1. Epidemiology and control of malaria during pregnancy
M. James Eliades, MD, MPH
Centers for Disease Control and Prevention
Division of Parasitic Diseases

2. Objectives of talk
Discuss the epidemiology of malaria during pregnancy in sub-Saharan Africa
Present evidence for current intervention strategies
Mention gaps in our knowledge

3. Epidemiology

4. Malaria during pregnancy: bad news
50 million women in malaria endemic areas become pregnant each year (UNICEF)
Malaria during pregnancy most widely evaluated in sub-Saharan Africa and estimated to account for:
400,000 cases of severe anemia in pregnant women (Guyatt 2001)
~ 35% of preventable low birth weight (Steketee 2001, Guyatt 2004)
3-8% of infant mortality (Steketee 2001, Guyatt 2001)
75, ,000 infant deaths annually (WHO/UNICEF Africa Malaria Report 2003)

5. Where in the World is Malaria Found?
Malaria is ubiquitous in the tropical regions of the world. It is found in Central America, the Island of Hispaniola in the Carribbean, the Amazon region of South America, throughout most of Sub-Saharan Africa, parts of the Arabian peninsula, the near East, and in parts of the South Pacific.
Many of these same regions also share heavy HIV/AIDS and TB burdens
Distribution of Malaria

6. Malaria during pregnancy
Maternal and perinatal effects depend on intensity of transmission: Plasmodium falciparum in high transmission areas is most well studied - responsible for most morbidity & mortality

7. Transmission intensity
“Stable” malaria
Prevalence persistently high
Transmission can continue with few vectors
Collective immunity is high
P. falciparum
Young children and pregnant women at greatest risk
Type: sub-Saharan Africa
“Unstable” malaria
Variability in space and time
Disease fluctuates (inc. epidemics)
Collective immunity is low
P. vivax, also P. falciparum
All ages at risk
Type: S.E. Asia

8. Malaria in Pregnancy
Transmission levels effect consequences of disease
Low transmission/little or no immunity
Symptomatic
Severe malaria
Anemia
Adverse birth outcomes
Moderate to high transmission/immunity
Asymptomatic
Severe anemia
Low birth weight
Adverse—spont abortions, premature labor, stillbirths; affects fewer infants, but disastarous consequences
High transmission—low level morbidity affecting more. In these areas, accounts for 30% of LBW and in sub-Saharan Africa accounts for 3-8% of all infant deaths

9. Malaria during pregnancy: stable transmission areas
P. falciparum malaria
Acquired immunity - high
1st & 2nd pregnancies at greatest risk
Prevention essential
Asymptomatic infection
Placental sequestration
Here is a diagram illustrating the effects of malaria in pregnancy in stable transmission areas. In these areas, P. falciparum is the most common species contributing to malaria. Also, in high transmission areas, there is a lot of acquired immunity to malaria therefore malaria infections are mostly asymptomatic. However, such infections can lead to anemia which can then cause LBW. In addition, the asymptomatic malaria can cause placental sequestration of infected red blood cells which alters the integrity of the placenta which in turn causes a chain reaction involving decreased nutrient transport, increased LBW, and infant mortality.
In stable tx areas, acquired immunity is high and women in their first and second pregnancies are at greatest risk of the adverse outcomes of MiP; thus prevention is essential.
Anemia
Nutrient transport
Low birth weight
Risk of infant mortality

10. Malaria during pregnancy: unstable transmission areas
Acquired immunity - low
All pregnancies affected equally
P. falciparum malaria
Clinical illness
Recognition and case management needed in addition to prevention
In areas with low or unstable malaria transmission, P. falciparum may still be the predominant species responsible for malaria infection, however, acquired immunity to malaria is low. Thus, pregnant women are at 2-3 fold higher risk of developing severe disease as a result of malaria infection compared to non-pregnant women in the same area. In these areas, maternal death may occur as a direct result of severe malaria or as an indirect result of malaria-related severe anemia. In addition, malaria in pregnancy in these areas may result in spontaneous abortion, neonatal death, and LBW.
In these areas, all pregnancies are affected equally and thus prompt recognition and case management is an essential tool
Severe disease
Risk to mother
(death)
Risk to fetus
(stillbirth, abortion)

