CS1 - NTD 1a Malaria Flashcards
What is malaise?
A general feeling of being ill or having no energy, or an uncomfortable feeling that something is wrong and cannot be changed.
What is myalgia, and what tissues can it involve?
Myalgia is muscle aches and pain, which can involve ligaments, tendons, and fascia—the soft tissues connecting muscles, bones, and organs.
Why is myalgia often observed in the lower limbs?
The lower limbs are frequently used and bear the body’s weight, leading to greater stress and susceptibility to pain and inflammation.
What is diaphoresis?
Sweating, especially to an unusual degree, as a symptom of disease or a side effect of a drug.
What are rigours?
Episodes where temperature rises rapidly, accompanied by severe shivering and a feeling of coldness (chills), often associated with high fever.
What is jaundice, and what causes it?
A condition where the skin, whites of the eyes, and mucous membranes turn yellow due to high bilirubin levels, a product of haemoglobin breakdown.
Is there a commercially available malaria vaccine for travelers?
No, there is currently no commercially available malaria vaccine for travelers.
What is dyspnoea?
Difficulty in breathing and the feeling of not getting enough air.
What is a differential diagnosis?
The process of distinguishing a particular disease or condition from others that present with similar clinical features.
What is pre-exposure prophylaxis (PrEP)?
PrEP involves taking medication before exposure to a pathogen to reduce the risk of infection, commonly used for diseases like malaria and HIV.
How does PrEP work in malaria prevention?
Travelers take antimalarial drugs (e.g., doxycycline or atovaquone-proguanil) before traveling to endemic areas to prevent the establishment of infection if exposed to Plasmodium parasites.
What is post-exposure prophylaxis (PEP)?
PEP involves taking medication after potential exposure to a pathogen to prevent the development of disease, such as after a needle-stick injury or high-risk exposure to HIV.
How is PEP used for malaria?
A: PEP for malaria is not standard but could involve starting antimalarial treatment soon after a suspected exposure, especially if symptoms arise, to prevent severe disease.
What is the primary goal of PrEP and PEP in infectious diseases?
The goal is to prevent infection or the progression of disease in individuals at risk of or recently exposed to a pathogen.
What is cerebral malaria?
Cerebral malaria is characterized by unrousable coma with peripheral Plasmodium falciparum parasitaemia >2%, after excluding other causes of encephalopathy.
What defines severe anaemia in malaria?
Severe anaemia involves normocytic, normochromic anaemia with hemoglobin (Hb) ≤80 g/L (normal 120-180 g/L) and haematocrit <15% (normal ~35-50%).
What is respiratory distress in severe malaria?
Respiratory distress includes pulmonary oedema or acute respiratory distress syndrome (ARDS), rapid labored ‘acidotic’ breathing, and acidosis (blood pH < 7.3).
How is renal failure in malaria defined?
Renal failure is characterized by urine output <400 mL/day (normal 800-2000 mL/day) and serum creatinine >3 mg/dL (normal 0.5-1.2 mg/dL).
What is considered hypoglycemia in severe malaria?
Hypoglycemia is a blood glucose level <2.2 mmol/L (normal fasting 3.9-5.6 mmol/L).
What is intraerythrocytic asexual reproduction in P. falciparum?
t is the process by which Plasmodium falciparum replicates within red blood cells (RBCs), consuming host hemoglobin (Hb) to sustain its growth.
How much of the host hemoglobin can P. falciparum consume?
t can consume up to 80% of the host hemoglobin.
What cytotoxic byproduct is released during hemoglobin consumption by P. falciparum?
Hemoglobin consumption releases free haem, which is a prooxidant and cytotoxic molecule.
How does P. falciparum mitigate the toxicity of free haem?
The parasite converts free haem into insoluble crystalline haemozoin, neutralizing its toxic effects
What is the proposed mechanism of action for quinine as an antimalarial?
Quinine is thought to inhibit nucleic acid and protein synthesis, as well as glycolysis. It specifically inhibits purine nucleoside phosphorylase and prevents haemozoin formation.
What stages of the Plasmodium life cycle does quinine target
Quinine acts as a blood schizonticide, targeting the blood stages of the parasite, but it has no lethal action on sporozoites or liver stages.
Is the precise mechanism of action for quinine fully understood?
No, the precise mechanism of quinine’s antimalarial activity is poorly understood.
What is the therapeutic index of quinine, and why is it significant?
Quinine has a low therapeutic index, meaning the margin between therapeutic and toxic doses is narrow.
What are mild adverse effects associated with quinine?
Mild effects include cinchonism, characterized by tinnitus, impaired hearing, headache, and nausea.
What are more severe adverse effects of quinine?
Severe effects include vertigo, vomiting, abdominal pain, diarrhea, marked auditory loss, and loss of vision (anticholinergic effects).
