Case 12: Malaria Flashcards
Malaria transmission
- Caused by Plasmodium protozoa spread by the female Anopheles mosquito (Anopheles gambiae)
- Four different types: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae
Characteristics of the 4 types of malaria
- Plasmodium falciparum is the most common and severe. Causes fatal and malignant disease
- Plasmodium vivax is the most common cause of benign malaria
- P.vivax and Ovale- rarely fatal, causes dormant liver stage
- P.malarie: can cause chronic infection over years
Protective factors for malaria
Sickle cell trait, G26PD deficiency, HLA-B53, absence of Duffy antigen.
Life cycle of malaria
- Following inoculation parasites (sporozoites) pass to the liver
- In the liver they divide asexually over 7 days, maturing into Schizonts which rupture. They emerge from the liver (as Merozoites) and infect red blood cells.
- Infected RBC’s are Trophozoites. They then divide and rupture infecting more RBC. Cycles of red cell rupture link with fever pattern
- The infected red blood cells are sequestered by various tissues of the body
- Gametocytes form from Trophozoites and are taken up by feeding mosquitos to spread
Malaria liver
- Plasmodium vivax and Plasmodium ovale (but not Plasmodium falciparum) lay down Hypnozoites in the liver
- these dormant forms are not affected by conventional antimalarial drugs and can reactivate after months or years
Fever by different Plasmodium species
- Plasmodium falciparum: Irregular fever patterns without clear periodicity.
- Plasmodium vivaxandPlasmodium ovale: Tertian fever pattern (every 48 hours).
- Plasmodium malariae: Quartan fever pattern (every 72 hours).
Clinical features of malaria
- Prodromal symptoms (7-30 days): malaise, headache, fatigue, myalgia. Precedes fever
- Fever: Hallmark of malarias, appears as paroxysms- periodic episodes of fevers with chills and rigors
- GI: N+V, adbo pain, diarrhoea, Hepatomegaly sometimes
- Splenomegaly: due to clearing erythrocytes can cause splenic rupture. Particularly P.vivax
- Anaemia and Haemolysis: Haemoglobinuria (blackwater fever) is rare and due to massive intravascular haemolysis and acute renal failure
- AKI
- Dermatological: jaundice due to haemolysis or hepatic dysfunction. Rarely urticaria or purpuria
Key symptoms of malaria
- FEVER (or history of fever)- from a malaria endemic region
- Rigors
- Headache +/- confusion
- Myalgia, arthralgia
- Nausea, vomiting, diarrhoea
- Dark urine (Haemoglobinuria)
Key signs of malaria
- Fever
- Jaundice
- Pallor
- Splenomegaly and Hepatomegaly
- Altered consciousness
- Focal neurological signs
- Coma
Symptoms of P.falciparum
- Respiratory: Cough, dyspnea, chest pain, or pleural effusion with severe P. falciparum infection due to pulmonary oedema or ARDS.
- Neurological: altered mental state, seizures, ataxia or coma due to Cerebral malaria. Signs include nystagmus, cranial nerve palsies and focal neurological deficit
- DIC: petechiae, and bleeding from venepuncture sites
P.falciparum pathophysiology
- Sequestration: less flexible, electrical charge, intra-cellular adhesion. More difficult to pass through the micro-circulation. More likely to adhere to each other and vessels
- Features: Cerebral malaria (reduced GCS, seizures), Renal failure (oliguria), ARD’s (pulmonary oedema), Tissue acidosis (multi-infarct in capillary beds), Coagulopathy
Complications of malaria (indications for IV treatment)
- Cerebral involvement - reduced GCS/seizures
- Anaemia – Hb < 8g/dL
- Lactic acidosis – pH<7.3
- Renal Failure: Oliguria <0.4ml/kg/hr, Creatinine > 265 (AKI)
- Pulmonary Oedema/ARDS
- Hypoglycaemia – BM <2.2 mmol/L
- Shock – BP <90/60 (refractory to fluids)
- Bleeding/DIC
- Haemoglobinuria
Malaria: classification of severity
- Parasitaemia: determined by looking at percentage of infected cells under thin films
- UNCOMPLICATED: All of the following: Parasitaemia <2% No schizonts, No clinical complications. Oral treatment
- POTENTIALLY SEVERE: Any of the following: Parasitaemia >2%, Parasitaemia <2% with schizonts or complications
- SEVERE: Complications present, regardless of parasitaemia
Benign malaria
- P.vivax: Asia, S.America
- P.ovale: west and central Africa
- Reduced sequestration in the micro-circulation to P.falciparum
- Benign disease <2% parasitaemia
- Hypnozoites: dormant liver stage, relapsing malaria
- P.malariae: least common, never causes severe disease, may persist for decades, rare cause of nephrotic syndrome
Malaria investigations
- Blood film: gold standard. Thick is more sensitive and thin determines species. Thin film uses Geimsa stain, Thick uses field stain
- FBC: Thrombocythemia (excess platelet production), neutropoenia, normochromic normocytic anaemia, reticulocytosis
- FBC which use flow cytometry show fluorescent populations of Malaria DNA/RNA
- Quantitative Buffy Coats (QBC): Malaria fluoresce under a microscope
- Immunochromatographic Rapid Diagnostic Tests: cant differentiate between types
- PCR: sensitive but slow, done if uncertain
- Antibody detection using immunoassays or fluorescence techniques: used to screen blood donations
Routine malarial diagnosis in newcastle
- FBC
- Thick and thin film: if suspicious of malaria but negative film repeat 12-24hrs and 48hrs
- Carestart Combo Rapid Test
Pregnancy malaria
- Pregnant women are advised to not travel where malaria is endemic
- chloroquine can be taken
- proguanil: folate supplementation (5mg od) should be given
- Malarone (atovaquone + proguanil): the BNF advises to avoid these drugs unless essential. If taken then folate supplementation should be given
- mefloquine: caution advised
- doxycycline is contraindicated
Complications Malaria
- Cerebral malaria
- Seizures
- Reduced consciousness
- Acute kidney injury
- Pulmonary oedema
- Disseminated intravascular coagulopathy (DIC)
- Severe haemolytic anaemia
- Multi-organ failure and death
General advise for preventing malaria
- Use mosquito spray (e.g., 50% DEET spray)
- Use mosquito nets and barriers in sleeping areas
- Seek medical advice if symptoms develop
Treatment for severe/complicated malaria
- IV Artesunate, Quinine is 2nd line
- If delay in treatment can give Quinine till Artesunate is available
- Manage in HDU or ICU
Quinine and Artesunate
- Quinine: Can cause Cinchonism (tetanus, blurred vision, vertigo). Cardiac toxicity monitor with ECG. Started IV then continue orally with second agent (Doxycycline, Clindamycin)
- Artesunate: minimum 24hr IV therapy. Side effects: delayed post treatment haemolysis
Uncomplicated malaria treatment
- Artemether-lumefantrine: first line in the UK
- Atovaquone/proguanil (Malarone): 4 ‘standard’ tablets daily for 3 days.
- Quinine sulphate for 5 - 7 days plus doxycycline (or clindamycin for pregnant women) for 7 days
Malaria- Hypnozoite therapy
- Prevention of relapse in vivax and ovale malaria
- Primaquine for 2 weeks
- G6PD deficiency are at rusk of haemoylsis with Primaquine
Treatment of malaria
- Due to P.falciparum if uncomplicated: Riamet (artemether and Lumefantrine)
- Due to P.malariae, vivax or ovale: chloroquine plus primaquine