MALARIA IN PREGNANCY

FAHAD ZAKWAN

Types of malaria•Plasmodium falciparum

• Most common• Multi-drug resistant• Most dangerous

•Plasmodium vivax• Latin America & Asia

•Plasmodium malariae

•Plasmodium ovale

Placental malaria

•Parasites accumulate and thrive in the placenta

•Only affects primigravidae in areas of high transmission

Gravidity and malaria•Primigravidae have no pre-existing immunity to

placental parasites and are highly susceptible

• In high transmission areas, primigravidae develop immunity to placental parasites and are protected in subsequent pregnancies

• In low transmission areas, multigravidae are unexposed and unprotected

Effects of malaria on pregnant women

•Poor birth outcomes• Low birth weight due to preterm delivery (PTD) and

intrauterine growth retardation (IUGR)• abortions, stillbirths

•Maternal outcomes•Anemia, maternal mortality

Maternal mortality

•Responsible for 0.5 – 23% of maternal deaths in Africa

•Malaria causes severe anemia and platelets can predispose to death from hemorrhage

Interventions

•Intermittent Preventive Therapy (IPT)•sulfadoxine-pyrimethamine (SP)

•Insecticide-Treated Nets (ITNs)

•RBM goals – 60% of pregnant women in endemic areas should have access to both by 2005

IPT•Two therapeutic doses of SP to all pregnant women at quickening and at 28-34 wks

• 2-dose coverage is still low (<25%)

•New recommendations include 4-doses or monthly SP

•Prevents 23-86% of severe maternal anemia

ITNs

•Reduce malaria, severe anemia and LBW by 30-50%

• Socially marketed nets (~$1.00)• Low uptake

• Freely distributed nets• High uptake and well utilized• Less sustainable

Malaria is the most common and easily preventable cause of poor birth outcomes in the

world

Pathogenesis of malaria in pregnancy

•During normal pregnancy, the cellular immune response (Th1) is suppressed to prevent fetal rejection

•Malaria stimulates the Th1 response intrauterine growth retardation

•Malaria stimulates expression of an HIV co-receptor (CCR5) in the placenta.

Malaria and HIV co-infections during pregnancy

• Up to 10% of pregnant women may be co-infected with both HIV and malaria

• HIV-infected pregnant women have more frequent and severe malaria

• Malaria infection might increase mother-to-child transmission of HIV

• Infant mortality rate for offspring of co-infected mothers is 3-8 fold higher than singly infected mothers

Effects of malaria on HIV

viral load

•Malaria is associated with 1.7-fold increase in peripheral HIV viral load and a 2-fold increase in placental viral load after adjusting for CD4 cell count and hemoglobin concentrations

•Since a 1-log increase in peripheral viral load is associated with a 2.5-fold increase in MTCT, then malaria might increase MTCT by 25%.

Does malaria promote MTCT of HIV?

•Study on-going, but to date, no association between malaria and MTCT seen•Currently, only 10% power to detect the 25% difference • Indirect evidence for an effect on MTCT•Malaria viral loadMTCT•Malaria fever MTCT•Malaria LBW MTCT

HIV and susceptibility to malaria

•HIV-infected pregnant women have more frequent and severe malaria

•Is the effect of HIV on malaria dependent on decreasing CD4’s or decreasing antibody?

HIV impairs immunity to malaria

Mount et al., Lancet, 2004

Important issues in malaria-HIV interactions1. Can prevention or treatment of malaria

delay progression of HIV disease?2. Does HIV affect susceptibility to malarial

disease in children?3. Does ART restore immunity to malaria?

IPT 2004

•2-dose IPT with SP ineffective in HIV-infected women

•SP IPT also losing effectiveness due to drug resistance

•What should replace SP?

Possible alternatives to SP

•SP-artesunate

•SP-azithromycin

•Amodiaquine

•Mefloquine

•Lapdap

New drugs for malaria

• DB289 developed by Tidwell group and for treatment of African sleeping sickness (supported by Gates Foundation)

• Effective in an initial trial against P. falciparum in Thailand curing >90% of patients (supported by MMV)

ON

N H 2H

2 N

NOCH

3H

3CO

Summary•Malaria is an enormous reproductive health problem, especially in sub-Saharan Africa

• IPT and ITNs are inexpensive and effective interventions

• Investment in malaria control can do the most good for the least amount of money