11. MALARIA IN PREGNANCY.pptx lecture notes for junior clerks

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1. MALARIA IN PREGNANCY PRESENTER: Dr Ochola Fredrick 1

2. Introduction Malaria is a tropic life threatening disease. Caused by plasmodium species Infection is naturally transmitted by bites from infective female Anopheles mosquito Over 156 plasmodium infect vertebrates Four plasmodium spps cause natural infection in man Symptoms may appear within weeks to months or even years. 2

3. Introduction Pregnant women are more susceptible than the general population to malaria. T hey are more likely to: become infected, have a recurrence, develop severe complications and to die from the disease. Malaria contributes very significantly to maternal and foetal mortality. 3

4. Epidemiology Globally, 125 million women are at risk of malaria every year . Malaria infection in pregnancy compromises the mother’s health and can lead to her death. In sub-Saharan Africa, the area most burdened by malaria, the disease is thought to cause as many as 10,000 cases of malaria-related deaths in pregnancy, mainly due to severe maternal anaemia . The World Malaria Report has identified that malaria appears to hit pregnant women and children in Africa the hardest, suggesting that countries prioritize support for these two at-risk groups. 4

5. Epidemiology In 2018, an estimated 11 million pregnant women living in 38 countries with moderate-to-high transmission in sub-Saharan Africa were infected with malaria (29% of all pregnancies ) Malaria in pregnancy also impacts the health of the fetus, which can lead to preterm birth and low birth weight, major contributors to neonatal and infant mortality. In 2018, an estimated 872 000 children in 38 African countries were born with a low birth weight due to malaria in pregnancy. 5

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7. Causative Organism Malaria vector borne disease caused by protozoan plasmodium 1.P.falciparum(most dangerous account for 90%death d/t malaria) 2.P.vivax(most widely spread species) 3.P.malariae 4.P.ovale 5.P.knowlesi(malaria in macaques but can infect human) 7

8. Transmission Malaria transmitted by mosquito female Anopheles 1.Bite of infected mosquito 2.Congenital infection 3.Blood transfusion 4.Contaminated needle 5.Organ transplantation 8

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10. Pathogenesis Parasite accumulation in the placenta. Infected erythrocytes (IE) containing mature trophozoite and schizont parasite stages accumulate in the intervillous spaces (the lake-like structures through which maternal blood circulates), sometimes to high densities. High placental parasitaemia has been associated with preterm delivery (PTD). 10

11. Placental IE can adhere to chondroitin sulphate A (CSA) and hyaluronic acid (HA). CSA and HA are expressed by syncytiotrophoblast that line the placental intervillous spaces. And yet many IE are not adherent to the syncytiotrophoblast; they may in part be retained by different glycoforms of CSA secreted into the intervillous space, or by fibrin deposition. 11

12. Rosette formation (the adhesion of two or more uninfected erythrocytes to IE) may be important in cerebral malaria pathogenesis, but plays little role in placental infection. 12

13. Parasite proteins causing placental infection. Placental IE express unique variant surface antigens (VSA), which: mediate placental adhesion, have unique antigenic properties, and are recognized in a gender- and parity-specific manner. The principal parasite ligand mediating CSA adhesion and believed to mediate placental sequestration , and the dominant VSA on the IE surface, is P. falciparum erythrocyte membrane protein 1(PfEMP1 ), encoded by the var multigene family. 13

14. Cellular immunity to placental malaria. Placental malaria may be accompanied by intervillous infiltrates of monocytes and macrophages, some containing malaria pigment (hemozoin). High density monocyte infiltrates are especially common in first pregnancy, and are associated with low birth weight (LBW) and anaemia . 14

15. Placental malaria disrupts the normal immune balance in the placenta, causing increased synthesis of inflammatory cytokines like TNF-a, interleukin (IL) 2, and interferon-g. Levels of TNF-a have been associated with LBW and anaemia. Chemokines produced by monocytes and syncytiotrophoblast may be important in attracting monocytes to the placenta, and infiltrates also include increased numbers of neutrophils and T cells. Although peripheral blood T cell responses may be decreased in malaria, this may be due to trafficking of memory T cells out of the circulation. 15

