Malaria Dr getenet from Ethiopian st.p.pptx

Is an acute illness characterized by paroxysms of fever, chills, sweats, fatigue, anemia, and splenomegaly.
With the revised WHO calculation, malaria accounts for 7.8 percent of the global disease burden (rather than 4.8 percent as reported previously).
The emergence of Plasmodium falciparum artemisinin partial resistance in the African region is of great concern,�Children with malaria often lack the typical paroxysms in adults (high fever, followed by shaking chills and then diaphoresis).
and may have nonspecific symptoms, including
fever (may be low-grade but is often >40°C [104°F]),
headache,
drowsiness,
anorexia, nausea, vomiting, and diarrhea.Leading cause of massive splenomegaly in malaria-endemic countries.
HMS is caused by a chronic antigenic stimulation derived from the malaria parasite.
The main, severe complications of HMS are acute infectious illnesses, haemolytic anaemia and splenic rupture.
Prolonged antimalarial prophylaxis (for at least 1 yr, typically with chloroquine, quinine, or mefloquine.
For patients not re-exposed to endemic areas, a short course of treatment is sufficient.Blood film
Thick smear
Laysed RBCS, many layers, large volume
Low density infection can be detected
Good screening test
Thin smear
Fixed rbcs, single layer, smaller volume
Identification of the malaria species
Useful in following the response to therapy.
Low density infection can be missed
Determination of the percentage of infecteDetect antigens from the malaria parasites in blood using an immune-chromatographic process.
An antigen-antibody reaction leads to a visible colour change that indicates a positive test result.
These tests use finger-stick or venous blood, take only few minutes.
Parasite antigens mainly histidine rich protein 2 (hrp2) or plasmodium lactate dehydrogenase (pldh).
Aldolase is another antigen that is used in some tests. �����Compared with thick and thin smears, sensitivity and specificity are nearly 100%.
Can be useful for confirmation and for diagnosis of multiple species of malaria,
But the time delay in availability of results generally precludes its use for acute diagnosis of malaria.
May detect asymptomatic parasitemia in children with very-low-level parasitemia.
Early detection of resistance to antimalarial drugs is another benefit of PCR-based techniques.ddxViral infections such as influenza and hepatitis,
Sepsis, pneumonia,
Meningitis, encephalitis,
Endocarditis,
Gastroenteritis, pyelonephritis,
Babesiosis,
Brucellosis, �AL plus single dose primaquine (0.25mg/kg) is the recommended first-line drug.
AL tablets are given according to body weight in six doses over three days.
AL should not be used as malaria prophylaxis either alone or in combination;
Persons with a previous history of reaction after using the drug, shouldn’t be used.
Persons with severe and complicated malaria should not be treated with oral medications. �� � �Hemoglobin 50% of the baseline
Hemoglobin < 7 g/dL AN

1. Malaria Getinet A(R3) Moderator- Dr.Solomie J (MD,MPH,ID consultant)

2. Outlines.. Introduction Epidemiology Pathogenesis Clinical manifestations Diagnosis Management

3. Introduction.. Is an acute illness characterized by paroxysms of fever , chills, sweats, fatigue , anemia, and splenomegaly . With the revised WHO calculation, malaria accounts for 7.8 percent of the global disease burden (rather than 4.8 percent as reported previously ). The emergence of  Plasmodium falciparum   artemisinin partial resistance in the African region is of great concern,

4. Transmission.. Transmitted most frequently via the bite of a female anopheles spp mosquito, Other rare mechanisms Congenitally acquired disease, Blood transfusion, Sharing of contaminated needles, Organ transplantation, and nosocomial transmission

5. Epidemiology.. Over 95 percent of the burden occurs in the African region of the WHO. Followed by 2 percent each in the southeast Asian and eastern Mediterranean regions, With the American and Western Pacific regions contributing the remainder. In Ethiopia about 75% of the total area of the country is considered malarious .

