Malaria 2024.pdf

Department Of Paediatrics And Child Health Niger Delta University Teaching Hospital Malaria Evinson T.D INTRODUCTION Malaria is an infectious disease caused by the parasite of the genus “Plasmodium” Plasmodium Species Commonest in Africa (98%) of ma...

Department Of Paediatrics And Child Health Niger Delta University Teaching Hospital Malaria Evinson T.D INTRODUCTION Malaria is an infectious disease caused by the parasite of the genus “Plasmodium” Plasmodium Species Commonest in Africa (98%) of malaria Falciparum Main cause of severe malaria Rapidly fatal Responsible for half of malaria cases outside Africa Vivax Contributes to malaria in horn of Africa Can cause severe malaria Mostly occurs in sub-Sahara Africa Ovale Incidence relatively low Malariae Distribution is everywhere Occurs as a zoonotic infection – Knowlesi Causes severe malaria and rapidly fatal  Global Malaria Burden (WMR 2023) Year Estimates 2020 241 million 2019 227 million 2016 217 million Endemicity of Malaria The spleen rate is the % of enlarged spleens in a sample of the population, usually children aged 2–10 years. The parasite rate is the proportion of a given population with malaria parasites in the blood. Hypoendemic Mesoendemic Spleen and parasite rates 1–10% Spleen and parasite rates 11–50%. Hyperendemic Holoendemic Spleen and parasite rates Spleen and parasite rates constantly > 50% constantly ≥ 75% with a low adult spleen rate. Parasite density decreases rapidly between 2 and 5 years of age Malaria Life Cycle (3-sites, 3-steps, 1 or 2-exit) Single Sporozoites Liver Multinucleated Asexual Phase Schizonts -I Many Merozoites Red Blood Single Trophozoites Cells Multinucleated Asexual Phase Schizonts - II Many Merozoites Zygote – Ookinete Mosquito Multinucleated Liver Exit I: Hypnozoites Sexual Phase Oocyst Many Sporozoites Blood Stream Exit II: Gametocytes P. Falciparum – Asexual Stages  Malaria Transmission Bites from infected female anopheles mosquito ○ The main method of transmission ○ Bites occur between dusk and dawn Accidental ○ Blood transfusion, needle stick injury Mother to Child ○ 1 in 20 mothers could infect their babies if they have malaria close to delivery Animal to Man ○ From close interaction with the Macaques monkeys  PATHOGENESIS Schizogony Release of new merozoites into the blood, plus Release of Plasmodium-derived hemozoin and Glycosylphosphatidylinositol (GPI) [common to merozoite surface proteins MSP-1,2 and 4 as malaria toxin Activation of macrophages and endothelial cells to secrete cytokines and inflammatory mediators like TNF, Interferon-y, IL-1, IL6 and IL8, lymphotoxin, Nitric oxide, etc Systemic manifestation of malaria In addition, the plasmodial DNA interacts with Toll-like receptor 9, resulting in prostaglandins production and fever. Human Response to Malaria Innate Genetic Acquired Humoral, Cellular, CytokineS Reticuloendothelial system polymorphisms  Classification of Malaria Uncomplicated Malaria Severe Malaria Symptomatic infection with malaria Acute falciparum malaria with parasitaemia without evidence of evidence of vital organ dysfunction vital organ dysfunction Or Patient with P. falciparum asexual parasitaemia and presence of one or more of the clinical or laboratory features listed. Clinical Features – Uncomplicated Malaria Symptoms The main manifestation is FEVER Cold Chills / Rigor Headaches and other body aches Malaise Nausea /Vomiting Joint weakness/pains Signs Fever Hepatosplenomegally Pallor Clinical Features – Severe Malaria Features Description Impaired A Glasgow coma score < 11 in adults or a Blantyre consciousness coma score < 3 in children Generalized weakness so that the person is unable to sit, stand or walk without assistance in a child who Prostration could previously do so and in the absence of impaired consciousness Multiple convulsions More than two episodes within 24 h A base deficit of > 8 mEq/L or, if not available, a plasma bicarbonate level of < 15 mmol/L or venous Acidosis plasma lactate ≥ 5 mmol/L. Clinical Features – Severe Malaria Features Description Blood or plasma glucose < 2.2 mmol/L (< 40 Hypoglycaemia mg/dL) Haemoglobin concentration ≤ 5 