16. Role of hemozoin Finally , hemozoin may also be seen in fibrin deposits. Detection of hemozoin alone indicates previous infection, and has been associated with decreased birth weight. The role of hemozoin in the pathogenesis of malaria in pregnancy remains to be elucidated. 16

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18. Susceptible group Primigravidae are at highest risk of malarial infection and serious complications . Pregnant women with one previous birth are also at higher risk. Primigravidae have no pre-existing immunity to placental parasites and are highly susceptible In high transmission areas, primigravidae develop immunity to placental parasites and are protected in subsequent pregnancies In low transmission areas, multigravidae are unexposed and unprotected 18

19. Susceptible group HIV positive mothers. Malaria stimulates expression of an HIV co-receptor (CCR5 ) in the placenta. Younger maternal age (particularly adolescence) carries a higher risk of infection and adverse effects. Second trimester carries the highest risk of infection. Those from areas of low endemicity, e.g. in Kisoro and Kabale. Sickle-cell disease 19

20. Presentation Symptoms Fever/chills/sweats Headache Muscle pain Nausea Vomiting Diarrhoea Cough General malaise Signs Jaundice Elevated temperature Perspiration Pallor Splenomegaly Respiratory distress 20

21. Atypical presentation of malaria is common in pregnancy , particularly in the second and third trimesters, so a high index of suspicion should be maintained in susceptible pregnant mothers. Fever; may be absent, low-grade or very high and may not behave in the classical quartian/tertian fashion. Anaemia is a common feature and may be the only clue to the illness in mature primigravidae living in endemic areas . Splenomegaly may occur but tends to regress in the second half of pregnancy. Complications, along with features of cerebral malaria (impaired consciousness, seizures) and jaundice can be the presenting features of an acute, severe illness. 21

22. Complications Maternal complications Severe malaria: one or more of the following, occurring in the absence of an identified alternative cause and in the presence of parasitaemia: Prostration Impaired consciousness Respiratory distress 22

23. Multiple convulsions Circulatory collapse, shock (blood pressure below 90/60mmHg) Abnormal bleeding, disseminated intravascular coagulopathy Jaundice Haemoglobinuria Renal impairment 23

24. Severe malarial anaemia: tends to occur between 16-29 weeks - due to haemolysis of parasitized cells and increased demands of pregnancy ± folate/iron deficiency. Severe anaemia eliminates any physiological reserve to cope with haemorrhage, making women more likely to die in childbirth . Acute pulmonary oedema: occurs much more commonly in pregnant women and may be the presenting feature. It carries a high mortality and is typically seen in the second and third trimesters. 24

25. Foetal complications Both P. falciparum and P. vivax can cause complications that affect the foetus. Foetal mortality is estimated at 15% for P. vivax and around 30% for P. falciparum . Common problems for the foetus include : Spontaneous abortion. Premature delivery. Stillbirth. Intrauterine growth restriction. Low birth weight - common. Intrauterine foetal death . 25

26. Neonatal and infant problems related to malaria include : Increased mortality rates. Congenital malaria. Anaemia. Increased rates of other infections. Under nutrition. Short stature, poor foetal mental development and an increased risk of metabolic disease in adulthood are the potential long term complications. 26

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28. Differential diagnosis The differential diagnosis include (but not limited to): Gastroenteritis Amebiasis Cholera HIV infection Otitis media Bacterial and viral pneumonia Toxic shock syndrome 28

29. Differential diagnosis in congenital malaria Rhesus incompatibility Cytomegalovirus infection Herpes infection Rubella Toxoplasmosis Syphilis 29

30. Investigations Diagnosis of falciparum malaria in pregnancy can be particularly difficult due to placental sequestration of parasites. Rapid diagnostic tests (RDTs) Thick and thin films for malarial parasites should be examined and the degree of parasitaemia determined. Parasites may not be detectable on peripheral blood films. blood glucose and LFTs including bilirubin levels should also be checked. CXR may reveal cases of pulmonary oedema. Polymerase chain reaction tests are available. 30