11. Vulnerable groups among pregnant women
Primigravidae
Adolescents
HIV-positive women
Women in rural areas
- So to recap, in general, primigravidae are at higher risk of MiP than women in higher gravidities.
- There is also accumulating evidence to suggest that adolescent girls are at greater risk of acquiring parasitemia during pregnancy and having a LBW outcome than adolescent secundigravidae or adult primigravidae.
- HIV infection reduces a pregnant woman’s ability to control malaria infection and contributes to more frequent and higher level of malaria parasitemia. More importantly, it eliminates the gravidity-specific pattern of malaria risk that I just described earlier. In other words, all HIV+ gravidae are at risk of malaria.
- Pregnant women living in areas with poor access to healthcare, such as those in rural areas, are also considered to be more vulnerable to MiP.

12. Placental parasitemia by pregnancy number, Kisumu, Kenya, 1996-98
Parasite density/mm3
% parasitemic
These are data out of Kenya that I just wanted to use for highlighting the typical decrease in both the prevalence and density of malaria parasitemia with increasing gravidity.
772
402
479
Adapted from Van Eijk et al.

13. Effects on Maternal Health
Severe anemia
Proportion in all gravidities attributable to malaria: 26%
Approximately 400,000 cases per year

14. Effects on Birth Outcome
Low Birth Weight
20% of LBW deliveries, 35% of preventable LBW
Responsible for at least 100,000 infant deaths
Intrauterine growth retardation (IUGR)
Preterm delivery
Stillbirth
Twice the risk with placental malaria(OR 2.19)

15. Low birth weight

16. Effects on Birth Outcomes: Low Transmission Settings
In Africa
LBW: 9.3%
Preterm delivery: 8.6%
Stillbirths: 3.7%
Outside Africa
LBW: 16.0%
Preterm delivery: 11.0%
Stillbirths: 3.0%

17. Neonatal Mortality Rates by Birthweight Mangochi, Malawi September 1987 - June 1989
1000
800
800
600
Deaths per 1000 Live Births
400
300
200
These data, out of Malawi, show the negative relationship between birthweight and risk of neonatal mortality. Compared to “normal” birthweight infants, the relative risk of death in the first 28 days of life increases dramatically from 2.4 to 31 as the birthweight drops from <2500 to <1500g. 49 26
<1500
³ 2500
Relative Risk 31
11.7
2.4
1.0
Adapted from Steketee et al.

18. Pathophysiology

19. Placenta Sequestration of parasites in the placenta
Red blood cells infected with P. falciparum attach to placenta
Can be present without peripheral parasitemia
Increased susceptibility of primigravidae

20. Congenital Malaria Can occur with all four species
Parasites cross the placenta and enter the fetal circulation
Immunity of mother affects severity
Non-immune: stillbirth, perinatal death, fever/anemia/jaundice/splenomegaly up to six weeks post-delivery
Immune: usually asymptomatic; parasties rapidly cleared
Crossing may be due to damaged syncitiotrophoblasts during active placental infection
Clearance of parasites may be passive protection from maternal antibodies, active immunity from exposure to soluble antigens in utero, high proportion of fetal hemoglobin which retards parasite growth

21. HIV Among Pregnant Women in sub-Sahara Africa
Estimated 27 million people in Africa living with HIV/AIDS
55% of sub-Sahara Africa adult HIV infection in reproductive-age women
Estimated increase in MIP attributable to HIV is 5.5% and 18.8% for populations with HIV prevalence of 10% and 40%

22. HIV Seroprevalence Among Women Attending Antenatal Clinics in Urban Areas
UNAIDS, Report on the Global HIV/AIDS Epidemic, 2002

23. HIV & Malaria During Pregnancy
HIV+ women have higher prevalences
and densities of parasitemia
All parities affected
Risk of infant mortality higher in
babies born to mothers co-infected
with HIV and placental malaria
Increased vertical transmission of HIV?

