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Shanyar Kadir
Shkar Dilshad
 Shvan Omar
What does Malaria mean?
          
The word “malaria” comes from the Italian
 mala aria, meaning “bad air.” When the term
 was coined, it was commonly believed that
 malaria was caused by breathing in bad air.
Overview
                   
 Malaria is a mosquito-borne parasitic disease caused
  by genus Plasmodium, affecting over 100 countries
  of the tropical and subtropical regions of the world.
 Around 400-900 million people are affected
 At least 2.7 million deaths annually.
 It is one of the major public health concerns
Epidemiology
                  
 Around 300-500 million clinical cases of malaria are
  reported every year, of which more than a million die of
  severe and complicated cases of malaria.

 Malaria is known to kill one child every 30 sec, 3000
  children per day under the age of 5 years.

 Malaria ranks third among the major infectious diseases
  in causing deaths after pneumococcal acute respiratory
  infections and tuberculosis, and accounts for
  approximately 2.6% of the total disease burden of the
  world.

Epidemiology (cont.)
            
 It mainly occurs throughout tropical regions
 515 million clinical cases per year
 An estimated 655,000 people died from malaria in
  2010
 with two-thirds of these occurring in sub-Saharan
  Africa
 especially amongst children and pregnant women
 the incidence of malaria was greatly reduced
  between 1950 and 1960
 but since 1970 there has been resurgence.
Who is at Risk?
                  
 Most people who get
  malaria are travelers or
  people who live in an
  area with malaria
  transmission.
 Young children and
  pregnant women.
 Poor people that live in
  rural areas who lack
  knowledge, money and
  the access to health care.
Causative Agent
               
 Malaria is caused by species of Plasmodium.
 The genus Plasmodium contains over 200 species
   at least 11 species infect humans. Most important are:
        Plasmodium falciparum
        Plasmodium malariae
        Plasmodium ovale
        Plasmodium vivax
        Plasmodium knowlesi
 Plasmodium parasites are highly
  specific with female Anopheles mosquitoes
Vector
                   
 Female mosquitos of genus Anopheles are primary
  hosts and transmission vectors.
 There are approximately 460 recognized species
 Over 100 can transmit human malaria
 Only 30–40 commonly transmit parasites of the
  genus Plasmodium
 Anopheles gambiae is one of the best known which
  transmits Plasmodium falciparum
Vector (cont.)
               
Only female mosquitoes feed on blood while
 the males feed on plant nectar and do not
 transmit the disease.
The females of Anopheles genus prefer to
 feed at night
They start searching for a meal at dusk and
 continue throughout the night until they take
 a meal
Life Cycle


   
Life Cycle & Pathogenesis
            
 Inside the vector (sexual reproduction):
 Young female mosquitoes ingest the malaria parasite by
  taking a blood meal from an infected human carrier
 The ingested gametocytes will differentiate into male and
  female gametes and then unite to form a zygote (ookinete)
  in the mosquito’s gut
 The resulting ookinete penetrates the gut lining to form
  an oocyst in the gut wall
 The oocyst ruptures to release sporozoites that migrate in
  the mosquito’s body to the salivary glands and are ready
  to infect new human hosts
Life Cycle & Pathogenesis
            
Inside humans:
 Malaria develops via two phases:
   Exoerythrocytic: involves infection of liver
   Erythrocytic phase: involves infection of RBC
    (erythrocytes)
Life Cycle & Pathogenesis
                         by taking a blood meal.
 A mosquito infects a person
  First, sporozoites enter the bloodstream, and migrate
   to the liver. They infect liver cells (hepatocytes),
   where they multiply into merozoites, rupture the
   liver cells, and escape back into the bloodstream.
  Then, the merozoites infect red blood cells, where
   they develop into ring forms, trophozoites and
   schizonts which in turn produce further merozoites.
  Sexual forms (gametocytes) are also produced,
   which, if taken up by a mosquito, will infect the
   insect and continue the life cycle.

