phylum: apicomplexa class: sporozoea sub-class: coccidia order: eucoccidia sub-order:...
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Phylum: Apicomplexa Phylum: Apicomplexa Class: SporozoeaClass: Sporozoea Sub-class: CoccidiaSub-class: Coccidia Order: EucoccidiaOrder: Eucoccidia Sub-order: HaemosporinaSub-order: Haemosporina Family: Plasmodidae Family: Plasmodidae Genus: PlasmodiumGenus: Plasmodium Sub-genus: Plasmodium Laverania Vinckeia …....Sub-genus: Plasmodium Laverania Vinckeia …....
Species: vivax falciparum bergheiSpecies: vivax falciparum berghei malariaemalariae ovaleovale
Causal Agents:Causal Agents:
There are approximately 156 named species There are approximately 156 named species of of Plasmodium Plasmodium which infect various species which infect various species of vertebrates. of vertebrates.
Four are known to infect humans:. Four are known to infect humans:.
P. falciparumP. falciparum, , P. vivaxP. vivax , , P. ovaleP. ovale and and P. P. malariaemalariae. .
P. vivaxmost widespread
P. falciparumprimarily tropics and subtropics
P. malariaesimilar range as P. falciparum
P. ovale
Distribution of Malarial Parasites
Malaria typesMalaria types
Malignant Tertian MalariaMalignant Tertian Malaria
Benign Tertian MalariaBenign Tertian Malaria
Benign Benign QuartanQuartanMalariaMalaria
Benign Tertian MalariaBenign Tertian Malaria
Anopheles mosqouiteAnopheles mosqouite
Vectores in IranVectores in Iran
An. StephenciAn. Stephenci ایران در ناقل پایدارترین و ایران مهمترین در ناقل پایدارترین و مهمترین
An. SuperpictusAn. Superpictus ایران در آنوفل ایران فراگیرترین در آنوفل فراگیرترین
An. DethaliAn. Dethali ایران شرق جنوب در آنوفل ایران کوچکترین شرق جنوب در آنوفل کوچکترین
An. CulicifaciesAn. Culicifacies
An. FluviatilisAn. Fluviatilis فالسیپاروم ناقل فالسیپاروم خطرناکترین ناقل خطرناکترین
An. MaculipennisAn. Maculipennis غرب شمال و درشمال اصلی غرب ناقل شمال و درشمال اصلی ناقل کشورکشور
An. Sacharovi An. Sacharovi کشور غرب شمال و درشمال اصلی کشور ناقل غرب شمال و درشمال اصلی ناقل
Life Cycle:
Life CycleLife Cycle
Geographic DistributionGeographic Distribution
ایران در ماالریا ایران شیوع در ماالریا شیوع
سال سال در کشور 1537815378: : 13811381در در مثبت کشور مورد در مثبت مورد
جمعیت 24/0 24/0 نفر هزار جمعیت در نفر هزار API:API:در
پالسمودیوم 68/1468/14 به مربوط آن پالسمودیوم درصد به مربوط آن درصدفالسیپارومفالسیپاروم
سال سال در منطقه 1161411614: : 13801380در در بیماری منطقه مورد در بیماری مورداست شده گزارش کشور شرقی است جنوب شده گزارش کشور شرقی ..جنوب
•natural (sporozoites/Anopheles)•blood transfusions
• shorter incubation period• fatality risk (P. falciparum)• no relapses possible (vivax/ovale)
•syringe sharing•congenital
• relatively rare although placenta is heavily infected
Malaria Transmission
Pf Pv/Po PmPrepatent Period 6-9 d 8-12d 15-18dIncubation Period 6-25 d 8-27d 16d-8w
Clinical featuresClinical features
History of exposure:(mostly: past travel or residence in disease-endemic areas). (mostly: past travel or residence in disease-endemic areas). Since untreated malaria can progress to severe forms that may be Since untreated malaria can progress to severe forms that may be
rapidly (<24 hours) fatal, malaria should always be considered in rapidly (<24 hours) fatal, malaria should always be considered in patients who have apatients who have a
ParoxsymParoxsym::
1-Chills ( Cold stage)1-Chills ( Cold stage) 2-Fever ( Hot stage)2-Fever ( Hot stage)3- Sweating stage3- Sweating stage
Other clinical features:
splenomegaly, anemia, thrombocytopenia, hypoglycemia, pulmonary splenomegaly, anemia, thrombocytopenia, hypoglycemia, pulmonary or renal dysfunction, and neurologic changes.or renal dysfunction, and neurologic changes.
