Malaria During Pregnancy
Slide 1
Hello. I am Dr. 'Dipo Otolorin, an Obstetrician/Gynecologist by training and Senior HIV/AIDS Advisor at JHPIEGO Corporation, Johns Hopkins University. I am going to talk about malaria during pregnancy.
Slide 2
The objectives of this presentation are first to describe the impact of malaria on pregnancy and newborns, second to discuss the impact of malaria on HIV-infected pregnant women, and lastly, to discuss malaria control during pregnancy, including the prevention and case management of malaria illness.
Slide 3
Why is malaria during pregnancy important?
Each year, more than 30 million women in Africa become pregnant in malaria-endemic areas. In these areas, malaria accounts for significant morbidity in pregnant women. For example, it accounts for 2-15% of maternal anemia and 5-14% of low birth weight. Of those newborns born with "preventable" low birth weight, 30% are due to malaria. Malaria also accounts for between 3-5% of all newborn deaths.
Slide 4
This slide summarizes results from studies in eight countries in Africa. In virtually all the countries listed, primigravid women had a higher prevalence of placental parasitemia when compared to multigravid women.
Slide 5
The intensity of malaria transmission in an area determines the effect of malaria on pregnancy. In areas of stable transmission, malaria is frequently transmitted by mosquitoes from one person to another resulting in high levels of acquired immunity. Pregnant women in these areas are semi-immune to malaria and have a low prevalence of peripheral parasitemia but a high prevalence of placental infection.
On the other hand, in areas of unstable transmission, malaria is infrequently transmitted from one person to another. Therefore, pregnant women in these areas have low levels of acquired immunity with heavy peripheral parasitemia and low or undetectable levels of placental infection.
Slide 6
How does malaria infection lead to low birth weight newborns?
This slide summarizes the sequence of events in stable areas of malaria transmission. In these areas, women have a high level of acquired immunity to Plasmodium falciparum malaria and are often asymptomatic due to low peripheral parasitemia. Pregnancy naturally lowers cell-mediated immunity and causes immunosuppression. In areas of stable transmission, the placenta is a protected site for parasite sequestration and growth. Its effect during pregnancy appears to be "parity-specific". During the first malaria-exposed pregnancy (that is, in primigravida), local immunity to malaria develops in the placenta. This immunity has no effect in the first pregnancy but is retained in the uterus and increases cumulatively in subsequent pregnancies. This is why women in their first and second pregnancies are more affected by malaria than women in subsequent pregnancies.
The malaria parasites in the placenta damage placental integrity and interfere with the ability of the placenta to transport nutrients and oxygen to the fetus, thereby causing intrauterine growth retardation, a factor for delivery of low birth weight newborns. A low birth weight newborn is defined as one that is born weighing 2500 grams or less. Another pathway to low birth weight is severe maternal anemia which is also caused by the malaria infection. In general, low birth weight babies have a higher risk of dying in infancy.
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What happens in areas of unstable malaria transmission?
Women in these areas have lower levels of acquired immunity. Therefore, they have an increased frequency and severity of malaria and anemia. Delayed recognition and inappropriate treatment may lead to a progression to severe disease, which has serious consequences for both the mother and the fetus. This effect is seen in virtually all pregnancies, irrespective of parity.
Slide 8
As stated earlier, the effect of malaria infection depends on the intensity of malaria transmission in the area, which in turn determines the woman's level of acquired immunity to malaria. Furthermore, birth order is also known to be a determining factor in the frequency and severity of malaria during pregnancy.
This table shows that primigravid women living in areas of stable malaria transmission have an increased risk of placental infection and severe anemia. They are less likely to suffer from complicated malaria which may present in the form of cerebral malaria, hypoglycemia, pulmonary edema and acute renal failure. On the other hand, women of any parity living in areas of unstable transmission have a higher risk of malaria fever illness, severe anemia and complicated malaria.
