Epidemiology and control of malaria during pregnancy in

sub-Saharan Africa

Mary Hamel, M.D.

Malaria Branch, CDC

Objectives

Discuss the epidemiology of malaria during pregnancy (MIP) in sub-Saharan Africa

Describe intervention strategies, challenges and successes

Discuss MIP and HIV interactions and strategies

Epidemiology

Malaria during pregnancy

50 million women in malaria endemic areas become pregnant each year

MIP estimated to account for:• 400,000 cases of severe anemia in pregnant

women Post-partum hemorrhage is a leading cause of maternal

mortality

• ~ 35% of preventable low birth weight (LBW) LBW is risk for infant mortality

• 3-8% of infant mortality• 75,000 - 200,000 infant deaths annually

Risks for MIP

Primi- or secundi- gravida• 1st or 2nd pregnancy, have not developed

pregnancy-specific acquired immunity

HIV-positive women • Eliminates gravidity-specific pattern

Young maternal age (ex. adolescents)

Current strategies, challenges and successes

Major strategies for malaria control during pregnancy

Drugs• Intermittent preventive treatment during

pregnancy (IPTp)• Febrile case management

Insecticide Treated Nets (ITNs)

Intermittent Preventive Treatment for pregnancy (IPTp)

IPTp to prevent MIP

Rationale for IPTp Prevents placental malaria (or clears established

placental infection), during period of rapid fetal growth Most commonly used regimen: • Sulfadoxine-pyrimethamine (SP) • At least 2 treatment doses (3 tablets) but best to have 3 or

more doses starting after quickening (~16 weeks gestation), provided at least 4 weeks apart Can be given monthly Can be given until end of pregnancy

• HIV infected need at least 3 doses for benefit None if taking daily septrin

IPTp to prevent MIP

SP works for IPTp despite high SP resistance and malaria treatment failures in young children• Acquired immunity• prevention vs. treatment• Confusing for policy makers and health workers (HWs)

Easily deliverable (single dose) Can be provided under directly observed therapy (DOT)

at clinic Well-tolerated, inexpensive

• Very few side effects• Rarely Stevens Johnson Syndrome (SJS) if allergy

If mucosal lesions, rash, stop SP and see doctor

Why is IPTp implementable?

In most African countries women attend antenatal clinic (ANC)

Typically begin ANC in 2nd trimester On average make 3-4 ANC visits during

pregnancy Ample time to provide at least 2 doses WHO recommendation to provide IPTp ~

1999

IPTp implementation

In most countries, less than 20% of pregnant women living at risk for malaria receive at least 2 doses of SP IPTp

Challenges in implementation: IPTp Malawi

IPTp adopted into policy ~ 1999 2002: 21% recently pregnant women

presenting to deliver at the major hospital in the capital city had received 2 doses IPTp

IPTp Malawi– Exploring poor uptakeHealth worker survey

Health workers (HW) reported:• Women arrive at ANC late in pregnancy• Women do not come to ANC• Women refuse IPTp• Women afraid to take IPTp on an empty

stomach• SP out of stock or reserved for treatment

Women told to cut grass around compound

• No water in the clinic for IPTp DOT

90% of women visited ANC Women come to ANC beginning in 2nd

trimester Average number of visits = 4 Women reported they go to ANC to get SP

and iron

IPTp Malawi– Exploring poor uptakeHousehold survey

SP in stock Nonetheless, women at clinic on day of

survey who were due for IPTp did not receive IPTp

IPTp Malawi– Exploring poor uptakeHealth facility survey

HWs confused about when IPTp should be provided• Old WHO recommendations confusing

Administer treatment dose of SP in 2nd and 3rd trimester, not last 4 weeks of pregnancy

• HWs could not accurately estimate trimesters

• HWs could not determine last 4 weeks of pregnancy Not necessary, theoretical risk of kinicterus not founded

As result, WHO issued simplified guidelines

IPTp Malawi– Exploring poor uptakeHealth worker observation

Current WHO recommendations for IPTp

Beginning after quickening, provide at least 2 doses of SP as IPTp no less than 4 weeks apart

New IPTp policy in Malawi

Memo circulated from MOH with new guidelines, instructing HWs to follow them

No change in SP supply, water supply, community mobilization or information for pregnant women

6 months after new guidelines, HF survey showed 71% of pregnant women had received SP IPTp

IPTp in Kenya IPTp adopted 1998, and new guidelines adopted in

2006 Malaria Indicator Survey (MIS) 2007

• 13% of women received 2 doses of SP IPTp

Similar results in western Kenya despite HW re-training and community mobilization

Similar memo circulated to health facilities Household survey: 41% of recently pregnant

women received 2 doses IPTp

MINSTRY OF HEALTH

RefXX/YY/ZZ 10, December, 2010

To: District Medical Offi cer of Health

-X District

-Y District

-Z District

Medical Superintendant

- X District Hospital

-Y District Hospital

-Z District Hospital

Re: Scale up of Intermittent Preventive Treatment for Malaria in Pregnancy (IPTp)

The Malaria Indicator Survey of 2007 showed that despite good antenatal clinic attendance, only 21% of women received the second dose of SP for IPTp. This is a commendable achievement from as low as 7%, but needs to be increased to achieve internationally set targets of 80%.

