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MANAGEMENT OF
MALARIA IN
PREGNANCY
Dr Kimambo Elisonguo
Resident OBGY
Muhimbili University of Health
and Allied Sciences (MUHAS)
Contents
 Introduction
 Pathophysiology
Placental malaria
 Clinical presentation
 Complications
 Management
 Prevention
 Conclusion
 References
Why should malaria in
pregnancy be a special
agenda?
Introduction
 Malaria is more common in
pregnancy compared to the general
population.
 The non- immune, primigravidae are
usually the most affected(prevalence & complications)
 The increased risk of contracting
malaria may be due to
 Decreased immunity
 Hormonal changes
Introduction cont..
 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 the life difficult for the
mother, the child and the treating
physician.
Introduction cont..
 In pregnancy, malaria tends to be
more atypical in presentation.
This could be due to the hormonal,
immunological and hematological
changes of pregnancy
Introduction cont..
 Some anti malarial drugs are
contraindicated in pregnancy and some
may cause severe adverse effects.
 Therefore Choice of medication becomes difficult.
 Management of complications of malaria
may be difficult
Pathophysiology
 Pathogenesis of malaria relates to the various
host and parasite factors
 Starts by inj of Plasmodium sporozoites via a
bite from an infected mosquito
 The sporozoites travel through the
bloodstream of the host to the liver, where they
invade hepatocytes.
 These cells divide many 1000-fold until mature
tissue schizonts are formed, each containing
thousands of daughter merozoites.
 This exoerythrocytic stage is asymptomatic
Pathophysiology cont..
 The liver schizonts rupture after a week or so
 This event releases thousands of merozoites into
the bloodstream, where they invade red blood
cells (the erythrocytic stage)
 At the completion of the schizogony within the red
cells,(48hrs for P. falciparum) newly developed merozoites are
released by the lysis of infected erythrocytes
 Along with them, numerous waste substances are
also released into the blood.
 These include red cell membrane products,
hemozoin pigment, and other toxic factors such as
glycosylphosphatidylinositol (GPI)
Pathophysiology cont..
 These products, particularly the GPI, activate
macrophages and endothelial cells to secrete
cytokines and inflammatory mediators such as
TNF-alpha, IFN-γ, Il-1, IL-6, IL-8, MCSF, and
lymphotoxin, as well as superoxide and nitric oxide
(NO).
 The systemic manifestations of malaria have been
largely attributed to these cytokines
Pathogenetic Characteristics of Severe
Malaria
 Cytoadherence
 Sequestration
 Rosetting
Placental Malaria
 Caused by P. falciparum–infected erythrocytes
that bind to placental tissue.
 Binding is mediated by VAR2CSA, a parasite
antigen which interacts with chondroitin
sulfate A (CSA) on the syncytiotrophoblast
 The VAR2CSA is coded by the var2csa gene
 By this process, the parasites avoid being
filtered through the spleen
 Also it impairs movements of nutrients across
the placenta
Placental Malaria cont..
 Consequences include maternal
anemia and fetal growth retardation.
 Antibodies against VAR2CSA occur
during pregnancy after exposure to
infected erythrocytes sequestering in
the placenta
 Concentrations of these antibodies
increase with parity.
 Placental changes due to malaria infxn (hemozoin deposition &
increased monocyte deposition) also contribute to placental
Clinical presentation
 Includes
 Fever
 Headache
 Joint pains
 Malaise
 Nausea +/-vomiting, +/- diarrhea
 Abdominal pain
 Poor appetite
 Palor
 Splenomegally
Clinical presentation cont…
 Severe malaria
 Presence of one or more of the following
 Prostration (extreme weakness),
 Impaired consciousness/coma
 Change of behavior
 Convulsions
 Jaundice
 Vomiting everything
 Circulatory collapse/shock
 Hyperparasitemia
 Bleeding tendency (DIC)
 Respiratory distress
Complications
 Anemia
 Abortion and its
complications
 Premature labour
 Cerebral malaria
 AKI
 Pulmonary edema
 IUGR
 Congenital infection
To the newborn
 Premature delivery
 Low birth weight
and its
complications
 Congenital/neonat
al malaria
To the mother To the fetus
Management
 Includes
 Investigations
 Treatment of malaria
 Management of complications
 Prevention
 Treatment of malaria in pregnancy should be
 Energetic :
 Don't waste any time.
