, leishmaniasis, Kala-azar, visceral L (VL), black fever, leishmaniasis, Dumdum fever, Assam FDumdum fever, Assam F
Mucocutaneous L, cutaneous L, bay sore, Mucocutaneous L, cutaneous L, bay sore, espundiaespundia, , mucosal L, post-kala-azar dermal L, viscerotropic L, mucosal L, post-kala-azar dermal L, viscerotropic L, forest yaws, Aleppo evilforest yaws, Aleppo evil
Baghdad sore, Biskra button, Chiclero ulcer, Delhi Baghdad sore, Biskra button, Chiclero ulcer, Delhi boil, Oriental sore, Rose of Jericho, Uta boil, Oriental sore, Rose of Jericho, Uta
Only a small fraction infected develop the d.Only a small fraction infected develop the d. A zoonosis; mammalian reservoirsA zoonosis; mammalian reservoirs ETIOLOGY: ETIOLOGY: Leishmania:Leishmania: obligate intracellular obligate intracellular
– One sp. can cause different syn.One sp. can cause different syn.– One syn. can be c/by different spp.One syn. can be c/by different spp.
Vector: Vector: femalefemale sand-fly. 2-3mm sand-fly. 2-3mm Phlebotomus & LutzomyiaPhlebotomus & Lutzomyia
ReservoirReservoir:: Indian KA: humanIndian KA: human rodents in Africa, foxes in Brazil, C. Asiarodents in Africa, foxes in Brazil, C. Asia dogs in the Mediterranean, Chinadogs in the Mediterranean, China
EPIDEMIOLOGYEPIDEMIOLOGY
Mediterranean & ChinaMediterranean & China
VectorVector lives in cracks of mud-houses, heaps of cow dung, in lives in cracks of mud-houses, heaps of cow dung, in rat burrows, bushesrat burrows, bushes
Feed mainly on cattle. Feed mainly on cattle. We are 2nd choice! More We are 2nd choice! More exposure:exposure:– extracting timber, mining, building damsextracting timber, mining, building dams– irrigation, road making in forestsirrigation, road making in forests
Transmission: Transmission: CommonCommon:: bitebite by by vector. Uncommon: vector. Uncommon:
– congenital, BT, needle sharingcongenital, BT, needle sharing– rarely: inoculation from culturerarely: inoculation from culture
IP: IP: Cut. L: ~several weeksCut. L: ~several weeks Visceral L: 6 w-6 mo (10 d-10 y)Visceral L: 6 w-6 mo (10 d-10 y)
3 syndromes of Leishmaniasis3 syndromes of Leishmaniasis Cutaneous LCutaneous L
– Old World: Old World: L tropica, L major,L tropica, L major, L aethiopica, L donovaniL aethiopica, L donovani , , L infantum,L infantum, L mexicanaL mexicana
– New World: New World: L amazonensis, L braziliensis, L panamensis, L guyanensis,L amazonensis, L braziliensis, L panamensis, L guyanensis, L chagasiL chagasi
Mucocutaneous LMucocutaneous L by by L braziliensis, L panamensis, L guyamenis, L L braziliensis, L panamensis, L guyamenis, L amazonensisamazonensis
VLVL by by L donovani,L donovani, L infantum, L chagasi,L infantum, L chagasi, L tropica,L tropica, L amazonensisL amazonensis
Post-kala-azar dermal L (PKDL)Post-kala-azar dermal L (PKDL)Old WorldOld World: : L donovani, L infantumL donovani, L infantum
New World: New World: L donovani chagasi:L donovani chagasi: Central &, S America Central &, S America
Life cycleLife cycle
2 forms 2 forms – amastigoteamastigote (no flagella) in host (no flagella) in host– promastigotepromastigote in vector & in vector & mediummedium
Amastigotes in blood meal become flagellate in vector & Amastigotes in blood meal become flagellate in vector & multiply over 6-9dmultiply over 6-9d
Following bite: flagellates enter RES & change to Following bite: flagellates enter RES & change to amastigote; amastigote; multiply by binary fissionmultiply by binary fission
PathogenesisPathogenesis
RES is invaded: RES is invaded: mainly spleen, liver, BMmainly spleen, liver, BM Monocytes spread parasitesMonocytes spread parasites Outcome: Outcome: virulence ~immunityvirulence ~immunity Marked Marked suppression of CMI. suppression of CMI. Overproduction of IgOverproduction of Ig