Clinical Features
               
 P. falciparum (malignant tertian):
 It is the most dangerous of the malarias
 Onset is insidious, with malaise, headache and
  vomiting… commonly mistaken for influenza
 The fever has no particular pattern.
 Jaundice is common due to hemolysis & hepatic
  dysfunction
 There is hepatosplenomegaly
 Anemia develops rapidly
Clinical Features
                
 P. falciparum complications:
 Cerebral Malaria: the most grave complication, causing
  either confusion or coma without localizing signs.
 Convulsions
 Hypoglycemia
 Acute pulmonary edema
 Acure renal failure (Blackwater fever )
 Metabolic acidosis
 Aspiration pneumonia
 Severe anemia
 Coagulopathy/Spontaneous bleeding
Causes of severe malaria
           
 P. falciparum-infected
  erythrocytes sequester in blood
  vessels, creating blockages.

 Infected erythrocytes also “stick to
  endothelium, platelets, and other
  erythrocytes”
 Rosetting -- cohesion of
  erythrocytes

 Leads to immune evasion because
  of lack of circulation through the
  spleen.

 Aids in the progression of the
  severity of malaria
Clinical Features
                
 P. vivax & P. ovale (benign tertian):
 In many cases the illness starts with several days of
  continued fever before the development of classical
  bouts of fever on alternate days. Fever starts with a
  rigor. The patient feels cold and the temperature
  rises to about 40 C. After an hour hot or flush phase
  begins. It lasts several hours and gives way to
  profuse perspiration and a gradual fall in
  temperature. The cycle is repeated 48 hours later.
 Anemia develops slowly
Clinical Features
                
P. malariae infection (quartan):
 This is usually associated with mild symptoms and
  bouts of fever every third day. Parasitemia may
  persist for many years with the occasional recurrence
  of fever, or without producing any symptoms.
Hypnozoites
                 
 It is the round or oval, uninucleate, dormant form of
  Plasmodium seen inside the liver cells during the
  intrahepatic (exoerythrocytic) stage of the parasite’s
  life cycle; it is believe to be the true latent stage
  associated with relapse in malaria.
 Hypnozoites are seen in:
    Plasmodium vivax
    Plasmodium ovale
Diagnosis
 Clinical
                     
    Fever, sweat, chills, headache and muscle pain
 Serology
    PCR
    ELISA
 Blood Film (gold standard)
    Banana-shaped intraerythrocytic gametocytes identify P.
     falciparum
    Enlarged erythrocytes with Schuffner’s dots are
     characteristics of P. vivax
    Schuffner’s dots in ovale-shaped red blood cells are
     characteristic of P. ovale
    Band-form trophozoites are seen in P. malariae

BinaxNOW®                 Malaria
                         
 Detects circulating
  malaria antigens in
  whole blood.
 15 minute test
 The only FDA cleared
  rapid malaria test.
How the test works?
            
 The test targets the histidine-rich protein II (HRPII)
  antigen specific to P. falciparum and a pan-malarial
  antigen (aldolase), common to all four malaria
  species capable of infecting humans - P. falciparum,
  P. vivax, P. ovale, and P. malariae.
 It is intended to aid in the rapid diagnosis of human
  malaria infections and to aid in the differential
  diagnosis of Plasmodium falciparum infections from
  other less virulent malarial infections. Negative
  results must be confirmed by thin / thick smear
  microscopy.
Prevention
                  
 Medications (will be mentioned in treatment)
 Vector control
 Mosquito nets and bedclothes
 Immunity (natural & vaccines)
 Education
Vector Control
                 
 Efforts to eradicate malaria by eliminating
  mosquitoes have been successful in some areas.
  Malaria was once common in the United States and
  southern Europe, but vector control programs, in
  conjunction with the monitoring and treatment of
  infected humans, eliminated it from those regions.
 Malaria was eliminated from most parts of the USA
  in the early 20th century by use of the pesticide DDT.
Mosquito nets
                 
 Mosquito nets help keep mosquitoes away from people
  and greatly reduce the infection and transmission of
  malaria. The nets are not a perfect barrier and they are
  often treated with an insecticide designed to kill the
  mosquito before it has time to search for a way past the
  net. Insecticide-treated nets (ITNs) are estimated to be
  twice as effective as untreated nets and offer greater than
  70% protection compared with no net. Since the
  Anopheles mosquitoes feed at night, the preferred
  method is to hang a large "bed net" above the center of a
  bed such that it drapes down and covers the bed
  completely.
Immunity
                     
