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UDOM CHAITHONG Ph.D. L’POOL

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OBJECTIVES : TO STUDY MORPHOLOGY LIFE CYCLE GEOGRAPHICAL DISTRIBUTION EPIDEMIOLOGY PATHOGENICITY DIAGNOSIS PREVENTION AND CONTROL

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OBJECTIVE :

Human Malaria Plasmodium malariae (Laveran,1880)

Plasmodium vivax (Grassi & Feletti,1890)

Plasmodium falciparum (Welch,1897)

Plasmodium ovale (Stephens,1922)

ZOONOSIS MALARIA

Plasmodium knowlesi Natural transmission of Plasmodium knowlesi to humans by Anopheles latens in Sarawak, Malaysia 2006

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Geographical Distribution

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HISTORY OF MALARIA

INDIA : AYURAVEDA

AIR, FIRE , WATER EARTH ,BREATH

MASAGAH IS VECTOR

GREEK : ILIAD (HOMER) “PYRETOS” ANOPHELES (HARMFUL) IS THE VECTOR

CHINA: HUANG TI HEADACHE CHILL FEVER “ YAU MU” QINGHAUSU

THAILAND ‘KASAI” FEVER ,CHILL

EGYPT “ AATA” MOSQUITO IS VECTOR

MALARIA HISTORY

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Geographical Distribution

P. malariae & P. vivax Tropical to Temperate Zone

P. falciparum Tropical & Subtropical Zone

P. ovale Tropical Africa & Eastern Asia

Thailand

P. falciparum > P. vivax > P. malariae > P.ovale

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MORPHOLOGY Base on thin blood film

1. Trophozoite 1.1 Early, young, trophozoite (ring form) -Infected red cell - Enlarge -Multiple infected - Common -Trophozoite - Signet ring -Cytoplasm - Light blue -Chromatin - 1 red dot

Plasmodium vivax

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1.2. Growing Trophozoite Form - Amoeboid

Cytoplasm - Light blue Chromatin - Red dot or thread Stippling - Schuffner’s dot Pink dot on cytoplasm Pigment - Fine yellow brown rodlets

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2. Schizont - Early - Chromatin 2 granules

- Growing - Chromatin 4 granules - Mature- Chromatin12-24merozoites - Schuffner’s dot - Pink dots - Pigments - Fine yellow brown

rodlets eccentric mass

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3. Gametocytes 3.1. Young - Cytoplasm - Light blue with no vacuole - Chromatin - Large piece of red dot - Schuffner’s dot - Pink dots - Pigment - Fine granules yellow brown rodlets

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3.2. Microgametocyte (Male gametocyte) Form - Spherical or oval Cytoplasm - Periphery pale blue Chromatin - Abundant or diffused pale pink Pigment - Fine yellow brown rodlets

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3.3.Macrogametocyte (Female gametocyte) Form - Spherical or oval Cytoplasm - Deep blue Chromatin - Compact eccentric pink Pigment - Coarse yellow brown Schuffner’s dot - Pink dots

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Ring form

Amoeboid form

Mature Schizont

Female gametocyte

Male gametocyte

Growing Schizont

WBC

WBC

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Plasmodium malariae 1.Trophozoite 1.1. Young , ring form Infected red cell - Normal Cytoplasm - Deep blue Chromatin - Large red dot compact ring

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1.2. Growing trophozoite 1.2.1.- Band form

Cytoplasm - Deepblue band across the cell Chromatin - Red dot or thread 12.2. - Compact form Cytoplasm - Deepblue compact ring Chromatin - Red dot Stippling Ziemann’s dot ( rare) 12.3. Erregular form

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2. Schizont Early - 2 red chromatin granules Growing - 4 red chromatin granules Late - 6 -12 merozoites (mature) ( rosset form ) Pigment Central blackbrownish mass

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3. Gametocyte

3.1. Microgametocyte Cytoplasm - Pale blue Chromatin - Abundant or diffused pinkish Pigment - Scattered coarse blackbrownish granules

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3.2. Macrogametocyte Cytoplasm - Deep blue Chromatin - Compact or eccentric pink Pigment - Coarse blackbrownish granules are crealy defined

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Ring form

Band form

Compact form

Mature Schizont

Female gametocyte

Male gametocyte

Female gametocyte

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Plasmodium falciparum 1. Trophozoite Infected red cell - Normal red cell Multiple infected - Very common Cytoplasm - Medium blue Chromatin - Red dot Frequently 2 signet rings 2 chromatins in one ring

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1.2. Growing trophozoite Cytoplasm - Medium blue Chromatin - Red dot Stippling - Maurer’s dot Pigment - Fine black granules

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2. Schizont

Early - 2 red dots chromatin

Growing - 4 red dots chromatin Mature - 16-24 merozoites Pigment - Central or eccentric solid fused dark brownish mass Early ,growing and mature are rarely seen in peripheral blood

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3. Gametocyte 3.1.Microgametocyte Form - Crescent, sausage or banana round end in shape Cytoplasm - Pale blue Chromatin - Central diffused pink Pigment - Dark brownish rodlets