24. Study 2. Placental parasitemia by HIV status and pregnancy number, Kisumu, Kenya, 1996-98
Parasite density/mm3
% parasitemic
231
159
197
772
402
479
HIV (+)
HIV (-)
Total n = 2263
Summary RR = 1.63 ( ), p<0.001

25. Intermittent preventive therapy by HIV status and SP efficacy
Management

26. Current strategies

27. Options for malaria control during pregnancy
Drugs
Chemoprophylaxis
Intermittent preventive treatment during pregnancy (IPTp)
Febrile case management
Insecticide Treated Nets (ITNs)
Prevention and treatment of anemia
Hematinic supplementation
Nutritional counseling
Vaccines?
In the absence of an effective vaccine, the main tools available for control of malaria in pregnancy are drugs and ITNs. Hematinic supplementation is also recommended for control of anemia. WHO recommends a package of the 3 highlighted interventions: IPT, ITNs and case management.

28. Chemoprophylaxis: no longer a recommended strategy in high transmission areas
Most regimens require weekly or more frequent dosing
Chloroquine (CQ) is the most commonly used drug
Usefulness limited by:
Difficulty in delivering and sustaining intervention
Poor adherence to regimen
Side effects of CQ (especially itching)
Rising levels of P. falciparum resistance to CQ
Poor program effectiveness of CQ chemoprophylaxis
Chemoprophylaxis is no longer a recommended strategy in high transmission areas. Chloroquine has been the most common drug used for chemoprophylaxis but it’s usefulness has been limited by:
-Difficulty in delivering and sustaining intervention
-Poor adherence to regimen
-Side effects of CQ (especially itching)
-Rising levels of P. falciparum resistance to CQ
-Poor program effectiveness of CQ chemoprophylaxis

29. Intermittent Preventive Treatment for pregnancy (IPTp)
So instead, efforts are being focused around intermittent preventive treatment or IPT

30. Intermittent preventive treatment (IPTp): an alternative strategy
Most studied regimen: Sulfadoxine-pyrimethamine (SP) 2 curative courses (3 tablets)
One course during second trimester
One course during third trimester
Inexpensive
Easily deliverable (can be given under direct observation)
Safe
Efficacious
IPT involves treatment doses of an efficacious antimalarial drug, which should be started in the 2nd trimester or after quickening. Doses should be at least 4 weeks apart.
There is a lot of experience with IPT using SP. It’s advantages include: It is administered as a single dose, it is cheap, and given under supervision in the ANC. It is given at least twice following quickening, however, 3 or more doses may be required in HIV+ women. The biggest disadvantage of IPT with SP at this time is development of increasing resistance to SP.

31. Intermittent preventive treatment -- the two dose SP strategy
Conception
Birth 20 30 10
Course 1
24-28 wks
Course 2
30-36 wks
Fetal growth velocity 
This diagram just shows the 2-dose strategy which is timed around the peak of the fetal growth velocity in the 2nd and 3rd trimesters of pregnancy.
Weeks of gestation

32. Intermittent preventive treatment (IPTp) with SP: results of clinical trials
The next two slides show key results from clinical trials and program effectiveness studies of the IPT strategy in Africa.
These studies have all been conducted in Africa.
As you can see, most trials reported a decrease in anemia and placental parasitemia, however, only the study in Mali reported a decrease in LBW.
CQ = chloroquine; SP = sulfadoxine-pyrimethamine; CM = case management;
LBW Low birth weight
NE = not evaluated; NS = not statistically significant (p > 0.05)
* Data in thesis; not included in published manuscript)

33. Intermittent preventive treatment (IPTp) with SP: program effectiveness evaluations
On the other hand, all four program effectiveness studies that have been done so far have shown a decrease in LBW associated with IPTp
SP = sulfadoxine-pyrimethamine; Hb Hemoglobin; LBW Low birth weight
NS = not statistically significant (p > 0.05)