Anemia lowers the woman's resistance to infection, thereby increasing the likelihood of puerperal sepsis. The risk of maternal mortality from malaria is higher among women living in areas of unstable malaria. The causes of death may include severe anemia, postpartum haemorrhage, puerperal sepsis or anemic heart failure.
Slide 9
With regards to the fetus and the newborn, primigravid women living in areas of stable malaria transmission are at higher risk of delivering low birth weight babies due to intrauterine growth retardation. Women of all parities living in areas of unstable malaria are at higher risk of premature delivery (that is, delivery before 37 completed weeks of gestation). They are also at higher risk of spontaneous abortions, stillbirths and congenital malaria. The consequences of these adverse effects is an increased risk of infant mortality among all babies born to mothers living in areas of unstable malaria transmission.
Slide 10
This study from Kenya looked at the relationship between placental parasitaemia and birth order. The study showed that women who are in their first pregnancies are more likely to have placental parasitemia than women in later pregnancies. This observation holds true for all levels of placental parasite density (that is, between 1-999, between 1000-9999 and 10,000 or more parasites per cubic millimeter).
Slide 11
This slide summarizes another study from Malawi examining the relationship between birth order, presence of malaria parasites in the placenta and the incidence of low birth weight. As shown, newborns with malaria parasites in their placenta (represented by the left bar in each cluster) had a higher risk of being born with a low birth weight when compared with newborns with no malaria parasites in their placenta (represented by the right bar in each cluster). This is true regardless of the birth order, which could be the first, the second or later pregnancy.
Slide 12
What is the relationship between HIV/AIDS and malaria during pregnancy?
HIV infection, which is becoming more prevalent in women of reproductive age, may diminish a pregnant woman's capacity to control Plasmodium falciparum malaria infections and lead to decreased efficacy of antimalarial interventions.
This graph summarizes the findings from a study in Kenya. The cluster of bars to the left represent HIV-positive mothers, and the bars to the right represent HIV-negative mothers. The data shows that, irrespective of placental parasite density or whether the women are in their first, second or later pregnancies, those who are HIV-positive are more likely to have malaria parasitemia when compared with those who are HIV-negative. Because the HIV virus is an immunodeficiency virus, HIV-positive women have lower levels of acquired immunity for all infections including malaria. The implication of this finding for treatment is that HIV-positive women have a reduced efficacy to antimalarial medication and need more doses of the medication than their HIV-negative counterparts.
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So, what components should be included in a strategic framework for controlling malaria during pregnancy?
Malaria control during pregnancy should address four components. The first component is quality focused antenatal care that includes health education and counseling about malaria during pregnancy. The second is intermittent preventive treatment (or IPT for short) which is also sometimes referred to as "intermittent presumptive treatment" or "intermittent protective treatment". For the purpose of this presentation, the World Health Organization's terminology "intermittent preventive treatment" will be used. The third component of malaria control is the use of insecticide-treated nets, and the fourth component is case management of malaria disease.
Slide 14
This slide shows that a significant proportion of pregnant women in Africa (between 35-95%) will attend the antenatal clinic at least once during pregnancy. This presents a unique opportunity to initiate the control of malaria during pregnancy and to reach as many women as possible.
Slide 15
For any program on malaria control during pregnancy to be successful, there must be a partnership between the providers of maternity services and malaria control staff. Antenatal clinic visits provide a unique opportunity to educate women about the effects of malaria on pregnancy and about what can be done to eliminate or minimize its adverse consequences. These interventions will include monitoring of maternal and fetal health, provision of micronutrient supplementation to reduce the risk of anaemia, education on the benefits of using insecticide-treated nets, application of intermittent preventive treatment and case management of malaria illness.
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What does a pregnant woman need to know about malaria?