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3.2. Macrogametocyte

Form - Crescent , sausage banana

pointed end Cytoplasm - Deep blue Chromatin - Compact eccentric red dot Pigment - scattered coarse granules are clearly defined in dark blackbrownish rodlets

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Ring form

Female gametocyte

Mature Schizont Male gametocyte

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Double chromatins

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Plasmodium ovale

1. Trophozoite

Infected red cell -Enlarge oval red blood cell 1.1. Early , ring Multiple infected - Rare Cytoplasm - Deep blue Chromatin - Large red dot

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1.2. Growing Trophozoite

Cytoplasm - Elongate or oval deep blue

Chromatin - Red dot or thread Pigment - Fine greenish brown granule Stippling - Schuffner’s dot - Pale bluish dots

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2. Schizont

Early - 2 red dots

Growing - 4 red dots Mature - 6-12 merozoites Pigment - Central or eccentric greenish brown mass

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3.Gametocyte 3.1. Microgametocyte Form - Oval or Tear dorp Cytoplasm - Pale blue Chromatin - Abundant diffuse pinkish Pigment - Fine greenish brown Schuffner’s dot - violet blueish dots

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3.2. Macrogametocyte

Form - Oval or Tear dorp

Cytoplasm - Deep blue Chromatin - Compact or eccentric red dot Pigment - Greenish brown granules

Schuffner’s dot - violet blueish dots

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Ring form

Female gametocyte Mature Schizont

Male gametocyte

Growing Schizont

Young gametocyte

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P. knowlesi in human infection could not easily differentiate with other Plasmodium species, especially for atypical form of P. vivax and P. malariae.

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LIFE CYCLE

1. EXOGENOUS PHASE OR MOSQUITO PHASE SEXUAL CYCLE OR SPOROGONY ANOPHELES MOSQUITOES 2. ENDOGENOUS PHASE OR HUMAN PHASE ASEXUAL PHASE OR SCHIZOGONY -A. EXO-ERYTHROCYTIC SCHIZOGONY

-B. ERYTHROCYTIC SCHIZOGONY

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ENDOGENOUS PHASE

A. EXOERYTHROCYTIC SCHIZOGONY

SPOROZOITES

BLOOD CERCULATION

PARENCHYMAL CELL

EXOERTHROCYTIC SCHIZOGONY HYPNOZOITES OR DORMOZOITES (TISSUE SCHIZOGONY)

EXOERYTHROCYTIC MEROZOITES

BLOOD CERCULATION

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B. ERYTHROCYTIC SCHIZOGONY

EXOERYTHROCYTIC MEROZOITES

RED BLOOD CELL

TROPHPZOITES

TROPHOZOITE

SCHIZONT

ERYTHROCYTIC

MEROZOITES

ASEXUAL CYCLE

YOUNG GAMETOCYTE

GAMETOCYTE

MICROGAMETOCYTE

MACROGAMETOCYTE

SEXUAL CYCLE

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EXOGENOUS PHASE

MACROGAMETOCYTE MICROGAMETOCYTE

MACROGAMETE MICROGAMETE

ZYGOTE

( EXFLAGELATION )

OOKINETE

PENETRATE TO MIDGUT WALL

OOCYST

SPOROZOITES

SPOROZOITES IN SALIVARY GLANDS

HUMAN

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Exogenous phase

Endogenous phase

Mosquito phase

Human phase

2 อาทิตย์ ที่ 25 o C

ต่่า กว่า 16 o C จะไม่เกิด Sporogony ในมาลาเรีย ทุกชนิด

Incubation period

PV 13 ( 12-17 ) PO 17 ( 16-18 ) PF 12 ( 9-14 ) PM 28 ( 18-40 )

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CLINICAL FEATURES AND PATHOLOGY THE CHARACTERISTIC FEATURE

OF MALARIA IS FEVER IT USUALLY OCCURS IN THREE STAGE

AS FOLLOWS: 1. COLD STAGE ; 15 - 60 Min. 2. HOT STAGE ; 2 - 6 Hrs. 3. SWEATING STAGE

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1. Cold stage : characterized by

- Rigor and headache

- Patients feel cold and shiver even

though their temperature are rising

- The skin pale and cyanotic

- Take 15 -60 Min.

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2. Hot stage.

The temperature rise to its maximum.

Severe frontal headache

Often vomiting and diarrhea

The skin becomes flushed

Take 2 - 6 Hrs.

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3. Sweating stage

The patient starts to sweat profusely and

usually begins to fell better.

Weak and exhausted and tend to asleep

The temperature is normal, headache and

other pains are relive until the next rigor

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Plasmodium vivax

P. ovale

Benign tertian malaria

Ovale tertian malaria

PERIODICITY P. vivax 48 Hrs. P. falciparum 36-48 Hrs. P. ovale 48 Hrs. P. malariae 72 Hrs.

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Plasmodium malrariae Quartian malarai

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P. vivax 48 Hrs. P. falciparum 36-48 Hrs. P. ovale 48 Hrs. P. malariae 72 Hrs.