Spleen:Spleen: Bag of parasites! Bag of parasites! – enlarged, soft, fragile, dilated BVenlarged, soft, fragile, dilated BV– Billroth cells Billroth cells are over-parasitized; are over-parasitized; No fibrosisNo fibrosis
Liver:Liver: Kupffer cells Kupffer cells over-parasitizedover-parasitizedBM: BM: parasitized monocytes replace normal tissueparasitized monocytes replace normal tissue
Kupffer cells (stellate Kupffer cells (stellate macrophagesmacrophages & & KupKup
ffer-Browicz cells)ffer-Browicz cells)
Cutaneous L.Cutaneous L. Bite site Bite site macule/nodule macule/nodule shallow ulcer,shallow ulcer, raised borders: raised borders:
commonly face, limbscommonly face, limbs May have satellite lesions & LAPMay have satellite lesions & LAP Self-healingSelf-healing in weeks-years with in weeks-years with atrophic (cigarette atrophic (cigarette
paper) scar.paper) scar. But can cause serious disfigurement But can cause serious disfigurement
On recovery: On recovery: immunityimmunity to infecting sp. to infecting sp.
CL. MANIFESTATIONSCL. MANIFESTATIONS
Typical C. LTypical C. L
Satellite lesionsSatellite lesionsCrater lesion of CLCrater lesion of CL
Diffuse CLDiffuse CL
Disseminate in skinDisseminate in skin Resistant to RxResistant to Rx DD from leprosyDD from leprosy
MCL (espundia)MCL (espundia)
Rare in children Rare in children Invasive Invasive disfiguringdisfiguring d.: destroys mucosa d.: destroys mucosa 90% in S America90% in S America Commonly around nose. Heals with Commonly around nose. Heals with scarsscars Significant mortality/morbiditySignificant mortality/morbidity Mucosa may perforateMucosa may perforate
MCL: mucocut. LMCL: mucocut. L
MCL: PerforationMCL: Perforation
CLCL
MCLMCL
Visceral L. (kala-azar)Visceral L. (kala-azar)Severest & Progressive. Severest & Progressive. Death Death in 2yin 2y Malnourished people most susceptibleMalnourished people most susceptible India-Bangladesh-Nepal: 300k/y. India-Bangladesh-Nepal: 300k/y. 200 million at 200 million at
riskrisk– 52 districts 52 districts of India of India – 45 ,, 45 ,, of Bangladeshof Bangladesh– 12 ,, 12 ,, of Nepalof Nepal
Control program in BD in 2007: new cases dropped Control program in BD in 2007: new cases dropped from 10k/y to 1463 in 2012, MR now close from 10k/y to 1463 in 2012, MR now close
to zero. BD is on track to eliminate VL/2015to zero. BD is on track to eliminate VL/2015
Typical PresentationTypical Presentation
Chr. F: double rise, good appetite, HSM, progressive pallor, Chr. F: double rise, good appetite, HSM, progressive pallor, weakness, wt. loss, darkening skinweakness, wt. loss, darkening skin
Panacytopenia, LAPPanacytopenia, LAP albumin, albumin, -Ig-Ig
2y infx. common2y infx. commonReactivation is common in HIV,Reactivation is common in HIV,TB, or immunodeficienciesTB, or immunodeficiencies
Jaundice Jaundice (10%)(10%) is rare: is rare: Bad prognosisBad prognosis Immune complexes: mild GNImmune complexes: mild GN Rh. Factor may be positiveRh. Factor may be positive Fulminant form Fulminant form mainly in children: pancytopenia & ALF (ac. mainly in children: pancytopenia & ALF (ac.
liver failureliver failure))
Skin lesions in VLSkin lesions in VL dark, dry, thin, scalydark, dry, thin, scaly diffuse wartydiffuse warty petechiae, bruisespetechiae, bruises hair losshair loss edemaedema
Atypical presentations of KAAtypical presentations of KA PUO/FUO: an important causePUO/FUO: an important cause Pancytopenia without splenomegalyPancytopenia without splenomegaly Immune hemolysisImmune hemolysis Generalized LAP with/-out HSMGeneralized LAP with/-out HSM Massive hepatic necrosisMassive hepatic necrosis Retinal bleedRetinal bleed
Severe Anemia in KASevere Anemia in KA BM replaced by parasitesBM replaced by parasites BM depression, splenic sequestration, hge, hemolysis, 2y inf.BM depression, splenic sequestration, hge, hemolysis, 2y inf.
