December 2007 - Volume 1, Issue 6

MALARIA IN PREGNANCY

Dr Safaa Bahjat

Mal aria: bad air (medieval Italian).

Malaria has stalked human history for the past 50,000 years, with mention of survivors from 27500 BC during the Xia dynasty in ancient China. In 1880, Charles Alfonso Louis Alphonso Lavaren identified the parasite (Plasmodium spp) responsible for malaria and at the turn of the century Sir Ronald Ross proved that it was the mosquito that spread the infection. For a while it become common to use malaria in targeting syphilis, at the time of mortal affliction. The patient would be deliberately infected with malaria to induce fever. This would be treated with quinine (isolated from an old Peruvian remedy) in the hope that the one illness be regulated, the other halted.

So long as woman has walked the earth, malaria has stalked her, however the problem of malaria in pregnancy was not described until the early 20th century. Over 50 million women are exposed to the risk of malaria in pregnancy every year. Pregnancy associated malaria results in substantial, and especially fetal and infant, morbidity, causing 7500-200000 infant deaths every year. Both Plasmodium falciparum and Plasmodium vivax infections can cause adverse pregnancy outcomes including maternal anemia and low body weight due to pre-term delivery and fetal growth restriction, but much could differ. Pregnant women are more susceptible to malaria than non-pregnant women, and this susceptibility is greatest in the first and second pregnancy. Although some other infectious diseases are also worse in pregnancy, malaria seems to be a special case. Susceptibility to pregnancy-associated malaria probably represents a combination of immunological and hormonal changes associated with pregnancy (although the nature of the latter is the subject of debate) combined with the ability of a subset of infected erythrocytes to sequester in the placenta. Extensive evidence confirms that antibodies directed against the surface of infected erythrocytes in the placenta are important in protection, and are usually absent in the first pregnancy(1). In high transmission areas such as Sub-Saharan Africa, malaria in pregnancy is predominantly asymptomatic and yet is a major cause of severe maternal anemia and low birth weight babies. In low transmission areas, such as in many parts of Asia and Latin America, women have a little acquired immunity to malaria by the time they become pregnant and so infections are often symptomatic and are more likely to become severe and result in maternal and fetal death.

On the basis of the above review, it is clear that the clinical consequences to mother and child, of malaria in pregnancy, and the magnitude of the problem, are enormous. However, we have very little information from Asia and Latin America, and even for Africa we are currently unable to make an evidence based statement on whether the overall burden of malaria in pregnancy has increased, decreased or remained at a steady state in the past few decades. At present there are substantial knowledge gaps regarding the burden of malaria in pregnancy, that impede our understanding of, and ability to control this important public health problem.

Rapid assessment of the burden of malaria in pregnancy has recently been developed and done in Asia (Bangladesh, India, Burma, Indonesia), in low transmission areas of French speaking Africa (Madagascar, Senegal, Niger, Mali ,and Mauritania), and will soon be done in North and Central America. However, these assessments have not always been done over a sufficient length of time (a full year). The first gap of knowledge is on the effect of a single plasmodium infection or asymptomatic infection on the burden of malaria in pregnancy. The second gap is on the effect of malaria in pregnancy (by gravidity) on infant and child health as well as the long-term cumulative effect of malaria on pregnancy. The third gap is on the burden of malaria in the first trimester and it's correlation with adverse outcomes. (2)

THE ECONOMIC BURDEN OF MALARIA IN PREGNANCY:

There are two possible approaches to estimating the economic burden of malaria in pregnancy. Microeconomic approaches are used to measure the effect of the disease on an individual or household, while macroeconomic approaches measure the effect of the diseases on an entire society. Taking a traditional micro level approach, economic cost can be categorized as direct, indirect and intangible and can be measured from the perspective of the government (mainly Ministry of Health ) ,and households.

The direct costs of malaria in pregnancy can be divided into:
1. the cost arising from interventions targeted at all pregnant women in malaria endemic settings.
2. the additional costs arising as a consequence of malaria infection in pregnant women .

