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Malaria in Maternal Health
William R Brieger
Senior Malaria Adviser, Jhpiego
June 11, 2011
National Press Foundation
Malaria Risk Measured by Parasites (top) and
Aridity/Humidity (bottom)
2
Maternal Mortality – Deaths per 1000 Live Births
http://www.who.int/making_pregnancy_safer/en/
3
Does this occur by chance?
Malaria
Maternal Mortality
4
Malaria is an Important Contributor to Maternal
Mortality in Endemic Countries
Anemia
11%
Other
5%
Haemorrhage
23%
Malaria
11%
Infection
17%
Obstructed
labour
11%
Unsafe
Abortion
11%
Toxemia/
Eclampsia
11%
5
Malaria during pregnancy: bad news
 Each year, more than 30 million women in Africa
become pregnant in malaria-endemic areas.
 Malaria during pregnancy in sub-Saharan Africa
is estimated to account for:
 400,000 cases of severe anemia in pregnant women
 ~ 35% of preventable low birth weight
 ~ 5% of infant mortality
– 75,000 - 200,000 infant deaths annually
6
Why Is Malaria in Pregnancy (MIP)
Important?
 MIP effects on Women
 2-15% of maternal anemia
 Possibly up to 10,000 maternal deaths annually
 Possible effects on pre-eclampsia
 Increased post-partum hemorrhage
Source: WHO Afro 2004
7
Placental Malaria in African Women: the First
Pregnancy Is Most Dangerous
Multigravida
i
al
aw
M
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ire
er
ia
N
ig
aU
G
am
bi
aR
am
bi
G
C
oa
a
Iv
or
y
an
i
Ta
nz
U
ga
nd
st
70
60
50
40
30
20
10
0
a
Prevalence %
Primigravida
Placental malaria deprives the fetus of nutrients
8
MIP effects on fetus/child
 13-70% intrauterine
growth retardation
 As high as 20% of low birth
weight newborns
 30% of “preventable” low
birth weight newborns
 8-36% of preterm births
 ~5% congenital malaria in
newborns
 3-5% of newborn deaths,
3-8% of infant deaths
 Miscarriage and stillbirth
9
Low Birth Weight Predisposes to Other
Causes of Neonatal and Infant Death
Frequency of Low Birth Weight by Placental Malaria Infection
% Low Birth Weight
35
30
With placental
parasites
25
20
Without placental
parasites
15
10
5
0
First
Pregnancy
Second
Pregnancy
Source: Steketee 2001: Malawi 1988-1991
Three or more
pregnancies
10
Characteristics of Malaria Transmission
Stable Areas
 Year-round
transmission e.g.
Nigeria
Unstable Areas
 Seasonal or epidemic
transmission e.g. South
Africa
 People receive frequent
 People are infrequently
infective mosquito bites
each month
 Levels of acquired
immunity are high
(pregnant women are
semi-immune to malaria)
 Low peripheral
parasitemia
 Heavy placental infection
exposed to malaria
 Levels of acquired
immunity are low
(pregnant women are
not immune)
 Heavy peripheral
parasitemia
 Low or undetectable
placental infection
11
Effect of MIP in Stable Transmission Areas
 Acquired immunity – high
 1st & 2nd pregnancies at
Plasmodium falciparum malaria
Asymptomatic Infection
greatest risk
 Prevention essential (as most
Placental Sequestration
Altered Placental Integrity
women are not symptomatic)
Reduced Nutrient and Oxygen Transport
Anemia
Low Birth Weight (IUGR)
Risk of Newborn Mortality
Source: WHO 2002.