Clinical case definition for KAClinical case definition for KAResiding/travelling in endemic areasResiding/travelling in endemic areasF. for >2w & any 1:F. for >2w & any 1:Splenomegaly or wt. loss or anemiaSplenomegaly or wt. loss or anemia
And ‘rk39’ test positiveAnd ‘rk39’ test positive
Clinical case definition for PKDLClinical case definition for PKDLResiding/travelling in endemic areasResiding/travelling in endemic areasRx of KA any time in pastRx of KA any time in pastSkin lesion lesions (macular, papular, nodular, or mixed) Skin lesion lesions (macular, papular, nodular, or mixed)
without loss of sensationwithout loss of sensationExclusion of other cause of skin d.Exclusion of other cause of skin d.‘‘rk39’ positive/slit skin smear positive/PCR positiverk39’ positive/slit skin smear positive/PCR positive
DefinitionsDefinitions Primary KA (PKA)Primary KA (PKA)Dx KA with case definition & not RxDx KA with case definition & not Rx
KA treatment failure(KATF)KA treatment failure(KATF)Dx. KA again with case defn. after Rx within last 1y. All efforts should Dx. KA again with case defn. after Rx within last 1y. All efforts should
be made to Dx parasitologically by splenic/BM smear or PCRbe made to Dx parasitologically by splenic/BM smear or PCR
Relapse KARelapse KADx KA with case defn. & Rx in past but not within last 1y. All efforts Dx KA with case defn. & Rx in past but not within last 1y. All efforts
are made to Dx parasitologically by splenic/BM smear or PCRare made to Dx parasitologically by splenic/BM smear or PCR
DxDx
Showing MOShowing MO
CL/MCL:CL/MCL: biopsy, scrapings, FNAC, biopsy, scrapings, FNAC, LN:LN: aspiration/ aspiration/ biopsy, biopsy, tissue tissue punch biopsypunch biopsy
VL: VL: spleen, BM, liver, LN puncturespleen, BM, liver, LN puncture
Blood culture may help (~1 mo): Novy-McNeal-Blood culture may help (~1 mo): Novy-McNeal-Nicolle medium (3N medium). Blood smears from Nicolle medium (3N medium). Blood smears from buffy-buffy-coat in HIVcoat in HIV
Immunological tests:Immunological tests:
Immunological testsImmunological tests
Specific: RDTSpecific: RDT (recombinant Ag.(recombinant Ag. rk39 rk39), DAT (IgM) at ), DAT (IgM) at early stage; ICT: highly sensitiveearly stage; ICT: highly sensitive
NonspecificNonspecific– CIE, CFT, IF Ab test: cross-react with leprosy, Chaga, CIE, CFT, IF Ab test: cross-react with leprosy, Chaga,
malaria, schistosomiasismalaria, schistosomiasis– Detection of hyper-Ig: AT. CT (3 mo)Detection of hyper-Ig: AT. CT (3 mo)
A negative serology does not exclude LA negative serology does not exclude L..