g/dL or a Severe malarial haematocrit of ≤ 15% in children < 12 years of anaemia age (< 7 g/dL and < 20%, respectively, in adults) with a parasite count > 10 000/Μl Plasma or serum creatinine > 265 μmol/L (3 Renal impairment mg/dL) or blood urea > 20 mmol/L Plasma or serum bilirubin > 50 μmol/L (3 Jaundice mg/dL) with a parasite count > 100 000/ μL  Clinical Features – Severe Malaria Features Description Radiologically confirmed or oxygen saturation < 92% on room air with a respiratory rate > 30/min, often with chest Pulmonary oedema in-drawing and crepitation on auscultation Including recurrent or prolonged bleeding from the nose, Significant bleeding gums or venepuncture sites; haematemesis or melena Compensated shock is defined as capillary refill ≥ 3 s or temperature gradient on leg (mid to proximal limb), but no Shock hypotension. Decompensated shock is defined as systolic blood pressure < 70 mm Hg in children or < 80 mmHg in adults, with evidence of impaired perfusion Hyperparasitaemia P. falciparum parasitaemia > 10% Clinical Features – Severe Malaria Features Description Respiratory distress Signs of respiratory distress which may be as a result of acidosis, anaemia and pulmonary oedema Haemoglobinuria Passage of cola coloured urine as a result of haemolysis CEREBRAL MALARIA Case Definition Unarousable coma: Motor response to noxious stimuli is non-localising or absent. Exclusion of other encephalopathies: E.g. Hypoglycemia, meningo- encephalitis, eclampsia, intoxications, head injuries, cerebrovascular accidents and metabolic disorders should be excluded as the cause of coma. Confirmation of P. falciparum infection: Asexual forms of P. falciparum must be demonstrated in peripheral blood or bone marrow smear during life, or in a brain smear after death.  PATHOPHYSIOLOGY Mechanical hypothesis: CM occurs as a result of microvascular obstruction with resulting hypoxia and substrate depletion. Two principal mechanisms have been proposed. 1. Decreased deformability: Of infected RBCs which allows for the RBCs to be retained in the capillaries leading to obstruction. 2. Cytoadherence: Of Infected RBCs to the microvascular epithelium. Uninfected red cells bind to the surface of red cells containing mature parasites causing ROSETTING and cerebral microcirculation obstruction Cytokines: WBC derived cytokines, particularly TNF, has been shown to play some roles via 20 mediators, e.g. NO and free O2 radicals PATHOPHYSIOLOGY  PATHOPHYSIOLOGY CONVULSIONS: ○ very high temperature, hypoglycaemia, severe anaemia or the effect of herbal concoction. HYPOGLYCAEMIA: ○ Decrease intake, increased glucose utilization, antimalarial mediated reduction, glycogen depletion or impaired gluconeogenesis. ACIDOSIS: ○ Elevated levels of lactic acid results from tissue anaerobic glycolysis, particularly in skeletal muscles.  PATHOPHYSIOLOGY RESPIRATORY DISTRESS: Heart failure resulting from severe anaemia. Pulmonary oedema (following administration of excessive fluids) Adult respiratory distress syndrome (occurs as a result of malaria parasites in the lungs and could be indistinguishable from pulmonary oedema). Acidosis causes deep and rapid respiration. Aspiration RENAL FAILURE: ○ Hypotension-shock, Acute tubular necrosis HAEMOGLOBINURIA: ○ Intravascular haemolysis HISTORY Bio data Age, place of residence, history of travel Common features of malaria Fever with chills and rigor, Body aches, body weakness etc Ask about features of severe disease Past medical history Drug history Family and Social history Use of insecticide treated nets, presence of stagnant water, bushes around residence EXAMINATION General Examination: Temperature, Pallor, hydration status, Cyanosis, Jaundice, Pedal oedema, Anthropometry Central Nervous System Assess the level of consciousness using an objective coma scale, Evidence of Seizure (motor deficits ,Posturing), Fundoscopy Respiratory System Check for respiratory distress, tachypnea, crepitations Cardiovascular Rate, volume of pulse, BP, S3, haemic murmur Abdomen Feel for the spleen and liver EXAMINATION EYE SIGNS < Diagnosis Of Malaria All suspected malaria cases should have a prompt parasitological confirmatory test using either microscopy or a malaria Rapid Diagnostic Test.  