34. IPTp with SP: summary of evidence and benefits
2 doses of IPT with SP is associated with:
Reduction in 3rd trimester maternal anemia
Reduction in placental malaria parasitemia
Reduction in low birth weight
At least 2 doses required for optimal benefit
Monthly dosing more beneficial in HIV+ women
Regimen is safe and well tolerated
So, in summary, …

35. Insecticide treated bed nets (ITNs)

36. ITNs-efficacy in pregnancy: design
The efficacy of ITNs in pregnancy has been studied in low, moderate and high transmission areas, across all trimesters of pregnancy, and in all different gravidities

37. ITNs during pregnancy
Meta analyses of 5 RCTs (4 from Africa, 1 from Thailand)
In Africa, ITNs reduced
placental parasitemia in all pregnancies (RR=0.79 [ ])
LBW (RR=0.77 [ ]) and stillbirths/abortions in G1-4 (RR=0.67 [ ])*
In Thailand, ITNs reduced anemia and stillbirth/abortions in all pregnancies
A recent meta analysis of the impact of ITNs during pregnancy shows, that in Africa…
*For anemia and clinical malaria, results favored ITNs but did not show statistical significance.
Take home message: While further evaluation of ITNs is required in areas with less intense and Pv transmission such as Asia and Latin America, at least for sub-Saharan Africa, ITNs do prevent adverse consequences of malaria during pregnancy, and should be part of a complete package in ANC.
Source: Gamble 2006

38. Case management of malaria and anemia
The third strategy promoted for control of malaria in pregnancy is effective case management of malaria illness and anemia. This includes iron supplementation for anemia as part of routine antenatal care, as well as screening for anemia and managing severe to moderate anemia according to national reproductive health guidelines.

39. Case management of malaria in pregnancy
Safe drugs
Chloroquine
Quinine / quinidine
Proguanil, chlorproguanil
Pyrimethamine
Sulfonamides
Dapsone (+pyrimethamine= Maloprim)
Mefloquine (prophylaxis)
Clindamycin (300 mg qid, 5-7 days)
Artemisinins (2nd and 3rd)
Drugs with questionable safety
or insufficient data
Mefloquine (treatment dose)
Artemisinins (1st)
Amodiaquine
Azithromycin
Lumefantrine (component of coartem/Riamet)
Combination therapy
Artemisinin derivative with other drugs
Lapdap (chlorproguanil-dapsone)
Atovaquone-proguanil (Malarone)
Amodiaquine-SP
On the left side of this slide, I have listed drugs considered to be safe for treatment of malaria in pregnancy. These include:…
The debate over whether or not there is sufficient evidence to recommend artemisinins for treatment of MIP is on-going so I have put a question-mark by that drug name.
On the right side of the slide are drugs that we think have questionable safety or insufficient data. These include: …

40. Antimalarials contra-indicated in pregnancy
Tetracycline
Doxycycline
Halofantrine
Primaquine
Tafenoquine
Note: if serious illness, and where limited number of drugs are available, it is necessary to balance the risk of maternal death with the hypothetical risks to the infant
And then these are antimalarials that are contraindicated in pregnancy: …

41. Antimalarial drug policy
An antimalarial drug policy must balance between:
Access
Rational use
Equitable access to reduce mortality and morbidity
Emphasis on community management (e.g. use of lay persons for distributing drugs)
Reduces development of resistance
Emphasis on regulation and controlled use (e.g. prescription only drugs)
At the end of the day, any antimalarial drug policy must strike a balance between access and rational use. Although it is important to have equitable access and emphasize community management, it is just as important to reduce the development of resistance by emphasizing regulation and controlled use of drugs.

