See separate related article Malaria.
Pregnant women are more susceptible than the general population to malaria: they are more likely to become infected, suffer a recurrence, develop severe complications and to die from the disease. Malaria contributes very significantly to maternal and fetal mortality - with at least 10,000 maternal deaths per annum attributable in sub-Saharan Africa.
Regardless of symptoms, the presence of plasmodial parasites in a pregnant woman's body will have a negative impact on her own health and that or her fetus. Restricting treatment to symptomatic pregnant women is an inadequate strategy to reduce the morbidity and mortality associated with malaria. Subclinical infection is common in areas where natural immunity is high (eg, sub-Saharan Africa), whereas symptomatic cases are more common in areas with low immunity (eg, the Asia-Pacific region, and South Africa).
Malaria in pregnancy is different to the disease in the non-pregnant state. The severity of malaria in pregnancy is thought to be due to general impaired immunity plus a diminution of acquired immunity to malaria in endemic areas. Placental malaria occurs where Plasmodium falciparum-infected erythrocytes accumulate in the intervillous space of the placenta but may be rare or absent in the peripheral circulation. Diagnosis by light microscopy of blood films is more difficult.
Treatment can be more difficult due to restrictions on anti-malarial agents. Many are unlicensed in pregnancy due to lack of clinical trials involving this important population, for fear of damaging the fetus. There is frequently a lack of good post-marketing surveillance where these drugs are routinely used in pregnancy. However, data support the safety of artemisinin-combined drugs (ACDs) and their advent has provided a useful therapeutic option. With regard to chemoprophylaxis, recent World Health Organization (WHO) recommendations and a large meta-analysis support the use of intermittent prophylactic treatment during the second and third trimester.
Concurrent HIV infection worsens this scenario significantly: HIV increases susceptibility to malarial infection and the presence of malaria causes an increase in HIV viral load.
Producing good estimates of the global burden of malaria is difficult due to poor numerator (number of women affected by malaria in pregnancy) and denominator (population at risk) data. However:
- Globally, 125 million women are at risk of malaria every year.
- In sub-Saharan Africa, the area most burdened by malaria, the disease is thought to cause as many as 10,000 cases of malaria-related deaths in pregnancy, mainly due to severe maternal anaemia.
- Infant mortality rates are very difficult to come by and lack of reliable data has been identified as a major problem in the planning of anti-malarial public health services. Statistics in 2010 suggested that there were 655,000 malaria-related deaths globally of which 86% were in children under the age of 5.The number related to malarial infection in pregnancy is, however, not known.
- A recent review of studies, carried out in sub-Saharan Africa between 2000 and 2011, reports that prevalence of malaria in pregnant women attending antenatal clinics was 29.5% in East and Southern Africa and 35.1% in West and Central Africa.
- Malaria in the Asia-Pacific region requires special consideration and it cannot be assumed that data deriving from Africa will be relevant to this area. Further studies of mortality and morbidity in pregnant women resident in this region are required.
- Malaria makes a large but unquantifiable contribution to low birth weight in infants in the developing world, a major cause of morbidity and mortality in infants and children. Preventing malaria in pregnant low gravid women:
- Reduces severe maternal anaemia by 38%
- Reduces low birth weight by 43%
- Reduces perinatal mortality by 27%
Preventing and treating malaria in pregnancy can be a key intervention to improving maternal, fetal and child health globally and is linked to three of the Millennium Development Goals (MDG-3 Maternal Health, MDG-4 Child Health, MDG-5 Combating Infectious Disease).
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- Primigravidae are at highest risk of malarial infection and serious complications. Pregnant women with one previous birth are also at higher risk.
- The effect of gravida status on complication risk is negated by concurrent HIV infection.
- Younger maternal age (particularly adolescence) carries a higher risk of infection and adverse effects.
- Second trimester carries the highest risk of infection.
- Some studies suggest the increased risk disperses quickly after delivery, others that the first two months postpartum continue to carry an increased risk of infection.
Atypical presentation of malaria is common in pregnancy, particularly in the second and third trimesters, so a high index of suspicion should be maintained in susceptible pregnant mothers.
- A travel history should be taken in any pregnant woman with unexplained fever or anaemia.
- Fever may be absent, low-grade or very high and may not behave in the classical quartian/tertian fashion.
- Other symptoms may include cough, malaise, headache, myalgia and diarrhoea.
- Anaemia is a common feature and may be the only clue to the illness in mature primigravidae living in endemic areas.
- Splenomegaly may occur but tends to regress in the second half of pregnancy.
- Complications (see 'Complications', below), along with features of cerebral malaria (impaired consciousness, seizures) and jaundice can be the presenting features of an acute, severe illness.
As for malaria in general, plus:
Diagnosis of falciparum malaria in pregnancy can be particularly difficult due to placental sequestration of parasites - seek expert help.