What is a particularly concerning adverse effect of quinine, especially in pregnant women?
Hypoglycemia is a significant concern, particularly in pregnant women.
What are less frequent but serious adverse effects of quinine?
Rare but serious effects include skin eruptions, asthma, thrombocytopenia, hepatic injury, and psychosis.
Why does quinine’s use face challenges despite its historical importance?
Quinine’s use is challenged by its poor tolerability, the complexity of dosing regimens, and the availability of more efficacious drugs.
How long has quinine been used as an antimalarial?
Quinine has been an important antimalarial for over 400 years since its effects were first documented.
What is “causal prophylaxis” in the context of malaria prevention?
Causal prophylaxis targets the early stages of malaria infection, specifically the liver stages (hepatic schizonts), preventing the development of blood-stage parasites.
What is “suppressive prophylaxis”?
Suppressive prophylaxis targets the blood-stage parasites of malaria, preventing the disease symptoms but not the initial liver-stage infection.
Why is bite prevention critical in malaria prophylaxis?
Bite prevention reduces the risk of being infected by Plasmodium species transmitted through the bite of an infected Anopheles mosquito.
What measures are used for bite prevention in malaria prophylaxis?
Measures include the use of insecticide-treated bed nets, wearing protective clothing, and applying insect repellents.
What is schizogony in the context of malaria?
Schizogony is the asexual reproduction process where the parasite divides within host cells, leading to the production of merozoites, which are released into the bloodstream to infect red blood cells.
What are hypnozoites in malaria?
Hypnozoites are dormant liver-stage forms of Plasmodium vivax and Plasmodium ovale that can remain in the liver for long periods and reactivate later, causing relapses of malaria.
Which species of Plasmodium are associated with relapsing malaria?
Plasmodium vivax and Plasmodium ovale are associated with relapsing malaria due to the presence of hypnozoites.
Why is malaria caused by P. vivax and P. ovale considered relapsing?
These species can form hypnozoites in the liver that remain dormant and later reactivate, leading to relapse of malaria after months or years.
What is causal prophylaxis in the context of malaria chemoprophylaxis?
Causal prophylaxis targets the liver stage of the parasite, which takes approximately 7 days to develop, preventing the parasite from progressing to the blood stage.
What is suppressive prophylaxis in malaria prevention?
Suppressive prophylaxis targets the red blood cell stages of the malaria parasite, preventing the multiplication of merozoites in the blood.
What is post-travel presumptive anti-relapse therapy?
Post-travel presumptive anti-relapse therapy targets the latent hypnozoite liver stages of Plasmodium vivax and Plasmodium ovale, preventing relapses months after infection.
How do haemoglobinopathies confer resistance to malaria?
Haemoglobinopathies such as G6PD deficiency, sickle-cell disease, and thalassaemias confer resistance through mechanisms including reduced erythrocyte invasion by the parasite, decreased intra-erythrocytic parasite growth, enhanced phagocytosis of infected erythrocytes, and increased immune response.
How do haemoglobinopathies affect the invasion of the parasite in red blood cells?
Haemoglobinopathies cause alterations in red blood cell surface and cytoskeletal proteins, which hinder the malaria parasite’s ability to invade erythrocytes.
How do haemoglobinopathies decrease intra-erythrocytic parasite growth?
n conditions like sickle-cell disease and thalassaemia, the altered red blood cell environment reduces the ability of the malaria parasite to grow within the erythrocytes.
How is the immune response enhanced in individuals with haemoglobinopathies?
: Individuals with haemoglobinopathies exhibit an enhanced immune response that leads to the faster phagocytosis of parasite-infected erythrocytes.
Why are haemoglobinopathies a significant global health concern?
Haemoglobinopathies, while providing resistance to malaria, are also a major health problem worldwide due to their association with severe anemia and other related health complications.
How does G6PD deficiency impart resistance to malaria?
G6PD deficiency provides resistance to malaria by reducing the invasion and growth of the malaria parasite in red blood cells due to the altered cellular environment, including reduced oxidative stress that the parasite requires for survival.
Why are some drugs contraindicated in G6PD-deficient patients?
Some drugs are contraindicated in G6PD-deficient patients because these drugs can cause oxidative stress, leading to hemolytic anemia, a condition in which red blood cells are destroyed faster than they can be replaced.
What is G6PD and its role in the body?
G6PD (Glucose-6-phosphate dehydrogenase) is a cytoplasmic housekeeping enzyme found in all cells. It plays a vital role in protecting cells from oxidative damage by preventing the accumulation of reactive oxygen species.
How does the lack of G6PD lead to hemolytic anemia?
In G6PD deficiency, the inability to neutralize oxidative stress leads to damage in red blood cells, causing their premature destruction (hemolysis) and resulting in hemolytic anemia.
