Malaria in Haiti Symposia, presented in Milot, Haiti at Hôpital Sacré Coeur. CRUDEM’s Education Committee (a subcommittee of the Board of Directors) sponsors one-week medical symposia on specific medical topics, i.e. diabetes, infectious disease. The classes are held at Hôpital Sacré Coeur and doctors and nurses come from all over Haiti to attend.

1. Anthony
Karabanow,
MD

3. 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

6. 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

8. 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

10. 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

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

12. 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

14. Clinical
disease
 MALARIA
IS
A
NON-­‐SPECIFIC
FEBRILE
ILLNESS

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

16. Clinical
disease
 Greatest
risk
for
severe
disease:
 Children
 Pregnant
women
 Non-­‐immune
individualized
 Immunocompromised

17. Clinical
disease

18. PHYSICAL
EXAM
VIDEO

19. CNS
disease
 Impaired
consciousness
 Delirium
 Seizures
 More
common
in
children
 If
untreated,
usually
fatal
 With
treatment,
mortality
is
15-­‐20%

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

21. Macular
whitening

22. White
re$nal
vessels

23. Re$nal
hemorrhage

24. Proposed
algorhythm

25. ARDS
 Non-­‐cardiogenic
pulmonary
edema:
 Parasite
sequestration
in
lungs
 SIRS

26. ARDS

27. Renal
failure
 Pathogenesis:
 Parasite
sequestration
in
renal
microcirculation
 Hemolysis
(“blackwater
fever”

ATN)
 Hypovolemia

28. Blackwater
fever

29. Anemia
 Pathogenesis:
 Hemolysis
 Cytokine
suppression
of
hematopoiesis

30. Severe
anemia

31. Hypoglycemia
 Pathogenesis:
 Increased
host
glucose
consumption
 Quinine
induced

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

34. Diagnosis
 Microscopy
(gold
standard)
 Rapid
Diagnostic
Tests
(RDTs)
 PCR

35. Microscopy
 Has
sensitivity
of
5
–
10
parasites/microL
 Thick
smears
 Measure
parasite
density
 Thin
smears
 Identification
of
malarial
species

40. 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

41. Calcula$ons
 Count
parasites
until
200
WBCs
have
been
seen
 Parasite
density
(#/microL)
=
 (#
parasites)
x
(WBC
count
/
200)
 %
Parasitemia
=
 (Parasite
density)
/
WBC

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

43. Op$MAL
assay

44. Op$MAL
assay

45. Problems
with
RDTs
 Decreased
sensitivity
at
low
parasitemia
 Cannot
quantify
parasitemia
 Positive
test
despite
parasite
clearance
 Higher
cost

46. PCR
 Can
detect
as
few
as
1
to
5
parasites/microL
 Cannot
quantify
infection
 Costly
 Requires
specialized
equipment
and
trained
staff

47. Treatment
 Good
news:
P.
falciparum
malaria
in
Haiti
is
chloroquine
sensitive
 Bad
news:
P.
falciparum
malaria
in
Haiti
can
still
prove
fatal

49. 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

50. 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

51. 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.

52. Management
of
severe
malaria
 Treat
the
parasitemia
 Treat
the
organ
dysfunction

53. 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).

54. 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

55. 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

58. ARDS

May
need
mechanical
ventilation

Avoid
volume
overload
leading
to
cardiogenic
pulmonary
edema

59. Renal
failure
 Infuse
isotonic
saline
to
maintain
euvolemia
 Dialysis
as
necessary

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

61. Hypoglycemia
 Follow
blood
sugars
routinely
 Use
IVF
with
D5
routinely
 Consider
in
pts
with
MS
changes

62. 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

63. Preven$on
 ITN
 IRS
 IPT
 Larval
control
 Repellants
 ?
vaccine

64. Malaria
elimina*on
on
Hispaniola
 The
Lancet
Infectious
Diseases
May
2010:
 What
is
needed
for
malaria
elimination
on
Hispaniola?

65. 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

66. 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

67. Mobilize
community
 To
seek
diagnosis
and
treatment
for
all
fevers
 To
understand
and
support
the
elimination
effort

68. Ini$a$ve
 Carter
Center
launched
initiative
to
eradicate
malaria
in
Haiti/DR
by
2010
 Will
likely
cost
$200
million