Malaria in Pregnancy Department of Obstetrics & Gynaecology

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Malaria in Pregnancy

• Department of Obstetrics Gynaecology
• M.K.C.G.MEDICAL COLLEGE
• BERHAMPUR, ORISSA, INDIA

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Malaria Menance

• World wide 103 countries with 2.5 billion people,
  developing countries worst affected.
• 40 of worlds population in shadow of Malaria.
• Deaths- Under estimated/Unknown,1.1 to 2.7
  million per year
• Gender related mortality - Females more
• Malaria in Pregnancy -
• Mutually aggravating
• Mortality is double
• Primigravidae - 60-70
• Highest prevalence in second half.
• Plasmodium Falciparum More common.

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Malaria in Pregnancy
Sinister Coincidence

• Malaria and pregnancy are mutually aggravating
  conditions.
• The physiological changes of pregnancy and the
  pathological changes due to malaria have a
  synergistic effect on the course of each other,
  thus making life difficult for the mother, the
  child and the treating physician.
• P. falciparum malaria can run a turbulent and
  dramatic course in pregnant women.
• The non- immune, primigravidae are usually the
  most affected.
• In areas where malaria is endemic, 20-40 of all
  babies born may have a low birth weight.

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Malaria in Pregnancy
Double Trouble

• More common.
• Malaria is more common in pregnancy compared to
  the general population probably due to Immuno
  suppression and loss of acquired immunity to
  malaria.
• More atypical.
• In pregnancy, malaria tends to be more atypical
  in presentation probably due to the hormonal ,
  immunological and haematological changes of
  pregnancy.
• More severe.
• Probably for the same reason, the parasitemia
  tends to be 10 times higher and as a result, all
  the complications of falciparum malaria are more
  common in pregnancy compared to the non-pregnant
  population.

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Malaria in Pregnancy
Double Trouble

• More fatal
• P. falciparum malaria in pregnancy being more
  severe, the mortality is also double (13 )
  compared to the non-pregnant population (6.5).
• Selective treatment
• Some anti malarials are contra indicated in
  pregnancy and some may cause severe adverse
  effects.
• Therefore the treatment may become difficult,
  particularly in cases of severe P. falciparum
  malaria.
• Other problems
• Management of complications of malaria may be
  difficult due to the various physiological
  changes of pregnancy.
• Careful attention has to be paid towards fluid
  management, temperature control, etc.
• Decisions regarding induction of labour may be
  difficult and complex.
• Foetal loss, IUGR, and premature labour are
  common.

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Pathology of Malaria in Pregnancy

• P. falciparum malaria can run a very turbulent
  course in pregnancy, particularly the first and
  second pregnancies.
• These complications are more common and severe in
  hyperendemic areas for falciparum malaria.
• Physiologic changes of pregnancy contribute to
  the aggravation of malarial infection.
• Changes in the hormonal milieu,
• Increase in the body fluid volume,
• Decrease in haemoglobin level and other changes
  add to the severity.

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Pathology of Malaria in Pregnancy

• There is a generalised immunosuppression in
  pregnancy with reduction in gamma globulin
  synthesis and inhibition of reticulo endothelial
  system, resulting in
• Decrease in the levels of anti malarial
  antibodies and loss of acquired immunity to
  malaria.
• This makes the pregnant woman more prone for
  malarial infection and the parasitemia tends to
  be much higher.

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Changes in Placenta

• Placenta is the preferred site of sequestration
  and development of malarial parasite.
• Intervillous spaces are filled with parasites and
  macrophages, interfering with oxygen and nutrient
  transport to the foetus.
• Villous hypertrophy and fibrinoid necrosis of
  villi (complete or partial) have been observed.
• All the placental tissues exhibit malarial
  pigments (with or even without parasites).

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Clinical features
Atypical manifestations of malaria are more
common in pregnancy, particularly in the 2nd half
of pregnancy.

