Malaria in pregnancy

• Introduction

• Malaria is a life-threatening disease caused by the protozoan plasmodium

that is transmitted to people through the bites of infected Anopheles
mosquitoes, called “malaria vectors” which bite mainly between dusk and
dawn.
• There are four protozoan species that cause malaria in humans:

– Plasmodium falciparum

– Plasmodium vivax

– Plasmodium malariae
 Cont…ed

• Plasmodium falciparum and Plasmodium

vivax are the most common.
• Plasmodium falciparum is the most deadly.
 Cont…ed

1.Malaria is caused by Plasmodiumspp.

2.Vector = Female Anopheles mosquito
3.Endemic in Africa; S.E. Asia; Central America
4.Origin:
Central Africa :5, 000 –10,000 years ago.
Deforestaionfor Agricultural purposes.
 Burden of the Disease:

• 2 billion people affected worldwide.

• 2-2.5 million deaths annually (mostly pregnant women, infants

0-5 years and HIV patients; 800,000in children 0-5 years).

• Plasmodium falciparumis cause of the most severe forms of

malaria. Malariais currently the most common parasitic
infection.

• Greatest challenge today is Resistance to Drugs.

 Complications of malaria during pregnancy

• Placental malaria doubles the risk of low birth weight.

Compared to multiparous women, primigravid women have
a two- to seven times the risk of low birth weight deliveries.
• Low birth weight in itself is a major risk factor for neonatal
mortality but Malaria-induced low birthweight is estimated to
be responsible for 3 to 17 deaths per 1000 livebirths. It is also
estimated that 11.4% of neonatal deaths and 5.7% of all infant
deaths in malaria endemic areas of Africa may be caused by
malaria in pregnancy-associated low birth weight.
 Cont…ed
• Malaria may lead to low birth weight through causation of
fetal growth restriction or preterm delivery. In high-
transmission areas, malaria-related fetal growth restriction
may be twice as high as malaria-related preterm delivery.
Contrastingly, in low-transmission settings, the predominant
cause of low birth weight is preterm delivery.
 Consequences of malaria in pregnancy

• Stillbirths, spontaneous abortions, fetal anaemia may also be

consequences of maternal parasitaemia.
• Placental malaria diminishes fetal cellular and antibody response to P
falciparum making the infant susceptible to malaria. Transplacenta
antibody transfer is also compromised, increasing susceptibility to othe
pathogens such as tetanus and Streptococcus pneumonia.
• HIV increases the risk of placental malaria infection, high density
parasitemia, febrile illness and worsens severe anaemia and low
birthweight. HIV also eliminates the gravidity specific pattern o
malaria in areas with stable transmission from paucigravid to al
pregnant women.
 Life cycles

1.Sexual Reproduction (In the Mosquito)

• Transformation of male and female gametes of Plasmodium
falciparum to sporozoites within salivary glands and stomach
of female Anopheles mosquito.
• Duration of process: 2 weeks
 Cont…ed

2. Pre-(Exo-) ErythrocyticPhase:
• Following a mosquito bite, the injected sporozoites
head for the human liver via the blood stream.
• During the next 10-15 days within the liver
hepatocytes, the sporozoites are transformed into
merozoites.
 Cont…ed

3. ErythrocyticPhase (Asexual Reproduction):

– Merozoites leave the liver hepatocytesto invade the red blood cells.

– Schizogony= Transformation of Merozoites to Schizonts.

– Duration of Schizogony:

– 36-48 hours(P. falciparum).

– 48 hours(P. ovale/ vivax).

– 72 hours(P. malariae).
 Cont…ed

4. Post Erythrocytic Phase:

• Rupture of RBCs leads to the release of transformed
schizonts as male and female gametes into the blood stream,
where they cause the syptoms of malaria (fever, rigors etc).
• Rupture of RBCs occur when the concentration of Schizonts
within the RBCs reach a critical minimum. The RBCs
rupture in synchrony and produce the clinical symptoms of
malaria.
note
– Clinical relapse may occur with P. vivax and P. ovale,
weeks to months after the first infection. This is because of
dormant liver forms known as hypnozoites (absent in P.
falciparum and P. malariae), which require special
treatment.(WHO 2014)
 Patterns of Immunity to Malaria

1. At the Community level:

• Epidemiologists describe 2 patterns:

– Stable Immunity (occurs in holo-endemic areas):

1. Malaria occurs throughout the year.

2. Community immunity is very high.
3. Epidemics are rare.
• (Full immunity is developed by age of 7 years).
 Cont…ed

• Unstable immunity:

1. Infection/ Transmission is intermittent (e.g. 3months in a

year).
2. Community immunity is very low.
3. Epidemics are frequent.
• (Full immunity is cannot be developed).
 Cont…ed

2. At the level of the Individual:

• Cellular Immunity:
– Mediated through macrophages of the Reticulo Endothelial
System (RES) resulting in phagocytosis of plasmodium
infected RBCs thus removing them from circulation.
 Cont…ed

• Humoral Immunity:
– Mediated by specific antibodies (IgGand IgM)against the
Erythrocytic phase of the infection.
 Cont…ed

Factors influencing the Extent to which Individual Immunity can be

developed:

1. Racial Factor (Phylogeny): e.g. Negroes and resistance against P. vivax.

2. Transmitted (Passive): short lasting (usually about a month); waxes and wanes.

3. Acquired (Active Immunity): Following repeated infections at very high cost.

The extent increases with Age and Parity.

