See separate related article Malaria.

Epidemiology

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:

• In Sub-Saharan Africa, the area most burdened by malaria, the disease is thought to cause 400,000 cases of severe maternal anaemia and between 75,000-200,000 infant deaths annually.¹ 25 million pregnant women are believed to be at risk of P. falciparum infection per annum in this region and 25% have evidence of placental infection at the time of delivery.⁵
• 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:⁵
  • 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 3 of the Millennium Development Goals (MDG-3 Maternal Health, MDG-4 Child Health, MDG-5 Combating Infectious Disease).⁶

Risk factors⁵

• Primigravidae are at highest risk of malarial infection and serious complications. Pregnant women with one previous birth are also at higher risk.⁷ The effect of gravida status on complication risk is negated by concurrent HIV infection.⁴
• 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.

Presentation

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.
• 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 below), along with features of cerebral malaria (impaired consciousness, seizures) and jaundice can be the presenting features of an acute, severe illness.

Differential diagnosis

As for malaria in general, plus:

• Rhesus incompatibility
• Cytomegalovirus infection
• Herpes infection
• Rubella
• Toxoplasmosis
• Syphilis

Investigations

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&E, blood glucose and LFTs including bilirubin levels should also be checked.
• CXR may reveal cases of pulmonary oedema.
• Polymerase chain reaction tests are available.
• There is an increasing number of rapid diagnostic tests (RDTs) for malaria. Problems remain with interspecies' cross-reactivity, variable sensitivity at high/low levels of parasitaemia and false positives/negatives but they continue to be sold to travellers for self-testing and are widely used.

Management

If malaria is suspected in a pregnant patient, refer immediately to secondary/tertiary care where infectious disease, obstetric and neonatal care is on hand and intensive care facilities, if needed.

• Drugs should be used at adequate doses and according to clinical condition and local resistance patterns. A recent Cochrane review pointed to the lack of quality data, particularly as regards drug safety in pregnancy.⁸
  • Chloroquine and quinine can be used safely in any part of the pregnancy, but resistance is common.
  • Artemisinins appear to be safe in the second and third trimesters.⁹
  • Mefloquine and pyrimethamine/sulphadoxine are safe in second and third trimesters.
  • Primaquine, tetracycline, doxycycline and halofantrine are contra-indicated. Current UK treatment guidelines¹⁰ 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.¹¹ Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contra-indicated in pregnancy so, following treatment, a pregnant woman should take weekly chloroquine prophylaxis until after delivery.
• 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.

Complications

Maternal complications

In endemic/high-transmission areas for malaria, baseline immunity to malaria is decreased by pregnancy. Sufferers are more likely to experience severe anaemia. A nonimmune 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% is thought to be attributable to malaria.⁵ Severe anaemia eliminates any physiological reserve to cope with haemorrhage, making women more likely to die in childbirth.
• 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.
• Hypoglycaemia - this complication of malaria is much more common in pregnancy. It can be aggravated by treatment with parenteral quinine.
• Cerebral malaria is much more common in pregnant women.¹²
• Disseminated intravascular coagulation can occur and carries a high mortality risk.

Fetal complications

Both P. falciparum and P. 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:¹³

• Spontaneous abortion
• Premature delivery - affects around 15-20%
• Still birth - affects around 4%
• Intrauterine growth retardation - affects around 20%
• Low birth weight - common

Neonatal and infant problems related to malaria include:⁵

• Increased mortality rates
• Congenital malaria
• Anaemia
• Increased rates of other infections
• Undernutrition

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 nonimmune 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 P. 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 of a febrile infant in the first 3 months of life of mothers who have travelled to or immigrated from malarial areas.¹⁴

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.⁵

Prognosis

It is difficult to estimate exact morbidity and mortality rates due to the heterogeneity of severity but with nonimmune patients there is a high risk of acute, severe complications and death if the illness is not diagnosed and treated quickly.

Prevention

See separate article Malaria Prophylaxis.

Document references

1. CDC Malaria in pregnancy (2004)
2. Nosten F, McGready R, Mutabingwa T; Case management of malaria in pregnancy. Lancet Infect Dis. 2007 Feb;7(2):118-25. [abstract]
3. Ward SA, Sevene EJ, Hastings IM, et al; Antimalarial drugs and pregnancy: safety, pharmacokinetics, and pharmacovigilance. Lancet Infect Dis. 2007 Feb;7(2):136-44. [abstract]
4. Herrero MD, Rivas P, Rallon NI, et al; HIV and malaria. AIDS Rev. 2007 Apr-Jun;9(2):88-98. [abstract]
5. 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. [abstract]
6. 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. [abstract]
7. Nnaji GA, Okafor CI, Ikechebelu JI; An evaluation of the effect of parity and age on malaria parasitaemia in pregnancy. J Obstet Gynaecol. 2006 Nov;26(8):755-8. [abstract]
8. Orton LC, Omari AA; Drugs for treating uncomplicated malaria in pregnant women. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD004912. [abstract]
9. Dellicour S, Hall S, Chandramohan D, et al; The safety of artemisinins during pregnancy: a pressing question. Malar J. 2007 Feb 14;6:15. [abstract]
10. UK malaria treatment guidelines, Lalloo DG, Shingadia D, Pasvol G, et al; J Infect. 2007 Feb;54(2):111-21. Epub 2007 Jan 9. [abstract]
11. Duffy PE, Fried M; Malaria in the pregnant woman. Curr Top Microbiol Immunol. 2005;295:169-200. [abstract]
12. Shulman CE, Dorman EK; Importance and prevention of malaria in pregnancy. Trans R Soc Trop Med Hyg. 2003 Jan-Feb;97(1):30-5. [abstract]
13. Kalanda BF, Verhoeff FH, Chimsuku L, et al; Adverse birth outcomes in a malarious area. Epidemiol Infect. 2006 Jun;134(3):659-66. Epub 2005 Oct 28. [abstract]
14. 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. [abstract]

Internet and further reading

• Malaria prophylaxis, Clinical Knowledge Summaries (2007)
• WHO Lives at risk: malaria in pregnancy, 2003; information sheet
• Malaria site: Malaria in pregnancy; Informative website
• Carroll ID, Williams DC; Pre-travel vaccination and medical prophylaxis in the pregnant traveler. Travel Med Infect Dis. 2008 Sep;6(5):259-75. Epub 2008 Aug 16. [abstract]

Acknowledgements