42. Interventions depend on level of transmission
High transmission areas
Women don’t feel sick- need prevention of adverse effects
Prevention by IPT and nets
Low transmission areas
IPT will not necessarily keep the woman well
Prevention by nets
Any role for chemoprophylaxis in select areas?
Both areas need prompt appropriate febrile case management
3 interventions have been highlighted so far: IPT, ITNs and case management.
The kind of intervention used may depend on the level of malaria transmission in a particular country or sub-district.
As mentioned before, in high transmission areas, women mostly experience asymptomatic infections. Therefore, we need interventions to prevent adverse effects. IPT and ITNs can be useful in these settings.
In low transmission areas, pregnant women experience an increased risk of severe disease and increased hospital admissions for malaria and malaria-associated deaths even during epidemics. In these settings, IPT may not necessarily keep the woman well. Prevention by ITNs may still work, and there may even be some role for chemoprophylaxis in some areas.
Case management is warranted in both high and low transmission areas.

43. The Results of Preventing Infection
Reduce the risk of severe maternal anemia: 38%
Reduce the risk of LBW: 43%
Reduce the risk of perinatal mortality: 27%

44. From Research to Policy to Implementation

45. African summit on Roll Back Malaria (RBM) – Abuja 2000
At least 60 percent of those at risk of malaria, particularly pregnant women and children under 5 years of age, benefit from the most suitable combination of personal and community protective measures such as insecticide-treated mosquito nets …
At least 60 percent of all pregnant women who are at risk of malaria, especially those in their first pregnancies, have access to intermittent preventive treatment.
In April 2000, 17 Heads of State as well as Ministers of Health and delegations from 44 African countries committed themselves to accelerate the fight against malaria within 10 yrs. This text is taken from the Abuja Declaration that was signed by these individuals.
It read…
Well, we’re in 2006 and the malaria community has a quite a ways to go before these commitments can be fulfilled.

46. Malaria during pregnancy: Research to program - a continuous cycle
Programmatically relevant research
Monitoring &
evaluation
Program
implementation
Although important progress has been made in the last decade, resulting in the introduction of IPTp and ITNs as key control strategies for MiP in Africa, the rate at which sufficient evidence became available, the process that has led to these policy changes and subsequent implementation has taken more than 15 years.
Policy change

47. Status of IPTp policy and implementation in Africa (2001)
For ex, the benefits of IPTp have been known since 1998, however, in 2001, only 5 African countries had IPTp as part of their national health policy for prevention of MiP.
Very little or no malaria (7)
No known IPT policy

48. Rapid assessment of burden of malaria during pregnancy
Survey at antenatal care:
peripheral malaria parasitemia and anemia
Survey at delivery units
Peripheral and placental parasitemia, birth weight, and gestational age
Other modules: severe disease, health facility assessment, rapid ethnographic evaluation
In order to expedite the path to effective program implementation, CDC in collaboration with other partners has developed a rapid assessment tools package. It allows for quick acquisition of knowledge on the burden of MiP in a given country/region, and opportunities for addressing the problem or improving existing interventions/efforts.
The package includes the following:

50. Example: Burkina Faso
Joint collaboration of CDC with JHPIEGO and Burkina Faso Ministry of Health
Baseline 2001 rapid assessment examined: rates of peripheral and placental parasitemia, maternal anemia, and low birth weight
>22% of women had placental parasitemia despite widespread use of chloroquine chemoprophylaxis
Pilot intervention of IPTp with 3 doses of SP begun in 2003; ITN distribution through NGO programs
Repeat rapid assessment (program evaluation) conducted in 2004
Just to give you an example of how these tools have been used in practice in BF.
In 2001, a baseline RA survey determined that >22% of women had placental par despite widespread use of CQ chemoprophylaxis.
Thus, a pilot intervention of IPTp with 3 doses of SP was begun in This was coupled with ITN distribution through NGO programs.
In 2004, a repeat RA survey was conducted to evaluate the pilot intervention.

51. Burkina Faso – 2004 program evaluation
High coverage with IPTp at delivery units (DU)
3 doses: 46.9%
 2 doses: 78.6%
1 dose: 93.5 %
High coverage with IPTp at antenatal clinics (ANC) - includes dose given on day of interview
3 doses: 20.9%
 2 doses: 57.6%
 1 dose: 96.2%
It showed a high coverage of IPTp both in the DU and ANC surveys, with almost 80% of women reporting having received >=2 doses of IPTp by the time of delivery.

