An estimated 125 million pregnancies per year are at risk of malaria around the world.1 For both mother and child, malaria is potentially life-threatening. MMV’s MiMBa strategy aims to raise the standard of care for pregnant women and their newborns affected by malaria. Key elements of the MiMBa strategy include: • Ensuring drug supplies for children and pregnant women; • Generating data on existing compounds to inform on their use in pregnant women and neonates; • Developing new antimalarial medicines to address the needs of pregnant women and neonates; • Strengthening the capture of safety data from routine clinical use of antimalarial medicines during pregnancy; • Advocating for changes in drug development that promote the safe inclusion of pregnant women into clinical studies, with the aim of generating data to support earlier access to innovative medicines for this population. • Pregnant women are especially susceptible to malaria infection. Without existing immunity, severe malaria can develop requiring emergency treatment, and pregnancy loss is common. In semi-immune women, consequences of malaria for the mother include anaemia while stillbirth, premature delivery and foetal growth restriction affect the developing foetus. Preventive measures include insecticide-treated nets and (in some African settings) intermittent preventive treatment. Prompt management of maternal infection is key, using parenteral artemisinins for severe malaria, and artemisinin combination treatments (ACTs) in the second and third trimesters of pregnancy. ACTs may soon also be recommended as an alternative to quinine as a treatment in the first trimester of pregnancy. Monitoring the safety of antimalarials and understanding their pharmacokinetics is particularly important in pregnancy with the altered maternal physiology and the risks to the developing foetus. As increasing numbers of countries embrace malaria elimination as a goal, the special needs of the vulnerable group of pregnant women and their infants should not be overlooked.

1. Malaria in Pregnancy
DR ALKA MUKHERJEE
NAGPUR M.S. INDIA

2. DR ALKA MUKHERJEE
MBBS DGO FICOG FICMCH PGDCR PGDMLS MA(PSY)
Director & Consultant At Mukherjee Multispecialty Hospital
MMC ACCREDITATED SPEAKER
MMC OBSERVER MMC MAO – 01017 / 2016
Present Position
 Director of Mukherjee Multispecialty Hospital
 Hon.Secretary INTERNATIONAL COUNCIL FOR HUMAN RIGHTS
 Hon.Secretary NARCHI NAGPUR CHAPTER (2018-2020)
 Hon.Secretary AMWN (2018-2021)
 Hon.Secretary ISOPARB (2019-2021)
 Life member, IMA, NOGS, NARCHI, AMWN & Menopause
Society, India, Indian medico-legal & ethics association(IMLEA),
ISOPRB, HUMAN RIGHTS
 Founder Member of South Rapid Action Group, Nagpur.
 On Board of Super Specialty, GMC, IGGMC, AIIMS Nagpur,
NKPSIMS, ESIS and Treasury, Nagpur for “ WOMEN SEXUAL
HARASSMENT COMMITTEE.”
mukherjeehospital@yahoo.com
www.mukherjeehospital.com
https://www.facebook.com/
Mukherjee Multispeciality
https://www.instagram.com/
Achievement
 Winner of NOGS GOLD MEDAL – 2017-18
 Winner of BEST COUPLE AWARD in Social
Work - 2014
 APPRECIATION Award IMA - MS
 Past Position
 Organizing joint secretary ENDO-GYN
2019
 Vice President IMA Nagpur (2017-2018)
Vice President of NOGS(2016-2017)
Organizing joint secretary ENDO-GYN
Organizing secretary AMWICON – 2019
ECTOPIC PREGNANCY

3. Malaria in Pregnancy
• Malaria parasitic infection transmitted by the female
anopheline mosquito and caused by the four species of
plasmodium that infect humans: vivax, ovale, malariae, and
falciparum - most deadly species.
• Pregnant women are three times more susceptible to suffer
from malarial infection specially in second trimester -
highest rate of infection.
• Monitoring the safety of antimalarials and understanding
their pharmacokinetics is particularly important in
pregnancy - altered maternal physiology and the risks to the
developing foetus.