What role does G6PD play in cellular metabolism?
G6PD catalyzes the rate-limiting first step of the pentose phosphate pathway, producing NADPH, which is essential for the synthesis of reduced glutathione (GSH).
Why is NADPH important for the cell?
NADPH is critical for the synthesis of reduced glutathione (GSH), one of the body’s most potent antioxidants, which helps protect cells from oxidative damage.
What is the pentose phosphate pathway, and what is its function?
The pentose phosphate pathway is a metabolic pathway that generates NADPH and ribose-5-phosphate, which are essential for antioxidant defense and nucleotide biosynthesis, respectively.
What happens when G6PD is deficient in the body?
In G6PD deficiency, the production of NADPH is impaired, leading to reduced levels of reduced glutathione (GSH), making cells more vulnerable to oxidative damage and resulting in conditions like hemolytic anemia.
Why are erythrocytes particularly vulnerable to reactive oxygen species (ROS)?
Erythrocytes are vulnerable to ROS because they are involved in oxygen transport and cannot replace cellular proteins once they are mature, leaving them more susceptible to oxidative damage.
What can result from inherited deficiencies of G6PD?
Inherited G6PD deficiency can lead to acute hemolytic anemia, particularly during conditions that cause increased ROS production.
How do antimalarial agents affect patients with G6PD deficiency?
Antimalarial agents are strongly associated with inducing hemolytic anemia in patients with G6PD deficiency, making caution necessary when prescribing these drugs.
Why should caution be exercised when prescribing antimalarial drugs to patients with G6PD deficiency?
Due to the increased risk of inducing hemolytic anemia, which can be triggered by oxidative stress in patients with G6PD deficiency, caution is required when prescribing antimalarial drugs.
How does G6PD deficiency affect erythrocytes during parasite invasion?
While parasite invasion to both G6PD-deficient and normal erythrocytes is similar, low G6PD levels in G6PD-deficient erythrocytes make parasitized cells more prone to damage and highly susceptible to phagocytosis.
What is the consequence of early phagocytosis of G6PD-deficient parasitized erythrocytes?
Early phagocytosis of G6PD-deficient parasitized erythrocytes occurs, limiting parasitaemia and reducing the pathogenic consequences of parasitized erythrocytes in the microcirculation.
How does G6PD deficiency impact the pathogenic consequences of parasitized erythrocytes?
G6PD deficiency results in earlier phagocytosis of parasitized erythrocytes, limiting the parasitaemia and reducing the negative effects on the microcirculation compared to normal parasitized erythrocytes.
What is sickle cell disease (SCD)?
Sickle cell disease (SCD) refers to a group of symptomatic disorders associated with the abnormal hemoglobin, HbS, leading to altered erythrocyte shapes and function.
Why is the sickle cell gene perpetuated in malarious regions?
The sickle cell gene is perpetuated in malarious regions because heterozygotes (HbAS) have increased resistance to malaria, providing a survival advantage in areas where malaria is endemic.
How does sickle cell disease affect erythrocytes?
In sickle cell disease, intra-erythrocytic HbS polymers lead to alterations in the shape of erythrocytes, causing them to resemble a “sickle” shape, impairing their function and leading to potential blockages in blood flow.
What are the genotypes associated with sickle cell disease?
The homozygous form of sickle cell disease is HbSS, which is fatal early in life without proper treatment. The heterozygous form is HbAS, which is associated with increased resistance to malaria.
How does HbAS genotype provide protection against malaria?
The HbAS genotype confers up to 90% protection against malaria by inhibiting intra-erythrocytic parasite growth through HbS polymerization, which affects the parasite significantly under deoxygenating conditions.
How does HbS polymerization affect malaria parasites?
HbS polymerization alters the nature of hemoglobin in deoxygenating conditions, which significantly impacts the malaria parasite’s ability to survive and replicate within the erythrocyte.
What happens to parasite-infected sickle cell erythrocytes compared to normal erythrocytes?
Parasite-infected sickle cell erythrocytes are more prone to phagocytosis by host immune cells, and they exhibit lower cytoadherence, meaning they do not stick to blood vessel walls, which protects against severe malaria complications.
What is the pathogenesis of thalassaemia?
Thalassaemia involves altered globin chain synthesis, leading to ineffective erythropoiesis, increased haemolysis, and deranged iron homoeostasis.
In which regions is thalassaemia prevalent, and why?
Thalassaemia is found in high prevalence in the Mediterranean, Southeast Asia, and the Pacific, likely as an adaptive response to malaria.
How does thalassaemia provide protection against malaria?
Thalassaemia may reduce parasite invasion and growth in red blood cells (RBCs), though the precise molecular mechanisms remain unclear. Studies suggest reduced binding of parasitized RBCs to endothelial cells, enhanced anti-malarial antibody binding, and increased phagocytosis of parasitized RBCs, which result in better immune clearance.
