[04.16b] Malaria (Part 2 )V2.pdf

Anemia

What is the most important clinical manifestation and issue of malaria, resulting from massive red blood cell destruction?

Red blood cell lysis

What is the main pathophysiologic mechanism in malaria?

Pallor, weakness, fatigue

Name three symptoms experienced by patients due to anemia from malaria?

Metabolic acidosis

What manifestation presents as myalgia, generalized body malaise, and rapid breathing?

Deep, labored breathing

What is Kussmaul breathing?

Rapid breathing

What breathing pattern initially occurs in metabolic acidosis to expel carbon dioxide and normalize blood pH?

Renal and respiratory systems

What two bodily systems compensate during acidosis to normalize blood pH?

Substrate-level phosphorylation

What process allows red blood cells to survive in a metabolic acidosis environment because they lack mitochondria and oxygen is depleted?

Metabolic acidosis

What environment promotes the different pathophysiologic mechanisms surrounding malarial infection?

Hypoglycemia

What very big threat in malaria patients is caused by the parasite competing with the human body for glucose?

Young patients and elderly patients

What two patient groups are more at risk for severe malaria due to fewer glycogen stores?

Liver, kidney, and muscles

Name three places where adult patients have glycogen stores?

Normotensive tachycardia

What condition explains weakness and palpitations in malaria patients as a consequence of anemia?

No volume loss

Why is the tachycardia in malaria referred to as normotensive?

Hyperbilirubinemia and thrombocytopenia

What combination of laboratory findings is highly sensitive for malaria infections in a patient with high-grade fever?

Jaundice

What clinical symptom is caused by hyperbilirubinemia due to red blood cell lysis?

Not clear

What is known about the pathophysiology of thrombocytopenia in malaria infections?

Platelets clump together, get activated, targeted, destroyed by white blood cells, and then destroyed by the spleen

What is the hypothesized fate of platelets in malaria infections?

Rashes

What clinical sign can thrombocytopenia possibly cause?

Exo-erythrocytic stage

During which stage of infection may hepatosplenomegaly be observed?

Liver

During the exo-erythrocytic cycle, which organ may exhibit enlargement (hepatomegaly)?

Spleen

During the erythrocytic cycle, which organ may exhibit enlargement (splenomegaly)?

Clear infected red blood cells

Why does the spleen work overtime during the erythrocytic cycle, leading to splenomegaly?

Impaired consciousness (including unrousable coma)

What is the clinical feature of severe malaria also known as cerebral malaria?

Prostration

What severe malaria clinical feature involves generalized weakness preventing a patient from sitting, standing, or walking without assistance?

More than two episodes within 24 hours

What defines multiple convulsions in severe malaria?

Deep breathing and respiratory distress (acidotic breathing)

What severe malaria clinical features are manifestations of metabolic acidosis?

Severe anemia and microinfarcts in pulmonary arteries and veins

What two factors cause acute pulmonary edema and acute respiratory distress syndrome in severe malaria?

< 80 mmHg

What systolic blood pressure defines circulatory collapse or shock in an adult?

< 50 mmHg

What systolic blood pressure defines circulatory collapse or shock in a child?

Renal impairment

What vital organ dysfunction is associated with high serum creatinine levels?

Abnormal bleeding

What clinical feature of severe malaria is due to thrombocytopenia?

Kidney and lung infarcts

What organ infarcts may occur due to the parasite’s adhesion proteins in severe malaria?

Metabolic acidosis and obstruction and hypoxia

Name two important pathophysiological mechanisms of severe malaria clinical features?

Cytoadherence and rosetting

What two processes involving RBC adherence cause blood vessel obstruction and hypoxia in severe malaria?

PfEMP-1

What variant surface antigen enables P. falciparum to cytoadhere and rosette?

Brain, kidneys, lungs, and liver

Name four end organs where blockage of blood vessels occurs, leading to ischemia and infarction in severe malaria?

Substrate-level phosphorylation

Ischemic cells downstream of blood vessel blockage rely heavily on what process for energy?

Anemia

What causes decreased oxygen delivery and erythropoiesis in malaria?

Bursting and lysis of red blood cells

What is the main pathophysiology of malaria that causes anemia?

Increased glycolytic requirements of the immune system

Why does the body need more glucose during malaria infection, contributing to hypoglycemia risk?

pLDH

What enzyme, present in all Plasmodium species, is useful in hypoxic, acidotic states and promotes substrate-level phosphorylation?

Wider temperature range

How does pLDH compare to human LDH regarding operating temperature?

To allow it to operate during the chills and sweating phases, not just during fever spikes

What is the adaptive advantage of pLDH having a wider temperature range?

Intraerythrocytic forms

In what forms of the parasite is pLDH present?