4. • Without existing immunity, severe malaria can develop
requiring emergency treatment, and pregnancy loss is
common.
• In semi-immune women, consequences of malaria for the
mother - anaemia while stillbirth, premature delivery and
foetal growth restriction affect the developing foetus.
• Preventive measures include insecticide-treated nets and (in
some African settings) intermittent preventive treatment.
• Prompt management of maternal infection - parenteral
artemisinins for severe malaria, and artemisinin
combination treatments (ACTs) in the second and third
trimesters of pregnancy.
• ACTs may soon also be recommended as an alternative to
quinine as a treatment in the first trimester of pregnancy.

6. Effect of Malaria on Pregnancy
• Sequelae in pregnancy
• A] The immunocompromised state of pregnancy and
• B] Additional placental sequestration of infected erythrocytes.
Hypothesized infected erythrocytes collected in the placenta
stimulate pancreatic B-Cell production of insulin, leading to
hyperinsulinemia and hypoglycemia.
• Other maternal effects of malarial infection result from the “
stickiness’’ of the infected erythrocytes that become in cerebral
malaria , renal failure, and thrombocytopenia. Sometimes malaria
infection can be with HELLP syndrome

8. Consequences of malaria in pregnancy
• The consequences vary with transmission intensity.
• When the transmission is high - maternal anaemia and
• - infant low birth weight due to foetal
growth restriction and/or premature delivery
• When transmission is low - when non-immune pregnant women
become infected, malaria infection may become severe and life-
threatening, requiring emergency treatment
• Maternal complications include
 Acute lung injury,
 Severe hypoglycaemia and
 Coma while pregnancy loss due to miscarriage or stillbirth is also
frequent.
 Malaria may be an under-recognized cause of maternal death

9. High Transmission Settings
Settings
High Low
• Where levels of acquired immunity tends to be high, the greatest degree
of placental infestation is seen in women who have the highest level of
immunity, leading to milder maternal symptoms, Fetal complication as
maternal anemia , and manifest as stillbirth , intrauterine growth
restriction, and low- birth weight neonate , at higher risk for neonatal
and newborn death.
• In high transmission settings the adverse effects of P. falciparum
infection in pregnancy are most pronounced for women in their first
pregnancy.
• Low women of reproductive age have relatively little acquired immunity
to malaria is associated with maternal anemia, spontaneous abortion,
stillbirth, prematurity, and low birth weight.

10. Clinical Manifestations
Complicated
• Clinical Manifestations
Complicated /Severe
• Uncomplicated malaria :- Symptoms positive parasitological test (
microscopy or rapid diagnostic test (RDT) no features of severe malaria
fever, rigors, headache, bodyache, fatigue , anorexia , and nausea as in
non- pregnant state.
• Severe malaria :- P. falciparum malaria as a patient with P. falciparum
asexual parasitemia with evidence of organ dysfunction
• (Cerebal malaria with generalized convulsions edema, severe anemia,
renal failure, hypoglycemia, metabolic acidosis circulatory collapse/
shock spontaneous bleeding and laboratory evidence of DIC,
macroscopic hemoglobinuria , hyperthermia, hyperparasitemia)

12. • Severe malaria loboratory findings can include :
• Hypoglycemia (blood glucose<2.2 mmol/I or<40mg/dl),
• Metabolic acidosis (plasma bicarbonate<15mmol/I, severe
normocytic anemia(hb<5g/dl),
• Hemoglobinuria,
• Hyperasitemia(>2%/100,000 per ul in areas of hight stable
malaria transmission),and
• Renal impairment (serum creatinine> 265umol/I)

14. Severe Malaria in Pregnancy
• Parenteral artesunate is the treatment of choice in all trimesters
• if artesunate is unavailable, intramuscular artemether should be given, and
• if this is unavailable then parenteral quinine should be started immediately
until artesunate is obtained
• Intravenous quinine is associated with recurrent hypoglycemia,
• In epidemic situations, if IV or intramuscular medication is unavailable,
patients should receive artesunate suppositories and be transferred to a
higher level facility.
• Severe malaria parenteral antimalarials, antibiotics, anticonvulsants,
antipyretics, intravenous infusion equipment and fluids, special nursing for
patients in coma, facilities for blood transusion, well – equipped laboratory,
and oxygen respirator.
• Hypoglycemia should be expected and it is often recurrent if the patient is
receiving quinine.
• Postpartum bacterial infection is a common complication and should be
managed appropriately.

