Malaria Notes

What is Malaria?

• Mosquito-borne infectious disease affecting humans and animals.

• Symptoms: fever, tiredness, vomiting, headaches; severe cases include jaundice, seizures, coma, or death.

• Transmitted by infected Anopheles mosquitoes carrying the Plasmodium parasite.

• Transmitted by female Anopheles mosquitoes mainly between dusk and dawn.

Causes & Transmission

• Predominantly caused by $P. falciparum$ in sub-Saharan Africa, New Guinea, and Hispaniola; $P. vivax$ more common in the Americas and western Pacific.

• Transmission via infected Anopheles mosquito and Plasmodium parasite.

• Mosquito bites skin parasites release in blood

• Sporozoyetes travel to the liver, mature, and infect red blood cells.

• Parasites multiply inside red blood cells, causing infected cells to burst and release merozoites (responsible for fever and symptoms) after an incubation period of about 2 weeks.

• Symptoms occur in cycles lasting 2-3 days as parasites continue to infect red blood cells.

Life Cycle of Plasmodium

1. Infected Anopheles mosquito transmits sporozoites into the bloodstream.

2. Sporozoites migrate to the liver, invade hepatocytes, and form schizonts (pre-erythrocytic stage).

   • This initial liver stage is asymptomatic but critical for the parasite's development.

3. Hypnozoites (quiescent stage in $P. vivax$ and $P. ovale$) can cause relapsed disease.

   • These dormant forms can reactivate weeks or months later, leading to recurrent malaria episodes.

4. Schizonts rupture, releasing merozoites into circulation to invade red blood cells (erythrocytic stage).

   • This stage is responsible for the clinical symptoms of malaria.

5. Merozoites mature into ring forms, then trophozoites, then schizonts. Artemisinins, atovaquone-proguanil, doxycycline, mefloquine, and chloroquine interrupt schizogony within red cells.

   • Different antimalarial drugs target specific stages of parasite development within red blood cells.

6. Some merozoites differentiate into gametocytes, ingested by mosquitoes, completing the cycle.

   • Gametocytes are the sexual forms of the parasite and are essential for transmission back to mosquitoes.

Clinical Manifestations: Uncomplicated Malaria

• Initial symptoms: nonspecific, including tachycardia, tachypnea, chills, malaise, fatigue, diaphoresis, headache, cough, anorexia, nausea, vomiting, abdominal pain, diarrhea, arthralgias, and myalgias.

• Physical findings: anemia and palpable spleen.

• Mild jaundice may occur in falciparum malaria.

• Febrile paroxysms occur at irregular intervals; temperature may rise above 40ºC, with tachycardia and/or delirium.

• Febrile convulsions may occur in children.

• Laboratory findings: parasitemia (usually <5000 parasites/microL), anemia, thrombocytopenia, elevated transaminases, mild coagulopathy, BUN/creatinine.

  • Laboratory confirmation is essential for accurate diagnosis and management.

Clinical Manifestations: Severe Malaria

• Results from parasitized RBCs adhering to small blood vessels, causing infarcts, capillary leakage, and organ dysfunction.

• Manifestations: altered consciousness, respiratory distress (ARDS), circulatory collapse, metabolic acidosis, renal failure, hemoglobinuria, hepatic failure, coagulopathy, severe anemia, hypoglycemia.

• Physical findings: pallor, petechiae, jaundice, hepatomegaly, splenomegaly.

• Diagnostic evaluation: parasitemia ≥4 to 10 percent, anemia, thrombocytopenia, coagulopathy, elevated transaminases, elevated BUN/creatinine, acidosis, and hypoglycemia.

Definition of severe falciparum malaria Manifestations

• Impaired consciousness: Glasgow coma score <11 24 in adults or Blantyre coma score <3 children

• Prostration: Generalized weakness Multiple convulsions: More than two episodes within hours Acidosis: A base deficit of>8 mEq/L or clinical indicators of acidosis

• Hypoglycemia: Blood or plasma glucose <40 mg/dL for children ≥5 years and adults; blood or plasma glucose <54 <5

• Severe anemia: Hemoglobin concentration ≤5 g/dL hematocrit ≤15 percent in <12 of age with parasite count>10,000/mcL

• Renal impairment: Plasma or serum creatinine >3 mg/dL or blood urea >20 mmol/L

• Jaundice: Plasma or serum bilirubin >50 mcmol/L with a parasite count >100,000/mcL

• Pulmonary edema Radiographically confirmed or oxygen saturation <92 percent on room air with respiratory rate>30/minutes

• Significant bleeding: Including recurrent or prolonged bleeding (from the nose, gums, or venipuncture sites), hematemesis, or melena

• Shock: Compensated shock is defined as capillary refill ≥3 seconds Decompensated shock is defined as systolic blood pressure <70 mmHg in children or <80 mmHg in adults

• Hyperparasitemia: P. falciparum parasitemia >10 percent (>500,000/mcL)

Clinical Manifestations: Cerebral Malaria

• Encephalopathy with impaired consciousness, delirium, and/or seizures; focal neurologic signs are unusual.

