|
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.
|