• Fever
• Patient may have different patterns of fever -
  from afebrile to continuous fever, low grade to
  hyper pyrexia.
• In 2nd half of pregnancy, there may be more
  frequent paroxysms due to Immunosuppression.
• Anemia
• In developing countries, where malaria is most
  common, anemia is a common feature of pregnancy.
• Malnutrition and helminthiasis are the commonest
  causes of anemia.
• In such a situation, malaria will compound the
  problem.
• Anemia may even be the presenting feature of
  malaria and therefore all cases of anemia should
  be tested for M.P.
• Anemia as a presenting feature is more common in
  partially immune multigravidae living in hyper
  endemic areas.

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Clinical features
Atypical manifestations of malaria are more
common in pregnancy, particularly in the 2nd half
of pregnancy.

• Splenomegaly
• Enlargement of the spleen may be variable. It may
  be absent or small in 2nd half of pregnancy.
• A pre-existing enlarged spleen may regress in
  size in pregnancy.
• Complications
• Complications tend to be more common and more
  severe in pregnancy.
• A patient may present with complications of
  malaria or they may develop suddenly.
• Acute pulmonary edema, hypoglycemia and anemia
  are more common in pregnancy.
• Jaundice, convulsions, altered sensorium, coma,
  vomiting / diarrhoea and other complications may
  be seen.

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Complications of Malaria in Pregnancy
Anemia

• Malaria can cause or aggravate anaemia due to
• Hemolysis of parasitised red blood cells.
• Increased demands of pregnancy.
• Profound hemolysis can aggravate folate
  deficiency.
• Anemia due to malaria is more common and severe
  between 16-29 weeks.
• It can develop suddenly, in case of severe
  malaria with high grades of parasitemia.
• Pre existing iron and folate deficiency can
  exacerbate the anemia of malaria and vice versa.

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Complications of Malaria in Pregnancy
Anemia

• Anaemia increases perinatal mortality and
  maternal morbidity and mortality.
• It also increases the risk of pulmonary oedema.
  Risk of post-partum haemorrhage is also higher.
• Significant anemia (Haemoglobin lt 7-8 g) may
  have to be treated with blood transfusion.
• In view of the increased fluid volume in
  pregnancy, it is better to transfuse packed cells
  than whole blood.
• Rapid transfusion, particularly whole blood, may
  cause pulmonary oedema.

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Complications of Malaria in Pregnancy
Acute pulmonary oedema

• Acute pulmonary oedema is also a more common
  complication of malaria in pregnancy compared to
  the non-pregnant population.
• It may be the presenting feature or can develop
  suddenly after several days. It is more common in
  2nd and 3rd trimesters.
• It can develop suddenly in immediate post-partum
  period. This is due to
• Auto transfusion of placental blood with high
  proportion of parasitised RBCs
• Sudden increase in peripheral vascular resistance
  after delivery.
• It is aggravated by pre existing anaemia and
  hemodynamic changes of pregnancy.
• Acute pulmonary oedema carries a very high
  mortality.

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Complications of Malaria in Pregnancy
Hypoglycaemia

• This is another complication of malaria that is
  peculiarly more common in pregnancy.
• The following factors contribute to hypoglycemia
• Increased demands of hypercatabolic state and
  infecting parasites.
• Hypoglycaemic response to starvation.
• Increased response of pancreatic islets to
  secretory stimuli (like quinine) leads to
  hyperinsulinemia and hypoglycemia..

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Complications of Malaria in Pregnancy
Hypoglycaemia

• Hypoglycaemia in these patients can remain
  asymptomatic and may not be detected, because
• all the symptoms of hypoglycemia are also caused
  by malaria viz. tachycardia, sweating, giddiness
  etc.
• Some patients may have abnormal behaviour,
  convulsions, altered sensorium, sudden loss of
  consciousness etc.
• These symptoms of hypoglycemia may be easily
  confused with cerebral malaria.
• Therefore, in all pregnant women with falciparum
  malaria, particularly those receiving quinine,
  blood sugar should be monitored every 4-6 hours.