52. Burkina Faso Delivery Units 2001 vs. 2004
Risk ratio
P-value
Peripheral parasitemia (delivery)
29.4%
19.4%
0.66
<0.0001
Placental parasitemia
22.6%
15.9%
0.71
0.0002
Low birth weight
14.4%
12.2%
0.85
0.15
Significant improvements were noted in the prevalence of …
Note: Unadjusted

53. Burkina Faso ANC 2001 vs. 2004 2001 2004 Risk ratio P-value
Peripheral parasitemia (ANC)
32.0%
15.7%
0.49
<0.0001
Any anemia (Hb < 11 g/dL)
79.9%
59.3%
0.74
Moderate-to-severe-anemia
13.0%
3.5%
0.27
And in the prevalence of…
Note: Unadjusted; women with 1 prior ANC visit; women in 3rd trimester only

54. Burkina Faso – Conclusions and recent events
Package of ITNs and IPTp with SP (3 dose strategy) may have resulted in decreased proportion of women with anemia, peripheral parasitemia, and placental parasitemia when comparing pre-program (2001) and post program (2004) assessments
In February 2005, based on data from Koupéla, Burkina MoH adopted IPTp as national policy (2 doses of sulfadoxine-pyrimethamine)

56. Status of IPTp policy and implementation in Africa (January 2005)
IPTp policy and widespread
IPTp program implementation (5)
IPTp policy and IPTp program implementation in progress (7)
IPTp policy but no implementation yet (3)
IPTp policy but extent of implementation unknown (4)
Thus, it took 4yrs to get one country to switch policy to IPTp. As of Jan 2005, WHO reported that at least another 7 countries were in the process of IPTp program implementation but another 25 malaria-endemic countries have no known IPTp policy (UPDATE THIS SLIDE).
Very little or no malaria (7)
No known IPTp policy (25)
IPTp implemented on small scale by NGOs but no national policy: Liberia and Somalia

57. Malaria during pregnancy: gaps in knowledge and future directions
Well, so after over half a century’s worth of work on MiP, what are the gaps in our knowledge surrounding this topic?

58. MiP Consortium
Focused on addressing gaps in knowledge regarding all aspects of MiP
Initial funding for meetings and development of review papers from Bill & Melinda Gates Foundation
Full research agenda to be finalized in 2006
Comprehensive reviews (7) published as part of an LID supplement
Not surprisingly, that’s precisely what the recently founded MiP consortium has tasked itself to identify and address. Its goal is to devise an integrated and prioritized global research agenda to support the control of MiP for the next 5 years such that optimal interventions will be used to reduce the adverse effects of MiP across a range of malaria transmission settings

59. Technical Reviews
Epidemiology and Burden of disease: M Desai, F ter Kuile, F Nosten, R McGready, K Asamoa, B Brabin, R Newman
Pathophysiology and immunology: S Rogerson R Leke, et al
Drug safety and kinetics: S Ward, E Sevene et al
Case management: F Nosten, R McGready, TK Mutabingwa
Prevention: C Menendez, F ter Kuile
Implementation and Policy: J Crawley, A Palmer, K Asamoa, R Steketee, et al
Economics of malaria in pregnancy: E Worrall, A Mills
Summary concept paper: B Greenwood, R Steketee and P Alonso

60. Priorities: Epidemiology and Burden
What is the importance of MiP in low transmission areas including areas where P. vivax is the dominant parasite ?
What is the impact of malaria in the first trimester ?
Is malaria an important cause of maternal mortality in medium to high transmission areas?

