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Malaria: Pathogenesis, Diagnosis, and Treatment

Presentation23 slidesB.Pharm, Pharm.D

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Detailed presentation on malaria covering causative agents, transmission, clinical features, diagnosis methods, and management strategies including drug regimens and special populations.

  • malaria
  • Plasmodium
  • antimalarial drugs
  • diagnosis
  • treatment

By Dr. Ayesha Fatima

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  1. Slide 1. MALARIA Dr. Ayesha Fatima Pharm D Assistant Professor Dept of Pharmacy Practice
  2. Slide 2. Malaria is a mosquito-borne infectious disease caused by protozoan parasites of the genus Plasmodium . It is characterized by characterized clinically by periodic fever with chills, sweating, anemia, splenomegaly, and in severe cases, multi-organ dysfunction. or Malaria is an acute febrile protozoal infection of humans caused by parasites of the genus Plasmodium , transmitted by the bite of an infected female Anopheles mosquito. Causative Organism ⮚ Malaria is caused by protozoan parasites of the genus Plasmodium , mainly: ⮚ Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae Vector ⮚ The disease is transmitted by the bite of the infected female Anopheles mosquito, which acts as the definitive host and biological vector. ⮚ Only the female mosquito transmits malaria because it feeds on human blood for egg development.
  3. Slide 3. Mode of Transmission 1. Malaria is transmitted primarily through the inoculation of sporozoites into human blood during the bite of an infected female Anopheles mosquito. ⮚ Less commonly, transmission may occur through: 2. Blood transfusion 3. Organ transplantation 4. Sharing contaminated needles 5. Transplacental transmission (congenital malaria)
  4. Slide 4. Human (Asexual) Cycle – In the Human Host 1️⃣ Inoculation of Sporozoites Infection begins when an infected female Anopheles mosquito bites a human. Sporozoites are injected from the mosquito’s salivary glands into the bloodstream. 2️⃣ Hepatic (Pre-erythrocytic) Stage Sporozoites rapidly reach the liver., invade hepatocytes (liver cells). Undergo asexual multiplication (schizogony/merogony). One sporozoite produces 10,000–30,000 merozoites. Infected liver cells rupture and release merozoites into circulation. In infections caused by: Plasmodium viva, Plasmodium ovale Some forms remain dormant in the liver as hypnozoites, causing relapse weeks to months later. PATHOGENESIS
  5. Slide 5. 3️⃣ Erythrocytic (Blood) Stage Merozoites invade red blood cells (RBCs). Inside RBCs they develop into: Ring form (early trophozoite, Trophozoite, Schizont The parasite multiplies (6–30 merozoites per RBC). RBC ruptures and releases merozoites. This cycle repeats every: 48 hours (most species), 72 hours in Plasmodium malariae Repeated RBC destruction causes: Fever with chills (periodic fever), Anemia Splenomegaly Severe disease is commonly caused by Plasmodium falciparum. 4️⃣ Gametocyte Formation After several asexual cycles: Some parasites differentiate into male and female gametocytes. These sexual forms circulate in the blood. They are infective to mosquitoes.
  6. Slide 6. B. Mosquito (Sexual) Cycle – In the Vector 5️⃣ Ingestion of Gametocytes When a female Anopheles mosquito bites an infected person, it ingests gametocytes. 6️⃣ Fertilization in Mosquito Gut In the mosquito midgut: Male gametocyte → microgamete, Female gametocyte → macrogamete Fusion forms a zygote . 7️⃣ Ookinete Formation Zygote elongates to form an ookinete, penetrates the gut wall. 8️⃣ Oocyst Formation Ookinete develops into an oocyst on the outer gut wall. Inside the oocyst, repeated asexual division occurs. 9️⃣ Sporozoite Formation Thousands of sporozoites are formed. They migrate to the mosquito’s salivary glands. Transmission to Another Human During the next blood meal, sporozoites are injected into a new human host.
  7. Slide 8. A. Human Host (Asexual Cycle) Infected Female Anopheles Mosquito Bite Sporozoites injected into bloodstream Sporozoites reach liver cells (Hepatic stage) Pre-erythrocytic schizogony (multiplication in hepatocytes) Thousands of merozoites released into blood Merozoites invade RBCs Ring form → Trophozoite → Schizont RBC rupture releases merozoites Fever cycle repeats every 48–72 hours Some parasites form gametocytes Dormant hypnozoites occur in: Plasmodium vivax, Plasmodium ovale B. Mosquito (Sexual Cycle) Mosquito ingests gametocytes during blood meal Male + Female gametes fuse in midgut Zygote formation Ookinete formation Oocyst develops in gut wall Sporozoites formed inside oocyst Sporozoites migrate to salivary glands Ready to infect next human