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Complications of Malaria in Pregnancy
Hypoglycaemia

• Hypoglycaemia can be recurrent and therefore
  constant monitoring is needed.
• In some, it can be associated with lactic
  acidosis and in such cases mortality is very
  high.
• Maternal hypoglycemia can cause foetal distress
  without any signs.

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Complications of Malaria in Pregnancy
Immunosuppression

• Immunosuppression in pregnancy poses special
  problems.
• It makes malaria more common and more severe. And
  to add to the woes, malaria itself suppresses
  immune response.
• Hormonal changes of pregnancy, reduced synthesis
  of immunoglobulins, reduced function of reticulo
  endothelial system are the causes for
  Immunosuppression in pregnancy.

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Complications of Malaria in Pregnancy
Immunosuppression

• This results in loss of acquired immunity to
  malaria, making the pregnant more prone for
  malaria.
• Malaria becomes more severe with higher
  parasitemia.
• Patient may have more frequent paroxysms of fever
  and frequent relapses.
• Secondary infections (U.T.I. and pneumonias) and
  algid malaria (septicaemic shock) are more common
  in pregnancy due to Immunosuppression.

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Risks for the foetus

• Malaria in pregnancy is detrimental to the foetus
  due to -
• high grades of fever,
• placental insufficiency,
• hypoglycaemia,
• anaemia and other complications.
• Both P. vivax and P. falciparum malaria can pose
  problems for the foetus, with the latter being
  more serious.

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Risks for the foetus

• The prenatal and neonatal mortality may vary from
  15 to 70.
• In one study, mortality due to P. vivax malaria
  during pregnancy was 15.7 while that due to P.
  falciparum was 33.
• Spontaneous abortion, pre mature birth, still
  birth, placental insufficiency and I.U.G.R.
  (temporary / chronic), low birth weight, foetal
  distress are the different problems observed in
  the growing foetus.
• Transplacental spread of the infection to the
  foetus can result in congenital malaria.

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Risks for the foetus
Congenital malaria

• It is very rare and occurs in lt 5 of affected
  pregnancies. Placental barrier and matenal Ig G
  antibodies which cross the placenta may protect
  the foetus to some extent.
• However, it is much more common in non-immune
  population and the incidence goes up during
  epidemics of malaria.
• Fetal plasma Quinine and Chloroquine levels are
  about one third of simultaneous maternal levels
  and this subtherapeutic drug level does not cure
  the infection in the foetus.

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Risks for the foetus
Congenital malaria

• All four species can cause congenital malaria,
  but it is proportionately more with P. malariae.
• The new born child can manifest with fever,
  irritability, feeding problems, hepato
  splenomegaly, anaemia, jaundice etc.
• The diagnosis can be confirmed by a smear for
  M.P. from cord blood or heel prick, anytime
  within a week after birth (or even later if
  post-partum, mosquito-borne infection is not
  likely).
• Differential diagnoses include Rh.
  incompatibility, infections with C.M.V., Herpes,
  Rubella, Toxoplasmosis, and syphilis.

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Diagnosis

• High level of awareness
• Peripheral blood smear
• Antigen detection techniques (PfHPR-2)
• Fluorescent staining
• PCR based assay
• Antibody test
• Placental blood smear

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Indicators of Poor Prognosis

• Hyper parasitemia - ?5 erythrocytes infested.
• Peripheral schizotaemia.
• Leucocytosis ?12,000/ cmm.
• Hb? 7.1 gm.
• PCV ?20 .
• Blood urea ?60 mg / dL
• Creatinine ?3 mg / dL.,
• Blood glucose ?40 mg / dL.
• High lactate and low sugar in CSF.     
• Low antithrombin III level.

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Management of Malaria in Pregnancy

• Management of malaria in pregnancy involves the
  following three aspects and equal importance
  should be attached to all the three.
• Treatment of malaria
• Management of complications
• Management of labour

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Treatment of Malaria in Pregnancy
Should Be Energetic, Anticipatory and Careful.