61. Priorities: Pathogenesis and immunity
How does malaria cause severe anemia in pregnancy ?
How does malaria cause low birth weight ?
What impact will the introduction of effective control measures have on naturally acquired immunity to malaria ?
Can malaria in pregnancy be prevented by:
partially effective pre-erythrocytic vaccines
a ‘malaria in pregnancy’ vaccine (anti-cytoadherence)

62. Priorities: Case Management
Can the diagnosis of malaria be improved ?
Which drugs can be used to replace CQ and SP for the treatment of malaria in pregnancy and how can the efficacy of new drugs best be measured ?
How are the pharmacokinetics of anti-malarial drugs (old and new) influenced by pregnancy ? Are there pharmacokinetic interactions between anti-malarials and ARVs ?
Are anti-malarials safe in pregnancy (pharmacovigilance) ?

63. Priorities: Prevention of MiP
How can current preventive strategies (ITNs, IRS, IPT, repellents) be used together most effectively in different epidemiological situations:
low or high transmission
areas with P. vivax infection
low or high HIV prevalence
What drug(s) can be used to replace SP for IPT? Do they need to be long acting ?
Are existing insecticides and new ones under development safe in pregnancy when used for ITNs or IRS ?
Pharmacovigilance

64. Priorities: Economic aspects of MiP
What is the overall economic burden of malaria in pregnancy ?
What are the comparative cost efficacies of different control measures in different circumstances ?

65. Priorities: Health systems research
How can usage of ITNs and IPT be scaled up most effectively and equitably in different situations ?
How can malaria control in pregnancy be integrated into reproductive health and HIV management programmes more effectively ?
Will new interventions be accessible, affordable and acceptable?

66. Overall priorities identified from technical reviews
New drugs for treatment
New drugs for prevention
Clarity on optimal methods of deploying combinations of interventions in different epidemiological settings
Improved delivery of existing recommendations to achieve high coverage
Each of the 6 reviews identified subject-specific priorities. However, 4 overall priorities have been identified for MiP research.

67. Areas for PMI to think about
How to get women to attend all their ANC visits and earlier
Integrating MIP with other ANC services (PMTCT, EPI, Reprod, Nutrition)
Creating demand (quality, wanted services)
Expanding commodity procurment to include iron/folate
Monitor efficacy of IPTp with SP resistance rising

68. Resources
MiP
Strategic framework for malaria prevention and control during pregnancy in the African Region (WHO/2005)
English, French, Portuguese (soon)
Rapid Assessment of Malaria during Pregnancy Toolkit (CDC/2005)
Malaria during Pregnancy Resource Package (JHPIEGO/2003)
English, French, Portuguese: all soon to be updated
Malaria in Pregnancy: Guidelines for Measuring Key Monitoring and Evaluation Indicators (WHO/Draft): available from CDC
IPTi
IPTi Consortium website:

69. EXTRAS

70. CDC’s contributions- General
Quantified the burden of adverse effects caused by MiP
Evaluated efficacy of novel strategies for prevention of MiP
Formulated strategies to deliver effective interventions
Worked with partners to scale-up interventions

71. CDC’s contributions- Specific
Risk of MiP-associated LBW (Steketee 2001)
Global estimates of burden (Steketee 2001, WHO-SEARO, WHO-AFRO)
Rapid assessment methodology (Parise 2003)
IPTp (Kayentao 2005, Parise 1998)
Impact of ITNs (ter Kuile 2003)
Interaction of malaria and HIV (ter Kuile 2004) and need for monthly IPTp in HIV+ women (Filler 2006)
Reduction of low birth weight: Determined the risk of malaria-associated low birth weight and shown how this risk could be reduced through the delivery of efficacious antimalarial drugs as part of routine antenatal care
Estimates of malaria burden: Updated estimates of the burden of anemia, low birth weight (due both preterm delivery and intrauterine growth retardation), and infant mortality associated with malaria infection during pregnancy [1]. With partners, have generated estimates of the burden of malaria during pregnancy in areas with limited data, including West Africa, areas of sub-Saharan Africa with low malaria transmission and South/ South East Asia.
Rapid assessment methodology: Developed a methodology that can be used by ministries of health to estimate the burden of malaria during pregnancy and assess how best to incorporate antimalarial interventions into the existing antenatal care system [2]. To date, CDC has provided training for this methodology in Asia, Africa, and the Americas.
IPTp: With partners, developed the strategy of IPTp, and demonstrated that this intervention was effective in reducing maternal anemia and delivery of low birth-weight babies in different settings in sub-Saharan Africa.
ITNs: Demonstrated that the use of ITNs by pregnant women can reduce severe malarial anemia during pregnancy and reduce delivery of low birth-weight infants.
Interaction of Malaria and HIV: Demonstrated both the higher burden of malaria in HIV-seropositive (compared to HIV-seronegative) pregnant women and their impaired response to antimalarial treatment.