She needs to know that pregnant women, especially, those in their first or second pregnancy or those who are HIV-positive are at higher risk of malaria. She needs to know that malaria is transmitted through mosquito bites so she can prevent mosquito bites. She needs to know that if malaria is untreated, it can cause severe anemia with some adverse consequences. She also needs to know that malaria can cause abortions, stillbirths and low birth weight newborns. She needs to hear the good news that malaria can be prevented through the use of intermittent preventive treatment with sulfadoxine-pyrimethamine (or SP) and by sleeping under insecticide-treated nets. She needs to know that uncomplicated malaria can be easily treated, but when neglected it can progress to severe disease that requires expensive specialized treatment.
Slide 17
The second component of the strategic framework for malaria control during pregnancy is "intermittent preventive treatment". Intermittent preventive treatment is an intervention for effectively preventing and controlling malaria during pregnancy. It is based on the assumption that every pregnant woman living in an area of stable or unstable malaria transmission has malaria parasites in the blood or in the placenta, and therefore, should be treated to minimize its effects on the mother and her fetus. Intermittent preventive treatment with SP is currently the most effective approach for the use of antimalarial drugs during pregnancy and is particularly attractive for use in areas with a high level of chloroquine resistance.
Slide 18
Sulfadoxine-pyrimethamine is the drug of choice in many countries for intermittent preventive treatment of malaria. SP, as it is often called, is a combination of two drugs. Each tablet contains 500 mg of sulfadoxine and 25 mg of pyrimethamine. A single dose consists of three tablets taken at once, preferably under direct observation by the healthcare provider. Fansidar is the most common brand of SP, but there are other brands such as Falcidin, Laridox and Maladox. SP is generally more effective than chloroquine due to the increasing prevalence of chloroquine resistance in many parts of Africa.
Slide 19
Shown here is evidence in support of the use of intermittent preventive treatment with SP. This table summarizes a study from Kenya in which data from three groups of pregnant women were analyzed. These were women who had case management for malaria illness, women who were protected by the two-dose SP regimen, and women protected by a monthly SP regimen. The groups protected with the two-dose or monthly SP regimens had higher mean blood hemoglobin levels than those in the malaria group. Also, the groups protected with SP had lower incidence rates of maternal parasitemia (9 and 7%) and placental parasitemia (12 and 9%) compared to women seen with malaria illness (27%).
The incidence of low birth weight newborns among those who were protected with SP (8%) was also lower than among those not protected with SP (which was 14%). The conclusion is that intermittent preventive treatment offers some protection from the adverse consequences of malaria during pregnancy.
Slide 20
Why give SP at a particular time during pregnancy?
The dotted line in this slide represents fetal growth velocity during pregnancy. Fetal growth velocity is relatively slow in the first half of pregnancy but increases rapidly in the second half of pregnancy. Because the presence of parasites in the placenta interferes with the transfer of nutrients to the fetus, it is important to ensure that the fetus's placenta is free of malaria parasites when fetal growth velocity is fastest.
Slide 21
Quickening refers to the time a mother feels the first movement of the fetus. It varies among women, with some women experiencing quickening as early as 16 weeks while others may not do so until 20 weeks gestation.
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The World Health Organization or WHO recommends a schedule of four antenatal clinic visits, with three visits occurring after quickening. At least two doses of IPT should be delivered at scheduled antenatal care visits after quickening until delivery. SP should not be given more frequently than every four weeks. The concern about neonatal jaundice resulting from SP given after 36 weeks of gestation does not appear to be a major one at this time.
Kenya, Malawi, Tanzania, Uganda and Zambia have embraced a two-dose SP regimen. In these countries, the first dose of SP is given between 24-28 weeks and the second dose is given between 30-36 weeks of pregnancy. No SP is given after 36 weeks. Countries with no policy should consider adopting a three-dose regimen that is in line with WHO’s 3 recommended scheduled antenatal visits after quickening.
Slide 23
SP should be avoided during the first 16 weeks of pregnancy which corresponds to the period of organ formation in order to avoid congenital malformations. It is best to clear the placenta of parasites during the period of maximum fetal growth as shown in the previous graph. IPT of malaria during pregnancy allows the mother to recover fully from anemia by clearing peripheral parasitemia.
