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MALARIA

Yuankai Wu

Department of infectious diseases

The Third Affiliated Hospital

Sun Yat-Sen Universicty

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Malaria a vector-borne disease caused by single

celled parasites, the Plasmodiumprotozoa, and transmitted by female

Anopheles mosquitoes.

Characterized by malarial paroxysm ofchills, fever and sweats.

Still an enormous pubichealth problem and one

of the most common

infectious diseases.

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History of malaria

Malaria has infected humans for over

50,000 years.

first recorded in 2700 BC in China.

originates from MedievalItalian:

mala aria "bad air";

was formerly called ague ormarsh feverdue to its association with swamps and

marshland
http://en.wikipedia.org/wiki/Middle_Ageshttp://en.wikipedia.org/wiki/Italian_languagehttp://en.wikipedia.org/wiki/Miasma_theory_of_diseasehttp://en.wikipedia.org/wiki/Miasma_theory_of_diseasehttp://en.wikipedia.org/wiki/Italian_languagehttp://en.wikipedia.org/wiki/Middle_Ages

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History of malaria

1880, a French army doctorfirst observed parasites inpatients RBC. the 1907 NobelPrize for Physiology or

Medicine.

1898, Britain's Sir RonaldRoss finally proved that

malaria is transmitted bymosquito.(1902 Nobel Prize)

Charles Louis Alphonse Laveran

MullerSwiss chemist, discovered DDT to kill mosquito in 1930 (1984 Noble)WagnerAustrian psychiatristused the high fever of malaria to treat dementia

in stage-III syphilis(1927 Nobel)
http://upload.wikimedia.org/wikipedia/commons/3/35/Alphonse_Laveran.jpghttp://upload.wikimedia.org/wikipedia/commons/3/35/Alphonse_Laveran.jpg

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Malaria

1. Etiology (life cycle) 2. Epidemiology

3. Pathogenesis and pathology

4. Clinical manifestation 5. Diagnosis

6. Differential diagnosis

7. Therapy

8. Prevention

9. Summary

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Etiology

Plasmodium protozoa

P. falciparum (the deadliest);

P. malariae ;

P. ovale ;

P. vivax(the most common);

Within each species there are variant

strains.

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Life cycle Sexual cycle in mosquito

Gametocyte, gamete, zygote,

ookinete, oocyst, sporoblast,

sporozoite

Asexual cycle in Human

Exoerythrocytic stage:

sporozoite, tachysporozoite

(12-20d), bradysporozoite

(hypnozoite) (6-11m),

merozoite, schizont,

Erythrocytic stage:

ring form, trophozoite, schizont,

gametocyte

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Ring form

Trophozoite

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Schizonte

Gametocyte

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Release

merozoites

Merozoite

SporozoiteTachysporozoite

Bradysporozoite

Release

merozoites

3-6 generations

in RBCs

Fertilization

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Epidemiology

Source of infection

Patients

Asymptomatic carriers

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Epidemiology

Route of transmission

Bite by female anopheles mosquitoes.

Vertical transmission (placenta)

Blood transfusion

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Epidemiology

Susceptibility

All susceptible

Travelers and foreigner

Children, pregnant women

Short immunity, without cross immunity.

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Epidemiology

Epidemiological feature

Seasons: Summer and Autumn (temperature)

In china,P. vivax is predominant,P. falciparum

second,P. malariae andP. ovale seldem.

Endemic areas: tropic or sub-tropic area.

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Endemic countries of malaria (2003)NOTE: In most of these countries malaria was limited to certain areas

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The mortality of malaria in china in 1952-1998

Year

D

eath

(/10,0

00

)

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Pathogenesis

Toxic mediators

Inflammatoryresponses

Hemolysis

Adhere to

blood vessels

hypoglycaemia

Chill, fever, sweat

Anemia

Obstruct

blood flow

Splenomegaly

hepatomegaly

Phagocytosis renal failure

Black water fever

metabolic

disturbances

Tissue hypoxia

Impaired

microcirculation DIC

Cerebral malaria

Pulmonary edema

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Clinical manifestation

Incubation period:

7~30d (7~12, 13~15, 24~30)

Malaria paroxysm:

chills, fever and sweating.