• Energetic
• Don't waste any time.
• It is better to admit all cases of P. falciparum
  malaria.
• Assess severity-
• General condition, pallor, jaundice, B.P.,
  temperature, haemoglobin, Parasite count,
  S.G.P.T., S .bilirubin, S.creatinine, Blood
  sugar.

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Treatment of Malaria in Pregnancy
Should Be Energetic, Anticipatory and Careful.

• Anticipatory
• Malaria in pregnancy can cause sudden and
  dramatic complications. Therefore, one should
  always be looking for any complications by
  regular monitoring.
• Monitor maternal and foetal vital parameters 2
  hourly.
• R.B.S. 4-6 hourly haemoglobin and parasite count
  12 hourly S. creatinine S. bilirubin and Intake
  / Output chart daily.

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Treatment of Malaria in Pregnancy
Should Be Energetic, Anticipatory and Careful.

• Careful
• The physiologic changes of pregnancy pose special
  problems in management of malaria.
• In addition, certain drugs are contra indicated
  in pregnancy or may cause more severe adverse
  effects. All these factors should be taken into
  consideration while treating these patients.
• Choose drugs according to severity of the
  disease/ sensitivity pattern in the locality.
• Avoid drugs that are contra indicated
• Avoid over / under dosing of drugs
• Avoid fluid overload / dehydration
• Maintain adequate intake of calories.

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Treatment of Malaria in Pregnancy
Choice of Anti malarials in pregnancy

• All trimesters
• First line - Chloroquine Quinine
• Second line - Artesunate / Artemether / Arteether
• 2nd / 3rd trimester with caution
• Pyrimethamine sulphadoxine Mefloquine
• Contra indicated
• Primaquine Tetracycline Doxycycline
  Halofantrine

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Treatment of Malaria in Pregnancy
Dose of Anti malarials

• Chloroquine
• 600mg (base) start, 300mg after 6 hours, 24 hours
  48 hours
• Quinine
• IV - 20mg/kg infusion over 4 hours, repeat 8
  hourly. Maintenance 10mg over 4 hours, 8 hourly.
  Follow with oral medication after clinically
  stable.
• Oral 600mg 8hourly ( maximum 2 gm / day) for 7
  days.
• Artesunate
• Oral-100mg BD on day 1, then 50mg BD for 4-6 days
  (Total dose 10mg/kg).
• IM / IV-120mg on Day 1 followed by 60mg daily
  for 4 days. In severe cases an additional dose of
  60mg after 6 hours on Day 1.

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Treatment of Malaria in Pregnancy
Dose of Anti malarials

• Artemether
• Six amp (480mg) IM in 5 / 3 days. 1x2x11x1x4 OR
  1x2x3.
• Arteether
• One amp (150mg) IM / day for3 consecutive days.
• Pyrimethamine 25mgsulphadoxine 500mg tablets
• Three tablets single dose.
• Mefloquine
• 15mg / kg body wt., up to 1 Gm in a single dose.
  OR
• Tablets of 250mg, 3 tab start, then 2 tab after
  6-8 hours. With body wt gt60kg, a third dose of 1
  tab after 6-8 hours.

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Management of complications

• Acute Pulmonary Oedema
• Careful fluid management back rest oxygen
  diuretics ventilation if needed.
• Hypoglycaemia
• 25-50 Dextrose, 50-100 ml I.V., followed by 10
  dextrose continuous infusion.
• If fluid overload is a problem, then Inj.
  Glucagon 0.5-1 mg can be given intra muscularly.
• Blood sugar should be monitored every 4-6 hours
  for recurrent hypoglycemia.
• Anemia
• Packed cells should be transfused if haemoglobin
  is lt5 g.
• Renal failure
• Renal failure could be pre-renal due to
  unrecognised dehydration or renal due to severe
  parasitemia.
• Treatment involves careful fluid management,
  diuretics, and dialysis if needed.