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What are some of the steps that should be taken when providing IPT with SP?
- Determine that quickening has occurred
- Inquire about any history of allergy to sulfonamides, including severe skin rash
- Inquire about the use of SP or any sulfonamides in the past month.
- If there are no contraindications for giving SP,
-- Provide three tablets of SP with clean water in a clean cup, and
-- Directly observe the woman taking the SP tablets in the clinic. This helps to ensure compliance.
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- Record “SP given” in the woman’s antenatal card and clinic record
- Instruct the woman to return at her next scheduled visit or earlier if she is feeling ill.
- Before giving any follow-up dose at the next visit, ask about side effects from the previous dose. A follow-up dose should not be given less than 4 weeks from the last dose.
Slide 26
The third component of the strategic framework for malaria control during pregnancy is the use of insecticide-treated nets to protect mothers and their newborns.
The use of insecticide-treated nets have been shown to result in a reduction in the proportion of newborns born with low birth weight or born prematurely (that is, before 37 completed weeks of pregnancy). Insecticide-treated nets also reduce malaria transmission by serving as a physical barrier between the vector mosquitoes and people sleeping inside the nets. They repel or kill mosquitoes that land on the net and can also kill bed bugs, lice, ticks, cockroaches and other insects around the house. They should be used by pregnant women as early as possible during pregnancy and their use should be continued throughout pregnancy and in the postpartum period.
A study from western Kenya showed that women who were protected by insecticide-treated nets every night during their first four pregnancies delivered approximately 25% fewer newborns who were either small for gestational age or born prematurely when compared to women who were not protected by insecticide-treated nets.
Slide 27
Shown here is the result of a study that examined the impact of insecticide-treated nets on fetal growth and the duration of gestation. The study showed that pregnant women protected by insecticide-treated nets (represented by the right bar in each cluster), 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 (represented by the left bars). This finding holds true irrespective of the patient’s parity, except for the incidence of small-for-gestational-age babies born to women with 4 or more pregnancies.
Slide 28
Among women in their first to fourth pregnancies, the use of insecticide-treated nets reduced the incidence of peripheral parasitemia by 38% and reduced the incidence of severe anemia by 47%. The use of insecticide-treated nets was also associated with a 23% reduction in placental malaria, 28% reduction in incidence of low birth weight newborns and a 25% reduction in any adverse birth outcome. There is, however, no evidence to suggest that the efficacy of insecticide-treated nets decreases with increasing levels of malaria transmission in the area.
Slide 29
The final component of the strategic framework for malaria control during pregnancy is case management. Effective drugs are needed for Plasmodium falciparum malaria because the disease can be fatal to both the mother and the newborn. The drug of choice for case management would depend on the profile of drug resistance in the country. For example, antimalarial drugs that would be considered appropriate for Uganda may be inappropriate for Tanzania. Chloroquine has been the drug of choice for many years and it will probably remain the drug of choice in some areas where it is still effective. But, because of the high incidence of chloroquine resistance in Africa, SP has become the alternative antimalarial drug of choice for treating uncomplicated malaria. Quinine given intramuscularly or intravenously is the drug of choice for the case management of complicated malaria.
Slide 30
In general, the drug of choice for treating uncomplicated malaria will depend on the local patterns of drug sensitivity. For example, some countries will treat uncomplicated malaria during pregnancy with a combination of SP and chloroquine. The need to treat fever with analgesics, diagnose and treat anemia, and to provide adequate fluids should also be addressed.
For complicated malaria, the drug of choice is intravenous or intramuscular quinine. The provider should determine the woman’s weight in order to be able to calculate how much quinine is needed. The provider should also treat the fever with analgesics and tepid sponging and provide rehydration as needed. Complications, such as severe anemia, hypoglycemia and acute renal failure should be detected early and appropriately managed. These life-threatening complications can be easily avoided if malaria is recognized early and is promptly and adequately treated.
