Communicable diseases - malaria as an example
MD, PhD, DTM&H, Specialist in Infectious diseases
IHCAR and Malaria Research Unit
Karolinska Institutet/Karolinska University Hospital
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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
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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%
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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
Discovered the parasite in human blood
Described the complete life cycle in birds (Nobel prize 1902)
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What is Malaria?
Parasitic disease caused by
members of genus Plasmodium
>100 species described in mammals, reptiles and birds
Five species infect humans
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
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
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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.
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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
Local spread airports
Controlled infection to treat other diseases, e.g. Neuro-syphilis
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Endemic: hypo (75%)
>10 infective mosquito bites per year (Entomological innoculation rate= EIR)
Aquired immunity small children + pregnant women affected
NO aquired immunity all age groups affected
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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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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
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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
If available poorly trained, heavy workload etc
Equipment available for diagnosis?
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!
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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?
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Driving forces behind drug development
Major obstacle for expansion of colonial empires
More lethal than bullets for soldiers
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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
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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 ....................
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New drugs needed for new wars
1934 German scientists developed chloroquine
Second world war
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1957-65 Reports from South-East Asia Colombia, Brazil!
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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.......
Used for fever treatment
in China since ancient days
Respons to mefloquine?
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Driving force for drug development
Not driven by the need of the poor in endemic areas
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Present drug policies
Two outstanding antimalarial drugs are based on herbal medicines
WHO advocates combination therapy to
Delay development of resistance
Artemisinin-based combination therapy (ACT)
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Global strategies to fight malaria