Слайд 2Malaria: Lecture Goals
Understand basic principles of malaria pathogenesis in the
context of relevance to clinical disease and epidemiology
Understand the clinical
symptoms of malaria
Understand the difference between uncomplicated and severe malaria
Understand how to choose an antimalarial
Understand where to find up-to-date resources for malaria
Слайд 3Outline
Background
Organism
Epidemiology
Pathophysiology
Clinical
Symptoms
Differential diagnosis
Malaria in a complex emergency
Who is at risk
How to
choose a medication
Слайд 4Malaria
Caused by a protozoal blood parasite
Plasmodium vivax
Plasmodium ovale
Plasmodium malaria
Plasmodium falciparum
Plasmodium
knowlesi
*Often cause severe malaria
Слайд 5Transmission: Anopheles mosquito
Wide spectrum symptoms
Fever
1927 Nobel Prize: pyrotherapy for syphilis
Geographical
distribution:
Tropic / Subtropics
350-500 million infections worldwide/year
1-2 million deaths worldwide/year
Слайд 7•Liver stage: Asimptomatic. With P. vivax and P. ovale, has
dormant form (hypnozoite) that can relapse much later. This form is
not killed by most malaria medications.
•Blood stage: Symptomatic. Notice the continuous circle. This will continue until medication or immune system eradicates (1-5+ years untreated). Once cycle 3-4 days, except P. falciparum.
Слайд 8Malaria: Endemicity and Resistance
POWELL B , FORD C Cleveland Clinic
Journal of Medicine 2010;77:246-254
Слайд 9% Malaria P. falciparum
9
http://www.who.int/gho/map_gallery/en/
Слайд 10Chloroquine resistance and P. falciparum overlap, with exceptions:
Central America West
of Panama Canal
Haiti/Dominican Republic
Middle East
Make easy: Rx P. falciparum with
ACT
Mixed infection possible
Asia 20-30%
Africa usually P. falciparum
Americas usually
P. vivax
Chloroquine Resistance
P. vivax
areas
P. falciparum
areas
Слайд 11P. falciparum: Dangerous
Infects various RBC stages
Makes RBCs “sticky”
Result:
Severe hemolysis
Obstruction of
microcirculation
Obstruction of capillaries
Holo/hyperendemic
Good News? Does not have hypnozoite
Hypnozoite: dormant liver form that
causes relapse with P. ovale, P. vivax
Слайд 12Malaria in a Complex Emergency: Symptoms
SEVERE
> 5% parasitemia
Severe anemia
Hemoglobinuria
Bleeding diathesis
Shock/Hypotension
Renal
failure
Hypoglycemia
Acidosis
Neurologic abnormalities
Biggest killer
UNCOMPLICATED
Fever
Not always cyclic!
Chills, sweats
Headache
Myalgia
Diarrhea, nausea, emesis
Anemia (pallor of
palms)
Thrombocytopenia
Hepatosplenomegaly
Слайд 13Malaria in a Complex Emergency: Who is at Risk for
severe disease?
Highest risk populations:
Non-immune
Immunocompromised, malnourished
Infants, young children, pregnant
Infected with P.
falciparum
In endemic areas, older children and adults develop partial immunity
Can have “asymptomatic” infection
Can have subacute or chronic symptoms
Слайд 14Malaria in a Complex Emergency
Displaced people within malaria endemic areas
creates risk for a severe epidemic, particularly if the displaced
persons are from less endemic areas (highlands to lowlands)
Laboratory diagnosis may be impractical
May become necessary to:
Treat some people based on clinical history
Do mass fever treatment
Слайд 15Malaria: Practical Aspects of Diagnosis
Presumptive treatment has been commonplace for
decades
Problematic, but hard to change
Even in holoendemic countries, WHO estimates
<1/3rd of febrile episodes due to malaria
In Africa, <20% of suspected cases receive a confirmatory diagnostic test
Слайд 16Malaria in a Complex Emergency
Important, when possible, to at least
establish a fever epidemic is due to malaria
Do some diagnostics
Combination
of smears and rapid diagnostic tests
To establish malaria as cause
To monitor epidemic curve
Evaluate for other diseases
Monitor clinical response
Слайд 17Malaria: Differential Diagnosis
Malaria can involve many organs
Coinfection well described
Differential diagnosis
is broad
Salmonella typhi and non-typhi
Staphylococcus aureus with focus (bone, joint,
muscle, lung, heart)
Dengue, yellow fever, japanese encephalitis
Pneumonia
Viral and bacterial meningitis/encephalitis
Leshmaniasis
Schistosomiasis
Tuberculosis
Liver abscess/cholangitis
Oncologic process
Слайд 18Malaria: Diagnostics
Lateral flow test, relies on antibody-antigen interactions
Some RDTs specific
for P. falciparum
WHO quality assurance programs underway
Clinician/Public acceptance large problem
USA:
only to confirm species
Microscopy
Thick: diagnosis
Thin
Identification and parasitemia
% parasitized RBCs
Rapid diagnostic test (RDT)
Слайд 19Clues to P. falciparum:
Trophozoites most commonly seen, and are small,
delicate rings, often multiple per RBC; infect all ages of
RBC. Gametocytes “banana” shaped.
