Lecture note MALARIA_IN_PREGNANCY(2)[1].pptx

malaria in pregnacy

1. MALARIA IN PREGNANCY PRESENTED BY: OKEDUSI DAMILOLA DEBORAH

2. OUTLINE Introduction Epidemiology Pathogenesis Symptoms Diagnosis Treatment Prevention Drug Interactions Vaccination Pharmacist’s role References

3. INTRODUCTION Malaria is a life-threatening disease caused by the protozoan plasmodium that is transmitted to people through the bite of an infected female Anopheles mosquito, called “malaria vectors”. There are 5 plasmodium spp that cause malaria in humans: Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi

4. INTRODUCTION Pregnancy increases the chances of developing malaria infection and severe diseases when infected. Pregnant women are particularly vulnerable to plasmodium falciparum infection because red blood cells infected with the parasite can sequester in the placenta(an additional organ during pregnancy), and thereby causing adverse fetal effects. If antimalarial drugs do not achieve therapeutic levels in the placenta, parasites sequestered there may be released intermittently into the peripheral blood and cause recurrent maternal infection. Malaria infection in pregnancy is a major cause of maternal death, maternal anemia, and adverse pregnancy outcome i.e spontaneous abortion, preterm delivery, growth restriction/low birth weight, stillbirth, congenital infection, neonatal mortality.

5. CONT’D Mostly affected women in their first ( primigravidal ) and second pregnancies, younger women and women who are HIV positive. The greatest degree of placental infestation is seen in women who have the highest immunity leading to milder symptoms and a disproportionate increase in fetal complications. It has been estimated that malaria is responsible for 25% of severe anemia during pregnancy (defined as hemoglobin less than 7gm/ dL ). Pregnant women with severe anemia are at higher risk for co-morbidities such as congestive heart failure, fetal demise, and mortality associated with hemorrhage at the time of delivery.

6. EPIDEMIOLOGY Malaria affects the lives of almost 40% of the world’s population, and the high risk group being pregnant women and young children(under 5-years of age) Also, in sub-Saharan Africa 20 per cent of pregnant women attending ante natal clinic tested positive for the malaria parasite  (Plasmodium Falciparum) as 72 per cent of pregnant women had at some point during their pregnancy Malaria complicates 8.4% to 58.1% of pregnancies in Nigeria About 10,000 women and 200,000 babies die annually because of malaria in pregnancy. Malaria causes about 20 per cent of still births and 11% of maternal deaths in Nigeria.

7. PLACENTAL PATHOLOGY Infected erythrocytes containing mature trophozoite and schizont parasite stages accumulate in the intervillous spaces (the lake-like structure through which maternal blood circulates), sometimes in high densities. High placental parasitemia has been associated with preterm delivery 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 and anemia. Hemozoin may also be seen in fibrin deposits. Hemozoin probably remains in the placenta for long period, but is diluted out by rapid placenta growth. The role of hemozoin in the pathogenesis of malaria in pregnancy remains unclear.

8. SYMPTOMS Fever Headache Chills and vomiting Bitter mouth Sweating Fatigue Muscle pain Severe anaemia Respiratory distress due to metabolic acidosis

9. PATHOGENESIS During a blood meal, mosquitoes inject the asexual forms or sporozoites into the blood stream of the human host. After a period of 9-16 days the sporozoites undergo an asexual multiplication ( exo-erythrocytic schizony ) in the liver to form merozoites which are then released into the blood to infect RBC. The merozoites develop into the trophozoites form in RBC and then undergo another asexual reproductive stage called erythrocytic schizogony to produce more merozoites . When the infected RBC ruptures, the merozoites attack new blood cells and repeat the erythrocytic cycle. In one or two weeks, the merozoites differentiates into the sexual forms, resulting in male and female gametocytes. If the gametocytes in the host blood are ingested by female anopheles mosquito during a blood meal, fertilization and an asexual division in the mosquito will propagate the infective sporozoites to complete the cycle.

