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Malaria “Bad Air”

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Malaria: Lecture GoalsUnderstand basic principles of malaria pathogenesis in the context of relevance to clinical disease and epidemiologyUnderstand the clinical symptoms of malariaUnderstand the difference between uncomplicated and severe malariaUnderstand how

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Слайд 1Malaria “Bad Air”

Malaria “Bad Air”

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
Malaria: Lecture GoalsUnderstand basic principles of malaria pathogenesis in the context of relevance to clinical disease and

Слайд 3Outline
Background
Organism
Epidemiology
Pathophysiology
Clinical
Symptoms
Differential diagnosis
Malaria in a complex emergency
Who is at risk
How to

choose a medication

OutlineBackgroundOrganismEpidemiologyPathophysiologyClinicalSymptomsDifferential diagnosisMalaria in a complex emergencyWho is at riskHow 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

MalariaCaused by a protozoal blood parasitePlasmodium vivaxPlasmodium ovalePlasmodium malariaPlasmodium falciparumPlasmodium 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

Transmission: Anopheles mosquitoWide spectrum symptomsFever1927 Nobel Prize: pyrotherapy for syphilisGeographical distribution:Tropic / Subtropics350-500 million infections worldwide/year1-2 million

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.
•Liver stage: Asimptomatic. With P. vivax and P. ovale, has dormant form (hypnozoite) that can relapse much

Слайд 11Malaria: Endemicity and Resistance
POWELL B , FORD C Cleveland Clinic

Journal of Medicine 2010;77:246-254

Malaria: Endemicity and ResistancePOWELL B , FORD C Cleveland Clinic Journal of Medicine 2010;77:246-254

Слайд 12% Malaria P. falciparum
9
http://www.who.int/gho/map_gallery/en/

% Malaria P. falciparum9http://www.who.int/gho/map_gallery/en/

Слайд 13Chloroquine 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

Chloroquine resistance and P. falciparum overlap, with exceptions:Central America West of Panama CanalHaiti/Dominican RepublicMiddle EastMake easy: Rx

Слайд 14P. 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
P. falciparum: DangerousInfects various RBC stagesMakes RBCs “sticky”Result:Severe hemolysisObstruction of microcirculationObstruction of capillariesHolo/hyperendemicGood News?	Does not have hypnozoiteHypnozoite:	dormant

Слайд 15Malaria 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
Malaria in a Complex Emergency: SymptomsSEVERE> 5% parasitemiaSevere anemiaHemoglobinuriaBleeding diathesisShock/HypotensionRenal failureHypoglycemiaAcidosisNeurologic abnormalitiesBiggest killerUNCOMPLICATEDFeverNot always cyclic!Chills, sweatsHeadacheMyalgiaDiarrhea, nausea,

Слайд 16Malaria 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
Malaria in a Complex Emergency: Who is at Risk for severe disease?Highest risk populations:Non-immuneImmunocompromised, malnourishedInfants, young children,

Слайд 17Malaria 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
Malaria in a Complex EmergencyDisplaced people within malaria endemic areas creates risk for a severe epidemic, particularly

Слайд 18Malaria: 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
Malaria: Practical Aspects of DiagnosisPresumptive treatment has been commonplace for decadesProblematic, but hard to changeEven in holoendemic

Слайд 19Malaria 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
Malaria in a Complex EmergencyImportant, when possible, to at least establish a fever epidemic is due to

Слайд 20Malaria: 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
Malaria: Differential DiagnosisMalaria can involve many organsCoinfection well describedDifferential diagnosis is broadSalmonella typhi and non-typhiStaphylococcus aureus with

Слайд 21Malaria: 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)

Malaria: DiagnosticsLateral flow test, relies on antibody-antigen interactionsSome RDTs specific for P. falciparumWHO quality assurance programs underwayClinician/Public

Слайд 22Clues to P. falciparum:
Trophozoites most commonly seen, and are small,

delicate rings, often multiple per RBC; infect all ages of

RBC. Gametocytes “banana” shaped.
Clues to P. falciparum:Trophozoites most commonly seen, and are small, delicate rings, often multiple per RBC; infect

Слайд 23Malaria: Treatment

Malaria: Treatment

Слайд 24CDC
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
CDCAlgorithm for Traveler Returned to US*Not the same as WHONote: CDC now recommending treating severe malaria with

Слайд 25Malaria: Treatment
WHO guidelines and update can be found at: http://www.who.int/malaria/publications/atoz/9789241549127/en/

Malaria: TreatmentWHO guidelines and update can be found at: http://www.who.int/malaria/publications/atoz/9789241549127/en/

Слайд 26Malaria: 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

Malaria: Therapy OptionsACT (Artemisinin based combination therapies)Artemethur + lemefantrine (coartem®)Artesunate + amodiaquine (coarsucam/ASAQ Winthrop®)Artesunate + mefloquine (AS+MQ)Artesunate

Слайд 27Suspected 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

Suspected malariaBlood films or RDT if availableCalculate parasitemiaRepeat each 12-24 hours for three setsEvaluate probability based on

Слайд 28Uncomplicated 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

Uncomplicated malaria: treatmentUse 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

Слайд 29Severe 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

Severe Malaria: WHO Criteriacreatinine > 265 μmol/l).(radiological)One or more of the following:Clinical features:Impaired consciousness, prostrationFailure to feedSeizuresRespiratory

Слайд 30If 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

If illness is with P. ovale/vivax, follow with primaquine if not G6PDGive oral or rectal until patient

Слайд 31Malaria: 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
Malaria: PreventionBed Nets!!!!!!1000 nets save 5 livesInsecticide impregnated bestCochrane Review, 2009Indoor/personal insecticidesVaccine: on the horizon?Some candidates reaching

Слайд 32Take 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
Take Home PointsMalaria endemicity and seasonality depends on mosquito habits, seasonality, and Plasmodium spp.Resistance to medications is

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