Слайд 21CDC
Algorithm for Traveler Returned to US
*Not the same as WHO
Note:
CDC now recommending treating severe malaria with artesunate; treat with
atovoquone- proquanil until it arrives (5-12 hours). To enroll a patient with severe malaria in this treatment protocol, contact the CDC Malaria Hotline: 770-488-7788 (M-F, 8am-4:30pm, eastern time) or after hours, call 770-488-7100 and request to speak with a CDC Malaria Branch clinician. http://www.cdc.gov/malaria/diagnosis_ treatment/treatment.html
Слайд 22Malaria: Treatment
WHO guidelines and update can be found at: http://www.who.int/malaria/publications/atoz/9789241549127/en/
Слайд 23Malaria: Therapy Options
ACT (Artemisinin based combination therapies)
Artemethur + lemefantrine (coartem®)
Artesunate
+ amodiaquine (coarsucam/ASAQ Winthrop®)
Artesunate + mefloquine (AS+MQ)
Artesunate + sulfadoxine-pyrimethamine (AS+SP)
Not
for P. vivax
Artesunate + doxycycline or clindamycin
Dihydroartemisinin plus piperaquine (DHA+PPQ)
Quinine + doxycyline or clindamycin
Atovaquone + proguanil (malarone®)
Mefloquine (larium®)
Chloroquine (widespread resistance)
Primaquine (kills liver phase for P. vivax/ovale)
IV and IM: Artesunate, artemethur, quinine
Rectal: Artesunate
Default ACT in the Interagency Emergency Health Kit
Слайд 24Suspected malaria
Blood films or RDT if available
Calculate parasitemia
Repeat each 12-24
hours for three sets
Evaluate probability based on local epidemiology
Categorize as
uncomplicated
Reassess
each 12-24 hours, evaluate alternative
Not available
Decision to treat
Decision not to
treat
-
+
causes
or severe
Слайд 25Uncomplicated malaria: treatment
Use local resistance patterns to choose medication:
•ACT
•artesunate plus
tetracycline
/doxycycline/clindamycin
•Quinine plus tetracycline
/doxycycline/clindamycin
•Atovoquone-proguanil
•Mefloquine
•Quinine + doxycycline
•* Re-dose if emesis within 30
min
Consider admission to monitor disease
P. falciparum possible by epidemiology or smear?
- +
progression
Слайд 26Severe Malaria: WHO Criteria
creatinine > 265 μmol/l).
(radiological)
One or more of
the following:
Clinical features:
Impaired consciousness, prostration
Failure to feed
Seizures
Respiratory distress
Circulatory collapse
Clinical jaundice
plus evidence of other vital organ dysfunction
Gross hemoglobinuria
Abnormal spontaneous bleeding
Pulmonary edema
Laboratory findings:
Hypoglycemia (blood glucose <
2.2 mmol/l or < 40 mg/dl)
Metabolic acidosis (plasma bicarbonate < 15 mmol/l)
Severe normocytic anaemia (Hb < 5 g/dl, packed cell volume < 15%)
Hemoglobinuria
Hyperparasitaemia (> 2%/100 000/μl in low intensity transmission areas or > 5% or 250 000/μl in areas of high stable malaria transmission intensity)
Hyperlactatemia (lactate > 5 mmol/l)
Renal impairment (serum
Слайд 27If illness is with P. ovale/vivax, follow with primaquine if
not G6PD
Give oral or rectal until patient can be transferred
to referral center:
rectal artesunate • quinine IM • artesunate IM •
artemether IM
Treat IV x 24 hours minimum
Artesunate IV or IM Artemethur Quinine
no
yes
Follow with full course of oral antimalarial:
ACT
artesunate plus clindamycin or doxycycline
Ongoing supportive care, including:
•evaluation for blood transfusion
•treatment for coinfection
•treatment of seizures
deficient
•quinine plus clindamycin or doxycycline
28
Слайд 28Malaria: Prevention
Bed Nets!!!!!!
1000 nets save 5 lives
Insecticide impregnated best
Cochrane Review,
2009
Indoor/personal insecticides
Vaccine: on the horizon?
Some candidates reaching clinical trials, with
short-lived efficacy
Слайд 29Take Home Points
Malaria endemicity and seasonality depends on mosquito habits,
seasonality, and Plasmodium spp.
Resistance to medications is species and location
dependant
If P. faliciparum, assume chloroquine resistant
Exception: Island of Hispaniola
Clinical:
Who is at highest risk
How to differentiate severe vs. uncomplicated malaria
Differential diagnosis
How to choose an anti-malarial treatment:
ACTs are preferred therapies, all species
ACT if oral, artesunate if IV
Severe malaria treated same regardless of species
Where to find up-to-date resources on Malaria
