Malaria

2014
 WHO – World Health Report of 2002 –
Leading Causes of Death
Infectious & parasitic disease deaths – total 10.9 million
 Acute respiratory infections 3.96 million
 HIV/AIDS 2.77 million
 Gastroenteritis 1.79 million
 Tuberculosis 1.56 million
 Malaria 1.27 million*
 Measles 0.61 million
 Bordetella pertussis 0.29 million
 Tetanus 0.21 million
 Dengue fever 0.18 million
 Meningitis 0.17 million
 STD’s 0.17 million
 Intestinal parasites 0.11 million
 Hepatitis B 0.10 million
*** 2013 now down to 207 million cases and 627,000 deaths per year.
WHO Report, 2002
 Malaria in Ghana

Malaria data from Ghana Health Service Report, 2011

Outpatient visits 40.2%

Hospital admissions 35.2%
Percent of Deaths 18.1%
Percent of Deaths <5YO 29.5%
Case fatality <5YO 1.20%
 History of Malaria
The Greeks drained swamps to stop “periodic fevers and
splenomegaly”
1700 – bark --quina-quina (cinchona) tree used for treatment
Mid-1800’s quinine is the active alkaloid for treatment
1891 – mosquitoes noted as part of the life cycle
1902 – Ross describes malaria life cycle and wins Nobel Prize
1948 – liver as site for exoerythrocytic development
1955 – WHO eradication program initiated
DDT to kill mosquitoes
Decrease mosquito reproduction by draining swamps
and covering water with oil
Chloroquine prophylaxis and treatment
1976 – WHO eradication program declared failure
 Classification of Malaria
 Kingdom – Protista
 Class – Sporozoa
 Genus – Plasmodium
 Species – falciparum, vivax, ovale, malariae

 Definitive host – Anopheles mosquito

 Intermediate host – Humans (monkeys, rodents,

birds, reptiles and have own species)
Life Cycle of Plasmodium
 Case #1 – Falciparum Malaria
A Medical Emergency
A 52-year-old male – 3 weeks in Ghana, Africa – no prophylaxis
One week after arriving back home, flu-like symptoms of chills,
fever, sweating, muscle aching and headache.
He called his physician who phoned in a prescription for an
antibiotic.
Two days – found unresponsive in his room.
One hour after arriving at SLC Hospital blood smear positive –
parasitemia 30% with P. falciparum malaria.
Started on malaria medication, and received an exchange
transfusion with 12 units of blood and his parasitemia
decreased to 10%.
48 hours later and a 2nd exchange transfusion his parasitemia
was less than 1%.
End organ damage resulted in treatment for a coma for two
weeks, mechanical ventilation for three weeks and renal
dialysis for 6 weeks.
 Virulence Factors for P. falciparum
 May invade all stages of red blood cells
can result in high level parasitemia
 Cyto-adherence -- Produces “knobs”
 Erythrocyte membrane adhesive protein
(PfEMP1)
 Protein receptors on venules and capillary
endothelium
 Rosetting – adhere to non-infected RBC’s
 Agglutination – adhere to infected RBC’s
Plasmodium falciparum: Blood Stage Parasites
Plasmodium falciparum: Ring Stage Parasites
Plasmodium falciparum: Gametocytes
 Case #2: Vivax or Ovale Malaria
A 22 yo female -- humanitarian group to Kenya to build schools.
Used insect precautions and faithfully took preventive medication
during travel and for four weeks after travel.
Twelve weeks later -- chills, fever, profuse sweating, muscle
aching and headache.
Emergency room and told the doctor that she might have
malaria. He laughed and said that it was not possible, but was
wise enough to order a malaria smear.
Malaria smear positive with 1% parasitemia.
RBC’s larger than the non-infected cells
Stippling consistent with Schüffner's dots
All forms of the RBC life cycle were visualize.
Treated
outpatient with Chloroquine for the RBC phase
followed by Primaquine to treat liver “hypnozoites”
Plasmodium vivax: Blood Stage Parasites
Plasmodium vivax: Ring Stage Parasites
Plasmodium vivax: Trophozoites
Plasmodium vivax: Schizonts
Plasmodium vivax: Gametocytes
 Case #3: Chronic Malaria with
Plasmodium malariae
74 yo female born and lived in Greece
Healthy life – no acute chills, fever and sweating.
1995 -- found to have an enlarged spleen.
Dx with lymphoma, started on methotrexate and
developed fever and chills about every 72 h
Antibody was present and reverse-transcription
Southern Blot was positive for P. malariae
Proteinuria
Treated with Chloroquine for malaria,
Splenomegaly resolved
No evidence of lymphoma
Plasmodium malariae: Blood Stage Parasites
Plasmodium malariae: Ring Stage Parasites
Plasmodium malariae: Trophozoites
Plasmodium malariae: Schizonts
Plasmodium malariae: Gametocytes
 Characteristics of Plasmodium Species
falciparum vivax ovale malariae
Distribution Tropics Tropics, Africa Subtropics
subtopics
Host resistance Sickle cell Duffy antigen
Hgb C,D,E receptor neg
Thalassemia
G6PD
Pyridoxine kinase
deficiency
Host RBC’s All RBC’s Young RBC’s (reticulocytes) Old RBC’s
Incubation 2 weeks 2 weeks 2 weeks 2 weeks
<25% 1 mo > 25% 6 mo >25% 6 mo Chronic
Avg # merozoite in
liver schizont 40,000 10,000 15,000 2,000
Avg # merozoite/RBC 8-24 12-24 8-12 6-12
Periodicity 48 hours 48 hours 48 hours 72 hours
Severity of attack ++++ +++ +++ +
 Characteristics of Plasmodium Species