What are some observed immune responses in individuals with thalassaemia and malaria?
Individuals with thalassaemia show greater anti-malarial antibody binding to parasitized RBCs and increased phagocytosis, contributing to enhanced immune clearance of the parasite.
How does the instability of hemoglobin (Hb) or globin chain imbalance affect the intracellular environment in thalassemia and sickle cell disease (SCD)?
Instability of Hb or globin chain imbalance leads to oxidative stress within the erythrocytes, creating a hostile intracellular environment.
What role does oxidative stress play in the pathogenesis of thalassemia and sickle cell disease?
Oxidative stress contributes to the pathogenesis of both thalassemia and SCD, potentially damaging red blood cells and altering their function.
How does oxidative stress contribute to protection from malaria in thalassemia and sickle cell disease?
The hostile oxidative intracellular environment in thalassemia and SCD is likely to contribute to the protection against malaria by affecting the parasite’s ability to grow and survive within the red blood cells.
How long does immunity to malaria last for adults who grew up in malarious areas?
Immunity to malaria in adults who grew up in malarious areas disappears within 6 months of the last exposure to malaria.
What is the malaria risk for individuals returning to malarious areas after losing immunity?
The risk for individuals returning to malarious areas is the same as for first-time travellers, as their immunity has diminished.
How does natural infection contribute to immunity to malaria?
Over time, natural malaria infection elicits a robust immune response against the blood stage of the parasite, providing protection against future infections.
What is the cause of the symptoms and signs in uncomplicated malaria?
In uncomplicated malaria, symptoms are caused by the periodic rupture of red blood cells (erythrocytes) infected with Plasmodium parasites, leading to the release of toxic by-products, such as hemozoin, and the immune response to these by-products. This results in fever, chills, malaise, myalgia, and headache.
What immune response is triggered in uncomplicated malaria?
The immune system responds to the release of parasite antigens during the rupture of infected erythrocytes. This activates cytokine production, leading to fever and systemic inflammation, contributing to symptoms such as chills and fatigue.
What are the pathophysiological mechanisms involved in severe malaria?
Severe malaria, especially caused by Plasmodium falciparum, is associated with high parasitemia, impaired microcirculation, and sequestration of parasitized erythrocytes in capillaries. This leads to complications such as cerebral malaria, severe anemia, respiratory distress, renal failure, and coagulation abnormalities.
How does cerebral malaria occur in complicated malaria?
Cerebral malaria occurs due to the sequestration of infected erythrocytes in cerebral capillaries, blocking blood flow and causing local hypoxia. This leads to inflammation, altered blood-brain barrier permeability, and cerebral edema, resulting in an unrousable coma and neurological deficits.
What contributes to severe anemia in malaria?
Severe anemia in malaria is due to a combination of parasitic destruction of erythrocytes (hemolysis), bone marrow suppression, and immune-mediated clearance of infected red blood cells. The body is unable to produce enough new red blood cells to replace the lost ones, leading to normocytic anemia.
How does respiratory distress occur in severe malaria?
Respiratory distress in severe malaria is often a result of acute respiratory distress syndrome (ARDS), which occurs due to widespread inflammation, pulmonary edema, and increased permeability of the alveolar-capillary membrane. This leads to impaired gas exchange and difficulty in breathing.
What causes renal failure in complicated malaria?
Renal failure in severe malaria is due to acute tubular necrosis, secondary to hemolysis, cytokine-induced inflammation, and the accumulation of free heme from lysed erythrocytes, which is toxic to kidney cells. This results in decreased urine output and elevated serum creatinine levels.
What is the cause of hypoglycemia in severe malaria?
Hypoglycemia in severe malaria is often caused by the consumption of glucose by the parasite, liver dysfunction, and the use of quinine, which can increase insulin secretion. This combination of factors can lead to low blood glucose levels, especially in pregnant women.
How does circulatory collapse (shock) occur in severe malaria?
Circulatory collapse in severe malaria is due to septic shock, characterized by low blood pressure, altered vascular tone, and inadequate perfusion of vital organs. This is often exacerbated by hypovolemia from fluid loss, capillary leak, and the release of inflammatory cytokines.
How does coagulopathy occur in severe malaria?
Coagulopathy in severe malaria is caused by disseminated intravascular coagulation (DIC), where there is excessive clotting and fibrinolysis. The release of parasite antigens triggers the clotting cascade, leading to widespread microvascular thrombi and hemorrhage, contributing to spontaneous bleeding.
Why is developing a malaria vaccine challenging?
