Anthony Karabanow, MD

Haiti
Each year, Haiti reports ~30,000 confirmed cases to

PAHO 200,000 cases are thought to occur annually Occurs mostly during the rainy season:
Primary peak November to January

Prevalence in Haiti
Emerging Infectious Diseases Journal (Volume 13,

Number 10October 2007):

Survey of 714 persons in Artibonite Valley during high

malaria season Prevalence of 3.1% by PCR 14.2% prevalence amongst febrile persons

Malaria after Jan 12

JAMA. 2010;303(20):2028-2029:
From Jan 12 to Feb 25, CDC received reports of 11

laboratory-confirmed cases of P. falciparum malaria acquired in Haiti 7 emergency responders, 3 Haitian residents, 1 US traveler 2 of the emergency responders required transfer to the US for ICU care

Biology
Vector: female Anopheles mosquito After inoculation, sporozoites go to liver in 1 to 2 hrs

Liver stage is asymptomatic

Incubation period is 12 to 14 days for Pf Symptomatic stage is RBC stage

Biology
Why is P.falciparum so virulent?
CYTOADHERENCE AND SEQUESTRATION

Biology
P. falciparum expresses knobs on the surface of

infected RBCs Knobs mediate cytoadherence to endothelial cells Leads to:

Small infarcts Capillary leakage Organ dysfunction

Clinical disease
MALARIA IS A NON-SPECIFIC FEBRILE ILLNESS

Severe malaria
Severe parasitemia (>5%) Organ dysfunction: CNS disease ARDS Circulatory collapse Renal failure Hepatic failure DIC Severe anemia Hypoglycemia

Clinical disease
Greatest risk for severe disease: Children Pregnant women Non-immune individualized Immunocompromised

Clinical disease

PHYSICAL EXAM

VIDEO

CNS disease
Impaired consciousness Delirium

Seizures
More common in children If untreated, usually fatal With treatment, mortality is 15-20%

Malarial retinopathy
MALARIAL RETINOPATHY: A NEWLY

ESTABLISHED DIAGNOSTIC SIGN IN SEVERE MALARIA Am. J. Trop. Med. Hyg., 75(5), 2006, pp. 790-797

Macular whitening

White retinal vessels

Retinal hemorrhage

Proposed algorhythm

ARDS
Non-cardiogenic pulmonary edema: Parasite sequestration in lungs SIRS

ARDS

Renal failure
Pathogenesis: Parasite sequestration in renal microcirculation Hemolysis (blackwater fever ATN) Hypovolemia

Blackwater fever

Anemia
Pathogenesis: Hemolysis Cytokine suppression of hematopoiesis

Severe anemia

Hypoglycemia
Pathogenesis: Increased host glucose consumption Quinine induced

Metabolic acidosis
Pathogenesis: Tissue shock sequestered parasites, hypovolemia Impaired renal/hepatic lactate clearance

Diagnosis
Microscopy (gold standard) Rapid Diagnostic Tests (RDTs)

PCR

Microscopy
Has sensitivity of 5 10 parasites/microL

Thick smears Measure parasite density

Thin smears Identification of malarial species

Identification tips
Infected RBCs are of normal size Ring forms are commonly seen Located at periphery of RBCs Multiple rings per RBCs may be present Schizonts, trophozoites are rarely seen Gametocytes have banana shape

Calculations
Count parasites until 200 WBCs have been seen

Parasite density (#/microL) = (# parasites) x (WBC count / 200)

% Parasitemia = (Parasite density) / WBC

RDTs
Detect malaria antigens: P. falciparum LDH Histidine-rich protein 2

OptiMAL assay

OptiMAL assay

Problems with RDTs

Decreased sensitivity at low parasitemia Cannot quantify parasitemia

Positive test despite parasite clearance

Higher cost

PCR
Can detect as few as 1 to 5 parasites/microL Cannot quantify infection

Costly
Requires specialized equipment and trained staff

Treatment
Good news: P. falciparum malaria in Haiti is

chloroquine sensitive
Bad news: P. falciparum malaria in Haiti can still

prove fatal

CQ resistance?
Emerging Infectious Disease Journal (Volume 15,

Number 5May 2009):

821 persons screened for malaria at Hopital Albert

Schweitzer between 2006-7 79 persons tested positive for P. falciparum PCR analysis detected 5 cases of CQ resistance

Uncomplicated malaria
Parasitemia < 5% No evidence of organ dysfunction

Able to take PO
General rule: Malaria can be fatal. If in doubt of

degree of severity, always treat more aggressively

Chloroquine
Adults: 600 mg base (=1000 mg salt) po immediately,

followed by 300 mg base (=500 mg salt) po at 6, 24, and 48 hours. Total dose: 1500 mg base (=2500 mg salt).
Children: 10 mg base/kg po immediately, followed by

5 mg base/kg po at 6, 24, and 48 hours. Total dose: 25 mg base/kg.

Management of severe malaria

Treat the parasitemia

Treat the organ dysfunction

Chloroquine
10 mg base/kg in isotonic fluid by constant-rate IV

infusion over 8 hours, followed by 15 mg/kg given over the next 24 hours. or 5 mg base/kg in isotonic fluid by constant-rate IV infusion over 6 hours, every 6 hours, for a total of 5 doses (i.e. 25 mg base/kg continuously over 30 hours).

Quinine
Loading dose: 20 mg salt/kg of body weight diluted in

10 ml isotonic fluid/kg by IV infusion over 4 hours Maintenance dose: 8 hours after the start of the loading dose, 10 mg salt/kg, over 4 hours. Repeat maintenance dose every 8 hours

Cerebral malaria
Follow the Glasgow/Blantyre scores LP to r/o bacterial meningitis

Seizure management (NOT PROPHYLAXIS): Diazepam 0.4 mg/kg IV/PR Lorazepam 0.1 mg/kg IV

ARDS
May need mechanical ventilation Avoid volume overload leading to cardiogenic

pulmonary edema

Renal failure
Infuse isotonic saline to maintain euvolemia Dialysis as necessary

Anemia
Exchange transfusion are of uncertain value Transfuse for Hg < 7 or compatible symptoms Diuretics often NOT needed as pts are usually

hypovolemic

Hypoglycemia
Follow blood sugars routinely Use IVF with D5 routinely

Consider in pts with MS changes

Other
Bacteremia (enteric, esp Salmonella) is a common

complication of severe malaria

Consider blood cultures and antibiotic therapy for

decompensated patients

DVT prophylaxis Nutrition via NGT

Fever control

Prevention
ITN IRS

IPT
Larval control Repellants ? vaccine

Malaria elimination on Hispaniola

The Lancet Infectious Diseases May 2010:

What is needed for malaria elimination on

Hispaniola?

Eliminate the human reservoir

Establish active case detection around patients

identified passively through health systems to detect asymptomatic infections

Mass detection and treatment of infection, particularly

during the extended dry season

Prevent transmission
Targeted insecticide-treated mosquito nets, indoor

residual spraying, or larval habitat management around foci of infection identified through passive to active case detection

Mobilize community
To seek diagnosis and treatment for all fevers

To understand and support the elimination effort

Initiative
Carter Center launched initiative to eradicate malaria

in Haiti/DR by 2010 Will likely cost $200 million