 Careful
 Choose drugs and dosage carefully
 Anticipatory
 One should always be looking for any complications by
regular monitoring
Investigations
 Includes
 Antigen detection techniques : - MRDT-(HRP-
2/pLDH(PfPAN))
 Peripheral blood smear for MPs( thin & thick films)
 PCR based assay
 Antibody test
 Placental blood smear(postpartum)
 Others depending on the clinical presentation
Treatment of malaria in
pregnancy
 Depends on
 Severity
 Gestational age
Treatment cont…
A: Uncomplicated malaria
 In the first trimester,
Pregnant women with uncomplicated
malaria should be treated with quinine
tablets for seven days
The dose is 10 mg/kg every 8 hours for
7days
Do not exceed a maximum dose of
600mg per dose
Treatment cont..
 In the second and third trimester
 Artemether-Lumefantrine should be used as
medicine of choice
 The dose is 4 tabs stat then 8hours after the first
dose then 12hourly for 2days (a total of three
days)
 Alternatively
 Dihydoartemisinin-Piperaquine (DPQ)
 Artesunate-Amodiaquine
Treatment cont..
 B: Severe malaria
 The primary objective of treatment in severe malaria is
to prevent death.
 The secondary objective is to prevent disabilities and
to prevent recrudescent infection
 In the first trimester
 The medicine of choice for treatment of severe
malaria in the first trimester is IV Quinine(dose)
Severe malaria Rx cont..
 In the second and third trimester
The medicine of choice for treatment of
severe malaria in 2nd and 3rd trimester of
pregnancy is Inj. Artesunate
 The dose is dose 2.4 mg/kg given at time 0 hour,
then at 12 hours and 24 hours
 Followed by ALu for 3days
 The first oral dose should start 8hrs after the last injection
 Quinine should be used only if Artesunate
injectable is not available.
Treatment cont…
 According to WHO recommendation,
 Treatment of severe malaria is with Inj Artesunate for
both children and adults including infants, pregnant
women in all trimesters and lactating women.
 Inj Artesunate should be given for at least 24hrs and
until patient can tolerate oral medication, then they
should complete treatment with 3days of ACT
 If Artesunate is unavailable, Inj Artemether (IM) should
be given
 If Artemether is unavailable, Inj Quinine should be
given(loading dose 1st)
Artesunate for injection
 Descpription
 Artesunate is a water-soluble derivative of
Artemisinin.
 The only Artemisinin analogue that can be
given intravenously
 It produces rapid parasite clearance in
falciparum malaria.
 Superior to Quinine in preventing death
Artesunate for injection cont..
 Three formulations are available:
 30mg,
 60mg and
 120mg of Artesunate for injection.
Table 14: Artesunate for injection
package by strength
Strength 30mg 60mg 120mg
Artesunate for
injection
1 vial of 30mg 1 vial of 60mg 1 vial of
120mg
5% Sodium
bicarbonate
1 Ampoule of
0.5mls
1 Ampoule of
1ml
1 Ampoule of
2.5mls
Sodium
chloride
1 Ampoule of
2.5mls
1 Ampoule of
5mls
1 Ampoule of
10 mls
Administration and dosage (60 mg
strength)
 Injectable Artesunate has 2-steps dilutions.
 Step 1:
 The powder for injection should be diluted with 1ml of 5%
sodium bicarbonate solution (provided in each box) and
shaken vigorously 2-3 minutes for better dissolving till the
solution becomes clear.
 Step 2:
 For slow intravenous infusion (3-4 minutes): Add 5 ml of
5% dextrose or normal saline, to obtain a Artesunate
concentration of 10 mg/ml
 For deep intra-muscular injection: Add 2 ml of 5%
dextrose or normal saline to obtain a Artesunate
concentration of 20 mg/ml
Quantity for dilution of Artesunate for
injection
ROUTE IV INJECTION IM INJECTION
STRENG
TH
30mg 60mg 120mg 30mg 60mg 120mg
5%
NaCO3
0.5mls 1ml 2mls 0.5mls 1ml 2mls
NS/5%
dextrose
2.5mls 5mls 10mls 1ml 2mls 4mls
TOTAL
(mls)
3mls 6mls 12mls 1.5mls 3mls 6mls
Artesunate
concentrati
on (Mg/ml)
10 10 10 20 20 20
Caution;
 The powder form for injection is difficult to
dissolve, care should be taken to ensure that it
is completely dissolved before parenteral
administration.
 If the solution is cloudy or a precipitate is
present, the parenteral preparation should be
discarded.