Developing a malaria vaccine is challenging due to the complex life cycle of the parasite, Plasmodium, which has multiple stages (liver, blood, and mosquito stages) that require different immune responses. Additionally, Plasmodium species, especially Plasmodium falciparum, exhibit antigenic variation and immune evasion mechanisms, making it difficult to design a vaccine that provides broad protection.
What are the challenges with the Plasmodium parasite’s life cycle in vaccine development?
The parasite has a complex life cycle with different stages: sporozoite, liver stage, merozoite, and gametocyte. Each stage expresses different antigens, requiring a vaccine to target multiple stages to be effective, complicating the development of a single vaccine.
Why does antigenic variation complicate malaria vaccine development?
Antigenic variation occurs as Plasmodium parasites change the proteins on their surface during different stages of infection. This makes it difficult for the immune system to recognize and destroy the parasite, and it poses a significant challenge for creating a vaccine that provides long-lasting immunity.
What role does the immune response play in malaria vaccine challenges?
The immune response to malaria is not always protective. Some individuals develop partial immunity after repeated exposure, but this immunity is not strong enough to prevent infection entirely. A vaccine must stimulate a strong and long-lasting immune response, which is difficult due to the parasite’s ability to evade immunity.
What is the current status of malaria vaccines?
The RTS,S/AS01 vaccine has shown limited efficacy in preventing malaria. Although it reduces clinical malaria in young children, its effectiveness wanes over time, and it does not provide complete protection, limiting its use as a standard vaccine for travelers.
Why is the RTS,S/AS01 vaccine not suitable for travelers?
The RTS,S/AS01 vaccine provides only partial protection, especially against Plasmodium falciparum, and the immunity it offers diminishes over time. This makes it unsuitable for travelers who may have limited exposure to malaria, as the vaccine may not offer sufficient protection during their trip.
What is the mechanism of action of doxycycline in suppressive malaria prophylaxis?
Doxycycline is a broad-spectrum antibiotic that inhibits protein synthesis in Plasmodium parasites by binding to the 30S ribosomal subunit. This prevents the synthesis of essential proteins, thereby inhibiting parasite growth during the blood stage of infection.
What are the common adverse drug reactions (ADRs) associated with doxycycline?
Common ADRs include:
Gastrointestinal issues (nausea, vomiting, diarrhea)
Photosensitivity (increased sensitivity to sunlight)
Esophageal irritation or ulcers (especially if taken without sufficient water or lying down afterward)
What are some serious ADRs of doxycycline in suppressive prophylaxis?
Serious ADRs, though rare, may include:
Hepatotoxicity (liver damage)
Severe allergic reactions (e.g., rash, anaphylaxis)
Blood dyscrasias (e.g., thrombocytopenia)
What are the cautions/contraindications for using doxycycline for malaria prophylaxis?
Cautions/contraindications include:
Pregnancy: Not recommended during pregnancy, especially in the second and third trimesters, due to risks of tooth discoloration and skeletal effects in the developing fetus.
Children under 8 years: Can cause permanent tooth discoloration and enamel hypoplasia.
Renal and hepatic impairment: Caution is needed in patients with liver or kidney disease.
Sun exposure: Patients should be advised to avoid excessive sun exposure to prevent photosensitivity reactions.
What is the mechanism of action of mefloquine in suppressive malaria prophylaxis?
Mefloquine interferes with the Plasmodium parasite’s ability to detoxify heme within red blood cells. By inhibiting the polymerization of heme into non-toxic hemozoin, mefloquine causes the buildup of toxic free heme, leading to parasite death during the erythrocytic stage of infection.
What are the common adverse drug reactions (ADRs) associated with mefloquine?
Common ADRs include:
Gastrointestinal issues (nausea, vomiting, abdominal pain)
Dizziness or vertigo
Sleep disturbances (e.g., vivid dreams or nightmares)
What are some serious ADRs of mefloquine in suppressive prophylaxis?
Serious ADRs may include:
Neuropsychiatric effects (e.g., anxiety, depression, confusion, hallucinations)
Cardiac arrhythmias (prolonged QT interval)
Severe allergic reactions (e.g., rash, anaphylaxis)
What are the cautions/contraindications for using mefloquine for malaria prophylaxis?
Cautions/contraindications include:
Psychiatric disorders: Mefloquine is contraindicated in individuals with a history of psychiatric conditions (e.g., depression, anxiety, psychosis) due to its neuropsychiatric side effects.
Cardiac issues: Mefloquine should be avoided in patients with a history of arrhythmias or prolonged QT intervals.
Pregnancy: It should be avoided during the first trimester of pregnancy but may be used in later trimesters under certain conditions.
Liver or kidney impairment: Caution is advised in patients with liver or kidney disease.
History of seizures: Mefloquine can lower the seizure threshold, so it should be avoided in patients with seizure disorders.
How do doxycycline and mefloquine compare in terms of their role in suppressive prophylaxis?