17. Box 2. Symptoms and signs of malaria
Symptoms
● Fever/chills/sweats
● Headache
● Muscle pain
● Nausea
● Vomiting
● Diarrhea
● Cough
● General malaise
Signs
● Jaundice
● Elevated temperature
● Perspiration
● Pallor
● Splenomegaly
● Respiratory

18. Diagnosis
• A] Microscopy of stained thick and thin blood smears
remains the gold standard for confirmation of diagnosis of
malaria as well to quantify the parasite load and to
distinguish different species of malaria parasites and their
different stages.
• B] RDTs are based on the detection of circulating parasite
antigens.
• C] In placental specimens, histopathology can also be used
to identify parasites and resultant inflammatory responses.
Other important prognostic factors that should be reported on a peripheral blood
smear result are:
● the presence and count of mature trophozoites and schizonts of P. falciparum
● finding malaria pigment in more than 5% of the polymorphonuclear leucocytes in
the peripheral blood film.

19. Diagnosis
• Microscopy
• Microscopy of stained blood smears remains widely
used to monitor the prevalence of malaria.
• For point-of-care testing, rapid diagnostic tests (RDT)
are very effective for the diagnosis of symptomatic
malaria infection, which tends to be accompanied by
high parasitaemia.
• These are less effective as screening tools, being
unable to reliably detect low-density infections which
are common.
• New, high-sensitivity RDTs will soon be evaluated in
pregnant women.
In a febrile patient, three negative malaria smears 12–24 hours apart rules out
the diagnosis of malaria.

21. Polymerase chain reaction (PCR)
• Polymerase chain reaction is highly sensitive, with
quantitative PCR able to detect very low-density malaria
infection
• a specialized laboratory with trained staff is required, and
assays are relatively time-consuming.
• Loop-mediated isothermal amplification (LAMP) has similar
sensitivity to PCR but is more rapid and robust, and
potentially applicable at the point of care. Both are presently
reserved for research settings.

22. Placental histology
• Histological examination of placental tissue at delivery is a
sensitive tool for detection of active or past malaria
infection.
• Past infection is detected as the malaria pigment,
haemozoin, most commonly in fibrin deposits.
• Active infection can be accompanied by leucocytes
infiltrates, principally monocytes, termed intervillositis,
particularly in first-time mothers with little pregnancy-
associated malaria immunity.
• It is strongly associated with low birth weight and maternal
anaemia.

24. How is malaria infection treated during pregnancy?
• Treat malaria in pregnancy as an emergency.
• Admit pregnant women with uncomplicated malaria to hospital and pregnant
women with severe and
• complicated malaria to an intensive care unit.
• Intravenous artesunate is the treatment of choice for severe falciparum malaria.
Use intravenous
• quinine if artesunate is not available.
• Use quinine and clindamycin to treat uncomplicated P. falciparum (or mixed, such
as P. falciparum and
• P. vivax).
• Use chloroquine to treat P. vivax, P. ovale or P. malariae.
• Primaquine should not be used in pregnancy.
• Seek advice from infectious diseases specialists, especially for severe and
recurrent cases.
• Do not persist with oral therapy if vomiting is persistent.
• Treat the fever with antipyretics.
• Screen women with malaria for anaemia and treat appropriately.
• Write a management plan for follow-up, to ensure detection of relapse.

27. have directly addressed the question of routine iron and folate supplementation as part of
uncomplicated malaria treatment. In P. falciparum malaria treatment trials in women with low
premunition, 90% of women developed anaemia (haemoglobin less than 10 g/dl), either on
admission or during follow-up.80 Premunition is the degree of naturally acquired host immunity
to malaria. It depends on repeated exposure to infectious anopheline bites, so most UK-based
residents will have low or no premunition. Mild and moderate malariaassociated anaemia is
treated with ferrous sulphate and folic acid at the usual doses.