72. CDC’s contributions- currently being studied
Evaluation of new antimalarial drugs (Mali-LapDap)
Evaluation of the combined benefit of IPTp and ITNs (Kenya)
Evaluation of a possible interaction between antimalarial drugs and folic acid (Kenya)
Development of an M&E system
Determine efficacy of IPTi for control of malaria and severe anemia in infancy (Kenya)
Comprehensive review of the epidemiology and burden of MiP to identify gaps in knowledge
Evaluation of new antimalarial drugs for pregnancy: In combination with international partners, CDC is working to evaluate the safety and efficacy of new antimalarial drugs and drug combinations for the treatment and prevention of malaria during pregnancy
Evaluation of the combined benefit of IPTp and ITNs: CDC is working on novel mechanisms for increasing the percentage of pregnant women with access to IPT and ITNs, and on measuring the combined impact of these interventions on preventing the adverse consequences of malaria during pregnancy
Interaction of antimalarial drugs and folic acid: CDC is evaluating a possible interaction between IPTp with sulfadoxine-pyrimethamine and administration of folic acid during pregnancy. There has been a theoretical concern that these two beneficial antenatal interventions could interfere with one another in practice; this research will help to answer that question
Development of a monitoring and evaluation system for malaria during pregnancy: In conjunction with WHO and other international partners, CDC has been developing a standardized system for monitoring the uptake of strategies to prevent malaria during pregnancy, as well as demonstrate impact on preventing anemia and low birth weight.
Studying the efficacy of IPTi for control of malaria and severe anemia in infancy: CDC is a member of the IPTi consortium and is conducting one of five large clinical trials that are currently under way in Africa to assess use of IPT at time of routine vaccinations as a control strategy for prevention of malaria and anemia in infancy.
Review of the global burden of malaria in pregnancy and identifying gaps in knowledge: CDC is writing a review of the current knowledge and gaps in the burden of malaria in pregnancy. This is one of six state-of-the-art comprehensive reviews being undertaken by the MiP consortium to develop a prioritized strategy defining the scope of future MiP studies.

73. Steps for effective intervention Rapid assessment - components
Antenatal Care Survey
Questionnaire re: fever, malaria, drug and ITN use
Blood films, Hemoglobin screening
Delivery Unit Survey
Blood films from peripheral, cord, and placental blood
Birth weight and gestational age of neonate
Over the years, a protocol for the rapid assessment of the malaria in pregnancy – one which looks at the nature of the problem and opportunities for intervention – has been developed. Dr. Parise, who is also here today, ahs worked extensively on this issue.
The assessment consists of:

74. Steps for effective intervention Rapid assessment - components (2)
Health Care Facility Evaluation
Supplies, drugs, policies, and practices
Observation of patient provider interactions
Ethnographic evaluation
Focus groups, in depth interviews
Identify barriers, taboos
Knowledge, Attitudes, Practices, Beliefs about malaria and drugs during pregnancy
For anyone interested in this tool, we would be happy to share it with you. Please feel free to contact us at CDC. (MONICA, OK WITH THIS?)

75. Steps for effective intervention Rapid assessment - utility
Determine burden of disease
Is an intervention needed?
Determine infecting species
What drug(s) appropriate?
Provide pre-intervention baseline data
Identify HCW training needs
Identify cultural aspects which will need to be addressed by intervention
Why do a rapid assessment:

76. Questions?