Both drugs are used for suppressive malaria prophylaxis, but they differ in their mechanisms and ADR profiles:
Doxycycline is an antibiotic that targets protein synthesis, and is effective against Plasmodium in the blood stage. It is generally well-tolerated but requires daily administration and may cause gastrointestinal issues and photosensitivity.
Mefloquine is an antimalarial drug that targets heme detoxification in the parasite. It is more effective for long-term prophylaxis but has a higher incidence of neuropsychiatric side effects, making it less suitable for individuals with a history of psychiatric or cardiac conditions.
Why is mefloquine considered a less favorable option in some patients?
Mefloquine is considered less favorable in patients with psychiatric conditions or cardiac arrhythmias due to its neuropsychiatric and cardiotoxic side effects. Additionally, it is contraindicated in individuals with a history of seizures or certain cardiac conditions (e.g., prolonged QT interval).
What is the mechanism of action of chloroquine (hydroxychloroquine) in “causal prophylaxis” of malaria?
Chloroquine (and its derivative hydroxychloroquine) works by inhibiting the parasite’s ability to detoxify heme, a byproduct of hemoglobin degradation. The drug interferes with the polymerization of free heme into hemozoin, leading to the accumulation of toxic free heme in the parasite. This results in parasite death during the blood stage of infection.
What are the common adverse drug reactions (ADRs) associated with chloroquine and hydroxychloroquine?
Common ADRs include:
Gastrointestinal symptoms (nausea, vomiting, abdominal discomfort)
Skin rash
Headache and dizziness
Visual disturbances (due to retinopathy with long-term use)
What are some serious ADRs of chloroquine and hydroxychloroquine in “causal prophylaxis”?
Serious ADRs include:
Retinopathy: Long-term use can lead to retinal damage, particularly with high doses, which can result in irreversible vision impairment.
Cardiotoxicity: Can cause arrhythmias, particularly in those with pre-existing heart conditions.
Severe allergic reactions: Anaphylaxis or angioedema.
What are the cautions/contraindications for using chloroquine or hydroxychloroquine for malaria prophylaxis?
Cautions/contraindications include:
Retinal disease: Hydroxychloroquine and chloroquine should be avoided in patients with pre-existing retinal diseases or those who are at risk of developing retinopathy.
Cardiac conditions: Use with caution in patients with heart rhythm disorders (e.g., QT prolongation) or those with a history of seizures.
Pregnancy: Generally considered safe during pregnancy for malaria prophylaxis, but caution is needed due to potential toxicity at higher doses.
G6PD deficiency: Increased risk of hemolysis in G6PD-deficient individuals.
What is the mechanism of action of proguanil in “causal prophylaxis” of malaria?
Proguanil is a prodrug that is metabolized into its active form, cycloguanil, which inhibits dihydrofolate reductase (DHFR). DHFR is essential for the synthesis of folate, which is crucial for DNA synthesis in the Plasmodium parasite. By inhibiting DHFR, proguanil prevents the replication of the parasite during the liver stage and early blood stage of infection.
What are the common adverse drug reactions (ADRs) associated with proguanil?
Common ADRs include:
Gastrointestinal disturbances (nausea, vomiting, abdominal pain)
Headache and dizziness
Skin rash
What are some serious ADRs of proguanil in “causal prophylaxis”?
Serious ADRs, though rare, may include:
Hepatotoxicity: Elevated liver enzymes and liver injury.
Bone marrow suppression: Long-term use may cause suppression of blood cell production.
Severe allergic reactions: Anaphylaxis, although rare.
What are the cautions/contraindications for using proguanil for malaria prophylaxis?
Cautions/contraindications include:
Renal impairment: Proguanil is excreted via the kidneys, so dosage adjustment is necessary in renal insufficiency.
Pregnancy: Generally not recommended during the first trimester, though it may be used in later stages under medical supervision.
Allergic reactions: Patients with a history of hypersensitivity to proguanil should avoid its use.
What is the mechanism of action of atovaquone in “causal prophylaxis” of malaria?
Atovaquone inhibits the parasite’s mitochondrial electron transport chain, specifically the cytochrome bc1 complex. This disrupts the parasite’s energy production and affects the synthesis of nucleic acids and the maintenance of mitochondrial membrane potential, ultimately leading to parasite death. Atovaquone is particularly effective against the liver stage and early blood stages of the parasite.
What are the common adverse drug reactions (ADRs) associated with atovaquone?
Common ADRs include:
Gastrointestinal issues (nausea, diarrhea, abdominal pain)
Headache
Dizziness
What are some serious ADRs of atovaquone in “causal prophylaxis”?
Serious ADRs, though rare, may include:
Liver toxicity: Elevated liver enzymes, hepatotoxicity.
Severe allergic reactions: Rash, anaphylaxis.