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Plasmodium falciparum

Malignant tertian malaria

P. vivax 48 Hrs. P. falciparum 36-48 Hrs. P. ovale 48 Hrs. P. malariae 72 Hrs.

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PATHOGENESIS OF MALARIA

PARASITES DEVELOPMENT IN RBC

1. METABOLISM OF HEMOGLOBIN

2. LYSIS OF INFECTED CELLS 3. SURFACE CHANGES IN RBC

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1. METABOLISM OF HEMOGLOBIN

HEMOZOIN FORMATION

Fe STORE DEPLETION

ANEMIA

TISSUE ANOXIA

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2. LYSIS OF INFECTED CELLS

Stroma

Splenomegaly

(P.falciparum) Increased destruction

normal Rbc

Black-water fever Anuria

Hb

Hemoglobinaemia

Hemoglobinuria

Antigen

+ Antibody

( P.malariae ) Nephritis

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3. SURFACE CHANGES IN RBC

(P. falciparum) Agglutination of parasitized rbc

disseminated intravascular coagulation

localized decreased microcirculation Tissue anoxia

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1, 2, 3 Tissue anoxia

Adrenal Cerebral G I Hepatic Pulmonary Renal shock dysentery edema

hyperpyrexia , coma Jaundice Anuria

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ADDITIONAL ASPECTS OF MALARIA INFECTION

1. Mixed infection

Two species are endemic

PV. + PF. Thailand

PV. + PM . Srilanka, Malasia

PF. + PM . Africa

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2. Chronic malaria - Recrudescence + - Relapses + - Reinfections MALARIA CACHEXIA

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3. Congenital Malaria Infected malaria RBC

Placenta

Fetus 4. Symtompless Parasitaemia

A. Blood Donor B. Highly Endemic Areas

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5. Blood Induced Infections Contaminated -Needles or Syringes

6. Imported Malaria

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Diagnosis 1. DEFINITIVE DIAGNOSIS - Laboratory Diagnosis

2. CLINICAL DIAGNOSIS - Historic - Fever

1. THIN BLOOD FILM 2. THICK BLOOD FILM 3. STAINED - GEIMSA OR WRIGHT STAINED

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THE ENUMERATION OF MALARIA PARASITES OBJCTIVE : TO DEMONSTRATE THE CONCENTRATION IN THE BLOOD AT A PARTICULAR TIMES

1. THICK SMEARS 2. THIN SMEARS

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TREATMENTS

1. BLOOD SCHIZONTOCIDE - CHLOROQUIN, QUININE, MEFLOQUINE, - HALOFANTHRINE, SULFADOXINE, - PYRIMETHAMINE, ARTEMISININE 2. TISSUE SCHIZONTOCIDE - PRIMAQUINE 3. GAMETOCYTOCIDE - PRIMAQUINE 4. SPORONTOCIDE OR ANTISPORGENIC AGENT - PRIMAQUINE, PYRIMETHAMINE

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MOSQUITO VECTORS

Anopheles minimus An. dirus An. maculatus An. aconitus An. sundaicus An. pseudowillmori

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PREVENTION AND CONTROL

1. BLOCKING MAN-VECTOR CONTRACT

2. VECTOR CONTROL 3. TREATMENT OF MALARIA IN CASE 4. DRUG PROPHYLAXIS

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DEGREE OF ENDEMICITY

THE MOST IMPORTANT INTERRELATED FACTORS ARE

1. THE PREVALENCE OF INFECTION IN MAN

- RESERVOIR

2. THE SPECIES OF INDIGENOUS ANOPHELES - VECTORS

3. THE PRESENT OF SUSCEPTIBLE HUMAN POPULATION - NEW HOST

4. LOCAL CLIMATIC CONDITION - GEOGRAPHIC AND HYDROGRAPHIC

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Plasmodium

vivax Plasmodium

malariae Plasmodium

ovale Plasmodium

falciparum

GEOGRAPHIC

ZONES tropics

subtropics

temperate

subtropics

temperate East Asia

subtropics

temperate

tropics

subtropics

PERIODICITY 48 hour

benign tertian 72 hour

quartan 48 hour

tertian 48 hour

malignant

tertian

AGE OF

INVADED

RBC

Reticulocytes Older Cells Reticulocytes All Ages

SIZE AND

APPEARANCE

OF PARASITIZED

RBC

Enlarged Normal or

Small Enlarged

60% oval

20%

fimbriated

edges

Normal

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Plasmodium

vivax Plasmodium

malariae Plasmodium

ovale Plasmodium

falciparum

INCLUSIONS Schuffner's Dots

Ziemann's Dots (rare)

Schuffner's Dots

Mauer's Dots

(rare)

APPEARANCE

OF GROWING TROPHOZOITE

Ameboid Compact and Band Forms

Compact N/A

FORMS IN

PERIPHERAL BLOOD

All

All

All

Rings Gametocytes

NUMBER OF

MEROZOITES IN SCHIZONT

12-24 Ave.16

6-12 , Ave 8

16-24

6-12 , Ave 8