10. DIAGNOSIS WHO recommends parasitological confirmation by microscopy or by Rapid Diagnostic Test (RDT) for all suspected cases of malaria before treatment is started. Thick and thin peripheral blood smears, stained with Giemsa stain, remain the gold standard for routine clinical diagnosis that permits the identification of species and quantification of parasites Malaria should not be excluded until at least 3 negative blood smears are obtained within 48 hours. Diagnosis should be promoted in pregnant women in endemic areas in order to ensure accurate diagnosis of malaria and to reduce unnecessary use of antimalarial in pregnancy.

11. TREATMENT OF UNCOMPLICATED MALARIA Pregnant women with symptomatic acute malaria are a high-risk group, and they must promptly receive effective antimalarial treatment. Antimalarial medicines considered safe in the first trimester of pregnancy for uncomplicated malaria are quinine, chloroquine , and proguanil . Quinine plus clindamycin to be given for 7 days ( artesunate plus clindamycin for 7 days is indicated if this treatment fails). If clindamycin is unaffordable or unavailable, then monotherapy should be given. 600mg every 8 hours for 7days(quinine sulfate) WHO had recommended quinine+clindamycin instead of ACTs for first trimester because there are potential teratogenicity of the artemisinin observed at preclinal animal studies.

12. For second and third trimester, ACT is known to be effective; Artemether / Lumefantrine , Artesunate / Amodiaquine , Dihydroartemisinin / piperaquine (DHAP), artesunate / mefloquine The current standard six-dose artemether + lumefantrine regimen (80/480mg) has been evaluated in >1000 women in second and third trimesters in controlled trials and have been found to be well tolerated. Mefloquine is considered safe in second and third trimesters; however, it should given only in combination with an artemisinin derivative. Quinine is associated with an increased risk for hypoglycemia in late pregnancy. Primaquine and tetracyclines should not be used during pregnancy

13. Dosing of ACTs Recommended dosage regimen : Artemeter + lumefantrine >35kg is (80/480mg) given twice a day for 3 days. The first 2 doses should be ideally, given 8 hours apart Absorption of lumefantrine is enhanced by co –administration with fat. Patients should be informed that this ACT should be taken immediately after food or a fat containing drink e.g milk, particularly on the second and third day of treatment. Artesunate + Amodiaquine >36kg is 2 tabs of 100/270mg (200/540mg) once a day for 3 days Artesunate + mefloquine >30kg (200/440) given once a day for 3 days DHAP; 36 to <60kg ; 3 tabs of 40/320mg (120/960) once daily for 3 days, 60 to <80kg 4 tabs (160/1280), > 80kg 5 tabs(200/1600) Piperaquine is eliminated more rapidly in pregnant women , shortening the post-treatment prophylactic effect of DHAP. DHAP should be administered between meals . Avoid high fat meals as they can significantly increase piperaquine absorption, thereby increasing the risk for potentially arrythmogenic delayed ventricular repolarization.

14. Pharmacodynamics In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin . The drug works against the erythrocytic stages of  P. falciparum  by inhibiting nucleic acid and protein synthesis. The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine  inhibits the formation of β- hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis The  quinoline -containing antimalarial drugs, chloroquine , quinine, piperaquine and mefloquine . These drugs are thought to act by interfering with the digestion of haemoglobin in the blood stages of the malaria life cycle

15. TREATMENT OF SEVERE MALARIA IN PREGNANACY WHO definition of severe malaria includes these clinical features: Impaired consciousness or coma Generalized weakness Failure to feed Multiple convulsions – more than 2 episodes in 24 hours Deep breathing, respiratory distress Circulatory collapse or shock, systolic blood pressure < 70mmHg in adults and <50mmHg in children. Pulmonary oedema Clinical jaundice plus evidence of other vital organ dysfunction Abnormal spontaneous bleeding

