Malaria “Bad Air”

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

choose a medication

knowlesi
*Often cause severe malaria

distribution:
Tropic / Subtropics
350-500 million infections worldwide/year
1-2 million deaths worldwide/year

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.

Journal of Medicine 2010;77:246-254

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

microcirculation
Obstruction of capillaries
Holo/hyperendemic
Good News? Does not have hypnozoite
Hypnozoite: dormant liver form that

causes relapse with P. ovale, P. vivax

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

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

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

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

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

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

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)

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

RBC. Gametocytes “banana” shaped.

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

+ 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

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

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

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

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

2009

Indoor/personal insecticides

Vaccine: on the horizon?
Some candidates reaching clinical trials, with

short-lived efficacy

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