Malaria Flashcards
What are the factors that contribute to the burden of Malaria?
- Drug resistance (malaria)
- Insecticide resistance (vector)
- Wars and civil disturbance
- Environmental changes
- Travel
- Population increase
- Pandemic
What is it transmitted by
Anopheles mosquitoes
(others: transfusion, congenital, lab-acquired)
What is the phylum?
Apicomplexa
What parasites cause?
Intracellular parasites (Plasmodium, Toxoplasma, Cryptosporidum)
Describe Plasmodium life cycle
Sporozoite in mosquito -> Merozoite in liver -> Asexual forms in RBC/Sexual forms - Gametocytes in RBC -> Mosquito
What causes the disease?
Development of Plasmodium spp. within host red blood cells
What diagnosis to take from patient?
Clinical, travel history, presence of parasites in peripheral blood
What Plasmodium spp.?
P.falciparum, P.vivax, P.malariae, P.ovale, P.knowlesi
What is the aim of blood examination for malaria parasites?
- If patient is infected
- Level of infection
- Which is the infected species
What are the laboratory diagnostic methods?
- Rapid diagnostic test
- Microscopic examination of blood films
- Nucleic acid amplification test
Describe the use of microscopy to diagnose
- Thin and thick blood smear + staining
- Gold standard
+ve: simple, cheap, sensitive, specific, quantitative
-ve: time consuming, laborious, requires trained personnel
What is the biosafety of laboratory diagnosis?
Pathogens (Hepatitis B, HIV) potentially found in blood
What does thick smear and thin smear detect?
Thick - presence of parasite
Thin - Malaria species
What is the Giemsa staining procedure?
- Make smear
- Fix in methanol (only for thin smear) for 30s
- Add Giemsa stain 5% stock in buffered water pH 7.2 for 20 minutes
- Flush with tap water
- Dry and observe under oil immersion (x100)
Describe the use of thick blood films and how do parasites appear
- Acts as concentration method
- Trophozoites: streaks of blue cytoplasm with detached nuclear dots
- Broken or irregular rings as commas, swallows, exclamation marks
- Schizonts and gametocytes retain normal appearance
How does Plasmodium falciparum appear in THIN blood films?
Ring form: cytoplasm fine and regular in outline, double chromatin dot, accloe forms, multiple infection in single RBC
Infected RBC: same size as uninfected cell, Maurer’s dots
Schizont: fills 2/3 RBC, contains 18-24 merozoites in grape-like cluster
Gametocytes: crescentic (sausage-shaped), larger than RBC
Malaria pigment: dark brown or blackish, solid mass
How does Plasmodium vivax appear in THIN blood films?
Ring form: cytoplasm thicker, small or large rings with vacuole, usually 1 nucleus
Growing form: irregular with vacuole, amoeboid form
Infected RBC: enlarged, Schuffner’s dots
Schizont: regular, almost completely fills RBC, contains 12-24 merozoites
Gametocytes: rounded, larger than RBC, Schuffner’s dots
Malaria pigment: yellowish brown, fine granules
How does Plasmodium malariae appear in THIN blood films?
Growing form: band-like, slightly amoeboid, vacuole disappears early
Infected RBC: same size, no Schuffner’s dots
*P.knowlesi can also display band forms -> misdiagnosis
Describe the antigen-capture approaches
- Detection of malaria antigens (histidine-rich protein-2, parasite lactate dehydrogenase)
- Rapid Diagnostic Tests (immunochromatographic, cassette/card format/dipstick)
+ve: easy to perform and interpret
-ve: expensive
Describe the molecular approaches to diagnose
- PCR (design nucleic acid primers to parasite DNA, amplify by PCR, run gel to visualise bands)
+ve: rapid, can identify all 4 species
-ve: expensive, inhibitory blood products
Which Plasmodium species is the most common? What does it cause? Where is it most prevalent in?
Plasmodium falciparum - responsible for majority of deaths
- Acute febrile illness
- Sub-saharan Africa
What is the second most significant Plasmodium species?
Plasmodium vivax
Describe the pathophysiology of Malaria
- Injection of sporozoites by infected Anopheles spp. mosquito vector
- About 10-100 sporozoites injected per feeding which attracts other mosquitoes to feed
- Within 30-60 minutes, sporozoites will enter hepatocytes - liver stage infection
- Parasites undergo asexual replication (exoerythrocytic/pre-erythrocytic schizogony) resulting in production of liver merozoites (some enter dormant phase and reactivate - hypnozoites - in P.vivax/ovale/cynomolgi)
- Liver stage P.falciparum merozoites invade erythrocytes while P.vivax invade reticulocytes
- Parasite starts a tropic period (feeding)
- Early trophozoites are ring-liked shaped (ring stage) - As ring grows, morphology changes and enter trophozoite stage
- Trophozoite ingest host cell cytoplasm breaking down hemoglobin into amino acids. The by-product is hemozoin (characteristic pigmentation to blood stage malaria)
- Trophozoites enter nuclear division (start of blood stage schizont)
- Schizogeny comprises 3-5 rounds of nuclear replication (segmentation of individual merozoites)
- RBC rupture releasing merozoites which will in turn inavde uninfected RBC
- Some parasites will enter sexual cycle and differentiate into female and male gametocytes which are ingested by feeding mosquito
- In mosquito gut, they form macrogametes (female) and microgametes (male) and fuse together to form zygotes -> ookinetes -> oocysts
- Oocysts enter asexual replication -> sporozoites
- Sporozoites migrate to salivary gland and transmitted during feeding
What are the first symptoms?
High fever, headache, myalgia, nausea, diarrhoea, anaemia, jaundice, flu-like symptoms, tiredness, shaking chills and vomiting (may be mild and difficult to recognise as malaria)
Can progress to severe illness and death if not treated within 24 horus
What do children with severe malaria develop?
Severe anaemia, respiratory distress in relation to metabolic acidosis, cerebral malaria
What is symptom is frequent in adults?
Multi-organ involvement
What are the 3 stages of periodic fever paroxysms?
- Cold - nausea, vomiting, chills
- Hot (39-41.5C)
- Sweating - weakness, exhaustion
What are the symptoms associated with?
Timing of rupture of RBC and increase levels of parasite is, cytoadherance, rosetting, autoagglutination, iRBC deformability
How to control?
- Insecticide
- Impregnated mosquito nets
What is the treatment for P.falciparum?
- Artesunate-Mefloquine
- Artemether-Lumefantrine
- Dihydroartemisinin-Piperaquine
- Artesunae-Sulfadoxine-Pyrimethamine
- Artesunate-amodiaquine
How to treat Plasmodium vivax?
- Chloroquine-Primaquine in combination with
- ACTs and primaquine
How to treat severe malaria?
- Adults: artesunate 2.4mg/kg body weight IV/IM at 12 and 24 hours then daily for at least 3 days
- Children: pre-referral treatment with rectal aretsunate
- Qunine
What is used for prophylaxis? Who cannot use?
Atovaquone-Proguanil (malarone)
- pregnant or breastfeeding women
- people with severe renal impairment