• Risk factors: age (children and older adults), pregnancy, poor nutritional status, HIV infection, host genetic susceptibility, and history of splenectomy.

• CSF examination may be normal or show slightly elevated protein and cell count.

• Retinal hemorrhages may be observed in 30-40% of cases.

• Untreated cerebral malaria is almost universally fatal; with treatment, mortality is 15-20%.

Diagnosis

• Suspect malaria in febrile patients with exposure to endemic regions.

• Methodology:

  • Parasite-based diagnosis

  • Clinical or presumptive-based diagnosis

• Differential diagnosis

Diagnosis: Parasite-Based

• Light microscopy: standard tool using Giemsa-stained blood smears.

• Allows species identification and quantification of parasitemia.

Blood Smear Preparation

• Capillary or anticoagulated venous blood.

• Thin smears: maintain integrity of erythrocytes for species identification and parasite density measurement.

• Thick smears: lyse red blood cells to visualize parasites, screen for presence/absence of parasites, and estimate density.

Rapid Diagnostic Tests (RDTs)

• Detect malaria parasite antigens; results in 15-20 minutes.

• Qualitative result only.

• Antigen-based tests: detect histidine-rich protein 2 (HRP2), Plasmodium lactate dehydrogenase (pLDH), and aldolase.

• Molecular tests:

  • Used in reference laboratories for research and epidemiology.

  • Nucleic acid tests (PCR) are gold standard in efficacy studies.

Diagnosis: Clinical Based

• Suspect malaria in febrile patients with exposure to endemic regions.

• No pathognomonic signs or symptoms.

• If parasite-based diagnosis is unavailable, start antimalarial therapy for suspected $P. falciparum$ infection.

• Clinical diagnosis is frequently incorrect, even in endemic areas.

Diagnosis: Differential Diagnosis

• Dengue fever: malaise, headache, fatigue, abdominal discomfort, and muscle aches.

• Chikungunya: milder than dengue, self-limiting, often with a rash.

• Meningitis: severe headache, but no neck stiffness or photophobia.

• Pneumonia: fever, cough, dyspnea, and sputum production.

• Sepsis due to bacteremia: fever, tachycardia, and altered mental status.

• Typhoid fever: fever, bradycardia, abdominal pain, and rash.

• Leptospirosis: fever, rigors, myalgia, and headache; may have petechial hemorrhages.

• Viral hemorrhagic fever: fever, malaise, systemic symptoms; may have petechial hemorrhages.

Treatment: General Principles

• Inform patients that malaria can recrudesce; repeat evaluation for subsequent febrile episodes.

• Malaria is a nationally notifiable disease.

• Identify if area is chloroquine-sensitive or resistant and use national protocols.

• Uncomplicated malaria: oral therapy with combination of two agents (chloroquine resistance) or chloroquine monotherapy (chloroquine sensitivity).

• Hospitalization indications: tolerance of antimalarial therapy, monitoring parasitemia reduction, and progression to severe disease.

  • Young children

  • Immunocompromised patients

  • Individuals with no acquired immunity

  • Hyperparasitemia (4 to 10 percent) without signs of severe infection

Treatment: Severe Malaria

• If Parenteral Artemesinin is available:

  • Artesunate IV/IM 2.4mg/kg at 0, 12, 24, 48

• If Parenteral Artemesinin is not available:

  • Artemether IM 3.2mg/kg; 1.6mg/kg OD

  • Quinine salt 20mg/kg infusion, then 10mg/kg Q8H

  • ACT+ Primaquine 0.75mg/kg on day 2

  • Quinine 10mg/kg Q8H plus Doxycycline 100mg OD or Clindamycin 10mg/kg BD (pregnancy, child <8)

  • Treatment strategies vary based on disease severity and availability of specific medications.

  • Close monitoring is essential to prevent complications and ensure effective treatment.

Traveler's Chemoprevention

• Tailor chemoprophylaxis to individual itineraries.

• For multiple destinations, select a single effective agent.

• Low-risk destinations: mosquito avoidance measures only.

• Chloroquine-resistant $P. falciparum$: mosquito avoidance plus atovaquone-proguanil, mefloquine, doxycycline, or tafenoquine.

• Chloroquine-sensitive $P. falciparum$: mosquito avoidance plus chloroquine, atovaquone-proguanil, tafenoquine, mefloquine, or doxycycline.

• Predominant species $P. vivax$