Periodicity: every 48h (P. vivax, P. ovale)

every 72h (P. malariae)

every 36-48h (P. falciparum) Between attacks:

feel fine (P. vivax, ovale or malariae)

or miserable (P. falciparum)

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typical attack

Chilling stage: 20min~1h, feel cold andtrue shaking chills, accompanied withmalaise, headache, vomiting or diarrhea.

Hot stage: 2~6h, T usually as high as41, tachycardia, hypotension, cough,headache, backache, but normalconsciousness.

Sweating stage: 30min~1h, T falls withdiaphoresis, fatigue and weak.

Common signs: anemia, splenomegaly.

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Intermittent fever of P. vivax

40

39

3837

12 3 4 5 6 7 8 9 10 11 12 13 Days

synchronization

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Intermittent fever

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severe attack

Cerebral malaria: P. falciparum infection, T, antimalarial drugs.

Obstruction of vessels and hypoglycemia.

Severe headache, high fever.

Impairment of consciousness: confusion,

obtundation, seizures and coma.

Neurologic sign: hyper-reflexion and bilateral

Babinskis sign. Focal neurologic finding

occurs rarely.

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The severtity of clinical manifestations

Parasitemia P. falciparum: 1,000,000/ mm3

P. vivax and P. ovale: 25,000/mm3

P. malariae: 10,000/mm3

Infected RBC P. falciparum: RBCs of any age.

P. vivax and P. ovale: younger RBCs.

P. malariae: older RBCs.

Multiply speed P. falciparum: 36-48h

P. vivax and P. ovale: 48h

P. malariae:72h

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Recrudescence and Relapse

Recrudescence: residual plasmodium in the bloodstream.

could be found in all the four species

infection. 1~4wk after relieved, or repeatedly.

Relapse:

hypnozoites in the hepatocytes.

only found in P. vivax and P. ovale.

usually 3~6mon after cured.

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special type

malaria in pregnancy:

main adult risk group.

80% death of malaria in Africa.

more aggravated: anemia, fever,hypoglycemia, cerebral malaria,pulmonary edema, puerperal(afte labor)

sepsis. Low birth weight, prematurity.

Vertical transmission.

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special type

Malaria infected by blood transfusion:

Symptoms: the same as malaria transmited bymosquitoes.

Shorter Incubation stage:7-10d.no exoerythrocytic stage

No hypnozoite, no relapse.

Malaria infected by vertical transmission: Symptoms: the same

Incubation stage: about 1wk after birth.

No hypnozoite, no relapse.

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Complications

Hemolytic urinemic syndrome (blackwater fever)

Pulmonary edema.

Hyperreactive malarial splenomegaly. Shock, hypotension.

Diarrhoea, jaundice, splenic rupture.

Anemia, hemorrhage, DIC. Hypoglycaemia, metabolic acidosis.

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Complications

Hemolytic urinemic syndrome

More common in adults, rare in children.

More frequent in patients without immunity

and with high parasitemia and G6PDdeficiency after quinine or primaquine.

Intravascular hemolysis, hemoglobinuria.

Lumbago, dark urine(black water), jaundice,oliguria, renal failure.

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Complications

Hemolytic urinemia syndrome(blackwater fever).

Pulmonary edema.




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Complications

Pulmonary edema

Uncommon, even in severe infection.

Patients with hyperparasitemia.

Results from capillary leak rather than

heart failure.

A fatal complication.

Treated with positive-pressure artificialventilation.

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Complications


Pulmonary edema.




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Complications

Hyperreactive malarial splenomegaly

Tropical splenomegaly syndrome (TSS).

Seen in older children and adults.

Associated with repeated infection In

hyperendemic area.

Anemia, massive splenomegaly, elevated IgM

levels and malarial antibody. Usually responds to prolonged treatment with

prophylactic antimalarial drugs.

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Complications


Pulmonary edema.


Diarrhoea, splenic rupture.

Hemorrhage, DIC. Hypoglycaemia, metabolic acidosis.

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Diagnosis

Epidemiological history

Traveled in endemic areas (bitten by a mosquito)

Blood transfusion or organ transplantion


Typical malaria paroxysm

Intermittent fever, Several small fever spikes

Pathogenic detection

Thick and thin film

Diagnositic therapy in atypical cases

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Diagnosis

Pathogenic Investigations Microscopic diagnosis

Quantitative buffy coat(QBC)

Antigen detection: RDTs

Serology test: ELISA, IFA

Molecular diagnosis: PCR

Other: complete blood count, blood chemical tests of liver

function and renal function.

