Updated Guidelines on Malaria Case Management

Updated Guidelines on Malaria Case Management

1. Updated Guidelines on Malaria Case Management 2023 NMEP Online Training Initiative Dr. Paul Boateng, NMEP

2. Introduction Classification Clinical Management Of Uncomplicated Malaria Treatment of Uncomplicated Malaria In Pregnancy Treatment Failure Recurrent p.f . malaria, relapse malaria Management of severe malaria Malaria chemoprevention for non-immune travelers Other Chemopreventive interventions Outline 2

3. Malaria is one of the Commonest Conditions in Ghana 12 million suspected cases of Malaria in 2021 (41% OPD cases) Over 5.7 million confirmed cases 2021 (20% OPD Cases) 21% of all admissions is due to malaria Malaria is endemic in Ghana/ entire population is at risk High risk- Children 5yrs, Pregnant women, Non-immune, immunocompromised (HIV, DM etc.), comorbidities-e.g., SCD Economic cost One of the Highest disease expenditure- NHIS GDP reduction by 0.25 - 6% Introduction (1) 3

4. Introduction (2) Caused by a parasite (plasmodium) 5 plasmodium species cause illness(malaria) in man: P. falciparum mono infection 97.4% P. malariae mono infection 1.1 % P. ovale mono infection 0.8% P. vivax P. knowlesi has recently been identified in Malaysia but not yet identified in Ghana 3 main modes of transmission Mainly bite of infective female anopheles mosquito An accidental transmission via blood transfusion or needle stick injury Congenital transmission from mother to child during pregnancy or parturition

5. Malaria Life Cycle 5

6. Progress with Malaria Control in Ghana (1) 6 Malaria Parasite Prevalence Among Children 6-59months in Ghana, 2011-2022

7. Progress with Malaria Control in Ghana (2)

8. Malaria Control Interventions in Ghana MVIP

9. Changes in Malaria Case Management Guidelines Changes to malaria treatment guidelines are made based on: Research findings Practice observations Malaria burden/ programme goals and objectives WHO recommendations etc. Some major changes in malaria guidelines include Change from chloroquine to ACTs Change from quinine to inj. Artesunate for severe malaria management From presumptive treatment to 3T policy (Test, Treat and Track) Current update on malaria case management Current update in February 2023 from the 2019 update This presentation will highlight the current guidelines, pointing out key changes to the guidelines

10. Classification of Malaria Uncomplicated malaria Fever or recent history of fever (past 2-3 days) No severe disease or evidence of vital organ dysfunction Positive malaria diagnostic test (RDT or Microscopy) Severe Malaria Fever Severe disease or evidence of vital organ dysfunction ( 1 or more ) Positive malaria diagnostic test (RDT or microscopy) The delay in diagnosis and inappropriate treatment of uncomplicated malaria

11. Signs of Severe Disease (IMCI): Inability to drink Vomiting everything Presence of convulsions Lethargy/ gen. weakness Unconsciousness Vital Organ Dysfunction (Signs) Brain/CNS Convulsions, unconsciousness, confusion, restlessness, lethargy Lungs Difficulty breathing, deep breathing, respiratory distress Heart: Shock: low BP, weak rapid pulse, cold extremities Liver Hypoglycemia, Jaundice Kidney Decreased urine output (< 0.5ml/kg/h over at least 6 h) *dark-colored urine Hematological Severe anemia, abnormal bleeding General Severe dehydration (sunken eyes etc.), high temp/ hypothermia, prostration, gen. weakness Signs/Symptoms of Severe Disease/ Vital Organ Dysfunction

12. Severe anaemia Hb <5g/dl for children or Hb <7g/dl for adults Hypoglycemia Treat for hypoglycaemia if blood sugar is <3mmol/L Renal Impairment High serum creatinine levels High Serum Urea levels Jaundice Plasma or serum bilirubin >50µmol/L Metabolic Acidosis Plasma bicarbonate <15mmol/L Hyperlactataemia Lactate > 5mmol/L Haemoglobinuria Positive blood on urine dip stick plus no RBCs in urine deposit Hyperparasitemia >500,000 p/ uL for Immune >100,000 p/ uL for Non-immune Pulmonary oedema Chest x-ray suggestive Lab Features of Severe Disease/ Vital Organ Dysfunction (Severe Malaria)

13. Malaria in Pregnancy- *Complications Pregnant women at increased risk of severe malaria Bleeding in pregnancy Miscarriage Preterm labor PPH Low birth weight, still birth etc. Hypoglycemia, Pulmonary edema*

14. Uncomplicated Malaria is confirmed by either; Microscopy (GOLD STANDARD) Quantitative test It is done by reporting on species, stage and parasite density when positive And reported No Malaria Parasites(No MPs) seen when Negative mRDT (Malaria Rapid Diagnostic Test) Qualitative test Reported as either Positive or Negative EITHER ONE CAN BE USED TO CONFIRM THE DIAGNOSIS Laboratory investigations 14

15. If test is positive Diagnosis of uncomplicated malaria is confirmed If test is negative Malaria is unlikely Investigate for other causes of the fever or illness If test is negative and you still strongly suspect malaria, you can conduct a different malaria test from the 1 st (RDT/Microscopy), repeat the test the ff. day, counsel patient for a short review date. Diagnosis of Uncomplicated Malaria 15