  8. Slide 9. When to Suspect Malaria Malaria should be suspected in: 1. Any patient with intermittent fever in endemic areas 2. Patients with recent travel history to endemic regions 3. Fever with chills without obvious source 4. However, malaria can mimic many infections, so other causes should be ruled out if the patient has: 1. Running nose and cough (respiratory infection) 2. Diarrhea or dysentery 3. Burning micturition (UTI) 4. Skin rash or abscess 5. Painful joint swelling 6. Ear discharge 7. Lymphadenopathy
  9. Slide 10. Clinical Presentation of Malaria Malaria presents with a wide spectrum of manifestations ranging from mild febrile illness to life-threatening complications. The severity depends on the species involved, parasite load, immunity of the patient, and timeliness of treatment. Severe disease is most commonly associated with Plasmodium falciparum. Uncomplicated (Classical) Malaria: Prodromal Symptoms These occur before the typical fever pattern: 1. Headache 2. Malaise 3. Myalgia 4. Arthralgia 5. Anorexia 6. Nausea and vomiting
  10. Slide 11. Classical Malarial Paroxysm (Intermittent Fever) The fever typically occurs in cycles (every 48–72 hours depending on species) and has three stages: 3. Sweating Stage Profuse sweating Temperature falls Weakness and fatigue General Physical Findings Pallor (due to anemia) Splenomegaly Mild hepatomegaly Tachycardia 1. Cold Stage Sudden onset of chills Rigors (shivering) Feeling extremely cold 2. Hot Stage High fever (often 39–41°C) Flushed face Headache Restlessness
  11. Slide 12. Severe (Complicated) Malaria: Seen mainly in infection with Plasmodium falciparum. Why These Symptoms Occur 1. Fever → Due to synchronized rupture of infected RBCs 2. Anemia → RBC destruction 3. Splenomegaly → Increased clearance of infected RBCs 4. Cerebral malaria → Sequestration of infected RBCs in brain capillaries • Altered sensorium • Seizures • Coma (Cerebral malaria) Neurological • Severe anemia • Hemoglobinuria • Spleenomegaly Hematological • Hypoglycemia • Metabolic acidosis Metabolic • Acute renal failure • Reduced urine output Renal • Acute pulmonary edema • Respiratory distress Respiratory
  12. Slide 13. Diagnosis of Malaria Early and accurate diagnosis is essential to prevent complications and reduce mortality. 1. Laboratory Diagnosis A. Peripheral Blood Smear (Gold Standard): Two types of smears: 1. Thick smear More sensitive Detects presence of parasites 2. Thin smear Identifies species Assesses parasite density Species commonly detected: 1. Plasmodium falciparum 2. Plasmodium vivax 3. Plasmodium ovale 4. Plasmodium malariae
  13. Slide 14. 4. Supportive Laboratory Findings • Anemia • Thrombocytopenia • Elevated bilirubin • Hypoglycemia • Elevated creatinine (in severe cases) 5. Diagnosis of Severe Malaria • Severe malaria is diagnosed when: • Peripheral smear shows parasitemia AND • There is evidence of organ dysfunction (coma, severe anemia, renal failure, acidosis, etc.) • Severe disease is most commonly caused by Plasmodium falciparum. 2. Rapid Diagnostic Tests (RDTs) • Detect specific malaria antigens in blood • Results within 15–20 minutes • Useful in remote areas • Cannot quantify parasite load 3. Polymerase Chain Reaction (PCR) • Highly sensitive and specific • Detects low-level parasitemia • Used mainly in research/reference laboratories
  14. Slide 15. Management of Malaria Type of Malaria Drug of Choice Dose & Duration Important Points Chloroquine- sensitive malaria Chloroquine Total 25 mg/kg over 3 days (Adult: 600 mg base initially, 300 mg after 6 hrs, then 300 mg daily × 2 days) Only in sensitive areas Chloroquine- resistant falciparum malaria Artemisinin-based Combination Therapy (ACT) - Artesunate + Amodiaquine Artesunate 4 mg/kg/day + Amodiaquine 10 mg/kg/day *3-day regimen Artemisinin should NOT be used as monotherapy Treatment of Uncomplicated Malaria Management of malaria depends on: 1. Species of Plasmodium 2. Severity (uncomplicated or severe) 3. Drug resistance pattern 4. Patient group (pregnancy, children, travellers)
  15. Slide 16. ACT Regimen Dose Duration Artemether + Lumefantrine 6-dose regimen 3 days Artesunate + Amodiaquine Artesunate 4 mg/kg/day + Amodiaquine 10 mg/kg/day 3 days Artesunate + Mefloquine Artesunate 4 mg/kg/day + Mefloquine 8.3 mg/kg/day 3 days Artesunate + Sulfadoxine- Pyrimethamine Artesunate 4 mg/kg/day × 3 days + Single dose SP (25/1.25 mg/kg) 3 days Dihydroartemisinin + Piperaquine DHA 4 mg/kg/day + Piperaquine 18 mg/kg/day 3 days WHO Recommended ACT Options Regimen Dose Duration Artesunate + Doxycycline / Tetracycline / Clindamycin Artesunate 2 mg/kg/day + partner drug 7 days Quinine + Doxycycline / Tetracycline / Clindamycin Standard quinine dose + partner drug 7 days Second-Line Treatment
