Malaria in Pregnancy Max Brinsmead MB BS PhD May 2015

Malaria in PNG Endemic & stable in coastal areas Endemic & stable in coastal areas Highlands subject to epidemics with high mortality Highlands subject to epidemics with high mortality More than 1.6M cases in 2008 with 23,500 admission and 638 deaths More than 1.6M cases in 2008 with 23,500 admission and 638 deaths About 15% of cases attending health centres or hospital are confirmed About 15% of cases attending health centres or hospital are confirmed 70 – 80% are due to P falciparum… 70 – 80% are due to P falciparum… The remainder are P vivax The remainder are P vivax P falciparum has a high rate of Chloroquine resistance P falciparum has a high rate of Chloroquine resistance Global Fund will spend $US147M Global Fund will spend $US147M

Plasmodium in Pregnancy Adults in endemic areas have partial immunity Adults in endemic areas have partial immunity And this is transmitted to the fetus And this is transmitted to the fetus Thus providing neonatal protection for about 6m Thus providing neonatal protection for about 6m The placenta acts as a barrier to fetal parasitaemia The placenta acts as a barrier to fetal parasitaemia And HBF-containing RBCs are relatively resistant to Plasmodium And HBF-containing RBCs are relatively resistant to Plasmodium But malaria still causes a high burden of illness during pregnancy… But malaria still causes a high burden of illness during pregnancy… And this is best studied in the two susceptible groups: And this is best studied in the two susceptible groups: The partially immune pregnant woman The partially immune pregnant woman The non immune pregnant woman The non immune pregnant woman

The Partially Immune Gravida Immunosupression of pregnancy results renders malarial attacks more common and severe Immunosupression of pregnancy results renders malarial attacks more common and severe Especially in the young and primigravida Especially in the young and primigravida Older multigravida develop anti-adhesive antibodies that provide more specific protection Older multigravida develop anti-adhesive antibodies that provide more specific protection Parasite density typically increases in pregnancy Parasite density typically increases in pregnancy Up to 12x higher than in non pregnant individuals Up to 12x higher than in non pregnant individuals Reaches a peak in mid pregnancy with splenic enlargement Reaches a peak in mid pregnancy with splenic enlargement Then, as the placenta takes on the phagocytic role, the spleen shrinks and parasite density falls towards term Then, as the placenta takes on the phagocytic role, the spleen shrinks and parasite density falls towards term But rebounds again in the puerperium But rebounds again in the puerperium But don’t miss a bacterial cause for puerpereal fever But don’t miss a bacterial cause for puerpereal fever

The Partially Immune Gravida(2) Malarial attacks are often asymptomatic Malarial attacks are often asymptomatic But haemolytic anaemia typically beginning at weeks and gets progressively worse But haemolytic anaemia typically beginning at weeks and gets progressively worse Is compounded by folate deficiency as erythropoiesis increases Is compounded by folate deficiency as erythropoiesis increases In the placenta the parasites cause intervillous inflammatory change, trophoblastic and BM damage that is partly immune mediated. In the placenta the parasites cause intervillous inflammatory change, trophoblastic and BM damage that is partly immune mediated. The results of this placental damage include… The results of this placental damage include… IUGR secondary to O 2 and nutrient deprivation IUGR secondary to O 2 and nutrient deprivation Risk of IUFD Risk of IUFD Premature labour perhaps due to the release of toxic cytokines Premature labour perhaps due to the release of toxic cytokines Will be aggravated by other causes of maternal anaemia and HIV Will be aggravated by other causes of maternal anaemia and HIV

Non Immune Gravida Are at risk of clinically severe malarial attacks Are at risk of clinically severe malarial attacks Including cerebral malaria Including cerebral malaria That has up to 50% mortality That has up to 50% mortality Complications include Complications include Severe anaemia Severe anaemia Hypoglycaemia Hypoglycaemia Sometimes from Quinine Rx Sometimes from Quinine Rx Acute pulmonary oedema Acute pulmonary oedema Especially immediately after delivery Especially immediately after delivery More prone to pneumonia and UTI More prone to pneumonia and UTI The high fever can cause The high fever can cause Premature labour Premature labour IUFD IUFD Fetal distress in labour Fetal distress in labour

Congenital Malaria Notwithstanding the usual placental block to Plasmodium… Notwithstanding the usual placental block to Plasmodium… Up to 15% of babies born to infected mothers have parasitaemia… Up to 15% of babies born to infected mothers have parasitaemia… Presumably due to breaches in the maternal-fetus interface during labour… Presumably due to breaches in the maternal-fetus interface during labour… But they are protected for up to 6m from clinical disease… But they are protected for up to 6m from clinical disease… By antibodies transferred from the mother. By antibodies transferred from the mother. However, babies born to non immune mothers may be in trouble However, babies born to non immune mothers may be in trouble