 Natural immunity occurs, but only in response to
  repeated infection with multiple strains of malaria.
 A completely effective vaccine is not yet available for
  malaria, although several vaccines are under
  development.
 SPf66 was tested extensively in endemic areas in the
  1990s, but clinical trials showed it to be insufficiently
  effective.
 Other vaccine candidates, targeting the blood-stage of the
  parasite's life cycle, have also been insufficient on their
  own.
 Several potential vaccines targeting the pre-erythrocytic
  stage are being developed.
Vaccines
                        
First proposed in 1960s, still nothing fully effective

Difficulties include :

   Intracellular parasites
   Polymorphism and clonal variation
   Parasite induced immunosuppression
   Antigenic variation
   Evaluation and trials difficult to interpret
   High level of parasite mutation
Education
                         symptoms of malaria
 Education in recognizing the
  has reduced the number of cases in some areas of the
  developing world by as much as 20%.
 Recognizing the disease in the early stages can also
  stop the disease from becoming a killer.
 Education can also inform people to cover over areas
  of stagnant, still water which are ideal breeding
  grounds for the parasite and mosquito, thus cutting
  down the risk of the transmission between people.
 This is most put in practice in urban areas where
  there are large centers of population in a confined
  space and transmission would be most likely in these
  areas.
Treatment
                     
 When properly treated, a patient with malaria can expect
  a complete recovery. The treatment of malaria depends
  on the severity of the disease; whether patients can take
  oral drugs or must be admitted depends on the
  assessment and the experience of the clinician.
 Uncomplicated malaria is treated with oral drugs. The
  most effective strategy for P. falciparum infection
  recommended by WHO is the use of artemisinins in
  combination with other antimalarials artemisinin-
  combination therapy, ACT, to avoid the development of
  drug resistance against artemisinin-based therapies.
Treatment
                     
 Severe malaria requires the parenteral administration of
  antimalarial drugs. Until recently the most used treatment
  for severe malaria was quinine but artesunate has been
  shown to be superior to quinine in both children and
  adults. Treatment of severe malaria also involves
  supportive measures.

 Infection with P. vivax, P. ovale or P. malariae is usually
  treated on an outpatient basis. Treatment of P. vivax
  requires both treatment of blood stages (with chloroquine
  or ACT) as well as clearance of liver forms with
  primaquine.
Chemoprophylaxis
Antimalarial tablets
                       dose
Chloroquine resistance high
                                
                       Adult prophylactic   Regimen



Mefloquine             250mg weekly         Started 2-3 weeks before
                                            travel and continued until
                                            4 weeks after
or Doxycycline         100mg daily          Started 1 week before and
                                            continued until 4 weeks
                                            after travel
Or Malarone            1 tablet daily       From 1-2 days before
                                            travel until 1 week after
                                            return
Chloroquine resistance absent
Chloroquine            300mg base weekly    Started 1 week before &
and proguanil          100-200mg daily      continued until 4 weeks
                                            after travel

Thank You!
    