INVESTIGATIONS Bedside/sidelab investigations Random blood glucose, malaria rapid diagnostic test, Packed cell volume and urinalysis Gold standard investigation Thick and thin film for malaria parasite Supporting investigations Full blood count and Differentials Serum electrolyte, Urea and Creatinine Lumbar puncture for Cerebrospinal fluid analysis Chest x-ray Blood culture Light Microscopy Thick Blood Film Thin blood film Parasite identification Speciation Parasite density Parasite Density Rapid Diagnostic Tests Involves identification of the parasitic antigen or the anti-plasmodial antibodies or the parasitic metabolic products. ○ RDTs PfHRPII antigens pLDH enzyme ○ OTHER TESTS Polymerase Chain Reaction Detection of antibodies by Radio immuno assay, immunofluorescence or enzyme immuno assay. Notes on RDT Malaria Rapid Diagnostic Test are very useful and reliable for the diagnosis of malaria. They offer the following qualities Accessible everywhere at anytime; useful at all health facilities Fast. Results available within -15 minutes Easy to perform Reliable; The result can be trusted to guide treatment Can be deployed to the lowest health facility levels May also identify non-falciparum species But have a very limited role in monitoring response to treatment Note: mRDT is NOT a screening test. It is a diagnostic test Rapid Diagnostic Tests` Detects specific antigens (proteins) produced by malaria parasites These antigens are present in the blood of infected or recently infected people. The RDT signifies their presence by a colour change on nitrocellulose strip RDTs: pLDH Based Test Dip stick coated with monoclonal antibodies against the intracellular metabolic enzyme parasite lactate dehydrogenase (pLDH) Allows for speciation between the pLDH isoforms. pLDH is produced only by live parasites, Hence the ability to differentiate live from dead organisms  HOW TO USE mRDT 1. Read the manufacturer’s instruction 2. Wear your latex gloves. 3. Open an RDT cassette and write the name of the patient and date. 4. Swab patient’s fourth finger (the left hand of a right handed person) with methylated spirit and allow to dry (this will ensure that the patient’s blood collects and not spread around the finger). 5. Take an unused lancet and prick the tip of the swabbed finger and discard lancet in the sharps quickly (do not re-cap the lancet). 6. Get the blood transfer device and collect the recommended volume of blood 7. Dispense the blood in the well (allow the transfer device to touch the pad in the blood well before releasing the content so that the blood collected is deposited fully – insufficient blood can give a false result). 8. Dispose blood transfer device immediately (do not leave on your table) 9. Put the recommended drops of buffer in the buffer well (ensure that the buffer container faces the well vertically, a little above the RDT cassette – do not allow buffer to spill on the side of the well) 10. Note the time immediately by writing the start time on the cassette. Also indicate the stop time by adding the recommended time for the test. For example, if you were to read the test result after 15 minutes, add 15 minutes to the start time to get the stop time. 11. Interpret the result at the recommended time and not after as this could give you a false result  HOW TO USE mRDT - Video https://drive.google.com/file/d/1f1QrPpjDmxYN0n-jJzVGDa0o0GJ8HaGI/view?usp=share_link Differential Diagnosis Meningitis Viral haemorrhagic fever Septicaemia Pneumonia Typhoid fever TREATMENT – UNCOMPLICATED MALARIA Artemisinin-based combination therapies (ACTs) are the recommended treatments for uncomplicated Plasmodium falciparum malaria. Arthemeter-Lumefantrine (AL), Artesunate-Amodiaquine (AA) and Dihydroartemisinine Piperaquine (DHP)are the medicines of choice for the treatment of uncomplicated malaria in Nigeria  TREATMENT – UNCOMPLICATED MALARIA Artemether-lumefantrine ○ 1.5/9 mg/kg twice daily for three days Artesunate-Amodiaquine ○ Artesunate 4 mg/kg + Amodiaquine 10mg base/kg once daily for 3-days Dihydroartemisinin+ piperaquine ○ In children