- Thick and thin films for malarial parasites should be examined and the degree of parasitaemia determined. Parasites may not be detectable on peripheral blood films.
- FBC, U&Es, blood glucose and LFTs including bilirubin levels should also be checked.
- CXR may reveal cases of pulmonary oedema.
- Polymerase chain reaction tests are available.
- Rapid diagnostic tests are useful and affordable and require further evaluation in the antenatal period.
If malaria is suspected in a pregnant patient, refer immediately to secondary/tertiary care where infectious disease, obstetric and neonatal care is on hand, together with intensive care facilities, if needed.
- Drugs should be used at adequate doses and according to clinical condition and local resistance patterns. Whilst a Cochrane review pointed to the lack of quality data, particularly with regard to drug safety in pregnancy, several innovations have since improved the risk-benefit ratio:
- Chloroquine and quinine can be used safely in any part of the pregnancy but resistance is common.
- Studies of pregnant women with malaria in Thailand found that artemisinin-combination therapy (treatment in which artemisinin is combined with other antimalarials) were safe in the first, second and third trimesters and provided fewer treatment failures than other commonly used regimes.
- Mefloquine and pyrimethamine/sulfadoxine are safe in the second and third trimesters.
- A Gambian study recommended quinine plus clindamycin for seven days as the first-line treatment for uncomplicated malaria and artesunate plus clindamycin for seven days if this treatment fails. Treatment, however, should not be delayed and should be started with the most readily available drug.
- Primaquine, tetracycline, doxycycline and halofantrine are contra-indicated. Current UK treatment guidelines suggest the use of quinine and clindamycin in place of doxycycline.
- Recurrence of malaria is common in pregnancy and resistance frequently reduces the usefulness of antimalarials. The WHO recommended a regimen of seven days of artesunate (2 mg/kg/day or 100 mg daily for seven days) and clindamycin (450 mg three times daily for seven days). Atovaquone-proguanil-artesunate and dihydroartemisinin-piperaquine have been used in pregnant women with multiple recurrent infections to good effect in the UK.
- Fluid replacement needs to be very carefully monitored to prevent pulmonary oedema.
- If anaemia requires transfusion (Hb <7-8 g/dL) then packed cells are preferred to avoid fluid overload.
- The complications of malaria should be carefully and aggressively managed.
- Involve the obstetric team early in case of premature labour.
In endemic/high-transmission areas for malaria, baseline immunity to malaria is decreased by pregnancy. Sufferers are more likely to experience severe anaemia. A non-immune pregnant woman (or one with low immunity from a low-transmission area) is likely to develop a severe form of the illness and complications.
- Anaemia tends to occur between 16-29 weeks - due to haemolysis of parasitised cells and increased demands of pregnancy ± folate/iron deficiency. 5-10% of pregnant African women have severe anaemia, of which 26% are thought to be attributable to malaria. Severe anaemia eliminates any physiological reserve to cope with haemorrhage, making women more likely to die in childbirth.
- An Indian study reported that pregnant women with malaria are at increased risk of hypoglycaemia, cerebral malaria, renal failure, hepatic failure and hypotension.
- Acute pulmonary oedema occurs much more commonly in pregnant women and may be the presenting feature. It carries a high mortality and is typically seen in the second and third trimesters.
- Disseminated intravascular coagulation can occur and carries a high mortality risk.
Both P. falciparum and Plasmodium vivax can cause complications that affect the fetus. Fetal mortality is estimated at 15% for P. vivax and around 30% for P. falciparum. Common problems for the fetus include:
- Spontaneous abortion
- Premature delivery
- Intrauterine growth restriction
- Low birth weight - common
- Intrauterine fetal death
Maternal infection can also be associated with missed abortion, preterm labour, intrauterine growth restriction and intrauterine fetal death.
Neonatal and infant problems related to malaria include:
- Increased mortality rates
- Congenital malaria
- Increased rates of other infections
Congenital malaria may occur by transplacental spread but has always been considered rare in children born in endemic areas and is more common in offspring of non-immune mothers with malaria. Treatment of the mother may not eradicate parasites from the fetus, due to lower drug levels. Congenital malaria tends to present with fever, irritability, feeding difficulties, hepatosplenomegaly, jaundice or anaemia. It is most commonly due to infection with Plasmodium malariae and can be diagnosed by blood films of cord or heel-prick blood within a week after birth. Always consider congenital malaria in the differential diagnosis of a febrile infant in the first three months of life of mothers who have travelled to or immigrated from malarial areas.
Longer-term developmental problems related specifically to malaria during pregnancy are harder to unpick from those related to low birth weight. It is thought that there may be long-term consequences such as short stature and an increased risk of metabolic disease in adulthood.
