Malaria in Maternal Health (Dr. William Brieger)

Malaria in Maternal Health

William R Brieger

Senior Malaria Adviser, Jhpiego

June 11, 2011

National Press Foundation

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Malaria Risk Measured by Parasites (top) and Aridity/Humidity (bottom)

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Maternal Mortality – Deaths per 1000 Live Births

http://www.who.int/making_pregnancy_safer/en/

http://www.who.int/making_pregnancy_safer/en/

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Does this occur by chance?

Malaria Maternal Mortality

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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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INTERVENTIONS TO CONTROL MALARIA IN PREGNANCY

WHO’s 3-pronged approach

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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




Quickening

Source: WHO 2002.

Last month

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Rationale for the Timing of the SP Doses




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


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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RDTs make diagnosis possible and save lives

http://www.fightingmalaria.info/vr3

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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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All Kinds of Malaria Drugs Are on the Market

… but not all are safe or appropriate

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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

INSECTICIDE TREATED NETS

Start net use as early in pregnancy as possible

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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

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CHALLENGES

Correct use and adequate coverage

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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Can We Prevent Net Misuse?

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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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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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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

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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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The Good News: Save the Children Documents Progress in Maternal Survival

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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