Malaria

1
Malaria

• Andreas Mårtensson
• MD, DTMH, Specialist in Infectious diseases
• Malaria Research Unit
• Dept. of Medicine
• Karolinska University Hospital
• E-mail andreas.martensson_at_ki.se

2
Burdon of malaria

• 2.5 billion people in gt90 countries at risk (40
  of world population)
• 300-500 million people experience clinical
  disease each year
• 1-2 million deaths each year
• gt1 death every 30 seconds
• Majority of deaths are children lt5 years in
  sub-Saharan Africa

3
(No Transcript)
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

5
Malaria major public health problemin the
developing world
6
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)

7
Malaria in Sweden

• In whole of Europe below 2000 m altitude
• Last case in Sweden 1933
• Known as intermittent summer fever summer
  agues
• 5 of mosquito population Anopheles
• Malaria disappeared due to improved
  socio-economic standard
• Today imported malaria circa 80-100 patients/year

8
What is Malaria?

• Parasitic disease caused by
• members of genus Plasmodium
• gt100 species described in mammals, reptiles and
  birds
• Five species infect humans
• P. falciparum
• P. vivax
• P. ovale
• P. malariae
• P. knowlesi !!

9
Differ in details of their lifecycles
10
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

11
To complete the lifecycle 3 players are needed

• Man Host
• Plasmodia Agent
• Anopheles mosquito Vector

12
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

13
Mosquito blood feeding behaviour - key to
tailor interventions

• Antropophilic vs zoophilic (humans cattle)
• Endophagic vs exophagic (feeding indoor
  outdoor)
• Endophilic vs exophilic (resting indoor
  outdoor)
• Time of feeding - dusk to dawn - early evening
  late night

14
EIR entomological inoculation rateStable
transmission 10
15
Malaria distribution
16
Fever most common symptom
17
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

18
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)

19
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

20
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........

21
Causes of death in malaria

• Death within 24-48 hours after onset of disease
  common!
• Anemia (lt2 years)
• Cerebral malaria (3-5 years)
• If surviving 5th birthday decreased risk of
  malaria associated death
• Protection against severe disease and death age
  dependent

22
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?

23
Driving forces behind drug development

• Malaria
• Major obstacle for expansion of colonial empires
• More lethal than bullets for soldiers

24
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

25
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 ....................

26
New drugs needed for new wars

• 1934 German scientists developed chloroquine
• Second world war

27
Chloroquine resistance

• 1957-65 Reports from South-East Asia Colombia,
  Brazil!
• Vietnam war...........

28
US army starts to act....

• 1967-74 New syntetic drugs under development
• 1975 Mefloquine (Lariam) introduced for treatment

29
China strikes back.......

• From 1979
• Artemisia annua
• Sweet Wormwood
• Used for fever treatment
• in China since ancient days
• Respons to mefloquine?

30
Driving force for drug development

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

31
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)

32
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! !

33
Modern control interventions- ACT (drugs)- ITN
(insecticide treated nets)- IRS (indoor
residual spraying)- IPT (Intermittent preventive
treatment)
34
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
• gt60 of malaria patients should access correct,
  affordable and appropriate treatment within 24
  hours
• gt60 at risk, children lt5 and pregnant women, to
  sleep under Insecticide treated nets (ITP)
• gt60 of pregnant women should have access to
  Intermittent Preventive Treatment (ITPp)

35
Millenium Development Goals

• Eradicate Extreme Poverty and Hunger
• Achieve Universal Primary Education
• Promote Gender Equality and Empower Women
• Reduce Child Mortality
• Reduce by two-thirds, between 1990 and 2015, the
  under-five mortality rate
• Improve Maternal Health
• Combat HIV/AIDS, Malaria and other Diseases
• Halt and begin to reverse the incidence of
  malaria and other major diseases
• Ensure Environmental Sustainability
• Develop a Global Partnership for Development

36
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??

37
Conclusions

• ACT and improved vector control (ITNs, LLINs )
  have reduced the prevalence and consequences of
  malaria infection
• Residents are accessing health facilities and ACT
  a majority of the time
• ITN/LLIN use is high and equitable
• Additional impact of ACT, ITN/LLINS and IRS and
  sustainability of these achievements should be
  measured
• Excellent possibility to study the socio-economic
  aspects of a rapid reduction of malaria on the
  village level