Anthony Karabanow, MD
Hai$
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 Hai$
Emerging Infectious Diseases Journal (Volume 13, Number 10–October 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 a.er 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 re$nopathy
MALARIAL RETINOPATHY: A NEWLY ESTABLISHED DIAGNOSTIC SIGN IN SEVERE MALARIA
Am. J. Trop. Med. Hyg., 75(5), 2006, pp. 790-‐797
Macular whitening
White re$nal vessels
Re$nal hemorrhage
Proposed algorhythm
ARDS
Non-‐cardiogenic pulmonary edema: Parasite sequestration in lungs SIRS
ARDS
Renal failure
Pathogenesis: Parasite sequestration in renal microcirculation Hemolysis (“blackwater fever” ATN) Hypovolemia
Blackwater fever
Anemia
Pathogenesis: Hemolysis Cytokine suppression of hematopoiesis
Severe anemia
Hypoglycemia
Pathogenesis: Increased host glucose consumption Quinine induced
Metabolic acidosis
Pathogenesis: Tissue shock – sequestered parasites, hypovolemia Impaired renal/hepatic lactate clearance
Diagnosis
Microscopy (gold standard) Rapid Diagnostic Tests (RDTs) PCR
Microscopy
Has sensitivity of 5 – 10 parasites/microL
Thick smears Measure parasite density
Thin smears Identification of malarial species
Iden$fica$on $ps
Infected RBCs are of normal size Ring forms are commonly seen
Located at periphery of RBCs Multiple rings per RBCs may be present
Schizonts, trophozoites are rarely seen Gametocytes have banana shape
Calcula$ons
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
Op$MAL assay
Op$MAL 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 5–May 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
Preven$on
ITN IRS IPT Larval control Repellants ? vaccine
Malaria elimina*on on Hispaniola
The Lancet Infectious Diseases May 2010:
What is needed for malaria elimination on Hispaniola?
Eliminate the human reservoir
Establish active case detection around patients identified passively through health systems to detect asymptomatic infections
Mass detection and treatment of infection, particularly during the extended dry season
Prevent transmission
Targeted insecticide-‐treated mosquito nets, indoor residual spraying, or larval habitat management around foci of infection identified through passive to active case detection
Mobilize community
To seek diagnosis and treatment for all fevers
To understand and support the elimination effort
Ini$a$ve
Carter Center launched initiative to eradicate malaria in Haiti/DR by 2010
Will likely cost $200 million