6. Epidemiology.. P. falciparum is the predominant species in Africa , Haiti, and New Guinea. P . vivax predominates in Bangladesh, Central America , India, Pakistan, and Sri Lanka. P . vivax and P. falciparum predominate in Southeast Asia, South America , and Oceania. P . ovale is the least-common species and is transmitted primarily in Africa.

7. Epidemiology.. In terms of parasitemia rates or palpable spleen rates in children two to nine years of age; Hypo-endemic (≤10 percent), Meso -endemic (11 to 50 percent), Hyper-endemic (51 to 74 percent), and Holo -endemic (≥75 percent). 

8. Pathogenesis..

9. Pathophysiology.. Fever; erythrocytes rupture and release merozoites into the circulation . Anemia-due to; Hemolysis, Impaired erythropoiesis, or bone marrow depression.

10. Severe malaria is more common in P. falciparum – Higher-density parasitemia Cyto -adherence polyclonal activation, Rosetting . The cumulative effects of these pathologic processes may lead to cerebral, cardiac, pulmonary, renal, and hepatic failure.

11. Clinical manifestations Incubation period 9-14 days for P. falciparum 12-17 days for P. vivax (can be as long as 6-12 mo ) 16-18 days for P. ovale 18- 40 days for P. malariae . Can be prolonged for patients with partial immunity or incomplete chemoprophylaxis. A prodrome lasting 2-3 days is noted in some patients before parasites are detected in the blood.

12. Clinical manifestations Children with malaria often lack the typical paroxysms in adults (high fever, followed by shaking chills and then diaphoresis). and may have nonspecific symptoms, including fever (may be low-grade but is often >40°C [104°F]), headache , drowsiness , anorexia , nausea, vomiting, and diarrhea .

13. Periodicity of fever Every other day (P. Vivax and P. Ovale )- (“ tertian” malaria ) Every 3rd day (P. Malariae )- (“ quartan ” malaria) Less apparent with P. Falciparum, and mixed infections and may not be apparent early on in infection.

14. World Health Organization Criteria for Severe Malaria, 2000 Impaired consciousness Prostration Respiratory distress Multiple seizures Jaundice Hemoglobinuria Abnormal bleeding Severe anemia Circulatory collapse Pulmonary edema

15. Congenital malaria Usually with P. Vivax or P. Malariae infection, Although it can be observed with any of the human malaria species. The first sign or symptom typically occurs between 10 and 30 days of age (range: 14 hr to several months of age). S/s include: fever, restlessness, drowsiness, pallor, jaundice, poor feeding, vomiting, diarrhea, cyanosis, and hepato -splenomegaly. Malaria in pregnancy is a major health problem in malaria endemic countries.

16. Hyper-reactive malarial splenomegaly (HMS) Leading cause of massive splenomegaly in malaria-endemic countries. HMS is caused by a chronic antigenic stimulation derived from the malaria parasite. The main, severe complications of HMS are acute infectious illnesses, haemolytic anaemia and splenic rupture. Prolonged antimalarial prophylaxis (for at least 1 yr , typically with chloroquine , quinine, or mefloquine . For patients not re-exposed to endemic areas, a short course of treatment is sufficient.

17. Diagnosis Blood film Thick smear Laysed RBCS, many layers, large volume Low density infection can be detected Good screening test Thin smear Fixed rbcs , single layer, smaller volume Identification of the malaria species Useful in following the response to therapy. Low density infection can be missed Determination of the percentage of infected erythrocytes

18. Malaria Rapid Diagnostic Testing Detect antigens from the malaria parasites in blood using an immune-chromatographic process. An antigen-antibody reaction leads to a visible colour change that indicates a positive test result. These tests use finger-stick or venous blood, take only few minutes. Parasite antigens mainly histidine rich protein 2 (hrp2) or plasmodium lactate dehydrogenase ( p ldh ). Aldolase is another antigen that is used in some tests.