 Dissolved artesunate should always be used
immediately after 2nd dilution
 Never store diluted Artesunate for further use
Supportive treatment in the
Management of malaria in
pregnancy
 Treatment of anemia (BT, FA)
 Correction of electrolyte imbalance
 Oxygen + Diuretics in pulmonary oedema
 Dialysis for ARF
 Anticonvulsants
 ICU care for CM
 Monitoring of the fetal growth & health
Prevention
 Available options are:-
 Vector control
 Insecticide Treated Nets (ITNs)
 Residual house hold spraying
 Environmental management
 Drug prophylaxis
 Intermittent preventive treatment (IPTp)
 Alternative- DPQ (not yet adopted)
 Vaccine?? –Still under development
Intermittent preventive treatment (IPTp)
 The medicine of choice for IPTp is
Sulfadoxine/Pyrimethamine (SP)
 Reduses the risk of
Placental malaria
Low birth weight and
Maternal illness
 Dosing should start as early as possible in the sec
trimester
 Should be given at least 1 month apart, at least
3doses
 SP can be administered up to the time of delivery
Conclusion
 Diagnosis and Management of malaria during pregnancy
can be challenging
 The primary objective in the management of severe malaria
is to prevent death
 Malaria preventive package during pregnancy includes:
 Intermittent preventive treatment with SP during antenatal clinic
visits
 Use of ITNs throughout pregnancy and in the postpartum period
 Prevention must be complemented by effective case
management of malaria for all women of reproductive age
References
 National Guidelines for Diagnosis and Treatment of Malaria-December
2014
 The diagnosis and treatment of malaria in pregnancy-Royal College of
Obstetricians and Gynecologists-April 2010
 A Review of Malaria Diagnostic Tools: Microscopy and Rapid Diagnostic
Test (RDT)-American journal of tropical medicine and hygiene
 http://www.uptodate.com/contents/pathogenesis-of-malaria
 http://www.malariasite.com/pathophysiology/
 https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-7-
133
 https://en.wikipedia.org/wiki/Pregnancy-associated_malaria
 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-015-
0576-8
References
 https://malariajournal.biomedcentral.com/arti
cles/10.1186/1475-2875-13-152
 http://www.ncbi.nlm.nih.gov/pmc/articles/PM
C3257207/
 https://diagnosticpathology.biomedcentral.co
m/articles/10.1186/1746-1596-8-59
 http://www.mjhid.org/article/view/338/460
 http://scialert.net/fulltext/?doi=jp.2015.120.12
6&org=10
 http://jcm.asm.org/content/40/1/306.full
Thank you….!

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Malaria in pregnancy

  • 1. MANAGEMENT OF MALARIA IN PREGNANCY Dr Kimambo Elisonguo Resident OBGY Muhimbili University of Health and Allied Sciences (MUHAS)
  • 2. Contents  Introduction  Pathophysiology Placental malaria  Clinical presentation  Complications  Management  Prevention  Conclusion  References
  • 3. Why should malaria in pregnancy be a special agenda?
  • 4. Introduction  Malaria is more common in pregnancy compared to the general population.  The non- immune, primigravidae are usually the most affected(prevalence & complications)  The increased risk of contracting malaria may be due to  Decreased immunity  Hormonal changes
  • 5. Introduction cont..  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 the life difficult for the mother, the child and the treating physician.