Plasma bicarbonate <15 mmol/l

What laboratory result indicates metabolic acidosis in severe malaria?

Hemoglobin <5 g/dl

What hemoglobin level indicates severe normocytic anemia in adults?

Packed cell volume <15%

What packed cell volume indicates severe normocytic anemia in children?

Lactate >5 mmol/l

What lactate level indicates hyperlactatemia in severe malaria?

Serum creatinine >256 micromol/l

What serum creatinine level indicates renal impairment in severe malaria?

Rupture of red blood cells

What causes severe normocytic anemia in severe malaria?

Hyperlactatemia

Metabolic acidosis in severe malaria is due to pLDH, which leads to what condition?

Fever of unknown origin

Malaria should be included in the diagnosis of what, regardless of travel history?

Blood thick and thin smears

What is the gold standard for the diagnosis of malaria?

Every 6-12 hours for 48-72 hours

How often are thick and thin blood smears performed?

To check for chronicity and paroxysm

Why are blood smears repeated every 6-12 hours for 48-72 hours?

Giemsa or Wright-stained

What two staining methods are used for blood smears?

Thick smear

Which blood smear is 20-40x more sensitive than the other?

Screening for presence of infection

What is the purpose of the thick smear?

Center of the thick smear

What part of the thick smear should be viewed for screening?

Thin smear

Which blood smear is used for parasite density quantification and species identification?

Quantify parasite density

What is the purpose of the thin smear to classify between mild and severe malaria?

Feathered edge

What part of the thin smear should be viewed for species identification and parasite quantification?

Administrative Order 2009-0001

What policy guidelines govern the use of RDTs?

Areas with no microscopy and travel time >2 hours to a diagnostic center

Name two indications for using RDTs when microscopy is unavailable?

Outbreaks and emergency cases

Name two clinical scenarios that warrant the use of RDTs?

Immuno-chromatographic antigen test

What type of test is an RDT classified as?

HRP-2 and pLDH and Aldolase

Name the three malarian proteins used in RDTs?

HRP-2

What malarian protein used in RDTs is P. falciparum-specific?

pLDH

What malarian protein used in RDTs can be P. falciparum-specific, P. vivax-specific, or pan-specific?

Aldolase

What malarian protein used in RDTs is pan-specific (present in all species)?

Maurer’s clefts

What stippling is associated with P. falciparum?

Schuffner’s dots

What stippling is associated with P. vivax?

James’ dots

What stippling is associated with P. ovale?

Zeimman’s dots

What stippling is associated with P. malariae?

Sinton and Mulligan’s dots

What stippling is associated with P. knowlesi?

P. falciparum

What species of Plasmodium infects all stages of red blood cells?

P. vivax and P. ovale

What two species of Plasmodium infect younger stage red blood cells (reticulocytes)?

P. malariae

What species of Plasmodium infects older red blood cells (crenated RBCs)?

Banana-shaped gametocyte

What morphological feature is unique to P. falciparum in a blood smear?

P. falciparum

Which species has the highest number of merozoites per schizont (~24)?

P. malariae

Which species has the lowest number of merozoites per schizont (~9)?

P. falciparum

Which species is always more dominant in co-infections with other Plasmodium species?

Irregular pattern

What characterizes the fever onset of P. falciparum?

Sudden

What characterizes the fever onset of non-P. falciparum species?

Malignant tertian

What is the periodicity of P. falciparum fever (24-48 hours)?

Benign Tertian

What is the periodicity of P. vivax and P. ovale fever (48 hours)?

Quartan

What is the periodicity of P. malariae fever (72 hours)?

Quotidian

What is the periodicity of P. knowlesi fever (24 hours)?

P. vivax

Which species has amoeboid trophozoites and enlarged parasitized RBCs?

P. malariae

Which species has trophozoites that tend to have a band shape and un-enlarged parasitized RBCs?

Oval shape with tufted ends

What characterizes P. ovale parasitized RBCs?

Chromatoidal body ("gemstone" on the ring)

What distinctive feature is noted in the P. vivax ring stage (Figure 4)?

Band form

What morphological feature is unique to P. malariae and P. knowlesi ring stages?

Early diagnosis and prompt, effective treatment

What is the priority in malaria treatment programs?

Within 24-48 hours of the onset of malaria symptoms

How quickly should treatment be provided to ensure effectiveness?

Metabolic acidosis and severe hypoglycemia

What two severe complications can lead to death within 12 hours if untreated?

Antimalarial drugs should be administered only to patients who truly have malaria

What is the principle of rational use of antimalarial drugs?

Combination therapy

What strategy involves treating malaria with at least two effective antimalarial medicines with different mechanisms of action?

To prevent antimicrobial resistance and treatment failure

What are two reasons for using combination therapy in malaria?