19. PCR Compared with thick and thin smears, sensitivity and specificity are nearly 100%. Can be useful for confirmation and for diagnosis of multiple species of malaria, But the time delay in availability of results generally precludes its use for acute diagnosis of malaria. May detect asymptomatic parasitemia in children with very-low-level parasitemia . Early detection of resistance to antimalarial drugs is another benefit of PCR-based techniques .

20. Differential Diagnosis Viral infections such as influenza and hepatitis, Sepsis, pneumonia, Meningitis, encephalitis, Endocarditis, Gastroenteritis, pyelonephritis, Babesiosis , Brucellosis, Leptospirosis, Tuberculosis, Relapsing fever, Typhoid fever, Yellow fever, Viral hemorrhagic fevers, Amebic liver abscess,

21. Treatment: uncomplicated malaria Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following ACTs: artemether + lumefantrine artesunate + amodiaquine artesunate + mefloquine dihydroartemisinin + piperaquine artesunate + sulfadoxine – pyrimethamine (SP) Duration: 3days

22. P.falciparum .. AL plus single dose primaquine (0.25mg/kg) is the recommended first-line drug. AL tablets are given according to body weight in six doses over three days. AL should not be used as malaria prophylaxis either alone or in combination; Persons with a previous history of reaction after using the drug, shouldn’t be used. Persons with severe and complicated malaria should not be treated with oral medications.

23. N ational malaria guideline 2022. Parasite Health post (RDT) Health centre /hospital(microscopy) p. vivax CQ + PQ (radical cure) CQ + PQ (radical cure) Uncomplicated p.falciparum AL + PQ (single dose) AL + PQ (single dose) Uncomplicated mixed infection AL + PQ (single dose) AL + PQ (radical cure) AL is not recommended for pregnant women in first trimester with uncomplicated malaria. Hence, use oral quinine in such cases . Give a single dose of 0.25 mg/kg primaquine with ACT to patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) to reduce transmission.

24. When to stop primaquine Hemoglobin < 5 g/ dL Hemoglobin drop of >50% of the baseline Hemoglobin < 7 g/ dL AND Hemoglobin drop from baseline of >25% Symptomatic anemia( fatigue, palpitation or dyspnea (shortness of breathing) on exertion Urine color: a score of 5 or above on the Hillmen urine colour chart

25. Alternate treatment for uncomplicated malaria Second-line treatment is used when the first line treatment is not available,or During failure or non-response to first-line treatment. The second line treatment for both P. falciparum and P. vivax is Dihydroartemisinin-piperaquine ( DHA-PPQ) instead of oral quinine.

26. Supportive treatment Paracetamol 15mg/kg every 4hrs if axillary temperature >37.5 (core temp. 38.5) Ibuprofen is no longer recommended because of adverse side effects. Vomiting Parenteral antimalarial treatment may be required until oral administration is tolerated. Use anti-emetics with caution because they can mask or confound diagnosis of severe malaria

27. Treatment failure Definition: failure of anti-malarial drug to resolve fever and/or parasitemia . Consider treatment failure in a patient with malaria who was treated for malaria in the past 28 days . May result from Drug resistance, Adherence Inadequate drug exposure ( i.E. From under-dosing, vomiting or unusual pharmacokinetic properties in that individual), Drug interaction, Misdiagnosis Substandard medicines .

28. Management of treatment failure If a cause is identified (e.g. anti-malarial drug is vomited), reinstitute treatment with the first-line anti-malarial drug; If a P. falciparum or P. vivax-infected patient returns with fever or history of fever between days 4 to 28 of treatment, a microscopic blood examination should be made (Note : do not use RDTs). If parasites are detected, the treatment should be changed to the second-line drug, In treatment failure after 28 days, the first-line antimalarial drug should be used; If the blood smear is negative and no other obvious causes are found, the patient should be re-evaluated , or referred to the next level of health care for proper management.