How do drug combinations like proguanil and atovaquone (Malarone) enhance the effectiveness of causal prophylaxis?
The combination of proguanil (a DHFR inhibitor) and atovaquone (which inhibits mitochondrial function) works synergistically to target different stages of the Plasmodium parasite. Proguanil acts on the liver stage and early blood stage, while atovaquone targets the blood stages. This combination enhances the efficacy and reduces the chance of resistance development compared to single-drug therapies.
What are the benefits and risks of drug combinations for malaria prophylaxis?
Benefits:
Increased efficacy: Combinations target different stages and mechanisms of the parasite, increasing the likelihood of success.
Reduced resistance: Using drugs with different mechanisms reduces the risk of developing drug-resistant malaria.
Risks:
Increased side effects: Combining drugs may increase the likelihood of experiencing adverse reactions from each drug.
Drug interactions: Caution is needed when combining drugs, especially with drugs that affect the metabolism of other medications.
What is the mechanism of action of primaquine in “causal prophylaxis” of malaria?
Primaquine is an 8-aminoquinoline antimalarial that works by targeting the liver stages of Plasmodium parasites, particularly the pre-erythrocytic stages (i.e., sporozoites and merozoites) and hypnozoites. It acts by generating reactive oxygen species (ROS) within the parasite, damaging cellular components such as lipids, proteins, and DNA, which results in parasite death. It is effective against the liver stages of Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae.
What is the mechanism of action of primaquine in “post-travel presumptive anti-relapse therapy” of malaria?
Primaquine is particularly effective in preventing relapses of Plasmodium vivax and Plasmodium ovale malaria, which form dormant liver stages known as hypnozoites. It targets the hypnozoites and eradicates them, preventing the recurrence of malaria after the initial infection. By eliminating these dormant stages, primaquine helps prevent the relapse of malaria months after the initial infection has been treated.
What are the common adverse drug reactions (ADRs) associated with primaquine?
Gastrointestinal disturbances: Nausea, vomiting, abdominal pain.
Headache and dizziness.
Rash and pruritus (itching).
Hemolysis in G6PD-deficient individuals.
What are the serious ADRs of primaquine in “causal prophylaxis” and “post-travel presumptive anti-relapse therapy”?
Serious ADRs, though rare, include:
Hemolytic anemia: Particularly in individuals with G6PD deficiency, primaquine can cause severe hemolysis, leading to anemia and jaundice.
Methemoglobinemia: In some cases, primaquine can cause elevated levels of methemoglobin, leading to cyanosis and potential respiratory distress.
Cardiotoxicity: In rare cases, primaquine may cause arrhythmias.
What are the cautions/contraindications for using primaquine in malaria prophylaxis and treatment?
Cautions/contraindications include:
G6PD deficiency: Primaquine can cause severe hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Testing for G6PD deficiency should be done before using primaquine.
Pregnancy: Primaquine is contraindicated during the first trimester of pregnancy due to its potential teratogenic effects. It may be used in later stages of pregnancy only if the benefits outweigh the risks.
Breastfeeding: Primaquine is excreted in breast milk, and its use during breastfeeding should be carefully considered, especially in infants under 6 months of age.
Hepatic impairment: Caution is needed in patients with liver disease, as primaquine is metabolized in the liver
What are the benefits of using primaquine in malaria prophylaxis and treatment?
The benefits of primaquine include:
Effective against liver stages: It is one of the few drugs that can target and eliminate liver stages, including hypnozoites, preventing relapses of malaria caused by P. vivax and P. ovale.
Post-travel prophylaxis: It is useful in individuals who have recently returned from malaria-endemic areas to prevent relapse in cases of P. vivax or P. ovale malaria.
Broad action: Effective against both the acute (blood stage) and dormant (liver stage) phases of the parasite, making it a valuable tool for comprehensive malaria treatment.
How is primaquine typically administered for “causal prophylaxis” and “post-travel presumptive anti-relapse therapy”?
Primaquine is typically administered as a daily oral dose. For causal prophylaxis, it is often taken in conjunction with other antimalarial medications (such as chloroquine or atovaquone-proguanil) for several days before and after potential exposure. For post-travel presumptive anti-relapse therapy, it is usually administered for a short course (7–14 days) following the end of treatment for an acute Plasmodium vivax or Plasmodium ovale infection, to prevent relapse.
How does primaquine compare to other antimalarial drugs in terms of its role in malaria treatment?
Primaquine is unique in its ability to target and eliminate the liver stages of malaria, particularly hypnozoites. While other antimalarials (e.g., chloroquine, artemisinin) are primarily effective against the blood stages of the parasite, primaquine’s ability to target the liver stages makes it crucial in preventing relapse, especially for Plasmodium vivax and Plasmodium ovale. It is often used in combination with other drugs to ensure both blood and liver stages are addressed.