16. TREATMENT CONT’D Laboratory findings: Hypoglycemia (blood glucose <2.2 mmol /l or 40mg/dl) Metabolic acidosis (plasma bicarbonate < 15 mmol /l) Severe normocytic anaemia ( Hb < 5g/dl, packed cell volume <15%) Haemoglobinuria Hyperparasitaemia (>2%/100000/µl in low intensity transmission areas or >5% or 250000/µl in areas of high stable malaria transmission intensity) Hyperlactataemia (lactate >5mmol/l) Renal impairment (serum creatinine >265µmol/l)

17. TREATMENT CONT’D In treatment of severe malaria, saving the mother’s life is the primary objective. Intravenous artesunate reduces more deaths related to severe malaria than intravenous quinine. WHO therefore recommends treatment of severe malaria in pregnancy with intravenous artesunate in the second and third trimester as quinine is associated with recurrent hypoglycemia Treatment should not be delayed. If only one of the drugs artesunate , artemether , or quinine is available, it should be administered immediately.

18. PREVENTION Prevention of malaria in pregnancy can be achieved by 2 strategies ; Vector control i.e the use of insecticide treated nets, indoor spraying with residual insecticides and Chemoprevention. Insecticide-treated mosquitos net (ITNs) Long-lasting insecticide nets (LLINs) are the preferred form of ITNs. It offers effective protection against malaria. WHO recommends that all at-risk persons, particularly pregnant women and infants, sleep under ITNs during the night. Indoor spraying with residual insecticides I ndoor residual spraying (IRS) refers to the spraying of all stable surfaces inside human habitations using an insecticide with residual action. IRS is a powerful way to rapidly reduce malaria transmission. It is effective for 3-6 months depending on the type of insecticide used.

19. PREVENTION CONT’D CHEMOPREVENTION WHO recommends intermittent preventive treatment (ITP) with sulfadoxine-pyrimethamine for pregnant women living in high transmission areas. Administration of 2 or more doses of chemoprophylaxis after 16 weeks of gestation or after quickening (first movement of the fetus) in an attempt to reduce subclinical malarial load.

20. PREVENTION CONT’D WHO recommends that in areas of stable malaria transmission, IPT with an effective antimalarial drug be provided as part of antenatal care Sulphadoxine / pyrimethamine combination is currently the most effective single dose antimalarial drug for the prevention of malaria during pregnancy. The first dose is given after 16 weeks of gestation or after quickening. SP should be ideally be administered as directly observed therapy (DOT) of three tablets sulfadoxine / pyrimethamine (each tablet containing 500/25mg) giving a total required dosage of 1500/75mg

21. Pharmacokinetics SP can be given either on an empty stomach or with food. SP has a long half life. 160 hours for pyrimethamine and 8 days for sulfadoxine , but distribution and metabolism, and the effective concentration of the drug can be altered in pregnancy. SP can be given every month until the time of delivery. SP should not be given more than once monthly.

22. Pharmacodynamics Mechanism of Action Sulfadoxine inhibits the enzyme dihydropteroate synthase and dihydrofolate reductase which are necessary in the conversion of Para- aminobenzoic acid (PABA) to folic acid. Plasmodium falciparum require folic acid for synthesis, repair and methylation of DNA which is vital for cell growth. With this vital nutrient lacking, the parasite has difficulty in reproducing.

23. SIDE EFFECTS Despite the known side effects associated with sulfonamides, SP for IPT in pregnancy is generally well tolerated. Mild and transient side effects include; Nausea Vomiting Weakness Dizziness have been reported by some women, particularly with the first dose of SP. Studies have shown it that side effects tend to decrease with the administration of other doses.

24. DRUG INTERACTIONS SP should not be administered to women receiving co- trimaxole prophylaxis due to a higher risk of adverse events (severe cutaneous reactions). WHO recommends the administration of folic acid at a dose of 0.4mg daily; this dose may be safely used in conjunction with SP. Folic acid at a daily dose equal or above 5mg should not be given together with SP as this counteracts its efficacy as an antimalarial.