It is difficult to estimate exact morbidity and mortality rates, due to the heterogeneity of severity but with non-immune patients there is a high risk of acute, severe complications and death if the illness is not diagnosed and treated quickly.
See separate article Malaria Prophylaxis.
Further reading & references
- Pregnancy and Malaria; Malaria Site
- Malaria prophylaxis, Prodigy (February 2012)
- Dhiman S, Yadav K, Goswami D, et al; Epidemiology and Risk Analysis of Malaria among Pregnant Women. Iran J Public Health. 2012;41(1):1-8. Epub 2012 Jan 31.
- Avery JW, Smith GM, Owino SO, et al; Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy. PLoS One. 2012;7(2):e31090. doi: 10.1371/journal.pone.0031090. Epub 2012 Feb 7.
- The Rapid Assessment of the Burden of Malaria during Pregnancy: A Toolkit, Centers for Disease Control and Prevention, 2010
- Nosten F, McGready R, Mutabingwa T; Case management of malaria in pregnancy. Lancet Infect Dis. 2007 Feb;7(2):118-25.
- Takem EN, D'Alessandro U; Malaria in pregnancy. Mediterr J Hematol Infect Dis. 2013;5(1):e2013010. doi: 10.4084/MJHID.2013.010. Epub 2013 Jan 2.
- Kayentao K, Garner P, van Eijk AM, et al; Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis. JAMA. 2013 Feb 13;309(6):594-604. doi: 10.1001/jama.2012.216231.
- Omoti CE, Ojide CK, Lofor PV, et al; Prevalence of parasitemia and associated immunodeficiency among HIV-malaria co-infected adult patients with highly active antiretroviral therapy. Asian Pac J Trop Med. 2013 Feb;6(2):126-30. doi: 10.1016/S1995-7645(13)60007-3.
- Conroy AL, McDonald CR, Kain KC; Malaria in pregnancy: diagnosing infection and identifying fetal risk. Expert Rev Anti Infect Ther. 2012 Nov;10(11):1331-42. doi: 10.1586/eri.12.123.
- World Health Statistics, World Health Organization, 2012
- Rijken MJ, McGready R, Boel ME, et al; Malaria in pregnancy in the Asia-Pacific region. Lancet Infect Dis. 2012 Jan;12(1):75-88. doi: 10.1016/S1473-3099(11)70315-2.
- Desai M, ter Kuile FO, Nosten F, et al; Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007 Feb;7(2):93-104.
- Filippi V, Ronsmans C, Campbell OM, et al; Maternal health in poor countries: the broader context and a call for action. Lancet. 2006 Oct 28;368(9546):1535-41.
- Herrero MD, Rivas P, Rallon NI, et al; HIV and malaria. AIDS Rev. 2007 Apr-Jun;9(2):88-98.
- Malaria treatment guidelines; Health Protection Agency
- Campos IM, Uribe ML, Cuesta C, et al; Diagnosis of gestational, congenital, and placental malaria in Colombia: comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology. Am J Trop Med Hyg. 2011 Jun;84(6):929-35. doi: 10.4269/ajtmh.2011.10-0507.
- The diagnosis and treatment of malaria in pregnancy, Green-top Guideline No. 54B, Royal College of Obstetricians and Gynaecologists (2010)
- Manirakiza A, Serdouma E, Heredeibona LS, et al; Rational case management of malaria with a rapid diagnostic test, Paracheck Pf(R), in antenatal health care in Bangui, Central African Republic. BMC Public Health. 2012 Jun 26;12:482. doi: 10.1186/1471-2458-12-482.
- Orton LC, Omari AA; Drugs for treating uncomplicated malaria in pregnant women. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD004912.
- McGready R, Lee SJ, Wiladphaingern J, et al; Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012 May;12(5):388-96. doi: 10.1016/S1473-3099(11)70339-5. Epub 2011 Dec 12.
- McGready R, White NJ, Nosten F; Parasitological efficacy of antimalarials in the treatment and prevention of falciparum malaria in pregnancy 1998 to 2009: a systematic review. BJOG. 2011 Jan;118(2):123-35. doi: 10.1111/j.1471-0528.2010.02810.x.
- Seal SL, Mukhopadhay S, Ganguly RP; Malaria in pregnancy. J Indian Med Assoc. 2010 Aug;108(8):487-90.
- Centers for Disease Control and Prevention; Intermittent Preventive Treatment of Malaria for Pregnant Women (IPTp), 2012.
- Hagmann S, Khanna K, Niazi M, et al; Congenital malaria, an important differential diagnosis to consider when evaluating febrile infants of immigrant mothers. Pediatr Emerg Care. 2007 May;23(5):326-9.
|Original Author: Dr Chloe Borton||Current Version: Dr Laurence Knott||Peer Reviewer: Dr Adrian Bonsall|
|Last Checked: 28/03/2013||Document ID: 2416 Version: 24||© EMIS|
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