Malaria in Maternal Health

1. Malaria in Maternal Health William R Brieger Senior Malaria Adviser, Jhpiego June 11, 2011 National Press Foundation

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

3. Maternal Mortality – Deaths per 1000 Live Births http://www.who.int/making_pregnancy_safer/en/

4. Does this occur by chance? Malaria Maternal Mortality

5. Malaria is an Important Contributor to Maternal Mortality in Endemic Countries

6. 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

7. 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

8. Placental Malaria in African Women: the First Pregnancy Is Most Dangerous Placental malaria deprives the fetus of nutrients

9. 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

10. 35 30 25 20 With placental parasites 15 Without placental parasites 10 5 0 Low Birth Weight Predisposes to Other Causes of Neonatal and Infant Death Frequency of Low Birth Weight by Placental Malaria Infection % Low Birth Weight First Pregnancy Second Pregnancy Three or more pregnancies Source: Steketee 2001: Malawi 1988-1991

11. 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

12. Effect of MIP in Stable Transmission Areas • Acquired immunity – high • 1st & 2nd pregnancies at greatest risk • Prevention essential (as most women are not symptomatic) Plasmodium falciparum malaria Asymptomatic Infection Placental Sequestration Altered Placental Integrity Reduced Nutrient and Oxygen Transport Anemia Low Birth Weight (IUGR) Risk of Newborn Mortality Source: WHO 2002.

13. Acquired Immunity – Low Clinical Illness Severe Disease Risk to Mother Risk to Fetus Effect of MIP Unstable Transmission Areas • Acquired immunity – low • All pregnancies affected equally • Prompt diagnosis and treatment needed in addition to prevention Source:WHO, 2002

14. Interventions to Control Malaria in Pregnancy WHO’s 3-pronged approach

15. 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

17. 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

18. 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

19. 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

20. Fetal Growth Velocity Fetal growth velocity  Last month 10 16 20 30 Weeks of gestation Birth Conception Source: WHO 2002.

21. Fetal Growth Velocity: Quickening Fetal growth velocity  Last month Quickening 10 16 20 30 Weeks of gestation Birth Conception Source: WHO 2002.

22. Rationale for the Timing of the SP Doses Fetal growth velocity  Rx Rx Last month Quickening 10 16 20 30 Weeks of gestation Birth Conception Source: WHO 2002.

23. 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

24. 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

25. 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

26. 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

27. SP IPTp – Monthly Dosing SP SP Fetal growth velocity  SP SP resistance shortens duration post-treatment prophylaxis 20 10 30 Conception Birth Weeks of gestation Source: CDC Scott Filler October 2007

28. 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

29. Appropriate case management Parasitological diagnosis Treatment with appropriate medicines Counseling to ensure adherence

30. 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

31. 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

32. RDTs make diagnosis possible and save lives http://www.fightingmalaria.info/vr3

33. 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

34. All Kinds of Malaria Drugs Are on the Market … but not all are safe or appropriate

35. 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

36. 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

37. Insecticide Treated Nets Start net use as early in pregnancy as possible

38. 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

39. 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

40. 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

41. 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

42. ITN: Impact on Fetal Growth and Duration of Gestation % Premature LBW Premature or LBW 45 40 35 control 30 Percentage bednets 25 20 15 10 5 0 G<3 G>4 G<3 G>4 G<3 G>4 Gravidity Source: ter Kuile et al 1999; LBW = Low Birth Weight

43. 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

44. 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

45. 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

46. Challenges Correct use and adequate coverage

47. Examples of MIP Data/Indicators(from surveys 2006-08) 80% was RBM target for 2010

48. Most women attend ANC in Africa, but they may not make two visits that support IPT compliance *E Eckert, A Hyslop, R Snow, MEASURE Evaluation, Macro International, APHA 2005

49. Senegal – who slept under a net? RBM 2010 Target is 80% 2008-09 Senegal Malaria Indicator Survey

50. Can We Prevent Net Misuse?