28. Does pregnancy affect the efficacy of malaria
treatments?
• Treatments in pregnancy may have lower efficacy than in non-pregnant patients
but this apparent effect could result from lowered concentrations of
antimalarials in pregnancy.26,30,32Women should be advised of the risk of
recurrence and a suitable follow-up plan devised; for example, if symptoms or
fever return, a repeat blood film is necessary. Alternatively, weekly screening by
blood film can provide early detection and treatment of malaria.
• Malaria in pregnancy is unique and the ability of P. falciparum to sequester in the
placenta challenges the normal way antimalarial drug efficacy is assessed.
Polymerase chain reaction (PCR)-confirmed prolonged submicroscopic carriage
with subsequent recurrence has been reported in pregnant women for months
following drug treatment for uncomplicated P. falciparum. Most recurrence is
around day 28–42 but later reported recurrence, so far unique to pregnancy, has
been reported to occur at 85 days with quinine,28 98 days with artesunate, 63
days with artemether-lumefantrine30 and 121 days with mefloquine. Weekly
screening by blood film until delivery allows these women to be detected
positive before becoming symptomatic.10

29. How should recurrence be treated?
• The treatment efficacy of antimalarials for recurrent malaria
in pregnancy has been described in only a handful of trials.
The cure rates for uncomplicated malaria with quinine fell
from 77.0% to 61.0% (P = 0.03) and for mefloquine from
72.0% to 62.5% (P > 0.05) when these drugs were used to
treat primary and recurrent infections.
• Infections that recur following treatment are likely to be
intrinsically less sensitive to the drugs used against them.
• A highly effective 7-day treatment has more chance of curing
the patient.
• All the trials of recurrent malaria in pregnancy rely on
artemisinin derivatives.

30. How are pregnancy-related complications of severe malaria
managed?
• Monitor for hypoglycaemia regularly, as it can be profound and
persistent in malaria in pregnancy and can be exacerbated by
quinine.
• Prevent mortality from pulmonary oedema and acute respiratory
distress syndrome by clinical assessment of jugular venous or
central venous pressure, aimed at keeping right arterial pressure
less than 10 cm H2O.
• Women who are severely anaemic should be transfused slowly,
preferably with packed cells and intravenous frusemide 20 mg.
Alternatively, exchange transfusion may be considered in centres
where this can be performed safely.
• Secondary bacterial infection should be suspected if the patient
becomes hypotensive.

31. • Severe malaria in pregnancy is a medical emergency and women should be treated in a
high-dependency or intensive care unit, according to their condition and without delay.
• hypoglycaemia, pulmonary oedema, severe anaemia and secondary bacterial infection can
occur in severe malaria in non-pregnant patients, they are more common and severe in
pregnant women.
• Hypoglycaemia is commonly asymptomatic, although it may be associated with fetal
bradycardia and other signs of fetal distress.
• In the most severely ill women, it is associated with lactic acidosis and high mortality.
• In patients who have been given quinine, abnormal behaviour, sweating and sudden loss of
consciousness are the usual manifestations.
• The hypoglycaemia of quinine is caused by hyperinsulinaemia and remains the most
common and important adverse effect of this drug.
• The hypoglycaemia may be profound, recurrent and intractable in pregnancy and regular
• monitoring of glucose is required while under quinine treatment.
• It may present late in the disease when the patient appears to be recovering.
• Quinine at treatment doses does not induce abortion or labor

32. Supportive clinical care in severe malaria
Manifestation or complication Management
 Coma (cerebral malaria) - Monitor using Glasgow Coma Score. Maintain airway,
place patient on her left side, exclude treatable causes of coma (e.g.
hypoglycaemia, bacterial meningitis)
 Hyperpyrexia - Administer tepid sponging, fanning and antipyretic drugs
 Convulsions - Maintain airway; treat promptly with intravenous or rectal
diazepam
 Hypoglycaemia - Check blood glucose regularly, correct hypoglycaemia and
maintain with glucose-containing (blood glucose < 2.2 mmol/l or infusion.
Quinine induced hypoglycaemia can occur quite late in the course even after the
< 40 mg/100 ml) patient appears to be recovering
 Severe anaemia - Transfuse with packed red cells (haemoglobin < 8 g/100 ml or
packed cell volume < 24%)