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Malaria

  • 2. What does Malaria mean?  The word “malaria” comes from the Italian mala aria, meaning “bad air.” When the term was coined, it was commonly believed that malaria was caused by breathing in bad air.
  • 3. Overview   Malaria is a mosquito-borne parasitic disease caused by genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions of the world.  Around 400-900 million people are affected  At least 2.7 million deaths annually.  It is one of the major public health concerns
  • 4. Epidemiology   Around 300-500 million clinical cases of malaria are reported every year, of which more than a million die of severe and complicated cases of malaria.  Malaria is known to kill one child every 30 sec, 3000 children per day under the age of 5 years.  Malaria ranks third among the major infectious diseases in causing deaths after pneumococcal acute respiratory infections and tuberculosis, and accounts for approximately 2.6% of the total disease burden of the world.
  • 5.
  • 6. Epidemiology (cont.)   It mainly occurs throughout tropical regions  515 million clinical cases per year  An estimated 655,000 people died from malaria in 2010  with two-thirds of these occurring in sub-Saharan Africa  especially amongst children and pregnant women  the incidence of malaria was greatly reduced between 1950 and 1960  but since 1970 there has been resurgence.
  • 7. Who is at Risk?   Most people who get malaria are travelers or people who live in an area with malaria transmission.  Young children and pregnant women.  Poor people that live in rural areas who lack knowledge, money and the access to health care.
  • 8. Causative Agent   Malaria is caused by species of Plasmodium.  The genus Plasmodium contains over 200 species  at least 11 species infect humans. Most important are:  Plasmodium falciparum  Plasmodium malariae  Plasmodium ovale  Plasmodium vivax  Plasmodium knowlesi  Plasmodium parasites are highly specific with female Anopheles mosquitoes
  • 9. Vector   Female mosquitos of genus Anopheles are primary hosts and transmission vectors.  There are approximately 460 recognized species  Over 100 can transmit human malaria  Only 30–40 commonly transmit parasites of the genus Plasmodium  Anopheles gambiae is one of the best known which transmits Plasmodium falciparum
  • 10. Vector (cont.)  Only female mosquitoes feed on blood while the males feed on plant nectar and do not transmit the disease. The females of Anopheles genus prefer to feed at night They start searching for a meal at dusk and continue throughout the night until they take a meal
  • 11. Life Cycle
  • 12. Life Cycle & Pathogenesis   Inside the vector (sexual reproduction):  Young female mosquitoes ingest the malaria parasite by taking a blood meal from an infected human carrier  The ingested gametocytes will differentiate into male and female gametes and then unite to form a zygote (ookinete) in the mosquito’s gut  The resulting ookinete penetrates the gut lining to form an oocyst in the gut wall  The oocyst ruptures to release sporozoites that migrate in the mosquito’s body to the salivary glands and are ready to infect new human hosts
  • 13. Life Cycle & Pathogenesis  Inside humans:  Malaria develops via two phases:  Exoerythrocytic: involves infection of liver  Erythrocytic phase: involves infection of RBC (erythrocytes)
  • 14. Life Cycle & Pathogenesis  by taking a blood meal.  A mosquito infects a person  First, sporozoites enter the bloodstream, and migrate to the liver. They infect liver cells (hepatocytes), where they multiply into merozoites, rupture the liver cells, and escape back into the bloodstream.  Then, the merozoites infect red blood cells, where they develop into ring forms, trophozoites and schizonts which in turn produce further merozoites.  Sexual forms (gametocytes) are also produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.
  • 15.
  • 16. Clinical Features   P. falciparum (malignant tertian):  It is the most dangerous of the malarias  Onset is insidious, with malaise, headache and vomiting… commonly mistaken for influenza  The fever has no particular pattern.  Jaundice is common due to hemolysis & hepatic dysfunction  There is hepatosplenomegaly  Anemia develops rapidly
  • 17. Clinical Features   P. falciparum complications:  Cerebral Malaria: the most grave complication, causing either confusion or coma without localizing signs.  Convulsions  Hypoglycemia  Acute pulmonary edema  Acure renal failure (Blackwater fever )  Metabolic acidosis  Aspiration pneumonia  Severe anemia  Coagulopathy/Spontaneous bleeding
  • 18. Causes of severe malaria   P. falciparum-infected erythrocytes sequester in blood vessels, creating blockages.  Infected erythrocytes also “stick to endothelium, platelets, and other erythrocytes”  Rosetting -- cohesion of erythrocytes  Leads to immune evasion because of lack of circulation through the spleen.  Aids in the progression of the severity of malaria
  • 19. Clinical Features   P. vivax & P. ovale (benign tertian):  In many cases the illness starts with several days of continued fever before the development of classical bouts of fever on alternate days. Fever starts with a rigor. The patient feels cold and the temperature rises to about 40 C. After an hour hot or flush phase begins. It lasts several hours and gives way to profuse perspiration and a gradual fall in temperature. The cycle is repeated 48 hours later.  Anemia develops slowly