cold stage• feeling of intense cold• vigorous shivering, rigor• lasts 15-60 min
hot stage• intense heat• dry burning skin• throbbing headache• lasts 2-6 hours
sweating stage• profuse sweating• declining temperature• exhausted, weak sleep• lasts 2-4 hours
• paroxysms associated with synchrony of merozoite release
• temperature is normal and patient feels well between paroxysms
• falciparum may not exhi-bit classic paroxysms• continuous fever• 24 hr periodicity
Malaria Paroxysm
tertian malariaquartan malaria
RelapseRelapse Hypnozoite (Resting stage)Hypnozoite (Resting stage) RecrudescenceRecrudescence Induced malariaInduced malaria HemozoinHemozoin
ها واژه ها توضیح واژه توضیح
Stippling dotsStippling dots
1) Schuffner’s dots1) Schuffner’s dots 2) Maurer’s dots2) Maurer’s dots 3) Ziemann’s dots3) Ziemann’s dots 4) Jame’s dots4) Jame’s dots
Sticky phenomen( knobs)Sticky phenomen( knobs)
Malignant Tertian MalariaMalignant Tertian Malaria Infections caused by Infections caused by P. falciparumP. falciparum can progress to severe; can progress to severe; 1-Cerebral malaria 1-Cerebral malaria 2-Black water fever ( severe anemia)2-Black water fever ( severe anemia) 3-Acute renal failure3-Acute renal failure 4- Algid malaria 4- Algid malaria 5- Respiratory distress syndrome (pneumonic malaria)5- Respiratory distress syndrome (pneumonic malaria) 6- Gastro-intestinal mlaria6- Gastro-intestinal mlaria Complications of Complications of P. vivaxP. vivax malaria include splenomegaly malaria include splenomegaly
(with, rarely, splenic rupture),(with, rarely, splenic rupture), and those of and those of P. malariaeP. malariae include nephrotic syndrome. include nephrotic syndrome.
Karunaweera et al (1992) PNAS 89:3200
• TNF = tumor necrosis factor- ()• proinflammatory cytokine (produced
in response to malarial antigens?)
rigor
sweating
Immunity• slow to develop• short lived
• ‘premunition’• non-sterilizing
• lower parasitemia• less symptoms
Anti-Parasite Immunity• immune response prevents
merozoite invasion, eliminates infected erythrocytes, etc.
Anti-Disease Immunity• eg., neutralization of exo-
antigens or toxic effects
Immunity in MalariaImmunity in Malaria
A) Natural immunityA) Natural immunity 1-Innate immunity1-Innate immunity 2- Genetic immunity2- Genetic immunity
B) Acquired immunityB) Acquired immunity 1-Exo-Erythrocytic stage1-Exo-Erythrocytic stage Premonition: prevents of super-infection no re-infection (stage Premonition: prevents of super-infection no re-infection (stage
specific).specific).