33.  Acute pulmonary oedema - Prevent by monitoring jugular venous
pressure(JVP)/central venous pressure (CVP) to keep
(possible overlay of acute respiratory right arterial pressure < 10
cm H2O. Treat by propping patient up at an angle of 45 degrees,
distress syndrome) give oxygen, give a diuretic, stop intravenous
fluids, intubate and add positive end-expiratory pressure
/continuous positive airway pressure in life-threatening
hypoxaemia
 Renal failure Exclude pre-renal causes, check fluid balance and
urinary sodium; if in established renal failure, add haemofiltration
or haemodialysis or, if unavailable, peritoneal dialysis. The
benefits of diuretics/dopamine in acute renal failure are not
proven

34.  Spontaneous bleeding and transfuse with screened fresh whole
blood (cryoprecipitate, fresh frozen plasma and platelets
Coagulopathy if available); give vitamin K by injection
 Metabolic acidosis prevent by careful fluid balance; observation of
JVP/CVP by central venous access helps optimise fluid balance and
avoids overfilling.
 Exclude or treat hypoglycaemia, hypovolaemia and septicaemia. If
severe, add haemofiltration or haemodialysis
 Shock suspect septicaemia, take blood for cultures; give
parenteral broad-spectrum antimicrobials,
 Correct haemodynamic disturbances

35. • Obstetric management specific to malaria infection in
pregnancy
• Preterm labour, fetal growth restriction and fetal heart rate
abnormalities can occur in malaria in pregnancy.
• In severe malaria complicated by fetal compromise, a
multidisciplinary team approach (intensive care specialist,
infectious disease specialist, obstetrician, neonatologist) is
required to plan optimal management of mother and baby.
• Stillbirth and premature delivery in malaria in pregnancy are
best prevented with prompt and effective antimalarial
treatment.
• Uncomplicated malaria in pregnancy is not a reason for
induction of labour.

36. • Pharmacological thromboprophylaxis should be weighed up
against the risk of haemorrhage and should be withheld if the
platelet count is falling or less than 100, indicating
thrombocytopenia.
• Peripartum malaria is an indication for placental histology and
placenta, cord and baby blood films to detect congenital malaria
at an early stage.
• Inform women of the risk of vertical transmission and, in the
presence of positive placental blood films, that fever in the infant
could indicate malaria; a blood film from the baby is required for
confirmation.
• Commonsense obstetrics applies to the management of the
adverse effects of malaria in pregnancy.
• Efficacious and prompt treatment of malaria in the woman
reduces the systemic effects of parasitaemia and reduces the
adverse effects on the fetus, such as fetal distress.

37. • In severe malaria, cardiotocograph monitoring may reveal fetal tachycardia, bradycardia or
late decelerations in relation to uterine contractions, indicating fetal distress, particularly in
the
• Paracetamol 1 g every 4–6 hours (to a maximum of 4 g/day) is safe and effective and
should be prescribed.
• Maternal hypoglycaemia should be excluded as the cause of fetal distress, particularly if
treatment is with quinine.
• Tocolytic therapy and prophylactic steroid therapy at the usual obstetric doses should be
considered if there are no Abnormalities in fetal and placental circulation have been noted
on Doppler studies.
• In women with severe malaria, obstetric advice should be sought at an early stage.
• The paediatrician should be alerted and the mother’s blood glucose checked frequently,
particularly when intravenous quinine is administered. Fetal distress is common and has
been related to malaria fever:
• late (type II) decelerations of the fetal heart rate were recorded in six women before
treatment but, in most women, signs of fetal distress diminished as the maternal
temperature fell.
• Standard obstetric principles apply: the life of the woman comes first. There are no formal
studies but instrumental birth in the second stage of labour in the presence of maternal or
fetal distress is indicated, if there are no contraindications.
• In severe malaria, the role of early caesarean section for the viable fetus is unproven.