rK39rK39 Rapid dipstick test Rapid dipstick test Based on the Based on the
recombinant k39 recombinant k39 proteinprotein
Test Test Sensitivity %Sensitivity % Specificity %Specificity %CFTCFT 70-8070-80 60-7360-73
DATDAT 91-10091-100 72-10072-100IFATIFAT 55-7055-70 70-8970-89ELISA (CSA)ELISA (CSA) 80-10080-100 50-7050-70ELISA ( rK39)ELISA ( rK39) 100100 9898rK39 rapid strip testrK39 rapid strip test 100100 88-9888-98
Latex agglutination Latex agglutination testtest
68-10068-100 100100
Spleen puncture
Slide preparation
A. intact macrophage full of LDB. B. Amastigotes are freed A. intact macrophage full of LDB. B. Amastigotes are freed from a rupturing macrophagefrom a rupturing macrophage
LeishmaniaLeishmania organisms in PBF in HIV organisms in PBF in HIV
Peripheral Blood PicturePeripheral Blood Picture Severe normocytic-chromic anemiaSevere normocytic-chromic anemia Leukopenic relative lymphocytosisLeukopenic relative lymphocytosis ThrombocytopeniaThrombocytopenia Raised ESRRaised ESR High Ig with reversal of AG ratioHigh Ig with reversal of AG ratio
BM aspirationBM aspiration Commonest method. Sensibility 86%. Safer than splenic Commonest method. Sensibility 86%. Safer than splenic
puncturepuncture
Splenic puncture: Splenic puncture: 98%. 98%. Risk: bleedRisk: bleed If BM is inconclusiveIf BM is inconclusive
DrugsDrugs Liposomal Amphotericin B: IV; Miltefosine: POLiposomal Amphotericin B: IV; Miltefosine: PO
LABLAB is now DoC; single dose works (97%) is now DoC; single dose works (97%) Amphotericin B. Amphotericin B. Na stibogluconate (SSG): IMNa stibogluconate (SSG): IM MiltefosineMiltefosine is newis new PentamidinePentamidine Paromomycin in VL. It is low-costParomomycin in VL. It is low-cost Ketoconazole, ItraconazoleKetoconazole, Itraconazole
The commonest drug for VL was The commonest drug for VL was SSGSSG x 4w; now variably x 4w; now variably resistant in many countriesresistant in many countries
TREATMENTTREATMENTCL CL may heal spontaneously. may heal spontaneously. TreatTreat if if
– disabling/disfiguring ulcers, late healing, MCLdisabling/disfiguring ulcers, late healing, MCL
S. American CL: S. American CL: ketoconazole, itra-, paromomycin, plus ketoconazole, itra-, paromomycin, plus local local heatheat
VLVL Bangladesh: most are still sensitive to SSGBangladesh: most are still sensitive to SSG
DoC: LABDoC: LAB MiltefosineMiltefosine is taken p.o. is taken p.o. Paromomycin Paromomycin has excellent safetyhas excellent safety
Always treat if MCL or VLAlways treat if MCL or VL
VL: Supportive RxVL: Supportive Rx– RestRest– High-calorie dietHigh-calorie diet– BTBT– Rx secondary inf.Rx secondary inf.
Symptoms rapidly improveSymptoms rapidly improve Spleen regresses over monthsSpleen regresses over months
Patients must be counseled about the importance ofPatients must be counseled about the importance ofFU for relapseFU for relapse
Post KA Dermal L (PKDL)(10%)Post KA Dermal L (PKDL)(10%) Follows Follows completecomplete Rx after 1-2y; Rx after 1-2y; may last up to 20ymay last up to 20y
No disability! No disability! Seek Rx for social stigma!Seek Rx for social stigma! SSG x 4 mo is potentially toxic & cumbersomeSSG x 4 mo is potentially toxic & cumbersome MiltefosineMiltefosine x12w is effective (93%) x12w is effective (93%) LAB 2 doses: LAB 2 doses: 5 mg/kg/w x 3w is successful5 mg/kg/w x 3w is successful Consider combinations of LAB & miltefosine, miltefosine & Consider combinations of LAB & miltefosine, miltefosine &
paromomycin, or miltefosine & SSGparomomycin, or miltefosine & SSG
DD of VLDD of VL Malaria, tropical splenomegaly syn.Malaria, tropical splenomegaly syn. EF, Portal HTNEF, Portal HTN Leukemias & lymphomasLeukemias & lymphomas Chr. hemolytic anemiaChr. hemolytic anemia
PKDLPKDL Yaws; Syphilis; LeprosyYaws; Syphilis; Leprosy
CL: CL: traumatic ulcerstraumatic ulcers
MCL: MCL: Leprosy; Sarcoidosis; Midline granuloma, Leprosy; Sarcoidosis; Midline granuloma, Histoplasmosis; Syphilis, tertiary yawsHistoplasmosis; Syphilis, tertiary yaws
