Communicable diseases - malaria as an diseases - malaria as an example Andreas Mrtensson MD, PhD, DTMH, Specialist in Infectious diseases IHCAR and Malaria Research Unit

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  • Communicable diseases - malaria as an example

    Andreas Mrtensson

    MD, PhD, DTM&H, Specialist in Infectious diseases

    IHCAR and Malaria Research Unit

    Karolinska Institutet/Karolinska University Hospital


  • 10 september 2010Andreas Mrtensson 2

    Why Malaria as an example?

    2.5 billion people in >100 countries at risk (40% of world population)

    ~300 million people experience clinical disease each year

    ~1 million deaths each year

    >1 death every 30-60 seconds

    Majority of deaths are children

  • 10 september 2010Andreas Mrtensson 3

  • 10 september 2010Andreas Mrtensson 4

    Economic analyses indicate that burden of malaria is enormous

    Highly malarious countries are among the poorest in the world

    Malaria obstructs economic development/growth

    Estimated annual loss of economic growth due to malaria 1.3%

    Accumulated loss during 15 years x 1.3% = 20%

  • 10 september 2010Andreas Mrtensson 5

    Malaria major public health problemin the developing world

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    Mal aria = bad air


    Ancient Chinese and Indian medical texts

    Hippokrates 500 B.C

    Linneus 1735

    Laveran 1880

    Discovered the parasite in human blood

    Ross 1898

    Described the complete life cycle in birds (Nobel prize 1902)

  • 10 september 2010Andreas Mrtensson 7

    What is Malaria?

    Parasitic disease caused by

    members of genus Plasmodium

    >100 species described in mammals, reptiles and birds

    Five species infect humans

    P. falciparum

    P. vivax

    P. ovale

    P. malariae

    P. knowlesi !!

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    The 5 species differ in: 1. morphology

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    Differ in details of their lifecycles

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    3. Differ in clinical manifestations

    Plasmodium falciparum

    Causes the most deadly and severe infections.

    Infects all ages of erythrocytes leading to a high parasitemia.

    Mature stages sequester in the capillaries leading to symptoms.

    Widespread drug resistance.

    Found in Tropics/Sub-Tropics

    Temperature 16-35oC

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    Plasmodium vivax

    P. vivax usually does not cause life-threatening infections.

    P. vivax only infects reticulocytes, gives low parasitemia

    P. vivax produces hypnozoites which are latent in the liver.

    Relapses can occur up to 5 years after infection

    P. vivax uses the Duffy blood receptor to enter erythrocytes

    P. vivax not found in West Africa.

    Found Temperate/Tropics/Sub-Tropics

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    Plasmodium ovale

    P. ovale resembles P. vivax in life cycle, appearance, clinical presentation and treatment.

    However, can infect Duffy negative individuals.

    Found in Africa

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    Plasmodium malariae P. malariae usually does not cause life-threatening infections. P. malariae causes low grade parasitemia Description of parasite persistence > 40 years exists.

    Found in Tropics/Subtropics

    Plasmodium knowlesi Macaca monkeys natural host Proposed as 5th human malaria parasite Resembles P. malariae in microscopy Can cause severe disease and death

    Found in South East Asia

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    To complete the lifecycle 3 players are needed Man = Host

    Plasmodia = Agent

    Anopheles mosquito = Vector

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    By female Anopheles mosquito

    Endemic areas

    Local spread airports

    Without mosquito


    Transfusion accidental

    Controlled infection to treat other diseases, e.g. Neuro-syphilis

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    Malaria epidemiology

    Endemic: hypo (75%)


    Stable transmission

    Continues exposure

    >10 infective mosquito bites per year (Entomological innoculation rate= EIR)