Slide 31
Resistance to drugs is an ever increasing problem and can occur very rapidly in as few as five years. To minimize this problem, women need to be encouraged to complete their medications as prescribed. For example, when women are told to take chloroquine, four tablets on the first day, four tablets on the second day and two tablets on the third day, they often tend to stop medication if they feel better after taking the first dose. This type of poor compliance encourages drug resistance. Service providers should educate clients about the importance of medication adherence whenever providing medications to clients to be taken outside the health facility.
In any case, because drug resistance is virtually inevitable, healthcare providers must stay informed about the changing policy of malaria drug therapy in their countries.
Slide 32
Some drugs should not be used during pregnancy. These include tetracycline, doxycycline, primaquine and halofantrine. Tetracycline can cause abnormalities of skeletal and muscular growth and damage the teeth of the newborns. While there are no controlled studies of doxycycline use in pregnant women to show safety, an expert review of published data on experiences with doxycycline use during pregnancy concluded that the available data are insufficient to state that there is no risk. The risk of cosmetic staining of the primary teeth by doxycycline is also undetermined (quantity and quality of data has been very limited). Doxycycline is excreted into breast milk. Short-term use by lactating women is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown.
Halofantrine has not been adequately studied in pregnant women. However, it has been found to cause unwanted effects in animals, including death of the fetus.
Primaquine, on the other hand, can cause jaundice in newborns who are relatively deficient in Glucose-6-Phosphate-Dehydrogenase enzyme.
The safety of other newer antimalarials such as mefloquine, artemisinin derivatives, malarone and co-artemether during pregnancy are still subjects of research.
Slide 33
The WHO has two laudable health programs, namely the “Making Pregnancy Safer” initiative and the “Roll Back Malaria” program. A partnership between both programs and national reproductive health programs is essential for the actualization of the 2000 Abuja Declaration in which regional leaders committed themselves to achieving 60% coverage of pregnant women in malaria-endemic areas by the year 2005.
Everyone needs to get involved. Act now by finding out how you can contribute to making pregnancy safe from the risks of malaria.
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What can we do at different levels of healthcare delivery in a country in order to move the agenda of malaria control during pregnancy forward?
At the national level, program leaders need to develop policies, standards, and guidelines; to advocate for financial support; to develop and disseminate information, education and communication (IEC) materials on malaria; to facilitate preservice and inservice training, and to strengthen support supervision, and monitoring and evaluation systems.
At the district level, district teams need to operationalize all guidelines and support supervision systems; provide proper logistics for drugs; sensitize the public about the importance of malaria control during pregnancy and promote the use of insecticide-treated nets.
At the facility level, an integrated health education system must be developed which addresses malaria by mobilizing the community about malaria control measures, encouraging increased utilization of health facilities, promoting the use of insecticide-treated nets, providing SP in antenatal clinics, ensuring prompt and adequate treatment of clinical cases of malaria, ensuring proper data collection, and surveying patient satisfaction for quality improvement.
Finally, at the community level, community health workers and traditional birth attendants need to help sensitize the community about malaria control and conduct home visits to follow up with those who have been treated in the facilities in order to ensure compliance with recommended antimalarial medication.
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In summary, malaria during pregnancy has been shown to have adverse consequences for both mothers and their babies. However, a malaria prevention package has also been shown to minimize these adverse events.
An effective preventive package includes intermittent preventive treatment with a dose of SP given at each antenatal care visit after quickening (but no less than 4 weeks apart) to ensure that the pregnant woman receives at least two doses. The package also includes the use of insecticide-treated nets throughout pregnancy and during the postnatal period. Preventive efforts must be complemented by case management of malaria illness with effective antimalarial medication for all women of reproductive age and should emphasize screening and prompt treatment of anemia. Successful programs can only emerge from partnerships between malaria control and reproductive health units.
For more information about malaria during pregnancy, visit the Resources section of this tutorial.
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