31. Practical guidelines in diagnosis During history taking and physical examination elicit signs and symptoms of severe malaria. Whenever malaria is suspected, laboratory confirmation of malaria parasites should be performed if possible. If laboratory facilities are not available, treatment should be started on the basis of clinical presentation. If a laboratory is present, a negative result does not rule out malaria. RDTs have an added value, as they can be positive even if parasites are hidden in the placenta. 31

32. Management Treatment of malaria in pregnancy should be Prompt, Anticipatory, and C areful. 32

33. Prompt Do not waste any time. Assess severity: general condition, pallor , jaundice , B.P., temperature, hemoglobin, parasite count, serum bilirubin , serum creatinine, blood sugar. 33

34. 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 fetal vital parameters 2 hourly. R.B.S . 4-6 hourly; hemoglobin and parasite count 12 hourly; serum creatinine; serum bilirubin and fluid Intake/Output chart daily. 34

35. Careful The physiologic changes of pregnancy pose special problems in management of malaria. Certain drugs are contra indicated in pregnancy . 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. 35

36. Antimalarial drugs in pregnancy All trimesters Q uinine can be used safely in any part of the pregnancy. Second and third trimesters Artemisinin-based combination therapies, mefloquine and pyrimethamine-sulfadoxine are safe in the second and third trimesters. 36

37. Management of uncomplicated malaria in pregnancy Definition of uncomplicated malaria: a patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) but no features of severe malaria. Treat uncomplicated malaria in second and third trimesters with artemisinin-based combination therapies (ACT): Artemether + lumefantrine Artesunate + amodiaquine Artesunate + mefloquine Dihydroartemisinin + piperaquine Artesunate + sulfadoxine-pyrimethamine (SP) 37

38. First line Artemether/Lumefantrine 80/480 mg 12 hourly for 3 days First line alternative Dihydroartemisinin/Piperaquine 3 tablets ( 1080 mg ) once daily for 3 days And if no response Quinine , oral 600 mg 8 hourly for 7 days 38

39. First trimester of pregnancy Treat pregnant women with uncomplicated P. falciparum malaria during the first trimester with 7 days of quinine oral 600 mg 8 hourly (if quinine not available , ACT may be used ). If the malaria species is not known with certainty, treat as for uncomplicated P. falciparum malaria. 39

40. Management of severe malaria in pregnancy Treat pregnant women in all trimesters and lactating women with intravenous or intramuscular artesunate for at least 24 h and until they can tolerate oral medication. Once a patient has received 24 h of parenteral therapy, complete treatment with 3 days of ACT (add single dose primaquine in areas of low transmission). If artesunate is not available, use artemether in preference to quinine. 40

41. First line IM/IV Artesunate 2.4 mg/kg at 0, 12 and 24 hours, then once a day until mother can tolerate oral medication. Complete treatment with 3 days of oral ACT. First line alternative IM artemether 3.2 mg/kg loading dose then 1.6 mg/kg once daily until mother can tolerate oral medication. Complete treatment with 3 days of oral ACT. If artesunate or artemether not available , use Quinine 10 mg/Kg IV every 8 hours in Dextrose 5 %. 41

42. Contraindicated drugs Primaquine, T etracycline , Doxycycline, and H alofantrine are contra-indicated. Current treatment guidelines suggest the use of quinine and clindamycin in place of doxycycline . 42

43. Management of complications 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. Severe anaemia (haemoglobin < 8 g/100 ml or packed cell volume < 24%): Transfuse with packed red cells. 43

44. Hypoglycaemia (blood glucose < 2.2 mmol/l or < 40 mg/100 ml) : Check blood glucose regularly, C orrect hypoglycaemia and maintain with glucose-containing or infusion. Quinine induced hypoglycaemia can occur quite late in the course even after the patient appears to be recovering. 44

