malaria in maternal health william r brieger senior malaria adviser, jhpiego june 11, 2011 national...
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Malaria in Maternal Health
William R Brieger
Senior Malaria Adviser, Jhpiego
June 11, 2011
National Press Foundation
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Maternal Mortality – Deaths per 1000 Live Births
http://www.who.int/making_pregnancy_safer/en/
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Malaria is an Important Contributor to Maternal Mortality in Endemic Countries
Infection17%
Toxemia/ Eclampsia
11%
Unsafe Abortion
11%
Obstructed labour11%
Malaria11%
Anemia11%
Other5% Haemorrhage
23%
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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
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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
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Placental Malaria in African Women: the First Pregnancy Is Most Dangerous
010203040506070
Pre
vale
nce
%
Primigravida Multigravida
Placental malaria deprives the fetus of nutrients
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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
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Low Birth Weight Predisposes to Other Causes of Neonatal and Infant Death
FirstPregnancy
SecondPregnancy
Three or morepregnancies
With placental parasites
Without placental parasites
% L
ow
Bir
th W
eig
ht
Source: Steketee 2001: Malawi 1988-1991
0
5
10
15
20
25
30
35
Frequency of Low Birth Weight by Placental Malaria Infection
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Characteristics of Malaria Transmission
Stable Areas Year-round transmission
e.g. Nigeria People receive frequent
infective mosquito bites each month
Levels of acquired immunity are high (pregnant women are semi-immune to malaria)
Low peripheral parasitemia
Heavy placental infection
Unstable Areas Seasonal or epidemic
transmission e.g. South Africa People are infrequently
exposed to malaria Levels of acquired
immunity are low (pregnant women are not immune)
Heavy peripheral parasitemia
Low or undetectable placental infection
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Acquired immunity – high
1st & 2nd pregnancies at
greatest risk
Prevention essential (as
most women are not
symptomatic)
Effect of MIP in Stable Transmission Areas
Asymptomatic Infection
Altered Placental Integrity
Reduced Nutrient and Oxygen Transport
Placental Sequestration
Low Birth Weight (IUGR)
Risk of Newborn Mortality
Plasmodium falciparum malaria
Anemia
Source: WHO 2002.
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Effect of MIP Unstable Transmission Areas
Acquired Immunity – Low
Clinical Illness
Severe Disease
Risk to Mother Risk to Fetus
Source: WHO, 2002
Acquired immunity – low
All pregnancies affected
equally
Prompt diagnosis and
treatment needed in
addition to prevention
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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
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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
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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
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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
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Fetal Growth Velocity
Conception Birth20 3010
Weeks of gestation16
Fetal growth velocity
Source: WHO 2002.
Last month
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Fetal Growth Velocity: Quickening
Conception Birth20 3010
Weeks of gestation16
Fetal growth velocity
Quickening
Source: WHO 2002.
Last month
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Rationale for the Timing of the SP Doses
Conception Birth20 3010
Weeks of gestation16
Fetal growth velocity
Quickening
Source: WHO 2002.
Last month
RxRx
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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
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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
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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
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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
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IPTp – Monthly Dosing
Weeks of gestationConception Birth
20 3010
Fetal growth velocity
SP
SP
SP
SP
SP resistance shortens duration post-treatment prophylaxis
Source: CDC Scott Filler October 2007
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Malawi Randomized Controlled Trial of IPTp:
Does monthly IPTp provide additional benefit over 2-dose 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
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APPROPRIATE CASE MANAGEMENT
Parasitological diagnosisTreatment with appropriate medicinesCounseling to ensure adherence
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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
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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
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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
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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
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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
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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
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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
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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 possible and use should be encouraged throughout pregnancy and in the postpartum period
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Impact on Fetal Growth and Duration of Gestation
Pregnant women protected by insecticide-treated 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
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ITN: Impact on Fetal Growth and Duration of Gestation
0
5
10
15
20
25
30
35
40
45
G<3 G>4 G<3 G>4 G<3 G>4
control
bednets
% Premature LBW Premature or LBW
Source: ter Kuile et al 1999; LBW = Low Birth Weight
Gravidity
Pe
rce
nta
ge
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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
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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
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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
Examples of MIP Data/Indicators(from surveys 2006-08)
Zambia Senegal Angola Tanzania Malawi Nigeria0
10
20
30
40
50
60
70
80
60
51
3
70
47
7
50
32
17
35 32
12
43
17 1420
26
5
IPTp2 Slept under Any Net Slept under ITN
Per
cen
tag
e
47
80% was RBM target for 2010
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Most women attend ANC in Africa, but they may not make two visits that support IPT compliance
0
10
20
30
40
50
60
70
80
90
100
GA
B
ZA
M
TA
N
GH
A
BE
N
MO
Z
CA
M
ER
I
MA
U
MA
L
ET
H
Av
e 2
0
% w
om
en
Any ANC visit IPT compatible
*E Eckert, A Hyslop, R Snow, MEASURE Evaluation, Macro International, APHA 2005
Senegal – who slept under a net?
All Households HH with LLINs0
10
20
30
40
50
60
70
80
27.9
41.5
24.1
39.1
26.8
44.2
Child <5 All Women 15-49 Pregnant Women
Percent
492008-09 Senegal Malaria Indicator Survey
RBM 2010 Target is 80%
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AN INTEGRATED APPROACH TO MIP CONTROL
Improved Health SystemsFocused Antenatal CareAttention to HIV/AIDSCommunity Involvement
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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
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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
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Malaria in Pregnancy Systems Readiness
Component Indicators
Community-based 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
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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
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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
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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 after test
As needed after test
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Bad Combination: Placental Parasitemia and HIV
05
10152025303540
G1 G2 G3 G1 G2 G3
1-999 1000-9,999 >10,000
Parasite density/mm3
% p
ara
site
mic
HIV (+) HIV (-)
231 159 197 772402 479
Total n = 2263Summary RR = 1.63 (1.41-1.89), p <0.001
Source: van Eijk AM et al 2001.
Placental Parasitemia by HIV Status and Pregnancy Number, Kenya, 1996-1998
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Nigeria MIP Community-Clinic Partnership for Community Directed Intervention
CLINIC
MIP performance
standards developed and implemented
COMMUNITY
MIP skills and responsibilities implemented
through community-
directed intervention
Training, Supervision, Mobilization, Commodities
Referrals, Records, Feedback
Community Directed Intervention Program Impact: Improved IPTp Uptake
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Intervention Control0
10
20
30
40
50
60
70
80
12 116 5
71
52
65
27
Baseline IPTp1 Baseline IPTp2Endline IPTp1 Endline IPTp2
61
ITN Use by Pregnant Women through Community Directed Intervention
Intervention Control0
5
10
15
20
25
30
35
40
45
28
20
40
30
Baseline ITN Endline ITN
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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
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Contact Information
William Brieger http://www.malariafreefuture.org/blog/Senior Malaria Specialist, JHPIEGO - http://www.jhpiego.org/whatwedo/malaria.htmProfessor, 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