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Diagnosis

Microscopic diagnosis

Blood smear (Gold standard)

The most preferred, economic, and reliable

Thick film: sensitive, diagnosis of infection

Thin film: identification of species

Giemsa's staining positive

Ring form and Gametocyte of P falciparum

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Ring form and Gametocyte ofP. falciparum

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Diagnosis

Pathogenic Investigations

Microscopic diagnosis

Quantitative buffy coat(QBC) Antigen detection: RDTs

Serology test: ELISA, IFA

Molecular diagnosis: PCR

others

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Differential diagnosis

Infectious diseases Influenza

Sepsis

Typoid, paratypoid fever

Leptosirosis Dengue fever

Japanese B encephalitis

toxic dysentery

Hemorrhagic fever withrenal failure

Acute intravascularhemolysis

Non-infectious diseases Lymphoma, leukaemia

Malignant histocytosis

Connective tissuediseases

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Prognosis

Curable if treated in early stage.

Chronic malaria in hyperendemic areas.

Kill up to 15%~20% children

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Treatment

Symptomatic and supportive measures

Relief of high fever

Intravenous injection to sustain fluid balance

Treatment hypoglycemia

Dehydration in cerebral malaria

Blood transfusion for severe anemia

Hemodialysis when renal failure

Antimalarial treatments.

A i l i l T

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Antimalarial Treatment

Tissue schizonticides (causal prophylaxis) Pyrimethamine and Primaquine

Blood schizonticides (terminate attacks) Chloroquine , Artemisinine, Quinine, Mefloquine, Halofantrine,

Pyrimethamine, Sulfadoxine, Sulfones, Tetracyclines,

Doxycycline

Tissue schizonticides (prevent relapse) Primaquine, tafenoquine and Pyrimethamine

Gametocytocides (block transmission) Primaquine, tafenoquine, Chloroquine, Quinine, Artemisinine

Sporozoitocides (ablate transmission of mosquito) Primaquine and proguanil

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Antimalarial strategy

Blood schizonticides

Gametocytocides /

Tissue schizonticides

Chloroquine

Artimesinine, Artesunate

Primaquine

Tafenoquine

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Available drugs

Quinine

0.65g tid7d

Seldom used now

The first effective treatment for malariacame from the bark of cinchona tree,which contains quinine.
http://upload.wikimedia.org/wikipedia/commons/6/66/Cinchona.pubescens01.jpg

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Available drugs

Chloroquine (phosphate) Most common used

1.0 po., 0.5 po.6~8h later on the first day

0.5 po. Qd on the second and third day

Drug resistance (P. falciparum)

Quinine +

Doxycycline/Tetracycline/clindamycin

Artemisinine or Artesunate

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Available drugs

Artemisinine and Artesunate

Powerful and less resistant

Artemisinine

1.0 po., 0.5 po.6~8h later on the first day

0.5 po. Qd on the second and third day

Artesunate

100mg bid1d50mg bid4d

Cerebral malaria and pregnant patients

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Available drugs

Primaquine (phosphate)

Most commonly used Gametocide

Prevent relapse and block transmission

7.5mg tid 8d

Acute intravascular hemolysis

(black water fever)

Routine G6PD test!!

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Cerebral malaria

Artesunate

60mg iv. drip, at 0, 4, 24, 48hr

50mg bid2~3d

Chloroquine

16mg/kg8mg/kg conscious po.

Quinine 500mg q12h conscious po.

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Caution

Repeat the thick and thin blood smear

Do not use Doxycycline, Primaquine,

Mefloquine, Atovaquone-proguanil in

Pregnant women.

Routine G6PD test?

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Prevention

Control the source of transmission

Cut off the route of transmission

Protection of susceptible population

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Prevention

Source of transmission

Cases management

Cure the patients and carriers

use gametocides and blood schizonticides simultaneously.

