Malaria
Richard Moriarty, MD
University of Massachusetts Medical School
Objectives
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Scope of the problem
The parasite
The symptoms
The treatment
Preventive measures
Questions
Malaria - worldwide
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1.5 billion live in endemic areas
over 500 million infected
1-2 million deaths per year
Most deaths in children < age 5 years
old
• Caused by protozoan from Plasmodium
genus
• Transmitted by female Anopheles
mosquito
Areas of Malaria Transmission and Antimalarial Drug Resistance
Malaria in Liberia
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Leading cause of morbidity and mortality
Year-long stable transmission
40% of outpatient visits
18% of inpatient deaths
21,000 deaths in <5 years of age
Only 18% households have bednets
Only 4% of kids get first choice med
From President’s Malaria Initiative Liberia’s Malaria Operational
Plan FY 2008
Life cycle of Plasmodium
• Asexual phase
http://www.who.int/tdr/diseases/malaria/lifecycle.htm
– Blood
– Liver
– RBC
• Sexual phase
– Blood
– Gut of female mosquito
– Saliva gland
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http://www.wellcome.ac.uk/stellent/groups/corporatesite/@msh_publis
hing_group/documents/web_document/wtd039685.swf
Life Cycle of Plasmodium falciparum
sporozoites
Rosenthal P. N Engl J Med 2008;358:1829-1836
The Numbers
• 70 kg person has @ 5 liters of blood = 5 x 103ml = 5 x
106μL times 5 x 106RBCs per μL of blood = 2.5 x
1013RBCs
• 1% parasitemia= 1 in 100 iRBCs= 2.5 x 1011 parasites
= 250 billion parasites
• P. vivax invades predominately reticulocytes and so
has a built-in ceiling, but P. falciparum can invade all
ages of RBCs.
• Pyrogenic density P. falciparum 10,000/uL
nonimmune; 100,000/uL immune; P. vivax100/uL
David Sullivan, MD; Johns Hopkins School of Public Health
Malaria species
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Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium falciparum
• www.rph.wa.gov.au/malaria/diagnosis.html
Plasmodium vivax
– ~43% of cases WW
– Paroxysms on a 48 hr cycle
– Relapses up to 8 years
– merozoites infect only young RBC’s
– RBC’s usually enlarged
– Schuffner’s dots
– common in temperate zones
Plasmodium malariae
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not found in contiguous distribution
~7% WW
72 hour cycle
second exoerythrocytic stage not observed
reactivation can occur up to 53 years postinfection!
• merozoites infect only old RBC’s
• low parasitemia
Plasmodium ovale
–rare in humans
–found in tropical S. Africa and
Western Pacific
–<1% WW.
–mildest and rarest form of
malaria
Plasmodium falciparum
• most pathogenic and virulent form
– common in tropics, formerly in temperate
zones
– ~50% WW
– greatest killer of humans in the tropics
– only one exoerythrocytic stage, no relapse
– merozoites invade RBC’s of all ages
– parasitemia very high
– Marginal forms; double chromatin dots
Why is P. falciparum so
dangerous?