    Aquired immunity small children + pregnant women affected

    Unstable transmission

    Low EIR

    NO aquired immunity all age groups affected

    Epidemic prone

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    Malaria in Sweden

    In whole of Europe below 2000 m altitude

    Last case in Sweden 1933

    Known as intermittent summer fever summer agues

    P. vivax hypnozoites needed to survive the winter

    5% of mosquito population Anopheles

    Malaria disappeared due to improved socio-economic standard

    Today imported malaria circa 80-100 patients/year

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    Malaria distribution

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    Fever most common symptom

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    P. falciparum in the African context

    Fever in an African child = presumed to be malaria


    Clinical diagnosis difficult

    Fever a cardinal symptom but not disease specific for malaria

    Fever overlaps with several other childhood illnesses, e.g. respiratory tract infections, flue, meningitis, septicemia

  • 10 september 2010Andreas Mrtensson 21

    How to diagnose Malaria?


    Needs skilled technician, microscope, slides, staining material etc

    Time consuming but relatively cheep

    Rapid Diagnostic Tests


    Minimum training needed

    Can not quantify parasites

    Remains positiv after treatment not monitor treatment outcome

    Polymerase chain reaction (PCR)

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    Reality is often: No or limited access to health care available..........

    A majority of fever sick children never reach formal health care

    Presumptive treatment given at home over/under diagnosis and treatment

    Often not correct dose and incomplete treatment course

    Drug resistance and increased morbidity & mortality

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    If reaching primary health care facility

    Staff available?

    If available poorly trained, heavy workload etc

    Equipment available for diagnosis?

    Drugs available?

    If need for referral to hospital few patients go........

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    Causes of death in malaria

    Death within 24-48 hours after onset of disease common!

    Anemia (

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    Malaria and co-infections

    Malaria can not be isolated in the African child -multiple exposures

    Co-infections a reality in rural Africa

    Worm infestations, respiratory tract infections, HIV/AIDS, Hepatitis B, malnutrition, poverty increased risk

    Measles decreased risk?

    Successful interventions agains malaria may have to be

    intergrated with other interventions holistic approach?

  • 10 september 2010Andreas Mrtensson 26

    Driving forces behind drug development


    Major obstacle for expansion of colonial empires

    More lethal than bullets for soldiers

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    Driving force?

    The climate of the insular coast is not unhealthy for Europeans, but it is impossible for white men to live in the interior of the island, the vegetation being rank and appearing always to be going on; and generally fever contracted in the interior is fatal to Europeans

    Ref: Burton RF. Zanzibar City, island and coast.1874

  • 10 september 2010Andreas Mrtensson 28

    Quinine - Jesuits Powder

    The drug that changed history!

    1600 Juan Lopez, fever tree bark from Peruvian Indians

    1643 Cardinal Juan de Lugo tried and supported use

    1747 Linneus namned the tree Cinchona officinalis

    1820 Quinine isolated by Pelletier and Caventou

    1854 large scale cultivation in Indonesia and India

    1914-18 Events during First world war indicated shortage of quinine ....................

  • 10 september 2010Andreas Mrtensson 29

    New drugs needed for new wars

    1934 German scientists developed chloroquine

    Second world war

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    Chloroquine resistance

    1957-65 Reports from South-East Asia Colombia, Brazil!

    Vietnam war...........

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    US army starts to act....

    1967-74 New syntetic drugs under development

    1975 Mefloquine (Lariam) introduced for treatment

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    China strikes back.......

    From 1979

    Artemisia annua

    Sweet Wormwood

    Used for fever treatment

    in China since ancient days

    Respons to mefloquine?

  • 10 september 2010Andreas Mrtensson 33

    Driving force for drug development

    Not driven by the need of the poor in endemic areas

  • 10 september 2010Andreas Mrtensson 34

    Present drug policies

    Two outstanding antimalarial drugs are based on herbal medicines



    WHO advocates combination therapy to

    Improve efficiacy

    Delay development of resistance

    Artemisinin-based combination therapy (ACT)

  • 10 september 2010Andreas Mrtensson 35

    Global strategies to fight malaria

    1955-70 Eradication