12
Effect of MIP Unstable Transmission Areas
 Acquired immunity – low
 All pregnancies affected
Acquired Immunity – Low
equally
 Prompt diagnosis and
Clinical Illness
treatment needed in
addition to prevention
Severe Disease
Risk to Mother
Source: WHO, 2002
Risk to Fetus
13
INTERVENTIONS TO CONTROL
MALARIA IN PREGNANCY
WHO’s 3-pronged approach
14
Three Main Control Tools
 IPTp = Intermittent preventive treatment in
pregnancy
 ITNs = Use of insecticide-treated nets, including
long lasting insecticide treated nets (LLINS)
 Case management of malaria disease
 Diagnosis with Rapid Tests, Microscopy
 Appropriate antimalarial drug for treatment
 Indoor Residual Spraying not specific to MIP, but
where offered should be mentioned in health
education to women
15
16
Intermittent Preventive Treatment in Pregnancy
 IPTp is an approach for effectively preventing
and controlling malaria during pregnancy that
 Is based on an assumption that every pregnant
woman in a malaria-endemic area is infected with
malaria, and
 Recommends that every pregnant women receive at
least two treatment doses of an effective antimalarial
drug as a preventive measure
 Sulfadoxine-pyrimethamine (SP) currently
considered the most effective drug for IPTp
17
IPTp with Sulfadoxine-Pyrimethamine
 SP is a combination of two different drugs. Each
tablet of SP contains:
 500 mg of sulfadoxine, and
 25 mg of pyrimethamine
 A single dose consists of three tablets taken at
once, preferably under direct observation of the
healthcare provider
 Fansidar is the most common brand name. Others
include Falcidin, Laridox, Maladox, Orodar, Maloxine
 SP is generally more effective than chloroquine
which is no longer effective in most countries
because of parasite resistance
18
Effect of IPTp with SP
 Case management alone does not reduce effects of
malaria in pregnancy as well as IPTp
 Not all women with malaria parasites have
symptoms, and therefore would not receive
treatment if we relied solely on case management
 IPTp produced better outcomes in terms of reducing
 Maternal and placental parasitemia
 Low birth weight
 IPTp is as effective as case management in terms of
improving hemoglobin levels
19
Fetal Growth Velocity
Fetal growth velocity 
Last
month
10
Conception
Source: WHO 2002.
16
20
Weeks of gestation
30
Birth
20
Fetal Growth Velocity: Quickening
Fetal growth velocity 
Last
month
Quickening
10
Conception
Source: WHO 2002.
16
20
Weeks of gestation
30
Birth
21
Rationale for the Timing of the SP Doses
Fetal growth velocity 
Rx
Rx
Last
month
Quickening
10
Conception
Source: WHO 2002.
16
20
Weeks of gestation
30
Birth
22
Key Issues About Timing of Doses
 SP should be avoided during the first 16 weeks
of pregnancy which is the period of initial
development of the fetus
 It is best to clear the placenta of parasites during
the period of maximum fetal growth
 IPTp allows the mother to recover from anemia
by clearing peripheral parasitemia
 A note for the future – SP resistance is growing,
and at some point a new medicine for IPTp will
be found
 More on this later
23
Steps for Providing IPTp with SP
 Determine quickening has occurred
 Inquire about history of severe skin rash from
previous SP use
 Inquire about use of SP in last month
 Provide three tablets of SP with clean water in a
clean cup
 Observe the patient swallowing all three tablets
(Directly Observed Treatment or DOT strategy)
 DOT is one reason to ensure that IPTp is an
essential component of an integrated ANC program
 Do not encourage women to undertake IPTp on their own
24
Steps for Providing IPTp with SP (continued)
 Record SP on the antenatal card and the clinic
record
 Instruct clients to return at next scheduled visit or
earlier if she is feeling ill
 Drop-out is a major challenge for successful IPTp
programs
 From 20-50% of women do not receive a second dose
 Inform clients that IPTp is most effective if they receive at
least two doses
 Ask about side effects from previous dose before
giving the next dose, which should not be less than
4 weeks from the last dose
25
SP Resistance and IPTp
 Waning efficacy of SP in treating symptomatic
children <5 years does not equate with waning
efficacy for prevention of malaria during
pregnancy
 IPTp with SP remains efficacious even in settings with
significant (<50%) treatment failure in symptomatic
children 6-59 months of age
 More than 2 doses are likely beneficial given rising
resistance
26
SP
IPTp – Monthly Dosing
SP
SP
Fetal growth velocity 
SP
SP resistance
shortens duration
post-treatment
prophylaxis
10
Conception
20
30
Weeks of gestation
Source: CDC Scott Filler October 2007
Birth
27
Malawi Randomized Controlled Trial of IPTp:
 Does monthly IPTp provide additional benefit over 2dose IPTp?