2- Erythrocytic stage2- Erythrocytic stageconcomitant immunity (stage specific & strain specific ):concomitant immunity (stage specific & strain specific ):- Ab mediated immunityAb mediated immunity- Ab dependent cell cytotoxicity (ADCC)Ab dependent cell cytotoxicity (ADCC)- Ab dependent phagocytosisAb dependent phagocytosis- Cellular immunityCellular immunity
Stable or Endemic Malaria
• ~constant incidence over several years• includes seasonal transmission
• immunity and disease tolerance correlates with level of endemicity (especially adults)
Unstable or Epidemic Malaria
• periodic sharp increase in malaria• little immunity• high morbidity and mortality
Malaria Epidemiology
EndemicityLevels:• holo-• hyper-• meso-• hypo-
Malaria laboratory diagnosisMalaria laboratory diagnosis
1) Microscopic identification:1) Microscopic identification: -preparing thick and thin biood smear -preparing thick and thin biood smear -comparison of plasmodium species-comparison of plasmodium species
2- Quality Buffy Coat ( QBC)2- Quality Buffy Coat ( QBC)
3) Immunochromatographic methods3) Immunochromatographic methods
4)Antibody Detection4)Antibody Detection
5) Molecular diagnosis techniques5) Molecular diagnosis techniques
Thin Thin Blood Blood SmearSmear
Thick Blood SmearThick Blood Smear
AA:: Immature schizont in a thin Immature schizont in a thin blood smear.blood smear.B:B: Mature schizont Mature schizont
A B
Multiply infected Multiply infected red blood cells red blood cells with appliqué with appliqué
forms in thin blood forms in thin blood smears smears
A B C
Ruptured schizonts in a thin blood Ruptured schizonts in a thin blood smearsmear..
C D
Malaria antibody detectionMalaria antibody detection The IFA procedure The IFA procedure Blood stage Blood stage PlasmodiumPlasmodium species schizonts species schizonts
(meronts) are used as antigen(meronts) are used as antigen
Enzyme immunoassays have also been employed Enzyme immunoassays have also been employed as a tool to screen blood donors,as a tool to screen blood donors,
but are not recommended for clinical diagnosis due but are not recommended for clinical diagnosis due to limited sensitivityto limited sensitivity
serologic testing is not practical for routine serologic testing is not practical for routine diagnosis of acute malaria. diagnosis of acute malaria.
Antibody detection may be useful Antibody detection may be useful for:for:
1- screening blood donors1- screening blood donors
2- Fever of Unknown Origin2- Fever of Unknown Origin
3- testing a patient who has been recently 3- testing a patient who has been recently treated for malaria but in whom the treated for malaria but in whom the diagnosis is questioned diagnosis is questioned
Species-specific testing is available for the Species-specific testing is available for the four human species: four human species: P. falciparumP. falciparum, , P. vivaxP. vivax, , P. malariaeP. malariae, and , and P. ovaleP. ovale. .
Cross reactions often occur between Cross reactions often occur between PlasmodiumPlasmodium species and species and BabesiaBabesia species. species.
Usefulness of Antibody Usefulness of Antibody Detection in the Detection in the
Diagnosis of Malaria Diagnosis of Malaria ParasitesParasites
Types of Serological Assays Types of Serological Assays MalariaMalaria
Antibody Detection:
Indirect Fluorescent Antibody
Enzyme immunoassays
Antigen Detection:
Immunochromatographic
Antibody DetectionAntibody Detection
=
Antigen-antibodycomplex
Patient’s serumcontains specificand non-specific
antibodies
+
Antigen
Antibody DetectionAntibody Detection
*-labeled antibody to
human antibody
+
Antigen-antibody-
*antibody complex
=
Antigen-antibodycomplex
Indirect Fluorescent Antibody Indirect Fluorescent Antibody (IFA)(IFA)
Microscope slide
Enzyme Immunoassay Enzyme Immunoassay (EIA/ELISA)(EIA/ELISA)
_
+enzymesubstrate
ELISA
Antigen DetectionAntigen Detection
Monoclonal antibody
=
Antigen-antibodycomplex
+
Antigen inpatient’s serum
Antigen DetectionAntigen Detection
=
Antibody-antigen-antibodycomplex
+
Immobilized
monoclonal
antibody
Antigen-antibodycomplex
Antigen DetectionAntigen DetectionMalaria Immunochromatographic Malaria Immunochromatographic
DipstickDipstickOptimal Assay
ControlPlasmodium pan specific
monoclonal antibody
P. falciparum specific
monoclonal antibody
Antigen DetectionAntigen DetectionMalaria Immunochromatographic Malaria Immunochromatographic
DipstickDipstickProblems: Problems: Low sensitivity with parasites density Low sensitivity with parasites density
<100/ml<100/ml
Currently only useful for detection ofCurrently only useful for detection of
P. falciparumP. falciparum infections infections
Diagnostic ToolsDiagnostic Toolsfor Human Infections with for Human Infections with
MalariaMalaria
Blood film Blood film examinationexamination
Serology - IFASerology - IFAPCRPCR
Malaria IFA TestMalaria IFA Test
Sensitivity = 98%Sensitivity = 98%
Specificity = 99.5%Specificity = 99.5%
Sulzer et al, Am J Trop Med Hyg 1969;18:199-Sulzer et al, Am J Trop Med Hyg 1969;18:199-205205
Sulzer et al, Bull Wld Hlth Org 1971;45:375-379Sulzer et al, Bull Wld Hlth Org 1971;45:375-379
P. malariae
P. malariae
P. malariaeP. malariae
P. falciparum
P. falciparum
P. falciparumP. falciparum
A:A: Positive IFA result with Positive IFA result with P. malariaeP. malariae schizont schizont
antigen.antigen.