  16. Slide 17. Trimester Recommended Treatment First trimester Quinine + Clindamycin × 7 days If failure Artesunate + Clindamycin × 7 days Second & Third trimester ACT OR Artesunate + Clindamycin OR Quinine + Clindamycin Treatment in Special Populations A. Pregnant Women B. Lactating Women Can receive ACT Avoid: Primaquine & Tetracycline C. Infants & Young Children ACT is first-line Ensure accurate dosing Rectal artesunate may be used if unable to swallow
  17. Slide 18. D. Travelers (Non-endemic Countries) Drug Options Duration Atovaquone + Proguanil 3 days Artemether + Lumefantrine 3 days Dihydroartemisinin + Piperaquine 3 days Quinine + Doxycycline / Clindamycin 7 days
  18. Slide 19. Aspect Treatment First-line drug IV Artesunate (preferred drug) Dose of IV Artesunate 2.4 mg/kg IV at 0 hr, 12 hr, 24 hr, then once daily Alternative (if artesunate unavailable) IV Quinine (with cardiac monitoring) After patient improves & can take oral drugs Complete full course of oral ACT (Artemisinin-based Combination Therapy) Management of hypoglycemia IV 25–50% dextrose Management of seizures IV diazepam / lorazepam Management of severe anemia Blood transfusion Fluid management Careful IV fluids (avoid overload) Renal failure Dialysis if required Monitoring Vital signs, blood glucose, parasite count, urine output Treatment of Severe / Complicated Malaria Admit in ICU Treat complications aggressively Start treatment immediately (do not delay for lab confirmation if strongly suspected)
  19. Slide 20. Patient Education and Counselling in Malaria Proper patient education helps in preventing infection, ensuring treatment success, and reducing reinfection. 1️⃣ About the Disease Patients should be informed that: 1. Malaria is caused by Plasmodium parasites transmitted by the bite of an infected female Anopheles mosquito. 2. Common symptoms include fever with chills, sweating, headache, body pain, nausea, and weakness. 3. Severe malaria can affect the brain, kidneys, and lungs 4. Early diagnosis and complete treatment prevent complications. 5. Relapse can occur in infections caused by Plasmodium vivax and Plasmodium ovale due to dormant liver forms. 6. Advise patients to seek medical care immediately if fever develops after travel to endemic areas.
  20. Slide 21. 1. Purpose of Medication 1. To kill malaria parasites in the blood. 2. To prevent relapse (if primaquine is prescribed). 2. Dose and Duration 1. Take medicines exactly as prescribed. 2. Complete the full course even if symptoms improve. 3. Artemisinin-based combinations must be taken for full 3 days. 3. Missed Dose Advice 1. Take the missed dose as soon as remembered. 2. Do NOT double the dose if it is close to the next dose. 4. Possible Side Effects 1. Nausea, vomiting 2. Dizziness 3. Abdominal discomfort 4. Mild headache 5. If severe side effects occur (persistent vomiting, rash, breathing difficulty), seek medical help. 5. Special Advice 1. Take medication with food if advised (improves absorption). 2. Avoid alcohol during treatment. 3. Inform doctor about pregnancy or other illnesses. Counselling About Medications
  21. Slide 22. Prophylaxis Advice for Travellers: Travellers to endemic areas should: 1. Start prophylactic medication before travel (as prescribed). 2. Continue during stay and for recommended period after return. 3. Seek medical attention if fever develops even after returning home. Lifestyle Modifications Use long-sleeved clothing and full-length pants Apply mosquito repellent creams or sprays (especially at night) Use insecticide-treated bed nets Use mosquito coils or vaporizers Sleep in screened or air-conditioned rooms
  22. Slide 23. Special Focus on Mosquito Control (Community Level) a. Environmental Control Avoid water stagnation (drain stagnant water weekly) Cover water storage containers Dispose of unused tires, cans, coconut shells Maintain clean surroundings b. Household Control Install window and door screens Use larvicidal agents if recommended Participate in community spraying programs Preventing Reinfection and Spread Do not delay treatment if symptoms reappear Encourage family members with fever to get tested Follow government malaria control programs Promote awareness in community

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