 In preventing placental malaria
 For HIV-positive/negative women
 Is SP efficacious for IPTp despite 31% SP failure
rate for treatment in young children?*
 For HIV-positive pregnant women, monthly SP IPTp
more efficacious than 2-dose SP IPTp in reducing
placental malaria
 For HIV-negative pregnant women, monthly SP
IPTp may have benefit over 2-dose SP IPTp
 Despite treatment failures in children, SP remains
efficacious for IPTp
*Malawi Ministry of Health and Population Report, 2004
28
APPROPRIATE CASE MANAGEMENT
Parasitological diagnosis
Treatment with appropriate medicines
Counseling to ensure adherence
29
Case Management: Drug Efficacy
 Malaria episodes in pregnancy are serious and
must be treated promptly with an appropriate
drug
 Effective drugs are needed for P. falciparum
malaria as it can be fatal to both mother and
child
 Remember differences between stable and
unstable transmission areas
 Note importance of diagnosis
30
Importance of diagnosis
 Laboratory/slide diagnosis is still the gold standard
 Few front line clinics have labs and/or trained staff
 Rapid diagnostic tests are becoming more available
 Can reduce treatment costs only treat ‘real’ malaria cases
 Storage issues in terms of temperature, expirey dates
31
RDTs make diagnosis possible and save lives
http://www.fightingmalaria.info/vr3
32
Drug Choice
 Drug of choice depends on the geographic drug
resistance profile and national malaria drug
policies
 Quinine is the drug of choice for malaria in first trimester
pg pregnancy
 SP is reserved for IPTp
 Artemisinin-based combination therapy (ACT) drugs can
be used after the first trimester
33
All Kinds of Malaria Drugs Are on the Market
… but not all are safe
or appropriate
34
Resistance to Drugs
 Resistance of P. falciparum to antimalarial drugs
is an ever increasing problem
 To minimize the problem of drug resistance,
encourage women to complete their course of
antimalarial drugs, even when they feel better
 Drug resistance is inevitable; therefore
healthcare providers must stay informed about
policy changes recommended by their Ministry
of Health
35
Drugs Not To Be Used During Pregnancy
 Tetracycline
 Cause abnormalities of skeletal and muscular growth,
tooth development, lens/cornea
 Doxycycline
 Risk of cosmetic staining of primary teeth is undetermined
 Excreted into breast milk
 Primaquine
 Harmful to newborns who are relatively Glucose-6-
Phosphatase-Dehydrogenase (G6PD) deficient
 Halofantrine
 No conclusive studies in pregnant women
 Has been shown to cause unwanted effects, including
death of the fetus, in animals
36
INSECTICIDE TREATED NETS
Start net use as early in pregnancy as possible
Insecticide-Treated Nets (ITNs)
 An ITN is a mosquito preventing bednet (or other
netting material such as curtains) that has been
soaked in a safe insecticide
 The insecticide kills the mosquito when it comes
near the sleeping person
 Traditional ITNs required re-treatment with
insecticide every six months
 While ITNs are still available in many countries,
most are switching to long lasting insecticide-treated
nets (LLINs) where the insecticide is applied at the
factory