16. Note: Don’t delay start of parenteral antimalarial START PARENTERAL Antimalarial immediately High parasitemia is not always present in severe disease, and the initial diagnostic test may be negative Where there is high clinical suspicion of malaria, the test should be r epeated at 12 hourly intervals up to 3 times within 24 hours(i.e., 0hr, 12hr and 24hrs) but rule out other differential diagnoses and this should not delay treatment 16 Diagnosis of Severe Malaria

17. Treatment of Uncomplicated Malaria

18. Treatment Objective The clinical objectives of treating uncomplicated malaria are to: cure the infection as rapidly as possible (Cure is defined as the elimination of all parasites from the peripheral blood) prevent progression to severe disease The public health objectives of treatment are to: prevent onward transmission of the infection to others prevent the emergence and spread of resistance to antimalarial drugs Treatment of Uncomplicated Malaria 18

19. Specific antimalarial treatment Supportive treatment Counselling Follow-up care Principles of Treatment 19

20. Treatment of Uncomplicated Malaria General Population 1 st line treatment options ASAQ, AL, Artesunate- Pyronaridine (AP) 2 nd line treatment option DHAP Pregnancy 1 st trimester AL Other ACTs except AP (ASAQ, DHAP) Quinine Clindamycin (QC) 2 nd, 3 rd Trimester and Puerperium ASAQ, AL, DHAP (but not AP) QC

21. Malaria Treatment Failure Treatment failure (recrudescence) operationally is the recurrence of asexual parasitemia within 4 weeks (28 days) after treatment due to recrudescence Treatment failure may be due to: Inadequate exposure to the drug- sub-optimal dosing poor adherence vomiting Substandard medicines Drug-drug interactions etc. True treatment failure (therapeutic failure)- suspect drug resistance or unusual pharmacokinetics

22. Managing Malaria Treatment Failure Remember: Need to prove treatment failure with Microscopy!! REFER Look out for other causes of fever!! True treatment failure (therapeutic failure): Give alternate 1 st line ACT / 2 nd line ACT (i.e. DHAP) Other forms of treatment failure (i.e., vomiting, non-compliance, under dosing, poor quality medicine etc.): Repeat same ACT (1 st line) or Alternate 1 st line ACT

23. Reinfection Reinfection operationally, parasitemia occurring after 4 weeks (28 days) of previous treatment Treatment: 1 st Line: ASAQ or AL or AP

24. Treatment of P. Ovale , P. Vivax (Relapse Malaria) Treat with ACTs + Primaquine To clear the hypnozoites in the liver Primaquine dosage regimen depends on G6PD status Primaquine is contra-indicated in: Pregnant women Infants less than 6 months old Mothers who are breastfeeding infants less than 6 months old Mothers breastfeeding older infants (>6 months old) whose G6PD status is unknown

25. Treatment of P. Ovale , P. Vivax (Relapse Malaria) No G6PD deficiency Primaquine 0.5mg/kg base daily for 7 days G6PD deficiency 0.75mg/kg base weekly for 8 Weeks Unable to conduct G6PD testing Weight risks against benefits Monitor closely

26. Treatment of relapse malaria 26

27. Comparing Qualitative and Quantitative G6PD Tests

28. Treatment of Severe Malaria

29. Prevent the patient from dying Prevent other complications Prevent disabilities Prevent recrudescent infection/drug resistance Specific Objectives in the Management of Severe Malaria 29

30. Management of severe malaria comprises: Resuscitation (Clinical assessment of the patient for urgent treatment of life- threatening problems) Specific antimalarial treatment Supportive care Counselling Follow-up care Referral Severe Malaria- Principles of Management 30

31. Specific Antimalarial All patients with Severe Malaria Must be ADMITTED at a HOSPITAL for PARENTERAL antimalarials Parenteral antimalarials MUST be given for at least 24 hours before switching to Oral medications (recommended ACTs for 3 days) The Preferred order for antimalarials and their route of administration is: IV Artesunate IM Artesunate Supp Artesunate (<25kg or <6years) IM Artemether IV Quinine infusion IM Quinine

32. Severe malaria in Pregnancy All patients with Severe Malaria Must be ADMITTED at a HOSPITAL for PARENTERAL antimalarials Parenteral antimalarials MUST be given for at least 24 hours before switching to Oral medications (recommended ACTs for 3 days) The Preferred order for antimalarials and their route of administration is: IV Artesunate (all trimesters) IM Artesunate (all trimesters) IM Artemether (second, 3rd trimester and puerperium) IV Quinine infusion (all trimesters) IM Quinine (all trimesters)

33. Severe Malaria Referral (Treatment) Pre-referral treatment (in order of preference) IM Artesunate or Rectal Artesunate (for under 6 years only) IM Artemether or IM Quinine

34. Treatment failures (Severe Malaria) Severe malaria treatment failure with injection artesunate: IV Artesunate+ IV Quinine