Therefore, severity of malaria depends on duration of stay and the

endemicity of the area.

 Maternal malaria

• In areas of epidemic and low (unstable) malaria transmission,

adult women have no significant level of immunity and will
develop clinical illness if they have parasitaemia.
• Pregnant women with no immunity are at risk of dying from
severe malarial disease and/or experiencing spontaneous
abortion, preterm delivery, low birth weight or still birth.The
prevalence and intensity of malarial infection during
pregnancy is higher in women who are HIV infected.
 Cont…ed
• All pregnant women are at similar risk for malarial infection,
irrespective of parity. Abortion is common in the first
trimester, and prematurity is common in the third trimester.
Other consequences during pregnancy commonly associated
with P. falciparum infection include: hypoglycaemia,
hyperpyrexia, severe haemolytic anaemia and pulmonary
oedema.
 Diagnosis

• Rapid diagnostics
– WHO recommends parasitological confirmation by microscopy
or by Rapid Diagnostic Test (RDT) for all suspected cases of
malaria before treatment is started. (WHO 2010)
– Rapid malaria tests require minimal skill to perform and interpret.
The rapid antigen detection test (RDTs) detects parasite proteins
in finger-prick blood, but its sensitivity falls with a low level of
parasitemia.(PAHO 2008)
 Cont…ed
• Traditional diagnostics

– Thick and thin peripheral blood smears, stained with Giemsa stain,
remain the gold standard for routine clinical diagnosis that permits
the identification of species and quantification of parasites. (PAHO
2008)
– Malaria should not be excluded until at least 3 negative blood
smears are obtained within 48 hours.(PAHO 2008)
– Diagnosis should be promoted in pregnant women in endemic areas
in order to ensure accurate diagnosis of malaria and to reduce
unnecessary use of anti malarial in pregnancy.(PAHO 2008
 Treatment

• Pregnant women with symptomatic acute malaria are a high-

risk group, and they must promptly receive effective anti
malarial treatment.
• First trimester (treatment of uncomplicated Falciparum
malaria)
• Despite a limited number of prospective studies, anti malarial
medicines considered safe in the first trimester of pregnancy
are quinine, chloroquine, clindamycin and proguanil.
• Quinine plus clindamycin to be given for 7 days (artesunate
plus clindamycin for 7 days is indicated if this treatment
fails).
• An ACT (artemisinin-based combination therapy) is indicated
only if this is the only treatment immediately available, or if
treatment with 7-day quinine plus clindamycin fails, or if
there is uncertainty about patient compliance with a 7-day
treatment.
 Cont…ed
• Second and third trimesters
– ACT known to be effective in the country/region or
artesunate plus clindamycin for 7 days or Quinine plus
clindamycin for 7 days. If clindamycin is unavailable or
unaffordable, then the monotherapy should be given.
 Treatment of severe malaria in pregnancy

• World Health Organization. Guidelines for the treatment of malaria. Second

edition. WHO. 2010.
• WHO definition of severe malaria

• Clinical features:
• impaired consciousness or unrousable coma
• prostration, i.e. generalized weakness so that the patient is unable to walk
or sit up without assistance
• failure to feed
• multiple convulsions – more than two episodes in 24 h
• deep breathing, respiratory distress (acidotic breathing)
• circulatory collapse or shock, systolic blood pressure < 70 mm
Hg in adults and < 50 mm Hg in children
• clinical jaundice plus evidence of other vital organ dysfunction
• haemoglobinuria
• abnormal spontaneous bleeding
• pulmonary oedema (radiological)
• Laboratory findings:

• hypoglycaemia (blood glucose < 2.2 mmol/l or <40 mg/dl)

• metabolic acidosis (plasma bicarbonate < 15 mmol/l)
• severe normocytic anaemia (Hb < 5 g/dl, packed cell volume <
15%)
• haemoglobinuria
• hyperparasitaemia (> 2%/100 000/μl in low intensity transmission
areas or > 5% or 250 000/μl in areas of high stable malaria
transmission intensity)
• hyperlactataemia (lactate > 5 mmol/l)
• renal impairment (serum creatinine > 265 μmol/l).
 Treatment of severe malaria in pregnancy

• In treatment of severe malaria, saving the mother’s life is the primary

objective.
• Intravenous artesunate reduces more deaths related to severe malaria
than intravenous quinine.
• WHO therefore recommends treatment of severe malaria in pregnancy
with intravenous artesunate in the second and third trimester.
 World Health Organization recommendations for the treatment of severe malaria in
pregnancy

First trimester Second to third trimester

P. falciparum Either IV artesunate or IV artesunate should be

quinine can be used in
used preference to quinine
P. vivax Either IVartesunate or IV artesunate should be
quinine Suppressive used in preference to
prophylaxis with quinine
chloroquine until delivery Suppressive prophylaxis
Post-delivery, women with
should receive radical chloroquine until delivery
treatment with primaquine Post-delivery women
should receive radical
treatment with primaquine

All severe malaria Treatment must not be delayed. If only one of the drugs
artesunate, artemether, or quinine is available, it should
be administered immediately