Direct cost to the health service arising from specific interventions for preventing or treating malaria in pregnancy include the cost of the Intermittent Preventive Treatment in Pregnancy (IPTp). Direct costs associated with malaria infections in pregnant women include the immediate costs of maternal infection and also the immediate and long term costs of treating the consequences of maternal infection on the infant, most of which relates to mitigating the consequences of low birth weight. Immediate costs are those of additional outpatient consultations, hospitalization, staff time, diagnostic tests, drugs and other supportive treatment. The cost incurred by the mother (or her household) include those of obtaining additional health care such as transport, drug costs and consultation fees.(3)

CASE MANAGEMENT OF MALARIA IN PREGNANCY(4)

*Diagnosis of malaria in pregnancy: In most malaria endemic regions women do not have access to parasitological diagnosis or even to treatment. In areas of high transmission, to leave parasitaemic but asymptomatic adults untreated is common practice. The assumption is that the natural immunity of such individuals will control the infection. However, in pregnant women the presence of malaria parasite, even transient without symptoms, is harmful for the mother and fetus, whether or not placental malaria is detected at delivery. The biological diagnosis of malaria during pregnancy is also essential to avoid the unnecessary exposure of the mother and fetus to antimalarial drugs. New treatments of malaria are more expensive and to confirm the diagnosis of malaria before treatment is cost effective, especially if one takes into account the added risks, both morbid and iatrogenic, to the fetus. The confirmation of malaria diagnosis can be done either by microscopic examination (the current gold stained) or by use of a rapid diagnostic test that detects specific parasite antigen. An experienced and well-equipped microscopist can detect 15 parasites per uL of blood. In most non-pregnant malaria cases, this is well below the pyrogenic density threshold above which patients present with symptoms. However, during pregnancy asymptomatic low parasite densities and parasites sequestered in the placenta are harmful to the mother and the fetus, so the sensitivity of microscopy is insufficient in these cases. Together with the practical strains of microscopy, the lack of sensitivity impairs the detection of pregnant women who need treatment and assessment of the efficacy of anti-malarials. More recently, rapid diagnostic tests have been developed. Such tests are practical but do not have the sensitivity needed in pregnancy. Polymerase chain reaction (PCR) is used in research settings or genotyping and detection of malaria parasites and is marginally more sensitive than microscopy. A microscopic blood examination or rapid diagnostic tests can be done either because a pregnant woman presents with symptoms (or a history of symptoms) compatible with malaria, or a part of systematic antenatal screening (bearing in mind the limitation of detection). In all malarious areas, every time a regnant woman is seen in an antenatal consultation, a blood test for malaria should be done and positive cases treated appropriately. In areas of intense and stable transmission, the absence of evidence of plasmodia in peripheral blood on a single occasion does not exclude infection. Parasitaemia can fluctuate and be kept under the level of detection (total biomass of about 1,000,000,000 parasites) by acquired immunity or self-medication, and Plasmodium falciparum can sequester in the placenta. These factors complicate the assessment of the efficacy of anti-malarial drugs and under line the need for more diagnostic tools .The earlier in pregnancy and the more frequent the antenatal consultations and blood screening, the more likely a malarial parasite will be detected and treated. This early detection and treatment has been shown to reduce the placental burden, a key step in reducing the harmful effects on the fetus. In the presence of a well implemented, effective, and safe prevention strategy intermittent preventive treatment and vector control) the frequency of antenatal visits could be limited.

CURRENT RECOMMENDATIONS FOR CASE MANAGEMENT

Uncomplicated falciparum malaria

First trimester

First episode quinine 10mg/kg three times a day for 7 days preferably with clindamycin 5mg/day three times per day for 7 days.

Subsequent episodes: repeat treatment with quinine, clindamycin as above, Artemsinin based combination therapy (ACT) that is locally effective, or artesunate 2mg per day for seven days with clindamycin as above

Second and third trimester

First episode: ACT that is locally effective or artesunate plus clindamycin as above. - Subsequent episodes: artesunate plus clindamycin as above; or quinine plus clindamycin as above.

Prevention

Intermittent preventive treatment with sulfadoxin-pyrimethamine where efficacy remains.

Severe malaria

Artesuminate 2-4mg/kg intravenously at hours 0, 12, and 24 and continued for 24 hours until the patient can tolerate aretsunate 2mg/g per dose and clindamycin 5mg/kg three times daily for 7 days,

OR

Intravenous quinine: loading dose 20mg/kg given over 4 hours after the loading dose is started, followed by 10mg/kg every 8 hours for 7 days. Once the patient has recovered sufficiently to tolerate oral medication both quinine 10mg/kg and clindamycin 5mg/kg three times daily, and continued for 7 days.

Non-falciparum malaria

Chloroquine phosphate (1 tablet contains 250mg salt equivalent to 155.3mg base). Dose is 10mg/kg base once a day for 3 days followed by 5mg/kg base on the third day. For chloroquine resistant p.vivax, amodiquanine, quinine or armetsinin derivatives can be used.

Prevention

Chloroquine phosphate 600 mg base on admission followed by 300 mg base per week.