35. Reducing Transmissibility of P. falciparum Malaria in low transmission areas 35

36. In low transmission areas ACTs are ineffective in clearing matured gametocytes. A single low dose of primaquine at 0.25 mg base/kg (maximum 15mg) is effective and unlikely to cause serious toxicity in individuals with any of the G6PD-deficiency variants. Added on the first day of ACT administration, preferably as DOT Do not give to Pregnant women, breastfeeding mothers, infants Clinically significant haemolysis is not expected to occur at this dose, hence no need for systematic testing for G6PD deficiency before administering the dose Reducing Transmissibility of P. falciparum Malaria 36

37. Deliberate deployment of MFT Deliberate deployment of multiple-first line Therapy (MFT) i.e. use of more than one 1 st line drug simultaneously Previously no recommendation on deliberate deployment* New recommendations- deliberately deploy MFT, take appropriate remedial measures to prevent drug resistance E.g. of ways/strategies to deliberately deploy MFT Geographic approach- deploy different mixes in different areas of a country Rotational approach– rotate 1 st lines e.g. every 3 months Age-based model– different age groups use different 1 st lines

38. Malaria Chemoprophylaxis for Non-immune travelers 38

39. DRUG DOSAGE ADVERSE EFFECTS COMMENTS Atovaquone-Proguanil combination tablet 11–20 kg: 62.5 m g atovaquone plus 25mg proguanil   21 – 30kg: 125 m g atovaquone plus 50mg proguanil   31-40kg:187.5 m g atovaquone plus 75mg proguanil >40kg: 250 m g atovaquone plus 100mg proguanil Common: Nausea, vomiting, abdominal pain, diarrhoea, increased liver enzyme level   Rare: Rash, Mouth ulcers, Seizures   Contraindication: -Hypersensitivity -Severe renal insufficiency Duration: Start 1 day before departure and continue for 7 days after return   -Not recommended for Pregnancy and Lactating mothers -Not recommended in <11kg -Take with food or milky products -may interfere with Rifampicin, Rifabutin, Metoclopramide, Tetracycline, Live Typhoid vaccine 39 Chemoprophylaxis for non-immune travelers

40. DRUG DOSAGE ADVERSE EFFECTS / CONTRAINDICATION COMMENTS Doxycycline Paediatrics: 1.5mgsalt/kg daily   Adult: 100mg daily   Common: Abdominal discomfort, photosensitivity   Rare: Worsening of renal function, blood dyscrasias, oesophageal ulceration Contraindication: Pregnant women and lactating mothers -Children < 8 years - Hypersensivity to Tetracyclines, including Doxycycline -Liver dysfunction Duration: Start 1-2 day before departure and continue for 4 weeks after return   -increase susceptibility to sunburn (use protection) -increase risk of candida infection -Should be taken with plenty water   40 Chemoprophylaxis for non-immune travelers

41. DRUG DOSAGE ADVERSE EFFECTS / CONTRAINDICATION COMMENTS Mefloquine Paediatric: 5mg/kg weekly   Adults: 250mg once weekly     Common: nausea, vomiting, diarrhoea, dizziness, headache, sleep disorders, nightmares, mood change   Rare: seizures, abnormal coordination, forgetfulness, anxiety, aggression, depression, Panic Attacks, Psychotic and Paranoid reactions, Suicidal ideation, Suicide (STOP THE DRUG) Contraindication: Hypersensitivity -Psychiatric Disorders (Depression, Seizure Disorder, Severe Neuropsychiatric disease) -Concomitant Halofantrine treatment -Treatment with Mefloquine in the previous 4 weeks Duration: Start at least 1 week (preferably 2-3 weeks before departure and continue for 4 weeks after return   -Safe in Pregnancy and Lactating mothers -Not recommended for children <5kg -Not to be given within 12 hours of quinine treatment -Not to be given with Oral Typhoid vaccine 41 Chemoprophylaxis for non-immune travelers

42. Use of Herbal Antimalarials MoH list of recommended herbal antimalarial medicines Must contain one or a combinations of the ff. medicinal plants: Cryptolepis sanguinolenta Morinda lucida Khaya senegalensis Cassia occidentalis and Azadirachta indica. All approved by the FDA- several brand names Not recommended for: Persons less than 12 years Severe malaria management Pregnant women Lactating mothers P. vivax and P. ovale treatment

43. “ New” Interventions – NMESP 2024-2028 Chemopreventive Interventions Intermittent Preventive Treatment of Malaria in School Children ( IPTsc ) Post discharge malaria chemoprevention (PDMC) Mass Drug Administration (MDA) 43

44. Conclusion: Summary of Key Changes Expanded list of 1st line treatment options Introduction of Artesunate Pyronaridine (AP) ACT use in the 1 st trimester of pregnancy Introduction of low dose primaquine for gametocyte clearance in low transmission areas Revision of primaquine for p. vivax and p. ovale radical cure/ treatment - 0.5mg/kg daily for 7 days More specific guidelines on use of herbal antimalarials MoH list of recommended herbal medicines for malaria included Inj. Artesunate + Inj. quinine for Inj. Artesunate failures Need to deploy deliberate efforts to prevent resistance development ( multiple first-line therapy )

45. Thank You