Communicable diseases - malaria as an example · Plasmodium malariae P. malariae usually does not cause life-threatening infections. P. malariae causes low grade parasitemia Description

Communicable diseases - malaria as an example

Andreas Mårtensson

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

IHCAR and Malaria Research Unit

Karolinska Institutet/Karolinska University Hospital

E-mail: [email protected]

10 september 2010Andreas Mårtensson 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 <5 years and pregnant women in sub-Saharan Africa



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%


Malaria – major public health problemin the developing world


History

� Mal aria = bad air

�Romans

�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)


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 !!


The 5 species differ in: 1. morphology


Differ in details of their lifecycles


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


� 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


� Plasmodium ovale

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

� However, can infect Duffy negative individuals.

� Found in Africa


� 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


To complete the lifecycle 3 players are needed� Man = Host

� Plasmodia = Agent

� Anopheles mosquito = Vector


Transmission

� By female Anopheles mosquito

� Endemic areas

� Local spread – airports

� Without mosquito

� Congenital

� Transfusion – accidental

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


Malaria epidemiology

� Endemic: hypo (<10%), meso (11-50%), hyper (50-75%), holo (>75%)

� Epidemic

� 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


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


Malaria distribution


Fever most common symptom


P. falciparum in the African context

� Fever in an African child = presumed to be malaria

� Problems

� 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


How to diagnose Malaria?

� Microscopy

� Needs skilled technician, microscope, slides, staining material etc

� Time consuming but relatively cheep

� Rapid Diagnostic Tests

� Expensive

� Minimum training needed

� Can not quantify parasites

� Remains positiv after treatment – not monitor treatment outcome

� Polymerase chain reaction (PCR)


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


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........


Causes of death in malaria

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

� Anemia (<2 years)

� Cerebral malaria (3-5 years)

� If surviving 5th birthday – decreased risk of malaria associated death

� Protection against severe disease and death age dependent


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?


Driving forces behind drug development

Malaria:

� Major obstacle for expansion of colonial empires

� More lethal than bullets for soldiers


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


Quinine - Jesuit’s 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 ....................


New drugs needed for new wars

� 1934 German scientists developed chloroquine

� Second world war


Chloroquine resistance

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

� Vietnam war...........


US army starts to act....

� 1967-74 New syntetic drugs under development

� 1975 Mefloquine (Lariam®) introduced for treatment


China strikes back.......

� From 1979

� Artemisia annua

� Sweet Wormwood

� Used for fever treatment

in China since ancient days

� Respons to mefloquine?


Driving force for drug development

� Not driven by the need of the poor in endemic areas


Present drug policies

� Two outstanding antimalarial drugs are based on herbal medicines

� Quinine

� Artemisinin-derivatives

WHO advocates combination therapy to

� Improve efficiacy

� Delay development of resistance

Artemisinin-based combination therapy (ACT)


Global strategies to fight malaria

� 1955-70 Eradication

� Vertical program

� Lack of commitment and community participation

� Miss use of chloroquine – added in Salt etc

� Chloroquine and DDT resistance

Failed – malaria stroke back! !


Present strategy

� To control malaria (and consider elimination where feasible)

� Early diagnosis and effective treatment

� Insecticide treated nets (ITN)

� Intermittent preventive treatment (IPT pregnancy/infants)

� Indoor residual spraying (IRS)

� Improvded diagnostics (Rapid Diagnostic Tests)

� Combination therapy (ACT)


Roll Back Malaria (Abudja, Nigeria, 2000)

� Halve the malaria mortality for Africa's people by 2010, through implementing the strategies and actions for Roll Back Malaria

� >60% of malaria patients should access correct, affordable and appropriate treatment within 24 hours

� >60% at risk, children <5 and pregnant women, to sleep under Insecticide treated nets (ITP)

� >60% of pregnant women should have access to Intermittent Preventive Treatment (ITPp)

� The above targets have later been revised to 80%


Millenium Development Goals

1. Eradicate Extreme Poverty and Hunger

2. Achieve Universal Primary Education

3. Promote Gender Equality and Empower Women

4. Reduce Child MortalityReduce by two-thirds, between 1990 and 2015, the under-five mortality rate

5. Improve Maternal Health

6. Combat HIV/AIDS, Malaria and other DiseasesHalt and begin to reverse the incidence of malaria and other major diseases

7. Ensure Environmental Sustainability

8. Develop a Global Partnership for Development


Is there hope for Africa in the battle against Malaria??� Probably yes!

� Malaria is on the agenda!

� Commitment higher from leaders

� International initiatives/collaborations more serious

� New donors - Thanks to Bill and Melinda Gates!

� Combined interventions giving positive results – Zanzibar

� Sustainability??


Thank you for your attention!

Communicable diseases - malaria as an example · Plasmodium malariae P. malariae usually does not cause life-threatening infections. P. malariae causes low grade parasitemia Description

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