2 MALARIA. Treatment, symptoms and signs

Containes the symptoms and treatments of uncomplicated and severe malaria

1. malaria Ihemba Agatha Samapimbi Pharmacist

2. contents Definition/Overview Pathophysiology Signs & Symptoms Types of Malaria Treatment MOAs/Side effects Prevention

3. INTRODUCTION- DEFINATION Malaria is a tropical life threatening disease caused by infection of a female anopheles plasmodium protozoa. The species include: Plasmodium falciparum 98%(commonest and most dangerous) Plasmodium vivax (relapse is common) Plasmodium ovale (relapse is common) Plasmodium malariae (can persist for years) Plasmodium knowlesi (common in monkeys) Malaria in Zambia has high prevalence in the Northwestern and Luapula province. Only about 1% of malaria cases is accounted for in Lusaka province.

4. MALARIA- CORE PRINCIMPLES Programs to ensure early diagnosis and prompt, effective treatment of malaria should be initiated at least within 48 hrs. of onset of malaria symptoms because: Uncomplicated falciparum malaria can progress rapidly to severe forms of the disease, especially in people with no or low immunity, and severe falciparum malaria is almost always fatal without treatment.

5. RISK FACTORS Pregnancy Immunocompromised Children <5 years Old age >65years Splenectomy Preexisting organ failure Lack of previous exposure

6. MALARIA-PATHOPHYSIOLOGY The pathophysiology of malaria is in 3 stages: Stage 1: Infection Involves injection of sporozoites from an infected anopheles mosquito into the blood of the host Stage 2: Asexual ExoerythrocyticPhase In this stage, sporozoites target liver cell (hepatocytes) where they mature into schizoits which rapture and give birth to merozoites and hypnozoites . Hypnozoites are domant daughter cell which can cause relapses (common in P. vivax and P. ovale )

7. MALARIA-PATHOPHYSIOLOGY Erythrocytic phase Merozoites invade the RBCs and evolve into trophozoites . Trophozoites are then converted in hemozoin which digest the globin. This leads to rupture of the RBCs, more morozoites are released and the process continues. Some parasites divide into garmetocytes (micro-male & macro-female). Stage 3: Sexual ( Sporogenic ) phases A mosquito ingest the gametocytes during a blood meal. The micro penetrates the macro which forms a zygote in the stomach of the mosquito

8. MALARIA- PATHOPHYSIOLOGY The zygote becomes elongated and motile ( ookinate ) thereby being able to invade the mid-gut wall of the mosquito where it/or they develop into oocytes. Oocytes grow, rupture and release sporozoites which make their way to the mosquitos salivary gland.

9. MALARIA- SIGNS AND SYMPTOMS Uncomplicated malaria: Symptoms are generally non-specific Fever/sweats/chills Malaise Weakness Gastrointestinal complaints (nausea, vomiting, diarrhoea) Headache Back pain Myalgia Cough

10. MALARIA- SIGNS AND SYMPTOMS Severe malaria Impaired consciousness or seizures Respiratory distress or acidosis (pH < 7.3) Hypoglycaemia (2.2 mmol /l) Severe anaemia (<8 g/ dL ) Prostration (inability to sit or stand without support) Parasitaemia > 2% red blood cells parasitized Multi organ injury

11. DIAGNOSIS RDT- RAPID DIAGNOSTIC TEST Fast and easy to us Cost effective Picks antibodies against malaria MPS- MALARIA PARASITE SMEAR Slow to held results Expensive and needs skilled experts to operate it Quantifies malaria parasites hence can be used as a monitoring parameter Other parameters like FBC, Blood glucose level, Liver function tests (LFTs) , Urea and electrolytes ( U/ Es ) and Symptomatic diagnosis can also be used to determine the extent of severity

12. Uncomplicated malaria treatment NOTE: All antimalarials are dosed based on patients weight Quinine is the first line drug in the 1 st trimester of pregnancy FIRST LINE Artemether Lumefantrine 20mg/120mg Alternative: Dihydrartermisinin -piperaquine (DHA-PQ) 20mg/160mg ( Schizonticidal ) SECOND LINE Quinine 300mg

13. Uncomplicated MALARIA CHILDREN <5kg Pyrimethamine/ Sulfadoxine (refer to experts for dosing) Artemether/Lumefantrine (20/120) >5kg to <15kg 1 tablet >15kg to <25kg 2 tablets >25kg to <35kg 3 tablets >35kg 4 tablets ADULTS 4 tablets

14. severe malaria treatment FIRST LINE Artesunate Injection 60mg Artesunate Inj @ 3.0mg/kg in Children <20kg and 2.4g/kg in adults @0hrs, 12hrs, 24hrs then once daily PREPARATION Reconstitution: 1 ml Sodium bicarbonate Dilution: 5ml NaCl or Dextrose intravenously (@ rate of 3-4mls/min). Painful intramuscularly hence smaller volume must be introduced

15. severe malaria treatment SECOND LINE Quinine Inj (300mg/ml) 10mg/kg in 5% or 10% dextrose LD: 20mg/kg in 10ml of 5% or 10% Dextrose IV infusion over 4hrs for 8hrs MD: 10mg/kg tds

16. Artemisinin combinations Other artemisinin combinations other than Artemether/Lumefantrine include: artesunate + amodiaquine artesunate + mefloquine dihydroartemisinin + piperaquine artesunate + sulfadoxine –pyrimethamine COMBINATION CRITERIA Slow resistance Synergism and potentiation

17. Mechanism of action Artemether/DHA-PQ: forms an endoperoxide bridge which interacts with the heam thereby blocking conversion to haemozoins . Releases free radicle which destroys parasites. Lumefantrine prevents detoxification and the toxic heam together with free radicles jointly kill the parasites Aetersunate : causes oxidative stress to the parasite in the red blood cells Quinine: Derived from the Cinchona tree. Schizonticidal (little resistance has been reported) Funcidar : Antifolate (folate is essential for DNA replication and cell division). Works at trophozoite to early schizont stage.

18. Side effects Common are GI disturbances, cardiovascular, CNS Pyrimethamine and sulfur drugs cause anaemia, cough , hepato and renal toxicity Quinine causes, hypoglycaemia, tinnitus and earing impairment, hypersensitivity reactions, temperal blindness, thrombocytopenia, renal failure

19. Intermittent presumptive treatment Pregnancy: Funcidar ( sulfadoxine 500mg/pyrimethamine 25mg) . At least 3 doses should be given monthly starting at 16 weeks gestation. Note: Patients on co-trimoxazole prophylaxis should not receive IPT with SP (increased risk of serious adverse effects) Sicklers : Deltaprim (dapsone 100mg/pyrimethamine 12.5mg) HIV Positive Sicklers : Dapsone daily and Deltaprim once weekly HIV Positive: Cotrimoxazole ( Sulphamethoxazole 80mg/Trimethoprim 400mg) Travelers: Mefoquine , Doxycycline, atovaquone-proguanil

20. MALARIA- PREVENTION Keep grass short and surroundings clean Sleep under a mosquito net Use mosquito repellents Avoid travel to endemic areas if necessary, be on prophylactic drugs at least 2 weeks before travel and continue a week after. Wear long sleeved and long bottoms to avoid exposure to mosquito bites