  • 6. Introduction cont..  In pregnancy, malaria tends to be more atypical in presentation. This could be due to the hormonal, immunological and hematological changes of pregnancy
  • 7. Introduction cont..  Some anti malarial drugs are contraindicated in pregnancy and some may cause severe adverse effects.  Therefore Choice of medication becomes difficult.  Management of complications of malaria may be difficult
  • 8. Pathophysiology  Pathogenesis of malaria relates to the various host and parasite factors  Starts by inj of Plasmodium sporozoites via a bite from an infected mosquito  The sporozoites travel through the bloodstream of the host to the liver, where they invade hepatocytes.  These cells divide many 1000-fold until mature tissue schizonts are formed, each containing thousands of daughter merozoites.  This exoerythrocytic stage is asymptomatic
  • 9. Pathophysiology cont..  The liver schizonts rupture after a week or so  This event releases thousands of merozoites into the bloodstream, where they invade red blood cells (the erythrocytic stage)  At the completion of the schizogony within the red cells,(48hrs for P. falciparum) newly developed merozoites are released by the lysis of infected erythrocytes  Along with them, numerous waste substances are also released into the blood.  These include red cell membrane products, hemozoin pigment, and other toxic factors such as glycosylphosphatidylinositol (GPI)
  • 10. Pathophysiology cont..  These products, particularly the GPI, activate macrophages and endothelial cells to secrete cytokines and inflammatory mediators such as TNF-alpha, IFN-γ, Il-1, IL-6, IL-8, MCSF, and lymphotoxin, as well as superoxide and nitric oxide (NO).  The systemic manifestations of malaria have been largely attributed to these cytokines
  • 11. Pathogenetic Characteristics of Severe Malaria  Cytoadherence  Sequestration  Rosetting
  • 12. Placental Malaria  Caused by P. falciparum–infected erythrocytes that bind to placental tissue.  Binding is mediated by VAR2CSA, a parasite antigen which interacts with chondroitin sulfate A (CSA) on the syncytiotrophoblast  The VAR2CSA is coded by the var2csa gene  By this process, the parasites avoid being filtered through the spleen  Also it impairs movements of nutrients across the placenta
  • 13. Placental Malaria cont..  Consequences include maternal anemia and fetal growth retardation.  Antibodies against VAR2CSA occur during pregnancy after exposure to infected erythrocytes sequestering in the placenta  Concentrations of these antibodies increase with parity.  Placental changes due to malaria infxn (hemozoin deposition & increased monocyte deposition) also contribute to placental
  • 14. Clinical presentation  Includes  Fever  Headache  Joint pains  Malaise  Nausea +/-vomiting, +/- diarrhea  Abdominal pain  Poor appetite  Palor  Splenomegally
  • 15. Clinical presentation cont…  Severe malaria  Presence of one or more of the following  Prostration (extreme weakness),  Impaired consciousness/coma  Change of behavior  Convulsions  Jaundice  Vomiting everything  Circulatory collapse/shock  Hyperparasitemia  Bleeding tendency (DIC)  Respiratory distress
  • 16. Complications  Anemia  Abortion and its complications  Premature labour  Cerebral malaria  AKI  Pulmonary edema  IUGR  Congenital infection To the newborn  Premature delivery  Low birth weight and its complications  Congenital/neonat al malaria To the mother To the fetus
  • 17. Management  Includes  Investigations  Treatment of malaria  Management of complications  Prevention  Treatment of malaria in pregnancy should be  Energetic :  Don't waste any time.  Careful  Choose drugs and dosage carefully  Anticipatory  One should always be looking for any complications by regular monitoring
  • 18. Investigations  Includes  Antigen detection techniques : - MRDT-(HRP- 2/pLDH(PfPAN))  Peripheral blood smear for MPs( thin & thick films)  PCR based assay  Antibody test  Placental blood smear(postpartum)  Others depending on the clinical presentation
  • 19. Treatment of malaria in pregnancy  Depends on  Severity  Gestational age
  • 20. Treatment cont… A: Uncomplicated malaria  In the first trimester, Pregnant women with uncomplicated malaria should be treated with quinine tablets for seven days The dose is 10 mg/kg every 8 hours for 7days Do not exceed a maximum dose of 600mg per dose
  • 21. Treatment cont..  In the second and third trimester  Artemether-Lumefantrine should be used as medicine of choice  The dose is 4 tabs stat then 8hours after the first dose then 12hourly for 2days (a total of three days)  Alternatively  Dihydoartemisinin-Piperaquine (DPQ)  Artesunate-Amodiaquine
  • 22. Treatment cont..  B: Severe malaria  The primary objective of treatment in severe malaria is to prevent death.  The secondary objective is to prevent disabilities and to prevent recrudescent infection  In the first trimester  The medicine of choice for treatment of severe malaria in the first trimester is IV Quinine(dose)
  • 23. Severe malaria Rx cont..  In the second and third trimester The medicine of choice for treatment of severe malaria in 2nd and 3rd trimester of pregnancy is Inj. Artesunate  The dose is dose 2.4 mg/kg given at time 0 hour, then at 12 hours and 24 hours  Followed by ALu for 3days  The first oral dose should start 8hrs after the last injection  Quinine should be used only if Artesunate injectable is not available.
  • 24. Treatment cont…  According to WHO recommendation,  Treatment of severe malaria is with Inj Artesunate for both children and adults including infants, pregnant women in all trimesters and lactating women.  Inj Artesunate should be given for at least 24hrs and until patient can tolerate oral medication, then they should complete treatment with 3days of ACT  If Artesunate is unavailable, Inj Artemether (IM) should be given  If Artemether is unavailable, Inj Quinine should be given(loading dose 1st)
  • 25. Artesunate for injection  Descpription  Artesunate is a water-soluble derivative of Artemisinin.  The only Artemisinin analogue that can be given intravenously  It produces rapid parasite clearance in falciparum malaria.  Superior to Quinine in preventing death
  • 26. Artesunate for injection cont..  Three formulations are available:  30mg,  60mg and  120mg of Artesunate for injection.