  • 20. Clinical Features  P. malariae infection (quartan):  This is usually associated with mild symptoms and bouts of fever every third day. Parasitemia may persist for many years with the occasional recurrence of fever, or without producing any symptoms.
  • 21. Hypnozoites   It is the round or oval, uninucleate, dormant form of Plasmodium seen inside the liver cells during the intrahepatic (exoerythrocytic) stage of the parasite’s life cycle; it is believe to be the true latent stage associated with relapse in malaria.  Hypnozoites are seen in:  Plasmodium vivax  Plasmodium ovale
  • 22. Diagnosis  Clinical   Fever, sweat, chills, headache and muscle pain  Serology  PCR  ELISA  Blood Film (gold standard)  Banana-shaped intraerythrocytic gametocytes identify P. falciparum  Enlarged erythrocytes with Schuffner’s dots are characteristics of P. vivax  Schuffner’s dots in ovale-shaped red blood cells are characteristic of P. ovale  Band-form trophozoites are seen in P. malariae
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  • 24. BinaxNOW® Malaria   Detects circulating malaria antigens in whole blood.  15 minute test  The only FDA cleared rapid malaria test.
  • 25. How the test works?   The test targets the histidine-rich protein II (HRPII) antigen specific to P. falciparum and a pan-malarial antigen (aldolase), common to all four malaria species capable of infecting humans - P. falciparum, P. vivax, P. ovale, and P. malariae.  It is intended to aid in the rapid diagnosis of human malaria infections and to aid in the differential diagnosis of Plasmodium falciparum infections from other less virulent malarial infections. Negative results must be confirmed by thin / thick smear microscopy.
  • 26. Prevention   Medications (will be mentioned in treatment)  Vector control  Mosquito nets and bedclothes  Immunity (natural & vaccines)  Education
  • 27. Vector Control   Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States and southern Europe, but vector control programs, in conjunction with the monitoring and treatment of infected humans, eliminated it from those regions.  Malaria was eliminated from most parts of the USA in the early 20th century by use of the pesticide DDT.
  • 28. Mosquito nets   Mosquito nets help keep mosquitoes away from people and greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier and they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net. Insecticide-treated nets (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Since the Anopheles mosquitoes feed at night, the preferred method is to hang a large "bed net" above the center of a bed such that it drapes down and covers the bed completely.
  • 29. Immunity   Natural immunity occurs, but only in response to repeated infection with multiple strains of malaria.  A completely effective vaccine is not yet available for malaria, although several vaccines are under development.  SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective.  Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have also been insufficient on their own.  Several potential vaccines targeting the pre-erythrocytic stage are being developed.
  • 30. Vaccines  First proposed in 1960s, still nothing fully effective Difficulties include :  Intracellular parasites  Polymorphism and clonal variation  Parasite induced immunosuppression  Antigenic variation  Evaluation and trials difficult to interpret  High level of parasite mutation
  • 31. Education  symptoms of malaria  Education in recognizing the has reduced the number of cases in some areas of the developing world by as much as 20%.  Recognizing the disease in the early stages can also stop the disease from becoming a killer.  Education can also inform people to cover over areas of stagnant, still water which are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people.  This is most put in practice in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas.
  • 32. Treatment   When properly treated, a patient with malaria can expect a complete recovery. The treatment of malaria depends on the severity of the disease; whether patients can take oral drugs or must be admitted depends on the assessment and the experience of the clinician.  Uncomplicated malaria is treated with oral drugs. The most effective strategy for P. falciparum infection recommended by WHO is the use of artemisinins in combination with other antimalarials artemisinin- combination therapy, ACT, to avoid the development of drug resistance against artemisinin-based therapies.
  • 33. Treatment   Severe malaria requires the parenteral administration of antimalarial drugs. Until recently the most used treatment for severe malaria was quinine but artesunate has been shown to be superior to quinine in both children and adults. Treatment of severe malaria also involves supportive measures.  Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient basis. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) as well as clearance of liver forms with primaquine.
  • 34. Chemoprophylaxis Antimalarial tablets dose Chloroquine resistance high  Adult prophylactic Regimen Mefloquine 250mg weekly Started 2-3 weeks before travel and continued until 4 weeks after or Doxycycline 100mg daily Started 1 week before and continued until 4 weeks after travel Or Malarone 1 tablet daily From 1-2 days before travel until 1 week after return Chloroquine resistance absent Chloroquine 300mg base weekly Started 1 week before & and proguanil 100-200mg daily continued until 4 weeks after travel
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  • 36. Thank You!