What is the mechanism of action of artesunate in treating malaria?
Artesunate is a water-soluble derivative of artemisinin. It exerts its antimalarial effect by generating reactive oxygen species (ROS) in the parasite. These ROS damage parasite proteins, lipids, and DNA, leading to the death of the Plasmodium parasite. Artesunate acts primarily on the blood stage of the parasite, killing the trophozoite and schizont forms of Plasmodium falciparum and other Plasmodium species.
What is the mechanism of action of Artemisinin Combination Therapy (ACT)?
ACT combines an artemisinin derivative (e.g., artemether or artesunate) with a partner drug (e.g., lumefantrine, piperaquine, or amodiaquine). The artemisinin derivative rapidly reduces parasite load by generating reactive oxygen species that kill the parasite. The partner drug targets different stages of the parasite life cycle, including the trophozoite and schizont stages, and inhibits further parasite replication. The combination enhances efficacy and reduces the risk of drug resistance.
How does artemether-lumefantrine work in treating malaria?
Artemether (an artemisinin derivative) rapidly kills Plasmodium parasites by generating ROS. Lumefantrine, a long-acting partner drug, inhibits the synthesis of heme within the parasite, interfering with the parasite’s ability to detoxify heme and disrupts its cellular processes. The combination provides synergistic action, increasing cure rates and reducing the risk of resistance.
How does artenimol-piperaquine work in treating malaria?
Artenimol is a longer-acting derivative of artemisinin that also generates reactive oxygen species to damage the parasite. Piperaquine, a partner drug, inhibits plasmodial heme polymerase, preventing the detoxification of heme. This disrupts the parasite’s ability to digest hemoglobin, effectively killing the parasite in its blood stage. The combination therapy enhances efficacy and helps reduce resistance risk.
What are the common adverse drug reactions (ADRs) of artesunate and ACT?
Common ADRs include:
Gastrointestinal symptoms: Nausea, vomiting, abdominal pain, and diarrhea.
Headache and dizziness.
Fatigue or weakness.
Rash and itching.
Palpitations or arrhythmias (particularly with lumefantrine or piperaquine).
What are the serious ADRs associated with artesunate and ACT?
Serious ADRs, although rare, may include:
Severe allergic reactions (anaphylaxis).
Cardiovascular effects: Prolonged QT interval, especially with lumefantrine and piperaquine, leading to arrhythmias.
Hemolysis in G6PD-deficient individuals (especially with artesunate).
Hepatotoxicity: Liver damage, especially in individuals with preexisting liver conditions.
Neurotoxicity: Neurological effects such as seizures (very rare).
What are the cautions/contraindications for using artesunate and ACT in malaria treatment?
Cautions/contraindications include:
G6PD deficiency: Artesunate and ACT (especially with artemether) can cause hemolytic anemia in individuals with G6PD deficiency.
Pregnancy: Artemisinin derivatives, including artesunate and artemether, are generally safe in the second and third trimesters, but should be avoided in the first trimester unless absolutely necessary.
Liver or kidney disease: Caution is needed in individuals with hepatic or renal impairment, as drug metabolism may be altered.
Cardiac disorders: Care should be taken when using lumefantrine and piperaquine, as they can cause QT interval prolongation and increase the risk of arrhythmias.
Children: Dosage should be adjusted for children, and use of piperaquine should be avoided in neonates.
What are the benefits of artesunate and ACT in treating malaria?
Benefits include:
Rapid parasite clearance: Artesunate and ACT rapidly reduce parasitemia and provide a high cure rate for uncomplicated and severe malaria.
Combination therapy reduces resistance: The use of combination therapies, such as artemether-lumefantrine or artenimol-piperaquine, reduces the risk of resistance by targeting multiple stages of the parasite’s lifecycle.
Effective in severe malaria: Artesunate is considered the treatment of choice for severe malaria caused by Plasmodium falciparum, as it quickly clears parasites and reduces mortality.
How does ACT compare to other antimalarial therapies?
ACT is currently the gold standard for treating uncomplicated malaria due to its high efficacy, rapid action, and reduced resistance potential. Compared to older therapies (such as chloroquine), ACT is much more effective in reducing parasite burden and providing rapid symptom relief. It is particularly effective in drug-resistant areas, where chloroquine and other older treatments are ineffective.
How is artesunate and ACT typically administered in malaria treatment?
Artesunate is typically administered as intravenous (IV) or intramuscular (IM) therapy in severe malaria, followed by oral artesunate or artemether when the patient is stable.
ACT (artemether-lumefantrine or artenimol-piperaquine) is administered orally, with multiple doses over 3 days for uncomplicated malaria. The combination therapy is taken with food to enhance drug absorption, especially lumefantrine.