  • 27. Table 14: Artesunate for injection package by strength Strength 30mg 60mg 120mg Artesunate for injection 1 vial of 30mg 1 vial of 60mg 1 vial of 120mg 5% Sodium bicarbonate 1 Ampoule of 0.5mls 1 Ampoule of 1ml 1 Ampoule of 2.5mls Sodium chloride 1 Ampoule of 2.5mls 1 Ampoule of 5mls 1 Ampoule of 10 mls
  • 28. Administration and dosage (60 mg strength)  Injectable Artesunate has 2-steps dilutions.  Step 1:  The powder for injection should be diluted with 1ml of 5% sodium bicarbonate solution (provided in each box) and shaken vigorously 2-3 minutes for better dissolving till the solution becomes clear.  Step 2:  For slow intravenous infusion (3-4 minutes): Add 5 ml of 5% dextrose or normal saline, to obtain a Artesunate concentration of 10 mg/ml  For deep intra-muscular injection: Add 2 ml of 5% dextrose or normal saline to obtain a Artesunate concentration of 20 mg/ml
  • 29. Quantity for dilution of Artesunate for injection ROUTE IV INJECTION IM INJECTION STRENG TH 30mg 60mg 120mg 30mg 60mg 120mg 5% NaCO3 0.5mls 1ml 2mls 0.5mls 1ml 2mls NS/5% dextrose 2.5mls 5mls 10mls 1ml 2mls 4mls TOTAL (mls) 3mls 6mls 12mls 1.5mls 3mls 6mls Artesunate concentrati on (Mg/ml) 10 10 10 20 20 20
  • 30. Caution;  The powder form for injection is difficult to dissolve, care should be taken to ensure that it is completely dissolved before parenteral administration.  If the solution is cloudy or a precipitate is present, the parenteral preparation should be discarded.  Dissolved artesunate should always be used immediately after 2nd dilution  Never store diluted Artesunate for further use
  • 31. Supportive treatment in the Management of malaria in pregnancy  Treatment of anemia (BT, FA)  Correction of electrolyte imbalance  Oxygen + Diuretics in pulmonary oedema  Dialysis for ARF  Anticonvulsants  ICU care for CM  Monitoring of the fetal growth & health
  • 32. Prevention  Available options are:-  Vector control  Insecticide Treated Nets (ITNs)  Residual house hold spraying  Environmental management  Drug prophylaxis  Intermittent preventive treatment (IPTp)  Alternative- DPQ (not yet adopted)  Vaccine?? –Still under development
  • 33. Intermittent preventive treatment (IPTp)  The medicine of choice for IPTp is Sulfadoxine/Pyrimethamine (SP)  Reduses the risk of Placental malaria Low birth weight and Maternal illness  Dosing should start as early as possible in the sec trimester  Should be given at least 1 month apart, at least 3doses  SP can be administered up to the time of delivery
  • 34. Conclusion  Diagnosis and Management of malaria during pregnancy can be challenging  The primary objective in the management of severe malaria is to prevent death  Malaria preventive package during pregnancy includes:  Intermittent preventive treatment with SP during antenatal clinic visits  Use of ITNs throughout pregnancy and in the postpartum period  Prevention must be complemented by effective case management of malaria for all women of reproductive age
  • 35. References  National Guidelines for Diagnosis and Treatment of Malaria-December 2014  The diagnosis and treatment of malaria in pregnancy-Royal College of Obstetricians and Gynecologists-April 2010  A Review of Malaria Diagnostic Tools: Microscopy and Rapid Diagnostic Test (RDT)-American journal of tropical medicine and hygiene  http://www.uptodate.com/contents/pathogenesis-of-malaria  http://www.malariasite.com/pathophysiology/  https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-7- 133  https://en.wikipedia.org/wiki/Pregnancy-associated_malaria  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-015- 0576-8
  • 36. References  https://malariajournal.biomedcentral.com/arti cles/10.1186/1475-2875-13-152  http://www.ncbi.nlm.nih.gov/pmc/articles/PM C3257207/  https://diagnosticpathology.biomedcentral.co m/articles/10.1186/1746-1596-8-59  http://www.mjhid.org/article/view/338/460  http://scialert.net/fulltext/?doi=jp.2015.120.12 6&org=10  http://jcm.asm.org/content/40/1/306.full