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Management of complications

• Septicaemic shock
• Secondary bacterial infections like urinary tract
  infection, pneumonia etc. are more common in
  pregnancy associated with malaria.
• Some of these patients may develop septicaemic
  shock, the so called 'algid malaria'.
• Treatment involves administration of 3rd
  generation cephalosporins, fluid replacement,
  monitoring of vital parameters and intake and
  output.
• Exchange transfusion
• Exchange transfusion is indicated in cases of
  severe falciparum malaria to reduce the parasite
  load. Patients blood is removed and it is
  replaced with packed cells.
• It is especially useful in cases of very high
  parasitemia (helps in clearing) and impending
  pulmonary oedema (helps to reduce fluid load).

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Management of Labour

• Anaemia, hypoglycaemia, pulmonary oedema, and
  secondary infections due to malaria in pregnancy
  lead to problems for both the mother and the
  foetus.
• Severe falciparum malaria in term pregnancy
  carries a very high mortality.
• Maternal and foetal distress may go unrecognised
  in these patients.
• Therefore, careful monitoring of maternal and
  foetal parameters is extremely important.
• Pregnant women with severe malaria are better
  managed in an intensive care unit.

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Management of Labour

• Falciparum malaria induces uterine contractions,
  resulting in premature labour. The frequency and
  intensity of contractions appear to be related to
  the height of the fever.
• Fetal distress is common and often unrecognised.
  Therefore only monitoring of uterine contractions
  and fetal heart rate may reveal asymptomatic
  labour and foetal distress.
• All efforts should be made to rapidly bring the
  temperature under control,
• By tepid sponging (cold sponging causes cutaneous
  vasoconstriction and can result in core
  hyperpyrexia).
• Anti pyretics like paracetamol etc.

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Management of Labour

• Careful fluid management is also very important.
  Dehydration as well as fluid overload should be
  avoided, because both could be detrimental to the
  mother and/or the foetus.
• In cases of very high parasitemia, exchange
  transfusion may have to be carried out.
• If the situation demands, induction of labour may
  have to be considered.
• Once the patient is in labour, foetal or matenal
  distress may indicate the need to shorten the 2nd
  stage by forceps or vacuum extraction.
• If needed, even caesarean section must be
  considered.

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Treatment of Vivax Malaria in Pregnancy
Radical cure

• Use of Primaquine Proguanil are not safe in
  pregnancy and also in lactating mothers.
• Therefore to prevent the relapse of vivax
  malaria, suppressive chemoprophylaxis with
  Chloroquine is recommended.
• Tablet Chloroquine 300 mg (base) weekly should be
  administered to all such patients until stoppage
  of lactation.
• At that point, a complete treatment with full
  therapeutic dose of Chloroquine and Primaquine
  (7.5mg b.I.d. or 15mg daily, for 14 days) should
  be administered.
• However in case of resistance, Primaquine or
  Proguanil may be given with caution in 2nd half
  of pregnancy.

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Chemoprophylaxis in Pregnancy

• Malaria being potentially fatal to both the
  mother and the foetus, this should be an
  important part of antenatal care in areas of high
  transmission.
• All pregnant women, who remain in the malarious
  area during their pregnancy, should be protected
  with chemoprophylaxis.
• Choice of anti malarials for chemo prophylaxis
• Chloroquine being the safest drug in pregnancy,
  should be the first choice.
• However, its use may be restricted due to the
  wide spread resistance to this drug.
• In areas with known resistance to Chloroquine
• Pyrimethamine Sulpha, Mefloquine or Proguanil
  can be used.
• But these drugs should be started only after 1st
  trimester only.

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Chemoprophylaxis in Pregnancy
DOSAGE

• Chloroquine - 300mg base, administered once
  every week.
• Pyrimethamine-25mg Sulphadoxine-500mg - One
  tablet once weekly.
• Mefloquine -250mg weekly.
• Dose may have to be increased in the last
  trimester, in view of the accelerated clearance
  of the drug.
• Proguanil - 150-200mg / day.

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FOR A HEALTHY MOTHER AND A HEALTHY BABY
Thank you