Malaria in Pregnancy

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11:39 PM. Malaria in Pregnancy - Prof.S.N.Panda. 2. Malaria Menance. World wide 103 countries with 2.5 billion people, developing countries worst affected. 40 % of world's population in shadow of Malaria.Deaths- Under estimated/Unknown,1.1 to 2.7 million per yearGender related mortality - Females

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Malaria in Pregnancy

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1. Malaria in Pregnancy Department of Obstetrics & Gynaecology M.K.C.G.MEDICAL COLLEGE BERHAMPUR, ORISSA, INDIA

2. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 2 Malaria Menance World wide 103 countries with 2.5 billion people, developing countries worst affected. 40 % of world’s 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.

3. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 3 Malaria in Pregnancy : 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.

4. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 4 Malaria in Pregnancy : 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.

5. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 5 Malaria in Pregnancy : 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.

6. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 6 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.

7. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 7 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.

8. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 8 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).

9. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 9 Clinical features 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.

10. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 10 Clinical features 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.

11. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 11 Complications of Malaria in Pregnancy 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.

12. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 12 Complications of Malaria in Pregnancy 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 < 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.

13. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 13 Complications of Malaria in Pregnancy 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 RBC’s 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.

14. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 14 Complications of Malaria in Pregnancy 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..

15. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 15 Complications of Malaria in Pregnancy 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.

16. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 16 Complications of Malaria in Pregnancy 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.

17. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 17 Complications of Malaria in Pregnancy 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.

18. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 18 Complications of Malaria in Pregnancy 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.

19. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 19 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.

20. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 20 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.

21. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 21 Risks for the foetus It is very rare and occurs in < 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.

22. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 22 Risks for the foetus 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.

23. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 23 Diagnosis High level of awareness Peripheral blood smear Antigen detection techniques : (PfHPR-2) Fluorescent staining PCR based assay Antibody test Placental blood smear

24. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 24 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.

25. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 25 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

26. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 26 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.

27. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 27 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.

28. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 28 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.

29. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 29 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

30. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 30 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.

31. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 31 Artemether: Six amp (480mg) IM in 5 / 3 days. 1x2x1+1x1x4 OR 1x2x3. Arteether: One amp (150mg) IM / day for3 consecutive days. Pyrimethamine 25mg+sulphadoxine 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 >60kg, a third dose of 1 tab after 6-8 hours.

32. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 32 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 <5 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.

33. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 33 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. Patient’s 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).

34. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 34 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.

35. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 35 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.

36. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 36 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.

37. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 37 Treatment of Vivax Malaria in Pregnancy 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.

38. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 38 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.

39. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 39 Chemoprophylaxis in Pregnancy 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.

40. 7:23 AM Malaria in Pregnancy - Prof.S.N.Panda 40

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