29. S evere malaria treatment Objectives To prevent the patient from dying: main Prevention of disabilities Prevention of recrudescent infection . Components of treatment Clinical assessment of the patient, Specific antimalarial treatment, Additional treatment and supportive care.

30. Clinical assessment ABC of life Asses GCS IV cannula inserted Send immediately RBS, CBC, parasitemia level, full biochemistry, blood culture, BG & Cross-matching LP for CSF analysis to rule out bacterial meningitis Avoid over or under-hydration. Empirical parenteral broad-spectrum antibiotics should be started. immediately, together with antimalarial treatment.

31. Specific antimalarial treatment Treat with intravenous or intramuscular artesunate for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of ACT. If artesunate is not available, use artemether . Quinine; if artesunate or artemether is not available or is contraindicated.

32. Artesunate and post-treatment haemolysis Delayed haemolysis starting >1 week after artesunate treatment of severe malaria has been reported in hyperparasitaemic non-immune travellers . Artesunate rapidly kills ring-stage parasites, which are then taken out of the red cells by the spleen; these infected erythrocytes are then returned to the circulation but with a shortened life span, resulting in the observed haemolysis .

33. Pre-referral treatment options Options for children <6yrs In descending order of preference: Intramuscular artesunate; Rectal artesunate(10mg/kg) Intramuscular artemether; Intramuscular quinine For older children and adults In descending order of preference: Intramuscular artesunate ; IM artemether IM quinine

34. Supportive care Frequent monitoring of vital signs, coma score and urine output. Monitor blood glucose every 4hrs Management of complications

35. Prevention Vector control: Advice the travelers to use mosquito repellent and sleeping under Long lasting insecticidal nets at night. Chemoprophylaxis is an option and mefloquine and atovaquone-proguanil can be used as anti-malarial chemoprophylaxis in Ethiopia Vaccine

36. .. WHO recommendations 2023

37. Intermittent preventive treatment of malaria in pregnancy ( IPTp ) In malaria-endemic areas, pregnant women of all gravidities Sulfadoxine-pyrimethamine (SP) has been widely used for malaria chemoprevention during pregnancy. Should start as early as possible in the second trimester and not before week 13 of pregnancy. Doses should be given at least one month apart, with the objective of ensuring that at least three doses are received. Is generally highly cost-effective, widely accepted, feasible for delivery

38. Perennial malaria chemoprevention In areas of moderate to high perennial malaria transmission, children belonging to age groups at high risk of severe malaria. Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa. Previously, PMC was recommended in infants (<12 months of age ), currently included for those 12- 24 months. Doses should be given at least one month apart.

39. Seasonal malaria chemoprevention (SMC) Is defined by the seasonality of malaria transmission and age groups at risk of severe malaria. To establish antimalarial drug concentrations in the blood that clear existing infections and prevent new ones during the period of greatest malaria risk. Is recommended in areas of seasonal malaria transmission. Sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) have been widely used for SMC in African children under 5 years. Monthly administration of SMC for 3–4 cycles in shorter transmission settings, and up to six cycles.

40. Others Intermittent preventive treatment of malaria in school-aged children ( IPTsc ), Post-discharge malaria chemoprevention (PDMC) Mass drug administration ( MDA)

41. Malaria vaccine.. The RTS,S/AS01 vaccine is the first and currently the on malaria vaccine to be recommended for use by WHO. For the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO. Should be provided in a four-dose schedule in children from 5 months of age . A five-dose strategy, in areas with highly seasonal malaria or with perennial malaria transmission with seasonal peaks. The vaccine was non-inferior to seasonal malaria chemoprevention. The combination of the vaccine and SMC was significantly better than either alone.

42. References.. Nelson textbook of pediatrics 21 st edition Uptodate 2023 WHO malaria guideline 2023 National malaria guideline 2022.

43. Thank you!!