Treatment of Malaria in Pregnancy Complicated by resistance of P. falciparum to Chloroquine Complicated by resistance of P. falciparum to Chloroquine So follow current local guidelines So follow current local guidelines Semi immune women can be treated as outpatients Semi immune women can be treated as outpatients Indications for hospitalisation Indications for hospitalisation Non immune women Non immune women Intolerant of outpatient therapy Intolerant of outpatient therapy Not responding to outpatient therapy Not responding to outpatient therapy Complicated malaria Complicated malaria Fluid replacement and fever control is important Fluid replacement and fever control is important Vivax usually responds to Chloroquine Vivax usually responds to Chloroquine

Complicated Malaria in Pregnancy Is a medical emergency Is a medical emergency Lumbar puncture to exclude bacterial meningitis Lumbar puncture to exclude bacterial meningitis The prognosis is poor when… The prognosis is poor when… >5% of RBCs are parasitised >5% of RBCs are parasitised There is severe leucocytosis There is severe leucocytosis CSF glucose is low CSF glucose is low HB is <7.0 or Haemotocrit <0.20 HB is <7.0 or Haemotocrit <0.20 Blood urea is is >11.0 Blood urea is is >11.0 Assume Chloroquine resistance and treat parenterally with drugs according to local guidelines Assume Chloroquine resistance and treat parenterally with drugs according to local guidelines Begin with a loading dose according to bodyweight and follow with maintenance therapy Begin with a loading dose according to bodyweight and follow with maintenance therapy

Complicated Malaria in Pregnancy (2) General measures General measures Nurse on the side Nurse on the side Ensure a clear airway Ensure a clear airway Reduce body temperature Reduce body temperature Careful fluid balance with IV and IDC Careful fluid balance with IV and IDC Monitor blood glucose and renal function tests Monitor blood glucose and renal function tests Treating Complications Treating Complications IV Diazepam for convulsions IV Diazepam for convulsions Transfusion for severe anaemia Transfusion for severe anaemia Frusemide for pulmonary oedema Frusemide for pulmonary oedema IV glucose for hypoglycaemia IV glucose for hypoglycaemia Fluid restriction, K-absorbing resins, IV glucose and insulin or dialysis for renal failure Fluid restriction, K-absorbing resins, IV glucose and insulin or dialysis for renal failure

Preventing Malaria in Pregnancy General measures to reduce mosquito bites General measures to reduce mosquito bites Especially the use of insecticide-treated nets (ITN) and indoor residual spraying (IRS) Especially the use of insecticide-treated nets (ITN) and indoor residual spraying (IRS) Routine chemoprophylaxis with antimalarials, iron and folate of partially immune gravida has been shown to reduce the risk of… Routine chemoprophylaxis with antimalarials, iron and folate of partially immune gravida has been shown to reduce the risk of… Maternal anaemia Maternal anaemia IUGR and IUFD IUGR and IUFD Premature labour Premature labour Especially in young primigravid women Especially in young primigravid women But at the risk of increasing the incidence of drug resistance But at the risk of increasing the incidence of drug resistance It is desirable to begin as early as possible and certainly before 20w when parasitaemia peaks It is desirable to begin as early as possible and certainly before 20w when parasitaemia peaks

Preventing Malaria in Pregnancy (2) Non immune mothers… Non immune mothers… Because some antimalarials are teratogenic and… Because some antimalarials are teratogenic and… Malaria is such a serious illness… Malaria is such a serious illness… Non immune gravidas should avoid travel to malarial areas if possible Non immune gravidas should avoid travel to malarial areas if possible Especially areas with Chloroquine-resistant P. falciparum Especially areas with Chloroquine-resistant P. falciparum Follow current chemoproprophylaxis guidelines Follow current chemoproprophylaxis guidelines Consult www Consult www And take general measures to avoid mosquito bites And take general measures to avoid mosquito bites

Current WHO Guidelines for Chemoprophylaxis Two doses of Pyrimethamine-Sulfadoxine (Fansidar) Two doses of Pyrimethamine-Sulfadoxine (Fansidar) After quickening After quickening Not more frequently than monthly Not more frequently than monthly However… However… This fails to eliminate parasites from peripheral or placental blood (or both) in ≈ 80% women in endemic areas This fails to eliminate parasites from peripheral or placental blood (or both) in ≈ 80% women in endemic areas Resistance is then a real issue Resistance is then a real issue And partial treatment may be more harmful than no treatment at all And partial treatment may be more harmful than no treatment at all But other regimens are associated with poor rates of compliance But other regimens are associated with poor rates of compliance

Hyperactive Malarial Spleen Syndrome A condition that predates pregnancy A condition that predates pregnancy With massive splenic enlargement With massive splenic enlargement Severe haemolytic anaemia complicated by bone marrow suppression of erythropoesis Severe haemolytic anaemia complicated by bone marrow suppression of erythropoesis So there is leucopenia and thrombocytopenia So there is leucopenia and thrombocytopenia Associated with immunological abnormalities and overproduction of IgM Associated with immunological abnormalities and overproduction of IgM In pregnancy the prognosis is serious In pregnancy the prognosis is serious Admit to hospital and treat with regionally-specific antimalarial drugs Admit to hospital and treat with regionally-specific antimalarial drugs Plus folate 5 mg/day Plus folate 5 mg/day

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