A
Malaria antibody detectionMalaria antibody detection for clinical diagnosis is performed using the indirect for clinical diagnosis is performed using the indirect
fluorescent antibody (IFA) test. fluorescent antibody (IFA) test.
The IFA procedure can be used as a diagnostic tool to determine The IFA procedure can be used as a diagnostic tool to determine if a patient has been infected with if a patient has been infected with PlasmodiumPlasmodium. .
Blood stage Blood stage PlasmodiumPlasmodium species schizonts (meronts) are used species schizonts (meronts) are used as antigenas antigen
Because of the time required for development of antibody and Because of the time required for development of antibody and also the persistence of antibodies, serologic testing is not also the persistence of antibodies, serologic testing is not practical for routine diagnosis of acute malariapractical for routine diagnosis of acute malaria. .
Enzyme immunoassays have also been employed as a tool to Enzyme immunoassays have also been employed as a tool to screen blood donors, but are not recommended for clinical screen blood donors, but are not recommended for clinical diagnosis due to limited sensitivitydiagnosis due to limited sensitivity
Antibody detection may be useful for:Antibody detection may be useful for:
1- screening blood donors involved in cases of transfusion-1- screening blood donors involved in cases of transfusion-induced malaria when the donor's parasitemia may be below induced malaria when the donor's parasitemia may be below the detectable level of blood film examination the detectable level of blood film examination
2- testing a patient with a febrile illness who is suspected of 2- testing a patient with a febrile illness who is suspected of having malaria and from whom repeated blood smears are having malaria and from whom repeated blood smears are negative ( Fever of Unknown Origin)negative ( Fever of Unknown Origin)
3- testing a patient who has been recently treated for malaria but 3- testing a patient who has been recently treated for malaria but in whom the diagnosis is questioned in whom the diagnosis is questioned
Species-specific testing is available for the four human Species-specific testing is available for the four human species: species: P. falciparumP. falciparum, , P. vivaxP. vivax, , P. malariaeP. malariae, and , and P. ovaleP. ovale. .
Cross reactions often occur between Cross reactions often occur between PlasmodiumPlasmodium species and species and BabesiaBabesia species. . species. .
A:A: Positive IFA result with Positive IFA result with P. malariaeP. malariae schizont antigen. schizont antigen.
A
Rapid Diagnostic Tests(dipstickor test strip)Rapid Diagnostic Tests(dipstickor test strip) (basedon the detection of antigens malaria parasites; Histiding- rich protein II) (basedon the detection of antigens malaria parasites; Histiding- rich protein II)
Comparison of Comparison of PlasmodiumPlasmodium Species Species
TreatmentTreatment• ChloroquineChloroquine
• Sulfadoxine-pyrimethamine (Fansidar) Sulfadoxine-pyrimethamine (Fansidar)
• Mefloquine (Lariam)Mefloquine (Lariam) • Quinine Quinine
• DoxycyclineDoxycycline • Artemisin derivativesArtemisin derivatives
Malaria ControlReduce Human-Mosquito Contact
• impregnated bed nets• repellants, protective clothing• screens, house spraying
Reduce Vector • environmental modificaton• larvacides/insecticides• biological control
Reduce Parasite Reservoir• diagnosis and treatment• chemoprophylaxis