 LLINs can withstand washing up to 20 times and
may last over 4 years
38
Use ITNs/LLINs
 The use of
ITNs/LLINs have
been shown to result
in reduction of
newborns born with
low birth weight or
prematurely
 ITNs reduce
transmission by
physically preventing
vector mosquitoes
from landing on
sleeping persons
39
ITN/LLIN Benefits
 Repel and kill
mosquitoes that
come in contact
with the net
 Kill other insects
like cockroaches,
lice, ticks and bed
bugs
 Should be used by
pregnant women
as early during
pregnancy as
40
Impact on Fetal Growth and Duration of Gestation
 Pregnant women protected by insecticidetreated nets were less likely
 To deliver prematurely or
 To have small-for-gestational-age newborns
 Compared to control groups who were not protected
by the nets
 This finding holds true irrespective of the
woman’s parity, except for the incidence of
small-for-gestational-age babies born to women
with 4 or more pregnancies
 Source: ter Kuile et al 1999
41
ITN: Impact on Fetal Growth and Duration of Gestation
%
45
Premature
LBW
Premature
or LBW
Percentage
40
35
30
control
25
bednets
20
15
10
5
0
Gravidity
Source: ter Kuile et al 1999; LBW = Low Birth Weight
42
Impact of ITNs on Maternal and Newborn
Health
 Among Gravidae 1-4,
ITNs were associated
during pregnancy
with:
 38% reduction in
peripheral parasitemia
 21% reduction in all
causes of anemia (Hb
< 11 g/dl)
 47% reduction in
severe malarial
anemia
Source: Shulman 2001: Western Kenya
43
Impact of ITNs at Delivery
 At delivery
 23% reduction in
placental malaria
 28% reduction in LBW
 25% reduction in any
adverse birth outcome
 No trend towards
decreasing efficacy
with increasing
transmission rate
44
ITN/LLIN Procurement and Management
 It is quite popular these days to provide ITNs within
childhood immunization campaigns
 It is less common to find that ITNs have been allocated
in adequate numbers to be given out as an essential
component of focused ANC
 The district health management team needs to meet and
plan for adequate nets, not only for children under five
years of age, but also ensure that adequate nets are
supplied to ANC clinics
 ITN/LLIN provision can be an important incentive to
attend ANC
 A woman should get a net on her first ANC visit when it
can offer the most protection during pregnancy
45
CHALLENGES
Correct use and adequate coverage
46
Examples of MIP Data/Indicators
(from surveys 2006-08)
80
70
70
Percentage
60
50
80% was RBM target for 2010
60
51
50
47
43
40
35
32
32
26
30
17
20
10
17
20
14
7
3
12
5
0
Zambia
IPTp2
Senegal
Angola
Tanzania
Slept under Any Net
Malawi
Nigeria
Slept under ITN
47
Most women attend ANC in Africa, but they may not
make two visits that support IPT compliance
100
90
80
% women
70
60
50
40
30
20
Any ANC visit
Ave 20
ETH
MAL
MAU
ERI
CAM
MOZ
BEN
GHA
TAN
ZAM
0
GAB
10
IPT compatible
*E Eckert, A Hyslop, R Snow, MEASURE Evaluation, Macro International, APHA 2005
48
Senegal – who slept under a net?
80
RBM 2010 Target is 80%
70
Percent
60
50
41.5
40
30
27.9
24.1
39.1
44.2
26.8
20
10
0
All Households
Child <5
All Women 15-49
2008-09 Senegal Malaria Indicator Survey
HH with LLINs
Pregnant Women
49
Can We Prevent Net Misuse?