PROGNOSISPROGNOSIS CL: CL: may be self-limiting. Excellentmay be self-limiting. Excellent Diffuse CL & MCL: Diffuse CL & MCL: good on Rxgood on Rx
VL: VL: fatal if untreated: mortality 10% in Rxfatal if untreated: mortality 10% in Rx
Causes of death in VLCauses of death in VL 2y infx.: pneumonia; septicemia2y infx.: pneumonia; septicemia DysenteryDysentery TB, HIVTB, HIV Cancrum oris, uncontrolled hgeCancrum oris, uncontrolled hge
KA elimination in SEA is possibleKA elimination in SEA is possible Confined to 3 countriesConfined to 3 countries Humans are the only reservoirHumans are the only reservoir Only 1 vector: control by indoor Only 1 vector: control by indoor residualresidual spray spray
Permethrin treated nets, good housing, screen, Permethrin treated nets, good housing, screen, clothing, repellent, minimum outdoor exposures clothing, repellent, minimum outdoor exposures dusk-dusk-dawndawn
A RDT is availableA RDT is available LAB & Miltefosine are safeLAB & Miltefosine are safe Strong political willStrong political will
Target:Target:To reduce incidence of KA &PKDL to <1/10k popn.:To reduce incidence of KA &PKDL to <1/10k popn.:Early Dx Early Dx & complete Rx: & complete Rx: stops transmissionstops transmissionSurveillance; health educationSurveillance; health educationReducing incidence in endemic communitiesReducing incidence in endemic communitiesReducing CFR (case fatality rates)Reducing CFR (case fatality rates)Rx PKDL to reduce the parasite reservoirRx PKDL to reduce the parasite reservoirPx & Rx of KA-HIV-TB co-inf.Px & Rx of KA-HIV-TB co-inf. Integrated vector managementIntegrated vector management
Integrated vector Mx (IVM)Integrated vector Mx (IVM)Indoor Residual Spray (IRS):Indoor Residual Spray (IRS):
Insecticide Deltamethrin; 6 rounds; 1 round in Insecticide Deltamethrin; 6 rounds; 1 round in
moderate & low endemic areasmoderate & low endemic areas
Piloting was done at Fulbaria in 2011Piloting was done at Fulbaria in 2011
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IRS AT DHANIKHOLA VILLAGE OF TRISHAL UPAZILLA
Dr. Shah GolamNabi, DPM, KEP, CDC, DGHS with the IRS Team ( Spray man, Team leader & 1st
Line Supervisor) at Dhanikhola Village, Trishal Upazilla.
Integrated Vector Mx (IVM)Integrated Vector Mx (IVM)
LLIN (Long Lasting Insecticidal Net)LLIN (Long Lasting Insecticidal Net) Distribution Distribution
Larvicide Spray in Cow & chicken shadeLarvicide Spray in Cow & chicken shade
Effective disease surveillanceEffective disease surveillance
WHO supported staffs for WHO supported staffs for strengthening Surveillancestrengthening SurveillanceNational ConsultantNational ConsultantSurveillance Medical OfficerSurveillance Medical OfficerData ManagerData Manager Regular collection of Data from Regular collection of Data from
all KA Endemic UHCall KA Endemic UHC Active case search for detection of Active case search for detection of
KA in household levelKA in household level
Social mobilization & Social mobilization & partnerships partnerships
Partnership with- WHO, MSF & icddr,b
MCQMCQ In L. spectrum d. the commonest is Kala AzarIn L. spectrum d. the commonest is Kala AzarKA, is 2nd biggest parasitic killer after malaria KA is spread by infected mosquitoKA is spread by infected mosquito Thrombocytopenia is a common featureThrombocytopenia is a common feature Reservoir in Indian KA is dogReservoir in Indian KA is dog LAB single dose is effectiveLAB single dose is effective
MCQMCQ
DAT is a specific test for KADAT is a specific test for KA ICT is a non-specific test for KAICT is a non-specific test for KA Splenic puncture more sensitive than BMSplenic puncture more sensitive than BM Most VL in Bangladesh is sensitive to SSGMost VL in Bangladesh is sensitive to SSG Severe anemia is common in KASevere anemia is common in KA HIV, TB & VL augments each otherHIV, TB & VL augments each other
Evening at TeknafEvening at Teknaf
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