falciparum vivax ovale malariae

Mortality 1-5% Rare Rare Very rare
Latent infection No Yes Yes No
Chronic persistence No No No Yes
Large RBC’s No Yes Yes No
Schüffner’s dots No Yes Yes No
All forms of life cycle
in peripheral bloo No Yes Yes Yes
Gametocyte Banana shaped Amoeboid Amoeboid Amoeboid
 Diagnosis
 Clinical symptoms – chills, fever, sweats,
headache, muscle aches
 Thick blood smear –
 Inexpensive
 Sensitive (0.001% parasitemia)
 Less accurate parasitemia
 More difficult to speciate
 Delay for smear to dry
 Requires an experience observer
 Artifacts may result in false positive
 Diagnosis
 Thin Smear
 Rapid (Wright’s vs. Giemsa stain)
 More accurate speciation
 Red cell morphology
 Inexpensive
 Less sensitive (<0.05% parasitemia)
 Better quantitation (except for falciparum)
 Requires an experienced observer
 Diagnosis
 PCR testing
 Sensitive
 Expensive
 Excellent speciation
 Mixed infections
 Rapid Diagnostic Test (RDT)
 Histidine-rich protein 2 (PfHRP2) antigen
 LDH antigen – less sensitive
 Sensitive
 Simple
 Relatively inexpensive
 May remain positive after infection
 Poor quantitation
 Prevention
Vaccination – not available but recent optimism
Insect precautions:
 Screened-in housing
 Mosquito netting over the beds
 Clothing
 Insect repellent – DEET
 Insecticides – Permethrin
Prophylactic medication
 Atovaquone/proguanil (Malarone)
 Mefloquine (Lariam)
 Doxycycline
 Chloroquine
 Malaria Treatment
 Oral medication
 Chloroquine  Treatment of
 Artesunate/Lumefantrine hypnozoites in the
 Atovaquone/proguanil liver for P.
 Mefloquine vivax/ovale
 Primaquine
 IV medication
 Artesunate
 Quinine (Quinidine)
 Medications

Agent Prevent Treatment Preg

Latent
Chloroquine Y Y Y N
Quinine N Y Y N
Mefloquine Y Y Y N
Artesunate N Y Y N
Lumefantrine N Y Y N
Doxycycline Y Y N N
Atovaquone/ Y Y N N
 Proguanil
Primaquine Y N N Y
 Medications
 Chloroquine – Resistance so used only in central Am, middle
East and Caribbean, Hypotension, cardio-toxicity, retinopathy,
 Quinine/Quinidine – Cinchonism, QT prolongation,
 Mefloquine – psychedelic dreams, seizures, psychosis
 Artemisinin – WHO drug of choice, kills marginated malaria of
Pf, relatively safe, rapidly excreted, frequent relapse if not
used with a second agent.
 Lumefantrine – Second agent with artesunate, acts rapidly,
minor toxicity
 Doxycycline – gastric irritation, photosensitivity, bone and
tooth deposit in children, weak anti-malarial.
 Atovaquone/proguanil – well tolerated, causal prophylaxis,
contraindicated in renal failure
 Primaquine – eradicates hepatic forms, massive hemolysis if
patient has G6PD so must test before prescribing, nausea,
vomiting, diarrhea, methemoglobinemia