50
AN INTEGRATED APPROACH TO
MIP CONTROL
Improved Health Systems
Focused Antenatal Care
Attention to HIV/AIDS
Community Involvement
51
Malaria in Pregnancy Systems Readiness
Component
Indicators
Policy
Policy, strategy and service delivery guidelines
developed and being used at all levels of the
health system
Commodities
Drug procurement and distribution systems
efficient; WHO-recommended medicines for
malaria and/ or MIP are always available;
ITNs always available
Quality
Assurance
MIP quality assurance standards have been
developed and are used in systematically;
supportive supervision for MIP services
utilized systematically
52
Malaria in Pregnancy Systems Readiness
Component
Indicators
Training
In-service training on MIP conducted for all
appropriate cadres of health service providers;
updated pre-service nursing, midwifery and
medical MIP curricula is being taught at all
academic institutions
Integration
Joint strategies, planning and sharing of
information between National Malaria Control
Programs at national level; district level
promotes integration of RH, HIV/AIDS and MIP
in administration and supportive supervision;
MIP, reproductive health and/or HIV/AIDS are
provided together in health services
53
Malaria in Pregnancy Systems Readiness
Component
Indicators
Communitybased MIP
Programs
Community action groups are strong partners in
national MIP prevention efforts; appropriate
resources widely available
M&E
HMIS systems strong; MIP indicators being
collected regularly; some endline studies
designed to capture achievements and / or
impact studies being conducted
Financing
National government has committed and
disbursed funds to MIP programs which
significantly contribute to projected costs;
ample donor funding exists
54
Antenatal Care as a Platform for MIP Control
 Antenatal visits provide a unique opportunity for:
 Monitoring of maternal and fetal health during pregnancy
 immunizations
 Provision of micronutrients (e.g., iron folate)
 Health education about malaria during pregnancy
 IPTp with sulfadoxine-pyrimethamine (SP)
 ITN distribution
 Prompt diagnosis and treatment of malaria
 Prevent mother-to-child transmission of HIV
 District health teams must promote timely ANC
attendance if MIP interventions are to reach the
maximum number of pregnant women
55
Focused Antenatal Care (FANC)
 Early detection and
treatment of problems
and complications
 Prevention of
complications and
disease
 Birth preparedness
and complication
readiness
 Health promotion
 First visit: Within 16
weeks or when woman
first thinks she is
pregnant
 Second visit: At 20-24
weeks or at least once
in second trimester
 Third visit: At 28-32
weeks
 Fourth visit: At 36
weeks or later
56
Summary of Malaria Activities at FANC
1st Visit
2nd Visit
3rd Visit
4th Visit
IPTp
Yes
(if after 16
weeks)
Yes
(if one
month
after 1st)
Yes
(if one
month
after 2st)
Additional
if not all
IPTp
received
ITN
Provide
Counsel
on use
Counsel
on use
Counsel
on use
Treatment
As
needed
after test
As
needed
after test
As needed As needed
after test
after test
57
Bad Combination: Placental Parasitemia
and HIV
% parasitemic
Placental Parasitemia by HIV Status and Pregnancy
Number, Kenya, 1996-1998
40
35
30
25
20
15
10
5
0
Parasite density/mm3
1-999
231
G1
159
G2
HIV (+)
197
G3
1000-9,999
772
>10,000
402
479
G1
G2
HIV (-)
G3
Summary RR = 1.63 (1.41-1.89), p <0.001
Total n = 2263
Source: van Eijk AM et al 2001.
58
Nigeria MIP Community-Clinic Partnership
for Community Directed Intervention
CLINIC
MIP
performance
standards
developed and
implemented
59
Training,
Supervision,
Mobilization,
Commodities
Referrals,
Records,
Feedback
COMMUNITY
MIP skills and
responsibilities
implemented
through
communitydirected
intervention
Community Directed Intervention Program
Impact: Improved IPTp Uptake
80
71
70
65
60
52
50
40
27
30
20
10
12
6
11
5
0
Intervention
Baseline IPTp1
Endline IPTp1
Control
Baseline IPTp2
Endline IPTp2
60
ITN Use by Pregnant Women through
Community Directed Intervention
45
40
40
35
30
30
28
25
20
20
15
10
5
0
Intervention
Control
Baseline ITN
Endline ITN
61
The Good News: Save the Children Documents
Progress in Maternal Survival
62
Summary
 Malaria during pregnancy has adverse
consequences for mothers and their babies
 Malaria preventive package includes:
 Intermittent preventive treatment during pregnancy with SP
during antenatal clinic visits
 Use of ITNs/LLINs throughout pregnancy and in the
postpartum period
 Prevention must be complemented by effective case
management of malaria illness for all women of
reproductive age
 Health Systems issues must be addressed from
national to facility level to ensure full delivery of MIP
services
63
Contact Information
William Brieger
http://www.malariafreefuture.org/blog/
Senior Malaria Specialist, JHPIEGO http://www.jhpiego.org/whatwedo/malaria.htm
Professor, Health Systems Program, Department
of International Health, The Johns
Hopkins Bloomberg School of Public Health
http://faculty.jhsph.edu/Default.cfm?faculty_id=90;
[email protected]; [email protected]
malaria updates at: http://twitter.com/bbbrieger
64