45. Acute pulmonary oedema (possible overlay of acute respiratory distress syndrome): Prevent by monitoring jugular venous pressure(JVP)/central venous pressure (CVP) to keep right arterial pressure < 10 cm H2O. Treat by propping patient up at an angle of 45 degrees, give oxygen, give a diuretic, stop intravenous fluids, intubate and add positive end-expiratory pressure/continuous positive airway pressure in life-threatening hypoxaemia 45

46. 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. 46

47. Renal failure: Renal failure could be pre-renal due to unrecognized dehydration or renal due to severe parasitaemia. Treatment involves careful fluid management, diuretics, and dialysis if needed . 47

48. S epticaemic shock: Secondary bacterial infections like urinary tract infection, pneumonia etc. are more common in pregnancy associated with malaria. When septicaemia is suspected, take blood for cultures; give parenteral broad-spectrum antimicrobials, correct haemodynamic disturbances. 48

49. Management of labour Anaemia, hypoglycaemia, pulmonary oedema, and secondary infections due to malaria in full term pregnancy lead to problems for both the mother and the foetus. Severe falciparum malaria in full term pregnancy carries a very high mortality. Maternal and foetal distress may go unrecognized in these patients. Therefore, with careful monitoring of maternal and foetal parameters, severe malaria are better managed in an intensive care unit. 49

50. 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. Foetal distress is common and often unrecognized. Therefore only monitoring of uterine contractions and foetal heart rate may reveal asymptomatic labour and foetal tachycardia, bradycardia or late deceleration in relation to uterine contractions, indicating foetal distress. 50

51. All efforts should be made to rapidly bring the temperature under control, by tepid sponging, fanning and using antipyretic drugs like paracetamol, etc. 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 parasitaemia, exchange transfusion may have to be carried out. 51

52. If the situation demands, induction of labour may have to be considered. Once the patient is in labour, foetal or maternal distress may indicate the need to shorten the 2nd stage by forceps or vacuum extraction. If needed, even caesarean section must be considered. 52

53. Prevention of malaria during pregnancy Primary prevention Use of insecticide-treated mosquito nets . It reduces mosquito-human contact by barricading, repelling or killing mosquitoes. These nets should be used even before the woman conceives, then throughout pregnancy, and thereafter with her new-born. Drain all stagnant water around the home. Wear protective clothing that covers the arms and legs in the evening. Use mosquito-repelling creams. Clear all tall bushes around the home. 53

54. Give all pregnant women intermittent preventive treatment (IPT) with pyrimethamine-sulfadoxine (SP) Give expectant mothers ferrous sulphate plus folic acid and mebendazole to complement SP in preventing maternal anaemia found in over 60% of all those attending ANC. Delay folic acid for 1 week after administration of SP to avoid antagonism between the two drugs. 54

55. Intermittent preventive treatment The drug of choice for IPT is sulfadoxine-pyrimethamine (SP) It is administered once a month starting at 13 weeks of pregnancy until delivery. IPT should be administered as direct observed treatment (DOT) during an antenatal care visit. If malaria is diagnosed after administration of IPT with SP a full treatment with antimalarials should be given. Pregnant women who are known to have hypersensitivity to sulphonamides should not receive SP for IPT. 55

56. References: World Malaria Report 2019, 4 December 2019 Centers for Disease Control and Prevention. Intermittent Preventive Treatment of Malaria for Pregnant Women ( IPTp ); Centers for Disease Control and Prevention, 27 Mar 2019 Ministry of Health. Uganda Clinical Guidelines; 2016 Royal College of Obstetricians and Gynaecologists. The diagnosis and treatment of malaria in pregnancy, Green-top Guideline No. 54B; April 2010 World Health Organization. Guidelines for the Treatment of Malaria, Third edition. Geneva: World Health Organization; 2015 . Rogerson SJ, Mwapasa V, and Meshnick SR. Malaria in Pregnancy: Linking Immunity and Pathogenesis to Prevention. American Journal of Tropical Medicine and Hygiene, 77( Suppl 6), 2007, pp. 14–22. 56