Chloroquine / artemisinine / artesunate

and primaquine / tafenoquine

P ti

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Prevention

Route of transmission

Vector control

Kill anopheles mosquitoes: insecticide spraying

Avoid multiply of mosquitoes:

Personal protection

Mosquito nets

Repellents

Long clothes

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P ti

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Prevention

Protection of susceptible population

Active prophylaxis

Vaccine

Under development

Passive prophylaxis

Chemoprophylxis

Chloroquine (sensitive, pregnant women or children)

Mefloquine, Doxycycline, Pyrimethamine.

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summary

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summary

Malaria is a vector-borne parasitic disease caused byplasmodium protozoa

All the four species plasmodium need anophelesmosquitoes and human to complete its life cycle.

Transmitted by a bite of anopheles mosquito.

Characterized by the malaria paroxysm (chill, highfever,and sweats)

The thick film and thin film can diagnose a malaria.

Use the blood schizonticides and gametocides

simultaneously to kill the parasite. Prevention refers to the cases management, vector control,

personal protection, vaccine and chemoprophylaxis.

Malaria is still a enomous public health problem world wide.

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THANK YOU!

Species P vivax P ovale Pmalariae P falciparum

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Species P. vivax, P. ovale P.malariae P. falciparum

Periodicity Tertian Tertian Quartan Irregular/tertian

Attacks Typical Typical Typical Intermittentirregular

Recrudesce

nce

Yes Yes Yes Yes

Relapse Yes Yes No No

Complicati

ons

Rare Rare Glomerulo-

nephritis

Nephriticsyndrome

Cerebral malaria

Black water fever

U f l Li k

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Useful Links

Centers for Disease Control and Preventionhttp://www.cdc.gov/Global Fund to Fight AIDS, TB and Malariahttp://www.who.int/malaria/Global Health AdvocatesInnovative Vector Control ConsortiumLubombo Spatial Development InitiativeMalaria Foundation InternationalMalaria JournalMalaria Vaccine Initiative

Medical Research CouncilMedicines for Malaria VentureMultilateral Initiative on MalariaNature Medicine (Malaria)President's Malaria InitiativeRoll Back Malaria PartnershipSouth Africa Department of Health (Malaria)East and Southern African Malaria Control

UNICEFWorld Health OrganisationWorld Bank

Why are malaria cases
http://www.cdc.gov/http://www.theglobalfund.org/http://www.ghadvocates.org/http://www.ivcc.com/http://www.malaria.org.za/lsdi/home.htmlhttp://www.malaria.org/http://www.malariajournal.com/http://www.malariavaccine.org/http://www.mrc.ac.za/http://www.mmv.org/rubrique.php3?id_rubrique=15http://www.nature.com/nm/focus/malaria/index.htmlhttp://www.mimalaria.org/http://www.nature.com/nm/focus/malaria/index.htmlhttp://www.fightingmalaria.gov/http://www.rbm.who.int/http://www.doh.gov.za/issues/malaria-f.htmlhttp://www.malaria.org.zw/http://www.unicef.org/http://www.who.int/malaria/http://www.worldbank.org/http://www.worldbank.org/http://www.who.int/malaria/http://www.unicef.org/http://www.malaria.org.zw/http://www.doh.gov.za/issues/malaria-f.htmlhttp://www.rbm.who.int/http://www.fightingmalaria.gov/http://www.nature.com/nm/focus/malaria/index.htmlhttp://www.mimalaria.org/http://www.mmv.org/rubrique.php3?id_rubrique=15http://www.mrc.ac.za/http://www.malariavaccine.org/http://www.malariajournal.com/http://www.malaria.org/http://www.malaria.org.za/lsdi/home.htmlhttp://www.ivcc.com/http://www.ghadvocates.org/http://www.theglobalfund.org/http://www.cdc.gov/

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Why are malaria cases

increasing?

Drug resistence

No vaccine

Wars

Do all mosquitoes transmit malaria?

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Do all mosquitoes transmit malaria?

No. So far, entomologists have identified over

2000 species of mosquito, but only the

Anopheles mosquito actually transmits malaria.

In Africa, the major vectors for malaria areAn.gambiae slcomplex andAn. funestus, and there

are many members of both groups of mosquito.

MostAnopheles mosquitoes do not feed during

the day but rather do so at dusk or during thenight.An. funestus for example feeds most

actively between 2am and 4am.

Documents

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