Numerous studies now show that it is beneficial to receive more than 2 doses of SP IPTp. All facilities in your district should now follow the current national guidelines on IPTp, which are:

1. All pregnant women should receive a treatment dose of IPTp at every antenatal clinic visit unless they have received SP in the prior four weeks.

2. Women who visit monthly for antenatal clinic should receive SP. 3. SP can be given in the last four weeks of pregnancy without risk to the mother or the baby. 4. Additional doses of SP IPTp, above two doses, reduces malaria in pregnancy and is beneficial to

the baby.

After this memo, there will be a national survey which will measure among other things, the number of women who receive 2 or more doses of IPTp. At that time, we hope to find over 85% of recently pregnant women received at least 2-3 doses of SP for IPTp.

Scaling up proven interventions is challenging

We may know what works, but finding out how to implement/scale-up is a different issue

Barriers perceived by HWs, policy makers, NGOs, not always true barriers

“Obvious” solutions don’t always work• Re-training, community mobilization/education

Measuring whether efforts are effective is essential

Insecticide treated bed nets (ITNs)

ITNs to prevent malaria in pregnancy

40% reduction in malaria parasitemia 50% reduction in severe malaria

anemia 35% reduction in placental malaria 30% reduction in LBW ITNs are life-saving

ITN scale up for MIP

WHO recommended ITNS for prevention of MIP ~ 1996

Initially promoted through “social marketing”• Radio spots, billboards, drama• Subsidized, ~8USD per ITN initially, later $0.70/net in ANC

By 2005, after nearly a decade of ITN promotion, <20% of pregnant women slept under ITN in most countries

Cost was major barrier

ITN scale up for MIP

Beginning 2005, national ITN distribution campaigns in many countries• Often paired with measles campaigns• Highly successful

In Kenya, resulted in increase from 4% of pregnant women sleeping under an ITN in 2003, to 40% in 2007

In many places, ITNs now provided free to pregnant women in ANC

Strategy for ITN scale up for MIP

Best approach combines strategies• Social marketing to build demand• Mass distribution campaigns every 3

years• Continuous supply through ANC for newly

pregnant mothers An ITN for mother, is an ITN for infant

• Others?

Case management of malaria

Case management of malaria in pregnancy

If fever, test for malaria and treat However, due to acquired immunity, in

areas of high malaria transmission, mother may not be sick• Reason behind IPTp

Some hospitals offer screening blood smears and treatment at ANC• Typically only first visit

Drugs used for malaria treatment during pregnancy in sub-Saharan Africa

Used frequently Quinine SP

Used with caution Artemether lumefantrine

(AL or coartem) Any artemisinin

combination

Antimalarials contra-indicated in pregnancy

Tetracycline Doxycycline Halofantrine Primaquine Tafenoquine

Malaria in Pregnancy and HIV

Malaria in Pregnancy and HIV

In sub-Saharan Africa, 55% of HIV infected adults are women of reproductive age

Malaria and HIV interact in ways that are bad for both the mother and the neonate

MIP and HIV Interaction

HIV infected pregnant women have increased• Peripheral and placental parasitemia

• Malaria parasite densities

• Febrile illnesses

• Severe anemia

• Adverse birth outcomes Low birth weight, preterm birth, IUGR

Acquired immunity resulting in partial protection to multigravidae lost

MIP and HIV Interaction

Conflicting results regarding MIP and HIV transmission to baby

HIV and Malaria Preventive Strategies

Prevention of Mother to Child Transmission of HIV strategies

Daily septrin for prevention of opportunistic infections protects against malaria in pregnancy• IPTp with SP not required and contraindicated –

two sulfa drugs

If unknown status in area of high HIV prevalence, test, or provide at least 3 doses SP IPTp

Malaria in PregnancyConclusions

Although preventable, a serious public health problem, associated with anemia, low birth weight, and infant deaths

A limited number of effective interventions exist• ITNs, IPTp, case management, daily septrin for HIV

infected women

Implementation and scale up is challenging• Evaluation of efforts is essential to ensure gains are

made