38. • There is usually no need for pregnant women with malaria infection to receive
thromboprophylaxis.
• Acute malaria causes thrombocytopenia105 and, in severe malaria, can cause
disseminated intravascular coagulation.50 Thrombocytopenia recovers with
treatment: 90% by day 7 and 100% by day 14, irrespective of the type of
antimalarial treatment.
• Antimalarial drugs can clear peripheral parasitaemia more quickly than from the
placenta.
• Maternal malaria close to delivery can result in congenital malaria, which can
cause significant mortality.
• Congenital malaria may present in the first weeks to months of life. A negative
placental blood film at delivery in a woman who has had malaria in pregnancy
eliminates the risk of congenital malaria significantly. Placenta- and cord-positive
blood films result in a higher chance of congenital malaria than placenta-positive,
cord-negative blood films.
• Send the placenta for histopathology, as it is more sensitive than microscopy for
detection of placental parasites

43. Women in the second or third trimester of pregnancy
• WHO all women in the second or third trimester of
pregnancy, who have uncomplicated P. falciparum malaria,
should be treated with ACT.
• Short- acting but potent artemisinin component (i.e.,
artemether, artesunate, or dihydroartemisinin) reduces the
number of parasites substantially during the first 3 days of
treatment.
• Longer- acting partner drug (i.e., lumefantrine , piperaquine,
amodiaquine, or mefloquine) eliminates the remaining
parasites, thereby preventing recrudescent malaria.
• Is also responsible for the post- treatment prophylactic
effect. ACT is not currently recommended for intermittent
preventive treatment in pregnancy and also not be given in
the first trimester of pregnancy

48. Prevention
• The world health organization (WHO) recommends a three-
pronged strategy for control of malaria in pregnancy
including
• Case management (prompt treatment with highly effective
drug),
• Use of insecticide-treated nets (itns) and
• Intermittent preventive treatment (iptp),
• The administration of a full treatment course of an effective
antimalarial at regular antenatal visits, usually a month
apart.

49. • An alternative to IPTp is IST. Using this approach, at each
antenatal visit, an RDT is performed, and women testing
positive receive an effective antimalarial, most commonly an
artemisinin combination treatment (ACT).
• Insecticide-treated nets (ITNs) and indoor residual spraying
• ITNs can prevent malaria and decrease low birth weight and
other adverse pregnancy outcomes, relatively cheap and
probably effective tool for malaria prevention in pregnancy
in India.
• Indoor residual spraying

50. Prevention
• Current prevention of malarial disease in pregnancy relies on
two main strategies
• Providing pregnant women with insecticide- treated bed
nets (ITN) and
• Intermittent presumptive treatment (IPT) with antimalarial
medications.
• Who least three doses of sulfadoxine pyrimethamine (sp) for
iptp, ideally at each of three antenatal care visits in the
second and third trimesters(these antenatal visits should
occur at 24-26 weeks, 32 weeks, and 36-38 weeks of
gestation)
Dihydroartemisinin - piperaquine is a promising agent
sulfadoxine – pyrimethamine has been found safe in
pregnancy when used intermittently as part of IPT.

51. Women Infected with HIV
• Monthly administration of SP – IPTp to reduce the risk of if
HIV + preg is on COTRIMOXAZOLE , then placental malaria do
not warrant IPTp during pregnancy,
• Travelers
• The agents of choice are chloroquine (for travel to areas with
chloroquine sensitive malaria) and mefloquine (for travel to
areas with chloroquine – resistant malaria).
• Vaccine
• Clinical trials for a VAR2CSA vaccine are ongoing, but
sequence variation needs to be carefully studied.

52. • Primaquine is contraindicated in pregnancy due to the risk of
severe haemolysis in glucose-6-phosphate dehydrogenase
(G6PD) deficient individuals & it is not possible to assess
G6PD status of a fetus in utero primaquine for radical cure
could be started after infant has been checked for G6PD
deficiency.
• Small amounts of primaquine enter breast milk, so G6PD
testing of the infant is recommended in lactating women
before they are prescribed primaquine
• Pregnant women may require suppressive treatment,
usually with chloroquine, until delivery.
• Tetracycline, doxycycline, primaquine, and halofantrine are
contraindicated in pregnancy and lactation.

53. Management of Newborn
• Congenital malariaia occurs due to trans- placental transmission
maternal infection.
• Clinical features fever, irritability, feeding problems , anemia,
hepatosplenomegaly, and jaundice.
• Commence only after 3 weeks due to the protective effect of
transplacentally transmitted antibodies.
• Infants are treated with acts in the doses upon their weight.
• Act-sp should be avoided in the first weeks of life because it could
aggravate neonatal hyperbilirubinemia.
• Primaquine should be avoided in the first 6 months of life and
• Tetracyclines should be avoided throughout infancy.