• Ability to infect all age of RBCs
• Higher multiplication capacity
• Sequestration (cytoadherance and
rosetting)
• Capillary leak syndromes
• End organ failure
Malaria Symptoms
• Early generalized symptoms
– Malaise, myagias, headache, low grade fever
– Fever is not always present
– Repeatedly infected adults may have few symptoms
• Paroxysms
– Chills, nausea, emesis, intense HA, fever
• Severe malaria
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Prostration, shock, metabolic acidosis
hypoglycemia
Severe anemia, jaundice
Organ failure (pulmonary edema, hemoglobinuria,etc)
Cerebral malaria
Physical Findings
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Fever
Tachycardia
Hypotension
Jaundice
Pallor
Splenomegaly
Later, hemoglobinuria, pulmonary
edema, bleeding, acute renal failure
Cerebral malaria
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Agitation
Seizures
Coma
Cytoadherence
CFR 20%
Significant
neurological
residua
Features, Outcome of CNS
Malaria in Kenyan Children
• 33% of ped admissions malaria 1st dx
• 47% of those had neurologic sx
– 37% seizures – multiple or prolonged
– 20% prostration
– 13% impaired consciousness or coma
• Neuro involvement associated with met
acidosis, hypoglycemia, hyperkalemia
• 2.8% mortality (75% of those had CNS)
JAMA 2007;297:2232-2240
Malaria Diagnosis
• Clinical diagnosis is inaccurate
• Blood smear
– Giemsa
– Field’s
• Rapid tests
– HRP-2: may stay + for >7 days
– pLDH: clears quickly
• PCR detection of antigen
in urine & saliva
http://www.wpro.who.int/sites/rdt
Malaria in Pregnancy
• Increased risk of spontaneous abortion,
stillbirth, pre-term birth and low birth weight
• Low birth weight is the single greatest risk
factor associated with perinatal mortality; up
to 200,000 newborn deaths/year occur in
Africa due to malaria
• Malaria parasites can cross the placenta and
cause malaria & anemia in the newborn
• HIV-malaria-infected women more likely for
anemia, preterm birth, IUGR, infant deaths
Increased risk
of HIV
transmission
Differential diagnosis
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Dengue
Typhoid
Sepsis/bacteremia
Acute schistosomiasis
Yellow fever
Leptospirosis
African tick fever
Treatment
• Quinine
– IV, oral,
rectal
• Quinidine
– Cinchonism: rashes, deafness, blurred
vision, confusion
• Chloroquine – resistance common
• Sulfadoxine-pyrimethamine –
resistance common
Treatment
• For children < age 5 years in a setting
of stable high transmission, consider
treating all febrile episodes if no other
cause of fever
• Liberia’s National Malaria control
Program does not support this; NMCP
supports confirmatory diagnosis with
RDT to encourage HCW’s to see other
diagnoses when RDT’s negative
Treatment - Artemesinins
• Rapid blood schizonticide
• Used with other med to
prevent recrudescence
• Recommended for
P. falciparum only
• Dose varies with preparation
• Possible neurotoxicity
• Increasing evidence of safety during
pregnancy
Artemisinin Preparations
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Artesunate
Artemether
Artemotil
Dihydroartemisinin
Rapidly eliminated
Reduces parasite load by 108
Paired with slowly eliminated drug
Allows effective treatment in 3 days
Very well tolerated; few side effects
Rx failure within 14 days is rare
Malaria Treatment
• Access to affordable appropriate drugs
– Chloroquine $0.20 but widespread
resistance
– Fansidar widespread resistance
– Artemether-lumefantrine (Coartem)
$0.90 – 2.40 (private $15)
– Artesunate-amodiaquine (ASAQ)
$0.50 but limited availability
Artemisinin Combination
Therapy
• Artemether / lumifantrine: Coartem
• Artesunate / amodiaquine: ASAQ
WHO Malaria Treatment Guidelines 2006
Treatment - supportive
• Transfusion may be lifesaving to
reverse tissue hypoxia and metabolic
acidosis
• Intermittent preventive treatment
during pregnancy
• IPTi
Preventive Measures
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Insecticide-treated bednets
Topical insecticides
Indoor residual spraying
Intermittent Preventive Treatment
during pregnancy: sulfadoxinepyrimethamine
• Counterfeit drugs
• ? Vaccine
Malaria
• Low tech solutions: prevention
– Insecticide-treated bed nets
– In-house spraying
– Drainage
• Higher tech solutions
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Intermittent preventive treatment in pregnancy
Intermittent preventive treatment in infancy
Prompt evaluation of febrile illnesses
Rectal quinine for acute management
• High tech solutions
– Drugs and vaccine
Liberia’s Goals for Malaria
• Rapid scale-up of
– ACT’s
– IPTp
– ITN’s
– IRS
• Expand microscopic diagnosis
• Use rapid tests until good microscopy
• $12.5 million budget
Treatment Miscellany
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Antipyretics?
What to do if an infant vomits a dose?
Transfuse at what level?
Steroids?
Anticonvulsants?
Concomitant antibiotics?
References
• WHO; Guidelines for the Treatment of
Malaria; 2006
• WHO; malaria life cycle
• CID; 2007;45:1446; intrarectal quinine
• PRESIDENT’S MALARIA INITIATIVE;
Malaria Operational Plan (MOP) LIBERIA
FY 2008