25. VACCINATION AGAINST MALARIA WHO recommends in the context of comprehensive malaria control the RTS,S/AS01 malaria vaccine be used for the prevention of P. falciparum malaria in children WHO also recommended a new vaccine, R21/Matrix-M, for the prevention of malaria in children Both vaccines are shown to be safe and effective in preventing malaria in children and when implemented broadly, are expected to have high public health impact.

26. VACCINATION Despite accounting for high cases of Malaria, Nigeria was in July excluded from the list of 12 African countries to receive 18 million doses of the vaccine from 2023 to 2025 At least, 28 countries in Africa plan to introduce a WHO-recommended malaria vaccine as part of their national immunization programs. The RTS,S vaccine will be rolled out in some African countries in early 2024, and the R21 malaria vaccine is expected to become available to countries mid-2024

27. PHARMACIST’S ROLE IN MALARIA MANAGEMENT Antenatal Screening: Pharmacists may be involved in providing malaria screening services to pregnant women during antenatal care visits. They can conduct rapid diagnostic tests (RDTs) to detect malaria infection and initiate prompt treatment when necessary. Patient Education and Counseling: Pharmacists offer education and counseling to pregnant women regarding the risks of malaria during pregnancy, including complications such as maternal anemia, low birth weight, preterm delivery, and fetal loss. They emphasize the importance of seeking timely medical care for malaria symptoms and adhering to recommended preventive measures. Preventive Measures: Pharmacists educate pregnant women on malaria prevention strategies, such as the consistent use of insecticide-treated bed nets and the avoidance of mosquito bites. They provide guidance on the proper application of insect repellents and advise pregnant women on travel precautions if they reside in or plan to visit malaria-endemic areas.

28. PHARMACIST’S ROLE IN MALARIA MANAGEMENT Collaboration with Healthcare Providers: Pharmacists collaborate with obstetricians, midwives, and other healthcare providers to ensure coordinated care for pregnant women with malaria. They communicate treatment plans and monitor patient responses, contributing to optimal maternal and fetal outcomes. Continuing Professional Development: Pharmacists engage in ongoing training and professional development activities to stay updated on the latest evidence-based guidelines and recommendations for managing malaria in pregnancy. They enhance their knowledge and skills to provide the highest quality care to pregnant women and contribute to positive health outcomes. Monitoring and Adverse Effects Management: Pharmacists monitor pregnant women receiving antimalarial treatment for any adverse effects and provide appropriate management recommendations. They advise patients on potential side effects of medications and encourage reporting of any unusual symptoms to healthcare providers.

29. REFERENCES Chico RM, Mayaud P, Ariti C, Mabey D, Ronsmans C, Chandramohan D. Prevalence of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review. JAMA. 2012 May 16;307(19):2079–86. Available from: http://dx.doi.org/10.1001/jama.2012.3428 Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, Newman RD. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007 Feb;7(2):93–104. Kovacs SD, Rijken MJ, Stergachis A. Treating severe malaria in pregnancy: a review of the evidence. Drug Saf . 2015 Feb;38(2):165-81. http://dx.doi.org/10.1007/s40264-014-0261-9 Pan American Health Organization, March of Dimes, Latin American Centre for Perinatology Women and Reproductive Health. Perinatal infections transmitted by the mother to her infant, education material for health personnel. Clap Scientific Publication. 2008. Available from: http://www.clap.opsoms.org/web_2005/BOLETINES%20Y%20NOVEDADES/EDICIONES%20DEL%20CLAP/CLAP%201567 -02.pdf

30. REFERENCES World Health Organization. Training module on malaria control: Case management. WHO. 2012. Available from: http://apps.who.int/iris/bitstream/10665/78070/1/9789241503976_eng.pdf World Health Organization. Training module on malaria control: Case management. WHO. 2013. Available from: http://www.who.int/malaria/publications/atoz/9789241503976/en/ World Health Organization. World Malaria Report 2014. WHO. 2014. Available from: http://www.who.int/malaria/publications/world_malaria_report_2014/en/ World Health Organization. Malaria. Fact sheet N°94. WHO. 2023. Available from: http://www.who.int/mediacentre/factsheets/fs094/en/